Industrial solvents and liver toxicity: risk assessment, risk factors and mechanisms

Organic solvents utilized in various industrial processes may be associated with hepatotoxicity. The hepatotoxicity of some of the solvents was recognized as early as 1887, 1889 and 1904. Factors contributing to the hepatotoxicity of solvents include 1) species differences, 2) liver blood flow, 3) protein binding, 4) point of binding intracellularly, 5) genetic factors, 6) different cellular enzymatic degradation, 7) age, 8) nutritional condition, 9) interaction with alcohol, and 10) interaction with medications of use and abuse. The hepatotoxicity of solvents in general and of carbon tetrachloride, trichloroethylene, tetrachloroethylene, toluene, and 1,1,1-trichloroethene are discussed. Experimental animal data, human data, and in vitro studies are explored. Suggested mechanisms of direct toxicity, indirect toxicity and autoimmune mechanisms are elaborated. The most important message from this review is that laboratory testing that is commonly used by clinicians to detect liver toxicity may not be sensitive enough to detect early liver hepatotoxicity from industrial solvents and new methodologies are being encouraged and utilized in the early recognition and diagnosis of hepatotoxicity for solvents. The final clinical assessment of hepatotoxicity and industrial solvents must take into account synergism with medications, drugs of use and abuse, alcohol, age, and nutrition. Early recognition and reporting will be helpful in further understanding the incidence, cofactors and possible mechanisms.