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International Notes Preliminary Report: 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure to Humans -- Seveso, Italy

At approximately noon on Saturday, July 10, 1976, an explosion occurred during the production of 2,4,5-trichlorophenol in a factory in Meda, about 25 km north of Milan, in the Lombardia region of Italy. A cloud of toxic material was released and included 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Debris from this cloud fell south-southeast of the plant on an area of about 2.8 km2 (700 acres), including parts of the towns of Seveso, Meda, Cesano Maderno, and Desio. The size of the contaminated area was estimated primarily by measuring TCDD in the soil; additional criteria included the presence of dead animals (e.g., birds, rabbits, chickens) and detection of dermal lesions among persons in the area. The contaminated area was divided into three zones (A, B, and R) depending on the concentration of TCDD in the soil (Table 1). An additional zone, Zone S, outside the contaminated area was examined as a control zone.* Zone A, the most heavily contaminated section, was further divided into seven subzones, A1-A7, based on increasing distance from the factory. The total amount of TCDD deposited in the contaminated area was initially estimated at about 165 g (1); subsequently, it has been estimated to be at least 1.3 kg (2). Within 20 days of the explosion, the Italian authorities had evacuated the 211 families (735 persons) from the area later defined as Zone A and had taken immediate measures to minimize the risk of exposure to residents in nearby areas (primarily those in Zone B). The Italian authorities were assisted by several national and international technical commissions in assessing adverse health effects. Residents of zones A, B, and R underwent extensive medical examinations from 1976 to 1985; chloracne, detected in a small segment of the population, was the only abnormal finding (3-6). Only one potentially exposed person was measured for TCDD; she was a 55-year-old woman residing in a portion of Zone A (mean TCDD soil concentration of 185.4 Lgmg/m2), who died from pancreatic adenocarcinoma 7 months after the explosion. Her TCDD whole-weight levels varied from 6 parts per trillion (ppt) in blood to 1840 ppt in adipose tissue** (7). In April 1988, a group of U.S. and Italian scientists convened to further examine the Seveso TCDD incident. Since more than 30,000 serum or plasma samples (volumes of 1-3 mL) had been collected from residents of the four zones from the end of July 1976 through 1985 and stored at -30 C (-22 F), the group agreed to assess whether methodology developed at CDC to measure TCDD in human serum (8) could be used to measure TCDD in these low-volume samples. This methodology, a lipid-based measurement highly correlated with paired measurements of TCDD in adipose tissue (p = 0.98) (9), has been used to evaluate U.S. Army veterans (10), U.S. Air Force Operation Ranch Hand veterans (11), and occupationally exposed persons (D.G. Patterson, Jr., et al., unpublished data). The preliminary Seveso study evaluated serum samples from five Zone A residents who developed the most severe types (III or IV) of chloracne; four Zone A residents who did not develop chloracne or other health problems (in 1976, each was greater than or equal to15 years of age); and five persons from Zone S. All these samples had been collected in 1976 and were sent without identification to CDC for analysis. These samples were analyzed for TCDD (8) on both a whole-weight and a lipid basis, using triglycerides and total cholesterol data provided for those samples by the laboratory of the hospital of Desio-Milan to calculate total lipids. The TCDD levels detected are the highest ever reported in humans (Figure 1). The three highest levels are from children who developed chloracne. Levels for the other two chloracne cases were similar to those in residents without chloracne. TCDD was not detected in four of the five controls. In one control, a level of 137 ppt TCDD on a lipid basis was detected; this value may represent either an actual level or the detection of a residue of less than 1% from a sample analyzed immediately before this sample. Reported by: P Mocarelli, MD, Institute of General Pathology, Univ of Milan and Hospital of Desio, Milan; F Pocchiari, PhD, Instituto Superiore di Sanita, Rome. N Nelson, PhD, New York Univ Medical Center, New York, New York. Center for Environmental Health and Injury Control, CDC.

Editorial Note

Editorial Note: Little is known about TCDD exposures and adverse health effects in humans. However, these Seveso samples are unique in that they were taken in proximity of time to an acute human exposure to TCDD. Thus, they and the subsequent samples allow for correlating TCDD levels and adverse health effects, if any, and for determining the half-life of TCDD in humans. This population has no apparent adverse health effects other than chloracne (4). These serum measurements confirm overt exposure to TCDD in those persons tested who resided in Zone A. The levels are of the same magnitude as those found in occupational studies (12,13) that estimate initial TCDD levels by extrapolating to the time of last exposure (by assuming first-order kinetics and a half-life of 7 years) (14). Although the three highest TCDD serum levels occurred in persons who developed chloracne, no threshold level for chloracne is obvious.


  1. Kimbrough RD, ed. Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins and related products. New York: Elsevier/North-Holland Biomedical Press, 1980:322-48. 2.Cerlesi S, Di Domenico A, Ratti S. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) persistence in the Seveso (Milan, Italy) soil. Presented at Dioxin '88, Umea, Sweden, August 21-26, 1988. 3.Mastroiacovo P, Spagnolo A, Marni E, Meazza L, Bertollini R, Segni G. Birth defects in the Seveso area after TCDD contamination. JAMA 1988;259:1668-72. 4.Mocarelli P, Marocchi A, Brambilla P, Gerthoux P, Young DS, Mantel N. Clinical laboratory manifestations of exposure to dioxin in children: a six-year study of the effects of an environmental disaster near Seveso, Italy. JAMA 1986;256:2687-95. 5.Caramaschi F, Del Corno G, Favaretti C, Giambelluca SE, Montesarchio E, Fara GM. Chloracne following environmental contamination by TCDD in Seveso, Italy. Int J Epidemiol 1981;10:135-43. 6.Pocchiari F, Silano V, Zampieri A. Human health effects from accidental release of tetrachlorodibenzo-p-dioxin (TCDD) at Seveso, Italy. Ann NY Acad Sci 1979;320:311-20. 7.Facchetti S, Fornari A, Montagna M. Distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the tissues of a person exposed to the toxic cloud at Seveso. Forensic Environ Appl 1981;1:1406-44. 8.Patterson DG Jr, Hampton L, Lapeza CR Jr, et al. High-resolution gas chromatographic/high- resolution mass spectrometric analysis of human serum on a whole-weight and lipid basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Anal Chem 1987;59:2000-5. 9.Patterson DG Jr, Needham LL, Pirkle JL, et al. Correlation between serum and adipose tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in 50 persons from Missouri. Arch Environ Contam Toxicol 1988;17:139-43. 10.CDC Veterans Health Studies. Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels in US Army Vietnam-era veterans. JAMA 1988;260:1249-54. 11.CDC. Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels in Air Force Health Study participants--preliminary report. MMWR 1988;37:309-11. 12.Fingerhut M, Sweeney M, Patterson D, Marlow D, Hornung R, Halperin W. Levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the serum of U.S. chemical workers exposed to dioxin-contaminated products. Presented at Dioxin '88, Umea, Sweden, August 21-26, 1988. 13.Beck H, Eckart K, Mathar W, Ruhl C-S, Wittkowski R. Levels of PCDDs and PCDFs in adipose tissue of occupationally exposed workers. Presented at Dioxin '87, Las Vegas, Nevada, October 4-9, 1987. 14.Pirkle JL, Wolfe WH, Patterson DG Jr, et al. Estimates of the half-life of 2,3,7,8- tetrachlorodibenzo-p-dioxin in Ranch Hand Veterans. J Environ Health Toxicol (in press). *Zone R was originally thought to be a reference zone, but on subsequent detection of TCDD concentrations in soil, Zone S was added. **Levels of TCDD in serum or adipose tissue of the general population are less than 20 ppt.

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