1-phenylethyl acetate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

other: Experimental study for structurally similar analogue included as relevant supporting information to strengthen the use of QSAR to address in vivo chromosome aberration test.

Adequacy of study:

key study

Study period:

Not reported.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A valid study is available for the analogue substance benzyl acetate. It is conducted in compliance with good scientific principles, with no or minor deviations from standard protocols. The read-across is considered to be suitable based on the structural and “mechanistic action” similarities between the target substance (1-phenylethyl acetate) and source substance (benzyl acetate) and their similar physico-chemical properties.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

not specified

Principles of method if other than guideline:

The test method employed demonstrates basic compliance with the guideline OECD 474.

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Benzyl acetate

EC Number:

205-399-7

EC Name:

Benzyl acetate

Cas Number:

140-11-4

Molecular formula:

C9H10O2

IUPAC Name:

benzyl acetate

Details on test material:

- Name of test material : Benzyl acetate- Smiles notation : c1(COC(C)=O)ccccc1- Structural formula attached as image file : see Fig.1- Molecular formula: C9H10O2- Molecular weight : 150.2 g/mol

Test animals

Species:

mouse

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

Not reported

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Corn oil

Details on exposure:

Males were injected intraperitoneally three times at 24 hour intervals with test substance dissolved in corn oil; the total dosing volume was 0.4 mL. Solvent control animals were injected with 0.4 mL of corn oil only. Animals were killed by cervical dislocation 24 hours after the third injection.

Duration of treatment / exposure:

3 single injections

Frequency of treatment:

Injections were 24 hours apart.

Post exposure period:

24 hours post the 3rd injection

Doses / concentrations

Remarks:

Doses / Concentrations:0, 312.5, 625 and 1250 mg/kgBasis:nominal conc.

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

The positive control animals received injections of dimethylbenzanthracene.

Examinations

Tissues and cell types examined:

Bone marrow cells were obtained from the femurs.

Details of tissue and slide preparation:

Smears were prepared from the bone marrow cells obtained from the femurs. Air-dried smears were fixed and stained.

Evaluation criteria:

2,000 polychromatic erythrocytes (PCEs) were scored for the frequency of micronucleated cells in each of five animals per dose group. The results were tabulated as the mean of the pooled results from all animals within a treatment group plus or minus the standard error of the mean.

Statistics:

Analysis of variance (ANOVA)

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

No increase in micronucleated polychromatic erythrocytes was observed in bone marrow smears of male mice treated by intraperitoneal injection three times at 24 hour intervals.ANALOGUE APPROACH JUSTIFICATION:- See attached “Justification for read-across” document for full details.- In summary, important considerations for the use of read-across for acute toxicity are: i) 1-phenylethyl acetate (the target chemical) has similar physico-chemical properties as benzyl acetate (the source substance), ii) there are structural similarities between the two chemicals, iii) the OECD QSAR Toolbox assigns an identical toxicity profiles to both chemicals, and iv) both chemicals have been tested for acute oral toxicity, which demonstrated that neither substance requires classification for acute toxicity and that the benzyl acetate will represent a worst-case scenario, and are adequate for classification and labelling and risk assessment purposes. The information reported in this summary is included to demonstrate comparability between the source (benzyl acetate) and target (1-phenyl-ethyl acetate) substance.

Any other information on results incl. tables

Table 1: Induction of Micronuclei in Mouse Bone Marrow Cells

Compound	Dose (mg/kg)	Micronucleated PCEs/1000 cells	PCEs (%)
Dimethylbenzanthracene	12.5	8.6 ± 0.64	51.7 ± 4.61
Benzyl acetate	0	3.0 ± 0.69	69.9 ± 2.37
	312.5	2.9 ± 0.60	65.8 ± 3.18
	625	3.2 ± 0.6	64.3 ± 5.41
	1250	1.8 ± 0.46	60.7 ± 3.08
		Trend test P = -0.076	ANOVA P = 0.0412

Applicant's summary and conclusion

Conclusions:

No increase in micronucleated polychromatic erythrocytes was observed in bone marrow smears of male mice treated by intraperitoneal injection three times at 24 hour intervals.

Executive summary:

The study was performed as part of a genetic toxicity review in the NTP (1993) study examining carcinogenicity and toxicity. The study was performed in line with good scientific principles and was performed to a method that was in basic compliance with OECD 474. No information relating to the GLP status of the study was reported. No increase in micronucleated polychromatic erythrocytes was observed in bone marrow smears of male mice treated with benzyl acetate (312.5 to 1250 mg/kg) by intraperitoneal injection three times at 24 hour intervals.