PULMONARY TOXICITY ASSESSMENTS OF INHALED ETHYLENE-OXIDE PROPYLENE-OXIDE COPOLYMER LUBRICANTS IN RATS

The pulmonary toxicities of 5 different ethylene oxide/propylene oxide (EO/PO) copolymer commercial lubricant candidates were assessed by ex posing groups of rats for 3 consecutive days (6 h/day) to aerosols of the different EO/PO test materials and evaluating pulmonary parameters at selected postexposure time periods. Because all 5 compounds could not be evaluated simultaneously, these studies were conducted over a p eriod of 2 wk. During wk 1 of the study, rats were exposed either to 2 2 mg/m(3) (mean value for the 3 days) of UCON 50-HB-5100 (50-HB-5100), to 110 mg/m(3) of Pluronic L31 (L31), or to 99.4 mg/m(3) of Pluronic L64 (L64). The mass median aerodynamic diameters (MMADs) for all 3 com pounds were <2.6 mu m. In the second group of studies, rat were expose d to 42 mg/m(3) of UCON 50-HB-2000 (50-HB-2000), or to 111 mg/m(3) of UCON 75-H-1400 (75-H-1400), with MMADs <1.8 mu m. Sham controls were e xposed to room air. One rat in the UCON 50-HB-5100 group died within 7 days postexposure. Similarly, 1 rat in the UCON 50-HB-2000 group died within 8 days postexposure. Within 48 h after exposure, the lungs of rats exposed to UCON 50-HB-5100 and 50-HB-2000 were edematous. The lun gs of rats were lavaged at 0 h (i.e., immediately after), 2 days, 1 wk , 1 and 3 mo post-exposure. Cellular and biochemical data on samples r ecovered from bronchoalveolar lavage (BAL) demonstrated a substantial pulmonary inflammatory response concomitant with increases in BAL flui d levels of lactate dehydrogenase (LDH), protein, alkaline phosphatase , and N-acetylglucosaminidase in the lungs of rats exposed to UCON 50- HB-5100. Similarly the BAL biochemical and pulmonary cell differential data for 50-HB-2000-exposed rats were similar but less severe to that previously measured in 50-HB-5100-exposed rats. In contrast, the lung s of rats exposed to Pluronic L31 and L64 and UCON 75 H-1400 demonstra ted only slight amd reversible pulmonary inflammatory effects. The res ults from this study validate this inhalation bioassay technique for p redicting the pulmonary toxicity study with these same compounds. In t he earlier study, UCON 50-HB-5100 and UCON 50-HB-2000 produced severe pulmonary toxicity in rats. The cellular and biochemical results prese nted here confirm the earlier findings of significant pulmonary toxici ty produced by inhalation of the UCON 50-HB-5100 and UCON 50-HB-2000 c ompounds. In contrast, the three other compounds (Pluronic L31, Pluron ic L64, UCON 75-H-1400) produced only weak pulmonary inflammatory effe cts following 3-day exposures at high aerosol concentrations.