may ensue, with the potential to exacerbate cardiovascular effects produced by the metabolic acidosis. Deposits of calcium oxalate crystals in the renal interstitium have been proposed as contributing to renal dysfunction through physical damage and blockage of the tubules. Evidence has also been presented that other acid metabolites, including glycolic acid and glyoxylic acid, contribute to renal toxicity through direct cytotoxic effects on the renal tubular epithelium. Frantz and colleagues (1996) demonstrated that differences in the metabolism and kinetics of ethylene glycol between mice and rats are related to the differential susceptibility of the two species to ethylene glycol. Metabolic acidosis and an increased osmolal gap may also contribute to renal toxicity by altering intracellular osmotic pressure.

Diethylene glycol shares with ethylene glycol the ability to produce renal toxicity (BIBRA, 1993; Snyder and Andrews, 1996). In contrast with ethylene glycol, however, it does not produce metabolic acidosis or calcium oxalate crystals. The observation that diethylene glycol produces identical lesions and is a more potent nephrotoxicant has been presented to support the contribution of non-oxalic acid metabolites to glycol-mediated nephrotoxicity.

Glycol ethers are used extensively in consumer products, including paints and textile dyes; as an anti-icer in brake fluids; and as a gasoline additive (Bruckner and Warren, 2001). This section discusses ethylene glycol monomethyl ether (EM), ethylene glycol monoethyl ether (EE), propylene glycol monomethyl ether (PM), and ethylene glycol monobutyl ether (EB) (see Figure 4.5 for structures).

FIGURE 4.5 Structure of glycol ethers and their metabolites.

a) ethylene glycol ethers, and b) propylene glycol ethers. Abbreviations: EM, ethylene glycol monomethyl ether; EB, ethylene glycol monobutyl ether; PM, propylene glycol monomethyl ether; PE, propylene glycol monoethyl ether; PB, propylene glycol monobutyl ether.

Although ingestion of glycol ethers is not acutely hazardous, reproductive toxicity and teratogenicity are of concern in connection with some of them (Bruckner and Warren,