Chapter 26

BIOSAFETY

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Appendix B. Pathogen and Toxin Lists

B.1  Introduction and Scope

Pathogens and toxins are discussed in detail in Work Process B.3.d, Pathogenic Agents and Toxins, of this manual. This appendix lists the following biological agents and toxins presented in Work Process B.3.d:

These lists are provided for convenience in this manual, but may not reflect the actual regulatory list or applicable agents or materials. Regulatory sources, standards, and Web links noted in this appendix and Work Process B.3.d should be consulted to confirm applicable agents or toxins.

B.2  NIH Guidelines Human Etiologic Agents

This section provides a list of human pathogens and their Risk Group (RG) 2, RG3, and RG4 designations as excerpted from Appendix B, Classification of Human Etiologic Agents on the Basis of Hazard, of the NIH Guidelines, amendment effective November 6, 2013.

B.2.1 Risk Group 1 Agents

RG1 agents are not associated with disease in healthy adult humans. Examples of RG1 agents include asporogenic Bacillus subtilis or Bacillus licheniformis (see NIH Guidelines, Appendix C-IV-A, Bacillus subtilis or Bacillus licheniformis Host-Vector Systems, Exceptions); adeno-associated virus (AAV, all serotypes); and recombinant or synthetic AAV constructs, in which the transgene does not encode either a potentially tumorigenic gene product or a toxin molecule and which are produced in the absence of a helper virus. A strain of Escherichia coli (see NIH Guidelines, Appendix C-II-A, Escherichia coli K-12 Host Vector Systems, Exceptions) is an RG1 agent if it (a) does not possess a complete lipopolysaccharide (i.e., lacks the O antigen) and (b) does not carry any active virulence factors (e.g., toxins) or colonization factors and does not carry any genes encoding these factors.

Those agents not listed in RGs 2, 3, and 4 are not automatically or implicitly classified in RG1; a risk assessment must be conducted based on the known and potential properties of the unlisted agents and their relationship to the listed agents.

B.2.2 Risk Group 2 Agents

RG2 agents are associated with human disease that is rarely serious and for which preventive or therapeutic interventions are often available.

Risk Group 2 Bacterial Agents, Including Chlamydia

Risk Group 2 Fungal Agents

Risk Group 2 Parasitic Agents

Risk Group 2 Viruses

B.2.3  Risk Group 3 Agents

RG3 agents are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available.

Risk Group 3 Bacterial Agents Including Rickettsia

Risk Group 3 Fungal Agents

Risk Group 3 Parasitic Agents

None

 

Risk Group 3 Viruses and Prions

B.2.4 Risk Group 4 Agents

RG4 agents are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available.

Risk Group 4 Bacterial Agents

None

 

Risk Group 4 Fungal Agents

None

 

Risk Group 4 Parasitic Agents

None

 

Risk Group 4 Viral Agents

B.2.5 Animal Viral Etiologic Agents in Common Use

The following list of animal etiologic agents is appended to the list of human etiologic agents. None of these agents are associated with disease in healthy adult humans; however, they are commonly used in laboratory experimental work. A containment level appropriate for RG1 human agents is recommended for their use. For agents that are infectious to human cells, e.g., amphotropic and xenotropic strains of murine leukemia virus, a containment level appropriate for RG2 human agents is recommended.

B.2.6 Murine Retroviral Vectors

Murine retroviral vectors to be used for human transfer experiments (less than 10 liters) that contain less than 50% of their respective parental viral genome and that have been demonstrated to be free of detectable replication-competent retrovirus can be maintained, handled, and administered under Biosafety Level (BL) 1 containment.

B.3  Select Agents and Toxins

symbol_biosecurity_low_res_white_backgroundTable B-1 provides the list of select agents and toxins on the National Select Agent Registry (NSAR) established by the Department of Health and Human Services (HHS) Centers for Disease Control and Prevention (CDC) and United States Department of Agriculture (USDA). The most recent online list may be found at http://www.selectagents.gov/index.html. Listed select agents and toxins are categorized as follows:

Table B-1.  National Select Agent Registry of Select Agents and Toxins

HHS and USDA Select Agents and Toxins
7 CFR Part 331, 9 CFR Part 121, and 42 CFR Part 73

HHS Select Agents and Toxins

  • Abrin
  • Botulinum neurotoxins*
  • Botulinum neurotoxin producing species of Clostridium*
  • Conotoxins (Short, paralytic alpha conotoxins containing the following amino acidsequence X1CCX2PACGX3X4X5X6CX7)
  • Coxiella burnetii
  • Crimean-Congo hemorrhagic fever virus
  • Diacetoxyscirpenol
  • Eastern Equine Encephalitis virus
  • Ebola virus*
  • Francisella tularensis*
  • Lassa fever virus
  • Lujo virus
  • Marburg virus*
  • Monkeypox virus
  • Reconstructed replication competent forms of the 1918 pandemic influenza virus containing any portion of the coding regions of all eight gene segments (Reconstructed1918 Influenza virus)
  • Ricin
  • Rickettsia prowazekii
  • SARS-associated coronavirus (SAARS-CoV)
  • Saxitoxin
  • South American hemorrhagic fever viruses (Chapare, Guanarito, Junin, Machupo, Sabia)
  • Staphylococcal enterotoxins A, B, C, D, E subtypes
  • T-2 toxin
  • Tetrodotoxin
  • Tick-borne encephalitis complex (flavi) viruses (Far Eastern subtype, Siberian subtype, Kyasanur Forest disease virus, Omsk hemorrhagic fever virus)
  • Variola major virus (Smallpox virus)*
  • Variola minor virus (Alastrim)*
  • Yersinia pestis*

Overlap Select Agents and Toxins

  • Bacillus anthracis*
  • Bacillus anthracis Pasteur strain
  • Brucella abortus
  • Brucella melitensis
  • Brucella suis
  • Burkholderia mallei* (formerly Pseudomonas mallei)
  • Burkholderia pseudomallei* (formerly Pseudomonas pseudomallei)
  • Hendra virus
  • Nipah virus
  • Rift Valley fever virus
  • Venezuelan equine encephalitis virus

USDA Select Agents and Toxins

  • African horse sickness virus
  • African swine fever virus
  • Avian influenza virus
  • Classical swine fever virus
  • Foot-and-mouth disease virus*
  • Goat pox virus
  • Lumpy skin disease virus
  • Mycoplasma capricolum
  • Mycoplasma mycoides
  • Newscastle disease virus 1
  • Peste des petits ruminants virus
  • Rinderpest virus*
  • Sheep pox virus
  • Swine vesicular disease virus

USDA Plant Protection and Quarantine (PPQ) Select Agents and Toxins

  • Peronosclerospora philippinensis (Peronosclerospora sacchari)
  • Phoma glycinicola (formerly Pyrenochaeta glycines)
  • Ralstonia solanacearum
  • Rathayibacter toxicus
  • Sclerophthora rayssiae
  • Synchytrium endobioticum
  • Xanthomonas oryzae

Source: NSAR list updated 10/5/2012

* Denotes Tier 1 Agent

 1 A virulent Newcastle disease virus (avian paramyxovirus serotype 1) has an intracerebral pathogenicity index in day-old chicks (Gallus gallus) of 0.7 or greater or has an amino acid sequence at the fusion (F) protein cleavage site that is consistent with virulent strains of Newcastle disease virus. A failure to detect a cleavage site that is consistent with virulent strains does not confirm the absence of a virulent virus.


Table B-2 provides additional information, permissible toxin amounts, and synonyms for biological toxins listed on the NSAR of select agents and toxins. A permissible toxin amount is the maximum quantity of biological toxin that can be under the control of a principal investigator at any time without regulation under CDC or USDA.

Table B-2. Additional Information for National Select Agent Registry Toxins

Name

(Permissible Toxin Amount)

Synonyms/Types (Strains)/ Key Words

CAS Numbers

Description

Abrin

(100 mg)

Abrina, Abrin B, Abrin C, Abrin D, Abrin reconstituted (A+B mix), Abrin agglutinin, Toxalbumin

1393-62-0 (Abrin)        53597-23-2 (Abrin A)

53597-24-3 (Abrin C)

A powerful phytotoxin present in the seeds of Abrus precatorius (common names include precatory bean, rosemary pea, and jequirity).

Botulinum neurotoxin

(0.5 mg)

Botulinum neurotoxin, Types A, B, C, C1, C2, D, E, F, and G (seven serotypes with a few subtypes). Clostridium botulinum toxin, botulinum toxin, botulinus toxin, botulin toxin

93384-43-1 (Type A)

Produced by the soil bacterium Clostridium botulinum under anaerobic conditions. The most potent toxin known but is heat labile and neutralized by specific antibodies.

Conotoxins

(100 mg)

Only short, paralytic alpha conotoxins containing the amino acidsequence X1CCX2PACGX3X4X5X6CX7 are HHS select toxins.

The specific conotoxins listed below may or may not meet NSAR’s more-specific 10/5/12 definition of conotoxins:

Conotoxins GI, GIA, GII, GIV, GIIIA, GIIIB, GIIIC, GIVA, GVIB, GVIC, Im1, MI,MVIIA,MVIIB, MVIIC,MVIIIv, MVIIDSIA, SVIB (plus more). Conus geographus venom, Conus magus venom, Conus straiatus venom

81133-24-6 (IV)

76862-65-2 (GI)

156467-85-5 (Im 1)             106375-28-4 (GVIA)        107452-89-1 (MVIIA)        147794-23-8 (MVIIC)       150433-82-2 (SVIB)

The above CAS numbers may or may not meet NSAR’s more specific 10/5/12 definition of conotoxins.

Small peptide venoms produced by cone shells (Conidia) and marine snails (carnivorous gastropod “cone” mollusks). Venoms vary between species. Act on neuronal communications but each (alpha-mu- and omega-conotoxins) target a different aspect of the process.

Diacetoxy-scirpenol

(1,000 mg)

Diacetoxyscirpenol; Anguidin; Auguidine; Insariotoxin; DAS; 4,15-Diacetoxyscirpen-3-OL; Scirpenetriol 4,15-diacetate; 4 beta, 15-diacetoxy-3-alpha-hydroxy-12, 13-epoxytrichotech-9-ene

2270-40-8

4297-61-4 (3-A-acetyldiacetoxyscir-penol).

Trichothecene compound toxins (mycotoxins) produced by various fungus Fusarium, which grow on barley, corn, rye, wheat, etc.

Ricin

(100 mg)

Ricinotoxin, Ricinus toxin, Ricin A, Ricin B, Ricin C, Ricin D, Ricin Toxin-Con A, Concanvalin A, Ricin nitrogen, Ricine, Ricin total hydrolysate, Ricinus lectin, Ricnus agglutinin

9009-86-3 (Ricin),

63099-95-6

9040-12-4 (Ricin D)              72514-84-2 (Ricin D ananine chain)

66419-04-03 (Ricin D iso-leucine chain reduced)

A powerful phytotoxin present in the seeds of the castor bean oil plant (Ricinus communis).

Saxitoxin

(100 mg)

Mytilotoxin; Saxitoxin hydrate; Saxitoxin hydrochloride; Saxitoxin dihydrochloride; STX dihydrochloride; neo-Saxitoxin (neo-STX); Saxitoxin p-bromo benzenesulfonate; Mytilus californianus poison/toxin; Saxidomas giganteus poison/ toxin; Gonyaulas catenella poison/ toxin; Saxitonin diacetate salt

35523-89-8             

35554-08-6

80450-05-01   

64296-20-4 (neo-STX from dinoflagellates)

220355-66-8 (Saxitoxin doacetate salt) 

Toxin produced by marine dinoflagellates and cyanobacteria and accumulate in organisms such as mussels (Mytilus), and clams (Saxidomas).

Staphylococcal enterotoxin

(5.0 mg)

Staphylococcus enterotoxins subtypes A,B,C, D, E are HHS select toxins. Enterotoxin F is the Toxic Shock Syndrome “Toxin-1” and is not a HHS select toxin.

11100-45-1 (Enterotoxin B)

Toxin produced by a strain of Staphylococcus aureus. Acts on receptors in gut.

Tetrodotoxin

(100 mg)

Fugu poison; fugtoxin; Anhydroepiterodotoxin;  Deoxytetrodotoxin; 4-Deoxytetrodotoxin; Deoxyterttoxin; Diateylanhydrotetrdotoxin; Diacetate 4,9-anhydrotetrodotoxin; Ethoxytetrodotoxin; Maculotoxin; Ethyl tetrodotoxin; 4-Deoxy tetrodotoxin; Spheroidine; Tarichatoxin; 4-amino-4-deoxy, 4,9-Anhydrotetrodotoxin; 8,8-Diacetate 4,9-anhydrotetrodotoxin; tetrodotoxin citrate; TTX; (4-alpha)-4-amino-4-deoxy-tetrodotoxin

4368-28-9 (tetrodotoxin) 13072-89-4 (4,9-anhydrotetrodotoxin)

13285-84-2 (8,8-diacetate 4,9-anhydro tetrodotoxin)

7724-38-1 ([4 alpha]-4-amino-4-deoxy-tetrodotoxin)

7724-41-6 (4-deoxy- tetrodotoxin)

18660-81-6 (Tetrodotoxin citrate salt)

7724-39-2

(O[sup 4]- methyl tetrodotoxin)

7724-40-5 (O[sup 5]-ethyl tetrodotoxin)

Highly lethal neurotoxin present in numerous species of puffer fish (Tetraodontoidea) and newts (Tarika).

T-2 Toxin

(1000 mg)

Toxin T-2; T-2 mycotoxin; T-2 hemisuccinate; T-2 tetraol; T-2 Toxin d3; T-2 Triol; 2,4,5-T-2 ethylhexyl ester; 2,4,5-T-2 methylpropyl ester; Insariotoxin; 12,13-tricothecene; Fusariotoxine T-2; Scirpenol

21259-20-1 (T-2 Toxin)       34114-99-3 (T-2 tetraol)     120467-83-6 (T-2 Toxind3)

34114-98-2 (T-2 triol)

1928-47-8 (2,4,5-T2 ethylhexyl ester)

4938-72-1 (2,4,5-T-2-methylproply ester)                 

Trichothecene compound toxins (mycotoxins) produced by various species of fungus Fusarium, which grows on barley, corn, rye, and wheat.

Source: LBNL EHS Division (July 2003), revised to reflect changes to NSAR effective 10/5/2012

B.4  Plant Pathogens

This appendix of the Biosafety Manual provides lists of bacterial, fungal, and viral plant pathogens that may be used to identify agents that might be considered plant pathogens. Current USDA Web sites and the USDA permit process may also be used to determine whether the USDA considers agents in specific locations (e.g., California) to be plant pathogens.

B.4.1  Plant Pathogen Bacteria (by Scientific Name)

Agrobacterium radiobacter, Agrobacterium rubi, Agrobacterium tumefaciens, Agrobacterium vitis, Burkholderia andropogonis, Burkholderia caryophylli, Burkholderia cepacia, Burkholderia cichorii, Burkholderia corrugata, Burkholderia gladioli pv. gladioli, Clavibacter michiganensis subsp. insidiosus, Clavibacter michiganensis subsp. michiganensis, Clavibacter michiganensis subsp. sepedonicus, Curtobacterium flaccumfaciens pv. flaccumfaciens, Erwinia amylovora, Erwinia carotovora subsp. atroseptica, Erwinia carotovora subsp. carotovora, Erwinia chrysanthemi, Erwinia chrysanthemi pv. chrysanthemi, Erwinia chrysanthemi pv. dieffenbachiae, Erwinia chrysanthemi pv. zeae, Erwinia tracheiphila, Pantoea stewartii subsp. stewartii, Pseudomonas syringae pv. apii, Pseudomonas syringae pv. atrofaciens, Pseudomonas syringae pv. coronafaciens, Pseudomonas syringae pv. glycinea, Pseudomonas syringae pv. lachrymans, Pseudomonas syringae pv. mori, Pseudomonas syringae pv. papulans, Pseudomonas syringae pv. phaseolicola, Pseudomonas syringae pv. pisi, Pseudomonas syringae pv. syringae, Pseudomonas syringae pv. tabaci, Pseudomonas syringae pv. tomato1, Ralstonia solanacearum2, Rhodococcus fascians, Spiroplasma citri, Streptomyces scabies, Xanthomonas campestris pv. armoraciae, Xanthomonas campestris pv. campestris, Xanthomonas campestris pv. carotae, Xanthomonas campestris pv. cucurbitae, Xanthomonas campestris pv. hederae, Xanthomonas campestris pv. juglandis, Xanthomonas campestris pv. papavericola, Xanthomonas campestris pv. pelargonii, Xanthomonas campestris pv. pruni, Xanthomonas campestris pv. raphani, Xanthomonas campestris pv. vitians, Xanthomonas campestris pv. zinniae, Xanthomonas fragariae, Xanthomonas phaseoli pv. alfalfae, Xanthomonas phaseoli pv. begoniae, Xanthomonas phaseoli pv. glycines, Xanthomonas phaseoli pv. phaseoli, Xanthomonas translucens pv. translucens, Xanthomonas vesicatoria.

B.4.2  Plant Pathogen Fungi (by Scientific Name)

CHYTRIDIOMYCETES

Physoderma maydis

OOMYCETES

Albugo candida, Peronospora sojae, Peronospora trifoliorum, Peronospora viticola, Phytophthora cactorum, Phytophthora capsici, Phytophthora cinnamomi, Phytophthora citricola, Phytophthora fragariae, Phytophthora infestans, Phytophthora megasperma, Phytophthora megasperma f.sp. medicaginis, Phytophthora rubi s.sp. fragariae, Phytophthora sojae, Plasmodiophora brassicae, Pythium aphanidermatum, Pythium arrhenomanes, Pythium graminicola, Pythium irregulare, Pythium ultimum, Sclerophthora macrospora.

ASCOMYCETES

Apiosporina morbosa (black knot), Botryosphaeria obtusa, Botryosphaeria ribis (B. dothidea, B. berengeriana), Claviceps purpurea, Cymadothea trifolii (sooty blotch), Diaporthe phaseolorum, Gaeumannomyces graminis, Gibberella zeae, Glomerella cingulata, Leptosphaerulina trifolii, Monilinia fructicola (Sclerotinia fructicola), Nectria cinnabarina, Ophiostoma ulmi (Ceratocystis ulmi), Pseudopeziza medicaginis, Pseudopeziza trifolii, Sclerotinia sclerotiorum (Whetzelinia sclerotiorum), Sclerotinia trifoliorum, Valsa ambiens, Venturia inaequalis (apple scab), Xylaria polymorpha.

Powdery Mildews

Erysiphe graminis, Microsphaera vaccinii (on Ericaceae), Podosphaera clandestina (on Rosaceae), Sphaerotheca Asteraceae, Cucurbitaceae, Scrophulariaceae), Sphaerotheca macularis (on hops and strawberry), Unicinula viticola.

Coelomycetes

Colletotrichum acutatum, Colletotrichum coccodes, Colletotrichum destructivum, Colletotrichum fragariae, Colletotrichum gloeosporioides, Colletotrichum graminicola, Colletotrichum trifolii, Macrophomina phaseolina (Macrophoma phaseolina, M. phaseoli, Botryodiplodia phaseoli), Phoma medicaginis, Phomopsis juniperovora, Phomopsis sojae, Phomopsis viticola, Septoria rubi, Septoria tritici, Sphaeropsis sapinea (Diplodia pinea), Stagonospora nodorum (Septoria nodorum), Stenocarpelia maydis (Diplodia zeae, D. zeae-maydis).

Hyphomycetes

Alternaria alternata, Alternaria solani, Bipolaris maydis (Heminthosporium maydis, Drechslera maydis), Bipolaris sorokiniana (Helminthosporium sorokiniana, Drechslera sorokiniana), Bipolaris victoriae (Helminthosporium victoriae, Drechslera victoriae), Botrytis cinerea.

Cercospora medicaginis, Cercospora zeae-maydis, Cladosporium herbarum, Drechslera avenae (on oats, other grasses), Drechslera graminea (on barley, other grasses), Drechslera poae (on grasses), Drechslera teres (on barley, other grasses), Drechslera tritici-repentis (on cereals, other grasses), Exserohilum turcicum (Helminthosporium turcicum, Bipolaris turcicum), Fusarium acuminatum, Fusarium avenaceum, Fusarium culmorum, Fusarium equiseti, Fusarium graminearum, Fusarium moniliforme, Fusarium oxysporum, Fusarium oxysporum, Fusarium roseum, Fusarium solani, Penicillium expansum, Rhynchosporium secalis, Thielaviopsis basicola, Verticillium albo-atrum, Verticillium dahliae.

HEMIASCOMYCETES

Taphrina caerulescens (leaf blister on oak, Ostrya, Rhus), Taphrina communis (plum pocket on Prunus), Taphrina deformans (peach leaf curl).

BASIDIOMYCETES

Wood Rotters and Root-Collar Rotters

Armillaria mellea, Ceratobasidium cerealea, Daedaleopsis confragosa (Daedalea confragosa), Ganoderma applanatum (Fomes applanatus), Ganoderma lucidum, Hirschioporus pargamenus (Trichaptum biformis, Polyporus pargamenus), Laetiporus sulphureus (Polyporus sulphureus), Phellinus gilius, Phellinus robiniae, Schizophyllum commune, Stereum ostrea, Trametes versicolor (Polyporus versicolor, Coriolus versicolor).

Rusts

Gymnosporangium clavipes (cedar-quince rust), Gymnosporangium globosum (cedar-hawthorn rust), Gymnosporangium juniperi-virginianae (cedar-apple rust), Puccinia coronata (on Rhamnaceae, Eleganaceae/Poaceae), Puccinia graminis (on Berberis/Poaceae), Puccinia recondita (on Ranunculaceae/Poaceae), Pucciniastrum americanum (late leaf rust on raspberry).

Smuts

Tilletia caries (Tilletia tritici), Tilletia laevis (Tilletia foetida), Ustilago avenae, Ustilago hordei, Ustilago tritici, Ustilago zeae.

Other Basidiomycetes

Rhizoctonia solani (Thanatephorus cucumeris), Sclerotium rolfsii.

B.4.3  Plant Pathogen Viruses (Regulated by the State of California)

Alfalfa mosaic, barley yellow dwarf, bean common mosaic, bean yellow mosaic, beet curly top, beet mosaic, cactus virus X, camellia yellow mottle, carnation mottle, cauliflower mosaic, chrysanthemum mosaic, chrysanthemum virus B, cucumber mosaic, cymbidium mosaic, dasheen mosaic, fig mosaic, impatiens necrotic spot, lettuce big vein, lettuce mosaic, lily symptomless, maize dwarf mosaic, odontoglossum ringspot, papaya ringspot, pepper mottle, plum line pattern, potato leafroll, potato virus S, potato virus X, potato virus Y, prune dwarf, prunus necrotic ringspot, squash mosaic, sugarcane mosaic, tobacco etch, tomato mosaic, tomato spotted wilt, turnip mosaic, watermelon mosaic virus 2, zucchini yellow mosaic.

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