An evaluation of the carcinogenic hazard of 1,4-dychlorobenzene based on internationally recognized criteria

1,4-Dichlorobenzene (1,4-DCB) was shown to induce the formation of male rat renal tubule tumors and male and female mouse liver tumors when administer ed in a chronic bioassay. Since the original carcinogenicity findings, an e xtensive body of mechanistic information has been developed to elucidate th e mode of action by which 1,4-DCB induces these effects and to evaluate the human relevance of the observed animal tumors. In addition, some regulator y and authoritative bodies (U.S. EPA and IARC) have developed rigorous scie ntific criteria for the amount and types of evidence needed to establish th at a material causes kidney toxicity and tumors in male rats through a spec ific mechanism, alpha-2u-globulin nephropathy. This paper summarizes the me chanistic data developed for 1,4-DCB, which affords an understanding of the lack of human relevance of the male rat renal tubule tumors and mouse Live r tumors; assesses that mechanistic data set utilizing the defined set of e valuation criteria formulated by U.S. EPA and IARC for alpha-2u-globulin ne phropathy; and discusses the predictive power of mechanistic data developed to elucidate the mode of action of 1,4-DCB in inducing mouse liver tumors. Finally, there is a discussion of how some, but not all, regulatory and au thoritative bodies have incorporated this substantial mechanistic data set for 1,4-DCB into their cancer hazard evaluations and concluded that 1,4-DCB presents Little, if any, cancer hazard to humans. (C) 1999 Academic Press.