Polychlorinated Dibenzodioxins and Polychlorinated Dibenzofurans - PSL1

Effects on Humans

Human populations appear to be less sensitive to the effects of dioxins and furans than most animal species which have been tested. Exposures in the workplace, or from industrial accidents or the Yusho and Yu-Cheng incidents, have resulted in changes to the skin (including chloracne) that can persist for many years. Such extensive exposures have also produced neurological and psychological effects (including sexual dysfunction), elevated blood levels of some enzymes, and adverse effects on the fetus in some instances. The evidence of a link between cancer incidence or mortality and exposure of human populations to dioxins and furans is equivocal. It is difficult to assess the effects that dioxins and furans may have on human health because of concomitant exposures to other chemicals and imprecise information on exposures.

Dioxins and furans occur only in mixtures as by-products of industrial emissions, combustion, or chemical production. Consequently, it is often difficult to identify clearly how they affect humans, because the influence of co-occurring exposures to chemicals other than dioxins and furans always confounds our ability to establish cause-effect and dose-response relationships.

Dioxins

Numerous industrial accidents around the world, although not in Canada, involving out-of-control reaction vessels used to manufacture chlorinated phenols or phenoxy herbicides have exposed workers to short-term, high-level doses of the dioxins that occur as contaminants of these substances. Although there is documentation describing the effects on more than 1300 exposed workers from 1910 to 1976, the rate, route and length of exposure differs in each report, and therefore the time-to-onset and severity of the signs and symptoms also differ. Nevertheless, exposures have frequently been associated with such effects as: acne-like skin lesions ("chloracne") and dermatitis; fluctuations in serum levels of liver enzymes; pulmonary deficiency; sensory changes such as numbness, nausea, headaches, loss of hearing, sleep disturbances, tiredness; sexual dysfunction; depression; and loss of appetite.⁵⁵

Populations exposed to dioxin-contaminated materials through non-occupational sources have experienced similar effects. For example, a small number of adults and children exposed to dioxin-contaminated soils in Missouri, USA, developed skin rashes, chloracne, headaches and lethargy.⁵⁵ The soil contained approximately 6000 micrograms of trichlorophenol, 33 micrograms of 2,3,7,8-tetrachlorodibenzodioxin and 1500 micrograms of PCBs in each gram of soil.

The best-studied exposure of a general population to dioxins occurred following the trichlorophenol reactor explosion in Seveso, Italy in 1976. Some 190 people developed chloracne. No other sustained or clear effects have been attributed to 2,3,7,8-tetrachlorodibenzodioxin exposure in eight years of study.⁵⁵

Some studies of populations in areas of Vietnam sprayed with dioxin-contaminated herbicides have concluded that these herbicides have had effects on human reproduction.⁵⁶ In contrast, studies of Vietnam veterans in the United States who fought in sprayed areas or worked with the defoliants have not revealed any significant related adverse health effects.⁵⁷

On two occasions scientists were exposed to pure mixtures of 2,3,7,8-tetrachlorodibenzodioxin in the laboratory.⁵⁸ They reported chloracne, insomnia, depression, inability to concentrate, decreased libido and, in some cases, effects on personality that emerged two years after exposure.

Epidemiological studies of exposed workers have not effects beyond prolonged chloracne. Some studies mortality⁵⁹ but others have not.⁶⁰

The linkage between cancer and exposure of workers to dioxin-containing chemicals such as herbicides or chlorophenols remains equivocal. Workers in Canada who used defoliants containing dioxin have claimed that cancer rates are higher than expected. In contrast, an excess incidence of cancer has not been observed in U.S. army technicians who used the same defoliants in the 1970s. The International Agency for Research on Cancer (IARC)⁶¹ has concluded that while there is limited evidence of carcinogenicity in humans exposed to chlorophenoxy herbicides and chlorophenols (substances that contain dioxins and furans), the supporting animal data are inadequate. Nevertheless, IARC considers these chemical groups to be possibly carcinogenic to humans. For 2,3,7,8-tetrachlorodibenzodioxin itself, IARC indicates that there is inadequate human data but sufficient animal data to conclude that this compound is possibly carcinogenic to humans.

Furans

There have been three notable accidental human population exposures to high concentrations of furans. All have been confounded by co-exposure to other chemicals.

In 1981, an electrical transformer, filled with transformer fluid containing 65 percent PCBs and 35 percent tri- and tetra-chlorobenzenes, exploded and burned in a Binghamton, New York office tower. The building was contaminated with soot that contained large amounts of furans and lesser amounts of dioxins.⁶²

The approximately 500 exposed individuals were not systematically monitored. However, of 50 that were clinically assessed, some had chloracne, some skin rashes, some minor serum enzyme changes and some effects on behaviour symptoms. No estimate of individual exposures was made in this study.

In 1968, a mass poisoning incident occurred in Japan due to the ingestion of rice oil contaminated with PCBs, furans and polychlorinated quaterphenyls.⁶³ The most common signs and symptoms of the resultant Yusho disease included: acne-like lesions of the skin; thickened rough texture of the skin on hands and feet; blackening of nails; dark discolouration of gums and skin; eye secretions; swelling of the eyelid and increased redness of the eyelids; sweating of the palms; and sensory changes, including weakness, itching, hearing and sight deficiencies.⁶⁴ While most of these effects subsided over a ten-year period, others were still evident ten years after exposure. Among the most persistent symptoms were:: nail pigmentation and deformation; skin cysts that replaced acne-like lesions; swelling of the eyelid and eye discharges; some sensory complaints; and impairment of lung function.

In the fat tissues of the Yusho patients, furan concentrations ranged from 6 to 13 nanograms per gram of fat, and furan concentrations in the liver from 3 to 25 nanograms per gram of fat. Although approximately 40 furan compounds were identified in the contaminated rice oil, many of these were not detected in the tissues of Yusho patients. The compounds that were retained included 2,3,6,8-tetrachlorodibenzofuran; 2,3,7,8-tetrachlorodibenzofuran; 1,2,4,7,8-pentachlorodibenzofuran; 2,3,4,7,8-pentachlorodibenzofuran; and 1,2,3,4,7,8-hexachlorodibenzofuran.⁶⁵

A similar mass food poisoning occurred in central Taiwan in 1979, again involving rice oils contaminated with PCBs, furans and polychlorinated quaterphenyls. Yu-Cheng disease resembled Yusho disease. The exposure occurred over approximately three to nine months and the onset of visible signs appeared over an average of three to four months. The furan compounds consumed and the total intakes of furans were similar to those in the Yusho poisoning.⁶⁴ Rough estimates of intakes of PCB, furans and poly-chlorinated quaterphenyls for Yu-Cheng patients are 973, 3.8 and 586 milligrams per adult, respectively⁶⁶ and for Yusho patients 633, 3.3 and 596 milligrams per adult, respectively.⁶⁷

Yu-Cheng children who were exposed while in the womb often died soon after birth, and had reduced size at birth, abnormal gums, skin, nails, teeth and lungs. Delays and deficits in mental development were also observed in surviving children.⁶⁸ Similar effects have been reported for Yusho children exposed in the same manner.

On the basis of animal studies with contaminated and uncontaminated PCBs, as well as correlation of the clinical signs and symptoms of disease with exposure concentrations, there is reasonably good evidence that Yusho and Yu-Cheng disease were caused primarily by furan contaminants in the rice oi1.⁶⁹

⁵⁵ WHO, 1989 (in press).

⁵⁶ Schecter, 1989 (personal communication).

⁵⁷  WHO, 1989 (in press); IARC, 1987; ATSDR, 1987.

⁵⁸  Holmstedt, 1980; Oliver, 1975.

⁵⁹  Honchar and Halperin, 1981; Thiess et al., 1982.

⁶⁰  Cook et al., 1980, 1987; Ott et al., 1980; Zack and Suskind, 1980; Zack and Gaffey, 1983.

⁶¹ IARC, 1987.

⁶²  Schecter and Tiernan, 1985.

⁶³  Masuda and Yoshimura, 1984.

⁶⁴  Kuratsure et al., 1972.

⁶⁵  Masuda et al., 1985.

⁶⁶ Chen et al., 1985.

⁶⁷  Hayabuchi et al., 1979.

⁶⁸  Rogan et al., 1988.

⁶⁹  NRCC, 1984.