Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

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-methylpropionitrile (solvent: water), at concentrations of 0.3, 1, 3, 10, 33, 100, 166 µg/plate in the presence and absence of mammalian metabolic activation using the pre-incubation method. Up to and including the highest concentration of 166 µg/plate, including cytotoxic concentrations, there was no evidence of induced mutant colonies over background, with or without metabolic activation, in any of the tested strains.

Negative results were also observed in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 at concentrations of 0, 6.1, 18.3, 55, 165 and 495 µg/plate 2-hydroxy-2-methylpropionitrile with and without metabolic activation in a plate incorporation assay using the method of Ames, McCann and Yamasaki (1981). Toxicity to bacteria was observed with metabolic activation at 495 µg/plate in all strains and without metabolic activation at 165 µg/plate in strains TA1537 and TA1538 and at 495 µg/plate in all remaining strains.

No mutagenic activity was observed in an in vitro mammalian cell forward gene mutation assay using the Chinese hamster ovary (CHO) cells at a concentration range from 100 µg/mL to 950 µg/mL 2-hydroxy-2-methylpropionitrile with and without metabolic activation (2 % S-9 preparation). Cytotoxicity with levels of at least 10 % survival and a plating efficiency in control cultures of at least 50 % was observed at 950 µg/mL.

No statistically significant increases in the frequency of chromosome aberrations compared with controls at any dose level were observed in bone marrow cells of Sprague-Dawley rats (6 rats/sex/group) taken 6, 12, 24 or 48 hours after administration of 0, 1.5, 5 or 15 mg /kg acetone cyanohydrin by gavage. 2-hydroxy-2-methylpropionitrile demonstrates a steep dose response curve for acute toxicity with little or no signs of toxicity at sub-lethal doses.

The same studies were reported from AEGL committee (US-NAC, Acetone Cyanohydrin, Interim Acute Exposure Guideline Levels (AEGLs), Interim final draft, 2005).

Under physiological conditions, 2-hydroxy-2-methylpropionitrile decomposes to yield its molar equivalent in hydrogen cyanide and acetone. Both degradation products are regardes as non genotoxic. The genotoxic and mutagenic activity of cyanides have been evaluated within the ECETOC Programm: ECETOC report (JACC No. 53, Volume I, 2007) for ACH and HCN or its alkali-salts, "valid data are available for all genetic endpoints. Under the test conditions of the standard mutagenicity tests there was no indication of mutagenic or genotoxic activity of cyanide". For acetone an assessment report has been composed within the OECD Programm on the investigation on existing chemicals: "Acetone has been repeated tested in a variety of prokaryotic and eukaryotic test systems without causing genotoxic effects" (quotation from SIDS International Assessment report on Acetone, OECD UNEP Publications, 1999).

In conclusion, there is no evidence of mutagenic or genotoxic activity of 2-hydroxy-2-methylpropionitrile.

Short description of key information:
Valid in vitro data from a bacterial reverse gene mutation assay are available for this endpoint. Supporting data are available from an additional bacterial reverse gene mutation assay, a mammalian cell gene mutation assay and an in vivo cytogenetics chromosomes abberation assay in rat bone marrow cells.
Under the test conditions of these standard mutagenicity tests, there was no indication for mutagenic or genotoxic activity of 2-Hydroxy-2 –methylpropanenitrile.

Further one, testing of the degradation products of 2-hydroxy-2-methylpropionitrile, HCN and acetone, in genetic toxicity tests gave consistently negative results as well.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

There is no evidence on intrinsic mutagenic or genotoxic activity of 2-hydroxy-2-methylpropionitrile. Thus 2-hydroxy-2-methylpropionitrile does not comply with the classification requirements regarding mutagenicity outlined in regulation (EC) 1272/2008 or the former directive on classification and labelling 67/548/EWG.