Table F.3.
PFCA reproductive 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 |
|---|---|---|---|---|---|---|
| Perfluorohexanoic acid (PFHxA) | ||||||
| PFHxA (> 99% purity) |
Sprague‐Dawley rats Gavage 0, 62.6, 125, 250, 500, or 1,000 mg/kg per day |
Cauda epidydimis sperm count Serum testosterone Oestrus cyclicity |
1,000 1,000 1,000 |
Plasma conc. (ng/mL) at 62.6 mg/kg bw per day: 378 ± 178 (m) 129 ± 16 (f) at 250 mg/kg bw per day: 1297± 265 (m) Liver conc (ng/g) at 250 mg/kg bw/day 655 ± 148 (m) |
NTP (2019a) | |
| Perfluorononanoic acid (PFNA) | ||||||
| PFNA (> 98% purity) |
Sprague‐Dawley rats Gavage Male: 0, 0.625, 1.25, 2.5 mg/kg bw per day Female: 0, 1.56, 3.12, 6.25 mg/kg bw per day |
Decreased epidydimal weight with histopathological findings. Reduced testis weight with histopathological changes Decrease serum testosterone |
0.625 0.625 |
0.625 1.25 1.25 |
Plasma conc. (ug/mL) at 0.625 mg/kg bw per day: 56.7 ± 1.9 (m) at 1.56 mg/kg bw per day: 26.4 ± 1.1 (f) Liver conc (u g/g) at 0.625 mg/kg bw per day 145.5 ± 2.7 (m) |
NTP (2019a) |
| PFNA 97% pure |
Male Parkes mice, 0, 0.2 and 0.5 mg/kg bw per day by oral feeding needle. 90 days exposure (PND 25 to PND 114) n = 14 per group 7 animals were selected for fertility test, the remaining 7 for assessment of toxicological parameters |
Reduced male fertility (reduced sperm number, viability and motility) Decreased cholesterol Decreased testosterone Reduced litter size Reduced expression of steroidogenic enzymes in testes Reduced PCNA (proliferation marker) and increased caspase3 (apoptosis marker) expression in testis Decreased SOD and catalase activity in testes |
0.2 0.2 0.2 0.2 0.2 0.2 n.d. |
0.5 0.5 0.5 0.5 0.5 0.5 0.2 |
Not reported | Singh and Singh (2019b) |
| PFNA 97% pure | Male Parkes mice, 0, 2, 5 mg/kg bw per day, by oral feeding needle for 14 days, from PND 25 to PND 38. 10 mice per dose group. 5 mice per dose group for some outcomes. |
Reduced body weight gain Reduced serum and testicular testosterone Degenerative changes in seminiferous tubules |
2 n.d. n.d |
5 2 2 |
Not reported | Sing and Singh (2019c) |
| PFNA 97% pure | Male Parkes mice, 0, 2, 5 mg/kg bw per day, by oral feeding needle for 14 days, from PND 25 to PND 38. 10 mice per dose group treated, but generally 5 mice per dose group for outcomes. |
Increased liver weight and hepatocellular hypertrophy. Altered proportions of 4C and 2C cells in testis |
n.d. n.d. |
2 2 |
Not reported | Singh and Singh (2019d) |
| Perfluorodecanoic acid (PFDA) | ||||||
| PFDA (> 97% purity) |
Sprague‐Dawley rats Gavage 0, 0.156, 0.312, 0.625, 1.25 and 2.5 mg/kg bw per day |
Reduced epidydimal weight and cauda epidydimis sperm count Reduced testis weight Reduced testosterone |
0.625 1.25 1.25 |
1.25 2.5 2.5 |
Plasma conc. (ug/mL) at 0.156 mg/kg bw per day: 8.5 ± .6 (m) 11.2 ± 0.4 (f) Liver conc (ug/g) at 0.156 mg/kg bw per day 44.7 ± 1.5 (m) |
NTP (2019a) |
| Perfluorododecanoic acid (PFDoDA) | ||||||
| PFDoDA (95% pure, salt not specified) |
Female Sprague‐Dawley rats, weaned (PND 21; 8 per group) 0, 0.5, 1.5, 3 mg/kg bw per day orally 28 days (PND 24 – PND 52) |
Body weight decreased Absolute and relative weight of uterus and ovary Age, weight at vaginal opening Oestrus cyclicity Increased cholesterol Decreased estradiol |
1.5 3 3 3 1.5 1.5 |
3 3 3 |
Not given | Shi et al. (2009a) |
| PFDoDA (95% pure, salt not specified) |
Male Sprague‐Dawley rats, weaned (PND21; 6 per group) 0, 0.02, 0.05, 0.2, 0.5 mg/kg bw per day orally 110 days exposure |
Body weight decreased Absolute and relative weight of testis, prostate, seminal vesicle, vas deferens Cholesterol Decreased testosterone |
0.2 0.5 0.5 0.2 |
0.5 0.5 |
Not given | Shi et al. (2009b) |
| PFDoDA (purity and salt not specified) |
Male Sprague‐Dawley rats 21 days old (8 per group) 0, 5, 10 mg/kg per day gavage 14 days exposure (sacrifice PND 35) |
Body weight decrease Decreased testis weight Decreased testosterone, LH, FSH Leydig and Sertoli cell number |
5 5 |
10 10 5 |
Not given | Chen et al. (2019) |
| Perfluorotetradecanoic acid (PFTeDA) | ||||||
| PFTeDA, (salt not specified), 96.5% pure |
Crl:CD(SD) rats, 12 males per group dosed for 42 days. Dosage 0, 1, 3 and 10 mg/kg bw per day, gavage. |
Decreased weight of seminal vesicles | 1 | Not reported | Hirata‐Koizumi et al. (2015) | |
n.d: not determined.