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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
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
GLP compliance:
yes
Type of assay:
rodent dominant lethal assay

Test material

Constituent 1
Chemical structure
Reference substance name:
o-cresol
EC Number:
202-423-8
EC Name:
o-cresol
Cas Number:
95-48-7
Molecular formula:
C7H8O
IUPAC Name:
o-cresol
Details on test material:
Test substance: o-cresol, purity: 99.7 %

Test animals

Species:
mouse
Strain:
ICR
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMAL
- Age at study initiation: 8 weeks
- Assigned to test groups randomly: yes
- Housing: males : individually females: in groups
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: 4 days
-body weights at initialtion and at termination of the assay

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
no further data
Duration of treatment / exposure:
once
Frequency of treatment:
once
Post exposure period:
6 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 75, 250, 750 mg/kg bw in corn oil
Basis:
actual ingested
No. of animals per sex per dose:
25 males per dose.
Control animals:
yes, concurrent vehicle
Positive control(s):
Triethylenemelamine
- Justification for choice of positive control(s):
- Route of administration: single i.p. injection
- Doses / concentrations: 0.3 mg/kg as a volume of 10 ml/kg,

Examinations

Tissues and cell types examined:
All females were examined for the number of live and dead implants within the uterine horn and whether the dead implants had occurred early or late in gestation. Live fetuses were identified as those which appeared to have a functional circulatory capacity.
Details of tissue and slide preparation:
no data
Evaluation criteria:
Statistically significant dose-related increase in the number of dominant leathals is considered as mutagenic in this system.
Statistics:
Chi-square test, ANOVA, Dunnett's one-tailed t test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Remarks:
concentrations were chosen based on dose-range toxicity study
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
see section : "Remarks on results"

Any other information on results incl. tables

--high dose males:
Mortality: 8/25 within 6 days post dosing.
Signs of intoxication: lethary, rough haircoat, languid, tremor, distended abdomen, squinted eyes; all surviving males recovered from these effects within 6 days after dosing.
No effects were observed on fertility index, total implants, mean implants per pregnant female, total live implants, total dead implants, and body weight gain of males.
The test article was considered negative for inducing dominant lethal mutations in germ cells of male mice under conditions of this assay.

Applicant's summary and conclusion

Conclusions:
The test article was considered negative for inducing dominant lethal mutations in germ cells of male mice under conditions of this assay.
Executive summary:

The test article was considered negative for inducing dominant lethal mutations in germ cells of male mice under conditions of this assay.