Individuals who are working with highly toxic chemicals, as identified in Chapter 3, section 3.C, should be thoroughly familiar with the general guidelines for the safe handling of chemicals in laboratories (see section 5.C). They should also have acquired through training and experience the knowledge, skill, and discipline to carry out safe laboratory practices consistently. But these guidelines alone are not sufficient when handling substances that are known to be highly toxic and chemicals that, when combined in an experimental reaction, may generate highly toxic substances or produce new substances with the potential for high toxicity. Additional precautions are needed to set up multiple lines of defense to minimize the risks posed by these substances. As discussed in section 5.B, preparations for handling highly toxic substances must include sound and thorough planning of the experiment, understanding the intrinsic hazards of the substances and the risks of exposure inherent in the planned processes, selecting additional precautions that may be necessary to minimize or eliminate these risks, and reviewing all emergency procedures to ensure appropriate response to unexpected spills and accidents. Each experiment must be evaluated individually because assessment of the level of risk for work with any substance depends on how the substance will be used. Therefore, it would not be prudent for the planner to rely solely on a list of "highly toxic" chemicals to determine the level of the risk; under certain conditions, even chemicals not on these lists may become highly toxic.

In general, the guidelines in section 5.C reflect the minimum standards for handling hazardous substances. They should become standard practice when highly toxic substances are handled in the laboratory. For example, it is always preferable to avoid working alone in laboratories. However, when highly toxic materials are being handled, it is essential that more than one person be present and that all people working in the area be familiar with the hazards of the experiments being conducted and with the appropriate emergency response procedures. Personal protective equipment to safeguard the hands, forearms, and face from exposure to chemicals, while desirable in most circumstances, is essential in handling highly toxic materials. Good housekeeping creates an intrinsically safer workplace and should be maintained scrupulously in areas where highly toxic substances are handled. Source reduction is always a prudent practice, but in the case of highly toxic chemicals it may mean the difference between working with toxicologically dangerous amounts of materials and working with quantities that can be handled safely with routine practice. Similarly, emergency response planning and training become very important when working with highly toxic compounds. Additional hazards from these materials (e.g., flammability and high vapor pressures) can complicate the situation, making operational safety all the more important.

5.D.1 Planning

Careful planning needs to precede any experiment involving a highly toxic substance whenever the substance is to be used for the first time or whenever an experienced user carries out a new protocol that increases substantially the risk of exposure. Planning should include consultations with colleagues who have experience in handling the substance safely and in protocols of use. Experts in the institution's environmental health and safety program are a valuable source of information on the hazardous properties of chemicals and safe practice. They also need to be consulted for guidance regarding those chemicals that are regulated by federal, state, and local agencies or by institutional policy. Training and documentation requirements may have to be incorporated into the experiment plan.

Effective planning is always guided by two principles: substitution of highly toxic substances with less toxic alternatives whenever appropriate and use of the smallest amount of material that is practicable for the conduct of the experiment. Other important factors to be considered in determining the need for additional safeguards are the likelihood of exposure inherent in the proposed experimental process, the toxicological and physical properties of the chemical substances being used, the concentrations and amounts involved, the duration of exposure, and known toxicological effects. It is also important to plan for careful management of the substances throughout their life cycle—from acquisition and storage through destruction or safe disposal.

5.D.2 Experiment Protocols Involving Highly Toxic Chemicals

Experiment plans that involve the use of highly toxic substances or high-risk protocols should be considered carefully, and experienced personnel or an appropriate source should be consulted about the risk. An experiment plan that describes the additional safeguards that will be used for all phases of the experiment from

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