Abstract

Long-term, high-level exposure to manganese (Mn) is associated with impaired central nervous system (CNS) function. We quantitatively explored relations between low-level Mn exposure and selected neurological outcomes in a longitudinal inception cohort of asymptomatic welder trainees. Welders with no previous occupational Mn exposure were observed approximately every three months over the course of the five-quarter traineeship. Fifty-six welders were assessed for motor function using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) and Grooved Pegboard tests. A subset of 17 also had MRI scans to assess T1-weighted indices. Personal exposure to Mn in welding fume was quantitatively assessed during the study period using a mixed model to obtain estimates of subject-specific exposure level by welding type. These estimates were summed to estimate cumulative exposure at the time of each neurological outcome test. When adjusting for possible learning effects, there were no associations between cumulative exposure and UPDRS3 score or Grooved Pegboard time. T1-weighted indices of the basal ganglia (caudate, anterior putamen, posterior putamen, and combined basal ganglia, but not the pallidal index) exhibited statistically significant increases in signal intensity in relation to increased cumulative Mn exposure. This study demonstrates that T1-weighted changes can be detected in the brain even at very low levels of exposure among humans before any clinically evident deficits. This suggests that with continued follow-up we could identify a T1 threshold of toxicity at which clinical symptoms begin to manifest.

Highlights

  • MethodsWelders with no previous occupational Mn exposure were observed approximately every three months over the course of the five-quarter traineeship

  • Manganism is a syndrome characterized by parkinsonism features, dystonia, and cognitive dysfunction, clinical features common to idiopathic Parkinson’s disease [3]

  • The American Conference of Governmental Industrial Hygienists’ (ACGIH) 8-hour timeweighted average threshold limit value (TWA TLV) for Mn in total inhalable dust was recently reduced to 0.1 mg/m3 and the respirable TLV was reduced to 0.02 mg/m3, based on neurological outcomes seen in workers exposed to low levels of Mn [8]

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Summary

Methods

Welders with no previous occupational Mn exposure were observed approximately every three months over the course of the five-quarter traineeship. Personal exposure to Mn in welding fume was quantitatively assessed during the study period using a mixed model to obtain estimates of subject-specific exposure level by welding type These estimates were summed to estimate cumulative exposure at the time of each neurological outcome test. Subjects included 56 welder trainees enrolled in a 5-quarter welding training program at a technical college in Washington State who joined our cohort prior to occupational exposure to Mn. All 56 enrolled subjects underwent longitudinal UPDRS3 and Grooved Pegboard tests, and 17 underwent repeat MRI measures. Upon entry to the study, and at the end of each academic quarter (approximately ten weeks), all subjects completed the Grooved Pegboard test and UPDRS3 examination. On completion of the study, co-investigators at Washington University (WU, St Louis, MO, USA) interpreted all UPDRS3 examinations and MRI scans, which had been stripped of any time- or subject-identifying information

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Conclusion

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