Hazard and Risk Assessment of Chemical Mixtures under REACH - State of the Art, Gaps and Options for Improvement. Swedish Chemicals Inspectorate , Report PM/3 2010

As demonstrated by several examples, humans and all other organisms in the environment are exposed to multi-component chemical mixtures. Empirical evidence on the toxicity and ecotoxicity of such chemical cocktails shows one common pattern, independent on the specific chemical composition of a particular mixture, the exposed organism or biological endpoint under observation: the joint toxicity of a chemical mixture is always higher than the individual toxic effect of even the most potent compound present. In particular, even low, individually non-toxic concentrations might result in a significant toxicity, if they co-occur as a chemical mixture. Given the actual exposure situation it has hence to be concluded that ecological or human-health standards for individual chemicals are only a first step. In addition, the toxicity of chemical mixtures has to be adequately considered in the regulatory risk assessment of chemicals. However, despite these facts and despite its professed aim to “ensure a high level of protection of human health and the environment” (article 1), REACH does not provide a mandate for considering the toxicity of so-called “coincidental” mixtures of industrial chemicals – multicomponent cocktails that are found in the environment or the human body as a result from the concurrent use of different chemicals in a given area. That the inclusion of such a mandate for mixture risk assessments provides a feasible option, at least for a certain regulatory groups of chemicals, is demonstrated by the forthcoming new legislation on plant protection products (PPP) (Common Position (EC) No 25/2008 adopted by the EP on 13 January 2009), which requests that PPP’s “shall not have any harmful effects on human health, including vulnerable groups, or animal health, taking into account known cumulative and synergistic effects”. However, comprehensive assessments of the (eco)toxicological impact from the plethora of all the chemicals that humans and the environment are exposed to would require more far-reaching regulatory efforts. There is the need to cut across the existing pieces of chemicals legislation, and not limited the assessment by substance- and product- oriented regulations such as REACH and PPP. Process- and media-oriented forms of legislation, such as for instance the Integrated Pollution and Prevention Control Directive (IPPC) and the Water Framework Directive (WFD) need to be included. Approaches that directly address cumulative exposure scenarios, as put forward for example in the WFD, might provide particularly valuable options for improved protection of humans and the environment from risks from mixtures of chemicals. Several approaches for the assessment of mixture (eco)toxicities have been described in the scientific literature, each with its own specific pros and cons. For prospective assessments in regulatory contexts (e.g. within REACH), the classic toxicological concepts of Concentration Addition and Independent Action seem to be the most promising methods. Especially Concentrations Addition has proven to provide generally good approximations of expectable mixture toxicities for a wide range of mixtures, exposed organisms and biological endpoints. In particular, synergistic (considerably more than concentration-additive) mixture toxicities seem to be rare. Concentration Addition also allows to predict the expected mixture toxicity (EC50 values) using the toxicological and ecotoxicological data that may be available by the registration of a compound under REACH. Two options for the risk assessment of “coincidental mixtures” within the context of REACH are discussed on this basis: (a) a default mixture assessment factor (MAF) and (b) scenario specific cumulative risk assessments. The actual implementation of these options are currently hampered 8 by substantial knowledge gaps, which, however, seem to be mainly empirical in nature. Especially knowledge on “typical” exposure scenarios involving REACH-chemicals is missing. Nevertheless, from a perspective beyond REACH, the trans-sectorial nature of mixtures of toxic compounds that coincidentally co-occur in an environmental compartment, the organisms living there, food and the human body poses a substantial challenge for the current system of chemical risk assessment and management.