Table F.8.

Perfluorooctanoic acid (PFOA) developmental toxicity studies with exposure in pubertal or adult animals

Substance/ (Purity)	Species/Experimental design and doses	Most sensitive endpoints	Highest dose with no effect (mg/kg bw per day)	Significant effect level (mg/kg bw per day)	Serum/tissue levels of compound	Reference
PFOA ammonium salt, 98% pure	BALB/c and C57BL/6 mice (comparative approach); n = 20 0, 1, 5, 10 mg/kg bw per day, 5 days per week Exposure: PND 21 for 28 days (pubertal period)	Increase of relative liver weight in both strains Delayed vaginal opening Balb/c mice Delayed vaginal opening C57BL/6 mice Dose‐dependent decrease uterine wet weight in Balb/c mice Increase of uterine wet weight for C57/BL6 mice Reduction of ductal length, number of terminal end buds and number of terminal ducts in Balb/c mice Increase of mammary gland parameters in C57/BL6 mice	n.d. n.d. 1 n.d. n.d. 1 n.d.	1 1 5 1 1 5 1	BALB/c at 0, 1, 5 ng/kg bw per day: < 10, 29,500, 109,000 ng/mL. C57BL/6 at 0, 1, 5, 10 ng/kg bw per day: < 10, 26,000, 68,200, 96,600 ng/mL	Yang et al. (2009)
PFOA ammonium salt, 98% pure	129/Sv wild‐type, PPARα knockout mice, humanised PPARα mice, adult 0, 1, 5 mg/kg per day, n = 8–10, 42 days	Sperm abnormalities, decreased testosterone level	n.d.	1		Li et al. (2011)
PFOA ammonium salt, 98% pure	Exposure: PND 21 for 28 days (pubertal period). 5‐10 mice per group. Dosing 5 days a week Balb/c: 0 and 2.5 mg/kg bw per day C57Bl/6: 0 and 7.5 mg/kg bw per day	Reduction in mammary gland development (reduced ductal length, number of terminal end buds, stimulated terminal ducts)		2.5 7.5	Balb/c < 10, 51,100 C57Bl/6 < 10, 93,400	Zhao et al. (2012)1
PFOA ammonium salt, 98% pure	CD1 mice PND18, three day uterotrophic assay 0, 0.01, 0.1, 1 mg/kg bw per day (n = 8)	1.46‐fold increase of uterine wet weight. Further supported by histopathological examination	n.d.	0.01		Dixon et al. (2012)
PFOA ammonium salt, 98% pure	BALB/c mice, adult 0, 0.31, 1.25, 5, 20 mg/kg bw per day, n = 16, 28 days	Sperm count reduced, sperm motility, sperm progression increased, percentage of teratosperm increased Testosterone and progesterone levels decreased Mild phenotype in seminiferous tubules	1.25 0.31 0.31	5 1.25 1.25		Zhang et al. (2014b)
PFOA, > 98% pure	Sprague‐Dawley rats, 10–11 weeks old at start. 0, 0.625, 1.25, 2.5, 5, 10 mg/kg bw per day, N = 10 per sex per group 28 days	Reduced epidydimal weight Reduced epidydimal sperm count	5 5	10 10	Plasma conc. (ug/mL) at 0.625 mg/kg bw per day: 50.7 + 2.2 (m) at 5 mg/kg bw per day: 110.7 + 3.8 (m) at 6.25 mg/kg bw per day: 491 + 72.1 (f) Liver conc (ug/g) at 0.625 mg/kg bw per day 54.6 + 2.2 (m)	NTP (2019a)

n.d.: not determined from the study; bw: body weight; f: female; m: male; PND: postnatal day.

¹Concentration in serum extracted from figure in Zhao et al. (2012).