Division of Immunology, Allergy Section, Department of Internal Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
Clin Rev Allergy Immunol. 2020 Aug;59(1):61-77. doi: 10.1007/s12016-020-08801-w.
Acid anhydrides are used by chemical industries as plasticizers. Trimellitic acid (TMA) is an acid anhydride widely utilized in factories to produce paints, varnishes, and plastics. In addition to causing direct irritant effects, TMA can augment antibody responses in exposed factory workers leading to occupational asthma. Therefore, industries producing TMA have implemented occupational immunosurveillance programs (OISPs) to ensure early diagnosis and medical management, involving exposure reduction/ complete removal of sensitized workers from exposure areas. Multiple animal models (mice strains, rat stains, guinea pig, swine) with different exposure patterns (dermal, nasal, vapor inhalation exposures for different time frames) have been described to elucidate the pathophysiology of TMA exposure. In TMA factories, in spite of implementing advanced environmental controls and personal protective measures to limit exposure, workers become TMA-sensitized. Animal models revealed sIgG, sIgE, sIgA, and sIgM along with pulmonary lesions, cellular infiltrates, alveolar hemorrhage, and pneumonitis associated with TMA exposure. Molecular studies showed involvement of specific functional gene clusters related to cytokine and chemokine responses, lung remodeling, and arginase function. However, thus far, there is no evidence supporting fetotoxic or carcinogenic effects of TMA. OISP data showed IgG and IgE responses in exposed factory workers. Interestingly, timelines for detectable sIgG response, in conjunction with its magnitude, have been shown to be a predictor for future sIgE response. OISPs have been very successful so far at creating a healthy and safe working environment for TMA-exposed factory workers. Graphical Abstract Trimellitic Acid (TMA), used to produce paints, varnishes and plastics, can cause irritant-mediated and immune-mediated occupational health problems. NCBI pubmed search indicated that multiple animal models (different animal types, with chronic vs. acute exposure type, using TMA dust/suspension applied via dermal or other routes) have been used by investigators to elucidate the pathobiology of TMA-exposure. Several outcomes have been measured including humoral, lung/ airway, lymph nodes and dermal/ ear thickening responses. Studies on human subjects have been conducted mostly as parts of Occupational immunosurveillance programs (OISPs) implemented to identify TMA-sensitized workers (using ImmunoCAP and Skin prick testing), monitoring them longitudinally and their medical management including exposure reduction/ complete removal of sensitized workers from exposure areas. Clinical management also includes identification of irritant-induced and/ or immune-mediated outcomes of TMA occupational exposure. Collectively, these studies have led to important insights into the pathomechanism of TMA-exposure and have been very successful at creating a safe working environment for TMA-exposed factory workers.
酸酐被化学工业用作增塑剂。偏苯三酸酐（TMA）是一种广泛应用于工厂生产油漆、清漆和塑料的酸酐。除了直接引起刺激性效应外，TMA 还可以增强暴露于工厂工人的抗体反应，导致职业性哮喘。因此，生产 TMA 的行业已经实施了职业免疫监测计划（OISP），以确保早期诊断和医疗管理，包括减少接触/将致敏工人从接触区域完全移除。已经描述了多种具有不同暴露模式（皮肤、鼻、蒸气吸入不同时间框架）的动物模型（小鼠品系、大鼠品系、豚鼠、猪），以阐明 TMA 暴露的病理生理学。在 TMA 工厂，尽管实施了先进的环境控制和个人防护措施来限制接触，但工人仍会对 TMA 产生过敏。动物模型显示 TMA 暴露与 sIgG、sIgE、sIgA 和 sIgM 以及与 TMA 暴露相关的肺损伤、细胞浸润、肺泡出血和肺炎有关。分子研究表明，与细胞因子和趋化因子反应、肺重塑和精氨酸酶功能相关的特定功能基因簇参与其中。然而，到目前为止，没有证据支持 TMA 具有致胎儿毒性或致癌作用。OISP 数据显示暴露于工厂工人的 IgG 和 IgE 反应。有趣的是，检测到 sIgG 反应的时间线及其幅度已被证明是未来 sIgE 反应的预测因素。到目前为止，OISP 在为 TMA 暴露的工厂工人创造健康和安全的工作环境方面非常成功。 图摘要 偏苯三酸酐（TMA）用于生产油漆、清漆和塑料，可引起刺激性和免疫介导的职业健康问题。NCBI pubmed 搜索表明，研究人员使用了多种动物模型（不同动物类型，慢性与急性暴露类型，使用 TMA 粉尘/悬浮液通过皮肤或其他途径应用）来阐明 TMA 暴露的病理生物学。已经测量了几种结果，包括体液、肺/气道、淋巴结和皮肤/耳部增厚反应。对人类受试者的研究主要作为实施职业免疫监测计划（OISP）的一部分进行，以识别 TMA 致敏工人（使用 ImmunoCAP 和皮肤点刺测试），对他们进行纵向监测，并进行医学管理，包括减少接触/将致敏工人从接触区域完全移除。临床管理还包括确定 TMA 职业暴露引起的刺激性和/或免疫介导的结果。总的来说，这些研究为 TMA 暴露的发病机制提供了重要的见解，并为 TMA 暴露的工厂工人创造了安全的工作环境。
