Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference
Reference Type:
publication
Title:
A study of the teratogenicity of butyiated hydroxyanisole on rabbits.
Author:
HANSEN, E., and MEYER
Year:
1978
Bibliographic source:
Toxicology, 10 (1978) 195--201

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
A teratogenicity study on the test chemical was carried out in SPF New Zealand White rabbits by gavage for day 7-18 of the gestation period at a doses of 0, 50, 200 and 400 mg/kg body wt./day.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):tert-butyl-4-methoxyphenol
- Molecular formula (if other than submission substance):C11H16O2
- Molecular weight (if other than submission substance):170.11
- Substance type:organic
- Physical state:Solid
Specific details on test material used for the study:
No Data Available

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Akers Krudtbruk, Sweden
- Age at study initiation: 7 weeks old
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: No Data Available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C +- 1,
- Humidity (%): 60 -+ 5%,
- Air changes (per hr): 8 air changes/h



Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
propylene glycol
Details on exposure:
No Data Available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data Available
Details on mating procedure:
Each female was mated twice a day (if possible) to 2 different males The day of observed copulation was considered as day 0 of gestation. Mated
females were weighed and placed on test.
Duration of treatment / exposure:
7-18 day
Frequency of treatment:
No Data Available
Duration of test:
28 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 200, and 400 mg/kg/day
Basis:
no data
No. of animals per sex per dose:
68 animals per dose
Control animals:
yes, concurrent vehicle
Details on study design:
No Data Available

Examinations

Maternal examinations:
weight of the intact uterus, number of corpora lutea (CL), of implantations
Ovaries and uterine content:
No Data Available
Fetal examinations:
number of fetuses, alive and dead. the fetuses were weighed, sexed and examined for gross external and visceral malformations were examined.
Statistics:
Student's t-test was performed on bodyweight and weight gain of the dams and mean weight of the intact uteri. Wflcoxon Ranks test [6] was performed on pup weight, preimplantation loss and postimplantation loss and critical values for testing two-by-two tables [7] on malformations of the head.
Indices:
No Data Available
Historical control data:
No Data Available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
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

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Changes in pregnancy duration:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Changes in number of pregnant:
no effects observed
Other effects:
no effects observed
Details on maternal toxic effects:
The maternal NOAEL for the test chemical was found to be 400 mg/kg bw/day.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
400 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: no effect observed

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
no effects observed
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The BHA has not given rise to any embryotoxic effect in this study.

Effect levels (fetuses)

Dose descriptor:
NOEL
Effect level:
400 other: mg/kg/day
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The developmental toxicity NOEL (No observed effect level) of the test chemical was observed at a dose concentration of 400mg/kg/day. At this dose there was no treatment related effects observed on the number of corpora lutea, implantations, fetuses (dead or alive), or on gross malformations, skeletal and internal malformations, and on the weight of fetuses.

Executive summary:

The teratogenicity study on the test chemical was carried out in SPF New Zealand White rabbits. Different parameters like gross malformations, incidence of variation in skeletal ossification, minor skeletal anomalies and major skeletal malformations were examined, the data do not show any difference among controls and the test chemical dosed animals. Thus from above findings we can conclude that administration by gavage of the test chemical to pregnant rabbits did not induce any teratological effect when given daily from day 7 to 18 of the gestation period in doses of 50, 200 and 400 mg/kg body wt./day