The IWG includes representatives from the following federal agencies: U. Department of Health and Human Services, U. Department of Agriculture, U. Department of State, U. Department of Veterans Affairs, U. In response, EPA revised its draft Reassessment and submitted it to the IWG in late , requesting input about the need and benefit of further review. EPA appropriations language for fiscal year also called for an IWG evaluation of the need for further review and provided specific issues to consider. The scope of work for the NRC review and interagency agreements for funding were developed through the IWG in the spring of These compounds contain the basic aromatic structure of a benzene ring, a hexagonal carbon structure with conjugated double bonds connecting the carbons Figure PCDDs and PCDFs have tricyclic triple-ring structures consisting of two benzene rings, with varying numbers of chlorines, connected by an oxygenated ring, with the oxygenated ring of PCDDs having two oxygen atoms a dioxin, Figure a and the oxygenated ring of PCDFs having a single oxygen atom a furan, Figure b.
PCBs have a variable number of chlorines attached to a biphenyl group two benzene rings with a carbon-to-carbon bond between carbon 1 on the first ring and carbon 1'. Each chemical compound from any of these subclasses is referred to as a congener. Brominated or mixed halogenated congeners within these classes of compounds or within other chemical classes, such as the polyhalogenated naphthalenes, benzenes, azobenzenes, and azoxybenzenes, have not been evaluated as extensively and are not addressed in the Reassessment.
TCDD, the most studied and one of the most toxic members of these classes of compounds, is the designated reference chemical for the Reassessment and for other related litera-. PCDDs and PCDFs are tricyclic aromatic compounds with similar physical and chemical properties—properties shared by specifically configured, or coplanar a flat configuration , dioxin-like PCBs. These are general terms that describe chemicals that share defined similarities, including chemical structure and biological and toxicological character.
However, of the several hundred HAH congeners, only 29 are considered to have significant toxicity and to induce a common battery of toxic responses through similar biological modes of action. The evaluation of dioxin-like congeners within the Reassessment focuses on dioxins and DLCs with TCDD-like toxicity and those generally considered the most associated with environmental and human health risks. The remaining evaluated TCDD-like congeners include the PCBs with four or more chlorines in the lateral positions 3, 3', 4, 4', 5, or 5' , with established TCDD-like environmental and biological behaviors, and particularly the mono- and non-ortho PCBs—that is, PCBs with one or no, respectively, chlorine substitution in the ortho position 2, 2', 6, or 6' on the benzene rings see Figure Evaluation of the chemical congeners addressed in the Reassessment is considered sufficient to characterize environmental chlorinated dioxins Reassessment, Part I, p.
Experimental evidence indicates that TCDD acts by way of binding to an intracellular protein, the aromatic hydrocarbon receptor AHR , a ligand-dependent transcription factor that functions in partnership with a second protein, the AHR nuclear translocator protein ARNT to stimulate alterations in gene expression that result in toxic and biological effects.
AHR is present throughout the animal kingdom, including invertebrates like the fruit fly and the clam. In addition to AHR binding, several other molecular events are necessary for AHR-dependent biological and toxic effects to occur, and there are significant species differences in those events, so quantitative cross-species comparisons based only on AHR binding may not provide accurate or dependable information about their AHR responsiveness or the possible AHR-dependent responses.
The invertebrate AHR does not bind xenobiotic ligands that is, TCDD, other dioxins, and DLCs , and it is not associated with toxic end points, suggesting that the role of AHR as a mediator of toxic or adaptive responses might be a function acquired during vertebrate evolution and superimposed on an endogenous physiological role. TCDD, other dioxins, and DLCs are generally present as complex mixtures in environmental, food, and biological matrices, including humans and other animals.
The TEF concept originated as a method for evaluating health risks associated with closely related chemicals with similar mechanisms of action but different potencies. By using those factors, the toxicity of a mixture is expressed in terms of its total toxic equivalent quotient TEQ , which is the amount of TCDD that it would take to equal the combined toxic effect of all contributing congeners within the mixture.
The TEF value of each congener within a mixture is multiplied. Human and mammalian TEFs were constructed by an approach that gave more weight to in vivo toxicity data than to in vitro data. Moreover, among the different in vivo studies available for establishing TEFs, the basis for selecting the most relevant in vivo toxicity study was the length of exposure, with chronic exposures ranking highest and acute exposures lowest in relevance.
TEF assignments continue to evolve in accordance with emerging science and iteration, and WHO recommended revisiting TEF values every 5 years, with review in To facilitate evaluation of human health risks and regulatory control of exposure to mixtures of TCDD, other dioxins, and DLCs, EPA, using all available data, has incorporated the TEF concept and method into the risk assessment process since The Reassessment considers the application, limitations, and uncertainties when using TEFs.
Overall, the use of the TEF method is currently the most reliable and best evaluated approach for assessing the potential toxic potency of complex mixtures of DLCs. EPA classifies sources of TCDD, other dioxins, and DLCs into five categories— 1 combustion; 2 metal smelting, refining, and processing; 3 chemical manufacturing and processing; 4 biological and photochemical processes; and 5 reservoir sources. Combustion sources include incineration of various types of waste municipal solid, sewage sludge, medical, and hazardous , burning of fuels coal, wood, and petroleum products ,.
Reprinted with permission; copyright , World Health Organization. Metallurgical operations e. PCDDs and PCDFs can also be formed under such environmental conditions as composting via microorganism action on chlorinated phenolic compounds. Studies have also reported that these chemicals form during photolysis of highly chlorinated phenols, such as pentachlorophenol, although it has been demonstrated only under laboratory conditions. Four of the source categories combustion, metallurgical processing, chemical manufacturing and processing, and biological and photochemical processes are collectively referred to as contemporary formation sources.
In contrast, reservoir sources are not considered in the quantitative inventory of contemporary formation sources because they involve the recirculation of previously formed compounds that have already partitioned into air, water, soil, sediment, and biota. However, the Reassessment recognizes that the contribution of reservoir sources to human exposure may be significant, perhaps contributing half or more of total background TEQ exposure. For any given time period, releases from both contemporary formation sources and from reservoir sources determine the overall amount of TCDD, other dioxins, and DLCs released to the accessible environment.
The decrease in estimated releases of PCDDs and PCDFs from to is largely attributed to reductions in air emissions from municipal and medical waste incinerators; further reductions are anticipated. A number of investigators have proposed that the U. Additional observations in the Reassessment regarding sources are concerns about insufficient data or estimates from nonpoint sources e.
Consequently, these intrinsically stable compounds are found throughout the world in practically all environmental media, including air, water, soil, sediment, food, and food products. The amount of time required for a chemical to lose one-half of its original concentration, known as its half-life, varies by substance. The chemical half-lives of mixtures change with time, as the shorter-lived substances disappear and the proportion with longer half-lives increases.
The Reassessment defines background exposure to TCDD, other dioxins, and DLCs as exposure that would occur in an area without known point sources of the contaminants. Background exposure includes exposure via the commercial food supply, air, or soil but not any significant occupational exposure. Background exposure estimates are based on the monitoring of data from environmental sites and other media void of known contaminant sources and on pharmacokinetic models using body burden data from nonoccupationally exposed populations.
High concentrations, measured in parts per trillion ppt and higher, are found in soil, sediments, and biota because of their recalcitrant nature and their physical-chemical properties. Estimates for background concentrations of DLCs in environmental media and in food are based on studies conducted at various locations in North America. The number of locations examined for environmental media estimates in those studies was small, and it is not known whether the estimates adequately reflect the full range of variation across the United States. Food estimates were derived from statistically based national surveys, nationwide sampling networks, food fat concentration measurements, samples collected from retail stores, and samples obtained from biohabitat.
2,3,7,8 -Tetrachlorodibenzo-p-dioxin (TCDD, "dioxin")
Measurable quantities of these in environmental media and food in the United States were found to be similar to quantities measured in Europe. Evidence from Europe suggests a decline in dioxin and furan concentrations in food products during the s. Although no systematic study of temporal trends in dioxin concentrations in food has been conducted in the United States, at least one study determined that meat now contains lower concentrations of TCDD, other dioxins, and DLCs than samples from the s through the s contained.
Department of Agriculture is conducting a nationwide survey of dioxin concentrations in beef, pork, and poultry that should allow for a time-trend analysis. This estimate suggests average tissue concentrations have declined from the estimated 55 ppt in the late s and early s. Because new emissions of TCDD, other dioxins, and DLCs have been declining since the s, it is reasonable to expect that concentrations in food, human diet, and, ultimately, human tissue have also declined during this time. The Reassessment acknowledges that characterization of national background concentrations of TCDD, other dioxins, and DLCs in tissue is uncertain because current data are not statistically representative of general populations.
Also, tissue concentrations are a function of age and year of birth. On a global scale, exposure to TCDD, other dioxins, and DLCs resulting from accidental, occupational, or incidental exposure through dermal contact, inhalation, or ingestion has been associated with adverse effects on human health. In the early s, workers involved in distilling, processing, or producing chlorine-based chemicals presented with symptoms characteristic of those currently associated with TCDD poisoning, including severe cases of chloracne and various degrees of fatigue.
Soil contaminated with TCDD at ppb caused the evacuation of the town of Times Beach, Missouri, and allegedly was responsible for the deaths of local animals and for a variety of human and animal illnesses. In a January press release, the Institute of Medicine announced that reexamination of six studies of herbicide-exposed veterans revealed sufficient evidence of an association between herbicide defoliants, or their contaminants, which included TCDD, sprayed by U.
The long-term effects of low-level exposure to TCDD, other dioxins, or DLCs normally experienced by the general population are not known, nor is the clinical significance of biochemical biomarkers, such as enzyme induction at or near background-level exposures. Focal points of research include organ and organ-system effects and elucidation of the cellular mechanisms through which these effects occur. The committee held three public meetings in Washington, DC, to collect information, meet with researchers and decision makers, and accept testimony from the public.
The committee met two additional times, in executive session, to complete its report. The committee also considered new peer-reviewed studies published since Part III of the Reassessment was last revised and before the committee held its final meeting in July TCDD is stable to heat, acids, and alkali and will decompose when exposed to ultraviolet light, including sunlight. Production of 2,4,5-T and silvex ceased in the United States in However, stockpiles of both products are still being distributed and used. TCP also is used in the production of hexachlorophene, a bactericide and fungicide.
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The combustion of 2,4,5-T can result in its conversion to small amounts 0. Also, the burning or heating of commercial and purified chlorophenates and pyrolysis of polychlorinated biphenyls PCBs contaminated with trichlorobenzenes have resulted in the production of TCDD. No occupational exposure standard exists for TCDD.
EPA temporarily suspended or banned most uses of 2,4,5-T and silvex in , although their use was allowed on sugarcane, orchards and for miscellaneous non-crop uses. It is not possible to estimate accurately the number of U. Occupational exposure to TCDD may occur during production of TCP; in decontamination of worksites from prior production or use of TCP, 2,4,5-T, or silvex; from waste materials such as reclaimed oil contaminated with TCDD; or from cleanup after fires in transformers containing polychlorinated aromatics.
Dust or soil particles contaminated with TCDD can remain airborne or accumulate on indoor or outdoor work surfaces and may present a potential exposure hazard.
Dioxins: Definition, dangers, sources, types, and more
Exposure to TCDD as a vapor will normally be negligible because of its low vapor pressure. Contact with TCDD-contaminated liquids is possible through the handling of drums or tanks containing the liquid or through dispersion of the liquid. TCDD is reported to be at least three times more potent than any other known compound in stimulating production of aminolevulinic acid synthetase ALA , the rate-limiting enzyme in porphyrin and heme synthesis.
TCDD administered at dosages of 0. Impairment of reproduction has been reported for rats ingesting 0. Significant decreased fertility, litter size, number of pups alive at birth, postnatal survival, and postnatal body weight of pups were evident in two successive generations delivered from male and female rats that ingested TCDD 90 days prior to first mating, during pregnancies, and for the durations of time between pregnancies.
TCDD induced immunological function alterations, expressed by decreased thymus-to-body weight ratios, in nursing newborn rats exposed through dosing of the lactating mother. Results of mutagenicity tests are inconclusive. Male rats fed dosages of 0. Male mice fed dosages of TCDD of 0. The only information on the health effects in humans from exposure to TCDD is from clinical or epidemiological studies of populations who were occupationally and non-occupationally exposed to 2,4,5-T and TCP contaminated with TCDD.
To date, no studies of humans include a quantitation of exposure to TCDD.
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Chloracne is a chronic and sometimes disfiguring skin eruption caused by exposure to halogenated aromatic compounds including TCDD. Chloracne is possibly a result of systemic effects of these compounds, although it also may occur as a contact dermatitis.
There are numerous cases of chloracne reported following accidental exposure to chlorinated aromatic chemicals which were probably contaminated with TCDD. Reproductive effects resulting from possible human exposure to TCDD are inconclusive. Data on male workers who applied agricultural sprays of 2,4,5-T or who produced TCDD-contaminated materials are consistent with the animal data which suggest no reproductive effects in males from TCDD exposure.
Studies of birth defects in populations that may have been exposed non-occupationally to TCDD have been conducted in Australia where a correlation was observed between 2,4,5-T use and seasonal variation in the rate of spinal cord and spine formation defects; no causal association could be drawn. EPA study found a positive relationship between spontaneous abortions and 2,4,5-T use in the Alsea, Oregon area.
Findings have been inconclusive in many mortality studies of workers with occupational exposure to TCDD-contaminated materials because of the small size of the study population and concomitant exposures to other substances. No excess mortality or tumor incidence was observed among Swedish railroad workers exposed to unknown amounts of 2,4-D, 2,4,5-T, and other herbicides but believed to have been exposed primarily to phenoxy acid herbicides for at least 45 days. Two cases of stomach cancer 0. Among Swedish forestry workers exposed to phenoxy herbicide preparations, supervisors, who had more extensive exposure to herbicides than the other forest workers, had a nonsignificant excess of deaths from all cancers.
Mortality associated with the presence of tumors was, however, lower than expected for the total group of exposed workers. In a group of 74 workers involved in an accident during TCP production in Germany, 21 deaths occurred during the following 27 years. Seven 7 malignant neoplasms vs. Several case control studies of cancer patients have yielded data on the carcinogenicity of phenoxyacetic herbicides. Two studies were conducted in Sweden following a clinical observation of patients with soft tissue sarcoma who had previous occupational exposure to the herbicides.
In other reports from Sweden, 11 of 17 patients with malignant lymphoma reported occupational exposures to phenoxyacetic acids or chlorophenols; 70 a case control study with malignant lymphoma cases found a significantly higher occupational exposure to phenoxyacetic acids primarily 2,4,5-T, and 2,4-D associated with the sarcoma cases than did the controls. Analysis by individual herbicide exposure was not possible.
Two additional studies conducted in Sweden for colon cancer and nasal and nasopharyngeal cancer did not demonstrate an elevated risk for occupational exposure to phenoxyacetic acids. Among four small groups of U. TCDD causes a variety of systemic and immunological effects in animals with wide variation among species in the dosage required to cause death. Studies using rats and mice have demonstrated that TCDD is an animal teratogen and carcinogen. Results of tests for mutagenicity are inconclusive. Humans exposed to materials reported to be contaminated with TCDD have developed chloracne and other signs of systemic poisoning.
Soft tissue sarcoma has been observed in excess among workers exposed to phenoxy herbicides. These data are inconclusive regarding TCDD toxicity in humans because the populations studied had mixed exposures making causal relationships between exposure and effect unclear. The data are, however, suggestive of an association between exposure to phenoxyacetic herbicides contaminated with TCDD and excess lymphoma and stomach cancer.