Select Toxins

Select Toxins

July 8, 2014

Select toxins are one of 9 specific toxic substances produced from plants, animals, microorganisms, or recombinant or synthesized nucleic acid molecules that the Federal government has deemed sufficiently hazardous to pose a severe threat to public health and safety.  

Because these biological toxins are capable of causing death or severe incapacitation at relatively low levels of exposure, the Federal government requires special measure to ensure these 9 Select Toxins may not be used as potential tools of bioterrorism.  

A UCLA Select Toxin Fact Sheet is available.  

Untitled Document

Overview

The Federal Select Agent Program (FSAP) under the CDC, regulates possession, use and transfer of specific microbes and biological toxins which they feel pose a severe threat to public health and safety.  While there are clearly concerns about safety while working with these "Select Agents and Toxins", FSAP also requires that biosecurity issues be properly addressed to ensure these Select Agents and Toxins acquired by unauthorized personel who may use them as potential tools of bioterrorism.  

The Select Agent and Toxin regulations require that any facility, personnel and agents involved in possession, use or transfer of Select Agents and Toxins must register with FSAP.  This process includes, among other measures, Security Risk Assessments for all personnel, development and review of biosafety, biosecurity and incident response plans, and regular inspections by the CDC.  

However, FSAP will permit researchers to possess and use very small amounts of Select Toxins without undergoing the rigorous FSAP registration process.  FSAP has defined permissible toxin amounts for each of the biotoxins.  If the cumulative amount under the control of a principal investigator and staff does not exceed, at any time, these amounts, the lab, personnel and facility do not have to undergo the FSAP registration process.  

Toxin use-- even in permissible amounts may still pose biosafety issue within a laboratory.  However, the biosecurity risks of having these small amounts were not viewed to be as acute to require registration. 

Select Toxins IN ANY AMOUNT must be registered with the UCLA Institutional Biosafety Committee (IBC) prior to acquision to ensure the proper biosafety measures are in place.  

The applicable safety standards relevant to use of biological toxins are described in the CDC BMBL, Appendix I and NIH Guideline Appendix F

In addition, FSAP requires that facilities have a mechanism to oversee and document continued compliance with the regulations-- even in permissible amounts.  The regulations were updated in 2012 to address concerns that individuals are prevented from amassing Select Toxins by acquiring small permissible amounts from multiple sources.  FSAP requires that all facilities transferring any Select Toxins in any amount (intramurally or extramurally) perform an document a due diligence assessment prior to transfer.  

Regulated Toxins and Permissible Amounts

HHS Toxins [§73.3(d)(3)]

Amount

Abrin

1000 mg

Botulinum neurotoxins

1 mg

Short, paralytic alpha conotoxins

100 mg

Diacetoxyscirpenol (DAS)

10,000 mg

Ricin

1000 mg

Saxitoxin

500 mg

Staphylococcal Enterotoxins (cumulative of all subtypes A, B, C, D, and E)

100 mg

T-2 toxin

10,000 mg

Tetrodotoxin

500 mg

Laboratory requirements for Select Toxin areas

All Select Toxins-- in ANY amount-- must be registered with the Institutional Biosafety Committe prior to acquisition in a UCLA laboratory.  The IBC typically expects the following measure are met:

Biosafety Level 2 Containment is appropriate for most Select Toxin Work (see the CDC/NIH BMBL, Appendix I)

Security measures must be in place to ensure only authorized personnel on the BUA have access to the Select Toxins (typically accomplished using locked freezers or lockboxes within the freezers)

Inventory control logs to demonstrate that the cumulative amount of Select Toxins in the laboratory at any moment in time.  These should document the amounts received, used/inactivated, or transferred

Documented toxin-specific SOPs and training, including the following provisions:

    • Onsite inactivation procedures for any toxin-containing materials or wastes prior to disposal.  (Note: EH&S Hazardous Waste cannot accept any Select Toxin materials until they have been deactivated according to a validated method.)
    • Equipment and work-surface decontamination procedures
    • Spill procedures
    • Sharps precautions and other operational-hazard precautions (based on the operations in the laboratory with toxins)
    • Hazard communication (including signs/symptoms of exposure, and any pre- or post-exposure occupational health requirements and procedures)
    • Reporting procedures for any expsosures, losses of containment, theft or unaccounted materials or other suspicious behaviors associated with the toxin use areas
    • Due diligence provisions and record-keeping for any transfer of Select Toxins (intramurally or extramurally).  See below for further information on Due Diligence requirements. 

Due Diligence Documentation

FSAP requires any individual transferring even small permissible amounts of Select Toxins (intramurally or extramurally) to assess and document that due diligence has been performed prior to transfer.  This requires evaulation that the recipient has a legitimate, peaceful purpose and intended us for the toxin.  Suspicious behavior or activities related to a Select Toxin must be immediately reported to the CDC

UCLA has developed a Select Toxin Transfer Due Diligence Form with instructions and assistance in documenting the process. The form needs to be submitted to EH&S Biosafety for review and approval prior to any transfer of Select Toxins.   

Failure to follow the Select Agent Regulations is considered violation of Federal Law and may be associated with criminal and civil liability. 

Unauthorized Select Toxin Possession or Use

Select Toxins-- in any amount--  require IBC approval prior to acquisition.  However, if you find Select Toxins that have not received IBC approval, this must be immediately reported this to the Biosafety Office.  Destruction or disposal of unauthorized Select Toxins without proper notification and documentation may, in some cases, be in violation of Federal Select Agent regulations. 

If the amounts are below permissible amounts, the Biosafety Officer will assist the lab in the proper inactivation/disposal and documentation procedures, or if the PI wishes to retain the material, will facilitate the application to the IBC. 

Inactivation procedures for Select Toxins

Inactivation and disposal of Select Toxins must be performed and documented by personnel on IBC-authorized BUAs according to the laboratory's SOPs before disposal or before closure of a laboratory.  

Several validated inactivation methods are available for Select Toxins, including the common ones shown below.  Please refer to the CDC/NIH BMBL, Appendix I or EH&S for futher details for other possible methods for inactivation:

Select ToxinDisinfectant for >30 minTiming
Abrin Autoclave 1 hour@121C, liquid exhaust
Botulinum neurotoxins >0.1% NaOCl >30 min
Short, paralytic alpha conotoxins typically, glutaraldehyde varies- contact Biosafety
Diacetyoxyscirpenol (DAS) >1% NaOCl 

>30 min
Ricin >1.0% NaOCl >30 min
Saxitoxin >0.1% NaOCl >30 min
Staphylococcus Enterotoxins >0.5% NaOCl >30 min
T-2 Toxin >2.5% NaOCl >30 min
Tetrodotoxin >0.5% NaOCl >30 min

Note: Materials that are highly acidic, basic, flammable, or have high protein content may require altered inactivation procedures to ensure compatibility with agents above.  Bleach may be incompatible with ammonium-based materials or acids, generating chlorine gas.  Please ensure your disinfectant procedures and subsequent disposal are compatible with other hazards in your wastes.