Age- and Concentration-Dependent Elimination Half-Life of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin in Seveso Children

Article excerpt

OBJECTIVE: Pharmacokinetic and statistical analyses are reported to elucidate key variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in children and adolescents.

DESIGN: We used blood concentrations to calculate TCDD elimination half-life. Variables examined by statistical analysis include age, latency from exposure, sex, TCDD concentration and quantity in the body, severity of chloracne response, body mass index, and body fat mass.

PARTICIPANTS: Blood was collected from 1976 to 1993 from residents of Seveso, Italy, who were < 18 years of age at the time of a nearby trichlorophenol reactor explosion in July 1976.

RESULTS: TCDD half-life in persons < 18 years of age averaged 1.6 years while those [greater than or equal to] 18 years of age averaged 3.2 years. Half-life is strongly associated with age, showing a cohort average increase of 0.12 year half-life per year of age or time since exposure. A significant concentration-dependency is also identified, showing shorter half-lives for TCDD concentrations > 400 ppt for children < 12 years of age and 700 ppt when including adults. Moderate correlations are also observed between half-life and body mass index, body fat mass, TCDD mass, and chloracne response.

CONCLUSIONS: Children and adolescents have shorter TCDD half-lives and a slower rate of increase in half-life than adults, and this effect is augmented at higher body burdens.

RELEVANCE: Modeling of TCDD blood concentrations or body burden in humans should take into account the markedly shorter elimination half-life observed in children and adolescents and concentration-dependent effects observed in persons > 400-700 ppt.

KEY WORDS: children, dioxin, elimination, half-life, model, pharmacokinetics.

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Shorter elimination half-lives for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) have been reported in human infants (Kreuzer et al. 1997; Leung et al. 2006) and in highly exposed adults (Aylward et al. 2005; Leung et al. 2005) compared with those in the general population. However, few published elimination half-life data are available for young children and adolescents 1-18 years of age. Needham et al. (1997/1998) presented TCDD decay curves for a 50-year-old Seveso male (initial TCDD concentration of 1,770 ppt) and a 6-year-old Seveso male (initial TCDD concentration of 15,900 ppt) and noted a much faster TCDD serum lipid decay for the child, especially over the 6-year period following exposure. Additional data on children are needed to further validate the two age-dependent PCDD/F half-life models that have been proposed for estimating childhood body burdens (Kerger et al. 2005; Kreuzer et al. 1997).

In this study we examined a database of longitudinal TCDD measurements in the blood lipids of children (ages 0.5-18 years) exposed during the 1976 trichlorophenol reactor explosion incident near Seveso, Italy. As many as 10 sequential measurements were made on some children. We evaluated changes in elimination rate of TCDD in blood lipids as influenced by age, latency from exposure, TCDD concentration or mass in the body, severity of chloracne, and body mass parameters potentially influencing the half-life in children, adolescents, and young adults. Our goal was to identify central tendency trends for the half-life versus age relationship that may be used to estimate childhood body burdens, particularly for children 1-7 years of age, an age range critical to understanding potential risks of PCDD/F intake during childhood (Kerger et al. 2005).

Materials and Methods

Data from the Seveso incident include fairly complete information on longitudinal blood TCDD measurements, sampling date, exposure zone, severity of chloracne, and age, height, and weight at the time of sampling (up to 16 years after the incident). …