Hepatic intoxication

Intoxication by aflatoxkis is referred to as aflatoxicosis. Edema and necrosis of hepatic and renal tissues seem characteristic of aflatoxicosis, and hemorrhagic enteritis accompanied by nervous symptoms often appear ki experimental animals. The mode of action of aflatoxkis kivolve an kiteraction with DNA and inhibition of the polymerases responsible for DNA and RNA synthesis (96). 

Acute intoxication with DHBs occurs mainly by the oral route symptoms are close to those induced by phenol poisoning including nausea, vomiting, diarrhea, tachypnea, pulmonary edema, and CNS excitation with possibiUty of seizures followed by CNS depression. Convulsions are more frequent with catechol as well as hypotension due to peripheral vasoconstriction. Hypotension and hepatitis seem more frequent with hydroquinone and resorcinol. Methemoglobinemia and hepatic injury may be noted within a few days after intoxication by DHBs. 

In the ED setting, the diagnosis of ketamine intoxication is a clinical one. Ketamine is not routinely detected by urine toxicology tests, although it can be detected with high-performance liquid chromatography (Koesters et al. 2002). As with MDMA, the initial assessment for ketamine intoxication includes the use of routine laboratory tests to detect electrolyte abnormalities and to evaluate renal and hepatic functioning (Koesters et al. 2002). 

No studies were located regarding gastrointestinal, hematological, musculoskeletal, or dermal effects in humans or animals after inhalation exposure to methyl parathion. Dean et al. (1984) reported that seven children exposed to methyl parathion by many routes exhibited pinpoint pupils, abdominal pain, and diarrhea. The respiratory, cardiovascular, hepatic, and renal effects reported by Fazekas (1971) that were found in humans acutely exposed to methyl parathion intoxication resulted from exposure by all three routes however, the results did not distinguish between the routes. 

Hepatic Effects. Liver lesions have been reported in humans acutely intoxicated by methyl parathion formulation (Wolfatox) (Fazekas 1971 Fazekas and Rengei 1964). These studies are discussed in detail in Section 3.2.2.1. Liver lesions were hepatocellular swelling, degeneration, and fatty change. 

Intoxicated patients surviving for 28 hours to 9 days had hepatocytes free in central or hepatic veins this finding was described as mobilization of liver cells. The role of methyl parathion in the induction of all of these lesions is unclear. 

The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from circulation by the liver and converted to urea. Only traces (10—20 Ig/dL) thus normally are present in peripheral blood. This is essential, since ammonia is toxic to the central nervous system. Should portal blood bypass the liver, systemic blood ammonia levels may rise to toxic levels. This occurs in severely impaired hepatic function or the development of collateral links between the portal and systemic veins in cirrhosis. Symptoms of ammonia intoxication include tremor, slurred speech, blurred vision, coma, and ultimately death. Ammonia may be toxic to the brain in part because it reacts with a-ketoglutarate to form glutamate. The resulting depleted levels of a-ketoglutarate then impair function of the tricarboxylic acid (TCA) cycle in neurons. 

Methods of detection, metabolism, and pathophysiology of the brevetoxins, PbTx-2 and PbTx-3, are summarized. Infrared spectroscopy and innovative chromatographic techniques were examined as methods for detection and structural analysis. Toxicokinetic and metabolic studies for in vivo and in vitro systems demonstrated hepatic metabolism and biliary excretion. An in vivo model of brevetoxin intoxication was developed in conscious tethered rats. Intravenous administration of toxin resulted in a precipitous decrease in body temperature and respiratory rate, as well as signs suggesting central nervous system involvement. A polyclonal antiserum against the brevetoxin polyether backbone was prepared a radioimmunoassay was developed with a sub-nanogram detection limit. This antiserum, when administered prophylactically, protected rats against the toxic effects of brevetoxin. 

Priest RJ, Horn RC. 1965. Trichloroethylene intoxication A case of acute hepatic necrosis possibly due to this agent. Arch Environ Health 11 361-365. 

Hepatic metabolism of ethanol involves a nonlinear saturable pathway. Young children have a limited ability to metabolize and thereby detoxify ethanol. Ethanol intoxication has been recorded in children with blood levels as low as 25 mg/dL. Alcohol has a volume of distribution of approximately 0.65 L/kg. Ingestion of 20 mL of a 10% alcohol solution will produce a blood level of 25 mg/dL in a 30 pound child. The American Academy of Pediatrics (AAP) Committee on Drugs recommends that pharmaceutical formulations intended for use in children should not produce ethanol blood levels of >25 mg/dL after a single dose. 

No data were found on the effects of silver compounds on avian or mammalian wildlife. All controlled studies with silver were with domestic poultry, livestock, or small laboratory mammals. Signs of chronic silver ion intoxication in tested birds and mammals included cardiac enlargement, vascular hypertension, hepatic necrosis, anemia, lowered immunological activity, altered membrane permeability, kidney pathology, enzyme inhibition, growth retardation, and a shortened life span (Smith and Carson 1977 Freeman 1979 Fowler and Nordberg 1986 USPHS 1990). 

Cyanide poisoning is associated with changes in various physiological and biochemical parameters. The earliest effect of cyanide intoxication in mice seems to be inhibition of hepatic rhodanese... 

Many commercial lots of technical PCP are known to contain small — but possibly biologically significant — amounts of highly toxic dioxins, dibenzofurans, and hexachlorobenzene. These contaminants may be responsible for most of the toxicity of technical PCP preparations (McConnell et al. 1980 Parker et al. 1980 Wollesen et al. 1986 Holsapple et al. 1987). However, both technical-and analytical-grade PCP can induce hepatic mixed-function oxidases in intoxicated rats and cattle. In cattle, this effect was observed in both calves and adults, and in hepatic as well as pulmonary microsomes, and seemed to be dose related (Shull et al. 1986). 

The toxic effects of the fungicide and environmental pollutant hexachlorobenzene (HCB) were first noted in the 1950s when people were exposed to high doses of HCB through intake of contaminated grain. Intoxicated individuals developed a variety of symptoms including hepatic porphyria, skin lesions, and arthritis. Symptoms were accompanied by infiltrates of inflammatory cells [11, 33],... 

If reduced plasma clearance of BSP were related to anesthetic induced alterations in hepatic blood flow it should be evident early in the course of the intoxication when these types of effects would be most pronounced. We have reported that significant plasma retention of BSP in rainbow trout occurred only within the first 24 h after treatment with MCB... 

After smoking the first puff, the acute intoxication starts within 6 to 12 minutes, and maximum effects occur at 15 to 30 minutes. Effects typicaiiy iast 2 to 4 hours. TFiC remains in fatty tissues and has a iong haif-iife of 57 hours. The iungs and iiver convert TFiC to the metaboiite 11-OFi-TFiC, which is aiso active. There is a recircuiation of 10-15% of hepatic metaboiites. 11-OFi-TFiC is further converted by the iiver to inactive metaboiites, which are eiiminated by the kidneys. 

Aspirin in doses used to treal rheumatoid arthritis can result in uncoupling of oxidative phosphorylation, increased oxygen consumption, depletion of hepatic glycogen, and the pyref c effect of toxic doses of salicylate. Depending on the degree of salicylate intoxication, the symptoms can vary from tinnitus to pronounced CNS and acid-base disturbance. 

Most cases of intoxication from industrial exposure have been mild, with rapid onset of eye irritation, headache, sneezing, and nausea weakness, light-headedness, and vomiting may also occur. Acute exposure to high concentrations may produce profound weakness, asphyxia, and death. Acrylonitrile is metabolized to cyanide by hepatic microsomal reactions. Deaths from acute poisoning result from inhibition of mitochondrial cytochrome oxidase activity by metabolically liberated cyanide. Inhalation of more moderate concentrations for a longer period of time leads to damage to the liver tissues in addition to central nervous system (CNS) effects. ... 

In animal studies, the oral LDso typically ranges between 800 and 1200mg/kg. Acute signs of intoxication include sedation, flaccid muscle tone, ataxia, and prostration death is due to CNS depression. In cases in which death does not occur until several days after acute exposure, hepatic and renal injury may be the cause of death. 

Reversibility of Noncarcinogenic Systemic Effects. Most case reports of humans intoxicated with carbon tetrachloride indicate that, if death can be averted, clinical signs of renal and hepatic dysfunction diminish within 1-2 weeks, and recovery often appears to be complete. This is primarily because both liver and kidney have excellent regenerative capacity and can repair injured cells or replace dead cells (Dragiani et al. 1986 Norwood et al. 1950). However, high doses or repeated exposure can lead to fibrosis or cirrhosis that may not be reversible. The depressant effects of carbon tetrachloride on the central nervous system do appear to be reversible, although any neural cell death that occurs (Cohen 1957) is presumably permanent. 

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