title: Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.
abstract: Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants.
authors.affiliation: Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA. Electronic address: hammjt@niehs.nih.gov.
authors.forename: Jon
authors.initials: J
authors.lastname: Hamm
authors.affiliation: Physicians Committee for Responsible Medicine, 5100 Wisconsin Ave NW, Ste 400, Washington, DC, USA.
authors.forename: Kristie
authors.initials: K
authors.lastname: Sullivan
authors.affiliation: PETA International Science Consortium Ltd., London, UK.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Clippinger
authors.affiliation: Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Strickland
authors.affiliation: Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Bell
authors.affiliation: The Dow Chemical Company, Midland, MI, USA.
authors.forename: Barun
authors.initials: B
authors.lastname: Bhhatarai
authors.affiliation: Institute for Risk Assessment Sciences, Division of Toxicology, Utrecht University, Utrecht, Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Blaauboer
authors.affiliation: NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, Research Triangle Park, NC, USA.
authors.forename: Warren
authors.initials: W
authors.lastname: Casey
authors.affiliation: North Carolina State University, Raleigh, NC, USA.
authors.forename: David
authors.initials: D
authors.lastname: Dorman
authors.affiliation: Stockholm University and Swedish Toxicology Sciences Research Center (Swetox), Södertälje, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Forsby
authors.affiliation: US Army Engineer Research and Development Center, Alexandria, VA, USA.
authors.forename: Natàlia
authors.initials: N
authors.lastname: Garcia-Reyero
authors.affiliation: Dow AgroSciences, Indianapolis, IN, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Gehen
authors.affiliation: European Union Reference Laboratory for Alternatives to Animal Testing, Ispra, Italy.
authors.forename: Rabea
authors.initials: R
authors.lastname: Graepel
authors.affiliation: The Dow Chemical Company, Midland, MI, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Hotchkiss
authors.affiliation: U.S. Environmental Protection Agency, Office of Pesticide Programs, Washington, DC, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Lowit
authors.affiliation: U.S. Consumer Product Safety Commission, Washington, DC, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Matheson
authors.affiliation: U.S. Environmental Protection Agency, Office of Pesticide Programs, Washington, DC, USA.
authors.forename: Elissa
authors.initials: E
authors.lastname: Reaves
authors.affiliation: U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics, Washington, DC, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Scarano
authors.affiliation: Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sprankle
authors.affiliation: SRC, Inc., Syracuse, NY, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Tunkel
authors.affiliation: The Dow Chemical Company, Midland, MI, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Wilson
authors.affiliation: National Center for Advancing Translational Sciences, Rockville, MD, USA.
authors.forename: Menghang
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Chemistry(,) Rutgers University-Camden, Camden, NJ, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA.
authors.forename: David
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authors.lastname: Allen
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D033161:Government Regulation; D057166:High-Throughput Screening Assays; D006801:Humans; D012106:Research; D023382:Toxicity Tests, Acute
keywords: 3Rs; Acute systemic toxicity; Alternatives; Dermal; In silico; In vitro; Inhalation; LD(50); Oral