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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Justification for Read Across is given in Section 13 of IUCLID

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1972
Report Date:
1972
Reference Type:
secondary source
Title:
Final Report on the Safety Assessment of Dilauryl Thiodipropionate
Author:
Liebert MA
Year:
1992
Bibliographic source:
Journal of the american college of toxicology

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
no justification for the use of hamsters, limited information on test item, animal husbandry and result
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
hamster
Strain:
other: Golden, outbred
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: no data, virgin
- Weight at study initiation: average 109 g
- Fasting period before study: no data
- Housing: individually housed in mesh bottom cages
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: controlled, but no further details given
- Humidity: controlled, but no further details given

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
no
Details on mating procedure:
Hamsters were mated (1 to 1) with mature males and the appearance of motile sperm in the vaginal smear was considered as Day 0 of gestation.
Duration of treatment / exposure:
Beginning on Day 6 and continuing daily through Day 10 of gestation
Frequency of treatment:
daily
Duration of test:
During pregnancy until day 14 (caesarian section).
Doses / concentrationsopen allclose all
Dose / conc.:
16 mg/kg bw/day (actual dose received)
Dose / conc.:
74 mg/kg bw/day (actual dose received)
Dose / conc.:
350 mg/kg bw/day (actual dose received)
Dose / conc.:
1 600 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
20 - 23, depending on the dose group
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
Body weights were recorded on Days 0, 8, 10, and 14 of the gestation period. All animals were observed daily for appearance and behaviour with particular attention to food consumption in order to better recognize any abnormalities resulting from anorexic effects in the pregnant animal.
Ovaries and uterine content:
On Day 14, all animals were subjected to Caesarian section under deep anesthesia and the numbers of implantation sites, resorption sites, live and dead foetuses were recorded. All live pups were weighed and the genital tract of each dam was examined for any anatomical abnormalities.
Fetal examinations:
All foetuses were examined grossly for the presence of external congenital defects and one-third of each litter underwent detailed visceral examination under 10X magnification. The remaining two-thirds of the pups were cleared in potassium hydroxide, stained with alizarin red dye, and examined for the presence of sketal abnormalities.
Statistics:
not performed.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
no effects

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: No clearly discernible effect on nidation or on maternal or foetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Maternal abnormalities

Abnormalities:
no effects observed

Results (fetuses)

Details on embryotoxic / teratogenic effects:
no effects

Effect levels (fetuses)

Remarks on result:
not determinable

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL (maternal) = 1600 mg/kg bw/day
Executive summary:

The toxicity potentIal of the substance to hamster development was evaluated in a prenatal developmental toxicity test similar to the OECD Guideline 414. 20 -23 hamsters were orally administered daily the substance (16, 74, 350 and 1600 mg/kg day) from day 6 to day 10 of gestation. Maternal body weights were recorded during the gestation period and all animals were observed daily for appearance, behaviour and food consumption. On Day 14, all animals were subjected to Caesarian section under deep anesthesia and the numbers of implantation sites, resorption sites, live and dead foetuses were recorded. All live pups were weighed and the genital tract of each dam was examined for any anatomical abnormalities. All foetuses were examined grossly for the presence of external congenital defects; one-third of each litter underwent detailed visceral examination; two-thirds of the pups were examined for the presence of skeletal abnormalities.

No maternal or embryotoxic/teratogenic effects were observed. There was no clearly discernible effect on nidation or on maternal or foetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

NOAEL (maternal) = 1600 mg/kg bw/day