Showing papers on "Toxicity published in 1974"

Clinical antitumor activity and toxicity of streptozotocin (NSC‐85998)

Abstract: Streptozotocin was administered to 106 patients with advanced malignancies. Therapeutic responses were observed in Hodgkin's disease, 7/16, lymphocytic lymphoma, 3/11, Burkitt's lymphoma, 1/12, and acute lymphocytic leukemia, 1/5. Two of 7 patients with islet cell carcinoma, 1 insulin-secreting and 1 serotonin-secreting, responded, but 8 patients with malignant carcinoid tumors originating from the ileum failed to demonstrate a reduction in either urinary 5-hydroxyindole acetic acid or tumor mass. Additional evidence of drug activity was observed in 2 patients with melanoma and 1 of 8 cases with sarcoma. There was no apparent cross resistance between Streptozotocin, a methyl nitrosourea, and BCNU, a chloroethyl nitrosourea. Hematologic toxicity was observed in 9% of cases, whereas renal damage demonstrated in 28% was the principal treatment-limiting drug effect. Ten to twenty percent of each total dose is excreted in the urine with an intact N-nitroso group within 2 hours after administration. Recommended maximum doses based on results of these studies are 500 mg/m2 for 5 days or 1.5 g/m2/week in patients with normal renal function.

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (tcdd) in c57bl/6 mice.

Abstract: Abstract Three-month-old male C57B1 6 mice were given single oral doses of 0, 100, 150, or 200 μg of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD)/kg. The LD50 was 114 μ/kgg. In mice that died, depletion of the thymus and spleen were consistently found and edema and terminal hemorrhages occurred frequently. In a second experiment, 4-month-old male mice were dosed po with 0, 0.2, 1.0, 5.0 or 25 μg/kg, once a week for 2 or 6 weeks. Some deaths and growth retardation occurred in the 25 μg/kg dose group. Significantly increased liver and decreased thymus weights were found in the 1, 5 and 25 μg/kg dose groups. Total neutrophils were increased significantly, whereas hemoglobin values and mean corpuscular hemoglobin concentrations were decreased significantly after 6 doses of 25 μg/kg. Total serum protein and α-, β-, and γ-globulins were significantly decreased. TCDD was porphyrogenic. The hepatic porphyria was probably associated with liver damage. Degenerative and necrotic changes in the liver were essentially centrilobular and were accompanied by cellular infiltrates and ceroid pigment deposition. Proliferation of bile duct and bile duct epithelial cells occurred. Lipid accumulation was centrilobulary localized in the mice receiving 0.2 μg/kg, was more pronounced in the mice of the intermediate dose levels, and involved hepatocytes throughout the lobule in the 25 μg/kg dose group.

Toxicity of new pyrethroid insecticide.

Abstract: THE mammalian toxicity of NRDC 156 and NRDC 161 (see accompanying paper1) was assessed in albino female, rats 10 to 12 week old.

Nutritional factors and susceptibility to lead toxicity.

Abstract: Although the quantities of lead (Pb) to which individuals are exposed vary widely, susceptibility of an individual to the effects of a specific level of exposure is another highly important factor in development of lead toxicity. For example, susceptibility to lead toxicity can be modified by several dietary factors. Low dietary intakes of calcium or iron (20% of recommended levels) substantially increase the toxicity of the same level of lead exposure to rats. In the studies of calcium effect, when calcium was fed to rats at (1/5) of the recommended intake, 12 mug Pb/ml drinking water produced the same degree of toxicity as did 200 mug Pb/ml with a normal calcium diet. The maximal dose for a 10-week period that does not impair heme synthesis or renal function in the rat has been established to be 200 mug Pb/ml drinking water. The role of low calcium diet on increasing susceptibility to lead has been confirmed in several species. Mechanisms explaining the effect of calcium on lead toxicity may be related to absorption of lead from the gastrointestinal tract or renal tubule or to function of the parathyroid. Preliminary histological investigations on the parathyroids of control and lead-treated rats on normal and low calcium diets show no effect of lead. Studies are currently underway to evaluate the lead, calcium and iron contents of the diets of children with normal and elevated concentrations of blood lead.

Correlation of serum magnesium levels and cardiac digitalis intoxication

Abstract: A prospective study was undertaken to compare the prevalence of hypomagnesemia and hypermagnesemia in patients with cardiac digitalis toxicity and in digitalized patients without toxicity. During an 8 month period on a general medical service, there were 38 patients with “definite” or “possible” digitalis toxicity, by serial electrocardiographic studies, among 120 digitalized patients whose serum magnesium levels were obtained. Serum magnesium concentrations were measured by atomic absorption spectrometry. Hypomagnesemia was present in 21 percent of patients with and 10 percent of those without digitalis toxicity. Hypomagnesemia was not more prevalent in patients with toxicity but relatively lower serum levels of digoxin or digitoxin. The presence of hypermagnesemia was significantly greater in patients with toxicity (18 percent) than in those without toxicity (5 percent), and appeared to be related to a significantly greater prevalence of abnormal renal function in the former group. The potential value of magnesium administration in hypomagnesemic patients with cardiac digitalis toxicity warrants investigation. Caution should be exercised in the administration of magnesium sulfate to digitalis-toxic, azotemic patients who may already be hypermagnesemic.

Chronic toxicity of nickel to the fathead minnow

Abstract: Chromotoxicity of nickel to the fathead minnow (Pimephales promelas Rafinesque) was determined while obtaining acute toxicity data to be used in calculating an application factor for nickel. Criteria for toxicity were effects on survival, growth and reproduction. The application factor was estimated by using the maximum acceptable toxicant concentration of the chronic test and the 96-hr TL50 of the acute toxicity bioassay.

Inhibition by Cysteamine-HCl of Oncogenesis Induced by 7,12-Dimethylbenz(a)anthracene without Affecting Toxicity

Abstract: The effects of cysteamine-HCl, a radical scavenger, on 7,12-dimethylbenz(a)anthracene-induced toxicity and oncogenesis were studied in vitro and in vivo . While the addition of cysteamine-HCl to mouse fibroblasts (M2 line) prior to and after the addition of 7,12-dimethylbenz(a)anthracene did not affect the carcinogen-induced toxicity (reduced plating efficiency), the number of transformed foci was markedly reduced. In vivo , the i.p. administration of cysteamine-HCl to Sprague-Dawley rats, prior to and following the injection of 7,12-dimethylbenz(a)anthracene i.v., did not affect the carcinogen-induced adrenal necrosis and lesions of the small intestinal epithelium. Similar treatment did, however, markedly reduce the number of mammary tumors formed. These results suggest that the toxic and oncogenic changes induced by 7,12-dimethylbenz(a)anthracene are due to two different metabolites, and support the concept that the latter effect may be mediated by a radical.

The Manganese Toxicity of Cotton

Abstract: Cotton plants (Gossypium hirsutum. Linn. var. Sankar 4) were grown at normal and toxic levels of substrate manganese, and the altered metabolism of manganese toxic plants was studied. The tissues of plants exposed to toxic levels of manganese had higher activities of peroxidase and polyphenol oxidase, and the activities of catalase, ascorbic acid oxidase, glutathione oxidase and cytochrome c oxidase were lowered. In addition, the high manganese tissue had lower contents of ATP and glutathione but higher amounts of ascorbic acid. The respiration of the partially expanded leaves and the growing tips of toxic plants were depressed when compared to that of the normal tissues. The metabolic changes of manganese toxicity of cotton are placed in the following order: accumulation of manganese in the leaf tissue; a rise in respiration; stimulation of polyphenol oxidase; the appearance of initial toxicity symptoms; the evolution of ethylene and stimulation of peroxidase; the presence of severe toxicity symptoms; the depression of terminal oxidases and respiration; abscission of the growing tip and proliferation of the stem tissue. The early stimulation of polyphenol oxidase may be used to detect potential manganese toxicity.

Acute Toxicity in Rats and Mice Exposed to Hydrogen Chloride Gas and Aerosols

Abstract: Hydrogen chloride (HC1) is one of the combustion products formed during the test firing of certain rocket and missile engines. A study was undertaken to determine the LC50 values for rats and mice exposed to various measured concentrations of either HC1 gas or HC1 aerosol for 5 and 30 minutes. This accomplished two objectives; first, to define short-exposure toxicity levels for HC1 in either form and second, to determine whether the aerosol form represented a greater hazard than the gas itself. The respiratory tract was the primary target for HC1 in either form, and lesions were similar to those produced by other severe pulmonary irritants. The results indicate that HC1 gas and HCI aerosol have comparable toxicity in rats and mice. Comparison of these results with another study of HCI gas toxicity in rabbits and guinea pigs showed that HCI gas had the same degree of toxicity in mice, rabbits and guinea pigs while rats were considerably more tolerant.

Lead Acetate Toxicity in Rats in Relation to Age and Sex

Abstract: The toxicity of lead acetate was determined in young (3-week-old) and adult (18-week-old) rats of both sexes 8 days after a single i.p. injection. The LD50 was lower in adult males than in adult females and both groups of young animals.

Relative toxicity of methotrexate in several tissues of mice bearing Lewis lung carcinoma.

Abstract: Mice bearing Lewis lung carcinoma were treated with methotrexate (MTX) by two different modes: single injection and constant infusion. The time course of the effect of these treatments was monitored by measuring the incorporation of 3 H-deoxyuridine into deoxyribonucleic acid (DNA) in three rapidly proliferating tissues: femur marrow, small intestine and subcutaneously growing Lewis lung tumor. Single injections of 5 mg/kg of MTX caused dramatic initial inhibition of deoxyuridine incorporation in all three tissues. Recoveries occurred in cyclic, variable and overshooting patterns as the plasma concentration of MTX fell to undetectable concentrations. Constant infusions resulted in a plateau plasma MTX concentration (mean ± S.D.) of 0.009 ± 0.003 µg ml (∼ 2 x 10 -8 M) for periods up to 100 hours. This concentration resulted in the following percent inhibitions of 3 H-deoxyuridine into DNA: small intestine, 90% from 10 hours on; marrow, 75% by 10 hours with recovery to control values and overshoot occurring even in the presence of constant plasma MTX: tumor, little evidence of any consistent effect that was different from untreated animals. These results indicate that at 2 x 10 -8 M MTX in the plasma, the relative degree of toxicity to tissues is: small intestine > marrow > Lewis lung tumor. Model simulations suggest that the reasons for this selective toxicity are a combination of differences in tissue permeability of MTX and differences in rates of new enzyme (dihydrofolate reductase) synthesis after exposure to MTX.

Influence of ethanol ingestion on lead toxicity in rats fed isocaloric diets.

Abstract: The influence of ethanol on tissue content of lead and measures of lead toxicity has been studied in rats fed isocaloric diets and controlled nutritional content, it is concluded that the synergistic effect of alcohol on lead toxicity is slight when compared to the influence of previously studied nutritional factors such as calcium and iron This study suggests, therefore, that the clinically suspected synergism between alcohol consumption and lead poisoning sometimes observed among industrial workmen is more likely due to nutritional factors than mutual enhancement of the closely related cellular effects of these two toxins

Respiratory Carcinogenesis in Rats after Inhalation of Radioactive Aerosols of Actinides and Lanthanides in Various Physicochemical Forms

Abstract: To study the role of the distribution of local tissue irradiation on the toxicity of alpha emitters, groups of 50 to 165 rats were exposed to aerosols of 244Cm(NO3)3, 241Am(NO3)3, 238Pu(NO3)4, 235Pu(NO3)4, 239PuO2, and 241AmO2 and observed for effects. Curium-244 was most evenly distributed in the lung and most effective in reduction of survival time followed in descending order by 238Pu(NO3)4, 241Am(NO3)3, 241AmO2, 239Pu(NO3)4, and 239PuO2, which was more heterogeneously distributed in the lung as particulate. The toxicity had 2 results: shortening of life span and cancer induction (about 50% bronchogenic carcinoma and 40% bronchiolo-alveolar carcinomas). There appeared to be no correlation between survival time and cancer induction or localization of the element in the lung and the starting point of the tumors. This histologic type of cancer was independent of the nature of the element. Toxicity and cancer induction appeared to depend on the homogenicity of radiation dose with the more evenly distributed dose being most effective.