in primates by the production of its metabolite formate at exposures that do not produce substantial CNS depression (ATSDR, 1993; Tephly, 1991); these effects occur after high-dose exposure. Considerable differences exist among species in the capacity of their folate-dependent one-carbon pool to metabolize formate. In nonprimates, formate is metabolized rapidly; in primates, it is metabolized slowly and accumulates, leading to metabolic acidosis and ocular damage. The relative deficit in formate metabolism in primates has been attributed to lower tissue folate concentrations. It is consistent with that hypothesis that nonprimate laboratory animals fed a folate-deficient diet demonstrate sensitivities to methanol that are similar to those seen in primates (Tephly, 1991; Valentine, 1990). Methanol-induced ocular lesions are characterized by a loss of retinal ganglion cells, retinal edema, and demyelination of the temporal retina. Necrosis of cells with or without hemorrhage in the basal ganglion and widespread hypoxia/ischemic damage are also associated with methanol intoxication. At low doses, however, the formate detoxification pathway is not overwhelmed, and formate does not build up.

FIGURE 4.3 Structure of various alcohols.

Administration of cyclohexanol to male gerbils and rats by subcutaneous injection (15 mg/kg/day) for 21 and 37 days, respectively, was associated with reproductive toxicity (Tyagi et al., 1979). The adverse effects observed included decreased weights of the testes, epididymis, seminal vesicles, and ventral prostate and degenerative changes in spermatozoa and spermatozoa precursors. Similar changes in the testes were seen in rabbits given cyclohexanol by gavage (25 mg/kg/day) for 40 days (Dixit et al., 1980). In contrast, no change in testicular weights was observed in Sprague Dawley rats given cyclohexanol by gavage (455 mg/kg/day) for 7 days (Lake et al., 1982).

Ethanol can elicit a wide array of serious adverse effects when ingested, but it is unlikely that such effects are associated with the internal doses likely to result from inhalation.

GLYCOLS

Glycols, which are characterized by the presence of two hydroxyl groups (see Figure 4.4 for structures), are major constituents of antifreeze, airplane deicers and anti-icers, brake fluids, and heat exchangers. Propylene glycol is used in cosmetics and foods and as a vehicle for drug delivery.



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