To Örebro University

Purpose: Occupational particle exposure constitutes a known health hazard in many occupations, while the risks are still largely unknown in more recent industries, like additive manufacturing. The purpose of this study was to investigate how particle exposure in different metal industries affects blood biomarkers known to indicate biological effects on lungs, cardiovascular system, liver, kidneys, and inflammation. The aim was also to understand if particle exposures from different work environments induce similar or distinct biological responses.

Methods: Five cohorts with particle exposure measurement and biomarker data were included in the study: two iron foundry cohorts (40 and 85 participants), one welding cohort (136 participants), one hard metal industry cohort (72 participants), and one additive manufactur-ing cohort (87 participants). Individual dust exposure levels were calculated based on respirable and on inhalable dust exposure measurements, adjusted for respirator use. Biomarker levels were compared to i) control groups vs. exposed individuals within each cohort, or ii) correlated to exposure across all cohorts. The five cohorts were combined into one comprehensive analysis to find common biomarkers of exposure. Biomarker levels were normalized across cohorts using the z-transform based on the control groups, and the normalized biomarker data were correlated to particle exposure levels. Kendall τ correlation was used without covariate correction, and Pearsson correlation as well as ANOVA analysis was used with covariates (age, BMI, sex, smoking, cohort).

The biomarkers were conceptually categorized into six groups, including biomarkers of lung injury (mucin 1, surfactant protein D, CC16, MMP7), cardiovascular impact (ApoA1, ApoB, ApoB/ApoA1 ratio, sST2, vWF, PON1 activity), liver toxicity (ASAT, ALAT, ALP), kidney toxicity (urinary a1 microglobulin), NLRP3 inflammasome activation (IL-1b, IL-18, IL-1Ra), and general inflammation (CRP, SAA, MIP4, sRAGE).

Results: The highest mean respirator adjusted dust exposure was found in the foundry cohorts, followed by additive manufacturing, welding, and finally hard metal industry. When comparing biomarkers of controls and exposed for the cohorts, cardiovascular markers were the once that were most consistently significantly different using Wilcoxon-test, with three out of five cohorts demonstrating differences in ApoB/ApoA1-ratio and sST2-levels. When comparing dust exposure to biomarkers across all cohorts, ALAT was significantly correlated to exposure using Kendall τ (p 0.03) as well as in ANOVA analysis, including correction for covariates (p 0.03). These results indicate that metal dust exposure may put a stress on the cardiovascular system and liver, regardless of metal industry exposure, and that exposure to secondary organs, during clearing of the particles from the lungs, is an important health aspect to consider in regard to exposure of inhaled metal particles.