Potential use of human tissues for toxicity research and testing.

Potential use of human tissues for toxicity research and testing.
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人体组织用于毒性研究和测试的潜在用途。

DOI:
10.1016/0041-008x(89)90243-3
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发表时间:
1989
影响因子:
3.8
通讯作者:
Ducat,L
Ducat,L
中科院分区:
医学3区
文献类型:
--
作者:
Frazier,JM;Tyson,CA;McCarthy,C;McCormick,JJ;Meyer,D;Powis,G;Ducat,L

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现代毒理学中最重要的当代问题之一是来自实验室动物的科学数据对人类毒理学风险评估的充分性和适用性。使用整个动物模型系统是因为直接使用人类进行毒理学研究和试验受到伦理考虑的严重限制。用于毒理学评价的人体毒性数据来源于关于意外接触有毒化学品的人的轶事报告,来自对职业接触人群的流行病学研究,有时也来自一般公众,以及来自药物临床试验,在这些试验中,化学剂在被引入一般用途之前在人群中进行测试。在人类志愿者中对商业产品(如化妆品)进行皮肤测试是人体测试的另一个领域。然而,这些机制并不能广泛应用于毒理学研究和测试。在所有这些情况下,只有在化学品被引入人类环境后才能获得人类数据。通过利用体外方法,人体组织对外源性物质的毒理学反应可以在人体暴露之前在受控的实验条件下直接评估。这种方法具有明显的优势,它消除了将动物模型的实验观察结果外推到人身上的必要性(图1)。因此,消除了使物种间外推成为一项困难任务的许多混杂因素,特别是当不同物种的数据相互矛盾时。这并不是说,采用人体组织和细胞进行体外毒理学研究和测试就可以消除所有外推问题。即使当一个特定的体内模型已经验证了与各种化学品的体内反应,人们仍然留下了如何将体外EC 50测量与通过特定暴露途径(吸入,摄入,皮肤接触)对人类的等效剂量相关联的问题。或用于药物的肠胃外注射)。未来的一个主要毒理学挑战将是发展定量方法,从体外剂量-反应关系预测体内安全性-风险关系。与此同时,使用人体组织进行irz pi-
One of the most important contemporary issues in modern toxicology is the adequacy and suitability of scientific data derived from laboratory animals for human toxicological risk assessment. Whole animal model sys-tems are utilized because the direct use of human beings for toxicological research and testing is severely limited by ethical considerations. Sources of human toxicity data for toxicological evaluations come from anecdotal reports on people accidentally exposed to toxic chemicals, from epidemiological studies of occupationally exposed populations, and occasionally the general public, and from clinical trials of pharmaceuticals in which chemical agents are tested in human populations before their introduction for general use. Skin testing of commercial products, such as cosmetics, in human volunteers is another area of human testing. However, these mechanisms are not available for broad application to toxicological research and testing. In all of these cases, human data are obtained only after the chemical is introduced into the human environment. By utilizing in vitro methodologies, the toxicological response of human tissues to xenobiotics can be directly assessed under controlled experimental conditions in advance of human exposure. This approach has the distinct advantage that it eliminates the necessity to extrapolate experimental observations from animal models to man (Fig. 1). Thus, many of the confounding factors that make interspecies extrapolation a difficult task, particularly when there are conflicting data from various species, are eliminated. This is not to say that in vitro toxicological research and testing employing human tissues and cells can eliminate all questions of extrapolation. Even when a particular in vifro model has been validated vis-&vis in vivo responses to a variety of chemicals, one is still left with the question of how to relate an EC50 measurement in vitro to an equivalent dose to humans via a particular route of exposure (inhalation, ingestion, dermal contact. or parenteral for pharmaceuticals). A major toxicological challenge for the future will be to develop the quantitative methodology to predict in viva exposure-risk relationships from in vitro dose-response relationships. In the meantime, the use of human tissues for irz pi-
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期刊: A M A Archives of Ophthalmology
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发表时间: 1986
影响因子: 4.4
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发表时间: 1986
影响因子: 3.5
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影响因子: 4.2
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