PubMed Health⌕ Search

Biomedical subjects

W F Durham

Publications and source records attributed to W F Durham.

14 recordsLinked to original sources

Six-month daily treatment of sheep with neurotoxic organophosphorus compounds.

The delayed neurotoxic effects of tri-o-cresyl-phosphate (TOCP), O-methyl-O-(4-bromo-2,5-dichlorophenyl) phenylphosphonothioate (leptophos), and O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN) at 5, 5, and 1 mg/kg/day, respectively, on male sheep were studied during 6 months of daily oral treatment under field conditions. A vehicle-control group of sheep given corn oil (0.1 ml/kg/day) only was used for comparison. All sheep were killed 24 h after the 180th daily treatment. Blood, brain, spinal cord, and sciatic nerve tissues were taken for histological and/or biochemical examinations. The results indicated that leptophos induced severe ataxia and paralysis in sheep following about 4 months of treatment. TOCP produced either mild ataxia or lameness in two of four sheep during the last week of experiment. On the other hand, none of the EPN-treated sheep showed clinical signs of neurotoxicity during the course of the experiment at the dosage tested. These clinical results were supported by histological findings and also by biochemical results with neurotoxic esterase (NTE) measurements. In the case of leptophos-treated sheep, numerous prominent degenerative lesions of axons were observed in spinal cords and brains. Similar but somewhat less numerous lesions were noted in sheep treated with TOCP. No histological changes were observed in similar tissues taken from EPN-treated sheep. The results also indicated that, for chronic exposure to these neurotoxic organophosphorus compounds in sheep, a threshold in excess of 60-70% prolonged inhibition of brain NTE, or 50-60% inhibition of spinal cord NTE must be exceeded to initiate clinical and/or histological neurotoxic effects.

Acetylcholinesterase↗

Disposition of 14C and/or 74As-cacodylic acid in rats after intravenous, intratracheal, or peroral administration.

The distribution, excretion, and possible metabolism of (14)C- and/or (74)As-cacodylic acid, an organoarsenical herbicide, was studied in rats following a single intravenous injection, intratracheal instillation or oral gavage. Male Sherman rats were dosed at levels ranging from 200 mg/kg to 120 mug/kg. The extent and rate of lung absorption was greater than gastrointestinal absorption. Concentrations in the liver and whole blood were higher after peroral dosing than intravenous administration. Levels observed in plasma and other tissues were similar after all three routes following the absorptive phase. The percent dose found in the whole blood, red blood cells, and plasma was similar for all doses given by these routes. Less than 0.1(1/2) of the administered dose was recovered as (14)CO(2) by any route at 24 hr after administration. Twenty-four hours after intravenous, intratracheal, and peroral administration, 71, 60, and 25%, respectively, was excreted in the urine. After intravenous administration of 200 mg/kg, sufficient (14)C-cacodylic acid was recovered in bile to account for the small amount excreted in the feces. Cacodylic acid is probably not metabolized to inorganic arsenic since the disposition of (14)C and (74)As-cacodylic acid were identical.Kinetic analyses of the plasma curve for (14)C-cacodylic acid (high dose) yielded three half-times; 0.014, 0.214 and 3.42 hr with an apparent volume of distribution of 15.3 ml. Highest initial concentrations were found in the whole blood, muscle, kidney, liver and lung. Levels in all tissues decreased rapidly, but remained high in whole blood. The red blood cells were found to be the major site of body burden of cacodylic acid.

Absorption↗

Exposure of apple thinners to parathion residues.

In studies of potential exposure of a volunteer working under controlled conditions during apple hand-thinning operations at 1, 24, 48, 72, 96, 168, and 240 hr after application of conventional 0.03% parathion spray, both dermal and respiratory exposure values were greater where water-wettable powder formulations were used than where emulsifiables were used. Residue levels of parathion on leaves from the two types of applications were about the same. Only trace amounts of paraoxon could be detected at one and seven days after application. Highest exposure values (14.2 mg/hr dermally and 0.15 mg/hr respiratorily) were obtained within 24 hr of application. Exposure was considerably less after residues were 72 hr old. Greatest exposure was on the forearms and hands. Urinary p-nitrophenol excretion indicated slightly more absorption following exposure in water-wettable powder experimental plots. Potential exposure values indicate that absorption could reach hazardous levels after one or two hr of work, even at the 96-hr residue period, if all the pesticide were absorbed. Considering that only a small fraction of the total amount would be absorbed, it is calculated that at 75-hr residue period poisoning should not occur. There was no significant change in blood cholinesterase activity of the volunteer worker. Variation in spray deposit within an orchard due to poor tank mixing did not appear to be great enough to be considered an important factor affecting exposure.

Administration, Topical↗