3. Moving from Hazard Assessment
to Risk Assessment in
Alternatives Assessment
Hans Plugge
3E Company
4. Hazard vs Risk
Hazard Assessment – the inherent hazard of a chemical via
specific or all routes of exposure without consideration of
exposure
Exposure Assessment – the likely amount of chemical
exposure to occur from a specific usage scenario for a
chemical/product
Risk Assessment – the probability of an effect resulting from
a particular chemical exposure scenario – for a single
chemical and scenario, the product of exposure and hazard
5. Hazard Assessment: Health Effects
List scores
Classification scores
Scientific data scores
Probabilistic data
6. Exposure Assessment
• Hundreds of scenarios available
• One exposure scenario at a
time
• Most exposures involve
multiple scenarios
• Need a way to sum exposure
Modeling
7. Spray Finishing
Activity
Chemical
h/day
Quantity Temp Room PPE
Product Liters °C Volume Value
Transport A, B, C 0.5 3.8 25 140 1
Mixing A, B 1.5 2 25 140 10
Spraying B 3 1.3 25 800 20
Flashing B 0.5 0.5 25 800 20
Cleaning C 1 1 25 140 10
Drying B 1.5 0.2 25 800 20
8. Exposure Assessment
Detailed analysis of scenarios
•May need multiple algorithms Population average vs high exposure
Need lots of physical chemistry data
Detailed chemical analysis of mixtures
Difficult to automate
Time-weighted average vs peak exposure
• Exposures modeled to be exceeding e.g. TWA need to be field verified
9. Exposure Screening
Single model for each scenario
Auto-selection of algorithms
Easy to obtain effect data
Auto-calculation of exposure and risk
Time-weighted summation of
exposures and hence risk
10. • Inherently simple
• Relative vs absolute risk
• Screening vs Regulatory Limits
• Occupational vs consumer
• Average vs sensitive vs high
exposure population
Risk Assessment
11. Potentials for Informing Exposure
Assessment through Life Cycle
Assessment
Erin Mulholland
thinkstep
12. Putting It All together: Integrating
Effects, Exposure and Life Cycle
Assessment
Hans Plugge
3E Company
13. Alternatives Assessment
Alternatives
Assessment is the
growing and rapidly
expanding art and
science of
evaluating the
relative hazards and
risks of existing
chemicals (or
products).
Informs the
scientific process of
substituting
functionally similar
chemicals with
reduced overall
health &
environmental risks.
Maintaining
functionality is of
utmost importance
– substitution must
provide similar
functionality within
a mixture (product)
or inherently makes
for an unacceptable
substitute.
14. Alternatives Assessment
• List based
• Classification based
• Scientific data based
Hazard
Assessment
• Screening
• Detailed
Exposure
Assessment
• Screening
• Detailed
Risk Assessment
Integrated Life
Cycle Assessment
15. WORSE
PRODUCT
COMPO-
SITION
CHEMICALS
OF
CONCERN
CHEMICAL
FUNCTIONALITY
EXISTING
ALTERNATIVES
R&D
DE NOVO
CHEMICALS
STRUCTURES
PHYSICAL
CHEMISTRY
CLASSICAL
IN VIVO
TOXICOLOGY
IN VITRO
ADVERSE
OUTCOME
PATHWAYS
ENZYME
DATA
TOXICOGENOMICS
DATA
ANALY-
TICS
DATA
GAPS
READ-ACROSS/ QSAR / MOLECULAR TOXICOLOGY
PRELIMINARY SCREENING HAZARD ASSESSMENT
(REGULATORY) HAZARD
ASSESSMENT
PHYSICAL
CHEMISTRY
EXPOSURE
ASSESSMENT
TOXICOLOGY
DATA
ECOTOXICOLOGY
DATA
(REGULATORY) RISK ASSESSMENT
REGULATORY ANALYSIS
INTERIM
LIFE
CYCLE
ASSESSMENT
SUSTAINABILITY ECONOMICS
ENGINEERING
PERFORMANCE
REGULATORY
ANALYSIS
ACCEPT
DOCUMENT
IMPLEMENT
FRAMEWORK FOR
ASSESSMENT OF CHEMICALS
GREEN CHEMISTRY AND ENGINEERING CONFERENCE
JUNE 14-16, 2016, PORTLAND, OR, USA
Hans Plugge & Longzhu Shen
3E Company & Yale University
Bethesda, MD & New Haven, CT
hplugge@3ecompany.com & longzhu.shen@yale.edu
After National Academy of Sciences, 2014
COMPUTATIONAL
CHEMISTRY
CHEMINFORMATICS
PROBABILISTIC
MODEL
WORSE
BETTER/EQUIVOCAL
BETTER/EQUIVOCAL
YES
NO
NO
YES
NO
17. Data Gaps
Read Across
• Homologues e.g.
octanal vs heptanal
• Analogues e.g.
octanal vs
octanone
QSAR Quantitative
Structure Activity
Relationships
• Based on existing
(classical) data
Molecular Toxicology
• Based on
enzyme/in vitro
data
22. WORSE
PRODUCT
COMPO-
SITION
CHEMICALS
OF
CONCERN
CHEMICAL
FUNCTIONALITY
EXISTING
ALTERNATIVES
R&D
DE NOVO
CHEMICALS
STRUCTURES
PHYSICAL
CHEMISTRY
CLASSICAL
IN VIVO
TOXICOLOGY
IN VITRO
ADVERSE
OUTCOME
PATHWAYS
ENZYME
DATA
TOXICOGENOMICS
DATA
ANALY-
TICS
DATA
GAPS
READ-ACROSS/ QSAR / MOLECULAR TOXICOLOGY
PRELIMINARY SCREENING HAZARD ASSESSMENT
(REGULATORY) HAZARD
ASSESSMENT
PHYSICAL
CHEMISTRY
EXPOSURE
ASSESSMENT
TOXICOLOGY
DATA
ECOTOXICOLOGY
DATA
(REGULATORY) RISK ASSESSMENT
REGULATORY ANALYSIS
INTERIM
LIFE
CYCLE
ASSESSMENT
SUSTAINABILITY ECONOMICS
ENGINEERING
PERFORMANCE
REGULATORY
ANALYSIS
ACCEPT
DOCUMENT
IMPLEMENT
FRAMEWORK FOR
ASSESSMENT OF CHEMICALS
GREEN CHEMISTRY AND ENGINEERING CONFERENCE
JUNE 14-16, 2016, PORTLAND, OR, USA
Hans Plugge & Longzhu Shen
3E Company & Yale University
Bethesda, MD & New Haven, CT
hplugge@3ecompany.com & longzhu.shen@yale.edu
After National Academy of Sciences, 2014
COMPUTATIONAL
CHEMISTRY
CHEMINFORMATICS
PROBABILISTIC
MODEL
WORSE
BETTER/EQUIVOCAL
BETTER/EQUIVOCAL
YES
NO
NO
YES
NO
23. Uses of Alternatives Assessment
Greener products
More acceptable
across supply
chain
Consumer vs
industrial
Ranking of existing
products/releases
Prioritize R&D
New products
Up front analysis
of greenness
Incorporate
sustainability into
supply chain
24. Future
Alternatives Assessment is a
long term interim solution for
selecting greener chemicals.
Increasingly de novo green
chemistry will be used to
influence the selection of
greener chemicals eventually
taking over the entire process
of selecting greener chemicals
Eventually we will achieve the
Holy Grail: integrating risk
assessment and LCA in a semi-
automated screening approach
25. Authors
• Ann Mason
American Chemistry Council, Washington, DC
Ann_Mason@americanchemistry.com
• Erin Mulholland
thinkstep, Boston, MA
erin.mulholland@thinkstep.com
• Hans Plugge
3E Company, Bethesda, MD
hplugge@3ecompany.com
