Abstract
Positive list system for utensils, container and packaging (UCP) was enforced in June, 2020 in Japan. The toxicity profiles of the designated substances should be evaluated for at least genotoxicity, and the assessment is ongoing by an Integrated Approach, reviewing experimental genotoxicity data combined with (Quantitative) Structure Activity Relationship ((Q)SAR).
4,4'-Oxybis(benzenesulfonohydrazide) is a listed substance for UCP and known to be an additive of polyvinyl chloride. There are a number of evidences which lead 4,4'-oxybis(benzenesulfonohydrazide) was genotoxic in vitro and classified as a genotoxic substance in Industrial Safety and Health Act in Japan. In our literature review, positive results were obtained in two independent Ames tests (TG471), an unscheduled DNA synthesis (UDS) test in hepatocyte primary culture, and an in vitro chromosome aberration test (TG473). Moreover, (Q)SAR analysis supported genotoxicity in vitro. On the other hand, one negative result was obtained for mammalian in vivo micronucleus test (TG474). No toxicity data were available on its carcinogenicity. To confirm in vivo mutagenicity, we conducted the transgenic rodent gene mutation assay (TG488). After the transgenic Muta™ mice were administered 4,4'-oxybis(benzenesulfonohydrazide) orally for 28 days, genomic DNA in liver and glandular stomach, a major metabolizing organ and a primary exposed area via gavage route, were examined. Negative results were obtained in both liver and glandular stomach. We conclude that 4,4'-oxybis(benzenesulfonohydrazide) is not genotoxic in vivo.
