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毒性研究的新方法:一种七气体预测模型和毒物抑制剂。

New approaches to toxicity: a seven-gas predictive model and toxicant suppressants.

作者信息

Levin B C

机构信息

Biotechnology Division, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA.

出版信息

Drug Chem Toxicol. 1997 Nov;20(4):271-80. doi: 10.3109/01480549709003885.

Abstract

Two new research approaches in combustion toxicology are: 1. the prediction of smoke toxicity from mathematical equations, which are empirically derived from, experiments on the toxicological interactions of complex fire gas mixtures and 2. the use of toxicant suppressants in materials or products to prevent the formation of toxic combustion products. The predictive approach consists of burning materials using a bench-scale method that simulates realistic fire conditions, measuring the concentrations of the primary fire gases--CO, CO2, low O2, HCN, HCl, HBr, and NO2--and predicting the toxicity of the smoke using either the 6- or 7-gas N-Gas Model. These models are based on the results of toxicological studies of these primary gases as individual gases and as complex mixtures. The predicted toxic potency is checked with a small number of animal (Fischer 344 male rats) tests to assure that an unanticipated toxic gas is not generated or an unexpected synergistic or antagonistic effect has not occurred. The results indicate if the smoke from a material or product is extremely toxic (based on mass consumed at the predicted toxic level) or unusually toxic (based on the gases deemed responsible). The predictions based on bench-scale laboratory tests have been validated with full-scale room burns of a limited number of materials of widely differing characteristics chosen to challenge the system. The advantages of this new approach are 1. the number of test animals is minimized by predicting the toxic potency from the chemical analysis of the smoke, 2. smoke may be produced under conditions that simulate the fire scenario of concern, 3. fewer tests are needed, thereby reducing the overall cost of the testing and 4, information is obtained on both the toxic potency of the smoke and the responsible gases. The N-Gas Models have been developed into the N-Gas Method (described in this paper) and these results have been used in computations of fire hazard. The 6-Gas Model is now part of the international standard ISO 13344 approved by 16 member countries of the International Standards Organization (ISO) and is also included in the U.S. national standard ASTM E1678 approved by the American Society for Testing and Materials (ASTM). In addition, the 6-Gas Model is used in the American National Standard--NFPA 269--approved by the National Fire Protection Association (Quincy, MA). The second new research approach, toxicant suppressants, examines the potential of chemical compounds, which when added to a material, to inhibit or reduce the concentration of a specific toxic gas normally generated during the material's thermal decomposition. The effectiveness of this approach was demonstrated at the National Institute of Standards and Technology (NIST) when HCN generation was reduced by 90% and the resultant toxicity of the combustion products was lowered by 50% when a flexible polyurethane foam (FPU) was treated with 0.1% (by weight) cuprous oxide (Cu2O). Copper and cupric oxide (CuO) also reduced the HCN generation but were not as efficient as Cu2O. Although melamine-treated FPU foams are being promoted as more fire safe than standard foams, a melamine-treated foam generated 10 times more HCN than a foam without melamine. The addition of Cu2O to this melamine foam also reduced the HCN generation by 90%.

摘要

燃烧毒理学中的两种新研究方法是

  1. 根据数学方程式预测烟雾毒性,这些方程式是从对复杂火灾气体混合物毒理学相互作用的实验中凭经验推导得出的;2. 在材料或产品中使用毒物抑制剂,以防止形成有毒燃烧产物。预测方法包括使用模拟实际火灾条件的小型试验方法燃烧材料,测量主要火灾气体(一氧化碳、二氧化碳、低氧、氰化氢、氯化氢、溴化氢和二氧化氮)的浓度,并使用六气体或七气体N-气体模型预测烟雾的毒性。这些模型基于对这些主要气体作为单一气体和复杂混合物的毒理学研究结果。通过少量动物(Fischer 344雄性大鼠)试验来检验预测的毒性强度,以确保不会产生意外的有毒气体,也不会出现意外的协同或拮抗作用。结果表明某种材料或产品产生的烟雾是否具有剧毒(基于在预测毒性水平下消耗的质量)或异常有毒(基于被认为起作用的气体)。基于小型实验室试验的预测已通过对有限数量具有广泛不同特性的材料进行全尺寸房间燃烧试验得到验证,这些材料被选来挑战该系统。这种新方法的优点是:1. 通过对烟雾进行化学分析预测毒性强度,从而将试验动物数量减至最少;2. 可以在模拟相关火灾场景的条件下产生烟雾;3. 需要的试验较少,从而降低了测试的总体成本;4. 可以获得有关烟雾毒性强度和起作用气体的信息。N-气体模型已发展成为N-气体方法(本文中描述),这些结果已用于火灾危险性计算。六气体模型现已成为国际标准化组织(ISO)16个成员国批准的国际标准ISO 13344的一部分,也包含在美国材料与试验协会(ASTM)批准的美国国家标准ASTM E1678中。此外,六气体模型还用于美国国家防火协会(马萨诸塞州昆西)批准的美国国家标准——NFPA 269。第二种新研究方法,即毒物抑制剂,研究化合物的潜力,这些化合物添加到材料中时,可抑制或降低材料热分解过程中通常产生的特定有毒气体的浓度。美国国家标准与技术研究院(NIST)证明了这种方法的有效性,当用0.1%(重量)的氧化亚铜(Cu2O)处理软质聚氨酯泡沫(FPU)时,氰化氢的生成量减少了90%,燃烧产物的毒性降低了50%。铜和氧化铜(CuO)也能减少氰化氢的生成,但不如Cu2O有效。尽管经三聚氰胺处理的FPU泡沫被宣传为比标准泡沫更具防火安全性,但经三聚氰胺处理的泡沫产生的氰化氢比未处理的泡沫多10倍。向这种三聚氰胺泡沫中添加Cu2O也能使氰化氢的生成量减少90%。

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