Respiratory peripheral chemosensory irritation, acute and repeated exposure toxicity studies with aerosols of triethylene glycol

The potential for adverse effects from exposure to respirable aerosols of triethylene glycol (TEG: CAS Number 112‐27‐6) was investigated by a peripheral chemosensory irritation study, and by acute and repeated exposure toxicity studies. The sensory irritation study, conducted with male Swiss Webster mice, showed an exposure concentration‐related depression of breathing rate that allowed the calculation of an RD50 of 5140 mg m−3. In an acute study male and female Sprague Dawley rats were exposed whole body to aerosols of TEG up to 6730 mg m−3 for 4 h. No mortalities occurred at this high concentration, but unexplained mortality occurred in female rats at 5230 mg m−3 at 2–3 days postexposure. Two repeats of the 5230 mg m−3 exposure did not cause mortality. Signs at 6730 and 5230 mg m−3 were limited to those of irritancy. For a 9 day repeated exposure study rats were exposed whole body to 0, 494, 2011 and 4824 mg m−3 TEG aerosols for 6 h day−1. Mortalities occurred at 4824 mg m−3 between exposure days 2 and 5. Nonspecific indications of toxicity at 2011 mg m−3 were signs of irritation, decreased body weight and increased food and water consumption; evidence of hepatic dysfunction was indicated by increased serum alkaline phosphatase and alanine aminotransferase activities, but liver histology was normal. Fluid imbalance was suggested by increases in water consumption, blood urea nitrogen, relative kidney weight and urine volume, with decreased urine osmolality, pH and N‐acetyl‐β‐D‐glucosaminidase activity. At 494 mg m−3 there were minimal signs of irritation, increased water consumption and slightly increased alkaline phosphatase; histology of the kidney was normal. Thus, in this 9 day repeated aerosol whole body exposure study a No‐Observed‐Effect‐Level (NOEL) could not be established. Since preening of the fur at these high aerosol concentrations exposures might have led to a confounding factor from the resultant oral intake, another 9 day repeated aerosol study was conducted, but by nose‐only exposure of rats for 6 h day−1 to TEG aerosol concentrations of 0, 102, 517 and 1036 mg m−3. In this study there were no clinical signs, no effects on food and water consumption, and no biochemical or histological evidence of hepatorenal dysfunction. By the end of the exposure period, male and female rats of the 1036 mg m−3 group had body weights lower than those of the controls, but not with statistical significance. Since there were no statistically significant effects on any monitors, 1036 mg m−3 is considered to be a threshold for toxicity by nose‐only exposure to TEG aerosol. The findings indicate that exposure to a respirable aerosol is not acutely harmful, but may cause sensory irritant effects. Repeated exposure to high concentrations of TEG aerosols may be harmful, particularly if there are contributions from additional routes of exposure. Copyright © 2006 John Wiley & Sons, Ltd.