Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary literature (cited in OECD SIDS 2003)

Data source

Referenceopen allclose all

Reference Type:
other: study reprot cited in OECD SIDS 2003
Title:
Unnamed
Year:
1986
Report Date:
1986
Reference Type:
review article or handbook
Title:
SIDS Initial Assessment Report (SIAR): 6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol CAS No: 119-47-1
Author:
OECD SIDS
Year:
2003
Bibliographic source:
OECD SIDS, UNEP Publications

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: chemically pure product, physical appearance: white powder

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
Housing: in groups of 6; cage type: Makrolon type 3, with wire mesh top and granulated softwood bedding; environment: air-conditioned, temperature: 22 +/- 3 degrees centigrade, relative humidity: 40 - 70%, 12 hours light/dark per day

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
polyethylene glycol 400 (PEG 400)
Details on exposure:
single application by gavage; the negative control groups received the test article vehicle (PEG 400); the test groups received 5000 mg/kg body weight of the test article
Duration of treatment / exposure:
single application
Frequency of treatment:
single application
Post exposure period:
24-, 48- and 72- hours intervals after treatment
Doses / concentrations
Remarks:
Doses / Concentrations:
5000 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
18 males and 18 females per group
Control animals:
yes, concurrent vehicle
Positive control(s):
positive control group: received 50 mg/kg body weight of cyclophosphamid dissolved in 0.9% saline solution immediately before application

Examinations

Tissues and cell types examined:
bone marrow from the femora
Details of tissue and slide preparation:
The bone marrow cells were prepared from the mouse femora and suspended in calf serum. The suspension was centrifuged, the supernatant discarded. The bone marrow cells were suspended in calf serum and a drop of this suspension was smeared on a slide; and allowed to dry overnight. Two slides per animal were prepared. The smears were stained according to the method developed by Pappenheim.

Statistics:
Estimation and testing were performed by maximum likelihood method (Armitage 1971)

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Results:
Clinical observations:
no death occured during the application period and no treatment-related 
clinical findings were observed.
No toxic effects of the test article were observed in the treatment group, 
compared to the negative control (indicated by the PCE/NCE ratio).

After a single application of 5000 mg/kg test substance, no significant test 
article-related increase of micronucleated polychromatic erythrocytes
was observed; at the three examination times: 24 h, 48 h, and 72 h.

Applicant's summary and conclusion

Executive summary:

The test substance 6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol was negative in the in vivo micronucleus assay (RCC 1986).