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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, sufficient documentation and acceptable for assessment.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Thiourea (thiocarbamide): adult life span animal feeding experiments with rats.
Author:
Hartzell, A.
Year:
1945
Bibliographic source:
Contributions from the Boyce Thompson Institute 13:501-513

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a chronic toxicity study, thiourea was administered daily in drinking-water at concentrations of 1.72, 6.88, or 27.5 mg/kg body weight to mice for 2 years and to rats for the duration of their lifetimes or a maximum of 3 years.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
not specified
Details on test material:
no data

Test animals

Species:
other: rat and mice
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on oral exposure:
Administration of thiourea in drinking water at concentrations of In a chronic toxicity study, thiourea was administered daily in drinking-water at concentrations of 1.72, 6.88, or 27.5 mg/kg body weight to mice for 2 years and to rats for the duration of their lifetimes or a maximum of 3 years.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
Duration of exposure:
mice for 2 years
rats for the duration of their lifetimes or a maximum of 3 years
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1.72 mg/kg bw/day
Basis:
nominal in water
Remarks:
Doses / Concentrations:
6.88 mg/kg bw/day
Basis:
nominal in water
Remarks:
Doses / Concentrations:
27.5 mg/kg bw/day
Basis:
nominal in water
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
no data
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
no data
Sacrifice and pathology:
no data
Other examinations:
no data
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
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
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
A reduction in body weight gain and an enlargement of the thyroid gland were observed only in the rats in the highest dose group, and no other changes were detected, either macroscopically or microscopically.

Effect levels

open allclose all
Dose descriptor:
LOAEL
Effect level:
27.5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: reduction of body weight and enlargement of thyroid gland
Dose descriptor:
NOAEL
Effect level:
6.88 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In a chronic toxicity study a LOAEL of 27.5 mg/kg bw and a NOAEL of 6.88 mg/kg bw was established for thiourea in rats.
Executive summary:

In a chronic toxicity study, thiourea was administered daily in drinking-water at concentrations of 1.72, 6.88, or 27.5 mg/kg body weight to mice for 2 years and to rats for the duration of their lifetimes or a maximum of 3 years. A reduction in body weight gain and an enlargement of the thyroid gland were observed only in the rats in the highest dose group, and no other changes were detected, either macroscopically or microscopically. A LOAEL of 27.5 mg/kg body weight per day (reduction of body weight and enlargement of thyroid gland) and a no-observed-adverse-effect level (NOAEL) of 6.88 mg/kg body weight per day for rats was established. The results of the publication by Hartzell (1945) are also cited in the "Concise International Chemical Assessment Document 49" (WHO, 2003).