Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

LAS IPA:

LAS IPA was tested in the Ames reverse mutation assay (GLP, Guideline study) using S. typhimurium and E. coli strains up to cytotoxic concentrations, both with and without metabolic activation. No significant revertant colonies were observed. No other tests are available with the substance per se addressing the genotoxicity endpoint; hence, the endpoint was addressed with information from LAS Na and IPA.

IPA:

IPA was not mutagenic in the Ames test (Zeiger, 1987).

In a GLP, Guideline study (Covance, 2010) the abilitiy of isopropylamine (IPA) to cause gene mutations on mouse lymphoma L5178Y cells was examined. The results showed that IPA does not induce mutation at the hprt locus of L5178Y mouse lymphoma cells under the specific conditions employed. This included treatments up to highly toxic concentrations in two independent experiments, in the absence and presence of a rat liver metabolic activation system.

In another GLP, Guideline study (Molinier, 1994), IPA did not cause chromosomal aberrations in human lymphocytes, when tested up to cytotoxic concentrations, both with and without metabolic activation. IPA is not clastogenic.

LAS Na:

LAS Na was not mutagenic in the Ames test (Schoeberl, 1993).

The potential of LAS Na to cause chromosomal aberrations in mammalian cells was examined with the use of Chinese hamster ovary cells, exposed to concentrations of 0.32 to 78 ug/ml with S9, and 1.25 to 156 ug/ml without S9. Positive responses were seen at cytotoxic concentrations only in the presence of S9. Concentrations below the level of cytotoxicty with S9 did not show positive results. The test substance is not clastogenic in the absence of metabolic activation, or with metabolic activation below cytotoxic concentrations. Chromosomal aberrations seen at cytotoxicity levels can be considered as a secondary effect. The result suggests that LAS is not clastogenic (Murrie & Innes, 1997).

In another test Chinese Hamster Ovary (CHO) cells were exposed to concentrations of 0, 0.6, 1, 1.8, 3, and 6 ug/ml without S9, and 0, 6, 10, 18, 30, and 60 ug/ml with S9. Preliminary tests show the test substance was cytogenic at concentrations of 50 ug/ml or greater with metabolic activation, and 100 ug/ml or above without metabolic activation. There was no biologically significant increase in mutation frequency in the treated groups and hence, LAS is considered not mutagenic to CHO cells both in the presence and absence of S9 (AVON, 1995).

Taken together, all the above information, indicate that LAS IPA


Justification for selection of genetic toxicity endpoint
The endpoint of genotoxicity is addressed with a weight of evidence approach. Therefore, one key study is not applicable. The database is considered sufficient to fulfil the specific requirement.

Short description of key information:
LAS IPA did not induce any bacterial gene mutations in the Ames test (GLP, Guideline study). The rest of the requirements were addressed with studies on LAS Na and IPA. MIPA did not cause gene mutations in mouse lymphoma L5178Y cells, or chromosomal aberrations in human lymphocytes, both with and without metabolic activation. Similarly, LAS Na did not induce any gene mutations or chromosomal aberrations in Chinese hamster ovary cells. Based on the above LAS IPA is not considered to be genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of the in vitro genetic toxicity studies, LAS IPA does not need to be classified for genotoxicity according to the Regulation (EC) No 1272/2008.