Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals 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.

Administration / exposure

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

Examinations

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

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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

Effect levels (maternal animals)

open allclose all
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

Results (fetuses)

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.

Effect levels (fetuses)

open allclose all
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

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

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).