Exposure at high concentrations may result in cardiac sensitization to epinephrine and similar compounds, as well as liver and kidney injury (see Table 14). In cases of chronic or repeated exposure to chloroform, liver injury is most typical (cf. the effects of carbon tetrachloride). Although injury to the kidney is not as common as that to the liver, it may be observed from either acute or chronic exposure.
Numerous reviews on the toxicity of chloroform are available (Challen et al., 1958; Davidson et al., 1982; NIOSH, 1974; Scholler, 1968; Van Dyke et al., 1964; Von Oettingen, 1955; Winslow and Gerstner, 1978; Zimmerman, 1968).
Considering the long history of chloroform, there is surprisingly little epidemiologic literature on chronic exposure to it. There have been almost no quantitative toxicologic studies of human responses to chronic exposure to chloroform. Challen et al. (1958) studied an industrial operation in which chloroform was being used. Groups exposed at 77–237 ppm exhibited definite symptoms. Apparently, there were also some high peak concentrations for very short periods. Symptoms were gastrointestinal distress and depression. Another group with shorter service was exposed at 21–71 ppm and had comparable symptoms. Both groups were tested for liver injury, but none was found. The authors believed, however, that there may have been mild liver injury, and they recommended that atmospheric exposure be kept below 50 ppm.
Bomski et al. (1967) reported on an investigation of a pharmaceutical plant that used chloroform as a solvent. Smaller amounts of methanol and methylene chloride were also used. Estimates of the airborne chloroform varied from 2 to 205 ppm (0.01–1.0 mg/L). Actual time-weighted average exposures of the workers were not reported; it is not clear if the room concentrations adequately described the workers’ actual exposure. Complaints of headache, nausea, eructation, and loss of appetite were reported, as well as enlargement of the liver (25% of workers) and spleen. Results of liver function tests were not remarkable.
When chloroform was given by gavage to male rats, an LD50 of 2,000 mg/kg (confidence range, 1,050–3,800 mg/kg) was determined (Torkelson et al., 1976). Deaths generally occurred in 2.4 h, but some were delayed as long as 2 wk after treatment. Gross pathologic examination showed liver and kidney changes at doses as low as 250 mg/kg. Thompson et al. (1974) fed chloroform to pregnant rats at 20 mg/kg per day for 10 d without effect on the dams; 50 mg/kg appeared to cause fatty changes. These data are discussed in more detail in the section on teratology below.
Oettel (1936) indicated that chloroform was more irritating to the skin and eyes than many other chlorinated solvents. Oettel’s conclusions have been confirmed by Torkelson et al. (1976), One or two 24-h applications on the skin of rabbits resulted in hyperemia and moderate necrosis. Healing of abraded skin appeared to be delayed by