Registration Dossier

Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test guideline (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1971
Report Date:
1971

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
F0:70 days
F1-F4: raised on treated diet
Doses / concentrations
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.

Examinations

Statistics:
Yes, one factor variance analysis, Fischer test, t-test, Chisquare test

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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 / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Details on results (P0)

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.

Effect levels (P0)

Key result
Dose descriptor:
NOAEC
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

Results: P1 (second parental generation)

General toxicity (P1)

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 / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P1)

Key result
Dose descriptor:
NOAEC
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

Results: F1 generation

General toxicity (F1)

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 (F1)

Developmental immunotoxicity:
effects observed, non-treatment-related

Details on results (F1)

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

Effect levels (F1)

open allclose all
Key result
Dose descriptor:
NOAEC
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
Key result
Dose descriptor:
NOAEC
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.

Results: F2 generation

General toxicity (F2)

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

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Key result
Dose descriptor:
NOAEC
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.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

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.