Concentration and age-dependent elimination kinetics of polychlorinated dibenzofurans in Yucheng and Yusho patients

Abstract

Half-life estimates of three polychlorodibenzofurans (PCDFs) were calculated using serial blood samples collected over a 15 to 19-year period. Blood fat PCDFs were modeled in eight individuals who were exposed to contaminated rice oil in Japan (Yusho, n = 5) and in Taiwan (Yucheng, n = 3). The elimination kinetics of PCDFs were concentration-dependent, with faster rates observed at higher concentrations and the apparent transition to slower rates occurring at about 1-3 ppb. Average half-lives of 1.1, 2.3, and 1.5 years above the transition concentration and 7.2, 5.7, and 3.5 years below it were estimated for 2,3,4,7,8-pentaCDF, 1,2,3,4,7,8-hexaCDF, and 1,2,3,4,6,7,8-heptaCDF, respectively. A positive linear correlation of half-life with age was observed for the combined group, with a rate of increase of 0.19, 0.12, and 0.05-year half-life per year of increase in age for penta-, hexa-, and hepta-CDF, respectively. The distinctly younger Yucheng patients exhibited far lower variability in half-lives and age-related trends that were quite consistent with the corresponding data on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for younger persons exposed in the Seveso incident. These age- and concentration-dependent half-lives for PCDFs may have important risk assessment implications for estimating body burdens. The current study provides limited additional evidence that PCDFs, like TCDD, are more rapidly eliminated in younger individuals.

Apparent Half-Lives of Dioxins, Furans, and Polychlorinated Biphenyls as a Function of Age, Body Fat, Smoking Status, and Breast-Feeding

“…This is consistent with a study on the Yusho and Yu-Cheng cohorts of half-lives of penta- (Pe), hexa- (Hx), and hepta (Hp) CDFs (Leung et al 2007). Studies on the Ranch Hand cohort show a slight negative association (Wolfe et al 1994) or no association (Michalek et al 1996), but this may be due to the narrow age range characterizing these cohorts.…”

“…Studies on the Ranch Hand cohort show a slight negative association (Wolfe et al 1994) or no association (Michalek et al 1996), but this may be due to the narrow age range characterizing these cohorts. Studies with child or infant subjects report significantly shorter half-lives than do studies with adult cohorts (Kreuzer et al 1997; Leung et al 2006, 2007). In children < 18 years of age exposed during the incident in Seveso, Italy, a strong association between half-life and age was found, and children had significantly shorter half-lives than did adults (Kerger et al 2006).…”

Change in decay rates of dioxin-like compounds in Yusho patients

“…Given their health implications, there has been a great deal of interest in the half-lives of these compounds in humans. In patients with high blood concentrations of dioxin-like compounds, half-lives of 1.1 years have been reported, increasing to 7.2 years in patients with low blood concentrations [5]. Other estimates on half-lives of dioxin-like compound include 8.9 years by Masuda et al [6], 9.6 years by Ryan et al [7] and 9.1 years by Iida et al [8].…”

Current skin symptoms of Yusho patients exposed to high levels of 2,3,4,7,8-pentachlorinated dibenzofuran and polychlorinated biphenyls in 1968

“…(a and b) The severity scores of black comedones ( ⁄⁄⁄ p < 0.001) and scar formation ( ⁄ p = 0.02) were positively correlated with the blood levels of 2,3,4,7,8-PeCDF, whereas those of black comedones ( ⁄⁄⁄ p < 0.001), scar formation ( ⁄⁄ p < 0.01), and pigmentation ( ⁄ p = 0.02) were significantly positively correlated with the blood level of total PCBs (c-e). hepta-CDFs (Leung et al, 2007). The effects of age on the half-lives of dioxins may also induce persistently higher levels of dioxins in elderly Yusho patients.…”