γ-butyrolactone

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Equivalent to current guideline method performed under GLP conditions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Reference 2

Reference Type:

publication

Title:

Chemical Mutagenesis Testing in Drosophila. X. Results of 70 Coded Chemicals Tested for the National Toxicology Program

Author:

Foureman, P et. al.

Year:

1994

Bibliographic source:

Environmental and Molecular Mutagenesis 23:208-227

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)

GLP compliance:

yes

Type of assay:

Drosophila SLRL assay

Test material

Test material information

Constituent 1

Reference substance name:

γ-butyrolactone

EC Number:

202-509-5

EC Name:

γ-butyrolactone

Cas Number:

96-48-0

Molecular formula:

C4H6O2

IUPAC Name:

dihydrofuran-2(3H)-one

Details on test material:

- Name of test material (as cited in study report): γ-Butyrolactone
- Physical state: Liquid
- Analytical purity: >97%
- Lot/batch No.: 600-BLO, from GAF Corporation (New York, NY)
- Stability under test conditions: Stable throughout study
- Storage condition of test material: In dark at 5 °C

Test animals

Species:

Drosophila melanogaster

Strain:

other: Canton-S Wild-Type

Sex:

male

Details on test animals or test system and environmental conditions:

Age at begining of treatment:
- Feeding Study - <24 hours old
- Injection Study - 24 to 72 hours old
Canton-S Wild-type males were mated to untreated Basc females.

Administration / exposure

Route of administration:

other: Oral feeding and injection

Vehicle:

Feeding Study: 5% sucrose
Injection Study: 0.7% saline

Details on exposure:

Canton-S males (10 to 20 flies/vial) were allowed to feed for 72 hours on the solution or were given a single injection and allowed to recover for 24 hours. Injections were given by anesthetizing the fly with ether and immobilizing it on double sided tape, then giving the injection directly into the thorax from under the wing with the aid of a dissecting microscope. Approximately 0.2 to 0.3 µL of solution was given to slightly distend the abdomen of the fly.

Duration of treatment / exposure:

Feeding: 72 hours
Injection: single dose

Frequency of treatment:

1

Post exposure period:

17 days

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
20 and 28 mg/L
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
15 mg/L
Basis:
other: Amt. injected

No. of animals per sex per dose:

Feeding (20 mg/L): ca 1000 chromosomes
Feeding (28 mg/L): ca 4000 chromosomes
Injection (15 mg/L): ca 5000 chromosomes

Control animals:

yes, concurrent vehicle

Examinations

Tissues and cell types examined:

Incidence of mutations was presumptive based on the absence of wild-type male offspring.

Evaluation criteria:

A test was considered to be positive if the P value was less than 0.05 and the frequency in the tested group was greater than 0.10%, or if the P value was less than 0.05 and the frequency in the treatment group was greater than 0.15%. A test was considered inconclusive if a) the P value was between 0.01 and 0.05 but the frequency in the treatment group was between 0.10% and 0.15%, or b) the P value was between 0.05 and 0.10 but the frequency in the treatment group was greater than 0.10%. A result was considered to be negative if the P value was greater than 0.10 or of the frequency in the treatment group was less than 0.10%.

Statistics:

Normal approximation to the binomial distribution test (Morgolin, et. al; 1983). Clusters were examined by Poisson analysis (Owen, 1962)

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

Concentrations set to produce ca. 30% mortality

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

not examined

Any other information on results incl. tables

Route of Exposure	Dose (ppm)	Percent Mortality	Percent Sterility	Lethals			Tests			Total Lethals	Total Tests	Percent Lethals	Cluster Removed
				Br 1	Br 2	Br 3	Br 1	Br 2	Br 3
Adult Feeding for three days	20000	20	13	0	1	1	427	411	311	4	5315	0.08	N
	0			1	2	0	2120	1847	1549	3	5516	0.05	N
	28000	38	2	2	0	0	1491	1405	1270	4	5315	0.08	N
	0			1	2	0	2120	1847	1549	3	5516	0.05	N
										P= 0.335
Adult Injection	15000	26	13	0	1	0	2156	1634	1156	1	4946	0.02	N
	0			0	1	1	1960	1671	1400	2	5031	0.04	N
										P= 0.713

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
No induction of sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaste was observed.