General Remarks on the Substances Considered

This eighty-eighth volume of IARC Monographs evaluates the available evidence on the carcinogenic potential in humans of formaldehyde, 2-butoxyethanol and 1-tertbutoxypropan-2-ol. Formaldehyde, a potential carcinogen that is found in the workplace and in the environment, has been studied the most widely and has been evaluated three times previously. In Volume 29 (IARC, 1982), the experimental animal data were evaluated as having sufficient evidence and the epidemiological studies as having inadequate evidence of carcinogenicity. In Supplement 7 (IARC, 1987), these data were updated and an overall evaluation was made that formaldehyde is probably carcinogenic to humans (Group 2A), based on limited evidence of carcinogenicity from studies in humans and sufficient evidence of carcinogenicity from studies in experimental animals. Formaldehyde was reconsidered again in Volume 62 (IARC, 1995), when the existing classification was reaffirmed. It is being re-evaluated this time following a recommendation from an Advisory Group (IARC, 2003) that identified formaldehyde as a high priority for future re-evaluation, based on the availability of complex mechanistic data and the anticipated publication of new epidemiological studies that became available soon afterwards. The same Advisory Group also identified 2-butoxyethanol and other glycol ethers as high priorities, based on the availability of new carcinogenesis bioassays conducted by the US National Toxicology Program. This is the first evaluation that IARC has made of the two glycol ethers. A theme common to these three evaluations is the consideration of mechanistic information to develop and evaluate hypotheses on the sequence of steps that lead to the induction of tumours in experimental animals. The hypothesized mechanisms described in this volume provide an interesting set of cases that range from a vast literature on respiratory tract tumours in rats induced by the inhalation of formaldehyde to some more tentative hypotheses on the various tumours observed in animals following exposure to glycol ethers. Both types of mechanistic datasets were of use in the evaluation process. This evaluation emphasizes the importance of mechanistic information in the classification of carcinogens. For example, the Working Group considered the extensive scientific database on the mechanisms by which formaldehyde can induce cancer in humans. The extensive mechanistic data for formaldehyde-induced respiratory cancer provide strong support for the empirical observation of nasopharyngeal cancer in humans. In contrast, the lack of such information on possible mechanisms by which formaldehyde