Genetically exposure assessment

Severn, D.J. (1982) Exposure assessment for agricultural chemicals, in Genetic Toxicology, and Agricultural Perspective, Fleck, R.A. and Hollander, A., Eds., Plenum Press, New York, pp. 235-242. 

Asthma rates in children in Southern California are high and oxidant pollution levels are likewise high. It is important to determine the relationship between the two. It is also important to determine whether there are chronic pulmonary effects produced by either these oxidants and/or particulate pollution. Since children spend more time outdoors than adults and since they exercise more while outdoors, the added assault from increased ventilation may be of importance. The studies feature a comprehensive exposure assessment that has led to a better understanding of the relationship between exposure and effects. It is also important to identify sub-populations of children and adults who are more susceptible to air pollution-related respiratory effects if they exist. Altered susceptibility could be based on genetic or non-genetic mechanisms (nutritional status for example). Both the epidemiologic and chamber studies provide opportunities to examine issues of hypersusceptibility and to determine the reasons for it if it exists. 

In the eighties and early nineties, the USEPA evaluated dietary risk with an analysis method known as the Dietary Risk Evaluation System (DRES) (USEPA, 1991), which was based on the USDA s 1977 to 1978 National Food Consumption Survey. Consequently, dietary exposure assessments became genetically referred to as DRES analyses. Currently, the USEPA is using the Dietary Exposure Evaluation Model (DEEM , Version 7.87) (Exponent, 2000), which allows exposure to be calculated from 1994 to 1996 CSFII along with the 1998 supplemental children s survey information. 

Even the most sophisticated risk assessment has limitations. It involves numerous assumptions about both exposure and hazard. Exposure assessments typically reflect modeled concentrations or extrapolations from measured data. The degree of exposure by different individuals may vary, and their response can depend on factors such as general health, genetic predisposition, or other factors. Dose-response factors are typically extrapolated from animal studies and thus inherently introduce the imcertainty of relating the response of laboratory animals to that of humans or one of the many species in an ecosystem. The endpoints characterized may not include all of the potential effects for example, the potential for endocrine disruption has not been considered in many risk assessments and in fact standardized testing methods were not published until approximately 2007 or later [90]. And risk assessment tools only model relatively simple scenarios. They rarely account for exposure to multiple chemicals, or fully accoimt for the effects on a complex web of organisms in an ecosystem. 

Extensive research is currently underway to use biological markers (biomarkers) in exposure and risk assessment. Biomarkers include the reaction products of chemicals or their metabolic products with biological macromolecules, especially with DNA. They also involve indicators of effect, such as chromosomal damage, and indicators of individual genetic susceptibility. 

In studies of the fate of hydrocarbons in terrestrial animals, considerable attention is directed toward relations between aromatic hydrocarbon metabolism, interactions of metabolites with macromolecules (e.g., DNA), and the formation of neoplastic lesions (] ). A broad perspective exists in studies with marine organisms. In the aquatic forms, exposure to pollutants that are rich in aromatic hydrocarbons, such as petroleum, leads to a wide variety of acute and chronic effects (2J. Attempts to delineate these effects require an understanding of the accumulation of the xenobiotics in tissues and an assessment of metabolite formation and retention. The important additional problem of the interaction of metabolites with genetic materials has not been studied to an appreciable degree in marine life. 

Houston and Houston and Stairs did clonal repeatability analyses to determine genetic control of tolerance in white pine with an ozone-sulfiir dioxide mixture and a 6-h exposure. Th used needle elongation and two injury estimates in assessing effects. The repeatability estimates indicated that tolerance to the pollutant mixture is under genetic control. The nature of the inheritance of tolerance is still not understood, but field selection of tolerant or susceptible individuals is possible. Demeritt et reported an evaluation system that used... 

JRC is structured into seven institutes, one of these being the Institute for Health and Consumer Protection (IHCP). The IHCP activities are related to genetically modihed organisms, biotechnology, chemicals and risk assessment, nano-biotechnology, exposure to environmental stressors, food contact materials and consumer products, and alternative methods to animal testing (IHCP 2006). 

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