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Success stories Published on 26-Feb-2004

DIOXIN RISK ASSESSMENT
Title How dangerous are dioxins?

Dioxins cause cancer and distort child development, so their presence in food generates substantial public fear. But scientifically derived safety thresholds differ by orders of magnitude, and there is international confusion about how to regulate these pollutants. Six European research centres have worked together for the past three years to unravel the mysteries of dioxin toxicity and to help establish precisely what level of exposure is safe. The research indicates that developmental effects, rather than cancer-causing properties, should be used to assess the safety of dioxins.

Baltic herring are high in dioxins due to pollution of the Baltic Sea.
Baltic herring are high in dioxins due to pollution of the Baltic Sea.
Dioxins are toxic organic pollutants produced by poor incineration, for example in power plants, or by chemical industrial processes. Several chemical accidents in the 1970s exposed local populations to high levels of dioxin. The most famous was the Seveso incident, when an explosion at a chemical plant in Italy created a cloud containing the most potent of all dioxins, tetrachlorodibenzodioxin, or TCDD. More recently, in 1999, dioxins in chicken and pork feed led to a ban on the export of Belgian meat products.

Dioxins are long-lived in the environment, and accumulate in fatty tissue. High levels have been found in human breast milk, and in fatty fish such as herring from the heavily polluted Baltic Sea. They have serious toxic effects, inducing cancer and causing developmental abnormalities such as cleft palate in animals.

How much is too much?
It is essential that dioxin levels in food be regulated at safe levels, but so far no one can agree on exactly what level is safe. Two years ago, an EU safety threshold of 10pg of TCDD equivalent/kg/day was reduced by more than half, following a World Health Organisation risk assessment. But the US Environmental Protection Agency calculated a safe intake of 0.0064 pg/kg/day, one part in 1 500 of the EU limit.

In a three-year project called Dioxin Risk Assessment, six academic groups from four countries affected by dioxin pollution have brought together European research on all aspects of dioxin toxicity, from cellular mechanism to environmental exposure. The project has shed light on the problems of dioxin risk assessment and made substantial progress towards a robust new calculation of safety levels.

Hamsters or guinea pigs?
The problem with dioxins is that their effects are varied, and different animals have very different sensitivities. You cannot experiment on people to find out how much of a toxin causes damage, so safety levels are usually assessed using animal models, such as rats. But it takes a thousand times more dioxin to kill a hamster than to kill a guinea pig. “We need to know if humans are hamsters or guinea pigs,” says project leader, Jouko Tuomisto, of Finland’s National Public Health Institute (KTL). “No one has the exact answer yet.” Since the mechanisms of dioxin toxicity are poorly understood, it is hard to see why hamsters and guinea pigs should have different responses.

Scientists from Stockholm and Lithuania worked on the genetics of animal response to dioxins. Which genes are activated by dioxin, and what are their effects? Exactly how different is the genetic sequence of an animal that is resistant to dioxins? A major finding was that animals with different dioxin receptor genes have the same developmental defects at low doses, but can be more or less sensitive to cancer at high doses. So the carcinogenic effects are produced by a fundamentally different and less direct mechanism than the low-dose effects. Oxygen radicals, created by other genes switched on by the dioxin receptor gene, and damaging the liver, could be responsible. This means that risk assessments based on extrapolating high-dose effects such as cancer may have over-estimated the toxicity of dioxins at low levels.

Bad teeth, but not cancer
Victims of the Seveso accident suffer from a range of dental problems – abnormal enamel, missing incisors and impacted canines.
Victims of the Seveso accident suffer from a range of dental problems – abnormal enamel, missing incisors and impacted canines.
Scientists at the University of Helsinki recently discovered dioxin poisoning could cause tooth defects, particularly in the molars. KTL studied the effect of dioxins on tooth development in young rats, and found their teeth were damaged by levels equivalent to those found in some European mothers’ breast milk. The Helsinki group worked closely with scientists from Milan to study the teeth of people involved in the Seveso accident, and found dental defects in those who were less than 9½ years old at the time.

The project included the first full-scale study of body dioxin levels in the general population in Finland. The good news is that levels are relatively low and still falling. Older people carry higher levels than young people, probably because dioxin levels in the environment were higher in the 1970s and 80s. Bad news for Baltic fishermen, though. Their bodies contain as much dioxin as people affected by the Seveso accident. The research looked at whether body dioxin levels were associated with the likelihood of suffering from a certain type of cancer, soft tissue sarcoma. Surprisingly, people with high levels of dioxin were less likely to have this cancer – the opposite of the anticipated result. “So present dioxin levels do not pose a risk of this kind of cancer,” says Tuomisto.

The crux of the matter is that dioxin effects occur in two distinct areas – low-dose direct effects, which interfere with development, and high-dose indirect effects, such as lethal cancers. “Developmental effects, not carcinogenicity, should be used as a basis for risk assessment,” Tuomisto stresses. “These effects are more sensitive, so limits based on them will take care of cancerous effects. Also, we can use animal models to evaluate them because mammals do not differ much in their low-dose effects.”

KTL has funding from the Academy of Finland to draw this work together in a risk assessment that defines a safe level of dioxin intake. “The difficulty now is to weigh up the risk from dioxins against the cardiovascular health benefits of eating fish. Should we be telling people in Finland not to eat fish?” Tuomisto asks. It is a tricky question.




  • Title
    Comprehensive risk analysis of dioxins: development of methodology to assess genetic susceptibility to developmental disturbances and cancer (DIOXIN RISK ASSESSMENT)
  • Reference
    QLK4-CT-1990-01446
  • Programme
    FP5: Quality of Life
  • Contact
    Professor Jouko Tuomisto
    Kansanterveyslaitos, National Public Health Institute
    Finland
    Fax: +358 17 201 265
    jouko.tuomisto@ktl.fi
  • Partners
    National Public Health Institute, Finland
    Institute of Dentistry, University of Helsinki, Finland
    Department of Cell and Molecular Biology, Karolinska Institute, Sweden
    Institute of Biotechnology, Lithuania
    Linkoeping University, Sweden
    Azienda Ospedaliera ‘Ospedale Civile di Vimercate’, Italy