Use of Hazardous Agents in Animal Experimentation
Many studies involve the use of hazardous agents in laboratory animals. Often the use of a hazardous substance is incidental to the research, whereas in other circumstances it is an integral component of the study intended to produce a particular experimental effect. Examples of the former include inhalant anesthetic agents (e.g., ether, sevoflurane, halothane or isoflurane), analgesic agents (e.g. secobarbital and other controlled substances, acetaminophen), and adjuvants (particularly Complete Freund’s adjuvant, FCA). Examples of the latter include carcinogens, teratogens, mutagens, toxicants, microbial pathogens, radionuclides, and organisms modified through recombinant DNA techniques. EHS representatives on the IACUC review team note the uses of hazardous agents in animals during protocol review, and verify or establish the conditions under which one can use the hazardous materials safely. In some cases, it may be necessary for the institution to engage outside expert consultants and work with the investigator to develop a more elaborate safety protocol and ensure appropriate personnel training before the animal studies can proceed.
Depending on the type of hazardous agent used in animal experimentation, you might have to include the following forms in your animal use applications. These forms are integrated into the protocol through the online Application to Use Live Vertebrate Animals (ACAP) system.
A. Use of Chemical Hazards in Laboratory Animals Form
Use this form if you will use hazardous chemical substances in live, vertebrate animals. You do not need to fill out this form for substances that you use on animal tissues post-mortem. Consult product labels, MSDSs, or hazardous chemical databases to determine whether your experimental agent requires completion of this form according to the criteria below, or contact EHS for a determination.
In general, the following chemical substances will require the completion of the Use of Chemical Hazards in Laboratory Animals form:
- Any substance that meets the definition of a toxic substance from the OSHA Hazard Communication Standard, meaning that it possesses any of these three characteristics:
- oral LD50 <500 mg/kg in albino rats
- skin absorption LD50 <200 mg/kg in albino rabbits
- inhalation LC50 <2000 ppm or 20 mg/L in albino rats.
- All substances that are known or suspected human carcinogens. This includes formaldehyde-based fixatives used for animal tissue perfusion while the animal is still alive.
- All substances that are known or suspected reproductive hazards.
- All substances classified as cytotoxic/antineoplastic agents.
- All investigational drugs with limited safety or toxicological data.
- All nanoparticles or nanoparticle formulations with limited safety or toxicological data.
- All inhalation anesthetic agents (e.g. isoflurane, sevoflurane, methoxyflurane, halothane, nitrous oxide, ether).
These forms are not required for agents used strictly for animal analgesia, or for injectable anesthetic agents (e.g. ketamine, xylazine, tribromoethanol) used for anesthesia. However, if you use these substances as experimental test agents, rather than for analgesia/anesthesia, and they are either toxic or carcinogenic as defined above, then you must complete a form. Many analgesics and anesthetics are also controlled substances. Refer to Chapter 9: Controlled Substances for more information on the safe use of controlled substances.
B. Use of Biohazardous Materials in Laboratory Animals Form
Use this form if you will work with any of the following materials in live, vertebrate animals:
- Human blood or body fluids, or other potentially infectious materials, including cell lines and neoplastic tissues.
- Microbial agents capable of causing human illness or infection, including various species of bacteria, viruses, protozoa, rickettsia, etc. Note: If you are using purified, isolated microbial components such as exotoxins or endotoxins (LPS), rather than the entire microbe, the Use of Chemical Hazards in Laboratory Animals form is more appropriate.
- Microbial vectors (such as phages, adenoviruses) used for delivery of genetic materials.
- Microbial toxins (such as cholera toxin, diphtheria toxin) which affect humans and may be shed in animal secretions.
Work with viral vectors and recombinant DNA, gene transfer experiments, and transgenic animals require the approval of the Institutional Biosafety Committee (IBC). IBC forms are integrated into the online Laboratory Safety Plan. To expedite IBC review, submit these forms for approval to EHS before the end of each month, so the IBC can review them at its meeting at the beginning of the month. Refer to Chapter 2: Laboratory Safety Plan for more information about the following forms.
- For recombinant DNA, viral vectors, gene transfer experiments, and transgenic animals created within your lab, use Schedule G: Recombinant DNA of the online Laboratory Safety Plan.
- For transgenic animals created in other labs or institutions, use Schedule H: Use of Transgenic Animals or Plants of the online Laboratory Safety Plan.
C. Use of Radioactive Materials in Laboratory Animals Form
Complete this form if you will use radionuclides in vivo. This includes short-lived isotopes such as 99Tcm with a radioactive half-life (T1/2) of 6 hours, as well as longer-lived isotopes (e.g. 3H, 32P, 35S, 125I). You do not need to complete this form in order to use sealed source radiation-producing equipment on animals, such as X-ray machines or 137Cs γ-irradiators.
For additional requirements for using radionuclides or radiation-producing equipment, consult the EHS Radiation Safety Manual.