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首页> 外文期刊>Environmental Science & Technology >Relative Susceptibility of Animals and Humans to the Cancer Hazard Posed by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Using Internal Measures of Dose
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Relative Susceptibility of Animals and Humans to the Cancer Hazard Posed by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Using Internal Measures of Dose

机译：使用剂量的内部量度，动物和人类对由2,3,7,8-四氯二苯并-p-二恶英构成的癌症危害的相对敏感性

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An analysis of the cancer dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans and animals was performed based on measured tissue and serum lipid TCDD concentrations and dosimetrics other than administered dose. Basic phar-macologic principles indicate that measures of internal dose such as AUC should be used to describe the dose-response relationship in cancer risk assessments of TCDD and other highly persistent compounds. The TCDD-related liver tumor response in female rats was compared to that in humans (respiratory tract cancer rates in Fingerhut et al.; 3). Three measures of lifetime dose were used: serum lipid TCDD area-under-the-curve (AUC), peak serum lipid concentration (C_(peak)), and average serum lipid concentration (C_(avg)). Serum lipid TCDD concentration vs time profiles forthe rat were constructed assuming first-order elimination and a half-life of 25 days. Concentration vs time profiles for humans were estimated based on measured serum lipid TCDD concentrations and known dates of first and last exposure, assuming a 7.5-year half-life and first-order elimination. A comparison of rat and human responses indicated that, using all three of these dosimetrics, humans are much less sensitive than rats to the carcinogenic effects of TCDD. For example, at the peak concentration measured in rats exposed to 0.1 μg kg~(-1) day~(-1) for 2 years, the human cancer response was more than 9-fold lower than that observed in rats. At comparable average lifetime serum lipid TCDD concentrations, the human cancer response was about 4-fold lower than observed in rats. When AUC was used as the dosimetric, the highest rat dose group (0.1 μg kg~(-1) day~(-1)) had a 9-fold greater response at approximately 1/10th the AUC of the most highly exposed human group; that is, the rat dose-response was more than 90-fold steeperthan the human dose-response. Interestingly, regardless of the dosimetric chosen, the cancer rate in humans in the NIOSH cohort, if due to TCDD, is almost completely insensitive to dose. Our analysis indicates that human exposure to background levels of TCDD (about 5 ppt serum lipid concentration) should not pose an incremental cancer risk.
机译：根据测得的组织和血清脂质TCDD浓度以及给药剂量以外的剂量学分析，对人和动物中2,3,7,8-四氯二苯并对二恶英（TCDD）的癌症剂量反应关系进行了分析。基本的药理学原理表明，在TCDD和其他高持久性化合物的癌症风险评估中，应使用内部剂量（如AUC）来描述剂量-反应关系。将雌性大鼠与TCDD相关的肝肿瘤反应与人的肝癌反应进行了比较（Fingerhut等人的呼吸道癌发生率； 3）。使用了终生剂量的三种测量方法：血清脂质TCDD曲线下面积（AUC），峰值血清脂质浓度（C_（peak））和平均血清脂质浓度（C_（avg））。建立大鼠的血清脂质TCDD浓度与时间的关系曲线，假设其具有一级消除作用，并且半衰期为25天。根据测得的血清脂质TCDD浓度以及已知的首次和最后一次暴露日期（假设7.5年半衰期和一级消除），估算了人类的浓度与时间的关系。对大鼠和人类反应的比较表明，使用所有这三种剂量学，人类对TCDD的致癌作用的敏感性要比大鼠低得多。例如，在暴露于0.1μgkg〜（-1）天〜（-1）2年的大鼠中测得的峰值浓度下，人类癌症反应比在大鼠中观察到的低9倍以上。在相当的平均终生血清脂质TCDD浓度下，人类癌症反应比在大鼠中观察到的反应低约4倍。当使用AUC进行剂量测定时，最高剂量组（0.1μgkg〜（-1）天〜（-1））在最高暴露人群的AUC的大约1/10处有9倍的响应。 ;也就是说，大鼠的剂量反应比人的剂量反应要陡峭90倍以上。有趣的是，无论选择哪种剂量学，如果由于TCDD，NIOSH队列中人类的癌症发生率几乎完全对剂量不敏感。我们的分析表明，人类暴露于TCDD的背景水平（约5 ppt血清脂质浓度）不应构成增加的癌症风险。

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