Trimethyl phosphate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

In a combined repeat dose and reproductive/developmental toxicity screening test (OECD 422)13 male and 13 female Crj: CD(SD) rats per dose received trimethyl phosphate via gavage at dose levels of 0, 40, 100 and 250 mg/kg bw/day. In male rats, the administration period was two weeks prior to mating, 2 weeks within the mating and 2 weeks after the completion of mating period (42 days). In females, in addition to maximum four weeks pre-mating and mating period, they were given through pregnant period until day 3 of post delivery (approximately 63).

The copulation rate of the paired animals was decreased significantly in the 250 mg/kg group and the fertility index and number of implantation sites were decreased significantly in the 40 mg/kg group. Therefore, the NOEL was less than 40 mg/kg/day reproductive toxicity.

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

40 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

guideline study reliability 1

Effects on developmental toxicity

Description of key information

In a combined repeat dose and reproductive/developmental toxicity screening test (OECD 422)13 male and 13 female Crj: CD(SD) rats per dose received trimethyl phosphate via gavage at dose levels of 0, 40, 100 and 250 mg/kg bw/day. In male rats, the administration period was two weeks prior to mating, 2 weeks within the mating period and 2 weeks after the completion of mating period (42 days). In females, in addition to maximum four weeks pre-mating and mating period, they were given through pregnant period until day 3 of post delivery (approximately 63).

Although this combined study was designed to investigate reproductive capability in parental generation as well as development in F1 offspring, parameters to evaluate developmental toxicity were limited to only body weights at day 0 and day 4 after birth, and autopsy findings at day 4.

For reproductive/developmental end-points, the fertility index and the number of implantation sites were decreased at the lowest dose. In addition, intrauterine mortality of embryos was also increased at that level.

However, no significant differences on the pup viability and incidence of the morphological abnormalities of pups were shown in the groups given 40 mg/kg when compared to the controls. Pup weights in the 40 mg/kg group were significantly higher than those in the control group up until terminal necropsy on day 4 of lactation. The NOAEL values for both parental and F1 offspring in reproductive toxicity are considered to be less than 40 mg/kg/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

40 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

guideline study reliability 1