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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:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: secondary source; the original reference was not available but is cited in the "Concise International Chemical Assessment Document 49-Thiourea" (WHO, 2003); data sufficient for assessment

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Thiourea. In: Some thyrotropic agents.
Author:
IARC
Year:
2001
Bibliographic source:
International Agency for Research on Cancer; IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 79; Some thyrotropic agents; 2001; pp. 703–725
Reference Type:
publication
Title:
Effects of hypothyroidism on reproductive behaviour in female sheep: clinical studies.
Author:
Nasseri, A.A. and Prasad, M.C.
Year:
1987
Bibliographic source:
Indian Vet J 11:191-199

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a study in which 66 female sheep (18 growing lambs, 18 maiden ewes, 9 pregnant ewes; controls: 9 growing lambs, 9 maiden ewes, 3 pregnant ewes) were orally administered 0 or 50 mg thiourea/kg body weight daily for 2, 4, or 6 months (six treated and three controls per group)
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
no details on test material are available

Test animals

Species:
other: lamb
Strain:
not specified
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
oral: unspecified
Type of inhalation exposure (if applicable):
other: not applicable
Vehicle:
not specified
Details on exposure:
no data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Details on mating procedure:
no data
Duration of treatment / exposure:
2, 4, or 6 month
Frequency of treatment:
daily
Duration of test:
no data
Doses / concentrations
Remarks:
Doses / Concentrations:
50 mg/kg bw/day
Basis:
nominal conc.
No. of animals per sex per dose:
6 animals per dose and treated group; 3 animals per control group
Control animals:
yes, concurrent no treatment
Details on study design:
66 female sheep (18 growing lambs, 18 maiden ewes, 9 pregnant ewes; controls: 9 growing lambs, 9 maiden ewes, 3 pregnant ewes) were orally administered 0 or 50 mg/kg bw daily for 2, 4, or 6 month

Examinations

Maternal examinations:
no data
Ovaries and uterine content:
no data
Fetal examinations:
no data
Statistics:
no data
Indices:
no data
Historical control data:
no data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
- abortion, stillbirth, birth of weak/low-weight lambs, dystokia, and retention of placenta were common features
- external genitalia were infantile and stunted in growing lambs, while they were pale anaemic and dry in maiden ewes
- none of the growing lambs showed signs of estrus
- mammary development was retarded
- the severity of changes was dependent upon the stage of gestation when hypothyroidism was induced

Effect levels (maternal animals)

Dose descriptor:
LOEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
birth of weak/low-weight lambs

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Thourea was shown to developmental toxicity in females at 50 mg/kg bw/day. The severity of changes was dependent upon the stage of gestation when hypothyroidism was induced.
Executive summary:

66 female sheep (18 growing lambs, 18 maiden ewes, 9 pregnant ewes; controls: 9 growing lambs, 9 maiden ewes, 3 pregnant ewes) were administered orally 0 and 50 mg thiourea/kg body weight daily for 2, 4, or 6 month. External genitalia were infantile and stunted in growing lambs and pale anaemic and dry in maiden ewes. The growing lambs did not show signs of estrus and mammary development was retarded. Thiourea administered to pregnant ewes induced abortion, stillbirth, birth of weak/low-weight lambs, dystokia, and retention of placenta. The severity of changes was dependent upon the stage of gestation when hypothyroidism was induced.