Budinsky R A, Rowlands J C, Casteel S, Fent G, Cushing C A, Newsted J, Giesy J P, Ruby M V, Aylward L L
The Dow Chemical Company, Toxicology and Environmental Research and Consulting, 1803 Building, Midland, MI, USA.
Chemosphere. 2008 Feb;70(10):1774-86. doi: 10.1016/j.chemosphere.2007.08.035. Epub 2007 Oct 22.
An in vivo pilot study of the oral bioavailability of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in two soils with distinct congener profiles (one dominated by PCDDs, the other by PCDFs) was conducted in rats and juvenile swine. The pilot study revealed potential confounding of relative bioavailability estimates compared to bioavailability in spiked corn oil gavage for tetrachlorodibenzofuran (TCDF) in the rat study due to differential EROD induction between groups receiving soil and those receiving spiked control PCDDs/PCDFs. A follow-up study in rats with the furan-contaminated soil was then conducted with reductions in the spiked control doses to 20%, 50% and 80% of the soil-feed dose in order to bracket hepatic enzyme induction levels in the soil group. When hepatic enzyme induction was matched between the soil and spiked control groups, the apparent relative bioavailability for TCDF was reduced significantly. Overall, after controlling for hepatic enzyme induction, estimates of relative bioavailability in rats and swine differed for the two soils. In the rat study, the relative bioavailability of the two soils were approximately 37% and 60% compared to corn oil administration for the PCDD- and PCDF- dominated soils, respectively, on a TEQ basis. In swine, both soils demonstrated relative bioavailability between 20% and 25% compared to administration in corn oil. These species differences and experimental design issues, such as controlling for differential enzyme induction between corn oil and soil-feed animals in a bioavailability study, are relevant to risk assessment efforts where relative bioavailability inputs are important for theoretical exposure and risk characterization.
在大鼠和幼猪中开展了一项体内初步研究,以探究两种具有不同同系物分布特征(一种以多氯二苯并 - 对 - 二噁英(PCDDs)为主,另一种以多氯二苯并呋喃(PCDFs)为主)土壤中PCDDs和PCDFs的口服生物利用度。初步研究表明,在大鼠研究中,由于接受土壤的组与接受加标对照PCDDs/PCDFs的组之间存在不同的乙氧基 - 罗丹明 - O - 脱乙基酶(EROD)诱导作用,与加标玉米油灌胃的生物利用度相比,四氯二苯并呋喃(TCDF)的相对生物利用度估计存在潜在混淆。随后在大鼠中针对受呋喃污染的土壤开展了一项后续研究,将加标对照剂量降低至土壤 - 饲料剂量的20%、50%和80%,以界定土壤组中的肝酶诱导水平。当土壤组和加标对照组之间的肝酶诱导作用相匹配时,TCDF的表观相对生物利用度显著降低。总体而言,在控制肝酶诱导作用后,大鼠和猪中两种土壤的相对生物利用度估计值有所不同。在大鼠研究中,以毒性当量(TEQ)为基础,与玉米油给药相比,PCDDs为主和PCDFs为主的两种土壤的相对生物利用度分别约为37%和60%。在猪中,与玉米油给药相比,两种土壤的相对生物利用度均在20%至25%之间。这些物种差异以及实验设计问题,例如在生物利用度研究中控制玉米油和土壤 - 饲料动物之间的差异酶诱导作用,对于风险评估工作具有重要意义,因为相对生物利用度输入对于理论暴露和风险特征描述非常重要。