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Toxicological information

Toxicity to reproduction

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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD combined repeat dose and reproductive/developmental toxicity screening test

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
thymol was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0 (vehicle), 8, 40, 200 mg/kg day.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: Thymol (purity: 99.6%)

Test animals

Species:
rat
Strain:
other: Crj:CD (SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 3% gum arabic solution
Details on mating procedure:
no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
males: 43 days
females: from 14 days before mating to day 3 of lactation
Frequency of treatment:
daily
Details on study schedule:
terminal kill:
males: 44 days
females: day 4 of lactation
Doses / concentrations
Remarks:
Doses / Concentrations:
0 (vehicle), 8, 40, 200 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
10 males + 10 females/group
Control animals:
yes, concurrent vehicle

Results and discussion

Results: P0 (first parental animals)

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: marginaly reduced birth weight at 200 mg/kg bw was related to higher litter size

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

The compound exerted no effects on reproductive parameters such as the estrous cycle, mating index, fertility index, gestation lenght, number of corpora lutea or implatations, the implantation index, gestation index, delivery index, parturition or maternal behaviour. Birth weight and body weight gain tended to be low in the 200 mg/kg group neonates. There were no significant differences in numbers of offspring or live offspring at birth, the sex ratio, live birth index or viability index. No abnormal findings ascribable to the compound were found on external examination, or in terms of clinical signs or necropsy finding for the neonates.

Applicant's summary and conclusion

Executive summary:

Thymol was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0 (vehicle), 8, 40, 200 mg/kg day.

The compound exerted no effects on reproductive parameters such as the estrous cycle, mating index, fertility index, gestation lenght, number of corpora lutea or implatations, the implantation index, gestation index, delivery index, parturition or maternal behaviour. Birth weight and body weight gain tended to be low in the 200 mg/kg group neonates. There were no significant differences in numbers of offspring or live offspring at birth, the sex ratio, live birth index or viability index. No abnormal findings ascribable to the compound were found on external examination, or in terms of clinical signs or necropsy finding for the neonates.

The NOELs for reproductive and developmental toxicity are considered to be 200 mg/kg/day for parental males and females, and 200 mg/kg/day for offspring (marginaly reduced birth weight at 200 mg/kg bw was related to higher litter size).