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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Principles of method if other than guideline:
The objective of this dominant lethal assay in mice was to determine the level of fetal death in untreated females following mating to males acutely treated with p-cresol. All stages of male germ cell development were evaluated (six mating periods).
GLP compliance:
yes
Type of assay:
rodent dominant lethal assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: p-cresol, 99.8% pure

Test animals

Species:
mouse
Strain:
ICR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: males: 9.5 weeks
- Weight at study initiation: 26.7 - 36.7 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study:
- Housing: males individually and females in groups
- Diet ad libitum
- Water ad libitum

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


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
all dosing solutions were prepared immediately prior to dosing

Duration of treatment / exposure:
Single dose
Frequency of treatment:
once
Post exposure period:
6 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 275, 550 (650) mg/kg bw diluted in corn oil
Basis:
actual ingested
No. of animals per sex per dose:
25 males/group were treated; 50 females /group
Control animals:
yes, concurrent vehicle
Positive control(s):
triethylenemelamine
- Route of administration: i.p.
- Doses / concentrations: 0.3 mg/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
Evaluation criteria:
statistically sognificant dose-related increase in the number of dominant lethals is considered as mutagenic in this testsystem.
Statistics:
Chi-square test, ANOVA, Dunnett's one-tailed t-test

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
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

Mortality: 
650 mg/kg bw: 10/25 males within the first week; as signs of toxicity mice exhibited rapid breathing, several became languid with mild clonic convulsions and squinted eyes and were prostrate  and had scruffy coats; 550 mg/kg bw: 6/25 males died during the test
body weight:
No significant reduction in body weight were observed in any of the males in any of the dose groups. The statistical evaluation of the parameters indicated that no significant effects of p-cresol were induced at any dose levels.
The treatment had no adverse effects with respect to number of early and  late resorptions, and live implants, indicating that the test compound  did not induce dominant lethal mutations in male germ cells of mice under  the conditions of this assay.
The concurrent positive control substance TEM induced  a significant  increase in :
the number of dead  implantations, in the portion of females with either  one or more dead implantations, the frequency of dead implants relative  to the total number of implants in each female during mating weeks 1  through 3  TEM induced a significant reduction in total implants relative to the  vehicle control group.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Executive summary:

p-Cresol did not induce dominant lethal mutations in male germ cells of mice under  the conditions of this assay when tested according to OECD TG 478 (Rodent Dominant Lethal Assay).