authors concluded that n-butyl acetate is not teratogenic (Elder, 1989). Unlike the ethylene glycol ethers, propylene glycol ethers and acetates, such as PGMEA, do not appear to have significant teratologic or reproductive toxicity effects. However, the PGMEA isomer 2-methoxy-1-propanol acetate, found as an impurity in commercial-grade PGMEA, has been reported to be teratogenic in both rats and rabbits. Because 2-methyoxy-1-propanol acetate can comprise as much as 5% of commercial PGMEA, the reproductive toxicity of this isomer may have implications for exposures to commercial-grade PGMEA.


Ketones, organic compounds that contain a carbonyl functional group (C=O), are widely used as solvents and in chemical manufacturing (Rosenstock and Cullen, 1986). The general ketone structure is shown in Figure 4.7.

In general, ketones are not considered to be acutely toxic, and acetone, the most widely used ketone, is considered relatively nontoxic (Bruckner and Warren, 2001). As previously mentioned, some ketones produce a specific type of peripheral neuropathy that is mediated by their common metabolite, 2,5-hexanedione. There is no evidence that any of the

FIGURE 4.7 Basic structure of ketones.

ketones thought to have been sent to the Gulf War cause that peripheral neuropathy or have 2,5-hexanedione as a metabolite. There is evidence, however, that coexposure to some of the compounds sent to the Gulf War (specifically, methyl ethyl ketone and methyl isobutyl ketone) can potentiate peripheral neuropathies induced by n-hexane and methyl-n-butyl ketone (ATSDR, 1999; Ichihara et al., 1998). Although the exact mechanism of that potentiation is not clear, urinary concentrations of 2,5-hexanedione increased with potentiation of n-hexane neurotoxicity by methyl-n-butyl ketone (Ichihara et al., 1998).


There was the potential for exposure to at least two refined-petroleum mixtures in the Gulf War: Stoddard solvent (dry-cleaning safety solvent) and naphtha. Stoddard solvent has many uses as a fuel or fuel additive, lubricant, dry-cleaning agent, chemical intermediate, and general cleaner and degreaser. Naphtha is used in paints, insecticide formulations, and solvent extraction processes and as a component in gasoline blending. Many fuels, including jet fuels, were used in the Gulf War. Those compounds are not reviewed in this volume of Gulf War and Health, however, because they will be reviewed in the next volume of Gulf War and Health.

Stoddard solvent is composed of a mixture of hydrocarbons (usually seven to 10 carbons long) that are produced during the refinement of crude oil. It is a colorless, flammable liquid that is insoluble in water. Naphtha is a general term for petroleum distillates that contain predominantly C5−C13 aliphatic hydrocarbons.

The relative percentage of individual components affects the toxicokinetics of Stoddard solvent. A hydrocarbon’s blood:air partition coefficient is a key factor in the rate

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