2-ethylbutyric acid

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test guideline 2

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Version / remarks:

T37-15: Chemical Substances Control Law of Japan

GLP compliance:

yes

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylbutyric acid

EC Number:

201-796-4

EC Name:

2-ethylbutyric acid

Cas Number:

88-09-5

Molecular formula:

C6H12O2

IUPAC Name:

2-ethylbutyric acid

Test material form:

not specified

Test animals

Species:

mouse

Strain:

other: T23-48:BDF1 (C57BL/6 x DBA/2)

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle/solvent used: Corn oil.

Duration of treatment / exposure:

48-hour experimental period

Frequency of treatment:

Twice at 0 and 24 hours (24-hour interval)

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Remarks:

Control

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

2 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

Five male animals per dose

Control animals:

yes, concurrent no treatment

yes, historical

Positive control(s):

Positive control based on historical data for mitomycin C (2 mg/kg i.p. single administration).

Examinations

Tissues and cell types examined:

Mouse bone marrow cells

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

See additional information.

Vehicle controls validity:

not specified

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

At 1000 and 2000 mg/kg bw/day, the ratio of polychromatic erythrocytes (PCE) to total erythrocytes (%) observed in mice significantly decreased. One animal died at 2000 mg/kg bw/day.

Applicant's summary and conclusion

Conclusions:

2-Ethylbutyric acid at ≤2000 mg/kg bw/day was determined not to be mutagenic as part of an in vivo mammalian erythrocyte micronucleus assay using mouse bone marrow cells.

Executive summary:

An in vivo mammalian erythrocyte micronucleus assay for 2-ethylbutyric acid was undertaken in line with Good Laboratory Practise (GLP), OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test), and T37-15: Guideline for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan). The purpose of the experiment was to determine the mutagenic potential of the registered substance in male mice (strain: T23-48:BDF1 (C57BL/6 x DBA/2)) following administration of 0 (untreated control), 500, 1000, and 2000 mg/kg bw/day in a corn oil vehicle via oral gavage twice with a 24-hour interval. The experiment ran for a 48-hour period. A dose-finding study was conducted initially to obtain the concentrations for the main test. Historical positive (mitomycin C 2 mg/kg i.p. single administration) and negative control data from 1986 - 2002 were referred to.

The study was reported to have satisfied validity criteria. That one animal died at 2000 mg/kg bw/day, and that a significant decrease in the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs) (%) was observed at 1000 and 2000 mg/kg bw/day, is suggestive of bone marrow toxicity induced by the substance. However, 2-ethylbutyric acid was ultimately concluded not to be mutagenic to mammalian cells in vivo given that there was no significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCE) in all treatment groups.