Mixed Routes of Exposure

J. J. Clary
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Abstract

While many human exposures to chemicals are by multiple exposure routes, one route usually predominates and there may be a tendency to think of the predominant route as the only route of concern. In environmental exposures a toxic material may be in the air, on food and/or in drinking water. Dermal exposure is possible if contaminated water is used for bathing. Inhalation exposure is also possible if the toxic material is volatile in hot water. The route of exposure(s) is a factor both in the design of toxicity studies and in the evaluation of a chemical's effect in humans. When testing a chemical for toxicity in animals, the route of primary concern should be the route of exposure(s) during human use. A whole-body exposure or a nose-only exposure might be used to judge the effect of pulmonary exposure. Whole-body inhalation will result in test material being deposited on the fur of experimental animals. Dermal and oral exposure, as a result of grooming, may result in a significant exposure under these conditions. The length of exposure period, short time, such as intravenous (instantaneous) or oral (bolus), compared with longer exposures such as in drinking water, inhalation exposure over a six hour period per day or continuous dermal exposure, may also be important for the response if multiple routes of exposure are of concern. A workplace exposure could result in both inhalation and dermal exposure. Absorption and metabolism most likely will proceed at different rates, and this possibly could affect the course and nature of the toxic response. Many regulatory agencies and industries rely on risk assessment in making risk management decisions. Risk assessments usually examine several routes of exposure, independently, and then the different routes of exposures are added together to define the total exposure and risk. Many times very conservative default assumptions are used. Keywords: nose-only; whole body; group versus individual housing; grooming; occupational exposure; environmental exposure; biological markers; risk assessment
混合暴露途径
虽然许多人类接触化学品是通过多种途径,但一种途径通常占主导地位,人们可能倾向于认为主要途径是唯一值得关注的途径。在环境暴露中,有毒物质可能存在于空气、食物和/或饮用水中。如果使用受污染的水洗澡,可能会接触皮肤。如果有毒物质在热水中挥发,也可能吸入接触。暴露途径是设计毒性研究和评价化学品对人体影响的一个因素。当对一种化学品进行动物毒性测试时,主要关注的途径应该是人类使用期间的暴露途径。全身暴露或仅鼻子暴露可用于判断肺部暴露的影响。全身吸入会导致试验材料沉积在实验动物的皮毛上。在这些条件下,由于梳洗,皮肤和口腔接触可能导致大量接触。暴露时间的长短,短时间,如静脉注射(瞬时)或口服(丸剂),与较长的暴露,如饮用水、每天超过6小时的吸入暴露或连续皮肤暴露相比,如果涉及多种暴露途径,也可能对反应很重要。工作场所接触可导致吸入和皮肤接触。吸收和代谢很可能以不同的速度进行,这可能会影响毒性反应的过程和性质。许多监管机构和行业依靠风险评估来做出风险管理决策。风险评估通常独立地检查几种暴露途径,然后将不同的暴露途径加在一起,以确定总暴露和风险。很多时候使用了非常保守的默认假设。关键词:nose-only;整个身体;集体住房与个人住房;梳理;职业暴露;环境暴露;生物标志物;风险评估
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