Cardiovascular effects in rats following exposure to a high-boiling coal liquid.

In previous work, increased blood pressure was observed in anesthetized rats following a subchronic aerosol exposure to solvent-refined coal heavy distillate (HD). To determine if this increase is a permanent, dose-related response, 11-week-old male rats were exposed by inhalation to 0, 0.24, or 0.70 mg/liter (control, low-exposure, and high-exposure groups, respectively) of HD for 6 hr/day, 5 days/week, for 6 weeks. In addition to blood pressure, select cardiovascular parameters were measured to obtain information on other possible toxic effects of the HD and also to gain some insight into potentially altered regulatory mechanisms that could be affecting the blood pressure. The angiotensin-aldosterone hormonal system, body fluid regulation, cardiac function and regulation, and pulmonary gas-exchange capabilities were examined. Two weeks after the end of exposure, mean blood pressures and heart rates of anesthetized animals in the low-and high-exposure groups were elevated relative to the controls. Plasma angiotensin concentrations decreased with increasing dose, whereas aldosterone concentrations were unaffected. In the high-dose group, blood and plasma volumes were 20 and 28%, respectively, higher than those of controls. Seven weeks after exposure, all measured cardiovascular parameters were similar to control values. Results from this study show that a 6-week exposure to HD resulted in dose-dependent, transient changes in a variety of physiological factors considered important in cardiovascular function.

Effects of subchronic inhalation exposure of mice to a high-boiling coal liquid.

Mice (CD-1) were exposed to aerosol concentrations of 0.0, 0.03, 0.14, or 0.69 mg/liter of heavy distillate (HD), a high-boiling coal liquid from the solvent-refined coal (SRC)-II process. Exposures were for 6 hr/day, 5 days/week for 13 weeks. Particle sizes ranged between 1.6 and 1.8 micron, mass median aerodynamic diameter, with a geometric standard deviation range of 1.9-2.5. Growth for high-dose males was significantly less than that of the control group. Compared to controls, weights of liver were significantly higher and those of ovaries and thymus significantly lower; these changes were significant on both absolute and relative weight bases. The number of red blood cells, volume of packed red cells, and hemoglobin concentration for animals from the high-dose group were significantly lower than those of controls. Microscopic examination of organ sections showed focal hepatic necrosis and nonspecific hepatopathy. Additionally, olfactory epithelial degeneration occurred in a dose-dependent manner. Results from this study indicated that exposure to HD caused adverse effects at the high dose and that these changes were either less severe or absent in middle-dose group mice. Comparison of these results with those for rats indicated that with rats the biological effects were more severe and present at lower doses than was observed for mice.

Effects of inhalation exposure to a high-boiling (288 to 454 degrees C) coal liquid.

Coal liquids have been evaluated in a variety of short-term toxicological assays; however, few studies have been conducted to determine the systemic effects after inhalation exposure to these materials. To extend the data base on potential health effects from coal liquefaction materials, we performed a study with solvent refined coal (SRC)-II heavy distillate (HD). Fischer-344 rats were exposed for 6 hr/day, 5 days/week for 5 or 13 weeks to an aerosol of HD (boiling range, 288 to 454 degrees C) at concentrations of 0.69, 0.14, 0.03, or 0.0 mg/liter of air for the high, middle, low, and control groups, respectively. Survival through 13 weeks of exposure was greater than 90% for all groups; body weights for exposed animals were decreased in a dose-dependent manner. Significant increases in liver weights and decreases in thymus and ovary weights were observed for treated animals compared with controls. There were also significant treatment-related decreases in erythrocytes, hemoglobin, volume of packed red blood cells, lymphocytes, eosinophils, and total white blood cells. After 5 weeks of exposure serum cholesterol concentrations increased in a dose-dependent manner for both sexes and serum triglyceride amounts decreased for males but not for females. After 13 weeks of exposure, high-dose animals had significant increases in cholesterol (males only), triglycerides, blood urea nitrogen, and serum glutamic pyruvic transaminase (SGPT; males) and significant decreases in albumin, SGPT (females), and lactate dehydrogenase (LDH). Examination of bone-marrow preparations from exposed animals demonstrated consistent decreases in the degree of cellularity, suggesting that this organ is a target for HD. Microscopic evaluation of organ sections indicated exposure-related changes for nasal mucosa, pulmonary macrophages, thymus, liver, kidney, bone marrow, ovaries, and cecum. Results from this study indicated dose-dependent increases in the severity of the lesions observed, with few effects in the low-exposure group that were attributable to the exposure.

Mutagenic and carcinogenic activity of a hydrotreated coal liquid.

A fuel-oil blend (FOB) and its hydrotreated product from the solvent-refined coal (SRC) II process were evaluated for their mutagenic and carcinogenic potential. The FOB was highly active in both cellular assays, as well as in animal (skin-painting) studies. Cell-transforming and mutagenic activities of hydrotreated FOB were consistently found to be lower than for untreated FOB. Finally, while most of the initiating activity (in the animal assay) was lost following hydrotreatment, the data indicate that the hydrotreated FOB still had significant skin-tumor-promoting activity.

Skin-tumor initiation activity of coal liquids with different boiling-point ranges.

High-boiling coal liquids from the solvent-refined coal-I and -II (SRC-I, -II) processes, respectively, were fractionally distilled. In the case of SRC-I process solvent (PS), 50 degrees F distillation cuts were obtained between 550 and 850 degrees F, while for the SRC-II material, the 50 degrees F cuts were only obtained between 700 and 850 degrees F. These cuts, as well as the parent material, were tested for their ability to initiate skin tumors by applying a single dose (25 mg) to the shaved backs of Charles River female CD-1 mice. After 2 weeks, the mice received twice weekly applications of 5 micrograms of the promoter, phorbol myristate acetate. Only a few tumors were found for SRC-I fractions boiling below 700 degrees F; tumor-initiating activity increased as the boiling point increased. A similar increase in response with increasing boiling point was seen for the SRC-II cuts. The initiating activities for the parent materials were similar to those observed for their respective 800 to 850 degrees F cuts.