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:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A non GLP study performed to sound scientific principles, following a methodology similar to the OECD guideline 474; and reported with a sufficient level of detail to assess the quality of the submitted data.

Data source

Reference
Reference Type:
publication
Title:
Study of Artificial Flavouring Substances for Mutagenicity in the Salmonella/Microsome, Basc and Micronucleus Tests
Author:
Wild D, King MT, Gocke E & Eckhardt K
Year:
1983
Bibliographic source:
Food and Chemical Toxicology, Vol. 21, No. 6, pp 707-719

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Principles of method if other than guideline:
Seventy six chemicals, which are used as artificial flavouring substances, were screened for mutagenic potential in a mouse micronucleus test. Male and female NMRI mice were treated with test material in a single exposure, at concentrations of 0, 625, 1250 and 1875 mg/kg, administered via intraperitoneal injection in olive oil. The mice were sacrificed and bone marrow smears prepared 30 hours after exposure. All slides were then stained and scored. The literature report provides limited details on the methodology; however the protocol is similar to that defined in OECD 474.
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2-phenoxyethyl isobutyrate
EC Number:
203-127-1
EC Name:
2-phenoxyethyl isobutyrate
Cas Number:
103-60-6
Molecular formula:
C12H16O3
IUPAC Name:
2-phenoxyethyl 2-methylpropanoate
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): 2-phenoxyethyl isobutyrate

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10-14 weeks
- Diet: Standard food ad libitum.
- Water: ad libitum.

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: olive oil.
Frequency of treatment:
A single exposure.
Post exposure period:
30 hours after treatment.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 625, 1250, 1875 mg/kg
Basis:
no data
No. of animals per sex per dose:
2 animals per sex per dose.
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
Mice were sacrificed 30 hours after treatment. Bone marrow smears were prepared and stained for examination and scoring.
Statistics:
Statistical significance was determined according to the methods of Kastenbaum & Bowman (1970).

Results and discussion

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

Any other information on results incl. tables

Table 1: Results

Dose Level (mg/kg) Surviving/ Treated Mice Mean No. of Micronucleated PE/1000 PE
1875 4/4 2.2
1250 4/4 1.3
625 4/4 1.3
0 4/4 0.8

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Under the conditions of the test, the test material gave negative results.
Executive summary:

The potential for the test material to cause genetic mutation was determined as part of a screening study, in which seventy six artificial flavouring chemicals were screened using a mouse micronucleus test. The study was reported in brief, but was performed to a guideline similar to OECD 474. Two male and two female NMRI mice were treated with test material in a single exposure, at concentrations of 0, 625, 1250 and 1875 mg/kg, administered via intraperitoneal injection in olive oil. The mice were sacrificed and bone marrow smears prepared 30 hours after exposure. All slides were then stained and scored. Under the conditions of the test, the test material gave negative results and is considered to be non-mutagenic.