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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Remarks:
fertility
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable and well documented

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1993

Materials and methods

Principles of method if other than guideline:
Groups of 10 mice of each sex were administered TCPA (tetrachlorophthalic anhydride) in corn oil by gavage at doses of 0, 94, 187, 375, 750, and 1500 mg/kg 5 days per week. All animals were observed twice daily for morbidity and mortality and detailed clinical signs. Food consumption was recorded weekly and individual body weights were recorded at study initiation and then weekly thereafter until study term. The examinations performed included reproductive system, clinical pathology, and histopathologic evaluations.
As a supplemental examination sperm morphology and vaginal cytology evaluations were performed on mice from the 0, 94, 375, and 1500 mg/kg dose groups.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
once daily
Duration of test:
13 weeks
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
94 mg/kg bw/day (nominal)
Dose / conc.:
187 mg/kg bw/day (nominal)
Dose / conc.:
375 mg/kg bw/day (nominal)
Dose / conc.:
750 mg/kg bw/day (nominal)
Dose / conc.:
1 500 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Groups of 10 mice of each sex/dose
Control animals:
yes, concurrent vehicle
Details on study design:
Histological examination of reproductive organs, sperm morphology and vaginal cytology evaluations

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
> 1 500 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No relevant toxicological effects on reproduction observed at the highest applied dose (1500 mg/kg day)

Any other information on results incl. tables

Sperm morphology evaluations revealed a statistically significant decrease in sperm motility in male mice in the 1500 mg/kg group (P≤0.01); values were not decreased, however, relative to historical control data. TCPA administration did not affect any other parameters measured in sperm morphology or vaginal cytology evaluations in mice.

Applicant's summary and conclusion

Executive summary:

Groups of 10 mice of each sex were administered TCPA (tetrachlorophthalic anhydride) in corn oil by gavage at doses of 0, 94, 187, 375, 750, and 1500 mg/kg 5 days per week. All animals were observed twice daily for morbidity and mortality and detailed clinical signs. Food consumption was recorded weekly and individual body weights were recorded at study initiation and then weekly thereafter until study term. The examinations performed included reproductive system, clinical pathology, and histopathologic evaluations.

As a supplemental examination sperm morphology and vaginal cytology evaluations were performed on mice from the 0, 94, 375, and 1500 mg/kg dose groups.

Sperm morphology evaluations revealed a statistically significant decrease in sperm motility in male mice in the 1500 mg/kg group (P≤0.01); values were not decreased, however, relative to historical control data. TCPA administration did not affect any other parameters measured in sperm morphology or vaginal cytology evaluations in mice. Therefore the NOAEL for fertility is > 1500 mg/kg bw.