Changes in Blood Manganese Concentration and MRI T1 Relaxation Time During 180 Days of Stainless Steel Welding-Fume Exposure in Cynomolgus Monkeys

Abstract

Welders are at risk of being exposed to high concentrations of welding fumes and developing pneumoconiosis or other welding-fume exposure-related diseases. Among such diseases, manganism resulting from welding-fume exposure remains a controversial issue, as although the movement of manganese into specific brain regions has been established, the similar movement of manganese presented with other metals, such as welding fumes, has not been clearly demonstrated as being similar to that of manganese alone. Meanwhile, the competition between Mn and iron for iron transporters, such as transferrin and DMT-1, to the brain has also been implicated in the welding-fume exposure. Thus, the increased signal intensities in the basal ganglia, including the globus pallidus and subcortical frontal white matter, based on T1-weighted magnetic resonances in welders, require further examination as regards the correspondence with an increased manganese concentration. Accordingly, to investigate the movement of manganese after welding-fume exposure, 6 cynomolgus monkeys were acclimated for 1 mo and assigned to 3 dose groups: unexposed, low dose of (total suspended particulate [TSP] 31 mg/m3, 0.9 mg/m3 of Mn), and high dose of total suspended particulate (62 mg/m3 TSP, 1.95 mg/m3 of Mn). The primates were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h/day in an inhalation chamber system equipped with an automatic fume generator for 6 mo. Magnetic resonance imaging (MRI) studies of the basal ganglia were conducted before the initiation of exposure and thereafter every month. During the exposure, the blood chemistry was monitored every 2 wk and the concentrations of metal components in the blood were measured every 2 wk and compared with ambient manganese concentrations. The manganese concentrations in the blood did not show any significant increase until after 2 mo of exposure, and then reached a plateau after 90 days of exposure, showing that an exposure period of at least 60 days was required to build up the blood Mn concentration. Furthermore, as the blood Mn concentration continued to build, a continued decrease in the MRI T1 relaxation time in the basal ganglia was also detected. These data suggested that prolonged inhalation of welding fumes induces a high MRI T1 signal intensity with an elevation of the blood manganese level. The presence of a certain amount of iron or other metals, such as Cr and Ni, in the inhaled welding fumes via inhalation was not found to have a significant effect on the uptake of Mn into the brain or the induction of a high MRI T1 signal intensity.

Comparison of High MRI T1 Signals with Manganese Concentration in Brains of Cynomolgus Monkeys After 8 Months of Stainless Steel Welding-Fume Exposure

“…Slight increases in the manganese concentration were also found in the substantia nigra and basal ganglia (Yu et al, 2003a). In contrast, the same study conducted on non-human primates showed different results from a rodent study, where prolonged inhalation of welding fumes was found to induce a high MRI T1 signal intensity in the basal ganglia with an elevation of the blood manganese level (Sung et al, 2007). Accordingly, to identify the relationship between the manganese concentration in the brain and a high MRI signal intensity in the corresponding brain region, the present study exposed nonhuman primate cynomolgus monkeys to stainless steel welding fumes, while monitoring the change in the MRI signal intensity and examining the distribution of Mn in the brain regions.…”

“…When the robotic arm approached the base stainless-steel plate (SUS 304, 2.5 cm thick) in a zig-zag motion, an arc was produced and the rod was consumed, generating welding fumes. The fumes were then moved into exposure chambers (whole-body type, each 1.5 m 3 , Dusturbo, Seoul) that were rectangular in shape and made of metal with a Plexiglas window (Sung et al, 2007). Each chamber was able to accommodate 2 monkey cages and the total volume occupied by the two monkeys in a chamber was estimated as 1.3%.…”

“…The welding fumes were generated using an automatic robotic arm as a holding support for the welding rod (KST 308, 2.6 × 300 mm, Korea Welding Electrode Co. Ltd, Seoul) (Sung et al, 2007). When the robotic arm approached the base stainless-steel plate (SUS 304, 2.5 cm thick) in a zig-zag motion, an arc was produced and the rod was consumed, generating welding fumes.…”

“…The presence of a certain amount of iron or other metals, such as Cr and Ni, in the inhaled welding fumes was not found to have a significant effect on the uptake of Mn into the brain or the induction of a high MRI T1 signal intensity (Sung et al, 2007). Several pharmacokinetic studies on inhalation exposure to manganese have demonstrated that manganese readily accumulates in the olfactory and brain regions.…”

Biomarkers of Occupational Manganese Toxicity

“…However, experimental studies on laboratory animals have reported similar results, but studies in human societies have reported conflicting results [23][24] . The use of manganese concentrations in the blood has been studied as a biomarker of exposure to manganese among welders, metal workers, miners and workers making dry batteries [25][26][27][28][29][30][31][32][33][34][35][36] .…”