Green Chemistrys Role in Resilience

Paul T. Anastas, Ph.D., ACS Green Chemistry Institute Julie Zimmerman, Ph.D., U.S. EPA U. Virginia

Designing Resilient, Sustainable Systems Environ. Sci. Technol., 37 (23), 5330 -5339, 2003.
Joseph Fiksel*

Traditional systems engineering practices try to anticipate and resist disruptions but may be vulnerable to unforeseen factors. An alternative is to design systems with inherent "resilience" by taking advantage of fundamental properties such as diversity, efficiency, adaptability, and cohesion.

Fundamental Properties
The complexity that results from systemsystem interactions outstrips our best highend computing capabilities and perhaps our human abilities of comprehension. Is there a reasonable approach that involves the design of fundamental properties of matter and energy that can play a role in resilience? Can this help to design for resilience?

Focus on Design
The moment a chemist puts pencil to paper, he/she is making choices about the human health and environmental impacts

Definition
GREEN CHEMISTRY: The design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances.

Principles of Green Chemistry

1. It is better to prevent waste that to treat or clean up waste after it is formed. 2. Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product. 3. Wherever practicable, synthetic methodologies should be designed to use and generate substances that possess little or no toxicity to human health and the environment. 4. Chemical products should be designed to preserve efficacy of function while reducing toxicity. 5. The use of auxiliary substances (e.g. solvents, separation agents, etc.) Should be made unnecessary wherever possible and, innocuous when used. 6. Energy requirements should be recognized for their environmental and economic impacts and should be minimized. Synthetic methods should be conducted at ambient temperature and pressure. 7. A raw material of feedstock should be renewable rather than depleting wherever technically and economically practicable. 8. Reduce derivatives - Unnecessary derivatization (blocking group, protection/ deprotection, temporary modification) should be avoided whenever possible. 9. Catalytic reagents (as selective as possible) are superior to stoichiometric reagents. 10. Chemical products should be designed so that at the end of their function they do not persist in the environment and break down into innocuous degradation products. 11. Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances. 12. Substances and the form of a substance used in a chemical process should be chosen to minimize potential for chemical accidents, including releases, explosions, and fires.

Twelve PrinciplesIsnt that how it is done now?

Entire industries are geared toward cleaning up after wasteful chemical syntheses. Todays scientific literature is filled with synthetic pathways that are inefficient by design. Reagents are seldom selected with regard to hazard. Industrial chemicals do not have minimal hazard as a performance criterion Persistence of chemicals in the biosphere and in our bodies is a major global health issue. (CDC 200 chemicals since 1945) The vast majority of organic chemicals are made by depleting (non-renewable) feedstocks Our chemical industry deals with safety through engineering and security through barricades.

Molecular Formulas: Function and Toxicity

Molecular formula (C3H6O) Methyl vinyl Acetone ether 9.0 g/kg 4.9 g/kg (oral(oralrat) rat) Allyl alcohol 0.06 g/kg (oralrat)

Name Toxicity LD-50

Molecular Formulas: Function and Toxicity

H2N lemon orange O CO2H NH2 HS CO2H NH2 anti-arthritis toxic sweet bitter

O N N O O sedativum teratogenic H O

O OH

N H

contraceptive b-blocker

Driver - State of the Science

Increased understanding on the molecular basis of hazard. Physical hazards, global hazards, and toxicological. Moving from descriptive toxicology to to mechanistic toxicology. Treating hazard as simply another physical/chemical property.

The Change in Thinking

Green Chemistry moves our consideration of how to deal with environmental problems from the circumstantial to the intrinsic. Hazard must be recognized as a design flaw

Circumstantial vs. Intrinsic

Circumstantial Intrinsic
Use Exposure Handling Treatment Protection Recycling Costly Molecular design for reduced toxicity Reduced ability to manifest hazard Inherent safety from accidents or terrorism Increased potential profitability

Risk
Risk = Hazard x Exposure
Green chemistry focuses primarily on reducing risk by reducing intrinsic hazard.

What is toxicology?
The traditional definition of toxicology is "the science of poisons." As our understanding of how various agents can cause harm to humans and other organisms, a more descriptive definition of toxicology is "the study of the adverse effects of chemicals or physical agents on living organisms".

Reversible or irreversible
Reversible effects are not permanent and can be changed or remedied.
Skin rash, nausea, eye irritation, dizziness, etc. Injury to the liver - can regenerate.

Irreversible effects are permanent and cannot be changed once they have occurred.
Injury to the nervous system is usually irreversible since its cells cannot divide and be replaced. Irreversible effects include birth defects, mutations, and cancer.

Dose-Response curve

 Knowledge of the shape and slope of the dose-response curve is extremely important in predicting the toxicity of a substance at specific dose levels. Major differences among toxicants may exist not only in the point at which the threshold is reached but also in the percent of population responding per unit change in dose (i.e., the slope). As illustrated above, Toxicant A has a higher threshold but a steeper slope than Toxicant B.

Toxicity and Dosage

The dosage is an important factor in determining if a substance will be an acute or a chronic toxicant. Virtually all chemicals can be acute toxicants if sufficiently large doses are administered. Often the toxic mechanisms and target organs are different for acute and chronic toxicity. Examples are:

Toxicity and Timing

Exposure to anti-androgen, Flutamide
Percentage of offspring affected
100 75 50 25 Abnormal seminal vessicles 16
Courtesy of Courtesy of J. Peterson Myers J. Peterson Myers

Males with areolae Hypospadias

Small prostate

Abnormal bladder

Day of exposure after conception

Foster and Harris 2005

17

18

19

Toxicity and Chemical Mixtures

The presence of other chemicals may decrease toxicity (antagonism), add to toxicity (additivity), or increase toxicity (synergism or potentiation) of some xenobiotics. For example:
alcohol may enhance the effect of many antihistamines and sedatives antidotes function by antagonizing the toxicity of a poison (atropine counteracts poisoning by organophosphate insecticides or nerve agents)

Interactions
Humans are normally exposed to several chemicals at one time. Examples are: hospital patients on the average receive 6 drugs daily home influenza treatment consists of aspirin, antihistamines, and cough syrup drinking water may contain small amounts of pesticides, heavy metals, solvents, and other organic chemicals air often contains mixtures of hundreds of chemicals such as automobile exhaust and cigarette smoke gasoline vapor at service stations is a mixture of 40-50 chemicals

Thoughts
What is the nature of synergism?

Thoughts
How does Persistence change the doseresponse relationship?

Thoughts
How to design around harmless chemicals activating genes in certain sub-populations?

Thoughts
How does one design resilience into a systems to understand and anticipate the intersection of mechanisms of action?

Thoughts
Susceptibility of system to penetration (GI tract curare, molecular chaperones, groundwater mobilization of metals, etc.)

Thoughts
Reliance of one system on another oxidations combustion atmospheric oceanic pH fisheries social structure

Thoughts
What effects will magnify with interactions with other systems?
Snail darters and PCBs

Thoughts
How do perturbations propagate?
bioaccumulation, endocrine disruption

Thoughts
What is the relationship between embedded or transformation energy and toxicity?