J Toxicol Env Heal A
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J Toxicol Env Heal A · Aug 1999
Lung injury from intratracheal and inhalation exposures to residual oil fly ash in a rat model of monocrotaline-induced pulmonary hypertension.
A rat model of monocrotaline (MCT)-induced pulmonary injury/hypertension has been recently used in particulate matter (PM) health effects studies, however, results have been equivocal. Neither the mechanism by which mortality occurs in this model nor the variation in response due to differences in PM exposure protocols (i.e., a bolus dose delivered intratracheally versus a similar cumulative dose inhaled over three days) have been fully investigated. Sprague Dawley rats (SD, 60 d old; 250-300 g) were injected with either saline (healthy) or MCT, 60 mg/kg, i.p. (to induce pulmonary injury/hypertension). ⋯ IL-10 and cellular fibronectin expression was only increased in MCT rats exposed to ROFA. In summary, only the bolus IT ROFA caused mortality in the rat model of lung injury/hypertension. Exacerbation of histological lesions and cytokine mRNA expression were most reflective of increased ROFA susceptibility in this model.
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J Toxicol Env Heal A · Oct 1998
Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light alkylate naphtha distillate in rats.
A 13-wk inhalation study was conducted with Sprague-Dawley CD rats (12/sex/group) were exposed by inhalation for 13 weeks to a light alkylate naphtha distillate (LAND-2, C4-C10; average molecular weight 89.2) at actual average concentrations of 0 (room air), 668, 2220, or 6646 ppm, 6 h/d, 5 d/wk; 12 additional rats/sex in the control and high dose groups were held after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. ⋯ Increased liver weights in both sexes at the highest dose had no microscopic correlate and appeared reversible after the 4-wk recovery period. Exposure to LAND-2 at any dose did not produce neurotoxicity measured by MA, FOB, or neuropathology. The no-observed-effects level (NOEL) for LAND-2 was 2220 ppm for subchronic toxicity and > or =26646 ppm for neurotoxicity.
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J Toxicol Env Heal A · Jul 1998
Inhibition of respiratory and bioenergetic mechanisms by hydrogen sulfide in mammalian brain.
The biochemical effects of hydrogen sulfide were investigated by treating enzyme homogenates and synaptosomes prepared from mammalian brain with sodium sulfide. Brain cytochrome c oxidase activity was highly sensitive to inhibition by sodium sulfide, as demonstrated by an IC50 of 0.13 microM. Sodium sulfide was also found to inhibit carbonic anhydrase activity in cerebellum, frontal cortex, and hippocampus. ⋯ Parallel studies conducted in vivo showed that rats exposed over a 5-d period to hydrogen sulfide (100 ppm for 3 h/d) had significantly higher concentrations of L-glutamate in the hippocampus compared to control animals. In summary, our results indicate that sulfide causes extensive disruption to respiratory and related mitochondrial functions in mammalian brain in vitro. The reduced capacity of nerve endings to take up L-glutamate may contribute to the raised L-glutamate levels observed in vivo.
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J Toxicol Env Heal A · Jan 1998
Comparative StudyEffect of inhalation of organic dust-derived microbial agents on the pulmonary phagocytic oxidative metabolism of guinea pigs.
The effect of inhalation exposure of various biological agents associated with organic dusts on the function of guinea pigs pulmonary phagocytes was investigated. Agents included antigens of Erwinia herbicola, Thermoactinomyces vulgaris, and Aspergillus fumigatus; endotoxin of Erwinia herbicola; bacterial protease; and a fungal glucan preparation. ⋯ However, the relative magnitude of the inflammatory response varied greatly among these biological agents. In general, antigens of Erwinia herbicola and Aspergillus fumigatus were most potent, while bacterial protease was least effective.