Jack M. Curtis

Teratogenic action of carbaryl in beagle dogs

Abstract Carbaryl (1-naphthyl- N -methyl carbamate; Sevin), a reversible cholinesterase-inhibiting insecticide, was incorporated into the feed of pregnant beagle dogs and fed throughout the gestational period at levels of 50, 25, 12.5, 6.25, and 3.125 mg/kg body weight daily. Effects observed included an unexplained number of animals with dystocia (difficult births) due to atonic uterine musculature, an apparent contraceptive effect at the highest dose level, and a teratogenic action of carbaryl seen at all but the lowest dose level. The teratism was seen in 21 of a total of 181 pups born, or 11.6%. The characterization of the fetal abnormalities included abdominalthoracic fissures with varying degrees of intestinal agenesis and displacement, varying degrees of brachygnathia, ecaudate pups, failure of skeletal formation, and superfluous phalanges. Several of the pups exhibited multiple defects that were difficult to categorize. It is concluded that carbaryl produces teratogenic and toxic effects in the pregnant beagle dog.

The use of the angular transformation in biological assays.

Abstract A comparison is made of the use of the angular transformation and the use of the probit transformation in evaluating results from biological assays having percentage responses. It is found that the angular transformation results in making the weights dependent on the number of animals used on each dose and if these are equal the weights are eliminated. The logit transformation is also cited. A two-dose assay design used in conjunction with the angular transformation results in a simplified calculation which can be put in the form of a graph and nomograph for use in the laboratory to estimate both potency and error of the assay as a per cent of the standard. A comparison of the calculation time involved shows that the probit method requires about twelve times as long as the angular transformation method involving graph and nomograph. A comparison of results obtained shows very little difference.

Diazinon toxicity—Comparative studies in dogs and miniature swine☆

Abstract Beagle dogs and Hormel-Hanford swine survived single oral doses of 300 or 500 mg/kg of diazinon. In addition, 4 daily doses of 50 mg/kg/day were tolerated. Dogs survived as long as 15 days and swine up to 30 days at doses of 25 mg/kg/day, although 2 female pigs died after 2 and 3 similar daily doses. In a chronic study, 30 beagle dogs and 30 Hormel-Hanford swine were distributed into 5 groups of 6 animals each. Diazinon, dissolved in corn oil, was given by capsule to the dogs at doses of 0, 2.5, 5.0, 10.0, and 20 mg/kg/day and to the swine at doses of 0, 1.25, 2.5, 5.0, and 10 mg/kg/day for 8 months. Consistent cholinergic signs were observed, primarily in the high-dose groups of both species. No marked changes in hematologic values were noted in these animals when measured at monthly intervals. Among the blood chemistry determinations made, increases with respect to control values were observed in the serum levels of amylase, lactic dehydrogenase, and ornithine carbamyl transferase. These responses were not sex-related. In the dose-range studies, gross pathologic findings included hemorrhages of the heart and congestion or hemorrhage of the gastrointestinal tract, along with marked edematous thickening of the duodenum and jejunum in some animals. In the chronic studies, thickening and occasional rupture of the intestinal wall were observed. In swine, ulcers were found in the duodenum and the livers were firm, gritty, and hard to cut. Histopathologically, slight cirrhotic changes of the liver and hemorrhage of the intestinal tract were seen most frequently. In 2 of the 3 male dogs in the high-dose group, testicular atrophy was observed. Myeloid:erythroid (M/E) ratios in excess of 100 1 were found in dogs which received 20 mg/kg/day of diazinon and died during the first 30 days of the experiment. Three of four pigs receiving 10 mg/kg/day of diazinon died in the same period and had and M/E ratio of 3.4 1 or more. Reticulocytopenia was found in both species, although classical aplasttic anemia was not produced in either species.

Ornithine carbamyl transferase as a liver function test comparative studies in the dog, swine, and man☆

Abstract Selective tissue damage was induced in groups of dogs and swine, either chemically by the nephrotoxic agent uranyl nitrate or the hepatoxic agent carbon tetrachloride, or surgically by biliary duct or coronary artery ligation. Human cases with myocardial infarction, pulmonary edema, myositis, viral and toxic hepatitis were included in this study. The following blood assays were monitored throughout the study: Cell counts, hemoglobin, hematocrit, coagulation tests, blood urea nitrogen, fasting blood sugar, isocitric dehydrogenase, lactic dehydrogenase, alkaline phosphatase, ornithine carbamyl transferase, glutamic oxaloacetic and glutamic pyruvic transaminase. Our data show that ornithine carbamyl transferase became elevated only when the hepatic parenchyma was damaged, and that this elevation became evident just as early and was much higher than that of the other enzymes assayed.

Progressive ultrastructural changes in the mucosal epithelium of the small intestine of beagle dogs fed methoxychlor

Abstract Methoxychlor was fed to a group of fourteen healthy 6-month-old dogs, at a dose of 2.5 gm/kg body weight/day, mixed in the feed. These animals were killed, one at a time, at various time intervals during the next 12 weeks. Tissue from the small intestinal mucosa was rapidly removed, properly processed and examined by electron microscopy. A progressive degeneration of the mitochondria marked in the early stages by matrical swelling and disruption of the cristae was the most pronounced finding. Later, myelin bodies appeared while the swollen mitochondria became vacuolated and their cristae were gone. One animal was taken off the methoxychlor diet after 12 weeks, fed the control diet for 3 weeks and then killed. The mitochondria of the intestinal epithelium were not so involved as those of the dogs fed methoxychlor for several weeks. A possible mechanism of pathogenesis is presented in the Discussion.