Relative Toxicity of Di(2-Ethylhexyl) Sebacate and Related Compounds in an in Vivo Hamster Bioassay

Abstract

The acute pulmonary toxicity of di(2-ethylhexyl) sebacate (DEHS) was examined in a bioassay and compared to the responses seen with other materials suggested as suitable aerosols for human studies. Suspensions of DEHS, di(2-ethylhexyl) phthalate (DEHP), com oil, mineral oil, and hexaethylene glycol (2.5%, w/v) in saline were instilled (0.15 ml/100 g body weight) into the lungs of hamsters. The resultant dose of oil was 3.75 mg/100 g. Control hamsters were instilled with physiological saline. One day later the hamsters were killed, and the lungs were lavaged. Biochemical and cellular components of the lavage fluid were then analyzed. Measurements included indicators of inflammation, edema, bleeding, macrophage phagocytosis, cell injury, and cell secretion. All values for these oils were either within or below control levels. In contrast, earlier studies with mineral dusts at the same dose demonstrated dramatic changes in these indicators. Our results suggest that DEHS, DEHP, corn oil, mineral oil, and hexaethylene glycol cause negligible acute pulmonary toxicity in hamsters when given at doses as high as 3.75 mg/100 g body weight. When these substances are used at far lower doses as inhaled aerosols for human studies of particle deposition or quantitative respirator fit testing, we believe it is unlikely that any acute pulmonary toxicity would result. The chronic effects and pharmacokinetics of these substances warrant further study, particularly if they are used in humans at higher concentrations or for chronic exposures.