6

Effects of Military Fuel Vapors on the Hematopoietic System

This chapter contains information on the toxic effects of exposure to the vapors of JP-5, JP-8, and DFM on the hematopoietic system in experimental animals. There is no information in the literature on these effects in humans.

HEMATOLOGICAL EFFECTS OF JP-5 FUEL VAPORS

The toxic effects of vapors from petroleum-derived and shale-derived JP-5 fuels were first reported in 1977 (MacEwen and Vernot, 1978, 1980, 1981, 1982, 1983, 1984; Gaworski et al., 1979). Summaries of these and later studies were presented by Gaworski et al. (1984) and MacEwen and Vernot (1985). JP-5 is of concern primarily to the Navy because it is used in Navy planes at sea. Because shale oil, in addition to petroleum, has been used



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Permissible Exposure Levels for Selected Military Fuel Vapors 6 Effects of Military Fuel Vapors on the Hematopoietic System This chapter contains information on the toxic effects of exposure to the vapors of JP-5, JP-8, and DFM on the hematopoietic system in experimental animals. There is no information in the literature on these effects in humans. HEMATOLOGICAL EFFECTS OF JP-5 FUEL VAPORS The toxic effects of vapors from petroleum-derived and shale-derived JP-5 fuels were first reported in 1977 (MacEwen and Vernot, 1978, 1980, 1981, 1982, 1983, 1984; Gaworski et al., 1979). Summaries of these and later studies were presented by Gaworski et al. (1984) and MacEwen and Vernot (1985). JP-5 is of concern primarily to the Navy because it is used in Navy planes at sea. Because shale oil, in addition to petroleum, has been used

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Permissible Exposure Levels for Selected Military Fuel Vapors as a source of jet fuel, the Navy compared the toxicity of petroleum-derived JP-5 fuel with that of shale-derived JP-5 fuel in several studies. These are discussed below. A study was initiated in which both male and female beagle dogs and F344 rats and female C57BL/6 mice were exposed continuously to vapors from either petroleum-derived or shale-derived JP-5 fuels for 90 days. Data were gathered on the hematocrit, hemoglobin, total erythrocytes, total leukocytes, differential counts, mean corpuscular volume, and mean corpuscular hemoglobin concentration. Clinical chemistry measurements were taken of sodium, potassium, calcium, albumin/globulin ratios, total protein, glucose, alkaline phosphatase, serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), bilirubin, creatinine, and blood urea nitrogen (BUN). In beagle dogs, most hematological and clinical chemical values after 90 days of exposure were within normal limits. A slight increase in erythrocyte osmotic fragility was observed after 90 days in animals exposed at 750 mg/m3. Erythrocytes, hematocrit, and hemoglobin showed marginal decreases that were not consistently significant. Other hematological and clinical chemical values appeared to be unaltered by exposure. In rats, blood determinations were performed immediately after 90 days of exposure or 19 months after the first exposure. Fluctuations in erythrocyte levels were observed in male rats exposed to either petroleum-derived or shale-derived JP-5 and in female rats exposed to petroleum-derived JP-5. Slight changes in hematocrit and hemoglobin were also observed. Females demonstrated a slight increase in leukocyte counts when exposed to petroleum-derived JP-5. After 19 months, petroleum-derived JP-5-exposed males exhibited a slight decrease in circulating erythrocytes, and females exhibited a slight increase. In neither case were changes detected in hematocrit, hemoglobin, or leukocyte counts. Shale-derived JP-5-exposed rats displayed a slight increase in leukocytes

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Permissible Exposure Levels for Selected Military Fuel Vapors but exhibited no other statistically significant change from controls. Other hematological and clinical chemical determinations were within normal values. No hematological effects were observed in C57BL/6 mice. Pathological studies (MacEwen and Vernot, 1983) in F344 rats exposed continuously to JP-5 for 90 days at doses of 150 or 750 mg/m3showed no dose-related increases in leukemia. Leukemia was reported in unexposed rats of both sexes. Using the same regimen in female C57BL/6 mice, no significant exposure-related increases in leukemia, lymphoma, or bone-marrow hyperplasia were found. Parker et al. (1981) exposed male Sprague-Dawley rats by gavage to either petroleum-derived JP-5 or one of three shale-oil preparations of JP-5 for 3 days at a dose of 24 mL/kg of body weight. At the end of each day, hematocrit, leukocytes, and erythrocytes were measured. No changes of significance were observed in erythrocytes or hematocrit. Total leukocyte counts were decreased after 1 or 2 days of treatment but returned to control values by day 3. HEMATOLOGICAL EFFECTS OF JP-8 FUEL VAPORS F344 male and female rats were exposed continuously to JP-8 vapor for 90 days at doses of 550 or 1,000 mg/kg (MacEwen and Vernot, 1983, 1984, 1985). Blood studies were performed in the males immediately after exposure and 2 weeks, 2 months, 9 months, and 21 months after cessation of exposure; blood studies were performed in the females immediately after exposure and again 9 months and 21 months after first exposure. Although statistically significant changes were observed in red blood cells, white blood cells, hemoglobin, hematocrit, and other measures of hematopoiesis, given the wide range of values in the controls and

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Permissible Exposure Levels for Selected Military Fuel Vapors the exposed animals under which the animals seem to function normally, it did not appear that any of the blood-related changes after exposure to JP-8 were biologically important. HEMATOLOGICAL EFFECTS OF DFM FUEL VAPORS Beagle dogs and F344 rats of both sexes and female C57BL/6 mice were exposed continuously to petroleum-derived DFM vapor for 90 days at doses of 50 or 300 mg/m3 (MacEwen and Vernot, 1978). A continuous-exposure regimen was chosen to simulate potential exposure on a ship at sea. Measurements were taken of hematocrit, hemoglobin, total erythrocytes, total leukocytes, differential counts, mean corpuscular volume, and mean corpuscular hemoglobin concentration. Clinical chemical measurements were taken of sodium, potassium, calcium, albumin/globulin ratios, total protein, glucose, alkaline phosphatase, SGPT, SGOT, bilirubin, creatinine, and BUN. Among the dogs, there was a slight treatment-related increase in erythrocyte fragility that was not considered biologically important. In both male and female rats, slight decreases were observed in erythrocytes and SGPT. Greater decreases observed in leukocytes were considered biologically important. Both male and female rats showed a slight decrease in circulating erythrocytes, hematocrit, and hemoglobin. Leukocytes were slightly decreased in males. In female mice, marginal increases in bone-marrow fibrosis and hyperplasia were reported. No evidence of treatment-related malignant lymphoma was observed. Male and female rats followed up 19 months after completion of the 90-day exposure exhibited no residual changes in blood levels of erythrocytes, leukocytes, hematocrit, or hemoglobin. The results of studies using DFM derived from petroleum and shale oil were similar.

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Permissible Exposure Levels for Selected Military Fuel Vapors Pathological studies of the mice (MacEwen and Vernot, 1982) revealed some evidence of bone-marrow fibrosis and hyperplasia, hematopoietic activity in the spleen, and plasmacytosis in lymph nodes. A similar study on shale-derived DFM (MacEwen and Vernot, 1980) reported no effects on osmotic fragility in beagle dogs. In rats, marginal changes in hematological and clinical chemical values still fell within the normal range and were not considered biologically important. CONCLUSIONS The data on the hematological effects of JP-5, JP-8, and DFM vapors are sparse. The results summarized here showed that male and female beagle dogs and F344 rats and female C57BL/6 mice exposed to vapors of petroleum-derived or shale-derived JP-5 continuously by inhalation for 90 days demonstrated no substantial adverse effects immediately after exposure or 19 months later. A comparison of the effects of three preparations of shale-derived JP-5 given by gavage to Sprague-Dawley rats also produced no important hematological changes. The single study of inhalation exposure of JP-8 fuel in male and female F344 rats for 90 days followed by blood studies conducted 2 weeks and 2, 9, and 21 months after exposure revealed no biologically important changes in blood values. When male and female beagle dogs and F344 rats and female C57BL/6 mice were exposed continuously to DFM vapor (derived from either petroleum or shale oil) for 90 days, decreases in circulating leukocytes and erythrocytes, in hematocrit, and in hemoglobin were observed. Nineteen months later, during which there was no further exposure, these effects had disappeared. Studies in mice suggested bone-marrow fibrosis and hyperplasia, hematopoietic activity in the spleen, and plasma cytosis in lymph nodes.