United States Government Accountability Office

Center for Science, Technology, and Engineering

Natural Resources and Environment

Report to Congressional Requesters

TECHNOLOGYASSESSMENT

Chemical Innovation

Technologies to Make Processes and Products 

More Sustainable

February 2018

GAO-18-307
The cover image displays a word cloud generated from the transcript of the meeting we convened with 24 experts in 

the field of sustainable chemistry. The size of the words in the cloud corresponds to the frequency with which each 

word appeared in the transcript. In most cases, similar words—such as singular and plural versions of the same word—

were combined into a single term. Words that were unrelated to the topic of sustainable chemistry were removed. The 

images around the periphery are stylized representations of chemical molecules that seek to illustrate a new 

conceptual framework, whereby molecules can be transformed to provide better performance; however, they are not 

intended to represent specific chemical compounds.
United States Government Accountability Office

Highlights of GAO-18-307, a report to 

congressional requesters

February 2018

TECHNOLOGY ASSESSMENT

Chemical Innovation

Technologies to Make Processes and 

Products More Sustainable

What GAO found

Stakeholders lack agreement on how to define sustainable chemistry and how to 

measure or assess the sustainability of chemical processes and products; these 

differences hinder the development and adoption of more sustainable chemistry 

technologies. However, based on a review of the literature and stakeholder 

interviews, GAO identified several common themes underlying what sustainable 

chemistry strives to achieve, including:

• improve the efficiency with which natural resources—including energy, 

water, and materials—are used to meet human needs for chemical 

products while avoiding environmental harm;

• reduce or eliminate the use or generation of hazardous substances in the 

design, manufacture, and use of chemical products;

• protect and benefit the economy, people, and the environment using 

innovative chemical tranformations; 

• consider all life cycle stages including manufacture, use, and disposal (see 

figure) when evaluating the environmental impact of a product; and

• minimize the use of non-renewable resources.

Life cycle of chemical processes and products 

View GAO-18-307. For more information, 

contact Timothy M. Persons at (202) 512-

6412, personst@gao.gov or John Neumann 

at (202) 512-3841, neumannj@gao.gov.

Why GAO did this study

Chemistry contributes to virtually every 

aspect of modern life and the chemical 

industry supports more than 25 percent 

of the gross domestic product of the 

United States. While these are positive 

contributions, chemical production can 

have negative health and environmental 

consequences. Mitigating these 

potential consequences requires 

thoughtful design and evaluation of the 

life cycle effects of chemical processes 

and products. 

GAO was asked to conduct a technology 

assessment to explore, among other 

things, the opportunities, challenges, 

and federal roles in sustainable 

chemistry. This report discusses (1) how 

stakeholders define and assess 

sustainable chemistry; (2) available or 

developing technologies to make 

chemical processes and products more 

sustainable; and (3) how the federal 

government, industry and others 

contribute to the development and use 

of such technologies. 

GAO selected for assessment three 

technology categories—catalysts, 

solvents, and continuous processing; 

interviewed stakeholders from various 

fields, such as government, industry, 

and academia; convened a meeting of 

experts on sustainable chemistry 

technologies and approaches; and 

surveyed a non-generalizable sample of 

chemical companies. GAO is not making 

recommendations in this report, but is 

identifying strategic implications.
United States Government Accountability Office

GAO identified three categories of more sustainable chemistry technologies—

catalysts, solvents, and continuous processing—that demonstrate both progress 

and potential. 

• Catalysts reduce the energy input required for a chemical process and allow 

for more efficient use of materials. Stakeholders suggested future research 

be directed at developing less toxic or renewable catalysts, including those 

that are metal-free or those from earth-abundant metals such as iron. 

• Solvents are used in many chemical processes but can create waste issues 

and be toxic. Alternatives include solvents from renewable, non-petroleum 

raw materials and solvents such as water that are less hazardous to human 

health and the environment, among other qualities. 

• An alternative to traditional batch processing is continuous processing, in 

which materials react as they flow along a system of channels, pipes, or 

tubes. Compared to batch processing, continuous processing uses materials

more efficiently, generates less waste, and has a smaller physical footprint.

The federal government and other stakeholders play several roles, sometimes in 

collaboration, to advance the development and use of more sustainable chemistry 

technologies. The federal government has supported research, provided technical 

assistance, and offered certification programs, while stakeholders have integrated 

sustainable chemistry principles into educational programs and addressed 

chemicals of concern in consumer products. While switching to more sustainable 

options entails challenges, this field has the potential to inspire new products and 

processes, create jobs, and enhance benefits to human health and the environment. 

Stakeholders identified strategic implications of sustainable chemistry and offered a 

range of potential options to address challenges and realize the full potential of 

these technologies, including the following:

• Breakthrough technologies in sustainable chemistry could transform how 

the industry thinks about performance, function, and synthesis. Sustainable 

chemistry creates opportunities to use a different conceptual framework 

that allows industry to create molecules with better performance. 

• The establishment of an organized constituency, with the involvement of 

both industry and government, could help make sustainable chemistry a 

priority. An industry consortium, working in partnership with a key 

supporter at the federal level, could lead to an effective national initiative 

or strategy.

• A national initiative that considers sustainable chemistry in a systematic 

manner could be useful. Such an effort could encourage collaborations 

among industry, academia and the government, similar to other national 

technology Initiatives.

• There are opportunities for the federal government to address industrywide challenges. Federal attention that facilitates development of standard 

tools for assessment and a robust definition could help clarify relevant 

participants in the field and improve information available for decisionmakers at all levels. 

According to stakeholders, transitioning toward the use of more sustainable 

chemistry technologies will require national leadership and industry, government,

and other stakeholders to work together. 
This is a work of the U.S. government and is not subject to copyright protection in the United States. The published 

product may be reproduced and distributed in its entirety without further permission from GAO. However, because this 

work may contain copyrighted images or other material, permission from the copyright holder may be necessary if you 

wish to reproduce this material separately.
Technology Assessment GAO-18-307 i

Table of Contents

Introduction ........................................................................................................................ 1

1 Background ...................................................................................................................... 4

1.1 Sustainability and the chemical industry...........................................................................4

1.2 Federal government agencies and other stakeholders.....................................................9

1.3 Legal framework ..............................................................................................................11

1.4 Supply, demand, and economics.....................................................................................12

1.5 The sustainability of catalysts..........................................................................................14

1.6 The sustainability of solvents ..........................................................................................16

1.7 The sustainability of batch processing ............................................................................19

2 Stakeholders vary in how they define and assess the sustainability of chemical 

processes and products.................................................................................................... 20

2.1 Stakeholder definitions of sustainable chemistry vary ...................................................20

2.2 Stakeholders vary in the approaches they use for assessing the sustainability of 

chemical processes and products.................................................................................21

2.3 Companies vary in which environmental and health factors they consider most 

important to optimize ..................................................................................................29

2.4 Stakeholders cite the importance of a standard definition and metrics for 

sustainability.................................................................................................................35

3 Technologies to make catalysts more sustainable ........................................................ 37

3.1 Earth-abundant metal catalysts.......................................................................................38

3.2 Organocatalysts...............................................................................................................41

3.3 Biocatalysts......................................................................................................................43

4 Technologies to make solvent use more sustainable.................................................... 49

4.1 Key properties of solvents...............................................................................................50

4.2 Sustainability challenges of solvents...............................................................................51

4.3 More sustainable solvent technologies...........................................................................54

5 Technologies as more sustainable alternatives to batch processing ............................ 70

5.1 Continuous processing ....................................................................................................71

5.2 Continuous flow microreactors for pharmaceuticals and fine chemicals.......................73

5.3 Disadvantages of and barriers to continuous manufacturing.........................................81
Technology Assessment GAO-18-307 ii

6 Roles of the federal government and other stakeholders in supporting the 

development and use of more sustainable chemical processes and products................ 83

6.1 Federal programs support research on the impacts of chemicals on human and 

environmental health...................................................................................................83

6.2 Federal agencies support the development and commercialization of more sustainable 

chemistry technologies ................................................................................................90

6.3 Federal programs aid market growth for products made with sustainable chemicals and 

processes......................................................................................................................99

6.4 Other stakeholders including the chemical manufacturing industry, academic 

institutions, states, and companies also support more sustainable chemistry .........105

7 Strategic Implications................................................................................................... 114

8 Agency and expert comments..................................................................................... 118

Appendix I: Objectives, scope, and methodology .......................................................... 119

Appendix II: Expert participation .................................................................................... 124

Appendix III: Industry participation ................................................................................ 126

Appendix IV: Survey of chemical companies’ sustainable chemistry activities ............. 127

Appendix V: The 12 Principles of Green Chemistry........................................................ 144

Appendix VI: Roles of selected federal programs and offices in supporting the 

development and use of more sustainable chemistry processes and products............ 146

Appendix VII: GAO contacts and staff acknowledgments.............................................. 149
Technology Assessment GAO-18-307 iii

Abbreviations

ACS American Chemical Society

AMO Advanced Manufacturing Office

ARS Agricultural Research Service

BEES Building for Environmental and Economic Sustainability

CSS Chemical Safety for Sustainability

DOD Department of Defense

DOE Department of Energy

DTSC Department of Toxic Substances Control

E factor environmental factor

EPA Environmental Protection Agency 

ESTCP Environmental Security Technology Certification Program

FDA Food and Drug Administration

GCI Green Chemistry Institute

GC3 Green Chemistry and Commerce Council

HHS Department of Health and Human Services

LCA life cycle assessment

NASA National Aeronautics and Space Administration

NGO nongovernmental organization

NIEHS National Institute of Environmental Health Sciences

NIFA National Institute of Food and Agriculture

NIH National Institutes of Health

NIST National Institute of Standards and Technology

NREL National Renewable Energy Laboratory

NRMRL National Risk Management Research Laboratory

NSF National Science Foundation

NTP National Toxicology Program

PGM platinum group metals

PMI process mass intensity

PNNL Pacific Northwest National Laboratory

R&D research and development

RAPID Rapid Advancement in Process Intensification Deployment

SERDP Strategic Environmental Research and Development Program
Technology Assessment GAO-18-307 iv

SBIR Small Business and Innovation Research

SNAP Significant New Alternatives Policy

STAR Science to Achieve Results

STTR Small Business Technology Transfer

SusChEM Sustainable Chemistry, Engineering, and Materials

ToxCast Toxicity Forecaster

Tox21 Toxicology in the 21st Century

TSCA Toxic Substances Control Act

USDA U.S. Department of Agriculture

VOC volatile organic compound
Technology Assessment GAO-18-307 1

441 G St. N.W.

Washington, DC 20548

Letter

February 8, 2018 

The Honorable Christopher Coons

Ranking Member

Subcommittee on Financial Services and General Government 

Committee on Appropriations

United States Senate

The Honorable Susan M. Collins

United States Senate

The Honorable Edward J. Markey

United States Senate

Chemistry contributes to virtually every aspect of modern life, from the production of food and 

clean drinking water to medicines, cleaners, personal care products, and a host of other 

products. According to one recent report, the chemical industry supports more than 25 percent 

of the gross domestic product of the United States and, in 2016, accounted for $174 billion (14 

percent) of U.S. goods exported.1 In addition, the Bureau of Labor Statistics reports that the 

chemical industry employed more than 821,000 people in October 2017 and the Department of 

Commerce estimates that the sector generates an additional 2.7 million indirect jobs via 

industry suppliers.2

Despite these positive contributions to quality of life and other social and economic goals, 

chemical production can result in negative health and environmental consequences. Mitigating 

these potential consequences requires thoughtful design and evaluation of the life cycle effects 

of chemical processes and products —that is, a thorough assessment of effects resulting from 

stages of the life cycle such as sourcing the raw materials, processing raw materials into 

products, handling and disposal of byproducts and industrial waste, product use, and end-of-life 

disposal or recycling. In addition, the United States faces a number of environmental challenges,

including water scarcity, reliance on nonrenewable resources including scarce metals and fossil 

fuels, and difficulty obtaining adequate information on chemical toxicity and exposure levels. 

Many in the chemical industry are working to address these issues through improving the 

environmental sustainability of their own chemical processes and providing more sustainable 

products and technologies to others.

 

1

American Chemistry Council, 2017 Elements of the Business of Chemistry (Washington, D.C.: 2017).

2

International Trade Administration, Department of Commerce, Chemical Spotlight: The Chemical Industry in the United States, 

accessed October 5, 2017, https://www.selectusa.gov/chemical-industry-united-states.
Technology Assessment GAO-18-307 2

In view of the potential benefits and nascent nature of the field of sustainable chemistry, you 

asked us to conduct a technology assessment to explore, among other things, the opportunities, 

challenges, and federal roles in this field. In response to that request, this report discusses (1) 

how stakeholders define sustainable chemistry and assess the sustainability of chemical 

processes and products; (2) technologies that are available or in development to make chemical 

processes and products more sustainable; and (3) how the federal government, industry, and 

others contribute to the development and use of such technologies.

To address these objectives, we reviewed key reports and scientific literature to establish 

background, identify appropriate technologies and their advantages and disadvantages, identify 

stakeholders, and inform survey questions. We also interviewed approximately 80 stakeholders 

including federal and state officials, chemical companies, industry and professional 

organizations, nongovernmental organizations (NGO), academics and educational institutions, 

and others; conducted site visits to federal laboratories; and attended two technical 

conferences.

In addition, we collaborated with the National Academies to convene a two-day meeting of 24 

experts on sustainable chemistry technologies and approaches. We selected participants from 

the chemical industry, academia, federal agencies including a national laboratory, professional

organizations, and others with expertise covering most significant areas of our review.3 During 

this meeting, we moderated discussion sessions on several topics, including examples of 

technologies to make chemical processes and products more sustainable; applications in 

industry; economic and business aspects of developing and implementing the technologies; 

approaches to assessing the sustainability of chemical processes and products; the role of 

standards, regulations, and related programs; and additional stakeholder perspectives. We 

continued to draw on the expertise of these individuals throughout our study and, consistent 

with our quality assurance framework, we provided them with a draft of our report and solicited 

their feedback, which we incorporated as appropriate.

We also surveyed a non-generalizable sample of 27 chemical companies to gather data on four 

primary topics: (1) approaches these companies use to assess the sustainability of their chemical 

processes and products; (2) the extent and perceived value of their interactions with other 

stakeholders, including federal agencies, customers, suppliers, academics, and NGOs; (3) 

challenges or gaps in stakeholder interactions; and (4) challenges or barriers to the development 

and use of more sustainable chemistry technologies.

We limited the scope of our review to selected technologies in three main categories: catalysts, 

solvent use, and alternatives to batch processing (i.e., continuous processing and continuous 

 3

After the expert meeting we changed one of our three target industry sectors from textiles/apparel to formulators (i.e., makers of 

personal care and cleaning products). We did not have a formulator represented at the meeting; however, we interviewed and

surveyed representatives from several formulator companies during the course of our study.
Technology Assessment GAO-18-307 3

flow microreactors). We did not assess all available or developing technologies in these three 

categories, nor did we assess technologies in other phases of the chemical product life cycle. For 

example, we did not assess technologies for recycling industrial waste into new feedstocks or for 

post-consumer recycling of chemical products. See appendix I for additional details on our scope 

and methodology, appendix II for a list of the experts who participated in our expert meeting, 

appendix III for a list of the chemical companies we interviewed and surveyed, and appendix IV 

for the questions in the survey instrument and the quantitative results (i.e., response counts) 

from the survey.

We conducted our work from October 2015 to February 2018 in accordance with all sections of 

GAO’s Quality Assurance Framework that are relevant to technology assessments. The 

framework requires that we plan and perform the engagement to obtain sufficient and 

appropriate evidence to meet our stated objectives and to discuss any limitations to our work. 

We believe that the information and data obtained, and the analysis conducted, provide a 

reasonable basis for the findings and conclusions in this product.
Technology Assessment GAO-18-307 4

1 Background

1.1 Sustainability and the chemical 

industry

The chemical industry relies on the use of 

natural resources as inputs to make chemical 

products, and the industry’s outputs, in turn, 

can have an impact on the environment.4 The 

International Trade Administration of the 

Department of Commerce identifies the 

chemical industry as one of the largest 

manufacturing industries in the United States, 

with more than 10,000 firms producing more 

than 70,000 products.5 It is comprised of 

several industry subsectors including 

formulators (makers of cleaning and personal 

care products), chemical manufacturers 

(makers of basic and specialty chemicals), and 

pharmaceutical companies.

6 Since the 

beginning of the 20th century, the chemical 

industry has depended on fossil fuels as both 

an energy source and a primary feedstock for 

manufacturing chemicals. The chemical 

industry is the second largest user of energy 

among manufacturing sectors, and more than 

 4

For purposes of this report, the term ‘chemical product’ 

includes a wide variety of products manufactured by chemical 

companies, including single chemicals (e.g., methanol, 

ammonia) and other products made with chemicals or mixtures 

of chemicals (e.g., pharmaceuticals, cleaning products, 

cosmetics).

5

International Trade Association, U.S. Department of 

Commerce, Chemical Spotlight: The Chemical Industry in the 

United States, accessed October 5, 2017, 

https://www.selectusa.gov/chemical-industry-united-states.

6

Cleaning and personal care products include soaps, 

detergents, cleaners, toiletries, and cosmetics. Basic chemicals 

include organic and inorganic chemicals, plastic resins, dyes, 

and pigments. Specialty chemicals include adhesives and 

sealants, water treatment chemicals, plastic additives, 

catalysts, and coatings. Pharmaceuticals include diagnostics, 

prescription drugs, vaccines, vitamins, and over-the-counter 

drugs for human and veterinary applications. 

98 percent of organic, or carbon-based, 

chemicals are derived from petroleum or 

natural gas (i.e., petrochemicals). Inorganic 

chemicals do not contain carbon as a principal 

element and the chemical industry generally 

derives these from metals and non-metallic 

minerals, some of which face supply 

limitations. The growth of the chemical 

industry in the 20th century also resulted in 

the production of large quantities of waste, 

including hazardous waste. 

Chemicals, including basic and specialty 

chemicals and pharmaceuticals, are 

manufactured through chemical synthesis—a 

process involving one or more chemical 

reactions.7 Chemical reactions generally 

follow a common pattern that chemists 

describe using a chemical equation as shown 

in figure 1.

Figure 1: A standard chemical equation

Although not shown in the figure, additional reactants may also 

be included above or below the arrow.

The left side of the equation shows one or 

more reactants—chemical substances that 

enter into and are chemically changed by the 

reaction. The arrow represents the reaction 

itself; additional information is often provided 

 7

Formulators generally make their cleaning and personal care 

products by mixing chemicals together rather than through 

chemical reactions. 
Technology Assessment GAO-18-307 5

above and below the arrow to describe 

reaction conditions—other factors that allow 

the reaction to occur optimally—which can 

include components that are not chemically 

changed during the reaction, such as 

catalysts, solvents, or other conditions such as 

a specific temperature or pressure. The right 

side of the equation shows one or more 

products—chemical substances that result 

from the reaction. In some cases, the goal is 

to produce only certain of these products; the 

others are often called ‘byproducts’ and may 

be commercially useful or considered waste.

Within the chemical industry, the product of 

one company may be the raw material for 

another. For example, bulk chemicals—a kind 

of basic chemical—are the building blocks for 

many chemical products. Other companies or 

industries can purchase bulk chemicals and 

incorporate them into other chemical 

products (e.g., chemical intermediates, 

pharmaceuticals) or manufactured products 

(e.g., textiles, automobiles), or use them in 

processing (e.g., pulp and paper, oil refining). 

For example, one chemical company may 

produce adipic acid, a bulk chemical used in 

the manufacture of one kind of nylon. 

Another chemical company may then buy the 

adipic acid as a raw material to produce nylon 

fiber, selling that product to textile companies 

that then incorporate it into other products 

such as apparel. In some cases, multiple steps 

may be required to produce a chemical 

intermediate or other product from a bulk 

chemical. Specialty chemicals, including fine 

chemicals, are often more technologically 

advanced and manufactured in lower 

volumes than basic chemicals. Specialty 

chemicals are used for a specific purpose and 

can also be incorporated into a range of other 

products. 

The term ‘sustainability’ can have many 

interpretations depending on the context in 

which it is used. The 1987 Brundtland report 

stated that sustainable development ‘meets 

the needs of the present without 

compromising the ability of future 

generations to meet their own needs.’8

Sustainability may refer to economic, 

environmental, or social sustainability. 

Achieving all three—a concept known as the 

‘triple bottom line’—has become a goal of 

some businesses, including many in the 

chemical industry. Sustainable development is 

relevant to the chemical industry as it 

concerns both the responsible use of natural 

resources—using natural resources at rates 

such that supplies remain available over the 

long term—as well as the minimization of 

pollution. Several organizations have 

attempted to define sustainability as it applies 

to chemicals and the chemical industry (see 

table 1). 

 8

World Commission on Environment and Development, Our 

Common Future, (Oxford University Press, 1987).
Technology Assessment GAO-18-307 6

Table 1: Example definitions of sustainable (or green) chemistry

Organization Definition 

Organisation for Economic 

Co-operation and 

Development

Sustainable chemistry is a scientific concept that seeks to improve the efficiency 

with which natural resources are used to meet human needs for chemical products 

and services. Sustainable chemistry encompasses the design, manufacture and use 

of efficient, effective, safe and more environmentally benign chemical products and 

processes, accessed January 4, 2018 (http://www.oecd.org/chemicalsafety/riskmanagement/sustainablechemistry.htm).

U.S. Environmental 

Protection Agency

Green chemistry is the design of chemical products and processes that reduce or 

eliminate the use or generation of hazardous substances. Green chemistry applies 

across the life cycle of a chemical product, including its design, manufacture, use, 

and ultimate disposal. Green chemistry is also known as sustainable chemistry, 

accessed June 19, 2017 (https://www.epa.gov/greenchemistry/basics-greenchemistry).

American Chemical Society Sustainable and green chemistry [is] a different way of thinking about how 

chemistry and chemical engineering can be done. Over the years different 

principles have been proposed that can be used when thinking about the design, 

development and implementation of chemical products and processes. These 

principles enable scientists and engineers to protect and benefit the economy, 

people and the planet by finding creative and innovative ways to reduce waste, 

conserve energy, and discover replacements for hazardous substances. [T]he scope 

of these green chemistry and engineering principles go beyond concerns over 

hazards from chemical toxicity and include energy conservation, waste reduction, 

and life cycle considerations such as the use of more sustainable or renewable 

feedstocks and designing for end of life or the final disposition of the product,

accessed January 4, 2018

(https://www.acs.org/content/acs/en/greenchemistry/what-is-greenchemistry/definition.html).

Source: GAO analysis of agency and other stakeholder documents. | GAO-18-307

As noted in table 1, green chemistry is 

another term that some associate with 

sustainability efforts in the chemical industry. 

Green chemistry reduces or eliminates the 

use or generation of hazardous substances in 

the design, manufacture, and application of 

chemical products using the 12 Principles of 

Green Chemistry (the 12 Principles).9 See

appendix V for the full list of the 12 Principles. 

According to the definitions of both the U.S. 

Environmental Protection Agency (EPA) and 

the American Chemical Society (ACS) shown 

in the table, the concepts of green chemistry 

 9

Paul T. Anastas and John C. Warner, Green Chemistry: Theory 

and Practice (New York: Oxford University Press, 1998). 

and sustainable chemistry are synonymous. 

Green chemistry is rooted in the Pollution 

Prevention Act of 1990, which marked a shift 

in regulatory policy from pollution control to 

pollution prevention.10 Staff in EPA’s Office of 

Pollution Prevention and Toxics first used the 

term green chemistry in the early 1990s. The 

Green Chemistry Institute (GCI)—an 

independent nonprofit organization 

dedicated to advancing green chemistry—was 

founded in 1997 and eventually became part 

of the ACS. 

 10Public Law 101-508 (Nov. 5, 1990).
Technology Assessment GAO-18-307 7

Life cycle assessment (LCA) is one tool for 

evaluating the relative sustainability of a 

process or product. While reducing or 

eliminating the use of hazardous substances 

(i.e., doing ‘green chemistry’) may offer one 

viable path for improving sustainability in the 

chemical industry, following these principles 

alone does not guarantee improved 

sustainability from a life cycle perspective. 

LCA is a method for systematically evaluating 

the environmental impact of a product 

through all the stages of its life cycle.11 As 

shown in figure 2, life cycle stages for 

chemical processes and products can include 

raw materials extraction and processing, 

 11The Coca Cola Company together with the Midwest Research 

Institute developed the original concept of analyzing a product 

life cycle in the 1960’s while trying to quantify the energy, 

material, and environmental impacts of different beverage 

containers. In the 1990’s, the Society of Environmental 

Toxicology and Chemistry coined the term LCA and coordinated 

the harmonization of terminology and methodology. The 

14040 series of the International Organization for 

Standardization contains standards and technical reports for 

LCA.

chemical processing, product use, and postconsumer or industrial disposal or recycling.12

By attempting to improve one stage of the life 

cycle without considering the others, 

chemists run the risk of moving sustainability 

problems around rather than solving them. 

Analyzing the full life cycle of a process or 

product can reveal benefits as well as 

tradeoffs or unintended consequences of 

different choices along the way. Practitioners 

use LCA to compare the environmental 

performance of processes and products under 

different conditions. 

 12Although sustainable chemistry technologies exist in each 

stage of the life cycle, we were not able to cover all life cycle 

stages in this report. 
Technology Assessment GAO-18-307 8

Figure 2: Life cycle of chemical processes and products

Transportation and distribution of materials and products, represented by the green arrows between stages, can also be considered 

a life cycle stage.

LCA practitioners can tailor the parameters of 

the assessment to meet their needs; 

however, the use of this assessment in the 

chemical industry still faces challenges. 

Generally, LCA practitioners select system 

boundaries depending on the goals of the 

assessment. Example boundaries are ‘cradleto-grave’—covering the entire supply chain 

from raw materials extraction to disposal, 

‘cradle-to-gate’—covering raw materials 

extractions and processing, and ‘gate-togate’—covering manufacturing or processing 

only. A number of quantifiable environmental 

indicators can contribute to the assessment 

including energy use, global warming, ozone 

depletion, human and environmental toxicity, 

and waste. The practitioner can also vary the 

relative importance of these indicators based 

on the needs of the assessment. The results 

of an LCA can depend on the amount and 

quality of data available as well as what the 

practitioner chooses to include. Therefore, 

different assessments of the same product or 

process can yield different results. A lack of 

data can be a challenge for the application of 

LCA to the manufacture of some chemical

products. Additionally, there is not a coherent 

framework for characterizing the toxicological 
Technology Assessment GAO-18-307 9

impacts of chemicals. LCA can also be costly. 

As a tool, LCA can be more useful for products 

or processes that are at a high technology 

readiness level or already commercially 

available than those earlier in development, 

for which simpler metrics may be more 

appropriate.

1.2 Federal government agencies and 

other stakeholders 

The federal government and other 

stakeholders play a number of roles, 

sometimes in collaboration, to advance the 

development and use of more sustainable 

chemical processes and products. Federal 

programs support research on the impacts of 

chemicals on human and environmental 

health. Federal programs also support the 

development of more sustainable chemical 

processes and their commercialization. 

Additionally, federal programs aid the 

expansion of markets for products 

manufactured with more sustainable 

chemicals and processes. Other stakeholders 

play similar roles and some additional roles 

that contribute to the development and use 

of more sustainable chemical processes and 

products.

Federal programs conduct and fund basic 

research on the characteristics and biological 

effects of chemicals that underpins the 

development and use of more sustainable 

chemistry products and processes. Decision 

makers must have a scientific understanding 

of the potential harmful impacts of exposure 

to chemicals for multiple reasons. For 

example, federal regulators need information 

to effectively minimize the harmful effects of 

chemicals through regulations and other 

means and to assess the regulated 

community’s compliance with them. Industry 

needs this information to make informed 

decisions about the selection, design, and use 

of more sustainable chemicals in their 

products and processes, including their 

impact on workers. 

Federal programs also seek to support the 

development of new, more sustainable 

chemistry processes and facilitate the 

commercialization of these processes. The 

federal government conducts and funds both 

basic and applied research in the 

development of more sustainable processes. 

In addition, federal programs seek to facilitate 

the transition of new technologies from the 

research and development phase to 

commercialization, a transition that can be 

expensive and challenging for researchers as 

well as small and medium companies, 

according to experts. To support the 

transition to commercialization, federal 

programs provide loan guarantees, grants, 

and technical assistance to researchers and 

companies and recognize innovative 

technologies through an award program, 

among other activities. 

Federal programs also aid market growth for 

products made with sustainable chemicals 

and processes by informing consumers about 

these products and by facilitating their 

purchase by federal offices. While growing 

numbers of consumers are seeking out 

“greener” or more sustainably manufactured 

products, it can be challenging for consumers 

to identify such products or verify company 

claims about their products. Companies 

seeking to manufacture more sustainable 

products strive to ensure that their products 

are differentiated from less sustainable 

products in order to reach these consumers. 

Federal sustainability certifications and 

evaluations are publically available to connect 
Technology Assessment GAO-18-307 10

interested consumers and purchasers with 

more sustainable products. Additionally, the 

Federal Acquisitions Regulation and Executive 

Order 13693—Planning for Federal 

Sustainability in the Next Decade—requires 

that federal agencies purchase selected 

products manufactured with more 

sustainable chemicals, creating a market for 

those products.13

Various agency programs play a role in the 

development and use of more sustainable 

chemistry processes and products. Some 

federal agencies have programs with goals 

that support the development and use of 

more sustainable chemistry and others have 

programs that do so consistent with broader 

goals. As part of its mission to protect human 

health and the environment, EPA has 

programs that conduct and fund research to 

evaluate the impacts of chemicals on human 

health and the environment. Additional 

programs support the development of 

products and processes that are more 

sustainable by awarding innovators of 

sustainable chemistry technologies and by 

evaluating and certifying those products and 

making the results available publically. 

Similarly, the Department of Health and 

Human Services (HHS) conducts and funds 

research on the impacts of chemicals as part 

of its mission to enhance and protect the 

health and well-being of Americans. The 

National Science Foundation’s (NSF) mission 

includes promoting the progress of science 

and advancing the national health, prosperity, 

and welfare. In terms of sustainable 

chemistry, NSF carries out this mission by 

funding research on the impacts of chemicals 

 13See Exec. Order No. 13963, Planning for Federal 

Sustainability in the Next Decade, 80 Fed. Reg. 15871 (March 

25, 2015); 48 CFR 1.102.

on human and environmental health and on 

developing sustainable chemistry 

technologies. Part of the U.S. Department of 

Agriculture’s (USDA) mission is to provide 

leadership on agriculture and rural 

development in order to provide economic 

opportunity, help rural America, and promote 

agriculture production. As part of that 

mission, USDA programs support the 

development and use of technologies that 

can convert agricultural and forestry biomass 

into fuels and other products such as 

chemicals, and thereby create markets for 

agricultural products. The biobased chemicals 

produced using these renewable resources 

rather than traditional non-renewable 

sources such as fossil fuels, may be more 

sustainable. A number of programs at the 

Department of Energy (DOE), which works to 

ensure America’s security and prosperity by 

addressing its energy, environmental, and 

nuclear challenges through science and 

technology, seek to reduce the energy used in 

manufacturing, including energy used by 

chemical technologies. The Department of 

Commerce’s National Institute of Standards 

and Technology (NIST) advances 

measurement science, standards, and 

technology, including those needed to 

measure sustainability. As part of its mission, 

the Department of Defense (DOD) protects 

readiness, people, and the environment by: 

(1) identifying and researching risks 

associated with chemicals; (2) developing, 

evaluating, and demonstrating sustainable 

solutions to meet DOD’s environmental and 

performance challenges, including more 

sustainable chemical products and processes;

and (3) ensuring DOD meets the requirements 

of applicable federal green procurement 

preference programs. 
Technology Assessment GAO-18-307 11

Other stakeholders, such as industry, 

companies and retailers, states, academic 

institutions, and NGOs also seek to influence 

the development and use of more sustainable 

chemistry processes and products through 

activities such as supporting workforce 

development and developing tools and 

resources for industry. These organizations 

may work collaboratively to share expertise 

and resources or to identify areas of common 

interest in order to promote mutual goals 

related to sustainable chemistry. By focusing 

on a wide range of approaches to supporting 

sustainable chemistry, from transforming 

education to developing industry-specific 

standards, together these groups may 

facilitate the transition of the chemical 

industry to a new, more sustainable 

framework for chemical technologies. 

1.3 Legal framework 

Consistent with the goals of sustainable 

chemistry that include making chemicals in a 

purposefully more environmentally benign 

way, several federal requirements and 

directives address chemical and other risks to 

public health and the environment. For 

example, EPA’s ability to effectively 

implement its mission of protecting public 

health and the environment is critically 

dependent on credible and timely 

assessments of the risks posed by chemicals. 

Such assessments are the cornerstone of 

scientifically sound environmental decisions, 

policies, and regulations under a variety of 

statutes, such as the Toxic Substances Control 

Act (TSCA),14 which provides EPA with 

 1415 U.S.C. § 2601 et. seq. After many years of congressional 

committees considering legislation aimed at reforming TSCA, in 

June 2016, Congress passed and the President signed the Frank 

R. Lautenberg Chemical Safety for the 21st Century Act, which 

authority to obtain information on chemicals 

and to regulate those that it determines pose 

unreasonable risks; the Safe Drinking Water 

Act (SDWA),

15 which authorizes EPA to 

regulate contaminants in public drinking 

water systems; the Clean Air Act,

16 which 

regulates air pollution from stationary and 

mobile sources; and the Clean Water Act, 

which aims to restore and maintain the 

chemical, physical and biological integrity of 

the nation’s waters.17 The Food and Drug 

Administration (FDA) oversees the safety of 

food, drugs and medical devices, and 

cosmetics under the Federal Food, Drug and 

Cosmetic Act.18 The Department of Defense, 

the General Services Administration, and the 

National Aeronautics and Space 

Administration jointly issue the Federal 

Acquisition Regulation19 for use by executive 

agencies for acquiring goods and services, and 

Executive Order 13693 encourages federal 

agencies, among other things, to acquire 

Safer Choice labeled products (chemically 

intensive products that contain safer 

ingredients).20

 gave EPA greater authority to improve its processes for 

assessing and controlling toxic chemicals. Pub. L. No. 114-182, 

130 Stat. 448.

1542 U.S.C. § 300f et. seq. 

1642 U.S.C. § 7401 et. seq. 

17The Federal Water Pollution Control Act Amendments of 

1972, Pub. L. No. 92-500, § 2, 86 Stat. 816, codified as 

amended at 33 U.S.C. §§ 1251-1387 (2013) (commonly referred 

to as the Clean Water Act). See 

https://www.gao.gov/products/GAO-14-80.

1821 U.S.C. § 301 et. seq.

19Title 48, Code of Federal Regulations.

20Exec. Order No. 13963, Planning for Federal Sustainability in 

the Next Decade, 80 Fed. Reg. 15871 (March 25, 2015), 

https://www.gpo.gov/fdsys/pkg/FR-2015-03-25/pdf/2015-

07016.pdf.
Technology Assessment GAO-18-307 12

1.4 Supply, demand, and economics

Various economic factors influence the 

development of sustainable products. 

Stakeholders described how interactions 

between the demand for and supply of 

sustainable products can influence the extent 

and pace of growth. For example, the supply 

of any product is strongly influenced by the 

costs of production, as well as costs of getting 

that product to market. Whether that cost is 

worth the undertaking depends on what 

consumers are willing to pay for the product 

and the overall consumer demand. 

Consumer demand can be influenced by a 

range of factors such as changes in mindset, 

an increased willingness to pay, and price 

sensitivity. Consumers are increasingly 

seeking products that help them reduce their 

own environmental footprint and the 

footprint of their supply chain. Hence, 

chemical companies are innovating to 

develop products made with safer chemicals 

and are also increasing the use of recycled, 

biobased, and renewable materials. When 

consumers are willing to pay a premium for 

such products, increasing demand, firms are 

incentivized to start producing more of them 

in order to preserve their market share, 

maintain their reputation, or even increase 

profits. According to a 2015 online survey of 

30,000 consumers in 60 countries by Nielsen, 

66 percent of consumers say they are willing 

to pay more for sustainable brands—up from 

55 percent in 2014 and 50 percent in 2013.21

Similarly, some large retailers such as 

Walmart and Target are also experiencing 

 21The Nielsen Company, The Sustainability Imperative, New 

Insights on Consumer Expectations, Global Sustainability Report

(October 2015), 2.

increased demand for more sustainable 

products. Target’s sales in natural and organic 

products are growing at a rate of about 15 to 

20 percent per year. This growth resulted in 

Target launching “Made to Matter” in 2014, 

an initiative showcasing a selection of the 

company’s “handpicked natural, organic, and 

sustainable” products. Walmart created a 

“Sustainability Leaders” website for 

consumers that rates suppliers on 

environmental and social criteria. 

The supply of such products can be influenced 

by the costs of production, competitive 

advantage and reputational effects. For 

example, if some technology or process offers 

a clear benefit to a firm in terms of lower 

costs of production, with no effect on quality, 

firms will have a natural incentive to adopt it. 

Similarly, if a more sustainable product or use 

of technology helps a firm differentiate from 

another firm and creates a competitive 

advantage that consumers recognize and 

value, it will encourage firms to create more 

sustainable products. The creation of more 

sustainable products may have a good 

reputational effect for a firm in the minds of 

consumers, which may even extend to other 

products made by that firm, regardless of 

whether those products are also more 

sustainable. As a result, consumers may start 

regarding the products of these firms to have 

a greater quality or additional benefits and 

show a willingness to pay a premium for 

them. According to a Nielsen study, 

commitment to social and environmental 

responsibility is becoming more important 

than other traditional influences on consumer 

loyalty and brand performance.22 Firms may 

also invest in sustainable chemistry to align 

 22Nielsen, The Sustainability Imperative, 3.
Technology Assessment GAO-18-307 13

with internal goals of corporate social 

responsibility.

There are a number of inherent challenges in 

the market for sustainable products in the 

industry, such as the upfront costs in the face 

of uncertain demand. For any new industry, 

the substantial upfront costs in the face of 

uncertainty and risk associated with 

consumer demand would be a substantial 

barrier or challenge. If the benefits are 

obvious, firms may be able to increase prices 

to consumers to recoup these costs without 

harming demand; however, if the benefits are 

not easily understood and measureable (e.g., 

long-term health benefits), or are external to 

consumers (e.g., broad environmental 

impacts), then consumers may not be willing 

to pay higher prices. Thus, the upfront costs 

required to create new products or use new 

technology can be a big challenge, especially 

when faced with uncertain demand.

In addition to market incentives that 

encourage firms to produce more sustainable 

products, government can offer subsidies, tax 

credits, and other incentives. For example, an 

Organisation for Economic Co-operation and 

Development report on sustainable chemistry 

patent data identifies positive and negative 

tools that aim to stimulate sustainable 

chemistry.23 Positive tools include such things 

as incentives for the adoption of green 

chemistry products, training, and award 

programs, while negative tools include such 

things as limits, bans, and taxes that 

discourage use of chemicals of concern. A 

report on the economic benefits of green 

 23Organisation for Economic Co-operation and Development, 

Environment Directorate, Sustainable Chemistry: Evidence on 

Innovation from Patent Data, No. 25 (Paris, France: Feb. 2011), 

43-45.

chemistry published by the University of 

Massachusetts found that appropriately 

designed regulations support innovation, 

productivity, and employment despite the 

frequent argument that imposing new 

standards on the chemical industry will 

damage competitiveness and cost the U.S. 

economy jobs.24 They argue that just as the 

federal government has supported innovative 

developments in agriculture, biotechnology, 

computers, and the Internet, similar support 

is needed to build a green chemical industry. 

The report also makes a case for 

dissemination of environmental and healthrelated information to help guide the choices 

of consumers, workers, downstream users, 

and investors. For new markets and 

investments to be realized, sufficient 

information is needed on the environmental 

damage and health hazards associated with 

chemicals and the possibilities that exist to 

develop alternatives that overcome these 

challenges.

Improving resource performance is also key 

to industry growth, according to a McKinsey 

report on the circular economy.25 A linear 

model of production and consumption in 

which goods are manufactured from raw 

materials, sold, used, and then discarded or 

incinerated as waste is reaching its limits, 

according to the report. In the face of ongoing 

resource depletion, McKinsey makes the case 

for a substantial improvement in resource 

 24James Heintz and Robert Pollin, Political Economy Research 

Institute, University of Massachusetts, Amherst. Blue Green 

Alliance, The Economic Benefits of a Green Chemical Industry in 

the United States, (2011), 6-7.

25A circular economy is an industrial model that decouples 

revenues from material input. World Economic Forum, 

Towards the Circular Economy: Accelerating the Scale-Up 

Across Global Supply Chains,” Ellen MacArthur Foundation and 

McKinsey & Company, (Geneva, Switzerland, 2014), 13.
Technology Assessment GAO-18-307 14

performance, urging firms to explore ways to 

reuse products or their components. 

Strategies to co-produce other products to 

make the main product more economically 

viable are also worth considering, according 

to the report, and may be another way to 

become more cost-competitive. 

1.5 The sustainability of catalysts

A catalyst is a substance that increases the 

rate of a chemical reaction without being 

substantially consumed in the process. Many 

chemical reactions require energy input 

(known as the activation energy) to get the 

reaction started by ‘pushing’ the reactants 

over an initial energy barrier. A catalyst 

increases reaction rates by providing the 

reactants with an alternative reaction 

pathway that has lower activation energy 

than the uncatalyzed reaction thereby 

reducing the energy input required for a 

process (see fig. 3). This is one of the main 

sustainability advantages provided by 

catalysts. 

Figure 3: Examples of catalyzed and uncatalyzed reaction energy paths

The activation energy for a catalyzed reaction is lower than the activation energy for an uncatalyzed reaction. Lower

activation energy results in a faster reaction.

In addition to reducing the energy input 

required for a process, catalysts allow for 

more efficient use of materials, thus reducing 

waste. For example, most catalysts can be 

recovered after the reaction and used again.26

 26A 2013 study by Bravo-Suárez and colleagues reported that, 

among all the catalytic processes used in the industry, 
Technology Assessment GAO-18-307 15

In addition, catalysts are generally only 

required in small quantities. They also help to 

minimize waste by creating a more targeted 

and selective reaction pathway that forms 

fewer byproducts. This property, called 

selectivity, is among the most important 

sustainability feature of catalysts.

One scientific paper reported that catalysts 

are a necessary and critical tool for achieving 

social and economic objectives as described 

in the 12 Principles, such as the economical 

use of materials, use of simple and safe 

processes, avoidance of toxic chemicals, and 

reducing or avoiding waste formation.27 (See 

app. V for a full list of the 12 Principles.) 

Today, catalysts play a critical role in 

promoting the feasibility, sustainability, and 

economics of over 90 percent of chemical 

processes.28 Specifically in the pharmaceutical 

industry, advances in catalysis have enabled 

the synthesis of highly complex active 

pharmaceutical ingredients (i.e., drugs) in 

fewer steps, with increased efficiency in 

material use, and often with high product 

 heterogeneous catalysts (where the catalyst and the reactants 

are in different phases; e.g., solid catalyst and gaseous 

reactants) were the most widely used and constituted 80 

percent of the market share. Homogeneous catalysts (where 

the catalyst and reactants are in the same phase) constituted 

17 percent of the market share, with enzymatic catalysts 

making up the remaining 3 percent. J. J. Bravo-Suárez, R. V. 

Chaudhari, and B. Subramaniam, Design of Heterogeneous 

Catalysts for Fuels and Chemicals Processing: An Overview (ACS 

Symposium Series, American Chemical Society: (Washington, 

D.C., 2013). According to one of our experts, heterogeneous 

catalysts are recyclable while homogeneous catalysts generally 

are not.

27G. Centi and S. Perathoner, “Catalysis and Sustainable 

(Green) Chemistry,” Catalysis Today, vol. 77 (2003). 

28F. Cavani, G. Centi, S. Perathoner, and F. Trifirò, Sustainable 

Industrial Chemistry: Principles Tools and Industrial Examples, 

Wiley-VCH (2009) 1-72.

yields.29 Without catalysts, many of the items 

we use each day such as medicines, fine 

chemicals, polymers, fibers, fuels, paints, 

lubricants, much of the food we eat, and a 

myriad of other products could not be 

produced in sufficient quantities to meet 

demand. For all of these reasons, catalysts

improve the sustainability of chemical 

processes. 

Despite their many benefits, the use of 

catalysts also raises sustainability concerns. In 

particular, most catalysts in use today are 

platinum group metals (PGM), which are 

scarce, nonrenewable, and potentially toxic.

Platinum group metals (PGM): PGMs are a 

group of six very similar chemical elements: 

platinum, palladium, ruthenium, rhodium, 

iridium, and osmium. Their leading role as 

catalysts stems from their unique 

characteristics and distinct advantages over 

other options, including chemical stability, 

selectivity, and predictable and well 

understood reaction mechanisms. PGMs are 

also resistant to the loss of catalytic activity 

known as catalytic poisoning.30 They have 

higher melting points than base metals—

more earth-abundant metals such as lead or 

copper— so they are very stable at high 

temperatures. As a result, they can retain 

their catalytic activity for a longer period than 

other materials when exposed to harsh 

conditions such as automotive exhaust. PGMs 

 29An active pharmaceutical ingredient is any component that is 

intended to provide pharmacological activity or other direct 

effect in the diagnosis, cure, mitigation, treatment, or 

prevention of disease. In this report, we refer to active 

pharmaceutical ingredients as “drugs.”

30Catalytic poisoning results from the capture of chemicals 

(often impurities) on sites that would otherwise be available 

for catalysis. Over time this results in the loss of catalytic 

activity.
Technology Assessment GAO-18-307 16

are also recyclable, which means they can be 

re-used many times, thus minimizing their 

impact on the environment. 

Despite their prevalence as catalysts, the 

scientific community has raised sustainability 

concerns about the continued use of PGMs by 

industry. For example, PGMs are scarce, 

generally nonrenewable, and susceptible to 

supply and price fluctuations. Their presence 

in the earth’s crust is orders of magnitude 

lower than that of earth-abundant metals. 

PGMs were included in the European Union’s 

Report on Critical Raw Materials because, by 

the year 2020, they are expected to have 

insufficient supply to meet demand. 

Furthermore, the limited availability of PGMs 

is exacerbated by the growing demand for 

these materials in other applications, such as 

newer organic light emitting diode displays in 

smart phones and televisions, and renewable 

energy systems, such as fuel cells, wind 

energy, and photovoltaics. Additionally, 

PGMs—mainly platinum and palladium—have 

proven to be indispensable in the automotive 

industry for catalytic converters, which has 

driven recent demand.31 Automotive 

emissions regulations in the United States and 

Europe and the burgeoning auto markets in 

China and India are expected to further strain 

the supply of these metals in the coming 

years. 

In addition, exposure to PGMs may be 

harmful to human health and the 

environment. As pollutants, PGMs are 

generally airborne particles; they are a health 

risk due to their small size and ability to react 

with many compounds in our body to form 

 31A catalytic converter is a device incorporated in the exhaust 

system of a motor vehicle, with a catalyst for converting 

pollutant gases into harmless products.

more toxic compounds. Wiseman et al. 

reported that exposure to PGMs can lead to 

oxidative stress, pulmonary inflammation, 

and increased risk of pneumonia and other 

respiratory diseases.32 There is also some 

evidence that PGMs can cause autoimmune 

diseases. The risks are especially high for 

children and the elderly. Bioaccumulation of 

these metals in the food chain is another 

concern even when the environmental levels 

are not high. 

For all of these reasons, the scientific 

community is actively researching options for 

the replacement of PGMs in catalysis. 

Potential alternative catalysts include earthabundant metals (iron, manganese, nickel, 

and cobalt) and metal-free catalysts such as 

organocatalysts and biocatalysts.33

We discuss sustainable alternatives to PGMs 

in chapter 3.

1.6 The sustainability of solvents

Rethinking solvent use in a number of 

different applications is another approach to 

increase sustainability in the chemical 

industry. A solvent is a substance capable of 

dissolving other substances in order to form a 

homogenous mixture, known as a solution 

 32C. L. S. Wiseman and F. Zereini, “Airborne Particulate Matter, 

Platinum Group Elements and Human Health: A Review of 

Recent Evidence,” Science of the Total Environment, vol. 407 

(2009). The authors of this paper did an assessment of the risk 

related to environmental exposures to PGMs, particularly in 

airborne particulate matter and highlighted the need to 

monitor environmental levels of PGMs and continue research 

on their associated toxicity to better assess their potential to 

elicit health effects in humans.

33Organocatalysts are organic (non-metallic, carbon-based) 

compounds that can serve as catalysts. Biocatalysts are 

enzymes (proteins originating from living cells) that are used in 

chemical processes to perform reactions.
Technology Assessment GAO-18-307 17

(see fig. 4).34 The chemical industry uses 

solvents for several different purposes, 

including (a) as media for chemical reactions, 

(b) in the separation and purification of 

chemicals, and (c) for cleaning the equipment 

used in chemical processes. Solvents may also 

be included as a primary component or 

ingredient in formulated products such as 

paints, inks, or cleaning and personal care 

products. These uses can be interrelated; for 

example, the choice of reaction medium can 

facilitate the separation and purification of 

products.

Figure 4: Substances dissolve in a solvent to form 

a homogenous mixture known as a solution

Given the variety and nature of their 

applications, solvents are used by a variety of 

industries and constitute a large portion of 

the total volume of chemicals used in 

industrial chemical processes. Benchmarking 

studies of the pharmaceutical industry by the 

 34A solution can be gaseous, solid, or liquid. 

ACS GCI Pharmaceutical Roundtable in 2007 

and 2008 showed that organic solvents 

constitute more than half of the materials by 

mass that are used to manufacture an active 

pharmaceutical ingredient. According to one 

analysis of papers published in 2010 in the 

journal Green Chemistry, much of the 

research on more sustainable solvents has 

focused on reaction media for chemical 

synthesis.35 However, this is not the only 

solvent use for which alternatives could be 

used. In the pharmaceutical industry, for 

example, the purification of chemicals can be 

the largest contributor to solvent waste.

Reducing overall solvent use, therefore, can 

impact the environmental performance, cost, 

and safety and health issues associated with a

process. Additionally, many industries use

solvents, including industries not related to 

chemical synthesis. For example, in addition 

to the chemical industry several other 

industries use solvents for cleaning 

equipment and other items, including the 

automotive, electronics, textiles, and paper

industries. 

Many conventional solvents are considered 

hazardous to both the environment and 

human health. Many conventional solvents 

are volatile organic compounds (VOC)—

organic compounds whose composition 

allows them to evaporate at normal 

temperatures and pressures.36 A low boiling 

 35P. G. Jessop, “Searching for green solvents,” Green 

Chemistry, vol. 13 (2011).

36There are multiple definitions of VOCs. EPA regulations 

define VOCs as any compound of carbon, with a few exclusions 

including carbon dioxide, which participates in atmospheric 

photochemical reactions, except those designated by EPA as 

having negligible photochemical activity (40 C.F.R. § 51.100). 

However, the more general definition used in this report aligns 

with the scientific literature and is also used by EPA in certain 

contexts.
Technology Assessment GAO-18-307 18

point is advantageous because it facilitates 

removal of the solvent when it is no longer 

needed; however, this solvent property is

associated with environmental health and 

safety concerns such as flammability and 

worker exposure. In addition, conventional 

solvents are often toxic to both humans and 

the ecosystem and can be air pollutants. For 

the above reasons among others, both 

legislation and voluntary control measures 

regarding solvents have been introduced.

There is not a single universal green or 

sustainable solvent; chemical processes or 

other solvent applications will have different 

specifications, and require alternative solvent 

options that still meet performance 

characteristics. Solvents can serve multiple 

purposes when used as reaction media for 

chemical processes. For example, the solvent 

can improve contact between the reactants.

Depending on its properties, a solvent can 

affect the outcome or increase the speed of a 

reaction. For example, a particular reaction 

may result in different products depending on 

the choice of solvent. It can also stabilize the 

transition state of the reactiona higher

energy species temporarily formed by 

reactants before forming the final 

productthus increasing the speed of the 

reaction. Solvents can also aid in heat 

transfer. For reactions that generate heat, for 

example, a solvent can absorb excess heat 

thereby preventing runaway, or 

uncontrollable, reactions. 

Solvents can be a primary component or 

ingredient in formulated products, and a 2015 

perspective article from the ACS GCI 

Formulator’s Roundtable highlighted the need 

for more sustainable solvent alternatives in 

formulations.37 Solvents serve a number of 

purposes in formulated products including 

dissolving raw materials or essential oils to 

form the product; or dissolving unwanted 

materials, for example grease or ink, for 

cleaning. The authors of the perspective 

article stated that suitable alternatives must 

continue to meet key performance 

characteristics for these products, including 

cleaning benefits such as grease removal, 

stabilizing the formulation by keeping other 

ingredients in solution, and modifying

particular physical properties in the final 

formulation. They also stated that alternative

solvents should:38

• be sourced from renewable, nonpetroleum feedstocks;

• undergo a life cycle assessment that

includes the impact of solvent 

manufacture in addition to solvent use;

• show no reproductive toxicity and have 

low toxicity, in general, to humans;

• be non-sensitizing and non-irritating; and

• have minimal odor or color.

We discuss more sustainable solvent use in 

chapter 4.

 37P. G. Jessop, F. Ahmadpour, M. A. Buczynski, T. J. Burns, N. B. 

Green II, R. Korwin, D. Long, S. K. Massad, J. B. Manley, N. 

Omidbakhsh, R. Pearl, S. Pereira, R. A. Predale, P. G. Sliva, H. 

VanderBilt, S. Weller, and M. H. Wolf, “Opportunities for 

Greener Alternatives in Chemical Formulations,” Green 

Chemistry, vol. 17 (2015).

38The authors also mentioned that alternative solvents should 

meet the EPA Design for the Environment criteria for 

acceptable formulation ingredients. The Safer Choice Label 

replaced the Design for the Environment label in 2015. For 

more on the EPA Safer Choice program see chapter 6. 
Technology Assessment GAO-18-307 19

1.7 The sustainability of batch 

processing 

Historically, industrial chemicals have been 

produced mainly using an approach known as 

batch processing. Batch processing is a 

discontinuous process. That is, finite 

quantities of raw materials (the reactants) 

and any other necessary components such as 

catalysts or solvents are combined in a closed 

vessel or vat—also called a batch reactor—

under appropriate conditions of temperature 

and pressure. The reaction takes place as the 

contents of the vessel are stirred and allowed 

to react together. When the reaction has 

proceeded as far as desired, the resulting 

mixture is transferred to the next vat or 

reactor for the next stage of processing, the 

first vat is cleaned, and the process is 

repeated with the next batch. Batch 

processing is typically suitable for higher 

value, small-scale production, and when a 

range of different products such as pigments, 

dyes, and polymers are all produced using the 

same equipment. It is also well suited for 

reactions with long reaction times. Batch 

processing is currently used in the chemical, 

pharmaceutical, and food process industries.

Batch processing can occur at small scales—

for example, a chemical synthesis could be 

done in a test tube or a flask—but in most of 

the chemical industry, it is typically a largescale approach. Therefore, batch reactors 

typically have a large physical footprint (i.e., 

require significant space). Batch processing 

raises other sustainability concerns as well. 

For example, cleaning the vats between 

batches can use significant amounts of 

cleaning solvents and energy. Researchers 

have reported that the large-scale operations 

often associated with batch processing may 

also pose a safety risk under some 

circumstances, such as when high pressures 

are required to complete a reaction or when a 

hazardous intermediate is produced during 

the course of a reaction.39 Other 

considerations include potentially long wait 

times while a batch is processing and high 

capital expenses. 

Continuous processing (also known as 

continuous flow) is an alternative that allows 

chemical reactions to occur as the reaction 

mixture is pumped through a continuous 

processing line composed of pipes or tubes 

where reactions take place continuously. 

Reactants can be introduced and byproducts 

removed at appropriate points along the line; 

finished product materials are continuously 

removed at the end of the line. 

Microreactors are a specific technology that 

allows continuous processing to be conducted 

in relatively small volumes.40 Continuous 

processing microreactors have enabled new 

paradigms in sustainable chemistry such as 

alternative reaction pathways, less hazardous 

and energy-efficient syntheses, and lowsolvent or solvent-free reactions, among 

others.

See chapter 5 for our discussion on the 

sustainability of continuous processing and 

microreactors.

 39B. P. Mason, K. E. Price, J. L. Steinbacher, A. R. Bogdan, and 

D. T. McQuade, “Greener Approaches to Organic Synthesis 

Using Microreactor Technology,” Chemical Reviews, vol. 107, 

no. 6 (2007).

40A microreactor can be defined as a technology that couples 

the miniaturization of chemical reactors with continuous flow. 

This approach can provide optimal reaction conditions and 

eliminate typical scale-up problems. In this technology 

assessment we focus on applications of microreactors in the 

pharmaceutical industry. In addition to microreactors there are 

other types of reactors reported in the literature for more 

sustainable chemical processing and synthesis, including 

spinning disk reactors, cavitational reactors, and membrane 

bioreactors, among others. We have chosen to not include 

these additional reactor types in this technology assessment. 
Technology Assessment GAO-18-307 20

2 Stakeholders vary in how they define and assess the sustainability 

of chemical processes and products

Stakeholders define sustainable chemistry in 

a variety of ways. In addition, they use many 

different approaches for assessing the 

sustainability of chemical processes and 

products. For example, some chemical 

companies have designed their own in-house 

tools for assessing the sustainability of their 

own processes and products, while others use

common methods considered appropriate by

their industry sector. Stakeholders such as 

federal agencies, professional associations, 

and non-governmental organizations have 

developed a variety of third-party certification 

and measurement programs to assess the 

sustainability of products and companies. 

However, these programs vary in the criteria 

they use and the factors they consider 

important to assess, making comparisons 

between them difficult. Similarly, chemical 

companies that responded to our survey vary 

widely on the environmental and health 

factors they consider most important to 

include when assessing sustainability. 

Nonetheless, most responding companies 

agreed that a standardized set of such factors 

for assessing sustainability across their 

industry sector and across the entire chemical 

industry would be somewhat or very useful. 

2.1 Stakeholder definitions of 

sustainable chemistry vary

Stakeholders do not agree on a single 

definition of sustainable chemistry, but there 

are some common understandings of what 

this term means. In total, we asked 71 

representatives of stakeholder organizations 

how they or their organization define 

sustainable chemistry.41 The most common 

response we received, with 28 respondents 

agreeing, was that sustainable chemistry 

includes minimizing the use of non-renewable 

resources such as feedstocks. The second 

most common response (27) was that 

sustainable chemistry is similar, synonymous, 

or interchangeable with green chemistry. 

However, 17 stakeholders described 

sustainable chemistry as broader than green 

chemistry. Stakeholders mentioned various 

ways in which sustainable chemistry may go 

beyond green chemistry, for example by 

considering the entire life cycle of a process 

or product, or by incorporating economic 

considerations. 

Other concepts that stakeholders commonly 

associated with sustainable chemistry 

included:

• minimizing the negative impact of 

chemicals, products, or processes on the 

environment (24) as well as human health 

and safety (17);

• considering various factors in each phase 

of the life cycle, including potential 

tradeoffs (23);

• minimizing the use of toxic or hazardous 

chemicals (22) and increasing the use of 

environmentally benign chemicals in 

products and processes (7);

 41Stakeholders we interviewed included federal and state 

officials, chemical companies, industry and professional 

organizations, academics and educational institutions, NGOs, 

and others.
Technology Assessment GAO-18-307 21

• minimizing energy (22) and water use 

(14);

• conserving or using resources and 

materials efficiently (21);

• minimizing waste and pollution, 

particularly hazardous waste (20); 

• including economic considerations such 

as cost (12);

• minimizing the impact of product end of 

life, for example by increasing 

biodegradability or recyclability (9); and

• encouraging innovation and the creation 

of new processes (9).

For the purposes of this report, we refer to a 

chemical process, product, or technology as 

‘more sustainable’ compared to a 

conventional alternative if it better aligns with 

one or more of the goals above or with one or 

more of the 12 Principles.

2.2 Stakeholders vary in the 

approaches they use for assessing the 

sustainability of chemical processes 

and products

Stakeholders such as chemical companies, 

federal agencies, and others use many 

different approaches for assessing the 

sustainability of chemical processes and 

products. For example, some chemical 

companies have designed their own systems 

for assessing sustainability, while others use a 

common approach considered appropriate by 

their industry sector. While the varying 

approaches provide flexibility to meet the 

priorities of the user, the lack of a 

standardized approach makes it very difficult 

for customers, decision makers, and others to 

compare the sustainability of various 

products to make informed decisions. 

2.2.1 Company-designed approaches

Some companies and organizations design 

their own approaches for assessing chemical 

sustainability and use those approaches to 

make internal decisions on product design 

and processing. For example, the 

pharmaceutical and healthcare company 

GlaxoSmithKline has created the GSK Solvent 

Sustainability Guide, which combines multiple 

health, environment, safety, and waste 

categories to reach a single composite score 

and color assignment for each of the 154 

solvents included in the 2016 version of the 

guide.42

Dow Chemical uses an internally developed 

metric called the Dow Chemical Sustainability 

Footprint Tool that asks 23 questions across 

six dimensions: economic, social, greenhouse 

gas emissions, water use, nonrenewable 

resource requirement, and a company 

dimension.

43 Many of the questions involve 

comparisons of a project or new idea with an 

incumbent project (the base case) that 

delivers an equivalent service to the end user. 

For example, one question asks the end user 

to assess whether the toxicity profile of the 

new product “is expected to: [considerably 

improve / slightly improve / remain the 

 42For additional details, see C.M. Alder, J.D. Hayler, R.K. 

Henderson, A.M. Redman, L. Shukla, L.E. Shuster, and H.F. 

Sneddon, “Updating and Further Expanding GSK’s Solvent 

Sustainability Guide,” Green Chemistry, vol. 18, no. 13 (2016).

43For additional details, see D. A. M. Russell and D. L. Shiang, 

“Thinking about More Sustainable Products: Using an Efficient 

Tool for Sustainability Education, Innovation, and Project 

Management to Encourage Sustainability Thinking in a 

Multinational Corporation,” ACS Sustainable Chemistry & 

Engineering, vol. 1, no. 1 (2013).
Technology Assessment GAO-18-307 22

same / get worse] compared to the current 

product-service provided to the end user.” 

The questions allow Dow to rate each project 

on a 7-point scale for each of the six 

dimensions, where a higher number is a less 

desirable (i.e., less sustainable) result. Dow 

then combines the scores for each of the six 

dimensions into a diagram that visually 

presents the sustainability footprint for the 

project (see fig. 5). The goal is to achieve a 

smaller footprint inside the web, indicating 

improved sustainability. For an entirely new 

project that has no incumbent project for 

comparison, Dow assigns the base case score 

of 5.0 to encourage future sustainability 

improvements.

Figure 5: A hypothetical result for the Dow Chemical Sustainability Footprint Tool 

Dow can use this tool to assess an entirely 

new project or to compare a newly developed 

approach (represented in this hypothetical 

example by the colored polygon) to an 

existing approach (represented by the blue 

hexagonal line at the 5.0 mark).

2.2.2 Common approaches used to assess 

sustainability

Some stakeholders assess the sustainability of 

chemical processes and products using a 

common approach that others also accept as 

appropriate. These include metrics, chemical 

selection guides, and third-party 

certifications. 
Technology Assessment GAO-18-307 23

Metrics

Companies in the chemical industry use 

several established metrics to measure their 

efficiency in using materials to generate 

products; each metric accounts for one or 

more factors related to the efficiency of 

chemical processes. For example, the 

scientific literature reports a variety of 

metrics including atom economy, carbon 

efficiency, mass intensity, process mass 

efficiency, solvent intensity, and wastewater 

intensity, among others.44 Each of these 

metrics is calculated using a different set of 

underlying factors, such as the amount of 

waste produced, the yield of the desired 

product, solvent use, and water use. The 

variety of metrics used—and variation in the 

underlying factors included in their 

calculation—hinders the ability of companies 

and others to compare the sustainability of 

chemical processes or products. 

Although a full discussion of these metrics

and others is beyond the scope of this report, 

mass-based metrics—that is, metrics that 

assess a chemical process based on the total 

mass of materials used or the mass of waste 

produced—are common. According to 

scientific literature, the Environmental factor 

(E factor) and process mass intensity (PMI) 

are two examples of commonly used massbased metrics.

E factor: R.A. Sheldon published the first 

paper describing the E factor in 1992, based 

on discoveries about the enormity of the 

waste problem resulting from methods in use 

 44See F. Roschangar, R. A. Sheldon, and C.H. Senanayake, 

“Overcoming Barriers to Green Chemistry in the 

Pharmaceutical Industry – the Green Aspiration Level 

Concept,” Green Chemistry, vol. 17, no. 2 (2015).

at that time across different segments of the 

chemical industry.45 He and his coworkers 

conducted an inventory of the amounts of 

waste generated in the production of fine 

chemicals, pharmaceutical intermediates, and 

some bulk chemicals. They calculated the 

results using a new quantitative metric:

In the original 1992 paper, Sheldon defined 

waste as “everything but the desired 

product,” including solvent losses but 

excluding water. An ideal process would have 

an E factor of zero (no waste produced), and

higher E factors indicate more waste and thus 

(presumably) greater negative environmental 

impact. Sheldon’s inventory indicated that the 

production of bulk chemicals had E factors 

ranging from less than 1 to 5—that is, up to 5 

kg of waste produced per kg of product. 

E factors for fine chemicals were higher, 

ranging from 5 to 50, and for pharmaceuticals 

the E factors ranged from 25 to greater than 

100 kg of waste produced per kg of product. 

According to Sheldon, lower E factors 

correlate well with reduced manufacturing 

costs for drug ingredients, which reflects 

lower materials input and reduced hazardous 

waste disposal, among other factors. This 

provides an economic incentive for 

companies to reduce waste in their chemical 

processes. However, simply reducing the 

amount of waste, even to a significant degree 

compared to the original process, does not 

 45R. A. Sheldon, “Organic Synthesis – Past, Present, and 

Future,” Chemistry and Industry, vol. 23 (1992).
Technology Assessment GAO-18-307 24

indicate an optimized process.46 The process 

may still be inefficient and have unnecessarily 

adverse environmental impacts. Specifically, 

two issues with the use of E factors affect the 

interpretation of results. First, the final 

E factor depends on the boundaries used for 

the calculation. Sheldon’s original formula set 

gate-to-gate boundaries—that is, the starting 

point was the material entering the factory 

gate and the end was the product leaving it. 

However, in a later paper Sheldon noted that 

this gate-to-gate approach could lead to 

inconsistencies in the application of E factors, 

given that purchasing an intermediate rather 

than producing it in-house can allow a 

company to claim a dramatically lower 

E factor.47 He suggests that one possibility to 

avoid this inconsistency is to define the 

starting point as a commodity-type, 

commercially available raw material. As an 

example, he describes a process for the 

manufacture of the drug ingredient sildenafil 

citrate in which using the original formula 

(including an estimate of 10 percent of 

solvents going to waste and excluding water) 

gives an E factor of 6.4 kg waste per kg 

product for the production process. However, 

one of the primary raw materials does not 

meet the definition of a commodity-type 

chemical; including the intrinsic E factor 

resulting from the production of that raw 

material more than doubles the E factor to 

13.8 kg waste per kg product. A second issue 

is that the E factor does not differentiate 

between wastes that are relatively benign and 

 46F. Roschangar, R. A. Sheldon, and C.H. Senanayake, 

“Overcoming Barriers to Green Chemistry in the 

Pharmaceutical Industry – the Green Aspiration Level 

Concept,” Green Chemistry, vol. 17, no. 2 (2015).

47R.A. Sheldon, “The E Factor 25 Years On: The Rise of Green 

Chemistry and Sustainability,” Green Chemistry, vol. 19, no. 1 

(2017).

those that are highly toxic and 

environmentally persistent. Therefore, one 

process with a low E factor (based on 

producing a relatively small amount of highly 

toxic waste) may actually be much more 

environmentally harmful than another 

process with a higher E factor where the 

waste, although produced in larger quantities, 

is environmentally benign.

Process Mass Intensity (PMI): The ACS GCI 

Pharmaceutical Roundtable has identified 

PMI as the key mass-based metric for the 

pharmaceutical industry. In a 2011 

publication discussing the rationale for this 

selection, the authors noted the routine use 

of PMI to benchmark the greenness of 

processes and to drive greater efficiency and 

innovation in the pharmaceutical and fine 

chemical industries.48

PMI is a measure of the total mass of 

materials used per mass of product:

The calculation includes the mass of 

reactants, reagents, catalysts, and solvents, 

including water, used for the reaction or for 

purification. In an ideal situation, no waste is 

produced and all materials are incorporated 

into the product, resulting in PMI = 1. 

Benchmarking analyses conducted by the 

Pharmaceutical Roundtable in 2008 indicated 

that solvents make up the majority (56 

 48C. Jimenez-Gonzalez, C.S. Ponder, Q.B. Broxterman, and J.B. 

Manley, “Using the Right Green Yardstick: Why Process Mass 

Intensity Is Used in the Pharmaceutical Industry To Drive More 

Sustainable Processes,” Organic Process Research & 

Development, vol. 15, no. 4 (2011).
Technology Assessment GAO-18-307 25

percent) of the total mass of materials used 

to manufacture drug ingredients, with water 

(32 percent) making up much of the 

remaining mass.49 The Roundtable uses PMI 

to compare data from each company on an 

equivalent basis, starting from commonly 

available materials. This approach accounts 

for all steps in the synthesis of a drug 

ingredient regardless of whether a company 

performs all steps in-house or outsources 

some of them. 

Although PMI does not account for many 

possible factors that a full LCA would include, 

the Pharmaceutical Roundtable reported that 

PMI correlates well with the life cycle global 

warming potential and life cycle water use of 

a portfolio of pharmaceutical chemical 

processes, and thus can be a convenient 

surrogate for a more time-consuming and 

complicated LCA.50 Further, they report that 

PMI is a better surrogate for assessing 

cumulative environmental effects than the 

E factor.

Chemical selection guides

In addition to common metrics, some sectors 

have developed guides that companies and 

others can use to compare the sustainability 

of materials used in chemical processes. 

These include solvent selection guides and 

reagent guides.

 49Jimenez-Gonzalez, Ponder, Broxterman, and Manley, “Using 

the Right Green Yardstick,” 913.

50Jimenez-Gonzalez, Ponder, Broxterman, and Manley, “Using 

the Right Green Yardstick,” 915.

Solvent selection guides: Several 

pharmaceutical companies as well as industry 

consortia, including the Pharmaceutical 

Roundtable, have developed or made publicly 

available solvent selection guides to help 

chemists make informed solvent choices for 

use in chemical processes.51 These guides 

assess both conventional and newer solvents 

based on a variety of sustainability criteria, 

such as life cycle analysis; environmental, 

health, and safety impacts; recyclability; and 

regulatory concerns, among others. Several 

pharmaceutical companies have published 

multiple iterations of their guides, expanding 

and updating them as new data and solvents 

become available. Some guides rank solvents 

by preference, while others do not give an 

overall recommendation but rather provide 

users with additional information to consider 

in conjunction with relevant process 

specifications. Many of the published guides 

attempt to present the data in a simplified 

manner, for example, by color coding solvents 

from the most (green) to least (red) 

sustainable, while still providing access to 

more detailed assessments in recognition that 

simple systems may mask the complexity of 

solvent selection (see fig. 6).

 51More information about solvents, including access to their 

solvent selection guide, is available from the Pharmaceutical 

Roundtable at 

https://www.acs.org/content/acs/en/greenchemistry/research

-innovation/research-topics/solvents.html (accessed 

September 12, 2017).
Technology Assessment GAO-18-307 26

Figure 6: Excerpt from the ACS GCI Pharmaceutical Roundtable solvent selection guide

The creators of these guides have stated a 

variety of goals for their development in 

addition to improving process sustainability. 

One pharmaceutical company reported that 

one aim of their guide is to highlight the use 

of more sustainable solvents including those 

of limited availability, thereby incentivizing 

manufacturers to increase supply. The 

increasing regulation of certain potentially 

hazardous solvents has also encouraged the 

development of selection guides. For 

example, another objective of some guides is 

to reduce the use of chlorinated solvents, 

which pharmaceutical companies widely use 

early in the drug development process. These 

solvents pose environmental health and 

safety issues and face a growing legislative 

burden in some cases. One pharmaceutical 

company reported a 50 percent decrease in 

the use of chlorinated solvents after the 

introduction of a solvent selection guide.

Reagent guides: The Pharmaceutical 

Roundtable and pharmaceutical companies 

have also released reagent guides with a 

similar aim of helping scientists to make 

informed decisions regarding reagent 

sustainability.52 The Pharmaceutical 

Roundtable organizes their guides by selected 

chemical transformations (e.g., oxidation of 

an alcohol functional group) and has 

assembled them together in an interactive 

online tool.53 Users can select a 

transformation to read an overview of various 

known methods, a list of reagents from which 

to choose, and a Venn diagram comparing the 

reagents (see fig. 7). Although the 

Pharmaceutical Roundtable designed the 

guides to promote green chemistry, they also 

included reagents not considered ‘green’ with 

the aim of creating a more exhaustive 

reference. The Venn diagram provides a visual 

depiction of which reagents meet the three 

criteria of wide utility, scalability, and 

greenness of the various reagents. In the 

ethos of the guides, the Pharmaceutical 

Roundtable encourages scientists to use the 

guides a part of a holistic approach—to 

 52In this case, a reagent refers to a substance that is added to a 

mixture to cause a reaction, which we generally refer to as a 

reactant in this report.

53The reagent guides are available at 

https://www.reagentguides.com/ (accessed October 20, 2017). 

The guides are available for use following registration.
Technology Assessment GAO-18-307 27

consider how reagent selection affects 

sustainability of the overall process and not 

just reagent ‘greenness.’ 

Figure 7: Example Venn diagram from the ACS 

GCI Pharmaceutical Roundtable reagent guide

Third-party certifications and assessment 

tools

NGOs, federal agencies, and professional 

associations are also developing methods for 

measuring and assessing the relative 

sustainability of products and processes, 

including product certification programs and 

assessment tools. One approach to measure 

sustainability is the use of third-party 

certifications. Companies that we surveyed 

told us that they use third-party certifications 

to provide independent verification of 

sustainability that may be attractive to 

customers. Certification programs examine a 

range of different sustainability factors for 

products and processes. Each program sets 

minimum criteria that products must meet to 

be certified, including, for example, 

biodegradability, toxicity, performance, or 

water and energy usage. Certifying bodies 

make databases of certified products 

available online for public access and allow 

manufacturers to affix certification labels or 

logos to their products. Certifications are 

available from federal offices, such as EPA’s 

Safer Choice or USDA’s BioPreferred 

programs, from non-profit organizations, such 

as the Cradle to Cradle Products Innovation 

Institute and Green Seal, or from private 

companies, such as UL’s EcoLogo program. 

See table 2 for examples of certification 

programs and a summary of the criteria each 

uses to measure sustainability. For additional 

information on certification programs, see 

chapter 6. 
Technology Assessment GAO-18-307 28

Table 2: Illustrative examples of product certification programs with criteria related to sustainable 

chemistry 

Certification logo Certification 

program and 

awarding 

organization

Selected examples of 

types of products 

certified

Criteria or standards for 

certification

Approximate 

number of 

products 

certified

BioPreferred

Department of 

Agriculture

Lubricants, inks, 

fertilizers, disposable 

cutlery, air fresheners, 

wood stains, and others

Products must meet or exceed a 

minimum percentage of biobased 

content based on their product 

category. 

3000

Cradle to Cradle

Cradle to Cradle 

Products 

Innovation 

Institute

Building materials, 

interior design products, 

paper and packaging, 

personal care products, 

textiles, and others

Products must meet minimum 

criteria in the use of safer 

chemicals, reuse of materials, 

renewable energy use, water 

stewardship, and social 

responsibility. 

490

EcoLogo

UL (Underwriters 

Laboratories)

Building materials, 

chemicals, plastics, 

cleaning products, 

personal care products, 

office products, 

electronics, and others

Products must meet minimum 

criteria on raw materials, energy, 

manufacturing and operations, 

health and environment, product 

performance and use, and 

product stewardship and 

innovation. Criteria include 

prohibiting or restricting harmful 

chemical ingredients.

6800

Green Seal 

Green Seal

Cleaning products, 

lighting, paper products, 

personal care products,

paints, vehicle 

maintenance products, 

and others

Products must meet categoryspecific environmental and heath 

requirements in processing, 

ingredients, and packaging as well 

as performance standards. 

Standards include prohibiting or 

restricting harmful chemical 

ingredients. 

6000

Safer Choice 

Environmental 

Protection 

Agency

Cleaners, paints, odor 

removers, laundry 

products, pet care 

products, and others 

Each chemical ingredient in a 

product must pose the least 

concern for human and 

environmental health among 

chemicals that perform the same 

function. The product must also 

meet minimum performance and 

packaging standards.

2350

Source: GAO analysis of agency and organization documents; United States Department of Agriculture; Cradle to Cradle Products Innovation Institute; UL LLC; GreenSeal; 

Environmental Protection Agency. | GAO-18-307

Note: USDA defines biobased products as those derived from plants and other renewable agricultural, marine, and forestry 

materials; 'Cradle to Cradle Certified’TM is a certification mark licensed by the Cradle to Cradle Products Innovation Institute.
Technology Assessment GAO-18-307 29

Furthermore, manufacturers and formulators 

can also make use of tools designed to 

facilitate internal or business-to-business 

assessments and benchmarking to measure

sustainability. For example, Clean Production 

Action Network, Lowell Center for Sustainable 

Production, and Pure Strategies developed 

the Chemical Footprint Project, an 

assessment tool for companies to measure 

their progress toward the use of safer 

chemicals. The tool measures company 

performance on a 100 point scale based on 

the company’s chemical management 

strategy and policies, chemical inventory and 

data collection practices, measures and goalsetting on sustainability, and public disclosure 

and verification practices. Another example of 

an assessment tool is the Higg Index. The 

index, an industry framework for measuring 

and evaluating sustainability at the brand, 

facility, or product level, was developed by 

the apparel and footwear industry, retailers, 

brands, suppliers, and other stakeholders 

working through the Sustainable Apparel 

Coalition. An internal tool that assesses 

sustainability across a product life cycle, the 

index measures a number of factors including 

energy use, greenhouse gas emissions, waste, 

water, chemical management, and social 

impacts, among others. A company can share 

its index performance score with other 

companies in its product supply chain. Project 

staff also aggregate and anonymize the scores 

so that companies can benchmark their 

progress against others in the industry and 

identify areas for improvement. For examples 

of questions used in the Chemical Footprint 

Project and Higg Index assessments, see table 

3.

Table 3: Selected questions from the Chemical 

Footprint Project and Higg Index assessment 

tools related to sustainable chemistry

Chemical Footprint Project

• Does your company have a chemicals policy that 

aims to avoid chemicals of high concern?

• What chemical information does your company 

collect from suppliers?

• How does your company assure conformance 

with your chemicals policy?

• How does your company assess the hazards of 

chemicals in its products beyond regulatory 

requirements?

• What information does your company disclose 

about the chemical ingredients in its products?

Higg Index – Facilities Module

• Does this facility systematically monitor 

applicable chemical use regulations on a regular 

basis to ensure compliance and to identify new 

or changing compliance requirements?

• Does this facility have a documented inventory 

of chemicals used to make your products, and 

the respective supplier for each chemical?

• Does this facility collaborate with brands and 

chemical suppliers to prioritize and select 

chemical alternatives assessment for substances 

of concern and/or restricted substance lists?

• Does this facility restrict chemicals used in 

manufacturing processes and/or residing in final 

product that goes beyond a list of regulated 

chemicals and RSLs?

Source: Chemical Footprint Project, Higg Index. | GAO-18-307

Note: The Higg Index has separate modules to assess the 

sustainability of brands, facilities, and products.

2.3 Companies vary in which 

environmental and health factors 

they consider most important to 

optimize

Companies weight various environmental and 

health factors differently when assessing 

sustainability. In order to examine these 

differences in detail, we surveyed 27 chemical 

companies and asked respondents to indicate 

the relative importance their company gives 
Technology Assessment GAO-18-307 30

to each of 13 environmental and health 

factors. Specifically, we presented the factors 

in pairs (e.g., factor A with factor B) and asked 

respondents to select the factor in each pair 

for which they considered it most important 

to maximize the sustainability benefit, even if 

that benefit came at the expense of the other 

factor in the pair. For example, a company 

might compare ‘energy use’ with ‘water use’ 

and determine that it was more important to 

their company to maximize the sustainability 

benefit relative to the ‘energy use’ of a 

process even if it resulted in less sustainable 

use of water. (See app. IV (question 6) for a 

complete list of response counts for each pair 

of factors.)

The 13 environmental and health factors we 

examined in the survey were: 

• Percentage of renewable or biobased 

content

• Amount of materials required

• Toxicity of required materials

• Energy use

• Water use

• Land use/physical footprint

• Greenhouse gas emissions

• Other air emissions

• Volume of process waste generated

• Toxicity of process waste

• Recyclability of (or other uses for) process 

waste

• Toxicity of the product

• Recyclability of the product

We analyzed the results by assigning 1 point 

for a factor each time a company chose that 

factor as more important than another factor 

and 1⁄2 point each time a company chose that 

factor as equal to another factor. Figure 8 

provides median of the company-assigned 

scores for each factor, with the 13 factors 

arranged from top to bottom in order based 

on the median score each factor earned. 

‘Toxicity of the product’ earned the highest 

median score of 11.5 points (i.e., most 

important factor) and ‘percentage of 

renewable or biobased content’ earned the 

lowest median score of 1.5 points (i.e., least 

important factor). 
Technology Assessment GAO-18-307 31

Figure 8: The median score assigned to each factor by the companies that responded to our survey

A low score for a given factor indicates that a company considered it more important to maximize the sustainability 

benefits of other environmental or health factors rather than the given factor. A higher score indicates that a 

company considered it important to maximize the sustainability benefits of the given factor rather than other factors.

In addition to the median scores, we also 

examined the full range of scores assigned to 

each factor by the companies that responded 

to our survey. A narrow range of responses 

indicates general agreement among the 15 

responding companies regarding the 

importance of that factor compared to the 

other 12 factors. Such factors include:

• toxicity of the product,

• volume of process waste generated, and

• land use/physical footprint.

For example, 7 of the responding companies 

gave ‘toxicity of the product’ a score of 12 

points (see fig. 9, top graph), indicating that 

these companies judged it most important to 

maximize the sustainability of this factor over 

any other factor. In fact, 10 of the 15 

respondents gave ‘toxicity of the product’ a 

score of at least 10.5 points. Interestingly, 3 

companies gave this factor a score of 0 points, 

meaning that they never judged it more 

important (or equally important) to maximize 

the sustainability of this factor compared to 

the other factors. 
Technology Assessment GAO-18-307 32

Figure 9: Company-assigned scores for three environmental or health factors

A low score for a given factor indicates that a company considered it more important to maximize the sustainability 

benefits of other environmental or health factors rather than the given factor. A higher score indicates that a 

company considered it important to maximize the sustainability benefits of the given factor rather than other factors.
Technology Assessment GAO-18-307 33

As shown in figure 9 (middle graph), scores 

for ‘land use/physical footprint’ were 

clustered from 0 to 4 points with the 

exception of a single score of 10 points. In 

fact, 12 of the 15 respondents gave ‘land 

use/physical footprint’ a score from 0 to 2 

points. That clustering of scores at the low 

end indicates that the responding companies 

generally agreed that this was a less 

important factor compared to the other 

factors, although one company had a very 

different view of this factor. Similarly, scores 

for ‘volume of process waste generated’ (fig. 

9, bottom graph) were generally clustered in 

the middle of the range (from 4 to 8.5 points), 

indicating agreement among most 

respondents that this factor is moderately 

important to maximize for sustainability 

compared to the other factors.

In contrast, figure 10 shows two factors that 

earned an exceptionally wide range of scores, 

indicating considerable lack of agreement

among responding companies regarding their 

importance:

• amount of materials required and

• greenhouse gas emissions.

Figure 10: Company-assigned scores for two environmental factors

A low score for a given factor indicates that a company considered it more important to maximize the sustainability 

benefits of other environmental or health factors rather than the given factor. A higher score indicates that a 

company considered it important to maximize the sustainability benefits of the given factor rather than other factors.
Technology Assessment GAO-18-307 34

As shown in figure 10 (top graph), scores for 

‘amount of materials required’ ranged from 0 

to 10.5 points, with no single score having 

agreement from more than 2 respondents. 

The scores for ‘greenhouse gas emissions’ (fig. 

10, bottom graph) exhibited an even wider 

range, from 0.5 to 12 points. From these data, 

it is clear that the responding companies had 

a wide range of views regarding the 

importance of maximizing the sustainability 

benefits of these two factors.

In addition to determining the individual 

company scores for each factor, we also 

added the points across all 15 responding 

companies to produce a total score for each 

factor, with a maximum possible score of 180 

points.54 We interpreted factors with higher 

overall scores to be relatively more important 

to our survey respondents as a group 

compared to factors with lower overall scores 

(see fig. 11). 

 54Fifteen companies responded to this question on our survey 

and each company could give a maximum score of 12 to a 

single factor, so the maximum possible score each factor could 

earn was 180 points (i.e., 12 points from a given company 

multiplied by 15 companies).

Figure 11: The total scores for each factor across 

all 15 responding companies

Note: Partial scores (e.g., 84.5) were rounded up to the next 

whole number.

Our survey respondents represented 

companies in three industry sectors: chemical 

manufacturing, pharmaceuticals, and 

formulators (i.e., makers of personal care and 

cleaning products). There were some 

noteworthy differences among sectors in 

their views on the importance of these 13 

factors (see table 4). 
Technology Assessment GAO-18-307 35

Table 4: Sector-specific differences in the importance of various environmental and health factors

Ranking of importance (out of 13 factors) by each sector based on the total of all company-assigned scores

Factor

Chemical manufacturing 

sector Pharmaceutical sectora Formulator sector

Toxicity of the product 1 5 1

Greenhouse gas 

emissions 3 7 3

Volume of process waste 

generated 7 4 7/8 (tie)

Recyclability of the 

product 12 13 6

Source: GAO analysis of survey data. | GAO-18-307

Note: Companies could self-identify with more than one sector.

a

Responding companies in the pharmaceutical sector ranked “toxicity of required materials” as the most important factor.

2.4 Stakeholders cite the importance 

of a standard definition and metrics 

for sustainability

The scientific literature and our analysis of the 

interviews and survey we conducted reveal 

significant variation in how stakeholders 

define sustainable chemistry and assess the 

sustainability of their chemical processes and 

products. For example, stakeholders in the 

sustainable chemistry community have 

reported in the literature that the lack of a 

clear definition and agreed upon standards 

for assessing the sustainability of chemical 

processes and products inhibits the 

advancement of the goals of sustainable 

chemistry. According to the Green Chemistry 

and Commerce Council (GC3), the lack of a 

clear definition and metrics for measuring 

green chemistry can lead to confusion in the 

marketplace. Such misunderstandings occur 

where innovations that are not truly “green” 

are mislabeled as such.55 Moreover, academic 

 55GC3 is a cross-sectoral business-to-business network of firms 

working collaboratively to accelerate green chemistry. See J.A. 

Tickner and M. Becker, “Mainstreaming Green Chemistry: The 

literature on green chemistry in the 

pharmaceutical industry has described the 

current green chemistry community as one 

that is dealing with a plethora of similar 

metrics without standardized definitions or 

agreed upon process starting points, 

inhibiting industry-wide green chemistry 

integration.56 It is difficult for consumers, 

purchasers, policymakers, and even 

manufacturers to compare the sustainability 

of one process or product with another when 

such processes and products are assessed 

using different metrics that incorporate 

different factors. 

The stakeholders we interviewed also had 

varying definitions of sustainable chemistry 

and disagreed about whether it was the same 

as green chemistry. In addition, the 

companies that responded to our survey 

varied significantly with regard to which 

environmental and health factors they 

 Need for Metrics,” Current Opinion in Green and Sustainable 

Chemistry, vol. 1 (2016).

56Roschangar, Sheldon, and Senanayake, “Overcoming Barriers 

to Green Chemistry,” 2015.
Technology Assessment GAO-18-307 36

considered most important to prioritize when 

optimizing the sustainability of a chemical 

process or product, as discussed in section 

2.3. Despite this variation of opinion on the 

importance of different factors, most 

companies responding to our survey agreed 

that it would be somewhat or very useful to 

have a standardized set of factors for 

assessing sustainability across their industry 

sector and (to a lesser degree) across the 

entire industry. Specifically, most respondents 

indicated that it would be useful for all 

companies in their sector to use a common 

set of factors for assessing sustainability (see 

table 5). Respondents also indicated that it 

would be useful for all companies across the 

entire chemical industry to use common 

factors, but the responses to that question 

were not as strong.

Table 5: Company responses when asked how useful it would be for all companies to use a standard set 

of factors when assessing sustainability

How useful would it be for all 

companies in your sector to use 

a standardized set of factors for 

assessing sustainability?

How useful would it be for all companies 

across the entire chemical industry to use 

a standardized set of factors for assessing 

sustainability?

Very useful 9 5

Somewhat useful 6 7

Slightly useful 1 3

Not useful 0 0

Do not know/cannot judge 1 1

Source: GAO analysis of survey data. | GAO-18-307

In summary, the literature and the results of 

our interviews and survey indicate that the 

lack of a standard definition for sustainable 

chemistry, combined with the lack of 

standard ways of measuring or assessing 

sustainability, hinder the development and 

adoption of sustainable chemistry

technologies.
Technology Assessment GAO-18-307 37

3 Technologies to make catalysts more sustainable

According to one of our experts, catalysts 

have long been known to provide economic 

and environmental benefits. For example, 

most chemical companies conduct significant 

research and development in catalysis (action 

of a catalyst), according to this expert.

Platinum group metals (PGMs) are the most 

frequently used catalysts for a variety of 

industrial applications. However, PGMs are 

expensive, scarce, generally non-renewable, 

and susceptible to supply and price 

fluctuations. Their continued use has raised 

sustainability concerns among the scientific 

community. Current research efforts are 

directed at finding alternatives to PGMs, such 

as earth-abundant metals. Metal-free 

catalysts such as organocatalysts and 

biocatalysts (catalysts having a biological 

origin) are other emerging options that are 

gaining popularity with the pharmaceutical 

and fine chemicals industries. Due to their 

potential advantages, the industry has begun 

to research and implement these options as 

alternatives to PGMs in some chemical 

processes. See table 6 for our assessment of 

alternative catalyst technologies; we provide 

additional details in the remainder of the 

chapter.

Table 6: Summary of assessment of selected catalyst technologies as alternatives to platinum group 

metals (PGM)

Technology Advantages Disadvantages

Earth-abundant 

metals

Relatively less costly with fewer supply

fluctuations than precious metals.

Abundance and relatively low toxicity 

relaxes the recycling and separation 

burden, resulting in lowering of operational 

costs.

Inherent reactivity (tendency to react with 

other elements) causes issues with its 

chemical stability, and selectivity, impeding its 

progress.

Limited scope of reaction—compatible with 

fewer functional groups.

Toxicity concerns with some earth-abundant 

metals remain.

Organocatalysts Metal-free and low-cost alternative to 

metal catalysts.

Ease of availability and ease of handling 

(inert towards water and air).

Sustainability benefits from the ability to 

use environmentally friendly solvents such 

as water or solvent-free conditions.

Potential to reduce energy consumption.

May need large amounts for an appreciable 

increase in reaction rate, especially for 

industrial use.

Difficulties in separation and reuse may limit 

their industrial applicability. 

Difficult to recycle.
Technology Assessment GAO-18-307 38

Technology Advantages Disadvantages

Biocatalysts Some reactions can be performed with 

higher selectivities, at ambient conditions, 

and with fewer steps, therefore producing 

less waste as byproducts and improving 

sustainability.

Biodegradable and derived from renewable 

resources.

Enzymatic polymerization can be used to 

synthesize commodity plastics, and new 

environmentally friendly polymers that 

may not have a traditional chemical route

of production.

Biocatalytic or enzymatic routes have 

realized significant improvements in 

productivity in the development of many 

life-saving pharmaceutical drugs.

The use of water as a solvent can result in a 

large amounts of water as a waste product 

that would typically need treatment leading to 

additional economic and energy costs.

Performing reactions in water instead of 

organic solvents can reduce the solubility of 

some reactants. 

Majority of biocatalysts are unstable, and 

difficult to recycle and reuse. However, 

immobilization techniques can help mitigate 

this problem and make their utilization in 

biotechnological processes more favorable.

Source: GAO. | GAO-18-307

3.1 Earth-abundant metal catalysts 

One option for improving the sustainability of 

catalysts is to replace PGMs with more earthabundant metals such as nickel, iron, cobalt, 

titanium, copper, and others. According to a 

company scientist we interviewed, these 

metals are not only more abundant in nature 

but are generally less toxic than PGMs. Nickel 

is one of the most commonly used earthabundant metals. It has chemical properties 

similar to palladium and platinum and is 

capable of performing many of the same 

reactions. Iron is the second most abundant 

metal in earth’s upper crust and is an 

essential element for human life. For 

example, the iron complex in hemoglobin (a 

protein contained in red blood cells) acts like 

a catalyst that binds to oxygen and helps 

transport it to the tissues of the body. Cobalt 

is also an essential metal for humans. It is 

present in vitamin B12 (cobalamin) and its 

radioactive form is widely used for medical 

applications. However, it is gaining traction as 

a catalyst as well.

Catalysts derived from these metals offer 

several advantages over PGMs but also have 

trade-offs that should be considered. These 

metals are used as catalysts in some key 

industrial processes and researchers are 

continuing to seek additional applications.

However, despite the recent advances in this 

field, the industry has generally been slow to 

replace PGMs for several reasons, including 

risk aversion and an incomplete 

understanding of the newer catalytic 

mechanisms, according to an ACS article.

Advantages and disadvantages of earthabundant metal catalysts 

Earth-abundant metal catalysts offer several 

advantages that could make chemical 

processes and products more sustainable, 

including generally lower toxicity, a range of 

applications, and reduced costs.

Relatively less toxic: Some earth-abundant 

metal catalysts are relatively nontoxic and 

environmentally friendly. For example, iron is 

relatively nontoxic compared to palladium 

and nickel. Titanium is also considered 
Technology Assessment GAO-18-307 39

nontoxic, and is biocompatible—attractive 

features for handling and disposal—and thus 

potentially a sustainable catalyst. Their low 

toxicity can mitigate the need for the often 

energy-intensive separation and recycling 

processes. That is, unlike PGMs, it is often 

acceptable if a trace amount of an earthabundant metal such as iron ends up in a final 

product; this might eliminate costly and timeconsuming purification processes.

Range of potential applications: Because 

earth-abundant metals such as nickel and iron 

have a wide range of available oxidation 

states, they are more versatile as catalysts.57

For example, depending on its oxidation 

state, iron can be used to either donate or 

accept electrons in a chemical reaction. Thus, 

iron catalysts can facilitate a broad range of 

synthetic transformations. In addition, nickel 

is reported to be enantioselective for many 

different reactions, offering the potential for 

reducing waste by avoiding unwanted 

byproducts.58

Reduced costs: Using earth-abundant metal 

catalysts such as iron and nickel in place of 

PGMs can help reduce costs. For example, 

various iron salts and iron complexes are 

commercially available on a large scale or are 

easy to synthesize, thus they are a low cost 

 57Oxidation state, also called oxidation number, is a number 

assigned to a particular atom in a molecular entity that 

represents the relative charge on that atom. For metals, it 

indicates the total number of electrons that the atom either 

gains or loses in order to form a chemical bond with another 

atom.

58An enantiomer is one of a pair of molecules which are nonsuperimposable mirror images of each other. Because 

enantiomers can have different properties, often one form is 

preferred over the other. Enantioselectivity is the preferential 

formation of one enantiomer over another in a chemical 

reaction, which reduces waste by reducing the amount of the 

unwanted enantiomer that forms.

alternative to PGMs. Similarly, nickel costs 

significantly less than PGMs—about 2,000 

times less than palladium and 10,000 times 

less than platinum, according to a published 

2014 review by academic researchers.

59 In 

addition, earth-abundant metals tend to have 

fewer supply fluctuations than PGMs. 

Furthermore, because these metals are less 

expensive and more abundant, it is not as 

crucial that they be completely recovered for 

reuse, which may also lift an economic 

burden. 

However, earth-abundant metal catalysts also 

have trade-offs that must be considered.

Instability and tendency to react with other 

elements: Earth-abundant metals have not 

been extensively studied as replacements for 

PGMs, and only recently have become a 

significant area of research. Furthermore, 

progress in earth-abundant metal catalysts 

has lagged due to challenges associated with 

their inherent reactivity (tendency to react 

with other elements), which causes instability 

as well as difficulties with selectivity and 

scope. That is, their selectivity is lower 

relative to PGMs and the scope of the 

reactions is limited.

Lack of “drop-in” substitutability: Another 

consideration is that earth-abundant metals 

cannot simply be interchanged in place of 

PGMs. New and more expensive ligands, 

mechanisms, and reaction conditions may be 

necessary in order to successfully use earthabundant metals as industrial catalysts.

60 In 

 59S. Z. Tasker, E. A. Standley, and T. F. Jamison, “Recent

Advances in Homogeneous Nickel Catalysis,” Nature, vol. 509 

(2014).

60A ligand is an ion or molecule that binds to a central metal 

atom to form a complex. 
Technology Assessment GAO-18-307 40

addition, earth-abundant catalysts are 

compatible with fewer functional groups 

compared with PGMs.61

Toxicity concerns: Some earth-abundant 

metal catalysts still raise toxicity concerns. For 

example, despite nickel’s presence in natural 

biological enzyme complexes and metabolic 

pathways, it may be carcinogenic. Therefore, 

despite its sustainability advantages over 

palladium and platinum, it can have 

significant drawbacks when used to catalyze 

pharmaceutical reactions. A recent study has 

reported that the concept of toxic heavy 

metals and safe nontoxic alternatives based 

on lighter metals should be re-evaluated.62

According to the authors of this study, a 

comparison of the toxicological data indicates 

that palladium and platinum compounds may 

be less toxic than previously thought, 

whereas complexes of nickel and copper, 

typically assumed to be sustainable 

alternatives, may possess significant toxicities 

due to their solubility in water and biological 

fluids. In addition, a pharmaceutical company 

official we interviewed told us that earthabundant metals can be just as toxic as rarer 

metals.

Applications of earth-abundant metal 

catalysts

Earth-abundant metals are used in some key 

industrial processes such as the Haber-Bosch 

process, a well-known but highly 

unsustainable reaction that uses iron as a 

 61A functional group is a group of atoms that helps define 

chemical properties of a molecule.

62K. S. Egorova and V. P. Ananikov, “Which Metals are Green 

for Catalysis? Comparison of the Toxicities of Ni, Cu, Fe, Pd, Pt, 

Rh, and Au Salts,” Angewandte Chemie International Edition, 

vol. 55 (2016).

catalyst for ammonia synthesis. More 

recently, some researchers are exploring ironcatalyzed reduction of carbon dioxide to 

methane to supplement fossil-fuel sources

and reduce greenhouse gas emissions.

Other examples of the use of earth-abundant 

catalysts include steam reforming, which uses 

nickel for the production of syngas; the 

Fischer−Tropsch synthesis, which uses cobalt, 

iron, and syngas for the production of 

hydrocarbon chains; and the water−gas shift 

reaction, which uses iron, chromium, copper, 

and zinc to convert carbon monoxide to 

carbon dioxide and hydrogen.63 More 

recently, applications of nickel catalysts 

instead of palladium-based catalysts in the 

Suzuki-Miyaura cross-coupling demonstrate a 

more sustainable alternative catalytic route.64

Cobalt is very promising in the activation and 

functionalization of bonds.65 Specifically, 

researchers have reported many 

functionalization strategies that use cobalt to 

form carbon-hydrogen bonds. These are 

viable replacements for current PGM catalytic 

approaches. Activation of the carbonhydrogen bond can improve the efficiency of 

a reaction by eliminating certain synthesis 

 63Syngas (or synthesis gas) is a mixture of hydrogen and carbon 

monoxide.

64Cross-coupling refers to one of the most fundamental 

reactions in organic synthesis for carbon–carbon bond 

formation. Cross-coupling reactions combine two molecular 

fragments and lead to the formation of new bonds. In 2010 the 

Nobel Prize in chemistry was awarded to Akira Suzuki and two 

other scientists for the development of palladium-catalyzed 

cross-coupling reactions. The committee recognized the 

remarkable impact of this class of reactions on academic 

research and the development of new drugs and materials.

65Carbon–hydrogen bond functionalization is a type of reaction 

in which a carbon–hydrogen bond is cleaved and replaced with 

a carbon-X bond where X is usually a carbon-, oxygen-, or 

nitrogen-containing group such as OH or NH2. 
Technology Assessment GAO-18-307 41

steps. It may also be useful in converting 

renewable feedstocks into high-value 

chemicals. Cobalt is also used in many other 

types of chemical reactions.

Titanium complexes are used to catalyze a 

broad range of transformations including 

polymerizations.66 For example, titanium 

dioxide has become an important 

photocatalyst in environmental biodecontamination for a large variety of 

organics, bacteria, viruses, and fungi.67

Titanium-based catalysts are commercially

used on a large scale for the selective catalytic 

reduction of nitrogen compounds in air 

pollution control. Researchers have shown 

that titanium-based catalysts can transform 

the toxic pollutants of automobile exhaust 

emissions under ultraviolet irradiation. This 

property is used to develop a titanium-based 

photocatalytic converter for automobiles, 

thereby avoiding the use of PGMs and 

reducing costs. Recently, Dow Chemical and 

BASF jointly developed an innovative 

sustainable hydrogen peroxide-to-propyleneoxide alternate route that uses a titaniumdoped catalyst for industrial manufacturing of 

propylene oxide (among the largest-volume 

industrial chemicals in the world and used in a 

vast array of products).68 This route 

eliminates most of the organic waste and 

byproducts and greatly reduces water and 

energy use.

 66Polymerization is the process of connecting monomers (small 

molecules) into a polymer (a longer chain of repeating units).

67A photocatalyst accelerates a photochemical reaction— that 

is, a chemical reaction caused by light or ultraviolet radiation.

68The Dow Chemical Company and BASF jointly won a 

Presidential Green Chemistry Challenge Award in 2010 for this 

innovative, environmentally benign production of propylene 

oxide. 

3.2 Organocatalysts 

Organocatalysts are metal-free small organic 

molecules that can catalyze many different 

reactions. Consequently, considerable effort 

has recently been directed toward the 

development of these metal-free catalysts. 

For example, Lelais and MacMillan reported 

on several significant organic chemical 

transformations that can be conducted with 

organocatalysts, providing a valuable 

complement to other routes.69 In many cases,

organocatalysts are complementary to metal 

and biocatalysts. That is, they can be used in 

place of PGMs, earth-abundant metal 

catalysts, and biocatalysts in some reactions. 

They are composed of nonmetallic elements 

such as carbon, hydrogen, nitrogen, oxygen, 

sulfur, and phosphorous. Among the most 

common examples are amino acids.70

Advantages and disadvantages of 

organocatalysts 

Organocatalysts offer several sustainability 

advantages including greater availability, ease 

of handling, the ability to use a more 

sustainable approach to solvents, and 

reduced energy consumption.

Ease of availability and handling: 

Organocatalysts offer ease of availability, an 

advantage compared to metals. Another 

advantage is easy handling; organocatalysts 

tend to be stable and unreactive in water and 

air. Thus the demanding reaction conditions 

 69G. Lelais and D. W. C. MacMillan, “Modern Strategies in 

Organic Catalysis: The Advent and Development of Iminium 

Activation,” Aldrichimica ACTA, vol. 39, no. 3 (2006).

70The amino acid known as proline was one of the earliest 

organocatalysts used.
Technology Assessment GAO-18-307 42

typically required of metal-catalyzed 

reactions—such as an inert atmosphere and 

low temperature—are usually not required 

with organocatalysts. 

Elimination of metal contamination risk: 

Organocatalysts eliminate the risk of metal 

contamination in the final product, which is 

especially valuable to the pharmaceutical 

industry.

Compatible with more sustainable solvent 

use: Many organocatalysts have been found 

to work better (e.g., to be more selective or 

more rapid) in water than in organic solvents. 

For example, a study by Breslow showed that 

certain organocatalyzed reactions were 

accelerated in water.71 Other researchers 

have also reported on efforts to develop 

organocatalyzed reactions with enhanced 

yield and enantioselectivity. Additionally, 

some reactions have been successfully 

demonstrated with organocatalysts under 

solvent-free conditions. For example, a recent 

review of advances in sustainable 

organocatalysis by Branco et al. reported two 

new catalysts for conducting organocatalytic 

reactions under neat (solvent-free) 

conditions.72 However, these often require a 

large amount of other substances involved in 

the reaction, which can present a waste 

problem similar to organic solvents. (See 

chapter 4 for more details on alternative 

solvents.) 

 71R. Breslow, “Hydrophobic Effects on Simple Organic 

Reactions in water,” Accounts of Chemical Research, vol. 24, 

no. 6 (1991).

72L. C. Branco, A. M. F. Phillips, M. M. Marques, S. Gago, and P. 

S. Branco, “Recent Advances in Sustainable Organocatalysis,” 

INTECH (2016).

Reduced energy consumption: The use of 

organocatalysts can reduce energy 

consumption, which is consistent with one of 

the 12 Principles—namely, number 6: design 

for energy efficiency (see app. V).

73

However, as with all catalysts, organocatalysts 

also have some disadvantages that must be 

evaluated against their advantages when 

choosing the best options for a particular 

reaction.

Need for large quantities: One disadvantage 

of organocatalysts is that a large amount may 

be needed for appreciable increases in 

reaction rates, especially for industrial use. 

However, organocatalysts are much cheaper 

than PGMs so the use of more catalyst may 

not necessarily translate to higher cost. This 

can depend on the cost of purification 

processes, but this tradeoff depends largely 

on the specifics of each process. Also, 

research has shown that while decreasing the 

amount of catalyst may decrease the reaction 

rate, it can increase stereoselectivity.74 That 

is, a slower reaction rate can produce a more 

uniform product, resulting in less waste. 

Difficulties with recycling: Organocatalysts 

can be challenging to recycle. Because many 

standard organocatalysts are dissolved in a 

reaction medium that is typically in the same 

phase as the reactants, they are difficult to 

separate and reuse, which can limit their 

industrial use. However, immobilization 

 73Branco, Phillips, Marques, Gago, and Branco, “Recent 

Advances in Sustainable Organocatalysis,” 141.

74Stereoselectivity is the preferential formation in a chemical 

reaction of one stereoisomer over another—stereoisomers are 

isomers that have the same chemical formula and functional 

groups but differ in the arrangement of their functional groups 

in space. Enantiomers are one example of stereoisomers.
Technology Assessment GAO-18-307 43

techniques are being studied to allow for 

easier recovery and reuse of 

organocatalysts.75 For example, Corma and 

Garcia have reported silica-bound 

organocatalysts as recoverable, recyclable 

catalysts in several organic transformations.76

Other immobilization methods involve 

electrostatically attaching the organocatalysts 

to solid supports; for example, relying on ion 

pairs to form between the solid support and 

the catalyst. Another technique involves the 

use of zeolite supports; this is somewhat 

analogous to immobilizing the catalyst in a 

cage. 

Unknown toxicity: Organocatalysts are now 

widely used in polymer synthesis as an 

alternative to traditional metal-based 

catalysts, in some cases because of concerns 

about metal toxicity. However, little is known 

about the toxicity of most organocatalysts. 

For example, a recent scientific study 

attempts to assess whether well-established 

organocatalysts may present a certain level of 

cytotoxicity when used to produce FDAapproved polyesters for use in food 

packaging.77

 75Immobilization means to restrict mobility in a fixed space. 

This technique is used for easy separation of the catalyst from 

the reaction mixture and minimizes the loss of catalyst in the

product.

76A. Corma and H. Garcia, “Silica-Bound Homogenous Catalysts 

as Recoverable and Reusable Catalysts in Organic Synthesis,” 

Advanced Synthesis and Catalysis, vol. 348, no. 12 (2006).

77A. Nachtergael, O. Coulembier, P. Dubois, M. Helvenstein, P. 

Duez, B. Blankert, and L. Mespouille, “Organocatalysis 

Paradigm Revisited: Are Metal-Free Catalysts Really Harmless?” 

Biomacromolecules, vol. 16, no. 2 (2015). Cytotoxic means 

poisonous to living cells.

3.3 Biocatalysts 

Biocatalysts, as might be expected from the 

name, have a biological origin. Typically these 

compounds are enzymes (natural compounds 

originating from living cells) or engineered 

enzymatic complexes (i.e., one part of the 

enzyme engineered to work somewhat 

differently than it would in a living organism)

that catalyze biochemical reactions in organic 

substances.

78 While these comprise only 3 

percent of the catalyst market (as of 2013), 

they are the most efficient and sustainable 

catalysts found in nature. Because 

biocatalysts come from natural sources, they 

are biodegradable and renewable.

79

Biocatalysts have been used for thousands of 

years—for example, to catalyze fermentation 

for brewing and baking.80 They are 

increasingly being used to improve the 

sustainability, efficiency, and cost of chemical 

production. In the past, biocatalysts were 

used in drug discovery and production. Today 

they are also being used to make nonmedicinal bulk chemicals such as biofuels, 

surfactants, and plastics. Molecular biology 

has expanded knowledge of enzymes and 

pathways and this has led to an increased use 

 78Enzymes are proteins that speed up a biochemical reaction. 

That is, they catalyze nearly all of the chemical reactions that 

occur in biological systems (chemical reactions that take place 

inside the cells of living things).

79In addition to organocatalysts and biocatalysts there 

are other categories of catalysts such as, nanocatalysts, 

solid acid catalysts, photocatalysts, and electrocatalysts 

that are also in use or being researched. However, we 

did not assess these technologies or their sustainability 

in this report.

80Fermentation is a biochemical process by which organic 

substances are decomposed by the action of enzymes to 

provide chemical energy, as in the production of alcohol.
Technology Assessment GAO-18-307 44

of biocatalyzed chemical processes. Recent 

research has led to the engineering of both 

reaction pathways and enzymes to make 

customizable biocatalysts starting from a 

natural process. Researchers have used such 

reaction pathways and biocatalyzed processes 

to develop or improve the production of 

many life-saving drugs.

Representatives we interviewed from the 

pharmaceutical industry told us that 

biocatalysts are a major area of development 

and investment for their industry. For 

example, researchers are exploring ways to 

replace metals, including PGMs, with 

enzymatic processes. Industry representatives

noted that they have used biocatalysts to 

perform syntheses that reduce waste and the 

use of solvents, thus improving the 

sustainability of their processes. 

Types of biocatalysts 

Biocatalysts can take two forms: fermentation 

and free enzymes. 

Fermentation: The earliest form of an 

industrial biocatalyst was fermentation. 

Brewing and baking employ this type of 

biocatalyst, usually in the form of yeast cells. 

At the outset of industrial fermentation, only 

natural products—substances that are 

naturally produced by living organisms—could 

be produced using biocatalysts, but today 

scientists are able to engineer cells to allow 

the production of compounds not 

traditionally made by an organism. For 

example, research efforts are underway to 

develop fermentation pathways to produce 

vitamins, steroids, solvents, valuable drugs, 

and polymer precursors. 

Free enzymes: Enzymes (proteins) are natural 

substances that catalyze almost all of the 

chemical reactions in living organisms. 

Without enzymes, these reactions would take 

place at a rate far too slow to sustain life. 

Several enzymatic reaction pathways have 

been researched and developed recently for 

the synthesis of chemical and pharmaceutical 

products. For example, enzymatic 

polymerization reactions can be used to 

synthesize commodity plastics, as well as new 

environmentally friendly polymers that may 

not have a traditional chemical synthesis 

route. For example, lipases (a class of 

enzymes) have shown industrial potential in 

polyester synthesis. Polyesters are an 

abundant organic material in living systems 

and many compounds in this class have 

commercial applications, especially in the 

biomedical field, so a lipase-based 

polymerization process can help make the 

chemical industry more sustainable. In 

addition, Patel and Kharat report that the 

application of enzyme engineering to the 

pharmaceutical industry is growing rapidly.81

Advantages and disadvantages of 

biocatalysts 

Biocatalysts offer several advantages 

compared with PGMs, including easier 

handling, higher selectivities, and reduced 

waste and energy use that can make them 

more cost-effective relative to traditional 

catalysts.

Easier handling: Unlike many industrial 

processes using traditional catalysts, 

 81H. H. Patel and A. R. Kharat, “Comparative Study of Free 

Enzyme & Immobilized Enzyme on BSA Digestion,” 

International Journal of Pharmaceutical Sciences and Research, 

vol. 3, no. 12 (2012).
Technology Assessment GAO-18-307 45

biocatalysts can generally be used at or near 

ambient temperature and pressure. Enzymes 

can also be used in water, unlike many 

industrial catalysts, which predominantly 

require organic solvents. 

Higher selectivities: Both forms of 

biocatalysts—fermentation and enzymes—

have higher selectivity than traditional 

catalysts. This includes high substrate 

specificity (meaning they only catalyze a 

specific chemical reaction) as well as 

stereoselectivity. Both features are important 

because they make enzymes promising as 

catalysts. Furthermore, high selectivity yields 

high purity products.

Reduced waste and energy use: Biocatalysts 

are also inherently more efficient than other 

catalysts because they tend to catalyze in one 

step without need for functional group 

protection, activation, or deprotection steps 

that generate more waste and use more 

energy. Furthermore, they can operate under 

moderate reaction conditions at near ambient 

temperature and pressure, thus resulting in 

reduced energy consumption. As a result, 

biocatalysts are often more cost effective 

than synthetic catalysts.

Biodegradable and renewable: Because 

biocatalysts come from natural sources, they 

are biodegradable and renewable. 

Furthermore, new methods and techniques 

have emerged that can use biocatalyzed

processes in the production of a variety of 

compounds from renewable feedstocks such 

as biomass.

As with other technologies designed to make 

chemical processes and products more 

sustainable, biocatalysts have tradeoffs from 

both a sustainability and a feasibility 

perspective. These include the potential for 

generating significant quantities of 

wastewater, limitations with use, and 

instability, among others.

Potential for large quantities of wastewater: 

The use of water as a solvent, while it 

provides some sustainability advantages over 

the use of organic solvents, can generate 

large amounts of wastewater. Unless this can 

be easily recycled, wastewater treatment 

typically involves additional economic and 

energy costs. Performing reactions in water 

instead of organic solvents can also reduce 

the solubility of some reactants. However, 

there are methods available to expand the 

utility of water as a reaction medium under 

these circumstances. (See chapter 4 for 

details). In addition, water-based solutions 

may need a large volume of solvents for 

product isolation, which minimizes the 

solvent-related gains of doing the reaction in 

water.

Limitations with use: Enzymes’ high substrate 

specificity, while generally an advantage as 

discussed above, can complicate the process 

of finding a well-suited enzyme to catalyze a 

particular chemical process. Furthermore, 

many enzymes are subject to product 

inhibition—the decrease in rate of reaction 

brought about by the addition of a substance. 

Researchers have attempted to solve this 

problem by forming molecular complexes 

with the product molecules, so these 

molecules are not able to inhibit the enzyme. 

Instability and difficulties with recovery: Most 

enzymes are fairly unstable. In addition, they 

are often hard to recover from the reaction 

mixture. Thus, industrial applications of 

enzymes are often constrained by a lack of 

long-term stability and the challenges 
Technology Assessment GAO-18-307 46

involved in their recovery and reuse. Enzymes 

are often immobilized to help mitigate these 

issues and make their use more favorable. 

Immobilization makes the enzyme easier to 

handle and easier to separate from the 

reaction mixture, which lowers the total 

production cost of enzyme-mediated 

reactions. 

Applications of biocatalysts 

Manufacturing of penicillin: The main starting 

block for the synthetic production of penicillin 

is a compound called 6-aminopenicillanic 

acid. Until the mid-1980s, the conventional 

chemistry used to produce this compound 

included environmentally unattractive 

features such as chlorinated reagents and a 

reaction temperature of –40 degrees Celsius 

(°C). In contrast, the newer enzymatic 

process for producing 6-aminopenicillanic 

acid uses penicillin amidase (an enzyme) in 

water at 37°C, without the use of chlorinated 

reagents. Currently the majority of this 

compound produced on a world-wide basis 

(more than 10,000 metric tons annually) uses 

the enzymatic route. A key sustainability 

advantage of the enzymatic process for the 

manufacture of 6-aminopenicillanic acid is the 

avoidance of protecting groups because such 

steps require additional reagents, use more 

energy, and generate waste.82 This also aligns 

with Principle 8 of the 12 Principles, which 

calls for minimization or avoidance of such 

steps (see app. V). 

 82A protecting group refers to a temporary functional group 

added during organic synthesis to prevent a portion of a 

molecule from reacting. While protecting groups play an 

important role in multistep organic syntheses, they are usually 

considered undesirable because it adds additional steps to the 

length of the overall synthesis. They can also have 

sustainability issues including the use of additional materials 

and production of additional waste.

Production of adipic acid: Production of adipic 

acid through an enzymatic route has been 

demonstrated in the scientific literature.83

This process can replace conventional 

synthesis routes that may have sustainability 

issues. Currently, the large scale manufacture 

of adipic acid, a commercially important 

compound used for nylon production, 

involves a multistep synthesis with several 

unsustainable features. For example, it 

requires the use of cyclohexane, which in turn 

is made from benzene. Benzene is flammable, 

highly toxic, and carcinogenic material. 

Furthermore, the production process involves

high temperature oxidation steps, and the use 

of corrosive reagents such as nitric acid. This 

is subsequently followed by an energyintensive distillation to recover and recycle 

the unreacted raw material. In contrast, 

producing adipic acid via fermentation could 

significantly improve the sustainability of this 

process. Researchers Draths and Frost 

received a Presidential Green Chemistry 

Challenge Award in 1998 for their 

development of an alternative synthesis of

adipic acid from glucose using fermentation. 

In this process, glucose is first converted to 

muconic acid using a single, genetically 

engineered microbe via a novel biosynthetic 

pathway that does not exist in nature. 

Muconic acid is subsequently hydrogenated in 

a fermentation broth using a platinum 

catalyst in a pressurized atmosphere of 

hydrogen at ambient temperature to yield 

adipic acid. Although the resulting process 

 83L. C. Webster, P. T. Anastas, and T. C. Williamson, 

“Environmentally Benign Production of Commodity Chemicals 

Through Biotechnology: Recent Progress and Future Potential,” 

ACS Symposium Series; American Chemical Society: 

Washington, DC (1996). 
Technology Assessment GAO-18-307 47

used a PGM catalyst, other sustainability 

gains were significant.84

Production of the drug sitagliptin: Enzymatic 

processes have been researched in recent 

years in the pharmaceutical industry as a 

sustainable and efficient biocatalytic 

manufacturing route to make certain drugs 

such as sitagliptin (the active ingredient in 

Januvia®

, a type 2 diabetes drug). The 

multistep manufacturing route used several 

complex reagents and solvents, high pressure 

hydrogenation reaction requiring expensive 

specialized equipment and a rhodium-based 

catalyst, and a yield-reducing crystallization 

 84According to one of our experts, Draths and Frost’s 

fermentation process is not used commercially, mainly because 

significant amounts of petroleum-derived adipic acid are 

produced overseas.

step (see fig. 12).85 In 2010, Merck and 

Codexis received a Presidential Green 

Chemistry Challenge Award for developing a 

more sustainable biocatalytic manufacturing 

process for sitagliptin using a transaminase 

enzyme.86 This approach eliminates several

unsustainable reaction steps to provide high 

purity sitagliptin directly, followed by a 

phosphate salt formation step to provide 

sitagliptin phosphate. The reported benefits 

of this process include a significant 

improvement in productivity by 56 percent 

with the existing equipment, a 10–13 percent 

increase in percentage yield, and a 19 percent 

reduction in overall waste. 

 85Hydrogenation is a chemical reaction in which hydrogen 

atoms add to carbon-carbon multiple bonds. In order for the 

reaction to proceed at a practical rate, a catalyst is almost 

always needed.

86Merck & Co., Inc. and Codexis, Inc. jointly won a Presidential 

Green Chemistry Challenge Award in 2010 for the greener 

manufacturing of sitagliptin enabled by a transaminase 

enzyme. 
Technology Assessment GAO-18-307 48

Figure 12: Conventional and biocatalytic routes for manufacturing sitagliptin (the active ingredient in Januvia®, a 

type 2 diabetes drug)
Technology Assessment GAO-18-307 49

4 Technologies to make solvent use more sustainable

There is not a single universal green or 

sustainable solvent; chemical processes or 

other solvent applications have different 

specifications and therefore may require 

different alternative solvent options. Solvents 

constitute a large portion of the total volume 

of chemicals used in industrial processes and 

thus have an influence on the overall 

environmental impact of those processes. 

Chemists consider a number of key properties 

when selecting a solvent for a particular 

application or seeking alternative solvent 

technologies. An overall assessment of the 

environmental impact of a solvent can include 

factors from both an environmental health 

and safety perspective and a life cycle 

perspective. Several commonly used solvents 

are problematic from a sustainability or 

regulatory perspective but have been 

particularly challenging to replace. However, 

there are more sustainable solvent 

technologies available to replace some 

conventional solvents, including a variety of 

biobased solvents; non-VOC solvents such as 

water, supercritical carbon dioxide, and ionic 

liquids; and solvent-free or reduced-solvent 

technologies. Table 7 summarizes our 

assessment of these technologies; we provide 

additional details in the remainder of the 

chapter.

Table 7: Summary of assessment of selected alternative solvent technologies

Technology Advantages Disadvantages 

Biobased solvents 

(volatile organic 

compounds (VOC) or 

non-VOC)

Sourced from renewable raw 

materials

Can be biodegradable 

Can be safer or less toxic than 

petroleum-derived solvents

Some can directly replace 

conventional solvents 

Some pose the same inherent 

risks as other VOCs such as 

atmospheric pollution, 

flammability, and user exposure

Can be more expensive than 

other materials

Can have variability in supply and 

quality control of feedstocks 

Challenges associated with 

building new processes at 

commercial scale 

Non- VOC solvents Water Environmentally benign, 

nontoxic, and nonflammable 

Abundant and inexpensive 

Some reactions proceed faster in 

water 

Many chemicals are not soluble in 

water

Reaction with water can compete 

with the desired reaction

Conventional solvents may be 

required to separate reaction 

products from water

Removing unwanted byproducts 

from water for recycling can be 

energy-intensive 
Technology Assessment GAO-18-307 50

Technology Advantages Disadvantages 

Supercritical 

carbon dioxide 

Environmentally benign, nontoxic 

and nonflammable 

Inexpensive 

Supercritical temperature and 

pressure are relatively mild 

compared to some other 

substances

Tunable (adjustable) solvent 

properties

Ease of separation from the 

reaction product

Requires elevated pressure 

Requires specialized equipment

and additional safety precautions

May not be a suitable solvent for 

reactions involving polar or high 

molecular weight chemicals

Ionic liquids Low volatility 

Tunable solvent properties 

Concerns over toxicity and 

environmental persistence and 

footprint

Can be complicated or costly to 

make

Solvent-free or 

reduced-solvent 

Reduces solvent use and waste

Decreases the need to recycle or 

dispose of used solvents

Solvents may still be required for 

product purification

Technical challenges to achieving 

solvent-free reactions on an 

industrial scale 

Source: GAO. | GAO-18-307

4.1 Key properties of solvents

There are a number of properties that 

influence which solvent to select for a 

particular use. For example, the polarity of a 

solvent—that is, the distribution of electrical 

charges within the solvent molecules—

significantly affects how that solvent behaves. 

Depending on its chemical structure, a solvent 

can be classified as polar or nonpolar.87

Electrons are not symmetrically distributed in 

molecules of polar compounds, resulting in 

partially positively and negatively charged 

regions.88 In contrast, molecules of nonpolar 

 87Although polarity is a property often used to predict the 

solubility of compounds, it can be difficult to quantify. 

Classifying solvents as polar or nonpolar is a simplification of 

the concept.

88Electrons are subatomic particles that have a negative 

electric charge.

compounds have a relatively symmetrical

distribution of electrons. Compounds can also

be ionicconsisting of positively and 

negatively charged component(s), or ions, 

held together by electrostatic forces.89 The 

concept of “like dissolves like” is a simplified 

rule for understanding solvents and solubility. 

For example, polar solvents tend to dissolve

other polar compounds or ionic compounds 

(e.g., salts), while nonpolar solvents tend to

dissolve other nonpolar molecules (e.g., fats

and oils).90 The term miscible describes two 

liquids that are completely soluble in each 

other. For example ethanol and water, which 

are both polar, are miscible, whereas 

 89Table salt, for example, is an ionic compound called sodium 

chloride, consisting of positively charged sodium ions and a 

negatively charged chloride ions.

90Hydrocarbons are compounds made up of only hydrogen and 

carbon atoms.
Technology Assessment GAO-18-307 51

hydrocarbons and water are not. Solvents and 

other compounds can also be classified as 

hydrophilic (having affinity for water, e.g., 

miscible with or soluble in water); 

hydrophobic (lacking affinity for water, e.g., 

not miscible with or soluble in water); or 

amphiphilic (molecules that contain both 

hydrophobic and hydrophilic regions, such as 

surfactants). 

Solvents can also be either protic or aprotic. 

Protic solvents contain hydrogen atoms 

bound to an electron-attracting atom such as 

an oxygen or nitrogen atom. These hydrogen 

atoms allow the solvent and solute molecules 

to form hydrogen bondsa strong 

interaction between or within molecules. 

Although aprotic solvents can also contain 

hydrogen atoms, those atoms are not bound 

to electron-attracting atoms such as oxygen 

or nitrogen and therefore do not participate 

in hydrogen bonding. Solvents that are both 

quite polar and aprotic are called dipolar 

aprotic.

4.2 Sustainability challenges of 

solvents

The environmental impact of a solvent can be 

assessed using an environmental health and 

safety method or a life cycle method, the 

results of which can be combined into an 

overall assessment. The goal of the 

environmental health and safety assessment 

method is to identify potential hazards of 

solvents. An environmental health and safety 

assessment considers factors such as the 

flammability, toxicity, and environmental 

persistence of the solvent. The LCA method 

evaluates the environmental impact of the 

solvent through all the stages of its life cycle, 

including production, use, and potential 

recycling or disposal (see chapter 1 for a more 

detailed discussion of LCA). An LCA considers 

factors such as nonrenewable resource 

depletion, emissions associated with the 

incineration of solvent waste, and the energy 

required for solvent recovery and recycling 

(see fig. 13).91 The combination of both 

assessments can help chemists to select 

solvents with the least environmental impact. 

These assessments can also be applied to new 

solvent technologies, some of which are 

discussed later in this chapter. 

 91Although we do not discuss it in depth in this report, solvent 

recycling can make an important contribution to the life cycle 

assessment of a process.
Technology Assessment GAO-18-307 52

Figure 13: The solvent life cycle

Note: Adapted with permission from J. H. Clark and S. J. Tavener, “Alternative Solvents: Shades of Green,” Organic Process Research 

& Development, vol. 11 (2007). Copyright 2007 American Chemical Society. 

There are several classes of solvents that are 

problematic from a sustainability or 

regulatory perspective but that are 

particularly challenging to replace. For 

example, halogenated compounds such as 

chlorinated solvents and dipolar aprotic 

solvents, among others lack sufficient 

replacement options.92 In December 2016, 

EPA released the list of the first 10 chemicals 

for assessment under the amended TSCA 

regulations; the list includes dipolar aprotic 

and halogenated solvents (see text box

below).93

 92Halogenated compounds contain one or more atoms from 

the halogen group such as fluorine, chlorine, or bromine. 

9381 Fed. Reg. 91,927 (December 19, 2016).
Technology Assessment GAO-18-307 53

Several regulations in the United States are relevant to solvent use in the chemical industry

In the United States, the Toxic Substances Control Act (TSCA) and the Clean Air Act both have implications for 

solvent use, as do FDA regulations and guidance. The Clean Air Act requires EPA to regulate hazardous air 

pollutantschemicals known or suspected to cause cancer or other serious health effects, such as reproductive 

effects or birth defects, or adverse environmental effectsfrom various industrial facilities. EPA is working with 

state, local, and tribal governments to reduce air emissions of 187 hazardous air pollutants, including some

commonly used solvents. The Clean Air Act also requires EPA to manage ozone-depleting substances, which also 

includes some solvents. FDA has regulations and guidance regarding solvents. FDA regulates additives in food and 

beverage, including some residual solvents, as well as the use of certain solvents as ingredients in cosmetics. FDA 

also provides guidance to industry on residual solvents in pharmaceuticals.

TSCA as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century act requires that EPA now 

systematically prioritize and assess existing chemical substances and manage identified risks. In December 2016, 

EPA published an initial list of 10 chemical substances that will be subject to assessment. Seven out of those 10 

chemical substances could be classified as solvents; 1,4-dioxane, 1-bromopropane, carbon tetrachloride, 

dichloromethane, N-methylpyrrolidone, trichloroethylene, and tetrachloroethylene. TSCA requires that EPA 

choose the first 10 chemical substances from the list of 90 chemical substances on the 2014 update of the TSCA 

Work Plan for Chemical Assessments. TSCA Work Plan chemicals were selected based on their hazard and 

potential exposure, as well as other considerations such as persistence and bioaccumulation.

Source: GAO analysis of scientific literature and agency documents. | GAO-18-307

Chlorinated solvents, such as 

dichloromethane and chloroform, are toxic to 

humans and pose risks to the environment.

While these solvents are widely used, some in 

the industry are making efforts to reduce 

their use. A recent study reported the 

atmospheric concentration of 

dichloromethane—an ozone-depleting 

substance—is increasing rapidly, and that 

continued growth of dichloromethane could 

delay recovery of the ozone layer.94 The 

authors note that it is probable that demand 

for dichloromethane for a number of 

applications is relatively high in developing 

countries such as India. Disposal of these 

solvents can also be challenging or costly. For 

example, the low flammability of 

 94R. Hossaini, M. P. Chipperfield, S. A. Montzka, A. A. Leeson, S. 

S. Dhomse, and J. A. Pyle, “The Increasing Threat to 

Stratospheric Ozone from Dichloromethane,” Nature 

Communications, vol. 8 (2017).

dichloromethane hinders incineration. Due to 

these issues, reducing the use of 

dichloromethane is a goal of many green 

chemistry programs within the 

pharmaceutical industry. Two pharmaceutical 

companies told us that they track use of 

chlorinated solvents as a percentage of total 

solvent use as a sustainability metric. One of 

those companies reported that 

dichloromethane has decreased from 35 

percent to 10 percent of total solvent use 

since they started tracking in 2012.

Chemists commonly use several dipolar 

aprotic solvents, however there are concerns 

regarding the associated toxicity and 

potential negative environmental impact of 

these solvents. Commonly used dipolar 

aprotic solvents include dimethylformamide, 

dimethylacetamide, and Nmethylpyrrolidone. However, these solvents 

are designated as reproductive toxins and 
Technology Assessment GAO-18-307 54

included on the European Union’s 

Registration, Evaluation, Authorisation and 

Restriction of Chemicals (REACH) substances 

of very high concern candidate list.95 Dipolar 

aprotic solvents are difficult to remove from a 

reaction mixture by distillation and therefore 

are usually extracted into water instead. 

Separation from water is also difficult and can 

be energy-intensive or costly. Release of 

wastewater contaminated with these solvents 

presents environmental challenges. 

Finding more sustainable replacements for 

dipolar aprotic solvents has been a challenge; 

however, researchers have reported the use 

of several alternatives. Dipolar aprotic 

solvents are particularly useful for certain 

reactions. For example, nucleophilic 

substitution reactionsa common type of 

reaction used in the pharmaceutical 

industrycan be up to 100,000 times faster 

in dipolar aprotic solvents as opposed to 

protic solvents. According to one study, a

survey of solvent usage in papers published in 

the journal Organic Processes Research and 

Development from the years 1997-2012 found 

that close to 50 percent of the usage of 

dimethylformamide, dimethylacetamide, Nmethylpyrrolidone, and dimethyl sulfoxide 

was in nucleophilic substitution reactions.96

One expert told us that currently there are 

not good replacements for these solvents. 

However, the study that conducted the 

 

95The substances of very high concern candidate list 

aims to ensure that the included hazardous chemicals 

are progressively replaced by less dangerous substances 

or technologies where technically and economically 

feasible alternatives are available.

96C. P. Ashcroft, P. J. Dunn, J. D. Hayler, and A. S. Wells, 

“Survey of Solvent Usage in Papers Published in Organic 

Process Research & Development 1997-2012,” Organic Process 

Research & Development, vol. 19 (2015).

survey cited successful examples of this type 

of reaction in more sustainable solvents, 

including ethanol and 2-

methyltetrahydrofuran (we discuss these 

solvents in more detail later in this chapter). 

Researchers have also recently demonstrated 

this type of reaction in water under mild 

conditions through the use of micellar 

catalysis, which we discuss later in this 

chapter.97 Other potential alternatives for 

dipolar aprotic solvents include organic 

carbonates and biobased cyrene. However, 

one expert told us that neither of these 

substitutes is currently widely employed.

4.3 More sustainable solvent 

technologies

We assessed three general classes of more 

sustainable solvent technologies: (1) biobased 

solvents (VOC or non-VOC)—that is, solvents 

produced from renewable rather than 

petrochemical resources, (2) non-VOC 

solvents, and (3) solvent-free or reducedsolvent strategies to decrease the volume of 

solvents required for a process.98

4.3.1 Biobased solvents

The benefits and challenges of biobased 

solvents—which can provide alternatives to 

petroleum-derived solvents as either a direct 

replacement or a substitute—vary based on 

 97N. A. Isley, R. T. H. Linstadt, S. M. Kelly, F. Gallou, and B. H. 

Lipshutz, “Nucleophilic Aromatic Substitution Reactions in 

Water Enabled by Micellar Catalysis,” Organic Letters, vol. 17 

(2015).

98We identified several other more sustainable solvent 

technologies that are in use or under investigation, including 

eutectic mixtures, fluorous solvents, liquid polymers, and 

switchable solvent systems. However, we did not assess these 

technologies in this report.
Technology Assessment GAO-18-307 55

the nature of each solvent. Biobased solvents

(whether VOC or non-VOC) are sourced from 

renewable raw materials such as forestry or 

agricultural materials. According to a 2013 

report by the International Energy Agency 

and others, use of biobased feedstocks for 

chemical production is a potential game 

changer in terms of reducing greenhouse gas 

emissions.99 The three main benefits are: (1) 

reduced dependency on fossil fuels, (2) 

absorption of carbon dioxide while the 

feedstock source is growing, and (3) the 

feedstock source is renewable and therefore 

may not experience the same price volatility 

in the future as fossil fuels. However, any 

reduction in greenhouse gas emissions must 

be weighed against the energy requirements 

for biobased production, according to the 

report. According to one expert, studies have 

shown that the manufacture of many, but not 

all, organic solvents from biomass may be 

more environmentally damaging or energy 

intensive than their manufacture from 

petroleum. 

Certain biobased solvents may be 

biodegradable or may be safer or less toxic 

than petroleum-derived solvents. However, 

many biobased solvents are VOCs and 

therefore maintain the inherent risks of VOCs 

including atmospheric pollution, flammability, 

and user exposure. Some are toxic or have 

other negative environmental health and 

safety properties. Some biobased solvents 

can serve as a direct replacement for 

conventional solvents without having to alter 

the equipment or process. Other biobased 

 99International Energy Agency (IEA), International Council of 

Chemical Associations, and Dechema Gesellschaft für 

Chemische Technik und Biotechnologie e. V., Technology 

Roadmap: Energy and GHG Reductions in the Chemical Industry 

via Catalytic Processes, (Paris, France: IEA Publications, 2013).

solvents are not direct replacements but may 

lead to opportunities for new technologies. 

One company told us that new biobased 

materials are frequently more expensive than 

other materials, which presents a challenge to 

their use. There is ongoing research in 

academia and industry examining chemical 

processes that may be suitable for these new 

solvents. 

We identified several examples of biobased 

solvents and the associated benefits and 

challenges they may face in industrial 

applications. Although a variety of solvents 

and solvent classes can be renewably 

sourced, current technology does not offer 

direct replacements for all conventional 

solvents. Because biobased raw materials, 

such as cellulose and starch, contain oxygen 

atoms, most biobased solvents are oxygencontaining compounds such as alcohols, 

esters, and ethers. Other solvents, such as 

certain hydrocarbons, can potentially be 

produced from cellulose and lignocellulose 

materials. Chlorinated solvents cannot 

currently be produced from biobased raw 

materials. However, as previously discussed,

many in the industry are already working to 

reduce the use of this class of highly regulated 

solvents in part due to their environmental 

and health hazards. We discuss several

biobased solvents below. 

Ethanol

Ethanol is a conventional solvent that can be 

renewably sourced for use in several 

industrial applications. Ethanol is an 

inexpensive product of fermentation of starch 

crops or can be produced from cellulose from 

waste materials. Ethanol is biodegradable, 

less toxic than some other solvents, and 

miscible with both water and many organic 
Technology Assessment GAO-18-307 56

solvents. However, ethanol is a volatile 

solvent and has a relatively low flash point, 

which can present hazards to users.100 A 

manufacturer of cellulosic ethanol cited 

several advantages, including that it is 

sourced from a non-food feedstock and its 

production uses less water compared to the 

conventional production of ethanol. They also 

told us that production of cellulosic ethanol as 

a replacement solvent faces challenges, 

including building a supply chain, variability in 

the supply and quality of agricultural 

feedstocks, scalability, public awareness, and 

public policy uncertainty. Ethanol is 

commonly used in products such as scents, 

flavors, and medicines. It is also 

conventionally used as a solvent in chemical 

processes including both reaction and 

separation applications. Ethanol can also 

serve as a solvent in formulated products. For 

example, DuPont and Procter & Gamble 

announced a partnership in 2014 to use 

ethanol derived from cellulose in Tide® Cold 

Water laundry detergent. 

1,3-Propanediol

1,3-Propanediol is another biobased solvent 

used in formulated products. A joint team 

from DuPont and Genencor International, Inc. 

won a Presidential Green Chemistry Challenge 

Award in 2003 for the microbial production of 

1,3-propanediol from glucose sourced from 

renewable cornstarch (see text box below).101

 100The flash point is the lowest temperature at which sufficient 

vapor of a volatile liquid has collected in order to form an 

ignitable mixture with air.

101For a full list of Presidential Green Chemistry Challenge 

Awards from 1996-2016, see 

https://www.epa.gov/sites/production/files/2016-

10/documents/award_recipients_1996_2016.pdf, accessed 

August 1, 2016.

Representatives from a chemical 

manufacturer told us that in addition to being 

sustainably and renewably sourced, 1,3-

propanediol is nontoxic and safe for food. 

They also mentioned that it is a USDA 

Certified Biobased Product and that there is 

customer and consumer value in biobased 

alternatives. However, they also mentioned 

that building new processes at commercial 

scale can be expensive and high-risk. 1,3-

Propanediol can be used as a solvent in 

personal care products as well as household 

cleaning products such as liquid laundry or 

hand detergents, dish detergent, hard surface 

cleaners, glass cleaners, and carpet and rug 

cleaners.

Presidential Green Chemistry Challenge Award 

for the Microbial Production of 1,3-

Propanediol

In addition to its use as a biobased solvent, 1,3-

propanediol is a building block for other chemical 

products. According to the Presidential Green 

Chemistry Challenge Award summary for this 

technology, for more than 50 years, scientists 

recognized the performance benefits of polyesters 

produced with 1,3-propanediol; however, the high 

cost of manufacturing the ingredient using 

petroleum feedstock and traditional chemistry kept 

it from the marketplace. The microbial process is 

both less expensive and more productive than the 

traditional chemical process. In terms of 

sustainability, the microbial process allowed 

replacement of a petroleum feedstock and increased 

both the energy efficiency and safety of the 

manufacturing process. Polymers containing 1,3-

propanediol are used in a variety of applications 

including apparel and upholstery. (For more 

information on the Presidential Green Chemistry 

Challenge Awards, see chapter 6.)

Source: GAO analysis of EPA documents. | GAO-18-307
Technology Assessment GAO-18-307 57

Glycerol

Biobased glycerol, produced from vegetable 

oils or as a byproduct of the biodiesel 

industry, and its derivatives can be used as 

solvents in biocatalysis, among other 

applications.102 Glycerol is inexpensive, 

renewable, nontoxic, and nonflammable. 

Glycerol is available in a variety of grades 

based on the level of purity. Crude glycerol is 

both the least expensive and the most 

environmentally-friendly grade because it 

requires the least amount of purification to 

produce. Glycerol is a polar solvent and has 

been shown to increase the rate of some 

organic reactions. However, it is not a good 

solvent for hydrophobic compounds or for 

certain gases including hydrogen, oxygen, and

carbon dioxide. Glycerol is also highly viscous, 

which can be drawback for certain chemical 

processes.103 The price of biobased glycerol is 

tied to fluctuations in the biodiesel market, 

which could affect its adoption as a solvent by 

the chemical industry. Researchers have 

demonstrated the use of biobased glycerol as 

a medium for a variety of reactions, including 

as a substitute for dipolar aprotic solvents. 

Glycerol and several derivatives show promise 

as a reaction medium for biocatalysis among 

a variety of other applications. Glycerol 

carbonate, for example, is an ingredient in 

personal care products. However, the 

synthesis required to make glycerol 

derivatives remains an issue from a 

sustainability perspective.

 102A derivative of a chemical is another chemical that is 

structurally similar to or made from it. See chapter 3 for more 

details on biocatalysis.

103A viscous liquid is resistant to flow, meaning it has a thick 

consistency. Molasses is a classic example of viscous liquid.

Methyl soyate

Methyl soyate is a type of biodiesel used 

industrially as a cleaning and degreasing 

solvent. Methyl soyate is produced from 

methanol and soybean oil—the predominant 

seed oil crop in the United States. Methyl 

soyate is nontoxic, nonhazardous, and 

biodegradable. Methyl soyate evaporates 

slowly and is not considered a hazardous air 

pollutant or an ozone-depleting substance; 

however if used alone it can leave behind a 

residue which is a drawback in certain

applications. In cleaning formulations, use of 

a more volatile co-solvent such as ethyl 

lactate can mitigate this drawback. Methyl 

soyate and ethyl lactate blends can replace 

chlorinated and other petroleum-derived 

solvents in applications such as paint 

strippers, printing ink cleaners, and graffiti 

removers. Other potential solvent 

applications of methyl soyate include 

household and industrial cleaners, paints, and 

oil spill cleanup. For extraction applications, 

the distribution behavior of various 

substances in methyl soyate in liquid-liquid 

extraction processes with water has been 

shown to be comparable to that of 

conventional solvent-water systems.

104

Ethyl lactate

Lactate esters such as ethyl lactate are 

another class of biobased solvents with a 

variety of applications. The parent compound 

for this class, lactic acid, is produced via 

fermentation of a variety of carbohydrates, 

such as corn starch, sugar beets, sugarcane, 

 104Liquid-liquid extraction is a technique to transfer a dissolved 

substance from one liquid phase to another (immiscible or 

partially miscible) liquid phase in contact with it and in which it 

is more soluble.
Technology Assessment GAO-18-307 58

or wheat. Ethyl lactate is produced through 

the reaction of ethanol and lactic acid in a 

low-cost process with water as the only 

byproduct. Lactate esters are generally 

biodegradable or recyclable and not 

corrosive, carcinogenic, or ozone-depleting. In 

addition to the environmental advantages 

associated with lactate esters, as a solvent 

ethyl lactate is compatible with water, 

miscible with organic compounds, and has a 

relatively high boiling point (154 °C). Ethyl 

lactate is a possible substitute for 

halogenated solvents. Industrially, ethyl 

lactate is used for several applications 

including as a solvent in the coatings and inks 

industry and as a biodegradable cleaning 

fluid. It has also been used as a reaction 

medium, although to a lesser extent than 

some other biobased solvents. 

2-Methyltetrahydrofuran

2-Methyltetrahydrofuran is a biobased 

solvent with growing use in industry. It can be 

produced from renewable raw materials 

including agricultural waste such as corncobs. 

This solvent has a number of properties in 

common with some conventional solvents 

such as tetrahydrofuran. However, 2-

methyltetrahydrofuran is less miscible with 

water than tetrahydrofuran, thus facilitating 

separation from water and reducing waste in 

some cases. 2-Methyltetrahydrofuran suffers 

from some of the same drawbacks as related 

solvents. For example, 2-

methyltetrahydrofuran is susceptible to the 

formation of peroxides when exposed to air if 

no stabilizer is present which can be explosive 

under certain circumstances. In preliminary 

toxicological studies, 2-

methyltetrahydrofuran was not associated 

with genotoxicity.

105 The use of 2-

methyltetrahydrofuran in industry is growing. 

For example, in 2011, the pharmaceutical 

company GlaxoSmithKline reported 16 

percent of the chemical processes in their 

pilot plants used 2-methyltetrahydrofuran in 

2007-2009, up from 3.5 percent in 2005-

2006.106 A study from 2015 proposed 2-

methyltetrahydrofuran as an industrial 

alternative to n-hexane in the extraction of 

vegetable oils from their source plants.107 It is 

also considered a viable substitute for 

chlorinated solvents in both extraction and 

reaction medium applications.

d-Limonene

Terpenes such as d-limonene are biobased 

hydrocarbons used in a number of 

applications. Terpenes are sourced from 

essential oils of plants, including citrus and 

conifers. d-Limonene, which is extracted from 

citrus peel waste, has the most widespread 

use as a solvent. In addition to being 

biobased, d-limonene is less volatile than 

conventional solvents and therefore poses a 

lower risk of exposure to humans and the 

environment. FDA regulations list d-limonene 

as a generally safe for use as a flavoring 

 105Genotoxic substances are a type of carcinogen, specifically 

those capable of causing genetic mutation and of contributing 

to the development of tumors. This includes certain chemical 

compounds, metals, and certain types of radiation. 

106R. K. Henderson, C. Jiménez-González, D. J. C. Constable, S. 

R. Alston, G. G. A. Inglis, G. Fisher, J. Sherwood, S. P. Binks, and 

A. D. Curzons. “Expanding GSK’s Solvent Selection Guide −

Embedding Sustainability into Solvent Selection Starting at 

Medicinal Chemistry,” Green Chemistry, vol. 13 (2011).

107A.-G. Sicaire, M. Vian, F. Fine, F. Joffre, P. Carré, S. Tostain, 

and F. Chemat. “Alternative Bio-Based Solvents for Extraction 

of Fat and Oils: Solubility Prediction, Global Yield, Extraction 

Kinetics, Chemical Composition and Cost of Manufacturing,” 

International Journal of Molecular Sciences, vol. 16 (2015).
Technology Assessment GAO-18-307 59

substance.108 However, the regionality and 

seasonality of the supply of the citrus 

feedstock can present a challenge to the 

production of d-limonene. d-Limonene has 

been used in a variety of products, including 

as an ingredient in household and personal 

care products due to its fragrance properties, 

and has promise as a cleaning or degreasing 

solvent. One formulator told us that dlimonene is one of the top 10 raw materials 

they use and it has been found to be ozonefriendly. Due to its low polarity, d-limonene

offers a replacement for petroleum-derived 

hydrocarbons, such as n-hexane, which are 

commonly used in the extraction of fats and 

oils from natural sources. One drawback of 

this approach is that separating d-limonene 

from the desired fats and oils after extraction 

may be more energy intensive than the 

removal of n-hexane given its higher boiling 

point. Although the use of d-limonene as a 

solvent for organic reactions has not been 

studied as extensively, researchers have 

reported examples of d-limonene as a 

reaction medium in catalytic reactions, 

including biocatalysis. d-Limonene has also 

found use as a solvent in the hydraulic 

fracturing industry (see text box).

 10821 C.F.R. §182.60.

Citrus terpenes and hydraulic fracturing

A representative from Florida Chemical, a company 

that produces terpene products, told us that the 

hydraulic fracturing industry is using d-limonene 

and other citrus terpenes as green solvents. The 

chemicals, as part of the fracking fluid mixture, are 

injected into a wellbore to break apart shale or 

sand and allow natural gas and crude oil products 

to escape. According to the representative, dlimonene is a better solvent for asphaltene and wax 

than the traditionally used fossil fuel products, and

the hydraulic fracturing industry is concerned about 

contamination of source and groundwater and 

therefore values the low toxicity of citrus terpenes.

Source: GAO analysis of industry interview. | GAO 18-307

4.3.2 Non-volatile organic compound 

(non-VOC) solvents

Water

Although water is in some ways considered an 

ideal sustainable solvent, it also faces certain 

challenges and tradeoffs. In addition to being 

environmentally benign, nontoxic, and 

nonflammable, water is also abundant and 

inexpensive. Water is sometimes referred to 

as ‘nature’s solvent’ as many biochemical 

reactions occur in water. However, many 

chemicals (e.g., nonpolar hydrocarbons) are 

not soluble in water. Other chemicals may 

react with water instead of undergoing the 

desired reaction. Many catalysts are 

moisture-sensitive and become inactive in the 

presence of water. Modern organic chemistry 

processes have been developed for the most 

part in conventional organic solvents. 

However, there are several methods available 

to expand the utility of water as a reaction 

medium when working with hydrophobic 

chemicals including aqueous-organic biphasic 

systems and micelles.
Technology Assessment GAO-18-307 60

The use of water as a reaction medium can 

sometimes affect the outcome of a reaction in 

advantageous ways. For example, some 

reactions have been shown to proceed faster 

in water than in conventional organic solvents 

even though the components may not fully 

dissolve. The hydrophobic effect—a 

phenomenon believed to contribute to this 

observation—describes the fact that nonpolar 

molecules tend to aggregate in water to 

minimize interactions with water molecules. 

Water can provide additional benefits as a 

reaction medium even in cases where it does 

not accelerate the rate of reaction—for 

example, through improved temperature 

control and easier product separation.

Despite its advantages, water is not always 

the most sustainable reaction medium, often 

due to issues associated with recovery of 

products or removal of byproducts. In some 

cases, large amounts of organic solvents are 

necessary to separate the desired product 

from the aqueous (water-based) reaction 

medium, which could counteract 

sustainability gains. The resulting aqueous 

solution could also be contaminated by 

organic compounds. In the case of reactions 

that generate salts as byproducts, such as 

certain metal-catalyzed cross-coupling 

reactions, removing the salt in order to 

recycle the water can be energy-intensive. In

contrast, when using a VOC solvent, 

unwanted salt byproducts can often be 

removed by filtration and the low-boiling 

solvent can easily be recovered by distillation. 

Chemistry in natural systems predominantly 

occurs in water as the solvent, making it a 

good solvent for related processes and 

chemicals. Water is used in many biocatalytic 

reactions. It is also a good solvent for many 

inorganic chemicals and certain organic 

chemicals such as sugars, proteins, and some 

acids. Chemists have also studied water as a 

reaction medium for transformations of 

biobased raw materials. For example, 

cellulose can be broken down in water to 

yield glucose under relatively mild reaction 

conditions. Water is also used in steam 

distillation, a process for isolating heatsensitive chemicals, such as essential oils. 

Aqueous-organic biphasic systems are an 

effective method for using water as a solvent 

when working with hydrophobic chemicals, 

which can facilitate additional sustainability 

benefits such as catalyst recycling. In a 

biphasic system, hydrophobic substances are 

dissolved in the organic phase while 

hydrophilic substances are dissolved in the 

water phase. Aqueous-organic biphasic 

systems can be especially useful for catalyst 

recycling. The catalyst can be selected to 

preferentially dissolve in the water phase, 

facilitating recovery and recycling from the 

rest of the reaction mixture, which remains in 

the organic phase. Vigorous stirring can be 

used to increase contact between the 

hydrophilic catalyst and hydrophobic 

reactants at the aqueous-organic interface. In 

another technique, a phase-transfer catalyst

is added to the reaction, which facilitates the 

transport of reactants between phases 

thereby increasing the rate of reaction. Water 

can also form biphasic systems with other 

non-VOC solvents such as supercritical carbon 

dioxide and others, further reducing the use 

of VOCs in a process. 

Micelles are another method for using water 

as a reaction medium with hydrophobic 

chemicals. A micelle is a sphere (or bubble) 

with a wall composed of a single layer of 

molecules. In water, micelles are formed by 

surfactants whose hydrophobic portions point 
Technology Assessment GAO-18-307 61

toward the center of the micelle to form the 

interior ‘lining’ of the bubble while the 

hydrophilic portions interact with water on 

the exterior of the micelle.109 Hydrophobic 

molecules will aggregate inside the 

hydrophobic center of these micelles and 

reactions can occur between the molecules 

gathered there. (See fig. 14.) One estimate is 

 109Commercial surfactants are typically derived from 

petroleum, but there are efforts underway to make from 

biobased feedstocks new surfactants that could be 

biodegradable or biocompatible. 

that micelles are used to produce ten million 

tons of polymer each year, primarily for use in 

environmentally friendly coatings.110 Micellar 

catalysis allows for catalysis of hydrophobic 

reactants or the use of hydrophobic catalysts 

in water. Micelles can be used with metal 

catalysts, nanoparticle catalysts, and 

organocatalysts.111

 110F. M. Kerton and R. Marriott, Alternative Solvents for Green 

Chemistry, 2nd ed. (Cambridge, U.K.: The Royal Society of 

Chemistry, 2013), 102.

111For more on different types of catalysts see chapter 3.
Technology Assessment GAO-18-307 62

Figure 14: Reactions between hydrophobic reactants can occur inside micelles in water

This figure depicts a cross-section of a spherical micelle.

There are several benefits to using micelles 

for catalytic purposes; however, there may be

a limitation to using this method on a large 

scale. In addition to allowing reactions to 

occur in water, micellar catalysis offers other 

sustainability benefits such as facilitating 

production extraction. Similar to biphasic

systems, an organic solvent that does not mix 

with water can be used to extract 

hydrophobic products from the mixture,

leaving the micelles and catalysts in the water 

phase, which facilitates catalyst recycling. In 

cases where the product is completely 

insoluble in water, it can be collected by 

filtration and product extraction with an 

organic solvent is not necessary. A potential 

limitation is that the amount of reactants 

inside the micelles may be lower than in 

conventional solvents. However, according to 

one of our experts, the limited volume inside 

the micelle can be an advantage, as the 

higher concentrations of reactants found 

there can allow some reactions that require 

the addition of heat when run in conventional 

solvents to proceed at ambient temperature 

instead.

One study by a pharmaceutical company 

found that use of surfactant technology in 

water in the synthesis of an active 

pharmaceutical ingredient provided both 

environmental and economic benefits as 
Technology Assessment GAO-18-307 63

compared to the conventional route.112 The 

study compared two possible synthetic routes 

to an active pharmaceutical ingredient: 

conventional catalysis using organic solvents, 

and catalysis using surfactant technology in 

water. The authors used the metric PMI to 

assess the environmental performance of the 

two routes.113 Using surfactant technology,

the authors carried out the entire multi-step 

synthesis in water and reduced the overall 

PMI by over 30 percent as compared to the 

conventional route. The overall yield

increased by five percent as well. Therefore, 

the authors reported both an environmental 

improvement and better process 

performance. In particular, the reduction in 

solvent use—approximately 50 percent—

provided most of the environmental benefits. 

The surfactant technology process produced a 

similar amount of water waste as the 

conventional process and the nature of the 

contamination did not vary, which the 

authors reported as a benefit. For the 

purposes of this study the authors did not 

attempt to recycle the catalyst system. The 

authors propose that the reported process 

could also result in economic benefits due to 

increased yield and decreased costs of raw 

materials, among other reasons.

Supercritical carbon dioxide

Supercritical carbon dioxide is an 

environmentally benign solvent with a 

 112F. Gallou, N. A. Isley, A. Ganic, U. Onken, and M. Parmentier, 

“Surfactant Technology Applied Toward an Active 

Pharmaceutical Ingredient: More than a Simple Green 

Chemistry Advance,” Green Chemistry, vol. 18 (2016). The 

authors reported that the process may involve a micellarassisted mechanism, although another mechanism is possible 

and further elucidation was still needed.

113See chapter 2 for a more detailed discussion of PMI.

number of interesting solvent properties; 

however, there are limitations to its use for 

certain applications.114 It is inexpensive, 

nontoxic, nonflammable, and the 

temperature and pressure at which it 

becomes a supercritical fluid are relatively 

mild compared to some other substances. 

However, the use of supercritical fluids also 

violates the green chemistry principle that 

synthetic methods should be carried out at 

ambient temperature and pressure. Chemists 

can adjust, or tune, the solubility of other 

substances in supercritical carbon dioxide by 

changing the pressure of the system. It can 

serve as an inert reaction medium or in 

reactions where carbon dioxide is consumed 

as one of the reactants. After a reaction, 

supercritical carbon dioxide can be separated 

from the product by depressurization, 

reducing energy consumption as compared to 

a process in which organic solvents must be 

removed. Many gases are soluble in 

supercritical carbon dioxide, which is not the 

case for most conventional solvents. 

However, it is nonpolar and may not be a 

suitable solvent for reactions involving polar 

or high molecular weight chemicals. Several 

techniques have been developed to mitigate 

this limitation including the use of cosolvents 

such as alcohols, or the introduction of agents 

such as surfactants to enhance solubility. 

There are several types of reactions for which 

supercritical carbon dioxide is potentially a 

suitable solvent; however, there are still some 

barriers to implementation on a commercial 

scale. Supercritical carbon dioxide may be a 

 114Supercritical fluids are substances that have properties in 

between those of a gas and a liquid at or above a given 

temperature and pressure, known as the critical point. Several 

other supercritical fluids are used by industry as solvents; 

however supercritical carbon dioxide is particularly relevant to 

sustainability efforts.
Technology Assessment GAO-18-307 64

particularly suitable solvent for reactions that: 

(1) run in nonpolar solvents, (2) are solventsensitive and thus likely to be 'pressuretunable', (3) use gaseous reactants, and (4) 

have products of high enough value to offset 

the capital investment required to implement 

this technology. In some cases, the use of 

supercritical fluids in industrial processes is 

not commercially viable, most often due to 

the perceived high energy and equipment 

costs of pressurizing and working with the 

fluids. Special reactors and additional safety 

precautions are usually required for 

conducting reactions at elevated pressure.

However, a 2015 study found that 

pressurizing carbon dioxide only accounted 

for a small portion of the total energy 

consumed in a pilot plant process, and 

therefore concluded that the perception that 

working at higher pressures means higher 

operating costs may not necessarily be 

true.115 A process for the production of 

fluoropolymers such as TeflonTM in 

supercritical carbon dioxide was 

commercialized; however, this process is no 

longer in use by that company.

116 Use of 

supercritical carbon dioxide improves several 

environmental health and safety issues 

associated with the aqueous process for 

certain fluoropolymers, such as eliminating 

the use and disposal of large quantities of 

acid, including the hazardous chemical 

perfluoroctanoic acid (PFOA).

 115L. Martin, C. Skinner, and R. J. Marriott, “Supercritical 

Extraction of Oil Seed Rape: Energetic Evaluation of Process 

Scale,” The Journal of Supercritical Fluids, vol. 105 (2015).

116According to an article written by one of the academic 

inventors of this technology and others, the licensing company 

did not scale the technology up beyond the initial investment, 

not due to problems with the technology but rather based on 

internal economic and other decisions. J. M. DeSimone, S. J. 

Mecham, and C. L. Farrell, “Organic Polymer Chemistry in the 

Context of Novel Processes,” ACS Central Science, vol. 2 (2016).

Supercritical carbon dioxide has been 

demonstrated as a solvent in a variety of 

other applications. For example, supercritical 

carbon dioxide can replace ultrapure water in 

the manufacture of circuits and eliminate the 

need to use an alcohol solvent as a drying 

agent, or replace hazardous dry-cleaning 

chemicals. It can also be used to separate or

purify substances in a process called 

supercritical fluid chromatography, providing 

an alternative to conventional liquid 

chromatography techniques that contribute 

significantly to organic solvent waste. One 

company representative we talked to told us 

that the use of this technology in the 

pharmaceutical industry has grown in the past 

5 to 10 years. However, the representative

cited the upfront costs of instrumentation 

and infrastructure, the high pressures 

required to run the process, and the solubility 

limitations of supercritical carbon dioxide due 

to its nonpolar nature as some of the 

challenges to implementation. Supercritical 

carbon dioxide is also a good extraction 

solvent because it is nontoxic; does not have 

a color, odor, or taste; and is easy to remove 

from the extracted materials, among other 

reasons. It is a potential replacement for nhexane due to its nonpolar nature. The 

beverage, food, flavor, and cosmetic 

industries have used supercritical carbon 

dioxide extraction to process various 

products, for example coffee decaffeination. 

Instrumentation for supercritical 

chromatography and extraction are 

commercially available for both large and 

small scale processes. 

Ionic liquids

The use of ionic liquids as sustainable solvents 

is a popular topic in research; however, there 

is some debate as to sustainability benefits of 
Technology Assessment GAO-18-307 65

this class of compounds. Ionic liquids are 

salts, usually composed of a positively 

charged organic ion and a negatively charged 

organic or inorganic ion, that are liquid at or 

below 100°C—the boiling point of water. Ionic 

liquids generally have low volatility, which is 

the primary potential sustainability gain they 

offer over conventional solvents. However, 

there are concerns about the toxicity as well 

as environmental persistence and footprint of 

ionic liquids. One of our experts told us that 

many ionic liquids have been shown to be 

acutely toxic. However, whether an ionic 

liquid is toxic or nontoxic depends on the 

compound, and according to scientific 

literature and one of our experts, more 

research and data are needed to fully 

understand the toxicity of these compounds. 

The complex synthesis required to make 

some ionic liquids may also reduce their 

sustainability or increase costs. Recent 

research efforts have attempted to address 

these challenges by reducing the toxicity and 

increasing the biodegradability of ionic 

liquids. According to one of our experts, a 

major disadvantage of ionic liquids is that 

often another solvent is required for product 

separation and purification, in which case 

recycling the ionic liquid is usually not 

possible or not economically viable.

Many ionic liquids are available and many 

more combinations of ions are possible, 

making it difficult to describe general 

properties of this class of solvents. Depending 

on their design, ionic liquids may be 

characterized by low volatility, overall 

robustness, and high heat capacity, among 

other properties.117 The solvent properties of 

 117The heat capacity of a substance describes the amount of 

heat required to increase the temperature of a particular 

quantity of the substance by one degree Celsius.

ionic liquids can be tuned by varying the 

positively and negatively charged components 

of the compound (see text box below for an 

example of federal efforts to support the 

development of ionic liquids). Research has 

demonstrated the use of ionic liquids in a 

wide range of applications, including 

extraction of renewable raw materials, 

catalysis, and degreasing. According to one of 

our experts, industry is commercializing 

applications of ionic liquids, but at a slow 

rate.

Example federal government program to 

support the development of ionic liquids

The National Institute of Standards and Technology 

(NIST) hosts an Ionic Liquids Database, ILThermo 

(http://ilthermo.boulder.nist.gov/). The database, 

which was created in 2006 in cooperation with the 

International Union of Pure & Applied Chemistry 

(IUPAC), is a free, web-based research tool that 

allows users worldwide to access current data on 

various properties of both pure ionic liquids and 

mixtures. In creating the database, NIST and IUPAC 

recognized the need for organized, reliable data on 

the properties of ionic liquids, which are critical 

when designing industrial processes.

Source: GAO analysis of agency announcement. | GAO-18-307

In one industrial example, employing ionic 

liquid technology resulted in several benefits,

including increased productivity and recycling 

of materials. This process, known as the 

BASILTM process (Biphasic Acid Scavenging 

utilizing Ionic Liquids), was established in 

2002 by BASF. This process replaces the 

conventional approach for making a raw 

material used in coating and ink technologies. 

In both the conventional and BASILTM 

approaches, hydrogen chloride forms as a 

byproduct of the process and significantly 

decreases the yield if not removed. In the 

conventional process, triethylamine was 
Technology Assessment GAO-18-307 66

added to scavenge hydrogen chloride. 

However, the resulting triethylammonium 

chloride formed a thick mixture that reduced 

the efficiency of the reaction. In the BASILTM 

process, 1-methylimidazole is added to the 

reaction mixture instead; it reacts with the 

hydrogen chloride to form an ionic liquid (1-

methylimidazolium chloride) which melts at 

around 75°C. These conditions reportedly 

increased the reaction rate and increased the 

yield from 50 to 98 percent. In addition, the 

pure product can be easily separated from 

the 1-methylimidazolium chloride, and the 

latter can be recycled back to 1-

methylimidazole and reused. The new process 

also allowed BASF to replace the use of batch 

processing in large reaction vessels with new 

reactor technologies, greatly increasing 

productivity. (For more on the disadvantages 

of batch processing, see chapter 5). 

Figure 15: The redesign of the sertraline manufacturing process

Note: Adapted with permission from G. P. Taber, D. M. Pfisterer, and J. C. Colberg, “A New and Simplified Process for Preparing N-[4-

(3,4-Dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine and a Telescoped Process for the Synthesis of (1S-cis)-4-

(3,4-Dichlorophenol)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine Mandelate: Key Intermediates in the Synthesis of Sertraline 

Hydrochloride,” Organic Process Research & Development, vol. 8 (2004). Copyright 2004 American Chemical Society. For simplicity 

we have omitted some details of the reaction conditions, such as catalysts or some reactants.
Technology Assessment GAO-18-307 67

4.3.3 Solvent-free or reduced-solvent 

technologies 

Reduction in reaction steps

The amount of solvent used in a chemical 

process can also be reduced by simplifying a 

multistep reaction scheme, thereby 

decreasing the volume and number of 

different solvents used. Many conventional 

chemical processes include multiple chemical 

reactions occurring in a stepwise manner. 

Often the desired intermediate compound 

produced in one step is isolated—separated 

from the rest of the reaction mixture—and 

purified before proceeding to the next step. 

The process of separation and purification can 

be solvent-intensive, leading to large 

quantities of solvent waste. Additionally, a 

multistep chemical process may use multiple 

solvents, and cross-contamination of solvents 

can make recycling a challenge.

Examples of this strategy come from the 

pharmaceutical industry, where complex 

multistep processes are commonly used in 

the synthesis of active pharmaceutical 

ingredients. Pfizer redesigned the synthetic 

process for sildenafil citrate (brand name 

Viagra®

) in transitioning from the medicinal 

chemistry route used in the early stages of 

drug development to the commercial route of 

production.118 Pfizer developed a more 

efficient synthetic process, while also moving 

steps involving toxic chemicals to the 

beginning of the process and the cleaner 

steps closer to the final product. The new 

process reduced the number of purification 

 118P. J. Dunn, S. Galvin, and K. Hettenbach, “The Development 

of an Environmentally Benign Synthesis of Sildenafil Citrate 

(ViagraTM) and Its Assessment by Green Chemistry Metrics,” 

Green Chemistry, vol. 6 (2004).

steps and consequently the volume of solvent 

used. The process change together with the 

introduction of a solvent recovery system 

reduced the volume of organic waste 

generated in the production of one kilogram 

of product from 1,300 liters to 7 liters. They 

also eliminated the use of chlorinated 

solvents and several other VOCs. In another 

example, Pfizer won a Presidential Green 

Chemistry Challenge Award in 2002 for 

redesigning the synthesis of sertraline, the 

active ingredient in the antidepressant 

marketed as Zoloft®

.

119 In redesigning the 

process, Pfizer streamlined a three-step 

sequence into a single step (see fig. 15).120

They also optimized the process by 

eliminating the need to use, distill, and 

recover four conventional VOC solvents—

dichloromethane, tetrahydrofuran, toluene, 

and hexane—by using the more benign 

solvent ethanol. The use of ethanol as a 

solvent also reduced the need for large 

quantities of a problematic chemical (titanium 

tetrachloride). The final process used two 

different solvents rather than five and 

reduced the total volume of solvent by 76 

percent. 

 119For a full list of Presidential Green Chemistry Challenge 

Awards from 1996-2016, see 

https://www.epa.gov/sites/production/files/2016-

10/documents/award_recipients_1996_2016.pdf, accessed 

September 10, 2017.

120G. P. Taber, D. M. Pfisterer, and J. C. Colberg, “A New and 

Simplified Process for Preparing N-[4-(3,4-Dichlorophenyl)-3,4-

dihydro-1(2H)-naphthalenylidene]methanamine and a 

Telescoped Process for the Synthesis of (1S-cis)-4-(3,4-

Dichlorophenol)-1,2,3,4-tetrahydro-N-methyl-1-

naphthalenamine Mandelate: Key Intermediates in the 

Synthesis of Sertraline Hydrochloride,” Organic Process 

Research & Development, vol. 8 (2004).
Technology Assessment GAO-18-307 68

Solvent-free or neat reactions

Chemical processes that do not use any 

solvents at all may offer the most sustainable 

option in terms of reducing waste. Solventfree reactions can occur between chemicals in 

the liquid, gas, or solid states. For liquid phase 

reactions with no added solvent, often one of 

the reactants may be used in excess, 

essentially forming a solution.121 With 

solvent-free processes there is no reaction 

medium to remove, recycle, or dispose of as 

waste. This can lead to cost savings in 

addition to potential sustainability gains. 

Solvent-free reactions can also be very rapid 

and high yielding. For example, researchers 

reported incorporating a solvent-free step 

into the synthesis of a potential 

antituberculosis drug, which had a higher 

yield than the same transformation 

conducted in ethanol.122 Introduction of a 

solvent-free reaction also facilitated the 

integration of multiple steps, thereby 

decreasing the number of energy-intensive 

separation and purification steps and further 

reducing solvent consumption. The optimized 

process including the solvent-free step 

allowed the authors to achieve almost three 

times the yield while using one-third as much 

solvent as compared to the original synthetic 

approach.

Although solvent-free reactions are common 

in some sectors of the chemical industry, 

there are technical challenges to achieving 

new solvent-free chemical processes, 

 121Such cases may be more appropriately referred as neat 

reactions rather than solvent-free.

122A. Orita, K. Miwa, G. Uehara, and J. Otera “Integration of 

Solventless Reaction in a Multi-Step Process: Application to an 

Efficient Synthesis of PA-824,” Advanced Synthesis & Catalysis, 

vol. 349 (2007).

especially on an industrial scale. Solvent-free 

reactions are well established in some sectors 

of the chemical industry. For example, gas 

phase chemical processes are common in the 

manufacture of bulk chemicals such as 

polyethylene. One drawback to solvent-free 

reactions is that without a reaction medium, 

it can be difficult for heat generated during 

the reaction to dissipate evenly throughout 

the mixture. This can lead to ‘hot spots’ and 

unwanted side reactions. Further, some 

chemical reactions may become explosive 

when conducted in the solid or neat liquid 

state, something which solvent use generally 

prevents. Additionally, these reactions can

lead to highly viscous or solid products, 

making industrial development a challenge. 

As VOCs are used for separation and 

purification in many solvent-free approaches, 

a reaction may be solvent-free while the

chemical process as a whole is not. 

There are techniques with the potential to 

overcome the challenges associated with 

solvent-free reactions at the industrial scale. 

In an approach called mechanochemistry, 

grinding is used to initiate chemical reactions 

in the solid state. One variant of this approach 

is the use of a ball mill—a vessel containing 

the reacting chemicals and ball bearings 

which is shaken at high speed. However, solid 

state reactions do not yet have widespread 

application in industry. In another approach, 

microwave reactors have been reported for 

use in solvent-free reactions that could be 

relevant to the pharmaceutical industry.123

(See text box below for some examples of 

low- and no-VOCs in formulations).

 123A. Kulkarni and B. Török, “Microwave-Assisted 

Multicomponent Domino Cyclization-Aromatization: An 

Efficient Approach for the Synthesis of Substituted Quinolines,” 

Green Chemistry, vol. 12 (2010).
Technology Assessment GAO-18-307 69

Low- or no-VOC formulations in coating technologies

Industry has developed a variety of new coating technologies in response to regulations and environmental 

concerns regarding volatile organic compounds (VOCs). Many industry sectors are currently using coatings, such 

as paints or printing inks, containing low or no VOCs or hazardous air pollutants (HAPs) in the formulation. 

Examples of these coatings include waterborne, biobased solventborne, and powder coatings, among others. 

Several new technologies for low-VOC coatings have received Presidential Green Chemistry Challenge Awards. For 

example, in 2011, Sherwin-Williams developed low-VOC waterborne paints made from recycled soda bottle 

plastic, acrylics, and soybean oil. They manufactured enough of these new paints in 2010 to eliminate over 

800,000 pounds of VOCs. In 2009, Procter & Gamble and Cook Composites and Polymers developed paint 

formulations using biobased Sefose® oils to replace petroleum-derived solvents. Sefose® oils, made from sugar 

and vegetable oil, enabled the production of paints with less than half the solvent. (For more information on the 

Presidential Green Chemistry Challenge Awards, see chapter 6.)

Powder coatings are applied to a surface as a dry powder and do not require any solvent. The powder is sprayed 

electrostatically and then heated to allow the coating to fuse. Powder coatings improve product durability as they 

can protect the product from scratches, corrosion, and other damage. In the 2015, the DOD’s Strategic 

Environmental Research and Development Program (SERDP) awarded its project-of-the-year award to the 

development of powder coating technology for Chemical Agent Resistant Coatings (CARC). (For more information 

on SERDP, see chapter 6.) According to a SERDP press release, at the time of the project the use of conventional 

CARC topcoats contributed 2.3 million pounds of VOCs and hazardous air pollutants to the environment each 

year. The key challenges to developing powder coatings suitable for this application were chemical warfare agent 

resistance, extremely low gloss, and high durability. A collaborative team from industry, academia, and the 

military successfully developed a CARC powder coating technology. These powder coatings emit nearly zero VOCs, 

can be recycled, and are compatible with existing CARC systems. Initial testing also indicates the powder coatings 

have better exterior durability than liquid CARC systems, which is important for corrosion prevention and 

mitigation.

Source: GAO analysis of scientific literature, agency documents, and an agency press release. | GAO-18-307
Technology Assessment GAO-18-307 70

5 Technologies as more sustainable alternatives to batch processing

The historical approach to chemical 

processing for centuries was batch 

processing, in which a chemical process was 

conducted in a closed vessel (batch reactor), 

the resulting mixture was transferred to a 

second vessel for the next step in the process, 

and so on, with the vats cleaned between 

batches so the process could be repeated. 

This approach, which is still widely used in 

some sectors of the chemical industry, raises 

a number of sustainability concerns—

especially when conducted on a large scale. 

These include the significant physical 

footprint required for the equipment; high 

energy and solvent use; and safety concerns 

under certain conditions, such as when high 

pressures are required or when a hazardous 

intermediate is produced in significant 

quantities. Furthermore, processing in batch 

reactors can be labor-intensive and require a 

lot of manual coordination to execute the 

process flow, according to one industry 

representative we interviewed. Therefore, 

the industry is researching and developing 

alternative technologies to improve 

efficiencies in manufacturing while also 

realizing significant gains in sustainability and 

environmental benefits. We assessed two 

such technologies—continuous processing 

and continuous flow microreactors—that can 

help chemical companies address some of 

these sustainability concerns. Table 8

summarizes some of the advantages and 

disadvantages of these two technologies; we 

provide additional details in the remainder of 

the chapter. 

Table 8: Summary of assessment of selected technologies as alternatives to batch processing

Technology Advantages Disadvantages

Continuous 

processing

Reduced physical footprint of a plant.

Savings in capital and operational 

expenditure; lower inventory costs.

Potential for improved product yield and 

quality.

Improved product safety; reduced product 

exposure to the environment, and to 

operators.

Process automation.

In-line analytics result in improved product 

consistency, high product quality, and more 

controllable and repeatable processes.

Global regulatory uncertainty—need to satisfy 

regulatory requirements in multiple countries.

Risk aversion (reluctance to change an already 

validated process).

Economic aspects: cost involved in developing 

new infrastructure for continuous manufacturing.
Technology Assessment GAO-18-307 71

Technology Advantages Disadvantages

Continuous flow 

microreactor

Process safety: smaller reaction volume, 

reduced worker exposure to chemicals, and 

safe completion of hazardous reactions 

involving unstable or potentially explosive 

intermediates.

Smaller scale: results in shorter reaction 

times, lower energy consumption, and 

improved efficiency.

Potential for improved product quality.

Hazard minimization: enhanced reaction 

control, superior heat dissipation, and 

smaller reactor volume allows high 

temperature and high pressure reactions to 

be conducted safely.

Prevention of waste through reduced need 

for solvents.

Ease of scale-up.

Process automation, faster screening of 

reagents, and reduced research and 

development cycle time.

In-line analytics capability results in 

improved product consistency, high product 

quality, and more controllable and 

repeatable processes.

Economic aspects: savings in capital and 

operational expenditure.

Global regulatory uncertainty—need to satisfy 

regulatory requirements in multiple countries.

Risk aversion (reluctance to change an already 

validated process).

Difficulties with reactions involving solids may 

limit the applicability of microreactors.

Highly specialized reactions or complex 

processing conditions can make the adoption of 

continuous manufacturing challenging for 

pharmaceutical and fine chemical industries.

Economic aspects: cost involved in developing 

new infrastructure for continuous manufacturing.

Workforce challenges: may need specialized 

personnel to design, develop, validate and 

operate a continuous flow process.

Source: GAO. | GAO-18-307

5.1 Continuous processing

In contrast to batch processing, in continuous 

processing the reaction mixture is 

continuously pumped through a reactor 

consisting of pipes or tube where reactions 

take place in a continuous mode. Reactants 

can be introduced and byproducts removed 

at appropriate points along the line, while

finished product materials are continuously 

removed at the end. For reactions consisting 

of multiple steps using different conditions or 

components, vessels with different purposes 

can be linked and reaction components can 

flow from one stage to the next. In 2007, the 

ACS GCI Pharmaceutical Roundtable 

highlighted continuous processing as a key 

area where research was required to facilitate 

the development of sustainable 

manufacturing.124

Continuous manufacturing is not new. It has 

been widely used by many sectors of the 

chemical industry for decades. Industries as 

diverse as oil, gas, chemicals, polymers, and 

food currently operate in continuous 

processing mode. One of our experts told us 

that his company uses continuous processing 

 124In 2005, the ACS GCI and global pharmaceutical 

corporations developed the ACS GCI Pharmaceutical 

Roundtable to encourage innovation while catalyzing the 

integration of green chemistry and green engineering in the 

pharmaceutical industry. The activities of the Roundtable 

reflect its member's shared belief that the pursuit of green 

chemistry and engineering is imperative for business and 

environmental sustainability.
Technology Assessment GAO-18-307 72

in most—estimated to be over 95 percent—of 

their production and generally at large scales. 

In contrast, the pharmaceutical industry has 

traditionally been dominated by batch 

processing and only recently has there been a 

drive towards continuous processing. The 

current adoption rate is approximately 5 

percent in the pharmaceutical sector, despite 

one report noting that up to 50 percent of 

reactions could benefit from a continuous 

process.125 In recent years, the 

pharmaceutical industry has started to 

research continuous processing as a 

manufacturing strategy to realize operational 

efficiencies and drive down cost. Continuous 

flow systems have become popular for the 

preparation of fine chemicals such as natural 

products and drugs, especially in academic 

research. For example, a collaborative effort 

between Massachusetts Institute of 

Technology (MIT) and the pharmaceutical 

industry at the Novartis-MIT Center for 

Continuous Manufacturing seeks to develop 

new technologies to replace the 

pharmaceutical industry’s conventional batch 

processing with continuous processing. 

Advantages of continuous processing

One of the key benefits of continuous 

processing is eliminating a fixed batch size, 

thus allowing operational flexibility. Because 

of operational efficiencies achieved with 

continuous flow, the processing time can be 

reduced from months to days. Continuous 

processing product lead times (i.e., the time 

 125T. S. Harrington, L. Alinaghian, and J. S. Srai, “Making the 

Business Case for Continuous Manufacturing in the 

Pharmaceutical Industry” (paper presented at the 25th Annual 

Production and Operations Management Society Conference, 

Atlanta, GA, May 2014).

from raw materials procurement to 

distribution of finished product) are typically 

significantly less than for batch, which can 

substantially reduce inventory carrying costs. 

According to a university research 

presentation, product yield and quality can be 

better in continuous processing compared to 

batch processes.126 Furthermore, continuous 

processing supports many of the key aspects 

of sustainable chemistry that are beneficial to 

workers and the environment, such as lower 

energy consumption, less waste production, 

less consumption of solvents, safer processes, 

and less exposure to chemicals. This 

technology can meet 10 out of the 12 

Principles as outlined by Anastas et al., 

according to authors of a recent scientific 

publication.127

According to one researcher, continuous 

processing is usually preferred for large-scale 

production and is particularly well-suited for 

cases involving considerable heat transfer and 

when high pressures and high or low 

temperatures occur.128 For example, the 

Haber-Bosch process for production of 

ammonia—a gas phase reaction run under 

very high pressure—is a good candidate for 

 126J. Srai, “Exploring Alternative Product-Process Supply 

Network Models in Pharma,” Engineering and Physical Sciences 

Research Council, Center for Innovative Manufacturing in 

Continuous Manufacturing and Crystallization, University of 

Cambridge, 2012, accessed December 20, 2017, 

https://www.cmac.ac.uk/files/media/Jag_Srai.pdf.

127C. Wiles and P. Watts, "Continuous Flow Reactors: A 

Perspective,” Green Chemistry, vol. 14, no. 38 (2012).

128S. Nanda, “Pharmaceutical Engineering: Reactors and 

Fundamentals of Reactors Design for Chemical Reaction,” 

Department of Pharmaceutical Sciences, Maharshi Dayanand

University, 2008, accessed November 14, 2017, 

https://pdfs.semanticscholar.org/e5c1/60655207fd7c0ba00e9

a02f0482a753704f7.pdf.
Technology Assessment GAO-18-307 73

continuous processing.129 Continuous 

processing is generally used for gaseous 

reactions, but is also suitable for some liquidphase reactions. It can reduce the physical 

footprint of a chemical process as well as 

labor costs through automation. This can 

reduce capital and maintenance costs, 

according to a company official we 

interviewed. The official noted that they 

recently converted from batch processing to 

continuous processing for their polystyreneto-styrene conversion process. The 

operational efficiency realized through

continuous processing was critical to making 

the economics workable for them. A leading 

pharmaceutical company told us that they 

have installed an integrated continuous 

processing system at one of their 

manufacturing sites for making tablets from 

drug powders.130 This approach resulted in 

lower upfront investment costs compared to 

traditional facilities, a reduced environmental 

footprint, and savings of up to 35 percent in 

energy and resource use compared to batch 

processing. Estimates from an experimental 

study of process equipment showed 

approximately 10 times less material usage 

and 10 times faster processing than 

conventional batch equipment.

According to a company’s technical product 

literature and a conference paper, the 

 129The Haber-Bosch process is used to synthesize ammonia 

from gaseous nitrogen and hydrogen under high pressure and 

temperature in the presence of a catalyst.

130One pharmaceutical company has adopted a hybrid 

manufacturing approach that incorporates the best of batch 

and continuous manufacturing. That is, only certain segments 

of their operation are run in a continuous mode while the rest 

of the line is still run in a batch mode. Company 

representatives told us that they have used this approach to 

produce drug powders using a batch processing mode and then 

make tablets from the drug powders in a continuous mode.

introduction of high levels of automation and 

reduced manual intervention, together with 

integrating inline analytical tools, provides 

significant benefits in terms of improved 

product consistency, high product quality, 

and a more controllable and repeatable 

process. Other benefits include faster time-tomarket for new drugs by saving time at the 

development stage and in the move from 

development to production. Furthermore, a 

continuous processing system also improves 

overall safety and reduces risk. 

Interconnected unit operations typical of 

continuous processing systems can mean less 

product exposure to the environment and to 

operators, leading to increased product 

safety. 

Pharmaceutical company representatives we 

interviewed told us that some of the 

challenges they face in implementing

continuous processing are: global regulatory 

uncertainty—that is, the need to satisfy 

regulatory requirements in multiple 

countries; risk aversion—a reluctance to 

change an already validated process, 

including the need to have changes in 

manufacturing approved by the Food and 

Drug Administration (FDA); and economic 

uncertainties related to costs involved in 

developing new infrastructure for continuous 

manufacturing. 

5.2 Continuous flow microreactors for 

pharmaceuticals and fine chemicals

Innovations in continuous processing have led 

to the development of new reactor designs 

and support apparatus that allow 

substantially smaller, cleaner, safer, more 

energy-efficient, and more scalable methods 

for the production of pharmaceutical and fine 

(specialty) chemical products. One such 
Technology Assessment GAO-18-307 74

reactor design that is gaining acceptance in 

pharmaceutical and fine chemicals industry is 

the continuous flow microreactor.

As the name indicates, these reactors have 

very small dimensions and use continuous 

flow for chemical processing. Microreactors 

can potentially improve chemical processes 

and routes. However, their integration into 

chemical production processes depends on 

many factors such as technical advancements, 

costs, and production logistics, among others. 

Microreactors have various designs, but one 

design consists of channels of small 

dimensions that are etched in glass, siliconglass, ceramic, polymers, or stainless steel 

that have volumes typically ranging from 50 

microliters to 100 milliliters and channel 

diameters from 50 to 1000 micrometers. The 

chemical reactions take place in a series of 

microchannels forming the core of the reactor 

(see fig. 16). Microreactors can include 

additional elements to precisely control the 

reaction parameters and improve energy 

efficiency. 

Microreactor technology has been adopted 

by companies in the pharmaceutical, flavor 

and fragrance, fine chemical, and agricultural 

chemical industries, among others. New 

generations of pharmaceutical drugs have 

been developed through research using 

microreactors. This technology enables costeffective synthesis and screening of novel 

chemicals with enhanced speed. 

Miniaturization of chemical reactors offers 

many fundamental and practical advantages 

to the pharmaceutical industry. Figure 17

illustrates a generic multi-step synthesis that 

uses continuous flow microreactors to 

produce a drug or other chemical.

Figure 16: Pictures of the channels of a 

microreactor and a production scale continuous 

flow microreactor
Technology Assessment GAO-18-307 75

Figure 17: A generic multi-step synthesis that uses continuous flow microreactors to produce a drug or 

other chemical

Recent publications report on the growing 

interest of pharmaceutical companies in the 

use of microreactor technology for the safe 

and efficient production of drugs. Figure 18

shows continuous flow microreactors used in 

a pharmaceutical production plant.

Figure 18: Continuous flow microreactors in a 

pharmaceutical production plant

According to many pharmaceutical company 

representatives we interviewed, their 

companies are researching continuous flow 

processes because this technology offers 

several benefits, including a smaller 

manufacturing footprint, higher throughput 

compared to a batch process, and safety, 

among others. 

Advantages of microreactor technology 

Innovations in the developing field of 

microreactors have delivered more 

sustainable chemical processes and 

technologies resulting in higher productivity 

and commercially viable high-purity products. 

The advantages inherent to microreactors—

enhanced reaction control, improved safety, 

reduced material inputs, and reduced levels 

of hazardous waste, among others—provide a 

more sustainable option for the chemical 

industry. 

Enhanced reaction control: According to some 

researchers, the key advantage of 

microreactors in organic synthesis is the 

ability to achieve a high degree of control 

over reaction parameters such as 

temperature, pressure, and residence time 

(i.e., the amount of time the reactants spend 

inside the system). The high surface-tovolume ratio of microreactors—potentially 

over 1000 times higher than a batch reactor—

and the reactor design allow for rapid and 

efficient mixing to achieve homogeneity, 

precise control of stoichiometry, high reaction 

speed, and improved heat transfer leading to 

enhanced temperature control compared to a 

batch reactor. According to pharmaceutical 

company representatives we interviewed, for 
Technology Assessment GAO-18-307 76

reactions requiring mixing, continuous 

processing achieves a higher degree of mixing 

than can be achieved in batch processing. 

Furthermore, at this scale the reactants do 

not mix by turbulent flow, as when a batch 

reactor is stirred, but rather diffuse together 

as they move along the channel, allowing for 

a highly controllable and repeatable process.

Microreactors are also much easier to 

pressurize, allowing for high pressure and 

high temperature operations that can be 

advantageous for some reactions. This offers 

additional flexibility for process chemistry. For 

example, solvents such as dichloromethane 

can be used at 70°C, or acetonitrile at 140°C, 

much above their respective boiling points.131

Additionally, the smaller reactor volume 

makes it relatively easier to scale-up 

exothermic reactions without the need for 

special equipment or additional 

precautions.132

Safe completion of hazardous reactions 

involving unstable or potentially explosive 

intermediates: According to pharmaceutical 

company representatives we interviewed, a 

continuous flow microreactor provides an 

opportunity to safely handle hazardous 

materials—including potentially explosive 

intermediates such as azides that may form 

during a reaction—because such 

intermediates move right into subsequent 

 131These solvents have boiling points of 40°C and 82°C 

respectively at normal atmospheric pressure. Thus, higher 

pressure operation elevates their boiling points so they can 

remain in liquid phase even at temperatures above their boiling 

points. Putting the solvent in a super-heated state above its 

normal boiling point speeds up the reaction.

132An exothermic reaction releases heat into its surroundings.

reactions as soon as they are produced.133 For 

example, a review article by Mason and 

colleagues reported a well-controlled and 

direct fluorination reaction (a carbon–fluorine 

bond-forming reaction that introduces 

fluorine into a compound) in microreactors.134

These reactions typically cannot be run on a 

large scale because of their exothermicity, 

potential for explosion, and lack of selectivity. 

According to one of our experts, while the use 

of inherently hazardous substances does not 

meet the goals of sustainable chemistry, a 

microreactor can make their use in a process 

possible. 

Furthermore, some exothermic reactions 

require extremely low temperatures to 

control—as low as –80°C, which can be very 

challenging to achieve, requiring costly 

cryogenic systems—and may not be practical 

on a large scale. For these processes, a 

continuous flow microreactor can be 

considered as an alternative to low 

temperature reactions, because at very small 

volumes, managing temperature becomes 

less important, according to pharmaceutical 

company representatives we interviewed. The 

unique heat transfer characteristics of a 

continuous flow microreactor allow highly 

exothermic reactions to be conducted in a 

controlled manner at significantly higher 

temperatures than in batch processing, thus 

decreasing the overall process energy 

demands. 

 133Azides are any class of chemical compounds containing 

three nitrogen atoms as a group, represented as (–N3). Most 

azides are unstable substances that are highly sensitive to 

shock and have explosive characteristics. 

134B. P. Mason, K. E. Price, J. L. Steinbacher, A. R. Bogdan, and 

D. T. McQuade, “Greener Approaches to Organic Synthesis 

Using Microreactor Technology,” Chemical Reviews, vol. 107, 

no. 6 (2007). Fluorinated molecules are valuable as 

pharmaceuticals and agricultural chemicals, among other uses.
Technology Assessment GAO-18-307 77

In another example, tetrazoles are not suited 

for large-scale synthesis since explosive 

reagents, toxic metal-containing compounds, 

or an excess of azide are required.135 The 

hazard with azide use is the generation of 

hydrazoic acid, which is a volatile and 

explosive liquid. Palde and Jamison reported a 

safe and efficient synthesis of tetrazole 

products from nitrile compounds and sodium 

azide performed in a flow microreactor that 

minimized safety risks while allowing a 

shorter reaction time due to the flexibility of 

operating at elevated temperature and 

pressure.136 The authors concluded that the 

most important attributes of this process—

high yield, near-equal nitrile:azide ratio, 

minimal hydrazoic acid generation, and short 

reaction time—are collectively possible only 

because the reactions can be conducted at

elevated temperature (190°C). This critical 

reaction feature is feasible only in the 

continuous flow format, wherein there is no 

headspace in which hydrazoic acid could 

accumulate to an explosive level. In contrast, 

a closed-system batch process at 190°C would 

be far too hazardous, and without elevation 

of the reaction temperature, the reaction rate 

would be well below a usable level. Thus, the 

continuous flow microreactor made it 

possible to safely produce tetrazoles on a 

commercial scale. 

Shorter reaction time: Continuous flow 

microreactors generally increase the 

 135Tetrazoles are an important class of cyclic compounds which 

are used in a wide range of applications such as organocatalysis 

and transition metal catalysis, as propellants and explosives, 

and perhaps most commonly in medicinal chemistry. Their 

wide utility has prompted significant efforts towards their safer 

synthesis.

136P. B. Palde and T. F. Jamison, “Safe and Efficient Tetrazole 

Synthesis in a Continuous-Flow Microreactor,” Angewandte 

Chemie International Edition, vol. 50, issue 15 (2011).

efficiency of a process, which is reflected in a 

decrease in total reaction time. This is 

possible through better temperature control 

compared to batch processing. Shorter 

reaction times allow for lower energy use, 

especially in high or low temperature 

reactions or for reactions requiring very 

precise temperature control. The improved 

efficiency also leads to more selective 

chemistry, which reduces waste. Therefore, a 

short reaction time generally correlates to 

lower waste, less energy consumption, and a 

more efficient reaction overall. For example, 

scientists from Eli Lilly reported on a multistep flow synthesis of the drug fluoxetine, the 

active ingredient in Prozac®

, in 2011. The flow 

reactor afforded a shorter reaction time and 

the safe handling of hazardous intermediates. 

In general, the hazard potential of strongly 

exothermic or explosive reactions can be 

significantly reduced because of ease of 

control of process parameters—including 

pressure, temperature, residence time, and 

flow rates—in reactions that take place in 

small volumes. 

Prevention of waste through optimization of 

solvents: According to authors of a recent 

scientific publication, reaction solvents 

contribute greatly towards waste generation 

in synthetic processes. Performing reactions 

under solvent-free conditions is still a 

desirable approach.137 However, in batch 

reactions, there is often poor thermal 

management and solvents are needed to 

keep solutions dilute and prevent an 

uncontrolled reaction. Thus, batch processes 

can be wasteful.138 In contrast, continuous 

 137Wiles and Watts, "Continuous Flow Reactors,” 38.

138For example, Gerogiorgis and Jolliffe reported that the Efactor (waste-to-product ratio) of a batch procedure could be 

as high as 25-100 for drugs, indicating that 25-100 kg of waste 
Technology Assessment GAO-18-307 78

flow microreactors have much better thermal 

management. Therefore, it is possible to 

manage such reactions in a safe and efficient 

manner in the absence of a diluting solvent. 

Thus, continuous flow microreactors help to 

prevent waste as they are more amenable to 

low-solvent or no-solvent reaction conditions. 

In this regard, Jamison and co-workers 

developed a continuous flow process using a 

microreactor for the synthesis of 

diphenhydramine hydrochloride, which is an

active ingredient in several widely used 

medications (e.g., Benadryl®

, Tylenol® PM) and 

has a worldwide demand higher than 100 

tons/year.139 By using a microreactor at 175°C 

with a residence time of 16 minutes, their 

process minimized waste and reduced 

purification steps and production time with 

respect to existing batch synthetic routes. The 

reaction rate was also enhanced by running 

the reaction at a higher temperature (above 

the boiling point of the reactant) under 

solvent-free conditions. Similarly, Merck and 

Lonza devised a simpler and safer continuous 

flow synthesis of efavirenz (an essential drug 

for the treatment of human 

immunodeficiency virus (HIV)) without the 

use of toxic solvents that led to its shortest 

manufacturing route. Continuous flow 

reactions also align with atom economy (a 

measure of the percentage of the mass of 

reactants that are incorporated into the 

product), another metric to assess waste. 

Because continuous flow allows for enhanced 

control over the reaction conditions, high-

 are generated for every 1 kg of drug produced. D. I. Gerogiorgis 

and H. G. Jolliffe, “Continuous Pharmaceutical Process 

Engineering and Economics,” Chimica Oggi - Chemistry Today, 

vol. 33, no. 6 (2015).

139D. R. Snead and T. F. Jamison, “End-to-End Continuous Flow 

Synthesis and Purification of Diphenhydramine Hydrochloride 

Featuring Atom Economy, In-line Separation, and Flow of 

Molten Ammonium Salts,” Chemical Science, vol. 4 (2013).

purity products can be produced. This reduces 

waste that may otherwise be produced from 

subsequent purification processes. 

Automated process optimization and analysis: 

According to a company’s microreactor

technology review, much of the effort of 

organic chemists is consumed in searching for 

optimal reaction conditions to achieve a 

particular transformation resulting in a 

specific molecular target. For example, many 

organic transformations depend on multiple 

factors that determine the outcome of the 

reaction. Thus, process optimization 

frequently requires an investment of time and 

large quantities of valuable starting materials. 

Additionally, in traditional batch processing, 

reactions may take days to optimize because 

processing takes place in a series of discrete 

steps, with hold times between steps so 

samples can be tested offline for quality. In 

contrast, in a flow process, a sequence of 

reactions can be run continuously through the 

system. High levels of automation and rapid 

screening of reaction conditions reduces 

processing time. That is, process monitoring is 

automated in continuous processing and is 

carried out more frequently than in batch 

processing. Reaction parameters such as 

reaction time, stoichiometry, temperature, 

and the timing for adding reactants can be 

varied in any combination. Each experiment 

consumes very little of the starting material—

as little as 100 microliters—according to one 

company’s product literature. This means that 

many experimental points can be generated 

in a short time, allowing the chemist to 

quickly identify the optimum conditions. This 

greatly reduces drug development time. A 

company’s product literature reported that 

continuous flow microreactors have the 

ability to accelerate the research and 

development phase in organic chemistry and 
Technology Assessment GAO-18-307 79

reduce development cost so that companies 

can benefit from much shorter time-tomarket for new drugs. 

Another advantage over batch processing is 

the tunable nature of continuous flow 

through the use of in-line analytics. In-line 

analytics are used to monitor the process in 

real-time and its implementation is 

considered key to quality control in 

continuous processing. The introduction of inline analytics improves the quality, 

consistency, and efficiency of process steps, 

leading to improved product quality. For 

example, real-time monitoring of continuous 

flow processes through the use of in-line 

analytics enables rapid identification and 

resolution of issues with product quality. Inline analytical tools such as Raman 

spectroscopy, infrared spectroscopy, and 

mass spectroscopy have been coupled to 

microreactors. These tools allow a researcher 

to monitor the reaction in real time, 

determine reaction parameters, and 

characterize intermediates. These data can 

help improve process understanding and 

control which may reduce the risk of wasting 

product because of non-compliance with 

desired product quality. Real time analysis 

also assists with the optimization of key 

reaction parameters such as residence time, 

temperature, reaction time, pressure, feed 

rate of contents, and concentration of 

reactants, leading to improved product 

quality and consistency. 

Ease of scale-up: One of the benefits of 

microreactor technology is its ease of 

scalability compared to conventional batch 

reactors.140 For example, continuous flow 

 140Scale-up in this case refers to increasing product output by 

adding more microreactors to the production line, rather than 

processes allow reactions to be conducted

with fewer steps and fewer formal protecting 

groups. This eliminates the need for extra 

purification steps and allows for more 

efficient use of time and materials. Overall, 

this enables a safer scale-up process, which is 

among the primary reasons companies 

consider using continuous flow microreactors, 

according to a review by Wiles and Watts.

141

Additionally, continuous manufacturing can 

potentially allow increased production 

volume without the bottlenecks related to 

scale-up, providing more response capacity. 

Eliminating such bottlenecks may facilitate 

rapid clinical development of breakthrough 

drugs. For example, the authors of a 

published review of drug synthesis using 

continuous flow chemistry reported on 

AstraZeneca’s scale-up efforts for their 

gastroesophageal reflux inhibitor target drug 

called AZD6906, which they achieved through 

better control of exothermic reaction with 

flow chemistry.142 In early development, this 

drug was prepared in batches. However, 

studies showed potential concerns regarding 

exothermic reaction profiles as well as 

product instability which needed to be 

addressed when moving to larger scale 

synthesis. They used microreactor flow

chemistry to circumvent some of these issues 

and subsequently developed a route to 

 increasing the reactor volume as is generally done during a 

scale-up operation.

141C. Wiles and P. Watts, “Continuous Process Technology: A 

Tool for Sustainable Production,” Green Chemistry, vol.16, no. 

55 (2014). According to the authors, a recent survey of 50 

European Companies reported that safety was the primary 

reason for choosing to implement or investigate flow 

processing.

142M. Baumann and I. R. Baxendale, “The Synthesis of Active 

Pharmaceutical Ingredients (APIs) Using Continuous Flow 

Chemistry,” Beilstein Journal of Organic Chemistry, vol. 11 

(2015).
Technology Assessment GAO-18-307 80

efficiently and reliably provide sufficient 

quantities of AZD6906 in continuous flow 

mode while addressing safety issues. The 

benefits of a continuous flow microreactor—

superior heat dissipation and improved 

temperature control due to reduced reaction 

volume—allowed the exothermic reaction to 

be carried out safely. More recently, scientists 

at Novartis developed a semi-continuous flow 

process for the synthesis of the oral antidiabetic agent vildagliptine. The flow process 

allowed for the instantaneous consumption of 

a hazardous intermediate formed during the 

reaction, thus allowing for a safe scale-up.

Savings in capital and operational 

expenditures: Pharmaceutical companies also 

consider using continuous processing in 

response to increasing research and 

development costs and competition from 

manufacturers of generic drugs. Several 

studies have reported that continuous 

manufacturing could reduce both operating 

expenditures and capital expenditures for the 

fine chemical and pharmaceutical 

industries.

143 According to the authors of 

these studies, capital expenditures are 

reduced because continuous manufacturing 

allows the use of smaller production facilities 

that also have a smaller plant footprint and 

fewer unit operations. Operational 

expenditures are lower in continuous 

manufacturing due to factors such as reduced 

 143T. Harrington, L. Alinaghian, and J. Srai, “Continuous 

Manufacturing and Product-Process Archetypes: Implications 

for Supply Network Design in Pharma” (paper presented at the 

24th Annual Production and Operations Management Society 

Conference, Denver, CO, May 2013). I. R. Baxendale, R. D. 

Braatz, A. J. Florence, B. K. Hodnett, K. F. Jensen, M. D. 

Johnson, P. Sharratt, and J. Sherlock, “Achieving Continuous 

Manufacturing: Technologies and Approaches for Synthesis, 

Work-up and Isolation of Drug Substance,” Journal of 

Pharmaceutical Science, vol. 104, no. 3 (2015). Gerogiorgis and 

Jolliffe, “Continuous Pharmaceutical Process Engineering,” 29.

labor, greater automation of the process

resulting in reduced manual intervention, 

increasing asset utilization (that is, operating 

on a 24-hour production cycle with minimal 

or no interruption, according to a company 

official we interviewed), reduced catalyst and 

solvent use, minimization of reaction time 

through better temperature control, effective 

scale-up of exothermic reactions without the 

need for special equipment, reduced 

inventory, less product reject due to real time 

monitoring, and reduced waste. According to 

a company scientist we interviewed, although 

an upfront capital investment is required to 

implement microreactor technology, the 

reactions associated with this approach are 

generally 5 to 10 times lower in cost. That is, 

the relatively smaller footprint of a 

continuous flow microreactor has an 

economic advantage compared to batch flow 

reactors. According to another company 

scientist we interviewed, continuous flow 

technology is a significant area of investment, 

justifying new development funding, because 

it ultimately reduces costs through lower 

energy usage and also reduces waste. 

Potential for improved product yield: A 

review article by Mason and colleagues 

reported that a Suzuki reaction—an 

important type of reaction—achieved 68 

percent conversion in a microreactor, a 

notable increase relative to the batch reaction

(10 percent yield).

144

 144Mason, Price, Steinbacher, Bogdan, and McQuade, 

“Greener Approaches to Organic Synthesis,” 2300.
Technology Assessment GAO-18-307 81

5.3 Disadvantages of and barriers to 

continuous manufacturing 

However, despite the many advantages 

offered by continuous processing and 

microreactors for some processes, there are 

also trade-offs. According to representatives 

of a pharmaceutical company we interviewed, 

some of the reasons for the slow adoption of 

continuous manufacturing by the 

pharmaceutical industry include risk aversion

and economic aspects—for example, the cost 

of building new infrastructure for flow 

systems. Batch manufacturing has been the 

process of choice for the pharma industry 

because of its familiarity, among other 

reasons. Industry scientists told us that it is 

challenging to change from what is proven 

and accepted to something new. 

Furthermore, pharmaceutical company 

officials we interviewed told us that the cost 

involved in developing new infrastructure for 

continuous processing may discourage the 

use of this technology.

Complex processing conditions: According to 

a white paper by Baxendale et al., the 

diversity and complexity of molecules of 

interest and the consequent need for diverse 

and complex processing conditions makes the 

adoption of continuous manufacturing 

challenging for the pharmaceutical and fine 

chemical industries.145 Pharmaceutical 

molecules typically have complicated 

synthetic routes requiring several steps that 

involve highly specialized molecular 

transformations, such as separation and 

purification steps. This is a key reason why 

 145Baxendale, Braatz, Florence, Hodnett, Jensen, Johnson, 

Sharratt, and Sherlock. “Achieving Continuous Manufacturing,” 

781.

batch processing dominates in 

pharmaceutical production: a small number 

of temperature- or pressure-controlled, 

agitated vessels can be used for virtually all of 

the necessary reaction, liquid-liquid 

extraction, distillation, adsorption, and 

crystallization steps associated with a drug’s 

synthetic route. Integrating these steps in a 

continuous process is challenging because it 

requires carefully controlled reaction rates 

that are coordinated with the process flows of 

sequential steps. Furthermore, most routes 

conceived during small-scale laboratory 

development have historically been batchbased and were scaled-up accordingly. 

Economic uncertainties: While cost savings 

can be expected from continuous processing 

in a microreactor through improved yield, 

automation, new reaction pathways such as 

solvent-free reactions, and improvements in 

safety, these economic gains are difficult to 

evaluate, according to the authors of a 

report.146 However, representatives from one 

pharmaceutical company we interviewed told 

us that they are manufacturing tablet drug 

products from drug powders—previously a 

batch operation—in a continuous mode. 

According to a company’s website article, 

tablet manufacturing is one area where 

pharmaceutical companies are choosing to 

demonstrate continuous processing in drug 

manufacturing. The reported benefits are 

increased equipment efficiency, savings in 

space, reduction of raw material and energy 

usage, reduction of scrap waste, and 

reduction of human interference, among 

others, which the company believes would 

 146D. M. Roberge, L. Ducry, N. Bieler, P. Cretton, and B. 

Zimmermann, “Microreactor Technology: A Revolution for the 

Fine Chemical and Pharmaceutical Industries?” Chemical 

Engineering & Technology, vol. 28, no. 3 (2005). 
Technology Assessment GAO-18-307 82

also result in lower costs of operations and 

improved safety.

147

Different reaction phases: While 

pharmaceutical companies are developing 

continuous processing to enhance operational 

efficiency and sustainability, it is not a 

universal solution for every reaction, 

according to scientists from one company we 

interviewed. For example, continuous 

processing is not well-suited to a slurry-based 

reaction.148 An analysis by Roberge et al. of 

various aspects and applicability of 

microreactor technology reported that 

continuous flow microreactors handle solids 

very poorly.149 Rather, they are suited for 

homogenous reactions—those occurring in a 

single phase—and, to some extent, gas-liquid,

or liquid-liquid reactions. The authors found 

that solids were present as catalysts, 

reactants, or products in more than 60 

percent of the reactions they studied. They 

noted that this limitation of microreactor 

technology is an important consideration, 

given that the number of potential candidates 

drops significantly after discounting reactions 

involving solids—unless technological 

capabilities are developed that allow 

microreactors to handle solids. 

Workforce challenges: According to the 

authors of a white paper, “Achieving 

Continuous Manufacturing,” another 

 147I. Backx, The Key to Continuous Manufacturing, accessed 

January 8, 2018, 

http://www.industry.siemens.com/verticals/global/en/pharma

-industries/continuous-manufacturing/Documents/Article-TheKey-to-Continuous-Manufacturing.pdf.

148A slurry is a semi-liquid mixture with fine particles 

suspended in water.

149Roberge, Ducry, Bieler, Cretton, and Zimmermann, 

“Microreactor Technology,” 318.

challenge with continuous manufacturing is 

that the skill set and capabilities required to 

design, develop, validate, and operate a 

continuous flow process are different from 

those required for conventional batch 

processing.150 Furthermore, according to a 

policy article on promoting continuous 

manufacturing in the pharmaceutical sector,

“designing, implementing, and adequately 

regulating these new approaches to 

manufacturing will require a highly skilled and 

well-trained workforce.”151

Global regulatory uncertainty: According to a 

policy article on continuous manufacturing 

and industry representatives we interviewed, 

the pharmaceutical sector is highly regulated, 

and any changes to an established 

manufacturing process may face regulatory 

delays.152 Therefore, global regulatory 

uncertainty may be another barrier to 

implementing continuous manufacturing in 

the pharmaceutical industry. Industry 

representatives we interviewed told us that 

while FDA may support continuous 

manufacturing, regulatory authorities in other 

countries may not be as accommodating or 

may impose a heavier burden in terms of 

having to demonstrate product equivalency 

for any process changes, among others. 

 150Baxendale, Braatz, Florence, Hodnett, Jensen, Johnson, 

Sharratt, and Sherlock. “Achieving Continuous Manufacturing,” 

781.

151Center for Health Policy at Brookings, Promoting 

Continuous Manufacturing in the Pharmaceutical Sector, 

Discussion guide, October 19, 2015, accessed November 17, 

2017, https://www.brookings.edu/wpcontent/uploads/2015/10/Continuous-manufacturingdiscussion-guide.pdf.

152Center for Health Policy at Brookings, Promoting 

Continuous Manufacturing, 2015.
Technology Assessment GAO-18-307 83

6 Roles of the federal government and other stakeholders in 

supporting the development and use of more sustainable chemical 

processes and products

The federal government and other 

stakeholders play a number of roles,

sometimes in collaboration, to advance the 

development and use of more sustainable 

chemical processes and products. First, 

federal programs and offices support research 

on the impacts of chemicals on human and 

environmental health. Second, federal 

programs and offices support the 

development of more sustainable chemical 

processes and their commercialization. Third, 

federal programs and offices aid in the 

expansion of markets for products 

manufactured with more sustainable 

chemicals and processes. In addition, other 

stakeholders play similar roles and some 

additional roles that contribute to the 

development and use of more sustainable 

chemical processes and products.

6.1 Federal programs support 

research on the impacts of chemicals 

on human and environmental health 

A number of federal programs and offices 

support basic research on the characteristics 

and biological effects of chemicals that 

underpins the development and use of more 

sustainable chemistry products and 

processes. Federal programs fund and study 

the impacts of chemicals on human health 

and the environment, develop new 

methodologies for testing and predicting 

these effects, award grants for research on 

chemicals and new methodologies, identify 

more sustainable chemical alternatives, and 

evaluate the risks of chemicals. See table 9 for 

selected examples of federal programs and 

offices that support research on the impacts 

of chemicals on human health and 

environment health. (For more information 

how these programs and offices were 

selected, see app. 1.)

6.1.1 The National Toxicology Program 

(NTP) conducts studies on chemical 

substances that inform regulatory 

agencies

NTP, headquartered at the National Institute 

of Environmental Health Sciences (NIEHS),

conducts and coordinates HHS toxicology 

research on the potential human health 

effects of chemicals, develops improved 

methods and approaches for testing these 

effects, and shares information about 

hazardous chemicals with decision makers. 

According to NTP’s 2016 Annual Report, the 

program’s budget was $131 million in fiscal 

year 2016.153

Since its inception in 1978, NTP has studied 

the health effects of more than 2,500 

chemical substances, including dietary 

supplements, industrial chemicals, consumer 

products, and complex mixtures. NTP selects 

which chemicals to study based on 

recommendations from a range of 

stakeholders, including academic institutions, 

advocacy groups, federal, state, and local 

 

153U.S. Department of Health and Human Services, 

National Toxicology Program Office of Liaison, Policy, 

and Review, Annual Report for Fiscal Year 2016

(Research Triangle Park, N.C.: 2017).
Technology Assessment GAO-18-307 84

agencies, industry, and programs within NTP. 

NTP’s current research portfolio focuses on 

testing synthetic industrial chemicals, 

pesticides, drugs, metals, and food additives. 

For example, NTP has investigated such things 

as the health effects of a flame retardant used 

in furniture materials, an artificial flavoring 

used in food and beverages, and a perfume 

ingredient used in soaps and shampoos. In 

2014, when about 10,000 gallons of coalprocessing chemicals spilled into the Elk River 

in West Virginia, the water source for the city 

of Charleston, West Virginia, NTP evaluated 

the potential toxicity of the chemicals to 

inform the public and federal and local 

decision makers.

Table 9: Selected federal programs and offices support research on the impacts of chemicals on human 

and environmental health

Federal program or office Selected activities related to sustainable chemistry

National Toxicology Program (NTP) - Department of 

Health and Human Services

Conducts toxicology research on the potential health 

effects of chemicals. 

Toxicology in the 21st Century (Tox21) program -

Department of Health and Human Services / 

Environmental Protection Agency

Seeks to improve how scientists predict the safety of 

chemicals by developing new testing methodologies.

Chemical Safety for Sustainability (CSS) program -

Environmental Protection Agency

Conducts research on the properties of chemicals and 

generates hazard, exposure, and risk assessment data. 

Science to Achieve Results (STAR) grant program -

Environmental Protection Agency

Funds academic research on new methodologies for 

testing and understanding chemicals and the effects of 

exposure.

Networks for Characterizing Chemical Life Cycles 

grant Environmental Protection Agency and the 

National Science Foundation

Funded research to build the scientific basis and 

evaluation tools required to understand and predict 

potential for manufactured chemicals and materials to 

impact human health and the environment.

National Institute for Environmental Health Sciences 

(NIEHS) Department of Health and Human Services

Funds research on the impacts of chemicals on human 

health.

Energy Frontier Research Centers Department of 

Energy

Centers seek to address long-term fundamental 

challenges in chemical research.

Significant New Alternatives Policy (SNAP) program 

Environmental Protection Agency

Evaluates alternatives for ozone-depleting substances to 

help industry identify acceptable alternatives in order to 

comply with Clean Air Act regulations. 

Chemical and Material Risk Management Program 

Department of Defense

Identifies and seeks to manage the risks associated with 

hazardous chemicals and materials. 

Source: GAO analysis of agency documentation. | GAO-18-307

NTP also develops new and improved testing 

methodologies to evaluate the human health 

effects of chemicals. While NTP generally 

conducts toxicological testing using rodent 

models, the program also seeks to develop 

faster and predictive tests for toxicological 

research that reduce or replace animal 

testing. NTP also participates in programs that 

support alternative testing methods including

the Toxicology in the 21st Century (Tox21) 

program (described in more detail below) and 

the Transform Tox Testing Challenge: 
Technology Assessment GAO-18-307 85

Innovating for Metabolism.154 NTP is also 

working to ensure that new tests are 

accepted for regulatory decision making. NTP 

manages the Interagency Coordinating 

Committee on the Validation of Alternative 

Methods, which includes representatives 

from 16 federal regulatory and research 

agencies and offices that use, generate, or 

disseminate toxicological and safety testing 

information, including the National Cancer 

Institute and Occupational Safety and Health 

Administration.155

NTP makes its research available to federal 

agencies, states, scientists, the medical 

community, and the public and provides 

guidance and interpretation of the scientific 

data and its appropriate use. NTP information 

is available through technical, toxicity, and 

research reports, federal register notices, 

journal publications, press releases, and 

online databases. Agencies use NTP’s 

research for decision making when 

developing guidelines and regulations to 

protect public health. For example, NTP 

findings are used by the EPA in its Integrated 

Risk Information System (IRIS), which 

identifies and characterizes the health 

hazards of chemicals found in the 

environment and by the Human Health Risk 

 154In 2016, EPA, NIH’s National Center for Advancing 

Translational Sciences, NIH’s NIEHS, and NTP announced the 

Transform Tox Testing Challenge: Innovating for Metabolism, 

which plans to award up to $1 million for improvements in the 

relevance and predictivity of data generated from automated 

chemical screening technology used for toxicity testing.

155The 16 agencies and offices include: Agency for Toxic 

Substances and Disease Registry, Consumer Product Safety 

Commission, DOD, DOE, Department of Interior, Department of 

Transportation, EPA, FDA, NIEHS, NIH, USDA, National Cancer 

Institute, National Institute for Occupational Safety and Health, 

National Institute of Standards and Technology, National 

Library of Medicine, and Occupational Safety and Health 

Administration.

Assessment program, which supports 

environmental decision making by assessing 

the human and environmental health risks 

posed by chemicals. Based on NTP’s study 

findings that hexavalent chromium in drinking 

water can cause cancer, California adopted 

drinking water standards for the chemical in 

2014. In 2016, citing NTP’s Report on 

carcinogens and others that found that the 

chemical trichloroethylene can lead to a 

cancer, the Department of Veterans Affairs 

amended its regulations regarding veteran’s 

service-connected disability benefits for 

service members exposed to the chemical in 

the water supply at U.S Marine Corps Base 

Camp Lejeune. NTP also interprets relevant 

scientific results for the public’s benefit 

through factsheets and podcasts. For 

example, NTP has compiled a factsheet and 

produced a podcast for the general public on 

the potential health hazards of bisphenol A 

(BPA), a chemical found in many plastic 

products such as water bottles.

6.1.2 HHS and EPA screen chemicals 

through the Tox21 program 

Tox21 seeks to improve how scientists predict 

the safety of chemicals by developing and 

applying new testing methods to accurately 

and quickly predict whether chemicals have 

the potential to affect human health. Tox21 

combines funding, expertise, data, and tools 

from NIH, including NTP at NIEHS and the 

National Center for Advancing Translational 

Sciences, and EPA and FDA. The Tox21 testing 

methods allow officials to prioritize chemicals 

for further, more costly and time-consuming 

toxicological evaluations and could be used to 

develop strategies that can be used directly 

by regulatory agencies to regulate chemicals). 

For example, high-throughput screening uses 

automated methods (including the robotic 
Technology Assessment GAO-18-307 86

arm pictured in fig. 19) to rapidly evaluate a 

large number of chemicals for biological 

responses to determine how the chemicals 

affect cellular functions that are linked to 

diseases. The partner agencies work together 

and solicit input from researchers, companies, 

and NGOs to select the chemicals and tests 

that will be performed as part of the Tox21 

program. Since 2008, the Tox21 partner 

agencies have used a high-throughput 

screening platform to assess approximately 

10,000 chemicals for their potential impacts 

on biological systems. The results of these 

tests, which are available free of charge, allow 

researchers to prioritize chemicals that have 

shown a potential to effect human health for 

testing and are also used by decision makers 

to assess health risks. For instance, the 

Minnesota Department of Health is using 

Tox21 data for assessing health risks 

associated with water contaminants. Tox21 

relies on voluntary budget allocations and in 

kind contributions from its partner agencies.

Figure 19: High throughput screening equipment

at the Toxicology in the 21st Century (Tox21) 

robotics facility at the National Institutes of 

Health National Center for Advancing 

Translational Sciences

6.1.3 EPA’s Chemical Safety for 

Sustainability (CSS) program generates

data and develops tools and public 

databases

The CSS research program develops tools and 

methodologies to test the properties of 

chemicals and generate hazard, exposure, 

and risk assessment data across the life cycle 

of thousands of chemicals. A number of EPA 

laboratories and centers contribute to the CSS 

research program, including the National 

Center for Computational Toxicology and the 

National Risk Management Research 
Technology Assessment GAO-18-307 87

Laboratory.156 According to EPA officials, CSS’s 

budget for fiscal year 2016 was $89 million.

CSS develops new methodologies, tools, and 

models for evaluating and predicting the 

safety of chemicals for human health and 

generates data using these tools. For 

example, the National Center for 

Computational Toxicology runs the Toxicity 

Forecaster (ToxCast) which uses high 

throughput screening data to identify and 

prioritize chemicals used in industrial and 

consumer products that may present a 

potential risk to human health. The Center, in 

partnership with the National Exposure 

Research Laboratory, also manages an 

Exposure Forecaster tool that predicts the 

potential for human and environmental 

exposures to chemicals. To address a critical 

gap in data on the potential of chemicals to 

disrupt neurodevelopment, CSS is also 

working to develop faster and less costly

methods for testing for neurodevelopmental 

toxicity, according to EPA officials. CSS uses 

these tools and others to identify the 

characteristics and potential human health 

risks of chemicals, evaluating thousands of 

chemicals more efficiently than is possible 

using traditional research methods such as 

animal testing. For example, over 1,800 

chemicals have been evaluated by ToxCast 

and the Exposure Forecaster has predicted 

exposures for almost 8,000 chemicals.

CSS develops public databases and tools to 

facilitate the use of chemical data by industry 

in the selection, design, and use of chemicals 

by federal regulators. For example, CSS has 

 156Other EPA entities that contribute to the CSS research 

program include the National Health and Environmental Effects 

Research Laboratory, National Exposure Research Laboratory, 

and National Center for Environmental Assessment. 

made the results of ToxCast and Tox21 testing 

publically available for decision makers 

through a ToxCast Dashboard and is 

developing guidance for decision makers on 

how to interpret and evaluate ToxCast data in 

several different decision contexts. CSS is also 

working on case studies to guide decisionmaking when using its data, including two

with the EPA’s Office of Pesticide Programs to 

support the prioritization of pesticide 

ingredients for further testing. CSS compiles 

and centralizes data for decision makers from 

a wide range of sources. One of these 

resources, the CompTox Chemistry 

Dashboard, provides users access to curated 

information from a wide variety of sources on 

the structures and properties of more than 

700,000 chemicals. According to EPA officials, 

the data in the dashboard can be used by 

decision makers to inform regulations, 

prioritize chemicals for additional testing, or 

support the use of alternative chemicals. 

Information generated by CSS supports 

decision making by federal and state actors. 

For example, CSS data are used to inform EPA 

legislative mandates and policies, including 

the Clean Air and Water Acts, Safe Drinking 

Water Act, Federal Food, Drug, and Cosmetic 

Act, and others. EPA’s Office of Chemical 

Safety and Pollution Prevention is using CSS 

tools and approaches to support the 

implementation of TSCA and the Federal 

Insecticide, Fungicide, and Rodenticide Act, 

according to EPA officials. To assist EPA in 

fulfilling its congressional mandate to screen 

certain chemicals for potential endocrine 

disruption,157 CSS used data from ToxCast, to 

 157Specifically, the Food Quality Protection Act requires EPA to 

develop a screening program to determine whether certain 

substances may have an effect in humans that is similar to an 

effect produced by a naturally occurring estrogen, and other 

other endocrine effects that EPA may designate. 21 U.S.C § 
Technology Assessment GAO-18-307 88

create a customized tool, the Endocrine 

Disruption Screening Program. According to 

officials, the State of California uses National 

Center for Computational Toxicology data to 

support risk assessments of pesticides and 

companies include the data in dossiers on 

their products submitted to the European 

Chemicals Agency. CSS works closely with the 

offices that administer federal regulations to 

shape CSS’s research plans to best meet their 

needs.

The National Risk Management Research 

Laboratory (NRMRL), one of the EPA offices 

that support CSS research, works to identify

risks to human and environmental health, 

including those posed by chemicals, and 

develops tools to help manage those risks. 

According to EPA officials, these tools and 

data enable decision makers to identify and 

design chemicals that are more sustainable. 

NRMRL also develops and conducts life cycle 

inventories to develop a base of information 

for use by decision makers in conducting 

LCAs. For instance, NRMRL is working with 

DOE’s National Renewable Energy Laboratory 

(NREL) on a life cycle model of electricity 

production and distribution that can be 

dropped into other analysis or tools that 

provide life cycle impact analysis for 

chemicals. NRMRL, along with EPA’s National 

Exposure Research Laboratory, is also 

developing a Life-Cycle Human Exposure 

Model that will allow decision makers to 

rapidly evaluate chemical and product safety 

by bringing together life cycle assessment and 

chemical exposure modeling.

 346a(p)(1). The substances include pesticide chemicals and 

those chemicals that may have an effect that is cumulative to 

an effect of a pesticide chemical if the Administrator 

determines that a substantial population may be exposed to 

such substance. 21 U.S.C § 346a(p)(3).

6.1.4 EPA, NSF, HHS, and DOE fund 

research on how chemicals impact human 

and environmental health 

Federal programs provide funding for 

research on the impacts of chemicals and how 

to measure those impacts. EPA and NSF fund 

academic research in the development of new 

methodologies and models for testing and 

understanding chemical effects and exposure 

through several grant programs. EPA’s 

Science to Achieve Results (STAR) grant 

program provides funding for research into 

safer, more sustainable use of chemicals in 

products. For instance, EPA awarded 

approximately $3.8 million in funding to six 

universities through the STAR Systems-Based 

Research for Evaluating Ecological Impacts of 

Manufactured Chemicals grant program to 

develop new methods for evaluating how 

exposure to chemicals influences the health 

of ecosystems and how to predict, prevent, 

and mitigate these effects. EPA and NSF 

jointly awarded grants through the Networks 

for Characterizing Chemical Life Cycles 

program which provided approximately $10 

million over four years to two interdisciplinary 

research teams that explored methods and 

tools to characterize and predict the impacts 

of chemicals. HHS provides funding through 

NIEHS to support research on the impacts of 

chemicals on human health, such as how 

bisphenol A (BPA) acts as an endocrine 

disruptor and evaluating the toxic and

carcinogenic potential of chemicals in dietary 

supplements and herbal medicines. DOE 

funds basic sustainable chemical research as 

well. For example, several of the Energy 

Frontier Research Centers focus on long-term 

fundamental challenges in chemical research 

including the Center for Direct Catalytic 

Conversion of Biomass to Biofuels and the 
Technology Assessment GAO-18-307 89

Integrated Mesoscale Architectures for 

Sustainable Catalysis.

6.1.5 EPA identifies substitutes for ozonedepleting substances

EPA’s Office of Air and Radiation Significant 

New Alternatives Policy (SNAP) program 

evaluates alternatives for ozone-depleting 

substances to help industry identify 

acceptable alternatives in order to comply 

with Clean Air Act regulations restricting use 

of these chemicals.158According to EPA, 

ozone-depleting substances accelerate the 

destruction of the stratospheric ozone layer 

which protects humans and the environment 

from damaging ultraviolet light. SNAP 

evaluates manufacturer, formulator, or userproposed substitutes for ozone-depleting 

substances. To do this, they use data primarily 

from the submitter of the substitute for 

review as well as data from a variety of

sources such as other federal agencies on the 

health and environmental impacts of 

substitutes for ozone-depleting substance

during the manufacturing, use, disposal, and 

recycling phases of the chemical’s life cycle. 

SNAP evaluates substitutes based on their 

atmospheric impacts, (e.g., ozone depletion 

potential, global warming potential, and air 

quality), toxicity, flammability, and effect on 

occupational and consumer health and safety, 

and ecosystem effects. SNAP also evaluates 

potential exposure of the substitute by 

manufacturing facility workers, servicing 

 158Title VI of the Clean Air Act required EPA to establish 

regulations protecting the ozone layer by phasing out the 

production of substances that deplete it. The Act requires EPA 

to publish a list of safe and unsafe substitutes for ozonedepleting substances, including chlorofluorocarbons (CFCs), 

halons, carbon tetrachloride, methyl chloroform, and 

hydrochlorofluorocarbons and to ban the use of unsafe 

substitutes. 42 U.S.C. §§ 7671-7671q.b.

technicians, and the general public. SNAP 

publishes an evolving list of acceptable and 

unacceptable substitutes in eight industrial 

sectors including, for example, refrigeration

and air conditioning, cleaning solvents, and 

fire suppression. In addition, SNAP publishes a 

series of factsheets and case studies on 

transitioning to alternatives. Companies can 

use the online list to identify alternatives to 

ozone-depleting substances to use in their 

manufacturing and products. 

6.1.6 DOD assesses chemical risks on 

human and environmental health

DOD’s Chemical and Material Risk 

Management Program is designed to manage 

risks associated with hazardous chemicals and 

materials in order to minimize adverse 

impacts on human and environmental health 

and DOD mission areas, as well as to reduce 

life cycle costs of weapons systems, 

platforms, equipment, and facilities. The 

program identifies and assesses the risks of 

emerging contaminants—chemicals that lack 

human health standards or have an evolving 

science and regulatory status. The program 

has scanned over 500 emerging contaminants 

to identify their importance to DOD, 

conducted approximately 50 impact 

assessments of emerging contaminants that 

pose risks to DOD, and developed 60 risk 

management actions for high-risk emerging 

contaminants. For example, the program 

issued an alert for decision makers on the 

potential risks to humans and the 

environment of the chemicals used in a fire 

suppressant for liquid fires, how to identify 

whether the chemicals were present, when 

the firefighting foams could be used, and how 
Technology Assessment GAO-18-307 90

to dispose of them properly.159 According to 

DOD, the budget authority for the program in 

fiscal year 2016 was $818,000.

6.2 Federal agencies support the 

development and commercialization 

of more sustainable chemistry 

technologies

Multiple federal agency programs and offices 

support the development of new more 

sustainable chemistry processes and facilitate 

the commercialization of these processes. 

These programs provide support in a variety 

of ways including conducting and funding

basic and applied research to develop more 

sustainable processes and products; providing 

loan guarantees, grants, and technical 

assistance to researchers and companies; and 

recognizing innovative technologies through 

an award program. The following are selected 

examples of federal programs and offices that 

support the development and 

commercialization of more sustainable 

chemistry technologies (see table 10).

6.2.1 NSF grant programs support

research to develop more sustainable 

chemistry processes 

NSF funds academic research on sustainable 

chemistry technologies through targeted 

grant funding from the Sustainable Chemistry, 

Engineering, and Materials (SusChEM) 

initiative as well as through its core research 

grant programs. In response to a 2011 law 

passed by Congress, NSF established the 

SusChEM program to support research into 

 159Chemical & Material Emerging Risk Alert: Aqueous Film 

Forming Foam (AFFF). Risk Alert #03-11. Department of 

Defense, Chemical and Risk Management Directorate. 

sustainable chemistry which would lead to 

clean, safe, and economical alternatives to 

traditional chemical products and practices.160

NSF awarded SusChEM grants for research 

throughout the life cycle of chemicals, but 

focused on awarding grants for research on 

improving the processing and use of raw 

materials. For example, Stanford University 

and IBM received a SusChEM grant to develop 

catalytic methods to produce biodegradable 

polymers that could be used to manufacture a 

range of plastic products, including medical 

stents and compostable plastic ware. Another 

SusChEM grant funded research at Arizona 

State University on the use of iron oxysulfide 

to replace the toxic materials currently used 

to manufacture solar cells. When determining 

what research it would fund, NSF officials 

considered the chemical breakthroughs and 

research priorities identified by participants in 

workshops they sponsored. Workshop 

participants included academic researchers, 

federal agency officials, representatives from 

the American Chemical Society, and chemical 

manufacturers and users. SusChEM awarded 

349 grants totaling about $134 million 

between 2013 and 2017.While the SusChEM 

program ended in fiscal year 2017 as planned, 

according to officials, NSF will continue to 

fund grants related to sustainable chemistry 

through its core research grant programs in 

the conventional scientific disciples.161 The

 160America Competes Reauthorization Act of 2010, PL 111-358, 

Section 509. 

161SusChEM is part of the NSF Science, Engineering and 

Education for Sustainability programs. When this program was 

initiated, it was envisioned as a limited-life focus, as is typical 

for NSF topical initiatives. SusChEM ended in fiscal year 2017 

along with the Science, Engineering and Education for 

Sustainability program. According to NSF officials, the Divisions 

of Chemistry; Chemical, Bioengineering, Environmental, and 

Transport Systems; Materials Research; Earth Sciences; and 

Civil, Mechanical and Manufacturing Innovation have pledged 

to continue to support sustainable chemistry technologies.
Technology Assessment GAO-18-307 91

results of NSF funded research are published 

in peer reviewed journals and freely available 

on the NSF website.

NSF also funds nine Centers for Chemical 

Innovation, research centers that include 

scientists from across academic institutions to 

focus on major chemical research challenges. 

According to NSF officials, five of the Centers 

focus on challenges related to sustainable 

chemistry technologies, including, for 

example, the Center for Enabling New 

Technologies through Catalysis and the 

Center for Sustainable Polymers. NSF funds 

Centers in two phases of research: Phase I 

Centers receive a total of $1.75 million over 

three years for the formation and 

development of a research center and Phase 

II grants provide follow-on, renewable 

funding of $4 million a year for five years to 

Centers. For example, the Center for 

Sustainable Polymers focuses on identifying 

and developing biobased, nontoxic, 

renewable, and functional polymer-based 

plastics, as opposed to traditional petroleumbased plastics. The Centers are collaborative, 

bringing together the expertise and 

perspectives of a variety of stakeholders, 

including scientists from different universities 

and industry. The Center for Selective C-H 

Functionalization—which explores methods 

for making organic molecules in a more 

streamlined, cost-effective, and 

environmentally benign way—includes 

collaborators from 14 universities, a research 

institution, international collaborators, and 

industry. The Centers also organize 

educational outreach programs for 

elementary, middle, and high schools, 

colleges and universities, and the community 

to increase understanding about chemicals. 

The NSF and EPA Networks for Sustainable 

Molecular Design and Synthesis grant

program funded research on the 

development of safe and sustainable 

chemicals, awarding approximately $19 

million over four years to four research 

groups. Each research group that received 

one of these awards was required to develop 

an innovation plan describing how the team 

would collaborate with industry or support 

technology transfer. For example, a University 

of Arizona research team worked with a 

startup company to commercialize a 

technology to develop a more sustainable 

surfactant. (For a list of all the selected grants 

described in this report, see table 12.)

6.2.2 USDA supports more sustainable 

biorefining technologies and biobased 

chemicals

USDA supports the development and 

commercialization of more sustainable 

chemistry technologies that convert 

renewable feedstocks into biobased products, 

including biobased chemicals. Biobased 

chemicals are chemicals that are 

manufactured using renewable resources 

such as municipal solid waste, algae, and the

byproducts of other processes—such as corn 

oil produced in the process of producing corn 

ethanol. While the goals of USDA’s support of 

biorefining are to increase the profitability 

and market for agricultural feedstocks and 

biobased products and to support the existing 

biorefining industry, there is also a 

sustainability benefit to replacing petroleumbased chemicals with those manufactured 

using renewable resources. The following are 

examples of USDA programs that support the 

development of more sustainable biorefining 

technologies and the manufacture of 

biobased chemicals. 
Technology Assessment GAO-18-307 92

Table 10: Selected federal programs and offices that support the development and commercialization 

of more sustainable chemicals and chemical processes

Federal program or office Selected activities related to sustainable chemistry

Sustainable Chemistry, Engineering, and Materials 

(SusChEM) - National Science Foundation

Funds research to develop clean, safe, and economical 

alternatives to traditional chemical products and practices.

Centers for Chemical Innovation - National Science 

Foundation

Funds research centers focused on fundamental chemical 

research challenges.

Networks for Sustainable Molecular Design and Synthesis –

National Science Foundation and Environmental Protection 

Agency

Funded research to develop safe, sustainable chemicals as 

well as safe, sustainable processes and procedures.

Agricultural Research Service (ARS) National Program on 

Biorefining - Department of Agriculture

Conducts research on feedstocks and commercially-viable 

technologies to convert agricultural material into 

biochemicals and other byproducts.

National Institute of Food and Agriculture (NIFA) -

Department of Agriculture

Funds research into the development of renewable 

feedstocks and biobased products.

Biorefinery, Renewable Chemical and Biobased Product 

Manufacturing Assistance Program - Department of 

Agriculture

Provides loan guarantees for developing, constructing, or 

retrofitting commercial-scale biorefineries.

Advanced Manufacturing Office (AMO) - Department of 

Energy

Supports the development of materials and technologies that 

reduce the energy intensity of sustainable chemistry 

technologies.

Manufacturing USA – Rapid Advancement in Process 

Intensification Deployment (RAPID) Institute - Department 

of Energy

Researches, develops, and demonstrates new chemical 

processes that save energy and reduce waste.

National Laboratories - Department of Energy Conduct research and provide unique scientific capabilities on 

sustainable chemistry technologies.

Department of Energy funding programs - Department of 

Energy

Provide funding and technical assistance to build knowledge 

that impacts the development of sustainable chemistry 

technologies.

Small Business and Innovation Research (SBIR) and Small 

Business Technology Transfer (STTR) grant programs -

Multiple agencies

Fund sustainable chemistry technological innovation and 

increase commercialization of innovations.

National Institute of Standards and Technology -

Department of Commerce

Develops methodologies and standards for measuring and 

evaluating the sustainability of chemicals and chemistry 

technologies.

Presidential Green Chemistry Challenge Awards -

Environmental Protection Agency

Recognizes chemical technologies that incorporate the 

principles of green chemistry into chemical design, 

manufacture, and use.

Strategic Environmental Research and Development 

Program (SERDP) and Environmental Security Technology 

Certification Program (ESTCP) - Department of Defense

Funds research on contaminants of concern to the DOD and 

for the validation and demonstration of new, more 

sustainable products.

Source: GAO analysis of agency documentation. | GAO-18-307
Technology Assessment GAO-18-307 93

The Agricultural Research Service (ARS) 

National Program on Biorefining conducts 

research on feedstocks and commerciallyviable technologies to convert agricultural 

material into biochemicals and other 

byproducts. For example, in 2015, researchers 

identified an enzyme that converts citrus peel 

waste into an acid that can be used for the 

development of fine chemicals, such as adipic 

acid. Adipic acid is used in making nylon, 

which is manufactured using benzene, a 

carcinogenic chemical manufactured from 

nonrenewable fossil fuels. Furthermore, the 

National Program on Biorefining 2014-2019 5-

Year Action Plan lists research on the use of 

biochemical conversion processes to create 

biobased chemicals, including alcohols, 

carboxylic acids, and biopolymers, as a way to 

maintain the economic viability of 

biorefineries in the face of the relatively low 

value of fuel products. The National Program

on Biorefining researchers coordinate with 

other USDA programs working on related 

research as well as with industry to ensure 

the research will benefit industry and 

maximize economic impacts. According to 

ARS officials, the National Program on 

Biorefining budget in fiscal year 2016 was 

approximately $15 million.

The National Institute of Food and Agriculture 

(NIFA) program awards grants for more 

sustainable chemistry technologies. For 

example, NIFA awards funding for research 

into the development of renewable 

feedstocks and biobased products and related 

analytical tools through the Biomass Research 

and Development Initiative, a partnership 

between NIFA, USDA’s Institute of Bioenergy, 

Climate, and Environment, and DOE’s Energy 

Efficiency and Renewable Energy Golden Field 

Office, Bioenergy Technologies Office. In 

2012, for instance, the Biomass Research and 

Development Initiative awarded a tire 

company approximately $6.9 million over five 

years to research biorefining technologies to 

convert a desert shrub into biobased 

polymers that could be used to replace 

petroleum-based polymers in rubber tires. 

The research team, which included academic 

and federal partners, successfully produced 

and tested concept tires that will be 

commercialized within the next two years, 

according to ARS officials. 

Through the Biorefinery, Renewable Chemical 

and Biobased Product Manufacturing 

Assistance Program, USDA supports the 

commercialization of biorefining technologies 

and production of biobased products by 

providing loan guarantees for developing, 

constructing, or retrofitting commercial-scale 

biorefineries that can convert biomass to 

biofuels, biobased chemicals, and other 

products. Eligible projects may receive loan 

guarantees through the program for up to 

$250 million, not to exceed 80 percent of the 

total project costs. According to USDA 

officials, as of October 2017, USDA has 

committed to conditional loan guarantees for 

nine projects. The budget authority for the 

program in fiscal year 2016 was $50 million, 

according to officials.

6.2.3 DOE programs seek to reduce 

energy use in chemical processing

DOE supports programs that seek to reduce 

the energy used in manufacturing, including 

by chemical processes and technologies. DOE 

funds research through cooperative 

agreements to reduce energy intensity in 

manufacturing and also supports technology 

transfer and the commercialization of the 

technologies developed through its research 

and grant programs. The following are 
Technology Assessment GAO-18-307 94

examples of DOE programs that support the 

reduction of energy use in chemistry 

technologies.

DOE’s Advanced Manufacturing Office (AMO) 

supports the development of materials and 

technologies that reduce the energy intensity 

of manufacturing processes throughout the 

life cycle of a product, including through 

sustainable chemistry technologies. For 

example, in order to support the 

development of less energy intensive 

manufacturing processes, AMO awards 

funding to scientists, consortia, national 

laboratories, companies, and state and local 

governments, and also provides technical 

assistance to industry. AMO funded a team of 

researchers at Purdue University in 

partnership with several chemical companies 

to develop an algorithm to increase energy 

efficiency in chemical distillation processes, 

for instance. With proof-of-principle financial 

assistance from AMO, a company 

commercialized a method for recycling nylon 

carpeting that recovers the chemical building 

blocks of nylon carpeting for reuse while 

consuming less total energy compared with 

conventional production. According to DOE 

officials, AMO identifies challenges to using 

sustainable chemistry technologies by 

conducting its own analysis and gathering 

information from stakeholders including 

companies, universities, and trade 

associations, and by holding workshops with 

stakeholders. 

DOE also supports reductions in energy 

consumption in chemical processes by 

sponsoring the Rapid Advancement in Process 

Intensification Deployment (RAPID) institute, 

one of 14 Manufacturing USA Institutes that 

seek to bring together industry, academia, 

and federal partners to create a national 

manufacturing research and development 

infrastructure.162 The mission of the RAPID 

institute is to research, develop, and 

demonstrate new chemical processes that will 

increase energy efficiency in a variety of 

chemical processes, including mixing, 

reaction, and separation. Launched in March 

2017, the RAPID Institute is led by the 

American Institute of Chemical Engineers and 

its members include 22 academic institutions, 

5 government and national laboratories, 18 

companies, and 4 NGOs. In addition, more 

than 130 institute partners committed to 

cost-shares of $70 million to match DOE’s 

contribution of $70 million over five years. 

Using cutting-edge scientific facilities and 

equipment, DOE scientists, engineers, and 

others employed at DOE’s 17 national 

laboratories carry out research and 

development on a range of topics, including 

research on sustainable chemistry 

technologies. In addition, the national labs 

support technology transfer and 

commercialization of processes and 

technology developed in the labs. According 

to officials at Pacific Northwest National 

Laboratory (PNNL) and Argonne National 

Laboratory (Argonne), technology transfer of 

lab-developed processes can be moved into 

commercial production through a range of 

activities including: direct interactions 

between scientists or engineers at a lab and a 

company, co-development of intellectual 

property, laboratory support during scale up, 

assistance with initial operations, and 

 162The Manufacturing USA initiative, also known as the 

National Network for Manufacturing Innovation, was 

authorized by Congress in December 2014 with the passing of 

the Revitalize American Manufacturing and Innovation Act. The 

Manufacturing USA network of institutes is operated by the 

interagency Advanced Manufacturing National Program Office, 

headquartered at NIST. 
Technology Assessment GAO-18-307 95

licensing agreements. Examples of programs 

at National Labs that support the 

development and use of more sustainable 

chemistry technologies include the following. 

• At NREL, scientists are researching 

materials and processes to efficiently 

convert biomass to high value, biobased 

chemicals. In addition, NREL develops 

analytical tools, methodologies, and 

studies to increase understanding of the 

potential impact and challenges of the 

emerging bioeconomy.

• Researchers at PNNL are developing new 

processes for the conversion of biomass 

into biobased chemicals. For example, 

PNNL developed an innovative catalytic 

process that converts plant-based 

feedstocks into propylene glycol, a 

chemical additive in liquid detergents, 

pharmaceuticals, and plastics typically 

made from petroleum. The research was 

supported by PNNL and cost-sharing 

agreements between DOE’s Office of 

Energy Efficiency and Renewable Energy, 

the National Corn Growers Association, 

and other companies. One of the 

companies licensed the technology from 

PNNL and began operating a full-scale 

production facility producing the chemical 

from soybeans and canola in 2011. 

• Argonne has a number of research 

initiatives that contribute to the 

development of more sustainable 

chemistry technologies. For example, 

Argonne is researching more sustainable

catalysts for converting renewable 

feedstocks to biofuels and biochemicals. 

The lab also conducts life cycle analysis of 

bioproducts. Argonne conducted a life 

cycle analysis to identify a sustainable 

process for converting non-recycled 

plastic into fuel, which can provide a 

viable waste management option for 

petroleum-based plastics.

To facilitate the development and 

commercialization of innovative technologies, 

DOE provides funding for research and to 

allow academic researchers and small 

businesses to take advantage of the state-ofthe-art facilities and scientific expertise at 

national labs. Some of this funding supports

the development and commercialization of 

sustainable chemistry technologies. For 

example, through cooperative agreements, 

the Bioenergy Technologies Office provided

$13.1 million to four research projects 

through the Bioproducts to Enable Biofuels 

Funding Opportunity to support the 

development of biomass conversion 

processes that can produce coproducts such 

as biobased chemicals along with biofuels. 

The Advanced Manufacturing Office’s 

Cyclotron Road program at Lawrence 

Berkeley National Laboratory helps 

entrepreneurs bridge the gap between early 

stage technology concepts and 

commercialization. Through the program, 

DOE awards two-year fellowships to scientists 

who are developing innovative energy 

technologies, and provides funding, lab space, 

access to scientists at the national lab, and 

business mentoring. For example, the 

founders of a company received funding from 

Cyclotron Road to develop a method to 

recycle waste carbon dioxide back into fuels 

and chemicals using only water and electricity 

as inputs. In 2015, DOE’s Office of Energy 

Efficiency and Renewable Energy launched 

the Small Business Vouchers Pilot to help 

small businesses overcome technology and 

commercialization challenges in bringing new 

clean technologies to market. Through the 

program, DOE provides businesses with 
Technology Assessment GAO-18-307 96

vouchers that can be used to request 

technical assistance from national labs for 

activities such as prototyping, scaling, 

regulatory compliance, or modeling and 

simulations. For example, in 2016, another 

company received $300,000 to use facilities at 

NREL and Lawrence Berkeley National 

Laboratory to scale up a new technology to 

produce biobased malonic acid, a chemical 

used to produce electronics, medicine, and 

fragrance, through a sugar and water 

fermentation process rather than the current 

process which uses toxic chemicals. The Office 

of Energy Efficiency and Renewable Energy 

announced that 38 small businesses would 

participate in the voucher program in fiscal 

year 2017. 

6.2.4 Federal small business programs 

encourage the development and 

commercialization of sustainable 

chemistry technologies

Federal agencies also support the 

development and commercialization of more 

sustainable chemistry technologies through 

the congressionally-mandated SBIR and STTR 

programs. The SBIR program was initiated in 

1982 and has four purposes: (1) to use small 

businesses to meet federal R&D needs, (2) to 

stimulate technological innovation, (3) to 

increase commercialization of innovations 

derived from federal R&D efforts, and (4) to 

encourage participation in technological 

innovation by small businesses owned by 

disadvantaged individuals and women. The 

purpose of the STTR program—initiated in 

1992—is to stimulate a partnership of ideas 

and technologies between innovative small 

businesses and research institutions through 

federally funded R&D. Together, the agencies 

that participate in SBIR and STTR have 

awarded more than $40 billion through the 

two programs since their inception.163 Some 

of the funding has been awarded to support 

the development of more sustainable 

chemistry technologies. Examples of two 

research efforts are included below.

• A company received SBIR funding from 

DOE and NSF to develop a catalytic 

process to convert lignin found in waste 

from paper pulping facilities and 

biorefineries into high value biobased 

chemicals. 

• A company that has developed a process 

to capture methane and convert it into 

various biobased products using bacteria 

has received two SBIR grants through NSF 

to support the production of biobased, 

biodegradable polymers from methane 

gas at a wastewater treatment plant. The 

company also received two STTR grants 

from the National Aeronautics and Space 

Administration (NASA) to modify their 

technology to produce biobased polymers 

in space, where they could be produced 

on-demand. 

6.2.5 NIST develops methodologies and 

standards for evaluating the sustainability 

of chemical technologies

NIST develops methodologies and standards 

for measuring and evaluating the 

sustainability of materials and manufacturing 

processes, including chemicals and chemistry 

technologies. In order to improve 

sustainability, industry needs to accurately 

measure and evaluate the consumption of 

 163SBIR participants include USDA, DOD, DOE, EPA, NSF, HHS, 

NASA and the Departments of Commerce, Education, 

Homeland Security, and Transportation. STTR participants 

include the DOD, DOE, HHS, NASA, and NSF.
Technology Assessment GAO-18-307 97

energy and materials, emissions, waste, and 

water usage, as well as environmental 

impacts, at each step in the life cycle (see 

chapter 2). NIST does not quantify the 

sustainability of technologies, but provides 

methodologies, standards, metrics, and 

validated data to decision makers to assess 

the sustainability of their choices on a caseby-case basis. NIST works with industry 

stakeholders to prioritize research goals and 

identify areas lacking standards. According to 

NIST officials, the Institute has engaged 

largely with traditional manufacturers, but is 

beginning to engage more with chemical 

manufacturers.

For example, NIST’s Sustainable 

Manufacturing project develops methods for 

characterizing the environmental aspects of 

manufacturing processes at the unit, factory, 

and network levels, which enables the 

evaluation of the sustainability of these 

processes. Additionally, according to NIST 

officials, NIST collaborates with standard 

setting organizations such as ASTM 

International to provide industry and federal 

agencies with protocols and methods for 

measuring the sustainability of manufacturing 

processes including inputs, outputs, and 

waste. NIST led the development of ASTM 

E3012-16, the Standard Guide for 

Characterizing Environmental Aspects of 

Manufacturing Processes, which enables 

manufacturers to virtually characterize their 

production processes as computer models, 

and then, using a standardized method, 'plug 

and play' the environmental data for each 

process step to visualize impacts and identify 

areas for improving overall sustainability of 

the system.

The Materials Science and Engineering 

Division, in partnership with industry, other 

government agencies, and academia, 

develops the measurement science, 

technology, and research required to support 

the design, manufacture, and use of 

materials, including chemicals. One program, 

the Sustainable Composites project, is 

developing tools to measure the 

characteristics of sustainable polymer 

composites in order to enable manufacturers

to develop high performance bio-based 

composites. According to NIST officials, other 

Division researchers are exploring using 

biomass to produce nanocellulose materials, 

a sustainable alternative to petroleum-based 

chemicals. Division officials also said they are 

coordinating with companies to develop 

methods for reducing the amount of solvents 

companies use and working to develop new 

solvents that are less toxic. The budget 

authority for the Materials Science and 

Engineering Division was approximately $25 

million in fiscal year 2016, according to NIST 

officials.

In addition, NIST maintains a number of tools 

that facilitate the selection and use of more 

sustainable chemicals and processes. For 

example, NIST maintains a database of 

information on the thermochemical 

properties of organic materials that can be 

used to calculate the energy content for 

various fuels and the energy used in chemical 

processes that industry decision makers can 

use to design more sustainable chemical and 

manufacturing processes and a database on 

chemical reactions that occur under gaseous 

conditions. NIST has also developed 

calculations that estimate the global warming 

potential of molecules, which allows for the 

screening and identification of candidate 

chemicals to replace hydrofluorocarbon 

refrigerants that cause climate change. To 

help industry measure their sustainability 
Technology Assessment GAO-18-307 98

performance, NIST’s Sustainable 

Manufacturing Indicator Repository provides 

access to centralized information on a range 

of sustainable indictors from sources such as 

Dow Jones, the United Nations, and Walmart.

6.2.6 EPA recognizes companies with 

innovative sustainable chemistry 

technologies

Since 1996, the EPA in partnership with the 

American Chemical Society Green Chemistry 

Institute has awarded the annual Presidential 

Green Chemistry Challenge Awards to 

academics and companies for the 

development of innovative, sustainable 

chemistry technologies. The awards are 

presented for new technologies that 

incorporate the principles of green chemistry 

into chemical design, manufacture, and use, 

including technologies that reduce toxicity, 

improve use of natural resources, or reduce 

the production of waste, among others.164

Awards are presented in six categories: 

Greener Synthetic Pathway, Greener Reaction 

Conditions, Design of Greener Chemicals, 

Small Business, Academia, and for Specific 

Environmental Benefit: Climate Change, for a 

technology that reduces greenhouse gas 

emissions. For example, in 2016, Newlight 

Technologies won the award in the Climate 

Change category for developing and 

commercializing a biocatalyst technology that 

combines captured methane, a potent 

greenhouse gas, with air to create a material 

that matches the performance of petroleumbased plastics at a lower cost. Several 

companies are now using this material to 

make a range of products including packaging, 

cellphone cases, and furniture. In 2017, the 

 164See appendix V for the 12 Principles of Green Chemistry.

companies Amgen, Inc. and Bachem won the 

Greener Reaction Conditions Award for their 

process for manufacturing the active 

ingredient in the drug ParsabivTM, which uses 

71 percent less chemical solvent. 

6.2.7 DOD funds research to develop 

products using more sustainable 

chemistry that also meet performance 

needs

DOD’s Strategic Environmental Research and 

Development Program (SERDP) funds basic 

and applied research on contaminants of 

concern to DOD and DOD’s Environmental 

Security Technology Certification Program 

(ESTCP) funds validation and demonstrations 

of new, more sustainable chemistry 

technologies and products, among other 

activities. SERDP is jointly managed by DOD, 

EPA, and DOE and research funding priorities 

for both programs are identified by these 

agencies, experts, and by DOD’s Emerging 

Contaminants program. SERDP and ESTCP 

fund federal organization and award 

contracts to universities and private industry. 

For example, according to DOD officials, after 

Camp Edwards was shut down in part 

because hazardous chemicals from flares 

were leaching into the community water 

supply, SERDP funded research to develop 

new flares without the chemicals of concern. 

According to officials, DOD has invested in 

research on new paint technologies that 

eliminate carcinogenic hexavalent chromium 

in paint primers and in research into methods 

for reducing or eliminating solvents. ESTCP 

funded research at the Army Armament 

Research, Development and Engineering 

Center to validate the performance of 

nontoxic, biodegradable biobased cleaner, 

lubricant, and preservative products as 

potential alternatives to petroleum-based 
Technology Assessment GAO-18-307 99

products or other products containing 

chemicals that may cause eye, skin, and 

respiratory irritation. SERDP and ESTCP make 

the results of funded research, development 

and demonstration, and validation efforts 

available to the public through its websites 

when possible. According to DOD officials, 

SERDP’s budget authority for fiscal year 2016 

was $54.3 million and ESTCP’s budget 

authority for the same time period was $51.4 

million.

6.3 Federal programs aid market 

growth for products made with 

sustainable chemicals and processes

Federal programs aid the growth of markets 

for products developed using more 

sustainable chemistry by informing 

consumers about these products and by 

facilitating their purchase by federal offices. 

For example, federal programs conduct 

evaluations of the chemical content of 

products, manage product certification and 

labeling programs, provide information to 

consumers and federal purchasers on the 

chemical content of products, and develop 

purchasing and sustainability plans to support 

agency purchase and use of more sustainable 

products. In addition, federal programs 

facilitate compliance with Executive Order 

13693 and the Federal Acquisitions 

Regulation federal regulations that require 

agencies to purchase certain more 

sustainable products when practicable. The

following are selected examples of federal 

programs and offices that facilitate the 

growth of markets for more sustainable 

products (see table 11).

Table 11: Selected federal programs and offices aid market growth for products manufactured with 

more sustainable chemicals and processes

Federal program or office Selected activities related to sustainable chemistry

Safer Choice - Environmental Protection Agency Certifies products that contain chemicals posing the least health 

and environmental risk.

BioPreferred - Department of Agriculture Maintains a catalog of biobased products and certifies products 

with minimum biobased content.

Building for Environmental and Economic 

Sustainability (BEES) - Department of Commerce, 

National Institute of Standards and Technology

Evaluates the life-cycle environmental and economic performance 

data of building materials and products.

Agency Sustainable Purchasing Plans and 

Sustainability Plans – Multiple Agencies

Develops plans to promote the acquisition and use of products 

manufactured with more sustainable chemicals and processes. 

Chemical and Material Risk Management Program, 

Sustainable Product Center, Sustainable Procurement 

Program - Department of Defense

Encourages and facilitates the purchase of more sustainable 

chemicals and products by DOD facilities.

Source: GAO analysis of agency documentation. | GAO-18-307
Technology Assessment GAO-18-307 100

6.3.1 Federal programs evaluate and 

share information about consumer 

products and their chemical content

EPA’s Safer Choice voluntary certification and 

labeling program supports the market for 

more sustainable products by helping 

consumers make informed purchasing 

decisions, and incentivizing manufactures to 

select more sustainable chemical alternatives 

when developing products by providing a way 

to differentiate and market their more 

sustainable products to interested 

consumers. More than 2,350 products from 

nearly 500 formulators and manufacturers 

currently qualify for the Safer Choice label, 

including products such as odor removers,

hand soap, and pet care products (see fig. 20). 

In order to carry the Safer Choice label, a 

third-party reviewer must certify that the 

chemical ingredients in the product comply 

with Safer Choice criteria on category specific 

attributes such as carcinogenicity, human and 

environmental toxicity, skin sensitization, and 

recyclability of packaging. Safer Choice 

evaluates each chemical ingredient by 

functional class (e.g., colorants, solvents, or 

preservatives), comparing the profiles of 

chemicals to identify those that pose the least 

health and environmental concerns among 

chemicals that serve a similar function. Safer 

Choice also evaluates product performance to 

ensure it is comparable to that of a similar 

conventional product. Safer Choice 

assessments focus on the health and 

environmental impacts of consumer and 

institutional use and disposal of chemicalbased cleaning and related products and do 

not assess chemical manufacturing processes 

or technologies. In addition to meeting all the 

Safer Choice criteria, manufacturers seeking 

certification must disclose all product 

ingredients on the product label or on the 

manufactures website and undertake 

continuous product improvement. Safer 

Choice has also developed the online Safer 

Chemical Ingredients List for manufacturers, 

which includes more than 800 chemicals that 

meet Safer Choice criteria. Safer Choice 

certified products are listed in the publically 

available Safer Choice database, facilitating 

their purchase by both consumers and federal 

agencies. Federal agencies are required by

Executive Order 13693 to purchase Safer 

Choice products when practicable.

Figure 20: The Environmental Protection Agency’s 

Safer Choice certification label

Safer Choice works closely with 

manufacturers and other stakeholders in 

developing program goals, logistics for 

certificate application, meeting standards and 

criteria, outreach, and selecting new product 

types to be included in the program. For 
Technology Assessment GAO-18-307 101

example, Safer Choice holds an annual 

summit to gather feedback from 

manufacturers, NGOs, and other stakeholders 

to improve the program and advises 

companies on identifying safer ingredients. 

Safer Choice conducts public outreach and 

awareness campaigns for the Safer Choice 

program, such as promoting the label in social 

media, through targeted factsheets, and 

through seasonal promotions. Through its 

“Safer Choice Partner of the Year Awards,” 

Safer Choice recognizes manufacturers for 

advancing the goal of chemical safety through

participation in or promotion of Safer Choice. 

For example, in 2017, a supermarket chain 

was recognized for its use of social media to 

promote the Safer Choice program. 

USDA’s BioPreferred program supports 

federal purchasing requirements and 

administers a voluntary labeling program to 

increase the purchase and use of biobased 

products in order to increase the use of 

renewable agricultural resources, minimize 

the use of petroleum, and reduce health and 

environmental impacts, according to USDA. 

The Farm Security and Rural Investment Act 

of 2002 (2002 Farm Bill) as amended in 2008 

and 2014 establishes federal purchasing 

requirements for biobased products. The act 

defines a biobased product as a product that 

is DOE determines is composed in whole or 

part of biological products or renewable 

agricultural materials, including plant, animal, 

and marine materials, or forestry materials.165

The BioPreferred program maintains a catalog 

through which consumers and federal 

purchasers can identify approximately 15,000 

 1657 U.S.C. § 8101(4). The term also includes intermediate 

ingredients and feedstocks. Id.

biobased products in 97 categories ranging 

from asphalt removers to deodorants. 

Product categories are added based on 

market research that identifies a government 

need as well as suggestions from 

stakeholders, such as industry associations or 

the public. To be included in the catalog, 

manufacturers must self-certify that a 

product contains the minimum required 

biobased content for a given product category 

as determined by the BioPreferred program. 

For example, general purpose carpet cleaners 

must have a minimum biobased content of 54 

percent to qualify and candles must have a 

minimum of 88 percent. To facilitate the 

purchase of products listed in the catalog by 

federal agencies, officials also provide 

acquisition tools and training resources for 

federal agencies. 

The BioPreferred program also manages a 

voluntary certification and labeling initiative 

that helps consumers identify and purchase 

products with a verified minimum of biobased 

content. Manufacturers can use USDA’s 

“Certified Biobased Product” label on their 

product after a third-party organization 

verifies the amount of biobased content (see 

fig. 21). BioPreferred has certified 

approximately 3,000 products, including stain 

removers, fertilizers, and notebooks. Certified 

products are also included in the BioPreferred 

Catalog and labeled as such. According to 

USDA officials, the fiscal year 2016 authorized 

budget for the Biopreferred program was $3 

million.
Technology Assessment GAO-18-307 102

Figure 21: The United States Department of 

Agriculture’s (USDA) BioPreferred label

Note: The above figure shows a sample of the BioPreferred 

label, showing the percent of biobased content in a 

hypothetical product and packaging.

NIST’s Applied Economics Office conducts life 

cycle analyses of building products to help 

decision makers, such as architects, builders, 

and product manufacturers, select more 

sustainable building materials through the 

online Building for Environmental and 

Economic Sustainability (BEES) tool. The BEES 

database includes life-cycle environmental 

and economic performance data for 256

building materials and products including wall 

insulation, floor coverings, interior wall 

finishes, and parking lot paving, based on data 

provided by product manufacturers. The data 

are made available through the interactive 

BEES tool that allows users to evaluate both

the cost and the environmental impacts of a 

material throughout its life cycle, including 

use of raw materials, transportation to site, 

and disposal. For example, a decision maker 

could use the BEES tool to compare the 

economics and environmental impacts of 

different types of flooring, such as wool or 

nylon carpet tiles, including their lifetime 

toxicity, ozone depletion, and use of fossil 

fuels. NIST conducts outreach to industry 

associations to increase industry participation 

in submitting data and for growing the user 

base for BEES, according to this official. In 

addition, according to officials, the Office is 

working with green building certification, 

standards, and codes development 

organizations, such as the U.S. Green Building 

Council, to align development of BEES with 

future stakeholder needs.

6.3.2 Agency plans encourage the 

purchase of products with more 

sustainable chemicals 

To encourage the purchase of more 

sustainable products, including those 

manufactured with more sustainable 

chemicals and processes, federal agencies 

have developed sustainable purchasing and 

sustainability plans and developed tools to 

facilitate green purchasing. Executive Order 

13693, “Planning for Federal Sustainability in 

the Next Decade,” issued in 2015, directs

agencies to develop plans to advance waste 

prevention and pollution prevention by, 

among other things, reducing or minimizing 

the quantity of toxic and hazardous chemicals 

and materials acquired, used, and disposed. 

For example, the Department of Housing and 

Urban Development’s 2016 Strategic 

Sustainability Performance Plan states that 

the agency will implement integrated pest 

management and improved landscape 

management practices to reduce and 

eliminate the use of toxic and hazardous 

chemicals and materials. Additionally, the

Department of Commerce Green 

Procurement Program states that the agency 

will provide preference to the purchase of 

nontoxic or less toxic product alternatives, 

including cleaning products that are nontoxic, 

non-volatile, and biodegradable. EPA enables 

federal purchasers and the public to identify 

more sustainable products by maintaining an 

online Sustainable Marketplace that 
Technology Assessment GAO-18-307 103

recommends greener products and services, 

standards, and ecolabels. The General 

Services Administration also provides a 

compilation of federal green purchasing 

resources.

DOD has several programs that encourage 

and facilitate the purchase of more 

sustainable chemicals products. DOD 

encourages acquisitions managers to 

purchase cost effective products that conform 

to federal sustainable procurement 

requirements by developing and testing 

products that contain more sustainable 

chemicals, setting purchasing policies and 

recommendations for these products, and 

providing DOD decision makers with data and 

demonstrations to inform purchasing 

decisions. DOD’s Chemical and Material Risk 

Management Program develops policies, 

procedures, and guidance to integrate life 

cycle environment, safety, and health 

considerations into DOD’s acquisition 

processes of products containing chemicals. 

For example, the program developed a policy 

to minimize the use of hexavalent chromium 

DOD-wide and developed an acquisitions rule 

that sought to minimize the chemical in new 

acquisitions. According to DOD officials, this 

requirement provided an incentive for the 

industry to create products without the 

harmful chemical. The program has also 

developed a life cycle analysis process that 

allows decision makers to accurately compare 

the life cycle impacts and costs of 

conventional and more sustainable 

alternatives. In addition, DOD’s Sustainable 

Products Center compiles information on 

sustainable products, evaluates the military’s 

need for more sustainable products, hosts 

sustainable product demonstrations, and 

highlights success stories and lessons learned.

DOD’s Sustainable Procurement Program 

encourages DOD programs to procure more 

sustainable products and conducts life cycle 

assessment to evaluate how improvements in 

sustainability may result in cost savings. 
Technology Assessment GAO-18-307 104

Table 12: Selected federal grants and awards supporting the development and use of more sustainable 

chemistry technologies

Grant program Agency Purpose of program

Biomass Research and Development Initiative Department of Agriculture / 

Department of Energy

Support the development of a biomassbased industry in the United States.

Sustainable Bioenergy and Bioproducts 

Challenge Area

Department of Agriculture Advance the bioeconomy by facilitating 

development of regional systems for the 

sustainable production of bioenergy, 

industrial chemicals, and biobased products.

Strategic Environmental Research and 

Development Program (SERDP) and 

Environmental Security Technology 

Certification Program (ESTCP)

Department of Defense Fund research on contaminants of concern 

and for the validation and demonstration of 

new, more sustainable chemistry 

technologies and products.

Manufacturing USA Institute - Rapid 

Advancement in Process Intensification 

Deployment (RAPID)

Department of Energy Research, develop, and demonstrate new 

chemical processes that will save energy and 

reduce waste in a variety of chemical 

reactions.

Bioproducts to Enable Biofuels Department of Energy Develop bioconversion processes that 

coproduce biofuels and bioproducts, 

including biochemicals.

Science to Achieve Results (STAR) Safer 

Chemicals

Environmental Protection Agency Support the development of safer, more 

sustainable use of chemicals in products.

Networks for Characterizing Chemical Life 

Cycles and Networks for Sustainable 

Molecular Design and Synthesis

Environmental Protection Agency 

/ National Science Foundation

Funded research to characterize and predict 

health impacts of chemicals on humans and 

the environment by studying chemicals 

throughout their life cycle and to develop

more sustainable chemicals.

Sustainable Chemistry, Engineering, and 

Materials (SusChEM)

National Science Foundation Support research leading to clean, safe, and 

economical alternatives to traditional 

chemical products and practices.

Centers for Chemical Innovation National Science Foundation Support research centers focused on major, 

long-term fundamental chemical 

research challenges.

Small Business Innovation Research (SBIR) 

and Small Business Technology Transfer 

(STTR) 

Multiple agencies Stimulate technological innovation and 

facilitate technology transfer.

Award program Agency Purpose of program

Transform Tox Testing Challenge Department of Health and 

Human Services and 

Environmental Protection Agency

Recognize innovative technological solutions 

to transform chemical testing methods.

Presidential Green Chemistry Challenge 

Awards

Environmental Protection Agency Recognize chemical technologies that 

incorporate the principles of green chemistry 

into chemical design, manufacture, and use.

Source: GAO analysis of agency documentation. | GAO-18-307
Technology Assessment GAO-18-307 105

6.4 Other stakeholders including the 

chemical manufacturing industry, 

academic institutions, states, and 

companies also support more 

sustainable chemistry 

Other stakeholders, including industry, 

academic institutions, state governments, 

NGOs, and companies seek to influence the 

development and use of sustainable 

chemistry through a variety of activities. For 

example, the chemical industry conducts and 

supports research into more sustainable 

chemistry technologies, collaborates with 

other stakeholders to support sustainability 

initiatives, and other activities. Large 

purchasers such as companies and retailers 

create demand for more sustainable products 

from their suppliers by setting sustainability 

criteria for purchases. Academic institutions 

conduct research on the impacts of chemicals 

and sustainable chemistry technologies and 

train the next generation of chemists and 

engineers. States seek to protect public 

health by regulating chemicals in products. 

NGOs also play a diverse range of roles such 

as supporting workforce development, 

facilitating collaboration between other 

stakeholders, and developing tools and 

resources for industry.

6.4.1 The chemical manufacturing 

industry collaborates with stakeholders to 

address common challenges and goals in 

using more sustainable chemistry

Interested companies in the chemical 

manufacturing industry collaborate with each 

other and other stakeholders to advance 

sustainable chemistry practices. These 

companies support the development and use 

of more sustainable chemistry through a 

variety of activities, including conducting and 

funding research, setting standards, and 

supporting sustainable chemistry education. 

For example, industry collaborates through 

the American Chemistry Society’s Green 

Chemistry Institute to encourage the 

integration of green chemistry and 

engineering throughout research, education, 

and industry. For example, the Green 

Chemistry Institute’s Pharmaceutical 

Roundtable brings together pharmaceutical 

manufacturers to implement green chemistry 

in the industry through activities such as 

developing solvent and reagent selection 

guides for decision makers and awarding 

grants to support academic research. Industry 

also collaborates with other stakeholders 

through the Green Chemistry and Commerce 

Council, a project of the Lowell Center for 

Sustainable Production at the University of 

Massachusetts, Lowell that seeks to integrate 

green chemistry across business sectors and 

the supply chain. Members include 

manufacturers, retailers, education 

institutions, and state and federal 

government agencies. Green Chemistry and 

Commerce Council activities include 

convening working groups, supporting 

education and training in sustainable 

chemistry, and developing tools for 

collaboration and information sharing. In an 

example of a public-private partnership, NIKE,

Inc. joined with NASA, the United States 

Agency for International Development, and 

the State Department to create the LAUNCH 

program, which funds innovative approaches 

to sustainability challenges, including a 2016 

Chemistry Innovation Challenge and a 2014 

Green Chemistry Challenge.

Among the 18 chemical companies that 

responded to our survey, 10 indicated that, 

with respect to the development and use of 
Technology Assessment GAO-18-307 106

sustainable chemistry technologies, they 

interacted a moderate or large amount with 

academics and 12 indicated that they 

interacted with scientific and professional 

organizations a moderate or large amount. 

Less than half of responding companies said 

they interacted a moderate or large amount 

with environmental advocacy groups. In 

terms of interactions with federal agencies 

related to sustainable chemistry technologies, 

half of the responding companies had 

performed collaborative research and 

development with a federal agency and 6 out 

of 18 had received federal funding for 

research and development. Of the responding 

companies, half had a large to moderate 

amount of interactions with EPA related to 

sustainable chemistry technologies, the most 

interactions of any of the federal agencies 

included in the survey. Of the companies 

surveyed that interacted with EPA with 

respect to the development and use of 

sustainable chemistry technologies, 9 found 

the interactions very or moderately valuable. 

For more information on the survey, see 

appendix IV.

6.4.2 Companies develop policies to 

encourage suppliers and others to 

develop products using more sustainable 

chemistry

Corporations that set policies on purchasing 

products manufactured with more 

sustainable chemistry may increase the 

incentive for the development and use of 

more sustainable chemistry technologies by 

chemical manufacturers and formulators. 

Selected companies, such as Target and Kaiser

Permanente, are developing policies and tools 

to ensure the products they purchase meet 

certain criteria with regard to chemical 

ingredients and other life cycle factors, and 

are working with purchasers and suppliers to 

encourage the development of these 

products. 

Target Corporation: Target, a retailer with 

more than 1,800 stores and sales of nearly 

$70 billion in 2016, has launched two major 

initiatives that seek to encourage and 

incentivize its vendors to supply products that 

use more sustainable chemistry technologies. 

According to a Target official, these efforts 

are driven by consumer concern about the 

safety of chemicals in the products they buy,

as well as to prevent regulatory fines by 

strengthening internal regulatory processes. 

In 2013, Target introduced a Sustainable 

Products Index, an internal tool that collects 

information from suppliers and assesses 

products based on sustainability criteria such 

as the presence of certain chemical 

ingredients, transparency about those 

ingredients, packaging, certifications, and 

sourcing information. The Index applies to the 

personal care, beauty, household cleaning, 

and baby care product categories. In 2017, 

Target introduced a new chemical policy and 

goals governing chemicals in products it sells 

in stores and uses operationally, as well as 

timelines for meeting these goals. Through 

the policy, Target commits to work toward 

full transparency of chemicals contained and 

used to make the products it sells, to 

collaborate with its business partners to 

managing chemicals through the supply chain, 

and to support initiatives seeking to identify, 

develop, and commercialize safer chemicals 

and processes. In addition, Target plans to 

contribute $5 million by 2022 to support 

research to identify methods for effectively 

communicating about green chemistry, to 

develop an infrastructure for information 

sharing about product ingredients, and to 

create industry-wide hazard profiles for 
Technology Assessment GAO-18-307 107

chemicals, as well as to invest in companies 

developing products with less hazardous 

chemicals through a green chemistry venture 

capital fund. Target also collaborates with 

other stakeholders. For example, it is a 

member of the Retailer Leadership Council, 

consisting of leaders from seven retailers and 

five chemical manufactures convened by GC3 

that are working together to promote safer 

chemicals, materials, and products across 

retail supply chains by committing to dialog 

around goal setting and continuous 

improvement, communication about green 

chemistry throughout the supply chain, 

sharing information on chemical hazards and 

risks, providing information across the value 

chain with consumers, and supporting green 

chemistry education.166

Kaiser Permanente: Kaiser Permanente, which 

spends approximately $5.8 billion per year on 

medical products and equipment, has 

developed goals, policies, and tools to 

support the purchase of products 

manufactured using more sustainable 

chemistry. According to Kaiser Permanente 

officials, the organization’s goal is to increase 

the percentage of products it purchases 

meeting its environmental standards to 50 

percent by 2025. In 2006, Kaiser Permanente 

created Environmentally Preferable

Purchasing Principles requiring that certain 

criteria on chemical content and waste be 

considered in all major purchasing decisions. 

In 2017, Kaiser Permanente extended and 

strengthened the Principles by introducing an 

Environmentally Preferable Purchasing 

 166The Retail Leadership Council membership includes officials 

from retailers Wal-mart; Staples; Target; Home Depot; Best 

Buy; Lowe’s Companies, Inc.; and CVS Health; and chemical 

manufacturers BASF Corporation, Chemours, Dow Chemical, 

AkzoNobel, and Eastman.

Standard that mandates specific 

environmental criteria in the area of 

chemicals and waste to be met in purchasing 

decisions. For example, products must not 

contain toxic chemicals, bisphenol A (BPA), or 

flame retardants. According to Kaiser 

Permanente representatives, if multiple 

suppliers can provide a product that equally 

meets the organization’s clinical, regulatory, 

and sourcing requirements, Kaiser 

Permanente can choose one over another 

based on sustainability factors. However, if 

Kaiser Permanente is procuring a product that 

does not meet the Environmentally 

Preferable Purchasing Standard then the 

organization informs the supply base that it is 

actively seeking alterative suppliers or 

negotiates contract terms that include 

sustainability requirements. In addition, when 

Kaiser Permanente has a particular sourcing 

requirement, they may have the purchasing 

power to ensure a new product is developed 

that meets its criteria. When the company 

decided it would no longer purchase exam 

and surgical gloves made from polyvinyl 

chloride, which produce toxic dioxin as a 

byproduct during the manufacturing process 

and disposal, the decision impacted the entire 

medical glove industry, according to 

organization representatives, because Kaiser 

Permanente purchases more than 50 million 

gloves each year. Kaiser Permanente relies on 

other organizations such as EPA, Healthcare 

Without Harm, and other NGOs for 

information on hazardous chemicals. Kaiser 

Permanente’s Division of Research also 

conducts studies on the impacts of chemicals 

on human health, including the effect of 

workplace exposure to bisphenol A (BPA). 

Kaiser Permanente collaborates with other 

stakeholders such as NGOs on a number of 

initiatives. For example, the organization’s 

Environmentally Preferable Purchasing 
Technology Assessment GAO-18-307 108

Standard was developed with expertise from 

the Center for Environmental Health, 

Healthcare Without Harm, Clean Production 

Action, and Practice Greenhealth, among 

others, and used benchmarks from other 

organizations including Green Seal, EcoLogo, 

Electronic Product Environmental Assessment 

Tool, and EPA’s Design for the Environment 

program.

6.4.3 Academic institutions train the next 

generation of chemists 

Academic institutions and the academics that 

work in them play a role in supporting the 

development and use of more sustainable 

chemistry technologies by training the next 

generation of chemists, conducting relevant 

research, and sharing their expertise in 

collaborations with other stakeholders. One 

barrier to the development and use of more 

sustainable chemistry technologies may be

the conventional chemistry methods and 

practices taught in schools, which has led to a 

chemistry workforce that may not understand 

the principles of sustainable chemistry, 

according to officials GAO interviewed. One 

faculty member GAO interviewed said that 

one of the challenges to changing curriculums 

is a lack of incentives for professors along 

with the significant time and resources 

required to do so. However, some colleges 

and universities are beginning to integrate 

sustainable chemistry programs and classes 

into their chemistry curriculum. In addition, 

some academic institutions are collaborating 

with businesses, state and federal 

government, and NGOs to support the 

development and use of sustainable 

chemistry technologies. The University of 

Toledo’s School of Green Chemistry and 

Engineering and University of California’s 

Berkeley Center for Green Chemistry are two 

examples of academic programs focusing on 

education and research in sustainable 

chemistry.

In 2011, the University of Toledo established 

the School of Green Chemistry and 

Engineering, which, together with other 

university departments, offers a range of 

classes in green chemistry and engineering to 

interested students (see text box below). The 

mission of the university is to promote the 

sustainable use, production, and recycling of 

chemical materials through research, 

education, and outreach. The university 

awards an undergraduate minor in Green 

Chemistry and Engineering as well as a

Professional Science Master's Degree in 

Green Chemistry and Engineering that 

requires students to incorporate aspects of 

business and other professional skills into 

their M.S. degree, including courses such as 

“Technology Commercialization” and “Supply 

Chain Management.” Students in the more 

traditional M.S. and Ph.D programs in 

chemistry and chemical engineering can take 

the sustainability-related courses.

Selected courses related to sustainable chemistry 

offered at the University Toledo by the School of Green 

Chemistry and Engineering and its partner 

departments

• Green Chemistry

• Green Engineering Principles for Chemical 

Processes

• Environmental Chemistry

• Green Engineering Applications in Chemical 

Industry

• Chemistry of Sustainable Energy Resources

• Biofuels

• Environmental Geochemistry

• Hazardous Waste Management

• Environmental Economics

• Environmental Policy 

Source: University of Toledo School of Green Chemistry and Engineering.|

GAO-18-307
Technology Assessment GAO-18-307 109

The Berkeley Center for Green Chemistry at 

the University of California at Berkeley is an 

interdisciplinary program that integrates 

teaching and research on chemistry, 

environmental health, and public and private 

governance and management with the goal of 

bringing about a generational change in the 

design and use of more sustainable chemicals 

and materials. One of the courses offered by 

the Center is Greener Solutions, an 

interdisciplinary, project-based class in which 

students partner with a company to develop 

solutions to a particular sustainable chemistry 

problem. For example, students partnered 

with a technology firm to address emerging 

contaminants in e-waste, with an outdoor 

clothing manufacturer on the design of 

nontoxic mosquito repellency for polyester 

clothing, and with a workspace furniture 

company on developing safer colorants for a 

polypropylene chair. The Greener Solutions 

program has been supported by the California 

Department of Toxic Substances Control and 

a Pollution Prevention Grant from EPA Region 

9.

6.4.4 States protect public health by 

establishing requirement that can 

encourage the use of sustainable 

chemistry in products

State officials are enacting regulations to 

protect the human and environmental health 

of citizens and ecosystems by requiring the 

use of more sustainable chemistry in products 

and manufacturing processes. An NGO official 

that we interviewed noted that states have 

the advantage of being able to move faster 

than the federal government in making 

regulations, allowing states to play a 

leadership role in this area. State regulations 

range from banning specific chemicals, to 

requiring the disclosure of chemical 

ingredients in certain types of products, to 

more comprehensive approaches to reducing 

toxic chemicals in products. State officials 

work together through organizations such as 

through the Interstate Chemicals 

Clearinghouse to collaborate and share 

information and grow state government 

capacity. Massachusetts’ Toxics Use 

Reduction Act and California’s Safer 

Consumer Products program are examples of 

state-level regulation that can support the 

use of more sustainable chemistry. 

The state of Massachusetts enacted the 

Toxics Use Reduction Act in 1989 to reduce 

the use of toxic chemicals to promote 

industrial hygiene, worker safety, and 

protection of the environment and public 

health.

167 State industry, labor unions, and 

regulatory bodies came together to negotiate 

the statewide policy, which is loosely based 

on the federal Toxic Release Inventory 

program, according to state officials.168

Under the act, facilities in the state that use 

defined amounts of approximately 1,500 

specific toxic chemicals are required to 

annually report their chemical use and

conduct toxic chemical use reduction 

planning biennially. Facilities that use toxic 

chemicals must also pay an annual fee based 

on the number of employees and toxic 

chemicals used at the facility. Two state 

offices and an academic institute work 

together to implement the act. The 

 167ALM GL ch. 21I, § 1 et. seq. 

168Under EPA’s Toxics Release Inventory program, more than 

22,000 U.S. facilities report how much of 675 toxic chemicals 

they released to the environment and/or managed through 

recycling, energy recovery and treatment. EPA compiles the 

information submitted by facilities into the Toxics Release 

Inventory in order to provide the public with information about 

chemicals that may pose a threat to human and environmental 

health. 
Technology Assessment GAO-18-307 110

Massachusetts Department of Environmental 

Protection enforces the law’s mandates for 

annual reporting and biennial planning. The 

Toxics Use Reduction Institute, hosted by the 

University of Massachusetts Lowell, assists 

companies in meeting the act’s requirements 

by conducting and funding research on safer 

chemicals and processes, and providing 

training and advice to companies. The Office 

of Technical Assistance provides confidential, 

free technical assistance to companies 

wishing to reduce their use of toxic chemicals, 

comply with regulations, or make their 

processes more sustainable. Officials said that 

resources for both the Office of Technical 

Assistance and the Department of 

Environmental Protection have been reduced, 

creating challenges for implementing the 

program, particularly given the numbers of 

chemicals entering commerce and pressure 

from companies that have the incentive and 

resources to fight new regulations. 

State officials work with a range of 

stakeholders to advance the provisions of the 

act. For example, the Toxics Use Reduction 

Act Advisory Committee includes members 

from organized labor, large and small 

businesses, state agencies, and health and 

environmental advocacy groups. State 

officials also work with EPA. For example, 

state officials said they partner with EPA on 

conducting trainings and have received grants 

from EPA’s Pollution Prevention program. 

Under California’s Safer Consumer Products 

program, established pursuant to state law, 

California’s Department of Toxic Substance 

Control (DTSC) identifies and evaluates 

chemicals of concern and their potential 

alternatives, to determine how best to limit 

exposure or to reduce the level of hazard. 

According to a DTSC official, state officials 

were frustrated the federal government was 

not taking action to update TSCA. DTSC, which 

oversees the Safer Consumer Products 

program, established a four-step iterative 

process to encourage the use of safer 

substitutes for chemicals of concern in 

consumer products. 

1. DTSC establishes a list of Candidate 

Chemicals that have at least one quality 

that could harm human health or the 

environment. The initial list of Candidate 

Chemicals, released in October 2013, 

contained approximately 1,200 chemicals.

2. DTSC releases a list of Priority Products 

that DTSC has proposed for regulation 

that contain one or more of the 

Candidate Chemicals. A list of three 

products containing specific harmful 

chemicals was released in March 2014, 

which included certain children’s foampadded sleeping products, spray 

polyurethane foam, and paint strippers.

3. Responsible entities, including 

manufacturers, importers, assemblers, 

and retailers, must notify DTSC if they are 

manufacturing or selling Priority Products

in California. The entities generally must 

perform an Alternatives Analysis for those 

products to identify how to reduce risks 

to human and environmental health by, 

for example, replacing the chemical or 

redesigning the product. Specific life cycle 

impacts must be evaluated as part of an 

Alternatives Analysis and DTSC provides 

guidance and training in conducting the 

analysis.169 According to officials, DTSC is 

 169Under California law, the following factors must be 

considered: (A) product function or performance; (B) useful 

life; (C) materials and resource consumption; (D) water 

conservation; (E) water quality impacts; (F) air emissions; (G) 

production, in-use, and transportation energy inputs; (H)

energy efficiency; (I) greenhouse gas emissions; (J) waste and 

end-of-life disposal; (K) public health impacts, including 
Technology Assessment GAO-18-307 111

expecting the first Alternatives Analysis 

from responsible entities in 2018.

4. Following the Alternatives Analysis, DTSC 

may choose to regulate a Priority Product 

or an alternative that a responsible entity 

selected to replace it if needed to protect 

human health and the environment.

DTSC works closely with a range of 

stakeholders to implement the Safer 

Consumer Products legislation and on 

broader sustainable chemistry issues. For 

example, DTSC maintains an online database 

(CalSAFER) where information and comments 

related to regulatory action can be uploaded 

and shared by state offices and other 

stakeholders. An advisory board with 

members from academic institutions, 

industry, federal and state agencies, and 

others, provides advice to DTSC on scientific 

and technical matters. In addition, DTSC has a 

memorandum of understanding with EPA and 

Oregon and Washington for collaboration and 

information sharing to advance sustainable 

chemistry and, according to a DTSC official, 

has worked with the European Chemicals 

Agency and Organization for Economic Cooperation and Development on issues related 

to safer chemicals. 

6.4.5 Non-governmental organizations 

play a range of roles in supporting the 

development and use of more sustainable 

chemistry processes and products

Through a range of activities and initiatives, 

often in collaboration with other 

stakeholders, NGOs encourage and support 

 potential impacts to sensitive subpopulations, including infants 

and children; (L) environmental impacts; and (M) economic 

impacts.

the development and use of more sustainable 

chemical processes and products. For 

instance, NGOs develop tools and resources 

to enable industry and consumers to choose 

more sustainable products and processes, 

support the integration of sustainable 

chemistry principles into educational 

programs, and develop standards and best 

practices to guide decision makers seeking to 

be more sustainable. The following 

organizations are examples of NGOs working 

though diverse means to support more 

sustainable chemistry.

Beyond Benign, founded in 2007, supports 

professional development of chemistry 

teachers and professors and the integration 

of green chemistry principles and practices 

into all levels of education. For example, the 

organization equips elementary, middle, and 

high school educators to teach green 

chemistry by conducting in-person and online 

teacher training for middle and high school 

teachers, and developing teaching and 

curriculum materials. Working with the State 

of New York’s Department of Environmental 

Conservation, Beyond Benign conducted a 

series of 13 trainings for high school teachers 

across the state, according to Beyond Benign 

officials. Beyond Benign also works with 

industry to incorporate case studies on the 

companies’ green chemistry technologies into 

curriculum. Through Beyond Benign’s Green 

Chemistry Commitment program over 40 

academic institutions have committed to 

implementing certain green chemistry 

learning objectives at their schools and 

collaborate to address common challenges. 

Clean Production Action acts as an umbrella 

organization over three programs that 

support the use of inherently safer chemicals, 

materials, and products through convening 
Technology Assessment GAO-18-307 112

collaborators to work on sustainable 

chemistry and developing and managing tools 

to support the use of more sustainable 

chemicals. 

• BizNGO is a working collaborative that 

brings together stakeholders to identify 

areas of consensus between business and 

environmental groups to advance the use 

of safer chemical alternatives in product 

areas such as electronics, building 

products, and health care, according to a 

Network official. For example, the group 

created a protocol for assessing chemical 

alternatives and case studies that 

identified less hazardous alternatives for 

specific chemicals (such as surfactants 

and flame retardants), according to a 

Network official.

• GreenScreen® is a chemical hazard 

assessment tool that can be used by 

industry, government, and NGOs to 

identify chemical hazards and safer 

alternatives. GreenScreen Benchmarks 

allow decision makers to identify and rank 

increasingly safer chemicals as defined by 

environmental persistence, 

bioaccumulation, human- and ecotoxicity, and other factors. GreenScreen 

benchmarks can also be used by 

companies and state and federal 

agencies. For example, Wal-mart used 

GreenScreen to identify priority chemicals 

for substitution in its chemicals policy, 

eight states recommend GreenScreen as a 

tool for hazard assessments, and the U.S. 

Green Building Council offers Leadership 

in Energy and Environmental Design 

credits for using GreenScreen.

• The Chemical Footprint Project allows 

manufacturers and retailers to 

benchmark and communicate their 

progress in chemicals management 

performance and in reducing potentially 

hazardous chemicals relative to industry 

peers.

Green Seal awards certifications for products 

in over 400 product and service categories, 

based on a number of sustainability criteria, 

including those for chemical ingredients. The 

criteria identify ineligible chemicals by class 

(such as carcinogens), sets requirements 

chemicals must meet (such as 

biodegradability), limits certain compounds 

(such as volatile organic compounds), and 

sets requirements for use or disposal. Both 

state and federal offices have policies 

recommending the purchase of Green Seal 

certified products in specific categories; for 

example, EPA recommends Green Seal

certified paints in its revised 

recommendations for federal purchasing. 

When developing a new standard for a 

product, Green Seal gathers information from 

a range of sources including the EPA’s 

Integrated Risk Information System (IRIS)

database, NTP, and NIH’s Hazardous 

Substances Data Bank, and solicits 

information and comments from stakeholders 

including industry, the public, federal and 

state government, academic experts, NGOs, 

and others. In addition, Green Seal provides 

technical advice and assistance for companies 

and organizations developing policies and 

purchasing plans that incorporate 

sustainability concerns. Green Seal developed 

a green purchasing manual for the National 

Cooperative Highway Research Program, for 

instance, that included specifications for 

environmentally preferable alternatives for 

products containing toxic chemicals that are 

frequently used by state departments of 

transportation. 
Technology Assessment GAO-18-307 113

GreenBlue seeks to provide tools and 

resources to industry decision makers to 

inform choices about the use of safer 

chemicals and materials in their products. The 

organization encourages industry to conserve 

material resources, eliminate toxicity 

throughout the supply chain, and recover and 

reuse materials. The following programs are 

examples of how GreenBlue advances these 

goals.

• The Sustainable Package Coalition, whose 

membership consists of industry 

(including, for example, brands, packaging 

designers, retailers, and the recycling 

community), academic institutions, and 

government agencies, supports 

collaboration, research, and tool 

development with the purpose of 

improving the sustainability of packaging. 

• CleanGredients is a database of chemical 

ingredients that have been pre-approved 

to meet EPA’s Safer Choice certification 

criteria. The database also includes 

information on products and 

manufacturers to help formulators more 

efficiently obtain Safer Choice 

certification.

• The Material IQ program is developing a 

standardized methodology to facilitate 

the communication of chemical 

information between manufacturers

without compromising proprietary 

information. 
Technology Assessment GAO-18-307 114

7 Strategic Implications 

Sustainable chemistry is an emerging, 

innovative field within the chemical sciences 

that has the potential to inspire new products 

and processes, create jobs, and enhance 

benefits to human health and the 

environment. Chemical companies engaged in 

sustainable chemistry are working to reassess 

the entire chemical product life cycle from 

cradle-to-grave, seeking new conceptual 

frameworks for producing chemicals. These 

companies can be highly motivated and cited 

several drivers for their sustainable chemistry 

efforts, including consumer demand, reduced 

business costs, and company culture or 

mission. The three technology categories we 

discussed in this report—catalysts, solvents, 

and continuous processing—offer illustrations 

of the progress and potential for creating 

more sustainable chemistry technologies. 

However, as our survey and interviews with 

industry and other stakeholders found, there

are a number of challenges to implementing 

more sustainable chemistry technologies.

The technologies we assessed offer a number 

of potential environmental and human health 

benefits. Earth-abundant metals and metalfree catalysts are often readily available, less 

expensive than current catalysts, and less 

toxic. In addition, they can provide greater 

selectivity while reducing solvent use and 

other waste. Alternatives to current solvent 

use, such as biobased solvents, water and 

other less toxic solvents, and solvent-free 

technologies, can be safer or less toxic than 

conventional solvents, reduce dependence on 

non-renewable resources such as petroleum, 

and limit the need for costly solvent removal 

and disposal. Continuous processing can offer 

a number of advantages over conventional 

batch processing, including improved safety 

for workers and the environment, cost 

savings, and the potential for more 

controllable and repeatable processes. The 

small scale of continuous flow microreactors 

allows further benefits including shorter 

reaction times, lower energy consumption, 

and improved efficiency.

However, technological challenges remain. 

Alternative catalysts can be challenging to 

separate and reuse. In addition, some have a 

limited scope of reaction that can make them 

less widely useful, while others can be 

required in large quantities in order to 

provide sufficient reaction speed. Some 

biobased solvents pose the same inherent 

toxicity and volatility risks as their 

conventional counterparts; in addition, they 

can vary in supply and quality and can be 

expensive. The use of water and other less 

toxic solvents may require specialized 

equipment, greater energy input, or elevated 

pressure, and can be difficult to scale up for 

industrial use. Continuous processing can 

require significant capital investment to 

develop new infrastructure as well as 

specialized personnel for effective operation, 

among other challenges.

In addition to these technological barriers, 

companies told us they face many business 

challenges in their efforts to implement more 

sustainable chemistry technologies. These 

include the need to prioritize product 

performance; weigh sustainability tradeoffs 

between various technologies; risk 

disruptions to the supply chain when 

switching to a more sustainable option; 

address limited and expensive supplier 

options; consider regulatory challenges; 

develop a business case for sustainability 

investments; and address the often higher 

initial cost of more sustainable options. If 
Technology Assessment GAO-18-307 115

these challenges can be overcome, then 

companies can see a variety of economic 

benefits. For example, more sustainable 

products or technology uses can help firms 

differentiate from one another; this can 

create a competitive advantage that 

consumers recognize and value, and 

encourage firms to create more sustainable 

products. Similarly, the creation of more 

sustainable products can have good 

reputational effects that extend to other 

products made by that firm, regardless of 

whether those products are also more 

sustainable.

Furthermore, as our survey and interviews 

with industry and other stakeholders found, 

there are several basic, industry-wide 

challenges to implementing more sustainable 

chemistry technologies, such as the lack of a 

standard definition for sustainable chemistry 

as well as the lack of agreement on standard 

ways of measuring or assessing it. Without a 

standard definition that captures the full 

range of activities within sustainable 

chemistry, it is difficult to define the universe 

of relevant players. Without agreement on 

how to measure the sustainability of chemical 

processes and products, companies may be 

hesitant to invest in innovation they cannot 

effectively quantify, and end users are unable 

to make meaningful comparisons that allow 

them to select appropriate chemical products 

and processes. 

Sector-specific challenges exist as well. For 

example, industry representatives from the 

pharmaceutical sector told us that they can 

incorporate more sustainable technologies 

early in the drug development process, but 

changing the manufacturing process for an 

already marketed drug triggers the need for 

revalidation, which can result in delays and 

additional costs—thus discouraging 

innovation that could make their chemical 

processes more sustainable. Experts also 

noted the challenge of overturning proven 

conventional practices, and acknowledged 

that existing capital investments in current 

technologies can create barriers for new 

companies to enter a field full of wellestablished players. 

The varied nature of chemical processes and 

the diverse range of stakeholders in the 

United States—ranging from private 

companies and government agencies to 

academics, states, and non-governmental 

organizations—also contribute to difficulties 

making progress within the field of 

sustainable chemistry. There is no mechanism 

for coordinating a standardized set of factors 

for assessing sustainability across these 

stakeholder groups at present, despite the 

motivation that specific sectors possess. 

Moreover, although the federal government 

has worked with stakeholders through its 

research support, technical assistance, and 

certification programs, among other efforts, 

there are still gaps in understanding. Many 

stakeholders told us that without such basic 

information as a standardized approach for 

assessing the sustainability of chemical 

processes and products, better information 

on product content throughout the supply 

chain, and more complete data on the health 

and environmental impacts of chemicals 

throughout the life cycle, they cannot make 

informed decisions that compare the 

sustainability of various products. Experts 

noted that much more work is needed to 

realize the full promise of sustainable 

chemistry. For example, they raised a range of 

concerns and potential solutions, such as: 
Technology Assessment GAO-18-307 116

• Sustainable chemistry creates 

opportunities to use a different 

conceptual framework that allows 

industry to create molecules with new 

functional performance. There are major 

innovations demonstrating that it isn’t 

just about being less toxic or less 

polluting; breakthrough technologies in

sustainable chemistry could transform 

how the industry thinks about 

performance, function, and synthesis. 

• The establishment of an organized 

constituency, with the involvement of 

both industry and government, could help

make sustainable chemistry a priority. An 

industry consortium, working in 

partnership with a key supporter at the 

federal level, could lead to an effective 

national initiative or strategy.

• A national initiative that considers 

sustainable chemistry in a systematic 

manner could be useful. Such an effort 

could encourage collaborations among 

industry, academia and the government, 

similar to the National Nanotechnology 

Initiative.170

• There are opportunities for the federal 

government to address industry-wide 

challenges. Federal attention that 

facilitates development of standard tools 

for assessment and a robust definition 

could help clarify relevant participants in 

the field and improve information 

available for decision makers at all levels. 

 170The National Nanotechnology Initiative is a U.S. government 

R&D initiative involving 20 departments and independent 

agencies working on science, engineering, and technology 

conducted at the nanoscale, which is about 1 to 100 

nanometers; a nanometer is one billionth of a meter.

• A research agenda that links research to 

policy is lacking. In Canada, for example, 

there is a coordinated technology effort 

that is focused on basic R&D and scale 

testing, addressing chemical substitution 

from the beginning to the end of the life 

cycle process.

• A focus on the bigger problems that need 

to be solved, such as supply chain issues, 

is an important priority. Federal agencies 

can play a role in demonstrating, piloting,

and de-risking some of these technology 

development efforts.

• STEM-related initiatives and intellectual 

property tools can add value. For 

example, R&D tax credits for qualified 

research expenses could provide 

subsidies to encourage business 

investment in research.171 In addition, 

patent term restoration, as has been 

applied to drug products, is designed to 

encourage innovation, as profits resulting 

from patent protection can serve as 

incentives for creating innovative 

products that benefit the public.172

Furthermore, students and adults could 

be empowered to create, innovate, and 

turn their ideas into new products, 

through either volunteerism or public 

service.

 171GAO, Tax Policy: The Research Tax Credit’s Design and 

Administration Can Be Improved, GAO-10-136 (Washington, 

D.C.: Nov. 6, 2009).

172Patents issued by the Patent and Trademark Office grant 

patent holders the right to exclude others from making, using, 

or selling an invention. The granting of this exclusive right is 

designed to encourage innovation. The patent holder is likely 

to reap greater profits if protected from direct competition. 

These profits are intended to serve as incentives for creating 

innovative products that benefit the public.
Technology Assessment GAO-18-307 117

• New training to upgrade the chemistry 

and manufacturing workforces could 

encourage innovation. Integrating 

sustainable chemistry principles into 

educational programs could bolster a new 

generation of chemists and advance 

student achievement in the field. 

According to experts, transitioning toward the 

use of more sustainable chemistry 

technologies requires that industry, 

government, and other stakeholders work 

together. As they and others noted, there is a 

need for new processes that make more 

efficient use of the resources that are 

available, reuse products or their components 

during manufacturing, and account for 

impacts across the entire life cycle of 

chemical processes and products. 

Furthermore, they highlight the importance 

of disseminating environmental and healthrelated information to help guide the choices 

of consumers, chemists, workers, 

downstream users, and investors to facilitate 

further progress. They also indicated that

momentum in this field will require national 

leadership in order to realize the full potential 

of sustainable chemistry technologies. 
Technology Assessment GAO-18-307 118

8 Agency and expert comments

We provided a draft of relevant excerpts from this report to the Department of Commerce 

(National Institute of Standards and Technology), Department of Defense, Department of 

Energy, Department of Health and Human Services, Environmental Protection Agency, National 

Science Foundation, and U.S. Department of Agriculture, with a request for technical comments. 

We incorporated the comments received into this report as appropriate. 

We also provided a draft of the key chapters of this report to the participants in our expert 

meeting with a request to review it for scientific and technical accuracy. Of these, six provided 

technical comments that we incorporated as appropriate. 

As agreed with your office, unless you publicly announce its contents earlier, we plan no further 

distribution of this report until 30 days from its issue date. At that time, we will send copies of 

this report to the appropriate congressional committees, relevant federal agencies, and other 

interested parties. In addition, the report will be available at no charge on the GAO website at 

http://www.gao.gov. 

If you or your staff members have any questions about this report, please contact Timothy M. 

Persons at (202) 512-6412 or personst@gao.gov or John Neumann at (202) 512-3841 or 

neumannj@gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs 

may be found on the last page of this report. GAO staff who made key contributions to this 

report are listed in appendix VII.

Timothy M. Persons, Ph.D.

Chief Scientist 

John Neumann

Director

Natural Resources and Environment
Technology Assessment GAO-18-307 119

Appendix I: Objectives, scope, and methodology

We describe our scope and methodology for 

addressing the three objectives outlined 

below, related to technologies for making 

chemical processes and products more 

sustainable.

Objectives

1. Identify how stakeholders define 

sustainable chemistry and approaches 

that are used to assess the sustainability 

of chemical processes and products.

2. Assess selected technologies that are 

available or in development to make 

chemical processes and products more 

sustainable.

3. Describe the contributions of the federal 

government, industry, and others to the 

development and use of such 

technologies.

Scope and methodology 

To address our objectives, we reviewed key 

reports and scientific literature to establish 

background, identify appropriate 

technologies and their advantages and 

disadvantages, identify stakeholders, and 

inform survey questions. We also convened 

an expert meeting with the assistance of the 

National Academies; interviewed 

representatives of federal and state agencies, 

chemical companies, industry and 

professional organizations, academic 

institutions, nongovernmental organizations

(NGO), and other stakeholders; conducted 

site visits to federal laboratories; fielded a 

survey of selected chemical companies; and

attended two technical conferences.

Limitations to scope

We limited the scope of our review to 

selected technologies in three main 

categories that are primarily related to the 

raw materials and chemical processing phases

of the product life cycle: catalysis, solvent use, 

and alternatives to batch processing. We did 

not assess all available or developing 

technologies in these three categories, nor 

did we assess technologies in other phases of 

the chemical product life cycle. For example, 

we did not assess technologies for recycling 

industrial waste into new feedstocks or for 

post-consumer recycling of chemical 

products. 

Expert meeting

Early in our study, we collaborated with the 

National Academies to convene a two-day 

meeting of 24 experts on sustainable 

chemistry technologies and approaches. 

Specifically, we collaborated with National 

Academies staff to select participants from 

the chemical industry, academia, federal 

agencies including a national laboratory, 

professional organizations, and others, with 

expertise covering most significant areas of 

our review.1 A conflict of interest was 

considered to be any current financial or 

other interest that might conflict with the 

service of an individual because it (1) could 

impair objectivity or (2) could create an unfair 

competitive advantage for any person or 

 1

After the expert meeting, we changed one of our three target 

industry sectors from textiles/apparel to formulators (i.e., 

makers of personal care and cleaning products); thus we did 

not have a formulator represented at the meeting. However, 

we interviewed and surveyed several formulator companies 

during the course of our study.
Technology Assessment GAO-18-307 120

organization. The 24 experts were 

determined to be free of conflicts of interest 

except those that were easily addressed, and 

the group as a whole was judged to have no 

inappropriate biases. (See appendix II for a list 

of these experts and their affiliations.)

During this meeting, we solicited input from 

the experts on the design for our work. 

Specifically, we moderated discussion 

sessions on several topics, including examples 

of technologies to make chemical processes 

and products more sustainable; applications 

of such technologies in industry; economic 

and business aspects of developing and 

implementing the technologies; approaches 

to assessing the sustainability of chemical 

processes and products; the role of standards, 

regulations, and related programs; and 

additional stakeholder perspectives. The 

meeting was recorded and transcribed to 

ensure that we accurately captured the 

experts’ statements. We also continued to 

draw on the expertise of these individuals 

throughout our study and, consistent with our 

quality assurance framework, we provided 

them with a draft of our report and solicited 

their feedback, which we incorporated as 

appropriate. 

Site visits

We conducted site visits to federal 

laboratories to discuss technologies that are 

in development, including challenges to 

developing and commercializing such 

technologies. Specifically, we visited the 

Toxicology in the 21st Century (Tox21) 

Robotics Facility at the National Center for 

Advancing Translational Sciences, as well as 

the National Institute of Standards and 

Technology’s (NIST) Materials Science and 

Engineering Division and Facility for 

Adsorbent Characterization and Testing. 

Additional interviews

We conducted a total of 82 interviews with 

representatives from the following groups of 

stakeholders:

• Federal and state agencies including the 

Department of Commerce and NIST, 

Department of Defense, Department of 

Energy including three of its national 

laboratories, Department of Health and 

Human Services including the Food and 

Drug Administration (FDA) and National 

Institutes of Health (NIH), Environmental 

Protection Agency (EPA), National Science 

Foundation (NSF), Small Business 

Administration, U.S. Department of 

Agriculture (USDA), the California 

Department of Toxic Substances Control 

(DTSC) Safer Consumer Products Program, 

and two Massachusetts state offices.

• Chemical companies that we or other 

interviewees identified as involved in 

developing and implementing relevant 

technologies. (See app. III for a list of 

participating chemical companies.)

• Industry and professional organizations 

including the American Chemical Society 

(ACS) and ACS’s Green Chemistry Institute 

(GCI); the American Chemistry Council 

(ACC); and the Society of Chemical 

Manufacturers and Affiliates (SOCMA).

• Academic institutions including the 

Berkeley Center for Green Chemistry, the 

University of Massachusetts – Lowell’s 

Toxics Use Reduction Institute (TURI), and 

the University of Toledo.

• NGOs including Beyond Benign, the Clean 

Production Action, the Green Chemistry 

and Commerce Council (GC3), GreenSeal, 

GreenBlue, and the Natural Resources 

Defense Council.
Technology Assessment GAO-18-307 121

• One institutional purchaser (Kaiser 

Permanente) and one retailer (Target 

Corporation).

Identifying interviewees 

Federal programs and offices

We relied on recommendations from federal 

agency officials to identify specific federal 

programs and offices that conduct work 

related to supporting the development and 

use of sustainable chemistry technologies. We 

then interviewed officials from those 

programs, gathered documentary evidence 

on their activities, and identified which of 

these programs and offices had activities 

directly related to sustainable chemistry 

technologies. Based on our analysis of the 

activities performed by those programs and 

offices, we identified three key roles federal 

agencies play in supporting sustainable 

chemistry technologies. For federal agencies, 

our goal was to identify all relevant federal 

programs that conduct activities to promote 

the development and use of sustainable 

chemistry technologies. We described 

selected programs and offices to illustrate 

each of these roles in the report.

Other stakeholders

Our aim was to identify stakeholders to serve 

as illustrative, non-generalizable examples of 

the roles that stakeholders play in supporting 

the development and use of sustainable 

chemistry technologies. Where appropriate, 

we sought diversity among the selected 

stakeholders with regard to their mission, 

sector focus, or policy orientation. Our 

primary method for obtaining specific names 

of organizations and individuals was to ask 

interviewees for recommendations of 

additional stakeholders; we supplemented 

this approach with other methods such as 

searching relevant grant databases and other 

lists. We ended this selection process when 

we felt that the representation of 

interviewees within each category was 

sufficient.

Company selection

To select companies for our interviews and 

survey, our purpose was to first identify three 

industry sectors on which to focus: basic 

chemical manufacturing, pharmaceuticals, 

and formulators (i.e., makers of personal care 

and cleaning products such as soaps, 

detergents, toiletries, and cleaning 

compounds). These sectors were chosen 

based on expert recommendations of sectors 

which are active in implementing more 

sustainable chemistry technologies, as well as 

the size of these sectors and the proportion of 

the chemical industry they represent. 

According to the Bureau of Labor Statistics 

within the Department of Labor, as of July 

2016 these three sectors were the three 

largest in the chemical industry in terms of 

number of employees. Specifically, basic 

chemical manufacturing (148,500 employees), 

pharmaceutical and medicine manufacturing 

(281,440 employees), and formulators (i.e., 

soap, cleaning compound, and toilet 

preparation manufacturing; 104,150 

employees) accounted for about 65 percent 

of the 819,700 employees across the chemical 

industry.

We then used an iterative process to identify 

companies within these sectors, relying on 

each of our interviewees to refer us to other 

companies that could provide perspectives on 

the development and implementation of 

technologies within our scope. Specifically, 

we first interviewed two chemical

manufacturers (Dow Chemical and Elevance) 

and two pharmaceutical companies (Merck 

and Pfizer) because representatives of these 
Technology Assessment GAO-18-307 122

companies participated in our expert meeting 

and thus had already demonstrated an 

interest in and knowledge of relevant 

technologies. As a second step, we contacted 

the ACS GCI to ask for a list of companies that 

belong to the three most relevant GCI 

industry roundtables: the Chemical 

Manufacturers Roundtable, the 

Pharmaceutical Roundtable, and the 

Formulators Roundtable. We believe that this 

was an appropriate approach for identifying 

companies because these companies, by 

voluntarily choosing to participate in the ACS 

GCI industry roundtables, have clearly 

demonstrated an interest in (and therefore 

increased likelihood of using) more 

sustainable chemistry technologies. Next, we 

asked each of our industry interviewees from 

these first two steps for additional 

suggestions of companies to interview and 

interviewed any within our target sectors that 

agreed to participate. We turned next to 

companies recommended by the federal 

agencies we interviewed and selected 

additional companies to contact, with a focus 

on small or medium-sized companies within 

our three target sectors because most of the 

companies from our first two rounds of 

interviews were large. 

In total we interviewed representatives of 27 

companies including 16 chemical 

manufacturers, 9 pharmaceutical companies, 

6 formulators, and 1 company from another 

industry sector. (See app. III for a list of 

participating chemical companies.) Some of 

the 27 companies identified themselves with 

more than one industry sector. In addition to 

conducting interviews with these companies, 

we also sent our survey to these same 

companies and received responses back from 

18 of the companies. Because this is a small 

and non-generalizable sample of the universe 

of U.S. chemical companies, the results of our 

interviews and survey are illustrative and 

indicative of important issues, but not 

generalizable.

Survey of selected chemical 

companies

We surveyed the same non-generalizable 

sample of 27 chemical companies we 

previously interviewed in order to collect data 

on several items that were relevant to our 

objectives.

Questionnaire design 

We designed a questionnaire covering four 

primary topics: (a) approaches the selected 

companies use to assess the sustainability of 

their chemical processes and products; (b) the 

extent and perceived value of their 

interactions with other stakeholders, 

including federal agencies, customers, 

suppliers, academics, and NGOs; (c) 

challenges or gaps in stakeholder 

interactions; and (d) challenges or barriers to 

the development and use of more sustainable 

chemistry technologies.

After drafting the questionnaire, we 

pretested it over the telephone with four 

officials from chemical companies. During 

these pretests we focused on making sure 

that (1) the questions were clear and logical, 

and (2) the questionnaire could be completed 

without undue burden on company officials. 

In three cases, the officials were from 

companies that would not receive the full 

survey; the final pretest was with a company 

that did receive the full survey. After each 

pretest we made revisions to clarify the 

questions, decrease the likelihood of 

inaccurate responses, and minimize response 

burden on company officials. The 

questionnaire was independently peerreviewed by a GAO survey specialist. 
Technology Assessment GAO-18-307 123

Appendix IV provides the questions in the 

survey instrument and quantitative results 

(i.e., response counts) from the survey. 

Survey administration 

The surveys were sent by email on January 4 –

6, 2017; in all cases they were sent to the 

same company officials who participated in 

our interviews with each company. A 

reminder email was sent one week after 

deployment and a similar reminder was sent 

on the original due date of January 18, 2017, 

to provide a one-week extension. In total, 

responses were received from 18 of the 

original 27 recipient companies, for a 67 

percent response rate.

Survey data analysis 

In general, our analysis involved primarily 

generation of frequency counts for all of the 

close-ended variables in our survey. We also 

performed cross-tabulations of our survey 

data by industry sector. 

There was one question in our survey that 

involved more advanced analytical 

techniques. This was the complex matrix 

question 6 that asked respondents to 

compare a set of 13 environmental and 

health factors, one by one, against each other 

factor. For each pairing, respondents were 

asked: “If your company could only achieve a 

benefit for one of the factors in the pair at the

expense of the other, for which factor would 

your company generally consider it more 

important to achieve a benefit?” To 

summarize the resulting data in a concise 

form and ascertain the relative importance of 

the 13 factors, we developed the following 

scoring approach: 

• Assign one point to a factor each time a 

company responded that it was more 

important to achieve a benefit for this 

factor than for the other factor in the 

pairing. 

• If the two factors were rated as equal, 

assign 0.5 points to both factors.

• If there was no answer provided or the 

company said it had no opinion, no score 

was assigned. 

• These scores were then added for each 

factor across every pair of factors. 

Results from these analyses are provided in 

chapter 2.
Technology Assessment GAO-18-307 124

Appendix II: Expert participation

We collaborated with the National Academies to convene a two-day meeting of experts to 

inform our work on sustainable chemistry technologies; the meeting was held on May 24-25, 

2016. The experts who participated in our study are listed below. Many of these experts gave us 

additional assistance throughout our work, including 12 who provided additional technical 

assistance during our study by sending additional technical material for our review, commenting

on the proposed scope of our technology chapters, or answering technical questions; 1 who 

pretested our survey; and 6 who reviewed our draft report for accuracy and provided technical 

comments.

Dave Allen

Melvin H. Gertz Regents Chair in 

Chemical Engineering

University of Texas at Austin

Joe Armstrong

Executive Director, Process Chemistry

Merck & Co., Inc.

Tina Bahadori

National Program Director, Chemical Safety for 

Sustainability National Research Program

Environmental Protection Agency

Eric Beckman

George M. Bevier Professor of Engineering

Co-Director, Mascaro Center for Sustainable 

Innovation

University of Pittsburgh

Paul A. Bertin

Research Group Leader, Innovation

Elevance Renewable Sciences

Henry Bryndza

Global Technology Director

DuPont Protection Solutions

R. Morris Bullock

Director of the Center for Molecular 

Electrocatalysis

Pacific Northwest National Laboratory

Terrence Collins

Teresa Heinz Professor of Green Chemistry

Carnegie Mellon University

David Constable

Director, ACS-Green Chemistry Institute

American Chemical Society

Ian Davies

Merck & Co., Inc.

Richard Engler

Senior Chemist

Bergeson & Campbell PC

John Frazier

Independent Consultant

Previously Senior Director of Chemistry, NIKE

Martin Green

Materials Research Engineer

National Institute of Standards and Technology
Technology Assessment GAO-18-307 125

Richard Helling

Director, Sustainable Chemistry

The Dow Chemical Company

Philip Jessop

Canada Research Chair in Green Chemistry

Queen’s University, Ontario, Canada

Bruce Lipshutz

Professor of Chemistry

University of California, Santa Barbara

Steve Maguire

Professor, Strategy and Organization

Director, Marcel Desautels Institute for

Integrated Management

McGill University, Quebec, Canada

Jennifer McPartland

Senior Scientist, Health Program

Environmental Defense Fund

KC Morris

Computer Scientist

National Institute of Standards and Technology

Robin Rogers

President/Owner/Founder, 

525 Solutions, Inc.

Adjunct Professor

McGill University, Quebec, Canada

Kevin Swift

Chief Economist and Managing Director, 

Economics and Statistics

American Chemistry Council

John Warner

President and Chief Technology Officer

Board of Directors

Warner Babcock

Todd Werpy

Senior Vice President and Chief Technology 

Officer

Archer Daniels Midland Company

Julie Zimmerman

Professor of Chemical & Environmental 

Engineering and Forestry & Environmental 

Studies

Yale University
Technology Assessment GAO-18-307 126

Appendix III: Industry participation

We interviewed and fielded our industry survey to representatives of 27 chemical companies. 

One of these companies both pretested and received the survey. We also spoke with 

representatives of 2 additional companies; these companies assisted us by pretesting the 

survey.

Chemical Companies

Agilyx Corporation 

Amgen 

Amway 

Asymchem 

BASF Corporation 

Bimax, Inc. 

Boerhinger-Ingelheim 

Chemours 

Connora Technologies 

Dixie Chemical 

Dow Chemical Company 

Dupont 

Elevance 

Eli Lilly 

Entropy Solutions 

Florida Chemical 

Genetech 

Glaxo Smith Kline 

Glycosurf 

Johnson & Johnson 

Mango Materials 

Merck 

Nissan Chemical America 

Novozymes 

Pfizer 

Proctor and Gamble 

Rochester Midland 

Seventh Generation 

State Industrial 

Industry groups or collaborations

American Chemical Society (ACS) – Green Chemistry Institute (GCI)

American Chemistry Council (ACC)

Less Energy-Intensive Alternative Separations Program (ALTSEP)
Technology Assessment GAO-17-75 127

Appendix IV: Survey of chemical companies’ sustainable chemistry 

activities

This appendix presents the questions from our survey of chemical companies and the 

corresponding response counts. The survey included a limited number of open-ended questions; 

we have omitted the narrative responses from this appendix.

SECTION 1: Demographics 

1. Which industry sectors accurately describe your company? (Check all that apply.)

Chemical 

manufacturing Formulatora Pharmaceuticals Other Number of respondents

11 4 7 —b 18

Notes: 

a

For purposes of our survey and report, formulator companies are makers of personal care and cleaning 

products.

b

Responses of “Other” were discussed with the respondents and converted to one of the three primary sectors.

If you checked more than one box above, is there one that you consider to be the primary 

industry sector for your company?

Narrative responses are intentionally omitted; all subsequent analyses included companies as 

members of any sector they checked in question 1, not just the primary sector they noted here.

2. Approximately how many employees does your company have? (Check only one box.)

Less than 100 100–499 500–999 1,000–4,999 5,000 or more Number of respondents

3 2 0 1 12 18
Technology Assessment GAO-17-75 128

SECTION 2: Assessing the Sustainability of Chemical Processes or Products

3. For each of the product development or manufacturing activities in column A, please 

identify which are conducted in-house as part of your company’s normal operations by 

checking the corresponding box in column B. (Check all that apply.)

For those activities that you checked in column B, please identify those that would 

typically include some type of sustainability assessment by checking the corresponding 

box in column C. (NOTE: For purposes of this survey, a sustainability assessment refers to 

some type of determination of the impact of a chemical process or product on one or more 

environmental or health factors such as energy use, toxicity, or volume of waste generated.)

A. Product Development or Manufacturing 

Activity

B. Does your company do 

this activity in-house as 

part of your normal 

operations?

(number checked)

(If applicable)

C. When your company does 

this activity, do you also

typically conduct some 

type of sustainability 

assessment?

(number checked)

Development of new products (including 

feasibility studies, R&D, and/or scale up)

18 18 of 18

Changes to the manufacturing process for an 

existing product

16 10 of 16

Reformulation of an existing product by changing 

one or more ingredients or the proportions of 

ingredients 

15 9 of 15

Changing one or more non-formulation features 

of an existing product, such as the packaging or 

source of ingredients

14 12 of 14

Number of respondents 18 18
Technology Assessment GAO-17-75 129

4. Thinking across the various types of sustainability assessments your company may conduct 

for chemical processes or products, how often does your company include each of the 

following life cycle phases in those assessments? (Check one.) 

A. Life cycle phase

B. How often does your company 

include each phase in its 

sustainability assessments?

(If applicable)

C. If you checked in column B 

that your company rarely or 

never includes this life cycle 

phase, please explain. 

Supply chain Always = 7 

Usually = 6

Sometimes = 5

Rarely = 0

Never = 0

[Number of respondents = 18]

Narrative responses 

intentionally omitted

Starting materials Always = 6 

Usually = 9

Sometimes = 3

Rarely = 0

Never = 0

[Number of respondents = 18]

Narrative responses 

intentionally omitted

Chemical processes within your 

facility (including waste streams)

Always = 10 

Usually = 5

Sometimes = 3 

Rarely = 0

Never = 0

[Number of respondents = 18]

Narrative responses 

intentionally omitted

Product characteristics (including 

packaging)

Always = 3

Usually = 7

Sometimes = 7

Rarely = 1

Never = 0

[Number of respondents = 18]

Narrative responses 

intentionally omitted

Product use Always = 5 

Usually = 5

Sometimes = 4

Rarely = 1 

Never = 3

[Number of respondents = 18]

Narrative responses 

intentionally omitted

Product disposal or recycling Always = 5 

Usually = 6

Sometimes = 4

Rarely = 2

Never = 1

[Number of respondents = 18]

Narrative responses 

intentionally omitted
Technology Assessment GAO-17-75 130

A. Life cycle phase

B. How often does your company 

include each phase in its 

sustainability assessments?

(If applicable)

C. If you checked in column B 

that your company rarely or 

never includes this life cycle 

phase, please explain. 

Other (please specify):

(Narrative responses 

intentionally omitted)

Always = 0 

Usually = 2

Sometimes = 0

Rarely = 0

Never = 0

[Number of respondents = 2]

Narrative responses 

intentionally omitted

5. Thinking across the various types of sustainability assessments your company may

conduct for chemical processes or products, how often does your company include each of 

the following environmental or health factors in those assessments?(Check one.)

For any factors that you rarely or never include in your sustainability assessments, please 

check any appropriate reason(s) in the corresponding box in column C.

A. Environmental or 

health factor

B. How often does your company 

include each factor in its 

sustainability assessments? (Check 

one.)

(If applicable)

C. If you checked in column B that your 

company rarely or never includes this 

factor, please check any appropriate 

reason(s). (Check all that apply.)

Percentage of renewable 

or biobased content 

Always = 3

Usually = 4

Sometimes = 3

Rarely = 5

Never = 3

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

3

0

1

0

3

Amount of materials 

required (e.g., ‘E factor’ or 

process mass intensity)

Always = 7

Usually = 5

Sometimes = 5

Rarely = 1

Never = 0

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

0

0

0

0

1

Toxicity of required 

materials

Always = 13

Usually = 3

Sometimes = 2

Rarely = 0

Never = 0

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

n

/

a
Technology Assessment GAO-17-75 131

A. Environmental or 

health factor

B. How often does your company 

include each factor in its 

sustainability assessments? (Check 

one.)

(If applicable)

C. If you checked in column B that your 

company rarely or never includes this 

factor, please check any appropriate 

reason(s). (Check all that apply.)

Energy use Always = 6

Usually = 4

Sometimes = 6

Rarely = 2

Never = 0

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

0

1

1

0

1

Water use Always = 4

Usually = 5

Sometimes = 7

Rarely = 2

Never = 0

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

0

2

0

0

0

Land use/physical 

footprint

Always = 1

Usually = 6

Sometimes = 7

Rarely = 2

Never = 1

[Number of respondents = 17]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

0

0

2

0

0

Greenhouse gas 

emissions

Always = 5

Usually = 6

Sometimes = 4

Rarely = 3

Never = 0

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

1

0

2

0

0

Other air emissions Always = 4

Usually = 7

Sometimes = 5

Rarely = 1

Never = 1

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

1

1

0

0

0
Technology Assessment GAO-17-75 132

A. Environmental or 

health factor

B. How often does your company 

include each factor in its 

sustainability assessments? (Check 

one.)

(If applicable)

C. If you checked in column B that your 

company rarely or never includes this 

factor, please check any appropriate 

reason(s). (Check all that apply.)

Volume of process waste 

generated

Always = 6

Usually = 7

Sometimes = 3

Rarely = 1

Never = 1

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

0

0

1

0

1

Toxicity of process waste Always = 9

Usually =2

Sometimes = 4

Rarely = 3

Never = 0

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

1

0

1

0

1

Recyclability of (or other 

uses for) process waste

Always = 2

Usually = 5

Sometimes = 7

Rarely = 4

Never = 0

[Number of respondents = 18]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

0

0

1

0

1

Other environmental or 

health factor (please 

specify):

(Narrative responses 

intentionally omitted)

Always = 4

Usually = 0

Sometimes = 3

Rarely = 0

Never = 0

[Number of respondents = 7]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

0

0

0

0

0

Other environmental or 

health factor (please 

specify):

(Narrative responses 

intentionally omitted)

Always = 2

Usually = 1

Sometimes = 2

Rarely = 0

Never = 0

[Number of respondents = 5]

Not relevant to my company

Data not available

Cannot be reliably measured

Too costly to include

Other (please specify): 

(Narrative responses intentionally 

omitted)

0

0

0

0

0
Technology Assessment GAO-17-75 133

6. When making a change to a chemical process or product, it may sometimes be necessary to 

make sustainability tradeoffs. That is, a given change may produce a sustainability benefit 

for one factor at the expense of reduced sustainability for the other factor. 

When comparing each pair of factors in the matrix below, if your company could only 

achieve a benefit for one of the factors in the pair at the expense of the other, for which 

factor would your company generally consider it more important to achieve a benefit? 

How to fill out this table: For each cell, compare the factor listed in the row (items down the 

left side, in red) with the factor listed in the column (items across the top, in blue). For each 

pair of factors, choose your response as follows:

Row – It is generally more important to achieve a benefit for the factor in the Row

Column – It is generally more important to achieve a benefit for the factor in the Column

Equal – We give the two factors Equal emphasis

None/NA – We have No opinion or Not Applicable

(Note: Unless otherwise noted, 15 of the 18 respondents answered this question for each cell 

in the matrix.)

(See the following pages for the matrix and results.)
Technology Assessment GAO-17-75 134

Rows are defined as follows: 

1 – Percentage of renewable or biobased 

content

2 – Amount of materials required 

(e.g., ‘E factor’ or process mass 

intensity)

3 – Toxicity of required materials 

4 – Energy use

5– Water use

6 – Land use/physical footprint

7 – Greenhouse gas emissions

8 – Other air emissions

9 – Volume of process waste generated

10 – Toxicity of process waste

11 – Recyclability of (or other uses for) 

process waste

12 – Toxicity of the product

Columns are defined as follows:

A – Amount of materials required (e.g., ‘E 

factor’ or process mass intensity)

B – Toxicity of required materials

C – Energy use

D – Water use

E – Land use/physical footprint

F – Greenhouse gas emissions

G – Other air emissions

H – Volume of process waste generated

I – Toxicity of process waste

J – Recyclability of (or other uses for) 

process waste

K – Toxicity of the product

L – Recyclability of the product

A B C D E F G H I J K L

1

2

3

4

5

6

7

8

9

10

11

12
Technology Assessment GAO-17-75 135

Question 6 results:

6. In each pair of factors, for which factor (row or column) would your company consider it 

more important to achieve a benefit? 

Number of respondents; most frequent 

response(s) in bold, dark red font

Cell 

Factors in the row and column;

most frequent response(s) in bold, dark red font Row Column Equal

None/

NA

1 A Row: Percentage of renewable or biobased content

Column: Amount of materials required

2 10 1 2 

1 B Row: Percentage of renewable or biobased content

Column: Toxicity of required materials

0 10 3 2

1 C Row: Percentage of renewable or biobased content

Column: Energy use

0 9 3 3

1 D Row: Percentage of renewable or biobased content

Column: Water use

1 6 4 4

1 E Row: Percentage of renewable or biobased content

Column: Land use/ physical footprint

5 5 2 3

1 F Row: Percentage of renewable or biobased content

Column: Greenhouse gas emissions

1 9 3 2

1 G Row: Percentage of renewable or biobased content

Column: Other air emissions

1 9 2 3

1 H Row: Percentage of renewable or biobased content

Column: Volume of process waste generated

1 10 1 3

1 I Row: Percentage of renewable or biobased content

Column: Toxicity of process waste

1 9 2 3

1 J Row: Percentage of renewable or biobased content

Column: Recyclability of (or other uses for) process waste

1 7 5 2

1 K Row: Percentage of renewable or biobased content

Column: Toxicity of the product

1 9 1 4

1 L Row: Percentage of renewable or biobased content

Column: Recyclability of the product

3 6 2 4

2 B Row: Amount of materials required

Column: Toxicity of required materials

1 11 3 0

2 Ca Row: Amount of materials required

Column: Energy use

6 3 4 1

2 D Row: Amount of materials required

Column: Water use

7 3 4 1

2 E Row: Amount of materials required

Column: Land use/physical footprint

10 3 1 1

2 Fa Row: Amount of materials required

Column: Greenhouse gas emissions

7 4 3 0

2 Ga Row: Amount of materials required

Column: Other air emissions

6 4 3 1

2 H Row: Amount of materials required

Column: Volume of process waste generated

2 3 9 1

2 I Row: Amount of materials required

Column: Toxicity of process waste

3 8 3 1
Technology Assessment GAO-17-75 136

Number of respondents; most frequent 

response(s) in bold, dark red font

Cell 

Factors in the row and column;

most frequent response(s) in bold, dark red font Row Column Equal

None/

NA

2 J Row: Amount of materials required

Column: Recyclability of (or other uses for) process waste

8 1 5 1

2 K Row: Amount of materials required

Column: Toxicity of the product

1 11 1 2

2 L Row: Amount of materials required

Column: Recyclability of the product

8 2 1 4

3 Ca Row: Toxicity of required materials

Column: Energy use

11 1 2 0

3 Da Row: Toxicity of required materials

Column: Water use

10 1 3 0

3 Ea Row: Toxicity of required materials

Column: Land use/physical footprint

12 1 1 0

3 Fa Row: Toxicity of required materials

Column: Greenhouse gas emissions

10 2 2 0

3 Ga Row: Toxicity of required materials

Column: Other air emissions

8 2 3 1

3 H Row: Toxicity of required materials

Column: Volume of process waste generated

10 1 3 1

3 I Row: Toxicity of required materials

Column: Toxicity of process waste

3 2 9 1

3 J Row: Toxicity of required materials

Column: Recyclability of (or other uses for) process waste

11 1 3 0

3 K Row: Toxicity of required materials

Column: Toxicity of the product

1 9 3 2

3 L Row: Toxicity of required materials

Column: Recyclability of the product

9 1 1 4

4 Da Row: Energy use

Column: Water use

8 2 4 0

4 Ea Row: Energy use

Column: Land use/physical footprint

10 1 2 1

4 Fa Row: Energy use

Column: Greenhouse gas emissions

5 3 6 0

4 Ga Row: Energy use

Column: Other air emissions

6 2 5 1

4 H Row: Energy use

Column: Volume of process waste generated

4 3 7 1

4 I Row: Energy use

Column: Toxicity of process waste

1 8 5 1

4 Ja Row: Energy use

Column: Recyclability of (or other uses for) process waste

7 2 3 2

4 K Row: Energy use

Column: Toxicity of the product

1 11 1 2

4 L Row: Energy use

Column: Recyclability of the product

8 2 1 4
Technology Assessment GAO-17-75 137

Number of respondents; most frequent 

response(s) in bold, dark red font

Cell 

Factors in the row and column;

most frequent response(s) in bold, dark red font Row Column Equal

None/

NA

5 Ea Row: Water use

Column: Land use/physical footprint

10 1 3 0

5 Fa Row: Water use

Column: Greenhouse gas emissions

3 9 2 0

5 Ga Row: Water use

Column: Other air emissions

3 3 7 1

5 H Row: Water use

Column: Volume of process waste generated

4 6 4 1

5 I Row: Water use

Column: Toxicity of process waste

3 9 3 0

5 Ja Row: Water use

Column: Recyclability of (or other uses for) process waste

6 3 4 1

5 K Row: Water use

Column: Toxicity of the product

1 11 1 2

5 L Row: Water use

Column: Recyclability of the product

7 4 0 4

6 F Row: Land use/physical footprint

Column: Greenhouse gas emissions

1 12 0 2

6 Ga Row: Land use/physical footprint

Column: Other air emissions

4 9 0 1

6 H Row: Land use/physical footprint

Column: Volume of process waste generated

1 11 2 1

6 I Row: Land use/physical footprint

Column: Toxicity of process waste

1 11 2 1

6 J Row: Land use/physical footprint

Column: Recyclability of (or other uses for) process waste

1 11 1 2

6 K Row: Land use/physical footprint

Column: Toxicity of the product

1 12 0 2

6 L Row: Land use/physical footprint

Column: Recyclability of the product

2 7 2 4

7 Ga Row: Greenhouse gas emissions

Column: Other air emissions

10 2 2 0

7 H Row: Greenhouse gas emissions

Column: Volume of process waste generated

6 6 3 0

7 I Row: Greenhouse gas emissions

Column: Toxicity of process waste

3 7 4 1

7 J Row: Greenhouse gas emissions

Column: Recyclability of (or other uses for) process waste

6 3 4 2

7 K Row: Greenhouse gas emissions

Column: Toxicity of the product

2 10 1 2

7 L Row: Greenhouse gas emissions

Column: Recyclability of the product

8 2 1 4

8 H Row: Other air emissions

Column: Volume of process waste generated

2 6 6 1
Technology Assessment GAO-17-75 138

Number of respondents; most frequent 

response(s) in bold, dark red font

Cell 

Factors in the row and column;

most frequent response(s) in bold, dark red font Row Column Equal

None/

NA

8 Ia Row: Other air emissions

Column: Toxicity of process waste

2 6 5 1

8 Ja Row: Other air emissions

Column: Recyclability of (or other uses for) process waste

4 3 5 2

8 Ka Row: Other air emissions

Column: Toxicity of the product

1 9 2 2

8 La Row: Other air emissions

Column: Recyclability of the product

9 2 0 3

9 I Row: Volume of process waste generated

Column: Toxicity of process waste

2 10 3 0

9 J Row: Volume of process waste generated

Column: Recyclability of (or other uses for) process waste

6 3 5 1

9 K Row: Volume of process waste generated

Column: Toxicity of the product

1 12 0 2

9 L Row: Volume of process waste generated

Column: Recyclability of the product

7 3 2 3

10 J Row: Toxicity of process waste

Column: Recyclability of (or other uses for) process waste

9 4 2 0

10K Row: Toxicity of process waste

Column: Toxicity of the product

1 10 2 2

10 L Row: Toxicity of process waste

Column: Recyclability of the product

8 2 2 3

11K Row: Recyclability of (or other uses for) process waste

Column: Toxicity of the product

1 11 1 2

11 L Row: Recyclability of (or other uses for) process waste

Column: Recyclability of the product

5 4 2 4

12 L Row: Toxicity of the product

Column: Recyclability of the product

11 0 0 4

a

Only 14 of the 18 respondents selected an answer for these cells.

7. Considering the sector(s) you selected for your company in Question 1, how useful would it 

be for all companies within your sector(s) to use a common set of factors for assessing the 

sustainability of chemical technologies, processes, or products?

Very useful

Somewhat 

useful

Slightly 

useful Not useful

Do not know/cannot 

judge

Number of 

respondents

9 6 1 0 1 17

Please explain your response.

Narrative responses are intentionally omitted.
Technology Assessment GAO-17-75 139

8. How useful would it be for all companies across the entire chemical industry to use a 

common set of factors for assessing the sustainability of chemical technologies, processes, 

or products?

Very useful

Somewhat 

useful

Slightly 

useful Not useful

Do not know/cannot 

judge

Number of 

respondents

5 7 3 0 1 16

Please explain your response.

Narrative responses are intentionally omitted.

SECTION 3: Third-Party Certifications

9. Which, if any, of the following third-party sustainability certifications does your company 

currently have, or currently seek, or did it previously have for one or more of your 

products? (If your company does not have and is not seeking a particular third-party 

sustainability certification, please choose “Do not have and not seeking.”) (Check all that 

apply.) 

Third-party certification

Currently 

have 

Currently 

seeking 

Do not have now 

but previously 

had 

Do not have 

and not 

seeking 

Environmental Protection Agency’s (EPA) 

Safer Choice / Design for the Environment

4 3 1 11

EPA’s Significant New Alternatives Policy 

(SNAP) Program 

1 0 1 15

U.S. Department of Agriculture’s (USDA) 

BioPreferred

8 2 0 10

EcoLogo 1 2 0 16

Green Seal 3 0 0 15

Other (please specify): 

(Narrative responses intentionally omitted)

11 6 1 9 

10. If you currently have, are currently seeking, or previously had any third-party 

certifications, what do you consider to be the primary benefit(s) and challenges of getting

those certifications?

Narrative responses are intentionally omitted.
Technology Assessment GAO-17-75 140

SECTION 4: Interactions with Stakeholders

PLEASE NOTE: The term “interaction” throughout Section 4 refers to how you engage with 

stakeholders in developing and using sustainable chemistry technologies. Examples of 

interactions might include meetings, conducting joint research and development (R&D), resource 

and information sharing, or responding to regulations.

11. With respect to the development and use of sustainable chemistry technologies, how 

much does your organization interact with the stakeholders listed below? (Note: In 

answering this question, consider both the duration and frequency of your interaction with 

the stakeholders. Check one.)

Stakeholders Not at all

Small/

limited 

amount

Moderate 

amount

Large 

amount

Number of 

respondents

Suppliers 0 2 10 6 18

Customers 1 3 5 9 18

Industry other than suppliers or customers 

(e.g., contractors, trade groups, 

roundtables)

0 2 12 4 18

Academics (e.g., individual researchers, 

research consortia)

1 7 8 2 18

Environmental advocacy groups 2 10 5 1 18

Consumer advocacy groups 5 11 1 1 18

Scientific and professional organizations 0 6 8 4 18

Department of Defense (DOD) 13 5 0 0 18

Department of Energy (DOE), including the 

national laboratories

11 3 3 1 18

Environmental Protection Agency (EPA) 6 3 6 3 18

Food and Drug Administration (FDA) 4 8 5 1 18

National Institute of Standards and 

Technology (NIST)

13 4 0 0 17 

National Science Foundation (NSF) 7 8 2 1 18

U.S. Department of Agriculture (USDA) 6 7 4 1 18

Other stakeholder (please specify):

(Narrative responses intentionally 

omitted)

3 2 1 1 —
Technology Assessment GAO-17-75 141

12. With respect to the development and use of sustainable chemistry technologies, how 

valuable are your interactions with the stakeholders listed below? (Please check one box 

per row.) 

Stakeholders

Not 

applicable; no 

interactions

Not at all 

valuable 

A little 

valuable

Moderately 

valuable 

Very 

valuable

Number of 

respondents

Suppliers 0 0 2 9 7 18

Customers 1 0 5 5 7 18

Industry other than suppliers 

or customers (e.g., other 

companies, trade groups, 

roundtables)

0 0 3 11 4 18

Academics (e.g., individual 

researchers, research 

consortia)

1 0 5 9 3 18

Environmental advocacy 

groups

2 0 7 5 3 17

Consumer advocacy groups 5 1 9 2 1 18

Scientific and professional 

organizations

0 0 3 10 5 18

Department of Defense (DOD) 14 1 1 2 0 18

Department of Energy (DOE), 

including the national 

laboratories

11 0 2 4 1 18

Environmental Protection 

Agency (EPA)

6 0 3 5 4 18

Food and Drug Administration 

(FDA)

5 1 5 6 1 18

National Institute of Standards 

and Technology (NIST)

14 1 2 1 0 18

National Science Foundation 

(NSF)

7 2 3 3 2 17

U.S. Department of Agriculture 

(USDA)

6 0 5 5 2 18

Other stakeholder (please 

specify):

(Narrative responses 

intentionally omitted)

3 0 0 3 1 —

13. For one or two of the most valuable interactions you identified in the previous question, 

please provide an example including the type of interaction and why the interaction is 

very valuable to your company.

Narrative responses are intentionally omitted.
Technology Assessment GAO-17-75 142

14. With respect to the development and use of sustainable chemistry technologies, are there 

gaps in or challenges to interactions among stakeholders that hinder the development and 

use of sustainable chemistry technologies?

Yes No Number of respondents

15 2 17

If yes, what are those gaps and challenges and how might they be addressed?

Narrative responses are intentionally omitted.

SECTION 5: Details on Company Interactions with Federal Agencies

For this section, we identify seven federal agencies with programs designed to promote the 

development and use of sustainable chemistry technologies, along with the types of activities in 

which agencies and companies might interact. 

15. Please check the relevant boxes to indicate which sustainable chemistry activities, if any, 

your company performed with each listed federal agency over the past three years. (Check 

all that apply.) (Note: There were 18 respondents for this question.)

Legend: DOD = Department of Defense; DOE/NL = Department of Energy including the national 

laboratories; EPA = Environmental Protection Agency; FDA = Food and Drug Administration; NIST = 

National Institutes of Standards and Technology; NSF = National Science Foundation; USDA = U.S. 

Department of Agriculture.

Sustainable chemistry activity

DOD DOE/ NL EPA FDA NIST NSF USDA

(number checked)

a. Received funding for research and 

development (R&D) from this federal 

agency 2 6 0 0 0 2 1 

b. Performed collaborative research and 

development (R&D) with this federal 

agency 1 6 1 0 4 3 1 

c. Provided input to this agency’s efforts to 

develop standards related to 

sustainable chemistry 0 1 5 1 1 5 1 

d. Sold products that involve the use of 

sustainable chemistry to this federal 

agency, either in response to the 

Federal Acquisition Regulations or for 

any other reason 1 1 0 0 0 0 0 

e. Worked on a life cycle assessment or 

methodology with this federal agency 0 1 3 0 0 1 0 

Please describe one example to 

elaborate on your response to 

question 15e. Narrative responses intentionally omitted

f. Used sustainable chemistry technologies 

to respond to a regulation from this 

federal agency 0 0 2 0 0 0 0 
Technology Assessment GAO-17-75 143

Sustainable chemistry activity

DOD DOE/ NL EPA FDA NIST NSF USDA

(number checked)

Please describe one example to 

elaborate on your response to 

question 15f. Narrative responses intentionally omitted

g. Other sustainable chemistry activity 

(please specify) 0 0 0 0 0 0 0 

Narrative responses intentionally omitted 

16. Please provide one or more examples of challenges or barriers, if any, that your company 

encountered when working with a federal agency on sustainable chemistry issues and 

describe how the agency might help mitigate the challenge(s) or barrier(s).

Narrative responses are intentionally omitted.

17. How, if at all, could the federal government help resolve key challenges or barriers that 

exist currently in developing and using sustainable chemistry technologies?

Narrative responses are intentionally omitted.

Concluding Question

18. Are there any additional thoughts or clarifying information you think would be helpful for 

us as we interpret the survey results? 

Narrative responses are intentionally omitted.
Technology Assessment GAO-17-75 144

Appendix V: The 12 Principles of Green Chemistry 

Principle 11

It is better to prevent waste than to treat or clean up waste after it is formed.

Principle 2

Synthetic methods should be designed to maximize the incorporation of all materials used in 

the process into the final product.

Principle 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.

Principle 4

Chemical products should be designed to preserve efficacy of function while reducing toxicity.

Principle 5

The use of auxiliary substances (e.g. solvents, separation agents, etc.) should be made 

unnecessary wherever possible and, innocuous when used.

Principle 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.

Principle 7

A raw material of feedstock should be renewable rather than depleting wherever technically 

and economically practicable.

Principle 8

Unnecessary derivatization (blocking group, protection/deprotection, temporary modification 

of physical/chemical processes) should be avoided whenever possible.

Principle 9

Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.

 1 Paul T. Anastas and John C. Warner, Green Chemistry: Theory and Practice (New York: Oxford University Press, 1998), 30.
Technology Assessment GAO-17-75 145

Principle 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.

Principle 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.

Principle 12

Substances and the form of a substance used in a chemical process should be chosen so as to 

minimize the potential for chemical accidents, including releases, explosions, and fires.
Technology Assessment GAO-17-75 146

Appendix VI: Roles of selected federal programs and offices in 

supporting the development and use of more sustainable chemistry 

processes and products

The following table, organized by federal agency, summarizes the roles played by the selected 

agency programs highlighted in chapter 6. This is not a comprehensive list of federal programs 

and agencies that play a role in supporting the development and use of more sustainable 

chemistry processes and products and represents only a selection of relevant federal 

activities. GAO selected the programs based on recommendations from agency officials and 

other experts and on GAO’s analysis of the relevancy of program activities. For more 

information about GAO’s methodology for selecting programs and offices, see appendix I. 

Table 13: Roles of selected federal programs and offices in supporting the development and use of 

more sustainable chemistry processes and products, by federal agency 

Seek to understand 

the impact of 

chemicals on 

human and 

environmental 

health

Support the 

development and 

commercialization 

of more sustainable 

chemistry 

technologies

Aid the growth of 

markets for products 

manufactured with 

more sustainable 

chemicals and 

processes 

Department of 

Agriculture

Agricultural Research Service 

National Program on 

Biorefining

X

BioPreferred X

Biorefinery, Renewable 

Chemical and Biobased 

Product Manufacturing 

Assistance Program

X

National Institute of Food 

and Agriculture (NIFA) 

Biomass Research and 

Development Initiative

X

Department of 

Commerce, 

National Institute 

for Standards and 

Technology

Building for Environmental 

and Economic Sustainability

(BEES) program

X

Sustainable Manufacturing 

Program

X

Materials Science and 

Engineering Division 

X
Technology Assessment GAO-17-75 147

Seek to understand 

the impact of 

chemicals on 

human and 

environmental 

health

Support the 

development and 

commercialization 

of more sustainable 

chemistry 

technologies

Aid the growth of 

markets for products 

manufactured with 

more sustainable 

chemicals and 

processes 

Department of 

Defense

Chemical and Material Risk 

Management Program

X X

Strategic Environmental 

Research and Development 

Program (SERDP)

X

Environmental Security 

Technology Certification 

Program (ESTCP)

X

Sustainable Product Center 

and Sustainable 

Procurement Program

X

Department of 

Energy

Advanced Manufacturing 

Office (AMO)

X

National Laboratories X

Multiple funding programs X

Manufacturing USA Institute 

- Rapid Advancement in 

Process Intensification 

Deployment (RAPID)

X

Department of 

Health and Human 

Services

National Toxicology Program 

(NTP)

X

Department of 

Health and Human 

Services / 

Environmental 

Protection Agency 

Toxicology in the 21st 

Century (Tox21) 

X
Technology Assessment GAO-17-75 148

Seek to understand 

the impact of 

chemicals on 

human and 

environmental 

health

Support the 

development and 

commercialization 

of more sustainable 

chemistry 

technologies

Aid the growth of 

markets for products 

manufactured with 

more sustainable 

chemicals and 

processes 

Environmental 

Protection Agency

Chemical Safety for 

Sustainability (CSS)

X

Presidential Green 

Chemistry Challenge Awards 

X

Safer Choice X

Science to Achieve Results 

(STAR) grant program

X

Significant New Alternatives 

Policy (SNAP) program

X X

Environmental 

Protection Agency / 

National Science 

Foundation

Networks for Characterizing 

Chemical Life Cycles / 

Networks for Sustainable 

Molecular Design and 

Synthesis grant programs

X X

National Science 

Foundation

Centers for Chemical 

Innovation 

X

Sustainable Chemistry 

Engineering Materials 

(SusChEM) grant program

X

Multiple Agencies Small Business Innovation 

Research (SBIR) and Small 

Business Technology 

Transfer (STTR) grant 

programs

X

Source: GAO analysis of agency documents. | GAO-18-307
Technology Assessment GAO-17-75 149

Appendix VII: GAO contacts and staff acknowledgments

GAO contacts

Timothy M. Persons, Chief Scientist, at (202) 512-6412 or personst@gao.gov

John Neumann, Director, at (202) 512-3841 or neumannj@gao.gov

Staff acknowledgments

In addition to the contacts named above, the following GAO staff made key contributions to 

this report:

Applied Research and Methods team

Center for Science, Technology, and Engineering

Karen Howard (Assistant Director), Nirmal Chaudhary (Analyst-In-Charge), 

William Carrigg, Rebecca Parkhurst, and Kiera Reifschneider

Center for Design, Methods, and Analysis

David Dornisch and Gina Hoover

Center for Economics

Namita Bhatia-Sabharwal

Natural Resources and Environment team

Diane Raynes (Assistant Director), Summer Lingard-Smith (Analyst-in-Charge), 

Bethany Atkins, Kazue Chinen, Krista Mantsch, and Alexandra Stone

Ramsey Asaly, Amy Bowser, Bruce Cain, Timothy Carr, Eric Charles, R. Scott Fletcher, Dani 

Greene, Gloria Hernandez-Saunders, Hayden Huang, Rich Johnson, Kayla Robinson, Dan 

Royer, Walter Vance, and Gene Wisnoski also made important contributions.

In addition, Taylor Camacho and Jennifer Subler contributed as student interns.

(100398)
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