Article

The value of acute toxicity studies to support the clinical management of overdose and poisoning: A cross-discipline consensus

National Centre for the Replacement, Refinement and Reduction of Animals in Research, London, UK.
Regulatory Toxicology and Pharmacology (Impact Factor: 2.14). 12/2010; 58(3):354-9. DOI: 10.1016/j.yrtph.2010.07.003
Source: PubMed

ABSTRACT Acute toxicity studies are no longer required to support first clinical trials of pharmaceuticals in man. However, it is unclear in the wording of the revised ICH M3 whether acute toxicity studies are required later in drug development (e.g., phase 3) in order to support the management of overdose. The NC3Rs held a workshop in January 2010 with representatives from international poison centres, the pharmaceutical and chemical industries, and regulatory and government bodies to explore further whether acute toxicity studies are used to support the clinical management of overdose of pharmaceuticals and whether this work can be translated to other sectors such as the chemical industry. The consensus formed at the workshop was that acute toxicity studies are not used for managing overdose of pharmaceuticals and are of little value in treating human poisoning from chemicals. In this paper, the authors describe the key considerations in treating human overdose and poisoning, challenge the value of the classification and labelling process of chemicals for this purpose and discuss how acute toxicity studies can be improved to better inform risk assessment.

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    • "Identifying studies that add little in terms of information on the hazardous properties of the substance, and are in effect 'redundant', is a relatively easy way to reduce animal testing and costs to industry, without adversely impacting on the level of protection of human or environmental health. Examples of where this approach has proved fruitful include a review of the need for dermal acute toxicity studies for industrial chemicals and pesticides (Creton et al., 2010) and a review of the need for single dose acute toxicity studies for medicinal compounds (Robinson et al., 2008) and for industrial chemicals (Chapman et al., 2010) all by the UK National Centre for the 3Rs, a review of the need for the second generation in reproductive toxicity studies by the Dutch National Institute for Public Health and the Environment (Janer et al., 2007), and a review of the need for carcinogenicity studies for medicinal products by the German Federal Institute for Drugs and Medical Devices (Friedrich and Olejniczak, 2011) and also by the US drug industry (Sistare et al., 2011). "
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    • "Additionally, acute toxicity studies are no longer used for managing overdose of pharmaceuticals and have been found to be of little value in treating human poisoning from chemicals. This consensus was reached at a workshop held by the NC3Rs which brought together clinicians, toxicologists, regulators and directors of Poison Centres (Chapman et al., 2010; Robinson and Chapman, 2009). In the absence of acute toxicity data, the necessary information can instead be obtained from short term studies (up to 7 days daily dosing) that are already an existing part of the drug development process. "
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