Chemical Terrorism Response Guide For Clinical Laboratories

Chemical Terrorism Response Guide
For
Clinical Laboratories
UTAH DEPARTMENT OF
HEALTH
Division of Disease Control and Prevention
Bureau of Chemical and Environmental Services Version 2011
Chemical Terrorism Response Guide For Clinical Laboratories
TABLE OF CONTENTS
Introduction ....................................................................................... Contact Information .............................................................................. Rapid Toxic Screen ............................................................................... Laboratory Response Network .................................................................. Specimen Collection, Packaging, & Shipping Instructions .................................. Questions .................................................................................. Specimen Collection ..................................................................... Whole Blood ....................................................................... Urine ............................................................................... Blanks .............................................................................. Labeling Specimens .............................................................. Specimen Packaging ..................................................................... Secondary Packaging for Blood Tubes ......................................... Outer Packaging for Blood Tubes .............................................. Secondary Packaging for Urine Cups .......................................... Outer Packaging for Urine Cups ................................................ Documentation ........................................................................... Specimen Shipping ....................................................................... Forms ............................................................................................... Urine Evidence Form ..................................................................... Urine Shipping Manifest Forms ......................................................... Blood Evidence Form ..................................................................... Blood Shipping Manifest Forms ......................................................... Chain of Custody Form ................................................................... Overview of Chemical Terrorism Agents ...................................................... Quick Resource for Specimen Collection and Shipping ..................................... 2 3 4 5 6 6 6 6 6 6 7 7 7 8 8 9 10 10 11 11 12 14 15 17 19 42
INTRODUCTION
The initial laboratory participating in an unannounced chemical terrorism event is likely to be a hospital-based or independent clinical laboratory. For clinicians, your laboratory may be the first to receive samples of urine and blood from exposed individuals. In such an event, there will be an unprecedented need to identify the chemical agent(s) used and determine the exposure levels patients received. To assist clinical laboratories in this effort, the Unified State Laboratories: Public Health has set up a chemical terrorism comprehensive response plan for rapid toxic screening of samples from patients exposed to chemical agents. This guide contains a summary of notification steps, specimen collection requirements, packaging and shipping instructions, and an overview of chemical terrorism agents. This guide is intended for use by laboratories whose staffs have been trained in chemical terrorism sample collection through programs offered by the Utah Department of Health Laboratory. This guide provides a resource for quick decision-making in response to a real or suspected chemical terrorism event. Integration of its contents must be done in accordance with the requirements of regulatory agencies and incorporated into facility specific plans through appropriate authorities in the approval and review processes. We suggest that this guide be stored near the laboratory workbench where it can be readily available to on-shift staff. It is designed to be a companion to the Bio-Terrorism Response Guide for Clinical Laboratories which is also available from the Unified State Laboratories: Public Health. Each person that may be involved with samples from patients potentially exposed to chemical terrorism agents should be trained in sample collection requirements, transporting protocols, and whom to contact if chemical terrorism is suspected. If you have any questions at any time, please call the Unified State Laboratories: Public Health at 801-965-2400 or see the contact information in this guide.
CONTACT INFORMATION
Unified State Laboratories: Public Health Division: Disease Control and Prevention Bureau: Chemical and Environmental Services Address: 4431 S 2700 W Taylorsville, UT 84119 Phone: 801-965-2400 (general line) Fax: 801-965-2486 URL: http://health.utah.gov/lab/chemistry/ Patrick Luedtke, MD Sanwat Chaudhuri, PhD Jack Oman Kyle Ashby, PhD Merril Chipman Sumaiya Islam Nick Oman Stephanie Rogers Robert Rolfs, MD Laboratory Director Bureau Director Assistant Bureau Director CT Lead Chemist Chemist Chemist/Microbiologist Chemist Bureau Secretary State Epidemiologist 801-965-2424 801-965-2470 801-965-2507 801-965-2484 801-965-2477 801-965-2502 801-965-2477 801-965-2508 801-538-6386
Centers for Disease Control and Prevention Division: National Center for Environmental Health, Division of Laboratory Science - Atlanta, GA Phone: 888-374-1764 Admin: 770-488-7950 URL: http://www.bt.cdc.gov/ CDC Laboratory Coordinator CDC Chemical Emergency Philip Holt Cecelia Sanders 770-488-7532 770-488-4034
RAPID TOXIC SCREEN

The rapid toxic screen includes methods and procedures for analyzing clinical samples for the presence of chemical warfare agents, certain biological toxins, incapacitating agents, and industrial chemicals. Though it is called a screen, it is actually quantitative analysis, which can be useful in determining patient exposure levels. Chemical warfare agents Nerve agents, e.g. sarin, soman, VX Sulfur mustards, e.g. HD, sesquimustards Nitrogen mustards, e.g. NH1, NH2 Cyanide Lewisite Toxins Ricin Saxitoxin Natural toxins Incapacitating agents Drugs of abuse, e.g. cocaine, opiates, PCP Others, e.g. scopolamine Industrial chemicals Volatile organic compounds, e.g. benzene, carbon tetrachloride Pesticides, e.g. malathion, parathion Heavy metals, e.g. lead, arsenic, mercury Others Toxic industrial chemicals are also of concern as agents of potential chemical terrorism. Their intentional release in a populated area is likely, since rail and truck transport them throughout the country every day. The rapid toxic screen procedure is performed under the direction of the Centers for Disease Control and Prevention (CDC) National Center for Environmental Health, Division of Laboratory Sciences (refer to the contact information in this guide). At the Unified State Laboratories: Public Health we have testing capacities for heavy metals, cyanide, tetramine, and volatile organic compounds, and are working to develop methods for Lewisite and nerve agent metabolites. Currently, we are validated for and participate in ongoing proficiency tests administered by the CDC, the results of which are reported through the LRN Laboratory Response Network.
LABORATORY RESPONSE NETWORK

Through CDC preparedness programs in partnership with the Association of Public Health Laboratories (APHL), other federal agencies, and state public health laboratories, the Laboratory Response Network (LRN) has been established in order to provide aid in terrorism response. For chemical terrorism, clinical laboratories are categorized into a three-tiered network from Level 1 to Level 3 based on sample collection capabilities and diagnostic instrumentation. In this plan, most hospital-based or independent clinical laboratories capable of collecting patient specimens of urine and blood are considered part of the LRN at Level 3. Clinical laboratories operating at Level 3 serve a critical role in initiating response plans and collecting patient specimens. Hospital emergency departments may be the first to observe unusual patterns of illness and/or receive patients exposed in a chemical terrorism event. Clinical laboratories servicing these types of facilities must initiate the LRN response by contacting their Level 2 coordinating agency. For the State of Utah, the Unified State Laboratories: Public Health is the designated Level 2 contact for dispatching the LRN response and subsequent rapid toxic screening process. Level 2 Laboratories conduct Level 3 activities and detect toxic agents, such as cyanide, nerve agents, and toxic metals in human samples. The Unified State Laboratories: Public Health has arranged with CDC and partnered with LRN Level 1 laboratories to perform analysis of chemical terrorism patient samples. There are two main reasons for coordinating the analysis of chemical terrorism patient samples. First, if the agent is unknown, samples can be sent to the CDC for quantitative analysis of 150 different chemical agents or their metabolites in urine, serum, and whole blood. Second, the CDC maintains the capability to perform PCR analysis for detection of Biosafety Level-4 biological agents, which could be vital in a potential dual-exposure event (combined biological and chemical). This initial screening by the CDC also helps to ensure the health and safety of persons working with chemical terrorism patient samples.
Chemical Terrorism Event
Samples from Patients to Clinical Labs
LRN Level 3
UDOH Contacted / Samples Transported Unified State Laboratories: Public Health LRN Level 2 Patient Exposure Data
Rapid Toxic Screen / Chemical Agent Detected Enhanced Testing Capabilities Surge Capacities CDC & LRN Level 1
SPECIMEN COLLECTION, PACKING, & SHIPPING INSTRUCTIONS1

Questions Any questions or problems regarding specimen packaging or shipment should be directed to the following contacts: Philip Holt, Incident Response Laboratory Coordinator E-mail: PHolt@cdc.gov Phone: 770-488-7532 Mobile: 678-525-2683 Cecelia Sanders, Chemical Emergency Response Team Leader E-mail: CSanders@cdc.gov Phone: 770-488-4034 Mobile: 770-294-4124 Specimen Collection Unless you are otherwise directed, collect whole blood and urine specimens from each person who may have been exposed, as explained below. Whole Blood Collect blood specimens from adults only unless you receive specific instructions from the CDC to collect blood from pediatric patients. Collect a minimum of 12 mL of blood. Use three 4-mL or larger vacuum-fill only (unopened), non-gel, purple-top (EDTA) tubes; use four tubes if using 3-mL tubes. Using indelible ink, mark each purple-top tube of blood in the order collected (e.g. #1, #2, #3 (and #4 if using 3-mL tubes). In addition, collect another specimen using one 3-mL or larger, vacuum-fill only (unopened), non-gel, green- or gray-top tube. Allow the tube to fill to its stated capacity. Urine Collect at least 25-50 mL from potentially exposed adults and children. Use a screw-cap plastic container; do not overfill. Freeze specimen as soon as possible (-70oC or dry ice preferred). If other than clean catch, note the method of collection on the specimen cup (e.g. obtained by catheterization). Blanks For each lot number of tubes and urine cups used for collection, provide the following to be used as blanks for measuring background contamination: Two (2) empty, unopened purple-top tubes. Two (2) empty, unopened green- or gray-top tubes. Two (2) empty, unopened, urine cups.
Adapted from Shipping Instructions for Specimens Collected from People Who May Have Been Exposed to Chemical-Terrorism Agents, Centers for Disease Control and Prevention, CT Clinical Specimen Handling Guidelines (CSH Guidelines Version 10.07)
Labeling Specimens Label specimens with labels generated by your facility and follow your facilitys procedures for proper specimen labeling. In addition to unique patient identifiers (e.g. medical records number, specimen identification number) labels should convey the collector's initials, date, and time of collection so that law enforcement officials may trace the specimen to the collector should investigations lead to legal action and the collector is asked to testify that he or she collected the specimen. If bar-coded labels are used, place the labels on the blood tubes and urine cups so that when these containers are upright, the bar code looks like a ladder. Maintain a list of names with corresponding specimen identification numbers at the collection site so that results can be reported to patients. It is recommended that you record additional data for use in the interpretation of results. Additional data may include: time of potential exposure, method of urine collection if other than clean catch, indication if sample was collected postmortem, and antidotes administered prior to sample collection. Information provided on labels and lists may prove helpful in correlating the results obtained from the CDC's Rapid Toxic Screen and subsequent analysis with the people from whom the specimens were collected. Specimen Packaging Packaging consists of the following components: primary receptacles (blood tubes or urine cups), secondary packaging (materials used to protect primary receptacles), and outer packaging (polystyrene foam-insulated, corrugated fiberboard shipper). Secondary Packaging for Blood Tubes To facilitate processing, package all blood tubes from the same patient together. Place absorbent material between the blood tubes and the first layer of secondary packaging. Use enough absorbent material to absorb the entire contents of the blood tubes. Separate each tube of blood collected from other tubes, or wrap tubes to prevent tube-to-tube contact. Regardless of the method used, the first layer of secondary packaging must be secured with one continuous strip of evidence tape and initialed half on the tape and half on the first layer of secondary packaging by the person making the seal. Examples of some ways to do this are to Pack blood tubes in a gridded box lined with absorbent material. Seal the top half of the box to the bottom half with one continuous piece of evidence tape and write your initials half on the tape and half on the box. Pack a sealable polystyrene foam container or blood tube shipment sleeve and transport tube with individually wrapped tubes. Seal the polystyrene foam container or transport tube with one continuous piece of evidence tape and write your initials half on the tape and half on the container. Wrap and seal the first layer of secondary packaging (e.g., gridded box) with absorbent material.
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Seal one wrapped gridded box or alternative container inside a clear, leak-proof biohazard polybag equivalent to Saf-T-Pak product STP-701, STP-711 or STP-731. Place this bag inside a white Tyvek outer envelope (or equivalent) and seal the opening with a continuous strip of evidence tape initialed half on the packaging and half on the evidence tape by the individual making the seal. According to 49 CFR 173.199(b), if specimens are to be transported by air, either the primary receptacle or the secondary packaging used must be capable of withstanding, without leaking, an internal pressure producing a pressure differential of not less than 95 kPa (0.95 bar, 14 psi). Verify in advance that the manufacturer of either the blood tube or secondary packaging used in your facility is in compliance with the pressure differential requirement. Outer Packaging for Blood Tubes Use polystyrene foam-insulated, corrugated fiberboard shipper (may be available from your transfusion service or send-outs department). For cushioning, place additional absorbent material in the bottom of the shipper. Add a single layer of refrigerator packs on top of absorbent material. Place the packaged specimens on top of the refrigerator packs. Use additional cushioning material to minimize shifting while the shipper is in transit. Place additional refrigerator packs on top of the secondary packaging to maintain a shipping temperature of 1C-10C for the duration of transit. Place blood shipping manifest in a sealable plastic bag and put on top of packs inside the shipper. Keep chain-of-custody documents for your files. Place lid on shipper and secure with filamentous shipping tape. Place your return address in the upper left-hand corner of the shipper top and put CDCs receiving address in center. Affix labels and markings adjacent to the shippers/consignees address that appears on the shipper. Place the UN 3373 label and the words Biological Substance, Category B adjacent to the label on the front of the shipper. Secondary Packaging for Urine Cups Separate each urine cup from other urine cups, or wrap individual urine cups to prevent contact between urine cups. Regardless of the method used, the first layer of secondary packaging must be secured with one continuous strip of evidence tape and initialed half on the tape and half on the first layer of secondary packaging by the person making the seal. Examples of some ways to do this are to Pack urine cups in a gridded box lined with absorbent material. Seal the top half of the box to the bottom half with one continuous piece of evidence tape and write your initials half on the tape and half on the box. Seal individually wrapped urine cups inside a clear, leak-proof biohazard polybag equivalent to Saf-T-Pak product STP-701, STP-711 or STP-731. Secure the closure of the bag with one continuous strip of evidence tape initialed half on the tape and half on the bag by the individual making the seal.
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Place urine cups, boxed or individually wrapped and secured properly with evidence tape, in the next layer of secondary packaging. An example of acceptable material is the Saf-T-Pak Disposable 2-Part Pressure Vessel system or its equivalent. Secondary packaging must have its closure secured with a single strip of evidence tape initialed half on the packaging and half on the evidence tape by the person making the seal. Outer Packaging for Urine Cups Use polystyrene foam-insulated, corrugated fiberboard shipper (may be available from your transfusion service or send-outs department). For cushioning, place additional absorbent material in the bottom of the shipper. Place a layer of dry ice on top of the absorbent material. Do not use flakes or large chunks of dry ice for shipment because large chunks have the potential for shattering urine cups during transport. Ensure that specimens will remain frozen or will freeze during transport. Place packaged urine cups in the shipper. Use additional absorbent or cushioning material between wrapped urine cups to minimize shifting while shipper is in transit. Place an additional layer of dry ice on top of samples. Place the urine shipping manifest in a sealable plastic bag and put on top of dry ice inside the shipper. Keep chain-of-custody documents for your files. Place lid on shipper and secure with filamentous shipping tape. Place your return address in the upper left-hand corner of the shipper top and put CDCs receiving address in center. Place the UN 3373 label and the words Biological Substance, Category B adjacent to the label on the front of the shipper. Place a Class 9/UN 1845 hazard label on the same side of the shipper as the UN 3373 marking. If the proper shipping name, (either dry ice or carbon dioxide, solid) and Class 9/UN 1845 is not preprinted on the hazard label, add it in an area adjacent to the label. Note the weight of dry ice (in kg) on the preprinted area of the hazard label, or place that information adjacent to the Class 9/UN 1845 hazard label. Orientation arrows are not required on a shipper containing Biological substance, category B. If you use arrows, be sure to orient the inner packaging so that closures are aligned with the arrows. If the shipper will be transported by a commercial air carrier, complete an airway bill. On the airway bill, note the proper shipping name and UN number for each hazardous material and identify a person responsible for the shipper per IATA packing instruction 650.
Documentation Since blood tubes and urine cups cannot be shipped together in the same package, prepare a separate shipping manifest for each. Note on shipping manifest if urine sample is collected by means other than clean catch (e.g. catheterization). Place each shipping manifest (with specimen identification numbers) in a plastic zippered bag on top of the specimens before closing the lid of the polystyrene foaminsulated, corrugated fiberboard shipper. Do not transport chain-of-custody forms with specimens. Each entity or organization handling the specimens is responsible for the specimens only during the time that it has control of the specimens. Each entity or organization receiving the specimens must sign-off on the chainofcustody form of the entity or organization relinquishing the specimens to close that chain. Electronic procedures such as electronic chain-of-custody and barcode readers will expedite this process. When receiving specimens, each new entity or organization must begin its own chain of custody. The entity or organization relinquishing the specimens must sign its chain of custody to close the chain and indicate that they have transferred the specimens. Note: When the person relinquishing the specimens (relinquisher) and the person receiving the specimens (receiver) are not together at the time of specimen transfer, the relinquisher must document on its chain-of-custody form that the receiver is the express courier (e.g., FedEx, Delta Dash, DHL, UPS) and must document the shipment tracking number or have the person transporting the specimens sign the chain-ofcustody to indicate that he or she has taken control of the specimens. Likewise, when receivers get the specimens, they will document on their chain-of-custody form that the relinquisher is the express courier (and provide the tracking number) or have the person transporting the specimens sign the chain-of-custody form. Specimen Shipping Follow the guidance provided in your states chemical-terrorism comprehensive response plan. If you are directed to ship the specimens to CDC, please ship the specimens to the following address via Federal Express: Centers for Disease Control and Prevention Attn: Lt. Ernest McGahee 4770 Buford Hwy. Building 110 Loading Dock Atlanta, GA 30341 (770) 488-7579 If directed to send the specimens to the Unified State Laboratories: Public Health a courier or other agency/ organization may be used: e.g. FBI, State Patrol, state lab personnel.
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Centers for Disease Control and Prevention NCEH/DLS 4770 Buford Hwy, NE MS F-20 Atlanta, GA 30341-3724
Unified State Laboratories: Public Health Chemical Terrorism Response 4431 S 2700 W Taylorsville, UT 84119
EVIDENCE FORM
Date of Shipping: Event Name: Date of Sample Collection: Facility Name:
For a group or a box of samples:
For an individual sample: Local ID:
CDC/NCEH Group ID:
CDC NCEH ID:
***** Urine Samples *****
CDC Sample ID: CDC Unique ID: For sample(s) from an exposed individual: Number of Urine Containers: Sample IDs:
Comments:
Signature/Name/CDC User ID of Person Sealing Shipper:

signature printed name User ID
Signature/Name/CDC User ID of Person Verifying Seal:

Local ID (non-CDC): Number issued by a non-CDC party submitting material to CDC. CDC NCEH ID: Internal NCEH number/ID, otherwise known as the lab-friendly number. CDC Sample ID: ID assigned to identify a specimen when first seen by CDC personnel. This number will be used as the parent number for all samples derived from the first identified and number specimen. (DASH number) CDC Unique ID: (ASTRO number) ID is unique to CDC and will be assigned to each sample or every specimen entity. CDC/NCEH Group or Box ID: ID defines the number assigned to the outer container for the specimens of a given tube or vial type.
Page ____ of ____ CENTERS FOR DISEASE CONTROL AND PREVENTION CHEMICAL TERRORISM URINE SPECIMEN COLLECTION SHIPPING MANIFEST Note: Blood tubes and urine cups cannot be shipped together in the same package, prepare a separate shipping manifest for each. Place each shipping manifest (with specimen identification numbers) in a plastic zippered bag on top of the specimens before closing the lid of the polystyrene foam-insulated, corrugated fiberboard shipper. Date Shipped: Shipped By:
Name
Date Received: Received By: Signature:

Agency
Contact Telephone: Signature:
URINE
Please include two (2) empty, unopened urine cups from each lot number collected for background contamination measurement. Total Number of Specimens this Container: Comments: Total Number of Blanks this Container:
Shipping Address:
Centers for Disease Control and Prevention, CDC ATTN: Lt. Ernest McGahee 4770 Buford Hwy Bldg. 110 Loading Dock Atlanta, GA 30341 (770) 488-7579
Please indicate the amount of urine collected in the urine cup (UC) column below. Patient/Victim ID Label UC Comments
Continue on next page...
...Continued from previous page Patient/Victim ID Label UC Comments
Page ____ of ____
Use additional copies of this page if necessary. NOTE: Please include 2 empty, unopened urine cups from each lot number collected for background contamination measurement.
Centers for Disease Control and Prevention NCEH/DLS 4770 Buford Hwy, NE MS F-20 Atlanta, GA 30341-3724
Unified State Laboratories: Public Health Chemical Terrorism Response 4431 S 2700 W Taylorsville, UT 84119
EVIDENCE FORM
Date of Shipping: Event Name: Date of Sample Collection: Facility Name:
For a group or a box of samples: CDC/NCEH Group ID:
For an individual sample: Local ID: CDC NCEH ID: CDC Sample ID: CDC Unique ID:
***** Blood
For sample(s) from an exposed individual: Number of Purpletop Tubes: Sample IDs:
Samples *****
Number of Green/Gray-top Tubes: Sample IDs:
Comments:
Signature/Name/CDC User ID of Person Sealing Shipper:

Signature/Name/CDC User ID of Person Verifying Seal:

Local ID (non-CDC): Number issued by a non-CDC party submitting material to CDC. CDC NCEH ID: Internal NCEH number/ID, otherwise known as the lab-friendly number. CDC Sample ID: ID assigned to identify a specimen when first seen by CDC personnel. This number will be used as the parent number for all samples derived from the first identified and number specimen. (DASH number) CDC Unique ID: (ASTRO number) ID is unique to CDC and will be assigned to each sample or every specimen entity. CDC/NCEH Group or Box ID: ID defines the number assigned to the outer container for the specimens of a given tube or vial type.
Page ____ of ____ CENTERS FOR DISEASE CONTROL AND PREVENTION CHEMICAL TERRORISM BLOOD SPECIMEN COLLECTION SHIPPING MANIFEST Note: Blood tubes and urine cups cannot be shipped together in the same package, prepare a separate shipping manifest for each. Place each shipping manifest (with specimen identification numbers) in a plastic zippered bag on top of the specimens before closing the lid of the polystyrene foam-insulated, corrugated fiberboard shipper. Date Shipped: Shipped By:
Name Agency
Date Received: Received By: Signature:
Contact Telephone: Signature:
BLOOD
Please include two (2) empty, unopened purple-top tubes and two (2) empty, unopened green- or gray-top tubes from each lot number collected for background contamination measurement. Total Number of Specimens this Container: Purple-top Tubes: Green- or Gray-top Tubes: Comments: Total Number of Blanks this Container: Blank Purple-top Tubes: Blank Green- or Gray-top Tubes:
Shipping Address:
Centers for Disease Control and Prevention, CDC ATTN: Lt. Ernest McGahee 4770 Buford Hwy Bldg. 110 Loading Dock Atlanta, GA 30341 (770) 488-7579
Place a in each box for samples shipped. Place an in each box for samples not shipped. Please indicate the size of the tube collected in the comments field. Collect a minimum of 12 mL of blood. Use three 4-mL or larger vacuum-fill (unopened), non-gel, purple-top (EDTA) tubes; use four tubes if using 3-mL tubes. Patient/Victim ID Label PT1 PT2 PT3 GT 1 Comments
Continue on next page...
...Continued from previous page Patient/Victim ID Label PT 1 PT 2 PT 3 GT 1
Page ____ of ____ Comments
Use additional copies of this page if necessary. NOTE: Please include two (2) empty, unopened purple-top tubes and two (2) empty, unopened green- or gray top tubes from each lot number collected for background contamination measurement.
Information:
Centers for Disease Control and Prevention NCEH/DLS 4770 Buford Hwy, NE MS F-20 Atlanta, GA 30341-3724 Unified State Laboratories: Public Health Chemical Terrorism Response 4431 S 2700 W Taylorsville, UT 84119 Page ____ of ____
CHAIN OF CUSTODY FORM

Collected By:
printed name signature date time
Reason:
Received By:
Reason: Received By:






Reason:
OVERVIEW OF CHEMICAL AGENTS

Slide 1 Hello, Im Dr. John Osterloh and Im a medical toxicologist with the Division of Laboratory Sciences at CDCs National Center for Environmental Health. Welcome to this presentation of An Overview of Chemical Terrorism Agents. Primarily, Ill discuss the history and clinical effects of chemical terrorism. A summary at the beginning should get us oriented and then Ill proceed with the specific agents.
An Overview of Chemical Terrorism Agents

John Osterloh, MD, MS, FACMT
Division of Laboratory Sciences National Center for Environmental Health
Slide 2 We usually think of chemical terrorism as a sudden event, for example, an explosion with a hot zone or a dead zone and surrounding zones of contamination around it.
Overt
Slide 3 But terrorism also can be covert, as evidenced by the recent ricin incidents where castor beans were ground up, extracted to obtain ricin and put it into the mail system, potentially harming individuals by inhalation of the powder.
Covert
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 4 In Public Health, whether its an infectious disease outbreak or a chemical event, we have similar aims. One is to identify the causative agent. Identification may be achieved by circumstantial information, prior intelligence or clinical syndromes. Also of use are environmental and the biological fluid assays the CDC and state laboratories are applying. We want to determine the temporal and geographical distribution of exposure to individuals, and determine relative exposures; that is, who has a high exposure versus a low exposure, identify the worried well, the people who have no exposures. Based on this and other information, we also want to provide guidance to public health officials and medical officials in terms of how to respond, treat, and intervene. And then, finally, provide continued surveillance and prevention. Slide 5 The measurement of chemicals in the blood and urine can help meet these goals. This is essentially why were here with you today. The objective being to measure these chemicals that can be used as terrorist agents.
CDC Public Health Aims

in a Chemical Event Identify the agent or cause
Circumstance, intelligence, clinical syndrome Environmental or biological fluids assay
Determine temporal or geographical distribution of exposure Determine relative (high/low) exposures Evaluate health implications Provide medical and public health guidance and support Provide continued surveillance and prevention
The measurement of chemicals in blood and urine can help meet these goals
Slide 6 How big a problem is terrorism and specifically chemical terrorism? If you look at all domestic terrorism events as recorded by the FBI, over a 20-year period, they reported 457 events. You can see that most of these events were bombings and other violent acts. Youll notice under weapons of mass destruction, there were only five cases or about 1% of all terrorism that occurred domestically.
Source: FBI, 1999
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 7 However, if you look at events recorded internationally over a period of about 40 years and limit the analysis to just chemical, biological, and radiological events, youll see that chemical terrorism represents a sizable percentage. Note that in this data from the Monterey Institute of International Studies; about 70% of these cases are international. You can also see that few of these are state-sponsored, and many of them are criminally motivated as opposed to politically or ideologically motivated. That is changing. The State Department enumerates about 400-600 events internationally each year, so this data from the Monterey Institute of International Studies, representing Chemical, Biological and Nuclear events, is still a small part of the total. Slide 8 We often think of the types of events that can occur with chemical terrorism as being, as I said earlier, a sudden event, a blast or a leak of a chemical. But there are many other types of exposures including spiking chemicals into alcohol or cosmetics, adhering them on surfaces so that hand-to-mouth transfer takes place, using them in closed spaces, such as airliners, or dispersal through mobile drive-by releases.
Source: Tucker, Monterey Institute of International Studies, 2004
Exposure Scenarios
Blast, leak Food, tobacco, alcohol Medications, blood products Cosmetics and personal hygiene products Surfaces (door knobs, utensils): hand-tomouth Fixed distribution systems: water, natural gas Ventilation ducts Closed spaces: subway cars, airliners Vehicular releases: drive-by, crop dusting
Slide 9
Actual exposure to individuals will be affected by a myriad of factors. Ive divided these into factors associated with the chemicals themselves, factors associated with physical environment, Exposure Affected By: and factors associated with the person. The state and form of chemical is important in determining other outcomes such as the Chemical Factors Physical Factors Individual Factors chemicals distribution and effects. Is it a gas, a liquid or solid? If Routes/sources Chemical state Wind we consider arsenic, arsenic comes in a number of flavors. Some of Intake rates Chemical form Humidity them are volatile, and some are not. Some of them might make Solubility Temperature Duration good agents to put into food or water, and some might be better to Age, sex, health Density Barriers release into the air. Factors such as solubility, density and stability Activities pH Matrix may derive from the chemical form. The pH of the matrix will Absorption Ionization Particle size determine how ionized the chemical is, which in turn determines Distribution Stability Distance solubility, which in turn can affect its toxicity. There are also Metabolism Amounts various external physical factors, such as barriers, temperature, Excretion wind, and humidity, which would affect the distribution of a chemical if its released into the air. Some chemicals may attach to particles, so particle size, which determines how respirable the particle is, also can be critical. When you get to individual factors, it becomes even more complex, particularly with respect to predicting how much chemical had entered into the body. There are various routes of entry and various durations of exposure. Ones personal habits, such as how often you rub your eyes can affect intakes. Toxicokinetic factors of absorption, distribution, metabolism and excretion are determined by genetics and constitutional differences, such as age, sex and body weight, adding layer upon layer of variability, making it nearly impossible to precisely predict what doses actually are in a particular persons system.
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 10 I cant discuss all toxicologic principles here, so I want to give you a few reminders. Exposures, like I just said, can be Exposure and Effects through any of several routes, but they can also occur -Remindersthrough simultaneous routes. If you look at the two pictures Exposure may be through here, you could have exposure that is dermal and at the same several routes: time you can have exposure that is inhalational. To Dermal, gastrointestinal, pulmonary, injected paraphrase Paracelsus, dose makes the poison. Not all Dose makes the poison things are toxic at the same amount. We consider chemicals 1mg/kg LD50 is considered that kill half the animals in an experiment (LD50) at a dose of extremely toxic 1 mg/kilogram to be very toxic. But there are lower potency Single dose of short or long duration chemicals, where exposure to larger amounts would produce Multiple doses of any timing serious toxicity. Also, remember that humans arent exposed in conveniently sized and timed doses when terrorism events occur. Doses can be either short or long of duration, or be multiple doses of almost any timing. So being able to put everything together in a nice package like you might do when injecting an animal in an experiment, it isnt that easy, when were dealing with people and events. Slide 11 As I said, different chemicals have different potencies in producing toxicity. In this graph, the Concentration Time product is used to represent the dose and time of exposure. Its a convenient way of expressing dose with respect to varying durations of exposure. 1 mg for 10 minutes would be similar to 10 mg for one minute of exposure. You can see that to kill half the animals exposed, chlorine requires a much higher concentration-time product than say something like sarin. A terrorist may consider availability and the form of chemical to use. If the choices were VX or chlorine and the aim were inhalational exposure, chlorine might be preferred, since one can easily release injurious amounts into the air, where as VX is more difficult to volatilize. Slide 12 Other important points to note are that the effects of any chemical can be acute, chronic, or delayed meaning that Exposure and Effects they can be immediate, they can be long lasting, or they can -Remindersbe postponed. In some situations, you might be dealing with Onset of effects can be: two time courses, where you have an immediate effect and Acute (immediate) then theres a downstream effect that may be of concern. Chronic: long lasting or recurrent Also, effects can be local or systemic, meaning getting into Delayed: accumulative or postponed the body and having effects elsewhere. So the local effect of Effects may be local or systemic a mustard agent might be on the skin, but if the absorbed Relation between dose (by any measure) and dose is high enough, you might also have delayed suppressive effect may be unknown or, at best, imprecise Variability of measures effects on the bone marrow. Finally, and Ive mentioned Variability in toxicokinetics and toxicodynamics once this already, the relationship between dose any effect, however you measure either of these, may be unknown or, at best, imprecise. The reason for this due to the variability in our measures of dose, variability in our measures of effect, and then the variability in the toxicokinetics, or what the body does to the chemical, and toxicodynamics, what the chemical does to the body.
Comparative Toxicity (lethal dose)

6000 5000
Ct50 3 3000 (mg-min/m )

2000 1000 0 chlorine phosgene HCN mustard sarin VX
4000
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 13 Though our ability to estimate the relation between dose and effects is poor, we can provide conservative estimates of Exposure Guidelines external concentrations that should protect people from adverse effects. These guidelines can be used in the Guideline Time Sarin Arsine workplace, but are unlikely to be helpful in an emergency, (mg/m ) (mg/m ) (Effect) primarily because measurements will not be performed IDLH 30 min (acute) 0.1 9.6 during a crisis, but also we will not know all the STEL 15 min x 4 0.0001 0.002 aforementioned chemical, physical and individual factors (acute) affecting variability. For instance, these workplace standards PEL, TLV 8 hr/d x 30yr 0.00003 0.2 only consider inhalational exposure and not other routes of (chronic) exposure. The table does, however, demonstrate the AEGL-3 30 min 0.19 2.0 (severe) influence of time. For instance, the IDLH is a NIOSH guideline, which stands for immediately dangerous to life and health. Compare that to the STEL, or the short-term exposure limit, an exposure for 15 minutes 4 times within a day, which is only twice the IDLH in terms of duration within a day, but the guideline level has decreased on the order of about 1,000. So time is a big factor when considering any exposure level.
3 3
Slide 14 With that background on exposure, I wanted to move on and speak more specifically about chemical terrorism. Of course, Chemical Warfare there is some history. We often can go back in Antiquity and -Examplesfind that what is new is really old. Just like the old western movies, the Greeks used the smoke em out strategy using Pitch and sulfur smoke used by allies of Sparta against Athenians in 423 BC sulfur fumes. In Roman times, Mithridates was fighting Mad honey used by Mithridates allies to Pompeys army, his allies poisoned Pompeys army by putting poison Pompeys army mad honey next to the side of the road. Mad honey results Mustard gas, chlorine, and phosgene used in from bees having fed on rhododendron plants, which contain WW I. Caused many casualties andromedotoxins, which cause the heart rate to slow and Mustard gas used by Iraq against Iran in blood pressure to drop, and even produce coma. Pompeys 1988, against Kurds in 1990s men got sick. They were defeated. In WWI, we have all Sarin used in Tokyo subway attack 1995 heard about the many casualties from the chemical warfare agents, and well talk about those as we proceed. Iraq used mustard gas against Iran and also against the Kurds. And, finally, more recently, and notoriously, sarin, a military nerve agent was used in the Tokyo subway in 1995 on two occasions. Slide 15 Such chemicals agents are defined by the military and are high on our worry list. The military classification, on the left, neither conveys how these chemicals would be used, nor does it include other types of chemicals. I tend to prefer the usage classification on the right, chemical warfare agents, toxic industrial chemicals, and chemicals that could be added into food and water pathways.
Chemicals in Terrorism
Military Classification Lung-damaging agents
Chlorine, phosgene
Blood agents
Cyanide, cyanogen chloride
Blister agents (vesicants)

Mustard gas, lewisite
Use classification Chemical Warfare Agents (CWA) Toxic Industrial Chemicals (TIC) Food and Water Agents (FWA)
Nerve agents
Sarin, Tabun, VX
Incapacitating agents
BZ, LSD
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 16 In the categorization table on this slide, we can see that for toxic industrial chemicals or chemical warfare agents, a mass Chemical Agents exposure from a blast or a leak may be the characteristic Agent Scene Time Route Avail- Deliverable? scenario. The time frame is likely to be acute. Exposure Frame ability routes are likely to be through the lungs and the skin. Where Mass Acute Lung, Limited - Safety CWA exposure Skin as toxic industrial chemicals are readily available, the military - Complexity to aerosol or gas agents are less so. Toxic Industrial Chemicals are easy and Mass Acute Lung, Very + Easy TIC cheap to acquire, whereas the military agents are complex to exposure Skin + Cheap from blast make and deliver, and safety is an issue in handling them. or leak When you look at a food and water agents scenario, the time Case by Acute, Oral, Some + Insidious FWA case course may be more like infectious diseases, with a case-bychronic, Skin - Dilution evolution delayed case evolution over time and space. And the toxicities may be acute, chronic and delayed. One of the advantages of this scenario is that it is insidious; a terrorist could add a toxin in the food chain, get away, and not be around when the event actually occurred. Slide 17 There are over six million chemicals registered in Chemical Abstracts but only about one and a half million chemicals Toxic Industrial Chemicals have been thought to be produced more than once. EPA has recorded about 86,000 chemicals that are for regular use or More than 6 million chemicals sale. There are about 2800 chemicals that are produced in 1.5 million thought to be made more than once quantities of more than a million pounds. Past industrial 86,100 for sale or in use (EPA) accidents have made us familiar with how terrorism events 2800 non-polymerics produced > 1 million lbs 3000 in DOT database, 600 in OSHA involving these agents might look. In Seveso, Italy, dioxins Learn from past accidents were released from an explosion and contaminated an entire Seveso, 1976; Bhopal, 1984; HAZMAT region of Italy. Methyl isocyanate was used to synthesize experiences Wide variety of sources insecticides at Bhopal. When that plant blew up, it caused Chemical plants, petroleum storage sites, widespread injury to thousands of individuals. Also, much of university and medical labs, transport vehicles our preparation for chemical terrorism is based on hazmat experiences, anything from the white powder on the highway to major industrial accidents. Also, one can imagine a wide variety of sources for toxic industrial chemicals, from chemical plants to university laboratories. Slide 18 Toxic industrial chemicals can be variously characterized according to some attribute of the chemical. Keep in mind is that though the chemical itself that may be of concern, the precursor chemicals or contaminant impurities may produce toxicity as well. Bhopal was an example of this is. Its true for the organophosphate pesticides also, which use toxic precursors such as dimethyl methylphosphate or oxychlorides like phosphorous oxychloride.
Toxic Industrial Chemicals

Flammables: gasoline, propane, acetylene Explosives: ammonium nitrate, TNT Metabolics: cyanide, dinitrophenol, fluoroacetate, carbon monoxide, arsine, diborane Pressurized gases: chlorine, ammonia, phosgene Corrosives (oxidants, acids, bases): chromates, nitric acid, hydrofluoric acid Pesticides: Organophosphates and precursors (dimethyl methylphosphate, phosphorus oxychloride), metal phosphides
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 19 For food and water poisonings, history provides us with both accidental and intentional events. In Staffordshire, England, arsenic was an inadvertent impurity in the sulfur use in a beer brewing process. Thallium was an intentional poison, added to tortillas in the Fresno area back in 1932. Though accidental, cooking oil contaminated with PCBs in Japan and China has educated us about the high dose toxicity of these toxins.
Food and Water Poisonings

May evolve like infectious disease outbreaks Arsenic: Staffordshire, 1900 Thallium: Fresno, 1932* Methyl Hg: Minamata Bay, 1950s Methanol: Atlanta, 1951 Hexachlorobenzene: Turkey, 1956 PCBs: Japan, China, 1968 Organophosphate: Romania, 1989* Cyanide: Chilean grape imports, 1989*
* Indicates intentional poisoning
Slide 20 Other recent situations, some real and some hypothesized, provide further demonic ideas. Cyanide was added to Tylenol capsules in the homicidal tampering cases of 1986. Another homicide brings to light what could be done with alcoholic beverages--formaldehyde and methanol added to Vodka went undetected until after a victims death. Weve had the ricin in the mail incidents. Like botulism, consideration has been given to the addition of other potent toxins, like amatoxin, to canned food. One evil-minded scenario that has been proposed is to place a potent carcinogen or teratogen in the food chain. If this happened, Public Health might be dealing with a possible excess of cancers or birth defects down the road. Slide 21 In reviewing the CT agents, we will not have time to address detection, treatment, and protection, but only focus on their major effects and background info.
Food and Water Threats

New situations Cyanide in medications Formaldehyde in alcoholic beverages Ricin in water Amatoxin in canned food Organophosphates in raw foods Dinitrophenol in weight program food
Detection, Protection & Treatment
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 22 Respiratory irritant gasses will be the first group of agents to address. These are also classified as choking or lungdamaging agents.
Respiratory Irritant Gases
Slide 23 Chlorine and phosgene are examples of industrial chemicals. Oxides of nitrogen are combustion products that are released from industrial processes as well as the exhaust of your car. Keep in mind that industrial products may only have local use. For example, in the 1980s, a small tanker truck was going under a bridge in the San Francisco area and the top turret was knocked off. A white gas was released; this was silicon tetrachloride, used in the Silicon Valley. In San Francisco, when the fog came in, as it does every afternoon, it mixed with this, and produced hydrochloric acid and became an irritant gas. Fortunately, few people were affected.
Respiratory Irritant Gases

Chlorine Phosgene Oxides of nitrogen Others: e.g., silicon tetrachloride
Slide 24 Experience with gas exposures has been gained in the industrial workplace. 5% of workplace deaths are due to toxic gases or gases that are asphyxiants. Many fires produce toxic gases. The main one of concern is carbon monoxide, but hydrogen cyanide is also released in fires. You may remember the MGM Grand high- rise fire that occurred back in the 1980s in Las Vegas. It was suspected that many of the deaths were due to cyanide poisoning and/or carbon monoxide poisoning.
Gas Exposures Are Common

Toxic gases and simple asphyxiants
Responsible for 4.9% of workplace deaths
Fires produce many toxic agents

HCN, HCl, acrolein, phosgene Major lethal gas is CO
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 25 Im going to take chlorine as an example because authorities are worried about it. Why is that? Because it is easy to get and theres so much of it in transport at any point in time. It has a wide variety of uses: for synthesizing other chemicals and in water and product disinfection, as examples. It is a gas and it is heavier than air, as are many of the gases well be talking about. It has a familiar pungent bleach-like odor which allows for moderate warning properties, in that you can smell it and get away before serious injury occurs.
Chlorine
High volume production
14 million tons 1998
Uses
bleaching paper and cloth synthetic rubber plastics and synthetics manufacturing chlorinated solvents water and product disinfection
Gas at STP (bp = -34 C), heavier than air Acrid, pungent odor
moderate warning property
Slide 26 Its been used in chemical warfare in WWI, primarily by the Germans. In Ypres, Belgium a release on allied forces caused over 2000 injuries and 800 deaths.
Chlorine in Chemical Warfare

WW I April 22, 1915 Ypres, Belgium Germans released 150 tons of chlorine from 6,000 cylinders 2,500 3,000 people incapacitated, 800 dead
Slide 27 This slide is actually a picture not of the Germans, but of the French releasing chlorine on the Germans with the help of prevailing winds to blow over the German trenches. This led the Germans to produce and use the more toxic, phosgene gas.
Source: Medical Aspects of Chemical and Biological Warfare, 1997
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 28 Generally, the effects of chlorine can be divided into lower concentration exposures and higher concentration exposures. Many are familiar with the effects of low concentration exposure. Its similar to how one feels after spraying mildew remover in your shower and you forget to leave the door open. The classic tickle in the nose and back of the throat and cough. With higher concentrations, depending on how reactive a persons airways are, airway constriction will occur. With still higher concentrations, enough chlorine reaches the alveoli to produce pulmonary edema. For immediately lethal concentrations, it is likely to appear as a cloud or mist.
Respiratory Effects of Chlorine

Low concentrations (1 5 ppm)
Eye, nasal irritation Sore throat Coughing
High concentrations (>15 ppm)

Chest pain Airway constriction Pulmonary edema
Lethal concentration > 1,000 ppm (causes death within a few minutes)
Slide 29 Most of the irritant gases, like chlorine, react directly with the tissues. These are direct chemical reactions that are mediated by pH, redox reaction, addition or substitution reactions. The net effect is that of causing physical structural alternations in lipid and protein molecules. Cells die when their proteins and lipids are degraded, precipitated or denatured. The ensuing inflammatory reaction can also contribute to the result and complications. One valuable rule-of-thumb for the irritant gases is that the site of lung injury depends on the water solubility of the chemical.
Effects of Irritant Gases

Direct chemical reaction with tissues
pH, redox, addition, substitution reactions
structural lipids and proteins denatured or degraded
Induced inflammatory reaction
Site of pulmonary injury is related to the water solubility of the gas
Slide 30 The highly water solubility gases are ones that easily mix with water. These tend to be trapped, in part, in the upper airways and so we sense irritation of the eyes and the nose. Swelling of the voice box, or laryngeal edema, and upper airways can cause hoarseness, wheezing and obstruction. A couple of good examples are ammonia and formaldehyde. Generally, if only minor upper respiratory effects are apparent, its unlikely to have lower pulmonary effects. In other words, if you can sense these agents and then get out of the area, youre unlikely to have the complications of obstructive airway disease.
Highly Water Soluble Gases

Easily dissolve in H2O of upper airways
Irritation of eyes, nose, throat Laryngeal edema & airway obstruction possible
Hoarseness, cough, wheezing, dyspnea
Examples: ammonia, formaldehyde, most strong acids If only mild upper respiratory symptoms, then possibility of lower pulmonary injury is remote Sequelae of obstructive or hypersensitivity disease
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 31 The less water soluble gases, of which nitrogen dioxide and phosgene are good examples, tend to cause few upper respiratory symptoms. We dont sense them, theyre not soluble in water, they have poor warning qualities, and hence they reach lower into the lung at higher concentrations. Reaching the alveoli can lead to pulmonary edema, that is, fluids from the blood stream moving into the air spaces. The sequelae of this can be scarring, dilation of the airways, a restrictive airway disease due to the scarring, or further progression to severe obliteration of the air space architecture of the lung.
Less Water Soluble Gases

Relatively water-insoluble
Cause few upper respiratory symptoms Higher concentrations reach the alveoli Poor warning (irritative) properties, so victims can tolerate much longer exposures E.g., nitrogen dioxide, phosgene
Lower airways injury is often delayed

Late pulmonary edema Permanent sequelae possible: bronchiectasis, restrictive airway disease (scarring, BOF)
Slide 32 Phosgene is another worrisome industrial chemical. It can be created from chlorinated solvents when theyre burned and when metals that were cleaned with chlorinated solvents are welded. Phosgene gas was used in WWI and it accounted for 80% of all gassing deaths. Its very dense and sinks to the bottom of recessed spaces; hence it was good for trench warfare. It has a low odor threshold, a smell of fresh mown hay, which can be misleading since it is a familiar smell. The effects are delayed pulmonary edema which occurs several days after the initial exposure.
Phosgene (Cl2C=O)
Sources
Manufacturing of dyes, resins, and pesticides Produced when chlorinated solvents are burned Welding of metal cleaned with chlorinated solvents
WWI gas: caused 80% of gassing deaths

3.4 x density of air (trench warfare) Low odor threshold of freshly mown hay
Effects
Delayed onset of pulmonary edema Late sequellae of BOF
Slide 33 So in summary, the irritant gases can be categorized by water solubility. If you look over on the right hand side of the table, you can see the correspondence with where the injury occurs. I talked about chlorine first and its somewhat in the middle, demonstrating both, upper and lower airway injury.
Summary: Irritant Gases

Gas HF HCl Chloramine Formaldehyde NH3 Acrolein SO2 Chlorine Phosgene Nitrogen dioxide Ozone
1 vs. 2
Density1 1.86 1.27 NA 1.04 0.59 1.9 2.26 2.47 3.48 2.62 1.66
air; in water;
3
Solubility2 Very High Very High Very High High High Med-High Med-High Medium Low Low Very Low
Airway Injury Upper Upper Upper Upper Upper Upper, late lower3 Upper, late lower3 Upper, late lower3 Lower Lower Lower
in large exposures
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 34 I want to move on to the next group of chemicals which include blood agents, as termed by the military, an inexact term. Such agents are better thought of as metabolic agents in that they interfere with biochemical process in the body.
Blood Agents and Metabolic Toxicants
Slide 35 Cyanide is at the top of the list. Azides and sulfides act by related mechanisms. Carbon monoxide would be a terrorists stealth agent for closed spaces. Fluoroacetates, or what we call out in the Southwest, coyote poison. Dinitrophenols, pentachlorophenols and others such as arsine gas and biotoxins such as amatoxin in amanita phalloides mushroom. There are many more. The list provided focuses mainly on those made in larger quantities.
Metabolic Toxicants
Cyanides Azides Sulfides Carbon monoxide Fluoroacetates Dinitrophenol, pentachlorophenol Many others
Slide 36 Cyanide leads the list and it comes in three types. Hydrocyanic acid gas has a bitter almond smell that about Cyanide half the people can detect just by smelling. But-- by the time you figured it out, you might be dead, because its a Hydrocyanic acid: a gas Bitter almonds smell (to 60% of fairly quick acting toxin. Its not a reliable detection people) mechanism. Hydrocyanic acid is produced in fires particularly Generated in fires of wool, nylon, polyurethane, nitrocellulose involving synthetic chemicals, like polyurethane and Cyanide salts: solids nitrocellulose. Cyanide salts are the forms that are most Easier to handle; used to generate gas useful. These are easier to handle and are often used to Industrial uses: Electroplating, generate hydrocyanic acid gas, when needed. Soluble gold and silver extraction, pest fumigation cyanide salts are used in industry as electroplating agents and Chemicals that produce for gold extraction, and, in years past, as a fumigation cyanide Cyanogenic glycosides, pesticide. There are also chemicals that produce cyanide. amygdalin, aliphatic nitriles We all know somewhat about amygdalin. Amygdalin is the extracted toxin from peach or apricot pits and was once used as an alternative medicine to treat cancer. You used to be able to buy it in Mexico, and notables like Steve McQueen were thought to cross the border for this purpose. Theres also cyanogenic glycosides found in some plant foods like cassava root which is widely used in some regions of Africa as a dietary staple. These release cyanide in low quantities, when metabolized in the body. Some agents like aliphatic nitriles that are industrial chemicals, and therapeutic agents, like nitroprusside, also release cyanide when metabolized in the body.
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 37 Cyanide has a long history. Its the gassing agent that was used against the Jewish and Polish peoples in WWII. Also, in U.S. prisons it has been used as a gassing agent. We know about the Tylenol tampering cases that I mentioned earlier. Then there was Reverend Jim Jones in Jonestown Guyana, whose followers committed mass suicide back in 1978. The picture in the lower right is shows the fatalities of the cyanide laced fruit punch. Each year over 300 cases of cyanide poisoning are reported to poison control centers. Most of these are accidental and industrial. Of the ten fatalities in 1998, seven were suicide attempts.
Cyanide-related Deaths
WW II Nazi concentration camps 1982 Seven deaths from cyanide- adulterated Tylenol Executions in US prisons 1978 Mass suicide of 913 followers of Rev. Jim Jones in Jonestown, Guyana 1998 359 cases via PCCs
301 accidental, 33 intentional 10 fatalities
Slide 38 Cyanide is interesting with respect to how it acts and its clinical effects can be derived from its action. The human Cyanide: Toxicological mode of body oxidizes substrates by removing electrons, all those action electrons have to go somewhere, and thats why we breathe Blocks electron transport in mitochondria oxygen. The electrons combine with oxygen and a couple of Binds to Fe+3 in cytochrome oxidase hydrogens to give water. Reduction of oxygen is stopped by Prevents electron transfer to oxygen cyanide. It binds to cytochrome oxidase, which is an enzyme Oxygen-rich red venous blood that helps transfer these electrons to oxygen. The net result Shift to anaerobic metabolism (glycolysis) is that oxygen is not removed from the blood and venous Lactate (metabolic) acidosis blood looks as red as arterial blood. Another effect of Oxygen-dependent tissues most affected cyanide is that substrate sugars cannot be oxidized any (CNS, heart) Agitation, seizures, coma, cardiac arrest, death further than pyruvate. The excess pyruvate is shifted into lactate. Lactate accumulates and a lactate acidosis occurs, so a victims blood pH goes down with an accrual of untitrated acids. Oxygen-dependent tissues are most sensitive to cyanide, those being the heart and the central nervous system. Slide 39 Cyanide might be an agent to put into food or water, but carbon monoxide would be the type of agent a terrorist would Carbon Monoxide put into a buildings ventilation system. Its invisible and odorless. It has to be on our list because its the number one #1 cause of acute toxic death chemical causing acute toxic death in this country, when #2 rank air pollutant after CO2 suicides, homicides and accidental deaths are included. In Vehicular, coal/oil burning, industrial terms of air pollution, it ranks behind carbon dioxide and as Invisible, odorless most of you know, its a result of incomplete combustion from Affinity for Hgb 220x greater than that of O2 all of the processes listed here. The reason its so toxic is Forms carboxyhemoglobin that it has a great affinity for hemoglobin, 220 times greater Proportionately decreases oxygen carrying capacity than oxygen, forming carboxyhemoglobin, which we can easily Red venous blood measure as an indicator of how poisoned somebody is. Binding to hemoglobin results in proportionate decreases in oxygen carrying capacity. Normally your hemoglobin is 95% bound with oxygen. If you have 50% carboxyhemoglobin, then it cant be anymore than 50% bound with oxygen. The observable effect here is also red venous blood, but not because the tissues arent taking up oxygen. Its because the spectrum of carboxyhemoglobin is as red as oxyhemoglobin.
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 40 Low level effects of carbon monoxide, as measured by carboxyhemoglobin, produce muscle aches, feeling tired, headaches, and nausea. If anybody has ever felt these effects, you know it feels like a hangover, if you have had that toxic experience. High levels cause confusion, stupor, shortness of breath, and coma. Acidosis also occurs. Death can occur at carboxyhemoglobin concentrations greater than 40%. A victim can survive concentrations of about that level with rapid oxygen therapy. On room air, the half-life of carboxyhemoglobin is about four hours, so if a victims carboxyhemoglobin is 50%, it takes four hours to get down to 25% when youre breathing room air. If you give 100% oxygen, the half-life is an hour. With hyperbaric chamber treatment, its only 20 minutes. Long term complications from acute carbon monoxide poisoning may include deficits in memory and learning. Slide 41 The last metabolic agent I will mention is hydrogen sulfide, which is familiar to most, from its rotten egg odor. Normally it is emitted as part of a natural process of decaying organic matter including sewer gas and rotting fish. It is also evident in petroleum refining, which you often smell as you drive past these facilities. The mechanism of action for hydrogen sulfide is not too dissimilar to cyanide, in that it inhibits another respiratory chain enzyme, cytochrome oxidase aa3, and produces similar effects.
Carbon Monoxide
Low levels: aches, tired, headache, nausea Higher levels: stupor, acidosis, dyspnea, unconsciousness, death (> 40%
carboxyHgb )
Rx = oxygen
Half-life of CarboxyHgb is 4 hours, room air 1 hr, 100% oxygen 20 min, hyperbaric therapy
Hydrogen Sulfide
Produced by: Decaying organic matter
sewer gas, manure pits, fishing boat holds
Industrial processes
petroleum refining, tanneries, mines, hot asphalt fumes
Natural hot sulfur springs Mechanism of Action: Inhibits cellular respiration by binding to cytochrome oxidase aa 3 (similar to cyanide)
Slide 42 The odor of rotten eggs is good early indicator that hydrogen sulfide is in the air. Odor thresholds are well below air standards of safety required for the workplace. One problem, however, is olfactory fatigue. At high concentrations, one might smell hydrogen sulfide for a short period of time, but with progressively lesser ability to detect it, leading one into a false feeling of security, perhaps leading to over-exposure. Very high concentrations are capable of producing unconsciousness in minutes, and could be used as a knockdown agent by terrorists.
Hydrogen Sulfide
Odor of rotten eggs: smell as low as 0.025 ppm
ACGIH TLV 10 ppm; OSHA PEL 20 ppm
Eye/Respiratory irritation: 50 ppm Olfactory fatigue and paralysis: 100-150 ppm

NIOSH IDLH: 100 ppm
Delayed pulmonary edema: 200-500 ppm Immediate lethality: > 700 ppm
Rapid knockdown No antidote
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 43 The next group of CT agents is the vesicants.
Vesicants
Slide 44 These are agents that act on the skin and mucosal surfaces, including sulfur mustard agents and lewisite. Nitrogen mustards have been synthesized, but they havent been used in warfare. However many derivatives of the nitrogen mustards have been used in cancer chemotherapy agents, because they can react with DNA and can stop the rapidly dividing cancer cells.
Vesicant Agents Mustard agents

Sulfur (military use) Nitrogen (chemotherapy)
Lewisite (2-chlorovinyl dichloroarsine)
Slide 45 In WWI, 80% of the chemical injuries were caused by the vesicants, affecting a million soldiers on both sides and with relatively low lethality. Vesicants are effective in reducing effectiveness of fighting troops, due to the incapacitation and long convalescence that result from these agents. Theyve been used in other military theaters including Italy and Japan and Iraq, and allegedly by the Egyptians against the Yemen.
Military Use of Vesicants

WWI Caused about 80% of chemical injuries
1.1 million soldiers (both sides) But few deaths, lethality under 5%
Long convalescence required Post WWI Italy against Ethiopia Japan against China Iraq against Iran, Kurds Alleged: Egypt against Yemen
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 46 Sulfur mustard is light brown oily liquid. Its not a gas. It has a low volatility and slight garlic odor. In order to use this agent, it must be sprayed as a mist or in small droplet form. It can be spread secondarily from other contaminated surfaces, such as hand to face.
Sulfur Mustard
Oily liquid
Freezes/melts at 57F Light yellow to brown
Vapor heavier than air Low volatility; persistent Garlic or mustard odor
Slide 47 The sulfur mustards come in a large variety, and usually we speak of HD or the Bis (2-chloroethyl) sulfide, the main agent used in the past. There are many derivatives built on this chemical backbone, as listed here.
Sulfur Mustards
HD, Bis(2-chloroethyl)sulfide Bis(2-chloroethylthio)methane 1,2-Bis(chloroethylthio)ethane 1,3-Bis(chloroethylthio)-n-propane 1,4-Bis(chloroethylthio)-n-butane 1,5-Bis(chloroethylthio)-n-pentane Bis(2-chloroethylthiomethyl)ether Bis(2-chloroethylthioethyl)ether
Slide 48 The targets of the mustard agents are other reactive molecules. It also reacts with water and hydrolyzes fairly quickly. So one of the primary treatments is to get water onto wherever there has been contact with the sulfur or mustard agents. The onset of effects is within 2 to 48 hours, and effects can be divided into two types of categories: Those that are acute and prolonged after direct contact with the eyes, airways and skin; and those effects that are delayed, resulting from higher doses that get into the body affecting the bone marrow, the gastrointestinal tract and lymphoid tissue.
Mustard: Targets
Reacts with molecules in skin cells within a few minutes Rapid decontamination is essential: water Onset: 2 to 48 hours Acute and prolonged:
Eyes Airways Skin
Systemic and delayed:

Bone marrow GI tract Lymphoid tissue
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Chemical Terrorism Response Guide For Clinical Laboratories Slide 49 Blister agents produce blisters, but you may also see small vesicles and redness of the skin. The eyes can show redness, or progress to ulceration, perforation, and blindness. For airway exposure, which is less common, the aerosol particles tend to be large and impinge in the upper airway, but can produce serious epithelial necrosis, sloughing and inflammation. This can lead to airway obstruction and death. If large doses are absorbed, death from sepsis is also possible.
Mustard: Effects
Skin: Erythema, vesicles, blisters/bullae Eye: conjunctivitis, edema, corneal clouding, ulceration, perforation, blindness Airways: Worsens in severity from upper toward lower airways
epithelial necrosis and sloughing airway obstruction pulmonary edema rare
Death:
respiratory obstruction or pneumonia sepsis secondary to bone marrow suppression
Slide 50 The last area I will review is the nerve agents. Nerve agents include chemicals in the organophosphorus class.
Nerve Agents
Slide 51 These are the five major nerve agents that the U.S. has in military storage. If you look where the little circles are on this slide, you can see that three of them have fluorides attached to them and the other agents two have different groups. When these agents react, either with water or in the body, these are the groups, the ones circled, that tend to be hydrolyzed off.
Nerve Agents
O O N P O CN O P F O O P F
Tabun (GA)
O P O F
Sarin (GB)
Soman (GD)
O P O S N
Cyclosarin (GF)
VX
35
Chemical Terrorism Response Guide For Clinical Laboratories Slide 52 The Germans had tabun during WWI but did not use nerve agents since they thought the allies had them too. The U.S. has large stockpiles of these agents remaining. For years now, out on Johnson Island in the middle of the Pacific, the United States has been trying to deactivate these nerve agents. Now there are eight facilities around the country which are working on the remaining 20,000 tons of nerve agents that are in existence. This slide shows a storage facility for the weaponized versions of the agents.
History
Germany (WW II) developed nerve agent munitions but didnt use Used by Iraq in IranIraq war U.S. stockpiles remain
8 U.S. facilities 23,000 tons
Slide 53 In Japan, when the Aum Shinrikyo cult released sarin gas in a subway, there were casualties and plenty of worried- well. The sarin was 25% pure, in this case, and was put into small plastic containers and bags. At the designated time the bags were broken open. Though Sarin is a liquid, it volatilizes well. The push and the vacuum of the air in the subway tunnel helped move the toxin along.
Terrorist Use of Sarin

Matsumoto, 1994
~200 casualties 7 deaths
Tokyo, 1995
~5,000 casualties 12 deaths
Slide 54 The nerve agents are not gases. They are liquids and soluble to a limited degree in both fat and water, so they can be absorbed in the respiratory tract and go through the skin. Tabun is the least available, since little new agent has been synthesized, following the development of the other agents. Sarin is the most volatile. Soman is the fastest aging which means its the least reversible, and Ill discuss that more in a minute. And VX is the most potent and persistent, though its also the least volatile. Thus there are trade-offs for each agent. There also are other nerve agents including later generations, which are derivatives of these five agents and binary products.
Physical Properties
Liquids at room temperature - not gases Soluble in fat and water
Absorbed through respiratory tract, skin, eyes
Phosphonate esters
Tabun (GA) - most unavailable Sarin (GB) - most volatile Soman (GD) - fastest aging VX - most potent and persistent
Other nerve agents
36
Chemical Terrorism Response Guide For Clinical Laboratories Slide 55 Heres a comparison of their toxicity. You can see tabun is 40 fold less toxic than VX. Again, these are listed by their concentration-time-product.
Toxicity
Agent LCt50 (mg-min/m3) Tabun (GA) 400 Sarin (GB) 100 Soman (GD) 70 Cyclohexyl Sarin (GF) 50 VX 10
Ct = concentration x time product
Slide 56 The way nerve agents work is by inhibition of the enzyme acetylcholinesterase, which breaks down the Nerve Agent: Mechanism neurotransmitter, acetylcholine, in the synaptic cleft, the space between two neurons. When one neuron stimulates the Inhibits breakdown of acetylcholine next neuron or its target cell, acetylcholine is release from (neurotransmitter) by the enzyme, the first neuron to stimulate the second neuron or target cell. acetylcholinesterase, in the synaptic cleft Inhibition of acetylcholinesterase allows a large amount of the Results in continued stimulation by acetylcholine to build up and continuously stimulate the acetylcholine Nicotinic sites effector cell. The effects can be divided into the types of Between two neurons of the autonomic nervous system cells, or receptors, stimulated. There are two nicotinic types Between nerve ending and skeletal muscle of receptors: The first type is when one neuron of the Muscarinic sites autonomic nervous system stimulates another at a junction Between nerve ending and responding smooth muscle or gland called a ganglion. The second type is when a motor nerve stimulates a skeletal muscle to cause contraction. Muscarinic sites include nerves of the autonomic nervous system which stimulate smooth muscle or glandular secretions. Many of the symptoms we will discuss relate to the muscarinic type of stimulation. Slide 57 This slide shows a nerve terminal on the left, in which an action potential, or electrical signal, has stimulated the nerve to release vesicles that contain the acetylcholine.
Nerve Transmission: Nerve to Nerve
ACh
37
Chemical Terrorism Response Guide For Clinical Laboratories Slide 58 Acetylcholine from those vesicles diffuses across the synaptic cleft to simulate the next nerve.
ACh
Slide 59 By binding to receptors and cause second nerve to depolarize and then send a signal down the length of that nerve.
ACh
Slide 60 The acetylcholine is broken down by enzyme, acetylcholinesterase. The pac-man figures here hydrolyze the acetylcholine into choline and acetate, thereby ending the stimulation, in this case, of the second nerve.
Stop Impulse: The Role of AChE
AChE
ACh
38
Chemical Terrorism Response Guide For Clinical Laboratories Slide 61 When nerve agent is present, the pink diamond shapes, the nerve agent will bind to the enzyme, thereby preventing the breakdown of acetylcholine.
Exposure to Nerve Agent
AChE
ACh
Slide 62 The accumulation of acetylcholine causes the second nerve to fire more rapidly, to the point that it no longer function. This is called a depolarizing block. Initially there is stimulation and then blockade. For a nicotinic effect on skeletal muscle, there is initial fasciculation or twitching of the muscle, followed by paralysis.
AChE Inhibition
AChE
ACh
Slide 63 Here is what happens biochemically. The serine hydroxyl group of the acetylcholinesterase forms a bond with the nerve Mechanism of Action of Nerve Agents agent which allows a fluoride atom to break its bond with the nerve agent. You can consider this stage (the figure on the O right) a transitional state, just like many of the chemical OH + F P reactions you learned about in chemistry, its an intermediate O O state. As long as the organophosphate is present in sufficient O P C holineste rase concentrations to interact with the enzyme, the O acetylcholinesterase will be inhibited. The nerve agent tends O to spend a longer time in the transitional state than would Boun d cholinesterase the natural substrate, acetylcholine. From here, there are O P OH two outcomes possible for the enzyme. In one, water may add across this newly formed bond and hydrolyze the nerve Bound and aged cho linest erase agent away from the enzyme, just as would occur for the natural substrate acetylcholine. The second possibility is for aging to occur. Aging means that a second leaving group will leave the nerve agent molecule, allowing the nerve agent to form a more stable complex and a permanent bond with the enzyme. When aged, the enzyme cannot regenerate, either spontaneously through hydrolysis or with use of special antidotes known as oximes. I mentioned soman earlier. Soman ages in a matter of minutes. So its very difficult to reactivate the acetylcholinesterase after soman exposure. Whereas with sarin, youd have a little bit of a time window, on the order of a few hours to reactivate and prevent the toxicity. 39
Chemical Terrorism Response Guide For Clinical Laboratories Slide 64 Lets discuss a little bit more about the toxicity. We often use the mnemonic DUMBELS to describe the muscarinic effects, also called cholinergic effects. Diarrhea, urination, miosis or pinpoint pupils, bronchoconstriction with a secretion of fluids into the airways. This is important to control since it can be life ending. You also have vomiting (emesis), lacrimation (or tearing) and excess salivation.
Muscarinic Effects of Nerve Agents

DUMBELS D - diarrhea U - urination M - miosis B - bronchoconstriction, bronchorrhea E - emesis L - lacrimation S - salivation
Slide 65 There are other effects including the nicotinic effects and those on the central nervous system. Such effects include the early fasciculations in muscles leading to paralysis. Paralysis of the respiratory muscle is another means to death. There are also direct effects on the central nervous system including confusion and fatigue which is seen when the amounts absorbed increase very incrementally. At very high doses, a loss of consciousness or seizures may occur.
Nicotinic and Other Effects

Stimulation of nicotinic receptors on skeletal muscle
Fasciculations (fine twitches) Weakness and paralysis Paralysis of respiratory muscle, apnea
CNS effects
Confusion, fatigue Loss of consciousness, seizures
Death (obstruction, paralysis, CNS depression)
Slide 66 One could never discuss all potential ways to chemically injury others in one lecture. I want to impress upon everybody that weve focused only on some obvious CT agents. There are many other possibilities including the biotoxins, such as: botulinum toxin, amatoxin or microcystins; and incapacitating agents used to cause loss of consciousness or incapacitation. We need to keep in mind that while our attention is focused on all of these obvious agents, that there could be somebody out there whos fairly crafty in putting something unique together.
Other Toxins
Biotoxins
E.g., Botulinum toxin, microcystins
Incapacitating agents and drugs

Seizures, unconsciousness, loss of coordination, confusion E.g., BZ, LSD, carfentenil
Protein synthesis inhibitors, channel blockers, receptor blockers, kinase inhibitors, others
40
Chemical Terrorism Response Guide For Clinical Laboratories Slide 67 Much of the source of information about the warfare agents can be found in the Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare. You can also go to the website at USAMRICD and look at a variety of sites that they have provided. Lastly, I want to acknowledge several people that given similar talks that have influence the information in this presentation. Ken Orloff of ATSDR and Paul Wax of the American College of Medical Toxicologists. Thank you.
ACKNOWLEDGMENTS
The Chemical Casualty Care Division, USAMRICD http://ccc.apgea.army.mil Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare. Eds Sidell FR, Takafuji ET, Franz DR. Office of the Surgeon General at TMM Publications, Washington D.C., 1997. Thanks to Ken Orloff, and Paul Wax, for slide information
41
CDC Specimen-Collection Protocol for a Chemical-Exposure Event

For detailed instructions see CDC's Shipping Instructions for Specimens Collected from People Who May Have Been Exposed to Chemical-Terrorism Agents.
Collect blood and urine samples for each person involved in the chemical-exposure event.
Note: For children, collect only urine samples unless otherwise directed by CDC.
Blood-Sample Collection
For each person, collect blood in glass or plastic tubes in the following order:1st: collect specimens in three (3) EDTA (purple-top) 4 mL or larger plastic or glass tubes; 2nd: collect another specimen in one (1) gray- or green-top tube. Collect the specimens by following the steps below:
Collect a minimum of 12 mL of blood in three (3) 4 mL or larger glass or plastic tubes. If using 3 mL tubes, use four tubes.
Mix contents of tubes by inverting them 5 or 6 times.
Place bar-coded labels on each tube, so that when the tubes are upright, the barcode looks like a ladder.
1
7 7 7 7
2
7
3
7 7 7 7
Tube #1
Tube #2
Tube #3
Tube #1
Tube #2
Tube #3
Do not use gel separators.
Label tubes in order of collection. #1, #2, #3
Store samples at 1C to 10C.
Do not freeze.
After collecting samples in the purple-top tubes, collect one (1) sample in a gray- or green-top tube (gray-top tube shown). Allow the tube to fill to its stated capacity.
Mix contents of the tube by inverting it 5 or 6 times.
Place bar-coded labels on the tube, so that when the tube is upright, the barcode looks like a ladder.
Do not use gel separators.
Store samples at 1C to 10C.
Do not freeze.
Urine-Sample Collection
For each person, collect 25 mL- 50 mL of urine in a screw-cap urine cup.
Place bar-coded labels on all cups so that when the cup is upright, the barcode looks like a ladder.
Label the urine cup with the appropriate bar-coded label as shown. Indicate on the cup how the sample was collected if the method was other than "clean catch" (i.e., catheterization). Freeze samples (optimally at -70C).
11/2006
Instructions for Shipping Blood Specimens to CDC after a Chemical-Exposure Event

Guidance in Accordance with Packaging Instructions International Air Transport Authority (IATA) 650 Biological Substance Category B
For detailed instructions see CDC's Shipping Instructions for Specimens Collected from People Who May Have Been Exposed to Chemical-Terrorism Agents.
Place purple- and gray- or green top tubes by patient number into griddedtype box lined with an absorbent pad. If using an alternative packaging method, pack all tubes from the same patient together while preventing tubeto-tube contact.
Seal gridded box or alternative secondary container with one continuous piece of evidence tape. The individual making the seal must initial half on the tape and half on the packaging.
Wrap gridded box in absorbent pad and tape to seal. Seal gridded box or alternative container inside a Saf-T-Pak clear inner, leak-proof polybag (or equivalent).
Place the sealed Saf-T-Pak inner leakproof polybag (or equivalent) inside a white Tyvek outer envelope (or equivalent). Note: If primary receptacles do not meet the internal pressure requirement of 95 kPa, use compliant secondary packaging materials.
Seal the opening of this envelope with a continuous piece of evidence tape. Write initials half on the evidence tape and half on the envelope.
10
Use polystyrene foam-insulated, corrugated fiberboard shipper to ship boxes to CDC. Place absorbent material in the bottom of the shipper.
Place refrigerator packs in a single layer on top of the absorbent material.
Place the packaged specimens in the shipper. Use cushioning material to minimize shifting while box is in transit. Place additional refrigerator packs on top of samples.
Place the blood shipping manifest in a sealable plastic bag and put on top of the sample boxes inside the shipper. Keep your chain-of-custody documents for your files. Place lid on the shipper.
Secure the shipper lid with filamentous shipping tape. Place your return address in the upper left-hand corner of the shipper top and put the CDC Laboratory receiving address in the center.
11
12
For questions concerning this process, please contact:

Centers for Disease Control and Prevention Attn: Cecelia Sanders, Chemical Emergency Response Team Leader 4770 Buford Hwy. Building 110 Loading Dock Atlanta, GA 30341 Office: (770) 488-4034 Cell: (770) 294-4124
Add the UN 3373 label and the words "Biological Substance Category B" on the front of the shipper. UN 3373 is the code identifying the shipper's contents as "Biological Substance, Category B."
Send shipment via FedEx to:

Centers for Disease Control and Prevention Attn: Lt. Ernest McGahee 4770 Buford Hwy. Building 110 Loading Dock Atlanta, GA 30341 (770) 488-7579
05 /2008

Chemical Terrorism Response Guide For Clinical Laboratories

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Chemical Terrorism Response Guide

Bureau of Chemical and Environmental Services Version 2011