Syntheses of D‐Labelled Oxidative Metabolites of Acrylamide and Acrylonitrile for the Quantification of Their Toxicities in Humans (Eur. J. Org. Chem. 26/2008)

The cover picture shows data on the total world‐wide industrial production of acrylonitrile and acrylamide. These monomers were found to be carcinogenic in rats, mutagenic in E. coli , harmful to blood and to the liver, as well as to the immuno, neuro, reproductive and respiratory systems. Their enzymatic epoxidation to even more poisonous oxiranes is believed to be responsible for the carcinogenic activity. In vivo, cyano‐ or carbamoyloxiranes readily react with glutathione and at the end of this metabolic path yield two regioisomeric S ‐alkylated N ‐acetylcysteins (see cover picture). Both acrylonitrile and acrylamide are present in cigarette smoke. Acrylamide has also been found in various starchy foods such as the ones shown, which have been roasted or baked. Though the possible risk of such food to public health is unclear, dietary intake of acrylamide contributes a lot to overall human exposure. For quantification of the oxidative metabolites of acrylonitrile and acrylamide in humans, two sets of the regioisomeric reference compounds were synthesized with deuterium labels. They may be used as “ideal” internal standards in all toxicological studies aimed at quantitative determination and product distribution of oxidative urinary metabolites of acrylonitrile and acrylamide. Details are discussed in the article by A. de Meijere et al. on p. 4417 ff. The authors acknowledge the support of this work by Irene Böttcher‐Gajewski (Göttingen), who provided the photographical content of the cover picture.