FIGURE 4.4 Structure of various glycols.

Ethylene glycol, propylene glycol, diethylene glycol, and hexylene glycol differ greatly in their potential to produce acute or chronic toxicity (ATSDR, 1997c; BIBRA, 1991, 1993; Lakind et al., 1999; Ruddick, 1972; Snyder and Andrews, 1996). Glycols are metabolized through successive oxidative steps, and the resulting metabolites account for the observed differences in toxicity among the glycols (ATSDR, 1997c; Lakind et al., 1999; Ruddick, 1972; Snyder and Andrews, 1996). Propylene glycol, which is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase to lactate, that can be used in gluconeogenesis, has low toxicity. The principal metabolic pathway for ethylene glycol proceeds through glycoaldehyde, glycolic acid, glyoxylic acid, and oxalic acid. The rate-limiting step in this pathway is the oxidation of glycolic acid to glyoxylic acid. As a result, substantial concentrations of glycolic acid accumulate. The buildup of glycolic acid is thought to be a major factor in the metabolic acidosis involved in the toxicity of ethylene glycol.

Renal toxicity of ethylene glycol or diethylene glycol has been observed in experimental animals (including rodents, primates, canines, and felines) after oral, dermal, and inhalation exposure (ATSDR, 1997c; Lakind et al., 1999; Snyder and Andrews, 1996). The renal lesions produced are similar among species, but humans and cats are 2–5 times more sensitive than rodents and dogs. The lesions observed include renal tubular epithelial degeneration and necrosis. The clinical signs associated with the renal toxicity include polyuria, anuria, crystaluria, and oliguria.

The mechanism of renal toxicity is a matter of debate, and several contributing mechanisms have been proposed (Lakind et al., 1999). The oxalic acid metabolite chelates calcium, generating calcium oxalate, which precipitates in numerous organs. Hypocalcemia



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