Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

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other: Non-GLP near guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.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 rats were given an intraperitoneal injection of 1.0 mL/kg mixed xylenes and then each was housed with 2 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 procedure repeated for a total of 10 weeks (the time of one complete sperm cycle). The females were killed on the 17th day following first contact with the male and the uteri examined for deaths and total implants, corpora lutea counts were made of each ovary.
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:
rat
Strain:
Long-Evans
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:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: none (used undiluted)
Duration of treatment / exposure:
Single injection to male rats immediately prior to initial mating.
Frequency of treatment:
Single injection
Post exposure period:
ten 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 2 females, males transferred to a new group of females at the end of a week for a total of 10 weeks (i.e. 200 females)
Control animals:
other: yes, injected with water
Positive control(s):
triethylenemelamine (TEM)
- Doses / concentrations: 0.25 mg/kg

Examinations

Tissues and cell types examined:
Uteri examined for deaths and total implants, corpora lutea counts were made of each ovary.
Evaluation criteria:
The weekly data from females was compiled to calculate the following indices (weekly and total based on entire 10 week cycle): pregnancy index (% pregnant), implantational index (% implantations) and mutagenic index
Statistics:
Chi square tests were carried out on the ratios representing total fertility, implantational 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:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

No deviations from negative control values. 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 rats, there was no evidence of mutagenicity.
Executive summary:

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