Carbon tetrachloride toxicity

Edwards, M.J., Keller, B.J., Kauffman, F.C. and Thurman, KG. (1993). The involvement of Kupffer cells in carbon tetrachloride toxicity. Toxicol. Appl. Pharmacol. 119, 275-279. 

Agarwal AK, Mehendale HM. 1984c. Excessive hepatic accumulation of intracellular calcium in chlordecone potentiated carbon tetrachloride toxicity. Toxicology 30(1) 17-24. 

Chaudhury S, Mehendale HM. 1991. Amplification of carbon tetrachloride toxicity by chlordecone Destruction of rat hepatic microsomal cytochrome P-450 subpopulation. J Toxicol Environ Health 32(3) 277-294. 

Rao SB, Young RA, Mehendale HM. 1989. Hepatic polyamines and related enzymes following chlordecone-potentiated carbon tetrachloride toxicity in rats. J Biochem Toxicol 4(1) 55-63. 

Soni MG, Mehendale HM. 1991a. Protection from chlordecone-amplified carbon tetrachloride toxicity by cyanidanol Biochemical and histological studies. Toxicol Appl Pharmacol 108(1 ) 46-57. 

Nachtomi E, Alumot E. 1972. Comparison of ethylene dibromide and carbon tetrachloride toxicity in rats and chicks Blood and liver levels lipid peroxidation. Exp Mol Pathol 16 71-78. 

Ruch RJ, Klaunig JE, Schultz NE, et al. 1986. Mechanisms of chloroform and carbon tetrachloride toxicity in primary cultured mouse hepatocytes. Environ Health Perspect 69 301-305. 

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... 

Many reported cases of carbon tetrachloride toxicity are associated with drinking alcohol. The frequent drinking of alcoholic beverages increases the danger from carbon tetrachloride exposure. 

A single dose oral LDso value of approximately 13,000 mg/kg was reported for mice, and 14 daily doses of 625 mg/kg were lethal for 6 of 20 exposed male mice (Hayes et al. 1986). In rats fed carbon tetrachloride in stock diets or protein-free diets, LDso values of 10,200 or 23,400 mg/kg, respectively were reported (McLean and McLean 1966). The authors attributed the difference in sensitivity in animals in this study to protein depletion which has reportedly afforded protection against carbon tetrachloride toxicity. This may result from protein depletion-induced reduction in cytochrome P-450 synthesis, with a consequent diminished metabolic activation of carbon tetrachloride to toxic metabolites. In other studies using rats, an LDso value of approximately 7,500 mg/kg was reported (Pound et al. 1973), while 17/20 animals were killed within 14 days of a single oral gavage exposure to 8,000 mg/kg (Thakore and Mehendale 1991). Doses as low as 400 mg/kg have resulted in the death of cats (Chandler and Chopra 1926). 

Death Many cases of human fatalities have occurred as the result of carbon tetrachloride exposure, both by ingestion and inhalation (Norwood et al. 1950 Umiker and Pearce 1953 von Oettingen 1964). Most fatal cases of carbon tetrachloride toxicity involve individuals with a history of alcohol consumption, while nondrinkers are considerably less susceptible. 

Hepatic Effects. Human and animals studies of carbon tetrachloride toxicity reveal that the principal adverse systemic effect in injury to the liver, as evidenced by clinical signs jaundice, swollen and tender liver), biochemical alterations (elevated levels of hepatic enzymes in the blood, loss of... 

Nutritional status can also influence the toxic potency of carbon tetrachloride. Animal studies have clearly demonstrated that brief fasting or consumption of diets low in antioxidants (vitamin E, selenium, methionine) can lead to increased carbon tetrachloride hepatotoxicity. The same may be true for humans, although this is not known for certain. Another aspect of nutritional status affecting carbon tetrachloride toxicity is hepatic energy status. Hepatic ATP levels might influence the ultimate outcome of toxicity (low levels may inhibit recovery mechanisms). 

A variety of conditions may predispose certain segments of the population to carbon tetrachloride toxicity. Persons with alcoholic cirrhosis, or other liver diseases which have significantly diminished the functional reserve of the liver, have a reduced capacity to tolerate carbon tetrachloride-induced hepatotoxicity. The same is true for carbon tetrachloride-induced nephrotoxicity in people with significant renal dysfunction from other causes. Diabetics may be particularly susceptible to carbon... 

Anon. 1992. Carbon tetrachloride toxicity. American Family Physician 46 1199-1207. 

David A, Frantik E, Holusa R, et al. 1981. Role of time and concentration on carbon tetrachloride toxicity in rats. Int Arch Occup Environ Health 48 49- 60. 

Day WW, Weiner M. 1991. Short communications Inhibition of hepatic drug metabolism and carbon tetrachloride toxicity in Fisher-344 rats by exercise. Biochem Pharmacol 42 181-184. 

Folland DS, Schaffner W, Ginn EH, et al. 1976. Carbon tetrachloride toxicity potentiated by isopropyl alcohol. J Am Med Assoc 236 1853-1856. 

Glende EA. 1972. Carbon tetrachloride-induced protection against carbon tetrachloride toxicity. The role of the liver microsomal drug-metabolizing system. Biochem Pharmacol 21 1697-1702. 

Kefalas V, Stacey NFI. 1991. Potentiating effects of chlorianted hydrocarbons on carbon tetrachloride toxicity in isolated rat hepatocytes and plasma membranes. Toxicol AppI Pharmaol 109 171-179. 

Murray M, Farrell GC. 1984. Different effects of carbon tetrachloride toxicity and cirrhosis on substrate binding to rat hepatic microsomal cytochrome P-450. Biochem Pharmacol 33 687-9. 

Rao VC, Mehendale HM. 1993. Effect of antimitotic agent colchine on carbon tetrachloride toxicity. Arch Toxicol 67 392-400. 

Recknagel RO, Glende EA, Dolak JA, et al. 1989. Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther 43 139-154. 

Slater TF, Cheeseman KFI, Ingold KU. 1985. Carbon tetrachloride toxicity as a model for studying free-radical mediated liver injury. Philos Trans R Soc Lond [Biol] 311 633-645. 

Figure 7.13 The sequence of events underlying carbon tetrachloride toxicity to the liver cell. Although the process starts in the smooth endoplasmic reticulum at CYP2E1, the destruction spreads throughout the cell.

The biochemical mechanism of carbon tetrachloride toxicity has been investigated in detail. The cytochrome P-450-dependent monooxygenase system acts on CC14 in the liver to produce the C13C free radical ... 

Manno M, Rezzadore M, Grossi M, Sbrana C. 1996. Potentiation of occupational carbon tetrachloride toxicity by ethanol abuse. Hum Exp Toxicol 15 294—300. 

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. 

---