0277.20 Attachment G

Pt. 158

40 CFR Ch. I (7–1–11 Edition)
Subpart E—Product Performance

PART 158—DATA REQUIREMENTS
FOR PESTICIDES

158.400 Product performance data requirements.

Subpart A—General Provisions
Subpart F—Toxicology

Sec.
158.1 Purpose and scope.
158.3 Definitions.
158.5 Applicability.
158.30 Flexibility.
158.32 Format of data submissions.
158.33 Confidential data.
158.34 Flagging of studies for potential adverse effects.
158.45 Waivers.
158.60 Minor use data policies.
158.70 Satisfying data requirements.
158.75 Requirements for additional data.
158.80 Use of other data.

158.500 Toxicology data requirements table.
158.510 Tiered testing options for nonfood
pesticides.

Subpart G—Ecological Effects
158.630 Terrestrial and aquatic nontarget
organisms data requirements table.
158.660 Nontarget plant protection data requirements table.

Subparts H–J [Reserved]
158.700–158.900

Subpart B—How To Use Data Tables

Subpart K—Human Exposure

158.100 Pesticide use patterns.
158.110 Required and conditionally required
data.
158.120 Determining data requirements.
158.130 Purposes of the registration data requirements.

158.1000 Applicator exposure—general requirements.
158.1010 Applicator exposure—criteria for
testing.
158.1020 Applicator exposure data requirements table.
158.1050 Post-application exposure—general
requirements.
158.1060 Post-application exposure—criteria
for testing.
158.1070 Post-application exposure data requirements table.

Subpart C—Experimental Use Permits
158.200 Experimental use permit data requirements tables.
158.210 Experimental use permit data requirements for product chemistry
158.220 Experimental use permit data requirements for product performance.
158.230 Experimental use permit data requirements for toxicology.
158.240 Experimental use permit data requirements for ecological effects.
158.243 Experimental use permit data requirements for terrestrial and aquatic
nontarget organisms.
158.250 Experimental use permit data requirements for human exposure.
158.260 Experimental use permit data requirements for environmental fate.
158.270 Experimental use permit data requirements for residue chemistry.
158.280–158.290 [Reserved]

Subpart L—Spray Drift
158.1100 Spray
table.

drift

data

requirements

Subpart M [Reserved]
158.1200–158.1299

[Reserved]

Subpart N—Environmental Fate
158.1300 Environmental fate data requirements table.

Subpart O—Residue Chemistry
158.1400 Definitions.
158.1410 Residue chemistry
ments table.

Subpart D—Product Chemistry

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[Reserved]

158.300 Definitions.
158.310 Product chemistry data requirements table.
158.320 Product identity and composition.
158.325 Description of materials used to
produce the product.
158.330 Description of production process.
158.335 Description of formulation process.
158.340 Discussion of formation of impurities.
158.345 Preliminary analysis.
158.350 Certified limits.
158.355 Enforcement analytical method.

data

Subparts P–T [Reserved]
158.1500–158.1900

[Reserved]

Subpart U—Biochemical Pesticides
158.2000 Biochemical pesticides definition
and applicability.
158.2010 Biochemical pesticides data requirements.
158.2030 Biochemical
pesticides
product
chemistry data requirements table.

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Environmental Protection Agency

§ 158.3
AUTHORITY: 7 U.S.C. 136–136y; 21 U.S.C.
346a.

158.2040 Biochemical pesticides residue data
requirements table.
158.2050 Biochemical
pesticides
human
health assessment data requirements
table.
158.2060 Biochemical pesticides nontarget
organisms and environmental fate data
requirements table.
158.2070 Biochemical pesticides product performance data requirements.
158.2080 Experimental use permit data requirements—biochemical pesticides.
158.2081 Experimental
use
permit
biochemical pesticides product chemistry
data requirements table.
158.2082 Experimental
use
permit
biochemical pesticides residue data requirements table.
158.2083 Experimental
use
permit
biochemical pesticides human health assessment data requirements table.
158.2084 Experimental
use
permit
biochemical pesticides nontarget organisms
and environmental fate data requirements table.

SOURCE: 72 FR 60957, Oct. 26, 2007, unless
otherwise noted.

Subpart A—General Provisions
§ 158.1 Purpose and scope.
(a) Purpose. The purpose of this part
is to specify the kinds of data and information EPA requires in order to
make regulatory judgments under
FIFRA secs. 3, 4, and 5 about the risks
and benefits of pesticide products. Further, this part specifies the data and
information needed to determine the
safety of pesticide chemical residues
under FFDCA sec. 408.
(b) Scope. (1) This part describes the
minimum data and information EPA
typically requires to support an application for pesticide registration or
amendment; support the reregistration
of a pesticide product; support the
maintenance of a pesticide registration
by means of the data call-in process,
e.g., as used in the registration review
program; or establish or maintain a
tolerance or exemption from the requirements of a tolerance for a pesticide chemical residue.
(2) This part establishes general policies and procedures associated with the
submission of data in support of a pesticide regulatory action.
(3) This part does not include study
protocols, methodology, or standards
for conducting or reporting test results; nor does this part describe how
the Agency uses or evaluates the data
and information in its risk assessment
and risk management decisions, or the
regulatory determinations that may be
based upon the data.
(c) Scope of individual subparts. (1)
Conventional pesticides. Subparts A, B,
C, D, F, G, K, L, N, and O apply to conventional pesticides.
(2) Biochemical pesticides. Subparts A,
B and U apply to biochemical pesticides.
(3) Microbial pesticides. Subparts A, B
and V apply to microbial pesticides.
(4) Antimicrobial pesticides. [Reserved]

Subpart V— Microbial Pesticides
158.2100 Microbial pesticides definition and
applicability.
158.2110 Microbial pesticides data requirements.
158.2120 Microbial pesticides product analysis data requirements table.
158.2130 Microbial pesticides residue data
requirements table.
158.2140 Microbial
pesticides
toxicology
data requirements table.
158.2150 Microbial pesticides nontarget organisms and environmental fate data requirements table.
158.2160 Microbial pesticides product performance data requirements.
158.2170 Experimental use permit data requirements—microbial pesticides.
158.2171 Experimental use permit microbial
pesticides product analysis data requirements table.
158.2172 Experimental use permit microbial
pesticides residue data requirements
table.
158.2173 Experimental use permit microbial
pesticides toxicology data requirements
table.
158.2174 Experimental use permit microbial
pesticides nontarget organisms and environmental fate data requirements table.

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Subpart W—Antimicrobial Pesticides
[Reserved]
158.2200

§ 158.3 Definitions.
All terms defined in sec. 2 of the Federal
Insecticide,
Fungicide,
and
Rodenticide Act apply to this part and

[Reserved]

Subpart X–Z [Reserved]
158.2300–158.2500

[Reserved]

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§ 158.5

40 CFR Ch. I (7–1–11 Edition)
submission is not accurate or complete.

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are used with the meaning given in the
Act. Applicable terms from the Federal
Food, Drug, and Cosmetic Act also
apply to this part. Individual subparts
may contain definitions that pertain
solely to that subpart. The following
additional terms apply to this part:
Applicant means any person or entity, including for the purposes of this
part a registrant, who submits, or is required to submit, to the Agency any
application, petition, or submission intended to persuade EPA to grant, modify, or leave unmodified a registration
or other approval required as a condition of sale or distribution of a pesticide. Such submissions may include,
but are not limited to, the following:
(1) An application for registration or
amended registration of a pesticide
product under FIFRA sec. 3 or 24.
(2) A submission of data required in
conjunction with reregistration of a
currently registered product under
FIFRA sec. 4.
(3) An application for an experimental use permit under FIFRA sec. 5.
(4) A submission of data in response
to a notice issued by EPA under FIFRA
sec. 3(c)(2)(B).
(5) A petition to establish or modify
a tolerance or an exemption from the
requirement of a tolerance for a pesticide chemical residue under FFDCA
sec. 408.
Registration includes a new registration, amended registration and reregistration, unless stated otherwise.

§ 158.30

Flexibility.

(a) FIFRA provides EPA flexibility to
require, or not require, data and information for the purposes of making regulatory judgments for pesticide products. EPA has the authority to establish or modify data needs for individual
pesticide chemicals. The actual data
required may be modified on an individual basis to fully characterize the
use and properties, characteristics, or
effects of specific pesticide products
under review. The Agency encourages
each applicant to consult with EPA to
discuss the data requirements particular to its product prior to and during the registration process.
(b) The Agency cautions applicants
that the data routinely required in this
part may not be sufficient to permit
EPA to evaluate the potential of the
product to cause unreasonable adverse
effects to man or the environment.
EPA may require the submission of additional data or information beyond
that specified in this part if such data
or information are needed to appropriately evaluate a pesticide product.
(c) This part will be updated as needed to reflect evolving program needs
and advances in science.
§ 158.32

Format of data submissions.

(a) General. (1) All data submitted
under this part must be formatted in
accordance with this section.
(2) The requirements of this section
do not apply to administrative materials accompanying a data submission,
including forms, labeling, and correspondence.
(b) Transmittal document. Each submission in support of a regulatory action must be accompanied by a transmittal document, which includes:
(1) Identity of the submitter.
(2) The transmittal date.
(3) Identification of the regulatory
action with which the submission is associated, e.g., the registration or petition number.
(4) A list of the individual documents
included in the submission.
(c) Individual documents. Unless otherwise specified by the Agency, each

§ 158.5 Applicability.
(a) The requirements of this part
apply to the following submissions:
(1) An application for new or amended registration under FIFRA sec. 3 or
24.
(2) An application for experimental
use permit under FIFRA sec. 5.
(3) A submission of data or information to support the continuation of a
registration under FIFRA sec. 3, 4, or
24.
(4) A petition to establish, modify or
revoke a tolerance or exemption from a
tolerance under FFDCA sec. 408.
(b) The information specified in this
part must be furnished with each submission described in paragraph (a) of
this section if it has not been submitted previously, or if any previous

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Environmental Protection Agency

§ 158.33
(2) Safety and efficacy information
means information concerning the objectives, methodology, results, or significance of any test or experiment
performed on or with a registered or
previously registered pesticide or its
separate ingredients, impurities, or
degradation products, and any information concerning the effects of such pesticide on any organism or the behavior
of such pesticide in the environment,
including, but not limited to, data on
safety to fish and wildlife, humans and
other mammals, plants, animals, and
soil, and studies on persistence,
translocation and fate in the environment, and metabolism.
(b) Applicability. (1) This section applies to information submitted pursuant to this part. It supplements the
general confidentiality procedures in 40
CFR part 2, subpart B, including
FIFRA confidentiality procedures at 40
CFR 2.307. To the extent that provisions in this section conflict with those
in 40 CFR part 2, subpart B, the provisions in this section take precedence.
The provisions of 40 CFR 2.308 do not
apply to information to which this section applies. In addition to complying
with the requirements of this section,
any confidentiality claims for information subject to 40 CFR part 174 (plantincorporated protectants) must be substantiated at the time of submission as
described in § 174.9 of this chapter.
(2) FFDCA sec. 408(i) protects confidential information submitted in connection with an application for a tolerance or exemption to the same extent
as FIFRA sec. 10. References in this
section to FIFRA sec. 10 are deemed to
apply equally to information submitted
pursuant to FFDCA sec. 408, pursuant
to the authority in sec. 408(i).
(c) Method of asserting business confidentiality claims—(1) Claim required. Information to which this section applies
(and which is submitted on or after the
effective date of this regulation) will
be deemed as not subject to a confidentiality claim unless a claim for that information is made in accordance with
the procedures specified in this paragraph. Information not subject to a
confidentiality claim may be made
available to the public without further
notice, subject to the requirements of
FIFRA sec. 10(g).

submission must be in the form of individual documents or studies. Previously submitted documents should
not be resubmitted unless specifically
requested by the Agency, but should be
cited with adequate information to
identify the previously submitted document. Each study or document should
include the following:
(1) A title page including the following information:
(i) The title of the study, including
identification of the substance(s) tested and the test name or data requirement addressed.
(ii) The author(s) of the study.
(iii) The date the study was completed.
(iv) If the study was performed in a
laboratory, the name and address of
the laboratory, project numbers or
other identifying codes.
(v) If the study is a commentary on
or supplement to another previously
submitted study, full identification of
the other study with which it should be
associated in review.
(vi) If the study is a reprint of a published document, all relevant facts of
publication, such as the journal title,
volume, issue, inclusive page numbers,
and date of publication.
(2) The appropriate statement(s) regarding
any
data
confidentiality
claims as described in § 158.33.
(3) A statement of compliance or noncompliance with respect to Good Laboratory Practice Standards as required
by 40 CFR 160.12, if applicable.
(4) A complete and accurate English
translation must be included for any
information that is not in English.
(5) A flagging statement as prescribed by § 158.34, if applicable.

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§ 158.33

Confidential data.

(a) Definitions. For the purposes of
this section:
(1) Registered or previously registered
pesticide means any pesticide containing an active ingredient contained
in a product that is, or has ever been,
an active ingredient in a product registered under sec. 3 of FIFRA. A registered pesticide that is the subject of
an application for a new use falls within the category of ‘‘registered or previously registered pesticide.’’

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§ 158.33

40 CFR Ch. I (7–1–11 Edition)

(2) Statement required. Upon submission to EPA, each document must be
accompanied by a signed and dated
document containing either the statements in paragraph (c)(2)(i) or (ii) of
this section. No claims or markings on
the document or any attachments,
other than these statements and attachments submitted in accordance
with paragraph (c)(3) of this section,
will be recognized as asserting a claim
of confidentiality. The format of data
submissions is set forth in § 158.32.
(i) No claim of confidentiality.

close) the identity or percentage quantity of any deliberately added inert ingredient of a pesticide must be individually identified in the confidential attachment as a claim for information
within the scope of FIFRA sec.
10(d)(1)(C).
(v) Information in the confidential
attachment that is designated in accordance with paragraphs (c)(3)(ii) (iv) of this section must be on a separate page from information that is not
so designated.
(4) Voluntary release of information to
States and foreign governments. (i) Submitters are encouraged to include with
the statement required under paragraph (c)(2) of this section an additional statement to allow EPA to share
information with State and foreign
governments. EPA will not consider
such a statement to be a waiver of confidentiality or proprietary claims for
the information. The statement is as
follows:

No claim of confidentiality, on any basis
whatsoever, is made for any information
contained in this document. I acknowledge
that information not designated as within
the scope of FIFRA sec. 10(d)(1)(A), (B), or
(C) and which pertains to a registered or previously registered pesticide is not entitled to
confidential treatment and may be released
to the public, subject to the provisions regarding disclosure to multinational entities
under FIFRA sec. 10(g).

(ii) Claim of confidentiality.

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Information claimed as confidential has
been removed to a confidential attachment.

I authorize the Environmental Protection
Agency to release any information contained
in this document to State or foreign governments, without relinquishing proprietary
rights or any confidentiality claims asserted
above.

(3) Confidential attachment. (i) All information claimed as confidential must
be submitted in a separate confidential
attachment to the document and cross
referenced to the specific location in
the document from which it was removed. The confidential attachment
must have its own title page and be
paginated separately from the non-confidential document.
(ii) All information in the confidential attachment that consists of (or
whose disclosure would in turn disclose) manufacturing or quality control processes must be individually
identified in the confidential attachment as a claim for information within
the scope of FIFRA sec. 10(d)(1)(A).
(iii) All information in the confidential attachment that consists of (or
whose disclosure would in turn disclose) the details of any methods for
testing, detecting, or measuring the
quantity of any deliberately added
inert ingredient of a pesticide, must be
individually identified in the confidential attachment as a claim for information within the scope of FIFRA sec.
10(d)(1)(B).
(iv) All information in the confidential attachment that consists of (or
whose disclosure would in turn dis-

(ii) Information designated as releasable to state or foreign governments in
accordance with this section may be
released to such a government without
further notice to the submitter. EPA
will inform the State or foreign government of any of the confidentiality
claims associated with the information.
(d) Release of information. (1) Safety
and efficacy information that was submitted to EPA on or after May 4, 1988
and that has not been designated by
the
submitter
as
FIFRA
sec.
10(d)(1)(A), (B), or (C) information in
accordance with the applicable requirements of this section is not entitled to
confidential treatment and may be disclosed to the public without further notice to the submitter, in accordance
with paragraph (d)(2) of this section.
Safety and efficacy information which
has been designated by the submitter
as FIFRA sec. 10(d)(1) (A), (B), or (C)
information is entitled to confidential
treatment only to the extent provided
by FIFRA sec. 10(b), this section, and
40 CFR 2.208.

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Environmental Protection Agency

§ 158.34

(2) Information that is not entitled to
be protected as confidential in accordance with FIFRA sec. 10(b), this section and with EPA confidentiality regulations at 40 CFR part 2, subpart B,
may be released to the public without
the affirmation of non-multinational
status provided under FIFRA sec. 10(g),
provided that the information does not
contain or consist of any complete unpublished report submitted to EPA, or
excerpts or restatements of any such
report which reveal the full methodology and complete results of the
study, test, or experiment, and all explanatory information necessary to understand the methodology or interpret
the results.

§ 158.34 Flagging of studies for potential adverse effects.
(a) Any applicant who submits a
study of a type listed in paragraph (b)
of this section must submit with the
study a statement in accordance with
paragraph (c) of this section.
(b) The following table indicates the
study types and the criteria to be applied to each. Column 1 lists the study
types by name. Column 2 lists the associated Pesticide Assessment Guideline
number. Column 3 lists the criteria applicable to each type of study. Column
4 lists the reporting code to be included
in the statement specified in paragraph
(c) of this section when any criterion is
met or exceeded.

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TABLE—FLAGGING CRITERIA
Study Type(s)

Guideline No.

Criteria: Treated animals show any of the following:

Carcinogenicity or combined carcinogenicity/chronic feeding study.

870.4200
870.4300

An incidence of neoplasms in males or females which
increases with dose (positive trend p≤ 0.05); or

1

........................................................

A statistically significant (pairwise p≤ 0.05) increase of
any type of neoplasm in any test group, males or females at any dose level, compared to concurrent control animals of the same sex; or

2

........................................................

An increase in any type of uncommon or rare neoplasms in any test group, males or females animals
at any dose level, compared to concurrent controls of
the same sex; or

3

........................................................

A decrease in the time to development of any type of
neoplasms in any test group, males or females at any
dose level, compared to concurrent controls of the
same sex.

4

Prenatal developmental toxicity ..........
Reproduction and fertility
Developmental neurotoxicity

870.3700
870.3800
870.6300

When compared to concurrent controls, treated offspring show a dose-related increase in malformations,
pre- or post-natal deaths, or persistent functional or
behavioral changes on a litter basis in the absence of
significant maternal toxicity at the same dose level.

5

Neurotoxicity .......................................

870.6100
870.6200

When compared to concurrent controls, treated animals
show a statistically or biologically significant increase
in neuropathological lesions or persistent functional or
behavioral changes.

6

Chronic feeding ..................................
Carcinogenicity
Reproduction and fertility
Prenatal developmental toxicity
Developmental neurotoxicity
Acute or 90–day neurotoxicity

870.4100
870.4200
870.3800
870.3700
870.6300
870.6200

The no observed adverse effect level (NOAEL) from
one of these studies is less than the NOAEL currently
used by the Agency as the basis for either the acute
or chronic reference dose.

7

(c) Identification of studies. For each
study of a type identified in paragraph
(b) of this section, the applicant shall
include the appropriate one of the following two statements, together with
the signature of the authorized rep-

resentative of the company, and the
date of signature:
(1) Study does not meet or exceed criteria.
I have applied the criteria of 40 CFR 158.34
for flagging studies for potential adverse effects to the results of the attached study.

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§ 158.45

40 CFR Ch. I (7–1–11 Edition)

This study neither meets nor exceeds any of
the applicable criteria.

ISTER announcing the decision. An
Agency decision denying a written request to waive a data requirement is a
final Agency action.

(2) Study meets or exceeds criteria.

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I have applied the criteria of 40 CFR 158.34
for flagging studies for potential adverse effects to the results of the attached study.
This study meets or exceeds the criteria
numbered [insert all applicable reporting
codes].

§ 158.60

Minor use data policies.

FIFRA sec. 2(ll) defines the term
‘‘minor use’’and FIFRA provides a
number of statutory provisions concerning minor uses. In addition, EPA
has established policies with respect to
minor uses of pesticides, including, but
not limited to, the following:
(a) A new data requirement pertinent
to both an unregistered minor use and
a registered major use will not be applied to a minor use applicant until it
is applied to the major use registration.
(b) EPA will accept appropriate and
adequate extrapolations and regional
data to support establishment of individual minor use tolerances.

§ 158.45 Waivers.
(a) The data requirements specified
in this part as applicable to a category
of products will not always be appropriate for every product in that category. Some products may have unusual physical, chemical, or biological
properties or atypical use patterns
which would make particular data requirements inappropriate, either because it would not be possible to generate the required data or because the
data would not be useful in the Agency’s evaluation of the risks or benefits
of the product. The Agency will waive
data requirements it finds are inappropriate, but will ensure that sufficient
data are available to make the determinations required by the applicable
statutory standards.
(b)(1) Applicants are encouraged to
discuss a data waiver request with the
Agency before developing and submitting supporting data, information, or
other materials.
(2) All waiver requests must be submitted to the Agency in writing. The
request must clearly identify the data
requirement(s) for which a waiver is
sought along with an explanation and
supporting rationale why the applicant
believes the data requirement should
be waived. In addition, the applicant
must describe any unsuccessful attempts to generate the required data,
furnish any other information which
the applicant(s) believe(s) would support the request, and when appropriate,
suggest alternative means of obtaining
data to address the concern which
underlies the data requirement.
(c) The Agency will review each
waiver request and subsequently inform the applicant in writing of its decision. If the decision could apply to
more than the requested product, the
Agency, in its discretion, may choose
to send a notice to all registrants or
publish a notice in the FEDERAL REG-

§ 158.70

Satisfying data requirements.

(a) General policy. The Agency will
determine whether the data submitted
or cited to fulfill the data requirements specified in this part are acceptable. This determination will be based
on the design and conduct of the experiment from which the data were derived, and an evaluation of whether the
data fulfill the purpose(s) of the data
requirement. In evaluating experimental design, the Agency will consider whether generally accepted methods were used, sufficient numbers of
measurements were made to achieve
statistical reliability, and sufficient
controls were built into all phases of
the experiment. The Agency will evaluate the conduct of each experiment in
terms of whether the study was conducted in conformance with the design,
good laboratory practices were observed, and results were reproducible.
The Agency will not reject data merely
because they were derived from studies
which, when initiated, were in accordance with an Agency-recommended
protocol, even if the Agency subsequently recommends a different protocol, as long as the data fulfill the
purposes of the requirements as described in this paragraph.
(1) The provisions in this part 158
should be read in conjunction with the

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Environmental Protection Agency

§ 158.80

provisions in § 152.85 to claim eligibility for the formulators’ exemption.
(2) [Reserved]
(b) Good laboratory practices. Applicants must adhere to the good laboratory practice (GLP) standards described in 40 CFR part 160 when conducting studies. Applicants must also
adhere to GLP standards when conducting a study in support of a waiver
request of any data requirement which
is within the scope of the GLP requirements.
(c) Agency guidelines. EPA has published Test Guidelines that contain
standards for conducting acceptable
tests, guidance on the evaluation and
reporting of data, definition of terms,
and suggested study protocols. Copies
of the Test Guidelines may be obtained
by visiting the agency’s website at
www.epa.gov/pesticides.
(d) Study protocols—(1) General. Any
appropriate protocol may be used to
generate the data required by this part,
provided that it meets the purpose of
the test standards specified in the pesticide assessment guidelines, and provides data of suitable quality and completeness as typified by the protocols
cited in the guidelines. Applicants
should use the test procedure which is
most suitable for evaluation of the particular ingredient, mixture, or product.
Accordingly, failure to follow a suggested protocol will not invalidate a
test if another appropriate methodology is used.
(2) Organization for Economic Co-Operation and Development (OECD) protocols.
Tests conducted in accordance with the
requirements and recommendations of
the applicable OECD protocols can be
used to develop data necessary to meet
the requirements specified in this part.
Applicants should note, however, that
certain of the OECD recommended test
standards, such as test duration and selection of test species, are less restrictive than those recommended by EPA.
Therefore, when using OECD protocols,
care should be taken to observe the
test standards in a manner such that
the data generated by the study will
satisfy the requirements of this part.
(e) Combining studies. Certain toxicology studies may be combined to satisfy data requirements. For example,
carcinogenicity studies in rats may be

combined with the rat chronic toxicity
study. Combining appropriate studies
may be expected to reduce usage of test
animals as well as reduce the cost of
studies. EPA encourages this practice
by including standards for acceptable
combined tests in the Pesticide Assessment Guidelines. Registrants and applicants are encouraged to consider
combining other tests when practical
and likely to produce scientifically acceptable results. Registrants and applicants, however, must consult with the
EPA before initiating combined studies.
§ 158.75 Requirements for additional
data.
The data routinely required by this
part may not be sufficient to permit
EPA to evaluate every pesticide product. If the information required under
this part is not sufficient to evaluate
the potential of the product to cause
unreasonable adverse effects on man or
the environment, additional data requirements will be imposed. However,
EPA expects that the information required by this part will be adequate in
most cases for an assessment of the
properties and effects of the pesticide.
§ 158.80 Use of other data.
(a) Data developed in foreign countries.
With certain exceptions, laboratory
and field study data developed outside
the United States may be submitted in
support of a pesticide registration.
Data generated in a foreign country
which the Agency will not consider include, but are not limited to, data from
tests which involved field test sites or
a test material, such as a native soil,
plant, or animal, that is not characteristic of the United States. Applicants submitting foreign data must
take steps to ensure that U.S. materials are used, or be prepared to supply
data or information to demonstrate the
lack of substantial or relevant differences between the selected material
or test site and the U.S. material or
test site. Once submitted, the Agency
will determine whether or not the data
meet the data requirements.
(b) Data generated for other purposes.
Data developed for purposes other than
satisfaction of FIFRA data requirements, such as monitoring studies,

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§ 158.100

40 CFR Ch. I (7–1–11 Edition)

may also satisfy data requirements in
this part. Consultation with the Agency should be arranged if applicants are
unsure about suitability of such data.

(c) Applicants unsure of the correct
use pattern for their particular product
should consult the Agency.
§ 158.110 Required and conditionally
required data.
The tables in this part use the
descriptors R (required), CR (conditionally required), and NR (not required) as a general indication of the
applicability of a data requirement. In
all cases, the test notes referred to in
the table must be consulted to determine the actual applicability of the
data requirement.
(a) EPA requires data designated as
‘‘required’’(R) for products with a given
use pattern in order to evaluate the
risks or benefits of a product having
that use pattern under any conditions
established by the test notes.
(b) Data designated as ‘‘conditionally
required’’ (CR) for products with a
given use pattern are required by EPA
to evaluate the risks or benefits of a
product having that use pattern if the
product meets the conditions specified
in the notes accompanying the requirement. The determination of whether
the data must be submitted is based on
the product’s use pattern, physical or
chemical properties, expected exposure
of nontarget organisms, and/or results
of previous testing (for example, tier
testing). Applicants must evaluate
each applicable test note for the conditions and criteria to be considered in
determining whether conditionally required data must be submitted.
(c) Data not required for the Agency’s assessment of the risks and benefits of a particular use pattern are designated ‘‘not required’’ (NR) in data tables.

Subpart B—How To Use Data
Tables

wreier-aviles on DSK7SPTVN1PROD with CFR

§ 158.100

Pesticide use patterns.

(a) General use patterns. There are six
broad use categories used in the data
tables. The six broad categories include
terrestrial outdoor uses, aquatic outdoor uses, greenhouse uses, forestry
uses, residential outdoor uses, and indoor uses of all types. The 6 broad use
categories are further subdivided into
12 general use patterns which are the
bases for data requirements established
by use pattern. Within the data tables,
general use patterns have been combined into single columns when the
data requirements are the same for the
combined uses. If there are no data requirements for a specific use, the column for that use is not included in the
table. The 12 general use pattern
groups used in the data table in this
part are:
(1) Terrestrial food crop use.
(2) Terrestrial feed crop use.
(3) Terrestrial nonfood crop use.
(4) Aquatic food crop use.
(5) Aquatic nonfood use.
(6) Greenhouse food crop use.
(7) Greenhouse nonfood crop use.
(8) Forestry use.
(9) Residential outdoor use.
(10) Residential indoor use.
(11) Indoor food use.
(12) Indoor nonfood use.
(b) Pesticide use site index. The Pesticide Use Site Index is a comprehensive list of specific pesticide use sites.
The index is alphabetized separately by
site for all agricultural and all nonagricultural uses. The Pesticide Use
Site Index associates each pesticide use
site with one or more of the 12 general
use patterns. It may be used in conjunction with the data tables to determine the applicability of data requirements to specific uses. The Pesticide
Use Site Index, which will be updated
periodically, is available from the
Agency or may be obtained from the
Agency’s website at http://www.epa.gov/
pesticides.

§ 158.120 Determining data requirements.
As with current practice, the actual
data and studies required may be modified on an individual basis to fully
characterize the use and properties of
specific pesticide products under review. While EPA is attempting to assist the applicant in this subpart, it is
important to emphasize that it is the
applicant’s obligation under FIFRA to
demonstrate that an individual product
meets the standard under FIFRA and/
or FFDCA. Accordingly, applicants are

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Environmental Protection Agency

§ 158.130

encouraged to consult with the Agency
on the appropriate data requirements
as set forth here as they relate to their
specific product prior to and during the
registration process.
(a) Finding the appropriate data table.
(1) Pesticide data requirements for conventional chemical active ingredients
and related substances are presented in
subparts D, E, F, G, K, L, N, and O of
this part in the form of a series of data
tables, each addressing a particular scientific discipline or data topic. Data
requirements for biochemical and microbial pest control agents are contained and are described separately
within subparts U and V of this part,
respectively.
(2) Key to table notations. R = required data; CR = conditionally required data; NR = Not required; MP =
manufacturing-use product; EP = enduse product; TEP = typical end-use
product; TGAI = technical grade of the
active ingredient; PAI = pure active ingredient; PAIRA = pure active ingredient, radiolabeled; Choice = choice of
several test substances depending on
studies required.
(b) Identifying required studies. To determine the specific kinds of data needed to support the registration use of
each pesticide product, the applicant
may:
(1) Refer to the applicable subpart(s)
of this part. These subparts describe
the data requirements including data
tables for each subject area.
(2) Select the general use pattern(s)
that best cover the use pattern(s) specified on the pesticide product label as
explained in § 158.100. All applicable use
patterns must be included.
(3) Proceed down the appropriate general use pattern column in the table
and note which tests are required (R),
conditionally required (CR), or not required (NR). Required and conditionally required studies are described
in § 158.110.
(4) Review the notes for each requirement to determine its applicability to
the specific product proposed for registration.
(5)(i) Proceed down the Test substance columns and determine the appropriate test substance needed for
that study. If the data are intended to
support a manufacturing-use product,

use the MP column. If the data are intended to support an end-use product,
use the EP column.
(ii) The test substances columns
specify which substance is to be used
for testing. Applicants should note
that the substance that must be used
when performing the study may or may
not be the product itself. For example,
the data from a certain study may be
required to support the registration of
an end-use product, but the test substance column may state that the particular test shall be performed using
the technical grade of the active ingredient(s) in the end-use product.
(iii)
Manufacturing-use
products
(MP) and end-use products (EP) containing a single active ingredient and
no intentionally added inert ingredients are considered identical in composition to each other, and to the technical grade of the active ingredient
(TGAI) from which they were derived.
Therefore, the data from a test conducted using any one of these as the
test substance is also suitable to meet
the requirement (if any) for the same
test to be conducted using either of the
other substances.
(6) Refer to the Pesticide Assessment
Guideline reference number for each
study located in the first column. See
§ 158.70(c) for information pertaining to
the guidelines and how to obtain copies.
§ 158.130 Purposes of the registration
data requirements.
(a) General. The data requirements
for registration are intended to generate data and information necessary
to address concerns pertaining to the
identity, composition, potential adverse effects and environmental fate of
each pesticide.
(b) Product chemistry—(1) Product composition. Data on product composition
are needed:
(i) To support the conclusions expressed in the statement of formula;
(ii) To compare to the composition of
materials used in required testing
under this part; and
(iii) To determine whether a product
is ‘‘identical or substantially similar’’to another product, a determination that involves the comparison of
product composition.

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§ 158.130

40 CFR Ch. I (7–1–11 Edition)

(2) Nominal concentration and certified
limits. The nominal concentration of a
product, defined as that concentration
that is expected to be present in a
product as a result of the production or
formulation process, is used to gauge
the acceptability of the certified limits, which define the outer limits of the
range of the product’s ingredients. The
certified limits are used to enforce the
composition of the product and to ensure the accuracy of hazard assessments.
(3) Physical and chemical characteristics. The physical and chemical characteristics of an active ingredient or
product are used:
(i) To confirm or provide supportive
information on the identity and composition of the product;
(ii) To assess the hazards of the ingredient or product; and
(iii) To trigger or evaluate certain
other studies required by this part.
(c) Product performance. Requirements to develop data on product performance provide a mechanism to ensure that pesticide products will perform as intended and that unnecessary
pesticide exposure to the environment
will not occur as a result of the use of
ineffective products. Specific performance standards are used to validate the
efficacy data in the public health
areas, including disinfectants used to
control microorganisms infectious to
man in any area of the inanimate environment and those pesticides used to
control vertebrates (such as rodents,
birds, bats and skunks) that may directly or indirectly transmit diseases
to humans.
(d) Toxicology-humans and domestic
animals. Data required to assess hazards to humans and domestic animals
are derived from a variety of acute,
subchronic and chronic toxicity tests,
and tests to assess mutagenicity and
pesticide metabolism.
(1) Acute studies. Determination of
acute oral, dermal and inhalation toxicity is usually the initial step in the
assessment and evaluation of the toxic
characteristics of a pesticide. These
data provide information on health
hazards likely to arise soon after, and
as a result of, short-term exposure.
Data from acute studies serve as a
basis for classification and pre-

cautionary labeling. For example,
acute toxicity data are used to calculate farmworker reentry intervals
and to develop precautionary label
statements pertaining to protective
clothing requirements for applicators.
They also provide information used in
establishing the appropriate dose levels
in subchronic and other studies; provide initial information on the mode of
toxic action(s) of a substance; and determine the need for child resistant
packaging. Information derived from
primary eye and primary dermal irritation studies serves to identify possible
hazards from exposure of the eyes, associated mucous membranes and skin.
(2) Subchronic studies. Subchronic
tests provide information on health
hazards that may arise from repeated
exposures over a limited period of
time. They provide information on target organs and accumulation potential.
The resulting data are also useful in selecting dose levels for chronic studies
and for establishing safety criteria for
human exposure. These tests are not
capable of detecting those effects that
have a long latency period for expression (e.g., carcinogenicity).
(3) Chronic studies. Chronic toxicity
studies (usually conducted by feeding
the test substance to the test species)
are intended to determine the effects of
a substance in a mammalian species
following prolonged and repeated exposure. Under the conditions of this test,
effects which have a long latency period or are cumulative should be detected. The purpose of long-term carcinogenicity studies is to observe test
animals over most of their life span for
the development of neoplastic lesions
during or after exposure to various
doses of a test substance by an appropriate route of administration.
(4) Developmental toxicity and reproduction studies. The developmental toxicity study is designed to determine
the potential of the test substance to
induce structural and/or other abnormalities to the fetus as the result of
exposure of the mother during pregnancy. Two-generation reproduction
testing is designed to provide information concerning the general effects of a
test substance on gonadal function,
estrus cycles, mating behavior, conception, parturition, lactation, weaning,

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Environmental Protection Agency

§ 158.130

and the growth and development of the
offspring. The study may also provide
information about the effects of the
test substance on neonatal morbidity,
mortality, and preliminary data on
prenatal developmental toxicity and
serve as a guide for subsequent tests.
(5) Mutagenicity studies. For each test
substance a battery of tests is required
to assess the potential to affect the
mammalian cell’s genetic components.
The objectives underlying the selection
of a battery of tests for mutagenicity
assessment are:
(i) To detect, with sensitive assay
methods, the capacity of a chemical to
alter genetic material in cells.
(ii) To determine the relevance of
these mutagenic changes to mammals.
(iii) When mutagenic potential is
demonstrated, to incorporate these
findings in the assessment of heritable
effects, carcinogenicity, and, possibly,
other health effects.
(6) Metabolism studies. Data from
studies on the absorption, distribution,
metabolism, and excretion of a pesticide aid in the valuation of test results from other toxicity studies and in
the extrapolation of data from animals
to man. The main purpose of metabolism studies is to produce data which
increases the Agency’s understanding
of the behavior of the chemical when
considering the human exposure anticipated from intended uses of the pesticide.
(e) Hazards to nontarget organisms—(1)
General. The information required to
assess hazards to nontarget organisms
is derived from tests to determine pesticidal effects on birds, mammals, fish,
terrestrial and aquatic invertebrates
and plants. These tests include shortterm acute, subacute, reproduction,
simulated field, and full field studies
arranged in a hierarchical or tier system which progresses from the basic
laboratory tests to the applied field
tests. The results of each tier of testing
must be evaluated to determine the potential of the pesticide to cause adverse effects, and to determine whether
further testing is required. A purpose
common to all data requirements is to
provide data which determine the need
for (and appropriate wording for) precautionary label statements to mini-

mize the potential adverse effects to
nontarget organisms.
(2) Short-term studies. The short-term
acute and subchronic laboratory studies provide basic toxicity information
which serves as a starting point for the
hazard assessment. These data are
used: To establish acute toxicity levels
of the active ingredient to the test organisms; to compare toxicity information with measured or estimated pesticide residues in the environment in
order to assess potential impacts on
fish, wildlife and other nontarget organisms; and to indicate whether further
laboratory and/or field studies are
needed.
(3) Long-term and field studies. Additional studies (i.e., avian, fish, and invertebrate reproduction, life cycle
studies and plant field studies) may be
required when basic data and environmental conditions suggest possible
problems. Data from these studies are
used to: Estimate the potential for
chronic effects, taking into account
the measured or estimated residues in
the environment; and to determine if
additional field or laboratory data are
necessary to further evaluate hazards.
Simulated field and/or field data are
used to examine acute and chronic adverse effects on captive or monitored
fish and wildlife populations under natural or near-natural environments.
Such studies are required only when
predictions as to possible adverse effects in less extensive studies cannot
be made, or when the potential for adverse effects is high.
(f) Applicator and post-application exposure. Data are used to evaluate exposures to persons in occupational and
non-occupational settings, including
agricultural, residential, commercial,
institutional and recreational sites.
Data include oral, dermal and inhalation exposure data, post-application
residue data, post-application monitoring data, use information, and
human activity information. These
data, together with toxicology data,
are used to determine whether application or post-application risks are of
concern, and, where appropriate, to develop
post-application
restrictions
such as reentry restrictions.
(g) Pesticide spray drift evaluation.
Data required to evaluate pesticide

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§ 158.130

40 CFR Ch. I (7–1–11 Edition)

spray drift are derived from studies of
droplet size spectrum and spray drift
field evaluations. These data contribute to the development of the overall exposure estimate and, along with
data on toxicity for humans, fish and
wildlife, or plants, are used to assess
the potential hazard of pesticides to
these organisms. A purpose common to
all these tests is to provide data which
will be used to determine the need for
(and appropriate wording for) precautionary labeling to minimize the
potential adverse effect to nontarget
organisms.
(h) Environmental fate—(1) General.
The data generated by environmental
fate studies are used to: Assess the toxicity to man through exposure of humans to pesticide residues remaining
after application, either upon reentering treated areas or from consuming
inadvertantly-contaminated food; assess the presence of widely distributed
and persistent pesticides in the environment which may result in loss of
usable land, surface water, ground
water, and wildlife resources; and, assess the potential environmental exposure of other nontarget organisms,
such as fish and wildlife, to pesticides.
Another specific purpose of the environmental fate data requirements is to
help applicants and the Agency estimate expected environmental concentrations of pesticides in specific
habitats where threatened or endangered species or other wildlife populations at risk are found.
(2) Degradation studies. The data from
hydrolysis and photolysis studies are
used to determine the rate of pesticide
degradation and to identify pesticides
that may adversely affect nontarget
organisms.
(3) Metabolism studies. Data generated
from aerobic and anaerobic metabolism
studies are used to determine the nature and availability of pesticides to
rotational crops and to aid in the evaluation of the persistence of a pesticide.
(4) Mobility studies. These data requirements pertain to leaching, adsorption/desorption, and volatility of pesticides. They provide information on
the mode of transport and eventual
destination of the pesticide in the environment. This information is used to
assess potential environmental hazards

related to: Contamination of human
and animal food; loss of usable land
and water resources to man through
contamination of water (including
ground water); and habitat loss of wildlife resulting from pesticide residue
movement or transport in the environment.
(5) Dissipation studies. The data generated from dissipation studies are
used to assess potential environmental
hazards (under actual field use conditions) related to: Reentry into treated
areas; hazards from residues in rotational crops and other food sources;
and the loss of land as well as surface
and ground water resources.
(i) Residue chemistry. (1) Residue
chemistry data are used by the Agency
to estimate the exposure of the general
population to pesticide residues in food
and for setting and enforcing tolerances for pesticide residues in food or
feed.
(2) Information on the chemical identity and composition of the pesticide
product, the amounts, frequency and
time of the pesticide application, and
results of tests on the amount of residues remaining on or in the treated
food or feed, are needed to support a
finding as to the magnitude and identity of residues which result in food or
animal feed as a consequence of a proposed pesticide usage.
(3) Residue chemistry data are also
needed to support the adequacy of one
or more methods for the enforcement
of the tolerance, and to support practicable methods for removing residues
that exceed any proposed tolerance.
(4) Accumulation studies. Accumulation studies indicate pesticide residue
levels in food supplies that originate
from wild sources or from rotational
crops. Rotational crop studies are necessary to establish realistic crop rotation restrictions and to determine if
tolerances may be needed for residues
on rotational crops. Data from irrigated crop studies are used to determine the amount of pesticide residues
that could be taken up by representative crops irrigated with water containing pesticide residues. These studies allow the Agency to establish label
restrictions regarding application of
pesticides on sites where the residues
can be taken up by irrigated crops.

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Environmental Protection Agency

§ 158.220

These data also provide information
that aids the Agency in establishing
any corresponding tolerances that
would be needed for residues on such
crops. Data from pesticide accumulation studies in fish are used to establish label restrictions to prevent applications in certain sites so that there
will be minimal residues entering edible fish or shellfish. These residue data
are also used to determine if a tolerance or action level is needed for residues in aquatic animals eaten by humans.

Subpart C—Experimental Use
Permits
§ 158.200 Experimental
use
permit
data requirements tables.
Sections 158.200 through 158.270 describe how to use these tables to determine the experimental use permit data
requirements for a particular pesticide
product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to
the designated test are listed at the
end of each table. Refer to 40 CFR part
172 for further information on experimental use permits.

wreier-aviles on DSK7SPTVN1PROD with CFR

§ 158.210 Experimental
data requirements
chemistry.
All product chemistry
scribed in § 158.310, must

use
for

permit
product

data, as debe submitted

to support a request for an experimental use permit.
§ 158.220 Experimental
use
permit
data requirements for product performance.
All product performance data, as described in paragraph (c) of this section,
must be submitted to support a request
for an experimental use permit.
(a) Use patterns. (1) The terrestrial
use pattern includes products classified
under the general use patterns of terrestrial food crop and terrestrial
nonfood crop. The aquatic use pattern
includes products classified under the
general use patterns of aquatic food
crop and aquatic nonfood crop. The
greenhouse use pattern includes products classified under the general use
patterns of greenhouse food crop and
greenhouse nonfood crop. The indoor
use pattern includes products classified
under the general use patterns of indoor food and indoor nonfood use.
(2) Data are also required for forestry
and residential outdoor uses.
(b) Key. CR=Conditionally required;
NR=Not
required;
R=Required;
MP=Manufacturing-use
product;
EP=End-use
product;
TEP=Typical
end-use product.
(c) Table. The following table shows
the experimental use data requirements for product performance. The
test notes are shown in paragraph (d)
of this section.

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Avian frightening agents

Bat toxicants and repellents

Commensal rodenticides

Rodenticides on farm and
rangelands

Rodent fumigants

Rodent reproductive inhibitors

Mammalian predacides

96–9

96–10

96–12

95–13

95–16

95–17

Avian repellents

Avian toxicants

96–7

96–6

96–5

Efficacy of vertebrate control agents

93–16

Efficacy of fungicides and nematicides

91–8

Sfmt 8010
R

R

R

R

R

NR

R

R

R

CR

NR

Food
Crop

R

R

R

R

R

NR

R

R

R

NR

NR

Nonfood
Crop

Terrestrial

NR

NR

NR

NR

NR

NR

NR

NR

NR

CR

CR

Food
Crop

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

CR

NR

Food
Crop

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

Nonfood
Crop

Greenhouse

Use Pattern

Nonfood
Crop

Aquatic

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

Forestry

R

R

R

R

R

NR

R

R

R

NR

NR

Residential
Outdoors

NR

R

R

NR

R

R

NR

NR

R

NR

NR

Indoor

TABLE—EXPERIMENTAL USE PERMIT DATA REQUIREMENTS FOR PRODUCT PERFORMANCE

Data Requirement

Efficacy of antimicrobial agents

Guideline No.

wreier-aviles on DSK7SPTVN1PROD with CFR

NR

NR

NR

NR

TEP

NR

NR

NR

NR

NR

NR

MP

EP

EP

EP

EP

EP

EP

EP

EP

EP

EP

EP

EP

Test substance to
support

1

1

1

1

1

1

1

1

1

1

1

Test Note
No.

§ 158.220
40 CFR Ch. I (7–1–11 Edition)

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Environmental Protection Agency

§ 158.230

(d) Test notes. The following test
notes apply to the data requirements
in the table to paragraph (c) of this
section.

submitted to support a request for an
experimental use permit.
(a) Use patterns. (1) Food use patterns
include products classified under the
general use patterns of terrestrial food
crop use, terrestrial feed crop use,
aquatic food crop use, greenhouse food
crop use, and indoor food use.
(2) Nonfood use patterns include
products classified under the general
use patterns of terrestrial nonfood crop
use, aquatic nonfood crop use, aquatic
nonfood
outdoor
use,
greenhouse
nonfood crop use, forestry use, residential outdoor use, indoor nonfood use,
and indoor residential use.
(b) Key. CR=Conditionally required;
NR=Not
required;
R=Required;
EP=End-use
product;
MP=Manufacturing-use
product;
PAIRA=Pure active ingredient radiolabeled; TGAI=Technical grade of the
active ingredient.
(c) Table. The following table shows
the experimental use data requirements for toxicology. The test notes
are shown in paragraph (d) of this section.

1. The Agency has waived the requirement
to submit efficacy data unless the pesticide
product bears a claim to control pest microorganisms that pose a threat to human
health and whose presence cannot readily be
observed by the user including, but not limited to, microorganisms infectious to man in
any area of the inanimate environment, or a
claim to control vertebrates (such as rodents, birds, bats, canids, and skunks) that
may directly or indirectly transmit diseases
to humans. However each registrant must
ensure through testing that his product is efficacious when used in accordance with label
directions and commonly accepted pest control practices. The Agency reserves the right
to require, on a case-by-case basis, submission of efficacy data for any pesticide product registered or proposed for registration.
2. [Reserved]
[72 FR 60957, Oct. 26, 2007, as amended at 73
FR 75596, Dec. 12, 2008]

§ 158.230 Experimental
use
permit
data requirements for toxicology.
All toxicology data, as described in
paragraph (c) of this section, must be

TABLE—EXPERIMENTAL USE PERMIT TOXICITY DATA REQUIREMENTS
Use Pattern
Guideline Number

Test substance to support

Nonfood

MP

EP

Test Note
No.

Data Requirement
Food

Acute Testing
870.1100

Acute oral toxicity - rat

R

R

MP and
TGAI

TGAI, EP

1

870.1200

Acute dermal toxicity

R

R

MP and
TGAI

TGAI, EP

1, 2

870.1300

Acute inhalation toxicity rat

R

R

MP and
TGAI

TGAI and
EP

3

870.2400

Primary eye irritation rabbit

R

R

MP

TGAI and
EP

2

870.2500

Primary dermal irritation

R

R

MP

TGAI and
EP

1, 2

870.2600

Dermal sensitization

R

R

MP

TGAI and
EP

2, 4

870.6100

Delayed neurotoxicity
(acute) - hen

CR

CR

TGAI

TGAI

5

870.3100

90–day Oral - rodent

R

NR

TGAI

TGAI

--

870.3150

90–day Oral - non-rodent

R

NR

TGAI

TGAI

--

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Subchronic Testing

Chronic Testing

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§ 158.240

40 CFR Ch. I (7–1–11 Edition)

TABLE—EXPERIMENTAL USE PERMIT TOXICITY DATA REQUIREMENTS—Continued
Use Pattern
Guideline Number

MP

EP

Test Note
No.

R

NR

TGAI

TGAI

6

Food
870.4100

Test substance to support

Nonfood

Data Requirement
Chronic oral - rodent

Developmental Toxicity and Reproduction
870.3700

Prenatal Developmental
toxicity - rat and rabbit, preferred

R

NR

TGAI

TGAI

7, 8

870.3800

Reproduction

R

NR

TGAI

TGAI

6

870.5100

Bacterial reverse mutation assay

R

NR

TGAI

TGAI

9

870.5300
870.5375

In vitro mammalian cell
assay

R

NR

TGAI

TGAI

9, 10

870.5385
870.5395

In vivo cytogenetics

R

NR

TGAI

TGAI

9, 11

Mutagenicity Testing

wreier-aviles on DSK7SPTVN1PROD with CFR

(d) Test notes. The following test
notes apply to the data requirements
in the table to paragraph (c) of this
section.
1. Not required if test material is a gas or
a highly volatile liquid.
2. Not required if test material is corrosive
to skin or has a pH of less than 2 or greater
than 11.5.
3. Required if the product consists of, or
under conditions of use will result in, a respirable material (e.g., gas, vapor, aerosol, or
particulate).
4. Required if repeated dermal exposure is
likely to occur under conditions of use.
5. Required if the test material is an
organophosphorus substance, which includes
uncharged
organophosphorus
esters,
thioesters,
or
anhydrides
of
organophosphoric,
organophosphonic,
or
organophosphoramidic acids, or of related
phosphorothioic,
phosponothioic,
or
phosphorothioamidic acids, or is structurally
related to other substances that may cause
the delayed neurotoxicity sometimes seen in
this class of chemicals.
6. These studies are seldom required to
support EUPs. They may be required if the
dietary exposure for these EUPs occupies a
large part, e.g., greater than 50%, of the reference dose.
7. The oral route, by oral intubation, is
preferred unless the chemical or physical
properties of the test substance or the pattern of exposure suggests a more appropriate
route of exposure.
8. May be combined with the 2–generation
reproduction study in rodents by utilizing a
second mating of the parental animals in either generation.

9. At a minimum, an initial battery of mutagenicity tests with possible confirmatory
testing is required. Other relevant mutagenicity tests that may have been performed,
plus a complete reference list must also be
submitted.
10. Choice of assay using either:
i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing
assay conditions for small colony expression
or detection;
ii. Chinese hamster ovary (CHO) or Chinese
hamster
lung
fibroblast
(V79)
cells,
hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an
appropriate in vitro test for clastogenicity; or
iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene
locus.
11. The micronucleus rodent bone marrow
assay is preferred; however, rodent bone
marrow assays using metaphase analysis (aberrations) are acceptable.
[72 FR 60957, Oct. 26, 2007, as amended at 73
FR 75596, Dec. 12, 2008]

§ 158.240 Experimental
use
permit
data requirements for ecological effects.
All data for terrestrial nontarget organisms and aquatic nontarget organisms as described in § 158.243 must be
submitted to support a request for an
experimental use permit. No data for
nontarget plant protection must be
submitted to support a request for an
experimental use permit.

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Environmental Protection Agency

§ 158.243

§ 158.243 Experimental
use
permit
data requirements for terrestrial
and aquatic nontarget organisms.
All terrestrial and aquatic nontarget
organism data, as described in paragraph (c) of this section, must be submitted to support a request for an experimental use permit.
(a) Use patterns. (1) The terrestrial
use pattern includes products classified
under the general use patterns of terrestrial food crop, terrestrial feed crop,
and terrestrial nonfood crop. The
aquatic use pattern includes products
classified under the general use patterns of aquatic food crop and aquatic
nonfood. The greenhouse use pattern
includes products classified under the
general use patterns of greenhouse food
crop and greenhouse nonfood crop. The
indoor use pattern includes products

classified under the general use patterns of indoor food and indoor nonfood
use.
(2) Data are also required for the general use patterns of forestry and residential outdoor use.
(b) Key. CR=Conditionally required;
NR=Not
required;
R=Required;
TEP=Typical
end-use
product;
TGAI=Technical grade of the active ingredient; commas between the test substances (e.g. TGAI, TEP) indicate that
data may be required on the TGAI or
TEP depending on the conditions set
forth in the test note.
(c) Table. The following table shows
the experimental use data requirements for terrestrial and aquatic nontarget organisms. The test notes are
shown in paragraph (d) of this section.

TABLE—EXPERIMENTAL USE PERMIT TERRESTRIAL AND AQUATIC NONTARGET ORGANISM DATA
REQUIREMENTS
Use Pattern
Guideline No.

Data Requirement

Terrestrial

Aquatic

Forestry

Residential
Outdoor

Greenhouse

Indoor

Test
substance

Test
Note
No.

Avian and Mammalian Testing
850.2100

Avian oral toxicity

R

R

R

R

CR

CR

TGAI

1, 2, 3

850.2200

Avian dietary toxicity

R

R

R

R

NR

NR

TGAI

1, 4

Aquatic Organisms Testing
850.1075

Freshwater fish toxicity

R

R

R

NR

NR

NR

TGAI,
TEP

1, 2, 5,
6, 11

850.1010

Acute toxicity freshwater
invertebrates

R

R

R

NR

NR

NR

TGAI,
TEP

1, 2, 6,
7, 11

850.1300

Aquatic invertebrate life
cycle (freshwater)

NR

R

R

NR

NR

NR

TGAI

1, 7, 8

850.1400

Fish early-life stage
(freshwater)

NR

R

R

NR

NR

NR

TGAI

1, 8, 9

Fish

CR

CR

CR

NR

NR

NR

TGAI or
PAIRA

10

Honeybee acute contact
toxicity

R

R

R

NR

NR

NR

TGAI

1

Accumulation Study
850.1730
Insect Pollinator Testing

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850.3020

(d) Test notes. The following test
notes apply to the data requirements
in the table to paragraph (c) of this
section.

1. Data using the TGAI are required to support all outdoor end-use product uses including, but not limited to, turf. Data are generally not required to support end-use products in the form of a gas, a highly volatile

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§ 158.250

40 CFR Ch. I (7–1–11 Edition)

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liquid, a highly reactive solid, or a highly
corrosive material.
2. For greenhouse and indoor end-use products, data using the TGAI are required to
support manufacturing-use products to be reformulated into these same end-use products
or to support end-use products when there is
no registered manufacturing-use product.
Avian acute oral data are not required for
liquid formulations for greenhouse and indoor uses. The study is not required if there
is no potential for environmental exposure.
3. Data are required on one passerine species and either one waterfowl species or one
upland game bird species for terrestrial,
aquatic, forestry, and residential outdoor
uses. Data are preferred on waterfowl or upland game bird species for indoor and greenhouse uses.
4. Data are required on waterfowl and upland game bird species.
5. Data are required on one coldwater fish
and one warmwater fish for terrestrial,
aquatic, forestry, and residential outdoor
uses. For indoor and greenhouse uses, testing
with only one of either fish species is required.
6. EP or TEP testing is required for any
product which meets any of the following
conditions:
i. The end-use pesticide will be introduced
directly into an aquatic environment (e.g.,
aquatic herbicides and mosquito larvicides)
when used as directed.
ii. The maximum expected environmental
concentration (MEEC) or the estimated environmental concentration (EEC) in the aquatic environment is ≥ one-half the LC50 or EC50
of the TGAI when the EP is used as directed.
iii. An ingredient in the end-use formulation other than the active ingredient is expected to enhance the toxicity of the active
ingredient or to cause toxicity to aquatic organisms.
7. Data are required on one freshwater
aquatic invertebrate species.
8. Data are generally not required for outdoor residential uses, other than turf, unless
data indicate that pesticide residues from
the proposed use(s) can potentially enter waterways.
9. Data are required on one freshwater fish
species. If the test species is different from
the two species used for the freshwater fish
acute toxicity tests, a 96 hour LC50 on that
species must also be provided.
10. Not required when:
i. The octanol/water partition coefficients
of the pesticide and its major degradates are
< 1,000; or

ii. There are no potential exposures to fish
and other nontarget aquatic organisms; or
iii. The hydrolytic half-life is < 5 days at
pH 5, 7 and 9.
11. The freshwater fish test species for the
TEP testing is the most sensitive of the species tested with the TGAI. A freshwater invertebrate must also be tested with the EP
or TEP using the same species tested with
the TGAI.
[72 FR 60957, Oct. 26, 2007, as amended at 73
FR 75596, Dec. 12, 2008]

§ 158.250 Experimental
use
permit
data requirements for human exposure.
No data for applicator exposure and
post-application exposure must be submitted to support a request for an experimental use permit.
§ 158.260 Experimental
data requirements
mental fate.

use
permit
for environ-

All environmental fate data, as described in paragraph (c) of this section,
must be submitted to support a request
for an experimental use permit.
(a) Use patterns. (1) The terrestrial
use pattern includes products classified
under the general use patterns of terrestrial food crop, terrestrial feed crop,
and terrestrial nonfood. The aquatic
use pattern includes the general use
patterns of aquatic food crop, aquatic
nonfood
residential,
and
aquatic
nonfood outdoors. The greenhouse use
pattern includes both food and nonfood
uses. The indoor use pattern includes
food, nonfood, and residential indoor
uses.
(2) Data are also required for the general use patterns of forestry use and
residential outdoor use.
(b) Key. CR=Conditionally required;
NR=Not
required;
R=Required;
PAIRA=Pure active ingredient radiolabeled; TGAI=Technical grade of the
active ingredient.
(c) Table. The following table shows
the experimental use data requirements for environmental fate. The test
notes are shown in paragraph (d) of
this section.

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Environmental Protection Agency

§ 158.300

TABLE—EXPERIMENTAL USE PERMIT ENVIRONMENTAL FATE DATA REQUIREMENTS
Use Pattern
Guideline No.

Data Requirement

Terrestrial

Aquatic

Greenhouse

Indoors

Forestry

Residential
Outdoors

Test
substance

Test Note
No.

R

R

R

NR

R

R

TGAI
or
PAIRA

1

R

CR

NR

NR

R

NR

TGAI
or
PAIRA

2

NR

R

NR

NR

NR

NR

TGAI
or
PAIRA

--

R

NR

NR

NR

R

NR

TGAI
or
PAIRA

3

Degradation Study - Laboratory
835.2120

Hydrolysis

Metabolism Studies - Laboratory
835.4100

Aerobic soil

835.4300

Aerobic aquatic

Mobility Study
835.1230
835.1240

Leaching and adsorption/
desorption

(d) Test notes. The following test
notes apply to the data requirements
in the table to paragraph (c) of this
section.

§§ 158.280–158.290

1. Study is required for indoor uses in cases
where environmental exposure is likely to
occur. Such sites include, but are not limited
to, agricultural premises, in or around farm
buildings, barnyards, and beehives.
2. Required for aquatic uses for aquatic
sites that are intermittently dry. Such sites
include, but are not limited to cranberry
bogs and rice paddies.
3. Adsorption and desorption using a batch
equilibrium method is preferred. However, in
some cases, for example, where the pesticide
degrades rapidly, soil column leaching with
unaged or aged columns may be more appropriate to fully characterize the potential mobility of the parent compound and major
transformation products.

§ 158.300

wreier-aviles on DSK7SPTVN1PROD with CFR

[72 FR 60957, Oct. 26, 2007, as amended at 73
FR 75596, Dec. 12, 2008]

§ 158.270 Experimental
use
permit
data requirements for residue
chemistry.
All residue chemistry data, as described in § 158.1410, are required for an
experimental use permit for which a
temporary tolerance under FFDCA section 408(r) is sought. Residue chemistry
data are not required for an experimental use permit issued on a crop-destruct basis.

[Reserved]

Subpart D—Product Chemistry
Definitions.

The following terms are defined for
the purposes of this subpart:
Active ingredient means any substance
(or group of structurally similar substances, if specified by the Agency)
that will prevent, destroy, repel or
mitigate any pest, or that functions as
a plant regulator, desiccant, defoliant,
or nitrogen stabilizer, within the
meaning of FIFRA sec. 2(b).
End-use product means a pesticide
product whose labeling:
(1) Includes directions for use of the
product (as distributed or sold, or after
combination by the user with other
substances) for controlling pests or defoliating, desiccating or regulating
growth of plants, or as a nitrogen stabilizer, and
(2) does not state that the product
may be used to manufacture or formulate other pesticide products.
Formulation means:
(1) The process of mixing, blending,
or dilution of one or more active ingredients with one or more other active or
inert ingredients, without an intended

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§ 158.310

40 CFR Ch. I (7–1–11 Edition)
Starting material means a substance
used to synthesize or purify a technical
grade of active ingredient (or the practical equivalent of the technical grade
ingredient if the technical grade cannot be isolated) by chemical reaction.
Technical grade of active ingredient
means a material containing an active
ingredient:
(1) Which contains no inert ingredient, other than one used for purification of the active ingredient; and
(2) Which is produced on a commercial or pilot plant production scale
(whether or not it is ever held for sale).

chemical reaction, to obtain a manufacturing-use product or an end-use
product, or
(2) The repackaging of any registered
product.
Impurity means any substance (or
group of structurally similar substances if specified by the Agency), in a
pesticide product other than an active
ingredient or an inert ingredient, including unreacted starting materials,
side reaction products, contaminants,
and degradation products.
Impurity associated with an active ingredient means:
(1) Any impurity present in the technical grade of active ingredient; and
(2) Any impurity which forms in the
pesticide product through reactions between the active ingredient and any
other component of the product or
packaging of the product.
Inert ingredient means any substance
(or group of structurally similar substances if designated by the Agency),
other than the active ingredient, which
is intentionally included in a pesticide
product.
Integrated system means a process for
producing a pesticide product that:
(1) Contains any active ingredient derived from a source that is not an EPAregistered product; or
(2) Contains any active ingredient
that was produced or acquired in a
manner that does not permit its inspection by the Agency under FIFRA
sec. 9(a) prior to its use in the process.
Manufacturing-use product means any
pesticide product other than an end-use
product. A product may consist of the
technical grade of active ingredient
only, or may contain inert ingredients,
such as stabilizers or solvents.
Nominal concentration means the
amount of an ingredient which is expected to be present in a typical sample of a pesticide product at the time
the product is produced, expressed as a
percentage by weight.

§ 158.310 Product chemistry data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the product chemistry data
requirements for a particular pesticide
product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to
the designated test are listed in paragraph (f) of the section.
(b) Use patterns. Product chemistry
data are required for all pesticide products and are not use-specific.
(c) Test substance. Data requirements
that list only the manufacturing-use
product as the test substance apply to
products containing solely the technical grade of the active ingredient and
manufacturing-use products to which
other ingredients have been intentionally added.
(d)
Key.
R=Required;
CR=Conditionally
required;
MP=Manufacturing-use
product;
NR=Not required; EP=End-use product;
TGAI=Technical grade of the active ingredient; PAI=Pure active ingredient.
(e) Table. The following table shows
the data requirements for product
chemistry. The table notes are shown
in paragraph (f) of this section.

PRODUCT CHEMISTRY DATA REQUIREMENTS
Use Pattern

wreier-aviles on DSK7SPTVN1PROD with CFR

Guideline
Number

Test substance to support

Data Requirement
All

MP

EP

Test Note
No.

Product Identity and Composition
830.1550

Product identity and composition

R

MP

EP

1

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Environmental Protection Agency

§ 158.310

PRODUCT CHEMISTRY DATA REQUIREMENTS—Continued
Use Pattern

Test substance to support

Guideline
Number

Data Requirement

830.1600

Description of materials used to produce the
product

830.1620

Description of production process

R

MP

EP

3

830.1650

Description of formulation process

R

MP

EP

4

830.1670

Discussion of formulation of impurities

R

MP, and possibly TGAI

EP, and possibly TGAI

5

830.1700

Preliminary analysis

CR

MP, and possibly TGAI

EP, and possibly TGAI

6, 9, 10

830.1750

Certified limits

R

MP

EP

7

830.1800

Enforcement analytical method

R

MP

EP

8

830.1900

Submittal of samples

CR

MP, PAI and
TGAI

EP, PAI, TGAI

All
R

MP
MP

EP
EP

Test Note
No.
2

9, 11

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Physical and Chemical Properties
830.6302

Color

R

MP and TGAI

EP

9

830.6303

Physical state

R

MP and TGAI

EP and TGAI

9

830.6304

Odor

R

MP and TGAI

EP

9

830.6313

Stability to normal and elevated temperatures, metals, and metal ions

R

MP and TGAI

EP

9, 12, 26

830.6314

Oxidation/reduction: chemical incompatibility

CR

MP

EP

13

830.6315

Flammability

CR

MP

EP

14

830.6316

Explodability

CR

MP

EP

15

830.6317

Storage stability

R

MP

EP

830.6319

Miscibility

830.6320

Corrosion characteristics

830.6321

CR

MP

EP

R

MP

EP

Dielectric breakdown voltage

CR

NR

EP

830.7000

pH

CR

830.7050

UV/visible light absorption

830.7100

Viscosity

830.7200

Melting point/melting range

830.7220

Boiling point/boiling range

R

830.7300

Density/relative density/bulk density

R

830.7370

Dissociation constants in water

R

830.7520

Particle size, fiber length, and diameter distribution

830.7550
830.7560
830.7570

R
CR

16

17

MP and TGAI

EP and TGAI

TGAI or PAI

NR

--

MP

EP

TGAI or PAI

TGAI or PAI

9, 20

TGAI or PAI

TGAI or PA

9, 21

MP and TGAI

EP and TGAI

9

TGAI or PAI

TGAI or PAI

9, 22

CR

TGAI or PAI

EP

23

Partition coefficient (n-octanol/water)

R

TGAI or PAI

TGAI or PAI

24

830.7840
830.7860

Water solubility

R

TGAI or PAI

TGAI or PAI

9

830.7950

Vapor pressure

R

TGAI or PAI

TGAI or PAI

9, 25

R

19

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§ 158.320

40 CFR Ch. I (7–1–11 Edition)

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(f) Test notes. The following test notes
are applicable to the product chemistry
data requirements in the table to paragraph (e) of this section:
1. Data must be provided in accordance
with § 158.320.
2. Data must be provided in accordance
with § 158.325.
3. Data must be provided in accordance
with § 158.330.
4. Data must be provided in accordance
with § 158.335.
5. Data must be provided in accordance
with § 158.340.
6. Data must be provided in accordance
with § 158.345.
7. Data must be provided in accordance
with § 158.350.
8. Data must be provided in accordance
with § 158.355.
9. If the TGAI cannot be isolated, data are
required on the practical equivalent of the
TGAI.
10. Data are required if the product is produced by an integrated system.
11. Basic manufacturers are required to
provide the Agency with a sample of each
TGAI used to formulate a product produced
by an integrated system when the new TGAI
is first used as a formulating ingredient in
products registered under FIFRA. A sample
of the active ingredient (PAI) suitable for
use as an analytical standard is also required
at this time. Samples of end-use products
produced by an integrated system must be
submitted on a case-by-case basis.
12. Data on the stability to metals and
metal ions are required only if the TGAI is
expected to come into contact with either
material.
13. Required when the product contains an
oxidizing or reducing agent.
14. Required when the product contains
combustible liquids.
15. Required when the product is potentially explosive.
16. Required when the product is an emulsifiable liquid and is to be diluted with petroleum solvent.
17. Required when the EP is a liquid and is
to be used around electrical equipment.
18. Required when the test substance is
soluble or dispersible in water.
19. Required when the product is a liquid.
20. Required when the TGAI is solid at
room temperature.
21. Required when the TGAI is liquid at
room temperature.
22. Required when the test substance contains an acid or base functionality (organic
or inorganic) or an alcoholic functionality
(organic).
23. Required for water insoluble test substances (>10-6 g/l) and fibrous test substances
with diameter of ≥0.1 μm.

24. Required if technical chemical is organic and non-polar.
25. Not required for salts.
26. Data on stability of the MP and TGAI
to storage at normal temperatures are required. Data on the stability of the TGAI to
high temperatures are required if the TGAI
is expected to be subjected to temperatures
>50 °C (122 °F) during production or storage.

§ 158.320 Product identity and composition.
Information on the composition of
the pesticide product must be furnished. The information required by
paragraphs (a), (b), and (f) of this section must be provided for each product.
In addition, if the product is produced
by an integrated system, the information on impurities required by paragraphs (c) and (d) of this section must
be provided.
(a) Active ingredient. The following information is required for each active
ingredient in the product:
(1) If the source of any active ingredient in the product is an EPA-registered product:
(i) The chemical and common name
(if any) of the active ingredient, as listed on the source product.
(ii) The nominal concentration of the
active ingredient in the product, based
upon the nominal concentration of active ingredient in the source product.
(iii) Upper and lower certified limits
of the active ingredient in the product,
in accordance with § 158.350.
(2) If the source of any active ingredient in the product is not an EPA-registered product:
(i) The chemical name according to
Chemical Abstracts Society (CAS) nomenclature, the CAS Registry Number,
and any common names.
(ii) The molecular, structural, and
empirical formulae and the molecular
weight or weight range.
(iii) The nominal concentration.
(iv) Upper and lower certified limits
of the active ingredient in accordance
with § 158.350.
(v) The purpose of the ingredient in
the formulation.
(b) Inert ingredients. The following information is required for each inert ingredient (if any) in the product:
(1) The chemical name of the ingredient according to Chemical Abstracts

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wreier-aviles on DSK7SPTVN1PROD with CFR

Environmental Protection Agency

§ 158.325

Society nomenclature, the CAS Registry Number, and any common names
(if known). If the chemical identity or
chemical composition of an ingredient
is not known to the applicant because
it is proprietary or trade secret information, the applicant must ensure that
the supplier or producer of the ingredient submits to the Agency (or has on
file with the Agency) information on
the identity or chemical composition
of the ingredient. Generally, it is not
required that an applicant know the
identity of each ingredient in a mixture that he uses in his product. However, in certain circumstances, the
Agency may require that the applicant
know the identity of a specific ingredient in such a mixture. If the Agency
requires specific knowledge of an ingredient, it will notify the applicant in
writing.
(2) The nominal concentration.
(3) Upper and lower certified limits in
accordance with § 158.350.
(4) The purpose of the ingredient in
the formulation.
(c) Impurities of toxicological significance associated with the active ingredient. For each impurity associated
with the active ingredient that is determined by EPA to be toxicologically
significant, the following information
is required:
(1) Identification of the ingredient as
an impurity.
(2) The chemical name of the impurity.
(3) The nominal concentration of the
impurity in the product.
(4) A certified upper limit, in accordance with § 158.350.
(d) Other impurities associated with the
active ingredient. For each other impurity associated with an active ingredient that was found to be present in
any sample at a level ≥0.1 percent by
weight of the technical grade active ingredient the following information is
required:
(1) Identification of the ingredient as
an impurity.
(2) The chemical name of the impurity.
(3) The nominal concentration of the
impurity in the final product.
(e) Impurities associated with an inert
ingredient. [Reserved]

(f) Ingredients that cannot be characterized. If the identity of any ingredient
or impurity cannot be specified as a
discrete chemical substance (such as
mixtures that cannot be characterized
or isomer mixtures), the applicant
must provide sufficient information to
enable EPA to identify its source and
qualitative composition.
§ 158.325 Description of materials used
to produce the product.
The following information must be
submitted on the materials used to
produce the product:
(a) Products not produced by an integrated system. (1) For each active ingredient that is derived from an EPA-registered product:
(i) The name of the EPA-registered
product.
(ii) The EPA registration number of
that product.
(2) For each inert ingredient:
(i) Each brand name, trade name,
common name, or other commercial
designation of the ingredient.
(ii) All information that the applicant knows (or that is reasonably
available to him) concerning the composition (and, if requested by the Agency, chemical and physical properties)
of the ingredient, including a copy of
technical specifications, data sheets, or
other documents describing the ingredient.
(iii) If requested by the Agency, the
name and address of the producer of
the ingredient or, if that information is
not known to the applicant, the name
and address of the supplier of the ingredient.
(b) Products produced by an integrated
system. (1) The information required by
paragraph (a)(1) of this section concerning each active ingredient that is
derived from an EPA-registered product (if any).
(2) The following information concerning each active ingredient that is
not derived from an EPA-registered
product:
(i) The name and address of the producer of the ingredient (if different
from the applicant).
(ii) Information about each starting
material used to produce the active ingredient, as follows:

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40 CFR Ch. I (7–1–11 Edition)

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(A) Each brand name, trade name, or
other commercial designation of the
starting material.
(B) The name and address of the person who produces the starting material
or, if that information is not known to
the applicant, the name and address of
each person who supplies the starting
material.
(C) All information that the applicant knows (or that is reasonably
available to him), concerning the composition (and if requested by the Agency, chemical or physical properties) of
the starting material, including a copy
of all technical specifications, data
sheets, or other documents describing
it.
(3) The information required by paragraph (a)(2) of this section concerning
each inert ingredient.
(c) Additional information. On a caseby-case basis, the Agency may require
additional information on substances
used in the production of the product.
§ 158.330 Description of production
process.
If the product is produced by an integrated system, the applicant must submit information on the production (reaction) processes used to produce the
active ingredients in the product. The
applicant must also submit information about the formulation process, in
accordance with § 158.335.
(a) Information must be submitted
for the current production process for
each active ingredient that is not derived from an EPA-registered product.
If the production process is not continuous (a single reaction process from
starting materials to active ingredient), but is accomplished in stages or
by different producers, the information
must be provided for each such production process.
(b) The following information must
be provided for each process resulting
in a separately isolated substance:
(1) The name and address of the producer who uses the process, if not the
same as the applicant.
(2) A general characterization of the
process (e.g., whether it is a batch or
continuous process).
(3) A flow chart of the chemical equations of each intended reaction occurring at each step of the process, and of

the duration of each step and of the entire process.
(4) The identity of the materials used
to produce the product, their relative
amounts, and the order in which they
are added.
(5) A description of the equipment
used that may influence the composition of the substance produced.
(6) A description of the conditions
(e.g., temperature, pressure, pH, humidity) that are controlled during each
step of the process to affect the composition of the substance produced, and
the limits that are maintained.
(7) A description of any purification
procedures (including procedures to recover or recycle starting materials,
intermediates or the substance produced).
(8) A description of the procedures
used to assure consistent composition
of the substance produced, e.g., calibration of equipment, sampling regimens,
analytical methods, and other quality
control methods.
§ 158.335 Description of formulation
process.
The applicant must provide information on the formulation process of the
product (unless the product consists
solely of a technical grade of active ingredient) as required by the following
sections:
(a) Section 158.330(b)(2), pertaining to
characterization of the process.
(b) Section 158.330(b)(4), pertaining to
ingredients used in the process.
(c) Section 158.330(b)(5), pertaining to
process equipment.
(d) Section 158.330(b)(6), pertaining to
the conditions of the process.
(e) Section 158.330(b)(8), pertaining to
quality control measures.
§ 158.340 Discussion of formation of
impurities.
The applicant must provide a discussion of the impurities that may be
present in the product, and why they
may be present. The discussion should
be based on established chemical theory and on what the applicant knows
about the starting materials, technical
grade of active ingredient, inert ingredients, and production or formulation
process. If the applicant has reason to
believe that an impurity that EPA

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Environmental Protection Agency

§ 158.345

would consider toxicologically significant may be present, the discussion
must include an expanded discussion of
the possible formation of the impurity
and the amounts at which it might be
present. The impurities which must
also be discussed are the following, as
applicable:
(a) Technical grade active ingredients
and products produced by an integrated
system. (1) Each impurity associated
with the active ingredient which was
found to be present in any analysis of
the product conducted by or for the applicant.
(2) Each other impurity which the
registrant or applicant has reason to
believe may be present in his product
at any time before use at a level ≥0.1
percent (1,000 ppm) by weight of the
technical grade of the active ingredient, based on what he knows about
the following:
(i) The composition (or composition
range) of each starting material used
to produce his product.
(ii) The impurities which the applicant knows are present (or believes are
likely to be present) in the starting
materials, and the known or presumed
level (or range of levels) of these impurities.
(iii) The intended reactions and side
reactions which may occur in the production of the product, and the relative
amounts of byproduct impurities produced by such reactions.
(iv) The possible degradation of the
ingredients in the product after its production but prior to its use.
(v) Post-production reactions between the ingredients in the product.
(vi) The possible migration of components of packaging materials into the
pesticide.
(vii) The possible carryover of contaminants from use of production
equipment previously used to produce
other products or substances.
(viii) The process control, purification and quality control measures
used to produce the product.
(b) Products not produced by an integrated system. Each impurity associated
with the active ingredient which the
applicant has reason to believe may be
present in the product at any time before use at a level ≥0.1 percent (1,000

ppm) by weight of the product based on
what he knows about the following:
(1) The possible carryover of impurities present in any registered product
which serves as the source of any of the
product’s active ingredients. The identity and level of impurities in the registered source need not be discussed or
quantified unless known to the formulator.
(2) The possible carryover of impurities present in the inert ingredients in
the product.
(3) Possible reactions occurring during the formulation of the product between any of its active ingredients, between the active ingredients and inert
ingredients, or between the active ingredient and the production equipment.
(4) Post-production reactions between any of the product’s active ingredients and any other component of
the product or its packaging.
(5) Possible migration of packaging
materials into the product.
(6) Possible contaminants resulting
from earlier use of equipment to
produce other products.
(c) Expanded discussion. On a case-bycase basis, the Agency may require an
expanded discussion of information on
impurities:
(1) From other possible chemical reactions.
(2) Involving other ingredients.
(3) At additional points in the production or formulation process.
§ 158.345

Preliminary analysis.

(a) If the product is produced by an
integrated system, the applicant must
provide a preliminary analysis of each
technical grade of active ingredient
contained in the product to identify all
impurities present at 0. 1 percent or
greater of the technical grade of the
active ingredient. The preliminary
analysis should be conducted at the
point in the production process after
which no further chemical reactions
designed to produce or purify the substances are intended.
(b) Based on the preliminary analysis, a statement of the composition of
the technical grade of the active ingredient must be provided. If the technical
grade of the active ingredient cannot

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§ 158.350

40 CFR Ch. I (7–1–11 Edition)

be isolated, a statement of the composition of the practical equivalent of
the technical grade of the active ingredient must be submitted.
§ 158.350 Certified limits.
The applicant must propose certified
limits for the ingredients in the product. Certified limits become legally
binding limits upon approval of the application. Certified limits will apply to
the product from the date of production to date of use. If the product label
bears a statement prohibiting use after
a certain date, the certified limits will
apply only until that date.
(a) Ingredients for which certified limits
are required. Certified limits are required on the following ingredients of a
pesticide product:
(1) An upper and lower limit for each
active ingredient.
(2) An upper and lower limit for each
inert ingredient.

(3) If the product is a technical grade
of active ingredient or is produced by
an integrated system, an upper limit
for each impurity of toxicological significance associated with the active ingredient and found to be present in any
sample of the product.
(4) On a case-by-case basis, certified
limits for other ingredients or impurities as specified by EPA.
(b) EPA determination of standard certified limits for active and inert ingredients. (1) Unless the applicant proposes
different limits as provided in paragraph (c) of this section, the upper and
lower certified limits for active and
inert ingredients will be determined by
EPA. EPA will calculate the certified
limits on the basis of the nominal concentration of the ingredient in the
product, according to the table in paragraph (b)(2) of this section.
(2) Table of standard certified limits.

STANDARD CERTIFIED LIMITS
The certified limits for that ingredient will be as follows:

If the nominal concentration (N) for the ingredient and
percentage by weight for the ingredient is:

Upper Limit

Lower Limit

N + 10%N

N - 10%N

1.0% ≤N ≤20.0% ..............................................................

N + 5%N

N - 5%N

20.0%≤N≤100.0% .............................................................

N + 3%N

N - 3%N

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N≤1.0% .............................................................................

(c) Applicant proposed limits. (1) The
applicant may propose a certified limit
for an active or inert ingredient that
differs from the standard certified
limit calculated according to paragraph (b)(2) of this section.
(2) If certified limits are required for
impurities, the applicants must propose a certified limit. The standard
certified limits may not be used for
such substances.
(3) Certified limits should:
(i) Be based on a consideration of the
variability of the concentration of the
ingredient in the product when good
manufacturing practices and normal
quality control procedures are used.
(ii) Allow for all sources of variability likely to be encountered in the
production process.
(iii) Take into account the stability
of the ingredient in the product and
the possible formation of impurities

between production and sale or distribution.
(4) The applicant may include an explanation of the basis of his proposed
certified limits, including how the certified limits were arrived at (e.g., sample analysis, quantitative estimate
based on production process), and its
accuracy and precision. This will be
particularly useful if the range of the
certified limit for an active or inert ingredient is greater than the standard
certified limits.
(d) Special cases. If the Agency finds
unacceptable any certified limit (either
standard, or applicant proposed), the
Agency will inform the registrant or
applicant of its determination and will
provide supporting reasons. The Agency may also recommend alternative
limits to the applicant. The Agency
may require, on a case-by-case basis,
any or all of the following:
(1) More precise limits.

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Environmental Protection Agency

§ 158.400

(2) More thorough explanation of how
the certified limits were determined.
(3) A narrower range between the
upper and lower certified limits than
that proposed.
(e) Certification statement. The applicant must certify the accuracy of the
information presented, and that the
certified limits of the ingredients will
be maintained. The following statement, signed by the authorized representative of the company, is acceptable:
I hereby certify that, for purposes of
FIFRA sec. 12(a)(1)(C), the description of the
composition of [insert product name], EPA
Reg. No. [insert registration number], refers to
the composition set forth on the Statement
of Formula and supporting materials. This
description includes the representations
that: (1) no ingredient will be present in the
product in an amount greater than the upper
certified limit or in an amount less than the
lower certified limit (if required) specified
for that ingredient in a currently approved
Statement of Formula (or as calculated by
the Agency); and (2) if the Agency requires
that the source of supply of an ingredient be
specified, that all quantities of such ingredient will be obtained from the source specified in the Statement of Formula.

§ 158.355
od.

Enforcement analytical meth-

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An analytical method suitable for enforcement purposes must be provided
for each active ingredient in the product and for each other ingredient or
impurity that the Agency determines
to be toxicologically significant.

Subpart E—Product Performance
§ 158.400 Product performance
requirements table.

(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the product performance
data requirements for a particular pesticide product. Notes that apply to an
individual test, including specific conditions, qualifications, or exceptions to
the designated test are listed in paragraph (e) of this section.
(b) Use patterns. The terrestrial use
pattern includes products classified
under the general use patterns of terrestrial food crop and terrestrial
nonfood crop. The aquatic use pattern
includes products classified under the
general use patterns of aquatic food
crop and aquatic nonfood. The greenhouse use pattern includes products
classified under the general use patterns of greenhouse food crop and
greenhouse nonfood crop. Data are also
required for the general use patterns of
forestry use, residential outdoor use,
and indoor use, which includes both
food and nonfood uses.
(c) Key. CR=Conditionally required;
NR=Not
required;
R=Required;
EP=End-use
product;
MP=Manufacturing-use
product;
TEP=Typical end-use product.
(d) Table. The following table lists
the data requirements that pertain to
product performance. The table notes
are shown in paragraph (e) of this section.

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Data Requirement

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Products for use on fabrics
and textiles

Air sanitizers

Products for control of microbial pests associated with
human and animal wastes

91–4

91–5

91–7

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Products for control of organisms producing mycotoxins

Avian toxicants

Avian repellents

Avian frightening agents

Bat toxicants and repellents

Commensal rodenticides

Rodenticides on farm and
rangelands

96–5

96–6

96–7

96–9

96–10

96–12

Efficacy of vertebrate control agents

93–16

Efficacy of fungicides and nematicides

Products for treating water
systems

Products requiring confirmatory data

91–3

91–8

Products for use on hard surfaces

91–2

Efficacy of antimicrobial agents

Guideline Number

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R

R

NR

R

R

R

CR

NR

NR

NR

NR

NR

NR

Food
Crop

R

R

NR

R

R

R

NR

NR

NR

NR

NR

NR

NR

Nonfood
Crop

Terrestrial

NR

NR

NR

NR

NR

NR

CR

CR

NR

NR

NR

NR

NR

Food

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

Nonfood

Aquatic

NR

NR

NR

NR

NR

NR

CR

NR

NR

NR

NR

NR

NR

Food
Crop

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

Nonfood
Crop

Greenhouse

Use Pattern

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

Forestry

TABLE—PRODUCT PERFORMANCE DATA REQUIREMENTS

R

R

NR

R

R

R

NR

NR

NR

NR

NR

NR

NR

Residential
Outdoor

NR

R

R

NR

NR

R

NR

CR

CR

CR

CR

CR

CR

Indoor

NR

TEP

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

MP

EP

EP

EP

EP

EP

EP

EP

EP

EP

EP

EP

EP

EP

EP

Test substance to
support

1

1

1

1

1

1

1

1

1

1

1

1

1

Test Note
No.

§ 158.400
40 CFR Ch. I (7–1–11 Edition)

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Rodent fumigants

Rodent reproductive inhibitors

Mammalian predacides

95–13

95–16

95–17

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R

R

R

R

R

R

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

R

R

R

NR

R

R

NR

NR

NR

EP

EP

EP

1

1

1

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§ 158.500

40 CFR Ch. I (7–1–11 Edition)

(e) Test notes. The following notes
appy to the data requirements table in
paragraph (d) of this section.

uct. Notes that apply to an individual
test and include specific conditions,
qualifications, or exceptions to the designated test in the table are listed in
paragraph (e) of this section.
(b) Use patterns. (1) Food use patterns
include products classified under the
general use patterns of terrestrial food
crop use, terrestrial feed crop use,
aquatic food crop use, greenhouse food
crop use, and indoor food use.
(2) Nonfood use patterns include
products classified under the general
use patterns of terrestrial nonfood crop
use, aquatic nonfood use, greenhouse
nonfood crop use, forestry use, residential outdoor use, and indoor nonfood
use.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product;
EP=End-use
product;
TGAI=Technical grade of the active ingredient; PAI=Pure active ingredient;
PAIRA=Pure active ingredient radiolabeled; Choice=Choice of several test
substances depending on study required.
(d) Table. The following table lists
the toxicology data requirements. The
table notes are shown in paragraph (e)
of this section.

1. The Agency has waived the requirement
to submit product performance data unless
the pesticide product bears a claim to control pest microorganisms that pose a threat
to human health and whose presence cannot
readily be observed by the user including,
but not limited to, microorganisms infectious to man in any area of the inanimate
environment, or a claim to control
vertebrates (such as rodents, birds, bats,
canids, and skunks) that may directly or indirectly transmit diseases to humans. However each registrant must ensure through
testing that his product is efficacious when
used in accordance with label directions and
commonly accepted pest control practices.
The Agency reserves the right to require, on
a case-by-case basis, submission of product
performance data for any pesticide product
registered or proposed for registration.
2. [Reserved]

Subpart F—Toxicology
§ 158.500 Toxicology
data
requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use the data
table in paragraph (d) of this section to
determine the toxicology data requirements for a particular pesticide prod-

TABLE—TOXICOLOGY DATA REQUIREMENTS
Use Pattern
Guideline
Number

Data Requirements
Food

Nonfood

Test substance to support
MP

EP

Test Note
No.

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Acute Testing
870.1100

Acute oral toxicity - rat

R

R

TGAI and
MP

TGAI, EP,
and
possibly
diluted
EP

1, 2

870.1200

Acute dermal toxicity

R

R

TGAI and
MP

TGAI, EP

1, 2, 3

870.1300

Acute inhalation toxicity - rat

R

R

TGAI and
MP

TGAI and
EP

4

870.2400

Primary eye irritation - rabbit

R

R

TGAI and
MP

TGAI and
EP

3

870.2500

Primary dermal irritation

R

R

TGAI and
MP

TGAI and
EP

1, 3

870.2600

Dermal sensitization

R

R

TGAI and
MP

TGAI and
EP

3, 5

870.6100

Delayed neurotoxicity (acute) - hen

CR

CR

TGAI

TGAI

6

870.6200

Acute neurotoxicity - rat

R

R

TGAI

TGAI

7

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Environmental Protection Agency

§ 158.500

TABLE—TOXICOLOGY DATA REQUIREMENTS—Continued
Use Pattern
Guideline
Number

Data Requirements
Food

Test substance to support

Nonfood

MP

Test Note
No.

EP

Subchronic Testing
870.3100

90–day Oral - rodent

R

CR

TGAI

TGAI

8, 9

870.3150

90–day Oral - non-rodent

R

CR

TGAI

TGAI

36

870.3200

21/28–day Dermal

R

NR

TGAI

TGAI and
EP

10, 11

870.3250

90–day Dermal

CR

R

TGAI

TGAI and
EP

11, 12

870.3465

90–day Inhalation - rat

CR

CR

TGAI

TGAI

13, 14

870.6100

28–day Delayed neurotoxicity-hen

CR

CR

TGAI

TGAI

6, 15

870.6200

90–day Neurotoxicity - rat

R

R

TGAI

TGAI

7, 16

870.4100

Chronic oral - rodent

R

CR

TGAI

TGAI

17, 18, 19

870.4200

Carcinogenicity - two rodent species - rat
and mouse preferred

R

CR

TGAI

TGAI

9, 17, 18,
19, 20,
21

TGAI

TGAI

22, 23, 24,
25, 26

Chronic Testing

Developmental Toxicity and Reproduction
870.3700

Prenatal Developmental toxicity - rat and
rabbit, preferred

R

R

870.3800

Reproduction and fertility effects

R

R

TGAI

TGAI

26, 27, 29

870.6300

Developmental neurotoxicity

CR

CR

TGAI

TGAI

27, 28, 29

Mutagenicity Testing
870.5100

Bacterial reverse mutation assay

R

R

TGAI

TGAI

30

870.5300
870.5375

In vitro mammalian cell assay

R

R

TGAI

TGAI

30, 31

870.5385
870.5395

In vivo cytogenetics

R

R

TGAI

TGAI

30, 32

870.7485

Metabolism and pharmacokinetics

R

CR

PAI or
PAIRA

PAI or
PAIRA

33

870.7200

Companion animal safety

CR

CR

NR

TGAI or
EP

34

870.7600

Dermal penetration

CR

CR

Choice

Choice

35

870.7800

Immunotoxicity

R

R

TGAI

TGAI

Special Testing

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(e) Test notes. The following test
notes apply to the requirements in the
table to paragraph (d) of this section:
1. Not required if test material is a gas or
a highly volatile liquid.
2. Diluted EP testing is required to support
the end product registration if results using
the EP meet the criteria for restricted use

classification under § 152.170(b) or special review consideration under § 154.7(a)(1).
3. Not required if the test material is corrosive to skin or has a pH of less than 2 or
greater than 11.5.
4. Required if the product consists of, or
under conditions of use will result in, a respirable material (e.g., gas, vapor, aerosol, or
particulate).

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§ 158.500

40 CFR Ch. I (7–1–11 Edition)

5. Required if repeated dermal exposure is
likely to occur under conditions of use.
6. Required if the test material is an
organophosphorus substance, which includes
uncharged
organophosphorus
esters;
thioesters
or
anhydrides
of
organophosphoric,
organophosphonic,
or
organophosphoramidic acids; or of related
phosphorothioic,
phosponothioic,
or
phosphorothioamidic acids; or is structurally
related to other substances that may cause
the delayed neurotoxicity sometimes seen in
this class of chemicals.
7. As determined by the Agency, additional
measurements may also be required, such as
cholinesterase activity for certain pesticides, e.g., organophosphates and some
carbamates. The route of exposure must correspond with the primary route of exposure.
8. Required for nonfood use pesticides if
oral exposure could occur.
9. The 90–day study is required in the rat
for hazard characterization (possibly endpoint selection) and dose-setting for the
chronic/carcinogenicity study. It is not required in the mouse, but the Agency would
strongly encourage the registrant to conduct
a 90–day range finding for the purposes of
dose selection for the mouse carcinogenicity
study to achieve adequate dosing and an acceptable study. The registrant is also encouraged to consult with the Agency on the
results of the 90–day mouse study prior to
conducting the carcinogenicity study.
10. Required for agricultural uses or if repeated human dermal exposure may occur.
Not required if an acceptable 90–day dermal
toxicity study is performed and submitted.
11. EP testing is required if the product, or
any component of it, may increase dermal
absorption of the active ingredient(s) as determined by testing using the TGAI, or increase toxic or pharmacologic effects.
12. Required for food uses if either of the
following criteria is met:
(i) The use pattern is such that the dermal
route would be the primary route of exposure; or
(ii) The active ingredient is known or expected to be metabolized differently by the
dermal route of exposure than by the oral
route, and a metabolite is the toxic moiety.
13. Required if there is the likelihood of
significant repeated inhalation exposure to
the pesticide as a gas, vapor, or aerosol.
14. Based on estimates of the magnitude
and duration of human exposure, studies of
shorter duration, e.g., 21– or 28–days, may be
sufficient to satisfy this requirement. Registrants should consult with the Agency to
determine whether studies of shorter duration would meet this requirement.
15.
Required
if
results
of
acute
neurotoxicity study indicate significant statistical or biological effects, or if other
available data indicate the potential for this

type of delayed neurotoxicity, as determined
by the Agency.
16. All 90–day subchronic studies in rats
can be designed to simultaneously fulfill the
requirements of the 90–day neurotoxicity
study using separate groups of animals for
testing. Although the subchronic guidelines
include the measurement of neurological
endpoints, they do not meet the requirement
of the 90–day neurotoxicity study.
17. Required if either of the following are
met:
(i) The use of the pesticide is likely to result in repeated human exposure over a considerable portion of the human lifespan, as
determined by the Agency;
(ii) The use requires a tolerance or an exemption from the requirement of a tolerance.
18. Based on the results of the acute and
subchronic neurotoxicity studies, or other
available data, a combined chronic toxicity
and neurotoxicity study may be required.
19. Studies which are designed to simultaneously fulfill the requirements of both the
chronic oral and carcinogenicity studies (i.e.,
a combined study) may be conducted. Minimum acceptable study durations are:
(i) Chronic rodent feeding study (food use)
- 24 months.
(ii) Chronic rodent feeding study (nonfood
use) - 12 months.
(iii) Mouse carcinogenicity study - 18
months.
(iv) Rat carcinogenicity study - 24 months.
20. Required if any of the following, as determined by the Agency, are met:
(i) The use of the pesticide is likely to result in significant human exposure over a
considerable portion of the human life span
which is significant in terms of either frequency, duration, or magnitude of exposure;
(ii) The use requires a tolerance or an exemption from the requirement of a tolerance; or
(iii) The active ingredient, metabolite,
degradate, or impurity (a) is structurally related to a recognized carcinogen, (b) causes
mutagenic effects as demonstrated by in
vitro or in vivo testing, or (c) produces a morphologic
effect
in
any
organ
(e.g.,
hyperplasia, metaplasia) in subchronic studies that may lead to a neoplastic change.
21. If this study is modified or waived, a
subchronic 90–day oral study conducted in
the same species may be required.
22. Testing in two species is required for all
uses.
23. The oral route, by oral intubation, is
preferred unless the chemical or physical
properties of the test substance or the pattern of exposure suggests a more appropriate
route of exposure.
24. Additional testing by other routes may
be required if the pesticide is determined to
be a prenatal developmental toxicant after
oral dosing.

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Environmental Protection Agency

§ 158.510

25. May be combined with the 2–generation
reproduction study in rodents by utilizing a
second mating of the parental animals in either generation.
26. Required to support products intended
for food uses and to support products intended for nonfood uses if use of the product
is likely to result in significant human exposure over a portion of the human life span in
terms of frequency, magnitude or duration of
exposure.
27. An information-based approach to testing is preferred, which utilizes the best available knowledge on the chemical (hazard,
pharmacokinetic, or mechanistic data) to determine whether a standard guideline study,
an enhanced guideline study, or an alternative study should be conducted to assess
potential hazard to the developing animal, or
in some cases to support a waiver for such
testing. Registrants should submit any alternative proposed testing protocols and supporting scientific rationale to the Agency
prior to study initiation.
28. Study required using a weight-of-evidence approach considering:
(i) The pesticide causes treatment-related
neurological effects in adult animal studies
(i.e.,
clinical
signs
of
neurotoxicity,
neuropathology, functional or behavioral effects).
(ii) The pesticide causes treatment-related
neurological effects in developing animals,
following pre- and postnatal exposure (i.e.,
nervous system malformations or neuropathy, brain weight changes in offspring,
functional or behavioral changes in the offspring).
(iii) The pesticide elicits a causative association between exposures and adverse neurological effects in human epidemiological
studies.
(iv) The pesticide evokes a mechanism that
is associated with adverse effects on the development of the nervous system (e.g., SAR
relationship to known neurotoxicants, altered neuroreceptor or neurotransmitter responses).
29. The use of a combined study that utilizes the 2–generation reproduction study in
rodents as a basic protocol for the addition
of other endpoints or functional assessments
in the immature animal is encouraged.
30. At a minimum, an initial battery of
mutagenicity tests with possible confirmatory testing is required. Other relevant mutagenicity tests that may have been performed, plus a complete reference list must
also be submitted.
31. Choice of assay using either:
(i) Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing
assay conditions for small colony expression
or detection;
(ii) Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells,
hypoxanthine-guanine phosphoribosyl trans-

ferase (hgprt) gene locus, accompanied by an
appropriate in vitro test for clastogenicity; or
(iii) CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene
locus.
32. The micronucleus rodent bone marrow
assay is preferred; however, rodent bone
marrow assays using metaphase analysis (aberrations) are acceptable.
33. Required when chronic or carcinogenicity studies are required. May be required if significant adverse effects are seen
in available toxicology studies and these effects can be further elucidated by metabolism studies.
34. May be required if the product’s use
will result in exposure to domestic animals
through, but not limited to, direct application.
35. A risk assessment assuming that dermal absorption is equal to oral absorption
must be performed to determine if the study
is required, and to identify the doses and duration of exposure for which dermal absorption is to be quantified.
36. A 1–year non-rodent study (i.e., 1–year
dog study) would be required if the Agency
finds that a pesticide chemical is highly bioaccumulating and is eliminated so slowly
that it does not achieve steady state or sufficient tissue concentrations to elicit an effect
during a 90–day study. EPA would require
the appropriate tier II metabolism and pharmacokinetic studies to evaluate more precisely bioavailability, half-life, and steady
state to determine if a longer duration dog
toxicity study is needed.

§ 158.510 Tiered testing
nonfood pesticides.

options

For nonfood use pesticides only, applicants have two options for generating and submitting required toxicology (§ 158.500) and human exposure
(§ 158.1020, § 158.1070, and § 158.1410) studies. Applicants are to select one of the
following:
(a) Acute, subchronic, chronic, and
other toxicological studies on the active ingredient must be submitted together. The specific makeup of the set
of toxicology study requirements is
based on the anticipated exposure to
the pesticide as determined by the
Agency. If hazards are identified based
upon review of these studies, specific
exposure data will be required to evaluate risk.
(b) Certain toxicological and exposure studies must be submitted simultaneously with the toxicology data
submitted in a tiered system. Exposure
data must be submitted along with

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§ 158.630

40 CFR Ch. I (7–1–11 Edition)

first tier toxicology data. The requirement for additional second and third
level toxicology testing will be determined by the Agency based on the results of the first tiered studies.
(1) The required first-tier toxicology
studies consist of:
(i) Battery of acute studies.
(ii) A subchronic 90–day dermal study
or a subchronic 90–day inhalation
study.
(iii) An acute and subchronic
neurotoxicity screening battery in the
rat.
(iv) Prenatal developmental toxicity
studies in both the rat and rabbit.
(v) Reproduction and fertility studies
in rats.
(vi) Battery of mutagenicity studies.
(vii) Immunotoxicity study.
(2) The conditionally required second-tier studies include:
(i) Subchronic 90–day feeding studies
in both the rodent and nonrodent.
(ii) Dermal penetration study.
(3) The conditionally required thirdtier studies include:
(i) Chronic feeding studies in the rodent.
(ii) Carcinogenicity.
(iii) Metabolism study.
(iv) Additional mutagenicity testing.

Subpart G— Ecological Effects
§ 158.630 Terrestrial and aquatic nontarget organisms data requirements
table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the terrestrial and aquatic
nontarget data requirements for a particular pesticide product. Notes that
apply to an individual test including
specific conditions, qualifications, or
exceptions to the designated test are
listed in paragraph (e) of this section.
(b) Use patterns. (1) The terrestrial
use pattern includes products classified

under the general use patterns of terrestrial food crop, terrestrial feed crop,
and terrestrial nonfood crop. The
aquatic use pattern includes products
classified under the general use patterns of aquatic food crop and aquatic
nonfood use patterns. The greenhouse
use pattern includes products classified
under the general use patterns of
greenhouse food crop and greenhouse
nonfood crop. The indoor use pattern
includes products classified under the
general use patterns of indoor food and
indoor nonfood use.
(2) Data are also required for the general use patterns of forestry and residential outdoor use.
(3) In general, for all outdoor enduses, including turf, the following studies are required: Two avian oral LD50,
two avian dietary LC50, two avian reproduction studies, two freshwater fish
LC50, one freshwater invertebrate EC50,
one honeybee acute contact LD50, one
freshwater fish early-life stage, one
freshwater invertebrate life cycle, and
three estuarine acute LC50/EC50 studies
-- fish, mollusk and invertebrate. All
other outdoor residential uses, i.e., gardens and ornamental will not usually
require the freshwater fish early-life
stage, the freshwater invertebrate lifecycle, and the acute estuarine tests.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; TGAI=Technical grade of the
active ingredient; TEP=Typical enduse product; PAI=Pure active ingredient; EP=end-use product. Commas
between the test substances (i.e., TGAI,
TEP) indicate that data may be required on the TGAI or the TEP depending on the conditions set forth in the
test note.
(d) Table. The following table shows
the data requirements for nontarget
terrestrial and aquatic organism. The
table notes are shown in paragraph (e)
of this section.

TERRESTRIAL AND AQUATIC NONTARGET ORGANISM DATA REQUIREMENTS
Use Pattern

wreier-aviles on DSK7SPTVN1PROD with CFR

Guideline Number

Data Requirement

Terrestrial

Aquatic

Forestry

Residential Outdoor

Greenhouse

Indoor

Test
substance

Test
Note No.

R

R

R

CR

CR

TGAI

1, 2, 3

Avian and Mammalian Testing
850.2100

Avian oral toxicity

R

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Environmental Protection Agency

§ 158.630

TERRESTRIAL AND AQUATIC NONTARGET ORGANISM DATA REQUIREMENTS—Continued
Use Pattern
Guideline Number

Data Requirement

Terrestrial

850.2200

Avian dietary toxicity

R

850.2400

Wild mammal
toxicity

CR

850.2300

Avian reproduction

R

850.2500

Simulated or actual field testing

CR

Aquatic

Forestry

Residential Outdoor

Greenhouse

Indoor

Test
substance

Test
Note No.

R

R

R

NR

NR

TGAI

1, 4

CR

CR

CR

NR

NR

TGAI

5

R

R

R

NR

NR

TGAI

1, 4

CR

CR

CR

NR

NR

TEP

6, 7

Aquatic Organisms Testing
850.1075

Freshwater fish
toxicity

R

R

R

R

CR

CR

TGAI,
TEP

1, 2, 8,
9, 26

850.1010

Acute toxicity
freshwater invertebrates

R

R

R

R

CR

CR

TGAI,
TEP

1, 2, 9,
10, 26

850.1025
850.1035
850.1045
850.1055
850.1075

Acute toxicity estuarine and
marine organisms

R

R

R

R

NR

NR

TGAI,
TEP

1, 9, 11,
12, 26

850.1300

Aquatic invertebrate life cycle
(freshwater)

R

R

R

R

NR

NR

TGAI

1, 10, 12

850.1350

Aquatic invertebrate life cycle
(saltwater)

CR

CR

CR

CR

NR

NR

TGAI

12, 14,
15

850.1400

Fish early-life
stage (freshwater)

R

R

R

R

NR

NR

TGAI

1, 12, 13

850.1400

Fish early-life
stage (saltwater)

CR

CR

CR

CR

NR

NR

TGAI

12, 15,
16

850.1500

Fish life cycle

CR

CR

CR

CR

NR

NR

TGAI

17, 18

850.1710
850.1730
850.1850

Aquatic organisms bioavailability, biomagnification,
toxicity

CR

CR

CR

CR

NR

NR

TGAI,
PAI,
degradate

19

850.1950

Simulated or actual field testing for aquatic
organisms

CR

CR

CR

CR

NR

NR

TEP

7, 20

850.1735

Whole sediment:
acute freshwater invertebrates

CR

CR

CR

CR

NR

NR

TGAI

21

850.1740

Whole sediment:
acute marine
invertebrates

CR

CR

CR

CR

NR

NR

TGAI

21, 23

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Sediment Testing

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§ 158.630

40 CFR Ch. I (7–1–11 Edition)

TERRESTRIAL AND AQUATIC NONTARGET ORGANISM DATA REQUIREMENTS—Continued
Use Pattern
Guideline Number

Data Requirement

Whole sediment:
chronic invertebrates freshwater and marine

Aquatic

Forestry

Residential Outdoor

Greenhouse

Indoor

Test
substance

Test
Note No.

CR

CR

CR

CR

NR

NR

TGAI

22, 23

Terrestrial

Insect Pollinator Testing
850.3020

Honeybee acute
contact toxicity

R

CR

R

R

NR

NR

TGAI

1

850.3030

Honey bee toxicity of residues on foliage

CR

CR

CR

CR

NR

NR

TEP

24

850.3040

Field testing for
pollinators

CR

CR

CR

CR

NR

NR

TEP

25

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(e) Test notes. The following test
notes apply to terrestrial and aquatic
nontarget organisms data requirements in the table to paragraph (d) of
this section:
1. Data using the TGAI are required to support all outdoor end-use product uses including, but not limited to turf. Data are generally not required to support end-use products in the form of a gas, a highly volatile
liquid, a highly reactive solid, or a highly
corrosive material.
2. For greenhouse and indoor end-use products, data using the TGAI are required to
support manufacturing-use products to be reformulated into these same end-use products
or to support end-use products when there is
no registered manufacturing-use product.
Avian acute oral data are not required for
liquid formulations for greenhouse and indoor uses. The study is not required if there
is no potential for environmental exposure.
3. Data are required on one passerine species and either one waterfowl species or one
upland game bird species for terrestrial,
aquatic, forestry, and residential outdoor
uses. Data are preferred on waterfowl or upland game bird species for indoor and greenhouse uses.
4. Data are required on waterfowl and upland game bird species.
5. Tests are required based on the results of
lower tier toxicology studies, such as the
acute and subacute testing, intended use pattern, and environmental fate characteristics
that indicate potential exposure.
6. Higher tier testing may be required for a
specific use pattern when a refined risk assessment indicates a concern based on laboratory toxicity endpoints and refined exposure assessments.

7. Environmental chemistry methods used
to generate data associated with this study
must include results of a successful confirmatory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available
as addenda to the guideline for this test requirement.
8. Data are required on one coldwater fish
and one warmwater fish for terrestrial,
aquatic, forestry, and residential outdoor
uses. For indoor and greenhouse uses, testing
with only one of either fish species is required.
9. EP or TEP testing is required for any
product which meets any of the following
conditions:
i. The end-use pesticide will be introduced
directly into an aquatic environment (e.g.,
aquatic herbicides and mosquito larvicides)
when used as directed.
ii. The maximum expected environmental
concentration (MEEC) or the estimated environmental concentration (EEC) in the aquatic environment is ≥ one-half the LC50 or EC50
of the TGAI when the EP is used as directed.
iii. An ingredient in the end-use formulation other than the active ingredient is expected to enhance the toxicity of the active
ingredient or to cause toxicity to aquatic organisms.
10. Data are required on one freshwater
aquatic invertebrate species.
11. Data are required on one estuarine/marine mollusk, one estuarine/marine invertebrate and one estuarine/marine fish species.
12. Data are generally not required for outdoor residential uses, other than turf, unless
data indicate that pesticide residues from
the proposed use(s) can potentially enter waterways.

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Environmental Protection Agency

§ 158.660

13. Data are required on one freshwater
fish species. If the test species is different
from the two species used for the freshwater
fish acute toxicity tests, a 96–hour LC50 on
that species must also be provided.
14. Data are required on one estuarine/marine invertebrate species.
15. Data are required on estuarine/marine
species if the product meets any of the following conditions:
i. Intended for direct application to the estuarine or marine environment.
ii. Expected to enter this environment in
significant concentrations because of its expected use or mobility patterns.
iii. If the acute LC50 or EC50 < 1 milligram/
liter (mg/l).
iv. If the estimated environmental concentration (EEC) in water is ≥ 0.01 of the
acute EC50 or LC50 or if any of the following
conditions exist:
A. Studies of other organisms indicate the
reproductive physiology of fish and/or invertebrates may be affected.
B. Physicochemical properties indicate
bioaccumulation of the pesticide.
C. The pesticide is persistent in water (e.g.,
half-life in water > 4 days).
16. Data are required on one estuarine/marine fish species.
17. Data are required on estuarine/marine
species if the product is intended for direct
application to the estuarine or marine environment, or the product is expected to enter
this environment in significant concentrations because of its expected use or mobility
patterns.
18. Data are required on freshwater species
if the end-use product is intended to be applied directly to water, or is expected to be
transported to water from the intended use
site, and when any of the following conditions apply:
i. If the estimated environmental concentration (EEC) is ≥ 0.1 of the no-observedeffect level in the fish early-life stage or invertebrate life cycle test;
ii. If studies of other organisms indicate
that the reproductive physiology of fish may
be affected.
19. Not required when:
i. The octanol/water partition coefficients
of the pesticide and its major degradates are
< 1,000; or
ii. There are no potential exposures to fish
and other nontarget aquatic organisms; or
iii. The hydrolytic half-life is < 5 days at
pH 5, 7 and 9.
20. Data are required based on the results
of lower tier studies such as acute and chronic aquatic organism testing, intended use
pattern, and environmental fate characteristics that indicate significant potential exposure.
21. Data are required if:
i. The half-life of the pesticide in the sediment is ≤ 10 days in either the aerobic soil or

aquatic metabolism studies and if any of the
following conditions exist:
A. The soil partition coefficient (Kd) is ≥
50.
B. The log Kow is ≥ 3.
C. The Koc ≥ 1,000.
ii. Registrants must consult with the
Agency on appropriate test protocols prior
to designing the study.
22. Data are required if:
i. The estimated environmental concentration (EEC) in sediment is > 0.1 of the acute
LC50/EC50 values and
ii. The half-life of the pesticide in the sediment is > 10 days in either the aerobic soil or
aquatic metabolism studies and if any of the
following conditions exist:
A. The soil partition coefficient (Kd) is ≥
50.
B. The log Kow is ≥ 3.
C. The Koc ≥ 1,000.
iii. Registrants must consult with the
Agency on appropriate test protocols prior
to designing the study.
23. Sediment testing with estuarine/marine
test species is required if the product is intended for direct application to the estuarine
or marine environment or the product is expected to enter this environment in concentrations which the Agency believes to be
significant, either by runoff or erosion, because of its expected use or mobility pattern.
24. Data are required only when the formulation contains one or more active ingredients having an acute LD50 of < 11 micrograms
per bee as determined in the honey bee acute
contact study and the use pattern(s) indicate(s) that honey bees may be exposed to
the pesticide.
25. Required if any of the following conditions are met:
i. Data from other sources (Experimental
Use Permit program, university research,
registrant submittals, etc.) indicate potential adverse effects on colonies, especially effects other than acute mortality (reproductive, behavioral, etc.);
ii. Data from residual toxicity studies indicate extended residual toxicity.
iii. Data derived from studies with terrestrial arthropods other than bees indicate potential chronic, reproductive or behavioral
effects.
26. The freshwater fish test species for the
TEP testing is the most sensitive of the species tested with the TGAI. Freshwater invertebrate and acute estuarine and marine organisms must also be tested with the EP or
TEP using the same species tested with the
TGAI.

§ 158.660 Nontarget plant protection
data requirements table.
(a)
General.
Sections
158.100
through158.130 describe how to use this
table to determine the nontarget plant

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§ 158.660

40 CFR Ch. I (7–1–11 Edition)

data requirements for a particular pesticide product. Notes that apply to an
individual test and include specific
conditions, qualifications, or exceptions to the designated test are listed
in paragraph (e) of this section.
(b) Use patterns. (1) The terrestrial
use pattern includes products classified
under the general use patterns of terrestrial food crop, terrestrial feed crop,
and terrestrial nonfood. The aquatic
use pattern includes only the general
use patterns of aquatic food crops and
aquatic nonfood.

(2) Data are also required for the general use patterns of forestry use and
residential outdoor use.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; TGAI=Technical grade of the
active ingredient; TEP=Typical enduse product.
(d) Table. The following table shows
the nontarget plant protection data requirements. The table notes are shown
in paragraph (e) of this section.

TABLE—NONTARGET PLANT PROTECTION DATA REQUIREMENTS
Use Pattern
Guideline Number

Aquatic

Forestry and
Residential
Outdoor

Test substance

Test Note
No.

TEP

1, 2, 7

Data Requirement
Terrestrial

Nontarget Area Phytotoxicity - Tier I
850.4100

Seedling emergence

R

R

R

850.4150

Vegetative vigor

R

R

R

TEP

1, 2, 3, 7

850.4400
850.5400

Aquatic plant growth
(algal and aquatic vascular plant toxicity)

R

R

R

TEP or
TGAI

1, 2, 7

TEP

1, 4, 5, 7

Nontarget Area Phytotoxicity - Tier II
850.4100

Seedling emergence

CR

CR

CR

850.4150

Vegetative vigor

CR

CR

CR

TEP

1, 3, 4, 5, 7

850.4400
850.5400

Aquatic plant growth
(algal and aquatic vascular plant toxicity)

CR

CR

CR

TEP or
TGAI

1, 4, 6, 7

Nontarget Area Phytotoxicity - Tier III
850.4300

Terrestrial field

CR

CR

CR

TEP

1, 7, 8, 10

850.4450

Aquatic field

CR

CR

CR

TEP

1, 7, 8, 10

Target area phytotoxicity

CR

CR

CR

TEP

1, 7, 9, 10

Target Area Phytotoxicity
850.4025

wreier-aviles on DSK7SPTVN1PROD with CFR

(e) Test notes. The following test
notes apply to the table in paragraph
(d) of this section.
1. Not required for contained pesticide
treatments
such
as
bait
boxes
and
pheromone traps unless adverse effects reports are received by the Agency.
2. Not required for known phytotoxicants.
3. Generally not required for granular formulations. May be requested on a case-bycase basis.
4. Required for known phytotoxicants such
as herbicides, desiccants and defoliants.
5. Required if a tested terrestrial species
exhibits a 25 percent or greater detrimental

effect in the Tier I study. When Tier II testing is required, the test species should be the
species that showed detrimental effects in
the Tier I testing.
6. Required if the tested aquatic species exhibits a 50 percent or greater detrimental effect in the Tier I study. When Tier II testing
is required, the test species should be the
species that showed detrimental effects in
the tier I testing.
7. Not required for aquatic residential uses.
8. Environmental chemistry methods used
to generate data must include the results of
a successful confirmatory method trial by an
independent laboratory.

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Environmental Protection Agency

§ 158.1020

9. Tests are required on a case-by-case
basis based on the results of lower tier
phytotoxicity studies, adverse incident reports, intended use pattern, and environmental fate characteristics that indicate potential exposure.
10. Registrants must consult with the
Agency on appropriate test protocols prior
to designing the study.

Subparts H–J [Reserved]
§§ 158.700–158.900

[Reserved]

Subpart K—Human Exposure

wreier-aviles on DSK7SPTVN1PROD with CFR

§ 158.1000 Applicator
exposure—general requirements.
(a) If EPA determines that industrial
standards, such as the workplace
standards set by the Occupational
Safety and Health Administration
(OSHA), provide adequate protection
from risk under FIFRA for a particular
pesticide use pattern, exposure data
may not be required for that use pattern. Applicants should consult with
the Agency on appropriate testing
prior to the initiation of studies.
(b) The Agency may accept surrogate
exposure data estimations from other
sources to satisfy applicator exposure
data requirements if the data meet the
basic quality assurance, quality control, good laboratory practice, and
other scientific requirements set by
EPA. In order to be acceptable, the
Agency must find that the surrogate
exposure data estimations have adequate information to address applicator exposure data requirements and
contain adequate replicates of acceptable quality data to reflect the specific
use prescribed on the label and the applicator activity of concern, including
formulation type, application methods
and rates, type of activity, and other
pertinent information. The Agency will
consider using such surrogate data for
evaluating human exposure on a caseby-case basis.
§ 158.1010 Applicator
exposure—criteria for testing.
Applicator exposure data described in
paragraph (d) of this section are required based on toxicity and exposure

criteria. Data are required if a product
meets, as determined by the Agency, at
least one of the toxicity criteria in
paragraph (a) of this section and either
or both of the exposure criteria in
paragraph (b) of this section.
(a) Toxicity criteria. (1) Evidence of
potentially significant adverse effects
have been observed in any applicable
toxicity study.
(2) Scientifically sound epidemiological or poisoning incident data indicate
that adverse health effects may have
resulted from handling of the pesticide.
(b) Exposure criteria. (1) Dermal exposure may occur during the prescribed
use.
(2) Respiratory exposure may occur
during the prescribed use.
§ 158.1020 Applicator exposure data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the applicator exposure data
requirements for a particular pesticide
product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to
the designated test are listed in paragraph (e) of this section.
(b) Use patterns. (1) Occupational use
patterns include products classified
under the general use patterns of terrestrial food crop, terrestrial feed crop,
terrestrial nonfood crop, aquatic food,
aquatic nonfood use, forestry, greenhouse food, greenhouse nonfood, indoor
food use, and indoor nonfood use. Occupational use patterns also include commercial (‘‘for hire’’) applications to
residential outdoor and indoor sites.
(2) Residential use patterns include
residential outdoor use and residential
indoor use. These use patterns are limited to nonoccupational, i.e., nonprofessional, pesticide applications.
(c)
Key.
R=Required;
CR=Conditionally
required;
TEP=Typical end-use product.
(d) Table. The data requirements listed pertain to pesticide products that
meet the testing criteria outlined in
§ 158.1010. The table notes are shown in
paragraph (e) of this section.

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§ 158.1050

40 CFR Ch. I (7–1–11 Edition)
TABLE—APPLICATOR EXPOSURE DATA REQUIREMENTS
Use pattern

Guideline
Number

Data requirement
Occupational
R

875.1200 ........

Dermal indoor exposure

R

R

TEP

1, 2, 4

875.1300 ........

Inhalation outdoor exposure

R

R

TEP

1, 2, 3

875.1400 ........

Inhalation indoor exposure

R

R

TEP

1, 2, 4

875.1500 ........

Biological monitoring

CR

CR

TEP

1, 2

875.1600 ........

Data reporting and calculations

R

R

TEP

5

875.1700 ........

Product use information

R

R

TEP

--

§ 158.1050 Post-application exposure—
general requirements.
(a) If EPA determines that industrial
standards, such as the workplace
standards set by the Occupational
Safety and Health Administration, provide adequate protection for a particular pesticide use pattern, post-application exposure data may not be required for that use pattern. Applicants
should consult with the Agency on appropriate testing before the initiation
of studies.
(b) The Agency may accept surrogate
exposure data from other sources to
satisfy post-application exposure data
requirements if the data meet the basic
quality assurance, quality control,
good laboratory practice, and other scientific needs of EPA. In order to be acceptable, among other things, the

TEP

Test Note No.

Dermal outdoor exposure

1. Protocols must be submitted for approval prior to the initiation of the study.
Details for developing protocols are available from the Agency.
2. Biological monitoring data may be submitted in addition to, or in lieu of, dermal
and inhalation exposure data, provided the
human pharmacokinetics of the pesticide
and/or metabolite/analog compounds (i.e.,
whichever method is selected as an indicator
of body burden or internal dose) allow for the
back calculation to actual dose.
3. Data are required if the product is applied outdoors.
4. Data are required if the product is applied indoors.
5. Data reporting and calculations are required when handler exposure data are submitted.

R

Test substance

875.1100 ........

(e) Test notes. The following notes
apply to the data requirements in the
table to paragraph (d) of this section:

wreier-aviles on DSK7SPTVN1PROD with CFR

Residential

1, 2, 3

Agency must find that the surrogate
exposure data have adequate information to address post-application exposure data requirements and contain
adequate replicates of acceptable quality data to reflect the specific use prescribed on the label and the post-application activity of concern, including
formulation type, application methods
and rates, type of activity, and other
pertinent information. The Agency will
consider using such surrogate data for
evaluating human exposure on a caseby-case basis.
§ 158.1060 Post-application exposure—
criteria for testing
Exposure
data
described
in
§ 158.1070(d) are required based upon
toxicity and exposure criteria. Data
are required if a product meets, as determined by the Agency, either or both
of the toxicity criteria in paragraph (a)
of this section and either or both of the
exposure criteria in paragraph (b) of
this section.
(a) Toxicity criteria. (1) Evidence of
potentially significant adverse health
effects have been observed in any applicable toxicity study.
(2) Scientifically sound epidemiological or poisoning incident data indicate
that adverse health effects may have
resulted from post-application exposure to the pesticide.
(b) Exposure criteria. The need for
data from potential exposure resulting
from situations not covered by this
paragraph should be discussed with the
Agency.
(1) For outdoor uses. (i) Occupational
human post-application exposure to

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Environmental Protection Agency

§ 158.1070

pesticide residues on plants or in soil
could occur as the result of cultivation,
pruning, harvesting, mowing or other
work-related activity. Such uses include agricultural food, feed, and fiber
commodities, forest trees, ornamental
plants, and turf grass.
(ii) Residential human post-application exposure to pesticide residues on
plants or in soil could occur. Such uses
may include turf grass, fruits, vegetables, and ornamentals grown at sites,
including, but not limited to, homes,
parks, and recreation areas.
(2) For indoor uses. (i) Occupational
human post-application exposure to
pesticide residues could occur following the application of the pesticide
to indoor spaces or surfaces at agricultural or commercial sites, such as, but
not limited to, agricultural animal facilities and industrial or manufacturing facilities.
(ii) Residential human post-application exposure to pesticide residues
could occur following the application
of the pesticide to indoor spaces or surfaces at residential sites, such as, but
not limited to homes, daycare centers,
hospitals, schools, and other public
buildings.

determine the post-application data requirements for a particular pesticide
product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to
the designated test are listed in paragraph (e) of this section.
(b) Use patterns. (1) Occupational use
patterns include products classified
under the general use patterns of terrestrial food crop, terrestrial feed crop,
terrestrial nonfood use, aquatic food,
aquatic nonfood use, forestry, greenhouse food, greenhouse nonfood, indoor
food, and indoor nonfood. Occupational
use patterns also include commercial
(‘‘for hire’’) applications to residential
outdoor and indoor sites.
(2) Residential use patterns include
residential outdoor use and indoor residential use. These use patterns are limited to nonoccupational, i.e., nonprofessional, pesticide applications.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; TEP=Typical end-use product.
(d) Table. The data requirements listed in the following table pertain to pesticide products that meet the testing
criteria outlined in § 158.1060. The table
notes are shown in paragraph (e) of this
section.

§ 158.1070 Post-application
exposure
data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to

wreier-aviles on DSK7SPTVN1PROD with CFR

TABLE—POST-APPLICATION EXPOSURE DATA REQUIREMENTS
Use Pattern

Guideline
Number

Data Requirement
Residential

Test Substance

Test Note No.

Occupational

875.2100 ........

Dislodgeable foliar residue and turf transferable residues

R

R

TEP

1, 2, 3, 4, 5

875.2200 ........
875.2300 ........

Soil residue dissipation

R

CR

TEP

1, 2, 6, 7

Indoor surface residue dissipation

R

R

TEP

1, 2, 8, 9

875.2400 ........

Dermal exposure

R

R

TEP

1, 2, 10, 11,
12

875.2500 ........

Inhalation exposure

R

R

TEP

1, 10, 11, 12

875.2600 ........

Biological monitoring

CR

CR

TEP

1, 12, 13

875.2700 ........

Product use information

R

R

TEP

--

875.2800 ........

Description of human activity

R

R

TEP

--

875.2900 ........

Data reporting and calculations

R

R

TEP

14

875.3000 ........

Nondietary ingestion exposure

NR

R

TEP

1, 11, 15

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§ 158.1100

40 CFR Ch. I (7–1–11 Edition)

(e) Test notes. The following test
notes apply to the data requirements
in the table to paragraph (d) of this
section:

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1. Protocols must be submitted for approval prior to the initiation of the study.
Details for developing protocols are available from the Agency.
2. Bridging applicable residue dissipation
data to dermal exposure data is required.
3. Turf grass transferable residue dissipation data are required when pesticides are
applied to turf grass. Dislodgeable foliar residue dissipation data are required when pesticides are applied to the foliage of plants
other than turf grass.
4. Data are required for occupational sites
if (i) there are uses on turf grass or other
plant foliage, and (ii) the human activity
data indicate that workers are likely to have
post-application dermal contact with treated
foliage while participating in typical activities.
5. Data are required for residential sites if
there are uses on turf grass or other plant foliage.
6. Data are required for occupational sites,
if (i) there are outdoor or greenhouse uses to
or around soil or other planting media, and
(ii) the human activity data indicate that
workers are likely to have post-application
dermal contact with treated soil or planting
media while participating in typical activities.
7. Data are required for residential sites if
the pesticide is applied to or around soil or
other planting media both outdoors and indoors, e.g., residential greenhouse or houseplant uses.
8. Data are required for occupational sites
if the pesticide is applied to or around on
non-plant
surfaces,
e.g.,
flooring
or
countertops, and if the human activity data
indicate that workers are likely to have
post-application dermal contact with treated
indoor surfaces while participating in typical activities.
9. Data are required for residential sites if
the pesticide is applied to or around nonplant surfaces, e.g., flooring and countertops.
10. Data are required for occupational sites
if the human activity data indicate that
workers are likely to have post-application
exposures while participating in typical activities.
11. Data are required for residential sites if
post-application exposures are likely.
12. Biological monitoring data may be submitted in addition to, or in lieu of, dermal
and inhalation exposure data provided the
human pharmocokinetics of the pesticide

and/or metabolite/analog compounds (i.e.,
whichever method is selected as an indicator
of body burden or internal dose) allow for a
back-calculation to the total internal dose.
13. Data are required when passive dosimetry techniques are not applicable for a particular exposure scenario, such as a swimmer
exposure to pesticides.
14. Data reporting and calculations are required when any post-application exposure
monitoring data are submitted.
15. The selection of a sampling method will
depend on the nondietary pathway(s) of interest. Data must be generated to consider
all potential pathways of nondietary ingestion exposure that are applicable (e.g., soil
ingestion, hand-to-mouth transfer, and object-to-mouth transfer of surface residues).

Subpart L—Spray Drift
§ 158.1100 Spray
ments table.

drift

data

(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the spray drift data requirements for a particular pesticide product. Notes that apply to an individual
test, including specific conditions,
qualifications, or exceptions to the designated test are listed in paragraph (e)
of this section.
(b) Use patterns. The terrestrial use
pattern includes products classified
under the general use patterns of terrestrial food crop and terrestrial
nonfood crop. The aquatic use pattern
includes products classified under the
general use patterns of aquatic food
crop and aquatic nonfood. The greenhouse use pattern includes products
classified under the general use patterns of greenhouse food crop and
greenhouse nonfood crop. Data are also
required for the general use patterns of
forestry use, residential outdoor use,
and indoor use.
(c) Key. CR=Conditionally required;
NR=Not required; TEP=Typical enduse product; MP=Manufacturing use
product; EP=End-use product.
(d) Table. The following table lists
the data requirements that pertain to
spray drift. The table notes are shown
in paragraph (e) of this section.

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Droplet size spectrum

Droplet size spectrum

202–1

Data Requirement

201–1

Guideline Number

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CR

CR

Food
Crop

CR

CR

Nonfood
Crop

Terrestrial

CR

CR

Food

CR

CR

Nonfood

Aquatic

NR

NR

Food
Crop

NR

NR

Nonfood
Crop

Greenhouse

Use Pattern

TABLE—SPRAY DRIFT DATA REQUIREMENTS

CR

CR

Forestry

NR

NR

Residential
Outdoor

NR

NR

Indoor

TEP

TEP

MP

TEP

TEP

EP

Test substance

1

1

Test Note
No.

Environmental Protection Agency

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§§ 158.1200 –158.1299

40 CFR Ch. I (7–1–11 Edition)

(e) Test notes. The following notes
apply to the requirements in the table
to paragraph (d) of this section:
1. This study is required when aerial applications (rotary and fixed winged) and mist
blower or other methods of ground application are proposed and it is estimated that
the detrimental effect level of those nontarget organisms expected to be present would
be exceeded. The nontarget organisms include humans, domestic animals, fish and
wildlife, and nontarget plants.
2. [Reserved]

Subpart M [Reserved]
§§ 158.1200 –158.1299

[Reserved]

Subpart N—Environmental Fate
§ 158.1300 Environmental fate data requirements table.
(a) General. All environmental fate
data, as described in paragraph (c) of
this section, must be submitted to support a request for registration.

(b) Use patterns. (1) The terrestrial
use pattern includes products classified
under the general use patterns of terrestrial food crop, terrestrial feed crop,
and terrestrial nonfood. The aquatic
use pattern includes the general use
patterns of aquatic food crop, and
aquatic nonfood. The greenhouse use
pattern includes both food and nonfood
uses. The indoor use pattern includes
food, nonfood, and residential indoor
uses.
(2) Data are also required for the general use patterns of forestry use and
residential outdoor use.
(c) Key. CR=Conditionally required;
NR=Not
required;
R=Required;
PAIRA=Pure active ingredient radiolabeled; TGAI=Technical grade of the
active ingredient; TEP=Typical enduse product.
(d) Table. The following table shows
the data requirements for environmental fate. The test notes are shown
in paragraph (e) of this section.

TABLE—ENVIRONMENTAL FATE DATA REQUIREMENTS
Use Pattern
Guideline Number

Data Requirement

Terrestrial

Aquatic

Greenhouse

Indoor

Forestry

Residential Outdoor

Test
substance

Test
Note No.

Degradation Studies - Laboratory
835.2120

Hydrolysis

R

R

R

CR

R

R

TGAI or
PAIRA

1

835.2240

Photodegradation
in water

R

R

NR

NR

R

NR

TGAI or
PAIRA

2

835.2410

Photodegradation
on soil

R

NR

NR

NR

R

NR

TGAI or
PAIRA

3

835.2370

Photodegradation
in air

CR

NR

CR

NR

CR

CR

TGAI or
PAIRA

4

wreier-aviles on DSK7SPTVN1PROD with CFR

Metabolism Studies - Laboratory
835.4100

Aerobic soil

R

CR

R

NR

R

R

TGAI or
PAIRA

5

835.4200

Anaerobic soil

R

NR

NR

NR

NR

NR

TGAI or
PAIRA

--

835.4300

Aerobic aquatic

R

R

NR

NR

R

NR

TGAI or
PAIRA

--

835.4400

Anaerobic aquatic

R

R

NR

NR

R

NR

TGAI or
PAIRA

--

Leaching and adsorption/
desorption

R

R

R

NR

R

R

TGAI or
PAIRA

6

Mobility Studies
835.1230
835.1240

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Environmental Protection Agency

§ 158.1300

TABLE—ENVIRONMENTAL FATE DATA REQUIREMENTS—Continued
Use Pattern
Guideline Number

Data Requirement

Terrestrial

Aquatic

Greenhouse

Indoor

Forestry

Residential Outdoor

Test
substance

Test
Note No.

835.1410

Volatility - laboratory

CR

NR

CR

NR

NR

NR

TEP

4

835.8100

Volatility - field

CR

NR

CR

NR

NR

NR

TEP

--

CR

NR

NR

CR

R

TEP

5, 7, 12

TEP

7, 8

Dissipation Studies - Field
835.6100

Terrestrial

R

835.6200

Aquatic (sediment)

CR

R

NR

NR

NR

NR

835.6300

Forestry

NR

NR

NR

NR

CR

NR

TEP

7, 9, 12

835.6400

Combination and
tank mixes

CR

CR

NR

NR

NR

NR

TEP

10

CR

NR

NR

NR

CR

CR

TEP

7, 9, 11

Ground Water Monitoring
835.7100

Ground water
monitoring

wreier-aviles on DSK7SPTVN1PROD with CFR

(e) Test notes. The following test
notes apply to the requirements in the
table to paragraph (d) of this section:
1. Study is required for indoor uses in cases
where environmental exposure is likely to
occur. Such sites include, but are not limited
to, agricultural premises, in or around farm
buildings, barnyards, and beehives.
2. Not required when the electronic absorption spectra, measured at pHs 5, 7, and 9, of
the chemical and its hydrolytic products, if
any, show no absorption or tailing between
290 and 800 nm.
3. Not required when the chemical is to be
applied only by soil injection or is incorporated in the soil.
4. Requirement based on use patterns and
other pertinent factors including, but not
limited to, the Henry’s Law Constant of the
chemical. In view of methodological difficulties with the study of photodegradation in
air, prior consultation with the Agency regarding the protocol is recommended before
the test is performed.
5. Required for aquatic food and nonfood
crop uses for aquatic sites that are intermittently dry. Such sites include, but are not
limited to, cranberry bogs and rice paddies.
6. Adsorption and desorption using a batch
equilibrium method is preferred. However in
some cases, for example, where the pesticide
degrades rapidly, soil column leaching with
unaged or aged columns may be more appropriate to fully characterize the potential mobility of the parent compound and major
transformation products.
7. Environmental chemistry methods used
to generate data associated with this study
must include results of a successful confirm-

atory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available
as addenda to the guideline for this test requirement.
8. Requirement for terrestrial uses is based
on potential for aquatic exposure and if pesticide residues have the potential for persistence, mobility, nontarget aquatic toxicity or
bioaccumulation. Not required for aquatic
residential uses. Field testing under the terrestrial field dissipation requirement may be
more appropriate for some aquatic food
crops, such as rice and cranberry uses, that
are managed to have a dry-land period for
production. The registrant is encouraged to
consult with the Agency on protocols.
9. Agency approval of a protocol is necessary prior to initiation of the study.
10. This study may be triggered if there is
specific evidence that the presence of one
pesticide can affect the dissipation characteristics of another pesticide when applied
simultaneously or serially.
11. Required if the weight-of-evidence indicates that the pesticide and/or its degradates
is likely to leach to ground water, taking
into account other factors such as the toxicity of the chemicals(s), available monitoring data, and the vulnerability of ground
water resources in the pesticide use area.
12. If the terrestrial dissipation study cannot assess all of the major routes of dissipation, the forestry study will be required.

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§ 158.1400

40 CFR Ch. I (7–1–11 Edition)

Subpart O—Residue Chemistry
§ 158.1400 Definitions.
The following terms are defined for
the purposes of this subpart:
Livestock, for the purposes of this section, includes all domestic animals
that are bred for human consumption,
including, but not limited to, cattle,
swine, sheep, and poultry.
Plant or animal metabolite means a
pesticide chemical residue that is the
result of biological breakdown of the
parent pesticide within the plant or
animal.
Residue of concern means the parent
pesticidal compound and its metabolites, degradates, and impurities of toxicological concern.
Tolerance, for the purposes of this
section, includes the establishment of a
new tolerance or tolerance exemption,
or amended tolerance or tolerance exemption.
§ 158.1410 Residue chemistry data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the residue chemistry data
requirements for a particular pesticide
product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to
the designated test are listed in paragraph (e) of this section.

(b) Use patterns. (1) Data are required
or conditionally required for all pesticides used in or on food and for residential outdoor uses where food crops
are grown. Food use patterns include
products classified under the general
use patterns of terrestrial food crop
use, terrestrial feed crop use, aquatic
food crop use, greenhouse food crop
use, and indoor food use.
(2) Data may be required for nonfood
uses if pesticide residues may occur in
food or feed as a result of the use. Data
requirements for these nonfood uses
will be determined on a case-by-case
basis. For example, most products used
in or near kitchens require residue
data for risk assessment purposes even
though tolerances may not be necessary in all cases.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; TGAI=Technical grade of the
active ingredient; PAI=Pure active ingredient; PAIRA=Pure active ingredient
radio-labeled;
Residue
of
concern= the active ingredient and its
metabolites, degradates, and impurities
of
toxicological
concern;
TEP=Typical end-use product.
(d) Table. The following table list the
data requirements for residue chemistry related to food uses. The table
notes are shown in paragraph (e) of this
section.

TABLE—RESIDUE CHEMISTRY DATA REQUIREMENTS FOR FOOD USES
Use Pattern
Guideline Number

Data Requirement

Terrestrial
Food or
Feed

Aquatic
Food

Greenhouse
Food

Indoor
Food

Residential
Outdoor

Test substance

Test
Note
No.

Chemical identity

R

R

R

R

R

TGAI

--

Supporting Information

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860.1100
860.1200

Directions for use

R

R

R

R

R

--

--

860.1550

Proposed tolerance

R

R

R

CR

NR

--

1

860.1560

Reasonable grounds in
support of petition

R

R

R

CR

NR

--

1

860.1650

Submittal of analytical reference standards

R

R

R

CR

NR

PAI and
residue
of concern

1, 2, 25

Nature of the residue in
plants

R

R

R

CR

CR

PAIRA

3, 4, 25

Nature of the residue
860.1300

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Environmental Protection Agency

§ 158.1410

TABLE—RESIDUE CHEMISTRY DATA REQUIREMENTS FOR FOOD USES—Continued
Use Pattern
Data Requirement

Terrestrial
Food or
Feed

Aquatic
Food

Greenhouse
Food

Indoor
Food

Residential
Outdoor

Test substance

Test
Note
No.

860.1300

Nature of the residue in
livestock

CR

CR

CR

CR

NR

PAIRA or
radiolabeled plant
metabolite

1, 6, 25

860.1850

Confined rotational crops

CR

CR

NR

NR

NR

PAIRA

7

860.1340

Residue analytical methods

R

R

R

CR

CR

Residue
of concern

1, 3, 8,
9, 10,
25

860.1360

Multiresidue method

R

R

R

CR

NR

Residue
of concern

1, 11,
25

860.1380

Storage stability

R

R

R

CR

CR

TEP or
residue
of concern

1, 3,
10, 12,
25

860.1500

Crop field trials

R

R

R

CR

CR

TEP

3, 10,
14, 24,
25

860.1520

Processed food or feed

CR

CR

CR

CR

NR

TEP

1, 15,
25

860.1480

Meat/milk/poultry/eggs

CR

CR

CR

CR

NR

TGAI or
plant metabolite

1, 16,
17, 18,
25

860.1400

Potable water

NR

R

NR

NR

NR

TEP

19, 25

860.1400

Fish

NR

R

NR

NR

NR

TEP

5, 25

860.1400

Irrigated crops

NR

CR

NR

NR

NR

TEP

20, 25

860.1460

Food handling

NR

NR

NR

CR

NR

TEP

1, 21,
25

860.1540

Anticipated residues

CR

CR

CR

CR

NR

Residue
of concern

1, 13,
22, 26

860.1900

Field rotational crops

CR

CR

NR

NR

NR

TEP

23, 25

Guideline Number

Analytical methods

Magnitude of the residue

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(e) Test notes. The following test
notes apply to the data requirements
in the table to paragraph (d) of this
section.
1. Required if indoor use could result in
pesticide residues in or on food or feed.
2. Material safety data sheets must accompany standards as specified by OSHA in 29
CFR 1910.1200.
3. Required for residential outdoor uses on
food crops if the corresponding agricultural
use is not approved or the residential use is

expected to produce higher residues based on
the label directions.
4. Required for indoor uses where the pesticide is applied directly to food, in order to
determine metabolites and/or degradates.
Not required when only indirect contact
with food would occur (e.g., crack and crevice treatments).
5. Data for fish are required for all pesticides applied directly to water inhabited,
or which will be inhabited, by fish that may
be caught or harvested for human consumption.

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wreier-aviles on DSK7SPTVN1PROD with CFR

§§ 158.1500–158.1900

40 CFR Ch. I (7–1–11 Edition)

6. Required when a pesticide is to be applied directly to livestock, to livestock
premises, to livestock drinking water, or to
crops used for livestock feed. If results from
the plant metabolism study show differing
metabolites in plants from those found in
animals, an additional livestock metabolism
study involving dosing with the plant metabolite(s) may also be required.
7. Required when the Agency determines
that it is reasonably foreseeable that a food
or feed crop could be subsequently planted
on the site of pesticide application after harvest or failure of the treated crop. Typically
not required for pesticide uses in permanent
food crops (e.g., various tree crops, vines) or
semi-permanent crops (e.g., asparagus, pineapples).
8. A residue analytical method suitable for
enforcement purposes is required whenever a
numeric tolerance (including temporary and
time-limited tolerances) is proposed.
9. New analytical methods to be used for
enforcement purposes must include results
from an independent laboratory validation.
10. A residue method, storage stability
data, and crop field trials are required for
the nonfood crop tobacco (green, freshly harvested). Depending on the level of residues
found on the green tobacco, additional data
may be required on cured/dried tobacco and
pyrolysis products.
11. Data are required to determine whether
FDA/USDA multiresidue methodology would
detect and identify the pesticides and any
metabolites.
12. Data are required for any magnitude of
the residue study unless analytical samples
are stored frozen for 30 days or less, and the
active ingredient is not known to be volatile
or labile.
13. Studies using single serving samples of
a raw agricultural commodity may be needed for acutely toxic pesticides and/or their
metabolites. These residue studies must be
conducted using a statistical design accepted
by the Agency.
14. Required for indoor uses which are direct postharvest treatments of raw agricultural commodities (e.g., fungicidal waxes or
stored grain fumigants).
15. Data on the nature and level of residues
in processed food/feed are required if residues
could potentially concentrate on processing
thus requiring the establishment of a separate tolerance higher than that of the raw
agricultural commodity.
16. Required when the pesticide use is a direct application to livestock.
17. Data are required if pesticide residues
are present in or on livestock feed items or
intentionally added to drinking water. These
studies, however, may not be required in
cases where the livestock metabolism studies indicate negligible transfer of the pesticide’s residues of concern to tissues, milk,

and eggs at the maximum expected exposure
level for the animals.
18. If results from the plant metabolism
study show differing metabolites in plants
from those found in animals, an additional
livestock feeding study involving dosing
with the plant metabolite(s) may also be required.
19. Data are required whenever a pesticide
may be applied directly to water, unless it
can be demonstrated that the treated water
would not be available for human or livestock consumption.
20. Data are required when a pesticide is to
be applied directly to water that could be
used for irrigation or to irrigation facilities
such as irrigation ditches.
21. Data are required whenever a pesticide
may be used in a food handling or feed handling establishment.
22. Required when residues at the tolerance
level may result in a risk of concern. These
data may include washing, cooking, processing or degradation studies as well as market basket surveys for a more precise residue
determination.
23. Typically required if pesticide residues
of concern greater than 0.01 ppm are found in
crops at the appropriate plant back intervals
(taking into account plant back restrictions
on product labels) in the confined rotational
crop study. If residues of concern in the confined study are greater than 0.01 ppm but less
than the limit of quantitation of the analytical method to be used on field trial samples,
the Agency will consider not requiring, on a
case-by-case basis, the limited field trials. If
there are particular toxicological concerns
with the parent pesticide or any metabolites,
limited field studies may be needed if such
residues are identified at levels below 0.01
ppm in the confined study.
24. Crop field trials are required to establish tolerances on rotational crops when
quantifiable residues of concern are observed
in the field rotational crops study.
25. Not required for an exemption from a
tolerance provided that dietary exposure estimates are not needed due to low toxicity or
that theoretical estimates of exposure are
adequate to assess dietary risk.
26. Not required for an exemption from a
tolerance.

Subparts P–T [Reserved]
§§ 158.1500–158.1900

[Reserved]

Subpart U—Biochemical
Pesticides
SOURCE: 72 FR 61002, Oct. 26, 2007, unless
otherwise noted.

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Environmental Protection Agency

§ 158.2010

§ 158.2000 Biochemical pesticides definition and applicability.
This subpart applies to all biochemical pesticides as defined in paragraphs (a), (b), and (c) of this section.
(a) Definitions. The following terms
are defined for the purposes of subpart
U of this part.
(1) A biochemical pesticide is a pesticide that:
(i) Is a naturally-occurring substance
or structurally-similar and functionally identical to a naturally-occurring
substance;
(ii) Has a history of exposure to humans and the environment demonstrating minimal toxicity, or in the
case of a synthetically-derived biochemical pesticides, is equivalent to a
naturally-occurring substance that has
such a history; and
(iii) Has a non-toxic mode of action
to the target pest(s).
(2) A Pheromone is a compound produced by a living organism or is a synthetically derived substance that is
structurally similar and functionally
identical to a naturally-occurring
pheromone, which, alone or in combination with other such compounds,
modifies the behavior of other individuals of the same species.
(i) An Arthropod Pheromone is a
pheromone produced by a member of
the taxonomic phylum Arthropoda.
(ii) A Lepidopteran Pheromone is an
arthropod pheromone produced by a
member of the insect order Lepidoptera.
(iii) A Straight Chain Lepidopteran
Pheromone is a lepidopteran pheromone
consisting of an unbranched aliphatic
chain (between 9 and 18 carbons) ending
in an alcohol, aldehyde, or acetate
functional group and containing up to
three double bonds in the aliphatic
backbone.
(b) Examples. Biochemical pesticides
include, but are not limited to:
(1)
Semiochemicals
(insect
pheromones and kairomones),
(2) Natural plant and insect regulators,
(3) Naturally-occurring repellents
and attractants, and
(4) Enzymes.
(c) Applicability. The Agency may review, on a case-by-case basis, naturally-occurring pesticides that do not

clearly meet the definition of a biochemical pesticide in an effort to ensure, to the greatest extent possible,
that only the minimum testing sufficient to make scientifically sound regulatory decisions would be conducted.
The Agency will review applications
for registration of naturally-occurring
pesticides to determine whether to review the pesticide under this subpart
U.
§ 158.2010 Biochemical pesticides data
requirements.
(a) Sections 158.2030 through 158.2070
identify the data requirements that are
required to support registration of biochemical pesticides. Sections 158.2080
through 158.2084 identify the data requirements that are required to support Experimental Use Permits (EUPs).
Variations in the test conditions are
identified within the test notes. Definitions that apply to all biochemical
data requirements can be found in
§ 158.2000.
(b) Each data table includes ‘‘use patterns’’ under which the individual data
are required, with variations including
food and nonfood uses for terrestrial
and aquatic applications, greenhouse,
indoor, forestry, and residential outdoor applications under certain circumstances.
(c) The categories for each data requirement are ‘‘R’’, which stands for
required, and ‘‘CR’’ which stands for
conditionally required. Generally, ‘‘R’’
indicates that the data are more likely
required than for those data requirements with ‘‘CR.’’ However, in each
case, the regulatory text preceding the
data table and the test notes following
the data table must be used to determine whether the data requirement
must be satisfied.
(d) Each table identifies the test substance that is required to be tested to
satisfy the data requirement. Test substances may include: technical grade
active ingredient (TGAI), manufacturing-use product (MP), end-use product (EP), typical end-use product
(TEP), residue of concern, and pure active ingredient (PAI) or all of the above
(All). Commas between the test substances (i.e., TGAI, EP) indicate that
data may be required on the TGAI or

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§ 158.2030

40 CFR Ch. I (7–1–11 Edition)

EP or both depending on the conditions
set forth in the test note.
(e) The data requirements are organized into a tier-testing system with
specified additional studies at higher
tiers being required if warranted by adverse effects observed in lower tier
studies. The lower tier studies are a
subset of those required for conventional pesticides, and the studies overall are generally selected from those
required for conventional pesticides.
(f) Two sets of guideline numbers are
provided for some of the environmental
fate data requirements. For ease of understanding, the current guidelines will
be used as an interim measure until
the new guidelines (in parentheses) are
finalized.
§ 158.2030 Biochemical
product chemistry
ments table.

data

pesticides
require-

(a) General. (1) Sections 158.100
through 158.130 describe how to use this
table to determine the product chem-

istry data requirements for a particular pesticide product. Notes that
apply to an individual test and include
specific conditions, qualifications, or
exceptions to the designated test are
listed in paragraph (e) of the section.
(2) Definitions in § 158.300 apply to
data requirements in this section.
(b) Use patterns. Product chemistry
data are required for all pesticide products and are not use specific.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; Residue
of concern=the active ingredient and
its metabolites, degradates, and impurities of toxicological concern; All=All
of the above.
(d) Table. The following table shows
the data requirements for biochemical
pesticides product chemistry. The test
notes are shown in paragraph (e) of this
section.

TABLE—BIOCHEMICAL PESTICIDES PRODUCT CHEMISTRY DATA REQUIREMENTS
Guideline Number

All Use
Patterns

Data Requirement

Test Substance
Test Notes
MP

EP

Product Identity and Composition
880.1100 ....................

Product identity and composition

R

TGAI,
MP

TGAI,
EP

1, 2

880.1200 ....................

Description of starting materials, production and formulation process

R

TGAI,
MP

TGAI,
EP

2, 3

880.1400 ....................

Discussion of formation of impurities

R

TGAI
and MP

TGAI
and EP

4

CR

TGAI
and MP

TGAI
and EP

5, 8

Analysis and Certified Limits
830.1700 ....................

Preliminary analysis

830.1750 ....................

Certified limits

R

MP

EP

6

830.1800 ....................

Enforcement analytical method

R

MP

EP

7

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Physical and Chemical Characteristics
830.6302 ....................

Color

R

TGAI

TGAI

8

830.6303 ....................

Physical state

R

TGAI
and MP

TGAI
and EP

8

830.6304 ....................

Odor

R

TGAI

TGAI

8

830.6313 ....................

Stability to normal and elevated temperatures, metals and metal ions

R

TGAI

TGAI

8, 17

830.6315 ....................

Flammability

CR

MP

EP

9

830.6317 ....................

Storage stability

R

MP

EP

--

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Environmental Protection Agency

§ 158.2040

TABLE—BIOCHEMICAL PESTICIDES PRODUCT CHEMISTRY DATA REQUIREMENTS—Continued
Guideline Number

All Use
Patterns

Data Requirement

CR

Test Notes
MP

EP

MP

EP

830.6319 ....................

Miscibility

830.6320 ....................

Corrosion characteristics

830.7000 ....................

pH

830.7050 ....................

UV/Visible light absorption

830.7100 ....................

Viscosity

CR

MP

EP

12

830.7200 ....................

Melting point/melting range

CR

TGAI

TGAI

8, 13

830.7220 ....................

Boiling point/boiling range

CR

TGAI

TGAI

8, 14

830.7300 ....................

Density/relative density/bulk density

R

TGAI
and MP

TGAI
and EP

8, 18

830.7520 ....................

Particle size, fiber length, and diameter distribution

CR

TGAI

TGAI

8, 15

830.7550 ....................
830.7560
830.7570

Partition coefficient (n-Octanol /Water)

CR

TGAI

TGAI

16

830.7840 ....................

Water solubility

R

TGAI

TGAI

8

830.7950 ....................

Vapor pressure

R

TGAI

TGAI

8, 19

(e) Test notes. The following test
notes are applicable to the data requirements for biochemical pesticides
product chemistry and are referenced
in the last column of the table in paragraph (d) of this section.

wreier-aviles on DSK7SPTVN1PROD with CFR

Test Substance

1. Data must be provided in accordance
with § 158.320.
2. If the MP and EP are produced by an integrated formulation system (non-registered
source), these data are also required on
TGAI.
3. Data must be provided in accordance
with §§ 158.325, 158.330, and § 158.335.
4. Data must be provided in accordance
with § 158.340.
5. Data must be provided in accordance
with § 158.345. Also, required to support the
registration of each manufacturing-use product (including registered TGAIs) and end-use
products produced by an integrated formulation system. Data on other end-use products
would be required on a case-by-case basis.
6. Data must be provided in accordance
with § 158.350.
7. Data must be provided in accordance
with § 158.355.
8. If the TGAI cannot be isolated, data are
required on the practical equivalent of the
TGAI. EP testing may also be appropriate.
9. Required if the product contains combustible liquids.
10. Required if the product is an emulsifiable liquid and is to be diluted with petroleum solvents.

R

MP

EP

--

CR

TGAI
and MP

TGAI
and EP

8, 11

R

TGAI

TGAI

--

11. Required if the test substance is soluble
or dispersible in water.
12. Required if the product is a liquid.
13. Required when the technical chemical
is a solid at room temperature.
14. Required when the technical chemical
is a liquid at room temperature.
15. Required for water insoluble test substances (>10-6g/l) and fibrous test substances
with diameter ≥0.1 μm.
16. Required for organic chemicals unless
they dissociate in water or are partially or
completely soluble in water.
17. Data on the stability to metals and
metal ions is required only if the active ingredient is expected to come in contact with
either material during storage.
18. True density or specific density are required for all test substances. Data on bulk
density is required for MPs or EPs that are
solid at room temperature.
19. Not required for salts.

§ 158.2040 Biochemical pesticides residue data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the biochemical pesticides
residue data requirements for a particular pesticide product and the substance that needs to be tested. These
data requirements apply to all biochemical pesticides, i.e., naturally occurring
insect
repellents
and

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§ 158.2040

40 CFR Ch. I (7–1–11 Edition)

attractants, semiochemicals (e.g., insect pheromones), natural and plant
growth regulators. Notes that apply to
an individual test and include specific
conditions, qualifications, or exceptions to the designated test are listed
in paragraph (e) of this section.
(b) Use patterns. (1) Data are required
or conditionally required for all pesticides used in or on food and for residential outdoor uses where food crops
are grown. Food use patterns include
products classified under the general
use patterns of terrestrial food crop
use, terrestrial feed crop use, aquatic
food crop use, greenhouse food crop
use, and indoor food use. Data are also
conditionally required for aquatic
nonfood use if there is direct application to water that could subsequently
result in exposure to food.
(2) Data are conditionally required
for nonfood uses if pesticide residues
may occur in food or feed as a result of
the use. Data requirements for these
nonfood uses would be determined on a

case-by-case basis. For example, most
products used in or near kitchens require residue data for risk assessment
purposes even though tolerances may
not be necessary in all cases.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required;
MP=Manufacturing
end-use
product;
EP=End-use
product;
TEP=Typical
end-use
product;
TGAI=Technical grade of the active ingredient; Residue of concern=the active
ingredient
and
its
metabolites,
degradates, and impurities of toxicological concern; All=All of the above.
Specific conditions, qualifications, or
exceptions to the designated test procedures appear in paragraph (e) of this
section, and apply to the individual
tests in the following table:
(d) Data requirements table. The following table shows the data requirements for biochemical pesticides residue. The test notes are shown in paragraph (e) of this section.

TABLE—BIOCHEMICAL RESIDUE DATA REQUIREMENTS FOR SPECIFIC USES
Use Patterns
Guideline
Number

Data Requirement

Terrestrial

Aquatic

Food/
Feed

Food

Greenhouse
Food

Indoor
Food

Test Substance

Test
Notes

Supporting Information
860.1100

Chemical identity

CR

CR

CR

CR

TGAI

1, 2, 4

860.1200

Directions for use

CR

CR

CR

CR

--

1, 3, 4

Nature of the Residue
860.1300

Nature of the residue in plants

CR

CR

CR

CR

TGAI

1, 4, 5, 6

860.1300

Nature of the residue in livestock

CR

CR

CR

CR

TGAI or
plant metabolite

1, 7, 8,
10, 13

860.1340

Residue analytical method

CR

CR

R

CR

Residue of
concern

4, 9, 10

860.1360

Multiresidue method

CR

CR

R

CR

Residue of
concern

10, 11

NR

CR

NR

NR

TGAI

1, 12

Magnitude of the Residue

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860.1400

Potable water

860.1400

Fish

NR

CR

NR

NR

TGAI

1, 13

860.1400

Irrigated crops

NR

CR

NR

NR

TGAI

1, 14

860.1460

Food handling

NR

NR

NR

CR

TGAI

1, 15

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Environmental Protection Agency

§ 158.2040

TABLE—BIOCHEMICAL RESIDUE DATA REQUIREMENTS FOR SPECIFIC USES—Continued
Use Patterns
Guideline
Number

Data Requirement

Terrestrial

Aquatic

Food/
Feed

Food

Indoor
Food

Test Substance

Test
Notes

860.1480

Meat/milk/poultry/eggs

CR

CR

CR

CR

TGAI or
plant metabolites

1, 7, 8, 10

860.1500

Crop field trials

CR

CR

CR

CR

TEP

1, 3, 4

860.1520

Processed food/feed

CR

CR

CR

CR

TEP

1, 16

860.1540

Anticipated residues

CR

CR

CR

CR

Residue of
concern

1, 10, 17

860.1550

Proposed tolerances

CR

CR

CR

CR

--

1, 18

860.1560

Reasonable grounds in support of the
petition

CR

CR

CR

CR

--

1, 10

860.1650

Submittal of
standards

CR

CR

CR

CR

TGAI and
residue of
concern

10, 19

analytical

reference

(e) Test notes. The following test
notes are applicable to the data requirements for biochemical pesticides
product chemistry and are in the last
column of the table contained in paragraph (d) of this section.

wreier-aviles on DSK7SPTVN1PROD with CFR

Greenhouse
Food

1. Residue chemistry data requirements
apply to biochemical pesticide products
when Tier II or Tier III toxicology data are
required, as specified for biochemical agents
in the biochemical human health assessment
data requirements, § 158.2050.
2. The same chemical identity data are required for biochemical product chemistry
data requirements, § 158.2030, with an emphasis on impurities.
3. Required information includes crops to
be treated, rate of application, number and
timing of applications, preharvest intervals,
and relevant restrictions.
4. Required for residential outdoor uses on
food crops if the corresponding agricultural
use is not approved or the residential use is
expected to produce higher residues based on
the label directions.
5. Required unless it is an arthropod
pheromone applied at a rate less than or
equal to 150 grams active ingredient per acre.
6. Required for indoor uses where the pesticide is applied directly to food, in order to
determine metabolites and/or degradates.
Not required when only indirect contact
with food would occur (e.g., crack and crevice treatments).
7. Required when a pesticide is to be applied directly to livestock, to livestock
premises, to livestock drinking water, or to
crops used for livestock feed.

8. If results from the plant metabolism
study show differing metabolites in plants
from those found in animals, an additional
livestock metabolism study involving dosing
with the plant metabolite(s) may also be required.
9. A residue analytical method suitable for
enforcement of tolerances is required whenever a numeric tolerance (including temporary and time-limited tolerances) is proposed.
10. Required if indoor use could result in
pesticide residues in or on food or feed.
11. Data are required to determine whether
FDA/USDA multiresidue methodology would
detect and identify the pesticides and any
metabolites.
12. Data are required whenever a pesticide
may be applied directly to water, unless it
can be demonstrated that the treated water
would not be available for human or livestock consumption.
13. Data on fish are required for all pesticides applied directly to water inhabited,
or which will be inhabited by fish that may
be caught or harvested for human consumption.
14. Data are required when a pesticide is to
be applied directly to water that could be
used for irrigation or to irrigation facilities
such as irrigation ditches.
15. Data are required whenever a pesticide
may be used in food/feed handling establishments.
16. Data on the nature and level of residue
in processed food/feed are required when
detectible residues could potentially concentrate on processing thus requiring the establishment of a separate tolerance higher

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§ 158.2050

40 CFR Ch. I (7–1–11 Edition)

than that of the raw agricultural commodity.
17. Required when residues at the tolerance
level may result in risk of concern. These
data may include washing, cooking, processing, or degradation studies as well as market basket surveys for a more precise residue
determination.
18. The proposed tolerance must reflect the
maximum residue likely to occur in crops, in
meat, milk, poultry, or eggs.
19. Required when a residue analytical
method is required.

§ 158.2050 Biochemical
pesticides
human health assessment data requirements table.
(a) General. (1) Sections 158.100
through 158.130 describe how to use this
table to determine the biochemical
human health assessment data requirements for a particular biochemical pesticide product.
(2) The data in this section are not
required
for
straight
chain
lepidopteran pheromones when applied
up to a maximum use rate of 150 grams
active ingredient/acre/year.
(b) Use patterns. (1) Food use patterns, in general, include products classified under the following general uses:
terrestrial food crop use; terrestrial
feed crop use; aquatic food crop use;
greenhouse food crop use.

(2) Nonfood use patterns include
products classified under the general
use patterns of terrestrial nonfood crop
use; aquatic nonfood residential use;
aquatic nonfood outdoor use; aquatic
nonfood industrial use; greenhouse
nonfood crop use; forestry use; residential outdoor use; residential indoor use;
indoor food use; indoor nonfood use; indoor medical use.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; Residue
of concern=the active ingredient and
its metabolites, degradates, and impurities of toxicological concern; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to
the individual tests in the following
table:
(d) Table. The following table shows
the data requirements for biochemical
pesticides human health assessment.
The test notes are shown in paragraph
(e) of this section.

TABLE—BIOCHEMICAL PESTICIDES HUMAN HEALTH ASSESSMENT DATA REQUIREMENTS
Use Patterns

Guideline Number

Test Substance

Data Requirement

Test Notes
Food

Nonfood

MP

EP

Tier I

wreier-aviles on DSK7SPTVN1PROD with CFR

Acute Testing
870.1100 ...........

Acute oral toxicity - rat

R

R

TGAI
and MP

TGAI and
EP

1

870.1200 ...........

Acute dermal toxicity

R

R

TGAI
and MP

TGAI and
EP

1, 2

870.1300 ...........

Acute inhalation toxicity - rat

R

R

TGAI
and MP

TGAI and
EP

3

870.2400 ...........

Primary eye irritation - rabbit

R

R

TGAI
and MP

TGAI and
EP

2

870.2500 ...........

Primary dermal irritation

R

R

TGAI
and MP

TGAI and
EP

1, 2

870.2600 ...........

Dermal sensitization

R

R

TGAI
and MP

TGAI and
EP

2, 4

none ..................

Hypersensitivity incidents

R

R

All

All

5

R

CR

TGAI

TGAI

6

Subchronic Testing
870.3100 ...........

90-day oral (one species)

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Environmental Protection Agency

§ 158.2050

TABLE—BIOCHEMICAL PESTICIDES HUMAN HEALTH ASSESSMENT DATA REQUIREMENTS—Continued
Use Patterns

Guideline Number

Test Substance

Data Requirement

Test Notes
Food

Nonfood

MP

EP

870.3250 ...........

90-day dermal - rat

CR

CR

TGAI

TGAI

7

870.3465 ...........

90-day inhalation - rat

CR

CR

TGAI

TGAI

8

R

CR

TGAI

TGAI

9

Developmental Toxicity
870.3700 ...........

Prenatal developmental - rat preferably

Mutagenicity Testing
870.5100 ...........

Bacterial reverse mutation test

R

CR

TGAI

TGAI

10

870.5300 ...........
870.5375

In vitro mammalian cell assay

R

CR

TGAI

TGAI

10, 11

CR

CR

TGAI

TGAI

13

Prenatal developmental

CR

CR

TGAI

TGAI

9

Immunotoxicity

CR

CR

TGAI

TGAI

12, 13

15

Tier II
Mutagenicity Testing (In vivo cytogenetics)
870.5385 ...........
870.5895

In vivo Mammalian Cytogenetics

Developmental Toxicity
870.3700 ...........
Special Tests
880.3550 ...........

Applicator/User Exposure
875.1100 ...........

Dermal outdoor exposure

CR

CR

TGAI

TGAI

875.1200 ...........

Dermal indoor exposure

CR

CR

TGAI

TGAI

15

875.1300 ...........

Inhalation outdoor exposure

CR

CR

TGAI

TGAI

15

875.1400 ...........

Inhalation indoor exposure

CR

CR

TGAI

TGAI

15

875.1500 ...........

Biological monitoring

CR

CR

TGAI

TGAI

15

Tier III
Chronic Testing/Special Testing
880.3800 ...........

Immune response

CR

CR

TGAI

TGAI

14

870.3800 ...........

Reproduction and fertility effects

CR

CR

TGAI

TGAI

16

870.4100 ...........

Chronic oral - rodent and nonrodent

CR

CR

TGAI

TGAI

17

870.4200 ...........

Carcinogenicity - two species - rat and
mouse preferred

CR

CR

TGAI

TGAI

18

870.5380 ...........

Mammalian spermatogonial chromosome
aberration test

CR

CR

TGAI

TGAI

19

Companion animal safety

CR

CR

NR

TGAI or EP

20

Special Testing

wreier-aviles on DSK7SPTVN1PROD with CFR

870.7200 ...........

(e) Test notes. The following test
notes are applicable to the data requirements for biochemical pesticides
human health assessment as referenced

in the last column of the table in paragraph (d) of this section.
1. Required unless the test material is a
gas or highly volatile (vapor pressure
>10-4torr (mm/Hg)).

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§ 158.2050

40 CFR Ch. I (7–1–11 Edition)

2. Required unless the test material is corrosive to skin or has pH <2 or >11.5.
3. Required when the pesticide, under conditions of use, would result in respirable material (e.g., gas, volatile substance or aerosol/particulate), unless it is a straight chain
lepidopteran pheromone.
4. Required if repeated contact with human
skin is likely to occur under conditions of
use.
5. Hypersensitivity incidents must be reported as adverse effects data.
6. Required for non-food uses that are likely to result in repeated oral exposure to humans.
7. Required to support uses involving purposeful application to the human skin or
which would result in comparable prolonged
human exposure to the product (e.g., insect
repellents) and if any of the following criteria are met:
i. Data from a 90–day oral study are not required.
ii. The active ingredient is known or expected to be metabolized differently by the
dermal route of exposure than by the oral
route and the metabolite is of toxicological
concern.
iii. The use pattern is such that the dermal
route would be the primary route of exposure.
8. Required if there is a likelihood of significant levels of repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol.
9. Required if the use of the product under
widespread and commonly recognized practice may reasonably be expected to result in
significant exposure to female humans (e.g.,
occupational exposure or repeated application of insect repellents directly to the skin).
Tier II data is required on a different test
species from Tier I data when developmental
effects are observed in the first study and information on species-to-species extrapolation is needed.
10. Required to support nonfood uses if either:
i. The use is likely to result in significant
human exposure; or
ii. The active ingredient (or its metabolites) is structurally related to a known
mutagen or belongs to any chemical class of
compounds containing a known mutagen.
Additional mutagenicity tests that may
have been performed plus a complete reference list must also be submitted. Subsequent testing may be required based on the
available evidence.
11. Choice of assay using either:
i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing
assay conditions for small colony expression
or detection;
ii. Chinese hamster ovary (CHO) or Chinese
hamster
lung
fibroblast
(V79)
cells,
hypoxanthine-guanine phosphoribosyl trans-

ferase (hgprt) gene locus, accompanied by an
appropriate in vitro test for clastogenicity; or
iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene
locus.
12. Required if there are effects on hematology, clinical chemistry, lymphoid organ
weights, and histopathology are observed in
the 90–day studies.
13. The micronucleus rodent bone marrow
assay is preferred; however, rodent bone
marrow assays using metaphase analysis (aberrations) are acceptable.
14. Required if adverse effects are observed
in the Tier II immunotoxicity study. The
protocol for evaluating adverse effects to the
immune response should be developed after
evaluating the effects noted in the
immunotoxicity study.
15. These data are required when the data
used for the human health assessment indicates that the biochemical may pose a potential hazard to the applicator/user.
16. Required if there is evidence of:
i. Endocrinological effects from the subchronic toxicity studies.
ii. Developmental effects in the prenatal
developmental toxicity study(s), or
iii. Genotoxicity to mammals based on results from the mutagenicity tests.
The use of a combined study that utilizes the
two-generation reproduction study in rodents (guideline 870.3800) as a basic protocol
for the addition of other endpoints or functional assessments in the immature animal
is encouraged.
17. Required if the potential for adverse
chronic effects is indicated based on any of
the following:
i. The subchronic effect level established in
the following Tier I studies: 90–day oral toxicity study, 90–day dermal toxicity study, or
90–day inhalation toxicity study.
ii. The pesticide use pattern (e.g., rate, frequency, and site of application).
iii. The frequency and level of repeated
human exposure that is expected.
18. Required if the product meets either of
the following criteria:
i. The active ingredient (or any of its metabolites, degradation products, or impurities) produce(s) in Tier I subchronic studies a
morphologic effect (e.g., hyperplasia or
metaplasia) in any organ that potentially
could lead to neoplastic change.
ii. Adverse cellular effects suggesting carcinogenic potential are observed in Tier II
immunotoxicity and Tier III immune response study or in Tier II mammalian mutagenicity assays.
In addition, a 90–day range finding study in
both rats and mice is required to determine
the dose levels if carcinogenicity studies are
required. If the mouse carcinogenicity study
is not required, the 90–day mouse subchronic
study is likewise not required.

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Environmental Protection Agency

§ 158.2060

19. Required if results from lower tiered
mutation or reproductive studies indicate
there is potential for chromosomal aberration to occur.
20. May be required if the product’s use
will result in exposure to domestic animals
through, but not limited to, direct application or consumption of treated feed.

(b) Use patterns. The terrestrial use
pattern includes products classified
under the general use patterns of terrestrial food crop, terrestrial feed crop,
and terrestrial nonfood/nonfeed crop.
The greenhouse use pattern includes
products classified under the general
use patterns of greenhouse food crop
and greenhouse nonfood crop. The indoor use pattern includes products
classified under the general use patterns of indoor food and nonfood use.
The remaining terrestrial uses include:
forestry and residential outdoor use.
Data are also required for the general
use patterns of aquatic food and
nonfood crop use.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; Residue
of concern=the active ingredient and
its metabolites, degradates, and impurities of toxicological concern; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to
the individual tests in the following
table:
(d) Table. The following table shows
the data requirements for biochemical
pesticides nontarget organisms and environmental fate. The test notes are
shown in paragraph (e) of this section.

§ 158.2060 Biochemical pesticides nontarget organisms and environmental fate data requirements
table.
(a) General. (1) Sections 158.100
through 158.130 describe how to use this
table to determine the terrestrial and
aquatic nontarget organisms and fate
data requirements for a particular biochemical pesticide product. Notes that
apply to an individual test including
specific conditions, qualifications, or
exceptions to the designated test are
listed in paragraph (e) of this section.
In general, for all outdoor end-use
products including turf, the following
studies are required: one avian acute
oral, one avian dietary, one acute
freshwater fish, one acute freshwater
invertebrate study, plant toxicity testing, and a honeybee acute contact
study.
(2) The data in this section are not
required for arthropod pheromones
when applied at up to a maximum use
rate of 150 grams active ingredient/
acre/year except when the product is
expected to be available to avian species (i.e., granular formulation).

TABLE—BIOCHEMICAL PESTICIDES NONTARGET ORGANISMS AND ENVIRONMENTAL FATE DATA
REQUIREMENTS
Use Patterns
Guideline Number

Data Requirement

Terrestrial

Aquatic

Greenhouse
Food/
Nonfood

Forestry,
Residential
Outdoor

Food/
Feed/
Nonfood

Food/
Nonfood

Food/
Nonfood

Indoor

Test
Substance

Test Notes

Tier I

wreier-aviles on DSK7SPTVN1PROD with CFR

Avian Testing
850.2100 .........

Avian acute oral toxicity

R

R

CR

R

CR

TGAI,
EP

1, 2, 3, 4

850.2200 .........

Avian dietary toxicity

R

R

CR

R

CR

TGAI,
EP

1, 2, 3, 4

R

R

CR

R

CR

TGAI,
EP

2, 3, 4, 5

Aquatic Organism Testing
850.1075 .........

Fish acute toxicity, freshwater

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§ 158.2060

40 CFR Ch. I (7–1–11 Edition)

TABLE—BIOCHEMICAL PESTICIDES NONTARGET ORGANISMS AND ENVIRONMENTAL FATE DATA
REQUIREMENTS—Continued
Use Patterns
Guideline Number

850.1010 .........

Data Requirement

Terrestrial

Aquatic

Greenhouse

Food/
Feed/
Nonfood

Food/
Nonfood

R

Aquatic invertebrate acute
toxicity, freshwater

Food/
Nonfood

Forestry,
Residential
Outdoor

Food/
Nonfood

R

CR

R

CR

TGAI,
EP

2, 3, 5

Indoor

Test
Substance

Test Notes

Nontarget Plant Testing
850.4100 .........

Terrestrial Plant Toxicity,
Seedling emergence

R

R

NR

R

NR

TGAI,
EP

5

850.4150 .........

Terrestrial Plant Toxicity,
Vegetative vigor

R

R

NR

R

NR

TGAI,
EP

5

Nontarget Insect Testing

R

R

R

R

NR

TGAI

14

Insect Testing
880.4350 .........
Tier II
Environmental Fate Testing
163-1
(835.1230).

Sediment and soil adsorption/desorption for parent and degradates

CR

CR

CR

CR

NR

TGAI

6

163-1
(835.1240).

Soil column leaching

CR

CR

CR

CR

NR

TGAI

6

163-2
(835.1410).

Laboratory volatilization
from soil

CR

NR

CR

CR

NR

TEP

7

161-1
(835.2120).

Hydrolysis

CR

CR

CR

CR

NR

TGAI

6

161-1
(835.4100).

Aerobic soil metabolism

CR

NR

CR

CR

NR

TGAI

6

161-2
(835.2240).

Photodegradation in water

CR

CR

CR

CR

NR

TGAI

6

161-3
(835.2410).

Photodegradation on soil

CR

NR

CR

CR

NR

TGAI

6

162-2
(835.4200).

Anaerobic soil metabolism

CR

NR

NR

NR

NR

TGAI

6

162-4
(835.4300).

Aerobic aquatic metabolism

CR

CR

CR

CR

NR

TGAI

6

162-3
(835.4400).

Anaerobic aquatic metabolism

CR

CR

NR

NR

NR

TGAI

6

880.4425 .........

Dispenser - water leaching

CR

NR

CR

CR

NR

EP

8

Nontarget Plant
850.4225 .........

Seedling emergence

R

R

NR

R

NR

TGAI

9

850.4250 .........

Vegetative vigor

R

R

NR

R

NR

TGAI

9

CR

NR

CR

NR

TGAI

10

wreier-aviles on DSK7SPTVN1PROD with CFR

Tier III
Aquatic Fauna Chronic, Life Cycle, and Field Studies
850.1300 .........
850.1400
850.1500

Freshwater fish/invertebrate testing

CR

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Environmental Protection Agency

§ 158.2060

TABLE—BIOCHEMICAL PESTICIDES NONTARGET ORGANISMS AND ENVIRONMENTAL FATE DATA
REQUIREMENTS—Continued
Use Patterns
Guideline Number

Data Requirement

Terrestrial

Aquatic

Greenhouse
Food/
Nonfood

Forestry,
Residential
Outdoor

Food/
Feed/
Nonfood

Food/
Nonfood

Food/
Nonfood

Indoor

Test
Substance

Test Notes

850.1025 .........
850.1035
850.1045
850.1055
850.1350
850.1400
850.1500

Marine/Estuarine fish/invertebrate animal testing

CR

CR

NR

CR

NR

TGAI

10

850.1950 .........

Aquatic field fish/invertebrate testing

CR

CR

NR

CR

NR

EP

10

Terrestrial Wildlife
850.2300 .........

Avian Reproduction

CR

CR

NR

CR

NR

TGAI

11

850.2400 .........

Wild mammal acute toxicity

CR

CR

NR

CR

NR

TGAI

11

850.2500 .........

Terrestrial field testing

CR

CR

NR

CR

NR

EP

11

CR

CR

NR

CR

NR

TEP

12

CR

CR

NR

CR

NR

TGAI

13

Beneficial Insects
850.3040 .........

Field testing for Pollinators

Nontarget Plants
850.4225 .........
850.4250
850.4300
850.4450

Nontarget plant

wreier-aviles on DSK7SPTVN1PROD with CFR

(e) Test notes. The following test
notes are applicable to the data requirements for biochemical pesticides
nontarget organisms and environmental fate as referenced in the last
column of the table contained in paragraph (d) of this section.
1. Required for the EP when any end-use
formulation may contain other ingredients
that may be toxic to nontarget organisms or
to support arthropod pheromones that would
be available to avian wildlife, (e.g., a granular product).
2. Tests for pesticides intended solely for
indoor application would be required on a
case-by-case basis, depending on use pattern,
physical/chemical properties, production volume, and other pertinent factors.
3. Not required for any use groups if the
pesticide is highly volatile (estimated volatility >5 X 10-5atm m3/mol).
4. Preferred test species are Upland game,
waterfowl, or passerine for avian acute oral
toxicity studies; Upland game and waterfowl
for avian dietary studies; and coldwater fish
species for acute freshwater fish studies.

5. Required for the EP when the end-use
formulation may contain other ingredients
that may be toxic to nontarget organisms.
6. Required on a case-by-case basis when
results from Tier I studies indicate adverse
effects.
7. Required when results of any one or
more of the nontarget organism studies in
Tier I indicate potential adverse effects on
nontarget organisms and the pesticide is to
be applied on land. In view of methdological
difficulties
with
the
study
of
photodegradation in air, prior consultation
with the Agency regarding the protocol is
recommended before the test is performed.
8. Required when results of any one or
more of the nontarget organism studies in
Tier I indicate potential adverse effects on
nontarget organisms and the pesticide is to
be applied in a passive dispenser.
9. Required to support registration of
known
phytotoxicants,
i.e.,
herbicides,
desiccants, defoliants, and plant growth regulators.
10. Required if environmental fate characteristics indicate that the estimated environmental concentration of the pesticide in
the aquatic environment is >0.01 of any EC50

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§ 158.2070

40 CFR Ch. I (7–1–11 Edition)

wreier-aviles on DSK7SPTVN1PROD with CFR

or LC50 determined in the aquatic nontarget
organism testing.
11. Required if either of the following criteria are met:
i. Environmental fate characteristics indicate that the estimated concentration of the
pesticide in the terrestrial environment is >
0.20 the avian dietary LC50 or equal to > 0.20
the avian oral single dose LD50 (converted to
ppm).
ii. The pesticide or any of its metabolites
or degradation products are stable in the environment to the extent that potentially
toxic amounts may persist in the avian or
mammalian feed.
12. Required when results of Tier I nontarget organism studies indicate potential adverse effects on nontarget insects and results
of Tier II tests indicate exposure of nontarget insects. Additional insect species may
have to be tested if necessary to address
issues raised by use patterns and potential
exposure of important nontarget insect species, (e.g., threatened or endangered species).
13. Required if the product is expected to
be transported from the site of application
by air, soil, or water. The extent of movement would be determined by the results of
the Tier II environmental fate studies.
14. Required depending on pesticide mode
of action, method and timing of application,
and results of any available efficacy data.
Typically the honeybee acute toxicity guideline (guideline 850.3020) satisfies this requirement, however, additional nontarget insect
species may have to be tested if necessary to
address issues raised by use patterns and potential exposure of important nontarget insect species, (e.g., endangered species.)

§ 158.2070 Biochemical
pesticides
product performance data requirements.
Product performance data must be
developed for all biochemical pesticides. However, the Agency typically
does not require applicants to submit
such efficacy data unless the pesticide
product bears a claim to control public
health pests, such as pest microorganisms infectious to man in any area of
the inanimate environment or a claim
to control vertebrates (including but
not limited to: rodents, birds, bats,
canids, and skunks) or invertebrates
(including but not limited to: mosquitoes and ticks) that may directly or indirectly transmit diseases to humans.
However, each registrant must ensure
through testing that his products are
efficacious when used in accordance
with label directions and commonly accepted pest control practices. The
Agency reserves the right to require,

on a case-by-case basis, submission of
efficacy data for any pesticide product
registered or proposed for registration.
§ 158.2080 Experimental use permit
data
requirements—biochemical
pesticides.
(a) Sections 158.2081 through 158.2084
describe the experimental use permit
(EUP) data requirements for biochemical pesticides. Variations in the
test conditions are identified within
the test notes. Definitions that apply
to all biochemical data requirements
can be found in § 158.2000.
(b) For general information on the
data
requirement
tables,
see
§ 158.2010(b)-(f).
§ 158.2081 Experimental use permit
biochemical
pesticides
product
chemistry data requirements table.
(a) General. (1) Sections 158.100
through 158.130 describe how to use this
table to determine the product chemistry data requirements for a particular biochemical pesticide product.
Notes that apply to an individual test
and include specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e)
of the section.
(2) Depending on the results of the required product chemistry studies, appropriate use restrictions, labeling requirements, or special packaging requirements may be imposed.
(b) Use patterns. Product chemistry
data are required for all pesticide products and are not use specific.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; Residue
of concern=the active ingredient and
its metabolites, degradates, and impurities of toxicological concern; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to
the individual tests in the following
table:
(d) Table. The following table shows
the data requirements for experimental

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Environmental Protection Agency

§ 158.2081

use permit biochemical pesticides product chemistry. The test notes are
shown in paragraph (e) of this section.
TABLE—EUP BIOCHEMICAL PESTICIDES PRODUCT CHEMISTRY DATA REQUIREMENTS
Guideline Number

Data Requirement

Test Substance

All Use Patterns

MP

EP

Test Notes

Product Identity and Composition
880.1100 .........

Product identity and composition

R

TGAI, MP

TGAI, EP

1, 2

880.1200 .........

Description of starting materials, production
and formulation process

R

TGAI, MP

TGAI, EP

2, 3

880.1400 .........

Discussion of formation of impurities

R

TGAI and MP

TGAI and EP

4

Analysis and Certified Limits
830.1700 .........

Preliminary analysis

CR

TGAI and MP

TGAI and EP

5, 8

830.1750 .........

Certified limits

R

MP

EP

6

830.1800 .........

Enforcement analytical method

R

MP

EP

7

wreier-aviles on DSK7SPTVN1PROD with CFR

Physical and Chemical Characteristics
830.6302 .........

Color

R

TGAI

TGAI

8

830.6303 .........

Physical state

R

TGAI and MP

TGAI and EP

8

830.6304 .........

Odor

R

TGAI

TGAI

8

830.6313 .........

Stability to normal and elevated temperatures, metals and metal ions

R

TGAI

TGAI

8, 17

830.6315 .........

Flammability

CR

MP

EP

9

830.6317 .........

Storage stability

R

MP

EP

--

830.6319 .........

Miscibility

10

830.6320 .........

Corrosion characteristics

830.7000 .........

pH

830.7050 .........

UV/Visible light absorption

830.7100 .........

Viscosity

830.7200 .........

Melting point/melting range

CR

830.7220 .........

Boiling point/boiling range

CR

TGAI

TGAI

8, 14

830.7300 .........

Density/relative density/bulk density

R

TGAI and MP

TGAI and EP

8, 18

830.7520 .........

Particle size, fiber length, and diameter
distribution

CR

TGAI

TGAI

8, 15

830.7550 .........
830.7560
830.7570

Partition coefficient (n-Octanol /Water)

CR

TGAI

TGAI

16

830.7840 .........

Water solubility

R

TGAI

TGAI

8

830.7950 .........

Vapor pressure

R

TGAI

TGAI

8, 19

(e) Test notes. The following test
notes are applicable to the data requirements for experimental use permit biochemical pesticides product

CR

MP

EP

R

MP

EP

--

CR

TGAI and MP

TGAI and EP

8, 11

R

TGAI

TGAI

--

CR

MP

EP

12

TGAI

TGAI

8, 13

chemistry and are referenced in the
last column of the table in paragraph
(d) of this section.

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§ 158.2082

40 CFR Ch. I (7–1–11 Edition)

wreier-aviles on DSK7SPTVN1PROD with CFR

1. Data must be provided in accordance
with § 158.320.
2. If the MP and EP are produced by an integrated formulation system (non-registered
source), these data are also required on
TGAI.
3. Data must be provided in accordance
with § 158.325, § 158.330, and § 158.335.
4. Data must be provided in accordance
with § 158.340.
5. Data must be provided in accordance
with § 158.345. Also, required to support the
registration of each manufacturing-use product (including registered TGAIs) and end-use
products produced by an integrated formulation system. Data on other end-use products
would be required on a case-by-case basis.
For pesticides in the production stage, a preliminary product analytical method and data
would suffice to support an experimental use
permit.
6. Data must be provided in accordance
with § 158.350.
7. Data must be provided in accordance
with § 158.355.
8. If the TGAI cannot be isolated, data are
required on the practical equivalent of the
TGAI. EP testing may also be appropriate.
9. Required if the product contains combustible liquids.
10. Required if the product is an emulsifiable liquid and is to be diluted with petroleum solvents.
11. Required if the test substance is soluble
or dispersible in water.
12. Required if the product is a liquid.
13. Required when the technical chemical
is a solid at room temperature.
14. Required when the technical chemical
is a liquid at room temperature.
15. Required for water insoluble test substances (>10-6g/l) and fibrous test substances
with diameter ≥0.1 μm.
16. Required for organic chemicals unless
they dissociate in water or are partially or
completely soluble in water.
17. Data on the stability to metals and
metal ions is required only if the active ingredient is expected to come in contact with
either material during storage.
18. True density or specific density are required for all test substances. Data on bulk
density is required for MPs or EPs that are
solid at room temperature.
19. Not required for salts.

§ 158.2082 Experimental use permit
biochemical pesticides residue data
requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the biochemical pesticides
residue data requirements for a par-

ticular pesticide product and the substance that needs to be tested. These
data requirements apply to all biochemical pesticides, i.e., naturally occurring
insect
repellents
and
attractants, semiochemicals (e.g., insect pheromones), natural and plant
growth regulators. Notes that apply to
an individual test and include specific
conditions, qualifications, or exceptions to the designated test are listed
in paragraph (e) of this section.
(b) Use patterns. (1) Data are required
or conditionally required for all pesticides used in or on food and for residential outdoor uses where food crops
are grown. Food use patterns include
products classified under the general
use patterns of terrestrial food crop
use, terrestrial feed crop use, aquatic
food crop use, greenhouse food crop
use, and indoor food use. Data are also
conditionally required for aquatic
nonfood use if there is direct application to water that could subsequently
result in exposure to food.
(2) Data are conditionally required
for nonfood uses if pesticide residues
may occur in food or feed as a result of
the use. Data requirements for these
nonfood uses would be determined on a
case-by-case basis. For example, most
products used in or near kitchens require residue data for risk assessment
purposes even though tolerances may
not be necessary in all cases.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required;
MP=Manufacturing
end-use
product;
EP=End-use
product;
TEP=Typical
end-use
product;
TGAI=Technical grade of the active ingredient; Residue of concern=the active
ingredient
and
its
metabolites,
degradates,and impurities of toxicological concern. All=All of the above.
Specific conditions, qualifications, or
exceptions to the designated test procedures appear in paragraph (e) of this
section, and apply to the individual
tests in the following table:
(d) Data table. The following table
shows the data requirements for biochemical pesticides residue. The test
notes are shown in paragraph (e) of this
section.

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Environmental Protection Agency

§ 158.2082

TABLE—EUP BIOCHEMICAL PESTICIDES RESIDUE DATA REQUIREMENTS
Use Patterns
Guideline Number

Data Requirement

Terrestrial
Food/
Feed

Test Substance

Test Notes

Indoor Food

Food

Greenhouse
Food

Aquatic

Supporting Information
860.1100

Chemical identity

CR

CR

CR

CR

TGAI

1, 2, 4

860.1200

Directions for use

CR

CR

CR

CR

--

1, 3, 4

860.1300

Nature of the residue in
plants

CR

CR

CR

CR

TGAI

1, 4, 5, 6

860.1300

Nature of the residue in
livestock

CR

CR

CR

CR

TGAI or plant
metabolite

1, 7, 8, 9,
13

Nature of Residue

Magnitude of the Residue
860.1400

Potable water

NR

CR

NR

NR

TGAI

1, 11

860.1400

Fish

NR

CR

NR

NR

TGAI

1, 12

860.1400

Irrigated crops

NR

CR

NR

NR

TGAI

1, 13

860.1460

Food handling

NR

NR

NR

CR

TGAI

1, 14

860.1480

Meat/milk/poultry/eggs

CR

CR

CR

CR

TGAI or plant
metabolites

1, 7, 8, 9

860.1500

Crop field trials

CR

CR

CR

CR

TEP

1, 3, 4

860.1520

Processed food/feed

CR

CR

CR

CR

TEP

1, 15

860.1540

Anticipated residues

CR

CR

CR

CR

Residue of
concern

1, 9, 16

860.1550

Proposed tolerances

CR

CR

CR

CR

--

1, 17

860.1560

Reasonable grounds in
support of the petition

CR

CR

CR

CR

--

1, 9

860.1650

Submittal of analytical
reference standards

CR

CR

CR

CR

TGAI and
residue of
concern

9, 18

wreier-aviles on DSK7SPTVN1PROD with CFR

(e) Test notes. The following test
notes are applicable to the data requirements for biochemical pesticides
product chemistry and are referenced
referenced in the last column of the
table contained in paragraph (d) of this
section.
1. Residue chemistry data requirements
apply to biochemical pesticide products
when Tier II or Tier III toxicology data are
required, as specified for biochemical agents
in the biochemical human health assessment
data requirements, § 158.2050.
2. The same chemical identity data are required for biochemical product chemistry
data requirements,§ 158.2030 with an emphasis on impurities.
3. Required information includes crops to
be treated, rate of application, number and

timing of applications, preharvest intervals,
and relevant restrictions.
4. Required for residential outdoor uses on
food crops if the corresponding agricultural
use is not approved or the residential use is
expected to produce higher residues based on
the label directions.
5. Required unless it is an arthropod
pheromone applied at a rate less than or
equal to 150 grams active ingredient per acre.
6. Required for indoor uses where the pesticide is applied directly to food, in order to
determine metabolites and/or degradates.
Not required when only indirect contact
with food would occur (e.g., crack and crevice treatments).
7. Required when a pesticide is to be applied directly to livestock, to livestock
premises, to livestock drinking water, or to
crops used for livestock feed. If results from

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§ 158.2083

40 CFR Ch. I (7–1–11 Edition)

the plant metabolism study show differing
metabolites in plants form those found in
animals, an additional livestock metabolism
study involving dosing with the plant metabolite(s) may also be required.
8. Livestock feeding studies are required
whenever a pesticide residue is present in
livestock feed or when direct application to
livestock uses occurs.
9. Required if indoor use could result in
pesticide residues in or on food or feed.
10. Data are required to determine whether
FDA/USDA multiresidue methodology would
detect and identify the pesticides and any
metabolites.
11. Data are required whenever a pesticide
may be applied directly to water, unless it
can be demonstrated that the treated water
would not be available for human or livestock consumption.
12. Data on fish are required for all pesticides applied directly to water inhabited,
or which will be inhabited, by fish that may
be caught or harvested for human consumption.
13. Data are required when a pesticide is to
be applied directly to water that could be
used for irrigation or to irrigation facilities
such as irrigation ditches.
14. Data are required whenever a pesticide
may be used in food/feed handling establishments.
15. Data on the nature and level of residue
in processed food/feed are required when
detectible residues could potentially concentrate on processing thus requiring the establishment of a separate tolerance higher
than that of the raw agricultural commodity.
16 Anticipated residue data are required
when the assumption of tolerance level residues would result in predicted exposure at an
unsafe level of exposure. Data, using single
serving samples of a raw agricultural commodity, on the level or residue in food as
consumed would be used to obtain a more
precise estimate of potential dietary exposure. These data may also include washing,
cooking, processing or degradation studies as
well as market basket surveys for a more
precise residue determination.
17. The proposed tolerance must reflect the
maximum residue likely to occur in crops, in
meat, milk, poultry, or eggs.
18. Required when a residue analytical
method is required.

§ 158.2083 Experimental use permit
biochemical
pesticides
human
health assessment data requirements table.
(a) General. (1) Sections 158.100
through 158.130 describe how to use this
table to determine the human health
assessment data requirements for a
particular biochemical pesticide product.
(2) The data in this section are not
required
for
straight
chain
lepidopteran pheromones when applied
up to a maximum use rate of 150 grams
active ingredient/acre/year.
(b) Use patterns. (1) Food use patterns, in general, include products classified under the following general uses:
terrestrial food crop use; terrestrial
feed crop use; aquatic food crop use;
greenhouse food crop use.
(2) Nonfood use patterns include
products classified under the general
use patterns of terrestrial nonfood crop
use; aquatic nonfood residential use;
aquatic nonfood outdoor use; aquatic
nonfood industrial use; greenhouse
nonfood crop use; forestry use; residential outdoor use; residential indoor use;
indoor food use; indoor nonfood use; indoor medical use.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; Residue
of concern=the active ingredient and
its metabolites, degradates, and impurities of toxicological concern; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to
the individual tests in the following
table:
(d) Table. The following table shows
the data requirements for experimental
use permit biochemical pesticides
human health assessment. The test
notes are shown in paragraph (e) of this
section.

wreier-aviles on DSK7SPTVN1PROD with CFR

TABLE—EUP BIOCHEMICAL PESTICIDES HUMAN HEALTH ASSESSMENT DATA REQUIREMENTS
Use Patterns
Guideline Number

Test Substance

Data Requirement

Test Notes
Food

Nonfood

MP

EP

Tier I

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Environmental Protection Agency

§ 158.2083

TABLE—EUP BIOCHEMICAL PESTICIDES HUMAN HEALTH ASSESSMENT DATA REQUIREMENTS—
Continued
Use Patterns
Guideline Number

Test Substance

Data Requirement

Test Notes
Food

Nonfood

MP

EP

Acute Testing
870.1100 .............

Acute oral toxicity - rat

R

R

TGAI
and MP

TGAI and EP

1

870.1200 .............

Acute dermal toxicity

R

R

TGAI
and MP

TGAI and EP

1, 2

870.1300 .............

Acute inhalation toxicity - rat

R

R

TGAI
and MP

TGAI and EP

3

870.2400 .............

Primary eye irritation - rabbit

R

R

TGAI
and MP

TGAI and EP

2

870.2500 .............

Primary dermal irritation

R

R

TGAI
and MP

TGAI and EP

1, 2

none ....................

Hypersensitivity incidents

R

R

All

All

4

R

NR

TGAI

TGAI

--

R

CR

TGAI

TGAI

5

Subchronic Testing
870.3100 .............

90-day oral (one species)

Developmental Toxicity
870.3700 .............

Prenatal developmental - rat preferably

Mutagenicity Testing
870.5100 .............

Bacterial reverse mutation test

R

CR

TGAI

TGAI

6

870.5300 .............

In vivo mammalian cell assay

R

CR

TGAI

TGAI

6, 7

CR

CR

TGAI

TGAI

5

Tier II
Developmental Toxicity
870.3700 .............

Prenatal developmental

wreier-aviles on DSK7SPTVN1PROD with CFR

(e) Test notes. The following test
notes are applicable to the data requirements for experimental use permit biochemical pesticides human
health assessment as referenced in the
last column of the table in paragraph
(d) of this section.
1. Required unless the test material is a
gas or highly volatile (vapor pressure >
10-4torr (mm/Hg)).
2. Required unless the test material is corrosive to skin or has pH <2 or >11.5.
3. Required when the pesticide, under conditions of use, would result in respirable material (e.g., gas, volatile substance or aerosol/particulate), unless it is a straight chain
lepidopteran pheromone.
4. Hypersensitivity incidents must be reported as adverse effects data.
5. Required if the use of the product under
widespread and commonly recognized practice may reasonably be expected to result in
significant exposure to female humans (e.g.,

occupational exposure or repeated application of insect repellents directly to the skin).
Tier II data is required on a different test
species from Tier I data when developmental
effects are observed in the first study and information on species-to-species extrapolation is needed.
6. Required to support nonfood uses if either:
i. The use is likely to result in significant
human exposure; or
ii. The active ingredient (or its metabolites) is structurally related to a known
mutagen or belongs to any chemical class of
compounds containing a known mutagen.
Additional mutagenicity tests that may
have been performed plus a complete reference list must also be submitted. Subsequent testing may be required based on the
available evidence.
7. Choice of assay using either:
i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing

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§ 158.2084

40 CFR Ch. I (7–1–11 Edition)

assay conditions for small colony expression
or detection;
ii. Chinese hamster ovary (CHO) or Chinese
hamster
lung
fibroblast
(V79)
cells,
hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an
appropriate in vivo test for clastogenicity; or
iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene
locus.

§ 158.2084 Experimental use permit
biochemical pesticides nontarget
organisms and environmental fate
data requirements table.
(a) General. (1) Sections 158.100
through 158.130 describe how to use this
table to determine the terrestrial and
aquatic nontarget organisms and fate
data requirements for a particular biochemical pesticide product. Notes that
apply to an individual test including
specific conditions, qualifications, or
exceptions to the designated test are
listed in paragraph (e) of this section.
In general, for all outdoor end-use
products including turf, the following
studies are required: one avian acute
oral, one avian dietary, one acute
freshwater fish, and one acute freshwater invertebrate study.
(2) The data in this section are not
required for arthropod pheromones
when applied at up to a maximum use
rate of 150 grams active ingredient/
acre/year except when the product is
expected to be available to avian species (i.e., granular formulation).

(b) Use patterns. The terrestrial use
pattern includes products classified
under the general use patterns of terrestrial food crop, terrestrial feed crop,
and terrestrial nonfood/nonfeed crop.
The greenhouse use pattern includes
products classified under the general
use patterns of greenhouse food crop
and greenhouse nonfood crop. The indoor use pattern includes products
classified under the general use patterns of indoor food and nonfood use.
The remaining terrestrial uses include
forestry and residential outdoor use.
Data are also required for the general
use patterns of aquatic food and
nonfood crop use.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; Residue
of concern=the active ingredient and
its metabolites, degradates, and impurities of toxicological concern; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to
the individual tests in the following
table:
(d) Table. The following table shows
the data requirements for experimental
use permit biochemical pesticides nontarget organisms and environmental
fate. The test notes are shown in paragraph (e) of this section.

TABLE—EUP BIOCHEMICAL PESTICIDES NONTARGET ORGANISMS AND ENVIRONMENTAL FATE DATA
REQUIREMENTS
Use Patterns

Guideline Number

Data Requirement

Terrestrial

Aquatic

Greenhouse
Food/
Nonfood

Forestry,
Residential
Outdoor

Food/
Feed/
Nonfood

Food/
Nonfood

Food/
Nonfood

Indoor

Test
Substance

Test Notes

Tier I

wreier-aviles on DSK7SPTVN1PROD with CFR

Avian Testing
850.2100 ................

Avian acute oral
toxicity

R

R

NR

R

NR

TGAI,
EP

1, 2, 3

850.2200 ................

Avian dietary toxicity

R

R

NR

R

NR

TGAI,
EP

1, 2, 3

R

R

NR

R

NR

TGAI,
EP

2, 3, 4

Aquatic Organism Testing
850.1075 ................

Fish acute toxicity,
freshwater

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Environmental Protection Agency

§ 158.2110

TABLE—EUP BIOCHEMICAL PESTICIDES NONTARGET ORGANISMS AND ENVIRONMENTAL FATE DATA
REQUIREMENTS—Continued
Use Patterns

Guideline Number

850.1010 ................

Data Requirement

Aquatic invertebrate
acute toxicity,
freshwater

Terrestrial

Aquatic

Greenhouse

Food/
Feed/
Nonfood

Food/
Nonfood

R

R

(e) Test notes. The following test
notes are applicable to the data requirements for experimental use permit biochemical pesticides nontarget
organisms and environmental fate as
referenced in the last column of the
table contained in paragraph (d) of this
section.
1. Required for the EP when any end-use
formulation may contain other ingredients
that may be toxic to nontarget organisms or
to support arthropod pheromones that would
be available to avian wildlife, (e.g., a granular product).
2. Not required for any use groups if the
pesticide is highly volatile (estimated volatility >5 X 10-5atm m3/mol).
3. Preferred test species are: upland game,
waterfowl, or passerine for avian acute oral
toxicity studies; upland game or waterfowl
for avian dietary studies; and coldwater fish
for acute freshwater fish studies.
4. Required for the EP when the end-use
formulation may contain other ingredients
that may be toxic to nontarget organisms.

Subpart V—Microbial Pesticides
SOURCE: 72 FR 61002, Oct. 26, 2007, unless
otherwise noted.

wreier-aviles on DSK7SPTVN1PROD with CFR

§ 158.2100 Microbial pesticides definition and applicability.
(a) This subpart applies to all living
or dead microbial pesticides as described in paragraphs (b) and (c) of this
section.
(b) Definition. Microbial pesticide is a
microbial agent intended for preventing, destroying, repelling, or mitigating any pest, or intended for use as
a plant regulator, defoliant, or desiccant, that:
(1) Is a eucaryotic microorganism including, but not limited to, protozoa,
algae, and fungi;

Food/
Nonfood

Forestry,
Residential
Outdoor

Food/
Nonfood

NR

R

NR

Indoor

Test
Substance

TGAI,
EP

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(2) Is a procaryotic microorganism,
including,
but
not
limited
to,
Eubacteria and Archaebacteria; or
(3) Is a parasitically replicating microscopic element, including, but not
limited to, viruses.
(c) Applicability. (1) This part applies
to microbial pesticides as specified in
paragraphs (c)(2), (3) and (4) of this section.
(2) Each new isolate of a microbial
pesticide is treated as a new strain and
must be registered independently of
any similar registered microbial pesticide strain and supported by data required in this subpart.
(3) Genetically modified microbial
pesticides may be subject to additional
data or information requirements on a
case-by-case basis depending on the
particular microbial agent and/or its
parental strains, the proposed pesticide
use pattern, and the manner and extent
to which the organism has been genetically modified.
(4) Pest control organisms such as insect predators, nematodes, and macroscopic parasites are exempt from the
requirements of FIFRA as authorized
by section 25(b) of FIFRA and specified
in § 152.20 (a) of this chapter.
§ 158.2110 Microbial pesticides data requirements.
(a) For all microbial pesticides. (1) The
following § 158.2120 through § 158.2150
identify the data requirements that are
required to support registration of microbial pesticides. The variations in
the test conditions are identified within the test notes.
(2) Each data table includes ‘‘use patterns’’ under which the individual data
are required, with variations including
all use patterns, food and nonfood uses

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§ 158.2120

40 CFR Ch. I (7–1–11 Edition)

for terrestrial and aquatic applications, greenhouse, indoor, forestry, and
residential outdoor applications under
certain circumstances.
(3) The categories for each data requirement are ‘‘R,’’ which stands for
required, and ‘‘CR’’ which stands for
conditionally required. If a bracket appears around the ‘‘R’’ or ‘‘CR,’’ the
data are required for both the registration and experimental use permit requests. Generally, ‘‘R’’ indicates that
the data are more likely required than
for those data requirements with
‘‘CR.’’ However, in each case, the regulatory text preceding the data table
and the test notes following the data
table must be used to determine whether the data requirement must be satisfied.
(4) Each table identifies the test substance that is required to be tested to
satisfy the data requirement. Test substances may include: technical grade
active ingredient (TGAI), manufacturing-use product (MP), end-use product (EP), typical end-use product
(TEP), residue of concern, and pure active ingredient (PAI) or all of the above
(All). Commas between the test substances (i.e., TGAI, EP) indicate that
data may be required on the TGAI or
EP or both depending on the conditions
set forth in the test note. Data requirements which list two test substances
(i.e., TGAI and EP) indicate that both
are required to be tested. Data requirements that list only MP as the test
substance apply to products containing
solely the technical grade of the active
ingredient
and
manufacturing-use
products to which other ingredients
have been intentionally added. Data requirements listing the EP as the test
substance apply to any EP with an ingredient in the end-use formulation
other than the active ingredient that is

expected to enhance the toxicity of the
product.
(b) Additional data requirements for genetically modified microbial pesticides.
Additional requirements for genetically modified microbial pesticides
may include but are not limited to: genetic engineering techniques used; the
identity of the inserted or deleted gene
segment (base sequence data or enzyme
restriction map of the gene); information on the control region of the gene
in question; a description of the ‘‘new’’
traits or characteristics that are intended to be expressed; tests to evaluate genetic stability and exchange; and
selected Tier II environmental expression and toxicology tests.
§ 158.2120 Microbial pesticides product
analysis data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the product analysis data requirements and the substance to be
tested for a particular microbial pesticide. Specific conditions, qualifications, or exceptions to the designated
test are identified in paragraph (d) of
this section, and the test notes appear
in paragraph (e) of this section.
(b)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to
the individual tests in the following
table:
(c) Table. The following table shows
the data requirements for microbial
pesticides product analysis. The test
notes are shown in paragraph (d) of
this section.

TABLE—MICROBIAL PESTICIDES PRODUCT ANALYSIS DATA REQUIREMENTS
Guideline Number

All Use Patterns

Data Requirement

Test Substance
Test Notes
MP

EP

wreier-aviles on DSK7SPTVN1PROD with CFR

Product Chemistry and Composition
885.1100

Product Identity

R

MP

EP

--

885.1200

Manufacturing process

R

TGAI and MP

TGAI and EP

--

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Environmental Protection Agency

§ 158.2130

TABLE—MICROBIAL PESTICIDES PRODUCT ANALYSIS DATA REQUIREMENTS—Continued
Guideline Number

885.1300

Test Substance

All Use Patterns

MP

EP

Deposition of a sample in a nationally recognized culture collection

R

TGAI

TGAI

--

Discussion of formation of unintentional ingredients

R

TGAI and MP

TGAI and EP

--

Data Requirement

Test Notes

Analysis and Certified Limits
885.1400

Analysis of samples

R

TGAI and MP

TGAI and EP

1

885.1500

Certification of limits

R

MP

EP

--

Physical and Chemical Characteristics
830.6302

Color

R

TGAI

TGAI

--

830.6303

Physical state

R

TGAI

TGAI

--

830.6304

Odor

R

TGAI

TGAI

--

830.6313

Stability to normal and elevated temperatures, metals and metal ions

R

TGAI

TGAI

--

830.6317

Storage stability

R

TGAI and MP

TGAI and EP

--

830.6319

Miscibility

R

MP

EP

2

830.6320

Corrosion Characteristics

R

MP

EP

3

830.7000

pH

R

TGAI

TGAI

--

830.7100

Viscosity

R

MP

EP

4

830.7300

Density/relative density/bulk density (specific gravity)

R

TGAI

TGAI

--

wreier-aviles on DSK7SPTVN1PROD with CFR

(d) Test notes. The following test
notes are applicable to the data requirements for microbial pesticides
product analysis as referenced in the
last column of the table contained in
paragraph (c) of this section.
1. Required to support registration of each
manufacturing-use product and end-use product. This analysis must be conducted at the
point in the production process after which
there would be no potential for microbial
contamination or microbial regrowth. For
full registration, generally an analysis of
samples is a compilation of batches, over a
period of time, depending on the frequency of
manufacturing.
2. Only required for emulsifiable liquid
forms of microbial pesticides.
3. Required when microbial pesticides are
packaged in metal, plastic, or paper containers.
4. Only required for liquid forms of microbial pesticides.

§ 158.2130 Microbial pesticides residue
data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the residue chemistry data
requirements and the substance to be
tested for a particular microbial pesticide. Specific conditions, qualifications, or exceptions to the designated
test appear in paragraph (d) of this section, and the procedures appear in
paragraph (e) of this section.
(b)
Key.
R=required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (d) of this section, and apply to
the individual tests in the following
table:

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§ 158.2140

40 CFR Ch. I (7–1–11 Edition)

(c) Table. The following table shows
the data requirements for microbial

pesticides residue. The test notes are
shown in paragraph (d) of this section.

TABLE—MICROBIAL PESTICIDES RESIDUE DATA REQUIREMENTS
Guideline Number

All Use Patterns

Data Requirement

Test Notes

885.2100 .................

Chemical Identity

CR

EP

1

885.2200 .................

Nature of the Residue in plants

CR

EP

1

885.2250 .................

Nature of the Residue in animals

CR

EP

1

885.2300 .................

Analytical methods - plants

CR

TGAI

1

885.2350 .................

Analytical methods - animals

CR

TGAI

1

885.2400 .................

Storage Stability

CR

EP

1

885.2500 .................

Magnitude of residue in plants

CR

EP

1

885.2550 .................

Magnitude of residues in meat, milk, poultry, eggs

CR

EP

1

885.2600 .................

Magnitude of residues in potable water, fish, and
irrigated crops

CR

EP

1

(d) Test notes. The following test note
is applicable to the data requirements
for microbial pesticides residue as referenced in the last column of the table
contained in paragraph (c) of this section.
1. Required when the results of testing:
i. Indicate the potential to cause adverse
human health effects or the product characterization indicates the microbial pesticide
has a significant potential to produce a
mammalian toxin; and
ii. The use pattern is such that residues
may be present in or on food or feed crops.

§ 158.2140 Microbial pesticides toxicology data requirements table.

wreier-aviles on DSK7SPTVN1PROD with CFR

Test Substance
Data to Support
MP or EP

(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the toxicology data requirements for a particular pesticide product. Notes that apply to an individual
test and include specific conditions,
qualifications, or exceptions to the designated test are listed in paragraph (d)
of this section.
(b)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (d) of this section, and apply to

the individual tests in the following
table:
(c) Table. The following table shows
the data requirements for microbial
pesticides toxicology. The test notes
are shown in paragraph (d) of this section.
TABLE—MICROBIAL PESTICIDES TOXICOLOGY
DATA REQUIREMENTS
Guideline
Number

Data Requirement

All
Use
Patterns

Test
Substance

Test
Notes

Tier I
885.3050

Acute oral toxicity/
pathogenicity

R

TGAI

1

885.3150

Acute pulmonary toxicity/pathogenicity

R

TGAI

--

885.3200

Acute injection toxicity/
pathogenicity/(intravenous)
Acute injection toxicity/
pathogenicity/
(intraperitoneal)

R

TGAI

2

885.3400

Hypersensitivity incidents

R

All

3

885.3500

Cell culture

R

TGAI

4

870.1100

Acute oral toxicity

R

MP ,
EP

1, 5

870.1200

Acute dermal toxicity

R

MP ,
EP

5

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Environmental Protection Agency

§ 158.2140

TABLE—MICROBIAL PESTICIDES TOXICOLOGY
DATA REQUIREMENTS—Continued
All
Use
Patterns

Test
Substance

Test
Notes

Acute inhalation toxicity

R

MP ,
EP

5, 6

870.2400

Acute eye irritation

R

MP ,
EP

5

870.2500

Primary dermal irritation

R

MP ,
EP

5

885.3550

Acute toxicology

CR

TGAI

7

885.3600

Subchronic toxicity/
pathogenicity

CR

TGAI

8

885.3650

Reproductive fertility
effects

CR

TGAI

9, 13

870.4200

Carcinogenicity

CR

TGAI

10, 13

870.7800

Immunotoxicity

CR

TGAI

11, 13

885.3000

Infectivity/pathogenicity analysis

CR

TGAI

12, 13

Guideline
Number

Data Requirement

870.1300

Tier II

Tier III

wreier-aviles on DSK7SPTVN1PROD with CFR

(d) Test notes. The following test
notes are applicable to the data requirements for microbial pesticides
toxicology as referenced in the last column of the table contained in paragraph (c) of this section:
1. The acute oral toxicity/pathogenicity
study is required to support the TGAI. However, it can be combined with the unit dose
portion of the acute oral toxicity study, with
an EP or MP test material to fulfill the requirement for the TGAI and the MP or EP in
a single study, if the new protocol is designed to address the endpoints of concern.
2. Data not required for products whose active ingredient is a virus. For test materials
whose size or consistency may prevent use of
an intravenous injection, the intraperitoneal
injection procedure may be employed.
3. Hypersensitivity incidents, including
immediate type and delayed-type reactions
of humans or domestic animals, occur during
the testing or production of the TGAI, MP,
or EP, or are otherwise known to the applicant must be reported if they occur.
4. Data must be submitted only for products whose active ingredient is a virus.
5. The 870 series studies for the MP and EP
are intended to provide data on the acute
toxicity of the product. Waivers for any or
all of these studies may be granted when the
applicant can demonstrate that the combination of inert ingredients is not likely to pose
any significant human health risks. Where

appropriate, the limit dose approach to testing is recommended.
6. Required when the product consists of,
or under conditions of use would result in, an
inhalable material (e.g., gas, volatile substances, or aerosol particulate).
7. Data required when significant toxicity,
in the absence of pathogenicity and significant infectivity, is observed in acute oral, injection, or pulmonary studies (Tier I).
Route(s) of exposure correspond to route(s)
where toxicity was observed in Tier I studies. The toxic component of the TGAI is to
be tested.
8. Data required when significant infectivity and/or unusual persistence is observed
in the absence of pathogenicity or toxicity in
Tier I studies. Routes of exposure (oral and/
or pulmonary) correspond to routes in Tier I
studies where adverse effects were noted.
Data may also be required to evaluate adverse effects due to microbial contaminants
or to toxic byproducts.
9. Data are required when one or more of
the following criteria are met:
i. Significant infectivity of the microbial
pest control agent (MPCA) was observed in
test animals in the Tier II subchronic study
and in which no significant signs of toxicity
or pathogenicity were observed.
ii. The microbial pesticide is a virus which
can persist or replicate in mammalian cell
culture lines.
iii. The microbial pesticide is not amenable to thorough taxonomic classification,
and is related to organisms known to be
parasitic for mammalian cells.
iv. The microbial pesticide preparation is
not well purified, and may contain contaminants which are parasitic for mammals.
10. Data may be required for products
known to contain or suspected to contain
carcinogenic viruses or for microbial components that are identified as having significant toxicity in Tier II testing.
11. Data may be required for products
known to contain or suspected to contain viruses that can interact in an adverse manner
with components of the mammalian immune
system.
12. An analysis of human infectivity/pathogenicity potential using scientific literature,
genomic analysis, and/or actual specific cell
culture/animal data may be required for
products known to contain or suspected of
containing intracellular parasites of mammalian cells for products that exhibit pathogenic characteristics in Tier I and/or Tier II,
for products which are closely related to
known human pathogens based on the product analysis data, or for known human
pathogens that have been ‘‘disarmed’’ or rendered non-pathogenic for humans.
13. Test standards may have to be modified
depending on the characteristics of the
microorganism. Requirements may vary for

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§ 158.2150

40 CFR Ch. I (7–1–11 Edition)

these studies depending on the active ingredient being tested. Consultation with the
Agency is advised before performing these
Tier III studies.

restrial uses include: Food, Feed, NonFood, Forestry, Residential outdoor,
greenhouse (food and food), Indoor
(food and nonfood), and Industrial.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to
the individual tests in the following
table:
(d) Table. The following table shows
the data requirements for microbial
pesticides nontarget organisms and environmental fate. The test notes are
shown in paragraph (e) of this section.

§ 158.2150 Microbial pesticides nontarget organisms and environmental
fate data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the terrestrial and aquatic
nontarget organisms data requirements for a particular microbial pesticide product. Notes that apply to an
individual test including specific conditions, qualifications, or exceptions to
the designated test are listed in paragraph (e) of this section.
(b) Use patterns. Aquatic uses include:
food and feed, nonfood uses (e.g., outdoor, residential, and industrial). Ter-

TABLE—MICROBIAL PESTICIDES NONTARGET ORGANISMS AND ENVIRONMENTAL FATE DATA
REQUIREMENTS
Use Patterns
Terrestrial
Guideline
Number

Aquatic

Data Requirement

Food/
Feed/
Nonfood

Forestry

Resi
dential

Greenhouse

Indoor

Outdoor

Food/
Nonfood

Food/
Nonfood

Industrial

Test
Substance

Test
Notes

Food/
Feed

Nonfood

R

R

R

R

R

CR

CR

CR

TGAI

1, 2

wreier-aviles on DSK7SPTVN1PROD with CFR

Tier I
885.4050 ...

Avian oral toxicity

885.4100 ...

Avian inhalation toxicity/pathogenicity

CR

CR

CR

CR

CR

CR

CR

CR

TGAI

1, 2,
3

885.4150 ...

Wild mammal toxicity/
pathogenicity

CR

CR

CR

CR

CR

NR

NR

CR

TGAI

1, 4

885.4200 ...

Freshwater fish
toxicity/ pathogenicity

R

R

R

R

CR

CR

CR

CR

TGAI
or
TEP

1, 2,
5

885.4240 ...

Freshwater invertebrate toxicity/pathogenicity

R

R

R

R

CR

CR

CR

CR

TGAI
or
TEP

1, 2,
5

885.4280 ...

Estuarine/Marine fish
testing
Estuarine and marine
invertebrate testing

CR

CR

CR

CR

CR

NR

NR

CR

TGAI

1, 6

885.4300 ...

Nontarget plant
testing

CR

CR

CR

R

CR

NR

CR

CR

TEP

1, 7

885.4340 ...

Nontarget insect testing

R

R

R

R

R

CR

NR

CR

TGAI

1, 8

885.4380 ...

Honey bee testing

R

R

R

R

R

CR

NR

CR

TGAI

1

Tier II

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Environmental Protection Agency

§ 158.2150

TABLE—MICROBIAL PESTICIDES NONTARGET ORGANISMS AND ENVIRONMENTAL FATE DATA
REQUIREMENTS—Continued
Use Patterns
Terrestrial
Guideline
Number

Aquatic

Data Requirement

Food/
Feed/
Nonfood
Food/
Feed

Nonfood

Forestry

Resi
dential

Greenhouse

Indoor

Outdoor

Food/
Nonfood

Food/
Nonfood

Industrial

Test
Substance

Test
Notes

885.5200 ...

Terrestrial environmental expression
tests

CR

CR

CR

CR

CR

NR

NR

CR

TGAI
or
TEP

9

885.5300 ...

Freshwater environmental expression
tests

CR

CR

CR

CR

CR

NR

NR

CR

TGAI
or
TEP

10

885.5400 ...

Marine or estuarine
environmental expression tests

CR

CR

CR

CR

CR

NR

NR

CR

TGAI
or
TEP

11,
12

885.4600 ...

Avian chronic pathogenicity and reproduction test

CR

CR

CR

CR

CR

NR

NR

CR

TGAI

12,
13

885.4650 ...

Aquatic invertebrate
range testing

CR

CR

CR

CR

CR

NR

NR

CR

TGAI

12,
14

885.4700 ...

Fish life cycle studies

CR

CR

CR

CR

CR

NR

NR

CR

TGAI

12,
14

885.4750 ...

Aquatic ecosystem test

CR

CR

CR

CR

CR

NR

NR

CR

TGAI

15

850.2500 ...
850.1950

Field testing for terrestrial wildlife and Field
testing for aquatic
organisms

CR

CR

CR

CR

CR

NR

NR

CR

TGAI
or
TEP

11,
16

850.2500 ...

Simulated or actual
field tests (birds,
mammals)

CR

CR

CR

CR

CR

NR

NR

CR

TEP

16,
17,
20

850.1950 ...

Simulated or actual
field test (aquatic organisms)

CR

CR

CR

CR

CR

NR

NR

CR

TEP

16,
18,
19,
20

850.2500 ...

Simulated or actual
field tests (insect
predators, parasites)

CR

CR

CR

CR

CR

NR

NR

CR

TEP

16,
18,
19,
20

850.3040 ...

Simulated or actual
field tests (insect
pollinators)

CR

CR

CR

CR

CR

NR

NR

CR

TEP

16,
18,
19,
20

850.4300 ...

Simulated or actual
field tests (plants)

CR

CR

CR

CR

CR

NR

NR

CR

TEP

16,
18,
19,
20

Tier III

wreier-aviles on DSK7SPTVN1PROD with CFR

Tier IV

(e) Test notes. The following test
notes are applicable to the data re-

quirements for microbial pesticides
nontarget organism and environmental

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§ 158.2150

40 CFR Ch. I (7–1–11 Edition)

wreier-aviles on DSK7SPTVN1PROD with CFR

fate as referenced in the last column of
the table contained in paragraph (d) of
this section.
1. Tests for pesticides intended solely for
indoor application would be required on a
case-by-case basis, depending on use pattern,
production volume, and other pertinent factors.
2. The preferred species for the avian oral
study is either the upland game or waterfowl. The preferred species for the avian inhalation toxicity/pathogenicity study and
the avian chronic toxicity/pathogenicity
study is the upland game. There is also the
option to test the passerine if there is a concern. The coldwater fish is preferred for
freshwater fish testing. However, two species
(coldwater and warmwater fish species are
the preferred species) must be tested for uses
involving direct freshwater exposure. Freshwater invertebrate testing is also required.
3. Data required when the nature of the microbial pesticide and/or its toxins indicates
potential pathogenicity to birds.
4. Required on a case-by-case basis if results of tests required by § 158.2140 are inadequate or inappropriate for assessment of
hazards to wild mammals.
5. Required when there will be significant
exposure to aquatic organisms (fish and invertebrates).
6. Required if the product is intended for
direct application into the estuarine or marine environment or expected to enter this
environment in significant concentrations
because of expected use or mobility pattern.
7. Required if the microbial pesticide is
taxonomically related to a known plant
pathogen.
8. Data are not required unless an active
microbial ingredient controls the target insect pest by a mechanism of infectivity; i.e.,
may create an epizootic condition in nontarget insects.
9. Required if toxic or pathogenic effects
are observed in one or more of the following
tests for microbial pesticides:
i. Avian acute oral or avian inhalation
studies.
ii. Wild mammal studies.
iii. Nontarget plant studies (terrestrial).
iv. Honey bee studies.
v. Nontarget insect studies.
10. Required when toxic or pathogenic effects are observed in any of the following
Tier I tests for microbial pest control agents:
i. Freshwater fish studies.
ii. Freshwater invertebrate studies.
iii. Nontarget plant studies (aquatic).
11. Required if product is applied on land or
in fresh water or marine/estuarine environments and toxic or pathogenic effects are observed in any of the following Tier I tests for
microbial pesticides:
i. Estuarine and marine animal toxicity
and pathogenicity.

ii. Plant studies - estuarine or marine species.
12. An appropriate dose-response toxicity
test is required when toxic effects on nontarget terrestrial wildlife or aquatic organisms
(including plants) are reported in one or
more Tier I tests and results of Tier II tests
indicate exposure of the microbial agent to
the affected nontarget terrestrial wildlife or
aquatic organisms. The protocols for these
tests may have to be modified in accordance
with results from the nontarget organism
and environmental expression studies.
13. Required when one or more of the following are present:
i. Pathogenic effects are observed in Tier I
avian studies.
ii. Tier II environmental expression testing
indicate that long-term exposure of terrestrial animals is likely.
14. Required when product is intended for
use in water or expected to be transported to
water from the intended use site, and when
pathogenicity or infectivity was observed in
Tier I aquatic studies.
15. Required if, after an analysis of the microbial pesticide’s ability to survive and
multiply in the environment and what ecological habitat it would occupy, the intended
use patterns, and the results of previous nontarget organisms and environmental expression tests, it is determined that use of the
microbial agent may result in adverse effects
on the nontarget organisms in aquatic environments. Testing is to determine if applications of the microbial pest control would be
expected to disrupt the balance of populations in the target ecosystem.
16. Tier IV studies may be conducted as a
condition of registration as post-registration
monitoring if the potential for unreasonable
adverse effects appears to be minimal during
that period of use due to implementation of
mitigation measures.
17. Required when both of the following
conditions occur:
i. Pathogenic effects observed at actual or
expected field residue exposure levels are reported in Tier III; and
ii. The Agency determines that quarantine
methods would not prevent the microbial
pesticide from contaminating areas adjacent
to the test area.
18. Short term simulated or actual field
studies are required when it is determined
that the product is likely to cause adverse
short-term or acute effects, based on consideration of available laboratory data, use patterns, and exposure rates.
19. Data from a long-term simulated field
test (e.g., where reproduction and growth of
confined populations are observed) and/or an
actual field test (e.g., where reproduction
and growth of natural populations are observed) are required if laboratory data indicate that adverse long-term, cumulative, or

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Environmental Protection Agency

§ 158.2171

life-cycle effects may result from intended
use.
20. Since test standards would be developed
on a case-by-case basis, consultation with
the Agency and development of a protocol is
advised before performing these Tier IV
studies.

(b) Additional data requirements for genetically modified microbial pesticides.
Additional requirements for genetically modified microbial pesticides
may include but are not limited to: genetic engineering techniques used; the
identity of the inserted or deleted gene
segment (base sequence data or enzyme
restriction map of the gene); information on the control region of the gene
in question; a description of the ‘‘new’’
traits or characteristics that are intended to be expressed; tests to evaluate genetic stability and exchange; and
selected Tier II environmental expression and toxicology tests.

§ 158.2160 Microbial pesticides product
performance data requirements.
Product performance data must be
developed for all microbial pesticides.
However, the Agency has waived all requirements to submit efficacy data unless the pesticide product bears a claim
to control public health pests, such as
pest microorganisms infectious to man
in any area of the inanimate environment or a claim to control vertebrates
(including but not limited to: rodents,
birds, bats, canids, and skunks) or invertebrates (including but not limited
to: mosquitoes and ticks) that may directly or indirectly transmit diseases
to humans. However, each registrant
must ensure through testing that his
products are efficacious when used in
accordance with label directions and
commonly accepted pest control practices. The Agency reserves the right to
require, on a case-by-case basis, submission of efficacy data for any pesticide product registered or proposed
for registration.

§ 158.2171 Experimental use permit
microbial pesticides product analysis data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the product analysis data requirements and the substance to be
tested for a particular microbial pesticide. Specific conditions, qualifications, or exceptions to the designated
test are identified in (d) of this section,
and the test notes appear in paragraph
(e) of this section.
(b)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to
the individual tests in the following
table:
(c) Table. The following table shows
the data requirements for experimental
use permit microbial pesticides product analysis. The test notes are shown
in paragraph (d) of this section.

§ 158.2170 Experimental use permit
data requirements—microbial pesticides.
(a) For all microbial pesticides. (1) The
following § 158.2171 through § 158.2174
identify the data requirements that are
required to support experimental use
permits for microbial pesticides. The
variations in the test conditions are
identified within the test notes.
(2) For general information on the
data
requirement
tables,
see
§ 158.2110(a)(2)-(4).

TABLE—EUP MICROBIAL PRODUCT ANALYSIS DATA REQUIREMENTS
Guideline
Number

All Use Patterns

Data Requirement

Test Substance
Test Notes
MP

EP

wreier-aviles on DSK7SPTVN1PROD with CFR

Product Chemistry and Composition
885.1100

Product Identity

R

MP

EP

--

885.1200

Manufacturing process

R

TGAI and MP

TGAI and EP

1, 2

Deposition of a sample in a nationally
recognized culture collection

R

TGAI

TGAI

--

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§ 158.2172

40 CFR Ch. I (7–1–11 Edition)

TABLE—EUP MICROBIAL PRODUCT ANALYSIS DATA REQUIREMENTS—Continued
Guideline
Number
885.1300

Data Requirement

Test Substance

All Use Patterns

MP

EP

R

TGAI and MP

TGAI and EP

2

Discussion of formation of unintentional
ingredients

Test Notes

Analysis and Certified Limits
885.1400

Analysis of samples

R

TGAI and MP

TGAI and EP

2, 3

885.1500

Certification of limits

R

MP

EP

--

Physical and Chemical Characteristics
830.6302

Color

R

TGAI

TGAI

--

830.6303

Physical state

R

TGAI

TGAI

--

830.6304

Odor

R

TGAI

TGAI

--

830.6313

Stability to normal and elevated temperatures, metals and metal ions

R

TGAI

TGAI

--

830.6317

Storage stability

R

TGAI and MP

TGAI and EP

--

830.6319

Miscibility

R

MP

EP

4

830.6320

Corrosion Characteristics

R

MP

EP

5

830.7000

pH

R

TGAI

TGAI

--

830.7100

Viscosity

R

MP

EP

6

830.7300

Density/relative density/bulk density (specific gravity)

R

TGAI

TGAI

--

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(d) Test notes. The following test
notes are applicable to the data requirements for experimental use permit microbial pesticides product analysis as referenced in the last column of
the table contained in paragraph (c) of
this section.
1. If an experimental use permit is being
sought, and if the pesticide is not already
under full-scale production, a schematic diagram and/or description of the manufacturing process suffices.
2. If an experimental use permit is being
sought, and if the product is not already
under full-scale production, a discussion of
unintentional ingredients is required to be
submitted to the extent this information is
available.
3. Required to support registration of each
manufacturing-use product and end-use product. This analysis must be conducted at the
point in the production process after which
there would be no potential for microbial
contamination or microbial regrowth. For
pesticides in the production stage, a preliminary product analytical method and data
would suffice to support an experimental use
permit. For full registration, generally an
analysis of samples is a compilation of

batches, over a period of time, depending on
the frequency of manufacturing.
4. Only required for emulsifiable liquid
forms of microbial pesticides.
5. Required when microbial pesticides are
packaged in metal, plastic, or paper containers.
6. Only required for liquid forms of microbial pesticides.

§ 158.2172 Experimental use permit
microbial pesticides residue data
requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the residue chemistry data
requirements and the substance to be
tested for a particular microbial pesticide. Specific conditions, qualifications, or exceptions to the designated
test appear in (d) of this section, and
the procedures appear in paragraph (e)
of this section.
(b)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; All=All

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Environmental Protection Agency

§ 158.2173

of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (d) of this section, and apply to
the individual tests in the following
table:
(c) Table. The following table shows
the data requirements for experimental
use permit microbial pesticides residue. The test notes are shown in paragraph (d) of this section.
TABLE—EUP MICROBIAL PESTICIDES RESIDUE
DATA REQUIREMENTS

Guideline
Number

Data Requirement

All
Use
Patterns

Test
Substance
Data to
Support
MP or
EP

Test
Notes

885.2100

Chemical Identity

CR

EP

1

885.2200

Nature of the Residue
in plants

CR

EP

1

885.2250

Nature of the Residue
in animals

CR

EP

1

885.2300

Analytical methods plants

CR

TGAI

1

885.2350

Analytical methodsanimals

CR

TGAI

1

885.2400

Storage Stability

CR

EP

1

885.2500

Magnitude of residue
in plants

CR

EP

1

885.2550

Magnitude of residues
in meat, milk, poultry, eggs

CR

EP

1

885.2600

Magnitude of residues
in potable water,
fish, and irrigated
crops

CR

EP

1

(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the toxicology data requirements for a particular microbial pesticide product. Notes that apply to an
individual test and include specific
conditions, qualifications, or exceptions to the designated test are listed
in paragraph (d) of this section.
(b)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (d) of this section, and apply to
the individual tests in the following
table:
(c) Table. The following table shows
the data requirements for microbial
pesticide toxicology. The test notes are
shown in paragraph (d) of this section.
TABLE—EUP MICROBIAL PESTICIDES
TOXICOLOGY DATA REQUIREMENTS
Guideline
Number

(d) Test notes. The following test note
is applicable to the data requirements
for experimental use permit microbial
pesticides residue as referenced in the
last column of the table contained in
paragraph (c) of this section.

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§ 158.2173 Experimental use permit
microbial pesticides toxicology data
requirements table.

1. Required when the results of testing:
i. Indicate the potential to cause adverse
human health effects or the product characterization indicates the microbial pesticide
has a significant potential to produce a
mammalian toxin; and
ii. The use pattern is such that residues
may be present in or on food or feed crops.

Data Requirement

All
Use
Patterns

Test
Substance

Test
Notes

885.3050

Acute oral toxicity/
pathogenicity

R

TGAI

1

885.3150

Acute pulmonary toxicity/pathogenicity

R

TGAI

--

885.3200

Acute injection toxicity/pathogenicity/
(intravenous)
Acute injection toxicity/pathogenicity/
(intraperitoneal)

R

TGAI

2

885.3400

Hypersensitivity incidents

R

All

3

885.3500

Cell culture

R

TGAI

4

870.1100

Acute oral toxicity

R

MP, EP

1, 5

870.1200

Acute dermal toxicity

R

MP, EP

5

870.1300

Acute inhalation toxicity

R

MP, EP

5, 6

870.2400

Acute eye irritation

R

MP, EP

5

870.2500

Primary dermal irritation

CR

MP, EP

5

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§ 158.2174

40 CFR Ch. I (7–1–11 Edition)

(d) Test notes. The following test
notes are applicable to the data requirements for experimental use permit microbial pesticides toxicology as
referenced in the last column of the
table contained in paragraph (c) of this
section:

§ 158.2174 Experimental use permit
microbial pesticides nontarget organisms and environmental fate
data requirements table.
(a) General. Sections 158.100 through
158.130 describe how to use this table to
determine the terrestrial and aquatic
nontarget organisms data requirements for a particular microbial pesticide product. Notes that apply to an
individual test including specific conditions, qualifications, or exceptions to
the designated test are listed in paragraph (e) of this section.
(b) Use patterns. Aquatic uses include:
food and feed, nonfood uses (e.g., outdoor, residential, and industrial). Terrestrial uses include: Food, Feed, NonFood, Forestry, Residential outdoor,
greenhouse (food and food), Indoor
(food and nonfood), and Industrial.
(c)
Key.
R=Required;
CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use
product;
TGAI=Technical
grade of the active ingredient; All=All
of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (e) of this section, and apply to
the individual tests in the following
table:
(d) Table. The following table shows
the data requirements for experimental
use permit microbial pesticides nontarget organisms and environmental fate.
The test notes are shown in paragraph
(e) of this section.

1. The acute oral toxicity/pathogenicity
study is required to support the TGAI. However, it can be combined with the unit dose
portion of the acute oral toxicity study, with
an EP or MP test material to fulfill the requirement for the TGAI and the MP or EP in
a single study, if the new protocol is designed to address the endpoints of concern.
2. Data not required for products whose active ingredient is a virus. For test materials
whose size or consistency may prevent use of
an intravenous injection, the intraperitoneal
injection procedure may be employed.
3. Hypersensitivity incidents, including
immediate type and delayed type reactions
of humans or domestic animals occur during
the testing or production of the TGAI, MP,
or EP, or are otherwise known to the applicant must be reported if they occur.
4. Data must be submitted only for products whose active ingredient is a virus.
5. The 870 series studies for the MP and EP
are intended to provide data on the acute
toxicity of the product. Waivers for any or
all of these studies may be granted when the
applicant can demonstrate that the combination of inert ingredients is not likely to pose
any significant human health risks. Where
appropriate, the limit dose approach to testing is recommended.
6. Required when the product consists of,
or under conditions of use that would result
in an inhalable material (e.g., gas, volatile
substances, or aerosol particulate).

TABLE—EUP MICROBIAL PESTICIDES NONTARGET ORGANISMS AND ENVIRONMENTAL FATE DATA
REQUIREMENTS
Use Patterns
Terrestrial

wreier-aviles on DSK7SPTVN1PROD with CFR

Guideline
Number

Aquatic

Data Requirement

Food/
Feed/
Nonfood
Food/
Feed

Nonfood

Forestry

Resi
dential

Greenhouse

Indoor

Outdoor

Food/
Nonfood

Food/
Nonfood

Industrial

Test
Substance

Test
Notes

885.4050 ...

Avian oral
toxicity

NR

R

R

R

R

NR

NR

NR

TGAI

1, 2

885.4200 ...

Freshwater fish toxicity/pathogenicity

NR

R

R

R

NR

NR

NR

NR

TGAI

1, 2,
3

885.4240 ...

Freshwater invertebrate toxicity/pathogenicity

NR

R

R

R

NR

NR

NR

NR

TGAI

1, 2,
3

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Environmental Protection Agency

Pt. 159

TABLE—EUP MICROBIAL PESTICIDES NONTARGET ORGANISMS AND ENVIRONMENTAL FATE DATA
REQUIREMENTS—Continued
Use Patterns
Terrestrial
Guideline
Number

Aquatic

Data Requirement

Food/
Feed/
Nonfood

Greenhouse

Indoor

Outdoor

Food/
Nonfood

Food/
Nonfood

Industrial

Test
Substance

Test
Notes

Food/
Feed

Nonfood

NR

NR

NR

R

NR

NR

NR

NR

TEP

1, 4

885.4300 ...

Nontarget plant
testing

885.4340 ...

Nontarget insect testing

R

R

R

R

NR

NR

NR

NR

TGAI

1, 5

885.4380 ...

Honey bee testing

R

R

R

R

NR

NR

NR

NR

TGAI

1

(e) Test notes. The following test
notes are applicable to the data requirements for microbial pesticides
nontarget organism and environmental
fate as referenced in the last column of
the table contained in paragraph (d) of
this section.

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Forestry

Resi
dential

1. Tests for pesticides intended solely for
indoor application would be required on a
case-by-case basis, depending on use pattern,
production volume, and other pertinent factors. Tests to support EUP’s are based on the
application timing and acreage.
2. The preferred species for the avian oral
study is either the upland game or waterfowl. The preferred species for the avian inhalation toxicity/pathogenicity study and
the avian chronic toxicity/pathogenicity
study is the upland game. There is also the
option to test a passerine species if there is
a concern. The coldwater fish is preferred for
freshwater fish testing. However, two species
(coldwater and warmwater fish are the preferred species) must be tested for uses involving direct freshwater exposure. Freshwater invertebrates are preferred for invertebrate testing.
3. Required when there will be significant
exposure to aquatic organisms (fish and invertebrates).
4. Required if the microbial pesticide is
taxonomically related to a known plant
pathogen.
5. Data are not required unless an active
microbial ingredient controls the target insect pest by a mechanism of infectivity; i.e.,
may create an epizootic condition in nontarget insects.

Subpart W—Antimicrobial
Pesticides [Reserved]
§ 158.2200

[Reserved]

Subparts X–Z [Reserved]
§§ 158.2300–158.2500

[Reserved]

PART 159—STATEMENTS OF
POLICIES AND INTERPRETATIONS
Subparts A–C [Reserved]
Subpart D—Reporting Requirements for
Risk/Benefit Information
Sec.
159.152 What the law requires of registrants.
159.153 Definitions.
159.155 When information must be submitted.
159.156 How information must be submitted.
159.158 What information must be submitted.
159.159 Information obtained before promulgation of the rule.
159.160 Obligations of former registrants.
159.165 Toxicological and ecological studies.
159.167 Discontinued studies.
159.170 Human epidemiological and exposure studies.
159.178 Information on pesticides in or on
food, feed, or water.
159.179 Metabolites, degradates, contaminants, and impurities.
159.184 Toxic or adverse effect incident reports.
159.188 Failure of performance information.
159.195 Reporting of other information.
AUTHORITY: 7 U.S.C. 136–136y.
SOURCE: 63 FR 49388, Sept. 19, 1997, unless
otherwise noted.

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