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Empirical approaches for the investigation of toxicant-induced loss of tolerance.

机译:调查有毒物引起的耐受性丧失的经验方法。

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摘要

It has been hypothesized that sensitivity to low-level chemical exposures develops in two steps: initiation by an acute or chronic chemical exposure, followed by triggering of symptoms by low levels of previously tolerated chemical inhalants, foods, or drugs. The Working Group on Toxicant-induced Loss of Tolerance has formulated a series of research questions to test this hypothesis: Do some individuals experience sensitivity to chemicals at levels of exposure unexplained by classical toxicological thresholds and dose-response relationships, and outside normally expected variation in the population? Do chemically sensitive subjects exhibit masking that may interfere with the reproducibility of their responses to chemical challenges? Does chemical sensitivity develop because of acute, intermittent, or continuous exposure to certain substances? If so, what substances are most likely to initiate this process? An experimental approach for testing directly the relationship between patients' reported symptoms and specific exposures was outlined in response to the first question, which was felt to be a key question. Double-blind, placebo-controlled challenges performed in an environmentally controlled hospital facility (environmental medical unit) coupled with rigorous documentation of both objective and subjective responses are necessary to answer this question and to help elucidate the nature and origins of chemical sensitivity.
机译:据推测,对低水平化学暴露的敏感性可通过两个步骤发展:通过急性或慢性化学暴露引发,然后通过低水平的先前耐受的化学吸入剂,食物或药物触发症状。毒物引起的耐受性丧失工作组提出了一系列研究问题,以检验这一假设:一些人是否经历过传统毒理学阈值和剂量反应关系无法解释的暴露水平对化学物质的敏感性,以及正常情况下预期的变异。人口?化学敏感的受试者是否表现出掩蔽性,可能会掩盖他们对化学挑战的反应的可重复性?是否由于急性,间歇或持续接触某些物质而产生化学敏感性?如果是这样,什么物质最有可能引发这一过程?针对第一个问题,概述了一种直接测试患者报告的症状与特定暴露之间的关系的实验方法,这被认为是一个关键问题。在环境控制的医院设施(环境医疗单位)中进行的双盲,安慰剂控制的挑战,加上对客观和主观反应的严格记录,对于回答此问题并有助于阐明化学敏感性的性质和起源是必要的。

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