Abstract

Sensory irritation is an acute adverse effect caused by chemicals that stimulate chemoreceptors of the upper respiratory tract or the mucous membranes of the outer eye. The avoidance of this end point is of uttermost importance in regulatory toxicology. In this study, repeated exposures to ethyl acrylate were analyzed to investigate possible carryover effects from day to day for different markers of sensory irritation. Thirty healthy subjects were exposed for 4 h on five subsequent days to ethyl acrylate at concentrations permitted by the German occupational exposure limit at the time of study. Ratings of eye irritation as well as eye blinking frequencies indicate the elicitation of sensory irritation. These markers of sensory irritation showed a distinct time course on every single day. However, cumulative carryover effects could not be identified across the week for any marker. The rhinological and biochemical markers could not reveal hints for more pronounced sensory irritation. Neither increased markers of neurogenic inflammation nor markers of immune response could be identified. Furthermore, the performance on neurobehavioral tests was not affected by ethyl acrylate and despite the strong odor of ethyl acrylate the participants improved their performances from day to day. While the affected physiological marker, the increased eye blinking frequency stays roughly on the same level across the week, subjective markers like perception of eye irritation decrease slightly from day to day though the temporal pattern of, i.e., eye irritation perception stays the same on each day. A hypothetical model of eye irritation time course derived from PK/PD modeling of the rabbit eye could explain the within-day time course of eye irritation ratings repeatedly found in this study more precisely.

中文翻译：

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一项短期吸入研究，用于评估人类志愿者感觉刺激的可逆性。

摘要

感觉刺激是由刺激上呼吸道化学感受器或外眼粘膜的化学物质引起的急性不良反应。避免这一终点在调节毒理学中至关重要。在这项研究中，分析了反复暴露于丙烯酸乙酯的情况，以调查每天对于不同的感觉刺激指标可能产生的残留影响。30名健康受试者在随后的5天中以研究时德国职业暴露极限所允许的浓度暴露于丙烯酸乙酯4小时。眼睛刺激的等级以及眨眼的频率表明诱发了感觉刺激。这些感觉刺激的标志每天都显示出不同的时间进程。然而，整个星期都无法确定任何标记物的累积残留效应。流变学和生化标志物不能揭示提示更明显的感觉刺激。既不能鉴定出神经源性炎症的增加的标记物，也不能鉴定出免疫反应的标记物。此外，神经行为测试的表现不受丙烯酸乙酯的影响，尽管丙烯酸乙酯有强烈的气味，参与者每天都在改善他们的表现。虽然受影响的生理标记物，眨眼频率的增加在整个星期内大致保持在同一水平，但是主观标记物（例如，对眼睛的刺激的感觉）每天都在稍微减少，尽管在每种情况下眼部刺激的时间模式都保持不变天。