Mathematical modelling to reduce animal use in neurodevelopmental safety assessment in humans

A problem presented at the UK MMSG Cambridge 2014.

Presented by:
Dr Richard Currie (Syngenta Ltd.)
J Chapman, R Currie, L Dyson, M Germain, B McMillan, D Reddyhoff, D Temko, J Ward, S Webb

Problem Description

All environmental pollutants, pharmaceutical, crop protection and industrial chemicals go through a battery of tests, many of which involve animals, to assess their potential for inducing adverse effects in humans and the environment. A common finding during these investigations is the induction of Phase II xenobiotic metabolism in rats. This results in increased thyroid hormone metabolism.

Thyroid hormones are essential for the control of metabolism and development, especially nervous system development. Therefore there is a concern that altered thyroid hormone levels during critical periods of development would result in adverse outcomes in the developing foetus. This has led to calls from the regulatory agencies, e.g. the US Environmental Protection Agency (US EPA) to perform additional "developmental thyroid" studies in rats to assess the risk to the foetus and infants.

By using mathematical modelling can we determine whether, and under what conditions, we can confidently use the no-effect level of drugs and chemicals on thyroid hormones in male adult rats to be suitably protective for human health, and negate the need for additional animal studies?

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Study Group Report

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