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pdfPerfluoroalkyl and Polyfluoroalkyl Substances (PFAS)
Exposure Assessment Technical Tools
Centers for Disease Control and Prevention (CDC)
Agency for Toxic Substances and Disease Registry (ATSDR)
July 2017
Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS)
Exposure Assessment Technical Tools
Table of Contents
Section
PFAS Exposure Assessment Framework: Using Serum Testing as a Component for Assessing Exposure
in Communities with Drinking Water Contaminated with Per- or Polyfluoroalkyl Substances (PFAS)
Page Number
I-1 – I-7
PFAS Exposure Assessment Technical Tools: Introduction
II-1 – II-3
PFAS Exposure Assessment in a Community: Sampling Strategy and Data Analysis Assistance
III-1 – III-8
PFAS Exposure Assessment Question Bank: Adults
IV-1 – IV-9
PFAS Exposure Assessment Question Bank: Child
V-1 – V-8
PFAS Exposure Assessment: Invitation Letter and Consent/Assent Forms
VI-1 – VI-6
PFAS Exposure Assessment: Result Letters for Participants
VII-1 – VII-11
PFAS Exposure Assessment: Serum Collection Protocol
VIII-1 – VIII-3
PFAS Exposure Assessment: Non-Federal Laboratories That Measure PFAS
IX-1
Laboratory Procedure Manual
X-1 – X-42
PFAS Exposure Assessment: Know your Audiences - Audience outreach materials for environmental
exposures
XI-1 – XI-6
The family tree of per- and polyfluoroalkyl substances (PFAS) for environmental health professionals
XII-1 – XII-2
The family tree of perfluoroalkyl and polyfluoroalkyl substances (PFAS)
XIII-1 – XIII-2
An Overview of Perfluoroalkyl and Polyfluoroalkyl Substances and Interim Guidance for Clinicians
Responding to Patient Exposure Concerns
XIV-1 – XIV-11
XV-1 – XV-2
PFAS ToxGuide for Perfluoroalkyls
Environmental Protection Agency References
XVI-1
Version Control Table
Version Number
3 (Current)
2
1
Modified By
NCEH/ATSDR
NCEH/ATSDR
NCEH/ATSDR
Modifications Made
Table of Contents Added
PFAS Family Trees Added
Initial Version
Date Modified
7/18/2017
6/19/2017
6/1/2017
PFAS Exposure Assessment Framework
Using Serum Testing as a Component for Assessing Exposure
in Communities with Drinking Water Contaminated with Peror Polyfluoroalkyl Substances (PFAS)
This framework document is designed to help state health departments when measuring and evaluating
community exposures to per- or polyfluoroalkyl substances (PFAS) in drinking water.
In this framework, a statistically based approach to recruit, measure, and evaluate community exposures to
PFAS includes:
Biomonitoring (serum testing),
Identifying exposure source(s), and
Administering questionnaires to provide an assessment of exposure source(s) along with the
magnitude and distribution of exposure in the community.
NOTE: This framework document does not assist in determining whether biomonitoring is appropriate or necessary. The
decision to conduct biomonitoring should be based on specific circumstances of affected communities along with
considerations related to human subjects’ protections. Health departments need to consider that the approach described
here will require identification of a funding source and specific staff expertise. CDC and ATSDR can provide technical
assistance to health departments to help develop and execute a biomonitoring effort. Finally, this framework may not be
applicable to all proposed biomonitoring efforts; that is, this framework should not preclude other approaches to
biomonitoring.
Centers for Disease Control and Prevention (CDC)
Agency for Toxic Substances and Disease Registry (ATSDR)
July 2017
I-1
PFAS Exposure Assessment Framework
Introduction
CDC’s National Center for Environmental Health (NCEH) and the Agency for Toxic Substances and Disease Registry
(ATSDR) work to protect communities from exposure to harmful chemicals.
PFAS have been detected in numerous public and private drinking water supplies throughout the United States.
State and local health departments requested CDC and ATSDR’s assistance on how to best assess exposure to
PFAS in communities where PFAS contamination of water is known or reasonably expected.
CDC and ATSDR understand and acknowledge that individuals may want to know the level of PFAS in their blood.
However, conducting biomonitoring on all individuals in a community may not be feasible. The statistically based,
scientific approach outlined in this framework allows for a practical and feasible approach for assessing potential
community exposures to PFAS and will provide estimated serum PFAS levels in the community members who
were not tested. If the state health or other entity opts for an alternate approach, we suggest use of statistical
participant selection/recruitment methods to ensure results can be generalized to the affected community.
8- Step Approach to Assess Community Exposures to PFAS1,2
CDC/ATSDR suggest the following approach to assess community exposure to PFAS from contaminated drinking
water.
1) Evaluate existing data on PFAS in drinking water and assess potential current or past community exposure.
Consider whether additional exposure pathway data are important (e.g., consumer products, dietary
sources including fish from PFAS-contaminated water bodies, crops grown in fields amended with
contaminated biosolids, and occupational exposure). ATSDR’s Public Health Assessment Guidance
Manual provides helpful information for evaluating existing data.
2) If PFAS was or is expected to be elevated in drinking water compared to EPA’s Lifetime Health Advisory
(HA) or state-specific threshold levels, identify variables expected to be associated with increased
exposure within the population. Examples of variables can include people in a particular geographic area
where elevated PFAS water concentrations existed in the past or currently exist, or people who have been
drinking contaminated water over a long period of time, etc. Develop a protocol that describes how these
factors will be assessed, and include provision of the variables in steps number 3 through 7 below.2
3) Develop and implement a communications plan.
4) Develop a questionnaire that includes demographics, geographic information, and factors influencing
exposure to PFAS in water and other potential sources of PFAS. The CDC/ATSDR PFAS Environmental
Assessment Technical Tools (PEATT) provide a questionnaire example with core questions.
5) Identify laboratories (with appropriate quality control assurance) capable of performing water PFAS
measurements using EPA Method 537. Likewise, identify a quality laboratory to perform serum PFAS
measurements. The PEATT provides serum sample collection, storage, and analysis information.
1
A detailed description and approach is provided in the NCEH/ATSDR PFAS Environmental Assessment Technical Tools
(PEATT) for PFAS evaluations:
2
Human subjects’ protection policies and procedures should be followed.
I-2
PFAS Exposure Assessment Framework
6) Develop a statistically based, community sampling design that will provide information about the range
of PFAS exposures in an affected community. Ensure that higher exposure groups and other subgroups of
interest are adequately sampled.3
a) People likely to have higher exposure to PFAS
b) Relevant demographic groups (e.g., children and adults; males and females; race/ethnic groups)
7) Administer the questionnaire, collect blood samples, and, if exposures are ongoing, collect home tap
water or other appropriate environmental samples.
8) Analyze data from step 6 to do the following.
a) Determine PFAS blood level estimates and the uncertainty for those estimates for the community
as a whole and for subgroups such as:
o Groups considered at risk for higher exposures
o Children and adults
o Males and females
o Race/ethnic groups (if relevant)
o Persons in different economic strata
o Different neighborhoods
o Different drinking water sources
o Other
b) Using questionnaire data, water PFAS information, and serum PFAS levels from the targeted
community exposure assessment, develop the best predictive multivariate model of serum PFAS
levels. This model can assist in predicting serum PFAS levels for persons who have water PFAS
measurements but have not had their blood tested.
Additional Considerations
Pilot sampling. A community may be particularly concerned about exposure and want to know the magnitude of
their PFAS body burden right away. A preliminary or pilot investigation may be useful while the exposure
assessment planning steps described above are ongoing. If so, based on known exposure sources and length of
time exposed, select a small number of individuals (e.g., 30–50) thought to have the highest exposures. While not
a statistically based sample, the results may provide rapid preliminary information on a subset of community
members suspected to be in the upper range of serum PFAS levels. These results may inform the communitybased sampling design.
NOTE: This pilot sample is not representative of the general community and, therefore, is not meant to be a substitute for
the statistically based, community sample described above in the 8-step approach.
Exposure and health effects. The approaches described above are exposure assessments and not epidemiologic
studies. A study may include a comparison group, an expanded health effects questionnaire, additional laboratory
data relating to potential health effects and, potentially, a medical records review. However, biomonitoring results
from the community exposure assessment may be compared to biomonitoring results in exposure/health effects
studies done in other population groups.
3
The approach described in the NCEH/ATSDR PEATT is appropriate for exposure assessment of a general population with
known or suspected exposure. Oversampling of subgroups that can be accomplished by simple stratification is also included.
However, for some subgroups of interest, such as children or pregnant women, consider more complex statistical sampling
approaches designed to measure blood PFAS exposure levels of a targeted population of interest.
I-3
PFAS Exposure Assessment Framework
CDC and ATSDR role. If requested, CDC and ATSDR will provide technical assistance to health departments to
develop and execute this exposure assessment approach.
Answers to Commonly Asked Question about PFAS and Biomonitoring
A scientifically designed community investigation allows for an assessment of the community’s exposure
profile in a timely manner (e.g., typically less than about two years for the community report, depending
on logistics, funding, etc.). This includes information about high and low exposure estimates, PFAS levels
in groups of special concern (e.g., children), and how personal factors such as drinking water source,
length of residence, age, and occupation may affect results.
The information derived from this approach can potentially be used to design a health study to monitor
for possible health effects in these groups, even if not all of the individuals within these groups
participated in biomonitoring.
What advice can be given to individuals who were not selected for biomonitoring?
Whether selected or not for biomonitoring, individuals should take practical steps to reduce current
exposure to PFAS. For example, use alternative water sources if advised by the local health officials.
The community biomonitoring report should provide information about the range of serum PFAS levels
and may provide information on how the levels vary among different population groups in the community.
From these data, people who were not tested should be able to get an estimate of their likely serum PFAS
level.
If for some reason an individual still desires personal serum PFAS results, they should be encouraged to
seek advice from their health care provider and other professionals (e.g., regional Pediatric Environmental
Health Specialty Units or PEHSUs).54
How can individual serum PFAS concentrations be interpreted?
Serum PFAS concentrations for individuals 12 years of age and older can be compared to U.S. population results
from CDC’s National Health and Nutrition Examination Survey (NHANES). Serum PFAS have been measured in
NHANES since 1999. As part of the ongoing NHANES, serum PFAS are measured in a one third sample of
participants, ages 12 and older. Population-based reference values are available by age group (12-19 years, 20+
years), sex, and race/ethnicity (non-Hispanic black, non-Hispanic white, Mexican American). Beginning in 2011,
the racial/ethnic groups of Asian (e.g., non-Hispanic Asian) and all Hispanics were added. The most recent survey
results (2011-2014) are included in Appendix A.
Typically, the 95th percentile is used as the upper end of the reference range for the U.S. population. For children
younger than 12 years, no national reference values exist.65
Biomonitoring sampling results cannot predict current or future health outcomes or diseases. That is, the results
are not currently clinically actionable. Further, the biomonitoring results will not likely result in any different
medical evaluations than just knowing or assuming that an individual was exposed to PFAS in contaminated
drinking water above EPA health advisory levels in addition to other possible exposure sources (e.g., diet,
occupation).There are no health-based screening levels for specific PFAS that clinicians can compare to the
5
Clinical guidance for healthcare providers can be found at: http://www.atsdr.cdc.gov/pfc/index.html
Some comparisons for children less than 12 years of age are available in the literature from studies in specific communities.
These are not generalizable to other communities or the United States.
6
5
I-4
PFAS Exposure Assessment Framework
concentrations measured in blood samples. As a result, interpreting PFAS concentrations in individuals is limited
in its use.
For More Information
For more information about PFAS, toxicity and exposure assessment, and clinical guidance for healthcare
providers, visit the CDC/ATSDR PFAS web page: http://www.atsdr.cdc.gov/pfc/index.html
For more information about biomonitoring and PFAS reference ranges for the U.S. population since 2001, visit
CDC’s national biomonitoring program web page: http://www.cdc.gov/biomonitoring/ and the Exposure Report
web page: https://www.cdc.gov/exposurereport/
I-5
PFAS Exposure Assessment Framework
Appendix A. Serum PFOS and PFOA in the U.S. Population, NHANES 2011-2014
Serum Perfluorooctanoic acid (PFOA) (2011 - 2014)‡
Geometric mean and selected percentiles of serum concentrations (in µg/L) for the U.S. population from the National Health
and Nutrition Examination Survey.
Total
Survey
years‡
11-12
13-14‡
Geometric
mean
Selected percentiles
(95% conf. interval)
50th
2.08
2.07
2.08
1.94
(1.95-2.22)
11-12
13-14‡
1.80
1.66
(1.71-1.91)
11-12
13-14‡
2.12
1.98
(1.98-2.28)
11-12
13-14‡
2.37
2.29
(2.22-2.53)
11-12
13-14‡
1.84
1.66
(1.68-2.01)
11-12
13-14‡
1.66
1.36
(1.37-2.02)
11-12
13-14‡
1.80
1.52
(1.71-1.90)
11-12
13-14‡
2.25
2.20
(2.05-2.47)
11-12
13-14‡
1.70
1.45
(1.48-1.95)
11-12
13-14‡
2.08
1.97
(1.83-2.36)
(1.76-2.14)
( 95% confidence interval)
(1.96-2.26)
(1.87-2.20)
75th
3.03
3.07
(2.76-3.27)
(2.67-3.37)
90th
4.35
4.27
(3.82-4.85)
(3.57-5.17)
95th
5.68
5.57
(5.02-6.49)
(4.60-6.27)
Sample
size
1904
2165
Age group
12-19 years
20 years and older
(1.50-1.84)
(1.79-2.19)
1.74
1.67
(1.67-1.89)
2.16
2.07
(2.01-2.33)
2.38
2.37
(2.26-2.56)
1.78
1.67
(1.62-1.98)
1.71
1.37
(1.32-2.23)
1.94
1.67
(1.76-2.09)
2.25
2.27
(1.98-2.48)
1.79
1.47
(1.59-1.95)
2.21
1.87
(2.04-2.27)
(1.37-1.97)
(1.90-2.27)
2.41
2.20
(2.17-2.62)
3.15
3.17
(2.90-3.36)
3.25
3.27
(3.00-3.56)
2.65
2.67
(2.34-3.14)
2.43
1.97
(1.98-2.98)
2.82
2.57
(2.65-2.95)
3.21
3.37
(2.90-3.50)
2.46
2.10
(2.15-2.91)
2.92
2.97
(2.55-3.45)
(1.97-2.57)
(2.77-3.47)
2.93
2.87
(2.68-3.19)
4.64
4.47
(3.93-5.25)
4.61
4.67
(4.11-5.02)
3.91
3.77
(3.36-4.99)
3.38
2.70
(2.43-4.48)
3.94
3.60
(3.51-4.40)
4.68
4.77
(3.95-5.35)
3.60
3.07
(2.95-4.48)
4.66
4.67
(3.42-5.79)
(2.57-3.40)
(3.70-5.27)
3.59
3.47
(2.93-4.25)
5.94
5.60
(5.34-7.45)
5.62
5.67
(4.85-6.20)
5.68
5.07
(4.33-8.45)
4.08
3.17
(2.98-6.15)
5.11
4.60
(4.40-5.79)
6.20
5.77
(5.34-7.74)
4.70
3.47
(3.87-5.94)
5.79
5.90
(4.93-8.91)
(2.87-4.37)
(4.67-6.40)
344
401
1560
1764
Gender
Males
Females
(2.09-2.50)
(1.48-1.87)
(2.17-2.57)
(1.47-1.87)
(2.87-3.60)
(2.27-3.07)
(3.77-5.60)
(3.37-4.70)
(4.67-6.27)
(4.07-6.70)
966
1031
938
1134
Race/ethnicity
Mexican Americans
Non-Hispanic blacks
Non-Hispanic whites
All Hispanics
Asians
(1.25-1.47)
(1.34-1.73)
(1.91-2.52)
(1.33-1.59)
(1.75-2.23)
Limit of detection (LOD, see Data Analysis section) for Survey year 11-12 is 0.1.
‡See
Calculation
of
PFOS
and
PFOA
as
the
(1.27-1.47)
(1.37-1.97)
(1.97-2.67)
(1.37-1.67)
(1.67-2.27)
Sum
of
Isomers
(1.87-2.10)
(2.17-2.97)
(2.77-3.77)
(1.97-2.40)
(2.47-3.57)
for
additional
(2.40-3.10)
(3.07-4.50)
(3.77-5.67)
(2.67-3.27)
(3.97-5.77)
information
about
(2.57-3.77)
(3.40-5.77)
(4.80-6.87)
(3.17-3.97)
(5.00-6.40)
Survey
years
211
332
485
455
666
861
406
537
291
234
2013-2014.
Source:
The National Report on Human Exposure to Environmental Chemicals, Updated Tables, December 2016. Complete
data tables for this and other chemicals measured in the U.S. population are available at:
https://www.cdc.gov/exposurereport/.
I-6
PFAS Exposure Assessment Framework
Serum Perfluorooctane sulfonic acid (PFOS) (2011 - 2014)‡
Geometric mean and selected percentiles of serum concentrations (in µg/L) for the U.S. population from the National Health
and Nutrition Examination Survey.
Total
Survey
years‡
11-12
13-14‡
Geometric
mean
Selected percentiles
(95% conf. interval)
50th
6.53
5.20
6.31
4.99
(5.84-6.82)
11-12
13-14‡
4.16
3.54
(3.70-4.68)
11-12
13-14‡
6.71
5.22
(6.24-7.20)
11-12
13-14‡
7.91
6.36
(7.19-8.70)
11-12
13-14‡
5.10
3.96
(4.70-5.53)
11-12
13-14‡
4.79
3.47
(4.07-5.64)
11-12
13-14‡
6.35
5.32
(5.41-7.46)
11-12
13-14‡
6.71
5.31
(6.15-7.32)
11-12
13-14‡
4.63
3.51
(3.86-5.55)
11-12
13-14‡
7.10
6.18
(5.80-8.68)
(4.50-5.52)
( 95% confidence interval)
(5.99-7.13)
(4.80-5.70)
75th
10.5
8.70
(9.78-11.1)
(7.90-9.40)
90th
15.7
13.9
(14.7-17.5)
(11.9-15.5)
95th
21.7
18.5
(19.3-23.9)
(15.4-22.0)
Sample
size
1904
2165
Age group
12-19 years
20 years and older
(3.17-3.96)
(4.70-5.81)
4.11
3.60
(3.48-4.65)
7.07
5.60
(6.65-7.52)
8.31
6.40
(7.35-9.15)
5.27
4.00
(4.67-5.64)
5.18
3.70
(3.92-6.33)
6.57
5.30
(5.71-7.65)
6.83
5.70
(6.07-7.73)
5.18
3.70
(4.41-6.19)
7.53
6.30
(5.96-9.25)
(3.10-4.20)
(5.10-6.00)
5.90
5.20
(5.14-7.25)
11.0
9.10
(10.4-11.9)
12.5
10.2
(11.4-13.5)
8.57
7.20
(7.87-9.30)
7.91
5.20
(6.18-9.48)
11.3
10.2
(9.74-13.9)
10.7
8.90
(9.89-12.2)
8.10
5.50
(6.64-9.78)
12.6
13.2
(10.8-17.0)
(4.60-6.20)
(8.20-10.2)
9.05
7.80
(6.49-10.8)
17.0
14.5
(15.3-18.5)
19.3
15.5
(15.7-21.4)
12.5
11.8
(11.0-14.9)
10.5
8.80
(8.50-12.6)
21.8
17.4
(13.9-31.3)
15.7
14.1
(14.8-18.1)
11.0
8.80
(9.96-12.6)
24.6
23.8
(19.1-33.3)
(7.00-8.90)
(12.9-16.1)
10.8
9.30
(8.52-14.2)
22.7
19.5
(20.4-24.8)
24.1
22.1
(22.2-28.5)
17.5
15.1
(14.9-20.5)
12.1
10.8
(10.0-14.4)
30.7
24.5
(21.6-45.1)
21.3
18.0
(18.7-23.5)
13.4
10.8
(11.5-16.1)
35.1
33.6
(26.4-42.3)
(7.90-11.7)
(15.8-23.0)
344
401
1560
1764
Gender
Males
Females
(5.62-7.20)
(3.60-4.35)
(5.70-7.30)
(3.60-4.60)
(8.70-11.5)
(6.40-7.70)
(13.2-19.8)
(9.70-13.6)
(16.7-26.9)
(13.9-17.3)
966
1031
938
1134
Race/ethnicity
Mexican Americans
Non-Hispanic blacks
Non-Hispanic whites
All Hispanics
Asians
(2.90-4.16)
(4.12-6.88)
(4.72-5.98)
(3.09-3.98)
(5.08-7.52)
Limit of detection (LOD, see Data Analysis section) for Survey year 11-12 is 0.2.
‡.See
Calculation
of
PFOS
and
PFOA
as
the
(3.00-4.40)
(4.30-6.80)
(5.10-6.40)
(3.20-4.20)
(5.00-7.90)
Sum
of
Isomers
(4.60-6.40)
(7.60-13.7)
(8.20-9.90)
(4.90-6.40)
(9.40-15.4)
for
additional
(6.40-10.3)
(12.4-24.5)
(12.2-15.6)
(8.00-9.70)
(15.2-33.9)
information
about
(9.20-11.8)
(16.3-39.7)
(15.5-20.4)
(9.70-12.1)
(20.1-69.0)
Survey
years
211
332
485
455
666
861
406
537
291
234
2013-2014.
Source:
The National Report on Human Exposure to Environmental Chemicals, Updated Tables, December 2016. Complete
data tables for this and other chemicals measured in the U.S. population are available at:
https://www.cdc.gov/exposurereport/.
I-7
Introduction
PFAS Exposure Assessment Technical Tools: Introduction
Per- or Polyfluoralkyl substances (PFAS) have been detected in drinking water supplies across the
United States, raising some concerns about possible health risks. One way to understand exposure to
PFAS is through biomonitoring. CDC/ATSDR created these tools to help state, local, tribal, and
territorial health departments conduct biomonitoring activities (when the principal source of PFAS
exposure is from drinking water).
Use of PFAS Has Decreased, But People are Still Exposed
Per- or polyfluoroalkyl substances (PFAS) are a large group of man-made chemicals that have been used since the
1950s. Use of some of these chemicals has greatly decreased in the United States over the last 10 years. Even
though PFAS is no longer manufactured in the United States, people can still be exposed because PFAS can be
found in certain drinking water sources, soil, food packaging and wrapping materials, homegrown vegetables
grown in contaminated soil or watered with contaminated water, and outdoor air in areas with frequent PFAS
use. PFAS can be found in certain consumer products such as stain resistant carpets, textiles and treated clothes.
Because of past episodes of environmental contamination, PFAS have been detected in numerous public and
private drinking water supplies throughout the United States. As a result, public health agencies may be
concerned about possible health risks from communities exposed to these drinking water supplies as well as other
sources of PFAS contamination. The US Environmental Protection Agency (EPA) established a health advisory level
of 70 parts per trillion for two PFAS chemicals (PFOA and PFOS—separately or combined) in drinking water
(https://www.epa.gov/ground-water-and-drinking-water/drinking-water-health-advisories-pfoa-and-pfos).
These values may be revised as the science of PFAS progresses or if new values of concern are created for other
PFAS. Finally, states may have their own advisory levels.
Blood Samples Can Help You Understand PFAS Exposure (with Limitations)
One way to better characterize exposures in people is the use of biomonitoring. Biomonitoring is the
measurement of the amount of a chemical inside the body from a blood or urine sample. PFAS biomonitoring is
currently performed using blood samples only. Results from PFAS biomonitoring activities can be used to better
understand exposures in a community or population, compare trends over time, provide a benchmark for
activities that further reduce exposure, and monitor public health interventions.
An important limitation of using biomonitoring for PFAS exposure is that currently, there are no health-based
screening levels for specific PFAS that clinicians can compare to the concentrations measured in blood samples.
As a result, interpreting PFAS concentrations in an individual is limited in its use. However, our knowledge of
these chemicals is advancing. Ongoing reassessment of new data will be necessary as progress is made in the
understanding of PFAS and their associated health effects.
This Toolkit Contains Protocols, Question Banks, Sample Letters, and More
This toolkit is intended to help state, local, Tribal, and territorial health departments conduct PFAS biomonitoring
activities should they choose to (with the assumption that the principal source of PFAS exposure is from drinking
water).
The toolkit contains the following components:
Biomonitoring sampling and analysis protocol
Laboratory biomonitoring sample collection and analysis protocols
II-1
Introduction
Water sampling protocols
Exposure and health effects question bank
Biomonitoring letters of interpretation, consent, and assent
Communication materials
Biomonitoring Sampling and Analysis Protocol
This section provides a step-by-step approach to create a one-stage cluster sample of households for
biomonitoring; calculate sample size using National Health and Nutrition Examination Survey (NHANES) national
population PFAS estimates; and analyze data. The simple approach of one-stage cluster sampling was selected
so that the biomonitoring results can be extrapolated to a local community.
Exposure and Health Effects Question Bank
This section contain questions to create adult and child exposure assessment questionnaires. CDC/ATSDR
designed the questions for current/long-term residents of a community where the primary suspected exposure
source for PFAS is or was drinking water.
The adult questions collect information on demographics, pregnancy status and breastfeeding history for females,
current drinking water habits, health conditions (see Appendix A), and occupational history. The child questions
additionally collect information on possible exposure at school/daycare. The bank also includes questions for
other community-specific exposure pathways (e.g., gardening in contaminated soil, fishing in contaminated water
bodies).
Biomonitoring Letters of Interpretation, Consent, and Assent
This section contain customizable templates for interpretation letters, informed consents, and assent documents.
The letter of interpretation is intended for participants who provided a blood sample for biomonitoring. It includes
reference ranges for the U.S. population ages 12 or older based on results from the 2011–12 National Health and
Nutrition Examination Survey (NHANES) and a customizable field for community results. Public health authorities
should check for up-to-date NHANES data that could be used for result comparison
(https://www.cdc.gov/exposurereport/). There is no reference data in NHANES for the 11 and younger age group;
however, limited data may be available in the scientific literature (instructions included in the letter).
Communications Materials
PFAS investigations to determine levels of risk or potential health effects can be complex and long-term rather
than immediate. Health departments share the common challenge of explaining the limitations of the
investigations, such as how much the science can actually show about the level of risk to a specific person, or to
their concerned communities. Effective communication can be helpful. This section includes items such as fact
sheets, frequently asked questions, audience outreach activities, and other materials to help inform the public
about PFAS.
Laboratory Biomonitoring Sample Collection and Analysis Protocols
This section contains the CDC PFAS laboratory manual/method and recommended serum collection procedures.
The measurement methods are technically difficult and require special equipment not available in most clinical or
hospital laboratories.
CDC is aware of several laboratories that measure PFAS, but does not endorse any specific laboratory. A list of
these laboratories is available upon request. The list does not imply a CDC endorsement, and CDC may not be
familiar with their operations or methods. In addition, the Association of Public Health Laboratories (APHL) may
be able to identify state laboratories that can measure PFAS. Information about APHL is available at
https://www.aphl.org/Pages/default.aspx.
II-2
Introduction
Appendix A: List of Potential PFAS-associated health conditions
This section provides the list of potential PFAS-associated health conditions or diseases based on the current
scientific literature. The list may not be all-inclusive as most studies have examined small numbers of PFAS and many
are cross-sectional studies. Investigators can use this list to create the health conditions section (Section C) based on
concerns from their communities and the current scientific literature. Investigators can also consult a health care
provider when developing the health conditions section.
Appendix B: Water Sampling Protocol
For a water sampling protocol, visit the U.S. Environmental Protection Agency’s (EPA) PFAS website
(https://www.epa.gov/pfas). This website provides information on EPA’s lab method recommended for water
testing—method #537, titled “Determination of Selected Perfluorinated Alkyl Acids in Drinking Water by Solid
Phase Extraction and Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS).”
EPA’s website also provides a technical advisory document, a general explanation, and questions and answers
regarding the methodology. For assistance with analysis and interpretation of water testing results, please contact
your
local
or
state
environmental
health
agencies
or
your
regional
EPA
office
(https://www.epa.gov/aboutepa/visiting-regional-office).
CDC/ATSDR Technical Assistance is Available
CDC/ATSDR will provide technical assistance to health departments in developing and executing this
biomonitoring and assessment approach. Please contact [email protected] if you would like to request assistance or
if you have any questions or suggestions.
II-3
PFAS Sampling Strategy and Data Analysis Assistance
PFAS Exposure Assessment in a Community:
Sampling Strategy and Data Analysis Assistance
Per- and Poly-fluoroalkyl Substance (PFAS) have been detected in numerous public and private
drinking water supplies in the United States. Health departments may need help determining how to
best assess exposure to PFAS. This document can help health departments conduct biomonitoring
activities in communities with PFAS contamination in the drinking water supply.
Consider Using a One-Stage Cluster Sample
A convenience sampling approach (i.e., a non-probability technique) is sometimes used for biomonitoring.
However, this approach recruits participants that are not representative of the entire community’s population,
and the results from convenience samples cannot be used to extrapolate to the larger at-risk or exposed
population in the community of concern.
A one-stage cluster sample, where the clusters are households and all individuals in each selected household are
included in the sample, is a statistically-based, community sampling design that can be used to administer
questionnaires and collect biomonitoring samples. It can also provide information about the range of PFAS
exposures in an affected community. This sampling design is representative of the local population, allowing for
inferences to be made on the entire sampling frame. This simple approach has been used by previous studies
where PFAS exposure in communities was assessed and biomonitoring was performed [1, 2].
This document provides information on how to:
Conduct a one-stage cluster sampling approach
Estimate the sample size at the household level
Analyze the data
This assistance assumes the biomonitoring activities are in a community with suspected or known current or
recent PFAS contamination in the drinking water supply and sampling at household level.
Step-by-Step Approach to One-Stage Cluster Sampling
Step 1: Eligibility Criteria
Create the eligibility criteria, based on the known or suspected PFAS exposure in a specific geographical area and
potential health concerns of the community. For example,
Individuals who are {specify age limit if applicable} currently living and had lived in the {specify affected
area (see step 2 below for examples)} prior to {insert date}.
Eligibility criteria will likely vary by community. Knowledge of historical contamination and exposure is helpful in
determining eligibility criteria.
Step 2: Sampling Frame
Identify the geographic area where PFAS exposure is known or suspected. A one-stage cluster sample requires a
complete list of all households in the geographic area of interest. This list will comprise the sampling frame.
III-1
PFAS Sampling Strategy and Data Analysis Assistance
a. If the geographic area is served by a potentially contaminated public water system, obtain a list of all
households served by the public water system from the water company or local municipal water supply
billing.
b. If residents in the geographic area with potentially exposed groundwater receives water from private
wells, obtain a list of households with private wells from the local health department.
Assign sequential numbers to each household on your list of households (1, 2, 3, …N) (N is the total number of
households in the geographic area). This is your sampling frame—the list from which you will draw the sample.
You can also select multiple sampling frames based on known or suspected PFAS exposure (e.g., areas with high
PFAS exposure and areas with low PFAS exposure). If you cannot obtain the sampling frame from water systems
or for private wells, then use census information.
Step 3: Select Households
Calculate the sample size (see section on sample size calculation below). Use a simple random number generator
(such as http://www.random.org/integers/) to select the sample, using your list of households and sample size.
For example, if your sample size is 94 households and your sampling frame contains 1,000 households, generate
94 random numbers between 1 and 1,000. Select the households corresponding to the 94 random numbers.
Step 4: Select Individuals
Recruit all household members, including children, from selected households to participate in the study. Previous
studies have used letters of participation, phone calls, or in-person visits to the households to recruit individuals.
You can use a method that will fit your needs. Ask one individual from each household to identify all members
currently living in the household.
Step 5: Collect Information
Once you have recruited all individuals from a selected household,
Administer consent and exposure assessment questionnaires (see Consent and Question Bank sections)
Collect blood samples from every household member who provides consent and agrees to participate in
the study (see Biomonitoring Sample Collection section).
For children under the age of 18, obtain assent from the child and consent from a parent or legal guardian (see
example letters and forms in the Toolkit). A parent or legal guardian can also answer exposure assessment
questionnaire for children.
You can administer biomonitoring sample collection and exposure assessment questionnaires at participants’
houses or at a designated study site (based on your available resources). If you select the latter, be aware of
potential human subjects’ privacy issues: participants may be providing consent, blood samples, and
questionnaire responses in a public setting (e.g., their identity is less confidential).
III-2
PFAS Sampling Strategy and Data Analysis Assistance
Sample Size Calculation
Consider the following approach to estimate the required sample size.
First, estimate the required number of individuals. Then, account for the sampling design to obtain the required
sample size of households. To normalize the distribution, we recommend using log (values). This is because lab
values are typically positive and have distributions that are skewed rather than symmetric. We assume the PFAS
values will also have a lognormal distribution.
n =
m=
α =
d =
σ =
sample size of households
sample size of individuals
level of significance
desired precision
standard deviation of the logarithm of measured PFAS levels.
The required sample size of individuals is given by:
𝑚= [
𝑧𝛼/2 ∗ 𝜎 2
]
𝑑
An example using National Health and Nutrition Examination Survey (NHANES) data is completely worked out
below, but you should use local data on serum PFAS levels of the affected community, if available. However, if
preliminary local data on PFAS exposure is not available, then use national data to help estimate sample size. For
the example below, we used national data from NHANES. The geometric mean for serum PFOS was 6.31 µg/L for
the US population in 2011–2012. The corresponding 95% confidence interval (5.84, 6.82) and the NHANES [3]
sample size of 1,904 are used to estimate the standard deviation of the log (values). For example, using the upper
limit of the confidence interval
𝜎̂ =
√1904 ∗ [log(6.82) − log(6.31)]
= 1.73
1.96
Then, the sample size of individuals to estimate the mean with precision 15% of the log (geometric mean), and 5%
level of significance is
1.96 ∗ 1.73 2
𝑚= [
] = 151
0.15 ∗ log(6.31)
Recall that N = the total number of households in the geographic area. Let M = the total number of individuals in
the geographic area. The average household size in the geographic area is M/N. So, accounting for the survey
design (including all individuals from each selected household in the sample), the required sample size of
households is given by n = m * (N/M).
For example, if m = 151, N = 1,000, M = 2,500, α = 0.05, and d = 0.15*log (6.31), then a sample of n = 61 households
is needed.
Adjust this sample size estimate to ensure adequate precision despite non-participating households (see section
on Participation Bias below). For example, if a response rate of 65% is expected, then use n = 61/0.65 = 94. This
example is only for illustrating the use of the formulas and not a recommendation of 94 as the required sample
size in any particular situation.
III-3
PFAS Sampling Strategy and Data Analysis Assistance
Once you determine the geographic boundaries, you can find the population total (M) for the area by using U.S.
Census Bureau data (see https://factfinder.census.gov/faces/nav/jsf/pages/searchresults.xhtml?refresh=t).
Data Analysis
This section suggests data analysis to estimate community-based PFAS exposure level. We recommend using the
geometric mean to minimize the effect of very high or low values. A highly skewed distribution is common in the
measurement of environmental chemicals in blood. In instances where the biomonitoring data are highly skewed,
geometric means are often used.
The geometric mean is the exponentiated value of the mean of the log-transformed measured values. The
geometric mean is influenced less by high values than is the arithmetic mean. Information on estimating the
geometric mean and its associated confidence interval that account for the one-stage cluster design is provided
below. However, if results are normally distributed, then base the analysis on the mean rather than the geometric
mean.
Estimate the Geometric Mean
Let n be the number of households in the sample, and mi be the number of individuals in the ith household of the
sample. Let yij be the measured value of the PFAS of interest for the jth individual in the ith household. Then,
estimate the geometric mean (GM) as:
𝑖
∑𝑛𝑖=1 ∑𝑚
𝑗=1 𝑙𝑜𝑔(𝑦𝑖𝑗 )
̂ = exp [
𝐺𝑀
]
∑𝑛𝑖=1 𝑚𝑖
So, an estimate of the geometric mean is simply obtained by finding the overall mean of the log (values) in the
sample and taking the exponentiation of that result. The mi serve as weights accounting for household size. If any
of the yij are below the limit of detection (LOD), then substitute LOD/√2.
Confidence Interval for the Geometric Mean
Let N be the total number of households and M be the total number of individuals in the sampling frame. Let 𝑓 =
n/N be the sampling fraction. Let 𝑎̅𝑖 and 𝑎̅ be the mean for household i and the overall mean of the log (values) in
the sample, respectively.
𝑚𝑖
1
𝑎̅𝑖 =
∑ log(𝑦𝑖𝑗 )
𝑚𝑖
𝑗=1
𝑚𝑖
𝑛
∑𝑖=1 ∑𝑗=1 𝑙𝑜𝑔(𝑦𝑖𝑗 )
𝑎̅ =
∑𝑛𝑖=1 𝑚𝑖
Use the variance for a ratio estimator because 𝑎̅ is a ratio estimator for a one-stage cluster design. Estimate the
variance of log(GM) by:
𝑛
𝑁 2 (1 − 𝑓)
̂ [log(𝐺𝑀)] =
𝑉𝑎𝑟
∑ 𝑚𝑖2 ( 𝑎̅𝑖 − 𝑎̅ )2
𝑀2 𝑛(𝑛 − 1)
𝑖=1
Then, a 95% confidence interval for the geometric mean is given by:
̂ [𝑙𝑜𝑔(𝐺𝑀)]]
𝑒𝑥𝑝 [𝑎̅ ± 1.96√𝑉𝑎𝑟
III-4
PFAS Sampling Strategy and Data Analysis Assistance
Stratification
When you need separate estimates for high and low exposure areas (or for more categories of exposure), then
add an extra stage (stratification) of sampling to the design. You can use this to recruit individuals of interest for
one or more strata.
Estimate separate sample sizes for each stratum, then use stratum PFAS estimates to calculate the overall
community PFAS estimate. You will also need stratum specific weights to calculate the overall PFAS estimates of
the community [4]. Use the description above (Data Analysis) for stratum-specific estimates for each geometric
mean and confidence interval calculations.
A description of how to combine the stratum-specific estimates to obtain the overall community PFAS estimate is
below:
Let L be the total number of strata and mih be the number of individuals in the ith household of the hth
stratum.
Let yijh be the measured value of the PFAS of interest for the jth individual in the ith household of the hth
stratum.
Divide the sampling frame into L strata containing N1, N2, . . . , NL households, respectively.
The stratum specific weight is Nh/N for the hth stratum. The sample sizes within the strata are denoted n1, n2, . . .,
nL, respectively. Let 𝑎
̅̅̅̅
𝑎ℎ be the mean for household i and the overall mean of the log(values) in hth stratum,
𝑖ℎ and ̅̅̅
respectively. Specifically,
𝑚𝑖ℎ
1
𝑎
̅̅̅̅
∑ log(𝑦𝑖𝑗ℎ )
𝑖ℎ =
𝑚𝑖ℎ
𝑗=1
ℎ
𝑖ℎ
∑𝑛𝑖=1
∑𝑚
𝑗=1 𝑙𝑜𝑔(𝑦𝑖𝑗ℎ )
̅̅̅
𝑎ℎ =
ℎ
∑𝑛𝑖=1
𝑚𝑖ℎ
Then, estimate the overall geometric mean as:
∑𝐿 𝑁 ̅̅̅
𝑎
̂ = exp [ ℎ=1 ℎ ℎ ]
𝐺𝑀
𝑁
Estimate the variance of log(GM) for stratum h by:
̂ [log(𝐺𝑀)ℎ ] =
𝑉𝑎𝑟
𝑁ℎ 2 (1 − 𝑓ℎ )
2
𝑀ℎ 𝑛ℎ (𝑛ℎ − 1)
𝑛ℎ
2
∑ 𝑚𝑖ℎ
(𝑎
̅̅̅̅
𝑎ℎ )2
𝑖ℎ − ̅̅̅
𝑖=1
Then, estimate the variance of the overall log(GM) by:
̂ [𝑙𝑜𝑔(𝐺𝑀)ℎ ]
∑𝐿 𝑁 2 𝑉𝑎𝑟
̂ [𝑙𝑜𝑔(𝐺𝑀)] = exp [ ℎ=1 ℎ
𝑉𝑎𝑟
]
𝑁2
Then, a 95% confidence interval for the overall geometric mean is given by:
∑𝐿ℎ=1 𝑁ℎ 𝑎
̅̅̅
ℎ
̂ [𝑙𝑜𝑔(𝐺𝑀)]]
𝑒𝑥𝑝 [
± 1.96√𝑉𝑎𝑟
𝑁
III-5
PFAS Sampling Strategy and Data Analysis Assistance
You can use a statistical analysis package such as SAS to account for the one-stage cluster design and stratification.
You can use SAS to estimate the geometric mean and obtain its confidence interval, as well as to obtain univariate
and multivariate analyses for all questionnaire and other survey data.
Participation Bias
It may not be possible to get household or individual participation, even after multiple contact attempts. Since
those that do not choose to participate may be substantively different from those that do, you may have
participation bias. However, all sampling designs are susceptible to participation bias. Do not replace households
that choose not to participate. This would increase the level of potential participation bias. However, it is
appropriate to replace households that do not meet the eligibility criteria.
A low participation rate will also result in less precision in sample estimates. Inflate the required sample size to
ensure adequate precision (see section on Sample Size Calculation above).
Data Analysis
Using a statistical package that includes a sample survey procedure (e.g., SAS® software) can improve accuracy
for calculating the geometric mean and confidence intervals. If needed, the statistical package should include an
algorithm that accounts for a one-stage cluster design and a second stage for stratification. For example, in SAS,
you can perform PROC GEOMEAN to estimate the geometric mean and its confidence interval. PROC GEOMEAN
accounts for the survey design and enables a univariate analysis. You can also use the statistical package to
perform univariate or multivariate analyses on the questionnaire data.
Estimate the Geometric Mean to Estimate PFAS Levels of a Community
The following example demonstrates how to calculate the geometric mean and confidence interval using the
formulas provided above. The sample size in the example is just n=4 households (HH). The table shows the number
of individuals in each HH (m) and measured PFAS level (y) in blood samples of household members in each HH:
HH
HH1
HH2
HH3
HH4
Number
of
individuals in HH
1
2
4
6
PFAS levels of household members (µg/L)
Member 1 Member 2 Member 3 Member 4
5
250 bar) error messages are observed, the
purge valve frit, the guard column, analytical column frit, HPLC
lines, needle seat, or injector components may need to be
replaced. See also section 8b.
(c) Reestablishment of performance and calibration. Every time the
system is disturbed for cleaning or maintenance, a mass spec
operational check standard is analyzed to assess the HPLC and
MS performance. For the mass spectrometer, a retune of the
system may or may not be necessary. If the instrument does not
pass this test, then the instrument is retuned using PPG as
described previously.
(3) Spark system
Preventative maintenance is done by a qualified engineer at least once a
year. Additional maintenance may be necessary if there is a general
decrease in instrument performance.
If the SparkLink error “HPD 1 high pressure problem” occurs, check the
SPE lines and HPD 6 port valve. The HPD valve stator and/or rotor may
need to be replaced.
The instrumentation used is serviced according to the manufacturer’s
guidance included in the instrument manuals or based on the
recommendation of experienced analysts/operators after following
appropriate procedures to determine that the instrument performs
adequately for the intended purposes of the method.
9. Reportable Range of Results
The linear range of the standard calibration curves and the method limit of detection
(LOD) determine the reportable range of results. The reportable range must be within
the range of the calibration curves. However, samples with concentrations exceeding
the highest reportable limit may be diluted, re-extracted, and reanalyzed so that the
measured value will be within the range of the calibration.
If a sample needs more than 100 times dilution (which would require using less than 1
μL of specimen) the dilution can be performed in at least two steps. For example, first,
at least 10 μL specimen is diluted up to 1 mL with water in a 2 mL Eppendorf tube (or
equivalent), then a second dilution is performed by aliquoting the appropriate fraction of
the dilute into an autosampler vial and adding 100 μL blank calf serum. With very
concentrated specimens it may be difficult to estimate the dilution that is necessary, and
the measured value may be higher than the highest calibration point even after the
dilution.
Formula to calculate the dilution factor to be entered into the Analyst batch file:
X-22
Laboratory Procedure Manual
D= (1000 / V 1st ) x (200 / V 2nd ).
Formula to calculate the volume of specimen to be entered into the Access database:
V= V 1st x (V 2nd / 1000)
Where V 1st is the volume of the aliquot taken from the original specimen and V 2nd is the
volume of the dilute measured into the autosampler vial.
1) Analytical Sensitivity
The limits of detection (LOD) for each analyte are listed in Table 6.
2) Analytical Specificity
This is a highly selective method that requires that the PFASs 1) elute at a
specific retention time; 2) have precursor ions with specific mass/charge ratios;
3) have specific product ions formed from the precursor ion with specific
mass/charge ratios.
3) Linearity Limits
The calibration curve is linear for all analytes (generally R2>0.95). The limit on
the linearity is determined by the highest standard analyzed in the method. Due
to the wide variation of PFASs levels in humans, we set our highest standard
near the high end of the linear range (Table 6). Unknown samples whose
concentrations exceed the highest standard concentration must be re-extracted
using a smaller aliquot. The low end of the linear range is limited by the method
LOD. Concentrations below the method LOD (or the concentration of the lowest
standard in the calibration curve) are reported as non-detectable.
X-23
Laboratory Procedure Manual
Table 6. Linear range (lowest – highest standard concentration) and LOD for
each PFAS measured in serum.
Analyte
Me-PFOSA-AcOH
PFBuS
PFHxS
n-PFOS
Sm-PFOS
PFHpA
n-PFOA
Sb-PFOA
PFNA
PFDeA
PFUA
PFDoA
LOD
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
Linear range
(ng/mL)
0.005-20
0.004-17.1
0.005-18.9
0.015-115
0.01-10
0.01-20
0.01-20
0.029-24.5
0.01-20
0.01-20
0.01-20
0.01-20
1) Accuracy
The accuracy of the method is determined by enriching serum samples with known
concentrations of PFASs and comparing the calculated and expected concentrations. To
examine their consistency over the range of levels encountered in serum, the
measurements are taken at 3 different concentrations, namely using standards near
3*LOD, middle level (~1.0 ng/mL, except n-PFOS (6 ng/mL), Sm-PFOS and Sm2-PFOS
(0.5 ng/mL), and Sb-PFOA (0.7 ng/mL)), and high level (~10.0 ng/mL, except n-PFOS
(60 ng/mL), Sm-PFOS and Sm2-PFOS (1.0 ng/mL), and Sb-PFOA (2.5 ng/mL)). The
accuracy is calculated from 5 independent measurements (Table 7).
X-24
Laboratory Procedure Manual
Table 7. Spiked recoveries of extracted standards in serum
Analyte
Me-PFOSA-AcOH
PFBuS
PFHxS
n-PFOS
Sm-PFOS
PFHpA
n-PFOA
Sb-PFOA
PFNA
PFDeA
PFUA
PFDoA
Accuracy (%)
at ~3*LOD/middle/high
105±20
93±5
101±3
113±25
105±19
110±12
106±12
98±5
98±6
110±14
99.7±6
97.0±2
105±23
92±4
90±4
115±12
110±11
103±10
92±14
105±5
101±2
112±15
106±8
102±5
95±13
103±7
102±3
103±13
96±6
98±4
92±17
102±3
101±3
110±22
96±10
101±3
1) Precision
The precision of this method is reflected in the variance of two quality control (QC)
pools over a period of three weeks. The coefficient of variation (CV) of repeated
measurements of these QC pools, which reflects both inter and intra-day
variations, is used to estimate precision (Table 8).
Table 8. Mean QC concentrations (ng/mL) and CV%
QCH
CV%
14.3
6.5
10.5
0.4
18.5
6.7
15.7
PFHxS
0.4
9.3
6.3
7.0
n-PFOS
1.0
10.6
15.8
9.8
Sm-PFOS
0.4
10.5
2.3
10.3
PFHpA
0.5
6.5
6.3
9.4
n-PFOA
0.4
13.6
7.4
12.0
Sb-PFOA
0.8
15.5
6.5
11.0
PFNA
0.4
10.6
8.1
9.4
PFDeA
0.5
10.9
6.3
9.7
PFUA
0.5
12.5
6.4
9.7
PFDoA
0.5
20.0
6.4
9.1
Analyte
VQC
CV%
Me-PFOSA-AcOH
0.4
PFBuS
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Laboratory Procedure Manual
10. Quality Control (QC) Procedures
a. Individual samples (i.e., standards, unknown samples, serum blanks, and quality
control (QC) materials) QC procedures
1) For each analyte, the relative retention time (RT) (ratio of RT analyte and RT IS ) of
standards, unknowns, and QCs should be checked. If the relative RT falls
outside the range, check the integration to make sure the analyte or IS peak
was properly picked up.
2) For each analyte, the IS area counts should meet minimum area count
requirements. Low IS area counts suggest a) strong ion suppression from the
matrix, or b) missing of IS. Depending on the findings, either re-extract the
sample as usual or re-extract the sample after dilution.
3) For each analyte, the calculated concentration of the calf serum blanks (SB)
should be less than three times the LOD. Using the current method, all
standards, blanks and unknown samples are prepared following the same
procedure, thus background blank values (reflected in the intercept of the
calibration curve) are automatically subtracted from the concentrations of
unknown samples. If background levels are above the threshold above, the
reagents used for sample preparation and (or) mobile phases need to be
checked for potential contamination.
4) For each analyte, if the concentration in an unknown sample is above the
highest calibration standard, the sample needs to be re-extracted with a
smaller volume of serum.
b. Quality control of the QC materials
1) QC Materials
The QC materials were prepared in bulk from calf serum (Gibco, Grand Island,
NY). The target ranges for the pools were set to encompass the expected
concentration ranges in human populations.
2) Preparation of QC Pools
The calf serum purchased was pooled and the QC pools were mixed uniformly,
divided into four subpools and stored frozen. One subpool was used as a blank
QC and to prepare the calibration standards, and the other three were enriched
with PFASs as needed to afford very low concentration (VQC, ~0.3-1.0 ng/mL),
low concentration (QCL, ~2.0 ng/mL) and high concentration (QCH, ~0.8-15.8
ng/mL) subpools. The QC pools were characterized to define the mean and the
95% and 99% control limits of PFASs concentrations by a minimum of 30
repeated measurements in a three week period. QC materials reextracted and
analyzed after the initial characterization showed that the PFASs remained stable
frozen for at least 3 months 21.
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Laboratory Procedure Manual
3) Characterization of QC Materials
For characterization, a minimum of 30 runs of QCL and QCH were measured
over 1 month. In each run, one pair of QCL and QCH materials were analyzed
and averaged. Using the pair average value from the 30 runs, the mean, and
upper and lower 99% and 95% control limits were established.
QC samples are analyzed along with unknown samples to monitor for accuracy
and precision throughout the analysis batch. Maximum 50 unknown samples are
run with randomly placed 2 QCL, 2 QCH, and 2 reagent blank samples. The
concentrations of the two QCL and two QCH in each batch are averaged to
obtain one average measurement of QCL and QCH.
4) Final evaluation of Quality Control Results
Standard criteria for run rejection based on statistical probabilities are used to
declare a run either in-control or out-of-control24.
QC rules for: Analytical run with 1 QC pool per run (must also include a blank
QC specimen):
One QC pool per run with one QC result per pool
1) If QC run result is within 2Si limits, then accept the run.
2) If QC run result is outside a 2Si limit - reject run if:
a) Extreme Outlier – Run result is beyond the characterization mean +/- 4Si
b) 1 3S Rule - Run result is outside a 3Si limit
c) 2 2S Rule - Current and previous run results are outside the same 2Si limit
d) 10 X-bar Rule – Current and previous 9 run results are on same side of the
characterization mean
e) R 4S Rule – The current and the previous run results differ by more than 4Si.
Note: Since runs have a single result per pool and only 1 pool, the R 4S rule is
applied across runs only.
One QC pool per run with two or more QC results per pool
1) If QC run mean is within 2Sm limits and individual results are within 2Si limits,
then accept the run.
2) If QC run mean is outside a 2Sm limit - reject run if:
a) Extreme Outlier – Run mean is beyond the characterization mean +/- 4Sm
b) 3S Rule - Run mean is outside a 3Sm limit
c) 2 2S Rule – Current and previous run means are outside the same 2Sm limit
d) 10 X-bar Rule – Current and previous 9 run means are on same side of the
characterization mean
3) If one of the two QC individual results is outside a 2Si limit - reject run if:
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Laboratory Procedure Manual
a) R 4S Rule – Within-run range for the current run and the previous run exceeds
4Sw (i.e., 95% range limit)
Abbreviations:
S i = Standard deviation of individual results (the limits are not shown on the chart
unless run results are actually single measurements).
S m = Standard deviation of the run means (the limits are shown on the chart).
S w = Within-run standard deviation (the limits are not shown on the chart).
QC rules for: Analytical run with 2 QC pools per run:
Two QC pools per run with one QC result per pool
1) If both QC run results are within 2Si limits, then accept the run.
2) If 1 of the 2 QC run results is outside a 2Si limit - reject run if:
a) Extreme Outlier – Run result is beyond the characterization mean +/- 4Si
b) 3S Rule - Run result is outside a 3Si limit
c) 2S Rule - Both run results are outside the same 2Si limit
d) 10 X-bar Rule – Current and previous 9 run results are on same side of the
characterization mean
e) R 4S Rule – Two consecutive standardized run results differ by more than 4Si. Note:
Since runs have a single result per pool for 2 pools, comparison of results for the R 4S
rule will be with the previous result within run or the last result of the previous run.
Standardized results are used because different pools have different means.
Two QC pools per run with two or more QC results per pool
1) If both QC run means are within 2Sm limits and individual results are within 2Si limits,
then accept the run.
2) If 1 of the 2 QC run means is outside a 2Sm limit - reject run if:
a) Extreme Outlier – Run mean is beyond the characterization mean +/- 4Sm
b) 3S Rule - Run mean is outside a 3Sm limit
c) 2S Rule - Both run means are outside the same 2Sm limit
d) 10 X-bar Rule – Current and previous 9 run means are on same side of the
characterization mean
3) If one of the 4 QC individual results is outside a 2Si limit - reject run if:
a) R 4S Rule – Within-run ranges for all pools in the same run exceed 4Sw (i.e., 95%
range limit). Note: Since runs have multiple results per pool for 2 pools, the R 4S rule is
applied within runs only.
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Laboratory Procedure Manual
QC rules for: Analytical run with 3 QC pools per run:
Three QC pools per run with one QC result per pool
1) If all 3 QC run results are within 2Si limits, then accept the run.
2) If 1 of the 3 QC run results is outside a 2Si limit - reject run if:
a) Extreme Outlier – Run result is beyond the characterization mean +/- 4Si
b) 3S Rule - Run result is outside a 3Si limit
c) 2S Rule - 2 or more of the 3 run results are outside the same 2Si limit
d) 10 X-bar Rule – Current and previous 9 run results are on same side of the
characterization mean
e) R 4S Rule – Two consecutive standardized run results differ by more than 4Si. Note:
Since runs have a single result per pool for 3 pools, comparison of results for the R 4S
rule will be with the previous result within the current run or with the last result of the
previous run. Standardized results are used because different pools have different
means.
Three QC pools per run with two or more QC results per pool
1) If all 3 QC run means are within 2Sm limits and individual results are within 2Si limits,
then accept the run.
2) If 1 of the 3 QC run means is outside a 2Sm limit - reject run if:
a) Extreme Outlier – Run mean is beyond the characterization mean +/- 4Sm
b) 3S Rule - Run mean is outside a 3Sm limit
c) 2S Rule - 2 or more of the 3 run means are outside the same 2Sm limit
d) 10 X-bar Rule – Current and previous 9 run means are on same side of the
characterization mean
3) If one of the QC individual results is outside a 2Si limit - reject run if:
a) R 4S Rule - 2 or more of the within-run ranges in the same run exceed 4Sw (i.e.,
95% range limit). Note: Since runs have multiple results per pool for 3 pools, the R 4S
rule is applied within runs only.
11. Remedial Action if Calibration or QC Systems Fail to Meet Acceptable Criteria
If the QC systems or the calibrations failed to meet acceptable criteria, operations are
suspended until the source or cause of failure is identified and corrected. If the source
of failure is easily identifiable (e.g., failure of the mass spectrometer or a pipetting error),
the problem is immediately corrected. Otherwise, fresh reagents are prepared and the
mass spectrometer is cleaned. Before beginning another analytical run, several QC
materials (in the case of QC failure) or calibration standards (in the case of calibration
failure) are reanalyzed. After calibration or quality control has been reestablished,
analytical runs may be resumed.
12. Limitations of Method; Interfering Substances and Conditions
Occasionally, the concentration of the PFASs in serum may be higher than the highest
standard in the calibration curves, and 0.1 mL of sample may be too much to use. This
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Laboratory Procedure Manual
is evident by the low recovery of the isotope-labeled standard after the SPE extraction.
In this case, a smaller aliquot of serum can be used. Most likely, the LOD is not higher
in this case because of the concentrated nature of the specimen.
13. Reference Ranges (Normal Values)
Results (http://www.cdc.gov/exposurereport) from the National Health and Nutrition
Examination Survey (NHANES) can be used as reference ranges for the general US
population 25.
14. Critical-Call Results (“Panic” Values)
Critical call values have not been established for any PFAS concentrations.
15. Specimen Storage and Handling During Testing
Specimens are stored in the laboratory frozen prior to analysis. Frozen samples are
allowed to thaw completely at room temperature prior to the initiation of the analytical
procedure.
16. Alternate Methods for Performing Test and Storing Specimens if Test System
Fails
Alternate procedures do not exist in-house for the measurement of PFASs. If the
analytical system fails, storage of samples refrigerated is recommended until the system
is operational again.
17. Test-Result Reporting System; Protocol for Reporting Critical Calls (If Applicable)
a. The Quality Control officer reviews each analytical run, identifies the quality control
samples within each analytical run and determines whether the analytical run is
performed under acceptable quality control conditions.
b. The data from analytical runs of unknowns are initially reviewed by the laboratory
supervisor.
c. If the quality control data and results are acceptable the laboratory supervisor
generates a memorandum to the Branch Chief reporting the results.
d. These data are then sent to the person(s) that made the initial request.
e. Final hard copies of correspondence are maintained in the office of the Branch
Chief and with the quality control officer.
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Laboratory Procedure Manual
18. Transfer or Referral of Specimens; Procedures for Specimen Accountability and
Tracking
Standard record keeping systems (e.g., notebooks, sample logs, data files) should be
employed to keep track of all specimens. One spreadsheet form with information for
receiving/transferring specimens is kept in the laboratory. In this form, the samples
received are logged in when received and when stored/transferred after analysis. For
NHANES samples, the person receiving the specimens signs and dates the shipping
manifests. The shipping manifests for NHANES and other samples are kept in a binder in
the Laboratory.
Use of trade names is for identification only and does not imply endorsement by the Public Health
Service or the U.S. Department of Health and Human Services.
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Laboratory Procedure Manual
2013-2014 Summary Statistics and QC Chart for 2-(N-methyl-PFOSA) acetate (ng/mL)
Lot
Start
N Date
End
Date
Standard Coefficient of
Mean Deviation
Variation
HQC-122014 50 02JUL14 11MAR15 7.09100
0.48089
6.8
LQC-122014 50 02JUL14 11MAR15 1.69470
0.13635
8.0
X-32
Laboratory Procedure Manual
2013-2014 Summary Statistics and QC Chart for Perfluorobutane sulfonic acid (ng/mL)
Lot
Start
N Date
End
Date
Standard Coefficient of
Mean Deviation
Variation
HQC-122014 50 02JUL14 11MAR15 5.629
0.548
9.7
LQC-122014 50 02JUL14 11MAR15 2.088
0.202
9.7
X-33
Laboratory Procedure Manual
2013-2014 Summary Statistics and QC Chart for Perfluorodecanoic acid (ng/mL)
Lot
Start
N Date
End
Date
Standard Coefficient of
Mean Deviation
Variation
HQC-122014 50 02JUL14 11MAR15 6.484
0.272
4.2
LQC-122014 50 02JUL14 11MAR15 2.461
0.129
5.3
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Laboratory Procedure Manual
2013-2014 Summary Statistics and QC Chart for Perfluorododecanoic acid (ng/mL)
Lot
Start
N Date
End
Date
Standard Coefficient of
Mean Deviation
Variation
HQC-122014 50 02JUL14 11MAR15 6.324
0.406
6.4
LQC-122014 50 02JUL14 11MAR15 2.390
0.263
11.0
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Laboratory Procedure Manual
2013-2014 Summary Statistics and QC Chart for Perfluoroheptanoic acid (ng/mL)
Lot
Start
N Date
End
Date
Standard Coefficient of
Mean Deviation
Variation
HQC-122014 50 02JUL14 11MAR15 6.458
0.328
5.1
LQC-122014 50 02JUL14 11MAR15 2.429
0.144
5.9
X-36
Laboratory Procedure Manual
2013-2014 Summary Statistics and QC Chart for Perfluorohexane sulfonic acid (ng/mL)
Lot
Start
N Date
End
Date
Standard Coefficient of
Mean Deviation
Variation
HQC-122014 50 02JUL14 11MAR15 6.105
0.243
4.0
LQC-122014 50 02JUL14 11MAR15 2.291
0.114
5.0
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Laboratory Procedure Manual
2013-2014 Summary Statistics and QC Chart for Perfluorononanoic acid (ng/mL)
Lot
Start
N Date
End
Date
Standard Coefficient of
Mean Deviation
Variation
HQC-122014 50 02JUL14 11MAR15 6.3701
0.3081
4.8
LQC-122014 50 02JUL14 11MAR15 2.3770
0.1517
6.4
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Laboratory Procedure Manual
2013-2014 Summary Statistics and QC Chart for Perfluoroundecanoic acid (ng/mL)
Lot
Start
N Date
End
Date
Standard Coefficient of
Mean Deviation
Variation
HQC-122014 50 02JUL14 11MAR15 6.223
0.297
4.8
LQC-122014 50 02JUL14 11MAR15 2.364
0.145
6.1
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Laboratory Procedure Manual
References
1. Houde, M.; Martin, J. W.; Letcher, R. J.; Solomon, K. R.; Muir, D. C. G. Biological
monitoring of polyfluoroalkyl substances: A review. Environ. Sci. Technol. 2006, 40
(11), 3463-3473.
2. Calafat, A. M.; Needham, L. L.; Kuklenyik, Z.; Reidy, J. A.; Tully, J. S.; Aguilar-Villalobos,
M.; Naeher, L. P. Perfluorinated chemicals in selected residents of the American
continent. Chemosphere 2006, 63 (3), 490-496.
3. Guruge, K. S.; Taniyasu, S.; Yamashita, N.; Wijeratna, S.; Mohotti, K. M.; Seneviratne, H.
R.; Kannan, K.; Yamanaka, N.; Miyazaki, S. Perfluorinated organic compounds in
human blood serum and seminal plasma: a study of urban and rural tea worker
populations in Sri Lanka. J. Environ. Monit. 2005, 7 (4), 371-377.
4. Olsen, G. W.; Huang, H. Y.; Helzlsouer, K. J.; Hansen, K. J.; Butenhoff, J. L.; Mandel, J.
H. Historical comparison of perfluorooctanesulfonate, perfluorooctanoate, and
other fluorochemicals in human blood. Environ. Health Perspect. 2005, 113 (5),
539-545.
5. Taniyasu, S.; Kannan, K.; Horii, Y.; Hanari, N.; Yamashita, N. A survey of perfluorooctane
sulfonate and related perfluorinated organic compounds in water, fish, birds, and
humans from Japan. Environ. Sci. Technol. 2003, 37 (12), 2634-2639.
6. Yeung, L. W. Y.; So, M. K.; Jiang, G. B.; Taniyasu, S.; Yamashita, N.; Song, M. Y.; Wu, Y.
N.; Li, J. G.; Giesy, J. P.; Guruge, K. S.; Lam, P. K. S. Perfluorooctanesulfonate
and related fluorochemicals in human blood samples from China. Environ. Sci.
Technol. 2006, 40 (3), 715-720.
7. Karrman, A.; Mueller, J. F.; van Bavel, B.; Harden, F.; Toms, L. M. L.; Lindstrom, G.
Levels of 12 perfluorinated chemicals in pooled Australian serum, collected 20022003, in relation to age, gender, and region. Environ. Sci. Technol. 2006, 40 (12),
3742-3748.
8. Harada, K.; Koizumi, A.; Saito, N.; Inoue, K.; Yoshinaga, T.; Date, C.; Fujii, S.; Hachiya,
N.; Hirosawa, I.; Koda, S.; Kusaka, Y.; Murata, K.; Omae, K.; Shimbo, S.;
Takenaka, K.; Takeshita, T.; Todoriki, H.; Wada, Y.; Watanabe, T.; Ikeda, M.
Historical and geographical aspects of the increasing perfluorooctanoate and
perfluorooctane sulfonate contamination in human serum in Japan. Chemosphere
2007, 66 (2), 293-301.
9. Calafat, A. M.; Kuklenyik, Z.; Reidy, J. A.; Caudill, S. P.; Tully, J. S.; Needham, L. L.
Serum concentrations of 11 polyfluoroalkyl compounds in the US population: Data
from the National Health and Nutrition Examination Survey (NHANES) 1999-2000.
Environ. Sci. Technol. 2007, 41 (7), 2237-2242.
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Laboratory Procedure Manual
10. Fromme, H.; Midasch, O.; Twardella, D.; Angerer, J.; Boehmer, S.; Liebl, B. Occurrence
of perfluorinated substances in an adult German population in southern Bavaria.
Int. Arch. Occup. Environ. Health 2007, 80 (4), 313-319.
11. Hansen, K. J.; Clemen, L. A.; Ellefson, M. E.; Johnson, H. O. Compound-specific,
quantitative characterization of organic: Fluorochemicals in biological matrices.
Environ. Sci. Technol. 2001, 35 (4), 766-770.
12. Kannan, K.; Corsolini, S.; Falandysz, J.; Fillmann, G.; Kumar, K. S.; Loganathan, B. G.;
Mohd, M. A.; Olivero, J.; Van Wouwe, N.; Yang, J. H.; Aldous, K. M.
Perfluorooctanesulfonate and related fluorochemicals in human blood from several
countries. Environ. Sci. Technol. 2004, 38 (17), 4489-4495.
13. Calafat, A. M.; Wong, L. Y.; Kuklenyik, Z.; Reidy, J. A.; Needham, L. L. Polyfluoroalkyl
chemicals in the US population: Data from the National Health and Nutrition
Examination Survey (NHANES) 2003-2004 and comparisons with NHANES 19992000. Environ. Health Perspect. 2007, 115 (11), 1596-1602.
14. Olsen, G. W.; Mair, D. C.; Church, T. R.; Ellefson, M. E.; Reagen, W. K.; Boyd, T. M.;
Herron, R. M.; Medhdizadehkashi, Z.; Nobilett, J. B.; Rios, J. A.; Butenhoff, J. L.;
Zobel, L. R. Decline in perfluorooctanesulfonate and other polyfluoroalkyl
chemicals in American Red Cross adult blood donors, 2000-2006. Environ. Sci.
Technol. 2008, 42 (13), 4989-4995.
15. Kennedy, G. L.; Butenhoff, J. L.; Olsen, G. W.; O'Connor, J. C.; Seacat, A. M.; Perkins, R.
G.; Biegel, L. B.; Murphy, S. R.; Farrar, D. G. The toxicology of perfluorooctanoate.
Crit Rev. Toxicol. 2004, 34 (4), 351-384.
16. Lau, C.; Butenhoff, J. L.; Rogers, J. M. The developmental toxicity of perfluoroalkyl acids
and their derivatives. Toxicol. Appl. Pharmacol. 2004, 198 (2), 231-241.
17. OECD . Co-Operation on Existing Chemicals. Hazard assessment of perfluorooctane
sulfonate (PFOS) and its salts. [http://www.oecd.org/dataoecd/23/18/2382880.pdf],
1-362. 2002. Organisation for Economic Co-operation and Development (OECD).
18. Butenhoff, J. L.; Kennedy, G. L.; Frame, S. R.; O'Connor, J. C.; York, R. G. The
reproductive toxicology of ammonium perfluorooctanoate (APFO) in the rat.
Toxicology 2004, 196 (1-2), 95-116.
19. Luebker, D. J.; York, R. G.; Hansen, K. J.; Moore, J. A.; Butenhoff, J. L. Neonatal
mortality from in utero exposure to perfluorooctanesulfonate (PFOS) in SpragueDawley rats: Dose-response, and biochemical and pharamacokinetic parameters.
Toxicology 2005, 215 (1-2), 149-169.
20. Salihovic, S.; Karrman, A.; Lindstrom, G.; Lind, P. M.; Lind, L.; van Bavel, B. A rapid
method for the determination of perfluoroalkyl substances including structural
isomers of perfluorooctane sulfonic acid in human serum using 96-well plates and
column-switching ultra-high performance liquid chromatography tandem mass
spectrometry. J. Chromatogr. A 2013, 1305, 164-170.
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Laboratory Procedure Manual
21. Kuklenyik, Z.; Needham, L. L.; Calafat, A. M. Measurement of 18 perfluorinated organic
acids and amides in human serum using on-line solid-phase extraction. Anal.
Chem. 2005, 77 (18), 6085-6091.
22. Lindstrom, G.; Karrman, A.; van Bavel, B. Accuracy and precision in the determination of
perfluorinated chemicals in human blood verified by interlaboratory comparisons. J.
Chromatogr. A 2009, 1216 (3), 394-400.
23. Van Leeuwen, S. P. J.; Karrman, A.; van Bavel, B.; De Boer, J.; Lindstrom, G. Struggle
for quality in determination of perfluorinated contaminants in environmental and
human samples. Environ. Sci. Technol. 2006, 40 (24), 7854-7860.
24. Caudill, S. P.; Turner, W. E.; Patterson, D. G. Geometric mean estimation from pooled
samples. Chemosphere 2007, 69, 371-380.
25. CDC . Fourth National Report on Human Exposure to Environmental Chemicals. Updated
Tables, February 2015.
[http://www.cdc.gov/biomonitoring/pdf/FourthReport_UpdatedTables_Feb2015.pdf]
. 2015. Atlanta, GA, Centers for Disease Control and Prevention; National Center
for Environmental Health; Division of Laboratory Sciences.
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Audience Outreach Materials
PFAS Exposure Assessment: Know your Audiences
Audience outreach materials for environmental exposures
CDC developed these optional audience outreach materials with input from state health department
communicators to help state and county health departments talk with communities about environmental
exposure concerns. The outreach suggestions, originally developed to help with cancer cluster communication,
were informed by risk communication principles such as those in CDC’s Crisis and Emergency Risk Communication
(CERC) manual and health department experiences working with communities around high-emotion
environmental concerns. For more information about how leaders can work with communities during public
health crises, visit https://emergency.cdc.gov/erc/leaders.pdf.
Although these materials are not specific to PFAS exposure, the basic principles of providing information in a
transparent way, identifying affected audiences, and listening to community concerns may help health
departments in talking with communities concerned about PFAS and other environmental exposures.
This section offers tips for communicating with communities and individuals most affected by environmental
exposures:
Community members, who are worried that they or their loved ones will be exposed or get sick;
Media, that have found a compelling story;
Elected officials, who react to constituents’ needs;
Physicians, who are often the first line of communication during an exposure;
Community groups, who are concerned about a potential exposure; and
Real estate agents, who work closely in communities and can have an unintentional impact on community
morale.
Community Members
Suggested Action Steps for State/Local Health Department
CDC’s Crisis and Emergency Risk Communication (CERC) manual focuses on these steps:
Be first: Crises are time-sensitive. Communicating information quickly is almost always important. For
members of the public, the first source of information often becomes the preferred source.
Be Right: Accuracy establishes credibility. Information can include what is known, what is not known, and
what is being done to fll in the gaps.
Be Credible: Honesty and truthfulness should not be compromised during crises.
Express Empathy: Crises create harm, and the suffering should be acknowledged in words. Addressing
what people are feeling, and the challenges they face, builds trust and rapport.
Promote Action: Giving people meaningful things to do calms anxiety, helps restore order, and promotes
a restored sense of control.
Show Respect: Respectful communication is particularly important when people feel vulnerable.
Respectful communication promotes cooperation and rapport.
XI-1
Audience Outreach Materials
CERC provides more details and examples applicable to many kinds of outreach challenges. You can access it online
here.
Suggestions for the First Contact
Public health officials should be trained in risk communication techniques. Show empathy. Listen to the story.
Provide local health information.
Try to learn as much as possible about the concerns, and assess the degree of distress in the affected
community.
Suggestions beyond the First Contact
Identify and proactively meet community stakeholders, including residents, key community leaders, and family
members.
Find the leaders who have the trust of the community—the people who are respected in the community.
Let the community know you are listening.
Provide plain-language, audience-appropriate materials.
o Address community concerns as specifically as possible.
o What scientifically sound information is available about this specific exposure?
o What are the causes and risk factors (if known)?
o How can it be prevented (if possible)?
Example Tactics to Share Information with Community
Plan and adapt your communication tactics to the specific needs of your audience.
If you’re dealing with people who use traditional media (e.g., newspapers, radio), don’t rely on social
media and other technology-based channels.
Remain open, transparent, and aware of audience feedback.
If your audience is already distrustful, be very clear. Ambiguous information may validate their
distrust.
Avoid speech or actions that frame the issue in terms of “them (community)” and “us (public
servants).”
Web Site: It may be helpful to update your Web site regularly (e.g. weekly or bi-weekly, depending on interest)
with baseline community health information and the latest news about the investigation. Share links to other
credible sources.
Community Panel: If the investigation expands, perhaps consider engaging community leaders and stakeholders
in a panel that will meet regularly with you to share community concerns and take information about the
investigation back to the community. In communities where trust is already damaged, a panel sponsored by the
health department may not be seen as credible or independent. If this is the case in your community, it may be
helpful to engage existing community groups and community leaders to sponsor it and maintain regular,
structured, two-way communication.
Community Meetings: Community meetings are one avenue of getting information to people. It may be helpful
to have a skilled facilitator and culturally competent spokespeople. Example types of community meetings include
the following (more than one type may be combined if appropriate):
XI-2
Audience Outreach Materials
Town-Hall Style
Public health officials lead this type
of large group meeting. Community
members can ask questions and make
comments.
Town-hall meetings can relieve
community stress and help community
members understand that the health
department is listening to their
concerns.
Keep presentations short and use
plain language.
Use a strong facilitator who will not
allow any one audience member to
dominate the conversation.
Have resources available at the
meeting for people who need stress
relief (e.g., mental health services).
Station Style
This type of meeting, more like a
health fair, consists of different tables
hosted by groups such as the health
department
or
environmental
protection agency, where one-on-one
conversations can happen.
Sometimes this type of meeting is
preferred because it is usually more
equitable—no one person or group
can dominate conversation.
If you choose this type of meeting,
invite various stakeholders to host
stations.
Small Group
This type of meeting can occur around
a table or in a home to keep
community members informed and
allow people to speak freely.
Media
Example Action Steps for State/Local Health Department
SUGGESTED GOAL: Provide ongoing
accurate information and education to the
Identify media outlets serving affected areas. Create and
community at large by working with the
maintain a media list so that it is available quickly for
media.
communication.
Target media that have demonstrated concern or interest.
Be proactive with the press; reach out to
them rather than waiting for their calls.
Provide a media education toolkit with information on the
type of exposure and related health effects, such as fact sheets,
Be aware of reporters’ deadlines.
FAQs, and other materials.
Keep media updated on the investigation’s progress, but not
preliminary findings before they are verified.
Point media to credible health information about chemicals (e.g., ATSDR ToxPortal Web site:
www.atsdr.cdc.gov/substances/index.asp).
Update your Web site as a tool to provide timely information.
Notify media of privacy laws, such as the Health Insurance Portability and Accountability Act (HIPAA) at the
beginning of the investigation. Be extremely careful not to disclose personal medical information.
Interview Suggestions
As much as possible, hold media interviews in person with local reporters. This will be an opportunity to build
rapport.
News Briefing Suggestions
XI-3
Audience Outreach Materials
Conduct news briefings focused on the circumstances of this investigation. Local and state health departments
should work together to make sure that efforts are synchronized.
General Suggestions
Manage expectations. Clarify the scope and limitations (e.g., authority, financial, scientific) of the
investigation. Preview the next steps.
Explain the difference between correlation and causation.
Be proactive. When possible, reach out to local media by using platforms that best suit your
community, such as letters to the editor, op-eds, or editorial boards.
Always have a backup. Keep another public information officer (PIO) or communication person
updated on the status of the investigation so that he or she can step in if you are not available.
Always be empathetic, even if the results seem to show nothing uncommon is happening. Persons and
families being affected will not want to read or hear that nothing is wrong.
Emphasize what is confirmed and what is possible. For example, although results may not tell us if the
PFAS exposure and health effects are linked, contaminated water can still be cleaned.
Keep track of each of your conversations with media and stakeholders (with dates). Also keep a list of
all the interested parties so that no one is left out when you have new information to share.
Consider publishing your protocol online where all stakeholders can find it and can see the steps in
this type of investigation.
Make sure that you reach consensus with all subject matter experts involved in the investigation
before you provide new information or before you translate data to a reporter. Be sure that your
quotes are in line with the agency position and that you’re not breaking protocol by making your
statement.
Suggestions for corresponding with reporters
Always keep reporters updated about the status of their
Suggestions for Dealing with Highly
request. Establish expectations. If the analysis will take several
Involved Reporters
weeks, check in periodically to let them know that you’re still
working on their request and to check for additional questions.
Always take the time to educate
Make sure reporters understand state health agency
reporters on the issue.
limitations.
Return calls promptly.
Be open and proactive. Let them
o Resources are limited, and at any given time the health
know that your agency is doing all
department may be facing a variety of public health
that it can do.
threats. Environmental investigations, like other public
Be empathetic.
health issues, are complex.
Have patience. Do not get
o Health departments should help communities develop
frustrated on the phone or in a
a clear understanding of the issues, and the potential
meeting. Impatience can make the
effectiveness of proposed solutions, before taking action.
reporter think they are close to
breaking a story and that you are
Communities and health departments can succeed if they
uncomfortable with it.
set clear goals and target resource usage efficiently.
Do not take an aggressive
Inform reporters why it would be damaging to the
reporter’s approach personally.
investigation to share any preliminary data or analysis and that
Avoid falling into an “us” vs. “them”
public health officers will share information when it is complete.
type of argument.
Example: “Public health officers are working to check all
the information and conclusions to ensure all appropriate
steps are being taken. Sharing any information before this
process is complete could result in inaccurate information
being published, which would not benefit any of the parties involved.”
XI-4
Audience Outreach Materials
Elected Officials
Suggested Action Steps for State/Local Health Department
Be an ACTIVE RESOURCE for elected officials and
appropriate/affected agency heads (e.g., Environment, Public
Works).
Establish two-way communication. Keep them informed from
the beginning.
Be frank and direct; explain investigative steps and available
statistics.
Educate your legislative liaisons. Make sure that they are
informed about environmental exposures and have the tools to
talk with elected officials when the situation arises. Tell them
where to go for answers.
Share with them the potential outcomes of community outrage.
SUGGESTED GOAL: Elected officials will
understand the challenges and
opportunities of the situation. With
coaching, elected officials will become
messengers of accurate information and
help manage community expectations.
Develop a relationship so they feel free to
share information from constituents with
the health department.
Example: “The reason we are coming to you is because people are afraid. Property values can be affected. This
situation may lead to angry and hurt families who feel they cannot trust anyone. We want to make sure that they
feel they can trust you and trust us.”
Manage expectations. Make sure the elected officials are aware of long-term implications of their actions and
statements. Advise them to refrain from making commitments they or the health department may not be able to
keep.
Physicians
Suggested Action Steps for State/Local Health Department
Identify residents who are physicians or public health
professionals who may be able to assist in education efforts
and serve as credible sources of information. These are the
sources that the media and others will seek out, so public
health officers want to make sure they have accurate
information. Help them understand the health department’s
messaging.
Consider a physician education package that would include
o A fact sheet
o Peer reviewed literature, and
SUGGESTED GOAL: With sound
information, area physicians will be
credible sources for accurate information
about risk.
They can and will help families work
through their feelings.
Make sure physicians are getting
accurate information.
If you partner with physicians, coach
them to provide a consistent, coordinated
message.
o Suggestions on how to talk to patients and families
about environmental exposures.
XI-5
Audience Outreach Materials
Community Groups
Suggested Action Step for State/Local Health Department
Create a list of respected community groups or
stakeholders with an interest or stake in the issue.
Include these groups in public outreach efforts. The groups
are resources for the community and can provide emotional
and educational support.
Train health department subject matter experts to use
empathy, plain language, and cultural competence in
presentations and communication with community groups.
SUGGESTED GOAL: Build a trusted third
party source of information for
communities by partnering early with local
groups to provide information, education,
and perhaps counseling for community
members.
Clear, concise, open dialogue is integral
to media relations.
Community members tend to trust local
and nonprofit groups.
Real Estate Agents
Suggested Action Steps for State/Local Health Department
SUGGESTED GOAL: Real estate agents or
Compile a list of real estate agencies and organizations in the
area.
Provide data and informational materials to ensure that
professional associations and real estate agents in the area have
accurate information.
Be available to answer questions.
local agent associations will be able to
explain the environmental investigation to
potential buyers without escalating
outrage. Real estate agents will be
productive participants in community
meetings and able to explain the potential
effect on housing prices of an
environmental investigation in the
community.
XI-6
The family tree of per- and
polyfluoroalkyl substances (PFAS) for
environmental health professionals
6/9/17
Names and abbreviations
This fact sheet tells you about chemical names within the family of per- and polyfluoroalkyl
substances (PFAS) and their basic chemical structure. It also spells out abbreviations for
common PFAS.
PFAS are a family of man-made chemicals that contain carbon, fluorine, and other elements.
The family tree image, Figure 1, shows some of the different families of PFAS. For simplicity, it
does not include all PFAS subfamilies. Follow along – starting at the “fallen apple” of PFC and
then continuing up the tree trunk into the branches.
PFC
In the past, PFC stood for
perfluorinated chemicals.
However, using the abbreviation
PFC can be confusing. This
abbreviation is also used
to mean perfluorocarbons.
Perfluorocarbons are a different
family of chemicals, also known as
greenhouse gases.
The term PFC has fallen off the
family tree, but it remains in the
diagram as a reminder of past use.
You may still see informational
materials using the term “PFC”
instead of PFAS.
PFHxS
PFOS
PFNA
Polyfluoroalkyls
Figure 1.
Family Tree
of Per- and
polyfluoroalkyl
Substances
PFOA
PFDA
Perfluoroalkyls
PFAS
PFC
PFAS
Current nomenclature favors “PFAS” which are per- and polyfluoroalkyl substances. The PFAS
family includes hundreds of chemicals. See Table 1 (next page) for some abbreviations and
chemical names.
Agency for Toxic Substances and Disease Registry
Division of Community Health Investigations
CS278160-C
XII-1
Page 1
Table 1. Common PFAS: Abbreviations and Names
Abbreviation
PFOS
PFOA (aka C8)
PFNA
PFDA
PFOSA (aka FOSA)
MeFOSAA (aka Me-PFOSA-AcOH)
Et-FOSAA (aka Et-PFOSA-AcOH)
PFHxS
Chemical name
Perfluorooctane sulfonic acid
Perfluorooctanoic acid
Perfluorononanoic acid
Perfluorodecanoic acid
Perfluorooctane sulfonaminde
2-(N-Methyl-perfluorooctane sulfonamido) acetic acid
2-(N-Ethyl-perfluorooctane sulfonamido acetic acid
Perfluorohexane sulfonic acid
Chemical Structure
All PFAS contain a chain of carbon atoms bonded
to fluorine atoms. Some also have a functional
group at the end of the chain. These structures
are the basis for different chemical properties and
different chemical names.
Figure 2. Perfluorooctanoic acid
(PFOA), a perfluoroalkyl substance
In perfluoroalkyl substances all carbons except the
last one are attached to fluorines. The last carbon
attaches to the functional group. See Figure 2.
In polyfluoroalkyl substances at least one (but not
all) carbons are attached to fluorines.
Image credit: NIEHS.
Note about Plurals
PFAS is the abbreviation for per- and polyfluoroalkyl substances (plural), so you don’t technically
need another “s.” You may see “PFASs” written, but ATSDR’s preference is to use PFAS. When you
write about PFAS make sure you use correct subject-verb agreement – PFAS is a plural noun,
so it must be used with a plural verb. For example “These are the most common PFAS found in
people.”
You can also use the term “PFAS family” with a singular verb.
It may feel awkward to use PFAS as a plural when it sounds singular, but with practice, it will
feel right.
References
Buck et al 2011. Perfluoroalkyl and Polyfluoroalkyl Substances in the Environment: Terminology, Classification, and Origins.
Integrated Environmental Assessment and Management. v7, (4), pp. 513–541.
CDC. 2009. Fourth National Report on Human Exposure to Environmental Chemicals. Atlanta, GA: Centers for Disease Control
and Prevention. p. 247 – 257.
XII-2
Page 2
The family tree of perfluoroalkyl and
polyfluoroalkyl substances (PFAS)
6/9/17
Names and abbreviations
This fact sheet tells you about chemical names within the family of
perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their basic chemical
structure. It also spells out abbreviations for common PFAS.
PFAS are a family of man-made chemicals that contain carbon, fluorine, and
other elements.
The family tree image below, Figure 1, shows some of the different families of
PFAS. For simplicity, it does not include all PFAS subfamilies. Follow along –
starting at the “fallen apple” of PFC and then continuing up the tree trunk into
the branches.
PFHxS
PFOS
PFNA
Polyfluoroalkyls
PFDA
Perfluoroalkyls
Figure 1.
Family Tree of
perfluoroalkyl and
polyfluoroalkyl
Substances
PFOA
PFAS
PFC
Agency for Toxic Substances and Disease Registry
Division of Community Health Investigations
CS278160-A
XIII-1
Page 1
PFC
In the past, scientists used the abbreviation PFC to stand for perfluorinated
chemicals.
However, using the abbreviation PFC can be confusing because it is also an
abbreviation for perfluorocarbons. Perfluorocarbons are an entirely different
family of chemicals, also known as greenhouse gases.
The term PFC has fallen off the family tree, but it remains in the diagram as a
reminder of past use. You may still see informational materials using the term
“PFC” instead of PFAS.
PFAS
Perfluoroalkyl substances and polyfluoroalkyl substances are called PFAS
for short. The PFAS family includes hundreds of chemicals. The different
structures of the PFAS molecules are the basis for different chemical
properties and different chemical names. See Table 1 for abbreviations and
chemical names.
Table 1. Common PFAS: Abbreviations and Names
Abbreviation
PFOS
PFOA (aka C8)
PFNA
PFDA
PFOSA (aka FOSA)
MeFOSAA (aka Me-PFOSA-AcOH)
Et-FOSAA (aka Et-PFOSA-AcOH)
PFHxS
Chemical name
Perfluorooctane sulfonic acid
Perfluorooctanoic acid
Perfluorononanoic acid
Perfluorodecanoic acid
Perfluorooctane sulfonaminde
2-(N-Methyl-perfluorooctane sulfonamido) acetic acid
2-(N-Ethyl-perfluorooctane sulfonamido acetic acid
Perfluorohexane sulfonic acid
XIII-2
Page 2
An Overview of Perfluoroalkyl and Polyfluoroalkyl Substances
and Interim Guidance for Clinicians Responding to Patient
Exposure Concerns
Interim Guidance
Revised in 05/2017
Introduction
The purpose of this fact sheet is to provide interim guidance to aid physicians and other clinicians with patient
consultations on perfluoroalkyl and polyfluoroalkyl substances (PFAS). It highlights what PFAS are, which chemicals
fall into this category of substances, identifies health effects associated with exposure to various PFAS, and suggests
answers to specific patient questions about potential PFAS exposure.
Background
What are PFAS?
PFAS, sometimes known as PFCs, are synthetic chemicals that do not occur naturally in the environment. There
are many different types of PFAS such as perfluorocarboxylic acids (e.g., PFOA, sometimes called C8, and
PFNA) and perfluorosulfonates (e.g., PFOS and PFHxS). PFAS may be used to keep food from sticking to
cookware, to make sofas and carpets resistant to stains, to make clothes and mattresses more waterproof, and
to make some food packaging resistant to grease absorption, as well as use in some firefighting materials.
Because PFAS help reduce friction, they are also used in a variety of other industries, including aerospace,
automotive, building and construction, and electronics.
Why are PFAS a possible health concern?
According to the U.S. Environmental Protection Agency (EPA), PFAS are considered emerging contaminants.
An “emerging contaminant” is a chemical or material that is characterized by a perceived, potential, or real
threat to human health or the environment or by a lack of published health standards.
PFAS are extremely persistent in the environment and resistant to typical environmental degradation
processes. The pathway for dispersion of these chemicals appears to be long-range atmospheric and oceanic
currents transport. Several PFAS and their potential precursors are ubiquitous in a variety of environments.
Some long-chain PFAS bioaccumulate in animals and can enter the human food chain.
PFOS and PFOA are two of the most studied PFAS. Exposure to PFOA and PFOS is widespread and global.
PFOS and PFOA also persist in the human body and are eliminated slowly. Both PFOS and PFOA can be found
in blood, and at much lower levels in urine, breast milk and in umbilical cord blood.
PFOS and PFOA may pose potential adverse effects for human health given their potential toxicity, mobility,
and bioaccumulation potential. The likelihood of adverse effects depends on several factors such as amount
and concentration of PFAS ingested as well as the time span of exposure.
Routes of Exposure and Health Effects
What are the main sources of exposure to PFAS?
For the general population, ingestion of PFAS is considered the major human exposure pathway. The major
types of human exposure sources for PFAS include:
-
-
Drinking contaminated water.
Ingesting food contaminated with PFAS, such as certain types of fish and shellfish.
Until recently, eating food packaged in materials containing PFAS (e.g., popcorn bags, fast food
containers, and pizza boxes). Using PFAS compounds has been largely phased out of food packaging
materials.
Hand-to-mouth transfer from surfaces treated with PFAS-containing stain protectants, such as carpets,
which is thought to be most significant for infants and toddlers.
National Center for Environmental Health
Agency for Toxic Substances and Disease Registry
PFAS Clinician Fact Sheet
-
Workers in industries or activities that manufacture, manipulate or use products containing PFAS may
be exposed to higher levels than the general population.
What are other low level exposure sources?
Individuals can also be exposed by breathing air that contains dust contaminated with PFAS (from soil, carpets,
upholstery, clothing, etc.), or from certain fabric sprays containing this substance.
Dermal exposure is a minor exposure pathway. Dermal absorption is slow and does not result in significant
absorption.
What are the potential PFAS exposure risks to fetuses and children?
Recent research evaluating possible health effects to fetuses from PFAS exposures have shown that developing
fetuses can be exposed to PFAS when umbilical cord blood from their mothers crosses the placenta during
pregnancy. It is important to note that different PFAS have varying levels of permeability to the placental
barrier.
Newborns can be exposed to PFAS through breast milk. The level of neonatal exposure depends on the
duration of breastfeeding. Older children may be exposed to PFAS through food and water, similar to adults. In
addition, young children have a higher risk of exposure to PFAS from carpet cleaners and similar products,
largely due to time spent lying and crawling on floors in their early years.
How long do PFAS remain in the body?
PFAS with long carbon chains have estimated half-lives ranging from 2-9 years such as:
•
PFOA 3 to 4 years
•
PFOS 5 to 6 years
•
PFHxS 8 to 9 years
What are exposure limits for PFAS in drinking water?
The Environmental Protection Agency (EPA) has published a Lifetime Health Advisory (LTHA) recommending
that the concentration of PFOA and PFOS in drinking water, either individually or combined, should not be
greater than 70 parts per trillion (0.07 parts per billion). The LTHA concentrations do not represent definitive
cut-offs between safe or unsafe conditions, but rather provide a margin of protection for individuals throughout
their life from possible adverse health effects. EPA health advisories are non-regulatory recommendations and
are not enforceable.
What are PFAS levels in the U.S. population?
Most people in the United States and in other industrialized countries have measurable amounts of PFAS in
their blood.
The National Health and Nutrition Examination Survey (NHANES) is a program conducted by the Centers for
Disease Control and Prevention (CDC) to assess the health and nutritional status of adults and children in the
United States. NHANES (2011–2012) measured the concentration of PFAS in the blood of a representative
sample of the U.S. population (12 years of age and older). The average blood levels found were as follows:
-
PFOA: 2.1 parts per billion, with 95% of the general population at or below 5.7 parts per billion
PFOS: 6.3 parts per billion, with 95% of the general population at or below 21.7 parts per billion
PFHxS: 1.3 parts per billion, with 95% of the general population at or below 5.4 parts per billion
In the last decade, major manufacturers of PFOA and PFOS related products joined EPA in a global stewardship
program to phase out production of these agents by 2015. Based on data collected from previous NHANES
XIV-2
cycle years, levels of PFOA and PFOS are generally decreasing in the blood of the general population as a result
of this important initiative.
Health Studies
How can PFAS potentially affect human health?
Studies in humans and animals are inconsistent and inconclusive but suggest that certain PFAS may affect a
variety of possible endpoints. Confirmatory research is needed.
Below are summaries of studies in animals and humans.
Animal Studies:
Adverse health effects have been demonstrated in animal studies, but these occurred at exposure levels higher
than those found in most people. The main health effects observed were: enlargement and changes in the
function of the liver, changes in hormone levels (e.g., reduced testosterone synthesis, potential to affect T4 and
TSH levels) and adverse developmental outcomes. Developmental and reproductive effects, including reduced
birth weight, decreased gestational length, structural defects, delays in postnatal growth and development,
increased neonatal mortality, and pregnancy loss have all been associated with prenatal rodent exposure to
PFOS and PFOA.
Human Studies:
C8 Health Project
The C8 Health Project was a large epidemiological study conducted because drinking water in six water districts
across two states near Parkersburg, West Virginia were contaminated by release of PFOA (also called C8) from
the 1950s until 2002 (when the contamination was discovered). These releases migrated and contaminated the
air, parts of the Ohio River, and ground water. The study included 69,030 persons >18 years of age. The C8
Science Panel analyzed study data and found probable links (as defined by litigation) between elevated PFOA
blood levels and high cholesterol (hypercholesteremia), ulcerative colitis, thyroid function, testicular cancer,
kidney cancer, preeclampsia, as well as elevated blood pressure during pregnancy. Residents in the area of
these releases showed 500 percent higher PFOA-concentrations in blood compared to a representative U.S.
population (i.e., NHANES).
Table 1: Overview of C8 and Other Human Studies
Cholesterol
Some epidemiological studies demonstrated statistically significant
associations between serum PFOA and PFOS levels and total cholesterol in:
-
workers exposed to PFAS, and
residents of communities with high levels of PFOA in the drinking water
compared to NHANES data that is representative of the U.S.
population.
Other studies have found no association between PFAS exposures and the total
cholesterol levels.
Uric acid
Several studies have evaluated the possible association between serum PFOA
and serum PFOS levels and uric acid. Significant associations were found
between serum PFOA and uric acid levels at all evaluated exposure levels.
Liver effects
A number of human studies have used liver enzymes as biomarkers of possible
liver effects. In occupational studies, no associations between liver enzymes
XIV-3XIIX
and serum PFOA or PFOS levels were consistently found. A study of highly
exposed residents demonstrated significant associations but the increase in
liver enzymes was small and not considered to be biologically significant.
Cancer
The International Agency for Research on Cancer (IARC) has classified PFOA as
possibly carcinogenic and EPA has concluded that both PFOA and PFOS are
possibly carcinogenic to humans.
Some studies have found increases in prostate, kidney, and testicular cancers in
workers exposed to PFAS and people living near a PFOA facility. Findings from
other studies report otherwise and most did not control for other potential
factors including heavy smoking. Additional research is needed to clarify if
there is an association.
Note: Additional studies have identified possible associations between ulcerative colitis, thyroid disease and
pregnancy induced hypertension and higher exposure to PFAS.
What health screenings were used in the C8 study?
The C8 Medical Panel suggested health screening to evaluate the C8 study population that included blood
tests for cholesterol, uric acid, thyroid hormones and liver function as well as other age or situationally
appropriate screenings like blood pressure and urine protein measures. For individual patients exposed to
PFAS who are not among the C8 study screening population, there are no official guidelines supporting
health screening. However the tests listed above are well established in clinical medicine and may be a
consideration to discuss with your patient based on the patient history, concerns and symptoms.
What are potential health effects from prenatal PFAS exposure to fetuses?
Multiple studies have reported an association between elevated maternal blood and cord blood
concentrations of PFAS (primarily PFOS and PFOA) and decreased birth weight. Specifically, one metaanalysis suggests that each 1 ng/mL increase in prenatal PFOA levels is associated with up to 18.9 g
reductions in birth weight (Johnson, 2014). Studies have also observed decreased birth weight with prenatal
exposures to PFOS. The association between maternal PFAS level and decreased birth weight is not
statistically significant across all studies. Further, the observed reduction in birth weight does not
consistently equate with increased risk of a low birth weight (LBW) infant. Only one study revealed a
statistically significant association between LBW risk and PFOS (Stein 2009); no studies have found a
statistically significant association between LBW risk and PFOA.
Additional studies are needed to conclusively link the relationships between fetal PFAS exposure and health
effects.
Patient Questions and Key Message Answers
As a clinician, you know careful listening and patient engagement is critical for ensuring quality patient care,
especially when health concerns are raised. Perhaps the most difficult challenge in speaking with patients
about their health concerns is addressing uncertainty. If your patient has concerns about an exposure to
PFAS, you may face the challenge of helping your patient cope with the uncertainty of potential health
effects from a PFAS exposure.
Based on feedback from clinicians and from individuals who have spoken to their health care provider about
their PFAS exposure concerns, a set of patient questions have been identified. To assist you in speaking
XIV-4XIIX
with your patients about their concerns, key messages and supporting facts needed to answer the
anticipated patient questions are provided in the table below for your information and potential use.
Table 2: Patient Questions and Key Message
Questions Patients
May Ask
Key Patient Messages
There are high levels of
PFAS in my water.
What should I do?
If the water you use is above the
EPA health advisory level for
PFOA and PFOS, you can reduce
exposure by using an alternative
water source for drinking, food
preparation, cooking, brushing
teeth or any activity that might
result in ingestion of water.
Key Message Supporting Facts
Potential health effects are
associated with exposure to PFAS.
EPA has established a lifetime
health advisory for PFOA and PFOS
in drinking water. This advisory
states that the concentration of
PFOA and PFOS in drinking water,
either individually or combined,
should not be greater than 70 parts
per trillion.
There needs to be additional
research to establish levels of health
risk, but patients may want to
reduce exposures below the EPA
health advisory level to be on the
safe side.
A home water filtration system can
reduce the contaminant levels in
drinking water. Researchers are still
clarifying how to best use home
filtration for PFAS contamination.
Installing a home filtration system or
using a pitcher-type filter may
reduce PFAS levels. However, these
filters may not reduce PFAS enough
to meet the EPA Lifetime Health
Advisory (LTHA) level. Three factors
determine how much PFAS are
removed by filtration. These factors
are the PFAS contaminant levels,
the type of filter, and how well the
filter is maintained. Manufacturers
of the filtration system may be able
to make recommendations to
optimize removal of PFAS. This
may include more sophisticated
media cartridges or increasing the
frequency of exchanging filter
media.
For bottled water questions (how it
is treated and if it is safe) contact
XIV-5XIIX
Questions Patients
May Ask
Key Patient Messages
Key Message Supporting Facts
the CFSAN Information Center at 1888-SAFEFOOD (1-888-723-3366).
Could my health
problems be caused by
PFAS exposure?
(Based on the health
problems the patient
has, there are two
possible responses to
this question.)
(a) If the patient’s health
problem is in the list
below, it may potentially
be associated with PFAS
exposure, based on
limited evidence from
human studies. The
potential health effects
include:
-
-
-
Thyroid function
(potential to
affect T4 and
TSH levels)
High cholesterol
Ulcerative colitis
Testicular cancer
Kidney cancer
Pregnancyinduced
hypertension
Elevated liver
enzymes
High uric acid
(b) If the patient’s health
problem is not in the
bulleted list above, then
there is no current
evidence that it is
related to PFAS
exposure. (However,
research is ongoing and
not all health outcomes
have been adequately
studied.)
(a) Although the evidence is not
conclusive, your health problem
could potentially be associated
with exposure to PFAS.
However, health effects can be
caused by many different
factors, and there is no way to
know if PFAS exposure has
caused your health problem or
made it worse.
For supporting facts on the listed
health effects in this question (a),
see “How can PFAS potentially
affect human health.” The
information on potential illnesses
and health effects will be briefly
reviewed for each of these illnesses
or health effects. This information
can be found in this fact sheet on
page 3 and 4.
If your patient presents with health
concerns that might be associated
with PFAS exposure, it is
appropriate to discuss the patient’s
concerns and perform a thorough
health and exposure history and also
a physical exam relative to any
symptoms reported.
(b) Based on what we know at
this time, there is no reason to
think your health problem is
associated with exposure to
PFAS.
XIV-6XIIX
Questions Patients
May Ask
Key Patient Messages
Key Message Supporting Facts
Are there future health
problems that might
occur because of PFAS
exposure?
We know PFAS can cause health
issues but there is no conclusive
evidence that predicts PFAS
exposure will result in future
health problems. We can watch
for symptoms related to PFAS
associated health problems and
investigate any that you notice,
especially those that reoccur.
Studies in humans and animals are
inconsistent and inconclusive but
suggest that certain PFAS can cause
possible health effects.
Should I get a blood
test for PFAS?
If you are concerned and choose
to have your blood tested, test
results will tell you how much of
each PFAS is in your blood but it
is unclear what the results mean
in terms of possible health
effects. The blood test will not
provide information to pinpoint
a health problem nor will it
provide information for
treatment. The blood test results
will not predict or rule-out the
development of future health
problems related to a PFAS
exposure.
There currently is no established
PFAS blood level at which a health
effect is known nor is there a level
that predicts health problems. Most
people in the US will have
measureable amounts of PFAS in
their blood. There are no healthbased screening levels for specific
PFAS that clinicians can compare to
concentrations measured in blood
samples. As a result, interpretation
of measured PFAS concentrations in
individuals is limited in its use. The
patient may be aware of blood and
urine test for PFAS being taken at
other locations. These tests are used
by public health officials to
investigate community-wide
exposure in order to understand the
kinds and amounts of PFAS
exposures in a community and how
those exposures compare to those
in other populations. Serum PFAS
measurements are most helpful
when they are part of a carefully
designed research study.
What do my PFAS
blood tests results
mean?
The blood test for PFAS can only
tell us the levels of specific PFAS
in your body at the time you
were tested.
There is currently no established
PFAS blood level at which a health
effect is known nor is there a level
that is clearly associated with past or
future health problems.
The blood tests results cannot be
interpreted and used in patient
care.
Additional research is needed to
better understand health risks
associated with PFAS exposure.
The individual patient’s blood
concentration of PFAS can only be
compared to the average
XIV-7XIIX
Questions Patients
May Ask
Key Patient Messages
Key Message Supporting Facts
The blood test results cannot
predict or rule-out the
development of future problems
related to a suspected exposure.
background blood concentration
levels for different PFAS that are
nationally identified through the
representative sampling of the
NHANES studies conducted by CDC.
A patient’s PFAS concentrations can
only show the patient if his or her
blood levels are within range of the
national norms or if the individual’s
levels are high or low compared to
the national background averages.
An adult patient asks:
“Should I be tested for
any of the potential
health effects
associated with PFAS
exposure (like
cholesterol and uric
acid levels, or liver and
thyroid function,
etc.)?”
Let’s look at your health history
and past lab results and discuss
what steps we may want to
consider moving forward.
One way we can address
cholesterol is through your
annual physical.
For others PFAS associated
conditions, we need to watch for
symptoms and investigate any
that you notice, especially those
that reoccur.
If any unusual symptoms occur,
we will investigate those and
treat as needed.
Health effects associated with PFAS
are not specific and can be caused
by many other factors.
There are no guidelines to support
laboratory testing to monitor PFAS
health concerns.
However, if your patient is
concerned about PFAS exposure,
discussing routine cholesterol
screening can reassure the patient
that his or her PFAS exposure
concerns are being addressed. Some
of the other possible health effects
can be screened for based on
symptoms.
Laboratory tests will not tell us if
PFAS are the cause of any of
your health symptoms or
abnormal lab results, but
conducting these routine health
screenings and watching for any
related symptoms do offer us a
way to better understand your
current health status.
A parent asks:
“Should I have my child
tested for any of the
potential health effects
associated with PFAS
exposure (like
cholesterol and uric
acid levels, or liver,
The American Academy of
Pediatrics has endorsed
cholesterol testing for children
starting at 9 years of age.
Following this guidance
cholesterol level testing can be
done for older children.
According to NHLBI guidelines
endorsed by the American Academy
of Pediatrics, all children should be
screened for cholesterol levels
between ages 9 and 11 years, and
again between ages 17 and 21 years,
even those who are not at an
XIV-8XIIX
Questions Patients
May Ask
thyroid function,
etc.)?”
Key Patient Messages
If cholesterol level measures are
outside the normal range, we
can discuss options for bringing
cholesterol levels within the
normal range for your child.
For very young children,
keeping well child visits is the
best plan of action to monitor
your child’s health and watch for
symptoms of illness.
We can discuss any symptoms
you notice, especially those that
reoccur.
If any unusual symptoms occur,
we will investigate those and
treat as needed.
Laboratory tests will not tell us if
PFAS are the cause of any of
your child’s health symptoms
and are not recommended.
Conducting routine well child
visits and watching for any
related symptoms do offer us a
way to better understand your
child’s current health status.
How will exposure to
PFAS affect my
pregnancy?
Exposure to PFAS before
pregnancy has been associated
with pregnancy-induced
hypertension and pre-eclampsia.
We will monitor your blood
pressure closely, as we do for all
pregnant women; however,
there is no need for additional
blood pressure measurements as
a result of your exposure.
Is it safe for me to
breastfeed my baby?
Breastfeeding is associated with
numerous health benefits for
infants and mothers.
At this time, it is recommended
that you as a nursing mother
continue to breastfeed your
baby.
Key Message Supporting Facts
increased risk of high cholesterol
and heart disease.
Health effects associated with PFAS
are not specific and can be caused
by many other factors.
There are no guidelines to support
use of laboratory testing to monitor
PFAS health concerns.
However, if your patient presents
with health concerns that have been
associated with PFAS exposures,
discussing recommended
cholesterol screening, can reassure
the patient’s parents that their
concerns are being addressed. Some
of the other possible health effects
can be screened for based on
symptoms.
Health effects associated with PFAS
are not specific and can be caused
by many other factors.
Pregnancy induced hypertension
occurs in many pregnancies and the
specific etiology is often unknown.
Extensive research has documented
the broad and compelling
advantages of breastfeeding for
infants, mothers, families, and
society.
Some of the many benefits include
immunologic advantages, lower
obesity rates, and greater cognitive
XIV-9XIIX
Questions Patients
May Ask
Key Patient Messages
Key Message Supporting Facts
The science on the health effects
of PFAS for mothers and babies
is evolving.
development for the infant as well
as a variety of health advantages for
the lactating mother.
However, given the scientific
understanding at this time, the
benefits of breastfeeding your
baby outweighs those of not
breastfeeding.
Even though a number of
environmental pollutants readily
pass to the infant through human
milk, the advantages of
breastfeeding continue to greatly
outweigh the potential risks in
nearly every circumstance.
Although few studies have
reported that PFOS and PFOA
might slightly lower the immune
response to some
immunizations, these studies
have not suggested a need to reevaluate the normal
immunization schedule.
A study with 656 children has
reported that elevated levels of
PFOA and PFOS in serum are
associated with reduced humoral
immune response to some routine
childhood immunizations (rubella,
tetanus and diphtheria) among
children aged five to seven years.
Will I need to get my
child vaccinated again?
There is no recommendation for
repeating any vaccinations.
Studies have not suggested a need
to re-evaluate the normal
immunization schedule nor the use
of an immunize booster for
impacted children.
I have been very
anxious about health
risks from PFAS
exposure. How can I
deal with this
uncertainty?
It is normal to be anxious about
uncertain risks.
Listen sympathetically and explore
the concerns of the patient
I am here to listen to your
questions and will do my best to
provide honest answers.
Check for serious stress issues such
as ongoing depression and treat
accordingly.
First let’s identify ways to reduce
ongoing exposures to PFAS so
that overtime we can lower your
health risks.
Review resources/references at the
end of this fact sheet.
How will exposure to
PFAS affect my child’s
immunizations?
Let’s set up appointment for (X
date) and we can discuss any
new questions you have and
check to see if there are any
changes in how you feel.
In the meantime, I have more
information that may answer
questions that you may have
later about PFAS.
XIV-10XIIX
Resources
Below is a list of resources that can be helpful to clinicians. These include the Pediatric Environmental Health
Specialty Units (PEHSU). The PEHSU are a national network of experts available to provide consultation and
education to clinicians and communities wishing to learn more about PFAS and other hazardous substances. These
units are staffed by clinicians with environmental health expertise in pediatrics, reproductive health, occupational
and environmental medicine, medical toxicology, and other related areas of medicine.
Resource
Link
ATSDR:
PFAS Overview
http://www.atsdr.cdc.gov/pfc/index.html
Toxic Substance Portal
http://www.atsdr.cdc.gov/substances/index.asp
ToxFAQs
http://www.atsdr.cdc.gov/toxfaqs/tf.asp?id=1116&tid=237
CDC: PFCs
http://www.cdc.gov/biomonitoring/PFCs_FactSheet.html
C8 Science Panel
http://www.c8sciencepanel.org/prob_link.html
http://www.c8sciencepanel.org/publications.html
C8 Medical Panel
http://www.c-8medicalmonitoringprogram.com/
http://www.c8medicalmonitoringprogram.com/docs/med_panel_education_doc.pdf
EPA: PFAS
https://www.epa.gov/chemical-research/research-perfluorooctanoic-acid-pfoaand-other-perfluorinated-chemicals-pfcs
IARC
http://www.iarc.fr/
NIEHS: PFAS
https://www.niehs.nih.gov/health/materials/perflourinated_chemicals_508.pdf
NHLBI Lipid Screening in
Children & Adolescents
https://www.nhlbi.nih.gov/health-pro/guidelines/current/cardiovascular-healthpediatric-guidelines/full-report-chapter-9
PEHSU
http://www.pehsu.net/
Uncertainty and Stress in
the Clinical Setting
Helping Patients and Clinicians Manage Uncertainty During Clinical Care https://publichealth.wustl.edu/helping-patients-and-clinicians-manageuncertainty-during-clinical-care/
Navigating the Unknown: Shared Decision-Making in the Face of Uncertainty J
Gen Intern Med. 2015 May; 30(5): 675–678. http://tinyurl.com/zrd587f
Patient Health Questionnaire to determine if patient is suffering from
depression. http://tinyurl.com/gv6h3wk
Uncertainty Toolbox: Principles in the Approach to Uncertainty in the Clinical
Encounter-J Gen Intern Med. 2015 May; 30(5): 675–678.
http://tinyurl.com/gtlf2mk
XIV-11XIIX
PFAS ToxGuide
ToxGuideTM is developed to be used as a pocket guide. Tear off at perforation and fold along lines.
The
Sources of Exposure
Toxicokinetics and
Normal Human Levels
Biomarkers/Environmental
Levels
General Populations
Toxicokinetics
Biomarkers
The major sources of exposure to
Limited data indicate that perfluoroalkyls
Measurement of serum or whole blood
perfluoroalkyls, especially
perfluuorooctanoic acid (PFOA) and
perfluorooctane sulfonic acid (PFOS), is
contaminated food and drinking water.
Industrial releases of perfluoroalkyls in
ambient air or surface water may also be
a source of exposure for the general
population.
The general population may also be
exposed to PFOS from mill treated
carpets and to PFOA from migration
from paper packaging and wrapping into
food and inhalation from impregnated
clothes.
Occupational Populations
The production of perfluoroalkyl and use
of perfluoroalkyl containing products are
sources of occupational exposure.
are absorbed from the respiratory tract.
Studies in animals suggest that many
perfluoroalkyls (including PFOA and
PFOS) are almost completely absorbed
from the gastrointestinal tract.
The available data suggest that
perfluoroalkyls are not metabolized or
undergo chemical reactions in the body.
Perfluoroalkyls are primarily excreted in
the urine.
There are substantial differences in the
elimination half-times across
perfluoroalkyl compounds and animal
species. The estimated elimination halftimes for PFOA, PFOS, perfluorohexane
sulfonic acid (PFHxS), perfluorobutane
sulfonic acid, and perfluorobutyric acid in
humans are 3.8 years, 5.4 years, 8.5 years,
665 hours, and 72 hours, respectively.
Much shorter half-times have been
estimated in experimental animals.
Normal Human Levels
Perfluoroalkyls appear to be ubiquitous
in human blood based on the widespread
detection of these substances in human
serum samples.
Mean serum concentrations of PFOA
perfluoroalkyl concentrations is the
standard accepted biomarkers of
exposure to perfluoroalkyls.
ToxGuideTM
for
Perfluoroalkyls
Environmental Levels
Air
Mean PFOA levels ranged from 1.54-
August 2015
Perfluoroalkyl levels in surface water
U.S. Department of Health and
Human Services
Public Health Service
Agency for Toxic Substances
and Disease Registry
15.2 pg/m3 in urban air samples in the
U.S., Norway, and Japan. PFOS levels in
ambient air are generally <5 pg/m3 and
levels of other perfluoroalkyls are
generally <1 pg/m3.
Water
samples are generally below 50 ng/L.
Soil
Background levels of perfluoroalkyls in
soil and sediment have not been located.
Reference
Agency for Toxic Substances and Disease
Registry (ATSDR). 2015. Toxicological
Profile for Perfluoroalkyls (Draft for Public
Comment). Atlanta, GA: U.S. Department
of Health and Human Services, Public
Health Service.
www.atsdr.cdc.gov
Contact Information:
Division of Toxicology
and Human Health Sciences
Environmental Toxicology Branch
1600 Clifton Road NE, F-57
Atlanta, GA 30329-4027
1-800-CDC-INFO
1-800-232-4636
www.atsdr.cdc.gov/toxpro2.html
and PFOS, and PFHxS in the U.S. were
3.07 and 9.32 ng/mL, respectively,
PFHxS levels were <4 and other
perfluoroalkyls were generally <1 ng/mL.
XV-1
PFAS ToxGuide
Chemical and Physical
Information
Perfluoroalkyls are Solids or
Liquids
Perfluoroalkyls are a class of
anthropogenic chemicals.
Routes of Exposure
Inhalation – Most likely route of
occupational exposure. Minor route of
exposure for the general population.
Oral – Most likely route of exposure for
the general population; food is expected
to be the primary source.
Perfluoroalkyls repel oil, grease, and
water and have been used in surface
protection products such as carpet and
clothing treatments, coating for paper
and cardboard packaging, and firefighting foams.
Companies have stopped production or
have begun changing manufacturing
practices to reduce releases and the
amounts of these chemicals in their
products.
Dermal – Potential route of exposure
particularly among workers who handle
perfluoroalkyl-treated products. -
Perfluoroalkyls in the
Environment
Perfluoroalkyls are very stable in the
environment and are resistant to
biodegradation, direct photolysis,
atmospheric photooxidation, and
hydrolysis.
Perfluoroalkyls are persistent in water
and soil. They are mobile in soil and
leach into groundwater.
Perfluoroalkyls biomagnify in the food
web and the highest concentrations are
found in apex predators. The
bioaccumulation potential of
perfluoroalkyls appears to increase with
increasing chain length.
Relevance to Public Health (Health Effects)
Health effects are determined Consistent findings were found for
associations between serum PFOA and
by the dose (how much), the
PFOS levels and increases in serum lipid
duration (how long), and the
levels, increases in uric acid levels, and
alterations in biomarkers of liver damage.
route of exposure.
Minimal Risk Levels (MRLs)
Inhalation
No acute-, intermediate-, or chronic-
duration inhalation MRLs were derived
for perfluoroalkyls.
Oral
No acute-duration oral MRLs were
derived for perfluoroalkyls.
An intermediate-duration (15-365 days)
oral MRL of 2 x 10-5 mg/kg/day was
derived for PFOA.
An intermediate-duration (15-365 days)
oral MRL of 3 x 10-5 mg/kg/day was
derived for PFOS.
No chronic-duration oral MRLs were
derived for perfluoroalkyls.
Health Effects
A large number of studies have examined
the possible relationship between levels
of perfluoroalkyls in blood and adverse
health effects in workers, residents living
near manufacturing facilities, and in the
general population. Although statistically
significant associations have been found;
the studies do not establish causality.
Additionally, the results were not always
consistent across studies.
The primary effects observed in animals
include liver toxicity, developmental
toxicity, and immune toxicity. There are
profound differences in the
toxicokinetics and mode of action of
perfluoroalkyls between humans and
experimental animals. Many of the
observed effects in animals result from
the ability of PFOA and PFOS to
activate peroxisome proliferatoryactivated receptor α (PPAR-α). Humans
are much less responsive to PPAR-α than
rodents and thus may not be as
susceptible to these types of effects.
Children’s Health
Children exposed to perfluoroalkyls
would be expected to experience effects
similar to those expected in adults.
Human studies suggest an association
between serum PFOA and PFOS levels
and decreases in birth weight. However,
the decreases in birth weight are small
and may not be biologically relevant.
XV-2
EPA References
Environmental Protection Agency References
Guidance from the Environmental Protection Agency can be found at
https://www.epa.gov/pfas.
This site includes:
Method 537. Determination Of Selected Perfluorinated Alkyl
Acids in Drinking Water by Solid Phase Extraction And Liquid
Chromatography/Tandem Mass Spectrometry (Lc/Ms/Ms)
Technical Advisory - Laboratory Analysis of Drinking Water Samples for
Perfluorooctanoic Acid (PFOA) Using EPA Method 537 Rev. 1.1
XVI-1
| File Type | application/pdf |
| File Modified | 0000-00-00 |
| File Created | 0000-00-00 |