Pharmacokinetics of 2,3,7,8-TCDD in man

A single dose of 1.14 ng of ³H-2,3,7,8-TCDD/kg bw, ingested by a human volunteer, was absorbed almost completely from the intestine (> 87 %). The resulting adipose tissue levels, measured 13 and 69 days after dosage were 3.09±0.05 and 2.85±0.28 ppt, respectively. The dioxin was cleared from the body with a half life of elimination of 2120 days.     

Demonstration of innovative remedial action technologies at United States military dioxin contaminated sites

The United States Air Force is currently seeking to resolve problems associated with soils contaminated with 2,3,7,8-tetrachlordibenzo-p-dioxin (dioxin). Air Force use of the phenoxy herbicide formulation known as Herbicide Orange has resulted in soil contamination of three military sites in the Continental United States. To resolve these problems, the U.S. Air Force Engineering and Services Laboratory and its prime contractor, EG&G Idaho, have initiated a research program to evaluate, under field conditions, technologies that may reduce the level of dioxins in contaminated soils. Two pilot-scale technologies: (1) advanced electric reactor, developed by the J.M. Huber Corp., Borger, Texas, and (2) thermal desorption/U.V. destruction, developed by the I.T. Corp., Knoxville, Tennessee, have been tested at a military installation in the Southeastern United States. Although independent confirmation of technology success is pending, preliminary test results indicate that both technologies are capable of reducing the levels of dioxin in contaminated soils from 240 parts per billion to less than 1 part per billion. These data suggest that either of the technologies could be employed for full-scale site restoration. Field trials of two additional technologies are scheduled for late 1985.     

Polychlorinated dibenzo-p-dioxins and dibenzofurans: Correlation between in vitro and in vivo structure-activity relationships (SARs)

Polychlorinated dibenzofurans (PCDFs) and dibenzo-p-dioxins (PCDDs) elicit a number of common biologic and toxic responses which are triggered by their initial binding to a cytosolic receptor protein. These effects include the induction of several cytochrome P-448 dependent monooxygenases (eg, aryl hydrocarbon hydroxylase, AHH), body weight loss and thymic atrophy. The dose-response effects of selected PCDFs on AHH induction in rat hepatoma H-4-II E cells and cytosolic receptor binding affinities have been determined. The results of these and studies demonstrate the remarkable effects of structure on the activity of PCDFs. A systematic study of each of the four different position for chlorine substitution in the dibenzofuran ring system showed that the toxic and biologic potencies of these compounds varied with respect to differential chlorine substitution at all four position, i.e. C-3(7) > C-2(8) >C-4(6) > C-1(9). SARs for PCDDs confirmed the importance of the lateral CI substituents and also showed that 1,2(or 6,7-) substituted PCDDs were more active than the corresponding 1,3-dichloro analogs. In addition, there were significant decreases in activity with increasing non-lateral CI substitution. The SARs for PCDFs were different from the PCDDs and this was directly related to the asymmetric structure of the former group of compounds.     

Rationale for assessment of risk from exposure to 2,3,7,8-TCDD

The human health risk assessment is supported by methodology for utilizing toxic effects in animals consisting of carcinogenic and noncarcinogenic responses as a result of chronic, subchronic and acute exposures. One of the initial steps in a risk assessment activity involves the estimation of exposure levels. These estimates are typically based on either direct environmental measurements or predictions obtained from fate and transport models. The decision to develop assessment of risk from chronic exposure based on a nonthreshold model is made if a chemical demonstrates carcinogenic activity in animal bioassays and/or in human epidemiological studies. In the absence of any positive human epidemiologic data, it is assumed that a substance which induces a statistically significant carcinogenic response in animals has the probability to cause cancer in humans. The carcinogenic potential of 2,3,7,8-TCDD has been established based on chronic exposure in rodents. In addition, 2,3,7,8-TCDD has also been shown to be a liver cancer promoter in rodents. In the risk assessment on dioxins based on chronic exposure in experimental animals, 2,3,7,8-TCDD is regarded as a carcinogenic substance. Carcinogenic data from animal bioassays are utilized for the assessment of risk for the purpose of estimating the likelihood of 2,3,7,8-TCDD being carcinogenic for humans and to determine the magnitude of the potential impact on public health.