Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
other: publication
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary literature, no details

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1991

Materials and methods

Principles of method if other than guideline:
no data
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no data

Test animals

Species:
other: mouse and rat
Strain:
other: B6C3F1 mice and F344 rats
Sex:
female
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
30 days
Frequency of treatment:
daily
Duration of test:
no data
Doses / concentrations
Remarks:
Doses / Concentrations:
10-800 mg/kg/day
Basis:
no data
No. of animals per sex per dose:
no data
Details on study design:
VCH and epoxide metabolites injected; some animals pretreated with chloramphenicol or phenobarbital
Statistics:
no data

Results and discussion

Observed effects

-mice:epoxides5-10 times more potent ovotoxins than VCH and in rats
-rats: 30 daily i.p. injections (800 mg/kg) of VCH failed to cause detectable ovotoxicity
-mice pretreated with chloramphenicol:69% inhibition of VCH epoxidation and protected mice from ovotoxocity.
- VCH epoxidation increased in phenobarbital pre-treated mice
-increasing VCH dose led to increase of circulating VCH epoxide (mice)

Applicant's summary and conclusion

Conclusions:
-VCH diepoxide is the most potent ovotoxic substance
- lack of ovotoxicity in VCH treated rats compared to mice because of slower rates of VCH biotransformation to epoxides and because of 20 fold higher rate of epoxide detoxification
- female B6C3F1 mouse : expression of P450IIA and P450IIB; female F344 rat: lack of related P450IIA mouse isoform and very low amounts of P450IIB