PRINCIPLES OF TOXICOLOGY - Biology East Borneo

16.13 TOXIC PROPERTIES OF REPRESENTATIVE HALOGENATED SOLVENTS 395damage and cardiac sensitization in animal studies, although the latter has been demonstrated inanimals only when adrenaline is injected and the practical significance of these findings to industry isconsidered to be low.Although studies with methylene chloride in an Ames test with Salmonella typhimurium TA98 andTA100 resulted in increased reversions in both strains of bacteria, observed effects were limited. Othertests of genotoxic potential are typically negative.Methylene chloride was not positive in a pulmonary tumor assay in strain A mice. Although it isregulated by USEPA and some occupational agencies as a potential carcinogen, methylene chloridedoes not appear to present a practical risk of carcinogenesis in humans at currently acceptable levelsof exposure.Chloroform (see Figure 16.22), or trichloromethane, was used for many years as an anesthetic,solvent, insecticide, and chemical intermediate. Because of delayed liver injury and reports of cardiacsensitization, its use as an anesthetic is obsolete. Chloroform is presently considered a carcinogen byUSEPA and some other agencies, based on animal studies. Chloroform may be produced at low levelsduring the chlorination/disinfection of water.As with other volatile solvents, inhalation is considered the main exposure route for chloroform.Much of the toxicological information available has been developed following the interest in chloroformas a CNS depressant or anesthetic, and high concentrations of chloroform may result in narcosis,anesthesia, and death. Rapidly absorbed and distributed in all organs, chloroform is exhaled for themost part unchanged, or as carbon dioxide. Chloroform appears to be the most cardiotoxic of theanesthetics, with effects that are the least reversible. It is known to cause permanent hepatic and renalinjury following sufficient exposures, and hepatic necrosis has been reported in humans followingingestion of pharmaceutical preparations containing 16.5 percent chloroform.Signs of severe chloroform exposure in humans include a characteristic sweetish odor on the breath,dilated pupils, cold and clammy skin, initial excitation alternating with apathy, loss of sensation,abolition of motor functions, prostration, respiratory depression, cardiac sensitization to adrenaline,unconsciousness, coma, and death. Lethal exposures to chloroform may be delayed and may resultfrom associated kidney or liver damage. Responses associated with exposure to chloroform concentrationsbelow the anesthetic level, including occupational exposures, are typically inebriation andexcitation passing into CNS depression.PHYSIOLOGIC RESPONSE TO CHLOROFORM IN HUMANSConcentration (ppm) Response200–300 Odor threshold4100 Vomiting, sensation of fainting14,000–16,000 Narcotic limiting concentrationChloroform appears to be unique among the smaller chlorinated aliphatics in that it is the only onethat has been reported to be teratogenic and highly embryotoxic in animals. It has been found inFigure 16.22 Chloroform.