Chemical Terrorism Response Guide for Clinical Laboratories

8/3/2019 Chemical Terrorism Response Guide for Clinical Laboratories

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Chemical Terrorism Response Guide For Clinical Laboratories

TABLE OF CONTENTSIntroduction ....................................................................................... 2

Contact Information .............................................................................. 3

Rapid Toxic Screen ............................................................................... 4

Laboratory Response Network .................................................................. 5

Specimen Collection, Packaging, & Shipping Instructions .................................. 6Questions .................................................................................. 6

Specimen Collection ..................................................................... 6

Whole Blood ....................................................................... 6

Urine ............................................................................... 6

Blanks .............................................................................. 6

Labeling Specimens .............................................................. 7

Specimen Packaging ..................................................................... 7Secondary Packaging for Blood Tubes ......................................... 7

Outer Packaging for Blood Tubes .............................................. 8

Secondary Packaging for Urine Cups .......................................... 8

Outer Packaging for Urine Cups ................................................ 9

Documentation ........................................................................... 10

Specimen Shipping ....................................................................... 10

Forms ............................................................................................... 11

Urine Evidence Form ..................................................................... 11

Urine Shipping Manifest Forms 12






CONTACT INFORMATIONUnified State Laboratories: Public Health

Division: Disease Control and PreventionBureau: 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 Laboratory Director 801-965-2424

Sanwat Chaudhuri, PhD Bureau Director 801-965-2470

Jack Oman Assistant Bureau Director 801-965-2507

Kyle Ashby, PhD CT Lead Chemist 801-965-2484

Merril Chipman Chemist 801-965-2477

Sumaiya Islam Chemist/Microbiologist 801-965-2502

Nick Oman Chemist 801-965-2477Stephanie Rogers Bureau Secretary 801-965-2508

Robert Rolfs, MD State Epidemiologist 801-538-6386

Centers for Disease Control and Prevention

Division: National Center for Environmental Health,

Division of Laboratory Science - Atlanta, GA

Phone: 888-374-1764Admin: 770-488-7950

URL: http://www.bt.cdc.gov/




RAPID TOXIC SCREENThe 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

CyanideLewisite

Toxins Ricin

Saxitoxin

Natural toxins

Incapacitating agents Drugs of abuse, e.g. cocaine, opiates, PCPOthers, 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




LABORATORY RESPONSE NETWORKThrough CDC preparedness programs in partnership with the Association of Public Health

Laboratories (APHL), other federal agencies, and state public health laboratories, theLaboratory 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 detecttoxic 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 wholeblood. 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




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: [email protected]

Phone: 770-488-7532

Mobile: 678-525-2683

Cecelia Sanders, Chemical Emergency Response Team Leader

E-mail: [email protected]

Phone: 770-488-4034Mobile: 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 fromthe 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




Labeling Specimens

Label specimens with labels generated by your facility and follow your facility’s

procedures for proper specimen labeling.

In addition to unique patient identifiers (e.g. medical records number, specimenidentification 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 thecollection 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 peoplefrom 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






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 tapeinitialed 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 largechunks 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

CDC’s receiving address in center.

Place the UN 3373 label and the words “Biological Substance, Category B” adjacent tothe 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.




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 cleancatch (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 foam-

insulated, 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 chain-

ofcustody 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-of-

custody 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 thatthe relinquisher is the express courier (and provide the tracking number) or have the

person transporting the specimens sign the chain-of-custody form.



Centers for Disease Control and Prevention Unified State Laboratories: Public Health

NCEH/DLS Chemical Terrorism Response

4770 Buford Hwy, NE MS F-20 4431 S 2700 W

Atlanta, GA 30341-3724 Taylorsville, UT 84119

EVIDENCE FORMDate of Shipping: Date of Sample Collection:

Event Name: Facility Name:

For a group or a box of samples: For an individual sample:

Local ID:

CDC/NCEH Group ID: CDC NCEH ID:

CDC Sample ID:

CDC Unique ID:

For sample(s) from an exposed individual:

Number of Urine

Containers: Sample IDs:

* * * * *

U r i n e

S a m p l e s

*





...Continued from previous page Page ____ of ____

Patient/Victim ID Label UC Comments



Centers for Disease Control and Prevention Unified State Laboratories: Public Health

NCEH/DLS Chemical Terrorism Response

4770 Buford Hwy, NE MS F-20 4431 S 2700 W

Atlanta, GA 30341-3724 Taylorsville, UT 84119

EVIDENCE FORMDate of Shipping: Date of Sample Collection:

Event Name: Facility Name:

For a group or a box of samples: For an individual sample:

Local ID:

CDC/NCEH Group ID: CDC NCEH ID:

CDC Sample ID:

CDC Unique ID:

For sample(s) from an exposed individual:

Number of Purple-

top Tubes: Sample IDs:

Number of Green-

/Gray-top Tubes: Sample IDs:

* * * * * B

l o o d

S a m p l e s

*



Page ____ of ____

CENTERS FOR DISEASE CONTROL AND PREVENTION

CHEMICAL TERRORISM BLOOD SPECIMEN COLLECTION

SHIPPING MANIFESTNote: 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: Date Received:

Shipped By: Received By:Name

Signature:

Contact Telephone:Agency

Signature:

BLOODPlease 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: Total Number of Blanks this Container:

Purple-top Tubes: Blank Purple-top Tubes:

Green- or Gray-top Tubes: Blank Green- or Gray-top Tubes:

Comments:

Shipping Address: Centers for Disease Control and Prevention, CDC

ATTN: Lt. Ernest McGahee

0 f d



...Continued from previous page Page ____ of ____

Patient/Victim ID Label PT 1 PT 2 PT 3 GT 1 Comments






OVERVIEW OF CHEMICAL AGENTSSlide 1

Hello, I’m Dr. John Osterloh and I’m a medical toxicologistwith the Division of Laboratory Sciences at CDC’s NationalCenter for Environmental Health. Welcome to thispresentation of “An Overview of Chemical Terrorism Agents.”Primarily, I’ll discuss the history and clinical effects of chemical terrorism. A summary at the beginning should getus oriented and then I’ll proceed with the specific agents.

Slide 2

We usually think of chemical terrorism as a sudden event, for example, an explosion with a hot zone or adead zone and surrounding zones of contamination around it.

Slide 3

OvertOvert

An Overview of ChemicalTerrorism Agents

John Osterloh, MD, MS, FACMT

Division of Laboratory SciencesNational Center for Environmental Health




Slide 4

In Public Health, whether it’s an infectious disease outbreakor a chemical event, we have similar aims. One is to identifythe causative agent. Identification may be achieved bycircumstantial information, prior intelligence or clinicalsyndromes. Also of use are environmental and the biologicalfluid assays the CDC and state laboratories are applying. Wewant to determine the temporal and geographical distributionof 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 provideguidance to public health officials and medical officials interms 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 canhelp meet these goals. This is essentially why we’re herewith you today. The objective being to measure these

chemicals that can be used as terrorist agents.

Slide 6

How big a problem is terrorism and specifically chemical

CDC Public Health Aimsin a Chemical Event

• Identify the agent or cause – Circumstance, intelligence, clinical syndrome

– Environmental or biological fluids assay

• Determine temporal or geographicaldistribution of exposure

• Determine relative (high/low) exposures• Evaluate health implications

• Provide medical and public health guidanceand support• Provide continued surveillance and

prevention

The measurement of

chemicals in bloodand urine can helpmeet these goals




Slide 7

However, if you look at events recorded internationally overa period of about 40 years and limit the analysis to justchemical, biological, and radiological events, you’ll see thatchemical terrorism represents a sizable percentage. Notethat in this data from the Monterey Institute of InternationalStudies; about 70% of these cases are international. You canalso see that few of these are state-sponsored, and many of them are criminally motivated as opposed to politically orideologically motivated. That is changing. The StateDepartment enumerates about 400-600 events internationally

each year, so this data from the Monterey Institute of International Studies, representing Chemical, Biological andNuclear events, is still a small part of the total.

Slide 8

We often think of the types of events that can occur withchemical 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 orcosmetics, adhering them on surfaces so that hand-to-mouthtransfer takes place, using them in closed spaces, such asairliners, or dispersal through mobile “drive-by” releases.

Slide 9

Actual exposure to individuals will be affected by a myriad of

Exposure Scenarios

• Blast, leak• Food, tobacco, alcohol• Medications, blood products

• Cosmetics and personal hygiene products• Surfaces (door knobs, utensils): hand-to-

mouth• Fixed distribution systems: water, natural gas

• Ventilation ducts• Closed spaces: subway cars, airliners• Vehicular releases: drive-by, crop dusting

Source: Tucker, Monterey Institute of InternationalStudies, 2004




Slide 10

I can’t discuss all toxicologic principles here, so I want togive you a few reminders. Exposures, like I just said, can bethrough any of several routes, but they can also occurthrough simultaneous routes. If you look at the two pictureshere, you could have exposure that is dermal and at the sametime you can have exposure that is inhalational. Toparaphrase Paracelsus, ‘dose makes the poison.’ Not allthings are toxic at the same amount. We consider chemicalsthat kill half the animals in an experiment (LD50) at a dose of 1 mg/kilogram to be very toxic. But there are lower potency

chemicals, where exposure to larger amounts would produceserious toxicity. Also, remember that humans aren’t exposedin conveniently sized and timed doses when terrorism eventsoccur. Doses can be either short or long of duration, or bemultiple doses of almost any timing. So being able to put everything together in a nice package like youmight do when injecting an animal in an experiment, it isn’t that easy, when we’re dealing with people andevents.

Slide 11

As I said, different chemicals have different potencies inproducing toxicity. In this graph, the Concentration Timeproduct is used to represent the dose and time of exposure.It’s a convenient way of expressing dose with respect tovarying durations of exposure. 1 mg for 10 minutes would besimilar to 10 mg for one minute of exposure. You can seethat to kill half the animals exposed, chlorine requires amuch higher concentration-time product than say somethinglike sarin. A terrorist may consider availability and the formof chemical to use. If the choices were VX or chlorine andthe aim were inhalational exposure, chlorine might bepreferred, since one can easily release injurious amounts intothe air, where as VX is more difficult to volatilize.

Exposure and Effects-Reminders-

• Exposure may be throughseveral routes: – Dermal, gastrointestinal,

pulmonary, injected

• ‘Dose makes the poison’ – 1mg/kg LD50 is considered

‘extremely toxic’

– Single dose of short or long

duration – Multiple doses of any timing

Comparative Toxicity(lethal dose)

0

1000

2000

3000

4000

5000

6000

Ct50

(mg-min/m3)

chlorine phosgene HCN mustard sarin VX




Slide 13

Though our ability to estimate the relation between dose andeffects is poor, we can provide conservative estimates of external concentrations that should protect people fromadverse effects. These guidelines can be used in theworkplace, but are unlikely to be helpful in an emergency,primarily because measurements will not be performedduring a crisis, but also we will not know all theaforementioned chemical, physical and individual factorsaffecting variability. For instance, these workplace standardsonly consider inhalational exposure and not other routes of

exposure. The table does, however, demonstrate theinfluence of time. For instance, the IDLH is a NIOSHguideline, which stands for immediately dangerous to life andhealth. Compare that to the STEL, or the short-termexposure 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 bigfactor when considering any exposure level.

Slide 14

With that background on exposure, I wanted to move on andspeak more specifically about chemical terrorism. Of course,there is some history. We often can go back in Antiquity andfind that what is new is really old. Just like the old westernmovies, the Greeks used the “smoke em out” strategy usingsulfur fumes. In Roman times, Mithridates was fightingPompey’s army, his allies poisoned Pompey’s army by puttingmad honey next to the side of the road. ‘Mad honey’ resultsfrom bees having fed on rhododendron plants, which containandromedotoxins, which cause the heart rate to slow andblood pressure to drop, and even produce coma. Pompey’smen got sick. They were defeated. In WWI, we have allheard about the many casualties from the chemical warfareagents and we’ll talk about those as we proceed Iraq used

Exposure Guidelines

30 min(severe)

8 hr/d x 30yr(chronic)

15 min x 4(acute)

30 min (acute)

Time(Effect)

2.00.19AEGL-3

0.20.00003PEL, TLV

0.0020.0001STEL

9.60.1IDLH

Arsine(mg/m3)

Sarin(mg/m3)

Guideline

Chemical Warfare-Examples-

• Pitch and sulfur smoke used by allies ofSparta against Athenians in 423 BC

• “Mad honey” used by Mithridates’ allies topoison Pompey’s army

• Mustard gas, chlorine, and phosgene used inWW I. Caused many casualties

• Mustard gas used by Iraq against Iran in1988, against Kurds in 1990’s

• Sarin used in Tokyo subway attack 1995






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 abeer brewing process. Thallium was an intentional poison,added to tortillas in the Fresno area back in 1932. Thoughaccidental, cooking oil contaminated with PCBs in Japan andChina has educated us about the high dose toxicity of thesetoxins.

Slide 20

Other recent situations, some real and some hypothesized,provide further demonic ideas. Cyanide was added to Tylenolcapsules in the homicidal tampering cases of 1986. Another

homicide brings to light what could be done with alcoholicbeverages--formaldehyde and methanol added to Vodka wentundetected until after a victim’s death. We’ve had the ricinin the mail incidents. Like botulism, consideration has beengiven to the addition of other potent toxins, like amatoxin, tocanned food. One evil-minded scenario that has beenproposed is to place a potent carcinogen or teratogen in thefood chain. If this happened, Public Health might be dealingwith a possible excess of cancers or birth defects down theroad.

Slide 21

In reviewing the CT agents we will not have time to address

Food and Water Poisonings

May evolve like infectious disease outbreaks

• Arsenic: Staffordshire, 1900• Thallium: Fresno, 1932*• Methyl Hg: Minamata Bay, 1950’s

• Methanol: Atlanta, 1951• Hexachlorobenzene: Turkey, 1956• PCBs: Japan, China, 1968

• Organophosphate: Romania, 1989*• Cyanide: Chilean grape imports, 1989*

* Indicates intentional poisoning

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




Slide 22

Respiratory irritant gasses will be the first group of agents to

address. These are also classified as choking or lung-damaging agents.

Slide 23

Chlorine and phosgene are examples of industrial chemicals.Oxides of nitrogen are combustion products that are releasedfrom 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 1980’s, a small tanker truck was goingunder a bridge in the San Francisco area and the top turretwas knocked off. A white gas was released; this was silicontetrachloride, used in the Silicon Valley. In San Francisco,when the fog came in, as it does every afternoon, it mixedwith this, and produced hydrochloric acid and became anirritant gas. Fortunately, few people were affected.

Slide 24

Experience with gas exposures has been gained in the

Respiratory Irritant

Gases

Respiratory Irritant Gases

• Chlorine

• Phosgene

• Oxides of nitrogen

• Others: e.g., silicon tetrachloride




Slide 25

I’m going to take chlorine as an example because authorities

are worried about it. Why is that? Because it is easy to getand there’s so much of it in transport at any point in time. Ithas a wide variety of uses: for synthesizing other chemicalsand in water and product disinfection, as examples. It is agas and it is heavier than air, as are many of the gases we’llbe talking about. It has a familiar pungent bleach-like odorwhich allows for moderate warning properties, in that you cansmell it and get away before serious injury occurs.

Slide 26

It’s been used in chemical warfare in WWI, primarily by theGermans. In Ypres, Belgium a release on allied forces causedover 2000 injuries and 800 deaths.

Slide 27

This slide is actually a picture not of the Germans but of the

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

Chlorine in Chemical Warfare

• WW I – April 22, 1915

• Ypres, Belgium

• Germans released 150 tons of chlorinefrom 6,000 cylinders

• 2,500 – 3,000 people incapacitated, 800dead






Slide 31

The less water soluble gases, of which nitrogen dioxide and

phosgene are good examples, tend to cause few upperrespiratory symptoms. We don’t sense them, they’re notsoluble in water, they have poor warning qualities, and hencethey 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. Thesequelae of this can be scarring, dilation of the airways, arestrictive airway disease due to the scarring, or furtherprogression to severe obliteration of the air space

architecture of the lung.

Slide 32

Phosgene is another worrisome industrial chemical. It can becreated from chlorinated solvents when they’re burned andwhen metals that were cleaned with chlorinated solvents are

welded. Phosgene gas was used in WWI and it accounted for80% of all gassing deaths. It’s very dense and sinks to thebottom of recessed spaces; hence it was good for trenchwarfare. It has a low odor threshold, a smell of fresh mownhay, which can be misleading since it is a familiar smell. Theeffects are delayed pulmonary edema which occurs severaldays after the initial exposure.

Slide 33

So in summary the irritant gases can be categorized by water

Less Water Soluble Gases

• Relatively water-insoluble – Cause few upper respiratory symptoms

– Higher concentrations reach the alveoli

– Poor warning (irritative) properties, so victims cantolerate 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)

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 34

I want to move on to the next group of chemicals which

include blood agents, as termed by the military, an inexactterm. Such agents are better thought of as metabolic agentsin that they interfere with biochemical process in the body.

Slide 35

Cyanide is at the top of the list. Azides and sulfides act byrelated mechanisms. Carbon monoxide would be a terrorist’sstealth agent for closed spaces. Fluoroacetates, or what we

call out in the Southwest, coyote poison. Dinitrophenols,pentachlorophenols and others such as arsine gas andbiotoxins such as amatoxin in amanita phalloides mushroom.There are many more. The list provided focuses mainly onthose made in larger quantities.

Slide 36

Cyanide leads the list and it comes in three types

“Blood Agents”

and Metabolic Toxicants

Metabolic Toxicants

• Cyanides

• Azides

• Sulfides

• Carbon monoxide

• Fluoroacetates

• Dinitrophenol, pentachlorophenol

• Many others




Slide 37

Cyanide has a long history. It’s the gassing agent that was

used against the Jewish and Polish peoples in WWII. Also, inU.S. prisons it has been used as a gassing agent. We knowabout 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. Thepicture in the lower right is shows the fatalities of thecyanide 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.

Slide 38

Cyanide is interesting with respect to how it acts and itsclinical effects can be derived from its action. The humanbody oxidizes substrates by removing electrons, all those

electrons have to go somewhere, and that’s why we breatheoxygen. The electrons combine with oxygen and a couple of hydrogens to give water. Reduction of oxygen is stopped bycyanide. It binds to cytochrome oxidase, which is an enzymethat helps transfer these electrons to oxygen. The net resultis that oxygen is not removed from the blood and venousblood looks as red as arterial blood. Another effect of cyanide is that substrate sugars cannot be oxidized anyfurther than pyruvate. The excess pyruvate is shifted intolactate. Lactate accumulates and a lactate acidosis occurs,so a victim’s blood pH goes down with an accrual of untitrated acids. Oxygen-dependent tissues are most sensitive to cyanide, those being the heart and thecentral nervous system.

Cyanide-related Deaths

• WW II – Nazi concentrationcamps

• 1982 – Seven deaths fromcyanide- adulterated Tylenol

• Executions in US prisons

• 1978 – Mass suicide of 913followers of Rev. Jim Jones in

Jonestown, Guyana

• 1998 – 359 cases via PCCs – 301 accidental, 33 intentional

– 10 fatalities

Cyanide: Toxicological mode ofaction

• Blocks electron transport in mitochondria

– Binds to Fe+3 in cytochrome oxidase

– Prevents electron transfer to oxygen

• Oxygen-rich red venous blood

• Shift to anaerobic metabolism (glycolysis)• Lactate (metabolic) acidosis

• Oxygen-dependent tissues most affected

(CNS, heart)• Agitation, seizures, coma, cardiac arrest, death




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 theseeffects, you know it feels like a hangover, if you have hadthat toxic experience. High levels cause confusion, stupor,shortness of breath, and coma. Acidosis also occurs. Deathcan occur at carboxyhemoglobin concentrations greater than40%. A victim can survive concentrations of about that levelwith rapid oxygen therapy. On room air, the half-life of carboxyhemoglobin is about four hours, so if a victim’s

carboxyhemoglobin is 50%, it takes four hours to get down to25% when you’re breathing room air. If you give 100%oxygen, the half-life is an hour. With hyperbaric chambertreatment, it’s only 20 minutes. Long term complicationsfrom acute carbon monoxide poisoning may include deficits inmemory and learning.

Slide 41

The last metabolic agent I will mention is hydrogen sulfide,

which is familiar to most, from its rotten egg odor. Normallyit is emitted as part of a natural process of decaying organicmatter including sewer gas and rotting fish. It is also evidentin petroleum refining, which you often smell as you drive pastthese facilities. The mechanism of action for hydrogen sulfideis not too dissimilar to cyanide, in that it inhibits anotherrespiratory chain enzyme, cytochrome oxidase aa3, andproduces 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 springsMechanism of Action:

• Inhibits cellular respiration by binding tocytochrome oxidase aa3 (similar to cyanide)




Slide 43

The next group of CT agents is the vesicants.

Slide 44

These are agents that act on the skin and mucosal surfaces,including sulfur mustard agents and lewisite. Nitrogenmustards have been synthesized, but they haven’t been used

in warfare. However many derivatives of the nitrogenmustards have been used in cancer chemotherapy agents,because they can react with DNA and can stop the rapidlydividing cancer cells.

Slide 45

In WWI 80% of the chemical injuries were caused by the

Vesicants

Vesicant Agents

• Mustard agents

–Sulfur (military use)

–Nitrogen (chemotherapy)

• Lewisite (2-chlorovinyl dichloroarsine)






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. Forairway exposure, which is less common, the aerosol particlestend to be large and impinge in the upper airway, but canproduce serious epithelial necrosis, sloughing andinflammation. This can lead to airway obstruction and death.If large doses are absorbed, death from sepsis is also possible.

Slide 50

The last area I will review is the nerve agents. Nerve agentsinclude chemicals in the organophosphorus class.

Slide 51

These are the five major nerve agents that the U S has in

Mustard: Effects

• Skin: Erythema, vesicles, blisters/bullae

• Eye: conjunctivitis, edema, corneal clouding,ulceration, perforation, blindness

• Airways: Worsens in severity from upper towardlower airways – epithelial necrosis and sloughing

– airway obstruction

– pulmonary edema rare

• Death: – respiratory obstruction or pneumonia

– sepsis secondary to bone marrow suppression

Nerve Agents




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 yearsnow, out on Johnson Island in the middle of the Pacific, theUnited States has been trying to deactivate these nerveagents. Now there are eight facilities around the countrywhich are working on the remaining 20,000 tons of nerveagents that are in existence. This slide shows a storagefacility for the weaponized versions of the agents.

Slide 53

In Japan, when the Aum Shinrikyo cult released sarin gas in asubway, 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 bagswere broken open. Though Sarin is a liquid, it volatilizes well.The push and the vacuum of the air in the subway tunnelhelped move the toxin along.

Slide 54

The nerve agents are not gases They are liquids and soluble

History

• Germany (WW II)developed nerveagent munitions butdidn’t use

• Used by Iraq in Iran-Iraq war

• U.S. stockpiles

remain – 8 U.S. facilities

– 23,000 tons

Terrorist Use of Sarin

• Matsumoto, 1994

– ~200 casualties

– 7 deaths

• Tokyo, 1995

– ~5,000 casualties

– 12 deaths




Slide 55

Here’s a comparison of their toxicity. You can see tabun is 40

fold less toxic than VX. Again, these are listed by theirconcentration-time-product.

Slide 56

The way nerve agents work is by inhibition of the enzymeacetylcholinesterase, which breaks down theneurotransmitter, acetylcholine, in the synaptic cleft, the

space between two neurons. When one neuron stimulates thenext neuron or its target cell, acetylcholine is release fromthe first neuron to stimulate the second neuron or target cell.Inhibition of acetylcholinesterase allows a large amount of theacetylcholine to build up and continuously stimulate theeffector cell. The effects can be divided into the types of cells, or receptors, stimulated. There are two nicotinic typesof receptors: The first type is when one neuron of theautonomic nervous system stimulates another at a junctioncalled a ganglion. The second type is when a motor nerve

stimulates a skeletal muscle to cause contraction. Muscarinicsites 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.

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

Nerve Agent: Mechanism

• Inhibits breakdown of acetylcholine(neurotransmitter) by the enzyme,

acetylcholinesterase, in the synaptic cleft

• Results in continued stimulation by

acetylcholine

– Nicotinic sites

• Between two neurons of the autonomic nervous system

• Between nerve ending and skeletal muscle

– Muscarinic sites

• Between nerve ending and responding smooth

muscle or gland






Slide 61

When nerve agent is present, the pink diamond shapes, the

nerve agent will bind to the enzyme, thereby preventing thebreakdown of acetylcholine.

Slide 62

The accumulation of acetylcholine causes the second nerve tofire more rapidly, to the point that it no longer function. Thisis 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.

Slide 63

Here is what happens biochemically The serine hydroxyl

Exposure to Nerve Agent

ACh

AChE

AChE Inhibition

ACh

AChE




Slide 64

Let’s discuss a little bit more about the toxicity. We often

use the mnemonic DUMBELS to describe the muscariniceffects, also called cholinergic effects. Diarrhea, urination,miosis or pinpoint pupils, bronchoconstriction with a secretionof fluids into the airways. This is important to control sinceit can be life ending. You also have vomiting (emesis),lacrimation (or tearing) and excess salivation.

Slide 65

There are other effects including the nicotinic effects andthose on the central nervous system. Such effects include theearly fasciculations in muscles leading to paralysis. Paralysis

of the respiratory muscle is another means to death. Thereare also direct effects on the central nervous system includingconfusion and fatigue which is seen when the amountsabsorbed increase very incrementally. At very high doses, aloss of consciousness or seizures may occur.

Slide 66

One could never discuss all potential ways to chemically

Muscarinic Effects of NerveAgents

“DUMBELS”

D - diarrhea

U - urination

M - miosis

B - bronchoconstriction,bronchorrhea

E - emesis

L - lacrimation

S - salivation

Nicotinic and Other Effects

• Stimulation of nicotinic receptors on skeletalmuscle – Fasciculations (fine twitches)

– Weakness and paralysis

– Paralysis of respiratory muscle, apnea

• CNS effects – Confusion, fatigue

– Loss of consciousness, seizures

• Death (obstruction, paralysis, CNSdepression)




Slide 67

Much of the source of information about the warfare agents

can be found in the Textbook of Military Medicine: MedicalAspects of Chemical and Biological Warfare. You can also goto the website at USAMRICD and look at a variety of sites thatthey have provided. Lastly, I want to acknowledge severalpeople that given similar talks that have influence theinformation in this presentation. Ken Orloff of ATSDR andPaul 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. Officeof the Surgeon General at TMM Publications,

Washington D.C., 1997.

• Thanks to Ken Orloff, and Paul Wax, for slide

information

CDC Specimen-Collection Protocol for a Chemical-Exposure Event



11/2006

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.

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:

Blood-Sample Collection

Urine-Sample CollectionFor each person, collect 25 mL- 50 mL of urine in a screw-cap urine cup.

Label the urine cup with the appropriate bar-coded labelas shown. Indicate on the cup how the sample wascollected if the method was other than "clean catch"(i.e., catheterization).

Place bar-coded labels on all cups so thatwhen the cup is upright, the barcode lookslike a ladder.

Freeze samples (optimally at -70°C).

For detailed instructions see CDC's Shipping Instructions for Specimens Collected from People Who May Have Been Exposed to Chemical-Terrorism Agents .

3 Place bar-coded labels on each tube, so that when the tubes

are upright, the barcode looks like a ladder.

Mix contents of tubes by inverting them 5 or 6 times.

7

1

Tube #1

7

2

Tube #2

7

3

Tube #3

Label tubes in order of collection. #1, #2, #3

2

Tube #1

7

Tube #2

7

Tube #3

7

Mix contents of the tube by inverting it 5 or 6 times.5 Place bar-coded labels on the tube, so that when the tubeis upright, the barcode looks like a ladder.6

Store samples at 1°C to 10°C.

After collecting samples in the purple-top tubes, collectone (1) sample in a gray- or green-top tube (gray-top tubeshown). Allow the tube to fill to its stated capacity.

4

Do not use gel separators.

7 7 7

1

Do not use gel separators.

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.

Do not freeze.

Store samples at 1°C to 10°C.Do not freeze.





Documents

Chemical Terrorism Response Guide for Clinical Laboratories