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Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Link to relevant study records
Reference
Endpoint:
two-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
GLP compliance:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: feed
Duration of treatment / exposure:
F0:70 days
F1-F4: raised on treated diet
Remarks:
Doses / Concentrations:
600-1500 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
20
Control animals:
yes, plain diet
Details on study design:
Groups of 20 male and 20 female Wistar SPF rats were fed 0 or 1% anethole in the diet (approximately 600-1,500 mg/kg bw/day) for 70 days prior to mating. Four paired groups were formed: (1) control males X control females; (2) control males X treated females; (3) treated males X control females; and (4) treated males X treated females. During the mating period of 15 days, the first 3 groups were maintained on basal diet; whereas, group 4 received treated diet. During gestation and lactation, females of groups 2, 3 and 4 were maintained on 1% anethole diet. Offspring from groups 1 and 4 were used for propagating the next generation and were raised on the same dietary treatment as their parents (70 days from time of weaning). At approximately 3 months of age, rats were bred to obtain the next generation. A similar procedure was followed to obtain the 3rd and 4th generations. The treatment groups for F1, F2 and F3 were: (1) control males X control females; and (2) treated males X treated females. Mortality, body weight, food consumption, and reproductive performance (fertility, sex ratio, date of birth, stillbirths, clinical observations, litter size, litter viability) were monitored.
Statistics:
Yes, one factor variance analysis, Fischer test, t-test, Chisquare test
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, non-treatment-related
Body weight and weight changes:
effects observed, non-treatment-related
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Food efficiency:
no effects observed
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
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
effects observed, non-treatment-related
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
P0: death of 1 control male and 1 treated female, no other deaths, decreased body weight in treated rats, decreased food consumption in treated rats, no effect on reproductive performance.
P1: no deaths, reduced body weight gain and body weight in treated rats, reduced food consumption in treated rats for 1st 2 weeks, no effect on reproductive performance.
Key result
Dose descriptor:
NOAEL
Effect level:
> 600 - < 1 500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, non-treatment-related
Body weight and weight changes:
effects observed, non-treatment-related
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: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
> 600 - < 1 500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
effects observed, non-treatment-related
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:
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified
Developmental immunotoxicity:
effects observed, non-treatment-related
F2 and F3: no deaths, reduced body weight gain and body weight in treated rats, reduced food consumption in treated rats for first 2 weeks, no effect on reproductive performance
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 600 - <= 1 500 mg/kg bw/day
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No effects on reproductive performance
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
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:
not specified
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Key result
Dose descriptor:
NOAEL
Generation:
F2
Effect level:
>= 600 - <= 1 500 mg/kg bw/day
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No effects on reproductive performance.
Key result
Reproductive effects observed:
no
Conclusions:
The reduced palatability of the diet was considered to be responsible for the lower body weight gain and body weights of the rats receiving anethole.
trans-Anethole did not affect the reproductive performance of rats over 4 generations.
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
600 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification