2,2-dimethylpropane-1,3-diol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Neopentyl glycol has no mutagenic activity in Salmonella typhimurium TA 100, TA 1535, TA 98, TA 1537, or in Escherichia coli WP2 uvrA tested with and without metabolic activation at dose levels up to 5000 µg/plate. These results were confirmed in a second independent study in TA 1535, TA 1537, TA 1538, TA 98, TA 100 with and without metabolic activation at dose levels up to 2500 µg/plate.
No chromosome mutagenic and no aneugenic activity were detected in Chinese hamster cells with and without metabolic activation at concentrations up to the recommended max. dose level of 1 mg/mL (ca. 10 mM).

Neopentyl glycol is not mutagenic in the HPRT locus assay under in vitro conditions in CHO cells in the absence and the presence of metabolic activation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Genotoxicity in vitro

The substance Neopentylglycol was assessed for its potential to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in Chinese hamster ovary

(CHO) cells in vitro (OECD 476). Two independent experiments were carried out, both with and without the addition of liver S9 mix from phenobarbital- and naphthoflavone induced rats (exogenous metabolic activation).

In two experiments performed independently of each other the test substance Neopentylglycol did not lead to a biologically relevant increase in the number of mutant colonies, either without S9 mix or after the addition of a metabolizing system. The mutant frequencies at any concentration were close to or within the range of the concurrent negative control values and within the range of the 95% control limit of our historical negative control data. Thus, under the experimental conditions of this study, Neopentylglycol is not mutagenic in the HPRT locus assay under in vitro conditions in CHO cells in the absence and the presence of metabolic activation.

In a Japanese study comparable to OECD Guideline 471 (Hatano 1993; GLP standards fulfilled; documentation sufficient for evaluation) Salmonella typhimurium TA100, TA1535, TA98, TA1537, and Escherichia coli WP2uvrA were tested in the plate incorporation assay with and without metabolic activation at dose levels of 0, 312.5, 625, 1250, 2500, 5000 µg/plate in 2 independent experiments. No increase in the number of revertants was found in comparison to the concurrent control at any concentration in any strain. No cytotoxicity was noted (but tested up to the recommended max. dose level of 5 mg/plate). The vehicle control and the positive control were valid. Conclusion: Neopentyl glycol has no mutagenic activity in Salmonella typhimurium TA 100, TA 1535, TA 98, TA 1537, or in Escherichia coli WP2 uvrA tested with and without metabolic activation at dose levels up to 5000 µg/plate.

These results were confirmed in a further Salmonella microsome assay (BASF 1979) comparable to OECD Guideline 471 with acceptable restrictions. The strains TA 1535, TA 1537, TA 1538, TA 98, TA 100 were exposed with and without metabolic activation to dose levels of 0 (vehicle control), 4, 20, 100, 500, 2500 µg/plate. The positive and negative controls were valid. No cytotoxic effects were detected at these dose levels. No increase in revertants was found at any dose level in any strain studied.

The study on cytogenetic effects was conducted according to Japanese guideline for screening mutagenicity testing of chemicals which is comparable to OECD Guideline 473 (Hatano 1993). GLP standards were fulfilled (acceptable restriction: no data available on the historical solvent control range of this laboratory, in the 2nd experiment without metabolic activation the positive control was not valid (but in others with similar experimental design). Chinese hamster cells were exposed with and without metabolic activation to dose levels of 0, 0.25, 0.5, 1.0 mg/mL. The high concentration corresponds to ca. 10 mM, the recommended limit dose according to OECD 473. Numerical and structural aberration were measured. Negative results were found at all dose levels in all trials with different experimental design. No cytotoxic effects were reported at concentrations up to 1 mg/mL. The relevant negative and positive controls were valid. In conclusion, no chromosome mutagenic and no aneugenic activity were detected in Chinese hamster cells with and without metabolic activation at concentrations up to the recommended max. dose level of 1 mg/mL (ca. 10 mM).

Justification for classification or non-classification

Classification is not warranted. The criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 are not met.