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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Dominant lethal study in which male mice were orally gavaged with test material and subsequently mated with untreated female mice over a period of six weeks. The number of females pregnant and number of offspring in each litter was determined.
GLP compliance:
no
Type of assay:
rodent dominant lethal assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
TK 12386 (25068-38-6)

Test animals

Species:
mouse
Strain:
other: Tif: MAG f (SPF)
Sex:
male
Details on test animals and environmental conditions:
Animals were 3-4 months of age at the time of test, were fed a standard rodent diet and water ad libitum, and were kept in environmentally-adequate housing facilities.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol (PEG 400)
Details on exposure:
The test material was administered orally in single doses to 20 male albino mice per group, which were then mated to untreated females from the same strain over a period of 6 weeks. At the end of each week, the 2 females per male were replaced by new ones, repeated for 6 weeks to cover the stages of the maturation of the germ cell from the A-spermatogonia to the mature spermatozoon. Doses of 3333 mg/kg and 10,000 mg/kg were given in polyethylene glycol (PEG 400). A control group was given only the vehicle.
Duration of treatment / exposure:
One dose. Test material was dissolved in polyethylene glycol 400.
Frequency of treatment:
once
Post exposure period:
Each male mouse was allowed to mate with two untreated females beginning six hours after receiving a single oral dose of test material. Each group of two untreated females remained with the treated male mouse for a week. After one week the females were removed and replace by another group of two untreated females.
Doses / concentrations
Remarks:
Doses / Concentrations:
Doses of 3333 mg/kg and 10,000 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
20 male mice/group
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
Females were necropsied on the 14 day of gestation. The number of live embryos and embryonic deaths were listed. In addition, the uteri were placed in a solution of ammonium sulphide in order to detect sites of early embryonic resorptions.
Statistics:
To compare the total number of implantations indicating pre-implantation loss, the t-test or Mann-Whitney's U-test was used. The total numbers of mated and pregnant dams or embryonic deaths were compared with the aid of the X2-test or Fisher's exact test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
In-life observations included diarrhea in males of the high dose group two days after treatment.
Vehicle controls validity:
valid
Additional information on results:
In-life observations included diarrhea in males of the high dose group two days after treatment. There were no adverse effects on females associated with any of the groups.

The data on mating ratio, numbers of implantations, and embryonic deaths are comparable for all groups.

Any other information on results incl. tables

The data on mating ratio, on the numbers of implantations and embryonic deaths were comparable for all groups.

The diarrhea observed two days after dosing male mice was most likely the result of the vehicle rather than the test material.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The test material was negative in the dominant lethal assay.
Executive summary:

A mouse dominant lethal study was conducted with DGEBPA. There was no evidence of an effect on male fertility or number of offspring/litter.