Regulating human safety: How dose selection in toxicity studies impacts human health hazard assessment and subsequent risk management options

Abstract

In the EU, one of the key determinants in the regulation and management of substances to ensure adequate protection of human health is the outcome of toxicity studies. These studies should therefore be performed in a way that the data generated are adequate to fulfil all regulatory requirements. However, in recent years, an increasing number of toxicity studies use dose levels that induce only slight, or even no toxicity, while the top dose lies well below the limit dose of 1000 mg/kg bw/d. The results of these studies have limited value for the hazard and subsequent risk assessment and risk management of substances. This paper shows why conducting toxicity studies with too low doses has severe consequences for among others classification and labelling, identification of endocrine disruptors, health impact assessment, and incident management. With this paper we aim to raise awareness on this issue and want to stress the importance of the use of sufficiently high dosing in toxicity studies. Given their central role in toxicity testing, it is therefore key to adapt where necessary the descriptions in OECD test guidelines and guidance documents on requirements for dose level setting, to make sure they are as explicit and unambiguous as possible.

Keywords: Classification; Human health; Low dosing; Regulatory impact; Toxicity studies.