ORGANOCHLORINES

Organochlorines constitute a large class of chemical compounds that have been in the channels of trade since the late 1800s. These compounds are lipid soluble, rapidly absorbed from most routes of exposure, and cross the blood-brain barrier. Their chemistry ranges from simple monochloromethane to the polychlorinated ethylenes and ethanes. Several alkyl-chlorocompounds and polyhalogenated compounds also exist. Many anesthetic gases are polyhalogenated alkanes, as are some of the freons and fire retardants.

The discussion here will be limited to the chlorinated short-chain alkanes and alkenes. The chloromethanes range from monochloromethane through tetrachloromethane. Monochloromethane and dichloromethane are industrial compounds that have been used in foods, drugs, and solvents. Trichloromethane is chloroform, an anesthetic gas that was discovered in the mid–nineteenth century. It is still used as a solvent, and up until very recently it was found in over-the-counter cough medicines, lozenges, and mouthwashes. Tetrachloromethane is carbon tetrachloride, a solvent used for many years in the dry cleaning industry and for personal use as a fabric cleaner. It was discovered at the same time and in the same laboratory as chloroform.

The toxicity of chloroform and carbon tetrachloride has been well studied. These compounds are highly toxic to the liver and kidney, though chloroform has a greater toxicity to the kidney while carbon tetrachloride has a much greater toxicity to the liver. These compounds are toxic to their target organs regardless of the route of exposure. Chloroform is positive in the rodent bioassay for carcinogenicity. Carbon tetrachloride is so toxic that long-term bioassays are difficult to conduct.

The chloroethanes are interesting compounds. Biologically they are relatively inert compared to carbon tetrachloride and chloroform. As long as there is one nonsubstituted site on one carbon the chemical is rapidly metabolized and excreted as ethanol. However, hexachlorethane exhibits some of the same toxicity as chloroform.

The more interesting compounds are the chlorethylenes. The double-bonded carbons render these compounds much more biologically active. Monochloroethylene is vinyl chloride. This compound has anesthetic properties, is used as a polymer precursor in plastic manufacturing, and is highly reactive. In rodent bioassays and in humans, vinyl chloride induces a relatively rare type of hemangiosarcoma, among other tumors. Vinyl chloride is one of those rare carcinogens that induces virtually identical cancers in animals and humans. In addition, vinyl chloride exhibits some mutagenic activity. Dichlorethylenes are much different in their structure and toxicity. Vinylidene chloride and 1,2-cisdichloroethylene appear to be more toxic than the transisomer, but their toxicity, mutagenicity, and carcinogenicity are much less than the potency of vinyl chloride, if they possess those properties at all.

Trichloroethylene (1,1,2-trichlorethylene [TCE]) was once widely used for several clinical and industrial application. TCE was a diluent in anesthetics until the 1970s. It was thought to be the agent that led to nausea and vomiting after gaseous anesthesia. TCE, an excellent degreasing agent and industrial solvent, was also used as a decaffeinating agent in coffees until banned by the regulatory agencies. There is a great deal of controversy over the potency of TCE as a toxicant. However, the compound exhibits enough water solubility to present a hazard in many drinking water supplies. TCE is mutagenic in several in vitro bacterial assays and is carcinogenic in some bioassays.

The next chemical in the series is tetrachloroethylene (perchloroethylene, PERC, or PCE). PERC is very lipid soluble but is also found in some water supplies. It was widely used as a dry cleaning agent and a degreaser for metal finishing. For many years PERC and TCE were used as a drug for the treatment of gut-dwelling parasites. These chemicals are not of the same class as the aromatic chlorinated compounds, but they are found as air pollutants and water pollutants throughout the world. Their use in foods and drugs in the United States and elsewhere has been curtailed. The danger of these compounds is the broad possibility for exposure. Industrial hygiene practices have limited exposure in the workplace, but exposure in the home and on the street is measurable. These are excellent solvents that remain in use in the channels of trade.

Michael Gallo

(see also: Carcinogenesis; Persistent Organic Pollutants [POPs]; Tetrachloroethylene; Toxicology )