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At least 19 recordsLinked to original sources

PubMed2005

Health status and plasma dioxin levels in chloracne cases 20 years after the Seveso, Italy accident.

BACKGROUND: The Seveso, Italy accident of 1976 exposed a large population to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or simply dioxin). The accident resulted, mostly among children, in one of the largest ever-reported outbreaks of chloracne, the typical skin disorder due to halogenated-hydrocarbon compounds. OBJECTIVES: Approximately 20 years after the accident, we conducted an epidemiological study in Seveso to investigate (a) the health status of chloracne cases; (b) TCDD-chloracne exposure-response relationship; and (c) factors modifying TCDD toxicity. METHODS: From 1993 to 1998, we recruited 101 chloracne cases and 211 controls. Trained interviewers administered a structured questionnaire assessing, among other epidemiological variables, information on an extensive list of diseases. During the interview, individual pigmentary characteristics were determined. We measured plasma TCDD levels using high-resolution gas chromatography/mass spectrometry. RESULTS: Plasma TCDD was still elevated (> 10 ppt) in 78 (26.6%) of the 293 subjects with adequate plasma samples, particularly in females, in subjects who had eaten home-grown animals, and in individuals with older age, higher body mass index and residence near the accident site. After 20 years, health conditions of chloracne cases were similar to those of controls from the Seveso area. Elevated plasma TCDD was associated with chloracne [odds ratio (OR) = 3.7, 95% confidence interval (CI) 1.6-8.8, adjusted for age, sex and residence]. Chloracne risk was higher in subjects younger than 8 years at the accident (OR = 7.4, 95% CI 1.8-30.3) and, contrary to previous hypotheses, did not increase at puberty onset or in teenage years. Subjects with elevated TCDD levels and light hair colour had higher relative odds of chloracne (OR = 9.2, 95% CI 2.6-32.5). CONCLUSIONS: Dioxin toxicity in chloracne cases was confined to the acute dermatotoxic effects. Chloracne occurrence appeared related to younger age and light hair colour. Age-related dioxin elimination or dilution must be taken into account in interpreting these results.

Accidents, Occupational↗

PubMed1984

Health status of workers with past exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the manufacture of 2,4,5-trichlorophenoxyacetic acid: comparison of findings with and without chloracne.

Chloracne was found in 52% of 226 workers in a 1979 cross-sectional survey at a plant where 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) had been manufactured from 1948 to 1969. Mean duration of residual chloracne was 26 years, and in 29 subjects, it had been present for 30 years. A significant increased prevalence of abnormal gamma-glutamyl transpeptidase (GGT) and higher mean GGT were found in those with chloracne, compared to those without. Although mean triglyceride values were higher in those with chloracne, the difference was not statistically significant. Neurological examination showed a statistically significant higher prevalence of abnormal sensory findings in those with chloracne. Increased prevalence of angina and reported myocardial infarction in those with chloracne was not significant when age-adjusted. Increased prevalence of reported sexual dysfunction and decreased libido in those with chloracne compared to those without was statistically significant after age adjustment. No differences were found between those with and without chloracne in serum cholesterol, total urinary porphyrins, or in reproductive outcome.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed1985

Cutaneous histologic findings in chemical workers with and without chloracne with past exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Histopathologic examination of the skin in seventy-seven chemical workers with past exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was performed in 1981 to determine whether changes specific for chloracne were present. Prior to biopsy, subjects had been classified as having clinical evidence of residual chloracne (48%), having a past history of chloracne but no current dermatologic evidence of it (24%), or never having had chloracne (27%). Follicular infundibular dilatation and/or comedones and cysts were found in 76%, 39%, and 32% of the current, past, and never chloracne groups, respectively; the differences were significant between current and never groups (p less than 0.001) and between current and past groups (p less than 0.01). A combined mean score of follicular infundibular dilatation, comedones, and cysts was significantly different only between the current and never groups (p less than 0.005). Solar elastosis, histologically present in all subjects, was related to age but not chloracne. No relationship was found between smoking habit and any of the histologic findings. Changes specific for chloracne were not found. Four-millimeter skin biopsy is unlikely to be either diagnostic or useful in persons with past exposure to TCDD that is ill defined or insufficient to produce chloracne.

Acne Vulgaris↗

PubMed1999

Blood lipid concentrations of dioxins and dibenzofurans causing chloracne.

Chloracne is caused by exposure to certain halogenated polycyclic hydrocarbons such as polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs). In chronic exposure it is not known what level of intoxication, represented by the level in blood lipids, is sufficient to cause chloracne. Blood levels of the congeners of PCDD/Fs were determined in four groups of humans. One group had clinically visible chloracne due to exposure in a hexachlorobenzene workshop of a large chemical factory. A second group was exposed in the same workshop, but had no skin changes. There were two control groups: one non-exposed group of maintenance workers from the same chemical factory, and one group of healthy individuals living elsewhere. Blood levels were converted to toxicity equivalents of tetrachlorodibenzo-p-dioxin (TCDD). In the chloracne group blood levels in toxicity equivalents (TEQs) ranged from 1168 to 22,308 pg/g blood lipid. In the exposed without chloracne this ranged from 424 to 662 pg/g. It is concluded that the level to develop chloracne is between 650 and 1200 pg/g TEQ. The contribution of TCDD was rather small, and the main causative congeners were the hexachlorinated dibenzodioxins and dibenzofurans (HxCDD/Fs); lipid-based blood levels in absolute amounts that may cause chloracne are in the range of 2-3.5 ng/g HxCDD, and 2-5 ng/g HxCDF.

Acne Vulgaris↗

PubMed2006

Dioxin-induced chloracne--reconstructing the cellular and molecular mechanisms of a classic environmental disease.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most toxic pollutants known to date that serves as a prototype for a group of halogenated hydrocarbon compounds characterized by extraordinary environmental persistence and unique ability to concentrate in animal and human tissues. TCDD can elicit a complex array of pleiotropic adverse effects in humans, although chloracne, a specific type of acne-like skin disease, is the only consistent manifestation of dioxin intoxication, thus representing a 'hallmark' of TCDD exposure. Chloracne is considered to be one of the most specific and sensitive biomarkers of TCDD intoxication that allows clinical and epidemiological evaluation of exposure level at threshold doses. The specific cellular and molecular mechanisms involved in pathogenesis of chloracne are still unknown. In this review, we summarize the available clinical data on chloracne and recent progress in understanding the role of the dioxin-dependent pathway in the control of gene transcription and discuss molecular and cellular events potentially involved in chloracne pathogenesis. We propose that the dioxin-induced activation of skin stem cells and a shift in differentiation commitment of their progeny may represent a major mechanism of chloracne development.

Acneiform Eruptions↗

PubMed1990

Chloracne associated with employment in the production of pentachlorophenol.

To evaluate the association between exposure to pentachlorophenol (PCP) and the occurrence of chloracne, we studied the medical and personnel records for individuals employed in the manufacturing of PCP. Forty-seven cases of chloracne were identified among 648 workers (7.0%) assigned to PCP production at a single plant between 1953 and 1978. The annual incidence rate varied considerably, ranging from 0 (in 1953) to 1.46 (in 1978). No linear trend in the risk of chloracne was observed with the duration of employment in the pentachlorophenol department. Workers with a documented episode of direct skin contact with PCP had a significantly increased risk of chloracne compared with workers who did not have a documented episode of direct skin contact (cumulative incidence ratio = 4.6; 95% confidence interval 2.6-8.1). Our results confirm that chloracne is associated with exposure to PCP contaminated with hexachlorinated, heptachlorinated, and octachlorinated dibenzo-p-dioxins and dibenzofurans.

Acne Vulgaris↗

PubMed1985

Chloracne, "the hallmark of dioxin intoxication".

Clinical experiences and laboratory studies are described involving a population of workers who were exposed in a plant making 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), including a trichlorophenol runaway reaction. Workers were followed for a period of four years, and 30 years later a mortality analysis was done on those exposed to runaway reaction material to determine possible increased risks for causes of death. Subsequently, a morbidity study on 436 employees involving three cohorts was carried out to determine the long-term health effects associated with the production of 2,4,5-T including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The mortality and morbidity studies demonstrated that the standardized mortality ratio for all causes of death was 69, and for cancer at all sites and cardiovascular disease it was 100 and 68, respectively. The most significant observations emerging from the morbidity study were that 86% of the exposed persons developed chloracne at some time and that 52.7% still had chloracne on examination 20 to 30 years after the initial exposure. There appeared to be no evidence, on a long-term basis, of increased risks for cardiovascular disease, hepatic disease, renal disease, central and peripheral nerve problems, reproductive problems, or birth defects among the exposed and those who had chloracne among the exposed. Studies on the cell kinetics and pathogenesis of chloracne indicate that TCDD induces the modulation of undifferentiated sebaceous gland cells to keratinocytes. This action results in a disappearance of sebaceous glands and substitution of closed comedones and keratin cysts. Production workers have the highest frequency and severity of chloracne and systemic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗

PubMedDate not supplied

Serum dioxin, chloracne, and acne in veterans of Operation Ranch Hand.

The possible relationship between exposure to Agent Orange and its contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), during the Vietnam War and chloracne was investigated. The index subjects were veterans of Operation Ranch Hand, the unit responsible for aerial herbicide spraying in Vietnam from 1962 to 1971. Other Air Force veterans who served in Southeast Asia during the same period, but who were not involved with spraying herbicides, served as comparisons. None of the Ranch Hand veterans were diagnosed with chloracne; therefore, we restricted our analyses to acne. We found no meaningful or consistent association between dioxin exposure and prevalence of acne without or with regard to anatomical location. These results suggested that exposure of Ranch Hand veterans to dioxin was insufficient for the production of chloracne or perhaps the exposure may have caused chloracne that resolved and was currently undetectable.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed1981

Chloracne following environmental contamination by TCDD in Seveso, Italy.

Data are presented on the occurrence of chloracne, clinical symptoms and biochemical changes in 164 children following environmental contamination by TCDD from an industrial accident in Seveso, Italy. An overall positive association was found between the territorial distribution of chloracne cases and the different levels of soil contamination in the affected area. Individual risk factors such as condition and length of exposure, intake via contaminated foods, etc. were evaluated; no single factor appeared to be associated with chloracne. Disturbances of the gastrointestinal tract were more frequently observed in children affected with chloracne in those from the same areas having no skin lesions. However, no clinically definable systemic disease has been diagnosed.

Accidents, Occupational↗

PubMed1996

Chloracne in the 1990s.

BACKGROUND: Chloracne is a disease associated with toxicity of halogenated compounds used in some industrial processes. A patient affected by chloracne led us to study a total of nine cases from a single factory. METHODS: We studied the clinical features of nine patients exposed chronically to chlorobenzenes. On all of them blood samples were drawn and biopsies of affected skin and liver were taken. Their work environment was visited and studied. RESULTS: All nine patients were men and had polymorphic skin lesions, characterized mainly by comedones and cysts. They had chronic conjunctivitis and seven had cysts in the Meibomian glands. All of them had polyneuropathy and liver damage and seven had hypertriglyceridemia. Compounds known to cause chloracne were found in exceedingly high concentrations in the water used in the workplace. CONCLUSIONS: Every patient exposed to halogenated compounds with the cutaneous manifestations of chloracne should be carefully investigated for systemic complications (such as ophthalmic, neuropathic, hepatic, and lipoprotein abnormalities).

Acne Vulgaris↗

PubMed1989

Follow-up of subjects who developed chloracne following TCDD exposure at Seveso.

Three follow-up surveys from 1976 to 1985 were carried out on 193 subjects who developed chloracne following the Seveso accident (1976). A comparison group, age and sex matched, was selected randomly from the list of residents of the town of Varedo (in the same health district but out of the dioxin-contaminated zone). At each follow-up a questionnaire was administered and biochemical tests, skin examination, and electrophysiologic measurements were performed. Biochemical indicators of hepatic function and nerve conduction studies did not show significant differences either between groups or for temporal trends. Chloracne was shown to be clinically reversible: all the chloracne cases (except for one subject) clinically recovered by 1983. The discrepancy between our results and those from other previous experiences can be related to a different type of exposure, the young age of the target population, and the interval since exposure.

Accidents↗

PubMed1985

Problems in the assessment of human exposure to tetrachlorodibenzodioxin (TCDD): the marker chloracne.

An epidemiological study, aiming to assess the extent of the exposure to tetrachlorodibenzodioxin (TCDD) of the population involved in the Seveso accident, needs an effective information system, able to answer the questions usually asked--such as: why? what? who? where? when? how long?--and therefore concerning the wide range of the expected events, from the early cases till the ones expected in the long term. The paper is concerned with evaluation of possible use of chloracne as indicator of human exposure to TCDD, taking into account from one hand chloracne itself (i.e. its latency period, sensitivity, specificity, predictive value of diagnosis, etc) and, from the other, the development of the observational process. Moreover, the paper points out the role of the dermatological findings as representative--more than and before the other clinical findings--of the exposure conditions in the polluted area. The group of subjects classified as "chloracne" by the end of the second screening (May, 1977) included 187 cases, 164 of which were children 0-14 yrs old by the 10th of July 1976; 34 out of 164 were diagnosed in September-December 1976, the other 130 were diagnosed within the screening program. The results of a survey concerning their exposure data, clinical and laboratory findings are detailed. Finally, some remarks are made related to the quality of data. The authors emphasize that the reliability of assessment of health status of the exposed population depends not only upon a comprehensive a posteriori analysis of the different sets of clinical findings, but also upon the degree of integration of the professional staffs involved at operational levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗

PubMed1991

Blood levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in chemical workers after chloracne and in comparison groups.

Nine production workers with a history of chloracne from exposure to polychlorinated dibenzo-p-dioxins (PCDDs) in 1971-1973 had a median level of 340 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) per gram blood lipid (range 98-659 pg/g) in 1990. This was significantly higher than blood levels in 4 reference subjects without chloracne and no known exposure from the same plant (median 18, range 8-28 pg/g) and in 17 external referents (median 16, range less than 5-23 pg/g). We therefore consider chloracne to be a reliable indicator of heavy dioxin exposure in a cohort of herbicide production workers and will use its former presence in 159 cases as a substitute for exposure when investigating cancer morbidity and mortality in a multicenter cohort study.

Acne Vulgaris↗

PubMed2002

Chloracne: histopathologic findings in one case.

BACKGROUND: Chloracne is an acneiform eruption due to poisoning by halogenated aromatic compounds having a specific molecular shape. This condition is always a symptom of systemic poisoning by chemical chloracnegens and not just a cutaneous disorder. METHODS: We have studied a patient with severe chloracne who showed cutaneous lesions involving mostly the face and the axillae. RESULTS: Histopathologic study of the facial lesions demonstrated that almost every vellus hair follicle was involved, showing a dilated infundibulum filled by a keratotic plug. This keratotic material was mostly composed of orthokeratotic basket-weave basophilic corneocytes, namely infundibular keratin, although there were also some dilated infundibula containing eosinophilic laminated or granular sebum at their center. Small infundibular cysts were more numerous than comedones. Mature and well-developed sebaceous glands were seen at the base of many of the dilated infundibula and no squamous metaplasia of the sebaceous glands or ducts could be demonstrated. Hyperpigmentation of the lesions resulted from hyperproduction of melanin by a normal number of melanocytes along the basal layer of the epidermis and infundibular epithelium. Abundant melanin granules also impregnated the corneocytes of the infundibular plugs. CONCLUSIONS: Our findings support the notion that tiny infundibular cysts rather than comedones represent the basic lesions of chloracne.

Acneiform Eruptions↗

PubMed1989

Incidence of chloracne among chemical workers potentially exposed to chlorinated dioxins.

Company medical charts were reviewed for 2192 chemical workers who were potentially exposed to chlorinated dioxins during 1940 to 1982 to determine whether they were ever diagnosed as having chloracne. Nearly 16% of the 2072 workers with medical records were found to have been so affected. The incidence of chloracne was noted to have been highest among the youngest workers, and among those who worked in the production of chlorinated phenols rather than with products derived from those materials. Chloracne incidence was found to increase with several measures of intensity and cumulative dose of tetra- and hexa- to octachlorinated dioxins, but these analyses were hampered somewhat by the limitations of both the exposure and medical outcome data.

Acne Vulgaris↗

PubMed1990

Chloracne. Clinical manifestations and etiology.

Chloracne is a rare but important acneiform eruption often associated with the ingestion of chlorinated phenolic agents such as dioxins with subsequent toxicity from these chemicals. Clinically, chloracne can be distinguished from acne vulgaris by the distribution and appearance of the lesions and by taking a detailed history. In some instances, it may be associated with particularly xerotic skin, pigmentation, follicular hyperkeratosis, conjunctivitis, and actinic elastosis. Histologically, the primary lesion is a follicular plug containing keratinous material. Chloracne is difficult if not impossible to treat adequately and once present, may persist for years. Consequently, good hygiene, safe manufacturing processes so that no inhalation or skin contact is possible, and the elimination of atmospheric contamination are all necessary in the prevention of this potentially debilitating disease.

Age Factors↗

PubMed1987

[Follow-up of patients with chloracne in the Seveso area].

Three follow-up surveys from 1976 to 1985 were carried out on 193 subjects who developed chloracne following the Seveso accident (1976). A comparison group, age and sex matched, was selected randomly from the municipal list of Varedo (in the same health district but out of dioxin polluted zone). At each follow-up a questionnaire was administered and biochemical tests, skin examination and electrophysiologic measurements were performed. Biochemical indicators of hepatic function and nerve conduction studies did not show either significant differences between groups or temporal trends. Chloracne was shown to be clinically reversible: all the chloracne cases (except for one subject) clinically recovered by 1983. The discrepancy between our results and the previous experiences can be related to: different type of exposure, target population and interval since exposure.

Accidents, Occupational↗

PubMed1994

Chloracne. Some recent issues.

Chloracne is an acneiform skin eruption that is still the most sensitive indicator of systemic poisoning caused by chemicals belonging to the group of chlorinated polycyclic aromatic hydrocarbons. Generally these chemicals are known as dioxins, dibenzofuranes, and PCBs. The cause of chloracne is probably interference of these chemicals with vitamin A metabolism in the skin, resulting in disturbances of the epithelial tissues of the pilosebaceous duct. A study of workers in a factory where chloracne is endemic is described. The product manufactured, pentachlorophenol, a wood preservative, was found to be contaminated with dioxins (congeners of TCDD) and dibenzofuranes. Blood levels of these chemicals in affected workers are given, along with supporting evidence of disturbances in vitamin A (retinoid) metabolism as demonstrated in skin biopsies.

Acne Vulgaris↗