Respiratory manganese particle size, time-course and neurobehavioral outcomes in workers at a manganese alloy production plant ; Neurotoxicology

The progression of manganism with chronic exposure to airborne manganese (Mn) is not well understood. Here, we further investigate the findings on exposure and neurobehavioral outcomes of workers from a silico- and ferromanganese production plant and non-exposed workers from the same community in 1990 and 2004, using a variety of exposure metrics that distinguish particle size and origin within the range of respirable airborne exposures. Mn exposure matrices for large respirable particulate (Mn-LRP, dust) and small respirable particulate (Mn-SRP, fume), based on process origins, were used together with detailed work histories since 1973 (plant opening), to construct exposure metrics including burdens and cumulative burdens with various clearance half-lives. For three out of eight 1990 neurobehavioral tests analyzed with linear regression models, duration of Mn exposure was the best predictor: Luria-Nebraska Neuropsychological Battery - Motor Scale, Trail-Making B and Finger Tapping. The Luria-Nebraska Motor Scale had the strongest association (t ∼ 5.0, p < 10(-6)). For outcomes on three other tests, the duration and Mn-SRP metrics were comparable: Trail Making Test A, Cancellation H and Stroop Color-Word Test (color/word subtest). Delayed Word Recall was best predicted by Mn-SRP (based on square root or truncated air-concentrations). The Word score on the Stroop Color-Word Test was the only outcome for which Mn-LRP was the leading predictor (t = -2.92, p = 0.003), while performance on the WAIS-R Digit Span Test was not significantly predicted by any metric. For outcomes evaluated in both 1990 and 2004, a mixed-effect linear regression model was used to examine estimates of within-individual trends. Duration and Mn-SRP were associated with performance on the Luria-Nebraska Motor Scale, as well as with other outcomes that appeared to have both reversible and progressive features, including Trail Making A and B, Cancellation H and Delayed Word Recall. With the mixed-effect model, Digit Span exhibited a ...