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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
reproductive toxicity, other
Remarks:
Teratogeneicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from authoritative database

Data source

Reference
Reference Type:
other: authoritative database
Title:
Reproductive toxicity of test material
Author:
Hazardous Substances Data Bank
Year:
2015
Bibliographic source:
Hazardous Substances Data Bank (HSDB), Hazardous Substances Databank Number: 593, 2015

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Reproductive toxicity of test material in hamsters
GLP compliance:
not specified
Limit test:
no
Justification for study design:
Not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material: Levomenthol- Common name : l-Menthol- Molecular formula: C10H20O- Molecular weight: 156.267 g/mol- Substance type: Organic- Physical state: solid-Smiles: C1[C@H]([C@@H](C[C@@H](C)C1)O)C(C)C-InChI: 1S/C10H20O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-11H,4-6H2,1-3H3/t8-,9+,10-/m1/s1

Test animals

Species:
hamster
Strain:
other: Syrian
Details on species / strain selection:
Not specified
Sex:
female
Details on test animals and environmental conditions:
Not specified

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
Not specified
Details on mating procedure:
Not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
5 days
Frequency of treatment:
Daily
Details on study schedule:
Not specified
Doses / concentrationsopen allclose all
Dose / conc.:
4.05 mg/kg bw/day
Dose / conc.:
21.15 mg/kg bw/day
Dose / conc.:
98.2 mg/kg bw/day
Dose / conc.:
405 mg/kg bw/day
No. of animals per sex per dose:
Not specified
Control animals:
not specified
Details on study design:
Not specified
Positive control:
Not specified

Examinations

Parental animals: Observations and examinations:
Survival was examined.
Estrous cyclicity (parental animals):
Not specified
Sperm parameters (parental animals):
Not specified
Litter observations:
Survival was examined.
Postmortem examinations (parental animals):
Not specified
Postmortem examinations (offspring):
Gross pathology and histopathology was examined.
Statistics:
Not specified
Reproductive indices:
Not specified
Offspring viability indices:
Not specified

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No effect on survival of treated female hamsters were observed.
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: estrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect on Reproductive performance of treated female hamsters was observed.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
405 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
mortality
reproductive performance
Remarks on result:
other: No effect observed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
No effect on fetal survival of treated female hamsters were observed.
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
no effects observed
Description (incidence and severity):
No dose-related number of abnormalities in soft or skeletal tissues were observed in fetus of treated hamsters were observed.
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
405 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality
histopathology: non-neoplastic
Remarks on result:
other: No effect observed

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 405.0 mg/kg bw for P and F1 generation when Syrian female hamsters were treated with test material orally by gavage during gestation days 6-10.
Executive summary:

In a Reproductive Toxicity study,Syrian female hamsters were treated with test material in the concentration of 4.05, 21.15, 98.2 and 405.0 mg/kg bw/day orally by gavage during gestation days 6-10. No effect on survival of treated female hamsters and fetus were observed. Similarly, No effect on Reproductive performance of treated female hamsters was observed.In addition, No dose-related number of abnormalities in soft or skeletal tissues were observed in fetus of treated hamsters were observed.Therefore, NOAEL was considered to be 405.0 mg/kg bw for P and F1 generation when Syrian female hamsters were treated with test material orally by gavage during gestation days 6-10.