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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive 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:
1979

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
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:
rabbit
Strain:
other: Mated female rabbits
Sex:
female

Administration / exposure

Route of administration:
not specified
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Administration of the substance to pregnant female rabbits at doses of 300, 1000 and 3000 mg/kg produced gastrointestinal effects (diarrhea) at the high level
Doses / concentrationsopen allclose all
Dose / conc.:
300 other: mg/kg
Dose / conc.:
1 000 other: mg/kg
Dose / conc.:
3 000 other: mg/kg
No. of animals per sex per dose:
15
Control animals:
not specified
Details on study design:
Administration of the substance to pregnant female rabbits at doses of 300, 1000 and 3000 mg/kg produced gastrointestinal effects (diarrhea) at the high level. Deaths which could not be attributed to other causes also occurred at the high dose level. There was a decrease in the mean body weight of females at the high dose level on Days 12, 18 and 29 of gestation.

Examinations

Litter observations:
observations of the uterine contents showed that the ratio of live fetuses/implantation sites is significantly decreased in the 3000 mg/kg group as compared to the controls.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
There was a decrease in the mean body weight of females at the high dose level on Days 12, 18 and 29 of gestation.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
effects observed, non-treatment-related
Description (incidence and severity):
The observations of the uterine contents showed that the ratio of live fetuses/implantation sites is significantly decreased in the 3000 mg/kg group as compared to the controls.

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P0)

Key result
Dose descriptor:
other: NOAC
Effect level:
3 000 mg/kg diet
Based on:
not specified
Sex:
female
Basis for effect level:
other: not specified

Target system / organ toxicity (P0)

Critical effects observed:
no
Organ:
not specified

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P1)

Based on:
not specified
Sex:
not specified
Remarks on result:
not determinable

Target system / organ toxicity (P1)

Critical effects observed:
not specified
Organ:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Based on:
not specified
Sex:
not specified
Remarks on result:
not determinable

Target system / organ toxicity (F1)

Critical effects observed:
not specified

Results: F2 generation

General toxicity (F2)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Based on:
not specified
Sex:
not specified
Remarks on result:
not measured/tested

Target system / organ toxicity (F2)

Critical effects observed:
not specified

Overall reproductive toxicity

Key result
Reproductive effects observed:
no
Lowest effective dose / conc.:
3 000 mg/kg diet
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
Evaluation of cleared specimens showed a significant increase in the number of uncommonly-encountered changes at the 300 and 1000 mg/kg dose levels. These changes were judged to reflect an inhibition in the rate of skeletal development and were not observed in the high dose tested group. The NOAC for maternal toxicity and reproduction toxicity is considered to be 3000 mg/kg.

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