METAL FUME FEVER - CHARACTERIZATION OF CLINICAL AND PLASMA IL-6 RESPONSES IN CONTROLLED HUMAN EXPOSURES TO ZINC-OXIDE FUME AT AND BELOW THETHRESHOLD LIMIT VALUE

Results from animal and preliminary human exposure studies have called into question whether the 5 mg/m(3) 8-hour time-weighted average thre shold limit value (TLV) for zinc oxide fume is sufficient to protect w orkers against metal fume fever. The objectives of this study were to determine the clinical effects of exposures to low concentrations of z inc oxide and to ascertain whether these exposures elevated circulatin g levels of specific cytokines, which could account for the symptoms o f the metal fume fever syndrome. Thirteen resting naive subjects inhal ed, on separate days, air and 2.5 and 5 mg/m(3) of furnace-generated z inc oxide fume for 2 hours. Subjects recorded symptoms and temperature and had blood drawn before and after each exposure. The mean (+/-SE) maximum rise in oral temperature at 6 to 12 hours after exposure was 1 .4 +/- 0.3 degrees F after 5 mg/m(3), compared with 0.6 +/- 0.5 degree s F after air exposure (P < 0.05), Mean temperature was also elevated after exposure to 2.5 mg/m(3) zinc oxide (1.2 +/- 0.3 degrees). In a p arallel fashion, plasma levels of interleukin 6 (IL-6), a pyrogen, wer e significantly elevated after exposure to 5 mg/m(3) zinc oxide. Mean IL-6 values (pg/mL) at pre-exposure and at 3 and 6 hours post-exposure were 1.9 (+/-0.6), 2.8 (+/-0.7), and 2.9 (+/-0.6), respectively, on t he air day and 1.6 (+/-0.6), 4.4 (+/-1.2), and 6.4 (+/-1.1) on the 5 m g/m(3) zinc oxide clay. Zinc oxide exposure did not significantly affe ct plasma levels of tumor necrosis factor. Total symptom scores peaked 9 hours after the 5 mg/m(3) zinc oxide exposure. Myalgias, cough, and fatigue were the predominant symptoms reported. Inhalation of zinc ox ide for 2 hours at the current TLV of 5 mg/m(3) produces fever and sym ptoms along with elevation in plasma IL-6 levels.