Environmental toxicity (Q)SARs for polymers as an emerging class of materials in regulatory frameworks, with a focus on challenges and possibilities regarding cationic polymers

Abstract

Polymers are highly diverse and understudied materials from an environmental toxicity point of view. For the past decades, polymers have largely been out of scope regarding detailed safety assessment in most regulatory programs as they are assumed to not possess relevant toxicological properties due to their size. This regulatory exclusion is currently being reconsidered. This chapter discusses the available information about selected cationic polymers and outlines (Q)SAR ((Quantitative) Structure-Activity Relationship) approaches that could be used to develop new models to demonstrate potential aquatic toxicity of polymers. The amount of publicly available, high-quality environmental toxicity data on industrial polymers such as cationic polyquaterniums is extremely limited. Given the large size (dimension and molecular weight) of the materials, typical hydrophobicity-driven toxicity is not expected. Relevant descriptors for cationic polymers need to be identified. Molecular weight and charge density are well-known physical-chemical attributes that are suspected to be correlated with aquatic toxicity, but there might be other relevant descriptors as well. We suggest models that predict polymer properties may be useful for estimating relevant properties regarding toxicity. Moreover, novel fragment-based 2D and 3D hologram (Q)SAR (H(Q)SAR) may prove relevant in determining these properties that can be used to derive hypotheses about toxic mechanisms and guide experimental test designs. In a regulatory context, (Q)SARs have to be transparent and scientifically robust which extends to fragment-based models that may be useful in categorizing polymers. The toxicity of category members can then be experimentally explored, and read-across strategies developed within the category. The authors of this chapter are pursuing polymer (Q)SAR strategies in the coming years via generation of novel experimental and computational data on polyquaterniums. We will also evaluate the potential for fragment-based (Q)SARs for polymers in REACH.