3,3'-methylenebis[5-methyloxazolidine]

Endpoint summary

Additional information

The substance was not mutagenic in genotoxicity assays in the bone marrow of mice. This indicates that the substance is not genotoxic distant from the site of first contact. However, mutagenicity assays in vitro reveal the reactivity of the substance towards DNA which corresponds to the reactivity of formaldehyde. Data on the hydrolysis product formaldehyde suggested more local than systemic mutagenic effects. Formaldehyde is genotoxic in vitro and it induces local clastogenic effects in vivo.

Short description of key information:
In Vitro
In the Salmonella microsome assay according to OECD 471 (Müller 1997 & Rajwani 2000) the test substance did not induce gene mutation in bacteria with and without metabolic activation. However, the test substance was not tested up to the cytotoxicity threshold limiting the validity of these studies.

In a 3rd Salmonella microsome assay (Bowles 2000, OECD guideline 471) an increased number of revertants was detected in TA98, TA100, and WP2uvrA with and without metabolic activation also at non-cytotoxic concentrations. But this increase was maximal 2-fold of the concurrent control indicating only weak mutagenic activity.

In the chromosome aberration test (OECD guideline 473; Wright 2001) the test substance has clastogenic activity and induces polyploidy even at non-cytotoxic concentrations with and without metabolic activation. Accordingly, predominantly chromosome mutagenic activity (increase in small colonies) was demonstrated in two independent mouse lymphoma tests with and without metabolic activation (Nolan, 2002& Durward/Noan 2001).

In Vivo
In the cytogenetic study (Mukherjee 2000; OECD guideline 475) a slight increase in % aberrant cells was observed but this effect was not statistically significant. The authors concluded that the test result was negative. It might be questioned, whether the maximum tolerated dose was reached in this study since 1) all animals were found to be without clinical symptoms after exposure and 2) no decrease in mitotic index was observed. No details were given about the determination of the MTD. In conclusion, ambiguous test results were presented in this study.
In a valid micronucleus test according to OECD guideline 474 (Leuschner 2002) no increase in the number of micronuclei at a dose level up to 300 mg/kg bw, the maximum tolerated dose, was detected indicating no aneugenic or clastogenic activity of the test substance.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

So far no labelling exist for the substance because the content of free formaldehyde is <1%; use concentrations were hydrolysis will occur are low and released formaldehyde is assumed to be again <1%.