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Biomedical subjects

R T Drew

Publications and source records attributed to R T Drew.

At least 55 records · Page 3Linked to original sources

The failure of aerosolized superoxide dismutase to modify pulmonary oxygen toxicity.

Superoxide (O2-.) is a highly toxic free radical that may be an important component of pulmonary O2 toxicity. The primary defense against this free radical is superoxide dismutase. Rats were exposed to aerosolized superoxide dismutase, and it failed to modify either the time course or the cumulative toxicity of 100 per cent O2. Because the aerosolized enzyme can be expected to be delivered only to the extracellular space of the lung, it is suggested that the primary site of production and of damage due to O2-induced free radicals must be within the intracellular space.

Aerosols↗

The effect of aerosol hair spray inhalation in the hamster.

Hamsters were exposed to a commercially available aerosol hair spray actuated for a total of 8 minutes over a 4-hour-period, 5 days/week. They were examined after 1, 2, 3, 4, and 6-week exposures, and 2,4 and 8 weeks after a 6-week exposure. There was a significant increase in the lung weight of exposed hamsters at every time point except 8 weeks after the 6-week exposure. Microscopic changes in the lung were characterized by the presence of a few to a moderate number of macrophages and neutrophils in the alveolar lumina. The number of macrophages and neutrophils appeared directly related to the duration of exposure. Lung changes were minimal during the first 2-weeks of exposure, and 8 weeks after the 6-week exposure (recovery period). Pathologic changes in the lungs of hamsters were reversible after cessation of the hair spray inhalation exposure.

Aerosols↗

Inhalation carcinogenicity of alpha halo ethers. I. The acute inhalation toxicity of chloromethyl methyl ether and bis(chloromethyl)ether.

A range of acute studies were performed with chloromethyl methyl either (CMME) and bis(chloromethyl)ether (BCME), including 14-day LC50's following single seven-hour inhalation exposures. The LC50's for CMME were 55 ppm for rats and 65 ppm for hamsters. The LC50's for BCME were 7 ppm for both species. All animals showed characteristic changes of acute irritation of the respiratory tract manifested by congestion, edema, and hemorrhage. Severe shortening of life span was seen in 30-day exposures of rats to CMME and in all studies with BCME. Incidences of mucosal changes, including atypia, were generally increased in a dose-related manner in both species. The carcinogenicity of BCME in these range finding experiments was demonstrated by a skin cancer in a rat after three exposures and a nasal tumor in a hamster after one exposure to 1 ppm BCME.

Animals↗

Inhalation carcinogenicity of alpha halo ethers. II. Chronic inhalation studies with chloromethyl methyl ether.

Rats and hamsters were exposed to 1 ppm of chloromethyl methyl ether six hours per day, five days per week, throughout their lifetime. Mortality and weight gain of the exposed animals paralleled that of the control animals. Malignant tumors of the respiratory tract were found in two rats. These were a squamous cell carcinoma of the lung with blood vessel invasion and an esthesloneuroepithelioma originating in the olfactory epithelium and invading the forebrain. One hamster was found to have an adenocarcinoma of the lung and another, a squamous papilloma of the trachea. A single exposed rat had a pituitary tumor of primitive cell type that may well have been coincidental.

Adenocarcinoma↗

Inhalation carcinogenicity of alpha halo ethers. III. Lifetime and limited period inhalation studies with bis(chloromethyl)ether at 0.1 ppm.

Rats and hamsters were exposed to 0.1 ppm bis(chloromethyl)ether (BCME) six hours per day, five days per week throughout their lifetime. Additional groups of rats were given 10, 20, 40, 60, 80, and 100 exposures to 0.1 ppm BCME and then held until death. Forty cancers originating in the respiratory tract were found in the 200 rats involved in these studies. These included 14 cancers of the lung and 26 cancers of the nasal cavity. They occurred in dose-related fashion. A single undifferentiated carcinoma of the lung was seen in a hamster.

Animals↗

Effects of vinyl chloride exposures to rats pretreated with phenobarbital.

Male rats were exposed to 10 consecutive days, 6 hr/day, to vinyl chloride vapors at an average concentration of 13,500 ppm. The exposed rats were divided into three groups of eight rats each: one group was pretreated with 3-methylcholanthrene, one group was pretreated with phenobarbital, and the third group received no treatment. Half the animals in each group were sacrificed 18 hr after the last exposure and half were sacrificed 4 days later. In a second experiment, four rats pretreated with phenobarbital were exposed to vinyl chloride vapors at a concentration of 17,300 ppm for 2 days and sacrificed about 9 A.M. on the third day. In both experiments control animals, also treated with phenobarbital or 3-methylcholanthrene, were exposed to air only. At the time of sacrifice, lungs, kidneys, spleen, heart, and a small piece of liver from each animal were preserved for histological examination. The remainder of the liver was processed for assay of microsomal enzyme activity. The following parameters were investigated: growth rate, organ weights, morphological changes, and both benzphetamine-N-demethylase activity and cytochrome P-450 content of microsomes prepared from the livers. In both experiments the only marked difference noted in any group was a decrease in the growth rate of the animals exposed to vinyl chloride and treated with phenobarbital. This decreased growth rate was particularly apparent on the third day of the vinyl chloride exposures. Occasional morphological changes were also seen in the livers of the animals treated with phenobarbital and exposed to vinyl chloride.

Animals↗

Cardiovascular effects of acute and chronic inhalations of fluorocarbon 12 in rabbits.

The effects of inhaling fluorocarbon 12, a common propellant in household aerosols, were studied in closed-chested rabbits. Inhalation of 10 or 20% fluorocarbon 12 produced a decline in cardiac output and a dose-related depression of peak left ventricular (LV) dP/dt without associated arrthythmias, hypoxemia or significant changes in LV end-diastolicpressue or heart rate. There was a small decline in LV systolic pressure without a significant drop in mean arterial pressure. Breathing fluorocarbon 12 for 30 minutes caused a decline in peak LV dP/dt, cardiac output, LV systolic pressure and mean arterial pressure which was present throughout the exposure period. The effects observed during acute fluorocarbon 12 exposure were not altered by previous chronic, intermittent exposure to 10% fluorocarbon 12.

Aerosol Propellants↗

Molecular basis of the biological function of molybdenum: the relationship between sulfite oxidase and the acute toxicity of bisulfite and SO2.

The administration of tungsten to rats maintained on a low molybdenum diet resulted in a dose- and time-dependent loss of sulfite oxidase (EC 1.8.3.1) and xanthine oxidase (EC 1.2.3.2) activities and hepatic molybdenum. These tungsten-treated animals appeared healthy, but were more susceptible to bisulfite toxicity. The median lethal dose for intraperitoneal bisulfite was found to be 181 mg of NaHSO(3) per kg for the animals deficient in sulfite oxidase, compared to 473 mg/kg for normal rats. The survival time of rats exposed to SO(2) at concentrations of 590 ppm and higher was seen to be inversely related to the level of SO(2). At 590 ppm and 925 ppm, control animals displayed symptoms of severe respiratory toxicity before death. At 2350 ppm of SO(2), death was preceded by seizures and prostration, symptoms observed with the systemic toxicity of injected bisulfite. At 590 ppm, animals deficient in sulfite oxidase were indistinguishable from control animals. However, at 925 ppm and 2350 ppm, the deficient animals displayed symptoms of systemic toxicity and had much shorter survival times. It is concluded that sulfite oxidase is instrumental in counteracting the toxic systemic effects of bisulfite, either injected or derived from respired SO(2). Respiratory death probably results from the toxicity of gaseous SO(2) before absorption as bisulfite and cannot be alleviated by sulfite oxidase. Sulfite oxidase does not appear to be inducible by either bisulfite or SO(2).

Animals↗