Human health effects 2.3.7.8- TCDD

This section presents information on human health effects, including those known to be associated and those possibly associated with exposure to CDDs (primarily 2,3,7,8-TCDD). Since limited data exist to assign a specific route of exposure (inhalation, oral, dermal) to human studies, the information in this section is organized by health effects—death, systemic, immunological, neurological, developmental, reproductive, genotoxic, and carcinogenic effects. These data are discussed in terms of three exposure periods—acute (14 days or less), intermediate (15-364 days), and chronic (365 days or more). 

Pocchiari F, Silano V, Zampieri A. 1979. Human health effects from accidental release of tetrachlorodibenzo-p-dioxin (TCDD) at Seveso, Italy. Ann NY Acad Sci 320 311-320. 

In Times Beach, Missouri, waste oil from 2,4,5-TCP/HCP manufacture, contaminated with 2,3,7,8-TCDD, was used to control dust on roads. The result was the well-known government buy-out of the town. Use of waste oil at several Missouri horse arenas resulted in acute human health effects and the death of sixty-five horses and several small animals. Subsequent use of the horse arena materials as fill at building construction sites resulted in further cleanup problems. 

Humans with a history of exposure to 2,3,7,8-TCDD have been studied most often. Therefore, I will devote most of the rest of this paper to a review of these studies. Although exposure to other PCDDs may be as prevalent or more prevalent in the general population, we have no information on the human health effects of the other PCDDs. 

In conclusion, the most prevalent lesion in humans after acute exposure to 2,3,7,8-TCDD is a skin lesion referred to as chloracne. This skin disease may be accompanied by hirsutism and hyperpigmentation. After acute exposure to toxic levels, liver function may be impaired and a sensory neuropathy may be present. There may be complaints of weakness, weight loss, severe fatigue, and a general malaise. Many of these acute symptoms and signs revert to normal when exposure ceases. The chloracne is probably the most persistent lesion. No convincing chronic human health effects, other than chloracne, have been reported, nor is the dose of 2,3,7,8-TCDD known that would cause systemic illness or death in humans. 

F. Pocchiari et al., "Human health effects from accidental release of TCDD at Seveso, Italy," Annals N.Y. Academy of Science, vol. 320, pp. 311-321, 1979. 

Although the effects of chronic exposure of humans to low levels of POPs are difficult to predict, some biological effects have been described. For example, exposure of children to PCBs and PCDD/Fs may be linked to an elevated risk for infectious diseases. Exposure of pregnant women to PCDD/Fs may cause lower fertility in their male offspring. The adverse effects to human health of acute and chronic exposure of high concentrations of POPs, especially among industrial workers exposed to daily intakes of chemicals, are more evident. Elevated concentrations of DDE and TCDD have been associated with the development of cancers such as breast cancer, leukaemia and thyroid cancer. Dioxin exposure may also be associated with immunotoxicity, reproductive diseases and neurotoxicity. Extreme exposure to chlorinated compounds has resulted in death [101]. 

Health Effects in Humans Associated with Estimated 2,3,7,8-TCDD Body Burdens... 

Comparison of Body Burden Effects Levels Among Humans and Animals 2-11 Toxicity Equivalency Factors (TEFs) for Halogenated Aromatic Hydrocarbons 2-12 Updated Toxic Equivalency Factors (TEFs) for Halogenated Hydrocarbons 2-13 Estimated Body Burdens of 2,3,7,8-TCDD That Correspond to MRLs 2-14 Health Effects in Animals Following Lactation-Only Exposure to 2,3,7,8-TCDD 2-15 Health Effects in Humans Associated with CDD and CDF Levels in Breast Milk 2-16 Genotoxicity of 2,3,7,8-TCDD In Vivo 2-17 Genotoxicity of 2,3,7,8-TCDD In Vitro... 

TCDD exposure levels and health effects. A common problem with most of the human studies is that the people are exposed to a number of chemicals at the same time. In most human health studies, we do not know how much 2,3,7,8-TCDD people were exposed to or how long the exposure lasted. In other studies, the people were examined many years after they were exposed and some of the effects may have not have been present at the time of examination or the effects observed may not have been caused by 2,3,7,8-TCDD. Some of the more recent studies have measured 2,3,7,8-TCDD levels in the blood or fat tissue of exposed populations. The levels of... 

Table 2-1. Health Effects Associated with Exposure to 2,3,7,8-TCDD and Body Burdens in Humans (continued)... 

Comparison of Estimated Body Burdens Associated with Effects in Experimental Animals and Humans. Estimated average body burdens of 2,3,7,8-TCDD in human populations in which various health effects of 2,3,7,8-TCDD are suspected range from 31 to 6,600 ng/kg (estimated body burdens at the time of exposure termination). See Table 2-1 for more information. The human body burden expected in populations exposed to background environmental levels of 2,3,7,8-TCDD has been estimated to be 1 ng TCDD/kg body weight (DeVito et al. 1995 Orban et al. 1994). This would suggest that effects of 2,3,7,8-TCDD in humans may occur at body burdens that are 30 to 6,600 times greater than background burdens for 2,3,7,8-TCDD. 

No clear picture regarding hematologic effects of 2,3,7,8-TCDD emerges from the studies in animals. From the limited data, it appears, however, that mice are less sensitive than other species. The relevance of the findings in animals to human health is difficult to ascertain. 

No information was located regarding health effects of other congeners in humans, and limited data exist about effects caused by an acute exposure to these congeners in animals. The information would be useful for populations living near hazardous waste sites who may be exposed to CDDs for acute durations. Should a case of high acute exposure to 2,3,7,8-TCDD occur in humans, prompt... 

Children s Susceptibility. A limited number of human studies have examined health effects of CDDs in children. Data from the Seveso accident suggest that children may be more susceptible to the dermal toxicity of 2,3,7,8-TCDD (chloracne), but it is not known if this would be the case for other effects. Follow-up medical surveillance of the Seveso children (including measurement of serum 2,3,7,8-TCDD levels) would provide information on whether childhood exposure would pose a risk when the individual matures and ages. The available human and animal data provide evidence that 2,3,7,8-TCDD can cross the placenta and be transferred to an infant via breast milk. Although information on the developmental toxicity of CDDs in humans is limited, there are extensive animal data that the developing... 

X] 3 for extrapolation from animals to humans- A comparison of species sensitivity suggests that even though there are wide ranges of sensitivity for some 2,3,7,8-TCDD-induced health effects, for most health effects, the LOAELs for the majority of animal species cluster within an order of magnitude. Based on the weight of evidence of animal species comparisons and human and animal mechanistic data, it is reasonable to assume that human sensitivity would fall within the range of animal sensitivity. 

A minimal risk level (MRL) is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration and route of exposure. These substance-specific estimates, which are intended to serve as screening levels, are used by ATSDR health assessors and others to identify contaminants and potential health effects thai may be of concern at hazardous waste sites. The chronic-duration oral MRL of 1 picogram/kilogram/day or pg/kg/day for TCDD, or total TEQs, (ATSDR 1999) was based on neurobehavioral effects in monkeys. Based on this value, an EMEG of 50 ppt (0.05 ppb) TCDD, which is equivalent to 50 ppt (0.05 ppb) TEQs, was derived for exposure from contaminated soil. Uncertainty factors of 90 (total) were used in the calculations of the MRL (for further details, see ATSDR 1999). Based on a review of more recent literature, ATSDR scientists conclude that the MRL of 1 pg/kg/day is approximately two orders of magnitude below the noncancer health effect levels observed in recent studies. This is also true for cancer effect levels. 

Pelclova D, Urban P, Preiss J, et al. Adverse health effects in humans exposed to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Rev Environ Health 2006 21(2) 119 38. 

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