toxicity and risk assessment meeting... · predicting bioaccumulation and toxicity accumulates* in...
TRANSCRIPT
Toxicity and Risk Assessment
Kevin Long
Terraphase Engineering Inc.
Learning Objectives
Identify the key human and ecological exposure pathways
Understand the potential adverse effects of PFAS exposure
Learn the basics of PFAS risk assessment and current challenges
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Topics PFAS exposure pathways
Effects of PFAS
Risk assessment approaches and challenges
Case examples
Take home messages It’s not just a drinking water issue
Not just PFOA and PFOS
Concentrations of PFAS at many sites can trigger need for assessment
Uncertainties and unanswered questions
Site-specific risk assessment possible
Overview
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4
Risk Assessment
ITRC 2015. Decision Making at Contaminated Sites: Issues and Options in Human Health Risk Assessment.
PFAS Exposures
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Environmental Fate
Range of behaviors leads to variety of compartments
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Source: Geosyntec
Environmental Fate and Transport
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ITRC 2018. Environmental Fate and Transport. PFAS Fact Sheets. March 2018.Adapted from figure by L. Trozzolo, TRC Solutions, used with permission.
Biological Fate
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99% of California
teachers with
detectable PFAS
https://www.fws.gov/alaska/fisheries/m
mm/polarbear/pbmain.htm
https://biomonitoring.ca.gov/
Partitions to protein, not fat/lipid
Blood, liver, kidney, muscle
Traditional models not useful for understanding or predicting bioaccumulation and toxicity
Accumulates* in plants (follows the water)
Not metabolized, or metabolizes to persistent PFAS (precursors)
* the accumulation in plants is an issue for sulfonates and shorter chain PFAAs only
Biological Fate (Long-Chain PFAAs)
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Readily absorbed
Distributed predominantly to the liver and blood (serum)
Not metabolized*
Reabsorbed in kidney tubules and from bile
Leaves the body through urine and feces
Can cross the placenta and be present in breast milk
Long-chain PFAA elimination half-life for
individuals exposed:
“One – Several Years”
* Precursors can metabolize to persistent PFAS
Bioaccumulation (Animals)
In animals, longer PFAS and sulfonated PFAS (e.g., PFOS) more bioaccumulative
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Source: Conder et al. (2008), Environ. Sci. Technol. 42:995-1003
Less
bioaccumulative
More
bioaccumulative
3
7
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Reprinted with permission from Conder, et al., 2008. Are PFCAs bioaccumulative? A
critical review and comparison with persistent lipophilic compounds. Env. Sci. & Tech.,
42:995-1003. Copyright 2008 American Chemical Society.
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More
bioaccumulative
Less
bioaccumulative
3
7
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Bioaccumulation (Plants)
Source: Geosyntec
Human Exposure Pathways
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Contact in the work place
Ingestion of food containing PFAS (believed to be principal source for general public)
Figures Courtesy K. Long
PFOA in Food (ng/g)(2009 Study from Texas)
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Data Source: Schecter et al. 2010. Perfluorinated compounds, polychlorinated biphenyls, and organochlorine pesticide contamination in composite food samples from Dallas, Texas, USA. Environ Health Perspect 118(6):796-802.
Human Exposure Pathways
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Contact in the work place
Ingestion of food containing PFAS (believed to be principal source for general public)
Ingestion of drinking water (living with PFAS-contaminated water supplies)
Figures Courtesy K. Long
2013-2015 list included 6 PFAAs (PFOS, PFOA, PFNA, PFHxS, PFHpA, PFBS)
Municipal systems >10,000 and selected smaller systems
Detected in ~4%, exceeded EPA LHAs in ~1.3%
High RLs and sampled only at entry points, not wellheads
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Figure used with permission from Andy Eaton, Eurofins-Eaton Analytical
UCMR3: PFOS and PFOA Detections
Did NOT test forPFBA or PFPeA
PFAS in Municipal Drinking Water Supplies
Detected < LHAExceeds LHA
Map data ©2019 Google
Human Exposure Pathways
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Contact in the work place
Ingestion of food containing PFAS (believed to be principal source for general public)
Ingestion of drinking water (living with PFAS-contaminated water supplies)
Direct contact with products (such as treated carpets and upholstery) or indoor dust
Figures Courtesy K. Long
Human Exposure Pathways
Major1,2
Diet (bioaccumulation)
Fish and seafood
Homegrown produce
Drinking water
Incidental soil/dust ingestion
Usually insignificant or minor Dermal absorption
Inhalation
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1 Oliaei et al., 2013. Environ. Sci. Pollut. Res. Manag. 20:1977-19922 Domingo, 2012. Environment International 40:187-195 Source: Open source, Pixabay
PFAS Serum Levels in Humans
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Data Source: CDC 2018. Fourth National Report on Human Exposure to Environmental Chemicals. March.
(General US Population, Geometric Mean)
Ecological Exposure Pathways
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Source: Figure Courtesy of Geosyntec
Incidental soil and sediment ingestion
Diet (biomagnification) Aquatic food webs susceptible
to longer-chained PFAS
Plants accumulate shorter-chained PFAS
Dermal absorption (Aquatic animals)
Example Aquatic Ecological and Human Health Risk Models for AFFF Sites
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Source: Larson, Arblaster, Conder, et al (2018, Chemosphere 201:335-341), Figure 1Used with permission
PFOS Concentrations in Fish
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ITRC 2018. Environmental Fate and Transport. PFAS Fact Sheets. March.
PFOS in SedimentAquatic sediment can sorb PFOS* and present potential risks to wildlife
PFOS in sediment as low as 10-30 ng/g, dw may indicate the need for investigation at some sites
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Avian NOAEL PFOS TRV
Source: Larson, Arblaster, Conder, et al (2018, Chemosphere 201:335-341), Figure 2
*Other PFAS can sorb to sediment.
PFOS in Sediment
Aquatic sediment can sorb PFOS and present potential risks to fishermen
PFOS in sediment as low as 1 to 5 ng/g, dw may indicate the need for investigation
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Source: Geosyntec
PFAS Effects
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Health Effects of PFOA and/or PFOS
* PFOA Only
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Animal
Liver effects
Immunological effects
Developmental effects
Endocrine effects (thyroid)
Reproductive effects
Tumors (liver, testicular*, pancreatic*)
Human (possible links)
Liver effects (serum enzymes/bilirubin, cholesterol)
Immunological effects (decreased vaccination response, asthma)
Developmental effects (birth weight)
Endocrine effects (thyroid disease)
Reproductive effects (decreased fertility)
Cardiovascular effects (pregnancy induced hypertension)
Cancer* (testicular, kidney)
Health Effects of PFOA and/or PFOS
Carcinogenicity
PFOA IARC - “Possibly carcinogenic to humans” (Group 2B)
USEPA - “Suggestive evidence of human carcinogenicity”
USEPA – oral cancer slope factor (SF) for PFOA of 0.07 (mg/kg-day)-1
PFOS USEPA – “Suggestive evidence of human carcinogenicity”
“Weight of evidence for relevance to humans was judged as too limited to support a quantitative assessment.”
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Toxicology of Other PFAS
Information for some PFAS in peer-reviewed literature and chemical registration information (REACH dossiers, TSCA submittals)
Most focused on the PFCAs and PFSAs, the perfluoroalkyl acid “families” to which PFOA and PFOS belong
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USEPA Draft Toxicity Assessments
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Source: https://www.epa.gov/pfas/genx-and-pfbs-draft-toxicity-assessments
Toxicology of Other PFAS
Information for some PFAS in peer-reviewed literature and chemical registration information (REACH dossiers, TSCA submittals)
Most focused on the PFCAs and PFSAs, the perfluoroalkyl acid “families” to which PFOA and PFOS belong
Long-chain PFAAs appear to have effects generally similar in animal studies (developmental, immune, liver, etc.)
Animal data for short-chain PFAAs show liver and kidney effects at high concentrations
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Toxicology of Other PFAS2900
12 12 15 12
1400
3.8
23
1
10
100
1000
10000P
FB
A
PF
PeA
PF
HxA
PF
Hp
A
PF
OA
PF
NA
PF
DA
PF
UA
PF
Do
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PF
TrD
A
PF
Te
DA
PF
BS
PF
HxS
PF
OS
PF
DS
3 4 5 6 7 8 9 10 11 12 13 4 6 8 10
PFCAs PFSAs
RfD
(ng
/kg
, b
w*d
)
L
L
L
Source: Geosyntec analysis of TECQ RfDs (http://www.tceq.texas.gov/assets/public/remediation/trrp/pcls.pdf) *Presenter/ITRC does not necessarily endorse or certify these values (use at your own discretion).
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Example Toxicity Values (Noncancer)
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Chemical TypeValue
(ng/kg-day)Source Notes
PFOA Oral RfD 20 USEPA 2016 (May)Mice: developmental - reduced ossification, accelerated puberty
2 NJDEP 2017 (March)Mice: increased liver weight, UF delayed mammary gland development
3 ATSDR* 2018 (June) DRAFTMice: altered activity and skeletal alterations in offspring
PFOS Oral RfD 20 USEPA 2016 (May) Rat: reduced pup body weight
1.8 NJDEP 2018 (June) Mice: decrease in antibody response
2 ATSDR* 2018 (June) DRAFTRat: delayed eye opening, decreased pup body weight, UF immune effects
PFNA Oral RfD 0.74 NJDEP 2015 (June) Mice: increased maternal liver weight
3 ATSDR* 2018 (June) DRAFTMice: decreased offspring body weight and developmental delays
PFHxS Oral RfD 20 ATSDR* 2018 (June) DRAFT Rat: thyroid follicular cell damage
* Intermediate Minimal Risk Level (MRL).UF = uncertainty factor
Example Noncancer Reference DosesPFOA and PFOS
Source
Reference doses for human health risk assessment (ng/kg body weight*day)
PFOABasis and Comparison to
USEPA (2016) PFOSBasis and Comparison to
USEPA (2016)
USEPA (2016) 20 Developmental effects (bones), accelerated male puberty in mice
20 Reduced growth in young rats/parents
ATSDR (2018) DRAFT
3 Effects on behavior and skeletal development in mice
Based on a study USEPA did not select for consideration, and a newer study from 2016
2 Same study, but selected different effect (delayed eye opening) and added a 10X conservativeuncertainty factor to protect for immunotoxicity
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Toxicology of PFAS to Non-human Receptors
Wildlife effects (mammals and birds) Effects on liver and kidney
Reproduction
Aquatic toxicity data (fish, invertebrates) for some compounds Most direct toxic effects occur at concentrations much higher than other
concerns (e.g., drinking water)
Plants and soil invertebrates relatively insensitive Effects occur in the mg/kg range (higher than other concerns)
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PFAS Risk Assessment Challenges
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What Types of Sites?
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Industrial Sites Petrochemical, chemical plants Textile, carpet manufacturers Leather, clothing, and fabric treatment facilities Metal coating and plating facilities
Sites Impacted by Fires Rail yards Current/former DoD sites Airports Training areas Crash sites (planes/cars)
Other Type of Sites Landfills Sewage sludge land applications Water treatment systems
Risk Assessment Challenges (Overview)
Not just PFOA and PFOS
Lack of toxicity values
Carcinogenicity and additivity
Background/anthropogenic impacts
Fate and transport
Lack of standard guidance
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Risk Assessment Challenges
It’s not just PFOA and PFOS…
16 other PFAS by USEPA Method 537 (Nov. 2018)
Additional 10-15 more PFAS via other methods
Dozens to hundreds of other PFAS in AFFF
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Risk Assessment Challenges
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Toxicity…
Variety in the existing available PFOA and PFOS noncancer toxicity values
Lack of ability to quantify cancer hazard
Additivity of PFAS?
Missing toxicity information for other PFAS
Risk Assessment Challenges
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Exposure…
Background/anthropogenic impacts
Assessing potential future exposures Fate and transport challenging due to lack of physical
chemical properties
Precursors
Risk Assessment Challenges
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Lack of Standard Guidance…
No standard guidance or models for PFAS risk assessment
Conceptual site models Sampling approaches Uptake Fate and Transport Toxicity
…. Yet
Case Examples
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PFAS Risk Assessment in Practice
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Risk Assessment
ITRC 2015. Decision Making at Contaminated Sites: Issues and Options in Human Health Risk Assessment.
Risk Assessment
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Risk Assessment
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Drinking Water Health Advisories
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Relative Source Contribution (RSC)
of 20%
Factors Impacting Numerical Value of PFAS Drinking Water Guidelines
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Factor Explanation Examples Impact
Reference Dose
(POD ÷ Total UF; also includes
animal-to-human extrap. factor)
Point of Departure (POD): • NOAEL• LOAEL• Benchmark Dose
(BMDL)
Dose (mg/kg/day) from animal study used as starting point
• LOAEL for ↓ offspring body weight in rats
• NOAEL for ↓ immune response in mice.
↑ POD ↑ Guideline
Uncertainty factors (UFs)• POD is divided by
individual UFs of 1-10• Total UF generally 30-300
• Interindividual• Animal-to-human• Data gaps
↑ Total UF ↓ Guideline
Animal-to-human doseextrapolation
To account for higher internal levels in humans than lab animals from same dose
• Serum PFAS levels as dose metric
• Human-to-animal half-life ratio
Depends on specifics of approach.
Exposure
Drinking water consumption rate
• L/kg/day.• Based on daily ingestion
(L/day) and body wt. (kg)
Infant > Lactating Woman > Default Adult
↑ Ingestion rate
↓ Guideline
Relative Source Contribution (RSC)
Accounts for non-drinking water exposure sources (e.g. food, air).
• Default - 20%• Up to 80% based on
chemical-specific data.
↑ RSC ↓ Guideline
Drinking Water Guideline = Reference Dose (mg/kg/day) x Relative Source Contribution (%)Drinking Water Consumption Rate (L/kg/day)
Case Example: NJDEP Fish Advisory
NJDEP used fish tissue sampling of various sites in New Jersey and risk assessment methodology to determine the need for fish consumption advisories for PFAS
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https://www.nj.gov/dep/dsr/njmainfish.htm https://www.nj.gov/dep/
PFAS Analyzed
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NJDEP 2018. Investigation of Levels of Perfluorinated Compounds in New Jersey Fish, Surface Water and Sediment. June.
Sampling Locations
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11 Waterways
Proximity to PFAS sources
Likelihood for recreational (fishing)
Fish Species
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NJDEP 2018. Investigation of Levels of Perfluorinated Compounds in New Jersey Fish, Surface Water and Sediment. June.
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Fish Tissue Sampling Results
Data from NJDEP 2018. Investigation of Levels of Perfluorinated Compounds in New Jersey Fish, Surface Water and Sediment. June.
Toxicity Values (Noncancer)
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Chemical TypeValue
(ng/kg-day)Source Notes
PFOA Oral RfD 20 USEPA 2016 (May)Mice: developmental - reduced ossification, accelerated puberty
2 NJDEP 2017 (March)Mice: increased liver weight, UF delayed mammary gland development
3 ATSDR* 2018 (June) DRAFTMice: altered activity and skeletal alterations in offspring
PFOS Oral RfD 20 USEPA 2016 (May) Rat: reduced pup body weight
1.8 NJDEP 2018 (June) Mice: decrease in antibody response
2 ATSDR* 2018 (June) DRAFTRat: delayed eye opening, decreased pup body weight, UF immune effects
PFNA Oral RfD 0.74 NJDEP 2015 (June) Mice: increased maternal liver weight
3 ATSDR* 2018 (June) DRAFTMice: decreased offspring body weight and developmental delays
PFHxS Oral RfD 20 ATSDR* 2018 (June) DRAFT Rat: thyroid follicular cell damage
Exposure Factors
Each meal assumed to be 8 ounces
70 kg body weight
Consumption frequencies No limit (unlimited consumption)
No more than 1 meal per week
No more than 1 meal per month
No more than 1 meal every 3 months
No more than 1 meal every year
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NJDEP 2018. Investigation of Levels of Perfluorinated Compounds in New Jersey Fish, Surface Water and Sediment. June.
Draft Preliminary Advisory Triggers
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NJDEP 2018. Investigation of Levels of Perfluorinated Compounds in New Jersey Fish, Surface Water and Sediment. June.
HQ: hazard quotient (unitless)
Cfish: fish concentration (ng/g)
M: # of meals
CR: fish consumption rate (g/meal)
BW: body weight (kg)
RfD: reference dose (ng/kg-day)
ATnc: averaging time (days)
Results
All 11 sites warranted fish consumption guidance for the general population ranging from one meal per week to one meal per year
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Site Advisory (Driven By)
Echo Lake Reservoir No more than once/month (PFOS, Largemouth Bass)
Passaic River 1&2 No more than once/3 months (PFOS, Largemouth Bass-Bluegill Sunfish)
Raritan River No more than once/month (PFOS, Common Carp-White Perch)
Metedeconk 1&2 No more than once/3 months (PFOS, Largemouth Bass)
Pine Lake No more than once/year (PFOS, American Eel-Largemouth Bass-Pumpkinseed Sunfish)
Horicon Lake No more than once/month (PFOS, Chain Pickerel)
Little Pine Lake No more than once/year (PFOS, Largemouth Bass-Yellow Perch)
Mirror Lake No more than once/3 months (PFOS, American Eel-Bluegill Sunfish-Largemouth Bass)
Woodbury Creek No more than once/3 months (PFOS, Largemouth Bass-Pumpkinseed Sunfish)
Fenwick Creek No more than once/month (PFOS, Common Carp)
Cohansey River 1&2 No more than once/week (PFOS, White Perch)
NJDEP 2018. Investigation of Levels of Perfluorinated Compounds in New Jersey Fish, Surface Water and Sediment. June.
Take-Aways
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Take-Aways
Not just a human health drinking water issue
Not just PFOS and PFOA
Concentrations of PFAS at many sites can trigger need for assessment
Uncertainties and unanswered questions
Site-specific risk assessment is possible
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Questions?