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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from a publication.

Data source

Reference
Reference Type:
publication
Title:
Absence of Teratogenic Effect the test chemical
Author:
D. J. CLEGG
Year:
1965
Bibliographic source:
Fd Cosmet.ToxicoL;1965

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The above experiment was performed to evaluate and assess the developmental toxicity of the test chemical in mouse.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,6-di-tert-butyl-p-cresol
EC Number:
204-881-4
EC Name:
2,6-di-tert-butyl-p-cresol
Cas Number:
128-37-0
Molecular formula:
C15H24O
IUPAC Name:
2,6-di-tert-butyl-4-methylphenol
Test material form:
other: Solid
Details on test material:
- Name of test material (as cited in study report):Butylated hydroxytoluene (BHT; 3,5-di-tert-butyl-4-hydroxytoluene)
-Synonyms-2,6-di-tert-butyl-p-cresol
- Molecular formula (if other than submission substance):C15H24O
- Molecular weight (if other than submission substance): 220.3536
- Substance type: organic
- Physical state: solid
- Impurities (identity and concentrations):Not available
Specific details on test material used for the study:
- Molecular weight (if other than submission substance): 220.3536 g/mol
- Substance type: organic
- Physical state: solid
- Impurities (identity and concentrations):Not available

Test animals

Species:
mouse
Strain:
other: Evans No.1
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Not available
- Age at study initiation:
- Weight at study initiation: Not available
- Fasting period before study: Not available
- Housing: Not available
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not available
- Humidity (%):Not available
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): Not available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Not available
DIET PREPARATION
- Rate of preparation of diet (frequency): Not available
- Mixing appropriate amounts with (Type of food): Not available
- Storage temperature of food: Not available

VEHICLE
- Justification for use and choice of vehicle (if other than water): arachis oil
- Concentration in vehicle: Not available
- Amount of vehicle (if gavage): Not available
- Lot/batch no. (if required): Not available
- Purity: Not available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data Available
Details on mating procedure:
No details of mating available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: Presence of vaginal plug.
Duration of treatment / exposure:
Dose regime 1: Daily administration for 32-46 days prior to mating and up to day 18 of pregnancy.
Dose regime 2: Daily administrationon days 1-18 of pregnancy
Frequency of treatment:
Daily for both the dose regimes
Duration of test:
Dose regime 1: 50-64 days
Dose regime 2: 18-21 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 750 mg/kg body weight
Basis:
no data
No. of animals per sex per dose:
Dose regime 1:10 females,
Dose regime 2:10 females(Including arachis oil control and untreated control.)
Control animals:
other: treated with arachis oil,untreated animals,positive control, only with ICI SPF mice
Details on study design:
The test chemical were administered as a solution in arachis oil by oral intubation. Daily administartion was given for :
1.Daily 32-46 days prior to mating and during pregnancy.
2.Daily only during pregnancy.

Examinations

Maternal examinations:
Mean body weight,fertility index and mating index.
Ovaries and uterine content:
The number of corpora lutea, numbers and positions of implantation sites (including resorption sites).
Fetal examinations:
Examined for gross abnormalities, skeletal abnormalities and sexed (by measuring the anogenital distance), weighed.
Statistics:
No Data available
Indices:
fertility index and mating index.
Historical control data:
No data

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
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
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
Details on results:
No Data Available

Maternal developmental toxicity

Number of abortions:
no effects observed
Description (incidence and severity):
No fetuses were aborted in both the dose regimes at any dose levels in the study.
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
effects observed, non-treatment-related
Description (incidence and severity):
Some sporadic cases were observed where early or late resorptions were observed.
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Other effects:
not specified
Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No significant change in body weight.
Dose regime 1:Mating index=88% and Fertility index =29%.
Dose regime 2: Mating index=Not available and Fertility index=25 %.

Effect levels (maternal animals)

Dose descriptor:
LOAEL
Effect level:
750 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
early or late resorptions
maternal abnormalities
number of abortions

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
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:
effects observed, treatment-related
Description (incidence and severity):
Microphthalmia was observed in the treated groups.
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No Embryonic or teratogenic effects observed in foetuse or offspring.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
750 other: mg/kg bw
Based on:
test mat.
Sex:
male/female
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 test chemical administered to female mice at a dose of 750 mg/kg bw daily for 70 days premating, during pregnancy and only during pregnancy showed no adverse effects either on parent or fetuses.
Executive summary:

In an experimental study, groups of mice of strain Evans No.1 were administered with the test chemical in oral dosage regime, with a daily dose of 0 and 750 mg/kg bw during the period before mating, continuing through mating and gestation up to the time when the animals were killed, and during pregnancy (1-18 days) only. The vehicle used for dosing the test chemical was Archias oil. The maternal animals were observed for Mean body weight,fertility index and mating index. In uterine observations, the animals were observed for the number of corpora lutea, numbers and positions of implantation sites (including resorption sites). After performing all the observations, No significant maternal toxicity and no significant embryotoxic effects were observed, as judged by examination of the skeletal or gross abnormalities of fully-developed fetuses. Thus, from all the observations, it was concluded that the NOAEL for embryotoxicity and teratogenicity was therefore considered to be 750 mg/kg bw.