Toxicity and Risk Assessment Meeting... · predicting bioaccumulation and toxicity Accumulates* in plants (follows the water) ... Example Toxicity Values (Noncancer) 31 Chemical Type

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.


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Ingestion of drinking water (living with PFAS-contaminated water supplies)


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


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Ingestion of drinking water (living with PFAS-contaminated water supplies)

Direct contact with products (such as treated carpets and upholstery) or indoor dust



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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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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http://www.tceq.texas.gov/assets/public/remediation/trrp/pcls.pdf

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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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


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Exposure…

Background/anthropogenic impacts

Assessing potential future exposures Fate and transport challenging due to lack of physical

chemical properties

Precursors


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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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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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Draft Preliminary Advisory Triggers

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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)


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?

Documents

Toxicity and Risk Assessment Meeting... · predicting bioaccumulation and toxicity Accumulates* in plants (follows the water) ... Example Toxicity Values (Noncancer) 31 Chemical Type