Kerger Brent D, Leung Hon-Wing, Scott Paul, Paustenbach Dennis J, Needham Larry L, Patterson Donald G, Gerthoux Pier M, Mocarelli Paolo
Health Science Resource Integration, Tallahassee, Florida, USA.
Environ Health Perspect. 2006 Oct;114(10):1596-602. doi: 10.1289/ehp.8884.
Pharmacokinetic and statistical analyses are reported to elucidate key variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in children and adolescents.
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.
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.
TCDD half-life in persons < 18 years of age averaged 1.6 years while those > or =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.
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.
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.
报告药代动力学和统计分析结果，以阐明影响儿童和青少年体内2,3,7,8-四氯二苯并对二恶英（TCDD）消除的关键变量。
我们利用血液浓度计算TCDD消除半衰期。通过统计分析研究的变量包括年龄、接触后的潜伏期、性别、体内TCDD浓度和含量、氯痤疮反应的严重程度、体重指数和体脂量。
1976年至1993年期间，从意大利塞韦索的居民中采集血液，这些居民在1976年7月附近的三氯苯酚反应堆爆炸时年龄小于18岁。
18岁以下人群的TCDD半衰期平均为1.6年，而18岁及以上人群的平均半衰期为3.2年。半衰期与年龄密切相关，显示出每增加一岁或自接触以来的时间，半衰期平均增加0.12年。还发现了显著的浓度依赖性，12岁以下儿童TCDD浓度>400 ppt时半衰期较短，纳入成年人后为700 ppt时半衰期较短。半衰期与体重指数、体脂量、TCDD含量和氯痤疮反应之间也存在中度相关性。
儿童和青少年的TCDD半衰期较短，且半衰期的增长速度比成年人慢，这种效应在体内负荷较高时会增强。
对人体TCDD血液浓度或体内负荷进行建模时，应考虑到在儿童和青少年中观察到的明显较短的消除半衰期，以及在浓度>400 - 700 ppt的人群中观察到的浓度依赖性效应。
