William K. Alexander

A REVIEW OF THE NEUROTOXICITY RISK OF SELECTED HYDROCARBON FUELS

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.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.

APPLICATION OF NEUROBEHAVIORAL TOXICOLOGY METHODS TO THE MILITARY DEPLOYMENT TOXICOLOGY ASSESSMENT PROGRAM

The military Tri-Service (Army, Navy & Marines, Air Force) Deployment Toxicology Assessment Program (DTAP) represents a 30-year (1996–2026) planning effort to implement comprehensive systems for the protection of internationally deployed troops against toxicant exposures. A major objective of DTAP is the implementation of a global surveillance system to identify chemicals with the potential to reduce human performance capacity. Implementation requires prior development of complex human risk assessment models, known collectively as the Neurobehavioral Toxicity Evaluation Instrument (NTEI), based on mathematical interpolation of results from tissue-based and in vivo animal studies validated by human performance assessment research. The Neurobehavioral Toxicity Assessment Group (NTAG) at the Naval Health Research Center Detachment-Toxicology (NHRC-TD), Dayton, OH, and associated academic institutions are developing and cross-validating cellular-level (NTAS), laboratory small animal (NTAB), nonhuman primate (GASP), and human-based (GASH) toxicity assessment batteries. These batteries will be utilized to develop and evaluate mathematical predictors of human neurobehavioral toxicity, as a function of laboratory performance deficits predicted by quantitative structural analysis relationship (QSAR-like) properties of potential toxicants identified by international surveillance systems. Finally, physiologically-based pharmacokinetic (PBPK) and pharmacodynamic (PBPD) modeling of NTAS, NTAB, GASP, GASH data will support multi-organizational development and validation of the NTEI. The validated NTEI tool will represent a complex database management system, integrating global satellite surveillance input to provide real-time decision-making support for deployed military personnel.

Risk Assessment in Navy Deployment Toxicology

The risk assessment process is a critical function for deployment toxicology research. It is essential to the decision making process related to establishing risk reduction procedures and for formulating appropriate exposure levels to protect naval personnel from potentially hazardous chemicals in the military that could result in a reduction in readiness operations. These decisions must be based on quality data from well-planned laboratory animal studies that guide the judgements, which result in effective risk characterization and risk management. The process of risk assessment in deployment toxicology essentially uses the same principles as civilian risk assessment, but adds activities essential to the military mission, including intended and unintended exposure to chemicals and chemical mixtures. Risk assessment and Navy deployment toxicology data are integrated into a systematic and well-planned approach to the organization of scientific information. The purpose of this paper is to outline the analytical framework used to develop strategies to protect the health of deployed Navy forces.

Rapid separation of nitroaromatic compounds by solvating gas chromatography.

Nitroaromatic compounds such as 2,4,6-trinitrotoluene are used in the production of explosives and munitions, and are environmental contaminants as a result of such use. Conventional methods to detect these compounds have relied on liquid and gas chromatography to isolate the individual compounds which may be present at low levels in complex environmental matrices before final detection and identification. A new method, solvating gas chromatography, was used to rapidly separate 8 nitroaromatic compounds, showing improved speed relative to conventional liquid and gas chromatography methods. Solvating gas chromatography allows near real-time detection for these energetic compounds, providing improvements in their detection as environmental contaminants, and as compounds of interest to law enforcement and military organizations.

Airborne aldehydes from heating rosin core solder and liquid rosin flux to soldering temperatures.

Gas phase aldehydes produced from heating rosin core solder and liquid rosin flux to temperatures commonly used in soldering were trapped on sampling tubes containing XAD-2 resin coated with the derivatizing agent 2-hydroxymethylpiperidine. Analysis of the resulting oxazolidine derivatives was performed using gas chromatography/mass spectrometry (GC/MS). The observed aldehyde derivatives included formaldehyde, acetaldehyde, propionaldehyde, acrolein, isobutyraldehyde, butyraldehyde, isovaleraldehyde, valeraldehyde, furfural, hexanal, cyclohexane carboxaldehyde and other unidentified compounds likely to be aldehyde isomers. Formaldehyde, acetaldehyde, and benzaldehyde were detected in blank samples. By comparison with an internal standard, a sample produced by drawing air with contaminants derived by heating rosin core solder through a sampling tube contained levels of formaldehyde and acetaldehyde much greater than seen in sampling tube blanks. Benzaldehyde was not shown to be present at a significantly greater level in samples from heating rosin core solder than in blanks prepared using the same analysis protocol. The use of National Institute of Occupational Safety and Health (NIOSH) method 2539 extraction procedures produced blanks with levels of formaldehyde significantly lower than with a modified extraction method (methylene chloride, no sonication). The modified extraction method produced significantly lower benzaldehyde levels in blanks compared with the NIOSH extraction method using toluene and sonication of sampling sorbent tubes.

BREATHING ZONE PARTICLE SIZE AND LEAD CONCENTRATION FROM SANDING OPERATIONS TO REMOVE LEAD BASED PAINTS

The relationship between lead concentration in the dry film of lead based paints applied to steel bulkheads aboard ship, the lead concentration found in the air when the paint is removed by mechanical means, and blood lead concentrations of workers involved in lead based paint removal has not been well characterized. Intuitively a direct relationship must exist but confounding factors confuse the issue. Simultaneous sampling procedures from the same paint removal operation may differ by several orders of magnitude. The process from dried film to aerosol (airborne dust) exposure, and on to dose can be separated into two major phases; (1) generation of the dust and its transport through the air to the worker and (2) uptake and dose related factors within the body. Both phases involve complex interactions and there are a number of factors within each phase that significantly affect the potential lead dose for the worker. This study attempts to clarify the mechanisms involved in the generation and transportation of the dust to the worker by evaluating the relationship of a number of key factors on particle size and lead distribution within the aerosol dust generated when lead based paint is removed by sanding. The study examined the relationship between particle size in the dust and grit size of the abrasive. It also examined the distribution of lead within selected particle sizes. The Mass Median Aerodynamic Diameter (MMAD) was used as an indicator of change in the particle size distribution. Particle size distributions were evaluated using a TSI Aerodynamic Particle Sizer, a five stage cyclone and scanning electron microscopy. Lead distribution was determined using the five stage cyclone, and personal or area samples analyzed using inductively coupled plasma (ICP). Mass concentrations were evaluated using a MIE Mass Concentration Analyzer and gravimetric analysis of filter samples collected in the breathing zone. Students t-tests were used to evaluate changes in MMADs, mass concentrations and other indices for inter and intra-grit size samples. Correlation coefficients (Pearsons r) were used to determine the relationship between factors. Findings of the research indicated that the particle size distribution in the dust is directly related to the grit size of the abrasive (i.e. inversely related to the abrasive grit number). Particulate mass concentrations of dust varied directly with abrasive grit number. The distribution of lead did not appear to be affected by grit size of the abrasive in that the lead distribution within the particle size ranges remained homogeneous and consistent with the lead concentration in the dried film. Mass concentrations of lead in air samples varied directly with lead concentration in the bulk coating. Results of this project, coordinated with deposition modeling and bioavailability studies will be useful in the development of a model to characterize lead dose to workers based on known parameters within the work specifications.