A Study on Critical Effects of Environmental Hazard Factors on Humans

为了促进工作场所环境危险因素的风险管理，采用了无观察到的不良影响水平（NOAEL）和最低观察到的不良影响水平（LOAEL）方法。然而，由于这种方法有许多缺点，例如，不能充分反映剂量反应的形状和不能适当地考虑研究规模，因此，在职业和环境健康科学中应用了基准剂量（BMD）方法，以便为低剂量外推提供一个起点。BMD被定义为通过基准反应（BMR）导致异常终点概率增加的水平，即BMD从P_0到P_0+BMR，当P_0和BMR分别代表未暴露受试者的终点异常概率和暴露受试者的超额风险时。基准剂量水平（BMDL）计算为BMD的统计95%置信下限。本研究的目的是：(1)估计血浆、血液和尿液中铅影响δ-氨基乙酰丙酸的临界剂量，(2)阐明日本儿童产前暴露于海鲜甲基汞对发育的影响，(3)估计酒精诱导肝细胞损伤的临界剂量，(4)研究有机溶剂对神经运动功能的亚临床影响。铅暴露工人血浆、血液和尿液中δ-氨基乙酰丙酸的BMDLs低于10 μg/dl，日本和马德兰7岁儿童脑干听觉诱发电位潜伏期的BMDLs低于10 μg/g。此外，日本男性的肝细胞损伤（即AST升高）被认为在乙醇水平超过50 g/天时出现。结论是，BMD计算为估计这些物质的阈值提供了一种有希望的方法。为了在环境和职业健康领域以证据为基础预防危险因素，需要进一步研究以重新评估这些临界剂量。少

In furtherance of the risk management of environmental hazardous factors at workplaces, the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) approach was used. However, since this approach has many shortcomings, e.g., not adequately reflecting the shape of the dose response and not appropriately accounting for study size, the benchmark dose (BMD) method has been applied in occupational and environmental health sciences, to provide a point of departure for low dose extrapolation. The BMD is defined as the level that results in an increased probability of abnormal endpoint by a benchmark response (BMR), i.e., from P_0 to P_0+BMR at the BMD, when the P_0 and BMR represent an abnormal probability of the endpoint in unexposed subjects and an excess risk in exposed subjects, respectively. The benchmark dose level (BMDL) is calculated as the statistical 95% lower confidence limit of the BMD.The objectives of this study are (1)to estimate the critical d … More ose of lead affecting δ-aminolevulinic acids in plasma, blood and urine, (2)to clarify the developmental effects of prenatal exposure to methylmercury from seafood in Japanese children, (3)to estimate the critical dose of alcohol inducing hepatocellular injury, and (4)to examine the subclinical effects of organic solvents on neuromotor functions.The BMDLs were below 10 μg/dl of the blood lead level for δ-aminolevulinic acids in plasma, blood and urine in lead-exposed workers, and below 10 μg/g of hair mercury for latencies of the brainstem auditory evoked potential in Japanese and Madeiran children at age of 7 years. Also, hepatocellular injury (i.e., AST elevation) in Japanese men was suggested to emerge at the ethanol level of more than 50 g/day. It is concluded that the BMD calculations provide a promising approach for estimating the threshold of such substances. For the evidence-based prevention of hazardous factors in fields of environmental and occupational health, further study is needed to reevaluate such critical doses. Less