Investigations on the mutagenicity of 1,4-dichlorobenzene and its main metabolite 2,5-dichlorophenol in vivo and in vitro

The genotoxic potential of 1,4-dichlorobenzene (1,4-DCB) has been extensive ly evaluated in vitro and in vivo. The majority of the studies demonstrated the absence of a genotoxic potential for 1,4-DCB. At variance are a bone m arrow micronucleus test (MNT) after intraperitoneal. (i.p.) treatment of NM RI mice [Mohtashamipur et al., Mutagenesis 2 (1987) 111-113] and a gene mut ation assay on mouse lymphoma cells [McGregor et al., Environ. Mol. Mutagen . 12 (1988) 85-145]. Therefore, we investigated 1,4-DCB and its main metabo lite 2,5-dichlorophenol (2,5-DCP) for both endpoints. In an MNT, male and f emale NMRI mice were treated orally with single doses of 2500 mg/kg 1,4-DCB and 1500 mg/kg 2,5-DCP, respectively. Smears were prepared 24, 48 and 72h thereafter. No induction of micronuclei was detected for both compounds. Al so under the conditions of Mohtashamipur et al. (1987), intraperitoneal tre atments of male and female mice with 2 x 177.5 and 2 x 355 mg/kg I,4-DCB fa iled to induce micronuclei. In addition, CHO/HPRT-gene mutation tests with 1,4-DCB and 2,5-DCP yielded negative results for both compounds with and wi thout metabolic activation system. Therefore, 1,4-DCB and 2,5-DCP are consi dered to be non-mutagenic in these test systems. (C) 2000 Elsevier Science B.V. All rights reserved.