2-hydroxy-2-methylpropionitrile

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: - Basic data given: comparable to guidelines/standards

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Test Method: Ames B. (1975) Mutation Research 11, 347-364

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-2-methylpropionitrile

EC Number:

200-909-4

EC Name:

2-hydroxy-2-methylpropionitrile

Cas Number:

75-86-5

Molecular formula:

C4H7NO

IUPAC Name:

2-hydroxy-2-methylpropanenitrile

Details on test material:

- Name of test material (as cited in study report): 2-Hydroxy-2-methyl-propane-nitrile (Acetone cyanohydrine), form Aldrich Chemical
- Lable purity: 98+ %
- Code 160, coded by the National Toxicology Program (NTP) chemical repository (result table)

Method

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium, TA100, TA1535, TA97, TA98

Metabolic activation:

with and without

Metabolic activation system:

S9-Mix fraction of Aroclor 1254-induced, male Sprague-Dawley rat and male Syrian hamster livers

Test concentrations with justification for top dose:

0.3, 1.0, 10.0, 33.0, 100.0, 166.0 µg/plate
Each chemical was tested initially at half-log dose intervals up to a dose that elicited toxicity, or to a dose immediately below one which was toxic in the preliminary toxicity test.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

Migrated to IUCLID6: for TA 1535, TA 100, without metabolic activation

Controls 2

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

Migrated to IUCLID6: for TA 97 without metabolic activation

Controls 3

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylenediamine for TA 98 without metabolic activation

Controls 4

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene, with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation assay as described by Haworth et al. 1983, with some differences.

- Salmonella typhimurium strains were obtained from Dr. Bruce Ames (University of California, Berkeley, U.S.A.) and were stored as recommended (Maron and Ames, 1983).
- Cultures were grown overnight with shaking at 37 °C in Oxoid No. 2 broth, and their phenotypes were analyszed prior to their use for mutagenicity assays.

- 300 chemicals were tested in several laboratories

Test protocol:
1) Testing in strains TA97, TA98, TA100, and TA1535 10% S-9 was used.
2) The first test of a chemical was without activation and with 10% S-9 in the S-9 mix. If a positive result was obtained the test was repeated. If the tests were negative they were repeated without S-9 and with 30% S-9.
3) The order of use of 10% and 30% S-9 was reversed.
4) Initial testing was in strains TA98 and TA100 without activation and with 30% rat and hamster S-9s. If a positive result was obtained in one of these
two strains it was repeated and the other strains were not used. If the tests were negative, the other strains were used with 30% and 10% S-9. A chemical was not designated nonmutagenic unless it had been tested in strains TA98, TA100, TA1535, and TA97 and/or TA1537, without activation and with 10% and 30% rat and hamster S-9. Ocasionally, 5% S-9 was also used in all protocol variations.

Evaluation criteria:

Evaluations were made at both the individual trial and overall chemical levels.
Individual trials were judged mutagenic (+), weakly mutagenic (+W), questionable (?), or nonmutagenic (-), depending on the magnitude of the increase of his + revertants, and the shape of the dose-response.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 97, TA 98, TA 100, TA1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: other: Salmonella typhimurium, TA100, TA1535, TA97, TA98

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Up to 166 µg/plate, 2-Hydroxy-2 -methylpropanenitrile did not induce biologically relevant increases in revertants in any of the tested strains,in neither case with or without metablolic activation.

Executive summary:

In a reverse gene mutation assay in bacteria similar to OECD TG 471, four strains of S. typhimurium (TA 1535, TA 100, TA 98, and TA 97) were exposed to 2-Hydroxy-2 -methylpropanenitrile (solvent: water), at concentrations of 0.3, 1, 3, 10, 33, 100, 166 µg/plate in the presence and absence of mammalian metabolic activation (preincubation method).

2-Hydroxy-2 -methylpropanenitrile was tested up to cytotoxic concentrations.

The positive controls induced the appropriate responses in the corresponding strains. Up to 166 µg/plate, 2-Hydroxy-2 -methylpropanenitrile did not induce biologically relevant increases in revertants in any of the tested strains,in neither case with or without metablolic activation.

There was no evidence of induced mutant colonies over background.