Environmental Chemicals That Accumulate in Fat

Background A crucial factor in evaluating the risk of dioxins, and related endocrine disruptor compounds (dioxins for short) in the human population is the accumulation of these chemicals in the human body. The "half-life" of the prototypical dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the human is estimated as ~7 years, as such accumulation of these chemicals in the body is an important issue. These lipophilic chemicals accumulate in adipose tissue, and (in a congener-dependent fashion) in the liver, so an accurate estimation of human body burden requires knowledge of their concentrations in liver, and adipose tissue. The concentration of these endocrine disruptors in blood is an essential piece of information for understanding how these chemicals dispose between the organs, and for calibrating tissue concentrations to the most common measurement of dioxins and in humans, which is a measurement of dioxins in blood.

However, human data on tissue background levels is extremely limited, and I am unaware of any studies in UK populations, although there are several European studies looking at blood levels of dioxins. There is one study in an American population, which features some people with a history of (presumably occupational) exposure to TCDD, but this was published in 1988, when background levels were considerably higher. Adipose tissue concentrations were 83 ± 178 ng of TCDD per kg lipid weight. There are three recent studies from Japan, spanning 1999-2007, so these should be indicative of the much lower current background level of dioxin exposure. Adipose tissue concentrations were 139 ng of TEQ (total dioxin-like compounds) per kg lipid weight (5.4 ± 4.6 ng of TCDD per kg lipid weight). However, given the different dietary habits of Japanese populations, compared to European populations, these estimates may differ considerably from UK values. Thus determining human tissue concentrations of dioxins is an important issue for assessing the risk to public health from these compounds, and this information is currently lacking for European populations. This information will also guide and inform the necessity fro continued measures to reduce the environmental dioxin levels in the UK.

A further topical issue relates to the body burden of dioxins in obese individuals, since an increased BMI is associated with increased blood concentration of dioxin and other lipophilic contaminants, and the impact of weight reduction upon the concentration and amount of dioxins in the body is unknown. There is the possibility that weight reduction could result in the release of dioxins from adipose tissue depots, as the adipose tissue is lost, and that the circulating dioxin levels (and other toxic lipophilic chemicals) could increase if the dioxin is maintained in the body, or alternatively as adipose tissue is lost dioxins may be concentrated in the remaining adipose tissue. Although there is some evidence that weight loss is associated with an increase in some lipophilic contaminants, dioxins have not been examined to see if these are increased after weight loss. If dioxin concentrations in lipids increase following weight loss, it will also be useful to evaluate whether those increased concentrations persist or rapidly equilibrate, and the data from this study may allow some evaluation of that question as well. The toxicodynamics information will allow estimation and prediction of what will happen to other lipophilic chemicals in the body.

Aims

Primary outcomes: