Over 1.3 million civilian and military personnel are occupationally exposed to hydrocarbon fuels, emphasizing gasoline, jet fuel, diesel fuel, or kerosene. These exposures may occur acutely or chronically to raw fuel, vapor, aerosol, or fuel combustion exhaust by dermal, respiratory inhalation, or oral ingestion routes, and commonly occur concurrently with exposure to other chemicals and stressors. Hydrocarbon fuels are complex mixtures of 150-260+ aliphatic and aromatic hydrocarbon compounds containing varying concentrations of potential neurotoxicants including benzene, n-hexane, toluene, xylenes, naphthalene, and certain n-C9-C12 fractions (n-propylbenzene, trimethylbenzene isomers). Due to their natural petroleum base, the chemical composition of different hydrocarbon fuels is not defined, and the fuels are classified according to broad performance criteria such as flash and boiling points, complicating toxicological comparisons. While hydrocarbon fuel exposures occur typically at concentrations below permissible exposure limits for their constituent chemicals, it is unknown whether additive or synergistic interactions may result in unpredicted neurotoxicity. The inclusion of up to six performance additives in existing fuel formulations presents additional neurotoxicity challenge. Additionally, exposures to hydrocarbon fuels, typically with minimal respiratory or dermal protection, range from weekly fueling of personal automobiles to waist-deep immersion of personnel in raw fuel during maintenance of aircraft fuel tanks. Occupational exposures may occur on a near daily basis for from several months to over 20 yr. A number of published studies have reported acute or persisting neurotoxic effects from acute, subchronic, or chronic exposure of humans or animals to hydrocarbon fuels, or to certain constituent chemicals of these fuels. This review summarizes human and animal studies of hydrocarbon fuel-induced neurotoxicity and neurobehavioral consequences. It is hoped that this review will support ongoing attempts to review and possibly revise exposure standards for hydrocarbon fuels.

Ob/ob mice (OB) with B16 melanoma become anorectic, but lean mice (LN) do not. Present studies suggest that this difference reflects a greater bent for OB to form conditioned taste aversions (CTA). In Exp 1, healthy OB formed stronger CTAs than LN to a saccharin taste paired with lithium chloride (LiCl, 3 mEq/kg ip). In Exp 2, the OB-LN difference of Exp 1 was decreased by giving naltrexone (10 mg/kg sc) before LiCl, which suggested opiate involvement. Exp 3 showed that OB tumor anorexia vanishes if foods dissociated from tumor growth are given: OB fed a constant diet became anorectic 16 days after B16 inoculation; giving a new diet on Day 16 delayed anorexia onset for 8 days; a second new diet on Day 32 abolished anorexia for 24 hr. LN with tumors ate all diets at nontumor control levels. OB survived melanoma longer than LN regardless of diet, but OB fed a varied diet died first; thus, anorexia may enhance OB survival.

Rabbits were implanted with chronic stimulating electrodes in white matter underlying lobule HVI of the cerebellar cortex. Stimulation elicited movements of the face or neck and, when paired with a tone conditioned stimulus (CS), produced learning comparable to that seen with peripheral unconditioned stimuli (USs). CS-alone trials produced extinction. Reinstatement of paired trials produced reacquisition with savings. Additional groups received either explicitly or randomly unpaired CS-US trials before paired conditioning. Low-frequency responding during these sessions indicated that the paired training results were associative and not due to pseudoconditioning or sensitization. Explicitly unpaired sessions retarded learning on subsequent paired trials compared with groups that received either randomly unpaired or no CS-US preexposure. These results are interpreted in terms of the role of the cerebellum and associated pathways in classical conditioning of motor responses.

No abstract

No abstract