Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline, without GLP (acceptable with restrictions)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

limited documentation (no evaluation criteria reported)

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

EC Number:

218-216-0

EC Name:

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Cas Number:

2082-79-3

Molecular formula:

C35H62O3

IUPAC Name:

octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Test animals

Species:

hamster, Chinese

Strain:

other: Cricetulus griseus

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: male 27-38 g, female 23-30 g
- Diet (e.g. ad libitum): Standard diet, NAFAG No.924
- Water (e.g. ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±1
- Humidity (%): 55±5
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: CMC (carboxymethyl cellulose)
- Concentration of test material in vehicle: 2 %
- Amount of vehicle (if gavage or dermal): 20 ml/kg bw

Duration of treatment / exposure:

2 days

Frequency of treatment:

once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
500, 1000 and 2000 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

4

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide
- Doses / concentrations: 64 mg/kg bw

Examinations

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
Based on the Lab results (PH 2.634, dated March 11, 1975), the oral LD was found to be >6000 mg/kg bw in Chinese hamster of either sex.

TREATMENT AND SAMPLING TIMES:
The treated groups consisted of four female and four male animals each. The control groups consisted of six female and six male animals each. The substance was administered orally once daily on 2 consecutive days. The animals were injected intraperitoneally with 10 mg colcemide/kg 2 h after the second dose and sacrificed 4 h later.

METHOD OF ANALYSIS:
Four animals (two females and two males) from each group treated with the various doses of the test article and from the negative and from the positive control group each were analysed by reference to the following criteria:
- Chromatid-type aberrations
- Chromosome-type aberrations
- Chromatid gaps
- Chromosome pulverizations
100 metaphases were analysed per animal.

Evaluation criteria:

no data

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF DEFINITIVE STUDY
- In the low-dose group one metaphase (out of 400 metaphases) was found showing a chromatid-type aberration in the form of a break. The chromosome displays from animals of the intermediate-dose, of the high-dose and of the control group showed no aberrations.
- In contrast to the test substance, cyclophosphamide, 64 mg/kg bw used as positive control caused an increase in all types of aberrations (chromatid-type aberrations 22.0%; chromosome-type aberrations 0.25%). The difference is highly significant (p<0.05).

Any other information on results incl. tables

The Effect of TK10044 and Cyclophosphamide on Bone Marrow Cells of Chinese Hamster

Parameters	Control	Cyclophosphamide	Irganoc 1076 (mg/kg bw)
	2% CMC	64 mg/kg bw	500	1000	2000
Percent of metaphases with specific aberrations	0	22	0	0	0
Chromatid-type aberrations (mean)	0	22	0.25	0	0
Chromosome-type aberrations (mean)	0	0.25	0	0	0
Chromatid gaps (mean)	2.25	17.5	2.5	2.75	2.25

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
It can be concluded from the results that the test substance exerted no mutagenic action in the Chinese hamster under the experimental conditions.