Triethyl phosphite

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

A reproduction/developmental toxicity screening test was performed (OECD TG 421, GLP) in Wistar rats, which were dosed with 10, 80, 320, and 640 mg/kg bw two weeks before mating, during the 2 week mating and 1-week remating period, during gestation, lactation and up to the day before necropsy (males were necropsied on day 36 to 37 of treatment, females between day 4 to 6 post partum; Bayer AG, 2002). In the parent animals mortality, observation, body weight, food consumption, water consumption, time to insemination, insemination index, fertility index, duration of gestation, gestation index, number of corpora lutea, number of implantations were examined. Pathological and histopathological observations of testes, epididymides, ovaries, mammae, uterus, vagina and organs with macroscopically altered tissues were performed.

General toxicity: Animals of both sexes in the high dose group (640 mg/kg bw/day) exhibited clear clinical signs of systemic toxicity (e.g. piloerection, sunken sides, tremors, salivation immediately after dosing, recumbency) and body weight loss (> 14% decrease relative to controls in males and females). All females of this group were killed in moribund condition. Similar signs of toxicity were seen in individual females of the 320 mg/kg bw/day group. Slight weight loss was recorded in individual females after exposure to 80 mg/kg bw/day before the increase of weight due to gestation. Salivation was observed in males of all dose groups with a dose-related increase and in females of the 80, 320 and 640 mg/kg bw/day groups.

Effects on Fertility: Histopathology showed minimal to slight degeneration in the germinal epithelium of testes, and apoptosis and/or regenerative hyperplasia in the testes and epididymides, after exposure to the clearly paternally toxic dose level of 640 mg/kg bw/day. Relative testes weights (%) were 0.87, 0.89, 0.91, 0.85, and 0.98 (statistically significant) for controls, 10, 80, 320 and 640 mg/kg bw/day groups, respectively. There was no significant difference in absolute testes weights between the groups. In females, histopathology revealed slight proliferation / secretion in the mammary gland together with mucification in the cervix and vagina in all females at 640 mg/kg bw/day, which were sacrificed in moribund state either after 8 to 10 days of pairing or during early gestation. No histopathological changes were recorded in reproductive organs up to and including a dose of 320 mg/kg bw/day. Only 5 of 12 females were inseminated in the 640 mg/kg bw/day group. Evaluation of other data regarding reproductive performance, including early postnatal development of pups for the 640 mg/kg bw/day group was not possible. At a dose level of 320 mg/kg bw/day an increase in time to insemination, slightly decreased duration of gestation, a severely reduced gestation rate, distinctly increased number of stillborn/dead F1 pups, and a distinctly decreased number of viable/total number of pups were recorded. Pups showed severely reduced birth weights, hypothermia and severely reduced survival. No effects on the other reproductive parameters (insemination index, fertility index, numbers of corpora lutea and implantation sites, prenatal loss, litter size) were detected up to and including a dose level of 320 mg/kg bw/day.

Conclusion: In a screening study in rats according to OECD TG 421, effects on fertility were seen in females at 320 mg/kg bw/day in the presence of general toxicity as an increase in time to insemination, severely reduced gestation rate, and an increase in stillbirths and dead pups. Male rats showed changes in the testes at the severely toxic dose of 640 mg/kg bw/day. (NOAEL females: 80 mg/kg bw/day; NOAEL males: 320 mg/kg bw/day).

Short description of key information:
In a screening study in rats according to OECD TG 421, effects on fertility were seen in females at 320 mg/kg bw/day in the presence of general toxicity as an increase in time to insemination, severely reduced gestation rate, and an increase in stillbirths and dead pups. Male rats showed changes in the testes at the severely toxic dose of 640 mg/kg bw/day. (NOAEL females: 80 mg/kg bw/day; NOAEL males: 320 mg/kg bw/day).

Effects on developmental toxicity

Description of key information

In a screening study in rats according to OECD TG 421, developmental toxicity was found at dose levels ≥ 320 mg/kg bw/day as evidenced by severely reduced survival and reduced pup birth weights (NOAEL: 80 mg/kg bw/day). 

Additional information

A reproduction/developmental toxicity screening test was performed (OECD TG 421, GLP) in Wistar rats, which were dosed with 10, 80, 320, and 640 mg/kg bw two weeks before mating, during the 2 week mating and 1 -week remating period, during gestation, lactation and up to the day before necropsy (males were necropsied on day 36 to 37 of treatment, females between day 4 to 6 post partum; Bayer AG, 2002). In the pups appearance (including externally visible malformations), general behaviour, mortality, sex ratio at birth, individual weights at birth and on day 4 after birth were examined (Bayer AG, 2002).

In F1, the sex ratio, mortality and weights were not affected by treatment up to and including doses of 80 mg/kg bw/day, while evaluation was not possible at higher doses as there were no surviving pups. No externally malformed pups were observed.

Conclusion:

In a screening study in rats according to OECD TG 421, developmental toxicity was found at dose levels ≥ 320 mg/kg bw/day as evidenced by severely reduced survival and reduced pup birth weights (NOAEL: 80 mg/kg bw/day).

Justification for classification or non-classification

The available data are insufficient for assessment of the reproductive toxicity of the test substance.