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Toxicological information

Genetic toxicity: in vivo

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992
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:
OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)
GLP compliance:
yes
Type of assay:
Drosophila SLRL assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
20 and 28 mg/L
Basis:
nominal in diet
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.