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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from handbook

Data source

Reference
Reference Type:
review article or handbook
Title:
Developmental Toxicity of 1H-benzimidazole in rat
Author:
Thomas H, Shepard M.D
Year:
2011
Bibliographic source:
Catalog of teratogenic agents,13th edition,2011

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: No data
Principles of method if other than guideline:
Reproductive toxicity study of 1H-benzimidazole in rats was evaluated.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzimidazole
EC Number:
200-081-4
EC Name:
Benzimidazole
Cas Number:
51-17-2
Molecular formula:
C7H6N2
IUPAC Name:
1H-1,3-benzodiazole
Details on test material:
SMILES:c1cccc2c1NC=N2
Specific details on test material used for the study:
- Name of test material: Benzimidazole
- IUPAC name: 1H-benzimidazole
- Molecular formula: C7H6N2
- Molecular weight: 118.1384 g/mol
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rat
Strain:
not specified
Details on species / strain selection:
No data
Sex:
female
Details on test animals or test system and environmental conditions:
No data

Administration / exposure

Route of administration:
not specified
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
No data
Details on mating procedure:
No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
5 days (day 8 to day 12)
Frequency of treatment:
Daily
Details on study schedule:
no data
Doses / concentrations
Dose / conc.:
53 mg/kg bw/day
Remarks:
upto
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
No data
Positive control:
No data

Examinations

Parental animals: Observations and examinations:
No data
Oestrous cyclicity (parental animals):
No data
Sperm parameters (parental animals):
No data
Litter observations:
Fetal weight were observed
Postmortem examinations (parental animals):
No data
Postmortem examinations (offspring):
Gross pathology were examined.
Statistics:
No data
Reproductive indices:
No data
Offspring viability indices:
No data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Details on results (P0)

Reproductive performance:
No effect on fetal growth were observed

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
53 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: No toxic effect were observed.

Target system / organ toxicity (P0)

Critical effects observed:
not specified

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
no effects observed
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Details on results (F1)

Body weight:
No effect on fetal body weight were observed in treated rats upto 53 mg/kg bw

Gross pathology:
No malformations were observed in treated rats upto 53 mg/kg bw

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
53 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
gross pathology
Remarks on result:
other: No toxic effect were observed

Target system / organ toxicity (F1)

Critical effects observed:
not specified

Results: F2 generation

General toxicity (F2)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Overall reproductive toxicity

Reproductive effects observed:
no
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 53 mg/kg bw for P and F1 generation when pregnant female rat were treated with 1H-benzimidazole orally.
Executive summary:

In a reproductive toxicity study 1H-benzimidazole was assessed for its possible reprotoxic nature.For this purpose pregnant female rat were treated with 1H-benzimidazole orally upto 53 mg/kg bw on day 8 through 12. The animals were observed for clinical sign, mortality, bodyweight, Food intake, gross and histopathology. The foetus  growth and malformation was observed. No significant effects were observed in treated female rats. No effect on fetal growth nor malformation were observed in treated female rats. Therefore, NOAEL was considered to be 53 mg/kg bw for P and F1 generation when pregnant female rat were treated with 1H-benzimidazole orally through 8-12 days of gestation.