Pulmonary Toxicity Assessments Of Inhaled Ethylene Oxide/Propylene Oxide Copolymer Lubricants In Rats

Abstract

The pulmonary toxicities of 5 different ethylene oxide/propylene oxide (EO/PO) copolymer commercial lubricant candidates were assessed by exposing groups of rats for 3 consecutive days (6 hlday) 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 period of 2 wk. During wk 1 of the study, rats were exposed either to 22 mg/m³ (mean value for the 3 days) of UCON 50-HB-5100 (50-HB-5100), to 110 mg/m³ of Pluronic L31 (131), or to 99.4 mg/m³ of Pluronic L64 (L64). The mass median aerodynamic diameters (MMADs) for all 3 compounds were < 2.6 μm. In the second group of studies, rats were exposed to 42 mg/m³ of UCON 50-HB-2000 (50-HB-2000), or to 111 mg/m³ of UCON 75-H-1400 (75-H-1400), with MMADs < 1.8 μm. Sham controls were exposed to room air. One rat in the UCON 50-HB-5W0 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-5W0 and 50-HB-2000 were edematous. The lungs of rats were lavaged at 0 h (i.e., immediately after), 2 days, 1 wk, 1 and 3 mo postexposure. Cellular and biochemical data on samples recovered from bronchoalveolar lavage (BAD demonstrated a substantial pulmonary inflammatory response concomitant with increases in BAL fluid 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 lungs of rats exposed to Pluronic 131 and L64 and UCON 75 H-1400 demonstrated only slight and reversible pulmonary inflammatory effects. The results from this study validate this inhalation bioassay technique for predicting the pulmonary toxicity of inhaled aerosols by confirming the effects measured in a previous 2-wk inhalation toxicity study with these same compounds. In the earlier study, UCON 50-HB-5W0 and UCON 50-HB-2000 produced severe pulmonary toxicity in rats. The cellular and biochemical results presented here confirm the earlier findings of significant pulmonary toxicity produced by inhalation of the UCON 50-HB-5W0 and UCON 50-HB-2000 compounds. In contrast, the three other compounds (Pluronic L31, Pluronic L64, UCON 75-H-1400) produced only weak pulmonary inflammatory effects following 3-day exposures at high aerosol concentrations.