Showing papers on "Toxicity published in 1971"
TL;DR: Thirty‐two patients with metastatic carcinomas treated with mitomycin C developed renal toxicity within 6 to 7 months of therapy and the toxic effect was mainly on the glomerular tuft and especially on the nuclei.
Abstract: Thirty-two patients with metastatic carcinomas were treated with mitomycin C. Three of them developed renal toxicity within 6 to 7 months of therapy. The toxic effect was mainly on the glomerular tuft and especially on the nuclei. Nephrotoxicity of mitomycin C has been noticed in rhesus monkeys, but has never been reported in man. Patients who are being treated with mitomycin C should be observed for a rising blood urea nitrogen, serum creatinine, and albuminuria.
110 citations
Journal Article•
TL;DR: The clinical tolerance to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was explored in patients with advanced cancer and Objective responses at toxic doses were seen in 2 of 5 patients with evaluable bronchogenic carcinoma and in both patients with malignant lymphoma.
Abstract: Summary The clinical tolerance to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was explored in patients with advanced cancer. This compound is related to 1,3-bis(2-chloroethyl)-1-nitrosourea, an agent of recognized antineoplastic effectiveness, but has only one chloroethyl group, is more lipid soluble, and is at least as active or more active against mouse Leukemia 1210. A single p.o. dose of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was given because of the superiority of widely spaced doses against Leukemia 1210 and the expected delayed hematological toxicity. The starting dose of 15 mg/sq m body surface area corresponded to one-third of the minimal toxic dose in the most sensitive animal species in preclinical studies. Large initial increments of drug dose at presumably nontoxic levels were followed by progressively smaller dose increments to the range of moderate, reversible toxicity. Forty patients with cancer received 82 treatments. Reproducible subtoxic decrease of thrombocytes occurred at the third dose step (50 mg/sq m); decrease of leukocytes occurred at the fifth dose step (100 mg/sq m). Dose-limiting toxicity resulting in delayed thrombocytopenia and leukopenia within 4 and 6 weeks, respectively, was reached at 130 mg/sq m. This dose was well tolerated in 6 patients when given at intervals of 6 weeks. Objective responses at toxic doses were seen in 2 of 5 patients with evaluable bronchogenic carcinoma and in both patients with malignant lymphoma. Marked neurological improvement was noted in all 3 patients with glioblastoma multiforme.
99 citations
TL;DR: It appears that a primary effect of cadmium was to prevent absorption of dietary iron in day-old coturnix birds.
Abstract: This study was designed to evaluate the effects of supplements of individual dietary components in altering the toxicity of dietary cadmium. Day-old coturnix (Japanese quail) were fed 75 mg Cd/kg of an adequate purified diet for 2- or 4-week periods. Cadmium produced moderate growth retardation, severe anemia, decreased ash content of the tibia, and deviations from the normal concentrations of zinc, iron, cadmium, copper, and calcium in one or more of the cells or tissues assayed (erythrocyte, liver, kidney, and tibia). Dietary supplements of zinc, iron(III), copper, and L-cysteine-HCl and injected ascorbic acid produced slight to moderate protection against cadmium-induced anemia, whereas iron(II), ascorbic acid, and D-isoascorbic acid had marked effects in preventing the anemia, growth retardation, poor bone mineralization, and perturbations in elemental concentrations of tissues. Chromium, cobalt, selenium, nickel, molybdenum, and pteroylglutamic acid had no effects. Cadmium did not affect the total ascorbate content of the liver. Removal of dietary ethoxyquin did not affect the toxicity of cadmium or the protective effects of ascorbic acid. Initiation of ascorbic acid feeding at 2 weeks was beneficial to birds fed cadmium throughout the 4-week experiment. Under the conditions of these experiments cadmium produced a functional iron deficiency and less clear-cutmore » affects on zinc function. It appears that a primary effect of cadmium was to prevent absorption of dietary iron. 33 references, 6 tables.« less
98 citations
TL;DR: The suggestion is made that the electron-transport lesion induced by bilirubin may not in itself bring about cell death, but that the primary lethal lesion may be on multiple cell membrane systems, perhaps brought about by some alteration of membrane lipids.
81 citations
TL;DR: The dietary influence may be explained by the low resting levels of the hepatic drug-metabolizing enzymes and by the failure of the enzyme levels to respond to repeated doses of AFB 1 in the livers of deficient rats.
72 citations
68 citations
TL;DR: Individual tolerance to single or widely spaced doses of methotrexate was explored in 49 patients with advanced cancer with normal serum creatinine and/or blood urea nitrogen, independent of previous chemotherapy or radiotherapy, weight loss, serum albumin or pretreatment serum folic acid levels.
Abstract: Individual tolerance to single or widely spaced doses of methotrexate was explored in 49 patients with advanced cancer with normal serum creatinine and/or blood urea nitrogen. Methotrexate was given as an intravenous infusion over 1 hour at initial doses of 80-120 mg./m(2) body surface area. The doses were increased by 50% increments every 2 weeks until moderate toxicity occurred, arbitrarily defined as leukopenia <5000/mm.(3), and/or thrombocytopenia <100,000/mm.(3), and/or the appearance of oral mucous or intestinal toxicity.The individual dose required to produce initial evidence of toxicity varied by a factor of 18 between 50 and 900 mg./m(2). Starting doses above 80 mg./m(2) were potentially hazardous. Dose limiting toxicity consisted of leukopenia with or without stomatitis in 81% of the patients, and stomatitis without leukopenia, in 19%. Thrombocytopenia was seen in 19% of the patients, but was never a dose limiting factor alone. Leukopenia always preceded thrombocytopenia. The nadir for haematologic toxicity varied considerably between day 5-15 and 9-14 for leukocytes and platelets, respectively, while oral ulcerations, when they occurred, consistently began between days 3-6 after drug administration. Other toxic manifestations included dermatologic changes in 8 patients, hepatic dysfunction in 7, conjunctivitis in 7, nausea and vomiting in 6, alopecia in 4, and diarrhea in 3 patients.The only factor which predicted toxicity was the patient's age. Drug tolerance was independent of previous chemotherapy or radiotherapy, weight loss, serum albumin or pretreatment serum folic acid levels.
65 citations
TL;DR: Systemic toxicity of bupivacaine is lower in man than might be predicted from acute toxicity studies in animals due to its shorter duration of action and lower plasma levels during prolonged analgesia.
Abstract: Bupivacaine hydrochloride has been administered to volunteers at a dose of 1.35 mg. per kilogram by intravenous infusion. No significant changes in blood pressure, electrocardiogram, or heart rate were observed. Subjective signs of toxicity were mild. Plasma levels were determined for 8 hours following injection and these indicated that, after an initial phaw of rapid changes in plasma levels due to distribution, bupivacaine has a half‐life of approximately 21,2 hours. The highest plasma level recorded was 22.5 Pg per milliliter in arterial blood. Less than 10 per cent of the dose administered was excreted unchanged in the urine and urinary excretion was complete within 24 hours. The maior route of clearance is through metabolism. Bupivacaine is more than 90 per cent bound to plasma proteins at concentrations of 1 Pg per milliliter. Hence systemic toxicity of bupivacaine is lower in man than might be predicted from acute toxicity studies in animals. The rate of clearance of bupivacaine is approximately the same as lignocaine and mepivacaine but it has a much longer duration of action. Consequently plasma levels of bupivacaine do not rise to the same extent as with lignocaine or mepivacaine during prolonged analgesia.
61 citations
TL;DR: In the present WCCCG study, 548 patients with disseminated cancer were treated weekly with 5‐FU, without a loading dose, by rapid intravenous injection, and increased to 20 mg/kg/week (if necessary) to levels producing mild toxicity or an antitumor effect.
Abstract: 5-Fluorouracil (5-FU) has usually been administered by rapid intravenous injection of 15 mg/kg daily for 3-5 days and 7.5 mg/kg every 2 or 3 days to toxicity, repeated monthly (antitumor response about 10-30%). Drug morbidity and mortality have been excessive. Modifications of this course have shown similar response rates but decreased toxicity and mortality. In the present WCCCG study, 548 patients with disseminated cancer were treated weekly with 5-FU, without a loading dose, by rapid intravenous injection, beginning at 15 mg/kg/week for one month, and increased to 20 mg/kg/week (if necessary) to levels producing mild toxicity or an antitumor effect. Of the 339 patients now evaluated for response, 6 had complete responses, 54 had decreases in tumor size > 50%, and 34 had decreases in tumor size of 25-50%. The response rates > 50% (I-B and I-C) for adenocarcinoma of the breast, stomach, and colon were 37.8%, 28.6%, and 16%, respectively. Of the 430 patients evaluated for toxicity, 62 manifested no toxicity, and 368 patients had mild-to-severe toxicity. There were 8 drug-related deaths in patients who received 5-FU in dosages higher than those allowed in the protocol. There were no drug deaths in patients who received 5-FU as stipulated by the protocol.
55 citations
TL;DR: 8-Hydroxyquinoline reduced the toxicity of N -2-fluorenylacetamide and led to a lower incidence of hepatic malignancies than when the carcinogen was fed alone in a time-limited test series.
49 citations
TL;DR: No progressive lesion of the liver followed by the hypertrophy of liver cells was noted in rats and mice fed on Furylfuramide and control diet for two years, and there was no difference in incidences between groups.
Abstract: As a model experiment on the study of toxicity of a compound, acute, short-term and long-term toxicity tests on Furylfuramide (2-(2-Furyl)-3-(5-nitro-2-8- furyl) acryl amide) were performed using Nitrofurazone (5-nitro-2-furaldehyde semicarbazone) and sorbic acid as control compounds As the most conspicuous changes, hypertrophy of liver cells with clear cytoplasm was noted within a week of feeding These cells were first located around the central vein and increased in number with time toward the peripheral portion of the lobule In spite of the long-term experiments up to two years in rats and mice, no progressive lesion of the liver followed by the hypertrophy No cumulative effect of Furylfuramide was noted in any organ The hypertrophy of liver cells was reversible, when animals were switched to basal diet and kept on it for a certain length of time A concentration of 0125% in the diet was considered to be the tolerable safe dose of Furylfuramide High incidence of spontaneous tumors developed in mice fed on Furylfuramide and control diet for two years was described There was no difference in incidences between groups
TL;DR: The results indicate CaEDTA is not primarily nephrotoxic in the dog and, therefore, renal failure probably is not the cause of death and the infusion of a very stable chelate, CrEDTA, was nontoxic.
TL;DR: Skin and eye irritation studies with products containing Na 3 NTA showed the products to be similar to current market products and no evidence was seen to indicate that sensitization occurred after multiple exposures of humans in a repeated insult patch test.
TL;DR: Sodium diethyldithiocarbamate (DDC) significantly increased toxicity of CuCl 2 in mice and increased retention of copper in the organism and elevated the copper content of various organs.
TL;DR: Results from toxicity studies in mice indicate that toxicity is not altered significantly after treatment with 3-methylcholanthrene, and chlordane treatment affords protection against the toxicity of parathion, suggesting that factors other than metabolism contribute to toxicity.
TL;DR: Total dosage and duration of treatment appear to be more important factors than peak levels of drug in the serum with reference to time of appearance of ataxia at the dosage levels studied.
Abstract: For determination of the importance of several factors affecting the vestibular toxicity of gentamicin in cats, several therapeutic regimens, routes of administration, and levels of dosage were examined. Cats were given high levels of gentamicin daily and observed for appearance of ataxia and impairment of the righting reflex. The time of appearance of ataxia was related to dosage. Death, attributed to renal toxicity, closely follows the appearance of ataxia after a dose of 60 mg/kg per day. At lower doses, there is a temporal separation between vestibular and renal toxicity. The renal damage is reversible, but the vestibular damage is not. Total dosage and duration of treatment appear to be more important factors than peak levels of drug in the serum with reference to time of appearance of ataxia at the dosage levels studied.
01 Jan 1971
TL;DR: An attempt will be made to review the toxic effects of ethanol in functional terms and wherever possible to relate these changes to biochemical events and structural alterations of cells.
Abstract: An attempt will be made to review the toxic effects of ethanol in functional terms and wherever possible to relate these changes to biochemical events and structural alterations of cells. Factors which contribute to ethanol toxicity, such as nutritional abnormalities, changes in hormones, catecholamines, serotonin, acetylcholine, and the like, changes in electrolyte balance and heavy metal content, will be discussed only as they relate directly to ethanol toxicity. Much of what is known about these contributing factors will be left to other chapters where they are dealt with specifically.
Journal Article•
TL;DR: The toxicities and immunosuppressive potencies of single doses of 6-mercaptopurine and azathioprine have been compared in mice, using the 30-day mortality as a measure of toxicity, and reduction in spleen plaque-forming cells in response to sheep erythrocytes as a measures of immunosppression.
Abstract: The toxicities and immunosuppressive potencies of single doses of 6-mercaptopurine and azathioprine have been compared in mice, using the 30-day mortality as a measure of toxicity, and reduction in spleen plaque-forming cells in response to sheep erythrocytes as a measure of immunosuppression. When compared on the basis of equivalent toxicity, 6-mercaptopurine was consistently the more effective agent by the intraperitoneal route. By the subcutaneous route, 6-mercaptopurine was more effective at doses above the LD-30; at lower doses, azathioprine was marginally better, but the difference was probably not significant. For the same cost in toxicity, azathioprine was six to seven times more effective as an immunosuppressive by the subcutaneous as by the intraperitoneal route.
01 Jan 1971
TL;DR: In young female rats histological alteration caused by exposure to DMF was influenced by the age of the rats, one day's exposure time, total exposed days, and the capacity of liver cells to regenerate.
Abstract: The inhalation toxicity of dimethylformamide (DMF) to female SD rats was histopathologically studied. Although the solvent obviously injured the liver, no abnormality was found morphologically in other organs. Hepatotoxicity was, on the whole, more remarkably observed in young rats than in adult ones. In young female rats histological alteration caused by exposure to DMF was influenced by the age of the rats, one day's exposure time, total exposed days, and the capacity of liver cells to regenerate. DMF was found to be less toxic than carbon tetrachloride in these rats.
Journal Article•
TL;DR: Toxicity was, however, markedly reduced when sodium nitrite was administered prior to dimethylamine, and the incidence of mortality and liver necrosis was dependent on the time interval separating successive administrations of Sodium nitrite and dimethyamine.
Abstract: Summary Combined p.o. administration of sodium nitrite and dimethylamine or methylbenzylamine to male mice produced acute synergistic toxicity, as evidenced by relative weight loss, mortality, and liver necrosis. Similar results were obtained when p.o. dosage of dimethylamine was followed by single administration of sodium nitrite at intervals up to 3 hr; toxicity was, however, markedly reduced when sodium nitrite was administered prior to dimethylamine. The incidence of mortality and liver necrosis was dependent on the time interval separating successive administrations of sodium nitrite and dimethylamine.
01 Jan 1971
TL;DR: The work was done to obtain information about the potential of the complexes for inducing dangerous toxicity in patients who might receive the agent in clinical trials against cancer.
Abstract: This report deals mainly with the pathological effects of polyinosinic-polycytidylic acid, poly (rI · rC), given in lethal or near lethal doses. The work was done to obtain information about the potential of the complexes for inducing dangerous toxicity in patients who might receive the agent in clinical trials against cancer. The experimental species studied included mice, rats, rabbits, and dogs.
TL;DR: The toxicity of a homologous series of twelve N,N-dimethylamides (Hallcomids) was assessed by the intravenous, intraperitoneal, intragastric, and percutaneous routes in mice and rabbits and it was concluded that the Hallcomids are slightly to moderately toxic.
Abstract: The toxicity of a homologous series of twelve N,N-dimethylamides (Hallcomids) was assessed by the intravenous, intraperitoneal, intragastric, and percutaneous routes in mice and rabbits. The ability of this unique and versatile class of dimethylamides to enhance skin penetration was studied by mixing the compounds with an organophosphorus compound (VX). The toxicity of the Hallcomids was compared with the toxicity of other common dimethyl compounds (dimethylsulfolane, dimethylacetamide, dimethylformamide, dimethylsulfoxide). It was concluded that the Hallcomids are slightly to moderately toxic, and precautions to prevent skin contact should be taken for safe use and handling.
TL;DR: It is suggested that renal function should be checked before prescribing tetracyclines, particularly in elderly patients, and that the blood urea level should be estimated if systemic deterioration occurs.
Abstract: The exacerbation of uræmia by tetracycline on 11 occasions in nine patients with chronic renal failure is described. It is suggested that renal function should be checked before prescribing tetracyclines, particularly in elderly patients, and that the blood urea level should be estimated if systemic deterioration occurs. The tetracyclines, except perhaps doxycycline, should be avoided in those with renal insufficiency.
TL;DR: It was concluded that useful systemic therapeutic application of poly I:C will require that the effective doses be quite small, but that, since daily doses of 2.0 mg/kg in the rat and 0.2 mg/ kg in the dog were well tolerated in subchronic experiments, cautious exploration of low systemic doses in man may be justified.
TL;DR: It is concluded that the syndrome of acute aflatoxin B 1 poisoning in primates is essentially like that in other species.
TL;DR: Of pertinence to this paper was the reference to studies indicating that vanadium toxicity was counteracted by subcutaneous injections, and little or no reference was made to studies involving birds.
TL;DR: Two salts of d -propoxyphene, the hydrochloride and the 2-naphthalene sulfonate (napsylate), were compared in short-term toxicity studies in rats and dogs and the effects produced by daily administration of equimolar doses of these salts were indistinguishable.
TL;DR: Definite histopathologic change in each of the patients who responded to therapy was the only consistent relationship noted, although the appearance of such changes did not necessarily indicate that tumor response could be expected.
Abstract: Pre- and post-therapy small bowel biopsies were obtained in 19 of 20 patients who received 5-fluorouracil for treatment of their malignant disease. Three parameters were evaluated: clinical response to therapy, which occurred in five cases (26%); development of gastrointestinal toxicity, which occurred in 13 (68%); and histopathologic change of small bowel mucosa, which was noted in 13 (68%). There was no correlation between clinical response to therapy and the development of toxicity, nor was there any between toxicity and histopathologic change in small bowel mucosa. Definite histopathologic change in each of the patients who responded to therapy was the only consistent relationship noted, although the appearance of such changes did not necessarily indicate that tumor response could be expected.