Current risk assessment guidance calls for an individual chemical-by-chemical approach that fails to capture potential interactive effects of exposure to environmental mixtures in the context of genomic influences. As an exploratory analysis, we develop a systematic review of prenatal and perinatal exposure to mixtures of lead (Pb), arsenic (As), cadmium (Cd), and manganese (Mn) and nonspecific developmental outcomes in children, including reduced IQ and decreased performance on developmental tests, using an adverse outcome pathway (AOP) framework to integrate lines of evidence based on evolving guidance developed by the Organization for Economic Cooperation and Development (OECD). Toxicological evidence suggests a greater than additive effect of combined exposures to As-Pb-Cd and Mn in the presence of one or more metals. Several epidemiologic studies also suggest synergistic effects from binary combinations of Pb-As and Pb-Cd. However, monitoring data from the National Health and Nutrition Examination Survey (NHANES) reveals the majority of the U.S. population has biomarker levels below those corresponding to exposure concentrations from the epidemiologic studies. This systematic review integrates relevant and diverse data sources using an AOP framework and provides an initial application of the OECD guidance in the context of potential neurodevelopmental toxicity of several metals, recognizing the evolving nature of regulatory interpretation and acceptance.

The ecosystem services (ES) concept holds much promise for environmental decision making. Even so, the concept has yet to gain full traction in the decisions and policies of environmental agencies in the United States, Europe, and elsewhere. In this paper we examine the opportunities for and implications of including ES in risk assessments and the risk management decisions that they inform. We assert that use of ES will: 1) lead to more comprehensive environmental protection; 2) help to articulate the benefits of environmental decisions, policies, and actions; 3) better inform the derivation of environmental quality standards; 4) enable integration of human health and ecological risk assessment; and 5) facilitate horizontal integration of policies, regulations, and programs. We provide the technical basis and supporting rationale for each assertion, relying on examples taken from experiences in the United States and European Union. Specific recommendations are offered for use of ES in risk assessment and risk management, and issues and challenges to advancing use of ES are described together with some of the science needed to improve the value of the ES concept to environmental protection. Integr Environ Assess Manag 2017;13:62-73. © 2016 SETAC.

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