Guidelines for Work With Toxins of Biological Origin

Biotoxins are toxic substances produced by microorganisms, plants, or animals. Unlike infectious agents, biological toxins are non-replicating and non-infectious; however, they may cause significant harm through accidental exposure during laboratory handling. Exposure risk typically occurs through inhalation of aerosols, mucous membrane contact, accidental injection, or ingestion.

At Cornell University, examples of biological toxins may include cholera toxin, Shiga toxin, diphtheria toxin, pertussis toxin, and botulinum neurotoxin.

Important: Some toxins are federally regulated Select Toxins. Depending on the total quantity possessed, registration with the CDC/USDA under the Federal Select Agent Program (FSAP) may be required. For details, refer to the Select Agents and Toxins page or visit the Federal Select Agent and Toxins List. For assistance, contact EHS Biosafety.

Plan Ahead: Risk Assessment and Toxin-Specific SOP Required

All work involving biological toxins must be supported by a toxin-specific Standard Operating Procedure (SOP). The SOP must reflect the specific toxin, quantity, form (lyophilized, liquid, recombinant), and experimental context. The SOP must be reviewed by all personnel and included in the applicable IBC MUA or IACUC protocol.

Download the Biotoxin SOP Template to begin drafting your SOP.

Your SOP and risk assessment must address the following:

1. Hazard Identification

   • Identify the toxin, LD50, exposure routes, target organs, and clinical signs of exposure.
   • Indicate whether the toxin is purified, recombinant, subunit-only, catalytically inactive, or genetically encoded.
   • Resources include the Toxin and Toxin-Target Database and the BMBL 6th Edition.

2. Engineering Controls and PPE

   Primary containment is critical for toxin work.

   • Manipulation of dry or lyophilized biological toxins should be conducted inside a certified Class II biological safety cabinet unless a documented risk assessment demonstrates that an alternative engineering control provides equivalent protection.
   • After resuspension, work with liquid toxin stocks should continue in a BSC unless a documented risk assessment supports an alternate method.
   • Chemical fume hoods may protect the worker from inhalation exposure; however, they exhaust unfiltered air outdoors. In contrast, a Class II BSC provides HEPA-filtered exhaust, protecting the worker, the laboratory environment, and the external environment.
   • Although individual toxin molecules are nanometer-scale proteins, they are aerosolized in droplets or particulates large enough to be effectively captured by HEPA filtration. HEPA filters remove ≥99.97% of particles at 0.3 µm (the most penetrating particle size) and are highly effective for both larger droplets and smaller particles via diffusion capture mechanisms.
   • For this reason, a Class II BSC provides meaningful containment for aerosolized toxin and represents the institutional standard for dry toxin reconstitution.
   • Appropriate PPE may include lab coat, double gloves, eye protection, and respiratory protection depending on form, quantity, and risk assessment.

3. Waste Treatment and Disposal

   • Toxin waste must be inactivated prior to disposal.
   • Under New York State regulation (6 NYCRR §365-2.6(b)(5)), autoclaving may be used to treat biological toxins only if:
     • The method is listed in the CDC BMBL, or
     • A scientific source documents autoclaving as effective for the specific toxin and matrix.
   • Chemical inactivation (e.g., appropriate hypochlorite solutions) must specify final concentration and contact time.
   • Free liquids may not be disposed of in red biohazard bags; liquids must be chemically inactivated and managed according to institutional waste procedures.

4. Medical Considerations

   • Consult Occupational Medicine (607-255-6960) to determine whether medical surveillance, vaccination, or health monitoring is appropriate.
   • Ensure personnel understand exposure response procedures and symptom recognition.

5. Emergency Response

   • For spills involving powdered toxin outside primary containment: evacuate, secure the area, and contact EHS (607-255-8200). Cleanup procedures will be determined based on toxin, quantity, and exposure risk.
   • See additional guidance on Biological Exposures and Biological Spills.

Registration, Storage, and Inventory

At Cornell, any biological toxin with an LD50 ≤ 100 µg/kg must be registered in the laboratory’s IBC protocol and tracked in the chemical inventory system.

1. Submit a completed Biotoxin SOP as part of your IBC MUA or IACUC protocol.
2. Store toxins in a locked, access-controlled location.
3. Maintain inventory logs documenting acquisition, use, and inactivation.
4. For Select Toxins, comply with all Federal Select Agent Program requirements, including transfer due diligence.

Dual Use and Emerging Federal Oversight (DURC/PEPP)

Projects involving toxins, modifications that increase toxin expression, or alterations that enhance stability, dissemination, or pathogenicity may be subject to review under the updated Policy for Oversight of Dual Use Research of Concern (DURC) and Potential Pandemic Pathogens (PEPP).

Cornell’s Biosafety Office supports investigators through risk assessment, regulatory interpretation, and mitigation planning. Early consultation is encouraged.

Safety Culture

Working with biological toxins requires deliberate planning, technical precision, and respect for the hazard. The goal of institutional oversight is not to restrict research, but to ensure that innovative work proceeds safely, responsibly, and in compliance with federal and state regulations.

If you are unsure whether your work requires additional review, containment measures, or regulatory registration, contact EHS Biosafety before initiating work.