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Green chemistry and the search for new plasticizers J. Patrick Harmon, and Rainer Otter ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.7b03508 • Publication Date (Web): 25 Dec 2017 Downloaded from http://pubs.acs.org on December 26, 2017

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ACS Sustainable Chemistry & Engineering

Sustainable Chemistry and Engineering Green Chemistry and the Search for New Plasticizers J. Patrick Harmon*† and Rainer Otter‡ †

BASF Corporation, 11750 Katy Freeway, Houston, Texas, 77079, United States. Email: [email protected]. ‡ BASF SE, Carl-Bosch-Strasse 38, Ludwigshafen am Rhein, D-67056, Germany

Abstract 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 widelyused 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 labelled 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.

KEY WORDS: GreenScreen®, SaferChoice, CleanGredients®, Alternatives Assessment, Hazard

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Introduction Green chemistry and sustainability are terms that are used frequently today, particularly in marketing promotions by a wide range of companies such as retailers, product manufacturers, and chemical companies. Sustainability is commonly understood as sustainable development: a balance between economic success, ecological protection, and social responsibility.1 Green chemistry “is the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances.”2 Unfortunately, common usage often ignores these definitions and makes it difficult to know what is actually “sustainable” or “green” about a product beyond the particular marketing label. For example, while shopping one of the authors found a serving bowl made from bamboo fiber; the label stated that it was made of “eco-friendly material” and was “BPA-, PVC-, and phthalate-free”. It was assumed that the free-of statements, together with the bamboo fiber, were the basis for their eco-friendly claim; however, these statements do not provide any clear details on what makes the product eco-friendly. Is bamboo fiber more sustainable than other materials used to make those types of bowls? The “free-of” statements only tell the consumer what materials are not in the product and say nothing about what it is made from (the author noted that the bowl did not appear to be 100% bamboo fiber). In addition, dishes and bowls such as the one described above typically are not made with PVC or phthalates; this is possibly a violation of the U.S. Federal Trade Commission (FTC) guidelines.3

Measures of Sustainability – How Do You Know? As one looks at various products online or in retail stores, a number of sustainability claims can be found about how they are made: • • • • • • •

Content of renewable raw materials Recycled material content Non-toxic Bio-based content Phthalate-free BPA-free No “black- or red-listed” ingredients


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Some of these are important and make sense as part of a plan to develop and market sustainable products. Products made with renewable feedstocks will be important for the future, recycling is an important way to reduce waste, and it may be important to eliminate certain materials from products to meet current or future regulatory and customer requirements. There are some limitations to these types of claims. First, the demands from definitions of sustainability and green chemistry presented at the beginning of this article cannot be satisfied with simple claims. Secondly, the “free-of” phrases only state what the products do not contain and say nothing about what they are made from – how do we know the ingredients used are less hazardous or more sustainable than the ones the product is “free-of”? And, for example, is the renewable material more sustainable than equivalent petrochemical-based materials when you look at the whole life cycle of the product? The better approach is to clearly identify and hopefully quantify the sustainability benefits of the product. This is particularly important if you want to make a difference in the world, instead of just “green washing” or marketing your product with popular phrases or free-of statements, but with nothing concrete to back up the claims. Companies successfully do this in different ways. Examples include: • • • • •

Life-cycle analysis (LCA) Eco-efficiency analysis (EEA) Sustainable Solutions Steering® or similar methodologies Hazard and risk assessments, especially if verified by third parties Third party certifications

“Show me the data” is the key element of a successful and legitimate sustainability strategy. With life-cycle analysis (LCA) the ecological footprint or impact of a product throughout its whole lifecycle can be measured.4 Eco-efficiency (EEA) is an overall study of alternative solutions to include a total cost determination and the calculation of ecological impact over the entire life cycle.5 BASF recently introduced Sustainable Solutions Steering® as a methodology to evaluate the impact of its entire portfolio over 10 different criteria based on market-place sustainability needs:6 • •

Cost savings downstream Climate change 3 ACS Paragon Plus Environment


• • • • • • • •

Energy Resource efficiency Health and safety Biodiversity Renewables Emission reduction Water UN Millennium Development Goals

Based on the results of the evaluation, products are clustered into four different categories: • • • •

Accelerator: A solution with a substantial sustainability contribution in the value chain in at least one of the 10 areas listed above Performer: A solution that meets the basic sustainability standards in the marketplace Transitioner: A solution for which a specific sustainability issue is actively addressed Challenged: A solution with a significant sustainability concern identified and for which an action plan is under development

This methodology is further used to “steer” the BASF portfolio to more innovative and sustainable solutions for customers. The company is using this methodology to help increase the share of “Accelerators” in its portfolio to 28% by 2020. Several retailers and consumer product manufacturers and states such as California, Maine, Washington, and Minnesota, have developed policies in a move toward “safer” chemistries. Most of these are driven by potential hazards and hazard-based regulations. If one wishes to participate in these important markets, it is important to have a sustainable chemistry program that uses alternatives assessment methodologies based on a wide range of hazard endpoints. In addition, risk analysis that incorporates hazard and exposure also is important to put any hazard concerns into context; this is particularly important when alternatives do not exist or are significantly more expensive and poorer performers. Third party verified assessments and certifications by competent and experienced organizations are important ways to carry out and communicate the results of these types of assessments. A recent paper about the 30-year anniversary of California’s Proposition 65 regulation also discussed the importance of “eco-labels”, transparency declarations, and product certifications for providing information to consumers.7 Proposition 65 is a right-to-know law that requires labelling of


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products that contain substances known to the state to cause cancer or reproductive or developmental effects, if exposures exceed safe harbor levels established by the state. The original supporters of Proposition 65 believed that the mandated warnings would “enable informed choices” by consumers; however, the author of the paper notes that the warnings are potentially confusing and misleading as a tool for communication about the safety of a product. For example, a warning label only identifies the presence of a listed chemical but does not say anything about potential risk to humans; in addition, the absence of a label says nothing about the safety of what materials are used in the product. The author suggests that “chemical assessment tools” and “ecolabels” can provide much better criteria-based information about the safety of a product than a Proposition 65 label. The disadvantage of “negative list” based regulations such as Proposition 65 or some purchasing policies is that they say nothing about the safety of materials used in products that “comply” with these criteria. “Positive list” certifications such as the EPA Safer Choice program and assessment tools such as GreenScreen® can be used to more effectively communicate the safety of the products to consumers, retailers, and consumer product manufacturers. Safer Choice and assessment tools such as GreenScreen® are unfortunately only hazardbased and in part rely on regulatory and other lists that differ greatly in their reliability and credibility. These programs are imperfect, but they are a step in the right direction toward helping companies quantify the hazards of ingredients in their products; when used in the right context they can be an important part of a successful sustainability strategy.

Why is it important to measure and quantify? Wise use of the tools and methodologies described earlier are critical for evaluating existing chemistries and to look for alternative materials when necessary. One reason this approach is important is to make “informed substitution”. For example, it is important for substitute materials to be lower hazard and risk and have an equal or better life cycle impact instead of just being “free-of” an incumbent regulated chemical.



Secondly, this approach is necessary to avoid “regrettable substitution”. No one wants to spend time and money on reformulation, only to have to reformulate a few years later because of a bad choice in a substitute. Bad choices can result in product failures and recalls because of performance issues, or if hazard and risk for the substitute are not clearly evaluated, one may find that the substitute is soon under regulatory scrutiny, also. Finally, this approach is the responsible way to look for alternatives. As an example, the flexible vinyl and plasticizers markets have been under attack and subject to regulatory action over the last 20 years, particularly in applications with close human contact such as toys and children’s products and medical devices. The regulatory and media attention to these uses have led to the replacement of restricted ortho-phthalate plasticizers with alternatives.8 Companies in the vinyl value chain should use solid methodologies to make informed decisions in order to avoid regrettable substitutions that could be impacted by future regulatory action or unfavorable public attention. In an interesting example that supports responsible decision making, the US Consumer Product Safety Commission (CPSC) notes in their guidance for companies that must comply with restrictions on certain ortho-phthalates, that manufacturers may use “unbanned” ortho-phthalates or alternative plasticizers for children’s toys and childcare articles. However, they add that “manufacturers are still responsible for ensuring that children's products are not considered ‘hazardous’ under the general requirements of the Federal Hazardous Substances Act (FHSA). It is the manufacturer's obligation to ensure that any alternative plasticizer that is used be adequately tested such that the manufacturer is confident it does not pose a risk of injury under normal use or reasonably foreseeable misuse.”9 This is an excellent example that shows the obligations for formulators to not only avoid restricted substances but also ensure that alternatives are adequately tested and safe. The Search for Alternative Plasticizers

Plasticizers are used in polyvinyl chloride (PVC, vinyl) or other plastic formulations to make inherently rigid materials soft and flexible. The most widely used plasticizers are orthophthalates, or 1,2-benzenedicarboxylic acid, diesters (also referred to generically as phthalate 6 ACS Paragon Plus Environment

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esters or phthalates). They are made from alcohols and phthalic anhydride; alcohols with total carbon lengths from 4 to 13 historically are the most useful in flexible vinyl applications. Over the past two decades some members of this chemical class have been subject to regulatory restrictions as well as deselection by retailers and consumer product manufacturers. Phthalates with straight alcohol side chains from 3 to 6 show clear adverse developmental effects and impair the male reproductive tract in rats (For example, di-n-octyl phthalate (DNOP) has a straight carbon chain of 8; di-2-ethylhexyl phthalate (DEHP) has a straight carbon side chain of 6 (hexyl with ethyl branching), but the total number of carbons is 8 for both. Toxicity to reproduction (i.e., impairment of fertility and developmental effects) are observed with DEHP but not with DNOP.).10 Although the potential hazard for humans is unclear and perhaps unlikely,11 restrictions by governmental agencies and various retailers and consumer product companies have resulted. These various restrictions have led to the use of existing alternative plasticizers and to the development of new ones. The three most important considerations in choosing a plasticizer are cost, performance, and the environmental, toxicological, and regulatory footprint (i.e., what are the hazards and risks, and may the product be used for a particular regulated application). Cost is somewhat self-explanatory but is more than just price. For example, for finished products sold by volume instead of weight, a plasticizer with lower density will result in a finished product with a higher volume for the same weight of plasticizer. Performance is one of the reasons flexible polyvinyl chloride is such an important material for a broad range of applications. The type of plasticizer plays a major role in determining the suitability of the vinyl formulation for an application. Plasticized vinyl can be used for jacketing and insulation in UL-rated wire and cable, flexible medical devices such as IV tubing and bags and blood collection and storage devices, resilient flooring, roofing membranes, automotive interior and exterior applications, consumer products, and many other types of products. DIDP and TEHTM (see Table 1 for acronyms and Fig 1 for representative structures) can be used to meet the requirements for UL



wire and cable ratings.12 DEHP, D9CH, DOTP, and TEHTM may be used for a number of medical applications.13 A number of specialty plasticizers have been commercially important for much of the last 60 years. Specialty non-phthalate plasticizers are used in applications where specific performance characteristics are needed. For example, di-2-ethylhexyl adipate (DEHA) and linear ortho-phthalates such as di-undecyl phthalate (DUP) and nonyl, undecyl phthalate (911P) provide good low temperature flexibility. Dibenzoates and alkyl sulfonates are high-solvating plasticizers and beneficial in many plastisol applications.12 It is not uncommon to see a new plasticizer described as “phthalatefree” or “non-phthalate”, implying that they are replacements for general purpose ortho-phthalates such as DEHP or DINP; however, one should keep in mind that the new product may be a plasticizer but might only be suitable for a few applications and not be a true replacement for incumbent orthophthalates.


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Table 1. Plasticizer Examples and Acronyms Plasticizer Di-2-ethylhexyl phthalate Diisononyl phthalate

Acronym DEHP, DOP DINP

Diisodecyl phthalate

DIDP

Di-2-ethylhexyl adipate Tri-2-ethylhexyl trimellitate Di-2-ethylhexyl terephthalate Cyclohexane-1,2-dicarboxylic acid, diisononyl ester

DEHA, DOA TOTM, TEHTM DOTP, DEHT D9CH

CAS No. 117-81-7 28553-12-0, 68515-48-0 68515-49-1, 26761-40-0 103-23-1 3319-31-1 6422-86-2 166412-78-8, 474919-59-0

Fig. 1 Plasticizer Structures

GreenScreen® for evaluation of alternative plasticizers GreenScreen® is a hazard assessment methodology developed by Clean Production Action (CPA).14 One strong point for the tool is that is a based on a publicly available, transparent methodology that may be used within individual companies or can be performed by one of four licensed profilers; the third-party assessments can be “certified” (i.e., done by a licensed profiler) or “verified” (subjected to a subsequent CPA verification process). It includes a broad range of hazard 9 ACS Paragon Plus Environment


endpoints with criteria for classifying the hazards as low, moderate, or high (and in some cases very low or very high). The endpoints are classified based on Globally Harmonized System (GHS) criteria, “authoritative” or “screening” lists, or other sources. In addition to the hazard classification for the individual endpoints, a final overall score or Benchmark is determined (see Table 2). The tool uses a methodology to determine each Benchmark score; one additional strong point is that there are minimum data requirements to reach each level; i.e., data gaps are clearly not rewarded. A Benchmark of U is assigned if too many data gaps are present to meet the Benchmark 2, 3, or 4 criteria. Table 2. GreenScreen® Benchmarks Benchmark Score

CPA Description

1

Avoid – Chemical of Concern

2

Use but Search for Safer Substitutes

3

Use but Still Opportunity for Improvement

4

Prefer – Safer Chemical

GreenScreen® is not perfect. As noted above, it is a hazard-only assessment. The best determination of safety is a risk assessment that looks at use and exposure data in addition to hazard. In order to reduce risk, you can lower hazard or exposure, so a hazard assessment can be useful as part of a more comprehensive alternatives assessment. For functionally equivalent alternatives, exposures may often be similar for different materials; in this case, the use of a less hazardous alternative would be the best route to reducing risk.15 GreenScreen® also defaults in some cases to authoritative lists for hazard classifications. This can make the assessment “easy”, but, unfortunately, some lists may be precautionary and not reflect the true hazard potential for humans (e.g., IARC and Proposition 65). In addition, some endpoints such as “endocrine activity” are quite subjective and may result in different classifications by two or more profilers. In one example that will be discussed later in the section, the manufacturer of a material is forced to “prove a negative” since there are no clear criteria for determining a low 10 ACS Paragon Plus Environment

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hazard for endocrine activity. In another case, arguably equivocal data might be resolved by some profilers by “rounding up” to the next hazard level with the desire to be precautionary; this may, however, result in conclusions that are in conflict with regulatory decisions by global governmental agencies. GreenScreen® may be particularly useful for certain markets. For example, in the U.S. Green Building Council (USGBC) LEED Version 4, this methodology may be used to obtain credits under the section called “Building Product Disclosure and Optimization”.16 Under Option 1 (Material Ingredient Reporting), the GreenScreen® Benchmark score can be reported for ingredients at >0.1% in the material. Option 2 awards credits for assessing ingredients down to 0.01% with the GreenScreen® methodology and for having no Benchmark 1 ingredients. In addition, GreenScreen® Benchmark scores may be reported on Health Product Declarations (HPD), another important tool for the building and construction industry.17 Plasticizer Assessments Table 3 shows the hazard classifications and Benchmark scores for several plasticizers; the classifications were determined by BASF or a third-party profiler. For the BASF assessments, hazards were assigned a Low (L), Moderate (M), or High(H) using summaries from the European REACH dossiers18 and manufacturer Safety Data Sheets (SDS) together with the GreenScreen® criteria. Classifications in bold letters are used when there was high confidence in the classification; italic letters are used if there is lower confidence based on the use of surrogate data (i.e., read across) or modelling. (GreenScreen® also includes reactivity and flammability as hazards. These are both low for the plasticizers discussed in this article.) Di-2-ethylhexyl phthalate (DEHP or DOP), one of the most widely used general purpose plasticizers, is used for comparison to the various alternatives. DEHP was classified using GreenScreen® criteria as a high (H) hazard for reproductive and developmental toxicity and for endocrine activity. These classifications are based on California Proposition 65 and European (EU) classifications, including its listing as a Substance of Very High Concern (SVHC) for reproductive and developmental toxicity and as an endocrine disruptor for humans and the environment. These 11 ACS Paragon Plus Environment


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“high” classifications result in a Benchmark score of 1. The carcinogenicity hazard is Moderate (M) based on its classification by the International Agency for Research on Cancer (IARC) as “possibly carcinogenic to humans” (2b). (DEHP is listed on Proposition 65 as a cancer hazard but is not classified as a cancer hazard in the EU.) Endpoint Assessment by: Cancer Mutagenicity Reproductive Developmental Endocrine Activity Acute Toxicity Systemic Toxicity Neurotoxicity Skin Sensitization Respiratory Sensitization Skin Irritation Eye Irritation Aquatic Toxicty Chronic Aquatic Toxicity Persistence Bioaccumlation GreenScreen® Benchmark

DEHP BASF M L H H H L M L L L L L L L vL L 1

Alt 1 BASF dg L L L dg L L L L L vH vH H M vL L U

Bio 1 BASF dg L L L dg L L L L L L L L L vL M U

Bio 2 BASF dg L dg L dg L L dg L dg L dg L dg vL L U

Bio 3 BASF dg L L dg dg L L dg L dg L L L dg vL L U

DOTP Profiler L L L L dg L L L L L L L L L vL L 3DG

D9CH Profiler L L L L M L L L L L M L L L M L 2

Table 3 – Hazard Classifications for Plasticizers The plasticizer referred to as Alt 1 was introduced to the market within the last 10 years (Example alternative plasticizers are identified in the paper as Alt 1 or Bio 1, 2, and 3, since the intent is to demonstrate differentiation between available data and hazard levels of various products without specific criticism of these materials. All examples are of current or historically commercial plasticizers.). It has quite attractive properties as a plasticizer and may be called a “non-phthalate”. Owing to its attractive properties, a sample was requested by the BASF Technical Service Laboratory. Upon arrival, it was discovered that the SDS had an important warning: “severely corrosive to skin and eyes!” As can be seen in Table 3, Alt 1 is classified very high (vH) for skin and eye irritation/corrosion and high for aquatic toxicity; other key endpoints such as reproductive, developmental, and systemic toxicity are low. This is an example of why an alternatives assessment using a tool such as GreenScreen® is important. Endpoints such as reproductive and developmental toxicity are particularly important for producers and downstream users. They also are important from 12 ACS Paragon Plus Environment

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a media perspective and have driven much of the recent regulatory action for ortho-phthalates; however, the effects are seen in rodents and not in primates, and occur at levels considerably higher than typical human exposures. On the other hand, skin and eye corrosivity are serious work place hazards as compared to other potential effects that may only present a minimal risk to most workers and consumers. Alt 1 is an example of why a simple search for a non-phthalate or phthalate-free alternative may result in a product that introduces more relevant hazards into the workplace. How about bio-based plasticizers? Bio 1, 2, and 3 are examples of plasticizers introduced to the market over the last 10 – 15 years that are at least partly based on renewable raw materials. All three are likely to be less hazardous than DEHP; however, they vary in the data available to make this determination. Bio 1 is low (L) hazard for almost all endpoints, with carcinogenicity as the only critical data gap – an endpoint data gap for many commercial chemicals. If the cost and performance meet customer requirements, it may be an attractive alternative. Bio 2 and 3 have data gaps for a few endpoints and rely on study data from similar substances (“read across” or surrogate data) or modelling for most of the other endpoints. Products with Bio 2 and 3 might be labelled as bio-based or phthalate-free, but should a formulator or end-product manufacturer choose them? How can suitability for safe-use be determined without sufficient and reliable data? Read across and modelling data may certainly be appropriate for some products and may be necessary for new substances just after introduction to the market; however, carrying out an alternatives assessment between data-rich products and those with little substance-specific data may result in the proverbial “apples and oranges” comparison. (A table showing the basis for classifications for some of the end points for Alt 1 and Bio 1, 2, and 3, may be found in the Supporting Information.) Interestingly, Bio 1, 2, and 3, have some limited food contact clearances, specifically for aqueous and low alcohol foods. Some formulators and product manufacturers interpret this as demonstration of the safety of the material for other uses. For the US FDA Center for Food Safety and Applied Nutrition (CFSAN), the data requirements depend on the expected migration under the approved conditions of use.19 Negligible migration takes place with these types of substances when exposed to aqueous and low-alcohol foods; therefore, little data then would have been required to 13 ACS Paragon Plus Environment


gain approval. This is, of course, fine for the specific food contact uses since there is minimal exposure and no risk; however, food contact clearance in this case does not provide any assurance for more general use of the products as alternatives to more well studied ortho-phthalates and other materials. The final two plasticizers discussed in the paper, di-2-ethylhexyl terephthalate (DOTP or DEHT; e.g. Palatinol® DOTP and Eastman® 168) and diisononyl 1,2-cyclohexanedicarboxylate (D9CH; e.g. Hexamoll® DINCH®) have complete data sets and demonstrated low toxicity concerns. DOTP, in a GreenScreen® assessment by a licensed profiler, was classified as low hazard for all end points with the exception of endocrine activity, which was assigned a data gap (“dg”).20 Almost all of the end points were based on animal studies using this material; i.e., with limited use of surrogate or modelling data. Respiratory sensitization was classified as low with lower confidence (“L”) based on a weight of evidence analysis performed in accordance with the endpoint specific guidance by ECHA.21 The overall Benchmark was 3DG (meets Benchmark 4 criteria except for a data gap). It is interesting that endocrine activity was classified as a data gap in recent assessments, since a collaborative GreenScreen® as part of a Green Chemistry and Commerce Council (GC3) project in 2012 classified it as “L”.22 After the assessment expired in 2015, three licensed profilers independently updated the assessment of this material. Two profilers classified endocrine activity as low (with lower confidence), while the original profiler changed their classification to a “data gap”. A “consensus” classification of “data gap” was finally determined by a panel from Clean Production Action. (The new GreenScreen® assessment20 is not yet publicly available; however, the assessment from 2012 is available online22 and may be consulted along with Reference 25 (Ball, et al.). Important new data since 2012 are discussed below.) As already noted above, endocrine activity is one endpoint open to interpretation and potentially to “speculative toxicology”. Based on the experience with DOTP, it appears unlikely that any substance can achieve a Benchmark 4 since no data gaps are allowed to achieve this score. The following data are available for DOTP to support a low hazard classification for this endpoint: 14 ACS Paragon Plus Environment

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•

No anti-androgenic effects similar to those observed with some ortho-phthalates23,24

•

No estrogenic effects in vitro or in vivo25

•

Inactive in a number of US EPA ToxCast and EDSP21 assays26,27

•

No suggestion of thyroid or adrenal gland effects from sub-chronic and chronic studies25

In addition, a recent review by the French ANSES under the EU RMOA process determined that there was “no alert . . . on potential endocrine disruption properties of the substance” and concluded there were no risk management measures necessary.28 D9CH was classified in a recent GreenScreen® assessment as a moderate hazard for skin irritation, persistence, and endocrine activity, with a final overall score of Benchmark 2; however, these conclusions must be considered appropriately.29 D9CH does not meet the U.S. or EU criteria for classification as a skin irritant; however, it does meet the strict GHS criteria used by GreenScreen® and some countries. It also has been shown to be non-irritating to human skin when used in vinyl films.25 It also is biodegradable, but with a half-life of 16 – 60 days it is classified as a “moderate” persistence hazard since it does not meet the “readily biodegradable” criteria.30 It is readily biodegradable with adapted sludge likely to be found in bio-treatment plants. D9CH clearly is not a concern for irritation or persistence; this is a clear example of why one should consider the results of such assessments qualitatively as well as quantitatively. (The new GreenScreen® assessment29 is not yet publicly available; however, the assessment from 2013 is available online31 and may be consulted along with Reference 33 (Bhat, et al.). Important new data since 2013 are discussed below.) D9CH surprisingly was assigned a classification of moderate (with low confidence) for endocrine activity after a consensus review organized by CPA. One licensed profiler classified it as a low hazard (with low confidence),29 while another classified it as moderate based on thyroid effects observed in chronic and sub-chronic rodent studies.31 In assessments by NICNAS (Australia),30 the European Food Safety Authority (EFSA),32 and NSF International,33 specific studies have shown that the thyroid effects are caused by an indirect mechanism and are not relevant to humans. Furthermore, the French ANSES concluded through the Risk Management Options Analysis (RMOA) 15 ACS Paragon Plus Environment


process that specifically focused on endocrine disruption, that no risk management measures were required, similar to the conclusions for DOTP.34 D9CH was found to be negative in an EPA screen for fetal testosterone effects.24 This work was done to identify possible anti-androgenic effects observed with some ortho-phthalates. D9CH also was negative for estrogen receptor bioactivity based on the ToxCast™ Endocrine Receptor Model26 and the various EDSP21 assays.27 These data and the weight-of-evidence from chronic and sub-chronic studies demonstrate that D9CH is not a concern for adverse endocrine effects. Regulatory and other assessments support this conclusion. As discussed earlier in this paper, the credibility of the current precautionary and speculative evaluation in the GreenScreen® assessment is in conflict with conclusions made by authoritative regulatory agencies following a more rigorous review of the data (it should be noted that the regulatory agencies referenced above had access to the full study reports, including single animal and historical control data).

Safer Choice and CleanGredients® The US Environmental Protection Agency (EPA) recently changed the name of its Design for the Environment program to SaferChoice. Through the SaferChoice program ingredient manufacturers may have their products reviewed by 3rd party profilers to determine if they meet established EPA hazard-based criteria for inclusion by CAS Number in the Safer Chemical Ingredients List (SCIL).35 Formulators who use ingredients from the SCIL may also have their finished products certified with the SaferChoice label. This label has predominately been used by the cleaning products industry, but EPA has added additional categories. The agency has expressed interest in establishing a category for plasticizers or plastic additives, but currently no plasticizers are included in the list. A non-governmental certification called CleanGredients® is available from GreenBlue; CleanGredients® is a database of chemical ingredients whose formulations have been pre-approved by the U.S. EPA to meet the criteria of the Safer Choice Standard.36 Third party profilers assess ingredients using the EPA SaferChoice criteria. With concurrence by EPA staff, products are listed 16 ACS Paragon Plus Environment

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by company and trade name under a CleanGredients® subscription. Two plasticizers, BASF Palatinol® DOTP and Eastman 168™ SG, are currently included in the list. CleanGredients® provides a tool for formulators to choose ingredients for their products that have been shown to have low hazard concerns. As discussed above, much energy has been spent over the past two decades defending flexible vinyl products from media, activist, political, and regulatory attention and in trying to keep some additives off of various regulatory and deselection lists. Positive lists such as the SCIL and CleanGredients® should be considered by the vinyl value chain as a way to promote the safety of their finished products. In particular, alternative plasticizers and other additives on these lists would be a better choice than ones claiming to be, for example, “phthalate-free” or “BPA-free”, with little hazard, risk, or life-cycle data available to support their safe use. This article is not a blind endorsement for SaferChoice or CleanGredients®, particularly since they only use hazard-based criteria; however, the two programs are a step in the right direction for providing a methodology for product makers to make good decisions when formulating new products.

Other Considerations As discussed earlier, hazard is not the only criteria for choosing alternative ingredients. Life cycle and eco-efficiency data are important to understanding the complete impact of a product, and exposure data are necessary to understand potential risks. In an eco-efficiency study from 2008 by BASF, which was recently updated, D9CH and DOTP were found to be the most eco-efficient in a comparison between five alternative plasticizers.37 The US CPSC Chronic Hazard Advisory Panel (CHAP) report from 2014, made clear the importance of exposure data for determining potential risk from plasticizers in children’s products; particularly important are human biomonitoring data to measure “background” exposures.38 These data are available for the most important commercial ortho-phthalates but not for most of the replacement plasticizers reviewed by the panel. Since completion of the panel’s work and prior to publication of their report, analytical methods have been developed for D9CH and DOTP. 17 ACS Paragon Plus Environment


European39 and U.S.40 exposure data for D9CH and European data for DOTP41 now are available. Human biomonitoring data will become increasing important for understanding human exposure to plastic additives and other materials. In addition, BASF products Hexamoll® DINCH® (D9CH) and Palatinol® DOTP (DOTP) have been classified as Accelerators under the BASF Sustainable Solutions Steering® methodology based on their contribution to meeting product health and safety needs in the market.

Conclusions Sustainability and green chemistry programs must be based on data to ensure that a company’s products are not promoted using simple “free-of” labels and other superficial marketing tools and that they make a clear, positive improvement in the life cycle and safety of the materials they go into. 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 SaferChoice and CleanGredients® also may be useful in selecting the right materials. “Phthalate-free” is a phrase often seen to promote new plasticizers for finished consumer products that are marketed as “green” or “eco-friendly”. Some alternative plasticizers have sufficient data and low hazard to support their use in consumer and other products. Other new plasticizers may be “phthalate-free” and are possibly safe for their intended uses, but insufficient data are available compared to widely-used ortho-phthalates and products such as DOTP and D9CH.


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ASSOCIATED CONTENT Supporting Information Summary - Basis for hazard classification

Author Information Corresponding Author *Email: [email protected]. Telephone: 346-252-4123. Notes The authors declare no competing financial interest.

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Hazard assessment methodologies and certifications are proposed as alternatives to “free of” claims for communicating the sustainability of products to consumers and others.


Green Chemistry and the Search for New Plasticizers - ACS Publications

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