Extrapolation and Modeling. Thomas B. Starr, ENVIRON Corporation, Arlington, VA
Dioxin exposure clearly causes a variety of toxicologic effects in laboratory animals, and scientists generally agree that most of theses effects are mediated through the Ah receptor. However, the exposures estimated to give rise to human background body burdens are far smaller than those known to cause toxicity, and thus the pivotal issue is whether adverse human health effects can reasonably be expected to occur at or near current background body burdens. Determining the appropriate metric (body burden vs. delivered dose) for measuring exposures for purposes of risk assessment is difficult because acute dioxin administration produces higher peak concentrations than exposure to the same total dose in small daily increments. The use of toxic equivalency factors (TEFS) requires that all of these compounds act in an additive manner. However, even if TEFs for some congeners are additive for specific endpoints, the data are currently insufficient to support the extrapolation to equivalent TEFs and their additivity for other endpoints.
Receptor theory predicts that binding of dioxins to the Ah receptor may be linear at very low exposures, so some binding may occur even at vanishingly small doses. However, this theory does not predict the shape of the dose-response curve for any biochemical or toxic response. In particular, it does not predict that responses will result whenever binding occurs. Thus, responses may exhibit thresholds.
With the exception of chloracne, evidence for effects in humans is quite limited. For cancer, where positive associations have been observed, they are weak, even among persons with presumed heavy exposure arising from chemical manufacturing processes or industrial accidents. Adverse developmental effects in rodents and humans show fundamental inconsistencies. Endocrine disruption has been cited as another adverse outcome of dioxin exposure, but the evidence is for high doses and even then is very weak. Finally, there is no evidence that dioxin exposure compromises immune function in humans. Thus, these limited observations may be suggestive, but they are not sufficient to conclude that people are at risk of reproductive, developmental, endocrine, or immune effects at or near current body burdens.