Relevant data as well as limitations for assessing possible effects of polyhalogenated dibenzo-p-dioxins and dibenzofurans on the human immune system

摘要

Numerous animal studies have been performed on the effects of PHDDs/PHDFs on varius immunological components and functions. Teh effects of such substances have also been studied by several authors in a few groups of human volunteers with higher body burdens than the not expecially exposed general population. In most of these clinical trials, persons exposed at the workplace have been studied. Most of these workers were exposed to a multitude of chemicals, with PHDDs/PHDFs often being trace contaminants. The exposures regularly occurred decades before the studies were conducted, and the PHDD/PHDF body burdens had already declined considerably. It must be taken into account that the effects observed in experimental animals were reversible. Therefore, it is likely that also in humans (just as in experimental animals) only the effects caused by the actual, but already decrease,d body burdens or possibly irreversible alterations can be revealed. Some minor, but statistically significant, deviations from the reference range were reported in some of the trials, but only trends could be found, with the values for almost all volunteers staying within the reference range. Furthermore, no biomarker was consistently found in more than one study (with the possible exception of increased complement concentrations in serum of highly exposed children). Statistical associations of immunological variables with the PHDD/PHDF body burdens (including regressio nanalyses) were extremely weak, if present at all. The influence of confounders (age, smoking, etc.) was generally much more pronounced than a possible effect of hte environmental exposure. Our data on residents of the Seveso area exposed to TCDD in 1976 have not yet been fully evalauted. However, the overall assessment certainly does not reveal pronounced negative deviation from the reference range, which is in accord with our studies on other groups of PHDD/PHDF exposed persons. Of special interest is the result that in a group of persons exposed to high TCDD levels, a prolonged response to tetanus vaccination was found. This certainly is not a "toxic" effect. Although not all endpoints studied in animals can be assessed in humans (e.g., resistance against infectiosn) with the same accuracy, the variables evaluated in our studies (e.g., possible changes in the expression of surface receptors on lymphocytes) are directly comparable in nonhuman primates and in humans (using exactly the same method). For the volunterrs included in the trials, actual TCDD body burdens ( as judged from concentrations in fat) were at least 50 times higher (up to 500 ppt) than those inducing effects on the immune system of a nonhuman primate (10 ppt). With respect to the variables evalauted, there is no evidence htat the human immune system is especially vulnerable to the adverse action of PHDDs/PHDFs. If there are deviations from the reference range, it concerns only a few volunteers while the majority of highly exposed persons show no effect. No informaiton is available on possible polymorphisms. Therefore, at present there is also no evidence tht variables of immunological components or functions can be taken as early and reliable indicators of an eposure to PHDDs/PHDFs (biomarkers of exposure or of effects).