Toxicology of perfluorinated compounds

Stahl, Thorsten; Mattern, Daniela; Brunn, Hubertus

doi:10.1186/2190-4715-23-38

Environmental Sciences Europe

Table 27 Studies on the reproduction and developmental toxicity of PFCs (from EFSA [15] and enhanced)

From: Toxicology of perfluorinated compounds

Substance	Experimental animal	Tested dosage and time point	Effects	NOAEL LOAEL^a	Reference
PFOS	Rats	1, 5, and 10 mg/kg BW/day; GD 6 to 15	Body mass of the maternal animal ↓and lens abnormalities	5 10	Gortner [291]
	Rats	5 and 10 mg/kg BW/day; GD 6 to 15	Weight loss of the maternal animal and developmental toxic effects: birth weight ↓, inner organ abnormalities, delayed ossification, and skeletal anomalies	1 5	Wetzel [292]
	Rats	1, 2, 3, 5, and 10 mg/kg BW/day; GD 2 to 21	Weight gain of the maternal animal ↓; serum T₄ and T₃ of the maternal animal ↓; at the highest dosage: body weight of the fetus ↓, cleft palate, anasarca, death rate 4 to 6 h after birth ↑; and from 2 mg/kg BW/day: postnatal growth rate, delayed opening of eyes, T₄ ↓	n.r.	Lau et al. [162]; Thiobodeaux et al. [114]
	Mice	1, 5, 10, 15, and 20 mg/kg BW/day; GD 1 to 18	Delayed opening of eyes and from 5 mg/kg BW/day: liver mass ↑	n.r.	Lau et al. [162]; Thiobodeaux et al. [114]
	Rats	0.4, 0.8, 1, 1.2, 1.6, and 2 mg/kg BW/day; 6 weeks before mating, during gestation, and up to the fourth day of nursing	From 0.8 mg/kg BW/day: gestation time and viability of the young animals ↓	n.r.	Lübker et al. [163, 170]
	Rats	0.1, 0.4, 1.6, and 3.2 mg/kg BW/day; 42 days before mating, during gestation, and nursing	At highest dosage: gestation time, number of implantation points, and litter size ↓; and at the second-highest dosage (F1): reduced viability, body weight of the newborn, delayed reflexes and physical development, food uptake after weaning ↓ and dosage (F2): birth weight ↓	0.1 0.4	Christian et al. [164]
	Rabbits	0.1, 1, 2.5, and 3.75 mg/kg BW/day; GD 6 to 20	Weight gain of the maternal animal ↓;and at the second highest dosage: birth weight ↓ and delayed ossification	0.1 1 1 2.5	Case et al. [293]
	Mice	1, 10, and 20 mg/kg BW/day; GD 0 to the end of the study	At the highest dosage (maternal animal): weight gain, feed ↓, water uptake ↑, liver mass ↑; body weight of the fetus ↓, enlargement of the neck, skeletal deformity; and newborn weak and inactive, lung atelectasis, aneurism of intracranial arteries, respiratory dysfunction to death	n.r.	Yahia et al. [294]
	Leghorn chickens	1, 2.5, and 5 mg/kg egg; before incubation	No effect on hatching rate, spleen mass ↑, right wings shorter, frequent occurrence of brain asymmetry, immunoglobulin (IgM, IgY) ↓, plasma lysozyme activity ↑; at the highest dosage: liver mass ↑; and at the highest dosage: body weight ↑	(1 mg/kg egg to 154 ng/g in serum)	Peden-Adams et al. [175]
	Mallard ducks and quail	10, 50, and 150 mg/kg of feed	Viability of the 14-day-old progeny↓; at the lowest dosage: slight increase in incidences of small testes (length); however, spermatogenesis and fertility were not affected	Quail, 10 mg/kg feed	Newsted et al. [177]
PFOA	Rats	1, 3, 10, and 30 mg/kg BW/day	Body weight ↓, liver and kidney mass ↑; and at the highest dosage: birth weight ↓, mortality after weaning ↑, delayed puberty	n.r.	Butenhoff et al. [125, 165]
	Mice	1, 3, 5, 10, 20, and 40 mg/kg BW/day; during gestation	Liver enlargement; full-term gestation, viable fetuses, fetus weight, postnatal viability ↓; and growth deficit, delayed opening of eyes, accelerated sexual maturity of male progeny	n.r.	Lau et al. [161]
	Mice	3 to 20 mg/kg BW/day	Liver mass of the maternal animal ↑; body weight gain ↓; and application during GD 7 to 17 and 10 to 17: delayed opening of eyes and growth of coat	n.r.	Wolf et al. [169]
	Mice	5 mg/kg BW/day; GD 1 to 17, 8 to 17, and 12 to 17	Body weight of young animals ↓ and abnormal development of the nursing process to retarded growth of progeny	n.r.	White et al. [295]
	Chickens	5, 20, 40 mg/kg egg; before incubation	Impaired hatching rate, high prevalence of splayed legs, and chicks with partial or complete loss of yellow pigment in the down	n.r.	Yanai et al. [174]
PFBS	Rats	30 to 1, 000 mg/kg	No impairment of fertility or reproduction, no developmental toxic effects aside from a slight delay in onset of puberty, and weight gain in male F1 rats of the group with the highest dosage	n.r.	Lau et al. [115]
PFHxS	Rats	n.r.	No effect on fertility, reproduction, or viability and growth of the progeny	10	York [181] cited in Lau et al. [115]
N-Et-FOSE	Rats	n.r.	Toxic effects similar to those of PFOS, still birth, and mortality in the first three days ↑; in addition, increase in the number of stillbirths and mortality in the F2 generation	n.r.	Christian et al. [164]; Lübker et al. [163] cited in Lau et al. [115]
PFBA	Mice	35, 175, and 350 mg/kg BW/day; GD 1 to 17	No adverse effects in regard to survival rate of the progeny or their postnatal growth, delayed opening of eyes, at the two highest dosages: delayed onset of puberty, and at the highest dosage: loss of complete litter	n.r.	Das et al. [180]
PFNA	Rats	1, 3, and 5 mg/kg/day; for 14 days	Cell apoptosis in the testes and imbalance between testosterone and estradiol	n.r.	Feng et al. [183]
PFDA	Mice	0.25, 0.5, 1, 2, 4, 8, and 16, 32 mg/kg BW/day; GD 10 to 13 and 0.03, 0.3, 1, 3, 6.4, and 12.8 mg/kg BW/day; GD 6 to 15	No deformities or other developmental toxic effects; the applied dosages also did not show toxic effects in the maternal animal	n.r.	Harris and Birnbaum [182]
8:2 FTOH	Rats	n.r.	Only mild effects similar to those caused by PFOA	200	Mylchreest et al. [58] cited in Lau et al. [115]

GD, gestation day; n.r., not reported; upward arrow, increased; downward arrow, decreased. ^aNOAEL/LOAEL, not reported in milligrams per kilogram body weight per day.

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