Trimethyl phosphate

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Trimethyl phosphate

EC Number:

208-144-8

EC Name:

Trimethyl phosphate

Cas Number:

512-56-1

Molecular formula:

C3H9O4P

IUPAC Name:

trimethyl phosphate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Duration of treatment / exposure:

Males: 42 days
Females: from 14 days prior to mating to Day 3 of lactation

Frequency of treatment:

7 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

40 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

100 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

250 mg/kg bw/day (nominal)

No. of animals per sex per dose:

13 animals/group

Control animals:

yes, concurrent vehicle

Examinations

Sperm parameters (parental animals):

The fertility index and number of implantation sites were decreased significantly in the 100 mg/kg group.

Results and discussion

Results: P0 (first parental generation)

Reproductive function / performance (P0)

Reproductive function: sperm measures:

effects observed, treatment-related

Description (incidence and severity):

The fertility index was decreased significantly in the 100 mg/kg group.

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

The copulation rate of the paired animals was significantly decreased in the 250 mg/kg group.

Effect levels (P0)

Key result

Dose descriptor:

NOEL

Effect level:

< 40 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

organ weights and organ / body weight ratios

Results: F1 generation

General toxicity (F1)

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

In the 40 mg/kg group, intrauterine mortality of embryos was increased significantly and pup weights were significantly greater than those in the control group.
No significant differences in the pup viability were found in the groups given 40 mg/kg when compared to the controls.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

In the 40 mg/kg group, pup weights were significantly greater than those in the control group up until terminal necropsy on day 4 of lactation.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

No significant differences in incidence of morphological abnormalities of pups were found in the groups given 40 mg/kg when compared to the controls.

Effect levels (F1)

Key result

Dose descriptor:

NOEL

Effect level:

< 40 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

body weight and weight gain

Overall reproductive toxicity

Key result

Reproductive effects observed:

yes

Lowest effective dose / conc.:

40 mg/kg bw/day (nominal)

Treatment related:

yes

Relation to other toxic effects:

reproductive effects in the absence of other toxic effects

Dose response relationship:

yes

Applicant's summary and conclusion

Conclusions:

The NOELs for reproductive/developmental toxicity are considered to be less than 40 mg/kg/day.