Pulmonary toxicity of components of textile paint linked to the Ardystil syndrome: Intratracheal administration in hamsters
Pulmonary toxicity of components of textile paint linked to the Ardystil syndrome: Intratracheal administration in hamsters
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DOI：
10.1136/oem.54.6.376
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发表时间：
1997-06-01
影响因子：
4.9
通讯作者：
Nemery, B
中科院分区：
文献类型：
--
作者：
Clottens, FL;Verbeken, EK;Nemery, B
目的-流行病学调查假设，在西班牙和阿尔及利亚，从Acramin FWR（一种聚脲）到Acramin FWN（一种聚酰胺胺）的配方变更导致纺织品印花喷雾器出现严重的肺部疾病。为了验证这一点，涉及的油漆系统的组件的肺毒性进行了评估，在实验animals. Methods的单个组件和相关的混合物，在磷酸盐缓冲盐水稀释，通过intraperitheal滴注2毫升/公斤仓鼠。在单次气管内滴注后第3、7、14、28和92天，通过组织学和测量湿肺和干肺重量、蛋白浓度、乳酸脱氢酶、碱性磷酸酶、β-N-乙酰氨基葡萄糖苷酶和γ-谷氨酰转移酶的活性、支气管肺泡灌洗液（BALF）中的炎性细胞数量和分布，结果：以半数致死剂量（LD（50）s）为基础，经气管内给药的各种成分的毒性比经口给药（根据大鼠经口LD（50）s）高10 ~ 1250倍。Acramin FWN、Acramin FWR、Acrafix FHN或其混合物引起肺损伤。BALF中蛋白质浓度、酶活性、细胞总数和中性粒细胞百分比在滴注后第一周内升高。肺部重量至少在一个月内保持在较高水平。组织学显示炎性细胞浸润和随后的纤维化伴胶原沉积。干燥肺组织中羟脯氨酸含量增加证实了这一发现。Acramoll W没有显示毒性作用。结论-该研究表明，在仓鼠中，Acramin FWR和Acramin FWN的急性肠道毒性之间没有重大差异。因此，流行病学假设没有简单的毒理学解释。然而，这些非刺激性聚合化合物的肺毒性令人惊讶地高。Ardystil灾难和这些结果应该作为一个强烈的警告，即传统的化学品毒性测试不一定能保护工人免受呼吸毒性。
Objectives-It was hypothesised from an epidemiological investigation that a formula change from Acramin FWR (a polyurea) to Acramin FWN (a polyamideamine) had led to severe pulmonary disease in textile printing sprayers in Spain and Algeria. To verify this, the pulmonary toxicity of the components of the paint systems involved was assessed in experimental animals.Methods-Individual components and relevant mixtures, diluted in phosphate buffered saline, were given by intratracheal instillation of 2 ml/kg to hamsters. Pulmonary toxicity was assessed on days 3, 7, 14, 28, and 92 after a single intratracheal instillation, by histology and by measuring wet and dry lung weight, protein concentration, the activities of lactate dehydrogenase, alkaline phosphatase, beta-N-acetyl-glucosaminidase, and gamma-glutamyltransferase, inflammatory cell number and distribution in bronchoalveolar lavage fluid (BALF), and hydroxyproline content in dried lung tissue.Results-Based on the doses that killed 50% of the animals (LD(50)s), the various components were found to be 10 to 1250 times more toxic when given intratracheally than when given orally (according to reported oral LD(50)s in rats). Acramin FWN, Acramin FWR, Acrafix FHN, or their mixtures caused lung damage. Protein concentration, enzyme activities, total cell number, and percentage of polymorphonuclear neutrophils were increased in BALF during the first week after intratracheal instillation. Lung weights remained high for at least a month. Histology showed inflammatory cell infiltration and subsequent fibrosis with collagen deposition. This finding was confirmed by an increased hydroxyproline content in dried lung tissue. Acramoll W did not show toxic effects.Conclusions-The study suggests that there is no major difference, in hamsters, between the acute intratracheal toxicity of Acramin FWR and that of Acramin FWN. Consequently, there is no simple toxicological explanation for the epidemiological hypothesis. However, the pulmonary toxicity of these non-irritant polymeric compounds is surprisingly high. The Ardystil disaster and these results should serve as a strong warning that conventional toxicity testing of chemicals does not necessarily protect workers against respiratory toxicity.