Select Toxin Guidance: List of Select Toxins and Non-Regulated Amounts

The following toxins are not regulated if the amount under the control of a principal investigator, treating physician or veterinarian, or commercial manufacturer or distributor does not exceed, at any time, the amounts indicated in the table below [1].

* C = Cysteine residues (indicated in bold) are all present as disulfides, with the 1st and 3rd Cysteine, and the 2nd and 4th Cysteine forming specific disulfide bridges; The consensus sequence includes known toxins α-MI and α-GI (shown above) as well as α-GIA, Ac1.1a, α-CnIA, α-CnIB; X1 = any amino acid(s) or Des-X; X2 = Asparagine or Histidine; P = Proline; A = Alanine; G = Glycine; X3 = Arginine or Lysine; X4 = Asparagine, Histidine, Lysine, Arginine, Tyrosine, Phenylalanine or Tryptophan; X5 = Tyrosine, Phenylalanine, or Tryptophan; X6 = Serine, Threonine, Glutamate, Aspartate, Glutamine, or Asparagine; X7 = Any amino acid(s) or Des X; and “Des X” = “an amino acid does not have to be present at this position.” For example if a peptide sequence were XCCHPA then the related peptide CCHPA would be designated as Des-X.

Note: Recombinant and/or synthetic nucleic acids, that encode for the toxic form(s) of select toxins if the nucleic acids can be expressed, are regulated. The aggregate toxin amounts stated above do not apply to regulated nucleic acids as any amount of these nucleic acids would be regulated.

With respect to a Principal investigator (PI), (defined as an individual who is designated by the entity to direct a project or program and who is responsible to the entity for the scientific and technical direction of that project or program) an entity is not required to register with FSAP as long as each PI possesses less than the regulated amount of select toxin.

If one PI transfers select toxin to another PI such that the receiving PI now possesses an amount of toxin above the regulatory amount, then the receiving PI and entity are both in violation of the SAR. The aggregate amount pertains to the PI and not the entity.

Regulated select toxin derivatives

A select toxin derivative is a select toxin that possesses modifications, such as the addition of a hydroxyl group, that make them different from the parent molecule in nomenclature but still retain toxicity similar to the parent. An example of a derivative that is regulated is the select toxin derivative HT-2. HT-2 has similar toxic properties as T-2 [2].

List of examples of unregulated non-functional select toxins

• Ricin immunotoxin
• T-2 glucoside
• Toxin subunits such as the light chain of BoNT or the Ricin subunit A only. (However, any reconstitution of the holotoxin with the heavy chain of BoNT or Ricin subunit B respectively would be regulated).
• Toxoids (A toxoid is a toxin whose toxicity has been inactivated or suppressed either by chemical or heat treatment. Other properties, typically immunogenicity, are maintained).

Select Toxin Genetic Elements, Recombinant and/or Synthetic Nucleic Acids, and Recombinant and/or Synthetic Organisms (Sections 3(c), 4(c))

The following genetic elements, recombinant and/or synthetic nucleic acids, and recombinant and/or synthetic organisms are regulated as select toxins (See sections 3(c) and 4(c) of 42 CFR Part 73external icon, 9 CFR Part 121external icon, and 7 CFR Part 331 3(c)external icon):

• Recombinant and/or synthetic nucleic acids that encode for the toxic form(s) of select toxins if the nucleic acids:
  • Can be expressed in vivo or in vitro, or
  • Are in a vector or recombinant host genome and can be expressed in vivo or in vitro.
• Select toxins that have been genetically modified.

Go to Guidance on the Regulation of Select Agent and Toxin Nucleic Acids for additional information.

Restricted Experiments for Select Toxins

The “restricted experiment” provisions are found in section 13 of 42 CFR Part 73external icon, 7 CFR Part 331external icon, and 9 CFR Part 121external icon:

• • (a) An individual or entity may not conduct or possess products resulting from the following experiments unless approved by and conducted in accordance with the conditions prescribed by the HHS Secretary or APHIS Administrator:
    • (2) Experiments involving the deliberate formation of synthetic or recombinant DNA containing genes for the biosynthesis of select toxins lethal for vertebrates at an LD[50] < 100 ng/kg body weight.
    • Note: Currently, only nucleic acids containing genes for the biosynthesis ofnativeBotulinum neurotoxinmeet the definition of 42 CFR § 73.13(a)(2). Any genetic modifications of other select toxins to increase their LD [50] to <100 ng/kg body weight would be subject to this provision.

For more information regarding restricted experiments please see the Restricted Experiment Guidance.

[1] Currently, USDA does not regulate any toxins.

[2] PLoS One. 2013;8(3):e60484. doi: 10.1371/journal.pone.0060484. Epub 2013 Mar 27. Influence of T-2 and HT-2 toxin on the blood-brain barrier in vitro: new experimental hints for neurotoxic effects. Weidner M1, Hüwel S, Ebert F, Schwerdtle T, Galla HJ, Humpf HU.