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Results for “Toxicity model”

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At least 19 recordsLinked to original sources
PubMed1979

Nutritional influences on metal toxicity: cadmium as a model toxic element.

The nutrient quality of the diet has been shown repeatedly to be a significant factor in modifying the response of man and animals to toxic element exposure. Deficiencies of several essential nutrients have been shown to exacerbate the effects of cadmium and supplements of such nutrients have been shown to ameliorate the toxicity. Thus the effects of exposure to a toxic element, such as cadmium, may vary, depending on interactions with other elements which are present in the diet in different concentrations.

Adolescent↗
PubMedDate not supplied

A toxicity estimation model.

A statistical model has been developed for estimation of acute toxicity. The model, currently operational for rat oral LD50, permits the estimation of rat oral LD50 for untested chemical compounds. Only the chemical structure, partition coefficient, and molecular weight for a compound are needed for estimation purposes. The chemical structure is partitioned into substructural fragments using the CIDS fragment keys. A regression model is developed on the basis of 425 compounds. A test of the regression equation with 100 compounds not used in its design shows that 56 percent of the compounds are predicted with less than 0.4 log unit deviation between extimated and measured LD50. This toxicity estimation model can be readily adapted to other species and to other measures of toxicity by the use of suitable design data bases. The model also identifies the contribution to toxicity of the fragments and physical characteristics. The use of this model can materially reduce the amount of toxicological testing for new compounds. It also permits the ranking of potentially toxic compounds to allow the most likely candidates to be tested. The method may also prove applicable to the determination of optimum dosages for new drugs.

Animals↗
PubMed1976

Triethyltin toxicity as a model for degenerative disorders.

Triethyltin (TET) toxicity in mice was examined as a model for certain degenerative disorders. Spontaneous and elicited behavioral tests, electrophysiological measures and nervous system protein characterizations were used to study anomalies resulting from TET treatments. TET animals exhibited lowered spontaneous locomotor activity levels, increased sciatic nerve excitation threshold and conduction velocities, and increased power levels in the slower frequency components of their electroencephalograms. Performance in an active avoidance task suggest that the gross ultrastructural changes commonly seen in TET intoxication are not primarily responsible for the observed neurophysiological changes. Possible sites of action of TET, in both the peripheral and central nervous systems, that would produce these neurophysiological changes and the relationship of these changes to the behavioral symptoms are discussed.

Animals↗
PubMedDate not supplied

[Highly-sensitive method of studying the toxicity of lipid peroxides].

A highly sensitive and simple method is developed for study of lipid peroxides toxicity with the use of quail developing embryos as a model. Toxicity of linolenic acid hydroperoxides, obtained by the lipoxygenase catalysis, was distinctly higher than the toxicity of the peroxides, produced alter autooxidation (LD50 = 0.12 and 0.38 mc-eq/embryo, respectively). Occurrence of toxic properties was observed in lipids, isolated from tissues of mice subjected to the oxygen stress. The advantages of the method described are discussed as compared with the published data.

Animals↗
PubMed1978

Pathophysiology of the atherosclerotic rabbit.

The pathophysiology and histopathology caused by feeding rabbits a diet containing 2% cholesterol is described. Cholesterol deposition was seen in almost all organs after 15 weeks on the diet. Lesions were seen as early as 7 weeks in the aorta and pulmonary vessels and by 11 weeks in the small intramyocardial arteries and arterioles. Evidence of myocardial ischemia could be elicited by stressing the heart by electrical pacing at rapid rates or by administration of pharmacological agents which increased oxygen consumption (isoproterenol) or decreased oxygen supply (ergonovine). Susceptibility to such stress was increased by isovolumic hemodilution which decreased the oxygen-carrying capacity of the blood. Myocardial fibrosis and infarction were evident by 15 weeks on the diet and cardiac reserve was depleted by 25 weeks as evidenced by the presence of ascites in all animals examined. The preliminary results reported here suggest that further evaluation of the atherosclerotic rabbit as a cardiac toxicity model is warranted.

Animals↗
PubMed1977

Liquid membrane capsules for treatment of uremia.

The objective of the program is to use ingested liquid membrane capsules (LMC) as gastrointestinal toxin traps as an adjunct to dialysis. Urea has been selected as the model toxic component to study before expanding the technology to other toxins. Transport across the small intestinal mucosa has been indicated to be adequate. There is no indication of reduction of mucosal transport or damage to the intestinal mucosa over short term but repetitive LMC perfusions. Performance of LMC perfused through Thiry Vella small intestinal loops is as good as in vitro performance and can be predicted. Substantial progress has been made toward developing LMC to perform in the more complex environment of the intact gastrointestinal tract. The demonstration of LMC performance in vivo with intact gastrointestinal tracts, and perhaps some increase in rate of toxin removal, will be required before LMC can be considered practical candidates for clinical use.

Administration, Oral↗
PubMed2026

ToxiVerse: chemical bioprofiling, toxicity data sharing and customizable predictive modeling.

MOTIVATION: Chemical toxicity assessment is critical for drug development and environmental safety. Computational models have emerged as a promising alternative to animal testing and now play a significant role in efficiently evaluating new chemicals. To address the urgent need for user-friendly machine learning tools in computational toxicology, we developed ToxiVerse, a public web-based platform. RESULTS: ToxiVerse provides automatic chemical bioprofiling, curated toxicity datasets, and a predictive modeling interface designed for researchers who lack programming expertise. The platform comprises three integrated modules: (i) Bioprofiler, which provides chemical descriptors by combining chemical-bioactivity data from PubChem assays with a machine learning-based data gap-filling procedure; (ii) Database, which hosts ∼50 000 curated chemicals covering diverse toxicity endpoints; and (iii) Cheminformatics, which enables dataset upload, chemical curation, and automatic generation of quantitative structure-activity relationship models for toxicity prediction. AVAILABILITY: The tool is accessible at www.toxiverse.com, and source code is available at https://github.com/zhu-research-group/toxiverse.

Quantitative Structure-Activity Relationship↗
PubMed1979

Clonazepam in a focal-motor monkey model: efficacy, tolerance, toxicity, withdrawal, and management.

Since the clinical data have been equivocal in regard to the effects of clonazepam (CZP) in focal-motor seizures, an alumina gel monkey model was used to evaluate quantitatively its efficacy with respect to this seizure category. The insolubility of CZP and its short biological half-life in monkey necessitated its evaluation in the model via constant-rate intravenous administration in a solution of polyethylene glycol 400 (PEG). Two groups of monkeys were given CZP in PEG (N = 6) or a PEG solution alone as a control compound (N = 5) for 6 weeks; these treatments were bordered at both ends by 3 weeks of treatment with saline only in order to establish a baseline. CZP was administered at a concentration sufficient to achieve a plasma level of 30 ng/ml in drug step I (3 weeks) and at least double that level in drug step II (3 weeks). As a solute for CZP, and when given by itself, PEG was always administered at a concentration of 35%. The results indicate that CZP is effective for focal-motor seizures and secondarily generalized tonic-clonic seizures, particularly when its concentration in plasma is higher than 60 ng/ml. Withdrawal seizures were evident on cessation of CZP administration. CZP appears to be a useful broad-spectrum anticonvulsant when managed carefully. An unexpected finding was the irreversibility of the pharmacological effect of PEG. Cessation of PEG administration significantly reduced seizure frequency in subsequent weeks to a level below the initial baseline level.

Aluminum Hydroxide↗
PubMed1977

Methyl alcohol poisoning. II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus monkey.

Rhesus monkeys were intoxicated with methyl alcohol, using an initial dose of 2 gm/kg and subsequent doses were administered in order to maintain an attenuated and prolonged state of intoxication. Arterial blood samples were drawn for methyl alcohol, formate, PO2, PCO2, and pH, which were monitored periodically throughout the course of the experiment. With the use of these procedures monkeys developed metabolic acidosis with the accumulation of formic acid in the blood and a corresponding decrease in blood bicarbonate. These animals served as models, which allowed for ocular evaluation for early signs related to methyl alcohol poisoning. A mechanism to explain toxicity is proposed and discussed.

Acidosis↗
PubMed1978

Nutritional considerations in designing animal models of metal toxicity in man.

In recent years, exposure of man to increasing amounts of metals has occurred rather generally from industrial contamination and variably from intake of dietary mineral supplements. Adverse effects of individual metals can be markedly altered by dietary levels of other essential and nonessential inorganic elements, essential organic nutrients and other nonessential dietary components. Experimental diets for establishing baseline responses to excess elements should be formulated to meet the animal's requirements only. These reference diets can then be modified to mimic man's average dietary intake as well as meal patterns. Improved animal models should provide better data for assessing hazards of excess metal intake by man.

Aging↗
PubMed1975

[A novel model of experimental toxic hepatitis/acute degenerative hepatitis induced by frog virus 3 (FV3) in the mouse (author's transl)].

The i.p. or i.v. injection of frog virus 3 (FV3) in mice produces a hepatitis which leads to the death of the animals within 24 h. This hepatitis is of a purely toxic nature since the virus does not develop at 37 degrees C. The toxic effect of the virus, which can be differentiated from the infectious effect, involves one or more structural proteins. The first pathological changes occur during the first few hours after the injection in the vicinity of the nuclei of the liver parenchyma cells in the form of changes in the chromatin and nucleoplasm. The inhibition of the synthesis of cellular macromolecules and of the function of nuclear enzymes points to the fact that it is the nucleus that is first and foremost attacked. Necrosis and biochemical disturbances in the vicinity of the cytoplasm appear later on. Premedication of the mice with a water-soluble silymarin salt leads to a distinct rise in the survival rate of the animals. The protective function of silymarin is dependent on the dose and on the duration of the premedication. The LD50 of FV3 in those mice which had previously been given silymarin, is approximately three times that of the animals which received no premedication.

Animals↗
PubMed1979

Lantadene A toxicity in sheep. A model for cholestasis.

Liver injury occurred after sheep were injected intravenously with the triperpene acid lantadene A, the toxic principle of the tropical plant Lantana camara. A single dose of 1--3 mg/kg of the compound caused mild hepatocellular injury characterized by transient rises in serum enzymes, with or without hyperbilirubinaemia. Higher doses resulted in hepatic necrosis. When low doses of the triterpene were given repeatedly over several days a cholestatic syndrome developed which appeared identical with that caused by consumption of the plant. This is a disease model which may be of value in experimental studies of intrahepatic cholestasis. This study provides evidence that lantadene A is hepatotoxic and does not require metabolism in the alimentray tract for toxicity in sheep.

Animals↗
PubMed1979

Current problems in the choice of animals for toxicity testing.

Animal models for the study of toxicity are chosen more for pragmatic reasons such as life-span, ease of handling, and economics than because of a comprehensive process of validation. There is also a tendency to seek the answers to nonspecific questions and then to use those answers in situations where they cannot lead to proper judgments. In some cases, such as in carcinogenicity testing, an uneasy compromise exists between the sensitivity of the model and the background noise. There is scope, by increased attention to both the control of environmental factors and the genetics of the animal models, to increase the sensitivity and validity of the systems that are used in toxicology.

Animals↗