1.1 本指南定义了急性动物毒性试验，并规定了评估生产的水溶性金属加工液急性毒性的程序参考。 1.2 尽管与水混溶的金属加工液通常以高稀释度使用，但稀释率差异很大。此外，也有可能暴露在制造的金属加工液中。 1.3 本标准并非旨在解决与其使用相关的所有安全问题（如有）。本标准的使用者有责任在使用前制定适当的安全、健康和环境实践，并确定监管限制的适用性。 1.4 本国际标准是根据世界贸易组织技术性贸易壁垒委员会发布的《关于制定国际标准、指南和建议的原则的决定》中确立的国际公认的标准化原则制定的。 ====意义和用途====== 4.1 本指南的应用将提供与水混溶的金属加工液的急性毒性信息，并将帮助用户评估该液的潜在健康危害和制定适当的工作实践。 与水混溶的金属加工液是一种浓缩液，设计用于在水中稀释使用。 4.2 与水混溶的金属加工液是复杂的化学混合物。美国职业安全与健康管理局（OSHA）危险沟通标准（见 第1.8条 )概述了混合物的危险性测定程序，并指出如果混合物没有作为一个整体进行测试，则应假设混合物与包含1 % （按重量或体积计）或更大，但如果混合物中含有浓度为0的成分，则应认为混合物具有致癌危险。 1. % 或更大，被认为是致癌物（如OSHA标准所定义 29 CFR 1910.1200）。何时对混合物进行整体测试以及哪些毒性测试适用于产品，必须由具有毒理学数据评估资格的卫生专业人员进行确定。 4.3 水溶性金属加工液的急性毒理学测试包括几个单独的测试，包括急性口服、皮肤或吸入毒性、眼睛刺激、皮肤刺激或腐蚀，或两者兼有，皮肤致敏和感觉刺激。急性口服、皮肤和吸入毒性试验的某些方案是极限试验； 进一步的多剂量测试（例如，测试方法 第103页 )如果在这些测试中发现有死亡，则应进行。参考协议规定了所需动物的种类和数量。所进行的试验的选择应尽量减少使用的动物数量。 4.3.1 急性口服毒性- 急性口服毒性试验（见 第1.1条 )提供关于通过口服途径短期接触可能产生的健康危害的信息。根据OSHA危险通信标准的要求，此类测试的结果用于在标签上制定警告声明 1910年《联邦法规汇编》第29卷。 1200（参见 第1.8条 )或《联邦危险物质法》（见 2010年10月 ). 这些也用于建立亚慢性和其他测试的剂量方案。终点:死亡率。 4.3.2 急性皮肤毒性- 急性皮肤毒性试验（见 第1.2条 )提供关于通过皮肤途径短期暴露可能产生的健康危害的信息，并且可以提供关于物质的皮肤吸收和毒性作用模式的初始信息。此外，可以通过观察施用时的局部组织损伤来获得由液体引起的刺激的一些测量。终点:死亡率。 4.3.3 急性吸入毒性- 急性吸入毒性试验给出了相对毒性的指示（见 第1.3条 ). 该结果表明，当吸入特定时间段时，液体可能会导致死亡和其他不良健康影响。终点:死亡率。 4.3.4 眼睛刺激- 眼睛刺激性测试提供了液体在直接接触时引起眼睛刺激或损伤的可能性的指示（见 第1.4条 ). 刺激物是指一种没有腐蚀性的化学物质，但通过接触部位的化学作用对活组织产生可逆的炎症作用。 终点:刺激程度。 4.3.5 皮肤刺激或腐蚀- 皮肤刺激或腐蚀测试表明液体可能对皮肤产生刺激或损伤（参见 第1.5条 ). 腐蚀性化学物质是指通过接触部位的化学作用对活体组织造成可见破坏或不可逆转的改变。终点:刺激或腐蚀。 4.3.6 皮肤致敏- 化学增敏剂是一种物质，在反复接触该化学物质后，会导致相当一部分接触过该化学物质的人或动物在正常组织中产生过敏反应。 有许多方法可用于测量皮肤致敏，但对于最合适的方法存在意见分歧。这是由于化合物给药和对致敏物质的反应程度的变化。有关各种协议，请参阅《联邦法规》（CFR）（参见 第1.6条 ). 此外，毒理学测试合同实验室可能有进行这些分析的标准程序。终点:致敏。 4.3.7 感官刺激- 一旦接触到感官刺激物，人类会感到眼睛、鼻子和喉咙的不适或灼烧感，还可能咳嗽。 试验方法 E981型 （参见 A1.2.5 )提供了一种评估空气中化学物质和混合物的感官刺激潜力的方法，以及评估化合物和制剂的相对刺激性的方法。然而，这种测试方法不能用于评估气味的相对毒性。终点:上呼吸道刺激。 4.4 许多联邦指南可用于制定金属加工液急性毒性测试的一般程序。中引用了一些参考文献 附件A1 无论使用何种方法，美国环境保护局（EPA 40 CFR 792）概述的《良好实验室规范》（见 第1.9条 )必须遵守。OSHA危险通信标准（参见 第1.8条 )概述了化学品制造商、进口商和雇主在确定化学品危害和交流有关这些危害的信息方面的责任。 4.5 本指南中引用的方法，或经济合作与发展组织（OECD）建议的适当替代方法，可用于测试与水混溶的金属加工液的急性毒性。对于中概述的每个测试 A1.1– 第1.5条 ，包括一个表，该表强调了测试协议之间的相似性和差异性。

1.1 This guide defines acute animal toxicity tests and sets forth the references for procedures to assess the acute toxicity of water-miscible metalworking fluids as manufactured. 1.2 Although water-miscible metalworking fluids are typically used at high dilution, dilution rates vary widely. Additionally, there is potential for exposure to the metalworking fluid as manufactured. 1.3 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use. 1.4 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee. ====== Significance And Use ====== 4.1 Application of this guide will provide information on the acute toxicity of water-miscible metalworking fluids and will assist the user in evaluating the potential health hazards of the fluid and developing appropriate work practices. A water-miscible metalworking fluid is a concentrate designed to be diluted in water for use. 4.2 Water-miscible metalworking fluids are complex chemical mixtures. The United States Occupational Safety and Health Administration (OSHA) Hazard Communication Standard (see A1.8 ) outlines procedures for the hazard determination of mixtures and states that if a mixture has not been tested as a whole, then the mixture shall be assumed to present the same hazards as do the components that comprise 1 % (by weight or volume) or greater of the mixture, except that the mixture shall be assumed to present a carcinogenic hazard if it contains a component in concentrations of 0.1 % or greater, which is considered to be a carcinogen (as defined in OSHA Standard 29 CFR 1910.1200). The determination of when to test a mixture as a whole and which toxicity tests are appropriate for the product must be made by a health professional qualified in evaluating toxicological data. 4.3 Acute toxicology testing of water-miscible metalworking fluids consists of several individual tests including acute oral, dermal, or inhalation toxicity, eye irritation, skin irritation or corrosion, or both, skin sensitization, and sensory irritation. Certain protocols for acute oral, dermal, and inhalation toxicity tests are limit tests; further multi-dose testing (for example, Test Method E1103 ) should take place if mortality is noted on any of these tests. The referenced protocols specify the species and number of animals required. Selection of tests conducted should be designed to minimize the number of animals used. 4.3.1 Acute Oral Toxicity— Acute oral toxicity tests (see A1.1 ) provide information on health hazards likely to arise from short-term exposure by the oral route. Results of this type of test are used to develop warning statements on labels as may be required by OSHA Hazard Communication Standard 29 CFR 1910.1200 (see A1.8 ) or Federal Hazardous Substances Act (see A1.10 ). These are also used to establish a dosage regimen for subchronic and other testing. Endpoint: mortality. 4.3.2 Acute Dermal Toxicity— Acute dermal toxicity tests (see A1.2 ) provide information on health hazards likely to arise from short-term exposure by the dermal route and may provide initial information on dermal absorption and the mode of toxic action of a substance. In addition, some measure of irritation caused by the fluid may be obtained by observing local tissue damage at the sight of application. Endpoint: mortality. 4.3.3 Acute Inhalation Toxicity— Acute inhalation toxicity tests give an indication of relative toxicity (see A1.3 ). The results provide an indication of the potential of the fluid to cause death and other adverse health effects when inhaled for a specified time period. Endpoint: mortality. 4.3.4 Eye Irritation— Eye irritation tests provide an indication of the potential of the fluid to cause eye irritation or damage upon direct contact (see A1.4 ). An irritant is defined as a chemical that is not corrosive, but causes a reversible inflammatory effect on living tissue by chemical action at the site of contact. Endpoint: degree of irritation. 4.3.5 Skin Irritation or Corrosion— Skin irritation or corrosion tests indicate the potential of the fluid to produce irritation or damage to skin (see A1.5 ). A corrosive chemical is one that causes visible destruction of, or irreversible alterations in, living tissue by chemical action at the site of contact. Endpoint: irritation or corrosion. 4.3.6 Skin Sensitization— A chemical sensitizer is a material that causes a substantial proportion of exposed people or animals to develop an allergic reaction in normal tissue after repeated exposure to the chemical. A number of methods are available for measuring skin sensitization, however, there are differences in opinion on the most appropriate method. These are due to variations in compound administration and degree of reaction to a sensitizing substance. Refer to the Code of Federal Regulations (CFR) for the various protocols (see A1.6 ). Additionally, toxicology testing contract labs may have standard procedures for conducting these assays. Endpoint: sensitization. 4.3.7 Sensory Irritation— Upon exposure to a sensory irritant, humans experience discomfort or a burning sensation of the eyes, nose, and throat, and may also cough. Test Method E981 (see A1.2.5 ) provides a means to evaluate the sensory irritant potential of airborne chemicals and mixtures, as well as a means to assess the comparative irritancy of compounds and formulations. However, this test method cannot be used to evaluate the relative obnoxiousness of odors. End point: upper respiratory tract irritation. 4.4 A number of federal guidelines can be used to establish general procedures for testing acute toxicity of metalworking fluids. Several references are cited in Annex A1 . Regardless of the method used, Good Laboratory Practices, as outlined by the United States Environmental Protection Agency (EPA 40 CFR 792) (see A1.9 ) must be followed. The OSHA Hazard Communication Standard (see A1.8 ) outlines the responsibilities of chemical manufacturers, importers, and employers in the determination of chemical hazards and communication of information on those hazards. 4.5 The methods referenced in this guide, or appropriate alternate methods such as those suggested by the Organization for Economic Cooperation and Development (OECD), are acceptable for testing the acute toxicity of water-miscible metalworking fluids. For each test outlined in A1.1 – A1.5 , a table is included that highlights the similarities and differences between the test protocols.