Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., compds. with isopropanolamine

Endpoint summary

Additional information

LAS MIPA:

LAS MIPA was tested in the Ames reverse mutation assay 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 addressing the genotoxicity endpoint; hence, the endpoint was addressed with information from LAS Na and MIPA.

MIPA:

MIPA was tested in the Ames reverse mutation assay using S. typhimurium strains TA98, TA100, TA1535 and TA1537 up to cytotoxic concentrations, with and without metabolic activation. The substance was not mutagenic in strains TA98, TA100 and TA1537. However, with S9 -activation the TA 1535 strain presented some weak positive results. This result was considered ambiguous (Zeiger et al., 1987). In contrast, in another Ames test MIPA was found not mutagenic in S. typhimurium strains TA98, TA100, TA 1535, TA1537 and TA 1538, and E. coli WP2 uvr A, incubated with 1 to 5000 µg MIPA/plate in the presence and absence of metabolic activation. Cytotoxicity was observed at the highest dose only (Shimizu et al., 1985).The substance purity in the 1st Ames test with ambigous result was 95% whereas substance purity in the second Ames-test with negative result was 97%. Therefore impurities are likely to be responsible for the ambigous result of the test-substance with the lower purity. Taken together, MIPA was not considered to be mutagenic.

Induction of gene mutations in mammalian cells by MIPA was investigated in an HGPRT assay using Chinese hamster ovary (CHO) cells at 156 to 2500 µg/mL, with and without metabolic activation. The results indicate that MIPA does not induce gene mutations in this assay. No cytotoxicity was observed (Dow, 1995).

 

MIPA tested at 83 - 1500 µg/mL (-S9) and 250 - 2500 µg/mL (+S9) did not induce significant increases in chromosomal aberrations using rat lymphocytes with and without metabolic activation. Cytotoxicity was observed without metabolic activation only, at 833 µg/mL. MIPA was judged as non-clastogenic (Dow, 1995).

 

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 cytotoxicity 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, the information described above, show that LAS MIPA is not a genotoxic substance.This conclusion is further supported by the negative in vivo results seen is studies performed with MIPA or LAS Na.

Justification for selection of genetic toxicity endpoint

No study was selected since all in vitro studies are negative.

Short description of key information:

LAS MIPA did not induce any bacterial gene mutations in the Ames tests. The rest of the requirements were addressed with studies with LAS Na and MIPA. MIPA did not cause gene mutations in Chinese hamster ovary cells (CHO/HGPRT), or chromosomal aberrations in rat 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 MIPA is not considered to be genotoxic.

In vivo studies performed with LAS Na or MIPA further support this negative result.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of the in vitro/in vivo genetic toxicity studies, LAS MIPA does not need to be classified for genotoxicity according to the EU Regulation 1272/2008.