尽管大多数生理化学终点是作物和化学活性物质的标准，但选择评估它们的正确测试方法是至关重要的。本博客评估了一些标准端点，并根据不断变化的监管期望和修订的难度测试方法来查看所使用的测试。
影响物理化学检测的不断发展的环境
关键物理化学端点established for many years and little has changed in this area of crop and chemical science. Physical chemistry testing is a critical foundational activity for all crop and chemical active substances and clear test guidelines exist for most endpoints. However, accompanying test guidance and methodologies have changed over time reflecting improvements in instrumentation and more rigorous data requirements from regulators, driven initially by regulations such as EU REACH (Registration, Evaluation, Authorisation and restriction of CHemicals). In addition, endpoints that were previously waived because the test methodology was unsuitable for a specific type of substance, e.g., partition coefficient for surface-active agents, can now be assessed with advances in methods. This may have implications for established chemicals and crop protection active substances that achieved approval based on older physical chemistry tests or data waivers.
Spotlight on some key physical chemical tests and their application
该following section focuses on three key endpoints where there have been changes in methodologies and testing approaches. The changes in methods have been driven by changes in regulatory requirements and this illustrates the importance of always considering your physical chemical endpoints within the current regulatory context.
Water solubility: using the critical micelle concentration (CMC) test for surfactants
水溶性是物质的基本物理化学参数;但如果那种物质是表面活性剂怎么办？表面活性剂或表面活性剂设计成减少液体的表面张力，以便更好地混合相或增加润湿。
确定水溶性的标准试验
该standard tests used for determining water solubility are经合组织105.和the equivalent欧盟A.6。该se tests recommend the column elution or flask methods for determining water solubility but neither is applicable to surface-active agents because emulsions, which prevent accurate analysis, can be generated in the test system, as undissolved material that cannot be removed from saturated test solutions.
Rationale for using the CMC test to determine water solubility
CMC是表面活性剂的重要特征，是定义as the concentration of surfactants above which micelles form, and all additional surfactant forms micelles. As increasing concentrations of surfactant are added to water, the surface tension decreases until the minimum surface tension is reached and micelles start to form – this is the CMC. After this point, further increases in surfactant concentration have little impact on surface tension, which remains relatively constant, as all additional surfactant forms micelles. In terms of water solubility, below the CMC, the surfactant is considered to be thermodynamically soluble in the water while, above the CMC, the solubility of the surfactant in water is exceeded. Thus, the water solubility of a surfactant may be expressed in terms of the CMC.
Utilizing the CMC test in practice
该key measurement used for determining CMC is surface tension, measured using a tensiometer. Simple dilutions of a strong, fully dispersed stock solution of test substance are used and the surface tension of each dilution is measured. Surface tension is then plotted against concentration using a logarithmic scale. Linear regressions are fitted to the two parts of the graph and the point of intersection determines the CMC – see the example.
Figure 1: Surface tension versus log concentration of a surface-active substance
对作物或化学活性物质注册或重新申请的影响
Older chemicals may not have data for water solubility estimated in this way and this could be a gap within existing dossiers.
分区系数：使用POW的物质OECD 123> 4
该分配系数is defined as the ratio of the equilibrium concentrations of a dissolved substance in a two-phase system consisting of two immiscible solvents. For testing purposes, this is usually the partition coefficient of the test substance between water and 1-octanol (POW). It is used to establish whether a substance tends to be hydrophobic or lipophilic and provides information about how the substance is likely to be distributed in animal tissues and the wider environment. The value obtained can indicate the bioaccumulation potential of the substance in the environment. However, not all tests are applicable for surface-active substances and, whilst, historically, regulators may have accepted the absence of partition-coefficient data on that justification, this is no longer sufficient as new methods to assess POW have become available.
Standard tests for determining partition coefficient
经合组织107是用于确定POW的标准方法，但仅适用于与-2至4之间的物质，因为摇瓶方法可以将辛醇微量水解物强制到水相中，导致用日志测试物质的物质在水中的高度估量。战略> 4。
POW assessment of gases can also be challenging but, by using variations of the standard OECD 107 test method, this can be successfully achieved.
Rationale for using the OECD 123 to determine POW
经合组织123.减少了Microdroplets引起的Pow伪饼 - 经合组织107的主要缺点。它通过使用缓慢搅拌的方法而不是经常经常调量的方法107中使用的摇瓶方法。
Utilizing the OECD 123 test in practice
For OECD 123, the test substance is equilibrated with water and octanol in a stirred chamber. Once equilibrium between the phases is reached, POW is measured directly in the same way as for OECD 107. The time required to reach equilibrium varies depending on the substance’s hydrophobicity; the more hydrophobic the substance, the longer it takes to reach equilibrium.
对作物或化学活性物质注册或重新申请的影响
Historically, if a substance had a POW >4, then no further quantification was made and the data waived. However, by using the stirred method, POW can now be estimated for these substances and data waivers may now be perceived as data gaps. This endpoint may need to be reassessed with this test to align with current standards.
易燃性和自燃：选择符合法规需求的正确测试方法
可燃性和自身的物理化学终点对于安全评估以及可活性物质的分类和标记是重要的。多年来，欧盟委员会方法（EU A9–A17) were the internationally recognized standard tests used for assessment of flammability endpoints and they are still valid and in use today. However, most of those EU tests have been superseded by test methods defined in the测试和标准手册当联合国关于运输危险货物，示范法规的建议和the Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Two key endpoints of note are flammability and autoignition of a solid, both of which influence the classification of a solid substance as flammable. The section below looks at the differences in the EU and UN methods used to assess those endpoints.
Test options for determining flammability of a solid: EU method A10 and UN method N.1
Both theEU A10和UN N.1.methods are similar and involve the construction of a 25-cm long mold of the solid test substance, which is then set on fire at one end. The time taken to burn from end to end is measured and used to classify flammability. ForUN N.1测试, there is a wet zone approximately halfway along the length of the mold to test if the flame can jump the wetted area.
Test options for determining autoignition of a solid: EU method A16 and UN method N.4
再次，这EU A16和联合国第n.4.方法旨在评估物质的自燃烧电位，并遵循普遍类似的设计。将测试物质填充到敞开的网状立方体中并悬浮在加热的烘箱中。在欧盟方法A16下，烘箱温度升至400℃，如果物质点燃，则观察到烘箱的物质温度急剧增加 - 自燃温度。在任何方法N.4下，通过在140℃下将立方体加热24小时来确认自点火。通过自点火指示阳性结果，或者如果物质的温度超过烘箱的温度超过60℃。
对作物或化学活性物质注册或重新申请的影响
虽然这些不同方法评估的关键可燃性终点是相同的，但用于评估它们的测试是巧妙的，但重要的是，不同。必须理解评估物理化学终点的监管背景，从而可以使用最合适的测试方法。
Conclusions
物理化学是发展的基础，随后批准作物或化学活性物质。确定评估关键物理化学参数的最佳方法需要了解测试材料的性质和将使用它的调节情况。将物理化学测试分类为您只需要通过的简单，无聊的东西进行分类，但它是非常重要的。对于许多较旧的物质，这些基本属性可能已经在非GLP设施中确定了可能不再符合最新测试指导的测试。对于新的和旧物质，对物理化学端点和测试的新鲜思考变得更加重要，特别是随着监管景观的变化。一个很好的例子是欧盟规定纳米材料，在粒径，形状和表面化学的物理化学参数中，都在纳米型分类中发挥重要组成部分。因此，珍惜无聊，并更加关注物理化学 - 它是您物质成功的基础。
For similar material on this subject, read our case study,Physicochemical Testing Case Study – Handling Difficult Substances – Gases或访问我们的网站。
