Subchronic Dermal Toxicity and Oral Neurotoxicity of Triethylene Glycol Monomethyl Ether in Cd Rats

Abstract

These studies were conducted to evaluate the potential for repeated subchronic administration of triethylene glycol monomethyl ether (TGME) to produce systemic toxicity in the rat following dermal application, and neurotoxicity in the rat following peroral administration. The route of administration and maximum dose levels for these studies were specified by the U.S. Environmental Protection Agency (EPA) in a testing consent order for TGME. In the subchronic dermal toxicity study, TGME (undiluted) was applied to the clipped backs of CD rats (10 rats/sex/group) for 6 h/day (occluded), 5 days/wk or 13 wk at dose levels of 0, 0.4, 1.2, and 4.0 g/kg/day. Four groups of satellite animals (5 rats/sex/group) employed for interim hematology and clinical chemistry measurements were dosed in the same manner for 31 days. Experimental evaluations included clinical examinations, food consumption, body weight, ophthalmology, estrous cyclicity, hematology, clinical chemistry, urinalysis, and necropsy for all animals and microscopic examination of a complete set of tissues (including bone marrow smears) for animals in the control and high-dose treatment groups. In addition, the testes and epididymides were processed for examination of spermatocyte development. None of the experimental endpoints included in this study to evaluate the potential for systemic toxicity were affected by treatment with TGME. For the neurotoxicity study, TGME was mixed in the drinking water and administered ad libitum to rats