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Abstracts: Session 3. Developments in Alternatives Assessment Methods

Hazard Assessment

Machine Learning of Toxicological Big Data for Read-Across Structural Activity Relationships (RASAR) to Support Alternatives Assessments
Stacie Abraham


To effectively meet regulatory drivers and consumer demands to identify, develop, and substitute safer alternative chemicals, it is critical to employ the concepts of informed substitution. This includes understanding the inherent hazards associated with the alternative chemicals to determine relative safeness compared to those being substituted. For years, animal test methods were the conventional means for chemical hazard assessment. However, there also are current regulatory mandates and ethical drivers to reduce, refine, and replace (the “3 R’s) such animal test methods with alternative non-animal methodologies. This creates a challenge for innovators, formulators, and companies who strive to foster green chemistry while adhering to the principles of the 3 R’s. In silico, or computational toxicology software offers an alternative method for predicting chemical hazards. Traditional Quantitative Structure Activity Relationship (QSAR) methodology employs simple analog identification and predicting hazard data from chemical analogs with known hazard data. This presentation will cover a novel in silico approach combining big data with advanced machine learning incorporating data fusion. The approach integrates novel models called RASARs (Read-across Structure Activity Relationship) with data fusion techniques that extend this concept by creating large feature vectors from all available property data on both the target and analogs rather than only the modeled hazard. This increases balanced accuracies from 70 – 80% seen in the simple models to 80 – 95% across 7 human health and 2 environmental hazards. Applications of predicted data to inform research and development, fill data gaps, and foster green chemistry will be illustrated.

Integrated Checklist Approaches to Rapid Screening, Testing, and Assessment for Safer Alternative or Innovative Chemical Substances
Sang-Tae Kim, Anthony Schatz


Advancing international regulations, along with the voice of society, are dictating safer chemical design as well as environmental-friendly product manufacturing and distribution processes. On the other hand, the number of new chemical substances to be used in industrial and consumer products has increased significantly in recent years. This creates a demand for faster screening of the hazardous properties of these new and existing chemical substances. As a result, the use of computer-based (quantitative/qualitative) Structure-Activity Relationship (qSAR) methods in place of traditional toxicology methods is becoming increasingly more important and widespread in predicting physicochemical properties, toxicological endpoints and other biological effects. At Ashland, we have developed an integrated checklist system to rapidly screen, test, and/or assess safer alternative or innovative substances. The checklists have been prepared for each of the following characteristics: (1) carcinogenicity, (2) developmental/reproductive toxicity, (3) organ toxicity at low doses, (4) sensitization and (5) persistent, bioaccumulative and toxic (PBT) chemical, in combination of traditional toxicology methods and qSAR/read-across. For sensitization characterization, for example, the checklist include the following elements: (1) molecular weight, (2) octanol/water partition coefficient, (3) number of structural alerts for sensitization, (4) in chemico direct peptide reactivity assay, (5) in vitro human cell activation test (h-CLAT), (6) guinea pig sensitization, (7) mouse local lymph node assay (LLNA), (8) human repeat insult patch test, and (9) other (specify: ). Structure and sensitization profiles of new chemicals or alternatives that mimic existing sensitizers can be eliminated from further consideration without any additional lengthy studies. The sensitization checklist also served as a gap analysis for further evaluation of selected substances. The checklist is not intended to be comprehensive. However, the checklist has improved the new chemicals or safer alternatives screening performance and helped us achieve more consistent results. It not only offers the possibility of verification but also instills the discipline of higher performance in safer chemical alternative assessment.

Best Practices for Addressing Human Health and Environmental Data Gaps in an Alternatives Assessment Context
Pamela Spencer1, Michelle Embry2, Lauren Heine3, Joanna Klapacz4, Margaret Whittaker5

1) The ANGUS Chemical Company, 2) Health & Environmental Sciences Institute, 3) Northwest Green Chemistry 4) The Dow Chemical Company, 5) ToxServices LLC

Alternative assessments (AA) is a process used to identify and compare alternatives to chemicals or technologies of concern and inform selection of a safer alternative based on hazards, performance, and sustainability. In the context of AA, not all chemicals will have data for every hazard endpoint, and when such critical endpoint data are absent, the chemical is considered to have a data gap. For comparisons of chemical alternatives, identifying and classifying the degree of hazard for human health and the environment is critical in the decision-making process, and filling these data gaps is vital for avoiding regrettable substitutions. To improve the ability to successfully select safer alternatives, the Health & Environmental Sciences Institute (HESI) Alternatives Chemical Assessment Technical Committee, a collaborative effort of academia, government, industry, and non-profit organizations, developed a best practice guidance to fill hazard data gaps in a tiered, systematic approach applicable to the product development process (idea stage to end of life), and relying on the integrated approaches to testing and assessment (IATAs). The context of AA is framed through problem formulation and early, sequential use of non-testing approaches as well as new alternative methods (NAMs) for addressing data gaps during iterative evaluations of the available evidence. The AA also considers the acceptable level of uncertainty and relies on elements of expert judgment during the weighing of the evidence (WoE). These collaboratively-developed best practices are described to characterize and address data gaps in physicochemical properties, environmental fate, aquatic toxicity, skin and eye irritation, acute toxicity, repeat dose toxicity, carcinogenicity, genotoxicity/mutagenicity, developmental/reproductive toxicity, and endocrine activity data gaps. A chemical case example of n-Propyl Acrylate (CAS 925-60-0) illustrates best practices to address numerous data gaps. Overall, this guide can inform research agendas, aid as a reference and training source, allow for a standardization of methodologies for predicting hazard endpoints, and encourage the selection of safer chemical alternatives. Furthermore, it may also have broad applicability beyond the AA practitioner as a useful resource for R&D chemist developing new chemistries, or supply chain partners whose goal is to substitute and source raw materials with lower adverse impacts to human health and the environment.

Case Studies for Using In vitro and In silico Models to Prioritize Chemicals of Concern in Children's Products
Marissa Smith

University of Washington

Predictive toxicology tools can be useful in prioritizing chemicals of concern found in children’s consumer products. Recent regulations limiting the concentration of some toxic chemicals in children’s consumer products have spurred the development of alternatives. However, it is challenging for traditional toxicity assessment approaches to keep up with the dynamic introduction of alternative chemicals. This presentation focuses on new predictive toxicology and chemical prioritization tools to help better characterize toxicity and exposure factors needed to make decisions that promote child health and development. Examples of chemical groups that will be discussed include engineered nanomaterials, phthalates, parabens and BPA. Predictive toxicology tools will be used to assess endocrine disruptor potential. This case study specifically determines whether in vitro and in silico models can be useful in filling data gaps needed for alternatives assessment. This project is supported by the Environmental Protection Agency (FP-91779601-0, RD 83573801, RD 83451401) and the National Institute of Environmental Health Sciences (5P01ES009601).

The Many Cards up ‘Computational Sleeves’: Reshaping In Silico Tools Used in Drug Discovery to Design Safer and Functional Chemicals
Jakub Kostal

The George Washington University

Computational methods have been increasingly used in hazard and alternatives assessments, alleviating economic and ethical burdens of animal testing however, their potential to inform safer chemical design has not been realized. Over the past 50 years, computers have revolutionized drug discovery by being both fast, virtually screening vast chemical libraries to find drug candidates against biological targets of therapeutic interest, and accurate, providing state-of-the art tools to optimize said candidates for greater activity. Nowadays, all pharmaceutical companies employ computational modeling, and many drugs on the market are an outcome of computer guided drug design. In developing pharmaceuticals, we seek to impart specific biological activity to a molecule but also to minimize any side effects caused by unintended activity. The latter is true for all commercial chemicals as our society has grown increasingly aware of the adverse effects chemicals can have on human and environmental health. Regrettably, to test every new chemical on animals to ensure its safety is unfeasible. Current in vitro and in silico methods offer a promising alternative however, their role is limited to screening existing chemicals rather than providing a holistic platform for safer chemical design. Inspired by the successes of computer aided drug discovery, our group has focused on transforming said techniques to aid in rational design of safer chemicals. Mimicking Lipinski’s rules for drug-likeness, we have developed broad, property-based guidelines that inform design of chemicals with minimal ecotoxicity. More recently, we have explored the utility of statistical free energy perturbations used in lead optimization of drug candidates to redesign existing toxicants for increased safety. Herein, we demonstrate our approach on organophosphorus flame retardants, and show that high-volume chemicals of concern, such as triphenyl phosphate, can be rationally modified to significantly decrease their activity against specific targets while preserving intended functionality. Our approach is i) fast, relying on validated computational methods, ii) suitable for other chemical classes, for which mechanism(s) of action are known, and iii) cost-effective, imposing minimal structural changes to existing commercial chemicals and thus applicable to incumbent product development processes.

Green Chemistry and the Search for New Plasticizers
Patrick Harmon


Consumers often see various “free-of” statements on labels that imply that the product is safer and more sustainable than others without such a label. The problem with these types of labels is that they say nothing about the ingredients a product is made with. Hazard assessment tools such as GreenScreen® provide a way to determine whether potential product ingredients have sufficient data and low hazard to support their long-term use. Third party certifications and “positive” lists such as EPA SaferChoice and CleanGredients® also may be useful in selecting the right materials. Use of these types of tools and methodologies allow formulators and processors, as well as retailers and consumer product makers, to make informed and responsible substitution decisions and to reduce the risk of future regulatory or customer restrictions. Examples of the use of GreenScreen® and CleanGredients® to evaluate plasticizers that are alternatives to widely-used ortho-phthalates are presented. Some alternative plasticizers have sufficient data and low hazard to support their use in consumer and other products. Others might be accurately labeled as “phthalate-free” and might be safe for their intended uses, but insufficient data are available to support their use as alternatives to data-rich ortho-phthalates. Products such as DOTP and D9CH can be shown to be both well-studied and free of relevant hazard concerns.

Certification of Safer Alternatives for PFAS-Free Firefighting Foams
Holly Davies1, Sheri Franjevic2, Erika Schreder3, Matthew Bangcaya4, Laurie Valeriano3

1) Local Hazardous Waste Management Program in King Co, Washington, 2) Clean Production Action, 3) Toxic Free Future, 4) LHWMP

Per- and polyfluorinated alkyl substances (PFAS) have emerged as a concern for human health and the environment, particularly through drinking water contamination from the use of firefighting foams. Washington State recently became the first state to prohibit the manufacture, sale and distribution of class B firefighting foam where PFAS chemicals have been intentionally added (RCW 70.75A). The law’s full provisions will take effect in 2020 and some users have already transitioned to PFAS-free foam. The Local Hazardous Waste Management Program in King County Washington, Clean Production Action, and Toxic Free Future have partnered to assist users in identifying safer alternatives. Users have been specifying their needs and sharing the importance of the market. We are using chemical analyses, bioassays, and third party certification to evaluate PFAS-free firefighting foams. Purchasers want to know that the PFAS-free product they are using or considering do not contain equally problematic chemicals. We have identified about 100 PFAS-free products from 24 manufacturers. Based on a review of material safety data sheets, none of these foams have full public disclosure of ingredients to allow for a chemical hazard assessment. We are using GreenScreen Certified™ to allow manufacturers of firefighting foam to confidentially disclose ingredients to a third party for hazard assessment using GreenScreen. We are also analyzing for semi-volatile organic compounds and testing for acute aquatic toxicity. Purchasers will be able to focus on their area of expertise - selecting an effective product at an acceptable price.


Comparative Exposure Evaluation and Consideration of Life Cycle Impacts

Qualitative Approach to Comparative Exposure in Alternatives Assessment
Jennifer Tanir1, William Greggs2, Thomas Burns3, Michelle Embry4, Peter Fantke5, Bonnie Gaborek6, Lauren Heine7, Olivier Jolliet8, Derek Muir9, Neha Sunger10, Margaret Whittaker11

1) Toward Safer LLC, 2) Soleil Consulting, 3) Novozymes, 4) Health and Environmental Sciences Institute, 5) Technical University of Denmark, 6) DuPont Haskell Global Centers for Health and Environmental Sciences, 7) Northwest Green Chemistry, 8) University of Michigan, 9) Environment and Climate Change Canada, 10) West Chester University, 11) ToxServices LLC

There are limited examples and methodologies for incorporating exposure into alternatives assessments (AAs). Many of the AAs published to date are largely compilations of human and environmental hazard information and do not take into account other sustainability considerations, including exposure, risk, life-cycle thinking, performance, cost, and social responsibility. The purpose of this study was to develop a methodology for comparative exposure assessment – a type of assessment that was recommended in the 2014 US National Academy of Sciences guide for chemical alternatives. A collaboration of scientists from academia, industry, government, and nonprofit organizations, developed a qualitative comparative exposure approach under the Health and Environmental Sciences Institute’s (HESI) Sustainable Chemical Alternatives Technical Committee. The qualitative comparative exposure assessment screens for chemical alternatives that are expected to have a higher or different route of human or environmental exposure potential, which together with consideration of the hazard assessment, could trigger a higher tiered, more quantitative exposure assessment, thus minimizing the likelihood of regrettable substitution. This presentation outlines the approach that considers chemical ingredient- and product-related exposure information in a qualitative comparison. The steps in the method include 1) using conceptual maps for human and ecological receptors to define the potentially relevant exposure pathways, 2) determining exposure parameter information for 16 ingredient-related parameters (25 including subparameters) and 13 product-related parameters (15 including subparameters), 3) comparing the exposure potential of alternatives, 4) considering relevance, confidence, and data gaps of the parameter information, and 5) summarizing the overall conclusions of the qualitative comparative exposure assessment. Two case studies further illustrate the application of the methodology: the replacement of musk xylene with Muscone in eau de toilette and the replacement of di(2-ethylhexyl) phthalate with di(2-ethylhexyl) terephthalate in toys. Key learnings and future research needs will also be summarized.

Bridging Life Cycle and Exposure Ontologies to Enable Integration of Data Streams for Rapid Exposure Estimation and Comparative Exposure Assessment
Elaine A Cohen Hubal, Peter P Egeghy, Shi Liu, David Meyer, Daniel Vallero

Office of Research and Development, US Environmental Protection Agency

The US EPA asked the NRC to recommend a framework to inform government and industry decisions about the use of chemical alternatives. The resulting NAS 2014 report, A Framework Guide for the Selection of Chemical Alternatives, has several important elements including an increased emphasis on comparative exposure assessment. Tools for more efficient exposure estimation have been advancing, and accessible exposure information has grown significantly in recent years. Data that have been developed and curated for exposure forecasting applications and for life cycle assessments (LCA) provide a rich source of information to support informed substitution. Integrating information from these separate knowledge domains and providing easy access to linked open data (LOD) will greatly enhance efficient comparative exposure assessment for chemicals in consumer products. The core ontology for LCA, called lcaMin, and the ontological framework for exposure science, called ExO, have been developed previously. With the availability of these core ontology pieces, it is possible to bridge the two domains and develop a harmonized framework to manage exposure data in a life cycle context. The objectives of this research are to bridge the exposure and LCA domains to support rapid exposure estimation across the product life cycle and to demonstrate this new ontology bridge using a case study. The resulting bridged ontologies will facilitate use of data streams from both fields for a wider range of chemicals management applications.

C2C Certified’s contextual material health methodology and its applicability to alternatives assessment
Matteo Kausch

Cradle to Cradle Products Innovation Institute

The Cradle to Cradle (C2C) Certified Material Health Assessment Methodology was developed to evaluate compliance with the C2C Certified Products Program. As part of this program the methodology has been vetted and refined for over two decades. Recent progress in its documentation and public availability, as well as renewed interest in simpler, qualitative approaches to exposure and risk assessment have coincided such that it can now be of broader use to alternatives assessment practitioners, beyond the focus of the certification program itself. The methodology is unique in that it combines a precautionary GHS-based hazard-assessment step with a qualitative, material and product-context dependent exposure assessment step. This exposure assessment step follows the precautionary principle by considering all intended and likely unintended exposure scenarios across a product’s post-manufacture life-cycle. It differs from both the traditional, quantitative exposure assessment approach and from the purely comparative approach outlined by the National Research Council (NRC) in its chemical alternatives assessment framework. Unlike traditional exposure and risk assessment, no attempt is made to quantify the amount of exposure that occurs. In contrast to the NRC framework, the intention is to determine whether a chemical with one or more identified hazards or hazard data gaps is “safe” given its physical characteristics and the specific material and product context of the application. It offers a structured approach and a set of relatively simple rules to determine whether or not a given hazard or data gap is relevant given the specific application context. Thus, this C2C Exposure Assessment Methodology, which is now freely available on the Institute website, can be a useful guide for practitioners wanting to evaluate chemical alternatives with a specific application in mind. In addition to the qualitative exposure step, the methodology provides a standardized framework for determining which chemicals in a product should be reviewed, how to assess the hazard of chemical mixtures, and how to assess special types of materials and substances, such as biological materials, geological materials, recycled content, polymers, and colorants. This framework could be useful to practitioners in holistically evaluating the substances or materials in a product and determining which substances should be prioritized for more detailed alternative assessment approaches.

Addressing Exposure to 8000+ Chemicals in Consumer Products with Quantitative High Throughput Methods for Alternatives Assessment
Olivier Jolliet1, Lei Huang1, Peter Fantke2

1) Department of Environmental Health Sciences, University of Michigan, 2) Quantitative Sustainability Assessment Division, Department of Management Engineering, Technical University of Denmark

Introduction: Evaluating exposure is an important component to identify viable alternatives to harmful chemicals in products. Yet, Alternatives Assessment (AA) methods lack efficient and flexible approaches to quantify exposure for the many thousand product-chemical combinations. To address this gap, we present an operational matrix-based high-throughput framework efficiently coupling multi-pathway near-field (worker and consumer) with far-field (general population) exposures for use in AA. Method: We first determine the chemical mass in a product and define the compartments in which chemicals enter the near- or far-field environment, e.g. ‘object surface layer’ for cleaning products. We then structure calculated fractions transferred to other compartments and humans in a matrix, using seven models (skin surface layer, object surface layer, article interior, indoor air, food contact material, pesticide, direct emission). Inverting this matrix yields cumulative environmental transfer fractions and Product Intake Fractions (PiF) linking chemical mass taken in by humans to a unit mass of chemical in the product. We finally determine exposure doses expressed in mg/kgBW/d or on a product function basis. Our framework was applied to generate high-throughput exposure results for 8000+ chemicals in Tox21 and for 9000+ product-chemical combinations commonly used in the US. Results: The PiF widely ranges from 0.7 ppm to 93% across the 8000+ chemicals. Resulting exposure doses for product users can vary from 1E-9 to 400 mg/kgBW/d, dominated by inhalation and dermal contact. For each product application, we are able to determine the chemical-specific contributions of pathways and population groups to overall exposure and compare the relative exposure magnitude for all chemicals in a given product. Combining these exposures with toxicity data, we are able to identify main chemicals of concern and rank alternatives. Systematic sensitivity studies enable us to identify the most important product and chemical attributes affecting the Product Intake Fraction and produce heat maps to easily determine exposure, for use in a screening AA, as will be illustrated for chemical alternatives in several product types. The more detailed mass-balanced-based framework is readily available for use by AA practitioners to screen a wide range of product-chemical combinations.

Toward a Parsimonious Life Cycle Based Alternatives Assessment
Peter Fantke1, Lei Huang2, Olivier Jolliet2

1) Quantitative Sustainability Assessment Division, Department of Management Engineering, Technical University of Denmark, 2) Department of Environmental Health Sciences, University of Michigan

Introduction: Methods are urgently needed to identify viable replacements to harmful substances used in industrial applications or consumer products. Alternatives Assessment (AA) is a suitable framework to rapidly screen and evaluate such replacements. However, current methods lack indicators addressing the various impacts along chemical and product life cycles. Hence, important trade-offs remain unassessed and burden might shift from one life cycle stage (e.g. manufacturing) to another (e.g. product use), ultimately leading to “regrettable substitutions”. To address this challenge, exposure and life cycle impacts need to be consistently integrated into AA, and outcomes compared to the local-to-global boundaries of our environmental support systems, while avoiding paralysis by analysis. Methods: We systematically evaluate the scope of AA and identify key elements for quantitatively considering exposure and life cycle impacts relevant for a given chemical-product application. Cumulative near- and far-field transfers and human and ecological exposure are linked to chemical mass used in given applications, related emissions, and toxicity information to characterize life cycle toxicity impacts. Other impacts (e.g. climate change) are screened for their contributions to overall product-related impacts per product application type. We test our approach in a case study of plasticizer in vinyl flooring and outline future research needs to operationalizing a consistent and Life Cycle-based Alternatives Assessment (LCAA). We finally outline how exposure and life cycle impacts should be compared to sustainability targets to identify robust substitutes. Results: We show that replacing e.g. DEHP by DIHP in vinyl flooring shifts from cancer to non-cancer burden, and that plasticizers contribute between 55 and 85% to total human toxicity burden from flooring. Comparing toxicity with other life cycle impacts emphasizes the relevance of toxicity for the studied chemical-product application. Our results demonstrate how all relevant exposure pathways, populations, and life cycle impacts can be consistently considered to avoid burden shifting resulting from disregarding chemical and product life cycles, and to prioritize the most relevant life cycle impacts. Further, we show that it is required to link the success of an AA to existing sustainability targets. This will help identifying truly sustainable solutions in line with defined global sustainable development targets.

The Supply Chain Dimensions of Alternatives Assessment
Michael Overcash1, Peter Fanke2, Olivier Jolliet3, Evan Griffing4

1) Environmental Genome Initiative, 2) Quantitative Sustainability Assessment Division, Department of Management Engineering, Technical University of Denmark, 3) Department of Environmental Health Sciences, University of Michigan, 4) Environmental Clarity

A growing challenge is to replace chemicals of concern in products and processes with viable alternatives, also referred to as chemical substitution. An example is wiring bundles (cables) in which brominated flame retardants, phthalate plasticizers, lead, and PVC are target constituents for substitution. Many substitution-related decisions are based on indicators for toxicity, carcinogenicity, hazard or other properties of interest measured for the current chemical versus the potential alternative chemicals as incorporated into products. These decisions and chosen alternatives in product with chemical A versus product with chemical B are often intuitive. Therefore, potential sustainability tradeoffs may be overlooked along the chemical life cycles. In practice, the environmental impact of product with chemical A versus chemical B may have substantially different long shadows (footprints). These shadows are associated with the cumulative energy use and chemical emissions that occur in chemical value chains as raw materials are built into molecular complexity creating chemicals with specific functional performance. To avoid regrettable substitutions, it is critical to consider the sustainability performance of chemicals along the entire life cycles. The environmental genome will consist of the 100,000 chemicals in commerce, used to make virtually all consumer and industrial products. The Environmental Genome Initiative has mapped production routes and environmental data for over 1600 of these chemicals and provides tools for using these data in alternatives assessment. Recent alternative assessments (e.g. phthalate plasticizers in vinyl floors) have demonstrated the usefulness of a combined approach of chemical substitution based on the environmental profile of the whole chemical supply chain. In our presentation, we describe the transparent, detailed life cycle inventory for this new framework, in the broad application for chemical substitution across product applications. The information feeds directly into manufacturing process improvement to reduce emissions, achieve cost reductions, and establish uniform analysis over whole chemical supply chains. It is compatible with quantitative exposure and impact assessment metrics, such as the product intake fraction linking population intake to mass in product of a particular chemical. The comparison of plasticizers is used to illustrate this larger comparison of alternatives in a practical example.

Stereolithography Resins: Many layers to a safer SLA resin
Thomas A. McKeag1, Justin Bours2

1) Berkeley Center for Green Chemistry, 2) Cradle2Cradle

In this discussion we will outline several years of work and refinement of criteria for safer stereolithography resins, spanning several different types of methods and collaborations towards a common goal. We will also discuss how this has led to our current pioneering partnership with chemical manufacturer Millipore Sigma and the US EPA to specify, reformulate and test a safer resin within the additive manufacturing (AM) community. The trajectory of collaborations started with an initial BCGC consulting contract with Autodesk as part of their Project Nido initiative, followed by a sponsored internship, partnership with the Greener Solutions graduate course at UC Berkeley, and directing of an AM industry roundtable with Northwest Green Chemistry. Through these evolving collaborations, we will track the phases of work starting with the development of baseline toxicology for stereolithography resins, searching for alternatives, the development of a novel and holistic sustainability framework, and its refinement into three prototypes for evaluating and comparing AM materials and printing processes. We then will discuss the different opportunities and challenges of these different collaboration types, the methods used within each phase, and the potential lessons for effecting change within the industry. Finally, we will outline our current project and discuss the current strategy for going beyond assessment to the design and actual introduction of a tangible material in a commercial marketplace based on green chemistry criteria.


Decision Analysis (including Hazard Assessment Scoring Methods) in Alternatives Assessment

Analyzing Chemical Substitution Decisions Among Chemical and Product Manufacturers
Vikram Rao1, Royce A. Francis1, Jennifer Y. Tanir2

1) The George Washington University, 2) Toward Safer LLC

Recently, there has been a trend towards encouraging companies and organizations to embrace greener and safer chemicals that are more aligned with current human and environmental sustainability goals. Criteria used in AA (Alternative Assessment) frameworks to evaluate and select potentially viable substitute chemicals include technical performance, economic feasibility, and human health and environmental hazards. While several such frameworks currently exist, providing decision support, there exists a need to characterize and understand relevant decision tradeoffs among product or chemical manufacturers seeking to substitute hazardous chemicals with safer alternatives. In this work, we present a survey, developed and distributed in collaboration with the Health and Environmental Sciences Institute’s Sustainable Chemical Alternatives Committee, used to characterize such tradeoffs from product or chemical manufacturers. A set of six factors to study, affecting product or chemical design, were chosen: Business Strategy, Economic Considerations, Functionality and Performance, Health/Environmental Endpoints, Public Perception, and Regulatory Factors. In our study, ‘product’ refers to finished goods, such as computer and electronic equipment, or furniture, while ‘chemical’ refers to chemicals such as resins, adhesives, basic chemicals, or agricultural chemicals. We assessed tradeoff weights for each factor and the degree of influence of factors on a recent product design or re-design. Results from the 33 completed surveys show that the two factors that are statistically different from equal weighting across the six factors are Health/Environmental Endpoints and Regulatory Factors. In addition, the factors were further disaggregated into 33 attributes distributed across the six factors. Principal component analysis on these attributes yielded a set of 9 principal components that loaded heavily on attributes such as Public Awareness of Human and Environmental Health Concerns, Company Reputation, Product Performance, and Product Price. The results from the survey identify the major influences on decision making, and provide support for the broader implication that business and economic concerns may be addressed via different contextual factors than health and environmental endpoint concerns. Our findings have the potential to inform AA practitioners and decision makers while also providing additional guidance for AA-based regulations.

Toward Safer Consumer Products: Exploring the Use of Multi-Criteria (MCDA) and Structured Decision Making (SDM) Approaches for Chemical Alternatives Assessment
Christian Beaudrie1, Tim Malloy2, Charles Corbett3, Tom Lewandowski4, Xiaoying Zhou5

1) Compass Resource Management Ltd, 2) University of California, Los Angeles, School of Law, 3) University of California, Los Angeles, Anderson School of Management, UCLA, 4) Gradient, 5) California Environmental Protection Agency, Department of Toxic Substances Control

Despite the increasing popularity of Alternatives Assessment (AA) as a tool for substituting chemicals of concern in consumer products, businesses, government, and NGOs face a number of hurdles when implementing AA in practice. In addition to the technical challenges of identifying viable substitutes and suitable hazard and performance data, decision makers face difficult choices involving values-based trade-offs between disparate health, environmental, technical performance, and cost attributes. While formal decision-analysis tools can support analysis and decision making in such challenging contexts, their application to ‘real world’ AA has not been fully explored. This talk presents findings from a two-day Society for Risk Analysis (SRA) and UCLA sponsored workshop with twelve AA practitioners to understand the decision making challenges they face, and to assess the utility of three common decision analytical approaches for analyzing trade-offs and selecting alternatives: ‘default’ or ‘ad-hoc’ approaches, Multi-Criteria Decision Analysis (MCDA), and Structured Decision Making (SDM). Prior to the workshop, participants applied their ‘default’ decision approach to an AA case study, establishing a baseline on a set of decision quality metrics, including: overall satisfaction with the approach understanding of values, information, and trade-offs ease of use transparency and how well a decision outcome reflects what matters to them for the decision. During the workshop, participants applied MCDA to a second case study individually or in a small group, and SDM to a third case study in a large facilitated group setting. Participants attached benefits to some aspects of their MCDA and/or SDM experience, such as increased reported confidence in the analysis and their ability to articulate values/weights, and satisfaction with decision outcomes compared to ‘default’ decision approaches. Additionally, some participants reported improved understanding of trade-offs, and outcomes that aligned better with ‘gut’ feelings about preferred alternatives. On the other hand, responses were not consistent across methods and participants, and not all participants reported higher overall satisfaction based on MCDA or SDM compared to their original default approach. Overall, the workshop suggests a more structured approach can be beneficial for decision making in the AA framework, but that further research is needed into what constitutes a "good" decision or process.

A Multi-Criteria Approach to Alternatives Assessment
Sharon Dubrow, Steve Risotto

The American Chemistry Council

In today’s age of increased inquiry into the health, safety, and environmental impacts of everyday products, how do retailers and brands respond to market pressures for more sustainable products? ACC’s Sustainability & Market Outreach division is collaborating with stakeholders to provide actionable information and tools for chemicals management policies and programs within the value chain. Central to chemicals management is a science-based approach to screening and prioritizing products and, where appropriate, evaluating potential alternatives to priority chemicals. Evaluating the potential substitution of chemical ingredients in formulations and manufactured products is a significant endeavor, which, to be successful, should consider factors evaluated during product development as well as tradeoffs that could be realized throughout the product’s useful life. Informed substitution of chemical ingredients in products and formulations requires an understanding of multiple product attributes, including lifecycle impacts, intrinsic hazard, and the potential for release and exposure to the chemical(s). A number of existing Alternatives Assessment (AA) frameworks discuss the importance of multiple attributes. The principal challenge is the consideration of tradeoffs between disparate factors such as performance, hazard, exposure, cost, and lifecycle impacts. ACC’s Sustainability and Market Outreach division is working to help solve this issue by incorporating decision science principles into AA methodologies to help users make informed decisions tailored to their preferences. Challenges related to data availability and data gaps will be discussed in this session, including that required for an assessment of human health risk. A comprehensive risk assessment requires extensive data input, and can involve technical models that are complicated to use without the requisite education and training. To address this issue, ACC developed a tiered approach to chemical screening that provides a simple, yet science-based, method for evaluating the potential for chemical exposure from a product. This approach includes higher-level tiers to assess whether exposure is likely based on chemical and product characteristics. In the year ahead, ACC expects to automate these tools to the extent possible, and provide a general platform through which stakeholders may perform screening-level assessments, or may incorporate this framework into their own methodologies.

Alternatives to the Biocides Methylisothiazolinone and Chloromethylisothiazolinone in Leather Tanning
Thomas A Lewandowski, Joel M Cohen, Kim R Reid


Biocides such as methylisothiazolinone and chloromethylisothiazolinone (MIT/CMIT), are commonly used as preservatives during stages of the leather tanning process to prevent spoilage of the leather by microorganisms such as bacteria and fungi. Residual isothiazolones present in leather products may come into contact with skin during use, particularly via the leaching action of sweat on leather. Consumers are also exposed to these chemicals via a wide range of products, including many personal care products applied to the skin. Over the past decade, there has been an increase in the prevalence of MIT/CMIT skin allergy, and it has been suggested that this is related to their increased presence in consumer products. It is therefore be desirable to find alternatives to these chemicals, at least in certain applications, to reduce overall exposure. However, the leather tanning process involves complex chemistry and not all antimicrobials will be suitable from a performance standpoint. Antimicrobials by their very nature are biologically active and so there is also a concern about regrettable substitution. Finally, the leather production industry operates on thin margins so hazard reduction is challenging. We used the Interstate Chemicals Clearinghouse (IC2) Alternatives Assessment Guidance to conduct a Level 1 assessment of possible alternatives to MIT/CMIT in leather. This involved evaluating readily available information on various aspects of alternatives (i.e., hazard, exposure potential, performance, availability and cost). Based on an initial review of the information, we found that there do appear to be several viable alternatives that could be used in leather tanning and that a more detailed evaluation (e.g., via IC2 Level 2) is warranted in which a more quantitative evaluation of MIT/CMIT and alternatives would be carried out. The presentation will identify key data gaps that will need to be addressed in such an analysis.

A Multi-Criteria Decision Analysis on Characterizing Data Sources for Chemical Hazard Assessment
Haoyang He1, Timothy F. Malloy2, Julie M. Schoenung1

1) University of California, Irvine, Department of Materials Science & Engineering, 2) University of California, Los Angeles, School of Law 

Chemical Hazard Assessment (CHA), which aims to investigate the inherent hazard potential of chemicals, has been developed with the purpose of promoting safer consumer products. Despite the increasing use of CHA in recent years, finding adequate and reliable toxicity data required for CHA is still challenging due to issues regarding data completeness and data quality. Also, collecting data from primary toxicity reports or literature can be time consuming, which promotes the use the secondary data sources instead. In this study, we evaluate and characterize numerous secondary data sources on the basis of five performance attributes: reliability, adequacy, transparency, volume and ease of use. We use is GreenScreenÒ for Safer Chemicals v1.3 as the CHA framework, which essentially defines the endpoints of interest. We focused upon seventeen data sources reflecting three types of secondary data: chemical-oriented data sources, hazard-trait-oriented data sources and predictive data sources. To integrate and analyze the evaluation results, we applied two multi-criteria decision analysis (MCDA) methodologies – multi-attribute utility theory (MAUT) and stochastic multi-objective acceptability analysis (SMAA). Overall, the findings in this research program allow us to explore the relative importance of performance criteria and the data source quality for effectively conducting CHA.

Implementation of Quantitative Hazard Assessment Scoring Methods for High-throughput Chemical Alternatives Assessment
J.P. Rinkevich1, P.J. Beattie1, C. McLoughlin1, K. Hoorspool2, R. Hackenmiller-Paradis2, S. Echols3, L. Gallegos4

1) Scivera, 2) Nike, Inc., 3) Programme Director of ZDHC Roadmap to Zero at Zero Discharge of Hazardous Chemicals, 4) Levi Strauss & Co

Leading consumer products companies are proactively addressing the need to select safer product and process chemicals based on increasingly sophisticated criteria. Advances in product quality and product stewardship, with direct links to corporate environment, sustainability, governance (“ESG”) efforts, put new demands on product development teams, sourcing, and the complex supplier networks inherent to consumer products. For these new methods, these companies are going beyond conventional chemical regulatory compliance, restricted substance list screening, and product testing efforts to meet market expectations, manage costs, and enhance value. Improvements in the ability to understand chemicals for underlying human and environmental health characteristics are enabling decision-makers to identify controversial chemicals prior to regulation or restriction as well as select safer alternatives based on full hazard assessment results. Chemical certification frameworks have improved how companies view chemicals in products. Yet the qualitative criteria inherent to most frameworks present challenges on a number of levels for teams tasked with finding safer alternatives for product and process chemistries. The introduction of quantitative methods for scoring individual chemicals, formulations, and materials creates exciting opportunities for participants in the consumer products value chain. Quantitative scoring of potential alternatives using transparent criteria and based on the accepted principles of qualitative approaches facilitates refined comparison between potential alternative chemicals. Quantitative methods also enable comparative review of full hazard assessment results for large numbers of potential alternatives with similar functional use. The authors have developed a quantitative hazard assessment scoring method to compliment the various qualitative assessment frameworks in use and to facilitate more efficient and effective alternatives selection, especially at scale. The addition of quantitative scoring methods enable more refined selection of preferred, safer, alternative chemicals and formulations, while dramatically reducing the cost of full hazard assessments, making this valuable knowledge accessible to a much broader audience in the consumer products supply chain. The authors present a quantitative method for scoring chemicals and compare this method to others to identify synergies and to illustrate improved results.


Policy and Practice

Experiences with Methods for Analysis of Alternatives in REACH Authorisation
Andreas Lüdeke

Federal Institute for Occupational Health and Safety (BAuA), Division 4: Hazardous Substances and Biological Agents, Germany

The substitution of substances of very high concern (SVHC) by less hazardous sub-stances or technologies is one of the most important aims of the authorisation procedure of the European chemical regulation REACH. Companies which apply for authorisation of import, manufacture or use of SVHCs must show in an Analysis of Alternatives (AoA) that no suitable alternatives exist. The assessment of alternatives comprises a proof of technical and economic feasibility and a comparison of the risks of SVHC and potential alternatives. The adequateness and conclusions of the AoA submitted by the companies are scrutinized by the two scientific committees of ECHA (Committee for Risk Assessment – RAC, Committee for Socio-Economic Analysis – SEAC) before the European Commission decides on authorisation. Up to now the committees have provided opinions for 126 applications for authorisation (AfA). Two different aspects of the process will be looked at a) the available and employed methods and b) the importance of Socio-Economic Analysis (SEA) in the framework of AoA. Several causes of uncertainties in assessment of alternatives and employed methods will be identified from the perspective of a SEAC member. The broad application area for the SVHC to be substituted was found to be one major cause. Another cause is seen in the availability and quality of information which cannot be reasonably assessed. However, the latter problem is also addressed in the REACH authorization process, e.g. by demanding further evidence from the companies or public consultations. Further instruments for improvements and experiences gained from the process will be discussed. The REACH-Guidance for an AoA does not provide advice in terms of a weighting between the three parts, technical, economic feasibility and risk assessment. Companies often set the focus on the assessment of technical feasibility, considering substance function and defined technical performance criteria. Socio-economic considerations are an important but sometimes disputed element of the REACH assessment of alternatives. Examples of socio-economic assessments for substitution of e.g. chromium trioxide, trichloroetylene are presented to illustrate the role of economic reasoning considering both, European and German regulation.

Development of a Methodological Document for the Comparison of Alternatives to Hazardous Substances
G. Argiles1, D. Brunet1, K . Fiore1, L. Verines-Jouin1, J.-F. Certin2, M. Baril2, C. Bayourthe2, C. Botineau2, J.-M. Brignon2, S. Calvez2, B. Dufeu2, L. Fillaudeau2, L. Garras2, M. Goliro2, P. Lambert2, A. Lattes2, S. Le Bouquin-Leneveu2, R. Vincent2

1) French Agency for Food, Environmental and Occupational Health and Safety (ANSES), 2) ANSES Working Group on Formaldehyde and Substitutes

The French Agency for Food, Environmental and Occupational Health and Safety (ANSES) has been requested by national Authorities for an “Opinion on the use of substitutes for formaldehyde in various sectors of activity." Before answering specifically the questions concerning formaldehyde, ANSES decided to first develop a method to compare and assess substitutes. The scientific literature on the subject was reviewed to define a working method that could then be applied not only in the various sectors of activity targeted by the request on formaldehyde but also for any other hazardous substances. The method developed is considered to be “mixed” because it is divided into two broad steps: the first which is sequential and the second which is simultaneous. The first sequential step involves studying the various alternatives identified through literature search and interviews of field professionals through three successive modules (“technical performance", “regulation” and “hazard”), each containing exclusion criteria. The second simultaneous step takes a comparative approach. The remaining alternatives are then studied in parallel through four modules (“hazard”, “estimation of substitution costs”, “exposure conditions” and “other impacts”). In conclusion, the method developed follows a multi-criteria approach. It is not aimed solely at assessing the hazards of alternatives but also at studying issues around their technical performance, the estimated costs of substitution the conditions of occupational exposure to the alternatives and other impacts which may be identified. The pragmatic working method developed aims to rule out non relevant potential alternatives in the preliminary step, thereby enabling more detailed data collection on a smaller number of alternatives with the aim of comparing them in the second step. The method aims at presenting the various alternatives with their advantages and disadvantages in order to enable the decision-makers to retain the best option, with full knowledge of the facts, in view of the criteria they consider high-priority and acceptable. Currently, this method has been applied to the substitution of the uses of formaldehyde in embalming processes and in animal feed, where formaldehyde is used as a processing aid for protection against ruminal degradation, giving rise to public consultation of two reports from July to September 2018. More information on

Customer Driven Material Selection Through Transparency and Market Access Requirements
Cory Robertson

HP Inc.

The field of alternatives assessment continues to grow at a rapid pace as does the number of quality assessments now available to stakeholders. To maximize the sustainable impact of alternatives assessment these assessments must be used to inform decision makers. The ultimate goal would be to make material selection transparent so that customers can make informed purchasing decisions. The use of alternatives assessment in the regulatory landscape is well known but there is an opportunity to increase the use of safer alternatives through voluntary market access requirements such as ecolabels. Alternative assessment and hazard assessment are starting to be incorporated into ecolabels and certification criteria. The U.S. Green Building Council’s LEED certification now incorporates hazard assessment into building material requirements. An important ecolabel for the electronics industry is TCO Development’s TCO Certified label. TCO has incorporated an accepted substance list for flame retardants based on the GreenScreen® for Safer Chemicals. In the United States, EPEAT certification is arguably the most important “Green Public Procurement” requirement that must be met in order to bid on many government purchasing contracts. A new revision of the EPEAT for personal computer products was published this year and included criteria for chemical assessment and selection. Aspects of these ecolabels will be presented as well as a discussion of their ability to influence real-world adoption of safer chemicals. While developing safer chemical criteria in ecolabels several competing interests where revealed. Stakeholders include manufacturers, suppliers, government agencies, NGOs and the chemical industry. Additionally, the owners of hazard assessment frameworks, such as the GreenScreen®, place conditions on market claims made using their methods. The BizNGO Alternatives Assessment Working Group led focused discussions on the various approaches to incorporating the GreenScreen® into ecolabel requirements. Best practices and implementation experience gained through development of ecolabel standards will be shared.

Incorporating Health Equity into Alternatives Assessment Frameworks: Perspectives from Pilot Interviews
Veena Singla1, Ann Blake2, Sally Edwards3

1) University of California, San Francisco, Program on Reproductive Health and the Environment, 2) Environmental & Public Health Consulting, 3) University of Massachusetts, Lowell Center for Sustainable Production

Toxic chemicals and their ‘regrettable substitutions’ disproportionately burden vulnerable populations, including low-wealth communities and people of color, contributing to health disparities in conditions such as asthma, cancer, and reproductive problems. To achieve health equity for these communities requires the elimination of existing toxic exposures and the selection of safer alternatives that are truly health protective. Existing alternatives assessments frameworks offer good guidance for identifying, comparing, and selecting safer options to chemicals of concern to reduce harm to human health and the environment however, these methods have not focused on protecting the health of vulnerable populations. Our research was designed to begin to address this key challenge in alternatives assessment and informed substitution. We interviewed five leaders working at the intersection of environmental justice, public health, and chemical policy to understand their viewpoints on how vulnerable populations can be protected via the alternatives assessment process. The principle of health equity, a fundamental priority and value in public health that means that everyone has the opportunity to obtain their highest level of health, guided our investigation. Three major themes emerged: information access and quality genuine stakeholder engagement and trade-offs that may impact vulnerable populations. Based on these themes, we suggest eight initial areas of focus for businesses and governments to strengthen the protection of vulnerable populations in an alternatives assessment process, including: creating a plan for stakeholder engagement guiding decision-making with principles that explicitly encompass equity and defining a minimum data set needed to evaluate alternatives. A truly equitable alternatives assessment process should engage and empower vulnerable populations, avoid regrettable substitutions, and ultimately improve the health and lives of those most impacted by toxic chemicals.

Not an Academic Exercise: the Greener Solutions Approach to Developing Safer Alternatives
Megan Schwarzman

University of California Berkeley, Center for Green Chemistry

In a classroom at University of California, Berkeley, graduate student teams of chemists, environmental health scientists, toxicologists, and engineers investigate –for example—safer preservatives for personal care products, non-fluorinated approaches to creating durable water-repellant coatings, and crosslinkers to replace formaldehyde in permanent press textiles or diisocyanates in spray polyurethane foam insulation. But it is not an academic exercise. Working with a partner company, students identify possible alternatives through a bio-inspired design process and then embark on a hazard assessment, comparing both chemical and non-chemical alternatives to substances of concern in their specific application. Over the course of the semester, students generate a focused alternatives assessment that considers technical performance, hazard, relative exposure potential, and feasibility, creating an “opportunity map” for their partner company and the industry sector. This presentation will discuss the approach we have developed and refined over the last 7 years of the Greener Solutions program, addressing key issues in the alternatives assessment field. We investigate complex materials involving chemical mixtures and work at the level of a chemical’s core function in a product, which allows us to consider non-chemical solutions to the problem. Because we take on challenges that are pre-competitive, our solutions can apply to a whole industry sector. Greener Solutions projects have generated intriguing possible solutions but –perhaps more critically—have produced models for addressing key challenges, such as presenting hazard data together with an analysis of its uncertainty, and developing an approach for characterizing and addressing the tradeoffs between hazard and efficacy. We will illustrate these methods with multiple examples of Greener Solutions projects.

Stakeholder Perception of Knowledge Gaps in the Alternatives Analysis Process toward Safer Consumer Products
Julie M. Schoenung1, Haoyang He1, Virginia Zaunbrecher2, Xiaoying Zhou3, Oladele A. Ogunseitan4, Timothy F. Malloy5

1) University of California, Irvine, Department of Materials Science & Engineering, 2) University of California, Los Angeles, Institute of the Environment and Sustainability, 3) California Environmental Protection Agency, Department of Toxic Substances Control, 4) University of California, Irvine, Department of Population Health & Disease Prevention, 5) University of California, Los Angeles, School of Law 

Alternatives Analysis (AA), which is designed to promote safer consumer products through alternatives evaluation and selection, is gaining popularity. The Department of Toxic Substances Control (DTSC) Safer Consumer Products regulations, which took effect in 2013, require manufacturers of products containing a Chemical of Concern to conduct an AA. Though its importance is recognized by various non-governmental and governmental organizations, some industry players and select groups of researchers, AA has not been widely applied yet. In order to meet the challenges and needs of the rapidly changing industry and business fields, methods to manage knowledge gaps in AA must be identified. To understand the knowledge gaps, we conducted a comprehensive survey of a wide range of stakeholders regarding seven AA focus areas: chemical informatics, life cycle assessment, relevant factor analysis, decision analysis, economic analysis, stakeholder education and technology gaps were evaluated. Each included several sub-issues. In particular, we collected data regarding stakeholder demographics, their familiarity with each focus area, and the perceived importance to them of each sub-issue. Results of the survey and corresponding analysis provide the foundation for establishing a research agenda to build the field of AA in an effort to expand its application.

Tools for Informed Substitution: Integrating Health and Safety Committee and Procurement Activities
Dorothy Wigmore1, Larry Stoffman2, Bev Thorpe3

1), 2) LDS Health & Safety Ltd., 3) Clean Production Action

Cleaning products – their toxic ingredients and their effects – are increasingly a topic of concern in consumer and occupational health circles. “Green” options are often touted as the solution. But what's toxic? How do you know? What harm matters? Does "green" really account for worker health? How are purchasing staff/decisions connected to those who care about occupational health hazards? These practical questions face occupational health and safety (OHS) professionals, joint OHS committees (required in Canadian workplaces), OHS activists and purchasing staff. A one-year project connected these dots for a public sector union and those responsible for providing cleaning services in British Columbia provincial government buildings. We obtained and analysed product data sheets. Using the ingredients, we evaluated specific screening tools (e.g., the GreenScreen® List Translator, ChemHAT, Risctox). Using our findings and conversations with the partners, we developed a toolkit that was presented to the union's health and safety conference and revised it accordingly. For a creative difference, we involved professional designers who created edgy graphics to introduce each section. The on-line document is designed for worker activists, joint OHS committee members, OHS staff/specialists, and procurement/purchasing staff. It helps users identify toxic ingredients in cleaning products. They learn to use informed substitution principles and on-line screening tools to find replacement ingredients, products, or methods. The multi-media format provides practical information about how to screen, identify and substitute less toxic chemicals in cleaning products, lays out best practices for procurement activities, and provides links to on-line tools and other resources. It can be adapted for training materials for a variety of audiences, especially with the graphics (which delighted those who saw them). This innovative, first-of-its-kind accessible on-line toolkit integrates purchasing criteria and advice with occupational health goals of preventing and reducing hazards related to cleaning products. With edgy graphics, background about the right-to-know and health effects of toxic cleaning products, clear step-by-step instructions for using on-line tools, and comprehensive international resources, it is a unique and important result of a relatively-short project. We hope to evaluate the toolkit in several Manitoba workplaces using a variety of chemical products.