Cresol

Genetic toxicity: in vivo

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 for cross-reference:

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

Test material information

Constituent 1

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:

IUCLID4 Test substance: other TS: o-cresol purity > 99%

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system 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.