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Key value for chemical safety assessment

Additional information

In vitro data

Several Ames test results for MBS have been reported. Although the study results are reliable the test design of the studies does not comply with the current guideline with regard to the number and kind of tester strains. However, several assays are comparable to a guideline study (Monsanto Co 1976, 1978ab, CMA 1981). In these studies no biologically relevant and dose dependent increases in revertants was evaluated in any of the tester strains evaluated with and without metabolic activation.

This finding was confirmed in two HGPRT-assays with CHO cells. The test substance was evaluated at concentrations of 0, 0.1, 0.3, 1, 3.0, 10, 30, 50, 100, 150, 300 µg/ml with and without metabolic activation. Cytotoxicity was indicated at 100 µg/ml and higher without metabolic activation and at 300 µg/ml with metabolic activation. At 50 µg MBS per ml (without metabolic activation) the relative survival was 43 % and the 150 µg MBS per ml (with metabolic activation) gave a 36 % relative survival. The test substance (OBTS purified) was negative in the CHO/HGPRT assay with and without metabolic activation (CMA 1981). In the second HGPRT assay, done with OPTS commercial, comparable results were obtained (CMA 1984).

However, the test substance MBS induced in several mouse lymphoma assays positive responses, mainly in presence of metabolic activation (Monsanto 1979, CMA 1981, Hinderer 1983). But all of these mouse lymphoma studies reveal limitations which lower the validity of these findings.

Moreover, the test substance was evaluated in an in vitro chromosome aberration assay, with limitations. CHO cells were treated with the test substance up to 10 µg/ml in presence and absence of metabolic activation. No biologically relevant increase in chromosome aberration was noted (Hinderer 1983).

Inconsistent findings were noted in two E. coli DNA repair assays and cell transformation assays, which showed positive and negative responses (CMA 1981, Hinderer 1983).

In vivo data

The test substance MBS was evaluated for genotoxicity in the dominant lethal test in groups of 10 Sprague-Dawley rats treated by gavage at dose levels of 0, 125, 250 and 500 mg/kg bw/day. Following a 56 day treatment each male was housed with two virgin female rats per week for two weeks. The females were sacrified thirteen days after mating for determination of dominant lethal effects. The treatment had no adverse effects with respect to clinical signs, mortality rate, body weight gain, or organ weights of adult rats. The treatment also had no effect on pregnancy, early foetal death, implantation, or pre-implantation losses in female rats; whereas treatment with the positive control triethylenmelamine produced the expected dominant lethal effects.

The findings of the study indicated that the test substance MBS was not mutagenic to the germ cells of male rats under the test conditions chosen.


Short description of key information:
The test substance MBS was investigated for its potency to induce gene mutation in bacteria and mammalian cells. However, some of the studies, e.g. the mouse lymphoma studies, have limitation and thus can only be used for supportive evidence. MBS was negative in several bacterial gene mutation studies and did not induce gene mutations at the hgprt locus. However, an increase in the mutation frequencies was noted in several mouse lymphoma assays, but these findings are questionable because of the low validity of these tests. In a limited in vitro Chromosome aberration assay no biologically relevant increases in aberrant cells were noted. Inconsistent responsive were noted in bacterial repair assays and cell transformation assays.
Thus, inconsistent in vitro genotoxic effects of the test substance were noted in several in vitro test systems. Some of the test systems are limited and artificial responses could not be excluded. However, under in vivo conditions the potency to induce genotoxicity could not be confirmed. In a dominant lethal test with Sprague-Dawley rats no dominant lethal effects of the test substance was noted. In addition, the test substance was negative in a well documented carcinogenicity study with rats. Thus, based on the findings discussed above MBS itself can be considered to have no in vivo genotoxic potential.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification is required according to the classification criteria 67/548/EWG and regulation no. 1272/2008 (GHS).