Pulmonary effects of machining fluids in guinea pigs and mice

Acute pulmonary effects of inhalation exposure to (unused) neat and in-use metalworking fluids (MWF) were studied to evaluate the potency of characterized MWF in terms of their effects on breathing and lung inflammation. Inhalation exposure of guinea pigs caused dose-dependent changes in respiratory rate and volume that were used to quantify potency. In-use MWF was consistently more toxic than the corresponding neat MWF. Significant predictors of respiratory responses were whether MWF was neat or in-use (p = 0.0001), exposure concentration (p = 0.022), MWF formulation (p = 0.031), and the particular in-use MWF tested (p = 0.032). Inhalation exposures to MWF biocides resulted in dose-dependent sensory irritation responses. Guinea pig studies revealed significant inflammation resulting from MWF exposure marked by change in bronchoalveolar lavage (BAL) fluid from 3% neutrophils (controls) to 60-79% (MWF-exposed) and 25-fold increase in total BAL cells. The in-use MWF ranged in endotoxin concentration from 280 to 1.7 x 10(5) endotoxin units (EU)/mL. To investigate the role of endotoxin, studies were carried out in mice sensitive (SEN) and resistant (RES) to endotoxin. SEN mice revealed a dose-dependent 10,000-fold increase in BAL neutrophils and a 100-fold increased concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) following inhalation exposure to in-use MWF. This inflammatory response was not observed with exposure to neat MWF or with sham exposure. RES mice demonstrated virtually no response to the inhaled MWF for total cells, neutrophils, IL-6, or TNF-alpha. Removal of microorganisms by filtration of the in-use MWF did not change the responses observed in either strain. These studies demonstrate that lung inflammation may be an important outcome from exposure to in-use MWF and that endotoxin is a toxicant of importance.