ELIMINATION OF POLYCHLORINATED DIBENZO-p-DIOXINS AND DIBENZOFURANS IN OCCUPATIONALLY EXPOSED PERSONS

Abstract

The elimination of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) was investigated in a group of n = 43 exposed workers with 2 blood measurements and n = 5 workers with 3 measurements. Under the assumption of a one-compartment, first-order kinetic model the median half-life for 2,3,7,8-TCDD was 7.2 yr, while for the other dioxins the estimates were between 3.7 yr for 1,2,3,4,6,7,8-HpCDD (hepta-chlorinated) and 15.7 yr for 1,2,3,7,8-PCDD (penta-chlorinated). For the furans median half-lives between 3.0 yr for 1,2,3,4,6,7,8-HpCDF and 19.6 yr for 2,3,4,7,8-PCDF were observed. There was no indication for a deviation from a first-order kinetic. Increasing age and percent body fat were associated with increasing half-life for most of the congeners. Smokers in general had a faster decay than non- and ex-smokers. In summary, the higher chlorinated PCDD/F like TCDD appear to be highly persistent in humans with half-lives ranging between 4 and 12 yr.

Concentration-dependent TCDD elimination kinetics in humans: toxicokinetic modeling for moderately to highly exposed adults from Seveso, Italy, and Vienna, Austria, and impact on dose estimates for the NIOSH cohort

“…That is, younger people appear to metabolize TCDD more rapidly than older persons, on average. This relationship held true for both male and female animals and was also similar to previous reports for humans (Flesch-Janys et al, 1996) and to the elimination behavior observed in rats (Jackson et al, 1998).…”

“…Elimination half-lives of less than 1 to 3.6 years were estimated in two women and one man who were exposed to very high levels of TCDD in Vienna, Austria, in 1997 (peak measured serum lipid levels of 144,000, 26,000, and 856 ppt) Geusau et al, 2002) and in adults during the first 3 years after the Seveso, Italy, accident (initial levels typically over 2,000 ppt) (Michalek et al, 2002). Previous estimates of the half-life of elimination for TCDD have ranged from about 7 to 9 years based on serial measurements in the Ranch Hand population or occupationally exposed workers (Flesch-Janys et al, 1996;Michalek and Tripathi, 1999;Rohde et al, 1999). These studies have typically involved 2-4 serial samples taken over several years from persons with serum lipid TCDD levels of less than about 500 ppt and have relied on an explicit assumption of first-order elimination behavior.…”

“…Estimates of exposure for these workers have generally been based on serum lipid levels of TCDD measured a decade or more after their last industrial exposure. These measured levels were used by several research groups (Aylward et al, 1996;Flesch-Janys et al, 1996;Steenland et al, 2001) to estimate, through backcalculations, peak levels at time of last exposure, assuming a simple first-order elimination rate with a fixed half-life ranging from 7.1 to 8.7 years. In this paper, we apply the modified toxicokinetic model (with parameters based on fits to the elimination data from the male Seveso patients) to measured serum lipid TCDD concentration and data on dates of employment for the 250 NIOSH workers for whom such data are available.…”

TCDD exposure estimation for workers at a New Zealand 2,4,5-T manufacturing facility based on serum sampling data

“…Concentrations of seven polychlorinated dibenzo-p-dioxin (PCDD) compounds, 10 polychlorinated dibenzofuran (PCDF) and selected polychlorinated biphenyl (PCB) compounds were measured in serum samples donated by 346 individuals (21.6% of the total group) who were employees of the plant for 3 days or more during the time period of trichlorophenol or phenoxyacetic acid manufacture and who resided within 75 km of the plant at the time of the blood draw. TCDD was the only congener that showed elevations above general population background levels, consistent with previous studies of 2,4,5-T manufacturing cohorts and data on product contamination (Nygren et al, 1988;Beck et al, 1989;Papke et al, 1992;Piacitelli et al, 1992;Smith et al, 1992;Ott et al, 1993;Littorin et al, 1994;Flesch-Janys et al, 1996;Heederik et al, 1998;Ryan and Schecter, 2000). The serum study is described in detail in an accompanying publication (Collins et al, 2008).…”

Serum dioxin levels in former chlorophenol workers

“…The first method assumes a one-compartment first-order kinetic model with a half-life of 9 or 7 years (Flesch-Janys et al, 1996). The second method uses a recently developed toxicokinetic model elimination of 2,3,7,8-TCDD (Aylward et al, 2005).…”