Ray L. Buschbom

Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth

Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats. The findings are generally consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations.

Inhaled radon-induced genotoxicity in Wistar rat, Syrian hamster, and Chinese hamster deep-lung fibroblasts in vivo

This study was performed (1) to provide a comparison of the genotoxic effects of inhaled radon and radon progeny, referred to as radon in this paper, among three species of rodents: Wistar rats, Syrian hamsters, and Chinese hamsters; (2) to determine if initial chromosome damage was related to the risk of induction of lung cancer; and (3) to evaluate the tissue repair and long-term presence of cytogenetic damage in respiratory tract cells. These species were selected because Syrian hamsters are very resistant to radon induction of lung cancer and Wistar rats are sensitive; no literature is available on the in vivo effects of radon in the Chinese hamster. Exposure-response relationships were established for the rats and Syrian hamsters while the Chinese hamsters received a single exposure of radon. At 4 h (0.2 days), 15 days, and 30 days after the highest WLM exposure to radon, Wistar rats, Chinese hamsters, and Syrian hamsters were killed, and lung fibroblasts were isolated and grown in culture to determine the frequency of induced micronuclei. Animals at each level of exposure showed an increase in the frequency of micronuclei relative to that in controls (P < 0.05). The exposure-response relationship data for rats and Syrian hamsters killed 0.2 days after the end of exposure were fit to linear equations (micronuclei/1000 binucleated cells = 15.5 +/- 14.4 + 0.53 +/- 0.06 WLM and 38.3 +/- 15.1 + 0.80 +/- 0.08 WLM, respectively). For the single exposure level used (496 WLM) in Chinese hamsters killed at 0.2 days after exposure, the frequency of micronuclei/1000 binucleated cells/WLM was 1.83 +/- 0.02. A comparison of the sensitivity for induction of micronuclei/WLM illustrated that Chinese hamsters were three times more sensitive than rats. The Syrian hamsters also showed a significantly elevated response (P < 0.05) relative to rats. These data suggest that initial chromosome damage is not the major factor responsible for the high rate of radon-induced cancer in rats relative to Syrian hamsters. The frequency of micronuclei in radon-exposed rats, Syrian hamsters, and Chinese hamsters significantly decreased (P < 0.05) as a function of time after the exposure. The rate of loss of damaged cells from the lung was greatest in the Chinese hamsters, followed by Wistar rats and Syrian hamsters, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Developmental Toxicology Evaluation of 60-Hz Horizontal Magnetic Fields in Rats

Abstract Epidemiological and laboratory studies have indicated various biological effects resulting from exposure to extremely low frequency magnetic fields. The possibility of early embryonic loss and fetal malformations arising from such exposures required investigation. A replicate study, using large numbers of animals, was conducted to determine if 60-Hz magnetic fields would produce developmental toxicity in rats. Systems used previously for electric field exposures were retrofitted to provide magnetic field exposures to small laboratory animals. Large coils, separated from the rat cages, were energized by computer-controlled function generators providing a relatively pure, 1000-μT, 60-Hz, horizontal magnetic field for the high exposure group. Leakage fields to a second system provided a second exposure group with average exposures of 0.61 μT. Ambient fields within a third (control) system were 0.09 μT. Field intensities utilized in this study represent a range of exposures encountered by humans; how...

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

Abstract 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°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.

Pulmonary function in elastase-treated guinea pigs and rats exposed to ammonium sulfate or ammonium nitrate aerosols.

Three weeks following intratracheal instillations of elastase dissolved in saline, or saline alone, guinea pigs and rats were exposed for 5 or 20 days, 6 hr/day, 5 days/week to filtered room air, 1 mg/m3 ammonium sulfate [NH4)2SO4) or 1 mg/m3 ammonium nitrate (NH4NO3) aerosols. Pulmonary function evaluations conducted in guinea pigs showed no detrimental effects of (NH4)2SO4 or NH4NO3 exposure and very little effect of elastase treatment. Lung function changes in elastase-treated rats were consistent with a condition of experimentally induced pulmonary emphysema. Rats exposed to NH4NO3 aerosols showed no consistent exposure-related changes. Compared with air-exposed animals, rats exposed to (NH4)2SO4 aerosols had increased values of residual volume and functional residual capacity and decreased slope of single-breath N2 washout curves. We conclude that elastase treatment had no significant effect on lung function changes resulting from inhalation of (NH4)2SO4 aerosols. Lung function was more affected by (NH4)2SO4 exposure than by NH4NO3 exposure, and lung function changes were more pronounced in rats than in guinea pigs.

Magnetic field characteristics of electric bed-heating devices.

Measurements of the flux density and spectra of magnetic fields (MFs) generated by several types of electric bed heaters (EBH) were made in order to characterize the MFs to which the fetus may be exposed in utero from the mothers use of these devices. Data on MPs were gathered from more than 1,300 in-home and laboratory spot measurements. In-home measurements taken at seven different positions 10 cm from the EBHs determined that the mean flux density at the estimated position of the fetus relative to the device was 0.45 microT (4.5 mG) for electric blankets and 0.20 microT (2.0 mG) for electrically heated water beds. A rate-of-change (RC) metric applied to the nighttime segment of 24 h EMDEX-C personal-dosimeter measurements, which were taken next to the bed of volunteers, yielded an approximate fourfold to sixfold higher value for electric blanket users compared to water-bed heater users. These same data records yielded an approximate twofold difference for the same measurements when evaluated by the time-weighted-average (TWA)MF exposure metric. Performance of exposure meters was checked against standard fields generated in the laboratory, and studies of sources of variance in the in-home measurement protocols were carried out. Spectral measurements showed that the EBHs measured produced no appreciable high-frequency MFs. Data gathered during this work will be used in interpreting results from a component of the California Pregnancy Outcome Study, which evaluates the use of EBHs as a possible risk factor in miscarriage.

Comparison of fetotoxic effects of a dermally applied complex organic mixture in rats and mice

A high-boiling (288-454 degrees C), coal-derived complex organic mixture (COM) has been shown to be teratogenic in rats following inhalation and oral routes of exposure. To determine whether similar changes also occur after dermal exposure to this COM, pregnant rats and mice were exposed during periods of organogenesis (Days 11 to 15 of gestation). Shaved backs were painted with 0, 500, or 1500 mg/kg of the COM (control, low, or high dose, respectively); the exposed area was not occluded. Maternal weight gain during the gestation period decreased with increasing dose in rats but not in mice. Examination of rat fetuses on Day 20 of gestation showed that resorptions had occurred in more than 90% of low- and high-dose litters (vs 6% in the control group). In mice, fetal examinations on Day 18 of gestation showed that resorptions occurred in 71% of litters from both exposure groups (vs 14% in the controls). Fetal measurements indicated that both the weight and the length of rat fetuses decreased with increasing dose, but mouse fetuses were unaffected. Cleft palates, absent in the control groups, were observed in 50 to 55% of the high-dose group and 5 to 8% of the low-dose fetuses of both species. Small fetal lungs occurred in nearly 100% of the exposed rat fetuses and in 25% of the high-dose mice; the incidence of small lungs was 1% in control animals. Other variations observed in exposed groups included edema and reduced ossification in the rat and renal pelvic cavitation in the mouse.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of sulfur dioxide or ammonium sulfate exposure, alone or combined, for 4 or 8 months on normal and elastase-impaired rats

Normal and lung-impaired rats were compared after exposure to SO2 and/or (NH4)2SO4 for 4 or 8 months, or for 8 months plus 3 months recovery. Young adult male Sprague-Dawley rats were pretreated intratracheally with either physiologic saline (normal lungs) or porcine pancreatic elastase (impaired lungs). Rats from each pretreatment group were exposed to filtered air (control), to SO2 (1 ppm) or (NH4)2SO4 (0.5 mg/m3), or to combined SO2 + (NH4)2SO4 for 5 hr/day, 5 days/week. Morphologic, physiologic, and immunologic criteria were evaluated. At 4 months cellular immunologic responsiveness was not impaired, but physiologic changes were detected. Morphologic changes were apparent in all time periods. Elastase-induced changes included greater lung volumes, emphysema, and alveolar interstitial fibrosis. Pollutant effects included bronchiolar epithelial hyperplasia and changes in alveolar mean chord length (MCL). Relative to controls, bronchiolar epithelial hyperplasia and MCL increased in saline/pollutant groups, but decreased in elastase/pollutant rats at 4 months. The pretreatment/pollutant interaction was not observed at 8 months. Elastase effects persisted throughout the recovery period. Pollutant effects were more transitory, although alveolar septal fibrosis was greater in saline/(NH4)2SO4 rats at 8 months. Pulmonary function changes associated with elastase included increases in residual volume, functional residual capacity, and the residual volume/total lung capacity ratios. The alveolar plateau of single-breath washout (N2 slope) was significantly steeper in elastase-treated rats but less steep in animals exposed to SO2 or to (NH4)2SO4 than in those exposed to air only.

Pulmonary toxicity of inhaled coal liquid aerosols (boiling range 230–450°C)☆

The biological activity of materials produced in the direct liquefaction of coal is being assessed by a variety of test systems. In this study, the pulmonary toxicity of process solvent (PS) from the solvent refined coal-I (SRC-I) process was determined by histamine aerosol challenge tests and pulmonary function and morphologic evaluations. Guinea pigs inhaled aerosols of PS (boiling range, 230 to 450 degrees C) for 6 hr/day, 5 day/week, for up to 12 days in three different experiments. In the first experiment, 8-week-old animals inhaled 0 (controls), 0.15, or 0.60 mg/liter PS aerosols with a mass median aerodynamic diameter (MMAD) of 1.3 micrometer. Exposure to 0.15 mg/liter PS for 12 days resulted in depressed weight gain and marked hypersensitivity to inhaled histamine compared with sham-exposed control animals. Four of five animals exposed to 0.6 mg/liter PS died of respiratory failure during exposure. During the second experiment, 14-week-old animals inhaled 0 (controls) or 0.19 mg/liter PS (MMAD, 1.3 microns) for 1, 3, or 12 days. Hypersensitivity to aerosolized histamine occurred only after 12 days exposure to PS aerosols. At that time, morphologic lung evaluations showed mild to moderate pneumonitis and accumulation of exudate in bronchioles of PS-exposed animals. In the third experiment, pulmonary function evaluations were conducted on 4-week-old animals exposed to 0 (controls) or 0.19 mg/liter PS for 8 days. Functional changes measured in these animals (compared to controls) included increased gas trapping at low lung volumes, decreased quasi-static compliance, and decreased diffusion capacity of the lung for carbon monoxide. These studies showed that measurable changes in lung function were produced in guinea pigs after 8 to 12 days exposure to 0.15 or 0.19 mg/liter PS and that exposure to PS affected weight gain only in younger animals (4 and 8 weeks old) but not in 14-week-old animals.

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.