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

Numerous animal studies have been performed on the effects of PHDDs/PHDFs o n various immunological components and functions. The effects of such subst ances have also been studied by several authors in a few groups of human vo lunteers with higher body burdens than the not especially exposed general p opulation. In most of these clinical trials, persons exposed at the workpla ce have been studied. Most of these workers were exposed to a multitude of chemicals, with PHDDs/PHDFs often being trace contaminants. The exposures r egularly occurred decades before the studies were conducted, and the PHDD/P HDF body burdens had already declined considerably. It must be taken into a ccount that the effects observed in experimental animals were reversible. T herefore, it is likely that also in humans (just as in experimental animals ) only the effects caused by the actual, but already decreased, body burden s or possibly irreversible alterations can be revealed. Some minor, but sta tistically significant, deviations from the reference range were reported i n some of the trials, but only trends could be found, with the values for a lmost all volunteers staying within the reference range. Furthermore, no bi omarker was consistently found in more than one study (with the possible ex ception of increased complement concentrations in serum of highly exposed c hildren). Statistical associations of immunological variables with the PHDD /PHDF body burdens (including regression analyses) were extremely weak, if present at all. The influence of confounders (age, smoking, etc.) was gener ally much more pronounced than a possible effect of the environmental expos ure. Our data on residents of the Seveso area exposed to TCDD in 1976 have not yet been fully evaluated. However, the overall assessment certainly doe s not reveal pronounced negative deviations 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 h igh TCDD levels, a prolonged response to tetanus vaccination was found. Thi s certainly is not a "toxic" effect. Although not all endpoints studied in animals can be assessed in humans (e.g., resistance against infections) wit h the same accuracy, the variables evaluated in our studies (e.g., possible changes in the expression of surface receptors on lymphocytes) are directl y comparable in nonhuman primates and in humans (using exactly the same met hod). For the volunteers 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 pri mate (10 ppt). With respect to the variables evaluated, there is no evidenc e that the human immune system is especially vulnerable to the adverse acti on of PHDDs/PHDFs. If there are deviations from the reference range, it con cerns only a few volunteers while the majority of highly exposed persons sh ow no effect. No information is available on possible polymorphisms. Theref ore, at present there is also no evidence that variables of immunological c omponents or functions can be taken as early and reliable indicators of an exposure to PHDDs/PHDFs (biomarkers of exposure or of effects).