Registration Dossier

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Individual data and analytical data are not available.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
See 7.5.1.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
See 7.5.1.
Details on mating procedure:
1:1 up to 2 weeks until presence of semen in vaginal smear or presence of vaginal plug
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
See 7.5.1.
Duration of treatment / exposure:
2 weeks before mating, during mating and during gestation up to day 4 of lactation for females (42-54 days) and 2 weeks before mating, during mating till 42 days in total for males
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:0, 100, 300 and 1000 mg/kg bw/dBasis:actual ingested
No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
Specific fertility parameters: number of pairs copulated, pairing days until copulation, gestation length, number of corpora lutea, number of implantations.
Oestrous cyclicity (parental animals):
mean time of estrous cycle and incidence of animals with estrous cycle other than a 4-day cycle per dose was determined beginning at the start of dosing until confirmation of mating
Sperm parameters (parental animals):
None
Litter observations:
Number of (live) pups and sex ratio on day 0 and 4
Postmortem examinations (parental animals):
See 7.5.1.
Postmortem examinations (offspring):
None
Statistics:
See 7.5.1.
Reproductive indices:
Copulation index, fertility index, gestation index, imlantation index, delivery index.
Offspring viability indices:
Birth index, live birth index, viability index.

Results and discussion

Results: P0 (first parental generation)

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
not examined
Reproductive performance:
effects observed, treatment-related

Details on results (P0)

- Estrous cycle: no treatment-related effect on incidence and length of estrous cycle- Reproductive performance: All animals copulated, but one case in the 1000 mg/kg bw/d group failed to become pregnant. The ovaries of this case showed follicle cysts with an increase in follicles in the closed state. No significant differences were observed between the control group and any of the treatment groups in impregnation rate, number of days to copulation or number of estrous during this period. No significant differences were observed for corpus luteum count, implantation count or implantation rate between control and treated groups. In the absence of other findings in other animals the one non-pregnant female is considered to be an incidental case.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: absence of effects

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings:
not examined

Details on results (F1)

No effect on birth index, live birth index, viability index or sex ratio was observed. Morphological observations on day 0 of lactation showed a kinked tail in one pup at 1000 mg/kg bw/d. As no tail abnormalities were observed in any of the other animals, this was considered to be a spontaneous malformation. At necropsy no tail abnormalities were found (not clear if pup with kinked tail had died or not).

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: absence of effects

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No reproductive effects were seen in a combined repeated dose/repro/developmental toxicity study in rats after oral gavage. The NOAEL was set at >=1000 mg/kg bw/d.
Executive summary:

No reproductive effects were seen in a combined repeated dose/repro/developmental toxicity study in rats after oral gavage. The NOAEL was set at >=1000 mg/kg bw/d.