Boron tolerable intake - Re-evaluation of toxicokinetics for data-derived uncertainty factors
Boron tolerable intake - Re-evaluation of toxicokinetics for data-derived uncertainty factors
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DOI：
10.1007/bf02783155
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发表时间：
1998-12-01
影响因子：
3.9
通讯作者：
Poirier, K
中科院分区：
文献类型：
--
作者：
Dourson, M;Maier, A;Poirier, K
硼在环境中普遍存在，对实验动物的发育和生殖产生影响。这一观察结果促使人们努力确定硼的容许摄入量。尽管风险评估者同意使用大鼠中观察到的胎仔体重下降作为适当的关键效应，但仍需就毒代动力学数据是否足以替代默认不确定性因子达成共识。对硼毒理学的现有数据进行了批判性分析，以澄清替换默认不确定因子的适当性（种间差异为10倍，种内差异为10倍）与数据衍生值。（动力学默认值为4倍，动力学默认值为2.5倍），因为大鼠中硼的清除率比人体高3- 4倍，并且无法获得动态差异数据（以修改默认值）。基于人类妊娠期间肾小球滤过率的变异性和缺乏关于动态差异的可用数据，认为数据衍生的6倍调整（动力学为1.8倍，动力学为3.1倍）而不是默认的10倍不确定因子适用于人内变异性。进一步研究硼在大鼠中的毒代动力学将有助于为种间变异的默认不确定性因子的替代提供更强的基础。
Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in experimental animals. This observation has led to efforts to establish a Tolerable Intake value for boron. Although risk assessors agree on the use of fetal weight decreases observed in rats as an appropriate critical effect, consensus on the adequacy of toxicokinetic data as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data on boron toxicokinetics was conducted to clarify the appropriateness of replacing default uncertainty factors (10-fold for interspecies differences and 10-fold for intraspecies differences) with data-derived values.The default uncertainty factor for variability in response from animals to humans of 10-fold (default values of 4-fold for kinetics and 2.5-fold for dynamics) was recommended, since clearance of boron is 3- to 4-fold higher in rats than in humans and data on dynamic differences-in order to modify the default value-are unavailable. A data-derived adjustment of 6-fold (1.8 for kinetics and 3.1 for dynamics) rather than the default uncertainty factor of 10-fold was considered appropriate for intrahuman variability, based on variability in glomerular filtration rate during pregnancy in humans and the lack of available data on dynamic differences. Additional studies to investigate the toxicokinetics of boron in rats would be useful to provide a stronger basis for replacement of default uncertainty factors for interspecies variation.