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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies

Data source

Reference
Reference Type:
publication
Title:
Proliferation ductulaire biliaire intra-hepatique chez la ratte gestante traitee par le 4,4'-diaminodiphenyl-methane(4,4DDPM)
Author:
Bourdelat D, Moulinoux JP, Chambon Y & Babut JM
Year:
1983
Bibliographic source:
Bull.Assoc.Anal. (Nancy) 67: 375-82

Materials and methods

Test guideline
Qualifier:
no guideline available

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Days 7-20 and 14-20
Frequency of treatment:
Daily
Duration of test:
21 days
Doses / concentrationsopen allclose all
Dose / conc.:
75 other: mg (300 mg/kg)/d
Dose / conc.:
12 other: mg (50 mg/kg)/
No. of animals per sex per dose:
75 mg (300 mg/kg)/day; 5 animals
12 mg (50 mg/kg)/day; 10 animals
(5 animals/cage dose groups, one animal in control group)
Control animals:
yes, concurrent no treatment
Details on study design:
The rats with an average weight of 260 g, were housed 5/cage, and given food and water ad libitum. There was a single control rat which received distilled water. The rats were sacrificed 24 hr before delivery. The maternal livers were examined macroscopically, and the foetuses were dissected.

Examinations

Maternal examinations:
Hepatic lesions were observed in mothers.
Fetal examinations:
The macroscopic, and microscopic, hepatic lesions in the foetus were examined.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Hepatic lesions

Effect levels (maternal animals)

Key result
Dose descriptor:
other: not given
Basis for effect level:
histopathology: non-neoplastic
Remarks on result:
not determinable

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Macroscopic, and microscopic hepatic lesions in the foetus were observed. At the higher dose there were sometimes neural tube defects without hepatic lesions.

Applicant's summary and conclusion

Conclusions:
Hepatic lesions were observed in the mothers, and in some cases there were macroscopic and microscopic hepatic lesions in the foetus. At the higher dose there were sometimes neural tube defects without hepatic lesions.