Document jg7m0dN5ZjbjM3rED8R99NoZR
1
Table: Results from studies on PFSAs
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
PFBS
PFBS (97.9% pure, K+-salt)
2-generation
Increased liver 100
reproduction study
weight
according to OECD
(maternal)
guideline 416
Increased
100
Sprague Dawley rats
hepatocellular
Gavage. 0, 30, 100, 300, hypertrophy (P
1000 mg/kg bw per day. and F1 adult
males)
Parental (F0) animals
(males and females,
Increased
100
n=29-30 per sex per
incidence of
group) dosed from 70
mild
days prior to mating,
microscopic
females were continued findings in
through gestation and kidney
lactation. F1 offspring
(maternal).
(n=29-30) was dosed
from weaning
Reproductive
(lactational day 22)
and
onwards. F2 generation developmental
was exposed through
toxicity findings
placenta and lactation. offspring not
Experiment was
observed
terminated at lactational (highest dose
day 22 of F2 generation LOAEL)
animals
Significant
30
increase in
diestrus cycling
only at 100
mg/kg bw/day
300 300 300 1000
100
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
Immune system, thyroid system?
Not determined
Lieder et al. 2009b
2
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
Crl:CD(SD)IGS BR
Decreased abs
60
VAF/PlusTM rats (m/f) &rel spleen
Based on OECD 408
weight(m)
Gavage: 0, 60, 200, or
Decr red blood
600 mg/kg bw per day cells (m)
600
200
Duration: 90 days
Decreased
No/sex/group: 10
hematocrit (m)
200
Decr
60
hemoglobin (m)
Increased
200
serum chloride 60
(m)
Decreased
600
serum albumin 200
and total
protein (f)
600 200
Decreased
100
300
PFBS,
Sprague Dawley rats
serum
potassium salt (m/f)
phosphorus and
(98.2% purity) Gavage: 0, 100, 300, or potassium (m)
900 mg/kg bw per day.
Incr rel and
300
900
Duration: 28 days
absolute liver
weight (m)
No/sex/group: 10
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
Not determined
Lieder et al. 2009a
Not determined
NICNA S, 2005
3
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
PFBS (97%
ICR mice
Decreased body 50
200
pure, K+-salt)
Dosing: 0, 50, 200, and weight from
500 mg/kg bw per day PND 1 to
from GD 1 -20, orally.
adulthood
Only female offspring
follow-up reported.
Delayed eye
50
200
opening
30 dams per dose group,
randomly allocated to
Delayed vaginal 50
200
three experimental sub- opening
groups per dose:
group 1: perinatal
Impaired
50
200
survival and growth,
ovarian and
pubertal onset, and
uterine
ovarian and uterine
development
development (10 dams,
50 female offspring per Delayed estrus 50
200
dose),
cyclicity and
group 2: hypothalamic- reduced E2/
pituitary-gonadal
increased LH
hormone and
hypothalamic-pituitary- Decreased
50
200
thyroid hormone levels T3/T4,
(10 dams, 30 PND 1
increased TSH
female offspring, 10
female PND 30 offspring, Decreased
50
200
and 10 PND 60 female
T3/T4,
offspring),
increased TSH
group 3: levels of serum at GD 20
PFBS (10 dams)
(maternal)
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
Mean (10 dams) serum concentration (ng/mL) on GD 20, 12h after last dosing, at 0, 50, 200 and 500 mg/kg bw per day: 1.73, 74, 332, 721.
Feng et al., 2017
PFBS (>97%
Sprague Dawley rats (m, Incr rel liver
62.6
purity)
f)
weigt (m)
Gavage: 0, 62.6, 125,
250, 500, or 1,000
Incr rel liver
62.6
125
mg/kg bw per day
weigt (f)
No/sex/group: 10 Duration: 28 days
Incr abs liver
125
125
weight (m)
Incr abs liver
250
weight (f)
Incr acyl-CoA-
250
oxidase activity
(m)
Decr
62.6
haematocrit
(m,f)
Decr RBC (m,f)
62.6
Decr chol (m,f)
62.6
Decr T3 (m,f)
62.6
Decr total+free
62.6
T4 (m,f)
Incr
albumin/globuli 62.6
125
n ratio (m,f)
Plasma conc. (ug/ml) at 62.6mg/kg bw/day: 2.2 + 4.8 (m) 0.2 + 0.05 (f) Liver conc (ug/g) at 62.6mg/kg bw/day 1.3 + 0.2 (m)
NTP, 2019b
4
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
PFBS, (L-7038, 98.2% pure)
PFHxS PFHxS (potassium salt; 99.98% purity)
male E3L.CETP mice on a C57Bl/6 background (a transgenic mouse model for human-like lipoprotein metabolism, APOE*3-Leiden.E3L CETP) Fed a western diet daily with 30 mg/kg bw/day for 4-6 weeks
Sub-chronic, duration: 42 days,OECD guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction/Developm ental Toxicity Screening Test) Sprague Dawley rats (m) Gavage: 0, 0.3, 1, 3, or 10 mg/kg bw per day. No/sex/group: 10 for clinical/chemical parameters, 15 dams per group
Reduced plasma triglycerides and cholesterol (VLDL-C an HDLC)
Incr rel liver weight Decr prothrombin time Decr serum cholesterol Decr hemoglobin Decr hematokrit Decr RBC Thyroid hypertrophy/hy perplasia No reproductive or developmental effect No treatment related effects in dams
30
1
3
0.3
0.3
0.3
1
1
3
1
3
1
3
10
10
mean serum concentration ~33-38 g/ml
Bijland et al., 2011
Concentration in g/g: m at 0.3 mg/kg bw per day: in liver 43.8 +/8.1, in serum 44.2 +/- 12.7
Butenh off et al., 2009
m at 3 mg/kg bw per day: in liver 339 +/- 128, in serum 128 +/10
m at 10 mg/kg bw per day in liver 593 +/81.4 in serum 201.5 +/- 20
Elaborated serum and liver values in dams and fetuses. Serum levels at study day 14 and GD 21 in dams were similar. For GD 21 females in serum and liver: 0 mg/kg per day: <LOQ of 0.1 g/mL and 0.1 g/g. 0.3 mg/kg per day: 3.32 g/mL and 0.79 g/g. 1 mg/kg per day: 10.65 g/mL and 2.61 g/g. 3 mg/kg per day: 32.75 g/mL and 7.80 g/g. 10 mg/kg per day: 59.80 g/mL and 16.53 g/g
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
5
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
PFHxS (3M, salt, purity not specified)
PFHxS (potassium salt, 97% purity)
SV129 mice (m) Duration: 7 days Gavage: 0, 3 or 10 mg/kg bw per day No/sex/group: 4
SV129 mice (m) Duration: 7 days Gavage: 0 or 10 mg/kg bw per day No/sex/group: 4
Incr rel liver weight Incr abs liver weight
Incr abs and rel liver weight Incr hepatic lipid and triglyceride content
3
3
10
10 10
Not reported
Rosen et al., 2017
Not reported
Das et al., 2017
6
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
PFHxS
Crl:CD1 (IRC) mice, OECD Incr abs & rel
0.3
1
(potassium salt; test guideline 422
liver weight (F0
98.9% purity)
(Combined
m,f)
1
Repeated Dose Toxicity Centrilobular
1
0.3
Study with the
hypertrophy (F0
1
Reproduction/Developm m)
ental Toxicity
Incr ALP (F0 m)
3
Screening Test),
modified (extended).
Decr Serum
3
cholesterol (F0
Duration: 42 days.
m)
Gavage: 0, 0.3, 1, 3
Necrotic
3
mg/kg bw per day
hepatocytes
and lipid
No/sex/group: 30
vesicles in
hepatocytes (F0
For F0 males treatment m)
from 14 days prior to
cohabitation for to at
least 42 days total (one
day post-last dosing).
Treatment of F0 females
started 14 days prior to
cohabitation with
continuation through
mating, gestation, and
lactation. F0 dams were
sacrificed on lactation
day 22 (one day after
last dosing). F1
offspring, first exposure
in utero and via
lactation. After weaning
(PND 22), F1 direct
dosing for 14 days at
maternal dose.
Liver conc. (g/g): F0M at 0.3 mg/kg bw/day: 25.9 3.5 F0M at 1 mg/kg bw/day: 98.5 22.7 F0M at 3 mg/kg bw/day: 281.1 45.4
Serum and liver in dams, and serum from pooled fetus on GD18: 0 mg/kg per day: <0.001 g/mL, <0.005 g/g and <0.001 g/mL. 0.3 mg/kg per day: 16.8 g/mL, 5.3 g/g, and 20.8 g/mL . 1 mg/kg per day: 51.5 g/mL, 15.1 g/g and 62.3 g/mL. 3 mg/kg per day: 111.3 g/mL, 88.4 g/g and 137.7 g/mL.
Chang et al., 2018
7
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
Toxicokinetic experiment: 12 animals per sex and dose. Subset 1 (5/sex/dose group) daily oral gavage for 14 days prior to sacrifice. Subset 2 (7/sex/dose group) dosing for 14 days prior to cohabitation. Serum and liver samples were collected at study day 14 for both sexes, at study day 28 for males and GD 18 (for females). On GD 18, pooled fetal blood and fetal liver samples were collected
Reduced litter size (without impact on born pup to implant ratio).
F1: Increased relative liver weight (m, f)
F1: Increased thyroid weight (m)
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
0.3
1
1
3
1
3
PFHxS ( potassium salt; >98% purity)
Sprague Dawley rats (m, f) Duration: 28 days Gavage: 0, 0.625, 1.25, 2.5, 5, or 10 mg/kg bw per day (males) 0, 3.12, 6.25, 12.5, 25, or 50 mg/kg bw per day (females) No/sex/group: 10
Incr rel and abs liver weight (m)
Incr rel and abs liver weight (f)
Decr T3 and cholesterol (m)
Decr total T4 (m)
Decr total T4 (f) Decr free T4 (m) Decr free T4 (f)
Incr acyl-CoAoxidase activity (m)
0.625 3.12 6.25
2.5
1.25
3.12
0.625
0.625
6.25 0.625
12.5 5
Plasma conc. (ug/ml) 0.625mg/kg bw/day: 66.8 + 3.5 (m) 3.12mg/kg bw/day: 37.0 + 1.7 (f)
NTP 2019b
Liver conc (ug/g) 0.625mg/kg bw/day 39.9 + 1.3 (m)
8
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
PFHxS, K+-salt, Wistar rats
Increased liver
5
25
purity > 98%
Dosing from GD 7 until weight, male F1
PND 22 (except for day
of delivery).
Increased liver
0.05
5
Gavage: 0, 0.05, 5, 25
weight, female
mg/kg bw per day
F1
Main study: 16 -20 time
mated rats per group
Pronounced
0.05
5
Dose range finding study reduction of T4
(8 time mated rats per levels, dams
group): 0, 25, 46 mg/kg
bw per day
Pronounced
0.05
5
reduction of T4
levels, F1
Serum levels in dam at PND 22 in the dose range finding study. 139 and 174 g/mL in 25 and 45 mg/kg bw per day groups, respectively
Ramh j et al. 2018
Mildly decreased body weight, male pups
5
25
Mildly
decreased body
0.05
5
weight, female
pups
No relevant effects on anogenital distance, nipple retention or organ weights
PFHpS: No studies identified PFOS
9
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
PFOS (91% K+- Reproductive/developm Decreased
1
2
Salt)
ental
postnatal
"Our analysis
survival
indicated that Sprague-Dawley rats
2
approximately
Decreased
71% of the
Exposure: 0, 1, 2, 3, 5, 10 growth in
1
chemical was
mg/kg per day per
surviving pups
straight-chain, gavage GD2 - GD21
and the
Delay in eye
remaining 29%
opening
1
2
was branched.
Additional
Decreased
analysis
thyroxin (pups) 1
2
indicated that
the chemical
No consistent
obtained from
change in liver
Fluka appeared
weight or
to be identical
relative liver
to that
weight in
produced by
surviving pups
3M."
PND 0-35
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
Read from figures. Serum in pups at pnd 1: Control: 0; 1 mg/kg: 36 g/mL; 2 mg/kg: 71 g/mL; 3 mg/kg: 85 g/mL; 5 mg/kg: 108 g/mL; Slightly lower at pnd 5
Lau et al. 2003
Liver in pups at pnd 1: Control: 0; 1 mg/kg: 45 g/g; 2 mg/kg: 68 g/g; 3 mg/kg: 100 g/g; 5 mg/kg: 160 g/g
PFOS (86.9%,
2-generations
F0 males and
0.4
1.6
K+-Salt. Lesser reproductive/developm females:
homologs (C4- ental
reduced bw
C7) at 8.4%;
gain.
impurities (by Sprague Dawley rats, 20
quantitative
dams per group.
In F0 shorter
1.6
3.2
19F Nuclear
gestation, lower
Magnetic
Exposure: 0, 0.1, 0.4,
n implantation
Resonance) at 1.6, and 3.2 mg/kg bw sites, increase
1.9%; metals
per day by gavage for 6 in stillborn pups
(calcium,
weeks prior to mating, or early
magnesium,
during mating, and
neonatal death
sodium, nickel, through gestation and of litter.
and iron) at
lactation, across two
1.5%; inorganic generations for females
fluoride at
(only 0, 0.1, 0.4 mg/kg
0.6%;
bw per day continued to
perfluorooctan F2). Cross fostering (0
oic acid at 0.3%; and 1.6 mg/kg bw per
nonofluoropent day) as follow up study
anoic acid at
0.3%;
heptafluorobut
yric acid at
0.1%.
Serum levels (g/mL) from cross foster study at end of lactation available.
Luebke r et al. 2005a
10
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
F1 reduced
0.4
1.6
survival and bw
gain.
Delayed eye
0.1
0.4
opening F1
Pre- and postnatal exposure was additive for pup toxicity
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
PFOS (86.9%,
Reproductive/developm Decrease in
BMDL05
K+-Salt.
ental, Sprague Dawley gestation length 0.31
Impurities as in rats, 35 dams per group.
Luebker 2005a Exposure: 0, 0.4, 0.8,
Decrease in
1.0, 1.2, 1.6, 2,0 mg/kg postnatal
BMDL05
bw per day by gavage
survival day 5 0.89
from 6 weeks prior to
mating to day four of
Decreased
lactation
mean pup
weight at birth BMDL05
0.39
Increase in
serum T4 on
lactation day 5
(F0 and F1)
0.4
Measured in dams GD 1, 7, 15 and 21. Constant GD 115, drop at GD 21. Serum levels GD 1-15 (g/mL): 0.1 mg/kg: 7.88.9 ; 0.4 mg/kg: 40.7- 41.4; 1.6 mg/kg: 154-160; 3.2 mg/kg: 275318
Luebke r et al 2005b
11
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
PFOS (98% K+- Developmental study,
Reduced weight 10
20
Salt)
ICR mice
gain (F0).
15 dams/goup (5 each Increased liver
selected for specific
weight (F0).
1
10
endpoints
Liver
Exposure: 0, 1, 10, 20
hypertrophy
mg/kg per day , GD 1 - (F0).
10
20
17/18
Decreased
neonatal
survival.
1
10
Developmental/
teratological
alterations.
1
10
Sternal defects.
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
Not reported
Yahia et al., 2008
1
Developmental study,
Decrease in NK 0.1
1
B6C3F1 mice.
cell activity at 8
weeks (F1 M).
Exposure: GD 1-17, 0,
Decrease in NK
0.1, 1.0, 5.0 mg/kg bw
cell activity at 8
per day by gavage.
weeks (F1 F).
1
5
Decrease in IgM
production
assessed by PFC
assay at 8
1
5
weeks (spleen)
(F1 M).
Decrease in IgM
production
assessed by PFC
assay at 8
weeks (spleen)
F1 F).
5
Not reported
Keil et al., 2008
12
Substance (%), EC/CAS, formula
PFOS (purity 98%, K+-salt)
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
Developmental study ICR mice
Exposure 0, 9, 13, 20, 30 mg/kg bw per day by gavage GD1-17 (3 dams/group).
Sharp increase in cleft palate between 13 (7.3%) and 20 (78.35) mg/kg per day.
20 mg/kg bw per day GD 1-17 and 50 mg/kg per day GD11 - 15.
5 - 8 dams per group 67 - 103 fetuses: (examined animals, total number higher).
20 mg/kg per day GD 115/18 for histology.
NO(A)EL (mg/kg bw/d)
13
LO(A)EL (mg/kg bw/d)
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
20
50 % effective dose expected 17.7 mg/kg per day
Serum level on GD17 (g/mL) reported for dams at 30 mg/kg per day and other values estimated from figure: 9 mg/kg bw per day: 58 in dam, 62 in fetus. 13 mg/kg bw per day: 105 in dam and fetus. 20 mg/kg bw per day: 135 in dam and fetus. 30 mg/kg bw per day: 162.3 in dams and 130 in fetus. 30 mg/kg bw per day: 162.3 in dams and 130 in fetus.
Era et al., 2009
50 % effective fetal serum concentration for cleft palate: 121 g/mL
13
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
PFOS (purity 98%, salt not specified)
Developmental study CD1 mice Exposure: 0, 0.3, 3 mg/kg per day GD1 - PND21 by gavage. Then no dosing in offspring until sacrifice at PND 63.
Dams: 6 per group (sacrifice after weaning (PND 21))
Increased abs. 3 liver weight P0
Increased dam's liver weight F1 0.3 M
Increased
relative liver
0.3
weight P0 and
F1
Offspring: animals per
Increased
treatment equally
HOMA-IR (P0). 3
distributed in a low and
a high fat feeding group. Increased
Termination on PND 63 HOMA-IR (F1)
3
Elevated fasting
glucose (F1 PND
21)
3
Elevated fasting
glucose (F1 PND
63)
0.3
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
Liver levels in dams at 0, 0.3 and 3 mg/kg per day: 0.15, 49.1 and 338.9 g/g.
Wan et al., 2014
Serum levels in pups PND21 at 0.3 mg/kg per day: 12.7 g/mL in males and 11.4 g/mL in females.
Serum levels at 3 mg/kg per day: 98.7 g/mL in males and 87.2 g/mL in females.
Liver levels in pups PND21 at 0.3 mg/kg per day: 20.1 g/g in males and 18.0 g/g in females Liver levels at 3 mg/kg per day: 243 g/g in males and 178 g/g in females
14
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
PFOS (purity
Developmental study
Body weight
2
8
not specified, CD1 mice
decrease (P0)
K+-salt)
Exposure: Gavage, 0,
0.5, 2, 8 mg/kg per day, Dose
GD11 - GD16
dependent
0.5
decrease of
10 dams per group
placental
weight and
capacity.
Dose
dependent
0.5
increase of
number of
resorptions and
dead foetuses.
Decrease in the
numbers of
glycogen
0.5
trophoblast
cells in the
junctional zone
and the number
of sinusoidal
trophoblast
giant cells in the
labyrinth zone.
Decrease of
mPL-II, mPLP-
C and mPLP-K
expression
levels and
0.5
serum
concentrations
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
Not reported
Lee et al., 2015
15
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
PFOS (>96% purity)
28 days toxicity study
Incr rel and abs
SD rats (m, f)
liver weight
(m/f).
Gavage: 0, 0.312, 0.625,
1.25, 2.5, 5 mg/kg bw
Incr acyl-CoA-
per day
oxidase activity 1.25
(m).
No/sex/group: 10
Decr blood
cholesterol (m)
Decr total and free T4 (m, f)
No change sin reporductive parameters (m) Increased probability of transitioning to extended diestrous in F (all exposure groups,Markov analysis).
0.312 2.5 0.312 0.312
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
Plasma conc. (ug/ml) at 0.312mg/kg bw per day: 23.7 + 1.1 (m), 30.5 + 0.9 (f).
Information available for all doses.
Liver conc (ug/g) at 0.312 mg/kg bw per day:
87.2 + 3.04 (m) information available for all doses (m only)
NTP, 2019b
PFOS, 98% PFOS, 98% PFOS, 98%
Repeated dose, immunotox. C57BL/6 mice (4-8 males per group), administered via diet for 10 days, at 0.001 or 0.02% (2 or 40 mg/kg bw per day) (0.02% equals a total of 6 mg/animal over 10 days) Repeated dose study, immunotox. C57BL/6 mice (4 males), restricted food diet, 10 days, 0.001, 0.002, 0.02 (1.6, 3.1 or 23.5 mg/kg bw per day)
Repeated dose study, immunotoxicity, Balb/c mice (8 per group, males and females), gavage, 5, 20 mg/kg bw per day, 14 days
Several immune parameters up or down, but also reduced body weight gain
Reduced B-cell numbers
Thymus and spleen histopathology, but in addition to liver effects and PPAR changes
0.001% (1.6 mg/kg bw per day)
5
0.02% (40 mg/kg bw per day)
0.02% (23.5 mg/kg bw per day)
20
340 g/mL
Qazi et al. (2009a ,b)
50.8 g/mL at 0.001%, 340 g/mL at 0.02%
Qazi et al. (2012)
4.89 g/mL at 5 mg/kg bw per day, 25.2 g/mL at 20 mg/kg bw per day
Wang et al. (2011a )
16
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
PFOS, 85%
Repeated dose study,
Values various
20
immunotoxicity,, Balb/c immune
mice (5 females per
parameters
group), gavage, 20
reduced, but in
mg/kg bw per day, 7
addition to
days
body weights
PFOS, 98%
Repeated dose study,
Inconsistent;
1
5
immunotoxicity,,
some ex vivo
C57BL/6 mice (12 males apoptotic
per group), gavage, 1, 5, parameters in
10 mg/kg bw per day, 7 splenocytes and
days
thymocytes up
and others go
down
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
Not reported
Vetvick a and Vetvick ova (2013)
24.37 g/mL at 1 mg/kg bw per day, 87.56 g/mL at 5 mg/kg bw per day
Zhang et al. (2013d )
PFOS, 98% PFOS, 85% PFOS PFOS, 98% PFOS, 98% PFOS, 98% PFOS, 98%
Repeated dose study, immunotoxicity, C57BL/6 mice (12 males per group), gavage, 5, 20, 40 mg/kg bw per day, for 7 days
Repeated dose study, immunotoxicity, BALB/c mice (5 females per group), gavage, 20 mg/kg bw per day, 21 days
Reduced NK activity, antibody response, lymphocyte proliferation
Reduced antibody response and NK activity, but accompanied by body weight effects
Repeated dose study,
Effects on body 0.25
immunotoxicity, B6C3F1 weight and liver
mice (5 males per
, no immune
group), food, 0.25 mg/kg effects
bw per day for 28 days
Repeated dose study, immunotoxicity, B6C3F1 mice (5 females per group), gavage, 0.0331, 0.0993, 9.3 mg/kg bw per day, 28 days
TNF and IL-6 up and down, but no doseresponse
5 30
0.0331
Repeated dose study, B6C3F1 mice (5-10 females), gavage, 3.31, 16.6, 33.1, 166 g/kg bw per day, 28 days
Increased ex vivo IL-6
0.00331
Repeated dose study, Sprague-Dawley rats (15 males or female per group), diet, 0.14, 1.33, 3.21, 6.31 mg/kg bw per day, 28 days
Repeated dose study, B6C3F1 mice (5 males or females per group), gavage, 0.166, 1.66, 3.31, 16.6, 33.1, 166 g/kg per day, 28 days
Reduced total IgG1 levels in serum
Reduced specific antibody Response (PFCs)
0.14
1.33
0.000166 0.00166
97.25 g/mL
Zheng et al. (2009, 2011)
Not reported
Vetvick a and Vetvick ova (2013)
11.6 g/mL
Qazi et al. (2010)
Not reported
Mollen hauer et al. (2011)
<1 ng/mL (LOQ)
Fair et al. (2011)
0.95 g/mL at 0.14 mg/kg bw per day, 13.45 g/mL at 1.33 mg/kg bw per day
17.8n/ ng/mL at 0.000166 mg/kg bw per day, 91.5 ng/mL at 0.00166 mg/kg bw per day
Lefebv re et al. (2008)
PedenAdams et al. (2008)
17
Substance (%), EC/CAS, formula
study design, species, route of exposure, doses (guideline/similar to guideline/nonguideline), n animals
Observed effects and remarks
NO(A)EL (mg/kg bw/d)
LO(A)EL (mg/kg bw/d)
PFOS PFOS, 98% PFOS, 98% PFOS, 98% PFOS, 98% PFOS (purity NR)
PFDS
Repeated dose study, B6C3F1 mice (30 females per group), gavage, 5, 25 g/kg per day, 21 days
Reduced survival after challenge with influenza virus
0.005
Repeated dose study, C57BL/6 mice (10-12 males per group), gavage, 8.3, 16.7, 83.33, 416.7, 833.3 g/kg bw per day for 60 days
Repeated dose study, C57BL/6 mice (6 males per group), gavage, 8.3, 16.7, 83.33, 416.7, 833.3 g/kg bw per day for 60 days
Repeated dose study, C57BL/6 mice (12 males per group), gavage, 8.3, 16.7, 83.33, 416.7, 833.3 g/kg bw per day for 60 days
Repeated dose study, C57BL/6 mice (4 per group), 6-8 weeks old, exposed to 2 mg PFOS/kg bw per day for 7 days
Repeated dose study, ICR mice (number, sex NR), sensitized to ovalbumin on day 0, and orally exposed to 50-150 mg PFOS/kg bw on days 9, 11, and 13
Antibody responses down.
IL-4 and IL-10, TNF-a, IL-1b, values up and down. IgM decrease IgG, IgE increase Apoptotic lymphocytes,
IL 12 production after Citrobacter rodentium infection Aggrevated allergic inflammation in an ovalbumin model
0.0083 0.0167 0.0167
0.025
0.0833
0.0833
0.0833
2
50 mg/kg, three times
Key parameters / targets not add-ressed
Serum/tissue concentrate-ion of PFAS /metabolites (time of sampling)
Refere nce
189 ng/mL at 0.005 mg/kg bw per day, 670 ng/mL at 0.025 mg/kg bw per day
0.84 g/mL at 0.0083 mg/kg bw per day, 8.21 g/mL at 0.0833 mg/kg bw per day
10.75 g/mL at 0.0833 mg/kg per day , 2.36 g/mL at 0.0167 mg/kg per day
Guruge et al. (2009)
Dong et al. (2009)
Dong et al., 2011
0.84 g/mL at 0.0833 mg/kg per day, not reported at 0.0167 mg/kg per day
Not reported
Dong et al., 2012
Suo et al., 2017
Not reported
Lee et al., 2018
TFMS