02532nas a2200385   4500000000100000008004100001260001500042653002800057653002400085653004600109653002200155653002600177100002000203700002300223700001900246700002400265700002100289700002700310700001800337700002200355700001700377700002400394700001800418700001500436700001400451700001500465700002100480700001700501245011200518856005000630300000900680490000600689520143700695022001402132       2023                            d  c2023-08-3010aAcute systemic toxicity10aanimal alternatives10ahazard classification and risk assessment10alethality testing10aRegulatory toxicology1 aJudy Strickland1 aEsther Haugabrooks1 aDavid G. Allen1 aLuciene B. Balottin1 aYoko Hirabayashi1 aNicole C. Kleinstreuer1 aHajime Kojima1 aClaudio Nishizawa1 aPilar Prieto1 aDeborah E. Ratzlaff1 aJayoung Jeong1 aJinHee Lee1 aYing Yang1 aPinpin Lin1 aKristie Sullivan1 aWarren Casey00aInternational regulatory uses of acute systemic toxicity data and integration of new approach methodologies  uhttps://doi.org/10.1080/10408444.2023.2240852  a1-270 v03 aChemical regulatory authorities around the world require systemic toxicity data from acute exposures via the oral, dermal, and inhalation routes for human health risk assessment. To identify opportunities for regulatory uses of non-animal replacements for these tests, we reviewed acute systemic toxicity testing requirements for jurisdictions that participate in the International Cooperation on Alternative Test Methods (ICATM): Brazil, Canada, China, the European Union, Japan, South Korea, Taiwan, and the USA. The chemical sectors included in our review of each jurisdiction were cosmetics, consumer products, industrial chemicals, pharmaceuticals, medical devices, and pesticides. We found acute systemic toxicity data were most often required for hazard assessment, classification, and labeling, and to a lesser extent quantitative risk assessment. Where animal methods were required, animal reduction methods were typically recommended. For many jurisdictions and chemical sectors, non-animal alternatives are not accepted, but several jurisdictions provide guidance to support the use of test waivers to reduce animal use for specific applications. An understanding of international regulatory requirements for acute systemic toxicity testing will inform ICATM’s strategy for the development, acceptance, and implementation of non-animal alternatives to assess the health hazards and risks associated with acute toxicity.  a1040-8444