We propose to study the exposure-response relationship between relatively low-level environmental exposure to lead in adults and chronic neurotoxicity. In a prospective epidemiologic study, neurologic function will be evaluated in adults at the beginning of their exposure to elevated levels of lead and again 1.0 to 3.5 years later. State-of-the-art biological markers of both lead exposure and subclinical neurotoxic effects will be used. Indicators of exposure to lead will include whole blood lead levels as well as bone lead content as determined by 109 cadmium (Cd) X-ray fluorescence (XRF) spectrometry. Determination of blood lead levels by atomic absorption spectrophotometry permits accurate assessment of current lead absorption. The XRF technology allows direct measurement of lead in bone in vivo, a biological marker of chronic cumulative absorption of lead. This index of cumulative lead exposure has not been used previously in the study of lead-related neurologic dysfunction. Measures of subclinical neurologic effects will include tests of central, peripheral and autonomic nervous system function. Both computer-administered and manually-administered neurobehavioral tests will be employed to assess central nervous system function. The 10 neurobehavioral tests included in this battery, which have been used extensively in prior epidemiologic investigations, will assess a range of functions including psychomotor abilities, memory, cognition, and mood. Peripheral nervous system functions to be measured include nerve conduction velocity measurements and quantitative cutaneous vibrotactile thresholds of both the upper and lower extremities. A new test of postural stability will be employed to assess the complex integrated central and peripheral nervous system functions necessary for maintenance of standing steadiness. Variability in heart rate at rest and during deep breathing will be measured as an index of autonomic nervous system function. Changes in neurologic function over the interval of observation will be compared with changes in blood and bone lead levels. The relative strength of relationships between biological markers of both acute and cumulative lead exposure and neurologic outcomes will be assessed. Dose-response relationships other than linear will be modeled and evaluated. This study will be significant because it will assess prospectively with sensitive outcome measures the subclinical neurotoxic effects of low-level environmental lead exposure in adults. It will be unique in its prospective examination of neurologic outcomes in relation to a cumulative biologic indicator of chronic lead exposure, lead content in bone. Never before has a biological measure of cumulative exposure to lead been related to neurologic outcomes in a prospective study of the potential effects of low-level exposure in adults.
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