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Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants (2005)

Chapter: 3 Uncombusted Fuels and Combustion Products: Background Information

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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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3
UNCOMBUSTED FUELS AND COMBUSTION PRODUCTS: BACKGROUND INFORMATION

In addition to the partially combusted crude oil associated with the well-publicized oil-well fires, several petroleum-derived fuels were present in the Persian Gulf region during Operation Desert Shield and Operation Desert Storm, including gasoline, kerosene, diesel, and jet-propulsion fuels JP-4, JP-5, and JP-8. Those fuels were used by the military to power aircraft, ground vehicles, tent heaters, and cooking stoves. They were also used for less conventional purposes, such as suppressing sand, cleaning equipment, and burning trash. Military personnel serving in the Gulf War theater of operations could have been exposed to the uncombusted fuels, the combustion products from the burning of those fuels, or a combination of uncombusted and combusted materials.

This chapter provides background information on fuels and their combustion products separately. Information on the individual components of combustion products are discussed when it is available and relevant. The main exposure routes of concern are inhalation and dermal; ingestion of fuels by Gulf War personnel is of much less concern. As noted in Chapter 2, the committee used data from animal and in vitro studies mainly as background information and to provide support, when possible, for its conclusions. They were also used in deciding whether there is a causal relationship between exposure and disease. Most of the compounds discussed here are common pollutants on which there is a large volume of literature, including numerous reviews. In light of the committee’s use of the data, this chapter provides an overview of the compounds and their toxicology. The reader is referred to reviews for more details; primary toxicology studies are discussed only as warranted.

UNCOMBUSTED FUELS

Petroleum-derived fuels are complex mixtures that contain hundreds of aliphatic and aromatic hydrocarbon compounds; most also contain performance-enhancing additives. The composition of a particular fuel varies from batch to batch, depending on such factors as the source of the crude oil from which it is derived, the refining process used in its production, and the product specifications. The toxicity of some components of the fuels (for example, benzene, toluene, and xylenes) has been well characterized, but the toxicity of many, particularly the longer-chained carbon compounds, has not been extensively studied.

This section provides an overview of toxicologic information on gasoline, kerosene, diesel, JP-4, JP-5, and JP-8. It begins with summaries of physical and chemical properties of the

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

various fuels and a compendium of exposure limits recommended by national and international government bodies and other organizations. That information is followed by a description of the toxicokinetics of the fuels and a summary of experimental studies conducted in humans and animals, focusing on studies that yielded information on chronic adverse health effects, on genetic susceptibility, or on interactions between fuels and other substances.

The fuels discussed here have been the subjects of comprehensive reviews by the Agency for Toxic Substances and Disease Registry (ATSDR 1995a, 1995b, 1995c, 1998, 1999b), the International Agency for Research on Cancer (IARC 1989), the National Research Council (NRC 1996b, 2003), and Ritchie et al. (2003). The reader is referred to those sources for more detailed reviews of the toxicologic data on those fuels.

Several components of hydrocarbon fuels—benzene, toluene, xylenes, and naphtha—were reviewed in Gulf War and Health, Volume 2: Insecticides and Solvents (IOM 2003) and will not be addressed individually here. The Committee on Gulf War and Health: Literature Review of Insecticides and Solvents found sufficient evidence of a causal relationship between benzene and both acute leukemia and aplastic anemia. The reader is referred to that volume for more information on adverse health effects associated with exposures to benzene, toluene, xylenes, and naphtha.

Physical and Chemical Properties

Some of the physical and chemical properties of gasoline, kerosene, diesel, JP-4, JP-5, and JP-8 are presented in Table 3.1. They are arranged in order of increasing carbon number, that is, according to composition of relatively longer hydrocarbon chains or heavier cut of distillates. Naphthas, middle distillates used in mixing gasoline and composed primarily of C5-C13 aliphatic hydrocarbons, would fall between gasoline and JP-4. Kerosene, JP-5, and JP-8 are very similar in composition, differing primarily in the additive packages that characterize them; hence they share several synonyms.

Exposure Limits

Limits of occupational exposures to several fuels have been recommended by such organizations as the American Conference of Governmental Industrial Hygienists (ACGIH), ATSDR, IARC, the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). Those values, as summarized in Table 3.2, give a sense of what fuel exposures are currently considered safe.

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

TABLE 3.1 Chemical Identity and Some Physical and Chemical Properties of Selected Fuels

Properties

Gasoline

JP-4

JP-5

JP-8

Kerosene

Diesel

Synonyms

Motor fuel, motor spirit, natural gasoline, petrol, mogas

MIL-T-5624-L-Amd. 1 wide cut (registered trade name)

NATO F-44, AVCAT, MIL-T5624M

NATO F-34, AVTUR, MIL-T83133B

Fuel oil no. 1, Deobase, kerosene, K-1, JP-1

Auto diesel, automotive diesel oil, diesel fuel oil, diesel oil, fuel oil no. 1-D, fuel oil no. 2, fuel oil no. 2-D, fuel oil no. 4, gas oil

 

aviation kerosene, kerosene, fuel oil no. 1, jet kerosene, turbo fuel A, straight run kerosene, distillate fuel oils light

 

CAS registry no.

8006–61–9

50815–00–4

8008–20–6 (kerosene) 70892–10–3 (fuel oil no. 1)

8008–20–6 (kerosene) 70892–10–3 (fuel oil no. 1)

8008–20–6

68334–30–5 (general diesel fuel)

Average molecular weight

108

No data found

No data found

No data found

No data found

No data found

Range of carbon numbers

C4-C13

C4-C16

C9-C17

C9-C17

C10-C16

C10-C19

Approximate composition

 

-Alkanes

54.3 (wt. %)

75–78 (wt. %)

84 (vol. %)

71–78 (vol. %)

78–96 (vol. %)

64–85 (vol. %)

-Alkenes

1.8

4–7

0.5

0.5–5

0–5

1–10

-Aromatics

30.5

14–15

16

12–22

4–25

5–30

Additives

Octane enhancers, antioxidants, metal deactivators, ignition controllers, icing inhibitors, detergents/dispersants, corrosion inhibitors

Icing inhibitors, antioxidants, corrosion inhibitors, metal deactivators, anti-static agents

Icing inhibitors, antioxidants, corrosion inhibitors, anti-static agents, lubrication improvers, biocides, thermal stability improvers

Icing inhibitors, static inhibitors, corrosion inhibitors, antioxidants, metal deactivators

No data found

Ignition improvers/centane enhancers, smoke suppressors/combustion enhancers, detergents, flow improvers, cloud-point depressors, wax anti-settlers, static inhibitors, corrosion inhibitors, antioxidants, anti-foam agents, dehazers, biocides, lubricants, odor maskers

Physical state

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Color

Colorless to pale brown

Colorless to straw colored

Clear

Clear

Colorless to brown

Colorless to brown

Odor

Gasoline-like

Like gasoline and/or

Kerosene-like

Kerosene-like

Kerosene-like

Kerosene-like

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Properties

Gasoline

JP-4

JP-5

JP-8

Kerosene

Diesel

 

kerosene

 

Melting point

−90.5–−95.4°C

−46°C

−46°C

−52°C

−45.6°C

−48–18°C

Boiling point

39–204°C

45–300°C

150–290°C

175–300°C

175–325°C

101–588°C

Density

0.7–0.8 g/ml (temperature not specified)

0.75–0.80 g/ml (at 15°C)

0.79–0.85 g/ml (at 15°C)

0.79–0.85 g/ml (at 15°C)

0.80 g/ml (at 20°C)

0.87–1.0 g/ml (at 20°C)

Solubility

 

-Water

Insoluble (at 20°C)

57 mg/L (at 20°C)

≈5 mg/L (at 20°C)

≈5 mg/L (at 20°C)

≈5 mg/L (at 20°C)

≈5 mg/L (at 20°C)

-Organic solvents

Absolute alcohol, ether, chloroform, benzene

Generally miscible with organic solvents

Miscible with other petroleum solvents

Miscible with other petroleum solvents

Miscible with other petroleum solvents

No data found

Flashpoint

−46°C

−23–1°C

60°C

38°C

38°C

38–58°C

NOTES: CAS=Chemical Abstracts Services; JP-4=jet-propulsion fuel 4; JP-5=jet-propulsion fuel 5; JP-8=jet-propulsion fuel 8.

When several data points were found for a property of a given fuel, they are presented as a range.

SOURCES: ATSDR (1995a, 1995b, 1995c, 1998, 1999b), Budavari et al. (1989), HSDB (2003a, 2003b), NRC (1996b, 2003), WHO (1996).

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

TABLE 3.2 Recommended Exposure Limits for Fuels

Organization

Fuel Type

Type of Exposure Limit

Recommended Exposure Value

Reference

Occupational Exposure Limits

ACGIH

Gasoline

TLV

STEL

300 ppm=890 mg/m3, A3 (adopted 1996)

500 ppm=1,480 mg/m3

ACGIH 2003

 

Diesel (as a total hydrocarbons)

TLV

100 mg/m3, A3, Skin (adopted 2001)

ACGIH 2003

 

Kerosene (8088–20–6) (as a total hydrocarbon vapor)

TLV

200 mg/m3, A3, Skin (proposed 2002)

ACGIH 2003

 

Jet fuels (94114–58–6) (as a total hydrocarbon vapor)

TLV

200 mg/m3, A3, Skin (proposed 2002)

ACGIH 2003

AFOSH

Petroleum distillates (naphtha)

PEL

STEL

400 ppm

500 ppm

Air Force 1989

 

JP-5

PEL

STEL

350 mg/m3 (interim)

1,000 mg/m3 (interim)

Ritchie et al. 2003

NIOSH

Gasoline

Carcinogen: lowest possible concentration

NIOSH 1998

 

Kerosene

REL

100 mg/m3

NIOSH 1997

 

Petroleum distillates (naphtha)

REL

85 ppm=350 mg/m3

NIOSH 1997

 

 

Ceiling (15-min)

438 ppm=1,800 mg/m3

 

 

 

IDLH

10,000 ppm

NIOSH 1997

OSHA

Gasoline (in workroom air)

PEL

STEL

300 ppm=900 mg/m3

550 ppm=1,500 mg/m3

OSHA 1989 (29 CFR 1910.1000)

 

Petroleum distillates (naphtha)

PEL

500 ppm=2,000 mg/m3

OSHA 1997 (29 CFR 1910.1000)

Exposure Limits for the General Population

ATSDR

Gasoline (automotive)

MRL

None developed because of data gaps

ATSDR 1995a

 

Diesel (fuel oil no. 2)

MRL

0.02 mg/m3 (acute inhalation exposure)

ATSDR 1995b

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Organization

Fuel Type

Type of Exposure Limit

Recommended Exposure Value

Reference

 

Kerosene (fuel oil no. 1)

MRL

0.01 mg/m3 (intermediate-duration inhalation exposure)

ATSDR 1995b

 

JP-4

MRL

9 mg/m3 (intermediate-duration inhalation exposure)

ATSDR 1995c

 

JP-5/JP-8

MRL

3 mg/m3 (intermediate-duration inhalation exposure)

ATSDR 1998

IARC

Gasoline

Evaluation of carcinogenicity

Possibly carcinogenic to humans (group 2B)

IARC 1989

 

Distillate (light) diesel

 

Not classifiable as to its carcinogenicity to humans (group 3)

 

 

Jet fuel

 

Not classifiable as to its carcinogenicity to humans (group 3)

 

NOTES: ACGIH=American Conference of Governmental Industrial Hygienists; TWA=Time-Weighted Average; TLV=Threshold Limit Value (TWA for 8-hr workday during 40-hr workweek); A3=Confirmed Animal Carcinogen with Unknown Relevance to Humans; Skin=potentially large contribution to exposure by dermal route; STEL=Short-Term Exposure Limit (15-min TWA); Ceiling=value never to be exceeded; AFOSH=Air Force Office of Safety and Health; ATSDR=Agency for Toxic Substances and Disease Registry; MRL=minimal risk level; JP-4, 5, or 8=jet-propulsion fuel 4, 5, or 8; IARC=International Agency for Research on Cancer; NIOSH=National Institute for Occupational Safety and Health; REL=Recommended Exposure Limit (TWA for 10-hr workday during 40-hr workweek); IDHL=Immediately Dangerous to Life or Health; OSHA=Occupational Safety and Health Administration; PEL=Permissible Exposure Limit (TWA for 8-hr workday during 40-hour workweek).

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Toxicokinetics

Given that gasoline, kerosene, diesel, JP-4, JP-5, and JP-8 are composed of hundreds of hydrocarbon compounds, it is impractical to describe here the toxicokinetics of each component. Because fuels contain many different components, they will exhibit a wide range of variability regarding absorption, metabolism, and excretion. General aspects of the toxicokinetics of JP-8 were presented in the recent National Research Council report Toxicologic Assessment of Jet-Propulsion Fuel 8 (NRC 2003). The principles are applicable to gasoline, kerosene, diesel, JP-4, and JP-5, and they are repeated here. The major determinants of hydrocarbon toxicokinetics after systemic uptake are disposition-related physiologic properties of the organism—such as alveolar ventilation, cardiac output and blood flow to the organs, and organ volume—and partition coefficients of the fuel components. Hydrocarbons with high blood:air partition coefficients are absorbed to a greater extent than compounds with poor blood solubility. Given that most hydrocarbons have fairly high fat:air and fat:blood partition coefficients, it is not surprising that fat or adipose tissue is a major storage depot for many of the fuel components. For hydrocarbons with high fat:blood partition coefficients, metabolic clearance after cessation of exposure is especially important. Hydrocarbons and their metabolites accumulate in lipid-rich tissues, so the absence of hydrocarbons and their metabolites in exhaled air, blood, or urine does not necessarily mean the absence of systemic exposure. Cytochrome P450 enzymes metabolize most hydrocarbons by such reactions as aliphatic hydroxylation, aromatic hydroxylation, and epoxidation. Alcohol and aldehyde dehydrogenases play an important role in metabolizing alcohols into their corresponding keto acids. Phase II reactions—including conjugation with glutathione, glucuronic acid, sulfate, and glycine—are important in formation of water-soluble metabolites.

Data on absorption, distribution, metabolism, and elimination of gasoline, kerosene, diesel, JP-4, JP-5, and JP-8 are sparse. The components of each of these fuels are processed primarily according to their own physicochemical properties. When Tsujino et al. (2002) applied 1ml of kerosene dermally to the abdomen of rats for 1, 3, or 6 hr, it was absorbed and distributed via blood circulation, but the aromatic compound trimethylbenzene was absorbed by the skin to a greater degree than the aliphatic hydrocarbons. Kimura et al. (1988) had similar results with inhaled gasoline and kerosene. Local and systemic effects observed after exposure to those fuels indicated that they are absorbed by the respiratory tract, the gastrointestinal tract, and the skin. Toxicokinetic information on several fuel components is available (in particular, benzene, toluene, and xylenes); but their interactions with each other and with other hydrocarbon components may affect their toxicokinetic properties (ATSDR 1989, 1990, 1991, 1995e; NRC 1996a).

Experimental Studies

Controlled studies of the toxicity of gasoline, kerosene, diesel, JP-4, JP-5, and JP-8 in humans and laboratory animals are summarized here, with emphasis on studies that addressed whether effects persist after cessation of exposure. Epidemiologic studies of the adverse health effects of the fuels will be discussed in later chapters.

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×
Cancer

MacFarland et al. (1984) exposed Fischer 344 rats and B6C3F1 mice to unleaded gasoline vapors by inhalation at up to about 2,000 ppm for 2 years. There was an increased incidence of hepatocellular adenomas and carcinomas in the exposed female mice but not in the exposed males. There was an increased incidence of renal adenomas and carcinomas in the exposed male rats, but not in the exposed females; these kidney tumors were probably related to a male-rat-specific nephropathy (see discussion of renal effects later in this section) that is not considered relevant to humans (ATSDR 1995a). Gasoline contains 2–3% benzene, a known human carcinogen that has been shown to cause an increased incidence of leukemia in occupationally exposed workers (ATSDR 1991; IARC 1989). No studies that assessed cancer in laboratory animals from dermal or oral exposure to gasoline were found.

Middle-distillate fuels (MDFs)—which include kerosene, diesel, JP-5, and JP-8—have been shown to cause skin tumors in mice (reviewed in IARC 1989; and also reviewed in Nessel 1999). MDFs have low or no mutagenic activity and no tumor-initiating activity. They are, however, active skin-tumor promoters, requiring chronic dermal irritation and skin injury. That profile indicates that dermal carcinogenesis associated with MDFs is the result of a nongenotoxic process (Nessel 1999). No carcinogenicity studies that assessed cancer in laboratory animals from inhalation or oral exposure to MDFs were found.

Genotoxicity

Several in vivo and in vitro assays have shown gasoline, kerosene, diesel, JP-5, and JP-8 not to be highly genotoxic (reviewed in ATSDR 1995a, 1995b, 1995c, 1998; NRC 2003). They are not mutagenic in multiple strains of Salmonella typhinurium with and without activation (Brusick and Matheson 1978a, 1978b; Conaway et al. 1984; Deininger et al. 1991; McKee et al. 1994, 1989; Nessel 1999). Mixed results have been reported concerning mutagenicity from the in vitro mouse lymphoma assay and from in vitro and in vivo assays of induction of sister-chromatid exchanges (API 1988a, 1988b).

Neurologic Effects

Several studies assessed nervous system effects after cessation of exposure of laboratory animals to hydrocarbon fuels. The relevance to humans of neurobehavioral effects observed in animals, however, is not well understood.

Kainz and White (1983) exposed CD-1 mice to diesel-fuel vapors at up to 204 mg/m3 for 8 hr/day for 5 days and followed the exposure with a 24-hr no-exposure period. They found that motor coordination, as measured by a rotarod test, was progressively decreased in the mice given the highest dose, but showed signs of recovery after 24 hr. Inconclusive results were reported for the hot-plate test, and no effects were observed when the mice were given the inclined-plane test or the corneal-reflex test.

A series of light naphtha distillates, which are used in mixing gasoline, were tested in Sprague-Dawley rats according to a common protocol: exposure at up to 7,500 ppm for 6 hr/day 5 days/week for 13 weeks followed by motor-activity evaluation, a functional observational battery, and a neuropathology examination after a 4-week no-exposure period. Significantly higher motor activity was observed in the males given high doses of light catalytic reformed naphtha, but no other nervous system effects were observed among rats exposed to that agent

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

(Schreiner et al. 2000), to light alkylate naphtha (Schreiner et al. 1998), or to light catalytic cracked naphtha (Lapin et al. 2001).

Nordholm et al. (1999) exposed Sprague-Dawley rats by inhalation to JP-4 vapors at 2,000 mg/m3 for 6 hr/day for 14 days and followed the exposure with no-exposure periods of 14 or 60 days. Similarly, Sprague-Dawley rats were exposed by inhalation to JP-8 or JP-5 vapors at up to 1,000 or 1,200 mg/m3, respectively, for 6 hr/day 5 days/week for 6 weeks, and the exposure was followed by a 65-day no-exposure period (Ritchie et al. 2001; Rossi et al. 2001). Subtle but apparently persistent changes in neurophysiologic and psychologic capacity detectable only with appropriate test batteries were observed, but no dose-response relationships were demonstrated.

Koschier (1999) reported that rats dermally exposed to hydrodesulfurized kerosene at up to 495 mg/kg for 5 days/week for 13 weeks followed by a 4-week no-exposure period did not show any adverse neurobehavioral or histologic effects compared with the control group.

Although this study was not an experimental investigation, former “gasoline-sniffers” (after at least a 6-month hiatus) showed higher rates of abnormal tandem gait, bilateral palmomental reflexes, and cognitive deficits in visual recognition memory and pattern-location paired associate learning than a control group (Goodheart and Dunne 1994). The magnitude of neurologic and cognitive effects correlated with duration of gasoline-sniffing and with blood lead concentrations, so the outcomes might not have been attributable entirely to the petrochemical components of the gasoline.

Respiratory Effects

Various respiratory effects (such as increased pulmonary resistance, interstitial edema, and damage to bronchiolar epithelium) have been observed in some subchronic and chronic animal studies immediately following exposure to hydrocarbon fuels but other studies did not find such effects (as reviewed in ATSDR 1995a, 1995b, 1995c, 1998; NRC 2003). It is not known whether the observed respiratory effects would have persisted or reversed themselves after a no-exposure period.

A single large study of persistence of respiratory effects after a no-exposure period in laboratory animals exposed to a hydrocarbon fuel was found. Bruner et al. (1993) exposed mice and rats of both sexes to JP-4 vapors at 1,000 or 5,000 mg/m3 for 12 months. Immediately after the 12-month exposure period, the low-dose female mice showed mild pulmonary inflammation and the low-dose males of both species showed hyperplasia of the nasolacrimal duct epithelium. No effects were present in either species 12 months after exposure.

Hepatic Effects

A number of studies have assessed the potential of subchronic or chronic exposure to hydrocarbon fuels to cause hepatic effects in laboratory animals immediately after exposure (as reviewed in ATSDR 1995a, 1995b, 1995c, 1998; NRC 2003).

Several studies of subchronic or chronic exposure of mice to unleaded gasoline vapors at about 2,000 ppm showed hepatic effects, such as hypertrophy, increased cytochrome P450 content, and tumor-related necrosis and hemorrhage. Other studies of subchronic or chronic exposure at similar concentrations did not find any adverse hepatic effects in rats and monkeys (ATSDR 1995a).

Increased liver weight has been associated with subchronic exposure of mice, rats, dogs, and monkeys to JP-4 vapors at up to 5,000 mg/m3 (MacNaughton and Uddin 1984). Reversible

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

hepatocellular fatty changes in mice, but not in rats and dogs, have been associated with subchronic exposure to JP-4 vapors at up to 1,000 mg/m3 (MacEwen and Vernot 1984).

Inconsistent results have been reported in inhalation-, oral-, and dermal-exposure studies of hepatic effects caused by kerosene, JP-5, and JP-8 (which are similar in composition). Several subchronic inhalation studies found hepatic effects: increased glycolysis in rats (Starek and Vojtisek 1986); increased hepatic basophilic foci in male rats but not in female rats or in mice (Mattie et al. 1991); and reversible diffuse mild swelling of hepatocytes, decreased serum glutamic pyruvic transaminase, mild hepatic hyperplasia, increased hepatocyte vacuolization, fatty changes in hepatocytes, and increased liver adenomas in rats, mice, and dogs and increased liver weight only in dogs (Keller et al. 1984). Other studies with similar exposure conditions did not report any hepatic effects (Bogo et al. 1983; Carpenter et al. 1976; Parton 1994).

Two studies assessed the persistence of hepatic effects after a no-exposure period in laboratory animals exposed to a hydrocarbon fuel. Dennis (1982) found no hepatic lesions 14 days after applying JP-4 at 2,000 mg/kg to the skin of rabbits. (Bruner et al. 1993) observed no liver toxicity in rats exposed to JP-4 vapors at 1,000 or 5,000 mg/m3 for 6 hr/day 5 days/week for 12 months. However, after a 12-month no-exposure period, non-dose-related decreases were found in the liver weights of the male, but not female, rats. Of mice exposed at the same concentrations and for the same duration, only high-dose females had an increase in lymphocytic inflammatory infiltrates in the liver at the end of the exposure period, but that effect was no longer found at the end of the 12-month no-exposure period (Bruner et al. 1993).

Cardiovascular Effects

Because hydrocarbons historically have been used as anesthetics and abused as narcotics, inhalation of hydrocarbons is well known to have acute effects on the cardiovascular system (NRC 1996b). They can induce potentially fatal cardiac arrhythmias, but for arrhythmias to occur epinephrine must be released simultaneously with inhalation (Garb and Chenoweth 1948). Chronic effects of hydrocarbon fuels on the cardiovascular system have not been well studied.

Gastrointestinal Effects

Gastrointestinal effects have been observed in laboratory animals after oral exposure to gasoline (gastric erythema, erosion of the gastric mucosa, and ulceration of the epithelium) and kerosene (gastritis and hyperplasia) and after inhalation exposure to JP-4 (emesis) (reviewed in ATSDR 1995a, 1995b, 1995c, 1995e, 1998).

Immimologic Effects

MDFs have been shown to be weak to moderate skin sensitizers in laboratory animals (Cowan and Jenkins 1981; Kanikkannan et al. 2000; Kimber and Weisenberger 1989; Kinkead et al. 1992a, 1992b; Schultz et al. 1981).

Dermal exposure of mice to several MDFs (kerosene, JP-5, and JP-8) has been found to cause a variety of local and systemic immune effects, such as decreases in relative weights of lymph nodes and thymus, in thymocyte counts, in bone marrow nucleated cell counts, in thymic cortical lymphocytes, and in cellularity of thymic lobules, and in suppression of contact and delayed hypersensitivity responses (Ullrich 1999; Upreti et al. 1989).

Immune-system effects have also been observed in rats exposed to diesel fuel aerosol and JP-8 aerosol by inhalation (Dalbey et al. 1987; Harris et al. 1997b, 1997a, 2000), but no immune-system effects were found in rats exposed to JP-8 vapor by inhalation or in rats or monkeys

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

exposed to gasoline by inhalation (Kuna and Ulrich 1984; Mattie et al. 1991). JP-8 aerosols are believed to be more immunotoxic than JP-8 vapors (NRC 2003).

Oral exposure of rats and mice to kerosene or JP-8 caused immune-system effects, such as decreases in white-cell count, in relative spleen weight, in thymic weight, and in antibody plaque-forming cell response to sheep red cells (Dudley et al. 2001; Mattie et al. 1995; Parker et al. 1981). Keil et al. (2003) found that in utero exposure of mice to JP-8 at 1,000 or 2,000 mg/kg by gavage on gestation days 6–15 impaired the immune function of the offspring later in life.

Renal Effects

Some hydrocarbon fuels have been shown to induce hydraline droplet nephropathy syndrome in male rats (but not in female rats or in males and females of any other species) exposed subchronically or chronically by inhalation or ingestion (reviewed in ATSDR 1995a, 1995b, 1995c, 1998; Bruner et al. 1993; Cowan and Jenkins 1981; Keller et al. 1984; Mattie et al. 1991, 1995; NRC 2003; Parker et al. 1981; Parton 1994). The components of hydrocarbon fuels determined to be largely responsible for the syndrome in the male rat are the branched alkane compounds with six or more carbons (ATSDR 1995a). Hydraline droplet nephropathy syndrome is sex- and species-specific and is not considered to be relevant to humans (Alden 1986; Flamm and Lehman-McKeeman 1991).

Reproductive and Developmental Effects

No developmental effects were observed in the fetuses of rats exposed to unleaded gasoline vapors at 1,600 ppm during gestation (Litton Bionetics 1978). Unleaded-gasoline vapors did not cause developmental defects (malformations, total variations, resorptions, low fetal body weight, or low offspring viability) in the offspring of rats exposed at up to 23,900 mg/m3 (9,000 ppm) for 6 hr/day on gestation days 6–19 (Roberts et al. 2001). Exposure to unleaded-gasoline vapors at about 2,000 ppm for 2 years did not lead to histologic changes in the reproductive systems of rats or mice (MacFarland et al. 1984). No reproductive effects were found in a two-generation reproduction-toxicity test in which male and female rats were exposed to vapors of gasoline (presumably unleaded) at up to 20,000 mg/m3 (McKee et al. 2000).

Inhalation exposure of pregnant rats to petroleum naphtha at 100 or 400 ppm on days 6–15 of gestation did not produce teratogenic effects (Beliles and Mecler 1982). A similar protocol to test for reproductive and developmental effects was used with three types of light naphtha distillates: alkylated (Bui et al. 1998), catalytic cracked (Schreiner et al. 1999), and catalytic reformed (Schreiner et al. 2000). The results were uniformly negative for all three test agents when male and female rats were exposed at up to 25,000 mg/m3, at 7,500 ppm, and at 7,500 ppm, respectively, daily from 2 weeks before mating through delivery.

No studies of the reproductive- or developmental-toxicity potential of JP-4 were found, but kerosene-related fuels have been tested for reproductive and developmental effects of dermal, oral, and inhalation exposure.

No reproductive or developmental effects were observed when male and female rats were dermally exposed to hydrodesulfurized kerosene at up to 494 mg/kg per day for 7–8 weeks from before mating through gestation (Schreiner et al. 1997). No histologic changes were observed in the reproductive systems of mice dermally exposed to JP-5 at up to 8,000 mg/kg 5 times per week for 13 weeks (NTP/NIH 1998).

No reproductive effects were observed in male and female rats exposed to JP-8 by gavage at up to 1,500 (females) or 3,000 (males) mg/kg per day before and during mating and, in the

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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case of the females, during gestation and lactation (Mattie et al. 2000, 1995). Maternal gestational weight gain and fetal body weights were reduced in rats exposed to JP-8 by gavage at 1,500 or 2,000 mg/kg per day on days 6–15 of pregnancy; the types of fetal abnormalities did not differ significantly between treated and nonexposed rats, and there was a progressive increase in the overall incidence of abnormalities with increasing dose from 500 to 1,500 mg/kg per day, but not 2,000 mg/kg per day (Cooper and Mattie 1996).

Inhalation of jet fuel A (a kerosene-like fuel) at 100 or 400 ppm on days 6–15 of gestation did not produce teratogenic effects in rats (Beliles and Mecler 1982). Similarly, exposing rats to fuel oil at concentrations of 100 or 400 ppm on gestation days 6–15 did not produce teratogenic responses (Beliles and Mecler 1982). Lock et al. (1984) also found that intermediate-duration exposure of rats to diesel-fuel aerosols did not lead to reproductive or developmental effects.

Dermal Effects

Several hydrocarbon fuels have been shown to be skin irritants. Gasoline caused dermal irritation when applied to the skin of rabbits (ATSDR 1995a). Case studies of individuals immersed in gasoline for several hours described chemical burns on the exposed skin (ATSDR 1995a). Case studies also report that dermal exposure to kerosene causes a variety of dermal effects (ATSDR 1995b). Dermal irritation was observed in laboratory animals exposed to JP-4, JP-5, and JP-8 (ATSDR 1995c, 1998).

COMBUSTION PRODUCTS

Combustion of fuels results in the formation of complex mixtures of gases and particles. The specific profile of combustion products is a function of what was burned and under what conditions the burning occurred. The primary constituents that characterize smoke from fires, exhaust from burning fuels, and products of other combustion sources are also those which characterize air pollution in general. The potential toxicity of combustion products varies with their composition, including particle size. The various components have differing toxicities, so the overall toxicity of the complex mixture will depend on the relative amounts of the individual components. Although great strides have been made in the learning about health effects of combustion products, how the relative amounts of components of the products correlate with potential health effects and how they interact with each other are not entirely understood (NRC 2004).

The gases in combustion products can include sulfur dioxide (SO2), ozone (O3), nitrogen oxide (NO), nitrogen dioxide (NO2), carbon monoxide (CO), carbon dioxide (CO2), hydrogen sulfide (H2S), and volatile organic compounds (VOCs) (the oxides of nitrogen as a group are referred to as NOx and the oxides of sulfur as SOx). VOCs were reviewed by the second Institute of Medicine Gulf War committee in conjunction with its review of solvents and are not reviewed here.

The chemical composition and physical composition of particles in general vary widely. They may include elemental and organic carbon, sulfates, nitrates, pollen, microbial contaminants, and metals. Photochemical reactions of fine particles with SO2 and NO2 in the atmosphere form strong acids, such as sulfuric acid, nitric acid, hydrochloric acid, and acid aerosols. Polycyclic aromatic hydrocarbons (PAHs) are formed by incomplete combustion, including combustion of fossil fuels, and can be adsorbed on particulate matter (PM). A number of other hazardous pollutants (such as toxic metals) can be associated with combustion. The

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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committee does not review the health effects of individual hazardous chemicals that might be adsorbed onto PM. The bioavailability and toxicity of such a chemical is affected by being adsorbed on the particle, so toxicity of the chemical alone cannot be directly extrapolated to its toxicity when adsorbed on the particle. In addition, the amounts of hazardous compounds adsorbed on PM are generally lower than the amounts that would be used in animal studies to assess the effects of the compounds themselves. Therefore, the committee focuses on studies of the toxicity of PM, not studies of the individual compounds that might be adsorbed on or incorporated into the PM.

Potential Exposures in the Gulf War

Gulf War veterans were involved in a number of situations with potential for considerable exposure to airborne products of combustion of petroleum or derivatives.

At the end of the Gulf War, over 600 Kuwaiti oil wells were ignited by retreating Iraqi troops. Large plumes of smoke rose from the fires. Occasionally, the smoke remained near the ground and enveloped US military personnel. No systematic monitoring occurred in the initial deployment in 1990 until May 1991, when several independent teams from multiple US and international agencies (including the US Army Environmental Health Agency and the US Environmental Protection Agency, EPA) went into Kuwait to monitor the ambient air contamination due to oil-well fire emissions (Spektor 1998). Smoke sampling was performed to improve understanding of the nature of the plumes generated by the burning oil wells. Most of the oil fires were still burning when measurements began.

Individual fires created distinct smoke plumes over short distances, but over longer distances the plumes merged into one “supercomposite” plume south of Kuwait City measuring about 40 km wide. At the base of the plume, oil falling in droplet form or emitted from uncapped wells collected in pools on the desert; the pools sometimes were on fire as well (Hobbs and Raadke 1992). The smoke plumes from individual fires varied in color and density. Black smoke plumes resulted from single well fires and had relatively high concentrations of carbon; they made up 60–65% of the fires. The densest black plumes were from the burning pools of oil. White smoke plumes, accounting for 25–30% of the fires, contained almost no carbon but had a higher concentration of inorganic salts, which is consistent with reports of the presence of brine solutions in the oil fields (Cofer et al. 1992; Spektor 1998).

The available monitoring data indicate that levels of nitrogen oxides, carbon monoxide, sulfur dioxide, hydrogen sulfide, other pollutant gases, and PAHs did not exceed those in the air of a typical US industrial city. Within the samples, PAH concentrations were low (PAC 1996). High concentrations of PM (sand and soot) were often observed at multiple monitoring sites; an estimated 20,000 tons of soot, or fine-particle mass, was generated by the fires (Thomas et al. 2000) and made up about 23% of the PM in the Persian Gulf, often at concentrations twice those considered safe (Rostker 2000).

In addition to air monitoring, potential exposures of troops to smoke and combustion products from the oil-well fires were modeled (Draxler et al. 1994). Daily and seasonal normalized air concentrations due to emissions from the oil-well fires were computed using a modified Lagrangian transport, dispersion, and deposition model for the period of February through October 1991. The highest normalized concentrations were located near the coast between Kuwait and Qatar. Peak values moved farther west and inland with each season (that is, the smoke and combustion products moved from over the Gulf in the spring to the west over the Saudi Peninsula by autumn).

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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In addition to exposure to smoke from oil-well fires, military personnel might have had exposures to combustion products because they were close to military vehicles, aircraft, and heaters in poorly ventilated tents.

Physical and Chemical Properties

As discussed above, combustion products are complex mixtures of substances. The physical and chemical properties of the major components of combustion products are discussed below.

Gases
Hydrogen Sulfide

As described by the (ATSDR 1999a), H2S is a colorless, flammable gas under normal conditions. H2S—also known as hydrosulfuric acid, stink damp, and sewer gas—has an odor similar to that of rotten eggs. It is a naturally occurring compound found in crude petroleum, natural gas, volcanic gases, and hot springs. It can also be made by people, and it can be found in human and animal waste, sewage-treatment facilities, sediments of fish aquaculture, and livestock barns or manure areas. Petroleum refineries, natural-gas plants, petrochemical plants, coke-oven plants, kraft-paper mills, food-processing plants, and tanneries are other sources of H2S (ATSDR 1999a).

Sulfur Oxides

SOx easily dissolve in water. Sulfur is found in raw materials, including crude oil, coal, and ore that contains common metals, such as aluminum, copper, zinc, lead, and iron. When fuel that contains sulfur is burned, SOx is formed. SOx can also form when gasoline is extracted from oil, or metals are extracted from ore.

SO2 dissolves in water vapor to form sulfuric acid, and it interacts with other gases and particles in the air to form sulfates and other products. Sources of SO2 include electric utilities, petroleum refineries, cement manufacturing, and metal-processing facilities. Locomotives, large ships, and some nonroad diesel equipment burn high-sulfur fuel and release SO2 into the air (EPA 2003b).

Nitrogen Oxides

From the human-exposure perspective, NO2 is the most important and common nitrogen oxide. NO2 is a reddish brown, water-soluble, moderately oxidizing gas. The primary atmospheric reaction for NO2 production is the rapid oxidation of NO by oxidants, such as O3. Major sources of NO2 include the combustion of fossil fuels from stationary sources for heating and power generation and in motor-vehicle internal-combustion engines. As in the case of many other outdoor pollutants, concentrations of NO2 can vary with the time of day, the season, meteorologic conditions, and human activities (Gong 1992). Unvented combustion appliances, such as gas stoves and gas-fired water heaters, are major sources of indoor NO2.

Carbon Monoxide and Carbon Dioxide

The fourth-most abundant gas in the earth’s atmosphere, CO2 is a colorless, odorless, and faintly acid-tasting gas at room temperature. It is transformed into sugars and other forms of energy by plants during photosynthesis, and it is exhaled by animals as a waste product of

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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cellular respiration and released into the air during the burning of carbon-containing fossil fuels (oil, coal, and natural gas).

CO, also a colorless and odorless gas, is highly toxic to humans. It is formed as a result of the incomplete combustion of carbon-containing compounds. Heaters, oil- and wood-burning furnaces, and nonelectric stoves and ranges used in confined or poorly ventilated spaces can rapidly accumulate CO to dangerous concentrations.

Ozone

Ground level O3 is a highly reactive and oxidative gas that is formed by photochemical reactions of sunlight, NO2, and hydrocarbon vapors. Ozone concentration peaks in the late morning or afternoon and declines in the evening because of its reactions with nitric acid and terrestrial surfaces. Because hydrocarbon vapors and NO2 persist in the atmosphere, O3 can form far downwind of the sources; O3 concentrations can be higher in suburbs and rural areas than in urban areas (Lippman 1992).

Particulate Matter

Airborne PM consists of a complex mixture of organic and inorganic solids and gas-liquids (aerosols) with heterogeneous physicochemical composition, size, and biologic activity (Gong 1992). PM is made up of particles of extremely diverse sizes. Particles of 3–50 nm in aerodynamic diameter are most prevalent in urban air adjacent to roadways as a result of vehicle emissions, but particles can be 100 nm or larger. The size of the PM dictates how deeply into the lungs the particles will penetrate, which is related to their potential for toxicity.

PM generated by combustion generally consists of different chemical species. PM can have adsorbed PAHs, aldehydes, sulfuric acid, and toxic metals. Even individual particles in an aerosol typically will have a complex chemical composition. The effects of a particular component of an aerosol may depend on its physical state, that is, whether it is part of a particle core or adsorbed onto the particle surface.

Toxicokinetics

Gases

Water solubility is the main determinant of how deeply into the lungs a gas penetrates. In general, highly soluble gases, such as SO2, do not penetrate farther than the nose. Insoluble gases, such as O3 and NO2, penetrate deeply into the lungs and are more toxic. Highly insoluble gases, such as CO and H2S, pass through the respiratory tract and are taken up into the bloodstream and distributed throughout the body.

Breathing rate, blood flow, and route of exposure (oral vs nasal) to the lungs also affect the bioavailability of gases. Increased airflow can increase the penetration of some gases (such as SO2) into the lungs. Therefore, a person who is exercising will have increased bioavailability of such gases. Increased blood flow to the lungs, as occurs during exercise, also increases the bioavailability of gases that are taken up into the bloodstream.

Particulate Matter

In general, large particles (over 10 µm) will not remain suspended in the air and will not enter the air passages and therefore are not bioavailable. As particles become smaller they are

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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deposited farther down the respiratory tract and particles smaller than 2.5 µm are deposited deep in the lung.

Other hazardous pollutants, such as toxic metals, can be adsorbed onto the surface of particles, and this leads to exposure to them. The reactivity and solubility of the components of the PM also affect their bioavailability. More-reactive and more-soluble compounds interact with the lungs and are deposited more proximally than less-reactive and less-soluble compounds, which can be deposited deeper in the lungs. PAHs, which also can be present on PM, can be absorbed in humans and animals. PAHs are widely distributed in animals (there are no comparable data on humans). Metabolism occurs via many pathways. The metabolites include epoxide intermediates, dihydrodiols, phenols, and quinines. The epoxide intermediates are electrophilic and are thought to mediate the genotoxicity of PAHs. In animals, the feces are the major route of excretion after inhalation.

Toxicity Studies

Toxicity studies have been conducted on combustion product mixtures and on the individual components of combustion products. This section discusses studies of mixtures of smoke or exhaust and then the health effects seen in relevant studies after exposures to some of the individual components of combustion products. The focus is on inhalation studies because the committee considered inhalation to be the route of exposure most relevant to potential exposures in the Gulf War. A brief discussion of the potential effects of PM after dermal exposure is included.

Experimental studies of the effects of combustion products after inhalation have been conducted in air chambers and with intratracheal instillation. The method of exposure should be taken into account in interpreting and extrapolating their results. It should also be noted that the committee has focused on the initiation or induction of disease and not on the exacerbation of disease states. This section therefore focuses on effects on normal, not compromised, animals.

Mixtures of Combustion Products

Two studies investigated the effects specifically of smoke from the Kuwaiti oil-well fires. Moeller et al. (1994) studied feral cats exposed to the smoke. Cats were collected from Kuwait about 8 months after the fires began. Twelve of the animals were from Kuwait City, which was relatively smoke-free and 14 were from Ahmadi, in which there was high smoke exposure. Histopathologic tests were conducted on all major organs (for example, lung, liver, and kidney), and lung, liver, kidney, urine, and blood samples were tested for the presence of various toxicants. The authors concluded that exposure to the smoke had little or no long-term effects on the animals.

Brain et al. (1998) compared the effects of intratracheal instillation of the particles from the oil fires (smaller than 3.5 µm) at 0.15, 0.75, and 3.75 mg/100 g of body weight with those of particles collected in St. Louis, Missouri, on pulmonary inflammation in hamsters. Twenty-four hours after instillation, the hamsters exposed to the oil-fire particles had effects qualitatively similar to those in hamsters exposed to the particles from St. Louis. But they had higher concentrations of macrophages and neutrophils and lower myeloperoxidase and lactate dehydrogenase activity in their bronchoalveolar lavage than the animals exposed to the St. Louis particles. Albumin and ss-N-acetylglucosaminidase activities were comparable. Most of the measures had returned to control values by 7 days after instillation. The authors concluded that

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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the responses in hamsters to particles from the oil fires were similar to those from typical urban summer pollution in St. Louis.

A number of acute-exposure toxicity studies have been conducted in laboratory animals, of which several are described here. A single exposure of sheep to wood smoke via inhalation resulted in dose-dependent injury to the tracheobronchial epithelium and lung parenchyma, but total antioxidant potential was not affected (Park et al. 2004). Ho and Kou (2002) studied the mechanism of wood-smoke-induced increases in nasal-airway resistance and airway reactivity in anesthetized rats. Reflex cholinergic and tachykininergic and possibly augmented nasal swelling appeared to be involved. The effects of subchronic exposure of brown Norway rats to relatively low concentrations of wood smoke—fine particles (smaller than 1 µm) at 1 or 10 mg/m3—5 days/week for 4 or 12 weeks in whole-body chambers were investigated by Tesfaigzi et al. (2002). Mild respiratory effects were seen. At the high concentration, pulmonary function and pulmonary resistance were somewhat affected. Mild chronic inflammation and squamous metaplasia were observed in the larynx of exposed groups. Alveolar macrophage hyperplasia severity was increased and pigmentation was increased with dose, and the alveolar septa were slightly thickened.

Because epidemiologic data indicate a possible association between exposure to smoke and respiratory cancer, toxicologic studies have been conducted to further investigate the association. Studies have indicated that smoke from cooking with biofuels was associated with increased micronuclei and chromosomal aberrations in Indian women; the extent of the effects depended on the cooking fuel (Musthapa et al. 2004). Lohani et al. (2000) investigated the genotoxicity of kerosene soot in vitro in Syrian hamster embryo fibroblasts. The significant increase in induced micronuclei seen after treatment with soot (0.5–1.0 µg/cm2 for 66 hr) indicated that kerosene soot can be genotoxic in vitro. Subcutaneous injection of extracts of soot from cooking fires into mice led to skin cancer (Liang et al. 1984), and dermal application of soot extracts from smoky-coal but not wood combustion could act as a complete carcinogen in mice (Mumford et al. 1990). Exposing rats and mice to coal and wood smoke by natural inhalation (placing the animals in rooms with cooking similar to what would occur in homes in some areas of China) resulted in a statistical increase in number of lung cancers (Liang et al. 1988). The larger increase was seen after exposure to coal smoke.

A great deal of research has also been conducted into the possible health effects of diesel exhaust, which is relevant not only because diesel fuel was burned in the Gulf War but because diesel exhaust contains many of the same components as other combustion products, such as smoke from oil-well fires. The potential health effects and experimental data on diesel exhaust have been reviewed and summarized by EPA (2002). Chronic exposure of animals to concentrations of diesel exhaust that are not acutely toxic have demonstrated respiratory effects (histopathologic and immunologic) in several animal species. Diesel exhaust has also been shown to be carcinogenic in a number of laboratory animals. Diesel exhaust given by inhalation at levels sufficient to induce particle overload has been shown to be carcinogenic in rats, but not in other rodent species (Nikula 2000). There is evidence that diesel exhaust, or some fraction of diesel exhaust, is mutagenic. What fraction might mediate effects is not well established (EPA 2002).

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Gases
Hydrogen Sulfide

Histologic and biochemical changes have been seen in the respiratory system after acute toxic exposures to H2S (for review, see ATSDR 1999a). The effects of lower concentrations of intermediate or chronic exposure are not as clear.

The Chemical Industry Institute of Toxicology (CIIT 1983a, 1983b, 1983c) exposed Fisher-344 rats, Sprague Dawley rats, and B6C3F mice to H2S at a time-weighted average concentration of 10.1, 30.5, or 80 ppm for 6 hr/day 5 days/week for 90 days. No treatment-related effects on the cardiovascular system, the gastrointestinal system, immune function, the renal system, the hepatic system, bone marrow or bones, or the hematologic system were seen. Body weight was decreased by 10% in female Sprague Dawley rats in the 80-ppm dose group, and inflammation of the nasal mucosa was seen in mice at that dose. CIIT also looked at behavior and neuropathology end points and reproductive effects; no effects on any of those end points were seen.

Curtis et al. (1975) exposed pigs to H2S at 8.5 ppm for 24 hr/day for 17 days; no effects on the gastrointestinal system were observed.

Hayden et al. (1990) saw an increase in parturition time and difficulty in delivery in 6 of 17 rats exposed to H2S at 20, 50, or 75 ppm but in only one of seven control animals; no statistical analyses were performed. Although few studies have been conducted, H2S does not appear to be genotoxic (ATSDR 1999a). No chronic bioassays have been conducted.

Researchers examined neurohistologic characteristics (Hannah and Roth 1991) and brain amino acid concentrations (Hannah et al. 1989) in rats exposed to H2S from gestational day 5 through postpartum day 21. Some alterations in the architecture and growth characteristics of Purkinje cell dendritic fields were seen after exposure to H2S at 20 ppm (Hannah and Roth 1991) and a decrease in brain amino acid concentrations at 75 but not 50 ppm (Hannah et al. 1989). Data from Skrajny et al. (1992) have also demonstrated altered neurotransmitter concentrations after exposure to H2S. A decrease in norepinephrine concentrations and an increase in serotonin concentrations were seen after exposure of rats to H2S at 20 ppm for 7 hr/day from gestational day 5 to postpartum day 21.

Taken together, the data on H2S do not demonstrate any consistent effects at concentrations that are below those which are acutely toxic.

Sulfur Dioxide

SO2 is a highly soluble irritating gas that is quickly absorbed in the nose and upper airway and does not reach the lower parts of the respiratory system under resting conditions (ATSDR 1998). Lower parts of the respiratory system can become targets during exercise. Immediate responses have been seen after exposure to SO2 in many controlled human experiments at 5 ppm and above (Costa 2001). Asthmatics appear to be more sensitive to the effects of SO2.

SO2 has been demonstrated to decrease mucociliary clearance. Prolonged exposure of donkeys to SO2 at 102 µg/m3 for 1 hr/day 5 days/week for 6 months (Schlesinger et al. 1979) and rabbits at 250 µg/m3 for 1 hr/day 5 days/week for 4, 8, or 12 months (Gearhart and Schlesinger 1989) caused persistent decreases in mucociliary clearance. Observed effects might have been mediated by a change in the mucus pH, composition, or consistency. Inhalation of SO2 might also have altered mucus production by increasing the number of mucus-secreting cells.

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Pulmonary changes due to SO2 have been seen in exposed animals. Mild lesions in the lungs were seen in hamsters exposed to SO2 at 650 ppm for 4 hr/day 5 days/week for 19–74 weeks (Goldring et al. 1970). Lung function was affected in rabbits exposed at 70–300 ppm for 6 weeks (Miyata et al. 1990) and guinea pigs exposed at 10 ppm for 1 hr/day for 30 days (Haider 1985). SO2-induced lung biochemical and histologic changes in laboratory animals were also seen by Krasnowska et al. (1998) (30–40 ppm for 1 hr/day 5 days/week for 12 weeks), Lamb and Reid (1968) (400 ppm for 3 hr/day 5 days/week for up to 42 days), and Basbaum et al. (1990) (400 ppm for 3 hr/day 5 days/week for up to 3 weeks).

In chronic studies, no respiratory, cardiovascular, hematologic, hepatic, or renal effects were seen after SO2 exposure of monkeys at 5.1 ppm for 23.3 hr/day 7 days/week for 78 weeks (Alarie et al. 1975) or guinea pigs at 5.72 ppm for 22 h/day 7 days/week for 52 weeks (Alarie et al. 1972). Oxidative effects (lipid peroxidation), however, were seen in the hearts of guinea pigs exposed at 10 ppm 1 hr/day for 30 days (Haider 1985).

Riedel et al. (1992) examined the effects of SO2 at 5 ppm for 8 hr/day for 5 days on immune function in guinea pigs. They found an increase in sensitization to ovalbumin but no other consistent immune effects.

Reproductive effects were not seen in mice or rabbits exposed in utero to SO2 (Murray et al. 1979; Petruzzi et al. 1996). No developmental effects were seen in mice exposed at up to 250 ppm from gestational day 7 through 17 (Singh 1982), but some neurodevelopmental effects were seen in mice exposed at 32 or 65 ppm from gestational day 7 through 18 (Singh 1989); effects on skeletal development were seen in mice at 25 ppm for 7 hr/day from gestational day 6 through 15 and rabbits at 70 ppm for 7 hr/day from gestational day 6 through 18 (Murray et al. 1979).

Peacock and Spence (1967) found some evidence of carcinogenicity of SO2. Possible lung carcinomas and lung adenomas were seen in mice exposed to SO2 at 50 ppm for 5 min/day 5 days/week for 2 years. However, only a single dose was tested, and further studies are needed to establish whether SO2 is carcinogenic in animals. Any malignant effects could be caused by chronic irritation of respiratory epithelium. In addition, data indicate that SO2 can be genotoxic (ATSDR 1998).

Nitrogen Oxides

Numerous laboratory-animal studies have been conducted on the toxicity of NOx; most focused on NO2. The toxicology of NO2 has been reviewed by the World Health Organization (WHO 1997), Environmental Protection Agency (EPA 1993), and the National Research Council (NRC 1985, 2002).

The primary target of NO2 is the lungs, although it can produce changes in the blood and other organs as well (EPA 1993). Acute high-dose exposure to NO2 can lead to hypoxia. NO2 reaches the lungs and rapidly diffuses to the blood, where it reacts with hemoglobin (Costa 2001). That reaction, however, is typically not seen with exposures at concentrations below 10 ppm. At lower concentrations, the main concerns about NO2 are effects on the lungs (for example, edema, congestion, and damaged cilia) and on the host defense system in the lungs (NRC 2002; WHO 1997). The observed effects are usually reversible, although a great degree of inflammation can lead to permanent lung damage or death.

Effects on the immune system and lungs are also the primary concern when laboratory animals are repeatedly exposed to NO2. For example, impaired resistance to Streptococcus sp. infections, defined as decreased survival and survival time, has been observed in mice after exposure at 0.5 ppm for 3 hr/day for 3 months (Ehrlich et al. 1979). The persistence of the effects, however, is not known. Furthermore, some data indicate that continuous exposure of

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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mice to NO2 at 0.5 ppm has effects, but that intermittent exposure does not (Ehrlich and Henry 1968). Immune suppression has also been observed in mice after exposure at above 5 ppm (Rose et al. 1988; Rose et al. 1989). Structural changes occurred in lungs of rats exposed to NO2 at as low as 0.5 ppm for up to 19 months (Hayashi et al. 1987). Studies in rabbits, rats, and beagles showed that chronic exposure to NO2 at 8, 15, and 0.64 ppm, respectively, led to emphysema of the type found in human lungs (WHO 1997).

Standard carcinogenicity bioassays of NO2 have not been conducted. Evidence from other types of studies (acute-, subchronic-, and chronic-exposure studies) in laboratory animals did not show that NO2 can cause tumors on its own (for review, see WHO 1997). Results of studies of the cocarcinogenic potential of NO2 are equivocal. Overall, the effects on the potential carcinogenicity of NO2 are inconsistent, and this requires further investigation.

Ozone

O3 is a highly reactive oxidant that does not appear to penetrate the liquid linings of the lung (Costa 2001; EPA 1996). It can disrupt the barrier function of the lung and lead to increased permeability by other compounds and produce inflammation. Inflammation could then lead to further lung damage and a thickening of the air-blood barrier. In a number of laboratory animals, O3 has consistently been shown to affect the ciliated epithelial cells of the airways, type 1 epithelial cells of the gas-air exchange region, and ciliated cells in the nasal region. Those effects result in a change in the cellular composition of the lung and can lead to a thickening of the air-blood barrier and decreases in mucociliary clearance.

With chronic exposure, there is an initial inflammatory response that peaks in the first few days of exposure. Epithelial hyperplasia then occurs but returns to normal on cessation of exposure. Fibrotic tissue changes occur gradually and can persist or even increase after cessation of exposure (Last et al. 1984). From studies in monkeys, it appears that intermittent exposures (for example, once a month) might have a greater effect than daily or continuous exposures at the same concentration (Reiser et al. 1987).

Pulmonary function changes are seen after acute exposures. The effects of long-term exposure on pulmonary function are not consistent and appear to be reversible on cessation of exposure (Chang et al. 1992; Costa et al. 1995; NTP 1994). Airway responsiveness was affected in animals sensitized to the allergen ovalbumin, but O3 alone at 0.3 ppm for 4 hr/day 4 days/week for 24 weeks had no effect (Schlesinger et al. 2002).

A great deal of research has investigated the effects of O3 on the immune system; animal studies support data from humans indicating that dose and duration are important in determining the effect. Early studies by Coffin and Blommer (1967) showed an increase in infectivity after O3 exposure. Gilmour et al. (1993) demonstrated that the increased infectivity might be due to altered phagocytosis. Osebold et al. (1980) demonstrated an increased immune response in animals sensitized with ovalbumin after O3 exposure. O3 has also been shown to affect macrophage functions (Cohen et al. 1996, 2001; Zelikoff et al. 1991), and cytokines (Cohen et al. 2001).

Chronic bioassays have indicated that O3 has some potential for carcinogenicity, but the results appear to depend on species and sex. In animals exposed at 0.12, 0.5, and 1.0 ppm of ozone for 6 hr/day 5 days/week or at 0.12 ppm for 2 years, the National Toxicology Program (NTP 1994) concluded that there is no evidence of carcinogenicity in rats. In male mice with the same treatments, increases in adenomas and carcinomas were observed in the lungs, but no concentration-dependent response was observed. In addition, in a lifetime exposure study, O3 at

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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0.5 ppm or 1.0 ppm for 125 weeks did not have tumor-promoting activity in mice treated with tobacco carcinogen (NTP 1994).

O3 can have other systemic effects. Because it does not pass the air-blood barrier, however, many of them are thought to be secondary to lung injury or due to reaction products of O3. Oxidative intermediates can be formed from the reaction of O3 with other compounds, and the intermediates could mediate some of the effects of O3.

Carbon Monoxide and Carbon Dioxide

CO and CO2 can both be toxic if the concentrations are high enough. Both can lead to death due to asphyxiation, although the underlying cause of the asphyxiation differs. The effects of both compounds at concentrations that do not cause overt symptoms, however, are not well studied.

The effects of chronic, low exposures to CO are thought to be mediated by effects of CO on oxygen-carrying capacity of the blood. Developmental effects have been seen after acute poisonings with CO in animals; the developing auditory system appears sensitive (Lopez et al. 2003; Stockard-Sullivan et al. 2003). Effects on the cardiovascular system have also been seen at concentrations that are below acutely toxic concentrations (Dubuis et al. 2002; Melin et al. 2002).

Particulate Matter

As discussed previously, the size of particles has a great effect on their toxicity. Concern typically begins with the PM that is 10 µm or less; the main concerns are associated with fine (less than 2.5 µm) and ultrafine (less than 0.1 µm) particles. Size not only affects particle deposition but also can affect the surface area and later the amount of hazardous materials adsorbed on particles. The effects of the PM found in diesel exhaust have been studied intensively. Unless results are directly related to the PM in diesel exhaust, those studies are discussed above under “Mixtures of Combustion Products”. The potential health effects of PM and research priorities have recently been reviewed (EPA 2003 a; NRC 2004).

One of the main concerns after exposure to PM is effects on the respiratory system. Chronic, noncancer respiratory effects seen in animals are in the lungs; dose-dependent inflammation and histopathologic changes have been seen in the lungs of rats, mice, hamsters, and monkeys (EPA 2003 a). The immune response appears to be affected by both fine and ultrafine particles (Zelikoff et al. 2003). Exposure of laboratory animals to residual oil fly ash (a product of the combustion of oil and residual fuel oil that contains transition metals) can lead to inflammatory lung injury (Ghio et al. 2002).

Cardiovascular effects have also been seen after animals have been exposed to PM. Changes in heart rate have been observed, but they were not accompanied by respiratory changes (EPA 2003a). It is thought that PM has its effects on the cardiovascular system through the uptake of particles into the circulation and the release of soluble substances into circulation or through effects on the autonomic control of the heart and the circulatory system. It is not known, however, whether this effect persists or is transient. The mechanism by which particulate matter increases cardiovascular effects is not known, but recent research suggests that when mediators enter the circulation, the bone marrow is stimulated and causes the release of white blood cell precursors into the bloodstream (Goto et al. 2004; Tan et al. 2000). That response may lead to increased cardiorespiratory morbidity and mortality.

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Other systemic effects have also been seen. Those effects, such as hemodynamic effects, increased the risk of heart attack and stroke and effects on hematopoiesis are thought to be secondary to the lung injury seen (EPA 2003a).

One component of PM that might provide some biologic plausibility for its toxic effects is PAHs. As discussed earlier, reactive epoxide intermediates can form in the metabolism of PAHs; the intermediates are genotoxic and could lead to carcinogenicity. Schulte et al. (1994) saw an increase in all lung tumors and a dose-dependent increase in malignant tumors in mice exposed to PAH-enriched exhaust containing benzo[a]pyrene at 0.05 or 0.09 mg/m3. Tumors of the nasal cavity, pharynx, larynx, and trachea were seen in a dose-dependent manner in hamsters exposed to benzo[a]pyrene at 9.5 or 46.5 mg/m3 for 109 weeks, but no lung tumors were seen in those animals (Thyssen et al. 1981). No effects were seen in the lungs, nose, and kidneys of Fischer rats exposed by nose to an aerosol of benzo[a]pyrene at 7.7 mg/m3 for 2 hr/day 5 days/week for 4 weeks (Wolff et al. 1989).

Skin disorders have been seen in animals after dermal exposure to PAHs. In an early study, suppression of sebaceous glands was seen in Swiss mice treated with benzo[a]pyrene, benz[a]anthracene, and dibenz[a,h]anthracene, but no controls were used (Bock and Mund 1958). Increased cell proliferation and inflammation were seen after exposure to a single treatment of 16, 32, or 64 µg once a week for 29 weeks (Albert et al. 1991). There is also evidence that PAHs are photosensitizers in mice, but that effect appears to be reversible (Forbes et al. 1976) and there is evidence of skin carcinogenicity in animals treated dermally with PAHs; a number of studies showed that intermediate exposure to PAHs produces skin tumors (ATSDR 1995d).

INDIVIDUAL SUSCEPTIBILITY

Because of variations in genetic makeup, a genetically susceptible person will exhibit responses to a hydrocarbon fuel or to combustion products different from those of most persons exposed to an identical dose.

Little has been documented about specific differences in genetic susceptibility to hydrocarbon fuels and their components, but exploration of the human genome promises advances in the near future. Some information suggests that people with an erythrocyte glucose-6-phosphate dehydrogenase deficiency may have increased susceptibility to the hemolytic effects of naphthalene (ATSDR 1999b). People with aryl hydrocarbon hydroxylase that is particularly susceptible to induction and people with genetic diseases associated with DNA-repair deficiencies (such as Down syndrome and familial retinoblastoma) may be particularly susceptible to the carcinogenic effects of PAHs (ATSDR 1999b).

Little is known also about specific differences in genetic susceptibility with respect to combustion products. Some components of combustion products are metabolized to active metabolites, which are later detoxified. Differences in the activity of the enzymes involved in those toxification and detoxification pathways can alter a person’s susceptibility to combustion-product components. For example, increased formation of the epoxide intermediates by increased activity of p450 enzymes that activate PAHs would increase a person’s susceptibility to PAHs, whereas increased activity of epoxide hydrolase, which detoxifies epoxide metabolites, would protect against the toxicity of PAHs (Klaassen 2001). In addition to altered susceptibility resulting from enzyme activity, whether genetic or by induction of enzymes by coexposure to other compounds, people could have altered susceptibility to combustion products because of

Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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illness. An example is asthma-related increased susceptibility to many of the effects of combustion products.

INTERACTIONS

Because hydrocarbon fuels and their combustion products contain hundreds of components, it is probably not possible to identify all the possible interactions between a fuel and other substances, between components of a fuel, between combustion products and other substances, or between components of combustion products. Additive, synergistic, or antagonistic effects might occur; however, data on such effects are sparse. For example, primarily as a consequence of modifications in enzyme induction, the toxicity of benzene, a component of hydrocarbon fuels, can be altered by alcohol, drugs, industrial chemicals, radiation, metals, halogenated hydrocarbons, and pesticides (ATSDR 1995a).

Several recent studies have evaluated interactions between a hydrocarbon fuel and other substances. Peden-Adam et al. (2001) assessed immunotoxic effects of concurrent exposure of mice to pyridostigmine bromide (an anti-nerve-gas agent), N,N-diethyl-m-toluamide (DEET, an insect repellent), and JP-8. The findings of their study indicate that combined exposure to those three materials does not significantly alter many immunologic end points (body, spleen, and thymus mass; spleen and thymus cellularity; peripheral white-cell populations; lymphocyte proliferation; macrophage nitrite production; and natural killer-cell and cytotoxic T-lymphocyte activity) but does selectively target functional end points, such as delayed-type hypersensitivity responses.

Baynes et al. (2001) studied the influence of three JP-8 performance additives on dermal disposition of two fuel components: naphthalene and dodecane. Jet-A, which has the same hydrocarbon composition as JP-8 but without the performance additives, was mixed with up to three performance additives, and disposition was assayed by using isolated perfused porcine skin flaps. The data show that various combinations of the three performance additives can potentially alter the dermal disposition of the fuel components and that products of two-factor interactions were not predictable from single-factor exposures. Riviere et al. (2002) also used the isolated perfused porcine skin-flap model to evaluate potential interactions among various combinations of low sulfur mustard, JP-8, DEET, and permethrin exposures. Data from the study suggest that JP-8 exposure may modulate transdermal flux of permethrin.

There has also been research on the components of combustion products that indicated that the presence of one component affects the toxicity of other components. For example, there is evidence of antagonistic effects between O3 and SO2 that depend on the end point (Schlesinger and Graham 1992), and, as discussed previously, components adsorbed on PM behave differently from those not adsorbed on PM.

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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Mattie DR, Marit GB, Cooper JR, Sterner TR, Flemming CD. 2000. Reproductive Effects of JP-8 Jet Fuel on Male and Female Sprague-Dawley Rats After Exposure by Oral Gavage. AFRL-HE-WP-TR-2000–0067. Wright Patterson Air Force Base, OH: Aerospace Medical Research Laboratory.

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×

NRC. 2002. Review of Submarine Escape Action Levels for Selected Chemicals. Washington, DC: The National Academies Press.

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×

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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"3 Uncombusted Fuels and Combustion Products: Background Information." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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The third in a series of congressionally mandated reports on Gulf War veterans’ health, this volume evaluates the long-term, human health effects associated with exposure to selected environmental agents, pollutants, and synthetic chemical compounds believed to have been present during the Gulf War. The committee specifically evaluated the literature on hydrogen sulfide, combustion products, hydrazine and red fuming nitric acid. Both the epidemiologic and toxicologic literature were reviewed.

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