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1. INTRODUCTION
In 1986, 1 published a review of the toxicology of acetamide (CAS #60-35-5), NN-dimethylacetamide (DMAC - CAS #127-19-5), N-methylacetamide (MMAC - CAS #79-16-3), formamide (CAS #7512-7), NN-dimethyl-formamide (DMF - CAS #6812-2), and N-methylformamide MM - CAS #12339-7) in Critical Reviews in Toxicology (Kennedy, 1986). These chemicals continue to have commercial importance, and the information generated in the intervening years has added considerably to our knowledge around the biological consequences of exposure in man. Thus, it is timely to consider updating the information that was reviewed in this journal more than a decade ago. The outline of the presentation is similar in that each chemical is reviewed individually in each of the various sections. It remains true that the biological responses do vary both qualitatively and quantitatively among these six chemicals, and that the type and amount of information available both reflects the biology of the material and its usage or proposed usage. Thus, data for each of the six chemicals is considered separately in each section and similarities/dissimilarities will be handled in the concluding section. Additionally, information on the environmental toxicology of these materials has been greatly expanded during the last 14 years and some of the data that was not in the 1986 review are included.
II. METABOLISM
The database on the metabolism of these chemicals has expanded rapidly both in looking for mechanisms) of action in animal models and the looking at biomonitoring in man to characterize integrated exposures (especially for DMAC, DMF). Work at our laboratory in conjunction with long-term bioassays has followed the distribution and metabolism of DMAC and DMF through both rats and mice. This information is also available in the primate studied during a 90day inhalation experiment. The best snapshot of the metabolism of these chemicals is found in the review of Gescher (1993). His laboratory has elucidated the metabolite profile of DMF and has looked carefully at the interactions of these conversion products with animal tissues in looking for mechanisms of effect.
The metabolism of DMF is fairly well documented. It has been shown that the initial step of DMF metabolism is to HMMF (N-hydroxymethylN-methylformamide), which can then be demethylated to MMF (N-methylformamide), or perhaps proceed directly through a loss of formaldehyde to a reaction...