An economic approach to non-animal toxicity testing for skin sensitisation

Abstract

Chemicals applied in products, such as food products, pharmaceuticals or cosmetics, create great benefits in society while posing risks to human health and the quality of the environment. To control those risks, it is mandatory to perform risk assessments of chemicals which require information on their hazardous properties. To meet these information requirements without sacrificing large numbers of animal tests, many non-animal testing methods and strategies have become available. Given the increasing needs for assessing chemicals’ risks, toxicity testing has become costly in terms of testing costs, time and animal welfare. Focusing on skin sensitisation as a case study, this thesis aims at introducing an economic approach towards the optimisation of toxicity testing strategies. Chapter 2 surveys the current status of non-animal toxicity testing strategies assessing skin sensitisation and compares criteria suggested in the toxicological literature with the conceptual and informational criteria introduced in this chapter for increasing resource-efficiency in the development of testing strategies. Chapter 3 extends to the development of a Bayesian Value-of-Information model for the optimisation of non-animal toxicity testing strategies. This optimisation model is applied to construct optimal non-animal toxicity testing strategies for the assessment of skin sensitisation potential. Chapter 4 focuses on the precision of testing methods and the impact of limited precision on the evaluation of test results. The borderline range of testing methods is quantified and applied as an additional evaluation measure in the prediction models of testing methods to identify substances as positive and negative (for substances yielding clear-cut test results), or as discordant (for substances yielding test results within the borderline range). Chapter 5 addresses the uncertainties underlying the predictive accuracy metrics for non-animal testing methods due to their limited precision, the sample size and composition of the samples of chemicals used to estimate the predictive capacity of testing methods. Chapters 4 and 5 focus on non-animal testing methods for the assessment of skin sensitisation potential. This thesis concludes that introducing the economic perspective into the construction of toxicity testing strategies is necessary to develop the means by which resource-efficiency in toxicity testing is achieved. Furthermore, the evaluation of testing methods should consider both predictivity and precision limitations such that decision makers can draw robust conclusions on the hazardous properties of chemicals.