U.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

Bisphenol A (CASRN 80-05-7) [CA Index Name: Phenol, 4,4' -(1-methylethylidene)bis-]

I. Overview

Bisphenol A (BPA) is a high production vol ume (HPV) chemical widely used in manufacturing polycarbonate plas tics and epoxy resins used in many industries. Humans appear to be exposed primarily through food packaging uses of products manufactured using BPA, although those products account for less than 5% of the BPA used in this country. Releases of BPA to the environment exceed one million pounds per year.

EPA intends to initiate rulemaking under sec tion 5(b)(4) of the Toxic Substances Control Act (TSCA) to identify BPA as a substance that ma y present an unreasonable risk of injury to the environment on the basis of (1) its adverse effect s on growth and development in aquatic species, (2) its substantial releases to and measured pr esence in the environment, and (3) studies that indicate some concern for potential estrogenic e ffects on aquatic organisms at low doses similar

to levels found in the environment. A notice of proposed rulemaking is intended to publish in autumn, 2010. In late 2010, EPA intends to also in itiate rulemaking under section 4(a) of TSCA to develop environmental effects data relevant to a determination that BPA does or does not present an unreasonable risk of injury to the environment. Beginning in January 2010, EPA

intends to initiate coll aborative alternatives assessment activities under its Design for the Environment (DfE) program to encourage reducti ons in BPA releases and exposures. One of

these activities will relate to thermal and carbonles s paper coatings, uses where alternatives may be readily available. This DfE environmental and health assessment is expected to be completed

in the latter half of 2011. Add itionally, EPA intends to conduct alternatives analyses for BPA used in foundry castings since foundries are account able for large releases of BPA as reported under the Toxic Release Inventory (TRI), and fo r BPA-based materials lining water and waste water pipes since this application ma y have a potential for human exposure.

EPA does not intend to initiate regulatory acti on under TSCA at this time on the basis of

human health. EPA remains concerned with human health, but notes that most human exposure, including exposure to children, comes through food packaging materials unde r the jurisdiction of the Food and Drug Administration (FDA). FDA is currently performing an in-depth reassessment on the potential risks of BPA to human health. The FDA reassessment is more comprehensive than the screening-level review undertaken by EPA during this action plan process, and EPA will continue to coordinate cl osely with FDA on this activity. To the extent that FDA may identify health concerns from BP A in food contact materials, EPA will work with FDA to identify and assess potential substitutes. Levels of exposure that may be identified by FDA as being of concern to human health, including children’s h ealth, will affect the extent to which EPA would take additional action to address potential risks to human health resulting from uses within TSCA jurisdiction.

EPA will monitor the resu lts of the $30 million resear ch program on BPA recently funded by the National Institute of Environmenta l Health Sciences (NIEHS), and will reassess the potential for regulatory action as appropriate based on any ne w information from this andU.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

2 other research. As part of the Agency's efforts to address BPA, EPA also intends to evaluate the potential for disproportionate impact on children and other sub-populations.

Because BPA is a reproductive, developmental, and systemic toxicant in animal studies and is weakly estrogenic, there are questions abou t its potential impact particularly on children’s

health and the environment. Most studies indica te that the levels of BPA in humans and the environment are below levels of potential conc ern for adverse effects. However, some nonguideline animal studies have s uggested the potential for endocrin e-related effects at much lower

dose levels than those at which effects were seen in studies conduc ted under established guidelines. FDA is addressing th ese studies in its human heal th assessment. These low-dose studies in animals are also potentially of con cern for the environment because the dose levels

identified with effects are similar to some cu rrent environmental exposure levels. Regulatory

authorities around the world that have reviewed the low dose studies have generally concluded that they are insufficient for use in risk assessm ent because of a variety of flaws in study design, scientific uncertainty concerning the relevance to health and ecological hazard of the reported effects, and the inability of other researchers to reproduce the effects in more rigorous studies. However, since guidelines for inte rpreting these studies have not yet been established and they do raise concerns for possible eff ects at levels similar to those found in the environment, some authorities, including Canada, have taken interi m risk management action to protect certain sensitive populations. Due in part to these concerns, EPA intends to initiate the risk management actions identified in this Plan to protect th e environment while further research continues.

II. Introduction

As part of EPA's efforts to enhance th e existing chemicals program under the Toxic Substances Control Act (TSCA) 1 , the Agency identified an ini tial list of widely recognized chemicals, including bisphenol A (BPA), for acti on plan development based on their presence in human blood; persistent, bioaccumulative, and toxic (PBT) 2 characteristics; use in consumer products; production volume; and other similar f actors. This Action Pl an is based on EPA’s initial review of readily available use, exposure, and hazard information 3 on BPA. EPA

considered which of the various authorities provided under TSCA and other statutes might be appropriate to address potential concerns with BPA in developing the Action Plan. The Action

Plan is intended to describe the courses of action the Agency plans to pursue in the near term to address its concerns. The Action Plan does not constitute a final Agency determination or other final Agency action. Regulatory proceedings indicated by the Action Plan will include appropriate opportunities for public and stak eholder input, incl uding through notice and comment rulemaking processes.

1 15 U.S.C. §2601 et seq.

2 Information on PBT chemicals can be found on the EPA website at http://www.epa.gov/pbt/

. 3 Information sources customarily employed include Inventory Update Reporting (IUR) submissions; Toxic Release Inventory (TRI) reporting; data submitted to the HPV Challenge Program; existing hazard and risk assessments performed by domestic and international authorities includi ng but not limited to U.S. Federal government agencies, the Organization for Economic Cooperation and Development, the Stockholm Convention on Persistent Organic Pollutants, Health and Environment Canada, the European Union; and others. Action plans will reference specific

sources used.U.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

3 III. Scope of Review

The FDA has jurisdiction over food additive s, which include food contact substances such as food packaging. These substances are no t regulated under TSCA. This review does not address potential risks from these food additive uses, which appear to comprise the bulk of human exposure. FDA is doing an assessment on those exposures.

Although most human exposure appears to come from food packaging materials (e.g., Willhite, 2008), less than 5% of the BPA produced is used in food contact applications. EPA’s review addresses the roughly 85-90% of BPA manufactured (includes imports) and used domestically that is subjec t to TSCA, including the manu facture of non-food-additive, nonmedical products. In conducting this review, EP A focused on the two areas with the most potential for environmental releases and expos ures: manufacturing and processing. EPA also considered potential human exposures to worker s during the manufacturi ng process and to the general population from the presence of BPA in drinking water sources and systems. Because the principal concern is for potential reproductive and developmental effects in early life stages, EPA considered exposures to children from the use of BPA in consumer products and exposure of children to BPA from drinking water. EPA al so examined potential ecological impact from the presence of BPA in the environment.

IV. Uses and Substitutes Summary

Bisphenol A (BPA) is a high production volume chemical with a U.S. volume estimated at 2.4 billion pounds in 2007, and an estimated value of almost $2 billion. It is a monomer used in manufacturing most or all polycarbonate plastic s, the majority of epoxy resins, and certain other chemicals such as flame retardants ( Mannsville 2008a) . Based on the nature of uses within product areas, EPA judges that the majority (p ossibly 85% to 90%) of BPA manufactured and used in the U.S. may fall within TSCA jurisdiction, as shown in Table 1 below

.

Table 1. BPA U.S. Consumption and A ssumed Share Within TSCA Jurisdiction

Product Percent of BPA U.S. 2007 Consumption 1 Assumed TSCA share 2

Polycarbonate resins 74% 62 - 64 % Epoxy resins 20% 18 - 20 % Flame retardants; Polyetherimides/ Polyarylates; Polysulfone resins; Unsaturated polyester resins 6% 5 - 6 %

Total 100% 85 - 90 %

1 Mannsville 2008a

2 EPA judgment, based on percentage of BPA consumption for each product area and use believed to fall within EPA jurisdiction under TSCA. Because the available data l ack specific detail, these are “ballpark” estimates only and the range may under- or over-estimate the TSCA share.

BPA-based materials are pervasive in the U.S. economy. Apart from food-related uses, they are used in automotive and other transpor tation equipment, optical media such as DVDs, electrical/electronics equipment, construction, li nings inside drinking water pipes, thermal and carbonless paper coatings, foundry casting, and else where. A handful of companies manufactureU.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

4 most BPA, as well as most BPA-based polycarbo nate and epoxy resins, but numerous companies process BPA-based materials into final goods.

BPA-based materials tend to be chosen fo r their performance ch aracteristics. For example, polycarbonates are lightweight and tough compared to glass. In uses subject to FDA jurisdiction, public concern has le d industry to move toward non- BPA-based materials in such products as baby bottles, cups, and spoons and adult drink bottles, a nd to explore alternatives in food can linings. A vast number of other uses ar e subject to EPA jurisdiction. EPA is aware that

substitutes for some of those uses include other epoxies, a wide variety of plastics (some of them blended with polycarbonate), glass, metals , and wood. However, EPA has not assessed the suitability and availability of substitutes for sp ecific uses in this screening-level review.

V. Hazard Identification Summary

Risk assessments for BPA have been c onducted by numerous governmental bodies and review panels. OPPT reviewed the following as sessments as well as numerous toxicological studies in assessing the hazard of BPA:

 Government Assessments:

o US (Federal) – Food and Drug Admini stration (FDA), National Toxicology Program/Center for Evaluation of Risk s to Human Reproduction (NTP/CERHR)

o US (State) - California Proposition 65 Developmental and Reproduction Toxicant Identification Committee (DARTIC)

o International – Japan, European Union (EU), European Food Safety Administration (EFSA) and Canada

 Other Reviews: Harvard Panel (Gray et al ., 2004 and Goodman et al., 2006); Chapel Hill Group (vom Saal et al., 2007; Cr ain et al., 2007); NSF Interna tional (Willhite et al., 2008)

Human Health Hazard Summary

There is general agreement that BPA is a reproductive and developmental toxicant at

doses in animal studies of > 50 mg/kg-bw/day (delayed puberty in male and female rats and male mice); > 235 mg/kg-bw/day (reduced fetal or birth weight or growth ear ly in life, effects on testis of male rats); and > 500 mg/kg-bw/day (possible decreased fertility in mice, altered estrous cycling in female rats, and reduced survival of fetuses). Systemic effects (reduction in body weight, changes in relative organ weights, and increases in liver toxicity) were observed at doses above 5 mg/kg-bw/day (identified as a NOAEL; LOAEL of 50 mg/kg-bw/day). There is controversy about whether effects seen at lower doses in animal s (less than 1 mg/kg/day) are meaningful and relevant to humans. These low- dose effects are endocri ne-related and include effects on puberty and developmental neurotoxicol ogical effects (brain, behavior) at doses in

animal studies as low as 2 μ g/kg-bw/day.

All of the government BPA assessments re viewed discuss these low-dose data and virtually all (the FDA, DARTIC, Japan, the EU, and EFSA) have considered them insufficient for the purposes of hazard evaluation/risk a ssessment, the exceptions being Canada and the NTP/CERHR. Canada acknowledged high uncertainty in the data, but took precautionary action to restrict BPA exposures to infants and young children. The NTP/CERHR observed that theU.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

5 uncertainty led to a conclusion of “some concer n” for potential effects. New information on these potential low-dose effects has been publis hed on an almost monthly basis over the past year, with some studies supporti ng the concept and others findi ng no effects. For example, a recent study performed by EPA scientists compar ing BPA with the oral contraceptive ethinyl estradiol (EE) found that low in utero doses of EE affected sexual differentiation in female rats,

but low in utero doses of BPA produced no such effects (Ryan et al. , 2009). The same investigators reported results in male rats in an earlier publica tion, also noting effects in males exposed in utero to EE, but not to BPA. (Howdeshell et al. 2008). In addition, the NIEHS recently awarded $30 million dollars in grants fo r a two-year program of research on these

issues.

Metabolism studies have been performed in multiple species (rats, mice, monkeys, and humans) and show that humans and rodents metabo lize BPA differently. Data in all four species indicate metabolism by conjugation in the liver w ith glucuronic acid to form the metabolite BPA-glucuronide (BPAG). The relative amount of free-BPA and BPAG circ ulating in mammals is important because free-BPA (“parent”) is known to be weakly estrogenic and BPAG is not. Data indicate that BPAG is more prevalent in primates and free-BPA is more prevalent in

rodents.

BPA has been found in human biological samples (serum, breast milk, urine, fetal blood) reported as total BPA, or free-BP A, or BPAG (except that BPAG has never been reported in fetal blood). In 2008, the National Report on Human E xposure to Environmental Chemicals reported

that BPA was detected in the urine of 93% of the 2,517 people tested in 2003-4 (Calafat et al., 2008). Recently, urinary BPA concentrations measur ed in premature infants from two separate

intensive care facilities showed that mean urinary concentrations of total BPA were an order of magnitude higher in the infants than in the ge neral population. Over > 90% of the BPA found in that study was as a glucuronide co njugate (Calafat et al., 2009), providing evidence of the ability for neonates to conjugate BPA into its non-estr ogenic form. The study authors noted, however, that this metabolic pathway would not be expected to be functional at ad ult rates until months

after birth.

There was a recent report suggesting that BPA levels in humans may be associated with a higher risk of diabetes, heart disease, and elevatio n of certain liver enzyme activities (Lang et al., 2008). The authors examined the human data from a sub-sample of the National Report cohort (Calafat et al., 2008). However, this report prompted an immedi ate review by the EFSA (2008b)

in late 2008 which concluded th at the study did not provide sufficient proof for the stated

associations.

Table 2 below is a list of each major assessment reviewed and the accompanying hazard value chosen in their respective assessments. So me assessments did not derive a hazard value per

se , but did make hazard/risk decisions:

 The California Proposition 65 Developmental and Reproductive Toxicant Identification Committee (DARTIC) voted on 7/15/09 not to list BPA as a developmental toxicant, a female reproductive toxicant, or a male reproductive toxicant (each by separate, unanimous votes of 7-0).U.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

6  Thirty-eight scientis ts (known as the “Chapel Hill Group” ) concluded that : (1) there is relevance of in vitro data to in vivo effects; (2) ecological studies are consistent with lab animal studies; (3) the low doses in animal studies are relevant to BPA levels found in humans; and (4) life stage is important in pharmacokinetics, exposure, & effects in

animals and humans.

 A Harvard Panel (Gray et al., 2004) concluded th at the low dose data are not relevant to humans (and reaffirmed this in an u pdate reported in Goodman et al., 2006).

 A National Toxicology Program (NTP) Cent er for Evaluation of Risks to Human Reproduction (CERHR) Panel (C ERHR/NTP, 2008) conclude d that rodent studies suggest that BPA causes “...neur al and behavioral alterations related to disruptions in

normal sex differences in rats and mice (0.01-0.2 mg/kg/day).”

Table 2: BPA Hazard Values for Human Health Assessments

Authors Hazard Value (mg/kg/day) 1 Endpoint (Animal dose in mg/kg/day) And Study
EPA (Integrated Risk Information System; IRIS (1993)) 0.05 Reduced body weight (5) NTP two year cancer study in both rats and mice (1982)

FDA (2008) 0.05 Systemic – reduced bod y wt and liver effects (5) Irreversible reproductive effects (50) Reversible reproductive effects (50) All based on both 2-generation mouse study (Tyl et al., 2008) and 3-generation rat study (Tyl et al., 2002) 0.05

0.5 EFSA (2006, 2008) and EU (2003, 2008) 0.05 Used 5 (lowest value in cited studies) Tyl et al., (2002 and 2008)

Japan (2004) 0.05

0.5 Body weight (5) Reproduction (50) Tyl et al., (2002, 2008)

0.046 Liver effects (23) NTP (1985) – continuous breeding study in mice

Canada (2008) Did not report

any Body weight reduction (5) and dev/repro effects (50) Tyl et al., (2002, 2008)

Cited numerous studies with effect levels ranging from 0.010 to 0.100 mg/kg/day for a variety of effects in mice and/or rats including changes in: maternal behavior, gender-specific behaviors; sexual performance; novelty-seeking/impulse behaviors; avoidance response; maze performance.
Willhite,et al., 2008 (NSF International) 0.016 Used 5 (lowest value in cited studies) Tyl et al., (2002 and 2008)

1 Most risk assessments take an exposure value from an animal study (dose in mg/kg-bw/day) and divide it by several uncertainty factors to arrive at an acceptabl e dose in humans. This value is what is shown here and what is compared to an expected /estimated exposure value in a risk assessment. The uncertainty factors used by the various assessments: EPA (IRIS) – 1000; FDA – either 100 (systemic or reversible effects) or 1000 (irreversible effects); EFSA/EU – 100; Japan – either 100 or 500; Canada – did not specify; and NSF

Int.’l – 300.

Environmental Hazard Summary

Many studies have been conducted to determ ine potential effects of BPA exposure on invertebrates, fish, amphibians , reptiles, birds, and wild ma mmals, and a thorough review isU.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

7 provided by Crain et al. (2007). EPA’s screening-level ecologi cal hazard review for this Action Plan focused on effects in freshwater aquatic species to provide a framework for determining whether toxicity may warrant further investigat ion or risk management action. A more robust review of effects in both terrestrial and aquatic (marine and freshwater) organisms will be conducted as the Agency proceeds with carrying out the activities identified in this Action Plan.

In general, studies have show n that BPA can affect growth and development in aquatic organisms. Among freshwater organisms, fish app ear to be the most sensitive species. Evidence

of endocrine-related effects in fish, aquatic invertebrates, am phibians and reptiles has been reported at exposure levels lower than those required for acute t oxicity. There is a widespread variation in reported values for endocrine-related effects, but many fall in the range of 1μg/L to 1 mg/L. (Canada, 2008).

The ecological hazard for BPA has been evaluated in three different risk assessments performed by the European Union (EU), Canada , and Japan as summarized below in Table 3. The different methodologies, endpoints and study results used by each country to derive these values highlight the significant uncertainty in the estimated hazard valu es. Canada used a study (Lahnsteiner et al, 2005) that reported reduced sperm quality and delayed ovulation in brown trout at a very low dose (1.75 μg/L). Other effect s such as decreased spermatogenesis, induction of vitellogenin, delayed or ceased ovulation, hi stological liver changes or the induction of

intersex or testes-ova in males were also reported in other st udies referenced in the EU and Japanese hazard evaluations. However, because there were no standardized test guidelines or risk assessment guidance for evaluating some of these endocrine-related effects 4 at the time of these assessments, the EU and Japan set ecotoxicologica l hazard values based on conventional effects (mortality and reproductive effects). Canada co ncluded in its hazard characterization that “[c]onsidered together, the data provide strong ev idence that bisphenol A is capable of eliciting adverse effects: (1) following pr olonged exposure at levels below those usually seen to elicit effects in standard toxicity tests (i.e., test s based on recognized methods which evaluate endpoints such as survival, reproduction and gr owth); (2) following brief low-dose exposure, particularly at sensitive developmental stages, with effects apparent later in the life cycle; (3) on filial generations following parent al exposure; and (4) using more than one mode of action.” (Canada, 2008).

Table 3: Summary of Bisphenol A Ecological Hazard Values

Country Predicted No

Effect

Concentrations 1
(μg/L) Endpoints

European

Union 1.5 The predicted no effect concentration (PNEC) for aquatic organisms (derived by using a stat istical analysis of data from

4 As part of its endocrine disruptor screening program, EPA developed a two-tiered approach to implement statutory testing requirements. The purpose of Tier 1 screening is to identify substances that have the potential to interact withthe estrogen, androgen, or thyroid hormone systems. The purpose of Tier 2 testing is to identify and establish a doseresponse relationship for any adverse effects that might re sult from the interactions identified through the Tier 1 assays. EPA has established Tier 1 screening test guidelin es. Tier 2 test guidelines will be developed after the completion of ongoing validation studies.U.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

8 Table 3: Summary of Bisphenol A Ecological Hazard Values

Country Predicted No

Effect

Concentrations 1
(μg/L) Endpoints

available data on freshwater a nd marine aquatic organisms (in this case, 16 different studie s, unpublished and published, from 10 different taxonomic groups) to ar rive at a value of 7.5 μg/L, which is divided by an uncertain ty factor of 5, resulting in a PNEC of 1.5 μg/L (EU, 2008).

Canada 0.175 This PNEC was derived by using a lowest observed effect concentration (LOEC) of 1.75 μg/L for reduced semen quality and delayed ovulation in a published brown trout study (Lahnsteiner et al, 2005) and appl ying an uncertainty factor of 10 (Canada, 2008). Japan 1.6 The PNEC was derived by using the 16 μg/L no effect concentration (NOEC) for egg hatchability in fathead minnows from the unpublished 3 generation study by Sumpter, et al. (2001) multigeneration fish study and dividing by an uncertainty factor of 10 (AIST, 2007).

1 In Europe, Canada, and Japan, a predicted no effect concentration (PNEC) is compared directly with an exposure

value to evaluate risk. If the ratio of environmental concen tration to PNEC is less than one, the risk is generally considered acceptable. As noted in the table, countrie s use different approaches for generating PNECs , and the precise values may differ even when based on the same studies.

VI. Fate Characterization Summary

BPA is a solid at room temperature. It has a low vapor pressure, moderate water solubility, and low volatility (H SDB, 2009). It has low to moderate mobility in soil. It is expected to biodegrade under environmental co nditions, although conflicting results have been obtained using biodegradation screen ing tests. However, the weight of evidence suggests that it is not expected to be persistent in the environment, and degrada tion is expected to occur. The rate of atmospheric photooxidation is rapid. Hydr olysis is expected to be negligible under

environmental conditions since BPA does not contai n functional groups that are susceptible to hydrolysis. BPA is expected to have low pers istence (P1) and low bioaccumulation potential (B1). (EU, 2003 and EU, 2008)

Any residual, unreacted BPA remaining in polycarbonate products and epoxy resins can leach out into food or the environment. Polycarbonate is generally stable, but some BPA can be released from polycarbonate when it is exposed to strongly basic cond itions, UV light, or high heat. Epoxy resins made with BPA are stable; only residual BPA is expected to be released from epoxy resins.

VII. Exposure Characterization Summary

BPA may be present in the environment as a result of direct releas es from manufacturing or processing facilities, fugitive emissions during processing and handling, or release ofU.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

9 unreacted monomer from products (CERHR/NTP, 2008). Accordi ng to the Toxics Release Inventory (TRI) Database, total release of BPA in 2007 was 1,132,062 pounds 5 , with releases of 122,965 pounds to air, 6,246 pounds to water (dir ect), 14,972 pounds released on-site to land, and 684,638 pounds transferred off-site to land (U SEPA, 2009). Sources of human exposure to BPA include dietary intake (e.g., migration from food packaging and from repeat-use polycarbonate containers, such as baby bottles), environmental media (ambient air, indoor air, drinking water, soil and dust), and use of consumer products. Given the tendency of young children to put inappropriate objects into their mouths, there is some potential for children to be exposed to BPA through their mouthing or accidental ingestion of such pr oducts as plastic toys, thermal paper, and possibly of toilet paper made fr om recycled materials. Dietary intake appears to be the primary source of human exposure. Ho wever, food packaging and food containers, such as baby bottles, are the purview of the Food and Drug Administration; therefore, OPPT’s human and environmental exposure characterization focuses on exposure from manufacturing; processing; industrial uses; commercial uses; se lected consumer uses; ingestion of BPA in drinking water, including drinking water contaminat ed by wastewater releases to surface water, drinking water drawn from ground water contamin ated by leachate from landfills, and drinking water distributed through BPA-ba sed water pipes; and ingestio n of BPA from infants’ and children’s toys and products. O PPT used release data, modeling, and information available in peer-reviewed articles and government publicati ons to obtain information on exposure to BPA.

Very little information is available on expos ure from consumer products. Miyamoto and Kotake (2006) estimated exposure to BPA for Ja panese infants from contact with consumer products such as toys. They estimated the mean in take of BPA from toys for male infants 0 to 5 months of age to be 0.026 μ g/kg bw per day and the mean intake for infants 6-11 months to be

0.069 μ g/kg per day.

Limited information is available for BPA concentrations in US water (Table 4). Most environmental monitoring results show that the concentrations of BPA in water bodies are lower

than 1 μ g/L, mainly due to its par titioning and biodegradability properties (Tsai 2006). BPA was

detected at a median concentration of 0.14 μ g/L and a maximum concentration of 12 μ g/L in 41.2% of 85 samples collected from US stream s in 1999 and 2000 (Kolpin et al. 2002). The

maximum concentration of 12 μ g/L is an outlier; the BPA concen tration in other US waters was much lower (as indicated by the median concentration of 0.14 μ g/L). In 2001 and 2002, BPA was not detected (< 0.001 μ g/L) in effluent from a wastewater treatment plant in Louisiana, and concentrations were not quantifiable in samples collected from surface waters in Louisiana and in drinking water at various stages of treatment at plants in Louisi ana (Boyd et al. 2003).

In 2000, the U.S. Geological Survey collect ed samples from 47 ambient groundwater sites (not drinking water wells) in 18 states and analyzed them for 65 organic wastewater contaminants (Barnes et al., 2008; USGS, 2008). BPA was detected in 29.8% of the sampled groundwater sites, with a mean detected concentration of 1.78 μ g/L and a range of 1.06 to 2.55

μ g/L (Barnes et al., 2008). BPA was among the t op five most frequently detected organic compounds (USGS, 2008).

5 This does not include off-site water transfer to POTWs (Publicly Owned Tr eatment Works) wastewater treatment facility (32,928 pounds) or transfer to incineration (2,759,705 pounds).U.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

10 In the summer of 2001, the U.S. Geological Surv ey collected samples from 74 sources of raw, untreated, drinking water in 25 states a nd Puerto Rico, in areas that were known or suspected to have at least so me human and/or animal wastew ater sources in upstream or upgradient areas. These sources comprise 25 gr oundwater and 49 surface water sources of drinking water serving populations ranging from one family to more than 8 million people. BPA

was detected in 9.5% of these sa mples at a reporting level of 1 μ g/L. The maximum concentration measured in these samples was 1.9 μ g/L (USGS, 2008; Focazio et al., 2008).

Landfill leachates from one U.S. study repor ted maximum BPA concentrations of 1.7

μ g/L in landfill leachate and 1.4 μ g/L in the receiving groundwater plume at a landfill on Cape Cod that was known to be leaking (Crain et al., 2007). Landfill leachate from other countries

contained more than 500 μ g/L of BPA, which is on the order of 500 times the BPA concentrations in water bodies (Tsai, 2006). Studie s conducted at Japanese landfills resulted in maximum untreated leachate concentrations of 17,200 μ g/L and treated leach ate concentrations

of 5.1 μ g/L (Crain et al., 2007).

Soil concentrations reported in CERHR/NT P 2008 were for soil samples taken from outdoor play areas of homes and daycares; BPA concentrat ions ranged from 4-14 ppb dry weight, with means of 6-7 ppb dr y weight. Klecka et al. 2009 re ported a median concentration of 0.6 ppb BPA in North American freshwater sediments, including nondetected samples; BPA concentrations in samples from the US range d from 1.4 to 140 ppb dry weight. US marine sediments were reported to have a median of 3.5 ppb of BPA and to range from 1.5 to 5 ppb dry weight (Klecka et al. 2009, Tsai 2006).

Table 4: U.S. Reported Environmental Concentrations of BPA

Location Mean or Range of Means (ppb) Range (ppb)

Surface Water 0.012 to 0.14 0.0009 to 12

Groundwater 0.0041 to 1.9 0.006 to 2.55 Drinking Water 0.005 to <0.1 <0.1 to 0.42

Wastewater <0.1 0.0036 to 50

Soils 6 to 7 4 to 14 Sediment, Fresh 0.6* † 1.4 to 140 †

Sediment, Marine 3.5* 1.5 to 5.0

* Value is median; mean values not reported

† median value includes nondetected values be low the MDL, while the reported range includes only detected values

E-FAST2 modeling of BPA releases in th e 2007 TRI showed the most conservative estimates of the potential acute dose rate for inge stion of BPA in drinking water by children ages 1-2 ranged from 0.0000531 to 16.5 μg/kg/day, and the mo st conservative estimates of the surface water concentration ranged from 0.000574 to 232 μg/L. The E-FAST2 model is intended to be used for screening level exposure characterizatio n. E-FAST2 is based on numerous assumptions that are designed to be conservative; for exampl e, E-FAST2 does not account for the half life of a chemical in surface water. The inputs select ed for the E-FAST2 mode ling of BPA were alsoU.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

11 selected to be conservative; for example, the bi oconcentration factor was selected to be at the high end of the range of values re ported for BPA in the literature.

FDA estimated exposure to BPA from food contact uses to be 0.185 μ g/kg bw/day for adults. The highest estimate by FDA is 2.42 μ g/kg bw/day for female infants, 1-2 months of age (U.S. FDA, 2008). Human exposures from food contact uses ar e consistently estimated by researchers to be higher than exposures fr om all other sources (e.g., Willhite, 2008).

Workers may be exposed to BPA by inhalation or skin contact duri ng the manufacture of BPA and BPA-containing products . No data were available for dermal exposures, and limited data were available for inhalation exposures. Table 5 summarizes EPA’s estimates for occupational exposures that may occur during manufacturing. These estimates were derived using models developed by EPA/OPPT for us e in preparing scr eening-level exposure

assessments of chemicals. These models do not take into account the effect of any personal protective equipment that may be used.

Table 5. Inhalation and Dermal Exposure Estimates to BPA During BPA Lifecycle Stages

Lifecycle Stage Exposure Type BPA Exposure Dose (mg/day)

Manufacturing Inhalation 0 – 9.6
Dermal (liquids and solids) 882 – 3,100 a

USE 1: Polycarbonates Inhalation 0.7 – 2.7 b

Dermal (solids) 0.31 – 3,100 c

USE 2: Epoxy Resins Inhalation 0 – 28
Dermal (solids) 3,100 c

USE 3: Flame Retardants Inhalation 0 d

Dermal (solids) 3,100 c
a – Exposure is in milligrams per event. Events can include sampling of solutions containing BPA or solid BPA and loading/unloading of BPA from containers. b – Exposure is to polycarbonate dust. c – Exposure is in milligrams per loading/unloading of BP A from containers, which is the only identified potential exposure during this st age of the lifecycle. d – Inhalation exposure to BPA during the production of flame retardants is not expected.

VIII. Risk Management Considerations

BPA is not a heavily regulated chemical in th e U.S., but has been identified as a chemical of potential concern si nce the early 1980’s.

U.S. EPA and State/Local Regul atory Reviews and Actions

BPA was included in the ini tial proposal of the Toxics Release Inventory (TRI) list published in 1987 (52 FR 21001). Th at initial list was mandated by the Emergency Planning & Community Right-to-Know Act (EPCRA) section 313(c), 42 U.S.C. § 11023( c), to include the substances specified by the Senate Environm ent and Public Works Committee Print 99-169, so there was no separate discussion of the justification for placing BPA on the initial TRI list.U.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

12 In 2009, the EPA Office of Water considered BPA during its development of the third Candidate Contaminant List (CCL3) of substanc es that might be appropriate candidates for future regulation. Although BPA appeared on th e potential CCL (PCCL) list used during the screening process, BPA did not meet the combined screening criteria of potential to occur in public water systems and potential for public health concern, and thus did not appear on the final CCL3 list. The notice publishing the final CCL3 list (74 FR 51850, 10/8/2009) does not specifically address BPA, but supporting materials available on the EPA website describe the process and criteria used in the development of the list, including the information on BPA ( http://www.epa.gov/og wdw000/ccl/ccl3.html ).

Connecticut, Minnesota, Chi cago and Suffolk County, N.Y., have banned the sale of polycarbonate baby bottles, food containers and c ups that contain BPA. The Connecticut ban also applies to infant formula cans and all reusable food and be verage containers. The Suffolk County ban went into effect in July 2009. The Minnesota ban will go into effect on 1/1/2010; the Chicago ban on 1/31/2010; and the Connecticut ban on 10/1/2011. A California bill to ban the use of BPA in baby bottles and cups and infant formula cans failed to pass in September 2009 by

six votes and was moved to the inactive file . It is eligible to be raised again.

International Regulator y Reviews and Actions

Numerous foreign governmental bodies and re view panels have conducted human health risk assessments for BPA in the recent past . Japan (AIST, 2007), the European Union (EU, 2008), and the European Food Safety Administrati on (EFSA, 2008) all concluded within the past two years that the studies indica ting low dose, endocrine-related e ffects were insufficient for the purposes of hazard evaluation/risk assessment. Using hazard values derived by dividing the doses used in animal studies by the respectiv e uncertainty factors applied by the different regulatory bodies, they concluded that expected exposures even from food contact uses, the largest expected source of expos ure, did not present concern for risk to human health.

Ecological risk for BPA has been evaluate d by the European Union (EU, 2008), Canada (Canada, 2008), and Japan (AIST, 2007). Japan conc luded that “the current exposure levels of BPA will not pose unacceptable risks to the local popul ations of aquatic life, particularly fish.” The EU concluded that although th e predicted exposure c oncentrations were significantly below its hazard values, there was a need for further in formation and/or testing on such organisms as

freshwater snails. Canada concluded that BPA concentrations in water have the potential to cause adverse effects on populations of pe lagic organisms in Canada and concentrations in biota have the potential to cause adverse eff ects in populations of wildlife in Canada, but that there is a low risk of direct adverse effects to sediment orga nisms and to avian wildlife species in Canada. In the conclusion of its risk assessment, Canada stat ed that it is considered appropriate to apply a precautionary approach when characterizing risk, observing “it is concluded that bisphenol A is entering the environment in a quantity or concen tration or under conditio ns that have or may have an immediate or long-term harmful effect on the environment or it s biological diversity.”

On June 26, 2009, Canada became the first c ountry to take regulatory action against BPA. Canada announced that it was moving forwar d with proposed regulations to prohibit the advertisement, sale and importation of polycarbona te plastic baby bottles that contain BPA, toU.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

13 reduce newborn and infant exposure to this substance. In making this decision, Canada indicated that its decision was grounded in the precautionary principle, noting “Science tells us that exposure levels are below those th at could cause health effects; however, due to the uncertainty raised in some studies relating to the potential effects of lo w levels of bisphenol A, the Government of Canada is taking action to enha nce the protection of infants and young children.” ( http://www.chemicalsubstanceschimiques.gc .ca/challenge-defi/bisphenol-a_fs-fr_e.html )

In August 2009, Taiwan designated BPA as a Class 4 toxic substance under the Toxic

Chemical Substances Control Act. A Class 4 toxi c substance is defined as a substance for which there is concern of pollution of the environment or the endangerment of human health. Handlers of Class 4 substances are require d to keep and report re cords of the toxicit y, production, release, and use of those chemicals, but the chemicals ar e not subject to other restrictions on handling, transportation, or use ( http://law.epa.gov.tw/en/laws/788537580.html ). Class 4 is the lowest designation for a toxic substance in Taiwan.

Ongoing Activities and Issues

The primary issue with regard to risk mana gement approaches to BPA is the uncertainty surrounding the actual determinati on of risk, particularly from low dose exposures. There is agreement among international regu latory authorities using generally accepted approaches to human health assessment that human exposures to BPA are below levels that would be associated with health effects, leading to determ inations that current us es of BPA do not present human health risks warranting further regulatory controls. Similarly, environmental exposures to BPA, apart from isolated hot spots, are estimated generally to be lower than the levels associated with effects in standard toxicological studies done according to established guidelines, indicating

low environmental risk from current uses of BPA on the basis of just those standard studies. The complicating factor, however, is the uncertain ty surrounding the meaning and relevance both to

humans and the environment of the effect s seen in low-dose studies, because some environmental exposures are similar to levels a ssociated with observed e ffects in those low-dose

studies.

Reproductive and developmental toxicity are the most sensitive e ffects in the guideline studies, while controversial, non -guideline studies suggest the pot ential for endocrine-related effects at much lower, environmentally-relevant levels than identified in the guideline studies. Accordingly, BPA exposures raise particular que stions concerning children’s health. Children may be exposed to BPA before birth through thei r mothers’ exposures, an d directly through the use of BPA in food packaging ma terials and child feed ing products (such as baby bottles, sippy cups, and spoons) within FDA jurisdiction. FDA is assessing potential health risks to both children and adults from exposure to BPA in f ood contact materials. Children may also be exposed to a lesser extent through other consum er products such as t oys and through contact with environmental media (e.g., air and water). Ch ildren’s exposures are gr eater than adults’ due to increased intakes of food, water, and air pe r pound of body weight, as well as child-specific exposure pathways such as mouthing of objects and ingestion of non-food items.

On October 28, 2009, the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health unde r the U.S. Department of Health and HumanU.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

14 Services, announced the award of $14 million in Recovery Act funds to support two-year research grants into the potential effects of BPA on human health. Including these Recovery Act funds, NIEHS is investing approximately $30 m illion over two years on BPA research. The new two-year animal and human studies will focus on either developmental exposure or adult chronic exposures to low doses of BPA. Researchers will be looking at a number of health effects including behavior, obesity, diab etes, reproductive disorders, deve lopment of prostate, breast and uterine cancer, asthma, cardiovascular diseases and transgenerational or epigenetic effects ( http://www.nih.gov/news/h ealth/oct2009/niehs-28.htm ).

Although there is controversy in interpreting some of the st udies and effects observed in the many aquatic toxicity studies performed thus far with BPA, a comparison of the range of predicted no effect concentration (PNEC) values used in the three intern ational regulatory risk assessments (0.175 to 1.6 μ g/L, Table 3) with measured con centrations in U.S. waters and sediments, which included values as high as 12 μ g/L (surface water), 2.55 μ g/L (ground water),

and 140 μ g/kg sediment (freshwater sediment) (Table 4), raises concern a bout possible risk of injury to aquatic organisms. However, limited info rmation is available for BPA concentrations in U.S. water, and most available environmental mon itoring results show that the concentrations of

BPA in water bodies are lower than 1 μ g/L (median concentration of 0.14 μ g/L, below any calculated PNEC). These environmental measuremen ts represent only isolat ed snapshots in time and do not provide an indication of how many areas may exceed PNEC values or concentrations of concern, how often or how long such concen trations may be exceeded, or the pathways leading to BPA presence in the environment from manufacturing, proc essing, distribution in commerce, use, or disposal.

IX. Next Steps

In conducting this review of bisphenol A, EPA considered a number of potential risk management actions, including regulatory actions under TSCA sections 4, 5 and 6; cooperative activities with other federal ag encies; and voluntary actions thr ough such programs as Design for the Environment (DfE).

Based on EPA’s screening-level review of hazard and exposure information, including the uncertainties surrounding the low-dose studies, EPA intends to initiate risk management action to protect the environment while further re search continues. Acco rdingly, EPA intends to:

1. Initiate rulemaking under section 5(b)(4 ) of the Toxic Substances Control Act (TSCA) to identify BPA as a substance th at may present an unreasonable risk of injury to the environment on the basis of (1) its adverse effects on growth and development in aquatic species, (2) its substa ntial releases to and measured presence in the environment, and (3) studies indicat ing some concern for potential estrogenic effects on aquatic organisms at low doses si milar to levels found in the environment. A notice of proposed rulemaking is in tended to publish in autumn, 2010.

2. Initiate rulemaking under section 4(a) of TSCA to develop data with respect to

environmental effects relevant to a determ ination that BPA does or does not present an unreasonable risk of injury to the e nvironment. This may include testing or monitoring data in the vicinity of land fills, manufacturing facilities, or similarU.S. Environmental Protection Agency Draft, 12/9/200 9 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

15 locations to determine the potential for BPA to enter the environment, including surface water, ground water, and drinking wa ter, at levels of potential concern particularly for environmental organism s, pregnant women, and children. EPA anticipates publishing an advance notice of proposed rulemaking in late 2010.

3. Initiate collaborative alte rnatives assessment activiti es under its Design for the Environment (DfE) program to encourage re ductions in BPA releases and exposures. One of these activities, intended to be initiated in January 2010, will address thermal and carbonless paper coatings, a use where pr eferable alternatives may be readily

available. This DfE environmental and health assessment is expected to be completed

in the latter half of 2011. Paper coatings are not a majo r use of BPA, but thermal paper has been reported to contain free BP A, which would be expected to be more available for exposure than BPA bound into resin or plastic. Popular uses of this paper include airline tickets, event and ci nema tickets, labels, and point of sale applications (receipts). While there is litt le concern for dermal absorption of BPA, free BPA can readily be transferred to sk in and residues on hands can be ingested. There is some potential for incidental expos ure of children since they are more likely than adults to mouth inappropriate objects. Use of BPA in paper also may contribute to the presence of BPA in the stream of r ecycled paper used in toilet paper, paper tableware, and other products. Additionall y, EPA intends to initiate alternatives analyses for BPA used in foundry castings since foundries are accountable for large releases of BPA as reported under TRI, a nd for BPA-based materials lining water and waste water pipes since this application may have a potential for human exposure.

EPA does not intend to initiate regulatory acti on under TSCA at this time on the basis of

human health. EPA remains concerned with human health, but notes that most human exposure, including exposure to children, comes through food packaging materials unde r the jurisdiction of the Food and Drug Administration (FDA). FDA is currently performing an in-depth reassessment on the potential risks of BPA to human health, and EPA will continue to coordinate closely with FDA on this activity. To the extent that FDA may identify health concerns from BPA in food contact materials, EPA will work with FDA to identify and assess potential substitutes. Levels of exposur e that may be identified by FDA as being of concern to human health, including children’s health, will affect the extent to which EPA would take additional action to address potential risks to human health resulting from uses within TSCA jurisdiction.

A substantial program of research is underway through NIEH S to resolve the uncertainties in the human health hazard of BPA, and EPA will monitor the results of that and other research to determine whether they may change the risk picture for human and environmental exposures from uses within TSCA jurisdiction.

As part of the Agency's efforts to address BP A, EPA also intends to evaluate the potential for disproportionate impact on children and other sub-populations.

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