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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1981
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: No data on GLP, study was performed with a route of exposure that is not relevant for humans. Evidence for the conclusion of "delayed heart development" was not presented.

Data source

Reference
Reference Type:
publication
Title:
Testing of selected workplace chemicals for teratogenic potential
Author:
Hardin BD, Bond GP, Sikov MR et al.
Year:
1981
Bibliographic source:
Scand J Work Environ Health 7(Suppl 4):66-75.

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
Young adult female Sprague-Dawley rats (250-300 g).

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
corn oil
Details on exposure:
Groups were injected ip with 170 mg/kg test material or corn oil daily from days 1-15 of gestation.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Young adult female Sprague-Dawley rats (250-300 g) were caged with breeder males of the same strain. Females were examined daily for the presence of sperm in a vaginal lavage. The day sperm was detected was designated as day 1 of gestation. Inseminated females were randomly allocated to a control or treatment group (N = 10-15/group).
Duration of treatment / exposure:
daily single i.p. dose
Frequency of treatment:
from days 1-15 of gestation
Duration of test:
On day 21 of gestation, the females were euthanized.
Doses / concentrations
Remarks:
Doses / Concentrations:
170 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
10-15 females/group
Control animals:
yes
Details on study design:
Young adult female Sprague-Dawley rats (250-300 g) were caged with breeder males of the same strain. Females were examined daily for the presence of sperm in a vaginal lavage. The day sperm was detected was designated as day 1 of gestation. Inseminated females were randomly allocated to a control or treatment group (N = 10-15/group). Groups were injected ip with 170 mg/kg test material or corn oil daily from days 1-15 of gestation.

On day 21 of gestation, the females were euthanized and the uterine contents were examined. The internal organs were examined grossly and the brain, heart, liver, lungs, spleen, kidneys, adrenals and ovaries were weighed and preserved in 10% formalin for histopathological examination.

The individual fetuses were weighed, measured for crown-rump length, sexed and examined for external malformations. One half to two thirds of each litter was preserved in Bouin's solution for internal examination by the Wilson method of free-hand razor-blade sectioning, and the rest of the fetuses were fixed in ethanol for clearing and skeletal staining with alizarin red.

Examinations

Maternal examinations:
On day 21 of gestation, the females were euthanized and the internal organs were examined grossly and the brain, heart, liver, lungs, spleen, kidneys, adrenals and ovaries were weighed and preserved in 10% formalin for histopathological examination.
Ovaries and uterine content:
On day 21 of gestation, the females were euthanized and the uterine contents were examined.
Fetal examinations:
The individual fetuses were weighed, measured for crown-rump length, sexed and examined for external malformations. One half to two thirds of each litter was preserved in Bouin's solution for internal examination by the Wilson method of free-hand razor-blade sectioning, and the rest of the fetuses were fixed in ethanol for clearing and skeletal staining with alizarin red.
Statistics:
Statistical methods were not listed. The level for significance was listed as p < 0.05.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
There was no treatment-related histopathological changes in maternal tissues. There was no effect of treatment on maternal organ weights.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
170 other: mg/kg bw
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The development of the heart was delayed by 1-2 days. There was no evidence of teratogenicity.

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEL
Effect level:
170 other: mg/kg bw
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEL
Effect level:
< 170 other: mg/kg bw
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

It was stated that the dose administered to females was one that did not cause mortality, no marked signs of toxicity and less than a 10% reduction in body weight gain over the course of 15 daily ip injections in previously tested non-pregnant rats.

It is unknown what is meant by "delayed heart development". Specific alterations in the hearts of fetuses were not mentioned.

Applicant's summary and conclusion

Conclusions:
Positive for fetal toxicity but was not teratogenic.