Henderson Rayetta G, Verougstraete Violaine, Anderson Kim, Arbildua José J, Brock Thomas O, Brouwers Tony, Cappellini Danielle, Delbeke Katrien, Herting Gunilla, Hixon Greg, Odnevall Wallinder Inger, Rodriguez Patricio H, Van Assche Frank, Wilrich Peter, Oller Adriana R
ToxStrategies, Inc., 9650 Strickland Rd., Suite 103-195, Raleigh, NC 27615, USA.
Eurometaux, Avenue de Broqueville 12, 1150 Brussels, Belgium.
Regul Toxicol Pharmacol. 2014 Oct;70(1):170-81. doi: 10.1016/j.yrtph.2014.06.021. Epub 2014 Jun 28.
Bioelution assays are fast, simple alternatives to in vivo testing. In this study, the intra- and inter-laboratory variability in bioaccessibility data generated by bioelution tests were evaluated in synthetic fluids relevant to oral, inhalation, and dermal exposure. Using one defined protocol, five laboratories measured metal release from cobalt oxide, cobalt powder, copper concentrate, Inconel alloy, leaded brass alloy, and nickel sulfate hexahydrate. Standard deviations of repeatability (sr) and reproducibility (sR) were used to evaluate the intra- and inter-laboratory variability, respectively. Examination of the sR:sr ratios demonstrated that, while gastric and lysosomal fluids had reasonably good reproducibility, other fluids did not show as good concordance between laboratories. Relative standard deviation (RSD) analysis showed more favorable reproducibility outcomes for some data sets; overall results varied more between- than within-laboratories. RSD analysis of sr showed good within-laboratory variability for all conditions except some metals in interstitial fluid. In general, these findings indicate that absolute bioaccessibility results in some biological fluids may vary between different laboratories. However, for most applications, measures of relative bioaccessibility are needed, diminishing the requirement for high inter-laboratory reproducibility in absolute metal releases. The inter-laboratory exercise suggests that the degrees of freedom within the protocol need to be addressed.
生物洗脱试验是体内试验快速、简便的替代方法。在本研究中，在与口服、吸入和皮肤接触相关的合成液中，评估了生物洗脱试验产生的生物可及性数据在实验室内和实验室间的变异性。使用一个既定方案，五个实验室测量了氧化钴、钴粉、铜精矿、因科镍合金、含铅黄铜合金和六水合硫酸镍的金属释放情况。重复性标准偏差（sr）和再现性标准偏差（sR）分别用于评估实验室内和实验室间的变异性。对sR: sr比值的检验表明，虽然胃液和溶酶体液具有相当好的再现性，但其他液体在各实验室之间的一致性并不好。相对标准偏差（RSD）分析显示，一些数据集的再现性结果更理想；总体结果在实验室之间的差异大于在实验室内部的差异。对sr的RSD分析表明，除了间质液中的一些金属外，所有条件下的实验室内变异性都很好。总体而言，这些发现表明，某些生物流体中的绝对生物可及性结果在不同实验室之间可能会有所不同。然而，对于大多数应用来说，需要相对生物可及性的测量方法，从而降低了对绝对金属释放中高实验室间再现性的要求。实验室间的实验表明，该方案中的自由度需要加以考虑。
