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Toxicologic Assessment of Jet-Propulsion Fuel 8 (2003)

Chapter: 8 Effects of Jet-Propulsion Fuel 8 on the Kidney

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Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." 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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Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." 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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Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." 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 103
Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." 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 104
Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." 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 105
Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." 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 106
Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 107
Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 108
Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 109
Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 110
Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 111
Suggested Citation:"8 Effects of Jet-Propulsion Fuel 8 on the Kidney." 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 112

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8 Effects of Jet-Propulsion Fuel 8 on the Kidney This chapter summarizes the findings on kidney toxicity of jet-propulsion fuel 8 (JP-8) and related fuels presented in the National Research C ouncil report Perm issible Exposure Levels for Selected Military Fuel Vapors (NRC 1996) and re- views additional studies, most of which were com pleted after the 1996 report was published. The subcommittee uses that information to assess the potential toxic effects of JP-8 on the kidney in humans. SUMMARY OF STUDIES DISCUSSED IN THE 1996 NATIONAL RESEARCH COUNCIL REPORT The National Research Council Subcommittee on Perm issible Exposure Levels for Military Fuels reviewed studies on the toxic effects of the vapors of JP-5, JP-8, and diesel fuel marine (D FM ) on the kidney (NRC 1996). That subcomm ittee reported that data on potential adverse health effects of JP-8 on the kidney were sparse. No hum an studies had examined kidney toxicity of JP-8. An acute exposure to hydrocarbon-based solvents at high concentrations (doses not specified) has been reported in a case study to pro- duce kidney failure (Beirne and Brennan 1972); the authors reported that a 101

102 Toxicologic A ssessment of Jet-Propulsion F uel 8 person exposed to jet fuel (type and dose not specified) while fueling aircraft in the U.S. Air Force had mild, reversible focal glomerulonephritis. One animal study that examined potential adverse effects of JP-8 exposure on the kidney was identified. M attie et al. (1991) showed that exposure to JP-8 causes kidney lesions in male rats. Male and female F344 rats and C57BL/6 mice were exposed to JP-8 vapor at 500 or 1,000 mg/m 3 for 90 days. After the 90-day exposure, a triad of lesions w ere found in the kidneys of male rats: dramatically exacerbated hyalin droplet formation, granular casts in the outer medulla, and increased incidence and severity of lesions undifferentiable from those of chronic progressive nephrosis. No such lesions were observed in female rats. In the male and female mice, no histopathologic lesions related directly to JP-8 w ere found. The increased incidence and severity of chronic progressive nephrosis persisted throughout the remainder of the lifetimes of the male rats. The kidney changes observed after 90 days were not reversible and were progressive. The severity of lesions was greater after the higher exposure. No kidney tumors were found in the study. No other animal stud- ies of the effects of JP-8 on kidneys were identified in the 1996 report. Several studies that examined kidney toxicity of jet fuels other than JP-8 were described in the 1996 report (Parker et al. 1981; Bogo et al. 1983; MacE wen and V ernot 1985; Bruner et al. 1993). The results of those studies were consistent with the results of the Mattie et al. (1991) study. Male rats exposed to JP-4, JP-5, or DFM vapors developed kidney lesions consistent with hyaline droplet degeneration and resembling what is known as alpha 2u- globulin nephropathy. The mechanisms that underlie the development of that lesion are believed to occur only to m ale rats. The 1996 subcommittee con- cluded that the lesion is not expected to occur in hum ans. EFFECTS OF EXPOSURE TO JP-8 IN HUMANS The effects of exposure to JP-8 on the human kidney were examined in a study recently completed by the U.S. Air Force. The preliminary results of that study are d escribed below and sum marized in Table 8-1. Snawder and Butler (2001) collected venous blood and urine from 107 people who worked at six U.S. Air Force bases (AFBs): Davis Monthan AFB, Arizona; Seymour Johnson AFB, North Carolina; Langley AFB, Virginia; Pope, AFB, N orth Carolina; Little Rock AFB, Arkansas; and Hurlbert Field, Florida. The exposed workers were fuel tank-entry personnel with persistent exposure to jet fuel (defined as a 1-hr entry twice a week for at least 9 months). The unexposed group consisted of Air Force personnel who had no important occupational exposure to hydrocarbon solvents or fuels. The participants

TABLE 8-1 Effects of JP-8 Exposure on the Kidney in Humansa Reference Exposure Concentration Exposure Duration Resu lts Snawder and Measurements taken in breathing zones High-exposure group had persistent Concentrations of Butler 2001 of subjects; median concentration of exposure to JP-8 (defined as at least 1 hr urinary neph-alpha naphthalene, 1.9 :g/m 3 (low-exposure twice a wk for 9 mo); low-exposure group GST and pi-G ST in group), 447 :g/m 3 (high-exposure had no significant exposure to jet fuel or subjects in normal group); median concentration of solvents range benzene, 3.1 :g/m 3 (low-exposure group), 242 :g/m 3 (high-exposure group) Butler et al. Measurements taken in breathing zones High- and moderate-exposure groups had Ana lysis of CY P2E I, 2001 of subjects; median concentration of persistent exposure to JP-8; low-exposure GSTT1, and NQO1 naphthalene, 1.9 :g/m 3 (low-exposure group had no significant exposure to jet fuel genotype d ata group), 10.4 :g/m 3 (moderate-exposure or solvents showed no group), 447 :g/m 3 (high-exposure statistically significant group); median concentration of interaction between benzene: 3.1 :g/m 3 (low-exposure those genotype s, group), 7.45 :g/m 3 (moderate-exposure alpha-G ST or pi- group), 242 :g/m 3 (high-exposure GST, and JP-8 group) exposure Gibson et al. Exposed group (5,706 people) had Not reported Analysis of medical 2001a potential occupational exposure to JP-8; records showed that control group (5,706 people) did not subjects in all groups work in occ upations in which exposure had similar health- to JP-8 would occur care visit rates; no (Continued) 103

TABLE 8-1 Continued 104 Reference Exposure Concentration Exposure Duration Resu lts differences among groups in kidney- related conditions Gibson et al. Measurements taken in breathing zones High- and moderate-exposure groups had Analysis of self- 2001b of subjects; median concentration of persistent exposure to JP-8; low-exposure assessment naphthalene, 1.9 :g/m 3 (low-exposure group had no significant exposure to jet fuel questionnaire did not group), 10.4 :g/m 3 (moderate-exposure or solvents report differences group), 447 :g/m 3 (high exposure am ong grou ps in group); median concentration of kidney-related benzene, 3.1 :g/m 3 (low-exposure conditions group), 7.45 :g/m 3 (moderate-exposure group), 242 :g/m 3 (high-exposure group) a Data co llected from volunteers (male and fem ale active-duty A ir Force person nel) at six Air Force bases in U nited States. Volunteers were divided into three exposure groups: high, moderate, and low. High-exposure group performed tasks associated with repairing aircraft fuel systems; moderate-exposure group performed tasks associated with fuel handling, distribution, recovery, and testing; low-exposure group does not routinely come into contact with jet fuel or solvents. Data were collected in morning before subjects went to work and after they completed their work for the day. Reported results are from preliminary analysis of data. Addition al background information about the se studies can be fo und in Appendix B. Abbreviations: GST, glutathione-S-transferase; CYP2E1, cytochrome P 2E1; NQO1, NAD (P)H quinone oxidoreductase.

Effects of Jet-Propulsion Fuel 8 on the Kidney 105 completed questionnaires providing job category, exposure level, and medical and demographic features. The exclusion criteria for participants were the presence of autoimmune disease, cancer, or diabetes and the use of immune- system altering drugs. Blood and urinary samples were collected before and after the shift at the AFB and shipped to a National Institute for Occupational Safety and Health laboratory in Cincinnati, O hio, for analysis. The markers of renal damage included urinary neph-alpha glutathione S-transferase (GST), an index of proximal epithelial cell function; pi-GST, an index of distal tubule epithelial cell function; and creatinine, a marker of renal function. With comm ercial immunoassay kits, the concentrations of urinary neph-alpha GST and pi-GST in control and exposed subjects were w ithin the normal range. Butler et al. (2001) further categorized exposed workers into three groups. The high-expo- sure group com prised subjects routinely performing tasks associated with repair of aircraft fuel systems; the moderate-exposure group comprised sub- jects involved in fuel handling, distribution, recovery, and testing; and the low- exposure group does not normally come into contact with jet fuel. There was no statistically significant change in urinary alpha-GST or pi-GST concentra- tions among any of the groups. Genotype was not considered a factor in renal response to JP-8 exposure in humans. The creatinine concentrations in urine of exposed personnel after the shift were higher than the creatinine concentra- tions in urine of unexposed subjects. However, even the highest urinary creati- nine concentrations were w ithin the normal clinical range; they were often indicative of mild dehydration. Data indicated that those sensitive measures of risk did not detect any adverse effect of acute JP-8 exposure on human renal function. Gibson et al. (2001a) examined the medical records of Air Force personnel occupationally exposed to JP-8 (5,706 people—242 women, 5,464 men) and compared them with records of unexposed personnel (5,706 people randomly selected from a population of 20,244 unexposed people). All were active-du ty members of the Air Force. A preliminary assessment of data showed that the total num ber of medical visits and the types of specific diseases—including circulatory, cardiovascular, and urogenital—were not markedly different be- tween groups. Gibson et al. (2001b) also conducted a self-assessment questionnaire survey of 328 exposed people, categorized into high-, moderate-, and low- exposure groups (as described above). A preliminary assessment of data showed that, in both men and women, the incidences of genitourinary, circula- tory, and cardiovascular illnesses w ere not different between the groups.

106 Toxicologic A ssessment of Jet-Propulsion F uel 8 EFFECT S OF EXPO SURE TO JP-8 IN EXPERIMENTAL ANIMALS In addition to the studies summ arized above, experimental-animal studies have been conducted to examine the effects of JP-8 exposure on renal func- tion; they are described below and sum marized in Table 8-2. Parton (1994) subjected male F344 rats to nose-only exposure to JP-8 aerosol (average particle size was 1.1054 ± 0.2918 mm) for 1 hr/day for 7 or 28 days at 500 mg/m 3 (low-dose group) or 1,000 mg/m 3 (high-dose group). Body weight gain in the 28-day groups was significantly reduced compared to controls, but the final body weights of the exposed groups were not markedly different from those of the concurrent control group. Kidney w eights w ere not significantly different between exposed and control groups. However, the relative kidney weight was increased in the low - and high-dose groups exposed for 7 days and in the high-dose group exposed for 28 days. There was no significant change in renal weight for the low-dose group exposed for 28 days. Histologic examination showed that the changes in relative kidney weight were accompanied by an increase in hyalin droplet form ation and in alpha 2u-globu- lin levels. There was no significant effect of JP-8 exposure on blood urea nitrogen measurements between exposed and concurrent control groups. The increase in relative kidney weight reflects the increase in alpha 2u-globulin, but renal function w as not com prom ised. The hyalin droplet formation associated with alpha 2u-microglobulin is gender- and species-specific with no relevance to humans (Flamm and Lehman-M cKeem an 1991). Mattie et al. (1995) administered JP-8 to Sprague-Dawley rats by oral intubation at 750, 1,500, or 3,000 mg/kg/day for 90 consecutive days. Urine simples w ere collected 24 hr before sacrifice. Blood and tissue sam ples were obtained at sacrifice. With respect to renal function, serum sodium and chlo- ride concentra tions increased only in the high-dose group. Serum creatinine concentrations increased in the low- and middle-dose groups but not in the high-dose group; however, urinary creatinine and protein concentrations were not significantly altered by JP-8. Urinary pH was significantly lower in the middle- and high-dose groups. The absolute renal weights were not altered in the exposed groups, but a significant increase in kidney:body weight ratio was found in the middle- and high-dose groups. The increase in renal weight was associated histopathologically with the accumulation of hyalin droplets in the cytoplasm of epithelial cells in the proxim al convoluted tubules. The renal- function test result changes w ere not dose-related, and the histopathologic

TABLE 8-2 Effects of Jet Fuel Exposure on the Kidney in Experimental Animals Fuel Exposu re Exposu re Type Species Concentration Duration Effec ts Reference JP-8 Male and 500 or 1,000 90 days Kidney lesions (hyalin droplets, granular casts Mattie et al. female F344 mg/m 3 (vapors, continuo usly in outer medulla, nephrosis) in male rats only; 1991 rats, male and whole-body) no kidney toxicity in female rats or male and fem ale female mice C57BL/6 m ice JP-8 Male F34 4 rats 500 or 1,000 1 hr/day for 7 Body weight gain in rats exposed for 28 days Parton 1994 mg/m 3 (aero sol, or 28 days significantly decreased; final body weights of nose-only) exposed animals similar to those of control anim als; relative kidne y weight incre ased in anim als expose d for 7 days and in anima ls exposed at high dose for 28 d ays; changes in relative kidney weight associated with increase in hyalin droplet formation and in alpha-2u- globulin; renal function not compromised JP-8 Male Sprague- 750, 1,500, or 90 days Serum sodium and chloride concentrations Mattie et al. Dawley rats 3,000 mg/kg consecutively increased in highest-dose group; serum 1995 (by gavage) creatinine concentrations increased in low- and m iddle-dose groups (but not in high-dose grou p); urinary crea tinine and protein concentrations not significantly altered by exposure; urinary pH significantly lower in the middle- and high-dose groups; exposu re did not alter absolute renal weights but produced (Continued) 107

TABLE 8-2 Continued 108 Fuel Exposu re Exposu re Type Species Concentration Duration Effec ts Reference significant increase in kidney: body weight ratio in the middle- and high-dose grou ps; increased renal weight caused by accu mu lation of hy alin droplets JP-8 Male Swiss- 1,000 mg/m 3 1 hr/day for 5 Exposure significantly altered abundance of Witzmann et Webster mice (aerosol, nose- days 56 proteins; concentrations of 21 proteins al. 2000a only) increased, concentrations of 35 proteins decreased , com pared with controls JP-8 Male Sprague- 1,000 mg/m 3 6 hr/day, 5 Renal GST homolog and 10- Witzmann et Dawley rats (vapor, whole- days/w k for 6 formyltetrahydrofate dehydrogenase increased al. 2000b body) wk in charge mo dification inde x; no change in abundance JP-8, JP-5 Male and Undiluted or 3 applications/ Exposu re produce d sign ificant incre ase in Easley et al. fem ale 50% diluted in wk for 60 wk water consu mption; anim als treated with 1982 C3Hf/Bd cyclohexane undiluted fuels had significantly increased mice (dermal) number of kidney lesions JP-5 Rats 24 mL/kg of 1 dose LD 50 about 60 mL /kg or higher; cyto plasm ic Parker et al. body weight (by droplets occurred in kidney s of male rats; 1981; Bogo gavage) serum creatinine and blood urea nitrogen et al. 1983 increased in m ale rats

JP-5 Rats, mice 150 or 750 90 days More than 75% of male rats exposed at either MacEwen mg/m 3 (vapor) continuo usly concentration showed nephrosis and tubular and Vernot damage; no kidney toxicity in mice 1985 JP-4 Male and 1,000 or 5,000 6 hr/day, 5 Alpha-2 u-globu lin nephropathy occu rred in Bru ner et al. female F344 mg/m 3 (vapor) day/wk for 12 males rats only; no kidney toxicity in mice 1993 rats, C57BL/6 mo mice Abbreviations: GST, glutathione-S-transferase; LD 50, dose that is lethal to 50% of the test anima ls. 109

110 Toxicologic A ssessment of Jet-Propulsion F uel 8 alterations are not relevant for human health risk assessment (Flamm and Lehm an-McK eeman 1991). Easley et al. (1982) dermally exposed male and female C3Hf/Bd mice to undiluted or diluted (50% weight/volum e dilution in cyclohexane) JP-8 or JP-5 three times per week for 60 wk. After 30 wk, the mice exposed to JP-8 and JP- 5 had significantly increased water consumption. A fter 60 wk, the animals treated with undiluted JP-8 and JP-5 had a significant increase in number of kidney lesions, compared with the control animals. Witzmann et al. (2000a) exposed male Swiss-Webster mice to JP-8 aerosol with a median mass aerodynamic diameter (MM AD) of 1.7-1.9 :m (M. W itten, University of Arizona, personnel communication, 2002) by nose-only inhala- tion. The total daily exposure time was 1 hr for a total of 5 days at an average JP-8 concentration of 1,000 mg/m 3. Control mice were subjected to ambient air. By means of various techniques—including electrophoresis, protein diges- tion, matrix-assisted laser desorption and ionization mass spectrometric pro- tein identification, and sequence tagging with electrospray mass spectrome- try— JP-8 exposure was shown to alter the abundance of 56 proteins. The concentrations of 21 proteins increased, and the concentrations of 35 proteins decreased; these 56 proteins accounted for 6% of all total resolved proteins. Only a single time-point and only one concentration were used, and the rele- vance of the findings to human health risk is not established. In a later study, Witzmann et al. (2000b) exposed male Sprague-Dawley rats to JP-8 for 6 hr/day, 5 days/wk for 6 wk. The concentration of JP-8 in the exposure cham- ber was 1,000 mg/m 3. Eighty-two days after exposure, there was no change in body w eights, and the general health of the rats appeared norm al. By means of electrophoresis, protein mass “fingerprinting,” and sequence tag analysis, renal GST homolog and 10-form yltetrahydrofate dehydrogenase showed an increase in charge modification index but not in abundance. Only a single measurement time (82 hr after exposure) and a single concentration of JP-8 were used. The relevance of these findings to hum an health risk is not estab- lished. CONCLUSIONS AND RECOMMENDATIONS F344 rats and C57BL/6 mice exposed on a continuous basis by inhalation to JP-8 vapors at concentrations of 500 or 1,000 mg/m 3 for 90 days showed induction of alpha 2u-globulin nephropathy in m ale rats but not in fem ale rats or in male or female animals of other species. Alpha-2u-globulin-induced nephropathy occurs only in male rats and is not relevant to humans.

Effects of Jet-Propulsion Fuel 8 on the Kidney 111 The subcom mittee recom mend s that kidney toxicity be evaluated in exper- imental animals exposed to JP-8 vapors and mixtures of vapors and aerosols by the inhalation route. REFERENCES Beirne, G.J., and J.T. Brennan. 1972. Glomeru lonephritis associated with hydrocar- bon solvents. Arch. Environ. Health. 25(5):365-369. Bogo, V., R.W. Young, T.A. Hill, C.L. Feser, J. Nold, G.A. Parker, and R.M. Cartledge. 1983. Pp. 46-66 in The Toxicity of Petroleum and Shale JP5. AFRRI SR83-26. Armed Forces Radiobiology Research Institute, Bethesda, MD. Brune r, R.H ., E.R. Kinkead, T.P. O ’Neill, C.D. Fleming, D.R. Mattie, C.A. Russell, and H.G. Wall. 199 3. The toxicologic and oncogenic potential of JP-4 jet fuel vapors in rats and mice: 12-month intermittent inhalation exposure s. Fundam . Appl. Toxicol. 20(1):97-110. Butler, M.A., C.A. Flugel, E.F. Krieg, J.E. Snawder, and J.S. Kesner. 2001. Gene- environment interaction s and exposure to JP8 jet fuel. Pp. 76-80 in JP8 Final Risk Assessment. The Institute of E nvironmental and Human Health (TIEH H), Lubbock, TX. August 2001. Easley, J.R., J.M. Holland, L.C. Gipson, and M.J. Whitaker. 1982. Renal toxicity of middle distillates of shale oil and petroleum in mice. Toxicol. Ap pl. Pharm acol. 65(1):84-91. Flamm, W.G., and L.D. Lehman-McKeem an. 1991. The human relevance of the renal tumor-inducing potential of d-lim onene in male rats: Implications for risk assessment. Regul. Toxicol. Pharmacol. 13(1):70-86. 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 H ealth (TIEHH), Lubbock, TX. August 2001. Gibson, R.L., S. Shanklin, and R.L. Warn er. 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. MacEwen, J.D., and E.H. Vernot. 1985. Investigation of the 1-hour emergency expo- sure limit of JP-5. Pp. 137-144 in Toxic Hazards Research Unit Annual Technical Rep ort: 198 5. AAM RL-TR-85-058. Aerospace Medical Research Laboratory, Wright-Patterson AFB , OH . Mattie, D.R ., C.L. Alden, T .K. N ewell, C.L . Gaworski, an d C .D. F lem ming. 19 91. 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 m ice. Toxicol. Pathol. 19(2 ):77-8 7. Mattie, D.R., G.B. Marit, C.D. Flemming, and J.R. Cooper. 1995. The effe cts of JP-8 jet fuel on male Sprague-Dawley rats after a 90-day exposure by oral gavage. Toxicol. Ind. Health 11(4):423-435. NRC (Na tional Research C oun cil). 1996. Permissible Exposure Levels for Selected Military Fuel V apors. Washington, DC: National Acad emy Press.

112 Toxicologic A ssessment of Jet-Propulsion F uel 8 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. Parton, K.H. 1994. The Effec ts of JP-8 Jet Fuel Inhalation on L iver and Kidney Function in M ale F -344 Rats. M .S. Th esis, University of Arizona. 76pp. Snawder, J.E., and M .A. Butler. 2001. Sensitive early indicators of hepatic and kidney damage in wo rkers expose d to jet fuel. Pp. 81-86 in JP-8 Final Risk Assessment Rep ort. The Institute of Environmental and Hum an Health (TIEHH), Lubbock, TX. August 2001. Witzmann, F. A., M.D. Bauer, A.M. Fieno, R.A. Grant, T.W. Keough, M.P. Lacey, Y. Sun, M.L. Whiten, and R.S. Young. 2000a. Proteomic analysis of the ren al effects of simulated occupational jet fuel exposure. Electrophoresis 21(5):976-984. Witzmann, F.A., R.L. Carpenter, G.D. Ritchie, C.L. Wilson, A.F. Nordho lm, and J. Rossi III. 2000b. Toxicity of chem ical mixtures: Proteomic analysis of persisting liver and kidney protein alterations induced by repeated exposure of rats to JP-8 jet fuel vapor. Electrophoresis 21(11):2138-2147.

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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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