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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo insect germ cell study: gene mutation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference
Reference Type:
publication
Title:
Genetic toxicity study of the test chemical
Author:
King et al
Year:
1979
Bibliographic source:
Mutation Research

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.5275 (Sex-linked Recessive Lethal Test in Drosophila melanogaster)
GLP compliance:
not specified
Type of assay:
Drosophila SLRL assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material: Acetylsalicylic acid
- Molecular formula: C9H8O4
- Molecular weight: 180.16 g/mol
- Substance type: Organic
- Physical state: Solid
- Impurities (identity and concentrations): The chemical was of the finest or spectroscopically pure grade

Test animals

Species:
Drosophila melanogaster
Strain:
other: Berlin K
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
The test chemical was dissolved in 5% sucrose solution containing 2% DMSO if necessary
Details on exposure:
The test chemical was given by diet to 1-2 day old Berlin K males for 3 consecutive days, normally at the single maximally tolerated dose level (up to the LD50).
Duration of treatment / exposure:
3 days
Frequency of treatment:
daily by diet
Post exposure period:
After treatment, a sequence of three brood periods (each lasting 3 days) was then initiated. At the end of each 3-day breeding period, treated males were transferred to new vials and mated individually with 3 virgin females. Typically, at least 1000 F1 females were handled in each brood.
Doses / concentrations
Remarks:
0 (vehicle and 10 mM
No. of animals per sex per dose:
Number of males not specified but at least 1000 F1 females were handled in each brood.
Control animals:
yes, plain diet
Positive control(s):
1,2 dichloroethane, which is a probable carcinogen in humans, was evaluated in addition to the test chemical for mutagenic effects in Drosophila.

Examinations

Tissues and cell types examined:
X-chromosomes
Details of tissue and slide preparation:
No details given.
Evaluation criteria:
Recessive lethal mutations frequencies in brood I, II, III, and I to III, in F2 and F3 generations, following treatment with the test chemical in males, were evaluated against solven control data using statistical analysis.
Statistics:
Kastenbaum-Bowman test

Results and discussion

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

Any other information on results incl. tables

Table 1. Data for solvent control and for the positive control (1,2-dichloroethane at 50 mM).

Conc.

Brood

Days after treatment

Number of X-chromosomes tested

Number of lethals

Recessive lethal mutation frequency (%)

P values

0

I

0-3

9565

24

0.25

 NS

0

II

4-6

6500

4

0.06

 NS

0

III

7-9

5983

19

0.32

 NS

0

I-III

0-9

22048

47

0.21

 NS

50

I

0-3

1185

6

0.51

 NS

50

II

4-6

1179

41

3.48

<0.01

50

III

7-9

156

2

1.28

 NS

50

I-III

0-9

2520

49

1.94

<0.01

NS = not statistically significant.

Note 1: The relatively low mutation frequency in brood II at 0 mM (of 0.06%) was consistent with historical control data.

Note 2: No tabular data was presented for the test chemical at 10 mM but it was concluded by the authors to be non-mutagenic in the text.

Applicant's summary and conclusion

Conclusions:
Three days treatment with the test chemical Drosophila at LD50 resulted in no significant increase in the frequency of sex-linked recessive lethal mutations in any of the broods or in all broods combined when compared to concurrent negative control data.
Executive summary:

The chemical was given via diet at 0 and 10 mM for 3 days to 1-2 day old Berlin K males. A single dose of 10 mM corresponded to the LD50 value and was regarded to be the maximally tolerated dose in the insects. Treated males were mated individually with 3 Basc virgin females. A sequence of three brood periods (each lasting 3 days) was then initiated. At the end of each 3-day breeding period, treated males were transferred to new vials and mated individually with 3 virgin females. Typically, at least 1000 F1 females were handled in each brood. Sex-linked recessive lethal mutations were scored in the F2 and F3 generations. Treatment with the test chemical resulted in no significant increase in the frequency of sex-linked recessive lethal mutation in any of the broods or in all broods combined when compared to concurrent negative control data. Treatment with 1,2 dichloroethane, which is a probable human carcinogen, at 50 mM resulted in a significant increase in the frequency of sex-linked recessive lethal mutations in brood 2 and in all broods combined when compared to control data, indicating that the assay was valid for detecting mutagenic effects.