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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.
References
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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