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Toxicologic Assessment of Jet-Propulsion Fuel 8 (2003)

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

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Suggested Citation:"10 Effects of Jet-Propulsion Fuel 8 on the Cardiovascular System." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
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Page 123
Suggested Citation:"10 Effects of Jet-Propulsion Fuel 8 on the Cardiovascular System." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 124
Suggested Citation:"10 Effects of Jet-Propulsion Fuel 8 on the Cardiovascular System." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 125
Suggested Citation:"10 Effects of Jet-Propulsion Fuel 8 on the Cardiovascular System." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 126
Suggested Citation:"10 Effects of Jet-Propulsion Fuel 8 on the Cardiovascular System." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 127
Suggested Citation:"10 Effects of Jet-Propulsion Fuel 8 on the Cardiovascular System." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 128
Suggested Citation:"10 Effects of Jet-Propulsion Fuel 8 on the Cardiovascular System." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 129

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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 Re- search 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 subcomm ittee 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 poten- tial to induce cardiac arrhythmias that can result in death. However, for the arrhythmias to occur, epinephrine must be released simultaneously with inhala- tion (Garb and Chenoweth 1948). No hum an stud ies that examined the car- 123

TABLE 10-1 Effects of Jet Fuel Exposure on the Cardiovascular System in Humans and Experimental Animals 124 Fuel Type Species Exposure Concentration Exposure Duration Effec ts Reference JP-8 Hum an, Exposed group had Not reported Medical records showed no Gibson et 5,706 potential occupational increase in medical visits related al. 2001a a exposed exposure to JP-8; control to card iovascular events subjects and grou p did not w ork in 5,706 occupations in which unexposed exposure to JP-8 would subjects occur JP-8 Hum an, 328 Measu rem ents taken in High- and Data co llected from self- Gibson et indiv iduals breathing zones of mod erate- exposure assessment questionnaire; al. 2001b a subjects; median groups had subjects in moderate- and high- concentration of persistent exposure exposure groups reported more naphthalene, 1.9 :g/m 3 to JP-8 (defined as heart palpitations and chest (low-exposure grou p), at least 1 hr twice tightness than subjects in low- 10.4 :g/m 3 (moderate- per w k for at least 9 exposure group; odds ratios for exposure group), 447 mo); low-exposure subjects in mod erate-exposure :g/m 3 (high-exposure group had no group, but not high-exposure group); median significant exposure group, were significantly greater concentration of benzene, to jet fuel or than for low-exposure group 3.1 :g/m 3 (low-exposure solvents group), 7.45 :g/m 3 (mod erate-exposure group), 242 :g/m 3 (high- exposure group)

Swed ish Hum an, 30 Average concentration, Mean, 17 yr Exposure may be associated Knave et military exposed about 300 mg/m 3 with acute symptoms, such as al. 1978 equivalent of subjects and palpitations and feeling of JP-4 30 pressure in chest unexposed subjects JP-8 F344 rat, 500 and 1,000 mg/m 3 (via 90 days No histopathologic changes to Mattie et C57BL/6 inhalation) continuously cardiovascu ar system w ere al. 1991 mou se observed JP-5 Sprague- 24 mL/kg (via oral 3 days No increase in serum creatinine Parker et Dawley rat gavage) phosphokinase concentrations al. 1981 was observed Deodorized Beagle, rat 20, 48, and 100 mg/m 3 6 hr/day, 5 days/wk No treatm ent-related ch anges in Carpenter kerosene (via inhalation) for up to 67 day clinical pathologic and et al. 1976 vapor histopathologicl measures of cardiovascu lar system we re observed; no electrocardiographic changes related to treatmen t were observed in dogs a Background information about these studies can be found in Appendix B. 125

126 Toxicologic A ssessment of Jet-Propulsion F uel 8 diovascular consequences of jet fuels were identified . Two studies in experi- mental animals examined the cardiovascular effects associated with oral admin- istration 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 m L/kg by oral gavage did not develop an increase in serum creatinine phosphokinase. Serum creatinine phosphokinase is indica- tive of cardiac-mu scle damage. The Subcom mittee 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 chem ical composition of the liquid JP-5 differs from that of the vapors (N RC 1996). EFFECTS OF EXPOSURE TO JET FUELS IN HUMANS No studies of hum ans that directly evaluate the potential effects of jet-fuel exposure on the card iovascular system have been conducted. G ibson 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 w omen) from a cohort of 20,244 Air Force unex- posed 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 inform ation on potential confounders, complete- ness 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 sym ptom s 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 associ- ated with aircraft fuel systems), moderate exposure (may have come into con- tact with jet fuel in the course of their duties), or low exposure (did not nor- mally com e into contact with jet fuel or other solvents while perform ing 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 palpita- tions and chest tightness, were higher in the high- and moderate-exposure groups than in the low-exposure group. Odds ratios for people in the

Effects of Jet-Propulsion Fuel 8 on the C ardiovascular System 127 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, fo- cusing on the nervous system end points, of 30 exposed and unexposed work- ers 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/m 3 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-w k, 2-mo, and terminal sacrifices for evaluation of blood chemistry. The exposures were well characterized with regard to concentration and chem- ical com position; no biologically significant changes were identified in clinical chem istry analyses. Forty tissues per animal were examined for histopatho- logic 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/m 3 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/m 3 (Carpenter et al. 1976). End points included histopathologic findings (lungs, kidneys, liver, heart, spleen, adrenals, thyroid s, trachea, and esophagus), hem atologic 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).

128 Toxicologic A ssessment of Jet-Propulsion F uel 8 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. How- ever, 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 am ong 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 reevalu- ated. The work of Mattie et al. suggests that continuous exposure of rats and mice to JP-8 vapor at up to 1,000 mg/m 3 for 90 days had no effect on the rodent cardiovascular system. R ats and dogs repeatedly exposed to kerosene at concentrations up to 100 mg/m 3 did not show any treatment-related effects. The subcomm ittee recommends that cardiovascular toxicity be evaluated in experimental anim als 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. The r. 94:12-18. Gibson, R.L., S. Sha nklin, and R.L. Wa rner. 2001a. Health effects comparisons. Pp. 125-129 in JP-8 Final Risk Assessment Report. The Institute of Environmental and Human H ealth (TIEHH), Lubbock, TX. August 2001. Gibson, R.L., S. Sha nklin, 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 H ealth (TIEHH), Lubbock, TX. August 2001. Knave, B., B.A. O lson, S. Elofsson, F. Gamberale, A. Isaksson, P. Mindus, H.E.

Effects of Jet-Propulsion Fuel 8 on the C ardiovascular System 129 Persson, G. Struwe, A. Wennberg, and P. W esterholm. 1978. Long-term expo- sure to jet fuel. II. A cross-sectional epidemiologic investigation on occupation- ally 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. Tox icol. Pathol. 19(2 ):77-8 7. NRC (National Research Council). 1996. Permissible Exposure Levels for Selected Military F uel V apors. Washin gton, DC : National Acade my 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 chem istry studies. Toxicol. Appl. Pharmacol. 57(3):302-317.

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This report provides a critical review of toxicologic, epidemiologic, and other relevant data on jet-propulsion fuel 8, a type of fuel in wide use by the U.S. Department of Defense (DOD), and an evaluation of the scientific basis of DOD's interim permissible exposure level of 350 mg/m3

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