Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
genetic toxicity in vivo
Remarks:
Type of genotoxicity: other: micronucleus assay
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no data on the ratio of normochromatic to polychromatic erythrocytes, no positive control
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
NTP Report on the toxicity studies of cresols in F344/N rats and B6C3F1 mice (feed studies). NTP TOX 9, 1990/1991
Author:
US Department of Health and Human Services
Year:
1991
Bibliographic source:
US Department of Health and Human Services (1990/1991) NTP TOX 9, 1990/1991

Materials and methods

Principles of method if other than guideline:
Method: Smears were prepared from peripheral blood samples obtained by cardiac punction of dosed and control animals at the termination
of the 13 week study. Polychromatic and normochromatic erythrocytes from each animal were scored for micronuclei
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
IUCLID4 Test substance: other TS: o-cresol purity > 99%

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
see the respective record in the chapter 7.5.1

Administration / exposure

Route of administration:
oral: feed
Vehicle:
see the respective record in the chapter 7.5.1
Details on exposure:
see the respective record in the chapter 7.5.1
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Post exposure period:
no
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 5000, 10000, 20000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment
Positive control(s):
no data

Examinations

Tissues and cell types examined:
erythrocytes from peripheral blood samples
Details of tissue and slide preparation:
Slides were stained with Hoechst 33258/pyrcein Y according to MacGregor et al (1983, no further data)
Evaluation criteria:
positive if a significant elevation in the frequenciy of micronucleated erythrocytes was observed either in males or in females.
Statistics:
yes, but method not mentioned

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
not examined

Any other information on results incl. tables

RS-Freetext:
Compound consumption:
dose---------male------female
[ppm]---------[mg/kg bw/d]
-----------------------------
5000 ---------794 -------935
10000--------2723------1663
20000--------2723------3205

No significant elevation in the frequency of micronucleated erythrocytes was observed in either male or female mice. NOAEL for systemic toxicity is 1250 ppm (199 and 237 mg/kg bw/d, respectively) based on increased relative and absolute liver and kidney weights without histopathological correlate from 2500 ppm onwards.

Applicant's summary and conclusion

Executive summary:

Following repeated oral dosing of mice over a period of 13 weeks with o-cresol, the MNT with peripheral erythrocytes yielded a negative result.