Selective Vulnerability of Dopaminergic Systems To Industrial Chemicals: Risk Assessment of Related Neuroendocrine Changes

Abstract

Increased serum prolactin (PRL) is a common finding among subjects exposed to styrene, perchloroethylene, lead (Pb), and manganese (Mn) at levels below the current threshold limit values. On a group basis, abnormally high basal PRL shows a dose-related distribution among workers exposed to styrene, Pb, and Mn. On the basis of dose-response relationships, the benchmark doses (BMD) for styrene metabolites in urine, lead in blood (Pb-B), and Mn in urine (Mn-U), are 4 mg/g creatinine, 112 μg/L, and 0.3 μg/L, respectively. Noteworthy, the BMD for Mn-U and Pb-B is well below the upper reference limit. A shift in the distribution but not in the prevalence of abnormally high values of serum PRL was observed among perchloroethylene-exposed dry cleaners, which makes interpretation in terms of risk difficult. The measurement of PRL thus provides opportunities for early identification of excess exposure to neurotoxic chemicals affecting dopaminergic control of pituitary secretion. For styrene, Pb, and Mn the BMD provides an objective and statistically determined threshold, which seems to be in good agreement with the estimated no-observed-adverse-effect-level (NOAEL). The NOAEL, however, is based on traditional approaches that require the application of uncertainty factors, e.g., a default factor of 10 when extrapolating the NOAEL from the lowest-observed- adverse-effect-level (LOAEL). Due to its sensitivity to a number of potential confounders, caution must be exercised when using PRL as a screening test at the individual level. Also, age and sex dependent variations in susceptibility may hamper extrapolations from the occupational settings to the general population.