Validity of self-reported concentration and memory problems: Relationship with neuropsychological assessment and depression.

BACKGROUND: This study investigated the validity of self-reported concentration and memory problems (CMP) in residents environmentally exposed to manganese (Mn). METHOD: Self-report of CMP from a health questionnaire (HQ) and the Symptom Checklist-90-Revised (SCL-90-R) was compared to neuropsychological assessment (Trails A&B; Digit Span; Digit Symbol; Similarities; Auditory Consonant Trigrams, ACT; NAB Memory; Rey-Osterrieth, Rey-O, Delayed). Participants included 146 residents from Ohio exposed to air-Mn, with a modeled average concentration of 0.55 µg m-3 (range = 0.01-4.58). RESULTS: Residents were primarily White (94.5%), aged 30-64 years (M = 51.24), with a minimum of 10 years of residence (range = 10-64). Ninety-four (65.3%) participants reported concentration problems, and 107 residents (73.3%) reported memory problems. More participants endorsed CMP on the SCL-90-R than on the HQ. The prevalence of self-reported CMP was higher for women than for men (88.4% vs. 68.3%). Point-biserial and Pearson's correlations between self-reported CMP and neuropsychological test scores were nonsignificant and weak for both the HQ (rpb = -.20 to rpb = .04) and the SCL-90-R (r = -.12 to r = .007). Greater levels of depression, anxiety, and female sex predicted having more self-reported CMP on both the HQ and the SCL-90-R. Air-Mn and blood-Mn were not associated with self-reported CMP. Residential distance from the Mn source accounted for a small proportion of variance (sr2 = .04), although depression remained the largest predictor (sr2 = .21). CONCLUSION: These results indicate that self-report of CMP in Mn-exposed residents appear to be invalid when compared to neuropsychological test scores. The participants' misperception of having CMP is associated with less education and higher levels of depression. Neuropsychological assessment is recommended to attain valid results.

A tissue dose-based comparative exposure assessment of manganese using physiologically based pharmacokinetic modeling-The importance of homeostatic control for an essential metal.

A physiologically-based pharmacokinetic (PBPK) model (Schroeter et al., 2011) was applied to simulate target tissue manganese (Mn) concentrations following occupational and environmental exposures. These estimates of target tissue Mn concentrations were compared to determine margins of safety (MOS) and to evaluate the biological relevance of applying safety factors to derive acceptable Mn air concentrations. Mn blood concentrations measured in occupational studies permitted verification of the human PBPK models, increasing confidence in the resulting estimates. Mn exposure was determined based on measured ambient air Mn concentrations and dietary data in Canada and the United States (US). Incorporating dietary and inhalation exposures into the models indicated that increases in target tissue concentrations above endogenous levels only begin to occur when humans are exposed to levels of Mn in ambient air (i.e. >10µg/m3) that are far higher than those currently measured in Canada or the US. A MOS greater than three orders of magnitude was observed, indicating that current Mn air concentrations are far below concentrations that would be required to produce the target tissue Mn concentrations associated with subclinical neurological effects. This application of PBPK modeling for an essential element clearly demonstrates that the conventional application of default factors to "convert" an occupational exposure to an equivalent continuous environmental exposure, followed by the application of safety factors, is not appropriate in the case of Mn. PBPK modeling demonstrates that the relationship between ambient Mn exposures and dose-to-target tissue is not linear due to normal tissue background levels and homeostatic controls.

Exposure-response relationship and risk assessment for cognitive deficits in early welding-induced manganism.

OBJECTIVE: The exposure-response relationship for manganese (Mn)-induced adverse nervous system effects is not well described. Symptoms and neuropsychological deficits associated with early manganism were previously reported for welders constructing bridge piers during 2003 to 2004. A reanalysis using improved exposure, work history information, and diverse exposure metrics is presented here. METHODS: Ten neuropsychological performance measures were examined, including working memory index (WMI), verbal intelligence quotient, design fluency, Stroop color word test, Rey-Osterrieth Complex Figure, and Auditory Consonant Trigram tests. Mn blood levels and air sampling data in the form of both personal and area samples were available. The exposure metrics used were cumulative exposure to Mn, body burden assuming simple first-order kinetics for Mn elimination, and cumulative burden (effective dose). Benchmark doses were calculated. RESULTS: Burden with a half-life of about 150 days was the best predictor of blood Mn. WMI performance declined by 3.6 (normal = 100, SD = 15) for each 1.0 mg/m3 x mo exposure (P = 0.02, one tailed). At the group mean exposure metric (burden; half-life = 275 days), WMI performance was at the lowest 17th percentile of normal, and at the maximum observed metric, performance was at the lowest 2.5 percentiles. Four other outcomes also exhibited statistically significant associations (verbal intelligence quotient, verbal comprehension index, design fluency, Stroop color word test); no dose-rate effect was observed for three of the five outcomes. CONCLUSIONS: A risk assessment performed for the five stronger effects, choosing various percentiles of normal performance to represent impairment, identified benchmark doses for a 2-year exposure leading to 5% excess impairment prevalence in the range of 0.03 to 0.15 mg/m3, or 30 to 150 microg/m3, total Mn in air, levels that are far below those permitted by current occupational standards. More than one-third of workers would be impaired after working 2 years at 0.2 mg/m3 Mn (the current threshold limit value).