Chloracne persistence

A study of 204 workers exposed for from 1 month to 20 years to 2,4,5-T and its contaminants (concentrations unspecified) showed no evidence of increased risk for cardiovascular disease, hepatic disease, renal damage, central or peripheral nervous system effects, reproductive problems, or birth defects. Clinical evidence of chloracne persisted in 55.7%, and an association between exposure and history of upper gastrointestinal tract ulcer was found. 

Chloracne and associated dermatologic changes are widely recognized responses to TCDD and other dioxin-like compounds in humans. Chloracne is a severe acne-like condition that develops within months of first exposure to high levels of dioxin. For many individuals, the condition disappears after discontinuation of exposure, despite serum levels of dioxin in the thousands of parts per trillion for others, it may remain for many years. The duration of persistent chloracne is on the order of 25 years although cases of chloracne persisting over 40 years have been noted [180]. 

The plant s product was hexachlorophene, a bactericide, with trichlorophenol produced ns an intermediate. During normal operation, a very small amount of TCDD (2,3,7,8 telrachlomdib zoparadioxin) is produced in the reactor as an undesirable side product. TCDD is perhaps the most ]in(enl toxin known to man. Studies have shown TCDD to be fatal in doses as small as lE-9 times die body weight, it insolubility in water makes decontamination very difficult. Nonlethal doses of TCDD result in chloracne, an acne-like disea.se that can persist for several years. 

Dioxins are prominent members of the class of polychlorinated hydrocarbons that also includes diben-zofuran, biphenyls and others. Dioxins are highly toxic environmental contaminants. Like others small planar xenobiotics, some dioxins bind with high affinity to the arylhydrocarbon (Ah) receptor. Dioxins activate the receptor over a long time period, but are themselves poor substrates for the enzymes which are induced via the Ah-receptor. These properties of the dioxins and related xenobiotics may be important for the toxicity of these compounds. Dioxins like 2,3,7,8-tetrachloro-p-dibenzodioxin can cause persistent dermatosis, like chloracne and may have other neurotoxic, immunotoxic and carcinogenic effects. 

Limited experience with humans has shown that exposure to even small amounts of the higher chlorinated derivatives, particularly hexachlorodiphenyl oxide, may result in appreciable acneform dermatitis. Chloracne is usually persistent and affects the face, ears, neck, shoulders, arms, chest, and abdomen (especially around the umbilicus and on the scrotum). The most sensitive areas are below and to the outer side of the eye (malar crescent) and behind the ear. The skin is frequently dry with noninflammatory comedones and pale yellow cysts containing sebaceous matter and keratin. 

In humans, systemic effects are anorexia, nausea, edema of the face and hands, and abdominal pain. In a survey of 34 workers exposed to concentrations of up to 2.2mg/m complaints were a burning sensation of the face and hands, nausea, and a persistent (uncharacterized) body odor. One had chloracne, and five had an eczematous rash on the legs and the hands. Although hepatic function tests were normal, the mean blood level of chlorodiphenyl in the exposed group was approximately 400 ppb, whereas none was detected in the control group. ... 

Accidental exposure to 2,3,7,8-TCDD in a 1949 explosion in a trichlorophenol plant in Nitro, West Virginia, resulted in an outbreak of severe chloracne. Moses et al. (1984) conducted a cross-sectional survey of workers in this plant in 1979. In reviewing the impact of the accident, the authors indicated that 117 workers had severe chloracne as a result of the explosion however, 111 additional workers were found to have had chloracne prior to the explosion. A cross-sectional study of 226 workers in 1979 indicated that 52% had chloracne which persisted for 26 years, and in 29 subjects it was still present after 30 years. Blood levels were not measured, but the air dust in the plant was suspected to have contained 2,4,5-T contaminated with 6 ppm 2,3,7,8-TCDD compared to 0.1 ppm in later years. Similarly, high incidences of chloracne were also found in other facilities (Jirasek et al. 1976 May 1973 Poland et al. 1971 Vos et al. 1978). Appearance of chloracne after accidental occupational exposure may be immediate or delayed since workers may not always be removed from the work environment, the duration of exposure and total exposure is difficult to assess. 

Skin lesions from environmental exposures to 2,3,7,8-TCDD have been most thoroughly studied in the population exposed in Seveso, Italy. Reggiani (1980) described dermal lesions for 17 persons (primarily children) hospitalized shortly after the accidental release in Seveso. Acute lesions probably due to alkali and bums were observed immediately and had a duration of up to 2 months chloracne in children occurred within 2 weeks (earliest occurrence was 3 days) and usually persisted for 8-26 months. Irritative lesions (characterized by erythema and edema of exposed areas, vesiculobollus and necrotic lesions, and... 

In occupationally exposed humans, chloracne, dermal effects and liver damage are the most common health effects. Some cases with fatal outcome have been reported. Symptoms of PCN poisoning include jaundice, constipation, abdominal pain, abdominal distension, anorexia, nausea, vomiting, anemia, skin problems, eye irritation, headache, fatigue and vertigo. Some of the toxic effects persisted for a long period after the exposure had ceased. In severe cases the patients died [1, 27, 264-266], Studies of experimentally induced chloracne show that tetra-, penta-, and hexaCNs have acnegenic properties when applied on the human skin [263,267]. 

For most of the PCDDs no information on human health effects is available except that during the production of pentachlorophenol workers have developed a skin disease, chloracne (13) and complaints such as neuralgic pain in the lower extremities, and symptoms such as persistent bronchitis, and eye irritation (14). The bronchitis seems to be more prevalent in workers exposed to technical pentachlorophenol than in those exposed to the other chlorinated phenols. 

In conclusion, the most prevalent lesion in humans after acute exposure to 2,3,7,8-TCDD is a skin lesion referred to as chloracne. This skin disease may be accompanied by hirsutism and hyperpigmentation. After acute exposure to toxic levels, liver function may be impaired and a sensory neuropathy may be present. There may be complaints of weakness, weight loss, severe fatigue, and a general malaise. Many of these acute symptoms and signs revert to normal when exposure ceases. The chloracne is probably the most persistent lesion. No convincing chronic human health effects, other than chloracne, have been reported, nor is the dose of 2,3,7,8-TCDD known that would cause systemic illness or death in humans. 

From 1935 to 1978, workers world-wide were exposed during periodic explosions at trichlorophenol production facilities as well as during their daily production activities. Table II illustrates some major industrial accidents which yielded published reports of health effects. Table III lists some major health outcomes reported following exposures to products contaminated with 2,3,7,8-TCDD. The primary dermal effect of exposure is chloracne, a persistent form of acne caused by exposure to a number of chlorinated organic compounds. Chloracne occurred in some exposed persons in all accidents, as well as in children in Seveso (2-4). Chloracne appeared with and without other health effects and persisted in some persons up to 28 years after exposure (5-6). 

Chloracne is a consequence of exposure to dioxin in some people and is persistent for many years in some workers. 

Acute exposure to high concentrations of PCBs causes a persistent form of acne called chlorine-acne or chloracne. Based on sufficient evidence of carcinogenicity in experimental animals, the EPA, the International Agency for Research on Cancerand the National Toxicology Program have all classified some PCBs as possibly causing cancer in humans. " ... 

This dioxin is also highly stable it persists in the environment and because of its fat solubility can be passed up the food chain. In sublethal amounts it can cause a disfiguring skin disease called chloracne. 

More than 20 outbreaks of dioxin chloracne, as well as its other health effects, have been reviewed (Taylor et al. 1977 Tindall 1985 Mukerjee 1998). Follow-up studies have shown persistence of chloracne in some cases. They also concluded that there is an increased risk of soft-tissue sarcoma in end-product use in Sweden, occupational exposure in the US and environmental exposure in Seveso, Italy. Although these conclusions are controversial, the International Agency for Research on Cancer has concluded that TCDD is a human carcinogen (Mukerjee 1998). Occupational exposures to TCDD in the herbicide and chemical plants was much greater than most other non-occu-pational exposures. Exposure would sometimes begin as a caustic chemical burn when the trichlorophenol reactors would over heat. These workers showed the earliest and most severe chloracne (Taylor 1979 Tindall 1985). 

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