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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:
other: Not fully to guideline and insufficiently reported.

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
Deviations:
not applicable

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
4,4’–Diaminodiphenylmethane, as its hydrochloride; in distilled water

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 / concentrations
Remarks:
Doses / Concentrations:
75 mg (300 mg/kg)/day; 5 animals: 12 mg (50 mg/kg)/day; 10 animals
Basis:
no data
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, of average weight 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. At the higher dose there were sometimes nrural tube defects without hepatic lesions.

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)

Dose descriptor:
other: no data given

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no data

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

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

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.