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 extensively 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 marrow micronucleus test (MNT) after intraperitoneal (i.p.) treatment of NMRI mice [Mohtashamipur et al., Mutagenesis 2 (1987) 111-113] and a gene mutation assay on mouse lymphoma cells [McGregor et al., Environ. Mol. Mutagen. 12 (1988) 85-145]. Therefore, we investigated 1,4-DCB and its main metabolite 2,5-dichlorophenol (2,5-DCP) for both endpoints. In an MNT, male and female NMRI mice were treated orally with single doses of 2500mg/kg 1,4-DCB and 1500mg/kg 2,5-DCP, respectively. Smears were prepared 24, 48 and 72h thereafter. No induction of micronuclei was detected for both compounds. Also under the conditions of Mohtashamipur et al. (1987), intraperitoneal treatments of male and female mice with 2 x 177.5 and 2 x 355mg/kg 1,4-DCB failed 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 without metabolic activation system. Therefore, 1,4-DCB and 2,5-DCP are considered to be non-mutagenic in these test systems.
Tegethoff
K
K
Institute of Toxicology, Bayer AG, P.O. Box 101709, D-42096, Wuppertal, Germany. kerstin.tegethoff.kt@bayer-ag.de
Herbold
B A
BA
Bomhard
E M
EM
D000818:Animals; D016466:CHO Cells; D002722:Chlorobenzenes / Q000378:metabolism / Q000633:toxicity*; D002733:Chlorophenols / Q000633:toxicity*; D006224:Cricetinae; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000235:genetics
D002722:Chlorobenzenes; D002733:Chlorophenols; C056892:2,5-dichlorophenol; C018511:4-dichlorobenzene; D007041:Hypoxanthine Phosphoribosyltransferase