Carbon tetrachloride kidney toxicity

Carbon tetrachloride is toxic by inhalation of its vapor and oral intake of the Hquid. Inhalation of the vapor constitutes the principal ha2ard. Exposure to excessive levels of vapor is characterized by two types of response an anesthetic effect similar to that caused by compounds such as diethyl ether and chloroform and organic injury to the tissues of certain organs, in particular the Hver and kidneys. This type of injury may not become evident until 1—10 days after exposure. The nature of the effect is deterrnined largely by the vapor concentration but the extent or severity of the effect is deterrnined principaHy by the duration of exposure (38). 

Carbon tetrachloride is toxic through both inhalation and ingestion. Toxic symptoms from inhalation tend to be associated with nervous system, whereas those from ingestion often involve the gastrointestinal tract and liver. Both the liver and kidney may be substantially damaged by carbon tetrachloride. 

A number of substances including ethanol, isopropyl alcohol, polybrominated biphenyls, phenobarbital, and benzo( )pyrene have been shown to synergistically affect carbon tetrachloride toxicity." Alcohol has been a concomitant factor in many of the human cases of poisoning, especially in cases in which severe liver and kidney damage have occurred. Some substances such as chlordecone greatly potentiate the toxicity of carbon tetrachloride at... 

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). 

Cardiovascular Effects. Inhalation and oral studies in humans and animals have not revealed any treatment-related histopathological lesions of heart tissue, or impairment of cardiac functions, even at dose levels causing severe liver and kidney damage (Adams et al. 1952 Stewart et al. 1961 Umiker and Pearce 1953). It is possible that high-level carbon tetrachloride exposure may produce cardiac arrhythmias by sensitization of the heart to catecholamines (Reinhardt et al. 1971). Accordingly, there is some concern for cardiovascular toxicity following substantial exposure to carbon tetrachloride. 

As noted above, persons who are moderate to heavy drinkers are at greatly increased risk of liver and/or kidney injury following ingestion or inhalation of carbon tetrachloride. Occupational exposure to isopropanol has also been reported to markedly potentiate the hepatorenal toxicity of carbon tetrachloride in men and women (Folland et al. 1976). This report and numerous animal studies indicate that primary, secondary, and tertiary alcohols, as well as their ketone analogues, can substantially enhance the toxic potency of carbon tetrachloride. Substantial exposures to alcohols and ketones may occur in occupational settings or in certain instances in the use of household products containing these chemicals. 

Carbon tetrachloride is a hepato toxic solvent, which causes centrilobular necrosis and fatty liver, liver cirrhosis, and tumors and kidney damage after chronic exposure. It is metabolized... 

Carbon tetrachloride causes centrilobular liver necrosis and steatosis after acute exposure, and liver cirrhosis, liver tumors, and kidney damage after chronic administration. The mechanism underlying the acute toxicity to the liver involves metabolic activation by cytochrome P-450 to yield a free radical (trichloromethyl free radical). This reacts with unsaturated fatty acids in the membranes of organelles and leads to toxic products of lipid peroxidation including malondialdehyde and hydroxynonenal. This results in hepatocyte necrosis and inhibition of various metabolic processes including protein synthesis. The latter leads to steatosis as a result of inhibition of the synthesis of lipoproteins required for triglyceride export. 

Lighter fuels, benzene, toluene, cleaning fluids (carbon tetrachloride), petrol, paraffin, and even the fluorocarbon propellants found in various household sprays and medications have all been used, particularly by children, to produce changes in consciousness. They are all inhaled, often with the aid of a plastic bag, and, since they are lipid-soluble, they are readily concentrated in brain tissue. As with many anesthetics there is an early period of hyperactivity, excitement, and intoxication, followed by sedation and confusion. Prolonged or regular use can cause serious toxicity, with bone-marrow depression, cardiac dysrhythmias, peripheral neuropathy, cerebral damage, and liver and kidney disorders (1). 

Exposures to chemical substances such as carbon tetrachloride, 1,1-dichloroeth-ylene, paradichlorobenzene, ethylbenzene, monochlorobenzene, tetrachloroethyl-ene, toluene, 1,1,2-trichloroethane, xylenes, cadmium, and lead are known to canse adverse effects on the kidney. The kidney is unusually susceptible because of its role in filtering harmful substances from the blood. Some of these toxicants canse acnte injury to the kidney, while others produce chronic changes that can lead to end-stage renal failure or cancer. Furthermore, evaluation of the nephrotoxicity of complex industrial waste mixtures with organic chemicals and metals reqnires more stndies. 

Apart from the effects of acute exposure, lower level, chronic exposure can also have toxic effects. For example, it is argued that solvent disease includes impairment of memory and coordination, and changes in personality, but this is a contentious issue. Effects on organs hke the liver and kidney certainly do result from both acute and chronic exposure to certain solvents, for example carbon tetrachloride, which was used in dry cleaning but has now been replaced. 

The kidney is also a major target of carbon tetrachloride toxicity. The characteristic injuries observed are nephritis, nephrosis, and proteinuria. Delayed pulmonary edema and renal failure may follow hepatic damage. Renal failure is the most frequent cause of death in carbon tetrachloride poisonings. 

Ethanol potentiates the toxicity of carbon tetrachloride. This phenomenon is exemplified by a report in the literature of human exposure to carbon tetrachloride. In two separate instances, acute liver and kidney poisoning ensued following exposure to carbon tetrachloride vapors from a discharged fire extinguisher. In both cases, other workers exposed to the same vapors for the same period of time showed no toxic signs or symptoms. Upon investigation, it was determined that the two injured individuals were chronic ethanol users, with daily consumptions of 120 and 250 g/day, respectively. Each of their nonaffected coworkers consumed less than 50 g of ethanol per dayJ13l... 

Chloroform is a volatile, sweet-tasting liqnid that was nsed for many years as an anesthetic. However, because of its toxicity (it can severely damage the liver, kidneys, and heart) it has been replaced by other componnds. Carbon tetrachloride, also a toxic substance, serves as a cleaning liquid, for it removes grease stains from clothing. Methylene chloride is nsed as a solvent to decaffeinate coffee and as a paint remover. 

Carbon tetrachloride Dry cleaners Liver and kidney toxicity... 

Ingestion of carbon tetrachloride can be fatal to humans, death resulting from acute liver or kidney necrosis. Chronic exposure may cause liver and kidney damage. Exposure to a 10-ppm concentration for several weeks produced accumulation of fat in the livers of experimental animals (ACGIH 1986). Substances such as ethanol and barbiturates cause potentiation of toxicity of carbon tetrachloride. Skin contact can cause dermatitis. 

---