Dioxin: An Overview

The terms dioxin, and TCDD, and 2,3,7,8-tetrachlorodibenzo-p-dioxin often are used interchangeably. They are not interchangeable. There are eight possible positions for chlorine atoms on the dioxin skeleton (Fig. 1), and there are 75 potential isomers of dioxin including 22 isomers of the tetra-chlorinated dioxin. 2,3,7,8-tetrachlorodibenzo-p-dioxin, or 2,3,7,8TCDD, is the specific dioxin identified as a contaminant in the production of the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and appears, from animal toxicology data, to be the most toxic of the dioxin isomers studied to date (International Agency for Research on Cancer 1978). Pentachlorophenol, a commonly and widely used wood preservative and biocide, is contaminated with the hexa-, hepta-, octa-, and possibly tetra-chlorinated dioxins (Buser and Bosshardt 1976; Plimmer 1973). 2,3,7,8-TCDD is synthesized as an undesirable contaminant of 2,4,5-trichlorophenol and products made from it, such as 2,4,5-T and hexachlorophene. The amount of contamination can be minimized by regulation of temperature, pressure, and solvent conditions, but when the production process goes out of control, large amounts of TCDD can be produced. There have been numerous occurrences over the past 30 years in which the reactors producing trichlorophenol either have vented to the atmosphere or exploded (Hay 1979). These episodes have contaminated not only the workers, but also the general population, as in the dramatic episode in Seveso, Italy, in 1976 (Hay 1977). A review of the chemical reactions involved in the synthesis of trichlorophenol, 2,4,5-T, and hexachlorophene will more clearly explain the production of TCDD. When tetrachlorobenzene is reacted in an alkaline solution, 2,4,5-trichlorophenol is produced. Trichlorophenol can be further reacted to hexachlorophene, an antiseptic, or it can be reacted with monochloroacetic acid to form the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Depending on the alkalinity, pressure and temperature of the reactions during production, two molecules of trichlorophenol can combine to form 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Fig. 2). Herbicide Orange (or Agent Orange) is also a loosely used term. Herbicide Orange was used in Vietnam as a defoliant along with herbicides termed Purple, Pink, Green, White and Blue (USAF Occupational and Environmental Health Laboratory 1978). Although picloram and cacodylic acid containing arsenic were constituents of Herbicide White and Herbicide Blue, most of these other colorful agents were combinations of the salts or esters of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Ten to twelve million gallons of Herbicide Orange, a 50:50 mixture of esters of 2,4-D and 2,4,5-T were sprayed over three to four million acres in Vietnam during the 1960's (USAF OEHL 1978). It is difficult to estimate the extent of TCDD contamination of the 2,4,5-T used in Vietnam because the levels of contamination during production were variable. The mean concentration of TCDD in Herbicide Orange available after usage was stopped is about two parts per million (USAF OEHL). Potential exposure to Herbicide Orange in Vietnam included not only ground troops and civilians, but also military personnel either preparing planes for spraying or doing the actual spraying. While Herbicide Orange sounds somewhat exotic, similar formulations have been used widely in the United States for such strategic purposes as weed control in suburban lawns, and management of forests and right-of-ways. Why have the chemicals 2,4,5-T and dioxin so caught the public's attention? The answers are relatively clear. First, animal studies have demonstrated the extraordinary toxicity of 2,3,7,8-TCDD. Second, a large volume of Herbicide Orange was applied in Vietnam, and some of the medical problems of over 300,000 Vietnam veterans are being attributed to it. The veterans want to know whether their medical problems are related to their Herbicide Orange exposure. This issue has implications not only for compensation, but also for prognosis. 2,4,5-T has had wide use as a defoliant in the United States and there have been claims of adverse health effects in civilians. Would renewed use of 2,4,5-T produced by new technologies and therefore with lower levels of dioxin contamination pose a threat to the public's health? The following review of the highlights of