10
Effects of Jet-Propulsion Fuel 8 on the Cardiovascular System

This chapter summarizes the findings on the cardiovascular system toxicity of jet-propulsion fuel 8 (JP-8) and related fuels presented in the National Research Council report Permissible Exposure Levels for Selected Military Fuel Vapors (NRC 1996) and reviews additional studies on cardiovascular system toxicity of JP-8 and related fuels. Those studies are summarized in Table 10-1. The subcommittee used the available information to assess the potential toxic effects of exposure to JP-8 on the cardiovascular system in humans.

SUMMARY OF STUDIES DISCUSSED IN THE 1996 NATIONAL RESEARCH COUNCIL REPORT

The National Research Council Subcommittee on Permissible Exposure Levels for Military Fuels reviewed studies on the toxic effects of hydrocarbon vapors on the cardiovascular system (NRC 1996; see Appendix A). Intentional or accidental inhalation of high concentrations of hydrocarbons has the potential to induce cardiac arrhythmias that can result in death. However, for the arrhythmias to occur, epinephrine must be released simultaneously with inhalation (Garb and Chenoweth 1948). No human studies that examined the car-



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10 Effects of Jet-Propulsion Fuel 8 on the Cardiovascular System This chapter summarizes the findings on the cardiovascular system toxicity of jet-propulsion fuel 8 (JP-8) and related fuels presented in the National Research Council report Permissible Exposure Levels for Selected Military Fuel Vapors (NRC 1996) and reviews additional studies on cardiovascular system toxicity of JP-8 and related fuels. Those studies are summarized in Table 10-1. The subcommittee used the available information to assess the potential toxic effects of exposure to JP-8 on the cardiovascular system in humans. SUMMARY OF STUDIES DISCUSSED IN THE 1996 NATIONAL RESEARCH COUNCIL REPORT The National Research Council Subcommittee on Permissible Exposure Levels for Military Fuels reviewed studies on the toxic effects of hydrocarbon vapors on the cardiovascular system (NRC 1996; see Appendix A). Intentional or accidental inhalation of high concentrations of hydrocarbons has the potential to induce cardiac arrhythmias that can result in death. However, for the arrhythmias to occur, epinephrine must be released simultaneously with inhalation (Garb and Chenoweth 1948). No human studies that examined the car-

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TABLE 10-1 Effects of Jet Fuel Exposure on the Cardiovascular System in Humans and Experimental Animals Fuel Type Species Exposure Concentration Exposure Duration Effects Reference JP-8 Human, 5,706 exposed subjects and 5,706 unexposed subjects Exposed group had potential occupational exposure to JP-8; control group did not work in occupations in which exposure to JP-8 would occur Not reported Medical records showed no increase in medical visits related to cardiovascular events Gibson et al. 2001aa JP-8 Human, 328 individuals Measurements taken in breathing zones of subjects; median concentration of naphthalene, 1.9 μg/m3 (low-exposure group), 10.4 μg/m3 (moderate-exposure group), 447 μg/m3 (high-exposure group); median concentration of benzene, 3.1 μg/m3 (low-exposure group), 7.45 μg/m3 (moderate-exposure group), 242 μg/m3 (high-exposure group) High- and moderate- exposure groups had persistent exposure to JP-8 (defined as at least 1 hr twice per wk for at least 9 mo); low-exposure group had no significant exposure to jet fuel or solvents Data collected from self-assessment questionnaire; subjects in moderate- and high-exposure groups reported more heart palpitations and chest tightness than subjects in low-exposure group; odds ratios for subjects in moderate-exposure group, but not high-exposure group, were significantly greater than for low-exposure group Gibson et al. 2001ba

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Swedish military equivalent of JP-4 Human, 30 exposed subjects and 30 unexposed subjects Average concentration, about 300 mg/m3 Mean, 17 yr Exposure may be associated with acute symptoms, such as palpitations and feeling of pressure in chest Knave et al. 1978 JP-8 F344 rat, C57BL/6 mouse 500 and 1,000 mg/m3 (via inhalation) 90 days continuously No histopathologic changes to cardiovascuar system were observed Mattie et al. 1991 JP-5 Sprague-Dawley rat 24 mL/kg (via oral gavage) 3 days No increase in serum creatinine phosphokinase concentrations was observed Parker et al. 1981 Deodorized kerosene vapor Beagle, rat 20, 48, and 100 mg/m3 (via inhalation) 6 hr/day, 5 days/wk for up to 67 day No treatment-related changes in clinical pathologic and histopathologicl measures of cardiovascular system were observed; no electrocardiographic changes related to treatment were observed in dogs Carpenter et al. 1976 aBackground information about these studies can be found in Appendix B.

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diovascular consequences of jet fuels were identified. Two studies in experimental animals examined the cardiovascular effects associated with oral administration of jet-propulsion fuel 5 (Parker et al. 1981). In one study, rats given JP-5 died from cardiovascular collapse unrelated to myocardial necrosis; in the other, rats given JP-5 at 24 mL/kg by oral gavage did not develop an increase in serum creatinine phosphokinase. Serum creatinine phosphokinase is indicative of cardiac-muscle damage. The Subcommittee on Permissible Exposure Levels for Military Fuels concluded that the animal data are not useful for determining permissible exposure levels (PELs), because the oral route of exposure was not directly relevant and the chemical composition of the liquid JP-5 differs from that of the vapors (NRC 1996). EFFECTS OF EXPOSURE TO JET FUELS IN HUMANS No studies of humans that directly evaluate the potential effects of jet-fuel exposure on the cardiovascular system have been conducted. Gibson et al. (2001a) examined the medical records of Air Force personnel occupationally exposed to JP-8 and compared them with records of unexposed (control) populations. The exposed group consisted of 5,706 people (242 women and 5,464 men). The control group consisted of 5,706 subjects randomly selected (equal numbers of men and women) from a cohort of 20,244 Air Force unexposed personnel. A preliminary assessment of medical records showed no increase in medical visits related to cardiovascular events. The study is limited by many factors, including information on potential confounders, completeness of health-event recording, differences among people in availability of health care, consequences of taking sick leave for health-care visits, differences in health-care-seeking behavior, and differences in amount of self-care or sensitivity to symptoms of illness. Gibson et al. (2001b) conducted a health survey with a self-assessment questionnaire on 328 Air Force personnel (276 men and 52 women). The subjects were categorized as having high exposure (performed duties associated with aircraft fuel systems), moderate exposure (may have come into contact with jet fuel in the course of their duties), or low exposure (did not normally come into contact with jet fuel or other solvents while performing their duties). A preliminary assessment of the data showed that the total number of medical visits and the number of visits for specific reasons, including palpitations and chest tightness, were higher in the high- and moderate-exposure groups than in the low-exposure group. Odds ratios for people in the

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moderate-exposure group, but not the high-exposure group, were significantly greater than for those in the low-exposure group. The study is limited by the self-reporting of symptoms, failure to control for subject bias, and the fact that no exposure empirical data were collected. Knave et al. (1978) conducted a cross-sectional epidemiologic study, focusing on the nervous system end points, of 30 exposed and unexposed workers in a jet-motor factory in Sweden. The workers were said to have been exposed to the Swedish military equivalent of JP-4 for a mean period of 17 years. The authors reported that acute symptoms—including respiratory tract symptoms (undefined), palpitations, and a feeling of pressure in the chest—may have been associated with the exposures. EFFECTS OF EXPOSURE TO JP-8 AND KEROSENE IN EXPERIMENTAL ANIMALS Male and female F344 rats and C57BL/6 mice were continuously exposed to JP-8 vapor by inhalation at 500 and 1,000 mg/m3 for 90 days (Mattie et al. 1991). Rats were sacrificed after 2 wk, 2 months (mo), or 90 days of exposure or 9 mo or 21 mo after termination of exposure. Blood was taken from rats at the 2-wk, 2-mo, and terminal sacrifices for evaluation of blood chemistry. The exposures were well characterized with regard to concentration and chemical composition; no biologically significant changes were identified in clinical chemistry analyses. Forty tissues per animal were examined for histopathologic changes; treatment-related histopathologic changes were limited to the kidney. There was no evidence that subchronic inhalation of JP-8 vapors at concentrations higher than the interim PEL of 350 mg/m3 caused adverse effects on the rat cardiovascular system. To determine the potential adverse health effects of repeated inhalation of deodorized kerosene vapor, groups of 25 male rats and four male beagles were exposed for 6 hr/day, 5 days/wk for up to 67 days at 20, 48, and 100 mg/m3 (Carpenter et al. 1976). End points included histopathologic findings (lungs, kidneys, liver, heart, spleen, adrenals, thyroids, trachea, and esophagus), hematologic and serum chemistry findings, and electrocardiographic findings (dogs only; baseline and after exposure). No treatment-related changes in clinical pathologic measures were found in rats or dogs. No treatment-related histopathologic lesions were found in either species. No electrocardiographic changes attributable to kerosene inhalation were noted in dogs (Carpenter et al. 1976).

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CONCLUSIONS AND RECOMMENDATIONS A preliminary comparison of medical records of Air Force personnel occupationally exposed to JP-8 with records of unexposed (control) personnel showed no increase in medical visits related to cardiovascular events. However, preliminary results of a health survey of Air Force personnel that used a self-assessment questionnaire showed that the total number of medical visits and the number of visits for specific reasons, including palpitations and chest tightness, were higher among high- and moderate-exposure groups than in the low-exposure group. The reported effects were not dose-related; the moderate-exposure group showed greater incidence of adverse effects than the high-exposure group. Many potential, uncontrolled biases are associated with those investigations, and the lack of adequate exposure data makes interpretation of the results difficult. The subcommittee recommends that when exposure-assessment data become available, the cardiovascular effects data be reevaluated. The work of Mattie et al. suggests that continuous exposure of rats and mice to JP-8 vapor at up to 1,000 mg/m3 for 90 days had no effect on the rodent cardiovascular system. Rats and dogs repeatedly exposed to kerosene at concentrations up to 100 mg/m3 did not show any treatment-related effects. The subcommittee recommends that cardiovascular toxicity be evaluated in experimental animals exposed to JP-8 vapors and mixtures of vapors and aerosols by the inhalation route. REFERENCES Carpenter, C.P., D.L. Geary Jr., R.C. Myers, D.J. Nachreiner, L.J. Sullivan, and J.M. King. 1976. Petroleum hydrocarbon toxicity studies. XI. Animal and human response to vapors of deodorized kerosene. Toxicol. Appl. Pharmacol. 36(3):443-456. Garb, S., and M.B. Chenoweth. 1948. Studies on hydrocarbon-epinephrine induced ventricular fibrillation. J. Pharmacol. Exp. Ther. 94:12-18. Gibson, R.L., S. Shanklin, and R.L. Warner. 2001a. Health effects comparisons. Pp. 125-129 in JP-8 Final Risk Assessment Report. The Institute of Environmental and Human Health (TIEHH), Lubbock, TX. August 2001. Gibson, R.L., S. Shanklin, and R.L. Warner. 2001b. Self-reported health status. Pp. 132-139 in JP-8 Final Risk Assessment Report. The Institute of Environmental and Human Health (TIEHH), Lubbock, TX. August 2001. Knave, B., B.A. Olson, S. Elofsson, F. Gamberale, A. Isaksson, P. Mindus, H.E.

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Persson, G. Struwe, A. Wennberg, and P. Westerholm. 1978. Long-term exposure to jet fuel. II. A cross-sectional epidemiologic investigation on occupationally exposed industrial workers with special reference to the nervous system. Scand. J. Work Environ. Health 4(1):19-45. Mattie, D.R., C.L. Alden, T.K. Newell, C.L. Gaworski, ans C.D. Flemming. 1991. A 90-day continuous vapor inhalation toxicity study of JP-8 jet fuel followed by 20 or 21 months of recovery in Fischer 344 rats and C57BL/6 mice. Toxicol. Pathol. 19(2):77-87. NRC (National Research Council). 1996. Permissible Exposure Levels for Selected Military Fuel Vapors. Washington, DC: National Academy Press. Parker, G.A., V. Bogo, and R.W. Young. 1981. Acute toxicity of conventional versus shale-derived JP5 jet fuel: Light microscopic, hematologic, and serum chemistry studies. Toxicol. Appl. Pharmacol. 57(3):302-317.