Addressing the Linkage between Exposure to Pesticides and Human Health Effects—Research Trends and Priorities for Research*Ritter, L.; Goushleff, N.C.I.; Arbuckle, Tye; Cole, Donald; Raizenne, Mark
doi: 10.1080/10937400600755895pmid: 17090482
In recent years, there has been escalating concern over the possible association between exposure to pesticides and adverse human health effects by a number of non-governmental organizations, professional and public interest groups. Recognizing the need to document the scientific basis of these concerns as a foundation for initiating a research theme devoted to linkages between exposures to pesticides and human health effects, the Canadian Institutes of Health Research (CIHR) requested a summary of recent research trends that address these linkages. Experts across Canada in the field of pesticide regulation and research were invited to participate in the review. The review summarizes the limitations of past and current studies related to pesticides and human health effects research and makes suggestions for future research priorities and proposed study designs that will improve the assessment of pesticide exposure, the associated health risks, and improved methodology for regulatory decision making.
From a Theoretical Framework of Human Exposure and Dose Assessment to Computational System Implementation: The Modeling ENvironment for TOtal Risk Studies (MENTOR)Georgopoulos, Panos G.; Lioy, Paul J.
doi: 10.1080/10937400600755929pmid: 17090483
Georgopoulos and Lioy (1994) presented a theoretical framework for exposure analysis, incorporating multiple levels of empirical and mechanistic information while characterizing/reducing uncertainties. The present review summarizes efforts towards implementing that framework, through the development of a mechanistic source-to-dose Modeling ENvironment for TOtal Risks studies (MENTOR), a computational toolbox that provides various modeling and data analysis tools to facilitate assessment of cumulative and aggregate (multipathway) exposures to contaminant mixtures. MENTOR adopts a “Person Oriented Modeling” (POM) approach that can be applied to either specific individuals or to populations/subpopulations of interest; the latter is accomplished by defining samples of “virtual” individuals that statistically reproduce the physiological, demographic, etc., attributes of the populations studied. MENTOR implementations currently incorporate and expand USEPA's SHEDS (Stochastic Human Exposure and Dose Simulation) approach and consider multiple exposure routes (inhalation, food, drinking water intake; non-dietary ingestion; dermal absorption). Typically, simulations involve: (1) characterizing background levels of contaminants by combining model predictions and measurement studies; (2) characterizing multimedia levels and temporal profiles of contaminants in various residential and occupational microenvironments; (3) selecting sample populations that statistically reproduce essential demographics (age, gender, race, occupation, education) of relevant population units (e.g., census tracts); (4) developing activity event sequences for each member of the sample by matching attributes to entries of USEPA's Consolidated Human Activity Database (CHAD); (5) calculating intake rates for the sample population members, reflecting physiological attributes and activities pursued; (6) combining intake rates from multiple routes to assess exposures; (7) estimating target tissue doses with physiologically based dosimetry/toxicokinetic modeling.
Evidence of Toxicity, Oxidative Stress, and Neuronal Insult in AutismKern, Janet K.; Jones, Anne M.
doi: 10.1080/10937400600882079pmid: 17090484
According to the Autism Society of America, autism is now considered to be an epidemic. The increase in the rate of autism revealed by epidemiological studies and government reports implicates the importance of external or environmental factors that may be changing. This article discusses the evidence for the case that some children with autism may become autistic from neuronal cell death or brain damage sometime after birth as result of insult; and addresses the hypotheses that toxicity and oxidative stress may be a cause of neuronal insult in autism. The article first describes the Purkinje cell loss found in autism, Purkinje cell physiology and vulnerability, and the evidence for postnatal cell loss. Second, the article describes the increased brain volume in autism and how it may be related to the Purkinje cell loss. Third, the evidence for toxicity and oxidative stress is covered and the possible involvement of glutathione is discussed. Finally, the article discusses what may be happening over the course of development and the multiple factors that may interplay and make these children more vulnerable to toxicity, oxidative stress, and neuronal insult.