Seveso Disaster, and the Seveso and Seveso II Directives 1 Seveso Disaster, and the Seveso and Seveso II Directives Pertti J Hakkinen but possibly other toxic substances as well.’’ They & 2005 Elsevier Inc. All rights reserved. requested the authorities to warn the population, and samples were sent by courier for examination to a company, Givaudan SA, in Switzerland. Givaudan SA, once one of ICMESA’s main customers, had tak- The Seveso Disaster en over ICMESA as a subsidiary in 1969. The Seveso disaster began on July 10, 1976 at Two days after the disaster, nearby residents were the Industrie Chimiche Meda Societa` Azionaria warned not to eat any vegetables from their gardens. (ICMESA) chemical plant in Meda, Italy. This event Four days after the disaster, the Technical Director of became internationally known as the Seveso disaster, Givaudan in Geneva informed the Technical Director after the name of the most severely affected commu- of ICMESA that the samples contained traces of nity. An increase in pressure due to an exothermic TCDD. Authorities were told much later about the reaction in a 2,4,5-trichlorophenol-production reac- TCDD. The Seveso disaster resulted in the highest tor caused the rupture disk of the safety valve to known TCDD exposure to residential populations, burst. About 3000 kg of chemicals were released into and has possibly been the most systematically studied the air. The release included 2,4,5-trichlorophenol, dioxin contamination incident in history. used in the manufacture of herbicides, and possibly The first sign of human health problems was burn- up to 30 kg of the dioxin TCDD (2,3,7,8-tetrachloro- like skin lesions, appearing on children after the ac- dibenzo-p-dioxin). Dioxin first came to widespread cident. Beginning in September of 1976, chloracne, a public notice during the Vietnam War, when it was severe skin disorder usually associated with dioxin, identified as a component of the defoliant Agent broke out on some people who were most exposed. Orange. Dioxin has also been considered to be the Authorities began an investigation five days after the most toxic human-made substance. accident, when large numbers of local animals such The chemicals released into the air from the chem- as rabbits began to die. After a linkage to dioxin was ical plant near Milan in northern Italy were carried made, over 700 hundred people living closest to the southeast by the wind towards Lake Como. The plant were evacuated within 3 weeks after the acci- dioxin cloud contaminated a densely populated area dent. In all, up to 2000 people were treated for about 6 km long and 1 km wide downwind from dioxin poisoning. Approximately 4% of the local the site. The four most impacted municipalities in- farm animals died, and B80 000 additional animals cluded Seveso (a 1976 population of 17 000), Meda were killed to prevent contamination from filtering (19 000), Desio (33 000), and Cesano Maderno up the food chain. (34 000). Two other municipalities, Barlassina The Seveso disaster areas were divided and sub- (6000) and Bovisio Masciago (11 000), were subject divided based on soil contamination levels. Zone A, to postaccident restrictions. Health monitoring was the most contaminated area with more than 50 mgof extended to a further five municipalities. The entire TCDD per square meter and covering 110 ha, was affected area is part of the Brianza, one of the completely evacuated and fenced-off with entry pro- wealthiest and most industrialized regions of Italy. hibited. Zone A was later turned into a park, the The economy of this area at the time of the disaster Seveso Oak Forest. In the next-most contaminated depended on small workshops and industries, mainly areas, zone B (between 5 and 50 mgmÀ 2) and zone R engaged in manufacturing furniture. (below 5 mgmÀ 2), farming as well as consumption of The Seveso disaster had a traumatic effect on the local agricultural goods and meats were strictly pro- minds of the local populations because its seriousness hibited. was recognized only gradually. People elsewhere in Professor Paolo Mocarelli of the University of the world also experienced heightened concern about Milano-Bicocca’s Hospital of Desio was put in charge chemical exposures and risks and the need for tighter of a laboratory setup two weeks after the accident to regulation of hazardous chemical manufacturing. test people for health problems. Dr. Mocarelli’s lab- The accident was not immediately noticed since no oratory has conducted neurological, obstetric, and one was at the plant when it happened. One day other tests that have surpassed 1 million in number, later, ICMESA managers informed local authorities and Dr. Mocarelli decided to save one sample of of the escape of a ‘‘cloud of herbicide that causes blood from each person just in case it would be pos- harm to agriculture,’’ stating that ‘‘in all likeli- sible to measure very low levels of TCDD in small hood the aerosol mixture which escaped consists of blood samples someday. This became possible in sodium trichlorphenate, caustic soda, and solvent, 1987, and Dr. Mocarelli has worked with the US 2 Seveso Disaster, and the Seveso and Seveso II Directives Centers for Disease Control and Prevention to anal- Further research on the children of victims of the yze the thousands of samples and to try to associate disaster is being conducted, as is research focusing on the levels with health effects. Reconstruction of dioxin’s long-term carcinogenic properties. For ex- the disaster using the samples taken over time has ample, 25 years after the Seveso disaster, human milk helped clarify how long dioxin stays in the human from mothers in Seveso was found to have TCDD body, and the different effects it has on children and concentrations more than twice as high as those in adults. central Milan and elsewhere in the areas near Seveso. One toxic effect of the Seveso dioxin exposure This suggests that breastfed infants in Seveso might was on reproduction. In the first 7 years after the have appreciable amounts of TCDD in their body accident, a very high proportion of females (46 fat; however, the health consequences remain to be females compared to only 28 males) were born to determined. parents who were exposed to the chemical cloud. In addition to monitoring victims and offspring of This was the first time a chemical had been obser- the accident, another type of monitoring that con- ved to change the sex ratio, implicating dioxin as a tinues concerns the Seveso Oak Forest’s two large hormone disrupter. TCDD is associated with in- concrete tanks lying beneath the surface. These tanks creased fetal loss and reduced birth weight in animal are the resting place of the top 40 cm of soil removed studies. after the disaster, and also are the final resting place The Seveso Women’s Health Study (SWHS) is a of the contaminated animals that were slaughtered, retrospective cohort study of people who resided in and the factory (disassembled brick by brick by the most contaminated areas, zones A and B. Serum workers in protective suits) and other buildings samples collected near the time of the explosion were exposed to the cloud. The area around the tanks is analyzed for TCDD. Also analyzed were pooled monitored for leaks, and the soil is said to now serum samples collected in 1976 from females who have lower dioxin levels than in average areas. The resided in the ‘‘unexposed’’ zone to assess concurrent area is now a place where families can gather and background exposures to other dioxins, furans, and animals have returned to the park and adjacent polychlorinated biphenyls (PCBs). The youngest chil- nature reserve. dren had the highest TCDD levels, which decreased After the Seveso disaster, investigation of the po- with age at explosion until B13 years of age and tential emission sources in the area and studies of were essentially constant thereafter. The zone of res- people not exposed to the cloud indicated that com- idence and age were the strongest predictors of bustion of wood residues from furniture factories TCDD level. Chloracne, nearby animal mortality, might be an additional and perhaps substantial local location (outdoors versus indoors) at the time of ex- source of dioxins, furans, and PCBs. plosion, and consumption of homegrown food were also related to serum TCDD levels. The serum pools The Seveso Directive from the ‘unexposed’ zone residents had TCDD con- centrations and average total toxic equivalent (TEQ) In 1982, the European Union’s Council Directive concentrations that suggested that the background 82/501/EEC on the major-accident hazards of cer- exposure to dioxins, furans, and PCBs unrelated to tain industrial activities, also known as the Seveso the explosion may have been substantial. Therefore, Directive, was adopted. The Directive was mostly the early SWHS studies that considered only TCDD designed to promote information flow and created exposure may have underestimated health effects due the requirement that each Member State (i.e., each to total TEQ concentrations. country belonging to the European Union) appoint a The early part of the SWHS looked at the relation Competent Authority to oversee safety issues. The of pregnancy outcome to maternal TCDD levels Seveso Directive was amended twice, following measured in serum collected shortly after the explo- major accidents at the Union Carbide chemical fac- sion. Ninety-seven pregnancies (10.9%) ended as tory in Bhopal, India in 1984 (a leak of methyl spontaneous abortions. TCDD was associated with a isocyanate caused thousands of deaths), and at the nonsignificant adjusted decrease in gestational age Sandoz chemical warehouse in Basel, Switzerland in and a 20–50% nonsignificant increase in the odds of 1986 (fire-fighting water contaminated with mercury, preterm delivery.