Significant association between decreased ALDH2 activity and increased sensitivity to genotoxic effects in workers occupationally exposed to styrene.

ALDH2 is involved in the metabolism of styrene, a widely used industrial material, but no data are available regarding the influence of this enzyme on the metabolic fate as well as toxic effects of this chemical. In this study, we recruited 329 workers occupationally exposed to styrene and 152 unexposed controls. DNA strand breaks, DNA-base oxidation in leukocytes and urinary 8-hydroxydeoxyguanosine (8-OH-dG) were assayed as biomarkers to measure genotoxic effects. Meanwhile, we examined the genetic polymorphisms, including ALDH2, EXPH1, GSTM1, GSTT1 and CYP2E1, and also analyzed the levels of styrene exposure through detecting urinary styrene metabolites and styrene concentration in air. In terms of DNA damage, the three genotoxic biomarkers were significantly increased in exposed workers as compared with controls. And the styrene-exposed workers with inactive ALDH2 *2 allele were subjected to genotoxicity in a higher degree than those with ALDH2 *1/*1 genotype. Also, lower levels of urinary styrene metabolites (MA + PGA) were observed in styrene-exposed workers carrying ALDH2 *2 allele, suggesting slower metabolism of styrene. The polymorphisms of other enzymes showed less effect. These results suggested that styrene metabolism and styrene-induced genotoxicity could be particularly modified by ALDH2 polymorphisms. The important role of ALDH2 indicated that the accumulation of styrene glycoaldehyde, a possible genotoxic intermediate of styrene, could account for the genotoxicity observed, and should be taken as an increased risk of cancer.

[Globally harmonized system of classification and labelling of chemicals (GHS) and its implementation in Japan].

The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is a set of recommendations by the United Nations, first issued in 2003 as a communication tool for the sound management of chemicals, comprising harmonized classification criteria for physical, health and environmental hazards, a unified format for material safety data sheets (MSDS), and labeling elements including pictograms and hazard statements preassigned to each classification category. The GHS has been introduced into Japan and implemented in the regulatory framework for chemical safety. The Japanese Industrial Standards (JIS) adopted the GHS, and the GHS-based JIS rules have become the Japanese standards for labels and MSDS. The use of the JIS format for labels and MSDS is recommended by several competent authorities in Japan although mostly on a voluntary basis. In the workplace, however, GHS-based JIS labels and MSDS have become legal requirements by the Industrial Safety and Health Law since 2006; namely, issuing MSDS in such a format is mandatory for the 640 specified chemicals and also labeling for the 99 targeted chemicals*. Although the GHS provides definitions and classification criteria for 10 classes of health hazards (acute toxicity, skin and eye corrosion/irritation, sensitization, germ cell mutagenicity, carcinogenicity, reproductive toxicity, specific target organ toxicity single/repeated exposures, and aspiration hazard), it does not provide actual classification of chemicals, so that competent authorities and industries need to classify a number of chemicals and/or mixtures. Weight-of-evidence judgment and/or expert judgment would be necessary in many cases. In this paper, the outline of the GHS classification is described and problems of the GHS and its implementation are discussed.