Registration Dossier

Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not documented
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Significant methodological deficiences Only one dose studied, only 5 animals used.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
The antifertility activity and toxicity of alpha-chlorohydrin derivatives in male rats
Author:
Brown-Woodman, P.D.C.
Year:
1979
Bibliographic source:
Contraception 19, 517-530 (1979)
Reference Type:
publication
Title:
Antifertility action of alpha-chlorohydrin derivatives in male rats and assessment of side effects
Author:
Brown-Woodman, P.D.C.
Year:
1976
Bibliographic source:
Theriogenology 6, 648 (1976)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: other. Details not available - see fields below for available information
GLP compliance:
not specified
Limit test:
no

Test material

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

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
No information provided

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
not specified
Details on exposure:
No information provided
Details on mating procedure:
No information provided
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No information provided
Duration of treatment / exposure:
Exposure period: 14 days
Premating exposure period (males): 7 days
Duration of test: 15 days
Frequency of treatment:
daily
Details on study schedule:
No information provided
Doses / concentrations
Remarks:
Doses / Concentrations:
3.3 mg/kg b.w.
Basis:

No. of animals per sex per dose:
No information provided
Control animals:
yes, concurrent vehicle
Details on study design:
No information provided
Positive control:
No information provided

Examinations

Parental animals: Observations and examinations:
No information provided
Oestrous cyclicity (parental animals):
No information provided
Sperm parameters (parental animals):
No information provided
Litter observations:
No information provided
Postmortem examinations (parental animals):
No information provided
Postmortem examinations (offspring):
No information provided
Statistics:
No information provided
Reproductive indices:
No information provided
Offspring viability indices:
No information provided

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-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:
not specified

Details on results (P0)

No effects observed on fertility. There was a reduction in the number of spermatozoa counted in vasa deferentia.
There was a reduction in the mean litter size, mean embryo weight and sperm motility.
No effect on bodyweight, testes and spleen weights; no epididymal or thymus hypertrophy observed.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
3.3 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: No adverse effects on fertility observed at this concentration

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
not specified
Body weight and weight changes:
effects observed, treatment-related
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Details on results (F1)

There was a reduction in the mean litter size and mean embryo weight.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

No effect on fertility.

Number of spermatozoa counted in vasa deferentia, mean litter size, mean embryo weight, sperm
motility reduced.
No effect on body, testes and spleen weight, epididymal and thymus hypertrophy.

Applicant's summary and conclusion

Conclusions:
In this reproduction toxicity study in the rat in male animals the number of spermatozoa and sperm motility was reduced after 14 days i.p. administration of glycidol. Furthermore mean litter size and mean embryo weights were decreased. The NOAEL was determined to be 3.3 mg/kg bw/day.
Executive summary:

In a study conducted by Brown-Woodman et al (1979), the test substance was evaluated for its ability to induce reproductive toxicity when administered to male Wistar rats via intraperitoneal injection over a period of 14 days. The test substance was administered at a concentration of 3.3 mg/kg b.w. Following 7 days of treatment, the males were cohabited with 2 females and the presence of spermatozoa in vaginal smears was taken as evidence of mating. Pregnancy and litter sizes in females were determined 20 days after mating. Under the conditions of this study, no effects were observed on fertility. There was a reduction in the number of spermatozoa counted in vasa deferentia, mean litter size, mean embryo weight and sperm motility. No effect on body, testes and spleen weight, epididymal and thymus hypertrophy. Based on these results, the NOAEL was determined to be 3.3 mg/kg bw/day.

Under the conditions of the key study, the test substance, Glycidol, does not require classification acording to Regulation EC No. 1272/2008 or Directive 67/548/EEC, although some effects were evident affecting

a reduction in the number of spermatozoa counted in vasa deferentia, reduced mean litter size, lower mean embryo weight and reduced sperm motility. Evidence from the supporting studies was equivocal, with no clearly identified effects on fertility or reproductive performance.

However, Glycidol is classified in Annex VI of Regulation 1272/2008 as a Repr. Cat 1B and despite the lack of confirmatory evidence in the studies presented in the dossier, the harmonised classification was adopted. Glycidol is therefore classified as Repr. 1B, H360F according to GHS and Repr. Cat 2, R60 may impair fertility in accordance with Directive 67/548/EEC (as subsequently amended).