PFAS: HUMAN & ECOLOGICAL HEALTH EFFECTS OF SELECT PFAS
7.1 Human Health Effects
 PFAS covered in this reading:
 PFCA  C4-C14
 PFSA  ≥ C4
 GenX chemicals
o HFPO-DA
o PFProPrA
o FRD-903
o ADONA
 Toxicity is typically induce at higher doses
for Short-chain PFAAS than Long-chain
PFAAS
7.1.1 Human Biomonitoring & Sources
of Exposure
 Human Biomonitoring
 Some PFAS, notably long-chain PFAAs,
are found to in blood serum of many US
individuals
o Serum PFAA originated from:
 Direct exposure
 Metabolism of precursor
compounds to PFAA in the body
 CDC conducts annual survey called
National Health and Nutrition
Examination Survey (NHANES) that
determines serum concentration
o Serum PFAAs level of general
populace have been declining
 Especially for PFOS
o Latest NHANES survey has been
conducted on 2017-2018
 8 PFAAs and 4 PFAS have
been detected
 5 PFAAs has not been
examined in this latest survey
 Exposure Sources
 For general population
o Primary PFAAs exposure sources
are food & food packaging,
consumer products and house dust
generated from that products
o Inhalation is also a possible
exposure route
o Banning the usage of PFOA &
PFOA resulted in the reduction of
exposure to these substances of
gen. pop
 Based on NHANES surveys
 Communities near sources of PFAS
concentration
o Exposure of these people are higher
than gen, pop
 Due to consumption of
contaminated drinking water
and/or consumption of fish from
contaminated water
o Occupation exposure tend to be
higher than exposure from
environment
7.1.2 Toxicokinetics
 PFAAs have unique toxicokinetic properties
in comparison to other Persistent Organic
Pollutants (POPs)
 PFAAs are water soluble
 PFAAs have affinity for proteins
 PFAAs are commonly distributed to
o Liver
o Blood serum
o Kidneys
 PFAAS, GenX Chemicals and ADONA
are not metabolized in the body
 Some PFAA precursors can be further
metabolized to PFAAs in the body
 Generally, short-chain PFAAs are excreted
more rapidly in humans and other mammals
 Excretion rate can vary depending on
species type as well as sex of species
 Half-lives of lab animals trend:
o Short-chain PFAAs  hours to
several days
o Long-chain PFAAs  hours to
several months
 Half-lives of lab estimate for humans
trend
o Short-chain PFAAs  several
days to one month
o Long-chain PFAAs  several
years
PFAS: HUMAN & ECOLOGICAL HEALTH EFFECTS OF SELECT PFAS
 Animal-to-human comparison must take
into account the higher internal dose in
humans
 Toxicokinetics – Developmental
Exposures
 Long-chain PFAAs have been
correlated with decreased fetal growth
 PFAAs cross the placenta barrier
 PFAAs can been found in:
o Breast milk
o Amniotic fluid
o Cord blood
 Exposure of infants to breast milk can
increase their long-chain PFAAs serum
levels
 Exposure of infants to formula prepared
with PFAS-contaminated water are
higher compared to older pop
o Due to higher fluid consumption
 Clearance Factors
 Clearance Factors – bioaccumulative
potential
o Relate external dose of PFOA &
PFOS (mg/kg day) to steady-state
serum levels
o These factors can be used to predict
that expected average increases in
PFOA/PFOS level in blood serum
(from long-term drinking water
exposure) are 100-fold or greater
than level in water
 Toxicokinetics in rodents and humans may
differ among isomers of same PFAA.
7.1.3 Human Epidemiology Studies
 Epidemiological studies for long-chain
PFAAs
 Some effects/changes evaluated in
numerous studies:
o Serum lipids
o Liver biomarkers
o Uric Acid levels
o Thyroid endpoints
o Vaccine response
o Fetal Growth
 These studies can be classified based
on population types assessed:
o General Population
o Communities with contaminated
drinking water
o Occupationally exposed workers
 Association of human epidemiological
studies with Animal Toxicity studies
 Association of human epidemiological
studies with Animal Toxicity studies are
generally consistent for some health
endpoints
o However, for Serum Lipids, there
are some conflicting studies
 Increases in humans,
Decreases in rodents
 This may be due to differences
in fat content of diet of the two
animals and/or;
 Differences in exposure levels
of humans vs animals
 Risk-based Toxicity Factors
 Most of Risk-based Toxicity Factors
developed by legislation are based on
Animal Toxicology Studies
o Human data are just supplementary
component in toxicity factor
development
o Serum levels of co-occurring PFAAs
tend to associate with each other
 Hence, it’s difficult to evaluate
the dose-relationship for indiv.
PFAAs
 Some Organizations that primarily
utilized human data
PFAS: HUMAN & ECOLOGICAL HEALTH EFFECTS OF SELECT PFAS

o German Human Biomonitoring

Commission & German Environment
Agency
o Developed Human Biomonitoring
Values – serum levels where
adverse effects aren’t expected