Toxic effects, chloroform

The toxic effects of chloroform resemble those of carbon tetrachloride. The probable effects of exposure to various atmospheric concentrations of chloroform are summarized in Table 4 (37). 

Biomarkers Used to Characterize Effects Caused by Chloroform INTERACTIONS WITH OTHER CHEMICALS POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE METHODS FOR REDUCING TOXIC EFFECTS... 

Musculoskeletal Effects. Little data is available that examines the effects of chloroform toxicity on the musculoskeletal system however, it appears that chloroform has few significant toxic effects on this system. 

Dermal Effects. No reports are available on the toxicity of chloroform to skin after inhalation and oral exposures in humans. Stratum comeum damage was reported after a topical exposure of chloroform of 15 minutes duration for 6 consecutive days (Malten et al. 1968). Chloroform was used as a vehicle for the topical application of aspirin for the treatment of painful herpes zoster lesions in male and female humans. The only reported side-effect was an occasional burning sensation to the skin as the chloroform evaporated after application (King 1993). 

This section will describe clinical practice and research concerning methods for reducing toxic effects of exposure to chloroform. However, because some of the treatments discussed may be experimental and unproven, this section should not be used as a guide for treatment of exposures to chloroform. When specific exposures have occurred, poison control centers and medical toxicologists should be consulted for medical advice. The following texts provide specific information about treatment following exposures to chloroform ... 

Despite a relatively fast clearance of chloroform from the body, toxic effects may develop in exposed individuals. No method is commonly practiced to enhance the elimination of the absorbed dose of chloroform. Although there is evidence that ethanol pretreatment of rats can increase the in vitro metabolism of chloroform (Sato et al. 1981), such treatment would not be recommended (Kutob and Plaa 1962) because it would increase the toxicity of chloroform and it is a very poor practice generally. 

Target organs of chloroform toxicity are the central nervous system, liver, and kidneys (see Section 2.2). Respiratory, cardiovascular, and gastrointestinal toxic effects have also been reported. Studies in animals also indicated that chloroform exposure may induce reproductive and developmental effects and cause cancer. Several studies investigated the possible mechanism for chloroform-induced toxicity (see Section 2.5). Proposed mechanisms of chloroform toxicity and potential mitigations based on these mechanisms are discussed below. The potential mitigation techniques mentioned are all experimental. 

McLean AEM. 1970. The effect of protein deficiency and microsomal enzyme induction by DDT and phenobarbitone on the acute toxicity of chloroform and a pyrrolizidine alkaloid, retrorsine. Br J Exp Pathol 51 317-321. 

Several substances alter the toxicity of chloroform in animals— most probably by modifying the metabolism to a reactive intermediate. Factors that potentiate chloroform s toxic effects include ethanol, polybrominated biphenyls, steroids, and ketones. Disulfiram, its metabolites, and a high-carbohydrate diet... 

Branchflower and Pohl (1981) postulated that this depletion might be associated with the potentiation of toxic effects from chloroform (CHCP) when coadministered with 2- hexanone, since depletion of hepatic GSH could allow more phosgene (COCI2) (the toxic oxidation product of chloroform) to react with sensitive tissue components. 

Inhaled anesthetics currently in use include halo-genated volatile liquids such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, and sevoflurane (Table 11-1). These volatile liquids are all chemically similar, but newer agents such as desflurane and sevoflurane are often used preferentially because they permit a more rapid onset, a faster recovery, and better control during anesthesia compared to older agents such as halothane.915 These volatile liquids likewise represent the primary form of inhaled anesthetics. The only gaseous anesthetic currently in widespread use is nitrous oxide, which is usually reserved for relatively short-term procedures (e.g., tooth extractions). Earlier inhaled anesthetics, such as ether, chloroform, and cyclopropane, are not currently used because they are explosive in nature or produce toxic effects that do not occur with the more modern anesthetic agents. 

The toxicities of alkyl halides vary a great deal with the compound. Although some of these compounds have been considered to be almost completely safe in the past, there is a marked tendency to regard each with more caution as additional health and animal toxicity study data become available. Perhaps the most universal toxic effect of alkyl halides is depression of the central nervous system. Chloroform, CHC13, was the first widely used general anesthetic, although many surgical patients were accidentally killed by it. 

Diethyl ether was found to be a much safer anesthetic than chloroform. Like chloroform, ether is more soluble in fatty tissue than in water, so it passes into the central nervous system and takes effect quickly. Ether is also volatile, making it easy to administer. But ether is much less toxic than chloroform because ether degrades to ethanol, which the body can oxidize. 

---