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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP near guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Deviations:
no
Principles of method if other than guideline:
Male mice of confirmed fertility were given a subcutaneous injection of 1.0 mL/kg mixed xylenes (diluted 10% in corn oil) and each housed with 3 virgin females for a period of 1 week. At the end of the week, the males were transferred to new groups of virgin females and the process repeated for a total of 8 weeks (the time of one complete sperm cycle). The females were killed on the 15th day following first contact with the male and the uteri examined for early and late deaths and total implants.
GLP compliance:
no
Type of assay:
rodent dominant lethal assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): mixed xylenes
- Substance type: petroleum fraction

Test animals

Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen Laboratories, Gilroy, California
- Age at study initiation: approx 10 weeks
No further details available

ENVIRONMENTAL CONDITIONS: No data

IN LIFE DATES: No data

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
Duration of treatment / exposure:
Single injection to male mice immediately prior to initial mating.
Frequency of treatment:
Single injection
Post exposure period:
eight weeks (of mating)
Doses / concentrations
Remarks:
Doses / Concentrations:
1.0 mL/kg
Basis:

No. of animals per sex per dose:
10 males each mated with 3 females, males transferred to a new group of females at the end of a week for a total of 8 weeks (i.e. 240 females)
Control animals:
yes, concurrent vehicle
Positive control(s):
triethylenephosphoramide (TEPA)
- Doses / concentrations: 7 mg/kg

Examinations

Tissues and cell types examined:
Uteri examined for early and late deaths and total implants.
Evaluation criteria:
The weekly data from females was compiled to calculate the following indices (weekly and total based on entire 8 week cycle): pregnancy index (% pregnant) and mutagenic index.
Statistics:
Chi square tests were carried out on the ratios representing total fertility and mutagenic indices for comparison of each group with the negative control. In addition, Chi square tests were run on any unusual weekly index and on any weekly mutagenic index greater than 10. Mutagenic indices below 10 are well within the normal range.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

No deviations from vehicle control values, except for a significantly reduced mutagenic index during the 3rd week of mating which resulted from an unusually high control value and was therefore considered not to be treatment-related. No evidence of decreased pregnancy rate or increased embryo loss.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
When the petroleum fraction "mixed xylenes" was tested in the dominant lethal assay in mice, there was no evidence of mutagenicity.
Executive summary:

When the petroleum fraction "mixed xylenes" was tested in the dominant lethal assay in mice, there was no evidence of mutagenicity.