Biologically-derived toxins are products of plants, animals, microorganisms (including, but not limited to, bacteria, viruses, fungi, or protozoa), that can cause adverse effects when inhaled, ingested, injected, or otherwise absorbed into the body. Biologically-derived toxins are unable to replicate and do not result in communicable diseases. They reside between traditional definitions of biological and chemical agents. Biologically-derived toxins encompass a vast range of peptides, small molecules, and macromolecular proteins that cause disease by interfering with biological processes.
Examples of biologically-derived toxins include Diphtheria toxin, Tetrodotoxin, and Pertussis toxin. Chemical compounds or pharmaceutical compounds such as those used for chemotherapy are not considered biologically-derived and are not under IBC purview.
IBC review is required for the use of unfractionated mixtures and purified preparations of biologically-derived toxins having:
- High acute toxicity (i.e., a mammalian LD50 of less than or equivalent to 100 micrograms/kg body weight)
- Significant potential for serious subacute or chronic toxicity (e.g., carcinogenicity).
If either of these conditions is met but a mammalian LD50 is not known, please submit an application. If in doubt, please submit an application.
Dual Use Screening Survey
Some toxins have been classified as Select Agents since they may pose a severe threat to human, animal, or plant health and/or safety.
Certain research with biologically-derived toxins may be considered ‘dual use’ if, based on current understanding, the research could be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences. These consequences could affect public health and safety, agricultural crops or other plants, animals, the environment, or national security.
As part of the IBC review process, the Dual Use Screening Survey must be completed and attached to the application for the proposed use of any toxin named on the Select Agents list, regardless to the quantity used. For example, the use of botulinum toxin and toxin producing strains of Clostridium botulinum would require a Dual Use Screening Survey.
Section 3 Biological Toxins Content Guidance:
1. To activate this section of the application, you must first select “Biological Toxins” in the Activities Include section of the application. After doing so, an “Add” and “Delete” button will appear in the top right corner of section 3)a so that you can populate the table.
2. Add biologically-derived toxins to section 3a as individual line items. Do not group multiple toxins together on one line item.
3. In the pop-up window (for each toxin), complete questions a-g.
4. In the pop-up window and if relevant, complete (f) for the administration to animals. Completing this section will activate Safety section 7)a)ii so that the proposed animal biosafety level(s) and housing locations can be indicated. Please ensure your IACUC application is current and information is congruent.
5. In the pop-up window and if relevant, complete (g). In rare cases, biologically-derived toxins may be used in a clinical study involving human subjects. Consider whether the use of the toxin in humans may be considered human gene transfer by NIH definition of the term. Generally, a recombinant agent producing a biological toxin used in clinical research would meet this definition. If so, then only the Human Clinical Trials (section 5) needs to be filled out.
6. If you are producing a biologically-derived toxin in your lab through recombinant techniques, then this also requires completion of the r/sNA molecule section (2) of the application.
7. If you are producing/purifying a toxin in your lab from a toxin-producing infectious microorganism then this also requires completion of the Infectious Agents section (4) of the application.
8. Section 3b should be completed to indicate where the biologically-derived toxin will be stored and any security measures in place for their storage. If the toxin will be weighed, then the location for this procedure and a biosafety cabinet certification date will need to be included.
9. In the Safety section 7)a)i, please include the work location where the biologically-derived toxin will be manipulated and describe your proposed BSL level. Generally, this is expected to be a BSL2 location.
10. For aerosol producing activities, such as pipetting or reconstituting the biologically-derived toxin, please include the use of a BSC and indicate its certification date in 7)b as well as section 3)b)v.
11. Please complete Safety question 7)e to indicate whether the toxin is considered a select agent.
12. Include SOPs in the Attachments section to detail how the biologically-derived toxins will be handled (PPE, practices, procedures, special containment equipment (e.g., BSC)). For guidance, see the BMBL (Appendix I, pg. 470)
- Be aware that a chemical fume hood may not provide the appropriate protection for work with the biologically-derived toxin. A biological safety cabinet is generally recommended or modification of your PPE (use of N95s) may be necessary if a BSC is not available.
- Consider reconstituting the biologically-derived toxin through the septum of the vial rather than weighing the powder to prevent aerosol exposures.
13. Include the names of the biologically-derived toxins within your Biological Decontamination and Spill Clean-up Plan in the box for “Biological Agent(s)/r/sNA/Biological toxin” and describe routine decontamination procedures and spill clean-up procedures (or check the appropriate boxes of the template).
- If you will use the biologically-derived toxin in an RAR space, please be aware that the Rescue disinfectant provided in RAR spaces may not be effective to inactivate the toxin. A 10% bleach solution may need to be provided by your lab.
14. Include the appropriate waste disposal procedures for the biologically-derived toxin within your Biological Waste Disposal form.
- Generally liquid waste disposal can be done with 10% (1:9 v/v) bleach for at least 30 minutes contact time.
- Provide a reference for other inactivation/waste disposal methods that may be used in your lab.
15. If applicable, complete and attach a Dual Use Screening Survey.