credits bmbl December 7 '06.doc - Central Michigan University

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Agent Summary Statements – Toxins (approximately 34 kD polypeptide) and a B-chain (approximately 32 kD). The A-chain is an N-glycosidase enzyme and a potent inhibitor of protein synthesis, whereas the B-chain is a relatively non-toxic lectin that facilitates toxin binding and internalization to target cells. 20 Ricin is much less toxic by weight than is BoNT or SE, and published case reports suggest that intramuscular or gastric ingestion of ricin is rarely fatal in adults. 22 Animal studies and human poisonings suggest that the effects of ricin depend upon the route of exposure, with inhalation and intravenous exposure being the most toxic. In laboratory mice, for example, the LD 50 by intravenous injection is about 5 μg/kg, whereas it is 20 mg/kg by intragastric route. 23,24 The ricin aerosol LD 50 for NHP is estimated to be 10-15 μg/kg. 17 The human lethal dose has not been established rigorously, but may be as low as 1-5 mg of ricin by injection 25 or by the aerosol route (extrapolation from two species of NHP). Diagnosis of Laboratory Exposures The primary diagnosis is through clinical manifestations that vary greatly depending upon the route of exposure. Following inhalation exposure of NHP, there is typically a latency period of 24-72 h that may be characterized by loss of appetite and listlessness. The latency period progresses rapidly to severe pulmonary distress, depending upon the exposure level. Most of the pathology occurs in the lung and upper respiratory tract, including inflammation, bloody sputum, and pulmonary edema. Toxicity from ricin inhalation would be expected to progress despite treatment with antibiotics, as opposed to an infectious process. There would be no mediastinitis as seen with inhalation anthrax. Ricin patients would not be expected to plateau clinically as occurs after inhalation of SEB. Gastric ingestion of ricin causes nausea, vomiting, diarrhea, abdominal cramps and dehydration. Initial symptoms may appear more rapidly following gastric ingestion (1-5 h), but generally require exposure to much higher levels of toxin compared with the inhalation route. Following intramuscular injection of ricin, symptoms may persist for days and include nausea, vomiting, anorexia, and high fever. The site of ricin injection typically shows signs of inflammation with marked swelling and induration. One case of poisoning by ricin injection resulted in fever, vomiting, irregular blood pressure, and death by vascular collapse after a period of several days; it is unclear in this case if the toxin was deposited intramuscularly or in the bloodstream. 25 Specific immunoassay of serum and respiratory secretions or immunohistochemical stains of tissue may be used where available to confirm a diagnosis. Ricin is an extremely immunogenic toxin, and paired acute and convalescent sera should be obtained from survivors for measurement of antibody response. Polymerase chain reaction (PCR) can detect residual castor bean DNA in most ricin preparations. Additional supportive clinical or diagnostic features, after aerosol exposure to ricin, may include the following: bilateral infiltrates on chest radiographs, arterial hypoxemia, neutrophilic leukocytosis, and a bronchial aspirate rich in protein. 24 290
Agent Summary Statements – Toxins LABORATORY SAFETY General considerations for the safe use and inactivation of toxins of biological origin are found in Appendix I. Precautions should be extended to handling potentially contaminated clinical, diagnostic and post-mortem samples because ricin may retain toxicity in the lesion fluids, respiratory secretions, or unfixed tissues of exposed animals. When the ricin A-chain is separated from the B-chain and administered parenterally to animals, its toxicity is diminished by >1,000-fold compared with ricin holotoxin. 26 However, purified preparations of natural ricin A-chain or B-chain, as well as crude extracts from castor beans, should be handled as if contaminated by ricin until proven otherwise by bioassay. Containment Recommendations BSL-2 practices, containment equipment and facilities are recommended, especially a laboratory coat, gloves, and protective mask, when handling ricin toxin or potentially contaminated materials. Ricin is a relatively non-specific cytotoxin and irritant that should be handled in the laboratory as a non-volatile toxic chemical. A BSC (Class II, Type B1 or B2) or a chemical fume hood equipped with an exhaust HEPA filter and charcoal filter are indicated for activities with a high potential for aerosol, such as powder samples, and the use of large quantities of toxin. Laboratory coat, gloves, and full face respirator should be worn if there is a potential for creating a toxin aerosol. SPECIAL ISSUES Vaccines No approved vaccine or specific antidote is currently available for human use, but experimental, recombinant vaccines are under development. Select Agent Ricin toxin is a Select Agent requiring registration with CDC and/or USDA for possession, use, storage and/or transfer. See Appendix F for additional information. Transfer of Agent Importation of this agent may require CDC and/or USDA importation permits. Domestic transport of this agent may require a permit from USDA/APHIS/VS. A DoC permit may be required for the export of this agent to another country. See Appendix C for additional information. Agent: Selected Low Molecular Weight (LMW) Toxins LMW toxins comprise a structurally and functionally diverse class of natural poisons, ranging in size from several hundred to a few thousand daltons, that includes complex organic structures, as well as disulfide cross-linked- and cyclic-polypeptides. Tremendous structural diversity may occur within a particular type of LMW toxin, often 291
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Biosafety in Microbiological and Bi
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SECTION VIII-H: Prion Diseases 299
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Forward Biosafety in Microbiologica
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Editors: L. Casey Chosewood, MD Dir
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Guest Editors: Matthew J. Arduino,
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Charles B. Millard, PhD Lieutenant
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Robert Bull Karen B. Byers Jane Cap
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Thomas L. Miller Douglas M. Moore M
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Robert Yarchoan Uri Yokel Lisa Youn
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Introduction laboratories chose not
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Introduction RISK CRITERIA FOR ESTA
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Introduction BMBL includes an impor
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Section II Biological Risk Assessme
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Biological Risk Assessment informat
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Biological Risk Assessment The NIH
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Biological Risk Assessment effectiv
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Biological Risk Assessment Third, m
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Biological Risk Assessment 14. Oxma
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Principles of Biosafety Safety equi
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Principles of Biosafety Often an in
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Principles of Biosafety Four standa
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Principles of Biosafety 4. Centers
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Laboratory Biosafety Level Criteria
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Section V Vertebrate Animal Biosafe
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Vertebrate Animal Biosafety Level C
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TABLE 1 SUMMARY OF RECOMMENDED BIOS
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Principles of Laboratory Biosecurit
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Occupational Health and Immunoproph
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Agent Summary Statements - Bacteria
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• Section VIII-B: Fungal Agents A
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Agent Summary Statements - Fungal A
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Agent Summary Statements - Parasiti
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• Section VIII-D: Rickettsial Age
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Agent Summary Statements - Ricketts
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Agent Summary Statements - Ricketts
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• Section VIII-E: Viral Agents Ag
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Agent Summary Statements - Viral Ag
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Appendix A Figure 11. A typical lay
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Appendix A REFERENCES 1. Centers fo
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Appendix B Decontamination and Disi
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Appendix B surfaces are contaminate
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Appendix B TABLE 1 DESCENDING ORDER
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Appendix B dioxide gas exits the ge
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Appendix B d The effectiveness of a
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Appendix C Transportation of Infect
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Appendix C 1600 Clifton Road, N.E.,
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Appendix C disease in humans or in
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Appendix C Biological specimen, Cat
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Appendix D Agriculture Pathogen Bio
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Appendix D 14. Pathological inciner
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Appendix D Wastes and other materia
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Appendix D Camelpox virus b a, b, c
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Appendix D SPECIAL ISSUES The impor
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Appendix D required by the USDA and
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Appendix D depression, anorexia, an
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Appendix D laboratory with enhancem
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Appendix D five day period of conta
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Appendix D slaughterhouses or indus
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Appendix D virus does not cause any
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Appendix D NDV is classified in the
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Appendix D movement permit is requi
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Appendix D Spring Viremia of Carp V
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Appendix D REFERENCES 1. Hess WR. A
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Appendix D 37. Alexander DJ. Newcas
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Appendix E Arthropod Containment Gu
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Appendix F Select Agents and Toxins
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Appendix G IPM issues and requireme
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Appendix H Working with Human, NHP
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Appendix I Guidelines for Work with
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decontaminated periodically, for ex
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0.25N, and/or sodium hypochlorite (
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k Irradiation causes a dose-depende
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7. Morin R, Kozlovac J. Biological
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Appendix J NIH Oversight of Researc
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Appendix K Resources for Informatio
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Appendix K E-mail: http://www2.gsu.
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Appendix K and http://www.who.int/c
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Appendix L HEPA High Efficiency Par
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