Acute Systemic Toxicity

Acute systemic toxicity testing is conducted to predict the effects of acute exposure to a chemical. Acute exposure refers to a single, short-term exposure to a substance (generally less than 24 hours) and the main routes of exposure are oral, dermal, and inhalation. Acute systemic toxicity data are required by various regulatory agencies before bringing a chemical to market.

With the goal of developing a strategy to replace in vivo acute systemic toxicity test methods, PETA Science Consortium International co-organised a series of webinars and the 2015 workshop, “Alternative Approaches to Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing”. The workshop proceedings were published in Toxicology In Vitro in 2017, and additional information on acute systemic toxicity testing requirements in the United States was published in Regulatory Toxicology and Pharmacology in 2018. The Science Consortium also delivered the keynote presentation at a 2019 follow-up workshop on acute systemic toxicity testing and co-authored the workshop report in ALTEX in 2021.

Acute Systemic Toxicity: Inhalation

In follow-up to the 2015 workshop, the Science Consortium also co-organised a series of six webinars and a workshop focused on alternative approaches for acute inhalation toxicity testing (here) and donated five VITROCELL^® inhalation exposure devices for researchers to assess the effects of inhaled substances in vitro (here). The Science Consortium has worked extensively on assessing the respiratory effects of chemicals in vitro.

Acute Systemic Toxicity: Oral

There are various in vitro and in silico approaches that can be used to address aspects of acute oral toxicity. For example, numerous in silico tools, such as CATMoS, OTTR, and the OECD QSAR Toolbox, can be used. For mixtures, the GHS mixtures equation can be used to predict the toxicity of the product based on the toxicity of the individual ingredients.

Acute Systemic Toxicity: Dermal

The acute dermal toxicity data requirement may be waived when there is no concern for dermal exposure, when the chemical is a gas or highly volatile liquid, when it is corrosive to the skin, or has a pH of less than 2 or greater than 11.5. Further, the acute dermal toxicity test may be waived when acute oral toxicity data exist. For example, the US Environmental Protection Agency Office of Pesticide Programs has guidance documents on waiving acute dermal toxicity testing for pesticide active ingredients and formulations when oral data are available, based on extensive retrospective data analyses showing that the acute oral toxicity data are almost always as or more protective than the dermal toxicity data.