The biocidal agent,
BIOBAN CS-1246 (7-ethyl bicyclooxazolidine, CAS# 7747-35-5,
CS-1246) induced a concentration-dependent mutagenic response in mouse
lymphoma (L5178Y TK+/-) cells both with and without the addition of S9 metabolic activation. Previous data indicating the ability of
CS-1246 to hydrolyze in aqueous media to generate
formaldehyde (FA), led us to investigate the potential role of FA in the CS-1246-induced mutagenic response in the mouse
lymphoma assay (MLA). To accomplish this, the MLA on
CS-1246 was repeated in the presence of a metabolizing system (
formaldehyde dehydrogenase/
NAD+), which was shown to successfully inhibit the mutagenic response of
formaldehyde in this assay system. Significantly, the observed mutagenicity of
CS-1246 was completely abrogated when the cultures were supplemented with
formaldehyde dehydrogenase/
NAD+, suggesting that the positive MLA response was attributable to the generation of FA in situ. These results demonstrate that in vitro mutagenicity of
CS-1246 in the MLA is most likely associated with FA. Negative results from two in vivo assays for genotoxicity were consistent with the known activity of FA in these assays. In the mouse bone marrow micronucleus (MNT), there were no significant increases in micronucleated polychromatic erythrocytes (with evaluation of 2000/animal),
after treatment with 0.5, 1, and 2 g/kg/day
CS-1246 (6/dose group) for 2 consecutive days and sacrifice 24 h later. Furthermore, in the unscheduled
DNA synthesis (UDS) study, male F344 rats (5 /dose group), given a single oral gavage (0, 1, and 2 g/kg) and evaluated at two time points (2-4 and 14-15 h post dosing), did not elicit an UDS response, indicating a lack of
DNA reactivity in vivo. Based on the negative in vivo findings, it can be inferred that the FA detoxification mechanisms that exist in intact organisms prevent the likelihood of generating FA at levels capable of causing genotoxicity following exposure to
CS-1246 at low, environmentally relevant concentrations. The extensive literature on FA would therefore be of value in assessing the carcinogenic risk to humans and animals from
CS-1246 exposure.