Toxicity central nervous system effects

The precise mechanism of dimethylhydrazine toxicity is uncertain. In addition to the contact irritant effects, the acute effects of dimethylhydrazine exposure may involve the central nervous system as exemplified by tremors and convulsions (Shaffer and Wands 1973) and behavioral changes at sublethal doses (Streman et al. 1969). Back and Thomas (1963) noted that the deaths probably involve respiratory arrest and cardiovascular collapse. The central nervous system as a target is consistent with the delayed latency in response reported for dimethylhydrazine (Back and Thomas 1963). There is some evidence that 1,1-dimethylhydrazine may act as an inhibitor of glutamic acid decarboxylase, thereby adversely affecting the aminobutyric acid shunt, and could explain the latency of central-nervous-system effects (Back and Thomas 1963). Furthermore, vitamin B6 analogues that act as coenzymes in the aminobutyric acid shunt have been shown to be effective antagonists to 1,1-dimethylhydrazine toxicity (reviewed in Back and Thomas 1963). 

Effect of Dose and Duration of Exposure on Toxicity. The severity of neurological effects in humans and animals after acute oral exposure to cyanide is dose-related (Chen and Rose 1952 Lasch and El Shawa 1981). Central nervous system effects have been observed following acute-duration exposures (Levine and Stypulkowski 1959a) and chronic-duration exposures (Hertting et al. 1960), via the inhalation and oral routes. Necrosis is the most prevalent central nervous system effect following acute-duration exposure to high concentrations of cyanide, whereas demyelination is observed in animals that survive repeated exposure protocols (Bass 1968 Ibrahim et al. 1963). 

The nervous system is the most sensitive target for cyanide toxicity, partly because of its high metabolic demands. High doses of cyanide can result in death via central nervous system effects, which can cause respiratory arrest. In humans, chronic low-level cyanide exposure through cassava consumption (and possibly through tobacco smoke inhalation) has been associated with tropical neuropathy, tobacco amblyopia, and Leber s hereditary optic atrophy. It has been suggested that defects in the metabolic conversion of cyanide to thiocyanate, as well as nutritional deficiencies of protein and vitamin B12 and other vitamins and minerals may play a role in the development of these disorders (Wilson 1965). 

Concurrent administration of lithium and selective serotonin re-uptake inhibitors, such as paroxetine, results in an increased risk of central nervous system effects and lithium toxicity has been reported. 

Cases of toxic encephalopathy and macro-qAic anemia have been reported from industrial exposures that may have been as low as 60 ppm. Symptoms were headache, drowsiness, lethargy, and weakness. Manifestations of central nervous system instability included ataxia, dysarthria, tremor, and somnolence. These effects were usually reversible. In acute exposures, the central nervous system effects were the more pronounced, whereas prolonged exposure to lower concentrations primarily produced evidence of depression of erythrocyte formation. When exposure was reduced to 20 ppm, no further cases occurred. 

Toxicology. Selenium is an essential trace element that can be toxic in excessive amounts. Elemental selenium and selenium compounds as dusts, vapors, and fumes are irritants of the eyes, mucous membranes, and skin. Chronic exposure may cause central nervous system effects, gastrointestinal disturbances, and loss of hair and fingernails. 

Magnesium deficiency, usually the result of decreased absorption or excessive excretion, results in neuromuscular weakness and ultimately convulsions. Dietary deficiency in catde is known as the grass staggers. Magnesium toxicity from impaired excretion or excessive consumption of antacids results in vomiting, hypertension, and central nervous systems effects. Inhalation of magnesium oxide from welding can cause metal fume fever similar to that from zinc. 

Cardiovascular Effects. Most studies of humans exposed to carbon tetrachloride by inhalation have not detected significant evidence of cardiovascular injury, even at exposure levels sufficient to markedly injure the liver and/or kidney. Changes in blood pressure, heart rate, or right- sided cardiac dilation have sometimes, but not always, been observed (Ashe and Sailer 1942 Guild et al. 1958 Kittleson and Borden 1956 Stewart et al. 1961 Umiker and Pearce 1953), and are probably secondary either to fluid and electrolyte retention resulting from renal toxicity, or to central nervous system effects on the heart or blood vessels. Carbon tetrachloride also may have the potential to induce cardiac arrhythmias by sensitizing the heart to epinephrine, as has been reported for various chlorinated hydrocarbon propellants (Reinhardt et al. 1971). 

Like many volatile halocarbons and other hydrocarbons, inhalation exposure to carbon tetrachloride leads to rapid depression of the central nervous system. Because of its narcotic properties, carbon tetrachloride was used briefly as an anesthetic in humans, but its use was discontinued because it was less efficacious and more toxic than other anesthetics available (Hardin 1954 Stevens and Forster 1953). Depending on exposure levels, common signs of central nervous system effects include headache, giddiness, weakness, lethargy, and stupor (Cohen 1957 Stevens and Forster 1953 Stewart and Witts 1944). Effects on vision (restricted peripheral vision, amblyopia) have been observed in some cases (e.g., Johnstone 1948 Smyth et al. 1936 Wrtschafter 1933), but not in others (e.g., Stewart and Wtts 1944). In several fatal cases, microscopic examination of brain tissue taken at autopsy revealed focal areas of fatty degeneration and necrosis, usually associated with congestion of cerebral blood vessels (Ashe and Sailer 1942 Cohen 1957 Stevens and Forster 1953). 

As shown in Figure 2-4, there is a considerable body of data on the health effects of carbon tetrachloride in humans, especially following acute oral or inhalation exposures. Although many of the available reports lack quantitative information on exposure levels, the data are sufficient to derive approximate values for safe exposure levels. There is limited information on the effects of intermediate or chronic inhalation exposure in the workplace, but there are essentially no data on longer-term oral exposure of humans to carbon tetrachloride, most toxicity studies have focuses on the main systemic effects of obvious clinical significance (hepatotoxicity, renal toxicity, central nervous system depression). There are data on the effects of carbon tetrachloride on the immune system, but there are no reports that establish whether or not developmental, reproductive, genotoxic, or carcinogenic effects occur in humans exposed to carbon tetrachloride. 

In addition to battlefield trauma, there is also the risk of exposure to chemical weapons such as the nerve agents, notably the organophosphorus gases (soman, sarin, VX, tabun) [6]. Organophosphorus toxicity arises largely from their ability to irreversibly inhibit acetyl-cholinesterases, leading to effects associated with peripheral acetyl-choline accumulation (muscarinic syndrome) such as meiosis, profuse sweating, bradychardia, bronchioconstriction, hypotension, and diarrhoea. Central nervous system effects include anxiety, restlessness, confusion, ataxia, tremors. 

Amantadine has a number of undesirable central nervous system effects, all of which can be reversed by stopping the drug. These include restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations, and confusion. Overdosage may produce an acute toxic psychosis. With doses several times higher than recommended, convulsions have occurred. 

Signs of methyl bromide toxicity following acute exposure include irritation of the eyes and respiratory tract, tremor, incoordination, depression of the central nervous system and convulsions. Long-term exposure induces pulmonary congestion, central nervous system effects, and renal and hepatic lesions. After oral administration to rats, hyperplasia and hyperkeratosis (and squamous-cell carcinomas) of the forestomach were observed (lARC, 1986). 

Some toxins in mushrooms are alkaloids that cause central nervous system effects of narcosis and convulsions. Hallucinations occur in subjects who have eaten mushrooms that contain psilocybin. The toxic alkaloid muscarine is present in some mushrooms. 

The most probable cause of a submarine sinking is flooding caused by an event that breaches the outer hull. The force required would have to be substantial. Potential causes include surface collision, grounding, external explosion, and catastrophic failure of a hull valve. It is likely that such an event also would start a fire within the submarine. The immediate concern for the crew is the release of toxic gases that are produced as the combustion products of on-board fires (U.S. Navy 1998). Human exposure to these gases can lead to adverse health effects, particularly respiratory and central nervous system effects, and even... 

Benzene also affects the central nervous system. Effects noted include drowsiness, dizziness, headache, vertigo, tremor, delirium, and loss of consciousness (Flury 1928 Greenburg 1926 Kraut et al. 1988 Yin et al. 1987b). Since benzene may induce an increase in brain catecholamines, it may also have a secondary effect on the immune system via the hypothalamus-pituitary-adrenal axis (Hsieh et al. 1988b). Increased metabolism of catecholamines can result in increased adrenal corticosteroid levels, which are immunosuppressive (Hsieh et al. 1988b). Further studies to determine the molecular mechanism of these effects could lead to additional approaches for reducing the toxic effects of benzene. 

SAFETY PROFILE Poison by ingestion. Moderately toxic by skin contact. A skin and eye irritant. Exposure causes blue coloration of internal organs and central nervous system effects, e.g., hyperexcitability, tremors, lack of coordination, hunched back, and loss of weight. It is slowly metabolized and excreted via feces. Symptoms persist for 90 days after exposure. Severity of symptoms seems proportional to length of exposure. It is freely absorbed via human skin. When heated to decomposition it emits acrid smoke and fumes. 

DOT CLASSIFICATION 6.1 Label Poison SAFETY PROFILE Poison by ingestion, inhalation, subcutaneous, intravenous, and intraperitoneal routes. Toxic effects resemble strychnine poisoning. Human systemic effects by inhalation somnolence, convulsions, and antipsychotic effects. Human central nervous system effects by inhalation. When heated to decomposition it emits highly toxic fumes of NOx. 

SAFETY PROFILE Poison by intraperitoneal and intravenous routes. Experimental teratogenic and reproductive effects. Human systemic effects by ingestion dilation of the arteries or veins. Many lysergic acid derivatives have central nervous system effects. When heated to decomposition it emits very toxic fumes such as Br" and NOx. See other lysergic acid derivatives. 

DOT CLASSIFICATION 2.2 Label Nonflammable Gas SAFETY PROFILE MUdly toxic by ingestion and inhalation. Can cause sUght transient effects at high concentrations. No anesthesia or central nervous system effects. Nonflammable gas. Mutation data reported. When heated to decomposition it emits highly toxic fumes of F". 

SAFETY PROFILE Mildly toxic by ingestion. Humans sustain central nervous system effects at low doses. A skin irritant. Flammable liquid. Explosion Hazard ... 

Flammable Liquid DOT Class 6.1 Label Poison, Flammable Liquid SAFETY PROFILE Moderately toxic by ingestion, inhalation, and intraperitoneal routes. A skin and eye irritant. Inhalation causes central nervous system effects in humans. A very dangerous fire hazard when exposed to heat or flame can react vigorously with oxidizing materials. A moderate explosion hazard when exposed to spark or flame. Violent reaction with Ca(OCl)2. WiU react with water or steam to produce toxic and flammable vapors. To fight fire, use CO2, dry chemical. When heated to decomposition or on contact with acid or acid fumes it emits highly toxic fumes of SOx. See also MERCAPTANS. 

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