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Biomedical subjects

D R Kalkwarf

Publications and source records attributed to D R Kalkwarf.

15 recordsLinked to original sources

Subchronic toxicity evaluation of lewisite in rats.

Health and exposure criteria have not been established for lewisite [dichloro(2-chlorovinyl)arsine], a potent toxic vesicant that reacts with the sulfhydryl groups of proteins through its arsenic group. Sixty Sprague-Dawley rats of each sex, 6-7 wk old, were divided into 6 groups (10/group/sex) and gavaged with either 0, 0.01, 0.1, 0.5, 1.0, or 2.0 mg/kg of lewisite in sesame oil 5 d/wk for 13 wk. No significant dose-related change in body weight was observed. At the high dose, serum protein, creatinine, SGOT, and SGPT were decreased in males; lymphocytes and platelets were increased in females. A treatment-related lesion was detected in the forestomach of both sexes at 2.0 mg/kg. These lesions were characterized by necrosis of the stratified squamous epithelium accompanied by infiltration of neutrophils and macrophages, proliferation of neocapillaries, hemorrhage, edema, and fibroblast proliferation. Mild acute inflammation of the glandular stomach was also observed in some cases at 1.0 and 2.0 mg/kg. Early deaths were attributed to severe inflammation of the upper and/or lower respiratory tract, possibly from deposition or reflux of test material into the pharynx. Estimated dose range for NOEL appears to be >0.5 and <1.0 mg/kg when administered orally.

Animals↗

Iron, radiation, and cancer.

Increased iron content of cells and tissue may increase the risk of cancer. In particular, high available iron status may increase the risk of a radiation-induced cancer. There are two possible mechanisms for this effect: iron can catalyze the production of oxygen radicals, and it may be a limiting nutrient to the growth and development of a transformed cell in vivo. Given the high available iron content of the western diet and the fact that the world is changing to the western model, it is important to determine if high iron increases the risk of cancer.

Animals↗

Emanation coefficients for Rn in sized coal fly ash.

Emanation coefficients for 222Rn in sized samples of dry coal fly ash were evaluated as a function of source and particle size using a modification of the "sealed-can, gamma-only" technique. The emanation coefficient is defined as the fraction of Rn atoms that escape the solid particles of a source. Diffusible Rn was separated from nondiffusible Rn by adsorption on charcoal, and each was measured independently by gamma-ray spectrometry of the Rn daughter, 214Bi. Samples of ash from eastern bituminous coal, western bituminous coal and mid-western bituminous coal with aerodynamic equivalent diameters of less than 15 micron were examined, and the measured emanation coefficients ranged from 0.098 down to 0.007. These values were dependent on both the size and source of the fly ash. The emanation coefficients and the specific activities generally decreased monotonically with increasing aerodynamic equivalent diameter. For unfractionated standard fly ash, SRM 1633a, from the U.S. National Bureau of Standards, the emanation coefficient for 222Rn was found to be 0.018. The results suggest that only a small fraction of the Rn in lung-deposited fly ash will be removed by exhalation.

Carbon↗

Lung-clearance classification of radionuclides in coal fly ash.

Lung-clearance classifications for 238U, 232Th, 230Th, 228Th, 226Ra, 210Pb and 210Po in respirable coal fly ash were estimated for use with the lung clearance model proposed by the ICRP Task Group on Lung Dynamics. Estimates were based on measurements of the dissolution rates for these radionuclides from sized fly-ash samples into simulated lung fluid at 37 degrees C. The estimates were expressed in the classification terms of the model, i.e. D, W and Y, indicating lung clearance half-times of 0-10 days, 11-100 days, and more than 100 days, respectively. Ash from eastern bituminous coal, western bituminous coal and mid-western bituminous coal was examined. Both Class-D and Class-Y components of 238U were found in all samples, whereas all the other radionuclides dissolved very slowly and were classified 100% Class Y. The fraction of 238U in Class D increased with decreasing particle size and increased linearly from 0.02 to 0.17 as the concentration of U in the volatile-metal portion of the samples increased. This relationship suggests that a major fraction of the U in coal fly ash may be shielded from exposure to simulated lung fluid by more-abundant metals deposited on the outer surface of fly ash during coal combustion.

Carbon↗

Dissolution rates of uranium compounds in simulated lung fluid.

Maximum dissolution rates of uranium into simulated lung fluid were measured at 37 degrees C to estimate clearance rates from the deep lung. The materials tested included: ore and yellowcake, an airborne sample from an industrial site, and purified samples of (NH4)2U2O7, U3O8, UO2 and UF4. A batch procedure was developed to test samples containing as little as 10 micrograms of natural uranium. Values of dissolution halftimes varied from 0.01 day to several thousand days depending on the physical and chemical form of the uranium. Dissolution occurred predominantly by formation of the #UO2(CO3)3 ]4-ion; and as a result, tetravalent uranium compounds dissolved slowly. Dissolution rates of size-separated yellowcake aerosols were found to be more closely correlated with specific surface area than with aerodynamic diameter.

Air Pollutants, Occupational↗

1976 Hanford americium exposure incident: urinary excretion of trace metals during DTPA treatments.

Urine samples from a person treated intravenously with diethyl-enetriaminepentaacetate (DTPA) salts for 3 yr to promote the excretion of 241Am were assayed for 24 elements including almost all of the trace metals currently recognized as essential for good health. Zinc was found to be the only metal excreted more rapidly than normal. An 18-mg urinary loss of body zinc was found to be associated with each 1-g injection of Na3CaDTPA. Use of either Na3ZnDTPA or Na3CaDTPA combined with oral dosages of ZnSO4 appeared to completely compensate for this loss, and it is unlikely that the patient experienced any zinc deficiency due to the DTPA treatment.

Accidents, Occupational↗

Sustained administration of cyclazocine for antagonism of morphine.

The plasma levels, distribution and excretion of tritium were determined after administration of a single or sustained dose of 3H-cyclazocine to naive and morphine-addicted rats. The plasma levels reached and maintainat animals tolerant to morphine were cross-tolerant to cyclazocine. Although only half the administered radioactivity was excreted after either a single dose or a continuous administration, no appreciable concentration was found in any of the organs studied. The behavior of a single or sustained dose of cyclazocine was also determined in rabbits to evaluate the effect of the implant site on the drugs release rate and tissue biocompatibility. The release-rate of 3H-cyclazocine from a glyceride matrix implanted subcutaneously or intramuscularly could be controlled by modification of the matrix itself or by manipulation of the drug concentration within the matrix. Durations of action between a few days and a month were obtained by these means from devices that were both biodegradable and tissue compatible. The results indicate that the procedures used here may provide a practical means for administering narcotic antagonists to addicts.

Animals↗

Sustained release of naltrexone from glyceride implants.

Solid dispersions of naltrexone in natural glycerides were used to form injectable implants which continuously release narcotic antagonists in vivo. The dispersions were formed and tested either as small cylindrical pellets, e.g. l x 3.0 mm in size, or as particles with diameters in size ranges between 125-250 mu, that are suspended in an aqueous methyl cellulose solution. Both types of implants delivered naltrexone to mice at rates that were effective in blocking the antiociceptive action of morphine for at least one month. The rate of naltrexone release was controlled by altering its concentration in the dispersion and by varying the glyceride composition. Degradation and absorption of the implants were found to depend on their composition, dimensions and location in the body. No appreciable tissue incompatibility was seen in mice, rats, rabbits, monkeys and swine, even when long-lasting preparations were removed a year after treatment.

Animals↗

Ion-diffusion potentials and electrical rectification across lipid membranes activated by excitation-induced material.

Membranes synthesized from sphingomyelin-tocopherol mixtures and treated with the protein, "excitation-inducing material," to increase their electrical conductance were tested for applicability of the Nernst equation and changes in electrical rectifying behavior with temperature. Above pH 7, and in the temperature range 303-323 degrees K, ion-diffusion potentials created by salts of monovalent cations showed that areas of the membrane activated by excitation-inducing material were only permeable to cations. Results also indicated that a parallel current with an activation energy of 1.00 eV per molecule passed through unactivated areas of the membrane. Below pH 7, the ratio of measured diffusion potentials to predicted values decreased steadily. Electrical rectification was exhibited by membranes activated by excitation-inducing material with positive current consistently passing preferentially from the side rich in excitation-inducing material to the opposite side. For a given membrane, the current-voltage curves did not change from 312 to 323 degrees K; but below 312 degrees K, the membrane suddenly increased its conductance and became ohmic. This phenomenon was independent of salt concentration and pH, and resembled a phase transition.

Diffusion↗

Subchronic toxicity evaluation of sulfur mustard in rats.

Occupational exposure criteria have not been established for sulfur mustard (bis(2-chlorethyl) sulfide), a strong alkylating agent with known mutagenic properties. Seventy-two Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12 of each sex per group) and gavaged with 0, 0.003, 0.01, 0.03, 0.1 or 0.3 mg kg-1 sulfur mustard in sesame oil for 5 days a week for 13 weeks. No dose-related mortality was observed. A significant decrease (P > 0.05) in body weight was observed in both sexes of rats only in the 0.3 mg kg-1 group. Hematological evaluations and clinical chemistry measurements found non consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathological evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg kg-1 and of males at 0.1 mg kg-1. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, apparent increase in mitotic activity of the basilar epithelial cells and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated no-observed-effect level (NOEL) for sulfur mustard in this 90-day study was 0.1 mg kg-1 day-1 when administered orally.

Animals↗