Administration of toxicants

As a rule, the highest concentrations of a poison are found at the site of administration. A large quantity of drug in the GI tract and liver indicates oral ingestion. The gastrointestinal (GI) tract may contain large amounts of unabsorbed toxicant. Cases that involve the oral administration of toxicants indicate analysis of GI contents. However, the presence of toxic material in the GI tract does not provide sufficient evidence that the agent is the cause of death. Absorption and transport of the toxicant to the site of action must be demonstrated. Blood and tissue analysis is necessary and would still be paramount. 

Ostadalova I, Babicky A, Kopoldova J. 1988. Selenium metabolism in rats after administration of toxic doses of selenite. Physiol Bohemoslov 37(2) 159-164. 

For biomarkers such as the troponins and enzymes, timing and sample collection are particularly critical for the detection of cardiac injury, and consideration must be given to the half-life of the molecule and its mass. Although some data are available for humans, data are sparse for the same measurements in laboratory animals. In general, the half-lives of these molecules are less in smaller animals. The importance of sample times has been shown in several studies where myocardial lesions have been induced by the administration of toxic doses of sympathomimetics (O Brien et al. 1997a, 2006 York et al. 2007). 

No macroscopic changes were observed in mice dying after intraperitoneal injection of lethal doses of yessotoxin [67], In contrast, the livers of mice receiving di-desnlfoyessotoxin became swollen and yellow in color within hours of administration of toxic doses [69], Consistent with the color change, an increase in hepatic fat levels was recorded in animals dosed with di-desulfoyessotoxin... 

Table 5.13 Examples of QSAR models for estimating acute mammalian toxicity after oral administration of toxicants log LD5Q correlations with various parameters... 

Banner et al. (1961) tested 37 species of animals and found only five were sensitive to oral administration of toxic fish flesh. The mouse, although sensitive. 

The effects of ischemia on taurine levels were measured in three types of animal models ligation of the circumflex artery in the dog perfusion of rat hearts with oxygen-deficient buffer and administration of toxic doses of DL-isoproterenol and methoxamine. 

Rosin has a low order of toxicity foUowing ingestion or skin contact. Rosin and its numerous derivatives have a number of permitted food packaging and other direct and indirect food contact uses throughout the world. Sanctioned uses appHcable in the United States are outlined in U.S. Food and Dmg Administration (U.S. FDA) Regulations (2). Material Safety Data Sheets (MSDSs) for specific rosins and thein derivatives should be consulted before thein use. 

Tetracyclines are used as alternative dnigs in a variety of circumstances when the patient is unable to take the dnig of choice, eg, in patients allergic to penicillin (88,89). Tetracyclines are widely known to cause staining of teeth (and are therefore contra-indicated in children developing permanent teeth), photosensitivity, and, in the case of minocycline, vestibular toxicity. Details of these adverse effects and others associated with administration of tetracyclines have been comprehensively reviewed (96—101). 

Administration of 5 ppm barium, the acetate, to mice in the drinking water in a life-time study had no observable effects on longevity, mortality, and body weights, or on the incidence of tumors (53). Long-term studies in rats exposed to Ba " in drinking water containing 5 mg/L, as acetate, or 10—250 mg/L, as chloride, resulted in no measurable toxic effects (47). 

As regards toxicity, pyrazole itself induced hyperplasia of the thyroid, hepatomegaly, atrophy of the testis, anemia and bone marrow depression in rats and mice (72E1198). The 4-methyl derivative is well tolerated and may be more useful than pyrazole for pharmacological and metabolic studies of inhibition of ethanol metabolism. It has been shown (79MI40404) that administration of pyrazole or ethanol to rats had only moderate effects on the liver, but combined treatment resulted in severe hepatotoxic effects with liver necrosis. The fact that pyrazole strongly intensified the toxic effects of ethanol is due to inhibition of the enzymes involved in alcohol oxidation (Section 4.04.4.1.1). 

The importance of the penicillins as a class of heterocyclic compounds derives primarily from their effectiveness in the treatment of bacterial infections in mammals (especially humans). It has been estimated that, in 1980, the worldwide production of antibiotics was 25 000 tons and, of this, approximately 17 000 tons were penicillins (81MI51103). The Food and Drug Administration has estimated that, in 1979 in the U.S.A., 30.1 x 10 prescriptions of penicillin V and 44.3 x 10 prescriptions of ampicillin/amoxicillin were dispensed. This level of usage indicates that, compared to other methods of dealing with bacterial infection, the cost-benefit properties of penicillin therapy are particularly favorable. Stated differently, penicillin treatment leads to the elimination of the pathogen in a relatively high percentage of cases of bacterial infection at a relatively low cost to the patient in terms of toxic reactions and financial resources. 

Polymeric ethyl cyanoacrylate exhibits very low toxicity properties. In tests with laboratory rats, oral administration of 6400 mg/kg of the polymer failed to harm the test animals. Some skin irritation did occur in tests on guinea pigs, but skin sensitization or absorption through the skin was not observed [45]. 

In experimental work, some accidental exposures, or in the administration of medicine, the dose may be a certain quantity of the chemical administered at one time, such as in a pill, an injection, or an accidentally swallowed poison. In industry, time is a factor in most exposures, and the dose is the result of both the concentration of the toxic agent and the duration of the exposure. 

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