The slide was presented at the 257th ACS National Meeting, Spring, Orlando, 2019

1. Green chemistry and open data
Jian Zhang*, Evan Bolton
257th ACS National Meeting, Orlando, April 2019

2. Outline ..
• Green chemistry brief
• EPA safer choice program
• Greener alternatives and safer examples
• Equation/formula to create greener list using GHS classification
• Open data platform, challenges and opportunities
• Summary

3. Green chemistry ..
EPA: Green chemistry is the
design of chemical products
and processes that reduce
or eliminate the generation
of hazardous substances.
Wiki: Green chemistry, also called
sustainable chemistry, is an area of
chemistry and chemical engineering
focused on the designing of
products and processes that
minimize the use and generation of
hazardous substances.

4. Green chemistry history ..
The green chemistry started in the early 1990s
https://greenchemistry.yale.edu/about/history-green-chemistry

5. Green chemistry’s 12 principles
1. Prevent waste: Design chemical syntheses to prevent waste. Leave no waste to treat or clean up.
2. Maximize atom economy: Design syntheses so that the final product contains the maximum
proportion of the starting materials. Waste few or no atoms.
3. Design less hazardous chemical syntheses: Design syntheses to use and generate
substances with little or no toxicity to either humans or the environment.
4. Design safer chemicals and products: Design chemical products that are fully effective
yet have little or no toxicity.
https://www.epa.gov/greenchemistry/basics-green-chemistry#twelve
Anastas and Warner, “Green Chemistry, Theory and Practice”, 1998

6. 12 Principles
5. Use safer solvents and reaction conditions: Avoid using solvents, separation agents,
or other auxiliary chemicals. If you must use these chemicals, use safer ones.
6. Increase energy efficiency: Run chemical reactions at room temperature and pressure
whenever possible.
7. Use renewable feedstocks: Use starting materials (also known as feedstocks) that are
renewable rather than depletable. The source of renewable feedstocks is often agricultural products or the
wastes of other processes; the source of depletable feedstocks is often fossil fuels (petroleum, natural gas, or
coal) or mining operations.
8. Avoid chemical derivatives: Avoid using blocking or protecting groups or any temporary
modifications if possible. Derivatives use additional reagents and generate waste.

7. 12 Principles
9. Use catalysts, not stoichiometric reagents: Minimize waste by using catalytic
reactions. Catalysts are effective in small amounts and can carry out a single reaction many times. They are
preferable to stoichiometric reagents, which are used in excess and carry out a reaction only once.
10. Design chemicals and products to degrade after use: Design chemical
products to break down to innocuous substances after use so that they do not accumulate in the environment.
11. Analyze in real time to prevent pollution: Include in-process, real-time monitoring and
control during syntheses to minimize or eliminate the formation of byproducts.
12. Minimize the potential for accidents: Design chemicals and their physical forms (solid,
liquid, or gas) to minimize the potential for chemical accidents including explosions, fires, and releases to the
environment.

8. Image credit: Google Images

9. Green chemistry focuses on greener and safer
chemicals while the current majority systems
focus on the toxicity and hazards on chemicals.

10. EPA Safer choice program
EPA’s Safer Choice is a voluntary program
that works to advance the mission of EPA
to protect human health and the
environment by helping product
manufacturers choose the safest chemical
ingredients possible.

11. List chemicals in EPA Safer Choice

12. EPA Safer choice ingredients criteria
Each chemical ingredient in a formulation has a function in making a
product work - whether it is to aid in cleaning by reducing surface
tension (surfactants), dissolve or suspend materials (solvents), or
reduce water hardness (chelating agents). Within these "functional
classes," many ingredients share similar toxicological and
environmental fate characteristics. As a result, Safer Choice focuses its
review of formulation ingredients on the key (environmental and
human health) characteristics of concern within a functional class.
This approach allows formulators to use those ingredients with the
lowest hazard in their functional class, while still formulating high-
performing products.

13. EPA Safer choice ingredients - master criteria
https://www.epa.gov/sites/production/files/2013-
12/documents/dfe_master_criteria_safer_ingredi
ents_v2_1.pdf

14. EPA Safer choice ingredients - master criteria
https://www.epa.gov/sites/production/files/2013-12/documents/dfe_master_criteria_safer_ingredients_v2_1.pdf
Toxicity data:
1. Acute Mammalian Toxicity
2. Carcinogenicity
3. Genetic Toxicity
4. Neurotoxicity
5. Repeated Dose Toxicity
6. Reproductive and Developmental Toxicity
7. Respiratory Sensitization
8. Skin Sensitization
9. Environmental Toxicity and Fate (ET&F)
10. Eutrophication
Ref sources:
• GHS
• EU Dangerous Substances Directive
• EPA’s New Chemicals Program
• National toxicology program (NTP)
• International Agency for research
on cancer (IARC)
• EU CMR list
• NIOSH carcinogen list
• … more

15. EPA Safer choice ingredients - master criteria
• H300: Fatal if swallowed
• H301: Toxic if swallowed
• H302: Harmful if swallowed
• H310: Fatal in contact with skin
• H311: Toxic in contact with skin
• H312: Harmful in contact with skin
• H317: May cause an allergic skin
reaction
• H330: Fatal if inhaled
• H331: Toxic if inhaled
• H332: Harmful if inhaled
• H334: May cause allergy or asthma
symptoms or breathing difficulties if
inhaled
• H350: May cause cancer
• H350i: May cause cancer by inhalation
• H351: Suspected of causing cancer
• H340: May cause genetic defects
• H341: Suspected of causing genetic
defects
• H360: May damage fertility or the unborn
child
• H361: Suspected of damaging fertility or
the unborn child
• H362: May cause harm to breast-fed
children
• H372: Causes damage to organs
• H373: May cause damage to organs
• H400:Very toxic to aquatic life
• H401:Toxic to aquatic life
• H410:Very toxic to aquatic life with long
lasting effects
• H411:Toxic to aquatic life with long
lasting effects
A chemical DOSE NOT pass the criteria if it carry one of the following GHS class

16. GHS review
GHS
H200: Physical hazards
H300: Health hazards
H400: Environmental hazards
https://pubchem.ncbi.nlm.nih.gov/ghs/

17. Green chemistry related chemicals - EPA
https://www.epa.gov/saferchoice/safer-ingredients
953 chemicals
within 16
functional use
classes

18. Green chemistry – EPA Safer Choice

19. Green chemistry related chemicals
Greener Alternative Product:
Adheres to one or more of The
12 Principles of Green Chemistry
704 chemicals
with 10 product
categories

20. Green chemistry related chemicals - ECHA
General concern was raised with regard to “green chemistry” …..
Kerton describes three categories of solvents: (Kerton, 2009)
Preferred
Useable
Undesirable

21. Green chemistry related chemicals

22. EPA ECHA Sigma GHS
1-butanol Preferred G H226;H302;H315;H318;H335;H336
acetone Yellow Preferred H225;H319;H336
ethyl acetate Half Preferred H225;H319;H336
acetic acid Green Usable H226;H314
heptane GREY* Usable G H225;H304;H315;H336;H410
Methylenechloride GREY* Undesireable H315;H319;H336;H351
methanol GREY* Preferred H225;H301;H311;H331;H370 **
isopropanol Green Preferred H225;H319;H336
Phosphoric acid Yellow G H314;H332
Green chemistry – Challenges: examples

23. Greener chemical chemistry – Challenges
• Criteria differ from one system to another
• Use/function class/category
• Toxicity – experimental vs modeled
• Standard sources: GHS, EU, EPA, NIOSH
• … more

24. Open data – green chemistry information in PubChem

25. Browse EPA safer choice ingredient data …

26. EPA Safer Choice chemical list

27. Using UN GHS classification to create greener compounds

28. Using UN GHS classification to create greener compounds
Compounds carry these 3 pictograms
are NOT green
Compounds not qualified for GHS

29. Using UN GHS classification to create greener compounds
Greener alternative equations:
Greener compounds = [ Not Classified ]
Less Green = [ whole set – ( ) – Not Classified ]
Not Green = [ ]

30. Using UN GHS classification to create greener compounds
Compounds carry these 3 pictograms
are NOT green
Compounds not qualified for GHS

31. Using UN GHS classification to create greener compounds
Greener alternative equations:
Greener compounds = [ Not Classified ] -> 1429
Less Green = [ whole set – ( ) – Not Classified ] -> 84246
Not Green = [ ] -> 34259

32. Submit data to PubChem

33. Summary
• Green Chemistry aims to bring safer and eco-friendly process and
products.
• GHS classification tree can be used to create green and less green
chemical alternatives.
• PubChem provides an open data platform to integrate green
chemistry related information.
• OPEN QUESTION: is it possible to build a harmonized system to
create green or greener alternatives ?

34. Thanks you ... This research was supported by the Intramural Research
Program of the NIH, National Library of Medicine.
Evan Bolton
Asta Gindulyte
Ben Shoemaker
Paul Thiessen
Siqian He
Bo Yu
Jie Chen
Tiejun Cheng
Jane He
Sunghwan Kim
Leon Li
Leonid Zaslavsky