Registration Dossier

Administrative data

Endpoint:
in vivo mammalian germ cell study: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Chemical Mutagenesis Testing in Drosophila. IX . Results of 50 Coded Compounds Tested for the National Toxicology Program
Author:
Foureman P, Mason JM, Valencia R, Zimmering S
Year:
1994
Bibliographic source:
Environmental and Molecular Mutagenesis 23(1):51-63

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)
Version / remarks:
The guideline is not specified but given the scientific description of the study, performance similar to OECD 477 is suggested.
Principles of method if other than guideline:
Method: Woodruff, RC et al., Env. Mutagen., 6, 189-202.
Adult Canton-S males were subjected to a 3 day feeding exposure. They were mated to Basc females using a 2 to 3 day brooding pattern for a total of
three broods spanning 7 days. If the feeding sex-linked recessive lethal (SLRL) test was negative, an injection exposure was performed. As in the feeding exposure, a 2 to 3 day brooding pattern for three broods was used.
GLP compliance:
not specified
Type of assay:
Drosophila SLRL assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Purity: 96.4 %
- Supplier: Aldrich (3803 LE)

Test animals

Species:
Drosophila melanogaster
Strain:
other: Canton S
Sex:
male

Administration / exposure

Route of administration:
other: In feed. If the results of the feeding SLRL test were negative, an injection exposure was performed.
Vehicle:
Water
Duration of treatment / exposure:
feeding study: 3 days; If the results of the feeding SLRL test were negative, a single injection exposure was performed.
Frequency of treatment:
continuously in feed
Doses / concentrationsopen allclose all
Dose / conc.:
24 250 ppm
Remarks:
feeding study
Dose / conc.:
1 940 ppm
Remarks:
injection
No. of animals per sex per dose:
no data
Control animals:
yes, concurrent no treatment

Examinations

Evaluation criteria:
A minimum of approximately 5,000 chromosomes were scored in each of the treated and concurrent control groups, unless the mutant frequency exceeded 1%. Clusters were identified using the Poisson distribution (Owen, 1962) and were removed before analysis.
Statistics:
The statistical evaluation of a SLRL test included a comparison with the concurrent solvent control using the normal approximation to the binomial distribution, as presented by Margolin et al. (1983), as well as a comparison with the historical control as described by Mason et al. (1992). In order to be considered mutagenic, the mutant frequency in the treated sample must exceed 0.15% with a P value of less than 0.05, or the treated frequency must exceed 0.1% with a P value of less than 0.01. If the treated frequency was between 0.1% and 0.15% and the P value was between 0.1 and 0.01; or if the treated frequency was higher than 0.15%, and the P value was between 0.1 and 0.05 the assay was considered equivocal. All other assays were considered negative.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not specified
Positive controls validity:
not specified

Any other information on results incl. tables

Table 1: Results of the drosophila testing in Mono-isopropanolamin.

Dose (ppm)

ROA

Percent mortality

Percent sterility

Lethals

Tests

Total lethals

Total tests

Percent lethals

 

 

 

 

Br 1

Br 2

Br 3

Br 1

Br 2

Br 3

 

 

 

24,000

feeding

5

17

1

0

2

2,658

1,421

847

3

4,926

0.06

0

 

 

 

1

0

1

2,875

2,748

2,414

2

8,037

0.02

1,900

injection

14

8

2

2

2

1,911

1,675

1,562

6

5,148

0.12

0

 

 

 

0

2

0

1,739

1,493

1,079

2

4,311

0.05

One cluster of 3 in the injection control and one of 4 in the treated feeding experiment

Applicant's summary and conclusion

Conclusions:
Under the conditions tested the test substance was not mutagenic in a Drosophila SLRL assay.
Thus, MIPA is not considered to be genotoxic.