Triethylene Glycol Ethers: Evaluations of In Vitro Absorption Through Human Epidermis, 21-Day Dermal Toxicity in Rabbits, and a Developmental Toxicity Screen in Rats

Abstract

The methyl, ethyl, and butyl ethers of triethylene glycol (TM, TE, and TB, respectively) were evaluated in three screening studies to assess their potential hazards to humans. The assessments included (1) an in vitro procedure to determine the ability of the materials to penetrate human skin, (2) a 21-day dermal limit test in rabbits to determine potential systemic toxicities, and (3) a screening procedure to evaluate the chemicals' potentials to induce developmental toxicity. In the in vitro dermal absorption procedure, the three test materials crossed human epidermis at molar rates 170-330 times more slowly than the lower molecular weight homolog ethylene glycol methyl ether (EM), a chemical known to induce systemic effects following skin application. In the 21-day dermal study, daily applications of 1000 mg/kg TM, TE, or TB did not produce systemic toxicity in male or female rabbits, including hematologic or testicular effects. The low dermal penetration rate of the triethylene glycol ethers may have played a role in this outcome. In the developmental toxicity screening test, oral doses of 1000 mg/kg given on Days 6-15 of gestation did not produce maternal toxicity in rats and had no effect on viability or growth of offspring, pre-or postnatally, indicating low developmental toxic potential for these compounds. The results of these studies indicate that triethylene glycol methyl, ethyl, and butyl ethers have very low capacities to be absorbed through the skin of exposed individuals, low potentials to produce systemic toxicity following oral or dermal exposures, and do not appear to be selectively toxic to the developing conceptus. The data clearly indicate that triethylene glycol ethers do not exhibit toxicologic profiles comparable to those of the methyl and ethyl ethers of ethylene glycol.