CIL and Italy...A Relationship that Began 40 Years Ago

On July 10, 1976, an explosion at the ICMESA chemical plant released a thick, white cloud that quickly settled on the town of Seveso in northern Italy. In the cloud was 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), a highly toxic material. First, animals began to die. Four days later, people began to feel ill effects – nausea, blurred vision, and, especially among children, the disfiguring sores of chloracne. It wasn’t until weeks later that the town itself was evacuated. Thousands of animals in the contaminated area died, and many thousands more were slaughtered to prevent TCDD from entering the food chain.¹

The disaster at the ICMESA (Industrie Chimiche Meda Società Azionaria) plant 40 years ago marks one of the earliest and most significant publicized dioxin contamination events in environmental history. In the early days following the accident significant work was conducted on health effects to humans and animals tragically exposed to the toxic cloud. However, because of limitations in analytical methodology, early studies focused only on epidemiological effects including analysis on the hepatic, lung, bone, and immune system function, on lipid metabolism, on the nerve systems, as well as studies on the ratio of spontaneous abortions and on the presence of congenital malformation events.² It was at this point that Dr. Joel Bradley, founder of Cambridge Isotope Laboratories (CIL), initially became involved, providing ¹⁴C-radioisotope labeled dioxin for tracer studies, and a ³⁷Cl-stable isotope-labeled dioxin internal standard. It wasn’t until several years later, however, that direct analysis of dioxin levels in humans could be accurately assessed.

In the early 1980s CIL was working with Dr. Larry Needham and Dr. Don Patterson of the US Centers for Disease Control (CDC) in Atlanta to develop standards for their analytical methods. Throughout the decade CIL provided many high purity native and ¹³C-stable isotope-labeled dioxins, dibenzofurans, and PCBs to support their work. In 1987 Dr. Patterson published a report on levels of dioxin in US military personnel exposed to “Agent Orange” in Vietnam. This study was notable for its use of blood serum samples for determination of dioxins in exposed humans. While earlier studies on dioxins in humans utilized adipose tissue samples, a high-fat tissue in which the lipophilic dioxins accumulate, collecting the tissue was extremely invasive and led to limited participation. For the new study, the CDC decided to work with blood serum samples as they are easier to obtain, though the small volume of sample available and the lower amounts of dioxin found in low-lipid serum presented a major challenge. To achieve the needed analytical sensitivity, the CDC employed the use of high-resolution mass spectrometry and many of CIL’s isotopically labeled internal standards.

The CDC serum method would provide a new opportunity to analyze dioxin levels in the people of Seveso. Local researcher Professor Paulo Mocarelli, director of the Department of Clinical Pathology at the University of Milan, who had wisely taken blood samples of the local population in the early days of the accident and frozen them for future use, was thus able to directly study dioxin levels in the exposed population. The new data was included in the overall study and confirmed the levels of exposure within the discharge area from the ICMESA plant explosion.

Recently the International Symposium on Halogenated Persistent Organic Pollutants (informally known as the “DIOXIN” conference), an annual international meeting for researchers from around the world, was held in the beautiful city of Firenze, Italy. The timing and location of the meeting was not coincidental, marking 40 years after the devastating accidental release of over 1 kg of “dioxin” (with some estimates ranging as high as 130 kg³) into the air less than 20 kilometers from the metropolitan city of Milan. In fact, the origins of the conference can be traced to a 1979 gathering of scientists in Rome to discuss the Seveso accident, and specifically the release of “dioxin” (hence the origins of the conference name). At the 2016 conference, CIL took special pride in recounting the partnership between our company and researchers in Italy 40 years earlier, and the important role we held in helping Professor Mocarelli develop techniques to determine direct dioxin exposure levels in the local populace.