Subchronic peroral toxicity of triethylene glycol in the Fischer 344 rat

Ethylene and diethylene glycols produce systemic toxicity, including nephro toxicity, by acute and repeated po dosing. To determine the Potential for t riethylene glycol (TEG; CAS Number 112-27-61) to produce nephrotoxicity, or other organ/tissue injury, a subchronic (90-d) study was conducted by cont inuous inclusion of TEG in the diet of Fischer 344 rats. This was preceded by a probe 14-d study. For both studies the dietary concentrations were 0 p pm (control). 10,000, 20,000 or 50,000 ppm TEG, resulting in daily TEG cons umptions in the 14-d study of 1132, 2311 or 5916 mg/kg with males, and 1177 , 2411 or 6209 mg/kg with females. The corresponding values for the 90-d st udy were 748, 1522 or 3849 mg/kg (males), and 848, 1699 or 4360 mg/kg (fema les). In the 14-d study there were no mortalities or clinical signs, and no effects on body weight, hematology, serum chemistry, organ weights. and gr oss or microscopic pathology. Food consumption was increased at the high do sage. Urinalysis showed increased urine volume and decreased pH with high d ose males and females. and increased volume with mid-dose males. In the sub chronic study there was neither mortality nor signs of toxicity. and no dos age-related effects with serum chemistry. gross and microscopic pathology. Body weights were reduced during the dosing period with both males and fema les of the high dosage, Body weight gains were reduced at all dosages with males and females. No hematological effects were seen with females, but mal es of the mid- and high-dosage groups had slightly reduced erythrocyte coun t and hematocrit, and high-dose males had decreased hemoglobin concentratio n with increased mean corpuscular volume. These were considered to reflect a mild hemodilution related to the absorption of large TEG doses. Urinalysi s showed dosage-related decreased pH, and increased urine volume mainly at the high dose. These were probably related to the renal excretion of absorb ed TEG and/or metabolites. Kidney weight was increased for high-dose female s, and increased relative (to body) weight of kidneys for males and females from the mid- and high-dose groups were observed, probably related to the renal excretion of the absorbed TEG and/or its metabolites. These findings indicate that the subchronic continuous po dosing of TEG to rats does not r esult in local or systemic specific organ or tissue toxicity. These finding s contrast with the known repeated po toxicity, notably nephrotoxicity, pro duced by ethylene and diethylene glycols. Thus, TEG has significantly lesse r potential for systemic toxicity by the po route than its lower molecular weight homologues.