Metal exposure from additive manufacturing and its effect on the nasal lavage fluid proteome - a pilot study

Abstract

The use of metal additive manufacturing (AM) is steadily increasing and is an emerging concern regarding occupational exposure. In this study, non-invasive sampled nasal lavage fluid (NLF) from the upper airways was collected from metal AM operators at the beginning and end of a workweek during two consecutive years with preventive interventions in the occupational setting in-between (n = 5 year 1, n = 9 year 2). During year one, NLF was also collected from welders (n = 6) from the same company to get a comparison with a traditional manufacturing technique with known exposure and health risks. The samples were investigated using untargeted proteomics, as well as using multi-immunoassay to analyze a panel of 71 inflammatory protein markers. NLF in AM operators from year 1 showed decreased levels of Immunoglobulin J and WAP four-disulfide core domain protein 2 and increased levels of Golgi membrane protein 1, Uteroglobin and Protein S100-A6 at the end of the workweek. At year two, after preventive interventions, there were no significant differences at the end of the workweek. In welders, Annexin A1 and Protein S100-A6 were increased at the end of the workweek. The analysis of 71 inflammatory biomarkers showed no significant differences between the beginning and the end of workweek year 1 in AM operators. We identified several proteins of interest in the AM operators that could serve as possible markers for exposure in future studies with a larger cohort for validation.

Occupational exposure and health surveys at metal additive manufacturing facilities

“…Our measurements confirm that, even though inhalable dust levels are generally low compared to Swedish OELs, specific work tasks can emit high levels of airborne particles, such as open powder handling or post-processing of builds, risking possible exposure. This is in line with our earlier studies on a single site that had potential exposure, which were reduced after the company introduced several preventive actions ( 5 , 32 , 36 ). Expanding our investigations by increasing the number of companies and AM processes, we confirm that the chosen methodology can be successfully applied in the AM setting.…”

“…We have earlier shown that virgin metal AM powder, when used in powder bed fusion laser beam (PBF-LB) machinery, changes to include a large bulk of smaller particles that may constitute different risks to the AM machine user (AMMU) ( 4 ). Furthermore, we have thoroughly investigated AMMU at a specific site with serial production of AM components, examining their exposure, biological markers, and effects in the nasal mucosa ( 5 , 32 , 36 ). However, these earlier studies were limited to a single AM technique, two different AM powders, and a smaller number of AMMUs.…”

Characterizing Nanoparticle Release Patterns of Laser Powder Bed Fusion in Metal Additive Manufacturing: First Step Towards Mitigation Measures

“…Recent Northern European studies, with results similar to ours in terms of concentration and size of metal NP, demonstrated skin and systemic exposure (detected in urine) in a AM facility workers, and consequent alterations in indicators of inflammation and liver function, with normalization after exposure prevention interventions (Ljunggren et al, 2019(Ljunggren et al, , 2021Assenhöj et al, 2021), stressing once again the need for adequate methods of assessment and control of exposure.…”

S100A6 Protein—Expression and Function in Norm and Pathology

“…It has been also detected in extracellular matrix of Wharton’s jelly [ 144 ], amnion fluid [ 145 ], pancreatic juice [ 107 , 146 ], urine [ 147 , 148 ] and tears [ 149 ]. Recent results have shown that S100A6 is present in nasal lavage fluid [ 150 ], and its level is elevated in the nasal swabs of COVID-19 patients [ 151 ]. The role of extracellular S100A6 has not been extensively studied.…”