Cumulative risk assessment lessons learned: a review of case studies and issue papers.

Cumulative risk assessments (CRAs) examine potential risks posed by exposure to multiple and sometimes disparate environmental stressors. CRAs are more resource intensive than single chemical assessments, and pose additional challenges and sources of uncertainty. CRAs may examine the impact of several factors on risk, including exposure magnitude and timing, chemical mixture composition, as well as physical, biological, or psychosocial stressors. CRAs are meant to increase the relevance of risk assessments, providing decision makers with information based on real world exposure scenarios that improve the characterization of actual risks and hazards. The U.S. Environmental Protection Agency has evaluated a number of CRAs, performed by or commissioned for the Agency, to seek insight into CRA concepts, methods, and lessons learned. In this article, ten case studies and five issue papers on key CRA topics are examined and a set of lessons learned are identified for CRA implementation. The lessons address the iterative nature of CRAs, importance of considering vulnerability, need for stakeholder engagement, value of a tiered approach, new methods to assess multiroute exposures to chemical mixtures, and the impact of geographical scale on approach and purpose.

The use of developmental neurotoxicity data in pesticide risk assessments.

Following the passage of the Food Quality Protection Act, which mandated an increased focus on evaluating the potential toxicity of pesticides to children, the number of guideline developmental neurotoxicity (DNT) studies (OPPTS 870.6300) submitted to the U.S. Environmental Protection Agency (EPA) Office of Pesticide Programs (OPP) was greatly increased. To evaluate the impact of available DNT studies on individual chemical risk assessments, the ways in which data from these studies are being used in pesticide risk assessment were investigated. In addition, the neurobehavioral and neuropathological parameters affected at the lowest observed adverse effect level (LOAEL) for each study were evaluated to ascertain whether some types of endpoints were consistently more sensitive than others. As of December 2008, final OPP reviews of DNT studies for 72 pesticide chemicals were available; elimination of studies with major deficiencies resulted in a total of 69 that were included in this analysis. Of those studies, 15 had been used to determine the point of departure for one or more risk assessment scenarios, and an additional 13 were determined to have the potential for use as a point of departure for future risk assessments (selection is dependent upon review of the entire database available at the time of reassessment). Analysis of parameters affected at the study LOAELs indicated that no single parameter was consistently more sensitive than another. Early assessment time points (e.g., postnatal day (PND) 11/21) tended to be more sensitive than later time points (e.g., PND 60). These results demonstrate that data generated using the current guideline DNT study protocol are useful in providing points of departure for risk assessments. The results of these studies also affirm the importance of evaluating a spectrum of behavioral and neuropathological endpoints, in both young and adult animals, to improve the detection of the potential for a chemical to cause developmental neurotoxicity.