Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
other information
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Abstract.

Data source

Reference
Reference Type:
publication
Title:
Long-lasting learning and memory impairments induced by prenatal exposure to 4-tert-butyltoluene in rats.
Author:
Hass U et al.
Year:
1996
Bibliographic source:
Teratology 53: 22A, abstract no. F15.

Materials and methods

Principles of method if other than guideline:
No data on method given.
GLP compliance:
not specified
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4-tert-butyltoluene
EC Number:
202-675-9
EC Name:
4-tert-butyltoluene
Cas Number:
98-51-1
Molecular formula:
C11H16
IUPAC Name:
1-tert-butyl-4-methylbenzene
Details on test material:
- Name of test material (as cited in study report): 4-tert-butyltoluene
- Physical state: liquid
- Analytical purity: no data
No further data

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
female Mol:WIST rats
no further data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
No details given.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No details given.
Duration of treatment / exposure:
days 7 through 20 of gestation
Frequency of treatment:
6 hours/day
Duration of test:
until 22 months after delivery
Doses / concentrations
Remarks:
Doses / Concentrations:
ca. 0.12 mg/l (20 ppm)
Basis:
nominal conc.
No. of animals per sex per dose:
no data
Control animals:
yes
Details on study design:
No further details given.

Examinations

Maternal examinations:
No details given.
Statistics:
No data.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Details on maternal toxic effects:
The dose level used, ca. 0.12 mg/l (20 ppm), did not induce maternal toxicity. No further data.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEC
Effect level:
> 0.12 mg/L air
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Effect level:
> 0.12 mg/L air
Basis for effect level:
other: other:
Remarks on result:
not determinable
Remarks:
no NOAEC identified
Dose descriptor:
NOAEC
Basis for effect level:
other: developmental toxicity
Remarks on result:
not determinable
Remarks:
no NOAEC identified

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Details on embryotoxic / teratogenic effects:
The dose level used, ca. 0.12 mg/l (20 ppm), did not induce decreased viability of offspring.
Lowered pup body weight until day 10 and delayed ontogeny of reflexes - also after correction for body weight - was recorded.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

At the age of 3 months, increased latencies and swim length were observed in the learning period of treated female offspring (p = 0.6%). Three weeks later, indications of memory impairments were noted. However, these increases were not statistically significant (p = 8.7%). No substance-related effects were observed at 17 months. At the age of 22 months, increases in latencies and swim length indicating memory impairments were observed in the first 3 trials and in the trials following a 4-days break in testing (p = 5.5%).
According to the authors, the impairment in exposed female offspring was not considered to be related to poorer swimming capability since swim lengths were increased in proportion to the increased latencies; swim speed was similar to control. The results indicated that substance-related neurobehavioral impairments could interact with the consequences of aging.

 

Applicant's summary and conclusion