1,4-DIOXANE IS NOT MUTAGENIC IN 5 IN-VITRO ASSAYS AND MOUSE PERIPHERAL-BLOOD MICRONUCLEUS ASSAY, BUT IS IN MOUSE-LIVER MICRONUCLEUS ASSAY

1,4-Dioxane, an animal carcinogen, was not previously genotoxic in in vitro assays. We reevaluated the compound's genotoxic potential in fiv e in vitro genotoxicity tests in the presence and absence of S9 mix us ing recommended new protocols. We used the bacterial reverse mutation assay with Salmonella TA and E. coli WP2 strains, including the plate and preincubation methods, the CHO chromosomal aberration assay, inclu ding examination of polyploid induction and extended sampling time, th e CHO sister-chromatid exchange assay with short and long treatment ti me, the mouse lymphoma ik assay (microtiter method), including longer treatment time (24 hr), and the CHO micronucleus assay with short and long treatment times. The highest concentration we used was five mg/ml or plate. We also evaluated the genotoxic effect of 1,4-dioxane in vi vo by conducting peripheral blood and liver micronucleus assays in the same mice after single oral administration of up to 3,000 mg/kg. All in vitro assays and the peripheral blood micronucleus assay were negat ive. The mouse liver micronucleus assay, on the other hand, was positi ve, indicating that 1,4-dioxane might be genotoxic. It is also conceiv able that the positive result in mouse liver micronucleus assay was du e to a nongenotoxic mechanism, i.e., errors in genetic repair followin g enhancement of hepatocyte proliferation. Environ. Mol. Mutagen. 32:2 69-280, 1998 (C) 1998 Wiley-Liss, Inc.