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Administrative data

Key value for chemical safety assessment

Toxic effect type:
concentration-driven

Effects on fertility

Link to relevant study records
Reference
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
Qualifier:
equivalent or similar to guideline
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:
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
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:
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
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:
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.
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:
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.
Reproductive effects observed:
not specified
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

Effects on developmental toxicity

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no
Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
Groups of 10 female rats were gavaged with anethole 0, 35, 175, or 350 mg/kg bw/day in corn oil for 7 days prior to co­ habitation with male rats until day 4 of lactation for those rats producing litters and day 25 of cohabitation for those rats without confirmed mating dates. Body weight and feed consumption was monitored. Fertility, gestation index, implantation sites, length of gestation, number of stillborn pups, litter size, pup viability, pup weight, and clinical observations of pups were recorded. On day 4 of lactation, pups were examined, killed, and discarded.
Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
Approximately 32 days
Frequency of treatment:
Daily
Duration of test:
Approximately 32 days
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Maternal examinations:
yes
Ovaries and uterine content:
yes
Fetal examinations:
yes
Statistics:
Yes, Bartlett's Test, ANOVA, Dunnett's test, Kruskal-Wallis Test, Dunn's test, Fischer's Test
Indices:
no data
Historical control data:
no data
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
At 350 mg/kg bw/day: significantly reduced mean body weight and feed consumption throughout study; 1 rat found dead on day 20 of gestation (necropsy showed congested lungs, but uterine contents showed 17 normal fetuses and 2 early resorptions); 2 rats had urine-stained abdominal fur during the premating period, one of these rats also "had a tan perivaginal substance and appeared pale on day 23 of gestation, and during lactation was emaciated and pale and had an ungroomed coat and red perioral and perivaginal substances"; in necropsy 1 rat had a raised yellow area in the liver, 1 rat had hematomas on the vessels supplying the implantation sites; average gestation duration was increased (number of dams delivering on days 23 and 24 was increased over controls); number of dams with stillborn pups and with all pups dying before postpartum day 4 was significantly increased (P less than or equal to 0.01).
At 175 mg/kg bw/day, mean body weight was significantly decreased on gestation days 6 and 14; feed consumption was significantly reduced during premating days 1-8 but not during gestation
Dose descriptor:
NOAEL
Effect level:
ca. 35 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
LOAEL
Effect level:
ca. 175 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
At 350 mg/kg bw/day, number of live born pups (75) was significantly decreased (P less than or equal to 0.01) compared to controls (147), number of stillborn pups (18) was significantly increased (P less than or equal to 0.01) compared to controls (0), number of pups dying on day 1 and days 2-4 (8 and 7 respectively) was significantly increased (P less than or equal to 0.01) compared to controls (0 and 0, respectively), viability index (number of live pups on postpartum day 4/number of live born pups on postpartum day 1) was significantly (P less than or equal to 0.01) decreased (80%) compared to controls (99.3%); number of surviving pups/litter on postpartum day 4 (7.5) was significantly (P less than or equal to 0.01) decreased compared to controls (14.6); live litter size on postpartum day 4 (12.0) was significantly (P less than or equal to 0.05) decreased compared to controls (14.6); pup weight/litter on postpartum day 1 (5.1 g) was significantly (P less than or equal to 0.05) decreased compared to controls (6.2 g).
No other effects were reported at the other doses. No anomalies were reported.
Dose descriptor:
NOAEL
Effect level:
ca. 175 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
reduction in number of live offspring
Dose descriptor:
NOAEL
Effect level:
ca. 350 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
reduction in number of live offspring
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
Anethole did not cause any developmental effects on the rat fetus at doses below those causing maternal toxicity (reduced body weight and feed consumption).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
35 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

Additional information