Intoxications

Thiophosphate insecticides are protoxins, as they are unable to phosphorylate the serine until after the first liver passage, during which the thiono group is replaced by an 0x0 group. Therefore, they are called indirect acetylcholinesterase inhibitors. 

OPi are very lipophilic and are readily absorbed both enterally and percutaneously. The adsorption rate is increased by simultaneous intake/appUcation of organic solvents or plant oils. 

The onset of intoxication symptoms is dependent on the pathway of absorption within a few minutes of inhalation, from 15 min to 1 h after swallowing, and 2-3 h after cutaneous resorption, a toxic concentration will be reached in the blood. With indirect acetylcholinesterase inhibitors, e.g. parathion, symptoms of poisoning occur later. No exact data exist about the extent of bioavaUability in the human body. 

Inhalation of cadmium oxide fumes, cadmium oxide dust, and cadmium pigment dust for prolonged periods of time can produce emphysematous changes in the lungs The exposure time has generally been several years. In animals exposed to cadmium dust the lungs showed interstitial pneumonia, sclerosis, and emphysema.  

Disturbed renal function, with proteinuria, glucosuria, and aminoaciduria, has been observed in woricers exposed to cadmium. The proteinuria in chronic cadmium poisoning is of the tubular type and is caused by decreased reabsorption of proteins. As mentioned previously, when the kidneys have been damaged by cadmium, the excretion of the metal increases and the kidney concentration of cadmium will diminish considerably.  

A relation between cadmium exposure and hypertension has been suggested but the data are still inconclusive.  

Other effects reported in humans after chronic exposure to cadmium are anemia, liver disturbances, and yellowing of the dental enamel. Teratogenic effects have been observed in longterm studies on mice, rats, and hamsters.  

Subcutaneous injections of cadmium salts in rats induce sarcoma at the site of injection and may also give rise to interstitial tumors in the testis. In human beings, cadmium has been suggested as an etiologic factor in the development of prostatic carcinoma and cancer of the respiratory tract.  

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Another danger, intoxication by inhalation, is related to the benzene content. A maximum limit is often set for this compound. 

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). 

A.lcohol and the Impaired Driver. Fi Manual on the Medicolegal Mspects of Chemical Testsfor Intoxication. American Medical Association, Chicago, lU., 1970. 

Aromatic Hydrocarbons. These are the most toxic of the hydrocarbons and inhalation of the vapor can cause acute intoxication. Benzene is particularly toxic and long-term exposure can cause anemia and leukopenia, even with concentrations too low for detection by odor or simple instmments. The currendy acceptable average vapor concentration for benzene is no more than 1 ppm. PolycycHc aromatics are not sufftcientiy volatile to present a threat by inhalation (except from pyrolysis of tobacco), but it is known that certain industrial products, such as coal tar, are rich in polycycHc aromatics and continued exposure of human skin to these products results in cancer. 

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. 

OtherMa.gnesium Disorders. Neuromuscular irritabHity, convulsions, muscle tremors, mental changes such as confusion, disorientation, and haHucinations, heart disease, and kidney stones have aH been attributed to magnesium deficiency. Excess Mg " can lead to intoxication exemplified by drowsiness, stupor, and eventuaHy coma. 

Glassification of Substance-Related Disorders. The DSM-IV classification system (1) divides substance-related disorders into two categories (/) substance use disorders, ie, abuse and dependence and (2) substance-induced disorders, intoxication, withdrawal, delirium, persisting dementia, persisting amnestic disorder, psychotic disorder, mood disorder, anxiety disorder, sexual dysfunction, and sleep disorder. The different classes of substances addressed herein are alcohol, amphetamines, caffeine, caimabis, cocaine, hallucinogens, inhalants, nicotine, opioids, phencyclidine, sedatives, hypnotics or anxiolytics, polysubstance, and others. On the basis of their significant socioeconomic impact, alcohol, nicotine, cocaine, and opioids have been selected for discussion herein. 

Tb allium, which does not occur naturaHy in normal tissue, is not essential to mammals but does accumulate in the human body. Levels as low as 0.5 mg/100 g of tissue suggest thallium intoxication. Based on industrial experience, 0.10 mg /m of thallium in air is considered safe for a 40-h work week (37). The lethal dose for humans is not definitely known, but 1 g of absorbed thallium is considered sufficient to kHl an adult and 10 mg/kg body weight has been fatal to children. In severe cases of poisoning, death does not occur earlier than 8—10 d but most frequently in 10—12 d. Tb allium excretion is slow and prolonged. For example, tb allium is present in the feces 35 d after exposure and persists in the urine for up to three months. 

The usual symptoms in human thaHotoxicosis resulting from acute, subacute, or chronic intoxication are generaHy the same. Common symptoms include nausea, vomiting, abdominal coHc, pain in legs, nervousness and irtitabHity, chest pain, gingivitis or stomatitis, and anorexia. Alopecia (hair loss) does not always occur, especiaHy in cases of mass intake of thallium and low resistance where the patient may die before the occurrence of hair loss. 

Tb allium intoxication during the first trimester of pregnancy can cause skeletal deformities, alopecia, rash, low birth weight, and premature birth (38). 

Poly(vinyl alcohol) has a low oral toxicity rating. The oral LD q is higher than 10,000 mg/kg (rats). Concentrations of up to 10,000 mg/L in water were tested for toxicity to bluegik sunfish. No mortaUty or response indicative of intoxication was observed (283). 

Vitamin D intoxication causes 25-hydroxy vitamin blood levels to go from a normal of 30—50 ng/mL to 200—400 ng/mL. At this high level, the metabohte can compete with 1 a-25-dihydroxy vitamin for receptors in the intestine and bone and induce effects usually attributed to the dihydroxy vitamin D. Thus, 25-hydroxy vitamin is beUeved to be the critical factor in vitamin D intoxication. Vitamin D2 is metabolized slower than vitamin and thus appears to be less toxic (218). 

Vitamin D withdrawal is an obvious treatment for D toxicity (219). However, because of the 5—7 d half-life of plasma vitamin D and 20—30 d half-life of 25-hydroxy vitamin D, it may not be immediately successful. A prompt reduction in dietary calcium is also indicated to reduce hypercalcemia. Sodium phytate can aid in reducing intestinal calcium transport. Calcitonin glucagon and glucocorticoid therapy have also been reported to reduce semm calcium resulting from D intoxication (210). 

Trichloroethylene is acutely toxic, primarily because of its anesthetic effect on the central nervous system. Exposure to high vapor concentrations is likely to cause headache, vertigo, tremors, nausea and vomiting, fatigue, intoxication, unconsciousness, and even death. Because it is widely used, its physiological effects have been extensively studied. 

Humans tolerate fairly large oral doses of copper without harmful effects, and it is used in various therapies (66). Copper sulfate is a powerful emetic and has been used clinically in the treatment of intoxications. 

Because alcohol intoxication may be simulated by many pathologic conditions, including diabetic acidosis, the postconvulsive depression of epilepsy, uremia, head injuries, and poisonings by any other central nervous depressant and some stimulants (280), a diagnosis of acute alcoholism should not be made casually chemical testing of blood, urine, or expired air is always desirable. 

Some authorities question whether dmnkeimess can result from the inhalation of ethyl alcohol vapors. Experience has demonstrated that in any event such intoxication is indeed rare (281). There is no concrete evidence that the inhalation of ethyl alcohol vapor will cause cirrhosis. Liver function is definitely impaired during alcohol intoxication (282), making the subject more susceptible to the toxic effects of chlorinated hydrocarbons. 

Lipopolysaccharide (LPS) endotoxins are characteristic Gram-negative outer-cell components which are produced by many cyanobacteria. Although LPS have been characterized and found to be toxic to laboratory animals after isolation from cyanobacteria, their toxicity to rodents is less potent than the endotoxins of enteric pathogens such as Salmonella Typical symptoms of animals suffering from LPS intoxication include vomiting, diarrhoea, weakness and death after hours rather than minutes. 

The ability to identify and quantify cyanobacterial toxins in animal and human clinical material following (suspected) intoxications or illnesses associated with contact with toxic cyanobacteria is an increasing requirement. The recoveries of anatoxin-a from animal stomach material and of microcystins from sheep rumen contents are relatively straightforward. However, the recovery of microcystin from liver and tissue samples cannot be expected to be complete without the application of proteolytic digestion and extraction procedures. This is likely because microcystins bind covalently to a cysteine residue in protein phosphatase. Unless an effective procedure is applied for the extraction of covalently bound microcystins (and nodiilarins), then a negative result in analysis cannot be taken to indicate the absence of toxins in clinical specimens. Furthermore, any positive result may be an underestimate of the true amount of microcystin in the material and would only represent free toxin, not bound to the protein phosphatases. Optimized procedures for the extraction of bound microcystins and nodiilarins from organ and tissue samples are needed. 

The hydrochloride of a natural product which is intoxicating and addictive produced the set of NMR results 53. What is the structure of the material What additional information can be derived from the NOE difference spectrum ... 

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