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Toxicologic Assessment of Jet-Propulsion Fuel 8 (2003)

Chapter: 7 Effects of Jet-Propulsion Fuel 8 on the Liver

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Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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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7
Effects of Jet-Propulsion Fuel 8 on the Liver

This chapter summarizes the findings on potential hepatic 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, most of which were completed after the 1996 report was published. The subcommittee uses that information to assess the potential toxic effects of JP-8 on the human liver.

SUMMARY OF STUDIES DISCUSSED IN THE 1996 NATIONAL RESEARCH COUNCIL REPORT

The National Research Council Subcommittee on Permissible Exposure Levels for Military Fuel Vapors reviewed studies concerning potential hepatic changes associated with exposure to the vapors of JP-8, JP-4, JP5, or diesel fuel marine (DFM) on the liver (NRC 1996).

One study examined the effects of JP-4 on the liver in humans. Dossing et al. (1985) reported that fuel-filling attendants exposed to JP-4 at an average of 31 mg/m3 for a mean of 6.4 years had a significantly faster antipyrine clearance (68 mL/min) than an referent population of office workers (58 mL/min).

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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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No marked differences were found in serum aspartate aminotransferase and alkaline phosphatase activity between the two groups. No studies were available that report the effects of JP-8, JP-5, or DFM vapors on the liver in humans.

Studies in rats and mice had examined the toxic effects of JP-8 on the liver (MacEwen and Vernot 1983, 1984,1985). In subchronic inhalation studies, male and female F344 rats (10 of each) and male and female C57BL/6 mice (10 of each) were continuously exposed to JP-8 vapor at 500 or 1,000 mg/m3 for 90 days. Some groups of animals were killed immediately after the 90-day exposure, and others 2 wk, 2 months (mo), 9 mo, or 21 mo after the exposure. Immediately after exposure ceased, male rats showed increases in liver weights and liver:body weight ratios at 1,000 mg/m3, decreases in serum glutamic-pyruvic transaminase (SGPT) activity at 500 and 1,000 mg/m3, and decreases in alkaline phosphatase activity at 1,000 mg/m3; and female rats showed increases in liver weights and liver:body weight ratios at 500 and 1,000 mg/m3, increases in alkaline phosphatase activity at 1,000 mg/m3, and decreases in SGPT activity at 500 and 1,000 mg/m3. Nine months after exposure, male rats showed decreases in SGPT activity at 500 and 1,000 mg/m3. Twenty-one months after exposure, male rats showed concentration-related increases in liver:body weight ratios at 500 and 1,000 mg/m3; and female rats showed decreases in serum glutamic oxaloacetic transaminase (SGOT) activity at 500 mg/m3 and decreases in SGPT activity at 500 and 1,000 mg/m3. It should be emphasized that despite the significant changes observed in SGOT and SGPT activities, the alterations were within the normal range and thus not clinically relevant. Support for relevant changes in liver function would necessitate the measurement of liver enzyme functions and histopathologic studies, which were not conducted. No data on mice were presented.

The available data on potential hepatic toxicity associated with subchronic exposure to JP-8 vapor are not definitive, because histopathologic examinations were not performed. The liver weight changes observed in rats might indicate hyperplasia or hypertrophy. Alternatively, the increases in liver:body weight ratios might reflect a loss of body weight in the test animals during the study. It is also possible that JP-8 was offensive to the animals, nauseating them and decreasing their food intake.

Animal studies had also examined the liver effects from dermal or inhalation exposure to JP-4 or JP-5. Mild liver changes were observed in male and female beagles, male and female F344 rats, and male and female C57BL/6 mice exposed to JP-5 vapor continuously at 150 or 750 mg/m3 for 90 days (MacEwen and Vernot 1978, 1980, 1981, 1982, 1983, 1985; Gaworski et al. 1984). Similar results were reported in beagles, F344 rats, and C57BL/6 mice exposed to JP-4 vapor at 500 or 1,000 mg/m3 for 90 days (MacEwen and

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

Vernot 1984); in F344 rats and C57BL/6 mice exposed to JP-4 vapor at 1,000 or 5,000 mg/m3 for 6 hr/day, 5 days/wk for 12 mo (Bruner et al. 1993; Wall et al. 1990; MacEwen and Vernot 1981, 1982); and in monkeys, dogs, rats, and mice exposed to JP-4 vapor at 2,500 or 5,000 mg/m3 for 6 hr/day, 5 days/wk for 8 mo (MacNaughton and Uddin 1984).

EFFECTS OF EXPOSURE TO JP-8 IN HUMANS

The effects of acute exposure to JP-8 on the liver in humans were examined in a study recently completed by the U.S. Air Force. The preliminary results of that study are described below and summarized in Table 7-1.

Snawder and Butler (2001) collected venous blood and urine from 107 people working at six Air Force bases (AFB): Davis Monthan AFB, Arizona; Seymour Johnson AFB, North Carolina; Langley AFB, Virginia; Pope, AFB, North Carolina; Little Rock AFB, Arkansas; and Hurlbert Field, Florida. The exposed workers were fuel tank-entry personnel with at least 9 mo of persistent exposure to jet fuel (defined as 1-hr entry, twice a week). The unexposed group consisted of Air Force personnel who routinely had no significant exposure to solvents or fuels. The participants completed questionnaires on job category, exposure, and medical and demographic items. The exclusion criteria for participants were the presence of autoimmune disease, cancer, or diabetes and the use of immune-system altering drugs.

Blood samples were collected before and after shift at each AFB and sent to a National Institute for Occupational Safety and Health (NIOSH) laboratory in Cincinnati, Ohio, for analysis. The markers of liver damage included serum alpha-glutathione S-transferase (GST) activity, an index of liver toxicity. In measurement with commercial immunoassay kits, hepatic alpha-GST activity in control and exposed subjects fell within the normal range. Butler et al. (2001) further categorized hepatic alpha-GST in three exposure groups to assess correlation of JP-8 exposure with potential liver toxicity. The high-exposure group consisted of subjects who routinely performed tasks associated with repair of aircraft fuel systems; the moderate-exposure group consisted of subjects who were involved with fuel handling, distribution, recovery, and testing; and the low-exposure group consisted of subjects who did not normally come into contact with jet fuel or solvents. That hepatic alpha-GST activity was not significantly different among those groups indicated a lack of interaction between exposure concentration and genotype, and there was no enzymatic induction. In addition, Butler et al. (2001) measured serum cytochrome P2E1 activity; cytochrome P2E1 is an enzyme involved in benzene metabolism to benzene oxide and phenol. Phenol via cytochrome P2E1

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

TABLE 7-1 Effects of JP-8 Exposure on the Liver in Humansa

Reference

Exposure Concentration

Exposure Duration

Results

Snawder and Butler 2001

Measurements taken in breathing zones of subjects; median concentration of naphthalene, 1.9 μg/m3 (low-exposure group), 447 μg/m3 (high-exposure group); median concentration of benzene, 3.1 μg/m3 (low-exposure group), 242 μg/m3 (high-exposure group)

High-exposure group had persistent exposure to JP-8 (defined as at least 1 hr twice per wk for 9 mo); low-exposure group had no significant exposure to jet fuel or solvents

Concentrations of serum hepatic alpha-GST activity in study subjects were within normal range

Butler et al. 2001

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; low exposure group had no significant exposure to jet fuel or solvents

Frequency of CYP2E1 and NQOI genotypes was similar in subjects in all exposure groups; no change in enzymatic activity

Gibson et al. 2001a

Exposed group (5,706 people) had potential occupational exposure to JP-8. Control group (5,706 people) did not work in occupations in which exposure to JP-8 would occur

Not reported

Analysis of medical records showed that subjects in all groups had similar health-care visit rates; no differences were noted among groups in digestive ailments

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

Reference

Exposure Concentration

Exposure Duration

Results

Gibson et al. 2001b

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; low-exposure group had no significant exposure to jet fuel or solvents

Analysis of self-assessment questionnaire did not report differences among groups in digestive ailments

aData collected from volunteers (male and female active-duty Air Force personnel) at six Air Force bases in United 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; and low-exposure group did not routinely come into contact with jet fuel or solvents. Data were collected in morning before subjects went to work and again after they completed their work for that day. Reported results are from preliminary analysis of data. Work referred to in table is part of larger study examining potential human health effects of acute exposure to JP-8. Additional background information can be found in Appendix B.

Abbreviations: GST, glutathione-S-transferase; CYP2E1, cytochrome P2E1; NQO1, NAD(P)H quinone oxidoreductase.

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

is oxidized to hydroquinone and other quinines, including benzoquinones. NAD(P)H quinone oxidoreductase (NQOI) then catalyzes conversion of benzoquinones to less-reactive metabolites. The frequency of the cytochrome P2E1 and NQOI genotypes was similar in subjects regardless of exposure concentration, and there was no change in enzymatic activity, so there was probably no hepatic metabolic induction. Data indicated that those sensitive measures of risk did not detect adverse effects of JP-8 at the assumed exposures on human liver function.

Gibson et al. (2001a) examined the medical records of Air Force personnel occupationally exposed to JP-8 and compared them with records of an unexposed population. The data used were from a population of 5,706 (242 women and 5,464 men) in the exposed group and a population of 5,706 (2,853 men and 2,853 women) randomly chosen from a cohort of 20,244 Air Force personnel who were not occupationally exposed to JP-8. The total number of health-event visits was not markedly different between groups. There was no association between JP-8 exposure and specific neoplasia or digestive ailments. Furthermore, Gibson et al. (2001b) conducted a self-assessment questionnaire on 328 exposed people, categorized into high-, moderate-, and low-exposure groups (as described above). In both men and women, the incidence of digestive ailments was not markedly different between the exposed and referent groups.

EFFECTS OF EXPOSURE TO JP-8 IN EXPERIMENTAL ANIMALS

Several studies have been conducted to examine the potential adverse effects of JP-8 on liver function. Those studies are described below and summarized in Table 7-2.

Parton (1994) subjected male F344 rats to nose-only inhalation exposure to JP-8 aerosols (average particle size was 1.1054 ± 0.2918 microns) at 500 or 1,000 mg/m3 for 1 hr/day for 7 or 28 days. Weight gain in the 28-day low-and high-dose groups was significantly decreased, but the final body weight was not markedly different between groups. Liver weights were not significantly different. There were no significant alterations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, indicators of hepatic function, and there were no marked changes in the liver histopathologic findings and cytochrome P450 content, a measure of xenobiotic metabolism.

Mattie et al. (1991) exposed male and female F344 rats and male and female C57BL/6 mice to JP-8 vapor at 500 or 1,000 mg/m3 for 90 days. Only

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

TABLE 7-2 Effects of Jet Fuel Exposure on the Liver in Experimental Animals

Fuel Type

Species

Exposure Concentration

Exposure Duration

Effects

Reference

JP-8

Male, female F344 rats

500 or 1,000 mg/m3 (vapor)

90 days continuously

Increased in liver weight and liver:body weight ratio, decreased in SGPT activity in males and females at 500 or 1,000 mg/m3; decreased alkaline phosphatase activity in males, increased alkaline phosphastase activity in females at 1,000 mg/m3

MacEwen and Vernot 1983, 1984, 1985

JP-8

Male F344 rats

500 or 1,000 mg/m3 (aerosol, nose-only)

1 hr/day for 7 or 28 days

Body weight gain in rats exposed for 28 days was significantly decreased; final body weights of exposed animals were similar to those of control animals; liver weights not significantly different between groups; relative liver weight increased in high-dose groups; no significant alterations in AST and ALT activity; no marked changes in liver histopathologic findings and CYP450 content

Parton 1994

JP-8

Male, female F344 rats, C57Bl/6 mice

500 or 1,000 mg/m3 (vapor)

90 days continuously

Male rats had a statistically significant increase in hepatic basophilic foci. Their presence in the livers of male rats is of uncertain biological significance. No alterations were found in hepatic tissue of female rats or in mice

Mattie et al. 1991

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

JP-8

Male Sprague-Dawley rats

750, 1,500, or 3,000 mg/kg (gavage)

90 days consecutively

Serum ALT and AST activity increased significantly in all groups, but increase was not dose-related; liver weight similar in all groups; increased relative tissue weight in high-exposure group; liver histologic findings similar in all groups (including control group)

Mattie et al. 1995

JP-8

Male Sprague-Dawley Rats

1,000 mg/m3 (vapor, whole-body)

6 hr/day, 5 days/wk for 6 wk

Hepatic lamin L83 abundance significantly decreased; lamin L603 abundance increased; total lamin A abundance not significantly altered by JP-8 exposure

Witzman et al. 2000

JP-8

Female B6C3F1, DBA/2 mice

1 or 2 g/kg per day (oral gavage)

7 days

Significantly increased body weights of B6C3F1 mice, but not DBA/2 mice; increased liver:body weight ratios in both strains; no marked change in expression of CYP1A1

Dudley et al. 2001

JP-5

Beagles, F344 rats, C57BL/6 mice

150 or 750 mg/m3 (vapor)

90 days continuously

Reversible diffuse mild swelling of hepatocytes, decreased SGPT activity, increased liver weight in dogs; mild hepatic hyperplasia, increased hepatocyte vacuolization in rats; fatty changes in hepatocytes, increased hepatocytic vacuolization, increased liver adenomas in mice

MacEwen and Vernot 1978, 1980, 1981, 1982, 1983, 1985; Gaworski et al. 1984

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

Fuel Type

Species

Exposure Concentration

Exposure Duration

Effects

Reference

JP-4

Male, female F344 rats, C57BL/6 mice

1,000 or 5,000 mg/m3 (vapor)

6 hr/day, 5 day/wk for 12 mo

Decreased liver weights, liver:body weight ratio, SGPT activity in male rats; decreased SGPT activity, presence of liver nodular hyperplasia in high-dose female rats; decreased incidence of adenomas in male high-dose mice; increased liver inflammatory infiltrates, incidence of hepatocellular adenomas in high-dose female mice

MacEwen and Vernot 1981, 1982; Wall et al. 1990; Bruner et al. 1993

JP-4

Beagle dogs, F344 rats, and C57BL/6 mice

500 or 1,000 mg/m3 (vapor)

90 days continuously

No effects in dogs; increased liver weight, decreased SGOT and SGPT activity in rats; increased hepatocellular fatty changes in mice

MacEwen and Vernot 1984

JP-4

Monkeys, dogs, rats, mice

2,500 or 5,000 mg/m3 (vapor)

6 hr/day, 5 days/wk for 8 mo

Increased liver weights; no histopathologic changes

MacNaughton and Uddin 1984

Kerosene

Rat

58 mg/m3 or 231 mg/m3 (vapor, possibly some aerosol)

Subchronic (duration not specified)

Decreased blood glucose at 58 mg/m3; increased blood lactate, pyruvate at 231 mg/m3

Starek and Vojtisek 1986 as cited in ATSDR 1998

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

Kerosene

Dogs, rats

100 mg/m3 (deodorized)

6 hr/day, 5 days/wk, 13 wk

No histopathological changes in the livers of dogs and rats; no liver weight changes in dogs

Carpenter et al. 1976

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CYP, cytochrome P; GST, glutathione-S-transferase; SGOT, serum glutamic oxaloacetic transaminase; SGPT, serum glutamic pyruvic transaminase.

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

in male rats were hepatic basophilic foci found—in livers of 11, 35, and 31% of control, low-dose, and high-dose groups, respectively. The increase in basophilic foci was statistically significant. Basophilic foci are not reliable predictors of potential hepatic carcinogenicity and their presence in the livers of the male rats is of uncertain biological significance. This finding is similar to the specific hyaline nephropathy found in male rats, which does not have biological relevance for humans (see Chapter 8). The observations that no other hepatic alterations were found in male rats and that no alterations were found in hepatic tissue of female rats or of mice diminish the biologic meaning of hepatic foci changes in male rat liver for humans.

In a study by Mattie et al. (1995), Sprague-Dawley rats were given JP-8 daily for 90 days at 750, 1,500, or 3,000 mg/kg by oral gavage. Serum samples were collected 24 hr before sacrifice. Blood and tissue samples were obtained at sacrifice. With respect to hepatic function, serum ALT and AST activity increased significantly in all three groups, but the change was not dose-related. Liver weight was similar in all groups, and relative tissue weight increased only in high-exposure group. Liver histopathologic findings were similar in all dose groups, and not different from the control group.

Dudley et al. (2001) administered JP-8 to female B6C3F1 and DBA/2 mice by oral gavage at 1 or 2 g/kg per day JP-8 for 7 days. Oral JP-8 was associated with a significant increase in body weight in the 1- and 2-g/kg groups of B6C3F1 mice but did not markedly affect body weight gain in DBA/2 mice. Liver weights were not reported, but both doses of JP-8 increased relative liver weight in both strains of mice. Measurement of hepatic cytochrome P1A1 with Western blot analyses revealed no marked change in expression. Reported tissue and body weight changes were not dose-related, and the doses used and the route of administration are of questionable relevance to occupationally-exposed humans. Witzmann et al. (2000) exposed male Sprague-Dawley rats to JP-8 aerosol with a mass median aerodynamic diameter of 1.7-1.9 mm (M. Witten, University of Arizona, personal communication, 2002) by inhalation for 6 hr/day, 5 days/wk for 6 wk. The concentration of JP-8 in the chamber was 1,000 mg/m3. Eighty-two days after exposure, there was no significant change in body weight, and the general health of the rats appeared normal. According to results of electrophoresis, protein mass “fingerprinting,” and sequence tag analysis, hepatic lamin L83 abundance was significantly decreased and lamin L603 abundance was increased. However, total lamin A abundance was not markedly altered by JP-8. Only one measurement time (82 hr after exposure) and one concentration were studied. The relevance of the Witzmann et al. (2000) findings for human risk assessment is not known.

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

Several animal studies have examined the effect of kerosene, the primary substance in JP-8, on liver function. Reductions in blood glucose concentrations were noted in rats after subchronic inhalation of kerosene vapor (and possibly some aerosol) at a mean of 58 mg/m3 (Starek and Vojtisek 1986 as cited in ATSDR 1998). Increased blood lactate and pyruvate concentrations were observed in rats exposed to kerosene at a mean of 231 mg/m3, but not at a mean of 58 mg/m3. The authors speculate that decreased circulating glucose concentrations were associated with increased glycolysis and the inhibition of gluconeogenesis. The effect of kerosene on glycolysis is supported by the findings of increased concentrations of lactate and pyruvate in the blood and liver and increased lactate dehydrogenase activity in the liver. The authors suggested that increased glycolysis was a result of inhibition of cellular respiration by kerosene. In another study, rats and dogs were exposed to deodorized kerosene at 100 mg/m3 for 6 hr/day, 5 days/wk for 13 wk (Carpenter et al. 1976). No histopathologic changes were observed in the livers of the rats or dogs, and no liver weight changes were noted in the dogs.

EFFECTS OF IN VITRO EXPOSURE TO JP-8

Grant et al. (2000) examined the in vitro cytotoxic potential of JP-8 in an H4IIE liver cell line. The H4IIE cell line is an established model used to assess hepatic function and responds to polycyclic aromatic hydrocarbons. In 72-hr viability assays, the concentration of JP-8 producing 50% inhibition (IC50) of growth in H4IIE cells was 12.6 ± 0.4 μg/mL. The relevance of the in vitro findings for humans is not known.

CONCLUSIONS AND RECOMMENDATIONS

In one experimental animal study, F344 rats and C57BL/6 mice continuously exposed to JP-8 vapors at concentrations up to 1,000 mg/m3 for up to 90 days did not show significant changes in hepatic function or structure. In another study, liver weights in male F344 rats exposed to JP-8 aerosols at up to 1,000 mg/m3 for 1 hr per day for 28 days were not significantly different from liver weights in control animals. There were no significant alterations in serum aspartate aminotransferase and alanine aminotransferase activities, indicators of hepatic function, and there were no marked changes in the liver histopathologic findings and cytochrome P450 content, a measure of xenobiotic metabolism. No liver toxicity was observed in rats and mice exposed to JP-4 vapors at up to 5,000 mg/m3 for 6 hr/day, 5 days/wk for 12 mo.

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×

The Subcommittee on Permissible Exposure Levels for Military Fuels, which wrote the 1996 National Research Council report Permissible Exposure Levels for Selected Military Fuel Vapors, used the latter study as a basis for derivation of the interim PEL. On the basis of a no-observed-adverse-effect level of 5,000 mg/m3 identified in rats given JP-4 and applying an uncertainty factor of 10 for interspecies extrapolation, the PEL was 500 mg/m3 (no intraspecies uncertainty factor was used).

The subcommittee recommends that liver toxicity be evaluated in experimental animals exposed to JP-8 vapors and mixtures of vapors and aerosols by the inhalation route. Because inhalation exposures greater than approximately 1,000 mg/m3 for pure JP-8 vapors are difficult to achieve, the Air Force should consider conducting studies with saturated vapor atmospheres on larger numbers of animals or employ longer exposure durations (i.e., longer than 90 days) to increase the power of the studies for observing adverse responses in various organ systems.

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Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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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Mattie, D.R., C.L. Alden, T.K. Newell, C.L. Gaworski, and 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.

Mattie, D.R., G.B. Marit, C.D. Flemming, and J.R. Cooper. 1995. The effects 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.

Suggested Citation:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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:"7 Effects of Jet-Propulsion Fuel 8 on the Liver." 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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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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