Central nervous system high-dose exposure effect

Pathological changes that may occur in the central nervous system during acute exposure to high doses may complicate recovery. Severe Parkinsonism was one of the effects noted in four case reports resulting from severe acute oral exposure to cyanide (Carella et al. 1988 Grandas et al. 1989 Rosenberg et al. 

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). 

Toxicology. o-Dichlorobenzene is a skin and eye irritant. At high doses, it causes central nervous system depression and liver and kidney damage in animals. Heavy exposure is expected to produce the same effects in humans. 

The principal effects of carbon tetrachloride in humans are on the liver, the kidneys and the central nervous system. These effects are apparent following either oral or inhalation exposure, and limited data indicate they can occur after dermal exposure as well. All of the effects seen in humans except renal injury are demonstrable at roughly comparable exposure levels in animals, although there are some variations in susceptibility between species that are likely to be related to differences in metabolism. No studies were located regarding reproductive and developmental effects in humans after exposure to carbon tetrachloride. In rats, carbon tetrachloride was not shown to adversely affect reproduction or development. Studies with both mice and rats suggest that sufficiently high doses of carbon tetrachloride may increase the risk of liver tumors in exposed humans. 

Other Systemic Effects. Studies in animals revealed that a number of other tissues besides liver, kidney, and the central nervous system can be affected by carbon tetrachloride, including the adrenals, pancreas, testes, pituitary, spleen and thyroid (Chatterjee 1966 De Castro et al. 1978 de Toranzo et al. 1978b Itoh et al. 1985 Kalla and Bansal 1975 Reuber and Glover 1970). However, effects on these tissues have been reported only after exposure to relatively high doses of carbon tetrachloride, indicating that these tissues are not as sensitive to carbon tetrachloride as liver, kidney, and brain. 

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. 

Hydrazine is toxic and readily absorbed by oral, dermal, or inhalation routes of exposure. Contact with hydrazine irritates the skin. eyes, and respiratory tract. Liquid splashed into die eyes may cause permanent damage to the cornea. Al high doses it can cause convulsions, but even low doses may result in central nervous system depression. Death from acute exposure results from convulsions, respiratory arrest, and cardiovascular collapse. Repeated exposure may affect the lungs, liver, and kidneys. Evidence is limited as to the effect of hydrazine on reproduction and/or development however, animal studies demonstrate that only doses that produce toxicity in pregnant rats result in embryo-toxicity. 

Neurological Effects. Chlorinated aliphatics as a class are known to cause central nervous system depression following high-level exposure in humans and animals. No reliable dose-response data were found on the central nervous system depression induced by 1,1-dichloroethane, though... 

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