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Lab Hazard Recognition and Analysis
1. Lab-HIRA: Hazard Identification
and Risk Analysis for the
Chemical Research Laboratory
Dr. David Leggett
Leggett Technical Consulting
Los Angeles, CA
243rd ACS National Meeting
San Diego CA, March 2012
2. Lab-HIRA: Hazard Identification and Risk Assessment
A straightforward technique designed to identify
and assess the hazards of conducting a chemical
synthesis in the research environment.
Once hazards have been recognized appropriate
risk minimization or mitigation measures can be
implemented by the researcher.
An additional formal hazard analysis for the
synthesis reaction may be recommended.
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3. Lab-HIRA: Hazard Identification and Risk Assessment
• An explosion at Sussex University (UK, 1988)
seriously injured a student.
o UK H&SE prosecuted SU for negligence.
o Today, British researchers are required to write down
risk assessments before every experiment.
• Univ. of California (Los Angeles), Texas Tech
Univ. & Univ. of Florida have had well-publicized
serious accidents in their chemistry labs
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4. Lab-HIRA: Hazard Identification and Risk Assessment
• Accident rate is 10 to 50 times higher than that in
industrial laboratories
o In industry scientists are required to do a careful hazard
analysis and follow strict safety precautions
o Very few [academic] scientists have taken formal
courses in safety, health, and toxicology
o Most relevant safety articles are published in journals
devoted outside of an academics major field of interest
A.K. Furr, Handbook of Laboratory Safety (2000)
US Chemical Safety Board, Texas Tech University Laboratory
Explosion Case Study (2010)
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5. Lab-HIRA: Hazard Identification and Risk Assessment
Chemical Industry Typically Requires Hazards Testing for
New Chemistry Destined for Full Scale Manufacture
Type of Hazard
Scale of Reaction Typical Approaches
Assessment
Research & Desktop Study Calculations, Literature,
Development Small Scale Testing DSC, Mixing Cal, RSST
Qualitative and Semi- Reaction Calorimetry,
Pilot or Kilo Lab
Quantitative Testing Adiabatic Calorimetry
Custom testing for DIERS, Dust, Reaction
Manufacturing
Engineering Design Calorimetry, Flammability
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6. Lab-HIRA: Hazard Identification and Risk Assessment
Lab-HIRA: Hazards Identification and Risk Analysis
for New Chemistry at Research Scale
Desktop Study Calculations, Literature
Small Scale Testing DSC, Mixing Calorimetry, RSST
SWIF or Simple HAZOP, if needed
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7. Lab-HIRA Step 1: Hazard Identification
Lab-HIRA uses the physical, chemical, and
health data for reactants and reactions:
• Flammability – vapors, liquids, solids
• Specific Chemical Hazards
• Health Data – toxicity, exposure, carcinogenicity
• Reaction Conditions
• Equipment such as radiation sources
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8. Lab-HIRA Step 1: Hazard Identification
Four Classes of Data Support Lab-HIRA
Class 1: Property Expressed as Specific Value
Class 2: Hazardous Characteristic of Molecule
Class 3: Reaction Hazards, by Type or Named Rxn
Class 4: Conditions of Synthesis
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9. Lab-HIRA Step 1: Hazard Identification
Properties Expressed as Discrete Values
Chemical / Energy
Property Value
Source
IDLH Hydrazine 50 ppm
LD50 (rats) 1,4-Dioxane 5,200 mg kg-1
TWA (OSHA) SO2 5 ppm
Flash Point THF -14 °C
Laser Source High intensity laser Class 4
Flammability Hexane Class IA
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10. Lab-HIRA Step 1: Hazard Identification
For discrete values, such as LD50, map values to an
index scale 0 thru’ 4
Hazard
Hazard Min Max
Index Value
0 No Hazard > 5,000
1 Minimal > 500 5,000
2 Minor > 50 500
3 Moderate 5 50
4 Major <5
United Nations, Globally Harmonized System of Classification and Labeling of
Chemicals (2005)
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11. Lab-HIRA Step 1: Hazard Identification
Properties are expressed in various units:
Hazard Index Value
Property
0 1 2 3 4
Flammability NF / NC IIIB II or IIIA IB or IC IA
Laser Source None Class 1 Class 2 Class 3 Class 4
UV Source, nm None 400-320 320-280 280-100 <100
MIE, mJ >5 2-5 0.5 - 2 0.05 - 0.5 < 0.05
Auto-Ign, C > 500 350 - 500 250 - 350 150 - 250 < 150
Hazard No Haz Minimal Minor Moderate Major
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12. Lab-HIRA Step 1: Hazard Identification
Four Classes of Data
Class 1: Property Expressed as Specific Value
Class 2: Hazardous Characteristic of Molecule
Class 3: Reaction Hazards, by Type or Named Reaction
Class 4: Conditions of Synthesis
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13. Lab-HIRA Step 1: Hazard Identification
Hazardous Characteristics of Molecules
Index Index
Specific Hazard Code Value
Pyrophoric: spontaneously flammable or
AIR 3
reactive with air < 130 F
Forms gaseous products during reaction –
GAS 2
CO2, CO, H2, N2, C4H10
Suspected carcinogen, teratogen, mutagen or
HLTH 4
reproductive hazard
Impact or friction sensitive IMPT 3
Molecule requires temperature controlled
TCN 2
storage or handling
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14. Lab-HIRA Step 1: Hazard Identification
Four Classes of Data
Class 1: Property Expressed as Specific Value
Class 2: Hazardous Characteristic of Molecule
Class 3: Reaction Hazards, by Type or Named Rxn
Class 4: Conditions of Synthesis
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15. Lab-HIRA Step 1: Hazard Identification
Hazardous Characteristics of Molecules
Index
Reaction Type Reaction Type
Value
Decarboxylation Removal of –COOH with CO2 evolved 2
Nitration Red fuming or white HNO3, N2O4 3
LiAlH4, N2H4 in KOH, NaBH4 in CH3OH 3
Reductions
BF3 / NaBH4, H2 + catalyst 2
Oxalyl chloride – high health hazard 3
Esterifications
RCOOH + SOCl2 followed by R’OH 2
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16. Lab-HIRA Step 1: Hazard Identification
Hazard Levels of Named Reactions
Index
Reaction Type Reaction Type
Value
Wolff-Kishner Reduction of RCHO or R2CO to RH with
3
Reduction H2NNH2
Reaction of R’MgCl to RCHO or RR”CO to
Grignard Reaction 3
form RR’CHOH or RR’R”COH
One-carbon oxidative degradation of
Kochi Reaction 1
R-COOH using a Pb(IV) reagent
Meerwein- The aluminum-catalyzed hydride shift from the
Ponndorf-Verley α-carbon of an alcohol reagent to RR’CO 2
Reduction forming RR’CHOH
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17. Lab-HIRA Step 1: Hazard Identification
Four Classes of Data
Class 1: Property Expressed as Specific Value
Class 2: Hazardous Characteristic of Molecule
Class 3: Reaction Hazards, by Type or Named Reaction
Class 4: Conditions of Synthesis
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18. Lab-HIRA Step 1: Hazard Identification
Properties are expressed in various units:
Synthesis Hazard Index Value
Conditions 0 1 2 3 4
150 -
TPROCESS, MAX ( C) < 75 75 - 150 250 - 400 > 400
250
PPROCESS (psig) < 10 10 - 25 25 - 75 75 - 150 > 150
TFEED ( C) < 35 35 - 60 60 - 80 80 - 100 > 100
Scale-up Ratio 1 1-5 5 - 50 50 - 500 > 500
Reaction Mass (kg) < 0.005 0.005 – 0.1 0.1 - 1 1-5 >5
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19. Lab-HIRA Step 1: Hazard Identification
Lab-HIRA compared to OSHA Lab Standard (29 CFR
1910.1450)
Health Properties: Lab-HIRA and 1910.1450
Physical and Chemical Properties: Lab-HIRA only
Reaction Conditions: Lab-HIRA only
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20. Lab-HIRA Step 1: Hazard Identification
Overall Hazard Index, OHI given by:
OHI IVD IS_PR IVD IS_C N D IV C H M _H Z IV N AM E IV T YPE
DIS_PR = Discrete property (LD50, Flash Pt.) mapped to range
DIS_CND = Discrete reaction condition (TRXN) mapped to range
CHM_HZ = Index value for specific chemical hazard (AIR, WAT)
NAME = Specific named reaction (Wolff-Kirshner)
TYPE = Type of reaction (Decarboxylation)
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21. Lab-HIRA Step 1: Hazard Identification
Case Study 1:
Diphenylmethane from Benzophenone, using Wolff-
Kishner reaction:
KOH, HOCH2CH2OH
H2NNH2 200 °C, Reflux
Populate Lab-HIRA Chemical Hazard Review form for:
• Benzophenone
• Potassium hydroxide pellets
• Hydrazine hydrate
• Ethylene glycol
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22. LEGGETT Slide A:22
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23. Toxicity LD50 oral (rat) 129 mg/kg
ACGIH TLVs TWA (ACGIH) 40 ppm
Exposure Limits
OSHA PEL & NIOSH IDLH TWA (OSHA) n/a ppm
Melting & Boiling Pt; AutoIgnition B Pt 113 °C
Lower Flam
Flammability (Liquid) LEL / UEL ; Fl Pt 5 v/v%
Limit
Radiation Sources, Nuclear, Laser, UV Nuclear n/a Radiation Type
LEGGETT Dust Expl Severity: ST / Pmax / MIE ST Dust Class n/a Slide A:23
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24. LD50 skin LC50 inhal
600 mg/kg 570 ppm
(rabbit) Gas (rat)
STEL (ACGIH) 1 ppm C (ACGIH) n/a ppm
PEL (OSHA) 1 ppm IDLH (NIOSH) 50 ppm
M Pt -52 °C AutoIgn Temp 270 °C
Upper Flam
98 v/v% Flash Point 72 °C
Limit
Laser Type n/a Laser Class UV Wavelength n/a nm
Pmax LEGGETT n/a psi Vapor MIE n/a mJ Slide A:24
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25. Lab-HIRA Step 1: Hazard Identification
Specific Index Index
Code
Data for Hydrazine Value
Hazard
Flash Point FlPt 72 °C 2
Flam. Liquid FLAM Class IIIA 2
Explosion EXPL LFL = 5; UFL = 98 v/v% 4
LD50 oral = 129mg kg-1; LC50 Inh =
Toxic Hazard TOXIC 2
570ppm; LC50 skin = 600mg kg-1
IDLH = 50 ppm;
Exposure EXPOS 4
PEL = 1ppm; TLV = 40ppm
AI Temperature AIT 270 °C 2
FlPt = 72 °C; BPt = 113 °C;
Fl. Pt vs BPt FPBP 2
Rxn T = 200 °C
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26. FlPt 2 FLAM 2 EXPL 4 TOXIC 2 EXPOS 4
AIT 2 FPBP 2
Susp. birth defects, cancer,
GAS Gas formed during reaction HLTH HIRR High reaction rate
mutagenic, teratogenic
POLY Easily polymerizes RDOX Strong oxidizer or reducer RUN Secondary runaway reaction
Temperature control needed
TCN WAT Water reactive
for storage
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27. Severe A formal Risk Analysis MUST be performed for this chemical
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28. Lab-HIRA Step 1: Hazard Identification
Repeat data entry for other reactants
Review results of Hazard Identification and Risk
Analysis on Reaction Summary:
• Potentially Hazardous Reaction Conditions
• Summary of Hazard Properties of all Reagents
• Potentially Hazardous Reaction Chemistry
• Additional Concerns
• Recommendations for Additional Hazard Review
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29. LEGGETT Slide A:29
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30. Hazards of Reaction Conditions (Check all that apply)
Hazardous Functional Group Added to Molecule (y/n) n
Conversion of Existing Hazardous Functional Group (y/n) n
Reaction performed less than 3 times (y/n) y
Reaction to be run unattended (y/n) y
Scale-up reaction? Enter scale-up factor (Default = 1) 1
Maximum reaction temperature 200 °C
Minimum reaction temperature 25 °C
Maximum temperature of feed 25 °C
Maximum pressure of reaction 0 psig
Maximum pressure of feed 0 psig
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Hazard Rating for Reaction Hazard
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31. LEGGETT
Technical Consulting
.
6
5
4
3
2
1
Check
Safeguards
Benzophenone
Compliance
Diethylene glycol
Hydrazine hydrate
Potassium Hydroxide
Toxic based on LC(D)50 values for
y
y
y
y
Oral, Skin or Inhalation
Exposure based on TLV,
y
y
n
n
PEL, or IDLH
Classification of Flammable or
y
y
n
n
TOXIC EXPOS FLAM
Combustible Liquid
Minimum Ignition Energy
n
n
n
n
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MIE-V
(Vapor or Gas)
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y
y
n
n
Autoignition Hazard
AIT
32. Named Reaction Hazard Rating
Wolff-Kishner Reduction
Wolff-Kishner Reduction
The reduction of aldehydes and ketones to alkanes. Condensation of the
carbonyl compound with hydrazine forms the hydrazone, and treatment with
base induces the reduction of the carbon coupled with oxidation of the
hydrazine to gaseous nitrogen, to yield the corresponding alkane. The
Huang-Minlon modification removes water and excess hydrazine by
distillation, using a Dean Stark distillation trap, so that he reaction
temperature can rise to 200 C. This allows the use of the cheaper hydrazine
hydrate in place of anhydrous hydrazine. The Clemmensen Reduction can
effect a similar conversion under strongly acidic conditions, and is useful if
the starting material is base-labile.
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Hazard Rating for Named Reactions
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34. Lab-HIRA Step 1: Hazard Identification
Case Study 2:
• Synthesis of a vinyldecane derivative using t-BuLi.
• Researcher was exposed to t-BuLi during a transfer.
• The nitrile gloves and synthetic sweater, worn by the
researcher at the time of the accident, caught fire;
the chemist was not wearing a lab coat at the time.
• She received burns over 40% of her body and died a
few weeks later.
How would Lab-HIRA have helped in this situation?
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35. Lab-HIRA Step 1: Hazard Identification
Use Describe
Safe- other risk
Safeguards Required to Work With This Material guard? reduction
Lab-HIRA produces (Y/N) measures
Confirm that only Class I Division 2 rated electrical
a Safeguards Com- 1 equipment will be used during this synthesis
pliance Checklist Hazard Codes: WAT, AIR, EXPL, FLAM
Consider using a glove box or bag to handle t-Bu Lithium
for each reagent, 2
Hazard Codes: WAT, AIR
including PPE Material transfers will be done in the hood, glove box or
3 bag. Open-bench work prohibited for this chemical
recommendations Hazard Codes: WAT, AIR, TCN
Handling techniques for these chemicals have been
13 reviewed and approved by Chemical Safety Committee
Hazard Codes: AIR
Written contingency plans are available covering worst
14 case accident scenarios
Hazard Codes: WAT, AIR
Signed: ____________________________________
Date:
Print Name: ________________________________
_________
Grad Student Post Doc Supervisor
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36. Lab-HIRA Step 2: Risk Assessment
Lab-HIRA may recommend a formal risk analysis
such as a What-If or procedural HAZOP
• Chose the hazard analysis technique
• Assemble necessary documentation
• Conduct risk analysis
• Evaluate recommendations for risk reduction
• Close out recommendations
o Items to be completed before beginning work
o Schedule other items for timely completion
• Document Lab-HIRA findings
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37. Lab-HIRA Step 2: Risk Assessment
A typical synthesis procedure for Case Study 1:
In a suitable fume hood set up a nitrogen-purged multi-neck flask
equipped with an agitator, reflux condenser, Dean-Stark trap, and
temperature controller.
Suspend the ketone (85 g) in an alkylene glycol (~2 L).
Place the flask in a room temperature oil bath then add KOH (70 g).
Gradually add 80% solution of hydrazine hydrate (65 mL).
Heat the reaction mixture slowly heated to 200oC ………
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38. Lab-HIRA Step 2: Risk Assessment
Action: Install and set a temperature controller for reactor
What-If Scenario 1: Temperature controller incorrectly set up
or fails
Consequence: Failure to control reaction temperature;
possible runaway reaction; possible loss of containment
Risk Assessment: Major, if consequence plays out
Current Safeguards: Chemist monitors reaction regularly
Recommendation: Determine if runaway is possible;
consider using redundant T controller if true
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39. Lab-HIRA Step 2: Risk Assessment
Action: Install and set a temperature controller for reactor
What-If Scenario 2: Runaway reaction occurs before evasive
action can be taken?
Consequence: Probable loss of containment; possible fire/
explosion
Risk Assessment: Severe, if consequence plays out
Current Safeguards: None at present – no GS willing to
camp out beside fume hood
Recommendation: Determine if runaway is possible;
consider using redundant T controller if true; do not perform
overnight runs for this reaction
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40. Lab-HIRA: Summary and Conclusions
• Lab-HIRA identifies and assesses reaction hazards
and gives guidance about formal hazard review.
• Designed for use by chemists who have sufficient
knowledge to safely handle the chemicals and the
equipment planned for the synthesis.
• The hazard potential may be estimated from readily
available physical, chemical, and health data.
• Thirty three parameters, indicative of one or more
hazardous properties of molecules or synthesis
conditions, are used to assess the reaction hazards.
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41. Lab-HIRA: Summary and Conclusions
• The risk-based assessments tend to be conservative.
• Once hazards have been recognized appropriate risk
reduction measures can be implemented.
• If a formal hazard analysis for the synthesis reactions
is indicated then techniques, such as Check-List,
What-If, SWIF or HAZOP are available.
• Thermal hazards testing may be required to quantify
the consequences of equipment upsets or procedural
short-comings.
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42. Lab-HIRA: Summary and Conclusions
Only open literature data are used.
Some hazards associated with the
synthesis reaction may be missed.
It is the responsibility of the user to
determine the adequacy of the
hazard identification and risk
analysis of their synthesis.
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43. Lab-HIRA: Publications
D. Leggett, Lab-HIRA: Hazard Identification and Risk Analysis
for the Chemical Research Laboratory: Part 1. Preliminary
Hazard Evaluation, J. Chem. Health & Safety, In press
DOI 10.1016/j.jchas. 2012.01.012
D. Leggett, Lab-HIRA: Hazard Identification and Risk Analysis
for the Chemical Research Laboratory: Part 2. Risk Analysis of
Laboratory Operations, J. Chem. Health & Safety, In press
DOI 10.1016/j.jchas.2012.01.013
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