Gordon W. Newell

Cholinesterase inhibition and toxicologic evaluation of two organophosphate pesticides in Japanese quail

Abstract A 5-week toxicologic study of two organophosphate insecticides, Azodrin® and Bidrin®, was undertaken with Japanese quail ( Coturnix coturnix japonica ). Birds fed Azodrin [3-(dimethoxyphosphinyloxy)- N -methyl- cis -crotonamide] at a dietary level of 5 ppm lost weight during the first week, but showed no decrease in egg production or reproduction. At 50 ppm, all females were dead in 2 weeks, and the males in 3 weeks. Whole blood cholinesterase was markedly inhibited at 0.5 ppm, but brain cholinesterase inhibition was marginal. Inhibited cholinesterase demonstrated a marked recovery during a 2-week posttreatment period. Bidrin [3-(dimethoxyphosphinyloxy)- N,N -dimethyl- cis -crotonamide] did not adversely affect body weight maintenance, feed consumption, egg production, or reproduction at 5 ppm in the diet. At 50 ppm, there was marked loss in body weight. Seven males and 9 females died during the 3-week feeding period. Whole blood cholinesterase was almost completely inhibited in both sexes at 0.5 ppm; brain enzyme inhibition was marginal at 5.0 ppm. Normal or near-normal activities of inhibited enzymes were attained during a 2-week recovery period. When fed to adult females, diets containing 0.5 or 5 ppm of either compound caused no adverse effect on the heartbeat of developing embryos throughout the incubation period.

A subacute toxicity study of N-(2-mercaptoethyl) benzenesulfonamide S-(O,O-diisopropyl phosphorodithioate) and phthalimidomethyl-O,O-dimethyl phosphorodithioate with Japanese quail☆

A 5-week toxicologic study of two organophosphate pesticides, Betasan® and Imidan®, was conducted with the Japanese quail, Coturnix coturnix japonica. Betasan did not adversely affect body-weight maintenance, egg production, or brain cholinesterase at the dietary levels used in this study. Egg hatchability was markedly reduced at the 1000-ppm dietary level, but fertility was unaffected. Whole blood cholinesterase was significantly inhibited at 100 ppm, but recovered during a 2-week posttreatment period. Imidan adversely affected feed consumption, body-weight maintenance, and egg production at 1000 ppm. Whole blood cholinesterase was markedly inhibited at 100 ppm. Marginal inhibition of brain cholinesterase occurred in females fed the 100-ppm level, and the enzyme was significantly inhibited in both sexes at 1000 ppm. Normal or near normal activity of the inhibited enzymes was attained during a 2-week recovery period. The Japanese quail is a feasible and practical tool for toxicologic investigations of pesticides. Problems encountered during this study are discussed in relation to further considerations of the species as a laboratory animal for investigating the hazards of agricultural chemicals to wildlife.

In vivo inhibition of rabbit whole blood cholinesterase following intravenous infusion of a diethyl organophosphate inhibitor and reactivation with 2-PAM☆

Abstract It is now generally accepted that the reaction of a dialkyl organophosphate with cholinesterase involves phosphorylation with the active site of the enzyme. Subsequent reactions of the phosphorylated enzyme include spontaneous reactivation and conversion, apparently first order, to a non-reversible or “aged” enzyme. The extent of these reactions is dependent on the alkyl substituents of the inhibitor and the enzyme source. Vandekar and Heath (1, 2) reported marked differences in the recovery rate of brain and erythrocyte cholinesterase activity following inhibition with “persistent” and “non-persistent” dimethyl phosphate inhibitors; enzyme recovery was more rapid after inhibition by the “non-persistent” inhibitors. However, spontaneous recovery of the enzyme, inhibited by “non-persistent” inhibitors, was markedly reduced following continuous intravenous infusion of the materials for several hours. These workers also reported that the spontaneous recovery of enzyme activity was high following short periods of compound infusion, which has been confirmed by Shellenberger et al. (2), using three dimethyl phosphate inhibitors. When these compounds were infused intravenously into rabbits for 2 hours or less, there was rapid but incomplete recovery of inhibited whole blood cholinesterase during the immediate post-infusion period. The spontaneous reactivation of diethyl-phosphoryl cholinesterase is generally of low magnitude, even though it may occur over several days (3). The reversal of diisopropyl-phosphoryl enzyme is negligible. However, the reversal depends on both the inhibitor and the enzyme source. Species differences and differences between true and pseudo-cholinesterase reactivation have been demonstrated. In the current study, rabbit whole blood cholinesterase was rapidly and almost completely inhibited during intravenous infusion of 2, 2-dichlorovinyl diethyl phosphate. There was little, if any, spontaneous reversal of inhibited enzyme during a subsequent 3-hour postinfusion period. Intravenous injection of 2-PAM immediately and up to 2 hours after infusion produced an immediate partial recovery of enzyme activity. The extent of recovery was directly related to the dosage level of injected reactivator.

Chronic effects of alcohol, muscatel, and sherry on the growth and performance of male rats.

Abstract An experiment was conducted to investigate whether the prolonged ingestion of ethyl alcohol and of inexpensive or expensive sherry or of inexpensive or expensive muscatel wine (each diluted to a concentration of 12% alcohol) adversely affected certain physiologic responses of rats. Weanling male rats given 12% alcohol or wine solutions over a 32-week period gained about 10% less weight than rats given water. This may have been due to the markedly lower fluid consumption by the alcohol- and wine-fed groups during the first weeks of the experiment. Examination of tissues at autopsy showed no gross abnormalities. Liver, kidney, spleen, heart, and testes weights of rats in all groups were not significantly different from those of the water control animals. Histopathologic examination of the tissues showed the presence of a slight fatty infiltration of the liver in all groups, regardless of the treatment. No other micropathology was observed. Bromosulfalein, audiogenic seizure, and electroshock data were the same for control and experimental animals. In the rotating bar test for neuromuscular coordination, control rats receiving water remained on the bar for longer periods than did alcohol- or wine-fed rats; this difference was apparently due to alcohol rather than to any other wine constituent.

A FIELD INVESTIGATION OF FLUOROSIS IN CATTLE.

A comparison has been made of the results of a detailed field investigation of the effects of fluoride on cattle with research results from controlled feeding experiments. Specifically, the comparison was made on the basis of the fluoride content in the feed, the fluoride content of the ribs, and fluoride content of the urine, and the fluoride effect on incisor teeth. Under the conditions prevailing at the time of this practical field study, it has been shown that fluorosis in cattle might be expected within a two-mile distance of these industrial plants. At this distance, the following conditions were determined: the forage contained more than 40-50 ppm F, approximately two mg F/kg of body weight per day, the fluoride content of the rib exceeded 4000 ppm, the fluoride content of the urine exceeded 15 ppm, and almost 50% of the incisor teeth examined were in Grades 4 and 5. Correlation of the results of a field experiment with the results of controlled feeding experiments was excellent. 8 references, 11 figures, 7 tables.

Modification of hexachlorophene toxicity by dieldrin and Aroclor 1254

Abstract Hexachlorophene (HCP) was fed singly or paired with either aflatoxin B1 (AF), Aroclor 1254 (AR), or dieldrin (D) to Fischer-344 rats for 8 weeks beginning at 5 weeks of age. For HCP fed singly, there was no mortality at 400 ppm or less, 80% mortality in males and 73% in females at 600 ppm, and 100% mortality in both sexes at 820 ppm. Paralysis was apparent in one female at 400 ppm and in all animals at 600 ppm. Minimal neuronal degeneration was evident in the brain at 50 ppm, focal necrosis and myelin vacuolization at 400 ppm or higher, and focal hemorrhage at 600 ppm. While addition of AF at 1 ppm did not affect the toxicity of 600 ppm of HCP, addition of AR at 160 ppm reduced mortality to less than 7%, and addition of D at 100 ppm to a diet containing 900 ppm of HCP reduced mortality from 100 to less than 4%. For both the HCP/AR and the HCP/D combinations, no paralysis was observed, although the histologic changes in the brain were still apparent.