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Diss Factsheets

Administrative data

Endpoint:
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:
1978

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
not specified
Remarks:
Not applicable ( prior to 1981)

Test material

Constituent 1
Reference substance name:
Reaction mass of phosphonic acid, methyl-, bis[(5-ethyl-2-methyl-2,2-dioxido-1,3,2-dioxaphosphorinan-5-yl)methyl] ester with (5-ethyl-2-methyl-2-oxido-1,3,2-dioxaphosphorinan-5-yl)methyl methyl methylphosphonate
EC Number:
915-680-2
Molecular formula:
not applicable for UVCB
IUPAC Name:
Reaction mass of phosphonic acid, methyl-, bis[(5-ethyl-2-methyl-2,2-dioxido-1,3,2-dioxaphosphorinan-5-yl)methyl] ester with (5-ethyl-2-methyl-2-oxido-1,3,2-dioxaphosphorinan-5-yl)methyl methyl methylphosphonate

Test animals

Species:
rat
Strain:
other: (CRL:COBS CD (SD) BR)
Details on test animals or test system and environmental conditions:
Female (CRL:COBS CD (SD) BR) rats were paired with a sexually mature male of the same strain. Females were examined daily for the presence of a copulatory plug. The presence of such a plug was taken as evidence of mating and designated as Day 0 of gestation. The female rats were 11 weeks of age at the time of the first dose. Mated female were assigned to groups so as to have 20 animals in control, 1000, 3000 and 10000 mg/kg dose level groups.

Administration / exposure

Route of administration:
oral: gavage
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Mated female were assigned to groups so as to have 20 animals in control, 1000, 3000 and 10000 mg/kg dose level groups.
Details on mating procedure:
Female (CRL:COBS CD (SD) BR) rats were paired with a sexually mature male of the same strain. Females were examined daily for the presence of a copulatory plug. The presence of such a plug was taken as evidence of mating and designated as Day 0 of gestation. The female rats were 11 weeks of age at the time of the first dose. Mated female were assigned to groups so as to have 20 animals in control, 1000, 3000 and 10000 mg/kg dose level groups.On Day 20 of gestation the adult female rats were anesthetized with chloroform and the visceral and thoracic organs examined. The uterus was removed and opened. The number of implantation sites and their placement in the uterine horns, live and dead fetuses and resorption sites were recorded. The fetuses were removed examined externally for abnormalities and weighed.
One third of the fetuses of each litter were fixed in Bouin’s fluid. These were later examined for changes in the soft tissues of the head, thoracic and visceral organs. The remaining fetuses of each litter were examined for skeletal abnormalities following staining with Alizarin Red S.
Doses / concentrationsopen allclose all
Dose / conc.:
1 000 mg/kg diet
Dose / conc.:
3 000 mg/kg diet
Dose / conc.:
10 000 mg/kg diet
No. of animals per sex per dose:
20
Details on study design:
Female (CRL:COBS CD (SD) BR) rats were paired with a sexually mature male of the same strain. Females were examined daily for the presence of a copulatory plug. The presence of such a plug was taken as evidence of mating and designated as Day 0 of gestation. The female rats were 11 weeks of age at the time of the first dose. Mated female were assigned to groups so as to have 20 animals in control, 1000, 3000 and 10000 mg/kg dose level groups.
On Day 20 of gestation the adult female rats were anesthetized with chloroform and the visceral and thoracic organs examined. The uterus was removed and opened. The number of implantation sites and their placement in the uterine horns, live and dead fetuses and resorption sites were recorded. The fetuses were removed examined externally for abnormalities and weighed.
One third of the fetuses of each litter were fixed in Bouin’s fluid. These were later examined for changes in the soft tissues of the head, thoracic and visceral organs. The remaining fetuses of each litter were examined for skeletal abnormalities following staining with Alizarin Red S.
The uterus and ovaries from the adult females were preserved in 10% formalin for possible future examination, but no further examinations were judged to be necessary.

Examinations

Maternal examinations:
On Day 20 of gestation the adult female rats were anesthetized with chloroform and the visceral and thoracic organs examined.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified

Maternal developmental toxicity

Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified

Effect levels (maternal animals)

Remarks on result:
not measured/tested

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Mean body weight and food consumption indicated no significant difference between control and treated pregnant rats.
Changes in sex ratio:
no effects observed
Other effects:
no effects observed
Description (incidence and severity):
Mean body weight and food consumption indicated no significant difference between control and treated pregnant rats.
Details on embryotoxic / teratogenic effects:
There was no evidence of substance teratogenicity, variation in sex ratio, embryo toxicity or inhibition of fetal growth and development.

Effect levels (fetuses)

Dose descriptor:
other: NOAC
Effect level:
ca. 3 000 mg/kg diet
Basis for effect level:
fetal/pup body weight changes

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
no
Lowest effective dose / conc.:
10 000 mg/kg diet

Applicant's summary and conclusion

Conclusions:
There was no evidence of substance teratogenicity, variation in sex ratio, embryo toxicity or inhibition of fetal growth and development. The NOAEC is therefore considered to be 10 000 mg/kg.