Dioxins

5. How can dioxin exposure be linked to health effects?

• 5.1 Is there a known relationship between dioxin exposure and cancer?
• 5.2 Can a model predict non-cancer effects?
• 5.3 How are dioxins mixtures accounted for?

5.1 Is there a known relationship between dioxin exposure and cancer?

5.1.1 Lifetime dose-effect relationships for cancer were derived from workers moderately exposed to dioxins. The results suggest that a continuous exposure at work to between 2 and 7 pg TCDD per kg body weight per day increases the risk of cancer by 1%. Over a lifetime, this would result in a body burden of 3 000 to 13 000 pg TCDD per kg body weight. More...

5.1.2 To compare humans and animals, only body burdens are relevant; indeed, rats and mice need to ingest much more dioxins than humans to reach the same body burden.

Two approaches were used to evaluate cancer risks from experimental animal studies and led to very different results. The first one is based on the knowledge of mechanisms that increase cell multiplication, inducing liver tumors in female rats. It concluded that a body burden of 2 600 pg per kg body weight increases the risks of cancer by 1%.

A second, graphical model used the results of a series of cancer studies on rats and mice; it concluded that a body burden of 10 000 to 746 000 pg per kg body weight increases the risk of cancer by 1%. More...

5.2 Can a model predict non-cancer effects?

Currently, models cannot adequately predict non-cancer effects in humans, partly because the mechanisms of action are not yet fully understood. However, they may provide additional insights in understanding the effects observed in experiments. More...

5.3 How are dioxins mixtures accounted for?

5.3.1 Dioxins are generally found in mixtures containing several kinds of dioxins and dioxin-like compounds, each having its own degree of toxicity.

Therefore each is attributed a specific toxic factor called Toxic Equivalency Factor (TEF). This factor indicates a relative toxicity compared to the most toxic dioxin 2,3,7,8-TCDD, which is given a reference value of 1 (see table 3). The TEF scheme refers only to adverse effects (e.g. cancer) following interactions with the cellular Ah-receptors Other toxic effects of dioxins and dioxin-like compounds cannot be quantified by this method.

The overall toxicity of a dioxin mixture is calculated by:

1. multiplying the individual quantity of each compound by its specific TEF value and
2. summing the values obtained to get a total TCDD "toxic equivalent" (TEQ) for the mixture.

TEF values are attributed on the assumptions that a compound must:

• show a structural relationship to the dioxins (PCDD's and PCDF's).
• bind to the dioxin cellular Ah-receptors.
• cause effects via this Ah receptor.
• be persistent and accumulate in the food chain.

More...

5.3.2 In the majority of experimental studies, the effects are additive and the TEQ calculation works well. However some non-additive effects of PCDD, PCDF and PCB mixtures have been reported. These may be due to effects of the individual compounds on each others metabolism and, for some PCBs, to other mechanisms of action than those occurring via the Ah-receptor.

When used with caution, the TEF approach is a valuable tool for expressing a daily intake for most dioxins and comparing it to the Tolerable Daily Intake (TDI). More...