Status of acute systemic toxicity testing requirements and data uses by U.S. regulatory agencies

Regul Toxicol Pharmacol. 2018 Apr:94:183-196. doi: 10.1016/j.yrtph.2018.01.022. Epub 2018 Feb 3.


Acute systemic toxicity data are used by a number of U.S. federal agencies, most commonly for hazard classification and labeling and/or risk assessment for acute chemical exposures. To identify opportunities for the implementation of non-animal approaches to produce these data, the regulatory needs and uses for acute systemic toxicity information must first be clarified. Thus, we reviewed acute systemic toxicity testing requirements for six U.S. agencies (Consumer Product Safety Commission, Department of Defense, Department of Transportation, Environmental Protection Agency, Food and Drug Administration, Occupational Safety and Health Administration) and noted whether there is flexibility in satisfying data needs with methods that replace or reduce animal use. Understanding the current regulatory use and acceptance of non-animal data is a necessary starting point for future method development, optimization, and validation efforts. The current review will inform the development of a national strategy and roadmap for implementing non-animal approaches to assess potential hazards associated with acute exposures to industrial chemicals and medical products. The Acute Toxicity Workgroup of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), U.S. agencies, non-governmental organizations, and other stakeholders will work to execute this strategy.

Keywords: Acute systemic toxicity; Alternative approaches; In silico; In vitro; LC(50); LD(50); Non-animal methods; Regulatory requirements.

Publication types

  • Review

MeSH terms

  • Animals
  • Government Agencies / legislation & jurisprudence*
  • Humans
  • Toxicity Tests, Acute*
  • United States