Chemical Alternatives Assessments

The Royal Society of Chemistry

Contents

Chemicals Alternatives Assessment (CAA): Tools for Selecting Less Hazardous Chemicals

MARGARET H. WHITTAKER AND LAUREN G. HEINE

ABSTRACT

Chemicals alternatives assessment (CAA) is a form of alternatives assessment that focuses on finding alternative chemicals, materials or product designs to substitute for the use of hazardous chemicals. Chemical hazard assessment (CHA) or comparative CHA is a method for comparing chemicals based on their inherent hazard properties. CAA is inclusive of CHA. However, a comprehensive CAA can be much broader and include information such as cost, availability, performance and social and environmental life-cycle attributes. CHA/CAA provides users with hazard-based information to make informed decisions when selecting less hazardous chemical alternatives. There are multiple CAA methods in use around the world and these methods share a common goal, namely, to support the intelligent design, use and substitution of chemicals to benefit humankind in a manner that will not harm our environment and its inhabitants. Ideally, a CAA/CHA will completely characterize a chemical's intrinsic human health and environmental hazards, in the process promoting the selection of less hazardous chemical ingredients, in addition to avoiding unintended consequences of switching to a poorly characterized chemical substitute.

CHA methods typically share common hazard endpoints related to human toxicity, environmental toxicity and environmental fate. The endpoints are evaluated based on criteria that allow for the use of measured or predicted data. Human health criteria in CHA evaluate endpoints such as potential carcinogenicity, mutagenicity, reproductive and developmental toxicity, endocrine disruption, acute and chronic or repeat dose toxicity, dermal and eye irritation and dermal and respiratory sensitization. Acute and chronic aquatic toxicity, terrestrial toxicity, persistence and bioaccumulation are commonly evaluated to predict a chemical's environmental toxicity and fate. Finally, some CHAs (such as Green-Screen™) also evaluate a chemical's physical characteristics such as flammability and reactivity.

Of the CAA methods listed, only the US Environmental Protection Agency (EPA)'s DfE program, CPA's GreenScreen™ and MBDC's Cradle to Cradle® paradigms are fully transparent and publicly available methods of assessment. Most other CAAs in use around the world do not fully disclose all of their reasoning or resources used for establishing threshold values for hazard criteria, prioritization of hazard endpoints and life-cycle concerns. Some CAA methods are limited to a focus on CHA whereas others such as MBDC's Cradle to Cradle® expand the focus to consider some life-cycle attributes. Whether the CAA method includes additional attributes or not, CHA can be used in a modular way, combining with other needed information to inform decision-making.

CAA provides a powerful means to improve upon the status quo by establishing methods to inform chemical substitution in a scientifically rigorous and defensible manner. Recognizing the value of CAA and fostering greater adoption of CAA methods provide stakeholders with much-needed tools to address a serious deficiency in the way in which chemicals are used in society, as maintaining the status quo is analogous to giving up. As humankind's understanding of the full costs and benefits of chemicals matures, it is critical that we cease using those chemicals that can permanently impair human health or the environment.

1.1 Introduction to Chemicals Alternatives Assessments

Chemicals alternatives assessment (CAA) is a form of alternatives assessment that focuses on finding alternative chemicals, materials or product designs to substitute for the use of hazardous chemicals in products. Chemical hazard assessment (CHA) or comparative CHA is a method for comparing chemicals based on their inherent hazard properties. CAA is inclusive of CHA. CHA/CAA provides users with hazard-based information to make informed decisions when selecting less hazardous chemical alternatives. The approach is used to assess a chemical's impact on human health and the environment. Hazard can be denned as the way in which a chemical, object or situation may cause harm. The degree of a chemical's capacity to harm depends on its intrinsic properties, such as its capacity to interfere with normal biological processes and its capacity to burn, explode or corrode (e.g., non-life-threatening allergic skin reaction to nickel jewelry, lethal egg-shell thinning in avian species attributed to exposure to the organochlorine pesticide DDT). The goal of a CAA is to find a science-based solution that identifies and completely characterizes chemical hazards, promoting the selection of less hazardous chemical ingredients, in addition avoiding unintended consequences of switching to a poorly characterized chemical substitute.

Hazard assessment is a systematic process of assessing and classifying hazards across an entire spectrum of endpoints and levels of severity It involves a characterization of the nature and strength of the evidence of causation. A comparative CHA is a type of hazard assessment that evaluates hazards from two or more agents, with the intent to guide decision-making toward the use of the least hazardous options via a process of informed substitution, as illustrated in Figure 1.1.

In practical terms, comparative CHA is a term that describes the practice of assessing hazards for specific items (such as chemicals, materials, products or technologies) and then comparing these hazards following a structured approach. Ideally, CHA minimizes subjectivity in hazard classification since a structured approach is used to assign hazards. Over the past 10 years, the number of comparative hazard tools has continued to increase. The Toxics Use Reduction Institute (TURI) at the University of Massachusetts presented a collection of over 100 tools for comparing hazard characteristics of different chemicals. CAAs have numerous applications, including the following:

• Enabling the prioritization of chemicals for reduction or phase-out:

* from any phase in product life-cycle (e.g., manufacturing, product design);

* from the whole supply chain.

• Assisting in the selection of alternatives for the following:

* banned or restricted chemicals or materials;

* chemicals that are perceived as hazardous by the public;

* identifying and classifying Restricted Use Materials (RUMs);

* developing environmentally preferred products.

Some CHA methods, such as GreenScreen™, focus solely on individual chemicals or materials and their subsequent health or environmental impacts while other CAA methods such as Cradle to Cradle® incorporate CHA in addition to certain life-cycle-based considerations such as energy use, water quality and efficiency, social responsibility and potential for material reuse.

To date, various CAA partnerships have brought together environmental agencies, such as the US EPA, industry organizations such as the Phosphorus, Inorganic and Nitrogen Flame Retardants Association (pinfa), academia (such as the University of Massachusetts at Lowell) and non-governmental organizations such as the United States Green Chemistry and Commerce Council (GC3) and Europe's ChemSec to evaluate environmental and health impacts of potential alternatives to problematic chemicals and chemical classes, such as phthalate esters (ubiquitously used in flexible plastics), flame retardants in furniture and printed circuit boards and nonylphenol ethoxylate surfactants (which are commonly used in laundry detergents and are exceedingly toxic to aquatic organisms). Such partnerships demonstrate that CAA can be employed to benefit both producers and users of the chemical to the improvement of ecological and human health.

The purpose of this collection of chapters in the Issues in Environmental Science and Technology series is to describe and exemplify several existing CAA methodologies currently being used in North America, Europe and China and to make suggestions on how to improve the overall CAA process, fostering the greater adoption of CAA around the world. This introductory chapter identifies a number of common themes among CAA methods and provides a broad overview of such methods.

1.2 Common Traits Among CAA Paradigms

CAA paradigms share a number of similarities that are implemented as part of a CAA and all have the common goal of identifying less hazardous chemicals. CAAs use standardized procedures to assess whether alternatives have the potential for an improved health and environmental profile. CAAs assess whether the adoption of an alternative chemical is likely to result in lasting environmental or public health improvement. Ideally, a CAA will also address whether chemical alternatives are commercially available, perform well and are cost-effective.

1.2.1 Step One: Hazard Assessment Through Literature Search and Data Identification

As a first step towards characterizing the human health and/or environmental hazards of a chemical, a CHA is performed. The practitioner assesses hazards for each chemical alternative across a range of health effects and environmental endpoints. Such endpoints generally include the following: acute and repeat dose toxicity, endocrine activity, carcinogenicity and mutagenicity, reproductive and developmental toxicity, neurotoxicity, respiratory and dermal sensitization, skin and eye irritation, acute and chronic aquatic toxicity, terrestrial toxicity and persistence and bioaccumu-lation. When measured data are not available or adequate for an endpoint, a hazard concern level can be assigned based on quantitative structure-activity relationships (QSARs or SARs) and expert judgment. This practice ensures that all endpoints are considered as part of the hazard assessment and that alternatives are evaluated based on a complete understanding of their potential human health and environmental hazards. A level of confidence associated with studies is often assigned.

Sources of information to evaluate and characterize human health and environmental hazards in a CAA include one of more of the following:

• Publicly available experimental data obtained from a literature review

* Sources of such toxicological and environmental fate and effects data include online databases indexing scientific literature, such as:

– ChemIDplus: http://www.cleanproduction.org/library /greenscreen-translator-benchmark1-possible%20benchmark1.pdf

– EPA High Production Volume Information System (HPVIS): http://www.epa.gov/hpvis/index.html

– UNEP OECD (Organisation for Economic Co-operation and Development) Screening Information Datasets (SIDS): http://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html

– European Chemical Substances Information System IUCLID Chemical Data Sheets (ESIS): http://esis.jrc.ec.europa.eu /index.php? PGM = dat

– United States National Toxicology Program (NTP): http://ntp.niehs.nih.gov/

– International Agency for the Research on Cancer (IARC): http://www.inchem.org/pages/iarc.html

– Human and Environmental Risk Assessment on ingredients of household cleaning products (HERA): http://www.heraproject.com/RiskAssessment.cfm

– European Chemicals Agency (ECHA): http://echa.europa.eu/

– ExPub (Expert Publishing): http://www.expub.com

* Experimental data that are not publicly available (such as industry- or trade association-sponsored studies)

* SAR-based estimations from predictive methods such as US EPA models (e.g., EpiSuite, Ecosar), European Union (e.g., VEGA, ToxTree) or OECD (e.g., OECD Toolbox), Derek, Topkat, among other predictive software algorithms.

1.2.2 Step Two: Hazard Classification and Benchmarking of Relevant Data

Once the literature search has been performed, relevant studies have been retrieved and data collected, the second step of a CHA generally entails assigning hazard scores for the criteria evaluated. For example, a Green-Screen™ will assign hazard scores of low, moderate, high (and, for some end-points, very low or very high) for 18 health and environmental fate and toxicity endpoints, as illustrated for an example chemical in Figure 1.2. Criteria for assigning hazard scores in a CAA are often based on the Global Harmonized System of Classification and Labeling of Chemicals (GHS) criteria, in addition to criteria from other authoritative lists. As an example, a complete version of GreenScreen™'s hazard criteria for each endpoint can be found at the CPA's website.

For several endpoints, such as acute mammalian toxicity, systemic toxicity, acute and chronic aquatic toxicity, persistence and bioaccumulation, hazard scores are often assigned based on specific dose thresholds and/or ranges. For example, the US EPA's Design for the Environment (DfE) Alternatives Assessment Criteria for Hazard Evaluation will assign a chemical a hazard score of Low for acute mammalian toxicity based on an oral LD50 of 2000 mg kg-1 or greater and a hazard score of Moderate for persistence based on a half-life in water that falls between 16 and 60 days.

For other endpoints, such as carcinogenicity, mutagenicity and reproductive and developmental toxicity, professional judgment and a clear understanding of the available data are necessary to draw a conclusion and assign a hazard classification. If a 2 year carcinogenicity study performed by the US National Toxicology Program (NTP) shows a statistically significant increase of hepatic tumors in rats, US EPA DfE and GreenScreen™ alternatives assessment criteria would assign a hazard score of High for carcinogenicity. In contrast, if a reproductive toxicity study reports a Lowest Observed Adverse Effect Level (LOAEL) of 250 mg kg-bw-1 d-1 in mice based on an effect such as decreased weight gain, US EPA and GreenScreen™ alternatives assessment criteria may or may not consider this effect relevant for purposes of assigning a hazard for reproductive toxicity depending on the chemical's mechanism of action. Ultimately, the hazard classification may come down to the professional opinion of the scientist performing the CAA. It is imperative to the integrity of a CAA that all hazard scores are based on sound scientific knowledge and can be properly supported and defended, if necessary.

Points to consider when determining the validity of available data include whether a study was performed following Good Laboratory Practices (GLP) or whether a study was conducted following a specific test guideline (e.g., OECD test guidelines). The level of detail reported in a study is also important, as is the source of the study. Primary sources such as peer-reviewed studies are preferred; however, high-quality secondary sources are acceptable, particularly when supported by a Klimisch score of 1 or 2 (1 = reliable without restrictions; 2 = reliable with restrictions), which provides an indication as to the reliability of the actual data.

In the case of conflicting data, weight of evidence should be used to assign the ultimate hazard score for a specific health effect/environmental endpoint. All professional judgments must be fully justified within the section of that end-point. The justification for a final hazard score must be transparent and easily understood by all who may read the CAA.

1.2.3 Step Three: CAA Report Preparation

Once the hazard assessment and classification portion of the CAA has been completed, a CAA report is written to provide contextual and supplemental information designed to aid in decision-making and may include descriptions of manufacturing processes, use patterns and life-cycle stages that may pose special exposure concerns. The CAA report may contain a description of the cost of use and the potential economic impacts associated with the selection of alternatives and may also contain information on alternative technologies that might result in safer chemicals, manufacturing processes and practices.

Examples of alternatives assessments can be found for numerous types and classes of chemicals, including nonylphenol ethoxylate surfactants, flame retardants in furniture and printed circuit boards, diethylhexyl phthalate and perchloroethylene.