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Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
other: publication
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from authoritative database: Japan Chemicals Collaborative Knowledge Database

Data source

Reference
Reference Type:
publication
Title:
Combined repeated dose Reproduction/ Developmental Toxicity Screening Test of Hydrazinecarbothioamide in rats
Author:
Hazard-Data Evaluation Committee of National Institute of Technology and Evaluation
Year:
2009
Bibliographic source:
Japan Chemicals Collaborative Knowledge Database (Japanese Ministry of Economy, Trade and Industry), 2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Thiosemicarbazide
EC Number:
201-184-7
EC Name:
Thiosemicarbazide
Cas Number:
79-19-6
Molecular formula:
CH5N3S
IUPAC Name:
hydrazinecarbothioamide
Constituent 2
Reference substance name:
thiosemicarbazide (Synonym: Hydrazinecarbothioamide)
IUPAC Name:
thiosemicarbazide (Synonym: Hydrazinecarbothioamide)
Test material form:
solid: crystalline
Details on test material:
CAS No: 79-19-6
Chemical Name: thiosemicarbazide (Synonym: Hydrazinecarbothioamide)
Nature of the chemical: Organic

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
Age at study initiation: 9 weeks old

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
M: 42days
F: 42 - 50 days (from 14 days before mating to day 4 of lactation)
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.4, 2, 10 mg/kg/day
Basis:
nominal in water
No. of animals per sex per dose:
Total: 136
0 mg/kg/day: 12 male, 12 female
0.04 mg/kg/day: 12 male, 12 female
2 mg/kg/day: 12 male, 12 female
10 mg/kg/day: 12 male, 12 female
For recovery group
0 mg/kg/day: 10 male, 10 female
10 mg/kg/day: 10 male, 10 female
Control animals:
yes, concurrent vehicle
Details on study design:
Rationale for selecting satellite groups: 10 male and 10 female rat for control and recovery group
- Post-exposure recovery period in satellite groups: 14 days

Examinations

Observations and examinations performed and frequency:
Cage side observations were performed
Other examinations:
Organ weight:
Absolute and relative Liver, kidney and thymus weight were recorded.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Mortality: One female rat died at 10 mg/kg/day dose group as compared to control. Clinical signs: Tonic convulsion in male and female rats and Excessive response to touch or tail pinch were observed in male rats at 10 mg/kg/day dose group as compared to control.
Mortality:
mortality observed, treatment-related
Description (incidence):
Mortality: One female rat died at 10 mg/kg/day dose group as compared to control. Clinical signs: Tonic convulsion in male and female rats and Excessive response to touch or tail pinch were observed in male rats at 10 mg/kg/day dose group as compared to control.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Decrease tendency in the body weight were observed in treatment and recovery at 10 mg/kg/day dose group as compared to control.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Food consumption: No effect was observed on food consumption of treated rats as compared to control. Compound intake: No data available
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
No effect was observed on blood hematology of treated rats as compared to control.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Increase in T-Cho level was observed in male rats in 10 mg/kg/day as compared to control.
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
No effect was observed on urinanalysis of treated rats as compared to control.
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Increase absolute and relative liver and kidney weight and Decrease in absolute and relative thymus weight were observed in male rats at 10 mg/kg/day does group as compared to control.
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Atrophy of the thymus in male rat and Pulmonary edama, increase in the karyorrhexis in the white pulp of the spleen, mandibular lymph node and mesenteric lymph node in dead female rats were observed in 10 mg/kg/day does group as compared to control.
Details on results:
NOAEL value was considered to be 2 mg/kg/day for thiosemicarbazide in Crj:CD (SD) male and female rats.

Effect levels

Dose descriptor:
NOAEL
Effect level:
2 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effect on survival, clinical sign, body weight, food consumption, urinalysis, hematology, clinical chemistry, organ weight and histopathology

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

NOAEL value was considered to be 2 mg/kg/day for thiosemicarbazide in Crj:CD (SD) male and female rats.

Applicant's summary and conclusion

Conclusions:
NOAEL value was considered to be 2 mg/kg/day for thiosemicarbazide in Crj:CD (SD) male and female rats.
Executive summary:

In a Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test (OECD TG422) was conducted. Crj:CD (SD) male and female rats were dosed orally at concentration 0, 0.4, 2, 10 mg/kg/day for 42days (male rats) & 42-50 days (Female-from 14 days before mating to day 4 of lactation). No effect were observed on food consumption, urinalysis and hematology of treated rats. One female rat died,Tonic convulsion in male and female rat and Excessive response to touch or tail pinch were observed in male rat and Decrease tendency in the body weight were observed in treatment and recovery at10 mg/kg/day dose group trreated rats as compared to control. Similarly,Increase in T-Cho level and Increase absolute and relative liver and kidney weight and Decrease in absolute and relativethymus weight were observed in male rats at 10 mg/kg/day does group as compared to control. Decrease in absolute and relativethymus weight was observed in male rats at 2 mg/kg/day does group. In addition, Atrophy of the thymus in male rat and Pulmonary edama, Increase in the karyorrhexis in the white pulp of the spleen, mandibular lymph node and mesenteric lymph node in dead female rats were observed in 10 mg/kg/day does group as compared to control. Therefore, NOAEL was considered to be 2 mg/kg/day when Crj:CD (SD) male and female rats were treated withHydrazinecarbothioamide orally by gavage.