[Frontiers in Bioscience E5, 418-434, January 1, 2013]

A step change towards risk assessment in the 21st century

Grace Y Patlewicz1, Deborah R Lander1

1DuPont Haskell Global Centers for Health and Environmental Sciences, 1090 Elkton Road, Newark, DE 19711, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Regulatory background
2.2. REACH
2.3. Integrated testing strategies
2.4. Non-testing approaches
2.5. Exposure assessment
3. Case study on selected methacrylates
3.1. Physicochemical properties
3.1.1. LogKow (octanol/water partition coefficient)
3.2. Mammalian toxicity
3.2.1. Skin sensitisation
3.2.2. Mutagenicity (in vitro): Ames
3.3. Environmental fate
3.3.1. Biodegradation
3.4. Ecotoxicity
3.4.1. Acute aquatic toxicity in fish
3.4.2. Acute aquatic toxicity in D. Magna
3.5 Summary remarks
4. Exposure assessment on methyl methacrylate
4.1. Dermal sensitisation exposure assessment
4.2. Determination of the local effects dermal DNEL
4.3. Methods for exposure assessment
4.4. Discussion
5. Summary and Perspectives
6. References

1. ABSTRACT

Chemical Regulation and the means by which data is generated for the purposes of risk assessment is undergoing a tremendous shift. There is a strong impetus in Europe, in particular, to move towards non-animal approaches to address data gaps for specific endpoints either in lieu of testing or as part of weight of evidence approaches within integrated testing strategies (ITS). An Exposure assessment considering workers and/or consumers is a critical component of a robust risk assessment. The EU chemicals legislation REACH, for example, provides considerable flexibility in the application of non-testing approaches such as (Q)SARs, chemical categories and read-across for data gap filling. There have been a number of efforts aimed at developing technical guidance, tools, and techniques for non-testing and tiered exposure approaches. Despite these efforts, there remains limited practical insight about how these approaches can be applied in the assessment of substances. Here, we first provide a background of the available approaches and how they can and should be practically utilised to address REACH requirements.