The efficacy and safety of chlorpyrifos (Dursban) for control of Myobia musculi infestation in mice.

Mite infestation in laboratory mice is a common, but troublesome problem in animal facilities. Recommended treatment regimens are frequently ineffective because of the short period of exposure to the control agent. In an effort to develop a time-release approach, we have investigated the use of Dursban granules applied in animal bedding. Initial toxicity studies indicated that this pesticide can be added to shoebox cage litter at levels three times that used for outdoor application (6 g per 27 by 48 cm shoebox cage) without producing clinical signs of toxicity. Metabolism studies demonstrated that although individual mice showed decreased brain acetylcholinesterase activity following treatment, liver cytosolic glutathione-S-transferase, liver microsomal aminopyrine N-demethylase, or aryl hydrocarbon hydroxylase were not induced after 1 week of exposure. Parasitological studies indicated elimination of mites and itching in an experimental infestation, as well as reduction of itching in severely symptomatic, naturally infested mice, following treatment with the granules. These studies demonstrate the nontoxic efficacy of Dursban in the control of Myobia musculi.

Hepatic, placental, and fetal trace elements following molybdenum supplementation during gestation.

The effect of dietary Mo (Na2Mo(4)2H2O) added to drinking water at levels of 0, 5, 10, 50, or 100 mg on hepatic (gestating dams), placental, and fetal Mo, Cu, Zn, and Fe contents of Sprague-Dawley rats was studied. These elements were determined by a polarographic catalytic procedure for Mo and by atomic absorption spectrophotometry for Cu, Fe, and Zn. Hepatic Mo increased two to sixfold (5-100 mg Mo). There was a 1.5-fold increase in hepatic Cu, significant only at the 50 to 100 mg Mo/L treatment levels. Although the hepatic Fe content of the gestating rats significantly increased with Mo supplementation, the extent of the increase appeared to be influenced by the litter size, fetal weights, and the degree of fetal resorption. Zinc values did not differ at any of the treatment levels. Placental Mo increased 3-76-fold, Cu one to threefold. No differences were observed in placenta Fe or Zn. Fetal Mo increased two to six-fold (10-100 mg/L) and Cu increased one to fivefold. There were no differences in the Fe and Zn content although both of these elements appeared to decline as the level of supplemental Mo increased. Significant correlations were also observed between hepatic, placental, and fetal Mo, Cu, Fe, and Zn. These results suggest that changes in trace mineral status in gestation, owing to high Mo intake, do occur and such occurrences are also reflected in the fetus.

Dietary calcium and development of hypertension in spontaneously hypertensive rats.

The purpose of the present study was to attempt to correlate four calcium diets (0.02, 0.1, 0.5 and 2.5%) with changes in the development of hypertension in both spontaneously hypertensive and Wistar-Kyoto rats. Our findings confirm that an inverse relationship exists between dietary calcium content and the development of hypertension. The relationship does not rely upon altered serum ionized sodium, potassium, or calcium or parathyroid hormone levels. In addition, no consistent dietary calcium-dependent changes were noticed in cardiovascular reactivity. In contrast, anesthesia with pentobarbital completely abolished the relationship. These data support the hypothesis that dietary calcium influences autonomic tone through some, as yet, undefined processes.

Inhibition of dietary fat-promoted colon carcinogenesis in rats by supplemental calcium or vitamin D3.

A 2 X 2 X 2 factorial experimental design was used to investigate the effects of supplemental calcium (Ca) (0.5% versus 1.0% of diet as Ca gluconate) and vitamin D3 (D) (1000 IU/kg diet versus 2000 IU/kg diet) on 1,2-dimethylhydrazine-induced colon carcinogenesis in male F344 rats promoted with a 20% corn oil diet. Animals on the high-fat (HF) diet had an increased tumor incidence compared to the low-fat (LF) control diet (86% versus 53%, P less than 0.05) and supplemental Ca or D reduced this to or below the LF incidence (HF + Ca: 53%, HF + D: 47%). However, supplemental Ca or D had no inhibitory effect with LF diets (LF + Ca: 67%, LF + D: 60%). The results of this study indicate a possible role for supplemental Ca or D in the prevention of colon cancer, effective only in HF diets.

Co-carcinogenic effect of carbon black ingestion with dietary fat on the development of colon tumors in rats.

Previous studies in our laboratory on the co-carcinogenic effect of the ingestion of an industrial carbon black (CB) on chemically induced colon cancer in rats and mice demonstrated no differences in tumor incidences attributable to CB feeding. The present study examined the effect of CB ingestion within the context of a high fat diet, formulated to simulate the typical diet of western industrialized nations. Corn oil was added to ground commercial chow at 20% by weight and CB added at 2.05 g/kg diet and fed for 52 weeks to female Sprague-Dawley rats. Colon tumors were induced with 16 weekly injections of 1,2-dimethylhydrazine (DMH, 10 mg/kg body weight). Tumor incidences in DMH-treated rats ingesting CB were significantly (P less than 0.05) higher than in those with no CB added to the diet (76% vs. 60%). The survival of CB + DMH treated animals (64%) was also lower than that of animals treated with DMH and not ingesting CB (80%). These findings may implicate CB ingestion as a co-carcinogen for industrial workers when acting in synergism with high fat diets and other unknown colon carcinogens.

Multiple dietary factors in the enhancement of dimethylhydrazine carcinogenesis: main effect of indole-3-carbinol.

The effects of multiple dietary influences on 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8]-induced colon cancer in rats were studied. A 2(4) factorial experimental design was used to examine the main and interactive effects of 15% wheat bran (WB), 1% cholesterol (CH) with cholic acid, 20% beef tallow (BT), and 0.1% indole-3-carbinol (IC) on 160 male F344 rats treated ip with DMH (10 mg/kg) weekly for 16 weeks. The test diets were fed for 3 weeks before, 16 weeks during, and 12 weeks after DMH administration. At necropsy, total weight gain, liver and spleen weights, serum CH levels, liver aryl hydrocarbon hydroxylase (AHH) activity, and the size, number, incidence, and location of intestinal tumors were analyzed for dietary factor effects. The most significant inducer of tumors was the combination of CH + BT + IC acting in synergism. The single main effect most responsible for tumor morbidity was IC, which appeared to enhance tumorigenesis via its role as an inducer of AHH activity. The WB decreased tumor incidence and burden when added to diets also containing CH, but it otherwise increased tumor burden per tumor-bearing animal and incidence in all other diets. This study demonstrated the need for examining synergistic and antagonistic interactions among dietary initiators and/or promoters of colon carcinogenesis, as well as implicating IC as a significant factor in the development of DMH-induced tumors in rats.

Effect of dietary selenium deficiency on incidence and size of 1,2-dimethylhydrazine-induced colon tumors in rats.

Torula yeast diets deficient (less than or equal to 0.02 ppm) in selenium (Se) and a control diet supplemented with sodium selenite (0.1 ppm Se), were fed to 52 male Sprague-Dawley rats per diet for 23 wk following weaning. 1,2-dimethylhydrazine (DMH) was administered (20 mg/kg body weight) in 20 weekly i.p. injections after 3 wk of feeding. After 23 wk, 67% of the rats fed the Se-deficient diet had intestinal adenocarcinomas versus 63% on the 0.1 ppm Se diets. Diet also had no effect on the number or size of tumors per tumor-bearing animal or on the location of the tumors within the colon. The effects of Se deficiency on the hematological variables of white blood cell count, hematocrit, serum urea nitrogen and cholesterol concentrations were examined. Serum urea nitrogen levels were lower in Se-deficient DMH-treated rats (9.6 +/- 0.7 vs. 13.7 +/- 0.9 mg/dl, P less than 0.01) and serum cholesterol was higher in Se-deficient DMH-treated animals (69.0 +/- 5.5 vs. 50.7 +/- 3.9 mg/dl, P less than 0.05). Body weights of the Se-depleted group were lower in the DMH-treated animals (P less than 0.01) although food consumption did not differ. Controls without DMH did not show differences due to Se status for any variable examined. Se deficiency appears to affect DMH toxicity but nutritional adequacy (0.1 ppm Se) does not inhibit tumor development. The results of this study do not support the belief that Se deficiency enhances colon carcinogenesis.

The effect of carbon black ingestion on 1,2-dimethylhydrazine-induced colon carcinogenesis in rats and mice.

The possible co-carcinogenic effect of ingestion of industrial carbon black was examined in female Sprague-Dawley rats and female CF1 mice treated with 1,2-dimethylhydrazine (DMH) to induce adenocarcinomas of the colon. Carbon black was added to the diet at 2.05 g/kg feed and fed for 52 weeks. No differences (P greater than 0.05) in tumor incidences were seen in rats or mice. Simultaneous 2-year feeding experiments with carbon black alone showed no increase in the development of spontaneous tumors. These findings are consistent with the belief that carbon blacks are ineffective as carcinogens because of their adsorptive properties.

Physiological significance of benzo(alpha)pyrene adsorbed to carbon blacks: elution studies, AHH determinations.

Desorption of benzo(alpha)pyrene from commercial carbon blacks by tissue fluids in vitro is compared to arylhydrocarbon hydroxylase induction in mice at three levels of carbon black exposure. Less than 0.005% of the adsorbed benzo(alpha)pyrene content determined by soxhlet extraction in toluene is eluted by human plasma, swine serum, swine lung homogenate and swine lung washings. Statistically significant differences in elution efficiency are observed by the various tissue fluids and carbon blacks. There is no detectable increase in AHH level in mouse lung or liver tissues even at the highest carbon black exposure and consumption rate of 1g/g bdywt/year.

Solvent extracts of carbon black--determination of total extractables and analysis for benzo(alpha)pyrene.

The efficiency of three organic solvents for extraction of adsorbates, including polycyclic aromatic hydrocarbons (PAH), on five rubber-grade oil furnace blacks was studied. Measurement of both the percent total extractables and the specific PAH, benzo(alpha)pyrene (B alpha P), showed toluene to be a better extractant than benzene and both to be superior to cyclohexane. Spectral analysis for B alpha P was preceded by chromatographic separation. A thin layer technique was shown to be a rapid and reliable replacement for paper chromatography.

A primate model for prolonged endotoxin shock. Blood-vascular reactions and effects of glucocorticoid treatment.

A primate model was developed to study sequential blood-vascular responses, primarily of the lung and liver, and hematologic changes during prolonged endotoxemia with or without glucocorticoid treatment. In this model, pairs of animals, one with intermittent glucocorticoid regimen, were continuously infused with endotoxin throughout the experimental period. The duration of the experiment and the onset of progressive shock could be adjusted by changing the rate of endotoxin infusion. Endotoxemia at a rate of 10 mg. per kg. per hour resulted in progressive shick which was significantly delayed with glucocorticoid treatment. Endotoxin-induced hematologic alterations included early leukopenia and gradual development of disseminated intravascular coagulation. Morphologic studies revealed margination of neutrophils and mononuclear cells in the microcirculation of lung and liver. These changes were associated with sustained phagocytosis of endotoxin by the sequestered leukocytes and Kupffer cells, degranulation of the hepatic sinusoids and spaces of Disse contained extensive fibrinous deposits which in advanced stages of shock were accompanied by midzonal and centrilobular necrosis. Pulmonary lesions included margination, degranulation and fragmentation of leukocytes, early appearance of fibrin in hepatic sinusoids, and rapid development of disseminated intravascular coagulation, endothelial damage and associated lesions of lung and liver. The results indicate that events relating to sustained phagocytosis of endotoxin by the marginating leukocytes initiate a state of intravascular inflammation with disseminated intravascular coagulation and play a vasic role in the pathogenesis of pulmonary and hepatic lesions during prolonged endotoxemia leading to shock. The findings also suggest that glucocorticoid treatment attenuates endotoxin-induced blood-vascular reactions thereby providing an early protection against the development of shock and structural damage to the lung and liver.