Evaluation of morpholine, 3-morpholinone, and N-substituted morpholines in the rat hepatocyte primary culture/DNA repair test.

Morpholine and a series of morpholine derivatives were assayed for the potential to induce DNA repair in the rat hepatocyte primary culture/DNA repair assay. Morpholine did not induce DNA repair at dose concentrations which were not toxic (0.0001-0.1 mg/ml). Two animal metabolites of morpholine, N- methylmorpholine oxide and N- hydroxymorpholine , also did not induce DNA repair at the non-toxic concentrations tested (0.0001-10 mg/ml and 0.0001-1 mg/ml, respectively). A putative metabolite of morpholine, 3- morpholinone , was inactive (0.001-10 mg/ml) and a polyurethane foam catalyst, N- butylmorpholine (0.0001-0.1 mg/ml) was also inactive. The chemical intermediate N- hydroxyethylmorpholine induced DNA repair in the dose range 1-5 mg/ml. It was concluded that genotoxicity of substituted morpholines is a function of the substituent moiety rather than morpholine itself.