You are here:
NEUROTOXIC EFFECTS OF ENVIRONMENTAL AGENTS: DATA GAPS THAT CHALLENGE DOSE-RESPONSE ESTIMATION
Citation:
Mendola, P, S. Gutter, S G. Selevan, AND D. Rice. NEUROTOXIC EFFECTS OF ENVIRONMENTAL AGENTS: DATA GAPS THAT CHALLENGE DOSE-RESPONSE ESTIMATION. Presented at International Society for Environmental Epidemiology, Vancouver, British Columbia, Canada, August 11-15, 2002.
Description:
Neurotoxic effects of environmental agents: Data gaps that challenge dose-response estimation
S Gutter*, P Mendola+, SG Selevan**, D Rice** (*UNC Chapel Hill; +US EPA, NHEERL; **US EPA, NCEA)
Dose-response estimation is a critical feature of risk assessment. It can be based on the results of epidemiologic, observational or clinical studies in humans and wildlife or laboratory-based animal studies. A systematic review of the epidemiologic literature on the potential neurotoxic effects of environmental agents was conducted. Effects have been relatively well described for lead across a spectrum of doses, but detailed dose-related information is generally lacking for other potentially neurotoxic compounds. In the example of methylmercury (MeHg), mental retardation, cerebral palsy and visual and auditory deficits have been observed in children of mothers exposed to high levels. At lower doses of MeHg exposure, a spectrum of functional deficits has been reported but the relation between dose and effect is less well understood. Other environmental agents such as polychlorinated biphenyls (PCBs) and related compounds, dioxins, pesticides, ionizing radiation, and environmental tobacco smoke have all been associated with adverse neurological and cognitive effects. With the exception of high dose ionizing radiation and PCB poisoning episodes, most observed effects for these agents have not included severe disability such as mental retardation, but have included poorer school performance and motor deficiencies. Among the maternal behavioral factors associated with neurotoxicologic effects, maternal alcohol, tobacco, marijuana and cocaine use were reviewed. For alcohol, the timing and conditions of exposure, as well as individual sensitivity of both the mother and fetus are important factors that moderate a potential dose-response relation. A spectrum of neurological effects is seen in infants exposed in utero to alcohol from serious disability to milder effects such poor metacognition and learning difficulties. In general, it appears that neurotoxic effects of environmental exposures range in severity from mental retardation and disability to attention deficits, problems in school performance, and aggressive tendencies depending on the timing and dose of the chemical agent, but many potential neurotoxic agents have very little human data on low dose effects. Identifying the appropriate neurological and cognitive outcomes is essential to characterizing the dose-response relationship at lower levels of exposure. In epidemiological studies, the problems of selection bias, such as that observed in the investigation of low dose exposure to ionizing radiation following the detonation of the atomic bomb, and residual confounding, as in studies of environmental tobacco smoke exposure, must be overcome to adequately estimate the dose-response relationship. Both observational epidemiology and animal toxicology research efforts that focus attention on the neurotoxic effects of lower level environmental exposures are needed.
This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.