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Inhalation study of very low dose of formaldehyde in mice relate to a model for multiple chemical sensitivity

小鼠极低剂量甲醛吸入研究与多种化学敏感性模型相关

基本信息

批准号：
13680635
负责人：
KUNUGITA Naoki
金额：
$ 2.05万
依托单位：
University of Occupational and Environmental Healtn
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Multiple chemical sensitivity (MCS) is characterized by various somatic symptoms which cannot be explained organically and by sensitivity to extremely low concentrations of chemicals including formaldehyde. Formaldehyde is a flammable, colorless and readily polymerized gas at ambient temperature. Formaldehyde exposure is considered to be one of initiating event for induction of MCS. In this study, we developed an animal model to investigate the effect of chronic exposure to low levels of formaldehyde in mice. Female mice (BALB/c and C3H/He) with or without ovalbumin (OVA)-immunization were exposed to either ambient air or formaldehyde gas obtained by depolymerization of paraformaldehyde at a dose of 80, 400 and 2000 ppb for four or twelve weeks (16 hours/day x 5 days/week). The formaldehyde gas concentration in the chamber was measured by a 2,4-dinitrophenylhydrazine (DNPH) - high performance liquid chromatography (HPLC). The body weights of animals exposed to formaldehyde were similar to those of their controls. Formaldehyde exposure did not show any adverse effects including epithelial cell proliferation, epithelial dysplasia and squamous metaplasia on morphology of the lung and trachea. We also investigated chronic effects of formaldehyde on the neuronal function, especially on hippocampus. We observed the decrease in recurrent inhibition in the dentate gyrus, that may contribute to alter the excitability of the hippocampus. As for changes in behavior, exposure to formaldehyde induced dose dependent increases in sneezing reflexes. Sneezing reflexes in the mice sensitized with OVA was significantly high compared with non-sensitized mice even in exposure to 80ppb formaldehyde. Further study is necessary to determine how theses changes could relate to a model for MCS.

多重化学敏感性（MCS）的特征是各种无法有机解释的躯体症状，以及对极低浓度的化学品（包括甲醛）的敏感性。甲醛是一种易燃、无色且在环境温度下容易聚合的气体。甲醛暴露被认为是诱导MCS的起始事件之一。在这项研究中，我们开发了一种动物模型，以探讨长期暴露于低水平的甲醛对小鼠的影响。将有或没有卵清蛋白（OVA）免疫的雌性小鼠（BALB/c和C3 H/He）暴露于环境空气或通过80、400和2000 ppb剂量的多聚甲醛解聚获得的甲醛气体中4周或12周（16小时/天× 5天/周）。通过2，4-二硝基苯肼（DNPH）-高效液相色谱（HPLC）测量室内甲醛气体浓度。暴露于甲醛的动物的体重与其对照组相似。甲醛暴露对肺和气管的形态没有显示任何不良影响，包括上皮细胞增殖、上皮异型增生和鳞状上皮化生。我们还研究了甲醛对神经元功能的慢性影响，特别是对海马的影响。我们观察到齿状回的复发性抑制减少，这可能有助于改变海马的兴奋性。至于行为变化，接触甲醛会导致打喷嚏反射的剂量依赖性增加。与未致敏小鼠相比，即使暴露于80 ppb甲醛，用OVA致敏的小鼠中的喷嚏反射也显著较高。有必要进一步研究，以确定这些变化如何与监控监模式相关。