Respirable indium exposures, plasma indium, and respiratory health among indium-tin oxide (ITO) workers

Abstract

Background: Workers manufacturing indium-tin oxide (ITO) are at risk of elevated indium concentration in blood and indium lung disease, but relationships between respirable indium exposures and biomarkers of exposure and disease are unknown.

Methods: For 87 (93%) current ITO workers, we determined correlations between respirable and plasma indium and evaluated associations between exposures and health outcomes.

Results: Current respirable indium exposure ranged from 0.4 to 108 μg/m(3) and cumulative respirable indium exposure from 0.4 to 923 μg-yr/m(3) . Plasma indium better correlated with cumulative (rs = 0.77) than current exposure (rs = 0.54) overall and with tenure ≥1.9 years. Higher cumulative respirable indium exposures were associated with more dyspnea, lower spirometric parameters, and higher serum biomarkers of lung disease (KL-6 and SP-D), with significant effects starting at 22 μg-yr/m(3) , reached by 46% of participants.

Conclusions: Plasma indium concentration reflected cumulative respirable indium exposure, which was associated with clinical, functional, and serum biomarkers of lung disease. Am. J. Ind. Med. 59:522-531, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Keywords: KL-6; SP-D; cumulative exposure; indium-tin oxide; spirometry.

FIGURE 1

Correlation between current (left) and cumulative (right) indium exposure and plasma indium concentration among workers at an indium-tin oxide facility. Current exposure values were assigned on the basis of indium concentrations measured for a participant’s current job; cumulative exposure values account for the time a participant spent in each job during employment at the facility. Both air and plasma values plotted using a log scale. The relationship between log transformed plasma indium and log transformed cumulative indium was given by the following equation: Ln (Plasma Indium) =−2.35 +0.662*Ln (Cumulative Indium), R² =0.60, P <0.05. r_s = Spearman’s rank correlation coefficient.

FIGURE 2

Restricted cubic splines show non-linear relationships between spirometric parameters (top) and serum biomarkers of interstitial lung disease (bottom) on the vertical axis and cumulative indium exposure on the horizontal axis, adjusted for smoking status (current/former/never). Splines for FEV₁/FVC ratio, KL-6, and SP-D are also adjusted for age (years). Cumulative indium exposure values account for the time a participant spent in each job during employment at the facility. The splines model the difference in the value of the health outcome at any given value of cumulative exposure compared to a cumulative indium exposure value of 0.44 μg/L. Individual cumulative indium exposure values (observations) are indicated by the crosses above the x-axis. FEV₁, forced expiratory volume in 1s; FVC, forced vital capacity; KL, Krebs von den Lungen; SP-D, surfactant protein-D; CL, confidence limit; Obs, observation.

FIGURE 3

Histograms showing the distributions of current (left) and cumulative (right) respirable indium exposures of the study participants. Reference lines show the percent of participants with exposures greater than those associated with changes in health outcomes. For cumulative exposure, reference lines indicate 46% >22 μg-years/m³ (decline in percent predicted FEV₁); 43% >30 μg-years/m³ (decline in FEV₁/FVC ratio); 36% >63 μg-years/m³ (increase in KL-6); 9% >232 μg-years/m³ (decline in percent predicted FVC); and 8% >240 μg-years/m³ (increase in SP-D). For current exposure, reference lines indicate 82% >0.6 μg/m³; 82% >0.8 μg/m³; 82% >1.6 μg/m³; 41% >5.8 μg/m³; and 41% >6 μg/m³. These values were chosen because they reflect the current exposures that would lead to cumulative exposures of 22, 30, 63, 232, and 240 μg-years/m³ after 40 years.