Analysis and reflection on the role of the 90-day oral toxicity study in European chemical risk assessment

Regul Toxicol Pharmacol. 2020 Nov:117:104786. doi: 10.1016/j.yrtph.2020.104786. Epub 2020 Sep 22.

Abstract

The 90-day toxicity study is one of the studies used in the safety assessment of food ingredients, medicines or other chemical substances. This paper reviews the current role of the 90-day oral toxicity study in European regulatory dossiers of chemicals by reviewing EU legislation and EU and OECD guidance documents. Regulatory provisions with regard to necessity, objectives and design of such 90-day toxicity studies vary between the different sectors addressed in this review. Most often the 90-day study is expected to be part of the standard test battery used for chemical risk assessment, without necessarily being a legal requirement and its objectives may vary between regulatory domains. Exceptions, when a 90-day study is not required are spelled out in the chemicals legislation and for food contact materials. The sectorial study design requirements of the 90-day toxicity study are very often embedded in the OECD TG 408 protocol. Differences in study objectives are not necessarily reflected in specific study designs. Considering the call for the reduction of using experimental animals for scientific purposes and the fact that a 90-day study may serve different purposes, consistency between the necessity to conduct such a study, its objectives and the study design to achieve these objectives may improve judicious use of laboratory animals. Thus there may be an opportunity to reflect and further optimise the design of in vivo toxicology studies, such as the 90-day study. This should be based on a systematic analysis of past studies and risk assessments.

Keywords: Chemical safety; ECHA; EFSA; EMA; Regulatory science; Risk assessment; Sub-chronic toxicity; Toxicology.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Animal Testing Alternatives / legislation & jurisprudence*
  • Animal Testing Alternatives / standards*
  • Animal Testing Alternatives / trends
  • Animals
  • European Union*
  • Humans
  • Organisation for Economic Co-Operation and Development / legislation & jurisprudence*
  • Organisation for Economic Co-Operation and Development / standards*
  • Organisation for Economic Co-Operation and Development / trends
  • Risk Assessment
  • Rodentia
  • Time Factors
  • Toxicity Tests / standards*
  • Toxicity Tests / trends