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Chapter: Basic & Clinical Pharmacology : Introduction to Toxicology: Occupational & Environmental

Solvents - Specific Chemicals

Halogenated Aliphatic Hydrocarbons, Aromatic Hydrocarbons.


Halogenated Aliphatic Hydrocarbons

These agents once found wide use as industrial solvents, degreas-ing agents, and cleaning agents. The substances include carbon tetrachloride, chloroform, trichloroethylene, tetrachloroethylene (perchloroethylene), and 1,1,1-trichloroethane (methyl chloro-form). However, because of the likelihood that halogenated ali-phatic hydrocarbons are carcinogenic to humans, carbon tetrachloride and trichloroethylene have largely been removed from the workplace. Perchloroethylene and trichloroethane are still in use for dry cleaning and solvent degreasing, but it is likely that their use will be very limited in the future. Dry cleaning as anoccupation is listed as a class 2B carcinogenic activity by the International Agency for Research Against Cancer (IARC). Fluorinated aliphatics such as the freons and closely related com-pounds have also been used in the workplace and in consumer goods, but because of the severe environmental damage they cause, their use has been limited or eliminated by international treaty agreements. The common halogenated aliphatic solvents also create serious problems as persistent water pollutants. They are widely found in both groundwater and drinking water as a result of poor disposal practices.

See Table 56–1 for recommended TLVs.

A. Mechanism of Action and Clinical Effects

In laboratory animals, the halogenated hydrocarbons cause central nervous system depression, liver injury, kidney injury, and some degree of cardiotoxicity. Several are also carcinogenic in animals and are considered probable carcinogens in humans. Trichloroethylene and tetrachloroethylene are listed as “reasonably anticipated to be a human carcinogen” by the US National Toxicology Program, and as class 2A probable human carcinogens by IARC. These sub-stances are depressants of the central nervous system in humans; chloroform is the most potent. Chronic exposure to tetrachloro-ethylene and possibly 1,1,1-trichloroethane can cause impaired memory and peripheral neuropathy. Hepatotoxicity is also a com-mon toxic effect that can occur in humans after acute or chronic exposures; carbon tetrachloride is the most potent of the series. Nephrotoxicity can occur in humans exposed to carbon tetrachlo-ride, chloroform, and trichloroethylene. With chloroform, carbon tetrachloride, trichloroethylene, and tetrachloroethylene, carcino-genicity has been observed in lifetime exposure studies performed in rats and mice and in some human epidemiologic studies. Reviews of the epidemiologic literature on the occupational expo-sure of workers to various halogenated aliphatic hydrocarbon sol-vents including trichloroethylene and tetrachloroethylene have found significant associations between exposure to the agent and renal, prostate, and testicular cancer. Other cancers have been found to be increased but their incidence has not reached statisti-cal significance.

B. Treatment

There is no specific treatment for acute intoxication resulting from exposure to halogenated hydrocarbons. Management depends on the organ system involved.

Aromatic Hydrocarbons

Benzene is used for its solvent properties and as an intermediatein the synthesis of other chemicals. The 2008 recommended TLVs are given in Table 56–1. Benzene remains an important compo-nent of gasoline and may be found in premium gasolines at con-centrations as high as 2%. In cold climates such as Alaska, benzene concentrations in gasoline may reach 5%. The PEL promulgated by OSHA is 1 ppm in the air and a 5 ppm limit for skin exposure. The National Institute for Occupational Safety and Health (NIOSH) and others have recommended that the exposure limitsfor benzene be further reduced to 0.1 ppm because excess blood cancers occur at the current PEL. The acute toxic effect of benzene is depression of the central nervous system. Exposure to 7500 ppm for 30 minutes can be fatal. Exposure to concentrations larger than 3000 ppm may cause euphoria, nausea, locomotor problems, and coma; vertigo, drowsiness, headache, and nausea may occur at concentrations ranging from 250 to 500 ppm. No specific treat-ment exists for the acute toxic effect of benzene.

Chronic exposure to benzene can result in very serious toxic effects, the most significant of which is bone marrow injury. Aplastic anemia, leukopenia, pancytopenia, and thrombocytopenia occur at higher levels of exposure, as does leukemia. Chronic expo-sure to much lower levels has been associated with leukemia of several types as well as lymphomas, myeloma, and myelodysplastic syndrome. Recent studies have shown the occurrence of leukemia following exposures as low as 2 ppm-years. The pluri-potent bone marrow stem cells appear to be a target of benzene or its metabo-lites and other stem cells may also be targets. Epidemiologic data confirm a causal association between benzene exposure and an increased incidence of leukemia in workers. Most organizations now classify benzene as a known human carcinogen.

Toluene (methylbenzene) does not possess the myelotoxicproperties of benzene, nor has it been associated with leukemia. It is, however, a central nervous system depressant and a skin and eye irritant. It is also fetotoxic. See Table 56–1 for the TLVs. Exposure to 800 ppm can lead to severe fatigue and ataxia; 10,000 ppm can produce rapid loss of consciousness. Chronic effects of long-term toluene exposure are unclear because human studies indicating behavioral effects usually concern exposures to several solvents. In limited occupational studies, however, metabolic interactions and modification of toluene’s effects have not been observed in work-ers also exposed to other solvents. Less refined grades of toluene contain benzene.

Xylene (dimethylbenzene) has been substituted for benzene inmany solvent degreasing operations. Like toluene, the threexylenes do not possess the myelotoxic properties of benzene, nor have they been associated with leukemia. Xylene is a central ner-vous system depressant and a skin irritant. Less refined grades of xylene contain benzene. Estimated TLV-TWA and TLV-STEL are 100 and 150 ppm, respectively.

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