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Detailed Contents

Chapter 7. DEHP


7.1 Overview for DEHP

7.2 DEHP Use Prioritization

7.3 DEHP Alternatives Identification and Prioritization

7.4 DEHP Alternatives Assessment

7.5. Summary and Conclusions

References

7.1 Overview for DEHP

Plasticizers are additives to otherwise rigid plastics that impart the flexibility required for certain applications. Phthalates are a class of plasticizers that are commonly used in a variety of applications, from consumer products to medical devices to industrial equipment. They are organic chemicals produced from petroleum and are the most commonly used plasticizers in the world. Over 90% of the phthalates produced are used specifically for their plasticizing function, giving plastics, primarily polyvinyl chloride (PVC), strength, flexibility and durability. The purity requirements for commercial plasticizers are very high; phthalate esters are usually colorless and are mostly odorless. Although the various kinds of plasticizers in use today have some structural similarity, each one is different in the way it performs.

Phthalates are products of simple esterification reactions, which can be carried out readily in heated kettles with agitation and provision for water take-off. While some manufacturing facilities produce plasticizers by such batch methods, newer, highly automated plants operate continuously, particularly if they emphasize a single product. Esterification catalysts speed the reaction and are neutralized, washed and then removed. The reaction usually requires an excess of alcohol, which is readily recycled. Analogous syntheses yield aliphatic dicarboxylic acid esters, benzoates and trimellitates (Stanley 2006).

Di (2-ethylhexyl) phthalate (DEHP) is the international standard PVC plasticizer and properties of other plasticizers are usually reported relative to those of DEHP. As a plasticizer for PVC, DEHP generally offers excellent compatibility, desirable fusion properties and a set of performance properties that, for many uses, require little modification with other types of plasticizers. The chemical structure of DEHP (C24H38O4) is illustrated in Figure 7.1 A.

DEHP (CAS No 117-81-7) is also known as di-octyl phthalate (DOP) or bis (sec) ethylhexyl phthalate. It is the most commonly used phthalate plasticizer with an estimated annual production in Western Europe of 500,000 metric tons per year (Greens 2004) and an estimated global annual production of between 1 and 4 million metric tons per year (Swedish Chemicals Inspectorate (KemI) 2003). The U.S. production of DEHP was 120,000 metric tons in 2002. This represented 18% of the total U.S. consumption of phthalate plasticizers (Bizzari et al. 2003).

7.1.1 Characteristics

DEHP is a colorless liquid with almost no odor. It represents one of the most versatile and widely used plasticizers in industrial applications primarily because of its overall performance characteristics and its wide range of appropriate properties for a great many cost-effective, general purpose products (Phthalates Information Centre Europe 2005).

Table 7.1 A: Chemical/Physical Characteristics of DEHP (USEPA 2005)

7.1.2 Health and Environmental Impacts

Summary

DEHP is present in many products that require the use of flexible plastics. With a relatively low vapor pressure and water solubility, the amount of DEHP in plastic products that will be released is fairly low relative to the amount in products. The amount released is affected by the medium it is in. In non-aqueous environments (e.g., fats) more DEHP will be released. Many studies indicate that the human body burden of DEHP has been increasing over the decades as flexible plastics find new uses. In addition, more recent studies that look at the presence of metabolites of DEHP excreted by humans provide supporting evidence that DEHP exposure to humans is in fact occurring. The following sections detail some of the more recent knowledge and generally accepted understanding of the health and environmental effects of exposure to DEHP.

Human Health Effects

Based on our current scientific knowledge, human exposure to DEHP during manufacture or consumer use occurs primarily through inhalation and oral exposure. There has been only limited study of dermal exposure to DEHP, but it is thought to be an insignificant mechanism for adverse human health effects. This is due to low absorption rate and limited human exposures through dermal contact. Exposure may also occur during medical fluid injection if DEHP leaches into the medical fluids as a result of direct contact with the DEHP-plasticized PVC materials used in some medical devices. When these fluids have high lipid content the likelihood of DEHP leaching into the fluids increases.
Information on the oral toxicity of DEHP in humans is limited to gastrointestinal symptoms (mild abdominal pain and diarrhea) based on the evidence of two individuals who ingested a single large dose of the compound (Agency for Toxic Substances and Disease Registry (ATSDR) 2002). Because of the dearth of scientific studies that have been conducted on humans, only limited information is available relative to the health effects of DEHP in humans following inhalation or dermal exposure, although recent studies are exploring the potential for effects (e.g., asthma) associated with inhalation of dusts containing DEHP (Børnehag et al. 2004).

When DEHP enters the human body, the compound is rapidly metabolized into various substances that are more readily excreted. The first of these metabolites to be created is mono-ethylhexyl phthalate (MEHP), which is thought to be responsible for much of DEHP’s toxicity. MEHP is primarily formed by the hydrolysis of DEHP in the gastrointestinal (GI) tract and then absorbed (Centers for Disease Control and Prevention (CDC) 2005). The enzymes (lipases and esterases) that break down DEHP into MEHP are found mainly in the GI tract, but also occur in the liver, kidney, lungs, pancreas, and plasma. MEHP is subsequently further metabolized by different oxidation reactions, creating a number of other metabolites, the most significant of which include (Koch et al. 2006):

  • 2-ethyl-5-hydroxyhexyl phthalate (5OH-MEHP)
  • 2-ethyl-5-oxy-hexylphthalate (5oxo-MEHP),
  • 2-ethyl-5-carboxy pentylphthalate (5cx-MEPP), and
  • (2-(carboxymethyl)-hexyl) phthalate (2cx-MMHP).

These secondary metabolites of DEHP represent the majority of DEHP metabolites (approximately 70%) excreted in urine versus MEHP, which is present in urine at approximately 6% of the total amount excreted (Koch et al. 2006). 5OH-MEHP and 5oxo-MEHP are produced by the oxidative metabolism of MEHP and are present at roughly three-to ten-fold higher concentrations than MEHP in urine (Koch et al. 2003). Because the majority of conversion of DEHP to MEHP occurs in the GI tract, exposures to DEHP by ingestion may be more hazardous than by intravenous exposure, which largely bypasses the GI tract. The primary purpose of studying these secondary metabolites is that the long half-times of elimination of the carboxy metabolites (5cx-MEPP and 2cx-MMHP) make them appropriate parameters for measuring time-weighted body burden of DEHP, while 5OH-MEHP and 5oxo-MEHP appear to more accurately reflect short-term human exposure to DEHP (Koch et al. 2006). However much less is known about the potential human effects of exposure to these secondary metabolites.

The initial metabolism of DEHP to MEHP is qualitatively similar among mammalian species, so that animal studies are likely to be useful in understanding the consequences of human exposure. The similarity of secondary metabolite creation among non-human species is less well known. There are a number of animal studies that have been conducted over the past several decades looking at potential health effects associated with exposure to DEHP. The primary studies have involved rodents (rats and mice) while more recently studies have been conducted on primates (such as marmosets and cynomolgus monkeys) and pigs. Studies of rats represent the most prevalent source of information on potential health effects associated with varying doses and exposure routes. Studies of primates focused on common marmosets (Kurata et al. 1998) and cynomolgus monkeys (Pugh et al. 2000).

Cancer Risk

DEHP is currently classified by the USEPA as a Class B2 carcinogen. This determination is based entirely on liver cancer in rats and mice. In 2000 IARC changed its classification for DEHP from "possibly carcinogenic to humans" to a Class 3 carcinogen "cannot be classified as to its carcinogenicity to humans," because of the differences in how the livers of humans and primates respond to DEHP as compared with the livers of rats and mice (ATSDR 2002).

Reproductive/Developmental Effects

No studies are currently available that directly indicate reproductive effects in humans after oral exposures of humans to DEHP, but many animal studies of this potential have been conducted. Studies in rodents exposed to doses in excess of 100 mg/kg/day DEHP clearly indicate that the testes are a primary target organ, resulting in decreased testicular weights and tubular atrophy. Weights of the seminal vesicles, epididymis, and prostate gland in rats and mice are also reduced by oral exposure to DEHP (Gray and Butterworth1980; Lamb et al. 1987). Studies suggest that nonhuman primates are less sensitive than rodents to the effects of DEHP on the degree and permanence of testicular damage (Kurata et al. 1998). Evidence suggests that MEHP might be the toxic metabolite in the testes. A review of various studies indicates that MEHP generally produces developmental, reproductive and hepatic toxicity in laboratory animals (ATSDR 2002). In one study, 1,055 mg/kg/day of DEHP administered for 5 days to rats did not affect testicular weight or structure, but an equimolar dose of MEHP had a significant effect (Sjoberg et al. 1986).

Based on current studies, and in accordance with the conclusions drawn by the NTP (ATSDR 2002), the developing organism is more sensitive to exposure to DEHP than the juvenile or adult organism. The age at first exposure to DEHP appears to have a clear influence on the degree and permanence of testicular damage (Gray and Butterworth 1980). Based on the multiple studies evaluated by the CERHR panel as part of its review of the reproductive toxicity of DEHP, they have determined that exposure of neonates to DEHP is a “serious concern” (National Toxicology Program Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) 2005). While there was insufficient human data to directly demonstrate reproductive effects in human, the Panel concluded that animal data suggest there is sufficient evidence that DEHP causes reproductive toxicity in female rats (decreased numbers of corpora lutea and growing follicles), in female marmosets (increased ovary weight and uterine weight) and in male rats for exposures that included gestational and/or peripubertal periods (NTP-CERHR 2005). The recent update of the NTP study of the toxicological effects of DEHP indicates that DEHP is considered to be of serious concern when critically ill infants are exposed to products containing this chemical (NTP-CERHR 2005). In particular, the NTP Panel has serious concern that intensively medically treated male infants may experience adverse affects on their reproductive tract development and function. As a result of its review of associated studies, the NTP has determined a LOAEL for exposure to DEHP of 38 – 144 mg/kg bw/day and a NOAEL for males of 3.7 mg/kg bw/day (NTP 2005).

Exposure Routes

The ATSDR has determined that because DEHP’s effects are exerted in animals in a dose-related manner and exhibit threshold responses, and because concentrations of DEHP in the environment are expected to be well below the established effect thresholds, DEHP is not expected to pose a serious public health concern for the vast majority of the population (ATSDR 2002). It is important to note that this opinion was offered prior to the availability of pertinent studies of the potential for exposure to DEHP in dust found in indoor environments. Specifically, studies have identified a somewhat elevated presence of DEHP in household dusts in homes with DEHP/PVC surfaces such as flooring and wall coverings (Børnehag et al. 2005). While this and related studies are preliminary and do not clearly indicate associated health effects, they do suggest that the general public may be exposed to DEHP in indoor environments.Because DEHP has a very low vapor pressure, little is found in air. DEHP molecules that are present in air will adsorb onto dust particles and will be deposited on surfaces through gravity, rain or snow. Indoor releases of DEHP to the air from plastic materials, coatings, and flooring in home and work environments, although small, can lead to higher indoor levels than are found in the outdoor air (Børnehag et al. 2005).

In its evaluation of the potential for reproductive toxic effects, the CERHR determined that there is some cause for concern relative to exposure of DEHP by the general population of infants and toddlers, and serious concern for neonates undergoing intensive medical treatment (NTP-CERHR 2005). The variation in level of concern is most closely related to the potential for exposure of subpopulations to have different weight-related doses due to body size and duration of exposure.

One of the primary routes of exposure to the general population is associated with the use of DEHP in flexible PVC medical devices. Parenteral16 medical exposure to DEHP of critically ill infants has been shown to exceed general population exposures by several orders of magnitude. Numerous studies have been conducted to determine or estimate the exposure level of neonates and infants to DEHP due to various medical procedures. Figure 7.1B presents a compilation of human exposure data associated with a variety of common medical procedures, as presented in the report entitled “Preventing Harm from Phthalates, Avoiding PVC in Hospitals” (Ruzickova et al. 2004). In it, the mean and range of exposure levels of DEHP measured in various studies are summarized based on specific medical procedures. Based on these data, one of the primary potential sources of exposure on a body weight basis is extracorporeal membrane oxygenation17 (ECMO) in infants.

Figure 7.1 B: Compilation of Various Peer-Reviewed Scientific Data Sources from the report “Preventing Harm from Phthalates, Avoiding PVC in Hospitals” June 2004 (Ruzickova et al. 2004)

In its 2002 report entitled “EAP on DEHP in Medical Devices MDB Report: An Exposure and Toxicity Assessment” (Health Canada 2002), the Medical Devices Bureau of Health Canada concluded that exposures of infants to DEHP occur as follows:

  1. Infants undergoing routine replacement blood transfusions may be exposed to doses of DEHP 1-2 orders of magnitude above general population exposures. Infants undergoing intensive therapies may be exposed to levels up to 3 orders of magnitude above general exposures.
  2. Infants receiving double volume exchange transfusion, which is the short-term procedure reported to give the highest acute exposure – up to 23 mg/kg body weight/day.
  3. ECMO for infants, which is the sub-acute medical treatment that results in one of the highest daily DEHP exposures per kg body weight and the highest daily exposure over a prolonged period of time – up to 14 mg/kg/day during the 3 to 30-day treatment period.

Other medical procedures that result in very high exposures relative to the general population exposure include cardiac bypass procedures, total parenteral nutrition therapy, infusion of lipophilic drugs using PVC bags and tubing (which is contraindicated in the directions for use), and possibly, respiratory therapy.

Environmental Hazards

DEHP is not chemically bound to the PVC polymer matrix and can therefore be released throughout the lifecycle of polymer products. Release of DEHP to the environment potentially occurs not only during the production, distribution and incorporation into PVC but also when the PVC material is heated or comes into contact with certain media. Consequently, DEHP may be lost from the finished products during their use or disposal. In general this is a relatively slow process as indicated by common flexible PVC products’ (e.g., vinyl flooring) ability to maintain flexibility.

The half-lives of DEHP and of phthalates in general in the environment are relatively short. Phthalates typically spend hours in the atmosphere and months in soil. However, phthalates adsorbed to soil and sediments can persist in the environment for years. Although DEHP has a low bioconcentration factor, it will preferentially bioconcentrate in aquatic organisms rather than remain in water due to its low water solubility. However, DEHP does not significantly bioaccumulate in the food chain, nor is it expected to bioconcentrate in terrestrial organisms. DEHP has a strong tendency to adsorb to soil and sediments. Experimental evidence demonstrates strong partitioning to clays and sediments (USEPA 2005). DEHP released to water systems will biodegrade fairly rapidly, exhibiting a half-life of 2 to 3 weeks. DEHP enters the environment through releases from manufacturing facilities that make or use DEHP and from consumer products that contain it. Over long periods of time, it can also migrate out of plastic materials and into the environment. Therefore, DEHP is widespread in the environment; about 291,000 pounds were released in 1997 from industries (USEPA 2005).

According to EPA, it is often found near industrial settings, landfills, and waste disposal sites. Based on the TRI report, a large amount of plastic containing DEHP is buried at landfill sites (USEPA 2005). When DEHP is released to soil, it usually attaches strongly to the soil and does not move very far away from where it was released. DEHP has also been found in groundwater near waste disposal facilities (USEPA 2005). When DEHP is released to water, it dissolves very slowly into underground water or surface waters that contact it.

DEHP can break down in the presence of other chemicals to produce MEHP and 2-ethylhexanol. Many of the properties of MEHP are like those of DEHP, and therefore its fate in the environment is similar. In the presence of oxygen, DEHP in water and soil can be broken down by microorganisms to carbon dioxide and other simple chemicals. DEHP does not break down very easily when deep in the soil or at the bottom of lakes or rivers where there is little oxygen.

7.1.3 Use and Functionality

As a plasticizer, the primary function of DEHP used in products is to soften otherwise rigid plastics and polymers, such as PVC. Most industry analysts agree that an estimated 90% of DEHP is used as a plasticizer for PVC. DEHP exhibits good gelation, plasticizing efficiency and adequate viscosity properties in PVC emulsions making it ideal for most plasticized PVC applications (Ecobilan 2001). As a result of DEHP’s plasticizing performance as well as its reasonable cost, DEHP is found in a wide variety of products in every day use. DEHP not only softens the PVC but enhances the colorfast, durable, low-maintenance qualities that make PVC desirable and useful in building materials, autos, toys, and medical devices. Table 7.1B presents a summary of information on the various uses of DEHP. Information about amounts used in products in the EU (and assumed to apply to the US) or manufactured in Massachusetts is provided when available.

Table 7.1 B: Survey of Uses of DEHP

7.2 DEHP Use Prioritization

Chemical Uses

The uses of DEHP in Massachusetts manufacturing are presented based on the 2003 TURA data (Toxics Use Reduction Institute (TURI) 2003). Over 3.5 million pounds of DEHP were used in Massachusetts in 2003. Further details are outlined in Table 7.2A below:

Table 7.2 A: Total DEHP Use in Massachusetts in 2003

Thirteen companies reported DEHP use in 2003 (TURI 2003). These include companies manufacturing various flexible PVC products such as flooring, molded products and medical devices, plastic compounders and chemical distributors. The company reporting the highest use of DEHP makes rubber and plastic commercial and industrial flooring products.

Uses in Products

TURI developed a list of products and/or applications where DEHP is used utilizing sources from both the EU and the US. Table 7.1B outlines the major known uses and applications of DEHP in products today. As shown, the primary products using DEHP for its plasticizer functionality include:

  • Adhesives and coatings;
  • Extrudable PVC molds and profiles (e.g., bumpers for marine applications);
  • Food packaging applications;
  • Footwear (in soles and in PVC design appliqués);
  • Medical devices (in a variety of bags and tubing devices);
  • Resilient PVC-based flooring materials;
  • Toys;
  • Vinyl wall coverings (as part of the PVC emulsion used to provide water resistance); and
  • Wire and cable coating and jacketing compounds.

In order to identify the priority uses of DEHP, a more comprehensive list of uses was presented to Massachusetts stakeholders, for their input (see Appendix B for this list of uses associated with DEHP). Stakeholders discussed the routes of DEHP exposure including oral exposure (e.g., mouthing toys, film covering foods), inhalation (e.g., off-gassing), dermal exposure, exposure from DEHP in dust, injection after leaching of DEHP into medical bag devices, etc.

Priority Uses

Table 7.2B summarizes the major uses of DEHP which were discussed with the stakeholders and their general comments.

Table 7.2 B: DEHP Uses and Stakeholder Discussion

The priority uses of DEHP were selected based on predetermined criteria (refer to Appendix A) including:

  • Quantity of DEHP in products and manufacturing in Massachusetts;
  • Potential environmental and occupational exposure; and
  • Availability of viable alternatives.

According to the criteria, the major DEHP uses that warranted further research in our alternatives assessment included:

Table 7.2 C: DEHP Preliminary List of Priority Uses

The Institute originally identified footwear as a priority industry for analyzing alternatives to DEHP. However, after further investigating DEHP use among Massachusetts footwear manufacturers, the Institute did not find any firms using DEHP in footwear. The one Massachusetts firm that manufactures footwear in the Commonwealth, New Balance, was contacted to discuss its use of DEHP. According to New Balance representatives, they phased DEHP out of their products several years ago. Several other footwear companies, including Timberland, Nike, and Adidas, have eliminated DEHP from products. Although there is likely some footwear imported into the Commonwealth containing DEHP, the Institute decided to focus its alternative analysis resources on vinyl wall coverings as the more pertinent consumer product use of DEHP. This list of priority uses does not include two products that are of particular interest to certain stakeholders – toys and wire and cable coating compounds. Toys were not included because further research showed that DEHP has been eliminated from toys manufactured in the US in almost all applications. One of our stakeholders commented, “The global market is moving away from phthalates in toys.” In addition, our conversations with toy manufacturers and their suppliers of plasticizers indicate that the US market has voluntarily moved away from the use of DEHP in response to the 1999 EU temporary ban on phthalates that was made permanent in 2004 (EU Marketing and Use Directive 76/769/EEC as amended) for certain phthalates present at greater than 0.1% for all toys and childcare articles. The Toy Manufactures of America (TMA) have stated that most manufactures of pacifier and toys have discontinued the use of the DEHP and DINP in their products (Hileman 2005).

The TMA set DEHP standards to less than 3% in pacifiers and teethers. This was done as part of an agreement with the U.S. Consumer Product Safety Commission (CSPC) in 1986. The CPSC stated that the projected cancer risk associated with exposure to DEHP has declined greatly after the phase of out of the chemical in pacifiers. However there is currently no federal US regulation restricting the use of DEHP in toys. Stakeholders expressed concern about imported products still containing DEHP. However, overall stakeholders saw little benefit from including this application in the alternatives assessment.

Wire and cable coating compounds were also not included because further research with local companies as well as the stakeholders indicates that DEHP use in wire and cable has already been greatly reduced in Massachusetts. This reduction is largely due to the availability of a number of viable alternatives The alternatives are also being simultaneously assessed by an EPA sponsored Design for the Environment project, which is performing a life cycle assessment of alternative constructions for three wire and cable applications18. Further research on the major DEHP uses was completed, presented and discussed at the third meeting with stakeholders. Additional feedback from the stakeholders was requested in order to identify the applications of DEHP to be examined for alternative applications. The final list of priority uses selected for further study is:

  • Resilient Flooring
  • Medical Devices (including sheet and tubing uses, with a specific focus on the use of these devices in neonatal care)
  • Vinyl Wall Coverings

7.3 DEHP Alternatives Identification and Prioritization

For the priority uses that have been selected, DEHP is used for its functionality as a plasticizer. Therefore, when considering alternatives to DEHP there are two distinct strategies that can be employed:

  1. Substitute an alternative plasticizer; or
  2. Substitute an alternative material or technology that does not require the use of a plasticizer.

These alternatives are referred to herein as plasticizer and material alternatives. Technological alternatives will be addressed on a use-specific basis as appropriate. As described within the methodology for this project (Appendix A), factors leading to determining priority alternatives include:

  • Performance criteria;
  • Availability of alternatives;
  • Manufacturing location;
  • Environmental, health and safety considerations;
  • Cost;
  • Global market effects; and
  • Other issues pertinent to that particular use.

These factors are not necessarily weighted the same for each use. The Institute determined which factors present the most significant role in determining preferred alternative plasticizers and materials. For material alternatives the Institute has also taken into account significant life cycle considerations when determining priority alternatives. Technological alternatives often require a more in depth life cycle assessment to evaluate how the alternative compares to the original technology. Therefore, unless existing life cycle assessments are available for technological alternatives (e.g., painting rather than covering walls with a material), the Institute did not focus its efforts on these alternatives to uses of DEHP.

7.3.1 Alternatives Associated with Resilient Flooring

Available Alternatives

This study focuses on alternatives to DEHP/PVC residential resilient flooring. Resilient flooring is defined as tile and sheet materials which have the ability to return to their original form after compacting (Vinyl by Design (VBD) 2006). When considering alternatives to DEHP in resilient flooring the comparison must include different materials as well as different plasticizers. Based on our evaluation, no specific technological alternatives are associated with this use. Plasticizer alternatives in resilient flooring that were identified from stakeholder conversations, discussions with industry experts and literature research include:

  • DINP (di isononyl phthalate) • DBP (dibutyl phthalate)
  • DIDP (di isodecyl phthalate)
  • DEHT (di(2-ethylhexyl)terephthalate)
  • BBP (butyl benzyl phthalate)
  • DGD (dipropylene glycol dibenzoate)
  • DEGDB (diethylene glycol dibenzoate)
  • DEHA (di(ethylhexyl) adipate)
  • DEHPA (di(2-ethylhexyl) phosphate)
  • DHP (di isohexyl phthalate)
  • BOP (butyl, 2-ethylhexyl phthalate)
  • TCP (tricresyl phosphate)
  • TEGDB (triethylene glycol dibenzoate)
  • ATBC (o-acetyl tributyl citrate)
  • DBS (dibutyl sebacate)
  • DIHP (di (isoheptyl)phthalate)
  • 97A (hexanadedioic acid, di-C7-9- branched and linear alkyl esters)
  • TXIB (butane ester 2,2,4-trimethyl 1,3- pentanediol di isobutyrate

Material alternatives were also considered as replacements for the DEHP/PVC blend used as resilient flooring in residential, industrial and commercial settings. The following list, developed based on literature and market research and discussions with industry experts, presents the material alternatives that were considered at this stage of the process:

  • Bamboo
  • Natural Linoleum
  • Cork
  • Polyolefin
  • Polyethylene/limestone blend
  • Rubber
  • Concrete
  • Terrazo
  • Concrete and recycled glass blend
  • Wood

Alternatives Screened Out for Resilient Flooring

The methodology for screening potential alternatives presented in Section 2 (and is presented in more detail in Appendix A) was applied to the plasticizer alternatives. Table C5 (in Appendix C) presents the information used to determine if any of the plasticizer alternatives had to be screened out based on being carcinogenic, on the list of more hazardous substances or a PBT. It is important to note on Table C5 that in several instances no data were available for one of the criteria for a specific alternative. In this case, the chemical was not eliminated from further study. Based on this analysis, the following chemicals were screened out for further analysis:

  • DIHP (di (isoheptyl) phthalate) - Failed due to sediment persistence and aquatic toxicity
  • 97A (hexanadedioic acid, di-C7-9-branched and linear alkyl esters) – Failed due to sediment persistence and aquatic toxicity
  • TXIB (butane ester 2,2,4-trimethyl 1,3-pentanediol di isobutyrate) – Failed due to sediment persistence and aquatic toxicity (also exhibits high bioaccumulation, though it does not exceed the screening level)

Several material alternatives were eliminated from further evaluation because they did not meet the resiliency criterion (i.e., able to return to their original form after compacting) associated with this specific use category. Those materials include:

  • Concrete
  • Terrazo
  • Concrete and recycled glass blend
  • Wood
  • Bamboo

Materials were not screened out from further evaluation because of other performance, environmental and human health, or economic considerations.

Priority Alternatives for Resilient Flooring

Based on our initial review of available alternatives it was apparent that there were a large number and variety of potential plasticizer alternatives available for resilient flooring. Therefore, in order to arrive at a manageable number of alternatives to assess fully, the Institute conducted a tiered approach to determining the priority alternatives.

Plasticizer Alternatives for Resilient Flooring

As part of the initial screening effort to determine alternatives to eliminate, several plasticizer alternatives were identified as having persistence, bioaccumulative or toxic values that exceeded the screening criteria (indicated as red on Table C5, Appendix C), with one of the other PBT criteria approaching a level of concern (indicated as orange on Table C5, Appendix C). Hence they were not screened out as PBTs, but have been flagged as being of concern because they approach the associated PBT screening levels. These “P, B or T” alternatives include:

  • DHP (di isohexyl phthalate)
  • BOP (butyl, 2-ethylhexyl phthalate)
  • DBP (dibutyl phthalate)
  • BBP (butylbenzyl phthalate)
  • TCP (tricresyl phosphate)
  • DEGDB (diethylene glycol dibenzoate)
  • TEGDB (triethylene glycol dibenzoate)
  • ATBC (o-acetyl tributyl citrate)
  • DBS (dibutyl sebacate)

Because there are numerous plasticizer alternatives available for this use that did not approach levels of concern, none of these alternatives were evaluated further. Institute staff met with a resilient flooring manufacturer in Massachusetts to tour their production facility and discuss the manufacturing process and the use of DEHP in its products. The manufacturer’s representative did indicate that alternative phthalates would potentially be appropriate alternatives to DEHP from a technical standpoint, but added that this would mean certain financial impacts associated with raw material costs and required process modifications. He further indicated that in today’s very competitive market, economic factors become primary operating considerations in this industry sector when choosing materials.

Several parameters were evaluated when determining which alternative plasticizers would be prioritized for further assessment. Specific performance considerations included the substance’s compatibility with PVC. According to industry experts, the volatility of the plasticizer should not be higher than that of DEHP to assure similar processability. Adoption of alternative plasticizers that approach the technical and economic profile of DEHP/PVC would likely be more attractive to industry for adoption.

According to plasticizer and flooring manufacturers, plasticizer cost is the most important consideration when designing and marketing a product. The flooring market is so competitive today that increasing the cost of a product by a few cents could determine whether a product sells. Table 7.3.1 A summarizes the considerations that the Institute used in determining if a plasticizer alternative would be eliminated from further evaluation.

Table 7.3.1 A: Considerations for Resilient Flooring Alternative Plasticizers

Table 7.3.1 B summarizes the cost, performance and environmental prioritization considerations for plasticizers that were factored into determining the alternatives to assess. Particular attention was paid to an alternative’s ability to approach the technical and economic profile of DEHP. Based on the considerations evaluated on Table 7.3.1B, the following alternative plasticizers appear to be suitable for further study for resilient flooring: DEHT, DINP, DGD, and DEHA.

Table 7.3.1 B: Resilient Flooring Plasticizer Prioritization Summary

Alternative Materials for Resilient Flooring

Considerations for alternative resilient flooring materials are outlined in Table 7.3.1 C. Material alternatives that do not satisfy any of these considerations are deemed less feasible as alternatives to DEHP/PVC flooring. As noted, the Institute included maintenance and durability as key considerations for comparing material alternatives to DEHP/PVC in addition to cost and performance considerations.

Table 7.3.1 C: Considerations for Resilient Flooring Material Alternatives

Table 7.3.1 D summarizes the cost, performance and environmental prioritization considerations for materials that were factored into determining the alternatives to assess. Particular attention was paid to an alternative’s ability to approach the technical and economic profile of DEHP/PVC. Based on the information presented in Table 7.3.1D, natural linoleum, cork and polyolefin all came through as priority alternatives for DEHP/PVC. Both the polyethylene/limestone blend and rubber are feasible alternatives to DEHP/PVC flooring based on the majority of the factors considered. However the Institute identified limitations for each of these materials that made them less favorable alternatives compared to the other materials identified and they were therefore not considered further in this study. Specifically, although the polyethylene/limestone blend looked like a very viable alternative to DEHP/PVC from a performance and cost standpoint, it is not manufactured or readily available in the US at this time. The one distributor identified was contacted and is apparently not actively marketing this product. While rubbers have clear applicability in certain industrial and high traffic commercial applications (e.g., in health care settings) at consistent cost and performance to DEHP/PVC, the limited nature of color alternatives makes rubber a less attractive alternative for light commercial (e.g., office) or residential applications. It should be noted however that the range of colors and patterns available in synthetic rubber floorings is increasing.

Table 7.3.1 D: Resilient Flooring Material Prioritization Summary

Alternatives to be Assessed for Resilient Flooring

Table 7.3.1 E presents the list of alternatives that were assessed more fully for resilient flooring uses:

Table 7.3.1 E: Priority Alternatives for Resilient Flooring

7.3.2 Alternatives Associated with Medical Devices for Neonatal Care

Available Alternatives

Information on available alternatives was obtained from technical experts in the manufacturing and health care industries, public health organizations, and academia and from literature searches. Because the focus was on medical devices for neonatal care, stakeholders pointed out the importance of a careful evaluation of alternatives, both to ensure reliable performance, and to minimize the risk to a sensitive population. One Massachusetts stakeholder is currently working on manufacturing non-DEHP devices, and specifically requested that the Institute assess DINCH, which is an alternative plasticizer that has received limited review by other sources. To obtain additional insight into the toxicology of DEHP and some of the alternatives, a meeting was held in Lowell with experts from industry, health care and academia.

There are two distinct categories of medical devices used for infants in neonatal intensive care facilities that were the focus of this study: bag/sheet devices containing plasticizers, and tubing containing plasticizers. As with the resilient flooring use, alternatives that are investigated for these applications include alternative plasticizers and alternative materials. For this use, process changes were not evaluated. Specifically, the option of foregoing medical procedures in order to avoid exposure to medical devices that contain DEHP is not an acceptable alternative.

Much work has been done to evaluate the material properties and processing of alternatives to DEHP plasticizers and PVC (one of the primary materials used) in the healthcare industry. The Danish Environmental Protection Agency has conducted significant research into alternatives for healthcare applications (Danish Environmental Protection Agency (DEPA) 2003), including conducting research to confirm certain technical parameters of a variety of alternative plasticizers in PVC. Health Care Without Harm (HCWH) is a leading advocacy and policy research organization concerned with identifying and promoting the use of safer materials in the healthcare environment. It has reported on alternatives, focusing primarily on alternative materials to PVC, in several reports, including “Neonatal Exposure to DEHP and Opportunities for Prevention” (Rossi 2002). While this report emphasizes alternatives to PVC, it includes detailed research and discussion on the use of DEHP in PVC-based products. Concurrently, many companies that manufacture medical devices have been developing products made from alternative materials. These represent some of the major sources of information the Institute used when identifying and prioritizing alternatives for medical devices used for neonatal applications.

Plasticizer Alternatives

The Danish EPA was interested in evaluating the performance and environmental issues associated with representative plasticizer alternatives. The suite of alternative plasticizers identified as warranting further investigation by this Danish agency includes:

  • DINP
  • DEHA
  • DEHS, di(2-ethylhexyl) sebacate
  • TOTM, triethylhexyl trimellitate
  • ATBC, acetyltributyl citrate
  • Benzoates (potentially DGD)
  • Polymeric adipates
  • Ethylene-acrylate-carbon monoxide terpolymer (Elvaloy®)

The HCWH evaluations were more focused on the use of alternative materials; however, they also assessed the availability, performance and EHS implications of various alternative plasticizers used in the US. Two alternative plasticizers they identified as being used or available in the US that were not identified as warranting further evaluation by the Danish EPA were:

  • DBS (di butyl sebacate)
  • BTHC (butyryl trihexyl citrate)

Finally, one of the study stakeholders, a manufacturer of medical devices in Massachusetts, specifically requested that the Institute include di (isononyl) cyclohexane-1,2-dicarboxylate (DINCH) in its alternatives assessment for medical device applications as it represents an emerging alternative plasticizer that they are considering.

Materials Alternatives

The options available for alternative materials in medical device applications are more limited. Again, the Institute relied on existing and timely research conducted by other organizations, as well as research into alternative materials hospitals and medical device manufacturers are currently using, to determine potentially suitable alternative materials. Five materials were identified:

  • Ethyl Vinyl Aacetate
  • Polyolefins (Polyethylene and Polypropylene)
  • Thermoplastic Polyurethane
  • Glass
  • Silicone

Priority Alternatives for Medical Devices for Neonatal Applications

When determining which plasticizer and material alternatives to prioritize for further study, the Institute relied heavily on existing and timely studies conducted by other organizations (primarily the Danish EPA and HCWH), and the feedback received from our stakeholders.

Plasticizer Alternatives

The Institute was interested in focusing on a representative set of alternatives that approaches the cost and performance characteristics of DEHP while not approaching levels of concern from an EH&S standpoint. Each of the alternatives listed above has been identified by the Danish EPA, HCWH and/or stakeholders because they are feasible alternatives from a performance basis. The Institute focused its research at this stage on EHS and cost considerations, and on choosing representative plasticizers when determining the final list of priority alternative plasticizers to assess for medical devices.

Of the plasticizer alternatives listed above, there is a wide range of plasticizer types represented, including phthalates (DINP), adipates (DEHA and polymeric adipates), sebacates (DEHS and DBS), trimellitates (TOTM), citrates (ATBC and BTHC), benzoates (DGD), a terpolymer (Elvaloy®) and carboxylates (DINCH). A review of PBT data (see Table C5 in Appendix C) indicates that the following plasticizers exhibit chronic aquatic toxicity and sediment persistence levels that approach or exceed levels of concern: ATBC, DGD and DBS. Therefore, these alternatives were not assessed further.

From a cost standpoint, many of the plasticizer alternatives are in a cost range that would likely be acceptable for the medical device industry. However other alternative plasticizers exhibit costs that may not be acceptable in this industry. Alternative plasticizers with higher costs (based on creating a functional plastic with a hardness rating of 70 Shore A19) include:

  • DINCH (cost ~$0.91 /lb – March 2006 industry data)
  • TOTM (cost $1.11 /lb – March 2006 industry data)
  • BTHC (cost ~$1.12 /lb – March 2006 industry data)
  • Elvaloy® (cost ~$4.10 /lb – based on Danish EPA information)
  • DEHS (estimated cost ~$4.50 /lb – based on Danish EPA information)
  • Polymeric adipate (cost ~$6.00 /lb – based on Danish EPA information)

Based on these figures, Elvaloy®, DEHS and polymeric adipate appear to be in a range that is significantly greater than the estimated cost of DEHP (~$0.70/lb) and therefore will not be assessed further.

Material Alternatives

Based on our review of the above-mentioned studies, the Institute determined that all five of the alternative materials to DEHP/PVC (i.e., ethyl vinyl acetate, polyethylene, polyurethane, glass, and silicone) warranted further assessment.

Alternatives to be Assessed for Medical Devices for Neonatal Applications

Table 7.3.2 A summarizes the final list of high priority alternatives for full assessment for medical device applications.

Table 7.3.2 A: Final Alternatives for Medical Device Neonatal Applications

7.3.3 Alternatives Associated with Wall Coverings

This study focuses on alternatives to DEHP/PVC, or vinyl, residential wall covering. When considering alternatives to DEHP in vinyl wall coverings the comparison must include different materials as well as different plasticizers. Process alternatives such as painting or paneling are alternatives that are also available for vinyl wall coverings.

Available Alternatives for Wall Coverings

Plasticizer alternatives for vinyl wall coverings that were identified from stakeholder conversations, discussions with industry experts and literature research include:

  • DINP
  • DIDP
  • TOTM
  • DEHA
  • DEHPA
  • TOP (tri (2-ethylhexyl) phosphate)

Material alternatives for DEHP/PVC blend used in wall coverings, developed based on literature and market research and discussions with industry experts, include:

  • Glass Woven Textiles
  • Wood Fiber/Polyester
  • Polyethylene
  • Cellulose/Polyester
  • Polyester
  • Biofibers
  • Polyolefins
  • Recycled Paper
  • Wool/Ramie

Finally, there are viable process alternatives to vinyl wall coverings, including painted wall surfaces or different wall materials (such as pine paneling). They differ significantly from wall coverings in terms of aesthetics, but can be functionally equivalent. These technological alternatives have many issues associated with them throughout their life cycle. Because a full life cycle assessment is beyond the scope of this study, and because many plasticizer and material alternatives are available for assessment, the Institute is not evaluating technological alternatives in the full assessment. However, it is important to note that painting and other wall materials are indeed viable alternative to the use of vinyl wall coverings.

Alternatives Screened Out

None of the plasticizer or materials alternatives identified above were screened out due to EH&S issues. However, the plasticizers that were screened out as discussed in the resilient flooring section (Section 7.3.1) were also not considered for this application.

Priority Alternatives for Wall Coverings

Based on our initial review of available alternatives it is apparent that there is a large number and variety of potential plasticizer alternatives available for wall coverings. Therefore, in order to arrive at a manageable number of alternatives to assess fully, the Institute conducted a tiered approach to determining the priority alternatives.

Plasticizer Alternatives for Wall Coverings

Several criteria were considered when determining which alternative plasticizers would be prioritized for further assessment. Plasticizers should exhibit equal or improved characteristics from an environmental and human health standpoint than DEHP. Adoption of alternative plasticizers that approach the technical and economic profile of DEHP/PVC will be more attractive to industry for adoption. Substances that are incompatible will not plasticize PVC properly. In addition, the volatility of the plasticizer should not be higher than that of DEHP in order to assure similar processability. According to plasticizer and wall covering manufacturers, plasticizer cost is the most important consideration when designing and marketing a product.

Table 7.3.3 A summarizes the considerations that the Institute used in determining if a plasticizer alternative would be eliminated from further evaluation.

Table 7.3.3 A: Considerations for Wall Covering Plasticizer Alternatives

Table 7.3.3 B: Wall Covering Plasticizer Prioritization Summary

Based on the information presented in Table 7.3.3C, the following plasticizer alternatives were identified to be assessed further: DEHA and DINP.

Alternative Materials for Wall Coverings

For material alternatives the Institute included maintenance/durability considerations as a key consideration for selecting alternatives to DEHP/PVC in addition to cost and performance considerations. Table 7.3.3 C summarizes the undesirable attributes for wall covering material alternatives.

Table 7.3.3 C: Considerations for Wall Covering Material Alternatives

The material alternatives to DEHP/PVC wall coverings are listed in Table 7.3.3 D. The table summarizes reasons why particular materials were eliminated from further study.

Table 7.3.3 D: Wall Covering Material Prioritization

Alternatives to be Assessed for Wall Coverings

Our prioritization evaluation of alternatives resulted in the following list of alternatives that will be assessed more fully (Table 7.3.3 E):

Table 7.3.3 E: Final Alternatives for Wall Coverings

7.4 DEHP Alternatives Assessment

This section reviews the various priority plasticizer and material alternatives to DEHP identified using the criteria and methods described in Section 7.3. The following sections outline the assessment of these potentially viable alternatives. The alternatives assessment for each use is organized by plasticizer and material alternatives, with specific discussions of EH&S, technical and economic factors for each use within that overall heading. However, there are also common issues for plasticizers that apply to all the applications. These issues are discussed in a separate section, below.

Common Issues for DEHP Plasticizer Alternatives

Various plasticizer alternatives were identified through a literature review and discussions with industry manufacturers, processors, and end users. The Institute established desired criteria for cost, performance, environmental health and safety and cost for each alternative plasticizer that were used in assessing the feasible alternatives. Table 7.4 A summarizes these criteria.

Table 7.4 A: DEHP Plasticizer Alternative Assessment Criteria

Technical Issues Associated with Plasticizer Alternatives

As indicated in Table 7.4A, some of the technical issues associated with plasticizer alternatives are common regardless of the application for the plasticizer. Below is a discussion of those common technical issues.

PVC Compatibility

One of the most important factors determining the feasibility of a plasticizer as an alternative to DEHP is its overall compatibility with PVC. Plasticizers are assessed on their PVC compatibility based on their ability to create a stable compound (i.e., create a single phase). An incompatible plasticizer will exude to the surface of the plastic making it more easily extracted by either volatilization into the air, or solubilization into the contact solution. In effect, this will result in a less flexible plastic than originally designed. In addition, the plasticizer needs to be compatible with any other additive that may be compounded into the plastic product. An indication of a poorly compatible plasticizer would be the loss of flexibility and/or a sticky or oily surface of the product. To process well, plasticizers must be absorbed into the PVC resin particles during the blending process (DEPA 2003). Known as processability, PVC resin, plasticizer(s), stabilizers and lubricants should blend together readily in a compounding operation.

Migration or Permanence of Plasticizer

DEHP can migrate out of the PVC matrix because it is not permanently or covalently bound to the plastic molecule, therefore exposure to DEHP from the polymer matrix is a possibility. The mechanisms that control migration from a plastic, excluding the effects of plastic weathering, are surface-controlled losses (such as volatility and aqueous solubility) and diffusivity. Most plasticizers have extremely low water solubility and therefore their losses into aqueous environments are controlled by surface mechanisms rather than by being drawn out of the plastic (diffused). Volatile losses of plasticizer are influenced by vapor pressure, solvency strength for the polymer and oxidative degradation of the plastic. Plasticizers like DEHP are highly lipid soluble and therefore, when in the presence of oily or fatty solutions, their losses from the plastic are controlled by diffusivity.

Financial Factors Associated with Plasticizer Alternatives

Because of extreme price competition in the PVC flooring and wall covering industry, even slightly more expensive plasticizers find difficulty gaining widespread acceptance. Depending on the application, the concentration of plasticizers in the polymer matrix can be up to 40% of the product by weight. In this case, and when dealing with low margin industries, the cost premiums associated with some of the alternatives to DEHP may be unacceptable from an industry standpoint. A mitigating factor here is that the plasticizers typically do not replace each other on a 1:1 basis. Some plasticizers are more efficient, and therefore less is required to achieve the same level of hardness of the plastic product. This “substitution factor” will be presented throughout the discussion to normalize the costs as much as possible. Table 7.4B presents estimates of plasticizer costs based on data obtained from industry sources in March 2006, and includes estimated substitution factors, which allow for a normalized comparison of costs based on how they are used to create a comparably flexible product (70 Shore A). For instance, DINP, with a substitution factor of 1.06, requires more plasticizer and DEHA with a 0.94 substitution factor requires less plasticizer to achieve the same hardness as DEHP.

It is important to note also that some of the plasticizer alternatives are relatively new, and cost may decrease as production increases. This trend, however, is limited by the molecular composition of the plasticizers; compounds with more carbon chains and more complex chemistries will necessarily be more expensive than simpler plasticizer molecules.

Table 7.4 B: Plasticizer Cost Estimates

Environmental and Human Health Issues Associated with Plasticizer Alternatives

As discussed in Section 7.2, the health and environmental impacts associated with the use of DEHP as a plasticizer relate first to potential exposures in manufacturing, and second to potential exposures due to leaching out of the PVC matrix. Other plasticizers may also produce exposure to humans or the environment by leaching out. The environmental and human health impact assessment of the use of alternative plasticizers will begin by examining the inherent hazards of the substances, followed by a review of the likelihood of migration out of a product, and continue with a discussion of the potential impacts associated with a resulting exposure. Specific criteria that will be focused on in our assessment have been identified in Table 7.4A.

7.4.1 Alternatives Assessment for Resilient Flooring

DEHP/PVC or vinyl flooring has been one of the most popular flooring types found from kitchens and bathrooms to hospitals and schools. In general, there are two types of DEHP/PVC flooring: sheet flooring (typically 6' or 12' wide) and tile (typically 12"x12" or 9"x9").

Composition

Vinyl sheet is made with a felt or vinyl backing and can be either rotogravure (printed) or inlaid. In rotogravure vinyl, a printed image is sandwiched between the backing, a mid layer and a top wear layer (see Figure 7.4.1A). Inlaid vinyl uses tiny vinyl granules from the backing all the way to the wear surface making it highly durable but available in fewer patterns and colors. DEHP/PVC flooring can also be finished with a polyurethane layer which increases wear resistance. The backing may be made up of cellulose fibers, glass fiber, styrene butadiene latex, or acrylic latex, along with inorganic fillers such as limestone and talc. The backing adheres to the plastisol PVC layer. Inlaid sheet DEHP/PVC may have a felt backing.

Figure 7.4.1 A: Common Rotogravure DEHP/PVC Sheet Construction

Vinyl composition tile (VCT) construction is very different from vinyl sheet. VCT contains a high proportion of inorganic filler (limestone) to increase its dimensional stability and reduce its elasticity. Vinyl flooring varies widely in grade and quality with thinner grades priced lower. Figure 7.4.1 B shows several DEHP/PVC flooring samples.

Figure 7.4.1 B: Typical DEHP/PVC Tile Samples

Table 7.4.1 A: Common Vinyl Flooring Compositions

Installation/Cleaning/Maintenance

Vinyl floors can be installed over wood, concrete or, in some cases, existing flooring. However, subflooring should be clean, smooth, of high quality and as flat as possible. Professional installation is often recommended to ensure long life. Daily sweeping or dust-mopping is recommended to remove grit and dirt. Floors should be damp-mopped with a neutral detergent. Spills should be wiped up before they dry with a damp, clean white cloth. Many manufacturers recommend stripping and refinishing vinyl floors on a routine basis.

Resilient Flooring Financial Considerations

Typically, commercial vinyl composition floor tile has an installed cost of between $1.40 to $8.70 per square foot, depending on the thickness and pattern (this includes materials, equipment and labor). Commercial sheet vinyl has an approximate installed cost of $2.64 to $5.50 per square foot (VBD 2006). Higher quality vinyl flooring is thicker and is expected to last nominally from 25 to 30 years with proper cleaning and maintenance.

Environmental and Human Health Issues

The principal environmental and human health issues associated with DEHP/PVC flooring are outlined in Table 7.4.1 B. The PVC supply chain, including intermediates manufacturing and the various processing steps from crude oil and rock salt extraction through vinyl chloride monomer production, plays a major role in PVC impacts. Other impacts include energy use impacts from manufacturing and transport and a lack of end-of-life recycling and recovery options.

Table 7.4.1 B: General DEHP/PVC Alternative Material Assessment Criteria

Even though there is a great deal of information in the literature concerning life cycle impacts of using DEHP/PVC blends, there is no scientific consensus. This assessment attempts to lay out the key potential issues, allowing readers to draw their own conclusions.

Specific Plasticizer Alternatives Assessed for Resilient Flooring

While DEHP is not the only plasticizer used in resilient flooring applications, it is the most commonly used plasticizer. Plasticizer alternatives that were prioritized for resilient flooring include DEHT, DINP, DGD and DEHA. These plasticizers represent a terephthalate, a phthalate, a dibenzoate and an adipate, as discussed in more detail below.

Di 2-Ethylhexyl Terephthalate (DEHT)

DEHT (di(2-ethylhexyl) terephthalate) is called a “phthalate like” plasticizer whose specific chemical structure is shown in Figure 7.4.1 C. DEHT has an isomeric structure of DEHP, which means that it has the same elements but has a different arrangement of the atoms. Although DEHT and DEHP are structurally similar, giving them almost identical physical-chemical properties, they have distinctly different toxicological properties. The performance of DEHT is similar to DEHP and its low cost often makes it a good alternative plasticizer. It is made by Eastman Chemical and known as Eastman 168 Plasticizer.

Figure 7.4.1 C: Chemical Structure of DEHT

Rubber mat manufacturers have tried substituting DEHT and found that it does not work. There were issues because DEHT does not ‘take up’ fast enough and slows the process down (Biltrite 2005). DEHT used in rubber or PVC applications can, if not formulated properly, exude to the surface under warm and humid conditions when used in tightly coiled (Teknor Apex 2006). In addition, DEHT is slightly more volatile than DEHP, indicating that more may be required to make up for fugitive emissions during processing.

There are no workplace air exposure standards for DEHT. In a study conducted in 2002, the NOAEL for reproductive toxicity associated with exposure of rats to DEHT was considered to be 10,000 mg/kg bw/day. The NOAELs for parental toxicity and neonatal toxicity were considered to be 3,000 mg/kg bw/day (Faber et al. 2002). The persistence of DEHT in sediments and air is estimated as 140 days using the PBT Profiler methodology. Based on these few sources of information on impacts to human and environmental health due to exposure to DEHT, it appears that DEHT is of low concern.

Diisononyl Phthalate (DINP)

DINP is a mixture of phthalates with branched alkyl chains of varying length (C8, C9 and C10). The chemical structure of DINP is depicted in Figure 7.4.1 D. The plasticizing efficiency of DINP is somewhat lower than DEHP and therefore more plasticizer is required to gain the same softness. Because the molecular weight of DINP (418) is greater than DEHP (390), DINP has better high temperature performance and extraction resistance. Because DINP is less volatile than DEHP, processing with DINP leads to lower plasticizer losses during compounding and calendaring, reducing emissions and occupational exposure. According to one industry source, when compared with DEHP, DINP processing emits noticeably lower levels of plasticizer mist from process equipment.

Figure 7.4.1 D: Chemical Structure of DINP

DINP is a “drop in replacement” for DEHP. Because DINP has a lower volatility (5.4 x 10-7 mm Hg) than DEHP (1.4 x 10-6 mm Hg) the emissions from the operation using DINP may be lower. In one Massachusetts factory, line workers observed a clearer room (less haze) when running with DINP compared with DEHP (Biltrite 2005). DINP’s processability is similar to DEHP’s. Exposure to DINP during processing or use of resilient flooring is expected to be minimal due to the lower emissions relative to DEHP. During use there is little likelihood of DINP migrating out of the polymer matrix and causing exposure. In the event that humans do become exposed to DINP from this use however, there may be associated health effects. Workplace air exposure standards have not been established for DINP, which although considered an animal carcinogen, has not been completely classified as to human carcinogenicity (CDC 2005).

According to the Chronic Health Advisory Panel, exposure to DINP results in potential acute toxic effects (Chronic Hazard Advisory Panel (CHAP) 2001). The NOAEL for systemic toxic effects induced in laboratory animals by exposure to DINP is estimated between 15 mg /kg bw/d and 88 mg/kg bw/d. To put this into context, a study by the Consumer Council Austrian Standards Institute (Fiala n.d.) used the lowest NOAELs for DINP and DEHP to determine a total daily intake level for these plasticizers (this study focused on the use of DINP and DEHP in children’s toys that would be mouthed, using a risk factor of 100) of 150 μg/kg bodyweight /day for DINP and 37 μg/kg bodyweight /day for DEHP. Based on this study, DINP is less toxic than DEHP. According to its review of relevant studies, the CHAP concludes that DINP is clearly carcinogenic to rodents, inducing hepatocellular carcinoma in rats and mice of both sexes, renal tubular carcinoma in male rats, and mononuclear cell leukemia in male and female rats. The studies they reviewed also suggest possible carcinogenicity in the testis, uterus, and pancreas in rodents (CHAP 2001). DINP has not been categorized by EPA or IARC as to its carcinogenicity.

Dipropylene Glycol Dibenzoate (DGD)

DGD is a benzoate plasticizer with great affinity for PVC; as a result, vinyls containing DGD show good resistance to solvent extraction and perform well in volatility tests. Figure 7.4.1 E illustrates its chemical structure. The volatility of DGD is only slightly higher than DEHP, indicating relatively similar plasticizer losses and emissions during processing. The compatibility with PVC is reported as good due to a vapor pressure that is similar to that of DEHP. Velsicol Chemical Corporation makes and markets this plasticizer under the name Benzoflex® 9-88.

Figure 7.4.1 E: Chemical Structure of DGD

Benzoate alternative plasticizers have been known for years as effective PVC plasticizers. Although they represent effective plasticizer substitutes, benzoates, and specifically DGD, have not been widely used. Serious consideration has been revived due to the search for substitutes caused by the ongoing phthalate controversies.

DGD is estimated as persistent in sediments for 140 days, and produces a chronic aquatic toxicity at 0.55 mg/L. While neither of these levels exceed methodology thresholds, they do suggest that precaution should be used when using DGD. The primary routes of exposure potentially associated with DGD are inhalation and dermal. According to the MSDS for this product, there is virtually no human toxicity anticipated based on rodent studies (Velsicol Chemical Corporation 2002). They estimate an oral LD50 of greater than 5000 mg/kg. However, this product does have a Risk Phrase of R-51/53 associated with it, indicating that it may cause long term toxic effects in the aquatic environment24. The MSDS also indicates that there may be irritation associated with inhalation, ocular and dermal contact to DGD. DGD is not a listed carcinogen, nor is there a specific water quality criterion established for this chemical.

Di (2-Ethylhexyl) Adipate (DEHA)

DEHA is an adipate plasticizer whose specific chemical structure is shown in Figure 7.4.1 F. Adipates are classified as low temperature plasticizers and are all relatively sensitive to water (DEPA 2001). Its low temperature properties make DEHA a potentially favorable plasticizer for materials used to store cold solutions (e.g., blood). DEHA is less compatible with PVC than DEHP, which can lead to exudation (i.e., plasticizer migrating to the surface). DEHA is known to be slightly more difficult to process compared to DEHP, though it exhibits relatively lower volatility than DEHP.

Figure 7.4.1 F: Chemical Structure of DEHA

The Danish EPA determined that DEHA has the potential to migrate from the PVC matrix into fatty solutions. They conducted a review of toxicological data associated with a number of plasticizers, including DEHA. A NOAEL of 610 mg/kg bodyweight/d has been reported (DEPA 2001), which is orders of magnitude higher (i.e., indicating lower toxicity) than the NOAEL for DEHP. However the Institute did not determine if any studies evaluating the impact of exposure on the male reproductive system have been conducted. The Chronic Health Advisory Panel for the US Consumer Product Safety Commission quotes a study that indicates a fetotoxicity issue associated with oral exposure to DEHA (CHAP 2001).

Summary of Plasticizer Alternatives Assessed for Resilient Flooring

Table 7.4.1 C summarizes the comparative assessment of plasticizer alternatives to DEHP for use in PVC resilient flooring. Refer to Table 7.3.1 B for associated data.

Table 7.4.1 C: Summary of Plasticizer Alternatives Assessment for Resilient Flooring

Material Alternatives for DEHP/PVC Resilient Flooring

Flooring Material Alternative #1: Natural Linoleum

A natural product is a non-petroleum based, biodegradable product. Linoleum products are typically available in sheet and square form. While natural linoleum can be found in hundreds of colors and patterns (see Figure 7.4.1 G), there are currently fewer choices than for DEHP/PVC.

Figure 7.4.1 G: Typical Color Choices for Linoleum

Construction

Natural linoleum is made from linseed oil, wood flour, resin, jute and limestone and calendared onto a natural jute backing. The table below lists materials commonly used in natural linoleum.

Table 7.4.1 D: Composition of Natural Linoleum Flooring25

Installation/Cleaning/Maintenance

Professional installation is recommended since over 95% of reported complaints are due to faulty installation (Forbo Holding 2006). Most manufacturers offer a line of finishing and cleaning products. Manufacturers recommend that natural linoleum flooring be protected with a wax type finish or polish 2-3 days after installation. Everyday cleaning includes keeping floor dirt-free with a dry dust mop and/or dust cloth and spot removal with a neutral cleaner and damp cloth.

Financial

Natural linoleum’s cost depends not only on the product and design, but also on the quantity of product purchased (as volume discounts are often available). Installation costs will vary according to contractor and location. Natural Linoleum flooring is expected to last between 25 and 40 years.

Table 7.4.1 E: Typical Costs Associated with Linoleum Flooring

Environmental and Human Health Issues

The chief environmental impact associated with natural linoleum is eutrophication from the use of nitrogen and phosphate fertilizers used to grow linseed. However the amount of eutrophication depends upon the growing conditions. For example, flax in the US is primarily grown in North Dakota in 3 to 6 year rotations with other crops and requires no added nitrogen. VOCs, generated during the manufacturing process, are another concern with linoleum. While most VOCs are emitted during the manufacturing and drying process, residual VOCs can off gas following installation. Other manufacturing-related pollution includes energy combustion and the associated greenhouse gases, particulate emissions and other air pollutants. Like DEHP/PVC, installation involves the use of water-based styrene butadiene floor adhesives. Linoleum is not recyclable but is compostable, however there is no infrastructure to collect and compost it at the end of life.

Table 7.4.1 F: Environment and Human Health Issues Associated with Natural Linoleum

Environment, Health, and Safety Comparison of DEHP/PVC and Linoleum

There are numerous fact sheets and studies comparing linoleum and DEHP/PVC flooring. Studies and reports that use a hazards based analysis rank linoleum as safer than both VCT and vinyl sheet, citing the hazards of PVC precursor chemistry, plasticizers, and dioxin formation in manufacture and end-of-life combustion under suboptimal conditions. Studies based on life cycle generally conclude that linoleum has comparable or slightly fewer environmental impacts when compared with PVC sheet flooring of equivalent quality in the production phase (VBD 2004). Several studies point to the importance of detergent or chemical use in cleaning and maintenance, since across the useful life of the product the use of the associated maintenance chemicals/materials can lead to significant impacts (VBD 2004). One study that focuses solely on the use phase suggests that in PVC might have advantages over linoleum in this phase. This result is dependent on the frequency of cleaning, and type of cleaning (wax or polish) process used (Paulsen 2003). However this study did not examine indoor air quality issues. Regardless of the floor type (e.g., DEHP/PVC or linoleum), wax-based systems are preferable to polish systems in many applications (Paulsen 2003).

Higher quality products that require less use phase maintenance can significantly lower life cycle impacts (VBD 2004). The forthcoming US Green Building Council combined life-cycle risk assessment of VCT, vinyl sheet, linoleum and cork should provide additional insight into the tradeoffs between these materials.

Table 7.4.1 G: Summary of Comparison between DEHP/PVC and Linoleum

Flooring Material Alternative #2 - Natural Cork

Cork oak trees grow in forests in Portugal, Algeria, Spain, Morocco, France, Italy and Tunisia (Jones 1999). Bark is first stripped when trees are roughly 25 years old and approximately every nine years thereafter. No more than 50% of the bark is removed, and most cork oak trees survive many generations. After being removed from the tree, workers cut large slabs into strips that are stored in the forest for seven months or more to cure (Expanko 2006).

After harvest, the best cork is punched out to make bottle stoppers. The remaining is ground into granules, combined with binders, and baked in molds. Various temperatures produce different colors of cork and dyes are never used for coloring. To produce floor tiles, the blocks of baked cork are cut into slabs, sanded and varnished. Color variations are achieved by varying baking temperature (Jones 1999). Table 7.4.1 H lists the main constituents in cork flooring and their origins or component materials.

Table 7.4.1 H: Composition of Cork Flooring

Installation/Cleaning/Maintenance

Any experienced hardwood and /or ceramic tile flooring installer can install cork (Expanko 2006). Regular cleaning includes vacuuming and light cleaning with a damp sponge mop. Ammonia-based cleaners or chemicals must not be used to clean cork floors. For routine care, sweep or vacuum to remove lose dirt before it can scratch or be ground into the floor’s surface.

Financial

Cork’s cost depends not only on the product and design, but also on the quantity of product purchased (as volume discounts are often available). Installation costs will vary according to contractor and location. Current cost estimates for cork flooring are:

  • Cost of material (per square foot): $4 - $6
  • Installation (per square foot): $ 6
  • Overall cost (per square foot): $10 - $12
  • Cork flooring is expected to last up to 80 years, which should factor into its overall cost when compared to other materials.

Environmental and Human Health Issues

There are relatively few environmental impacts associated with the growing and harvesting of cork. No fertilizers or pesticides are used to promote tree growth or kill pests. Cork forests are managed carefully in many countries (Jones 1999). The main issue associated with cork flooring manufacturing is the binders use to hold together the cork granules. Binder types include ureamelamine, phenol-formaldehyde (see Chapter 4 for discussion of EH&S issues associated with formaldehyde binders), or polyurethane.

During the installation phase, indoor air quality problems can exist with the adhesives, finishes, or sealers used. Both water-based and polyurethane-based adhesives are used. Cork is also finished similarly to wood, using wax or polyurethane. Off-gassing will depend on the type of finish applied. Pre-finished cork tiles are on the market, eliminating the need for on-site finishing, but this results in a lack of sealing around the individual tile joints (Jones 1999). Unlike with other floorings, cork can be installed as a floating floor, with no adhesive use required.

Table 7.4.1 I: Environment and Human Health Issues Associated with Cork

Environment, Health, and Safety Comparison of DEHP/PVC and Cork

There are numerous fact sheets and studies comparing cork and DEHP/PVC flooring. Studies and reports that use a hazards based analysis rank cork as safer than both VCT and vinyl sheet, citing the hazards of PVC precursor chemistry, plasticizers, and dioxin formation in manufacture and end-oflife combustion under sub-optimal conditions.

A combined life-cycle risk assessment of VCT, vinyl sheet, linoleum and cork has been conducted by Georgia Technical Research Insitute (Jones 1999) using the EPA BEES (Building for Environmental and Economic Sustainability) software. It is an extensive assessment that can be viewed at the Georgia Tech website26. In general, it indicates that cork has a better life cycle profile than the vinyl flooring alternatives. Another study compared cork flooring to cork finished with a PVC top laminate to protect the cork surface. This study found that cork flooring with a PVC top laminate had significantly higher ecological impacts than cork without the laminate, even if cork polyurethane refurbishing interval was assumed to be every 2 years (Althaus and Richter 2001).

Table 7.4.1 J: Summary of Comparison between DEHP/PVC and Cork

Flooring Alternative #3 – Polyolefin Flooring

A combination of synthetic copolymer resins and limestone, this material is manufactured by Amtico Company, based in Coventry, United Kingdom, under the name Stratica. This flooring material was specifically designed for large, high-traffic commercial areas and is used in health care facilities, ships, shopping centers, and airports. According to the Stratica website27, the product offers the convenience and durability of DEHP/PVC flooring and is easy to install.

Construction

Polyolefin flooring consists of two layers of polymers. The bottom layer is made from ethylene copolymers and includes chalk and clay as filler materials. The top layer consists of an ionomer coating called Surlyn™, created from ethylene/methacrylic acid copolymers.

Table 7.4.1 K: Composition of Polyolefin Flooring

Installation/Cleaning/Maintenance

Polyolefin flooring is installed using VOC-free adhesives. Cleaning and maintenance are simple. Flooring can be swept or vacuumed and mopped with water when necessary. Amtico says the flooring is scuff-resistant and that in abrasion tests, it performed 10 times better than linoleum, and twice as well as quality vinyl tiles and laminates (Fisher 1999).

Financial

Polyolefin flooring comes in a variety of patterns that mimic natural flooring, including solids, marbles, granites, stones, terrazzos, and woods. Polyolefin flooring is priced slightly higher than high-end vinyl flooring. The manufacturer claims that the cost savings in installation and maintenance over the long term result in significant overall cost saving. Purchase and installation costs are estimated to be $5 to $6 per square foot. The lifespan of polyolefin flooring is anticipated to be higher than DEHP/PVC flooring, though less than that of cork (Lent 2006).

Environmental and Human Health Issues

The chief environment and human health issues associated with polyolefin center around the extraction and processing steps. Impacts include extraction and refining of ethylene and mineral feedstocks and the greenhouse gas and other air pollutants associated with these activities. One of the chief benefits of polyolefin flooring is during the use phase due to its durability and ease of maintenance. Polyolefin flooring can be cleaned with a mild detergent. No polishing or waxing or other finishing (unlike DEHP/PVC tile and sheet, linoleum or cork) is required. In addition, unlike DEHP/PVC tile and sheet and linoleum, polyolefin flooring has very low VOC emissions associated with it once installed.

Table 7.4.1 L: Environment and Human Health Issues Associated with Polyolefin Flooring

Environment, Health, and Safety Comparison of DEHP/PVC and Polyolefin Flooring There are several green building websites and fact sheets comparing polyolefin and DEHP/PVC flooring. Studies and reports that use a hazards-based analysis rank polyolefin preferably to VCT and vinyl sheet, citing the hazards of PVC precursor chemistry, plasticizers, and dioxin formation in manufacture and end-of-life combustion under sub-optimal conditions. According to Environmental Building News, the German Frauenhoffer Institute prepared a LCA comparing polyolefin and vinyl flooring. It appears that this is the only LCA study on polyolefin flooring that has been conducted to date. The study found that the production of polyolefin flooring requires 30% less energy and 29% less water than the production of vinyl, resulting in 33% less contribution to global warming and 54% less acidification (Healthy Building Network (HBN) 2005). The Institute was unable to independently review the Frauenhoffer study to examine boundary conditions and other important study assumptions.

Summary of Material Alternatives Assess for Resilient Flooring

Table 7.4.1 M summarizes the Institute’s assessment of material alternatives to DEHP/PVC resilient flooring:

Table 7.4.1 M: Materials Alternatives Assessment Summary for Resilient Flooring

7.4.2 Alternatives Assessment for Medical Devices for Neonatal Care:

Sheet and Tubing Applications

PVC is widely used as a plastic in medical sheet and tubing type devices. Studies suggest that as much as 25% of all plastics used in hospital environments are PVC. Regardless of the material or plasticizer used in a medical device, however, there are certain characteristics that are desirable for these applications.

Figure 7.4.2 A, created by BASF28 illustrates a common use of both sheet and tubing in medical applications, in this case enteral feeding.

Figure 7.4.2 A: Example of medical sheet and tubing application

Technical Considerations for Medical Devices in General

Medical devices used in neonatal procedures include bags used to store a variety of medical solutions, and tubing used to transfer those solutions to the neonate. An interesting issue associated with DEHP as the plasticizer is that it apparently functions as an inadvertent preservative for blood platelet storage. It is now well established that red blood cells can be stored for up to 72 hours in DEHP plasticized blood bags. The required shelf life of red blood cells in storage is a 75% survival for 24 hours after infusion on the last day of storage. DEHP improves red blood cell storage by reducing haemolysis and membrane loss (Hill et al. 2001). The result is that red blood cells stored in PVC bags plasticized with DEHP have a shelf-life of up to 42 days (American Association of Blood Banks (AABB) 2006). Baxter, the leading manufacturer of blood bags in the United States, introduced a non-DEHP PVC red blood cell bag in 1991 (Plastics Week 1992). That bag, plasticized with butyryl-trihexyl citrate (BTHC) performs as well the DEHP bag, with the same shelf life as the DEHP bags (Food and Drug Administration (FDA) 1999).

One study looked at the effect of DEHP plasticizer on stored platelets (Racz and Baroti1995). They found that platelet aggregation was the only parameter that was slightly inhibited in DEHPplasticized bags indicating that the presence of DEHP had no harmful effect during storage especially if bags are manufactured to assure higher gas permeabilities. However, the majority of platelets used in the US today are stored in non-DEHP bags. For platelets, a 40% recovery after 72 hours of storage is generally considered acceptable (FDA 1999).

In vitro studies showed that DEHP reduced platelet functions such as aggregation responses and the percentage of hypotonic shock responses. It also prevented morphological changes in platelets which are frequently seen in TOTM and BTHC plasticized PVC bags (Racz and Baroti 1995). These changes have been explained on the basis of the migration of DEHP into the plasma stabilizing platelet membrane and thereby preventing changes. This apparent preservative function seems to only be a factor in the storage of blood platelets, and therefore will not be described in more detail here.

Characteristics that are important to consider for medical device applications include aesthetic properties and physical properties. Desirable aesthetic properties of materials used in medical devices include color, clarity and odor. When choosing a material for medical devices it is important to also consider tensile strength, cold flexibility and elastic recovery. In addition, the choice of material or plasticizer must consider post manufacture technical issues, primarily its ability to withstand harsh sterilization procedures.

Aesthetic Properties of Medical Devices

Color is considered important in that it conveys "purity of product" to the user. Plasticizers are therefore more desirable if they result in colorless compounds and articles. PVC additives that produce materials that are semi-opaque or yellow in appearance may be perceived by medical staff and hospitals to be imperfect or contaminated.

In general, medical device manufacturers and users prefer that the devices be colorless and clear or transparent. Transparency allows for the end user to see the contents of any article or device made from the material, which is not only important from a perception standpoint, but also from a safety standpoint, so that medical staff can visually confirm that they have the solution they intend to be using, that the amount they need is present, and that there are no obstructions or contaminants present. For the purposes of this assessment the Institute focused its assessment of aesthetic properties purely on color and clarity.

Physical Properties of Medical Devices

For medical device manufacturing, the design of the device must consider physical properties that influence processing and use. Medical device materials need to have sufficient tensile strength to ensure that the article remains durable and intact throughout its intended service life. Issues can arise around potential mishandling or inappropriate storage of the device. Therefore the tensile strength of the material used should be sufficient to allow the medical device to be maintained throughout the intended service life of the product.

The material needs to retain its flexibility at low temperatures, as products are likely to be used or stored in low temperature environments. In particular, blood storage must be maintained at temperatures ranging from 2°C (for whole blood and red blood cells) to 20°C (for platelets) when not in use. The cold flexibility of the material needs to be maintained throughout the service life of the product to avoid breakage due to embrittled materials. The rate or degree at which a material returns to its original shape after being deflected – its elastic recovery – is another important physical property of a medical device for many applications, though especially in flexible PVC tubing (e.g., for use in peristaltic pumping applications). The possibility of a kink developing in a tubing device could result in inefficient delivery of the intended medical solution thereby potentially endangering the health of the patient.

One of the primary considerations of choice of plasticizer or material for medical devices relates to its ability to be sterilized as a whole unit. Sterilization of medical devices must reach 121°C to meet FDA criteria (for IV solutions), and is done through three basic mechanisms: gamma radiation, ethylene oxide and steam (autoclaving). Another sterilization process used by some healthcare facilities is electron beam sterilization, however this is much less widely practiced. Specific considerations associated with sterilization using the three primary mechanisms are summarized in Table 7.4.2 A.

Table 7.4.2 A: Medical Device Sterilization Requirements

Designing a medical device to withstand the sterilizing conditions it will likely be subjected to is essential. When evaluating plasticizers for PVC, it is also important to consider the potential of the plasticizer to migrate out of the PVC matrix and interact with the substance (e.g., drug, blood, solution) that it will come into contact with. As mentioned previously, DEHP does interact with blood platelets, resulting in a preservative effect. The United States Pharmacopoeia (USP) has created standards that devices must adhere to in order to minimize the potential for undesirable migration into the medical solution. Plasticized materials must meet USP29 Class VI standards30. The goal is to avoid any adverse impact on drug efficiency, and to minimize the potential for the plasticizer to migrate into the substance, thereby entering the body during use. Because of this issue, DEHP/PVC is generally not recommended for packaging certain medications with high lipid content (e.g., Taxol).

Financial Considerations for Medical Devices in General

Several companies market DEHP-free products in the US. In general, the cost of the non-DEHP devices is greater than that of DEHP-containing devices. The status of relative costs may change as the demand for DEHP-free products increases. In addition, some of the alternative materials to DEHP/PVC may have longer shelf lives or allow for multiple usage that would result in an overall cost savings over time. When evaluating alternative plasticizers or materials it is valuable to consider both the raw material costs, the cost savings from increased shelf life and multiple usage, as well as the impact on usage costs such as modified sterilization requirements. Because most of this information is proprietary, anecdotal or situation-specific, this assessment does not address economic considerations in detail.

Environmental and Human Health Considerations for Medical Devices in General

The primary concerns associated with the use of DEHP in medical devices for neonatal care is its ability to migrate out of the polymer matrix resulting in a direct exposure to a very vulnerable population. Once exposed to DEHP, the human body metabolizes it into chemicals that, along with DEHP, exhibit potential reproductive toxicity, particularly in males. In fact, in its 2002 Public Health Notification the Food and Drug Administration recommended that health providers consider using alternatives to DEHP-containing medical devices when high-risk procedures are to be performed on male neonates, pregnant women who are carrying male fetuses, and peripubertal males (FDA 2002).

When assessing alternative plasticizers, the ability of the plasticizer to migrate, or exude, out of the polymer matrix is particularly pertinent, as is assessing the potential additional effect of metabolites on the neonate.

Specific Plasticizer Alternatives Assessed for Medical Devices

Plasticizer alternatives that were prioritized for medical devices include TOTM, DEHA, BTHC, and DINCH. These plasticizers represent a trimellitate, an adipate a citrate and a carboxylate, which are discussed in more detail below. A short discussion of the technical, economic and environmental, health and safety attributes will be presented for each alternative, then the information for allalternatives will summarized and compared.

Sheet Devices

In its 2000 report entitled “Use of DEHP in PVC Medical Devices: Exposure, Toxicity and Alternatives”, the Lowell Center for Sustainable Production reports that the medical sheet or bag market can broadly be divided it into three use categories: 1) IV solution, 2) blood, and 3) other bags, such as collection and specimen bags. IV bags represent the largest end-use, with 55% of the U.S. PVC medical bag market, followed by blood bags (25%) and other bags (20%) (Tickner 2000). Based on our alternatives prioritization process, the following plasticizers were assessed for medical sheet device applications: TOTM, DEHA, BTHC and DINCH. The following is a summary of these plasticizer alternatives, focusing on the associated technical, cost (when available and not addressed previously) and EHS considerations.

TOTM

TOTM (trioctyl trimellitate, or tri (2-ethylhexyl) trimellitate) is a clear oily liquid that is a high production volume31 plasticizer in the US. Its specific chemical structure is shown in Figure 7.4.2 B.

Figure 7.4.2 B: Chemical Structure of TOTM

TOTM is manufactured in the US by BASF under the brand name Palatinol®. According to the manufacturer, the performance of TOTM as a PVC plasticizer is similar to DEHP. TOTM is significantly less volatile than DEHP, which potentially results in less occupational exposure to fugitive emissions during manufacture. TOTM is therefore used in applications where low volatility is desirable.

TOTM has good PVC compatibility and is resistant to extraction by soapy water (an indication of its lipid solubility). In addition, TOTM plasticized bags possess sufficient gas permeability to be suitable for storage of platelets for over 72 hours (Nair 2002). In the medical device industry, TOTM is currently used primarily in blood and bag infusion sets. While one study reported that trimellitates migrate to the blood faster than DEHP (Yin et al. 1999), the majority of other studies reviewed found that it was more difficult to exude TOTM into lipid-soluble solutions than DEHP. The manufacturer’s literature refers to the cost of TOTM as “relatively low” and March 2006 data obtained from an industry source indicates that the cost is approximately 1.5 times that of DEHP (Teknor Apex 2005). According to the Danish Study, the price of TOTM was significantly lower than they expected. It is not expected that the cost of TOTM will be an insurmountable issue in the use of medical devices.

An industry consortium in Japan conducted a review of data available on the environmental and human health impacts of TOTM in 2002 (Organization for Ecocnomic Cooperation and Development (OECD) 2002)32. This evaluation indicated that TOTM exhibits weak toxicity in aquatic environments, and may pose a reproductive toxicity concern as evidenced by exposure to male rats. The primary routes of human exposure to TOTM during manufacture are anticipated to be via dermal contact or inhalation of mist. However studies have shown that TOTM is difficult to extract from its polymer matrix (OECD 2002) and is therefore not expected to present a significant exposure concern for patients for whom medical devices containing TOTM are used.

DEHA

DEHA is an adipate plasticizer whose specific chemical structure is shown in Figure 7.4.1F. Adipates are diesters of aliphatic dicarboxylic acids and are produced with varying alcohol groups. The low-temperature properties of DEHA potentially make it a favorable plasticizer for materials used to store cold solutions (e.g., blood). DEHA is known to be slightly more difficult to process compared with DEHP. DEHA is less compatible with PVC than DEHP, which can lead to exudation (i.e., plasticizer migrating to the surface), increasing the potential for DEHA to enter the medical solution and, through use, the patient’s body. The Danish EPA determined that DEHA has the potential to migrate from the PVC matrix into fatty solutions. They conducted a review of toxicological data associated with a number of plasticizers, including DEHA. The most sensitive population potentially exposed to DEHA as a plasticizer in medical devices is neonatal patients (as it is with DEHP). A NOAEL of 610 mg/kg bw/day has been reported (DEPA 2001), which is less toxic than the NOAEL for DEHP. However the Institute did not identify any studies evaluating the impact of exposure on male reproductive system. The Chronic Health Advisory Panel for the US Consumer Product Safety Commission quotes a study that indicates a fetotoxicity issue associated with oral exposure to DEHA (CHAP 2001).

The primary metabolite associated with human exposure to DEHA is 2-ethylhexanoic acid (EHA). The Institute did not identify any specific health hazards associated with exposure to EHA.

BTHC

Butyryl trihexyl citrate (BTHC) is a higher molecular weight plasticizer specifically designed for use in medical articles especially blood storage bags. The chemical structure of BTHC is shown on Figure 7.4.2 C.

Figure 7.4.2 C: Chemical Structure of BTHC

According to the manufacture (Morflex, Inc.), its BTHC plasticizer (Citroflex® B-6) is a component of several FDA approved blood bag systems and provides improved low temperature properties relative to the phthalate plasticizers and superior long-term stability for red blood cells. Citroflex® B- 6 has low extractability into lipid media, making it particularly useful for blood products. According to Morflex, Citroflex® B-6 is a specially formulated citric acid ester for use in PVC medical articles such as tubing and IV bags where the content medium is aqueous-based. The manufacturer therefore claims that BTHC nearly duplicates the properties of DEHP for these applications33. According to industry experts, the cost of BTHC is significantly higher than DEHP, with raw material costs estimated at $1.15/lb (compared to DEHP’s cost of $0.70/lb).

Very little information is available on this plasticizer’s migration potential from the PVC matrix or on its potential health effects if patients are exposed to it. BTHC is metabolized to butyric acid, hexanol, and citrate. When exposed to butyric acid humans may experience gastrointestinal, liver and/or skin effects.

DINCH

Di (isononyl) cyclohexane-1,2-dicarboxylate (DINCH) is manufactured exclusively by BASF under the brand name Hexamoll®. DINCH is the hydrogenated product of the corresponding di C9 phthalate ester (DINP). Its performance characteristics in PVC are expected to be similar to the phthalate counterpart, except for having less solvency for PVC. The manufacturer of DINCH reports that it does not appreciably migrate out of the PVC matrix when used in medical devices. Manufacturer experience indicates that the plasticizer does not alter the properties of PVC nor change its final characteristics, so that it can be processed on existing processing equipment (Sparrow 2002). Many PVC alternative materials require new production lines or extensive retrofitting, thus increasing overall costs beyond what the marketplace will bear. Processing of PVC plasticized with DINCH only requires fine-tuning the formulation and the processing temperature to achieve the same results. In a fact sheet prepared by Eastman Chemical (Eastman Chemical Company 2004) a comparison of certain performance characteristics for various plasticizers is presented. In this technical fact sheet, Eastman shows that DINCH is comparable to DEHP and DINP in tensile strength, elongation and modulus, but that it requires more time and energy to fuse with PVC. This may be an issue for certain medical devices, however no other indication of this drawback could be found during our research.

Very little information is available from the manufacturer on the cost, performance or EH&S considerations associated with DINCH, other than what has been discussed above. Other industry sources have provided a cost estimate of $0.21 more per pound than DEHP for 70 Shore A compounds. Bayreuth, a German medical device manufacturer, has switched to manufacturing its medical devices using DINCH. "If you consider the current status of the toxicological tests, then the market will likely be prepared to accept the slightly higher price. Hexamoll® DINCH offers good value for money overall," states Bayreuth’s managing director Jürgen Rotter (Sparrow 2002). In addition, by removing the aromatic ring associated with DINP, the overall toxicity associated with DINCH is expected to be reduced. BASF indicates that it has much lower potential for negative impacts on human or environmental health; consequently, BASF has introduced DINCH as a candidate for medical device applications such as for use with neonates. BASF is currently in discussions with FDA concerning submission of DINCH for approval for use in medical devices (Schaefer 2006).

Tubing Devices

Medical tubing is made from a variety of materials including metal, plastic, and synthetic rubber. Some medical tubing features diameters that measure in the thousandths of an inch, with walls thinner than a human hair. These small, specialty tubes can cost many times more than conventional high-volume tubes, but are well-suited for catheters and other medical devices that are inserted into a patient’s cardiovascular system. In general, medical tubing manufacturers seek to reduce the outside diameter (OD) of their products while maintaining as large an inside diameter (ID) as possible. Figure 7.4.2 D illustrates cross-sections of some common tubing configurations.

Figure 7.4.2 D: Common configuration cross-sections of medical tubing devices

The plasticizer alternatives being assessed for tubing uses are limited to DINP and DEHA. Discussions of each chemical are found previously in this section of the report. The primary factor that delineates tubing uses from sheet uses in medical device applications is the requirement for elastic recovery.

DINP

DINP is a mixture of phthalates with branched alkyl chains of varying length (C8, C9 and C10). The chemical structure of DINP is depicted in Figure 7.4.1B. DINP has been used as a plasticizer in medical tubing devices because it exhibits similar clarity and elastic recovery properties to DEHP. Workplace air standards for external exposure have not been established for DINP, which although considered an animal carcinogen, has not been classified as to human carcinogenicity (CDC 2005).

When introduced into the human body, DINP is metabolized through similar mechanisms as described for DEHP metabolism. The primary metabolite for DINP is MINP (mono-isononyl phthalate). People exposed to DINP will excrete small amounts of MINP in their urine (CDC 2005).

Studies of oral exposures of DINP to rats indicate that it is primarily metabolized in the body, with the majority of the un-metabolized DINP and its metabolites being excreted within days of exposure. The major routes of excretion for orally administered DINP in rats were urine and feces, with about equal amounts excreted by either route at low doses, but more excreted in feces at high doses (Midwest Research Institute (MRI) 1983). Repeated dosing caused no accumulation of DINP or its metabolites in blood or tissue, but resulted in increased formation and elimination of the monoester side-chain oxidation products (MRI, 1983).According to the Chronic Health Advisory, exposure to DINP results in potential acute toxic effects (CHAP 2001). The NOAEL for systemic toxic effects induced in laboratory animals by exposure to DINP is estimated between 15 mg/kg bw/d and 88 mg/kg bw/d. To put this into context, a study by the Consumer Council Austrian Standards Institute (Fiala) used the lowest NOAELs for DINP and DEHP to determine a total daily intake level for these plasticizers (this study focused on the use of DINP and DEHP in children’s toys that would be mouthed and used a safety factor of 100) of 150 μg/kg bw/d for DINP and 37 μg/kg bw/d for DEHP.

According to its review of relevant studies, the CHAP concludes that DINP is clearly carcinogenic to rodents. The studies they reviewed also suggest possible carcinogenicity in the testis, uterus, and pancreas (CHAP 2001). DINP has not been tested for carcinogenicity in young rodents, an important limitation with respect to this assessment, as it is exposure to the very youngest population that the Institute is focusing on for medical device applications. However, DINP has not been listed as an EPA or IARC possible human carcinogen.

DEHA

In addition to the discussion of DEHA for medical sheet uses, it is important to also consider a key performance parameter for DEHA use in tubing – elastic recovery. DEHA is reported to exhibit similar elastic recovery properties to DEHP (DEPA 2003). When exposed to the human body, DEHA can be metabolized into EHA, which does not have clearly identified human health concerns associated with it. Table 7.4.2 B summarizes the assessment criteria associated with plasticizer alternatives to DEHP in medical devices34.

Table 7.4.2 B: Medical Device Plasticizer Alternative Assessment Criteria

Summary of Plasticizer Alternatives Assessed for Medical Devices

Table 7.4.2 C summarizes the plasticizer alternatives assessment in comparison to DEHP for use in medical devices for both sheet and tubing applications. Recall that only DINP and DEHA were evaluated for tubing applications. Refer to Table 7.4 A for specific information associated with determining the comparative assessment of plasticizer alternatives for this application. Refer to Table 7.4.2B for other data.

Table 7.4.2 C: Summary of Plasticizer Alternatives Assessment for Medical Devices

Medical Device Material Alternatives

In addition to considering alternative plasticizers for PVC, there are alternative materials that would not require a plasticizer, either because they are inherently flexible, or because they fulfill the function without being plasticized. For materials that are inherently flexible, the potential for the material to become brittle due to loss of plasticizer is eliminated, therefore these materials may have longer shelf lives than their PVC-based counterparts and the possibility of leached plasticizer entering the body is eliminated (important considerations in the medical device industry). Types of alternative materials that are appropriate for medical devices and will be further evaluated include an inorganic substance (glass, which is not a flexible polymer, but the material has been used historically for many medical applications), an elastomer (silicone), a copolymer (ethylene vinyl acetate, EVA), thermoplastic olefins (polyethylene, PE, and polypropylene, PP) and a thermoplastic resins (thermoplastic polyurethane, TPU).

Manufacturers of medical devices such as Hospira and Baxter, who together command approximately 90% of the market, have been in the news lately, touting their new lines of sheet devices (i.e., IV bags) that are ‘PVC-free’ and therefore, DEHP-free (Waldman 2006). In addition, many large hospital chains have increasingly been making purchasing decisions that include DEHP and/or PVC-free materials35. Therefore the availability of feasible alternatives to DEHP in PVC sheet and tubing materials for the medical device industry can be expected to continue to increase in the near future. The performance criteria discussed for medical devices in the beginning of Section 7.4.2 also apply for material alternatives for medical devices. The following sections summarize the alternatives appropriate for sheet and tubing devices.

Sheet Devices

The type of material used for sheet devices is dependent upon the material being stored. There are four broad groups of medical solutions that are packaged in bags:

  1. Blood products (whole blood, red blood cells, platelets and fresh frozen plasma)
  2. Intravenous (IV) solutions
  3. Total parenteral nutrition (TPN) and enteral feeding products
  4. Medications

Table 7.4.2 D summarizes the general categorization of materials that are acceptable for these packaged groups.

Table 7.4.2 D: Packaged Medical Solution and Storage Material Alternatives

The primary products derived from whole blood are red blood cells, plasma, and platelets. Whole blood, the unseparated blood that comes from a donor, is typically stored in DEHP/PVC bags. Using a centrifuge, whole blood is separated into platelet-rich plasma and red blood cells. Figure 7.4.2 E shows an example of an IV bag made from a polyolefin sheet material that is commercially available. When evaluating alternative materials for sheeting in the medical device industry, the ability of the sheet or film to provide a barrier to gas exchanges between the stored solution and the surrounding environment is important. Specifically, for the storage of sensitive solutions such as blood and platelets, minimizing the gas exchange of carbon dioxide and oxygen will result in a longer shelf life for the solution. Shelf-life is a critical factor driving material selection for packaging blood products because a container with a longer shelf-life reduces product losses. Other performance criteria discussed in Section 7.4 (with the obvious exception of PVC compatibility) also apply when evaluating material alternatives.

Figure 7.4.2 E: Typical Polyolefin Intravenous Bag

Ethylene Vinyl Acetate (EVA)

EVA is a copolymer blend of vinyl acetate, ethylene, and ethyl acetate and may contain other compounds in trace amounts. EVA has been used for medical sheet (or film) applications for parenteral and enteral solutions for many years. Empty EVA bags are also used for custom mixing of drugs by pharmacies, and because bags for these uses do not need to be steam sterilized, the temperature resistance capabilities of flexible PVC are not required. The EHS characteristics of EVA are summarized in Table 7.4.2 E.

Table 7.4.2 E: Ethylene Vinyl Acetate Considerations

EVA bags can be sterilized by gamma radiation or ethylene oxide (EO) without negative impact on their physical properties; because the melt temperature is below 121°C EVA cannot be autoclaved (steam sterilized) and is therefore not appropriate for use in IV solution storage. Flexible films made with EVA exhibit excellent clarity and, because they are manufactured without plasticizer, they are well suited for packaging and administration of lipophilic fluids. EVA films are also promoted as combining toughness and low-temperature sealability with impact and puncture resistance (Ellay 1997). The water vapor transmission rate from EVA film is less than that of PVC film; however, its gas exchange rate is approximately twice that of PVC film (Lipsitt 1997). EVA is thus more suited for parenteral and enteral solution and drug storage rather than blood and platelet storage.

As with PVC, EVA bags can be manufactured using radio-frequency sealing equipment that provides a highly reliable seal. Based on our review, EVA is expected to be currently only slightly more expensive than PVC for these applications. Because the density of EVA is less than that of PVC, film manufactured using EVA can be of a smaller gauge than similar PVC film. This can lead to a cost reduction, making EVA overall a cost-competitive alternative to PVC.

Polyolefins - Polyethylene (PE) and Polypropylene (PP)

The polyelefins PE and PP are widely used compounds that are valued for their flexibility, transparency and toughness. PE is manufactured in high density and low density forms (HDPE and LDPE). PE and PP are stable and inert polymers that exhibit very high resistance to chemical attack. PE resins, for example, are almost insoluble at room temperature in all organic solvents although some absorption, softening or embrittlement may occur. LDPE is more readily impacted by exposure to chemicals than HDPE. Some chemicals such as detergents and silicone oil will cause the phenomenon known as environmental stress cracking. PE and PP are very resistant to water and water vapor, which is an advantage when storing aqueous solutions which normally require an extra overwrap layer on top of PVC. The EHS characteristics of polyolefins are summarized in Table 7.4.2 F.

Table 7.4.2 F: Polyolefin Considerations

All oils attack polyolefins to some extent. Mineral oils will dissolve the polymer at elevated temperatures and at lower temperatures they can be absorbed causing swelling, discoloration and in the extreme, disintegration. Vegetable and animal oils do not have such a pronounced effect but some may cause environmental stress cracking to occur. The influence of oily substances on the structural integrity of polyolefins can be an issue when considering the use of these polymers in medical devices as the stored solutions are often oily or lipophilic in nature. Metallocene polyethylene (mPE) is a modification of the PE copolymer resin that uses a metallocene catalyst to control the molecular architecture of the PE resin, allowing for very low densities and narrow molecular-weight distributions. Metallocene-catalyzed PE copolymer resins (mPE) are made with specific gravities in the range of 0.86 – 0.92. mPE has greater strength and toughness, better heat-sealing properties, greater clarity and low catalyst residues compared with conventional PE (Eastman 2006). Use of mPE allows for the storage and transportation of human plasma, bone marrow, and other biologically active materials that require extremely low temperatures, from -78° to -195°C, whereas PVC is very brittle at these very low temperatures (Esposito 1997).

The toughness of mPE resins can allow for thinner, lighter-weight films, and the lower density of the mPE films results in a higher yield than is possible with PVC, producing more film area per pound (Lipsitt 1997). This can result in a lower c