U.S. Environmental Protection Agency 3/29/2010

Bisphenol A Action Plan (CASRN 80-05-7) [CA Index Name: Phenol, 4,4' -(1-methylethyl idene)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 consider initiating immediat e actions addressing BPA in the environment based on concerns for potential effects in aquatic species. At the same time, EPA will continue to work with the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and the National Institute of Environmental Health Sciences (NIEHS) to

better determine and evaluate the human health consequences of BPA exposures. Based on the results of those efforts, EPA will consider whether further action is needed to address human health risks resulting from non- food-packaging uses of BPA.

EPA intends to consider initiating rule making under section 5(b)(4) of the Toxic Substances Control Act (TSCA) to identify BPA on the Concern List as a substance that may present an unreasonable risk of injury to the environment on the basis of its potential for longterm adverse effects on growth, reproduction and development in aquatic species at concentrations similar to those found in the environment. A notice of proposed rulemaking is intended to publish in autumn, 2010. In late 201 0, EPA intends to consider also initiating rulemaking under section 4(a) of TSCA to devel op environmental effects data relevant to a further determination that BPA either does or does not present an unreasonable risk of injury to the environment. Beginning in April 2010, EPA in tends to initiate colla borative alternatives assessment activities under its Design for th e Environment (DfE) program to encourage reductions in BPA manufacturing and use to facili tate reductions in environmental releases and subsequent exposures. One of these activitie s will relate to thermal and carbonless paper coatings, including those on cash regi ster receipts, which are uses where alternatives to BPA 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 may have a potential for human and environmental exposure.

EPA does not intend to initiate regulatory acti on under TSCA at this time on the basis of human health. EPA remains committed to protecti ng human health, but notes that most human exposure, including exposure to children, co mes through food packaging materials under the jurisdiction of FDA. Food, food additives, drugs, co smetics, and medical devices, all regulated by FDA, are specifically excluded from the defi nition of chemical substance under TSCA. FDA, together with CDC and NIEHS, is investing in important new hea lth studies in both animals and humans to better determine and evaluate the pot ential health consequen ces of BPA exposures.U.S. Environmental Protection Agency 3/29/2010

EPA will continue to coordinate closely with FDA, CDC, and NIEHS 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 exposure 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.

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. Studies employing st andardized toxicity te sts used globally for regulatory decision-making indicate that the levels of BPA in hu mans and the environment are below levels of potential concern for adverse effects. However, results of some recent studies using novel low-dose approaches and examining di fferent endpoints describe subtle effects in laboratory animals at very low concentrations. Some of these novel low-dose studies in animals are potentially of concern for the environment b ecause the concentration levels identified with

effects are similar to some current environmen tal exposure levels. Regul atory authorities around

the world that have reviewed these low-dose studies have gene rally concluded that they are

insufficient for use in risk assessment because of a variety of flaws in some of the study designs, 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 standardized studies. Although there is disagreement about the interpretation of these low-dose studies, they do raise potential concerns for long-term effects at simila r concentrations, and some authorities, including Canada and some U.S. state and county government s, have taken interim risk management action to protect certain sensitive populations, such as infants and toddlers. For example, the Canadian government is taking steps to ban baby bottl es that are manufactured with BPA.

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 initia l list of chemicals, including bisphenol A (BPA), for action plan development ba sed on one or more of the following factors: their presence in human blood; persiste nt, bioaccumulative, and toxic (PBT) 2 characteristics; use in consumer products; production volume; and other similar factors. This Action Plan is based on and encompasses EPA’s initial review of r eadily available use, exposure, and hazard

information 3 on BPA. EPA considered which of the various authorities provided under TSCA and other statutes might be appr opriate to address potential con cerns with BPA in developing the

Action Plan. The Action Plan is intended to desc ribe the courses of action the Agency plans to pursue in the near term to address its concer ns. The Action Plan does not constitute a final

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. References to specific sources used in this Action Plan are provided in the individual sections discussing use, exposure, and hazard information.

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Agency determination or other final Agency action. Regulatory procee dings indicated by the Action Plan will include appropriate opportunitie s for public and stakeholder input, including through notice and comment rulemaking processes.

III. Scope of Review

In conducting this review, EPA focused on th e two areas with the most potential for environmental releases and exposures: manufacturing and processing. EPA also considered potential human exposures to workers during the manufacturing process and to the general population from the presence of BPA in drinki ng 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 drinking water and from the use of BPA in consumer products. EPA also examined potential ecologica l impact from the presence of BPA in the

environment.

Although most human exposure appears to co me 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.

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 and NIEHS are doing additional studies on the potential risks from these exposures, and the U.S. Department of Hea lth and Human Services (HHS) has provided recommendations for parents and families to take reasonable steps to reduce exposures, especially for young children. 4

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 products 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 United States may fall within TSCA jurisdiction, as shown in Table 1, below

.

4 Recommendations released by HHS on January 15, 2010 can be found at http://www.hhs.gov/safety/bpa/

.

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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 transportation 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 manufacture 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 assessments as well as numerous toxicological studies in assessing the hazard of BPA:

• Government Assessments:

o US (Federal) – Food and Drug Administ ration (FDA, 2008), National Toxicology Program/Center for Evaluation of Risk s to Human Reproduction (NTP-CERHR, 2008)

o US (State) - California Proposition 65 Developmental and Reproduction Toxicant Identification Committee (DAR TIC) (California, 2009a)

o International – Japan (AIST, 2007), European Union (EU) (EC, 2003, 2008), European Food Safety Administra tion (EFSA 2006, 2008a-b) and Canada (Canada, 2008)

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• Other Reviews: Harvard Panel (Gray et al ., 2004; 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 neurotoxicological effects (brain, behavior) at doses in

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

All of the government BPA assessments reviewed by EPA discuss these low-dose data and virtually all (FDA, 2 008; California, 2009a; AIST, 2007; EC, 2003, 2008; EFSA, 2006, 2008a-b) have considered them insufficient for the purposes of hazard evaluation/risk assessment, the exceptions being Canada (C anada, 2008) and the NTP-CERHR (NTP-CERHR, 2008). 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 the uncertainty led to a conclusion of “some concern” 5 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 comparing 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 eff ects (Ryan et al., 2010). 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). On the other hand, a different study reported that prenatal BPA exposure (again at low doses) in mice leads to adverse effects on the female reproductive tract later in life (Newbold et al., 2009). In addition, the NIEHS recently awarded $30 million dollars in grants for a two-year program of research on these issues (NIEHS, 2009). FDA announced on January 15, 2010 that it shared the perspective of the NTPCERHR and would undertake additional research in this area. (FDA, 2010).

Given the laboratory animal data, it is impor tant to note that metabolism studies have been performed in multiple spec ies (rats, mice, monkeys, and hu mans) and show that humans and rodents metabolize BPA differently. Data in all four species indicate metabolism by

5 NTP’s possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. “Some concern” thus represents the mid-point of a five-level scale of concern used by the NTP. In the case of BPA, the NT P stated it “expressed “some concern” for potential exposures to the fetus,

infants and children. There are insufficie nt data from studies in humans to reach a conclusion on reproductive or developmental hazards presented by current exposure s to bisphenol A, but th ere is limited evidence of developmental changes occurring in some animal studies at doses that are experienced by humans. It is uncertain if similar changes would occur in humans, but the possibility of adverse health effects cannot be dismissed.”

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conjugation in the liver with gl ucuronic acid to form the me tabolite BPA-glucuronide (BPAG).

The relative amount of free-BPA and BPAG circulat ing in mammals is important because freeBPA (“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. These differences in metabolism suggest that rodents may be more sensitive to effects from BPA than humans.

BPA has been found in human biological sample s (serum, breast milk, urine, fetal blood, and umbilical cord blood). The litera ture reporting these results reflects both a variety of analytical techniques and the BPA forms measur ed (i.e., total BPA , free-BPA and BPAG). In 2008, the CDC reported that BPA was detected in the urine of 93% of the 2,517 people tested in

the 2003-4 National Health and Nutrition Examina tion Survey (NHANES) (Calafat et al., 2008). Recently, urinary BPA concentrations measured 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 general popula tion. Over 90% of the BP A found in the urine in that study was in the form of a glucuronide conj ugate (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 adult rates

until months after birth. The aut hors also noted that the infa nts underwent intensive medical intervention, and that so me of the BPA exposure may have b een attributable to contact with

medical devices.

There was a recent report in which a cross- sectional study design was used to suggest an

association between BPA levels in humans and a higher risk of diabetes, heart disease, and elevation of certain liver enzyme activities (La ng et al., 2008). The authors examined the human data from the 2003-4 NHANES population. However, this report prompted an immediate review by the European Food Safety Authority (EFSA) (EFSA, 2008b) in late 2008 which concluded that the study did not provide su fficient proof for the stated a ssociations. EPA notes that the same investigative group recently published an on line research article repeating their original findings for heart disease but not diabet es on a second NHANES population from 2005-6 (Melzer et al., 2010).

Table 2 below is a list of each major assessment reviewed and the accompanying intake limits chosen in their respective assessments. So me assessments did not derive an intake limit

per se , but did make hazard/risk decisions:

• The California Proposition 65 Developmental and Reproductive Toxicant Identification Committee (DARTIC) voted on July 15, 2009 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) (California, 2009a).

• Thirty-eight scientists (k nown as the “Chapel Hill Group” ; vom Saal et al., 2007) concluded that: (1) th ere is relevance of in vitro data to in vivo effects; (2) ecological

studies are consistent with la b 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, and e ffects 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).

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• A National Toxicology Program (NTP) Cent er for Evaluation of Risks to Human Reproduction (CERHR) Panel (N TP-CERHR, 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 Intake Limits for Human Health Assessments

Authors Intake Limit (mg/kg/day) 1 Endpoint (Animal dose in mg/kg/day) And Study
USEPA (Integrated

Risk Information System; IRIS (1993)) 0.05 Reduced body weight (5) NTP 1982 two year cancer study in both rats and mice (as cited in USEPA 1993)

0.005 Systemic – reduced bod y wt and liver effects (5)

0.05 Irreversible reproductive effects (50) FDA (2008)

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

0.05

0.5 Body weight (5) Reproduction (50) Tyl et al., (2002, 2008) Japan (AIST, 2004)

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, 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 acceptable dose in humans. This value is what is shown here as

an “intake limit” and is what is co mpared to an expected/estimated ex posure value in a risk assessment. The uncertainty factors used by the various assessmen ts are: EPA (IRIS) – 1000; FDA – either 1000 (systemic or irreversible effects) or 100 (reversible 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 mammal s, and a review is provided by Crain et al. (2007). EPA’s screeni ng-level ecological hazard review for this Action Plan focused on effects in freshwater aquatic species to provi de a framework for determining whether toxicity may warrant further investigati on or risk management action.

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In general, studies have shown that BPA can affect grow th, reproduction and development in aquatic organisms. Among freshwat er organisms, fish appear to be the most sensitive species. Eviden ce of endocrine-related effects in fi sh, aquatic invertebrates, amphibians and reptiles has been reported at environmentally relevant exposure levels lower than those required for acute toxicity. Ther e is a widespread variation in reported values for endocrinerelated 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 (EC), 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 novel low-dose 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 eff ects such as the induction of intersex (or testes-ova in males and female s), decreased spermatogenesis, induction of vitellogenin, delayed or ceased ovulation, or hist ological liver changes were also reported in other studies referenced in the EU and Japane se hazard evaluations. However, because there were no standardized test guidelines or risk assessment guidance for evaluating some of these

endocrine-related effects 6 at the time of these assessments, the EU and Japan set ecotoxicological hazard values based on conventiona l effects (mortality and reproducti

from standardized studies. Canada concluded in its hazard characterizat ion that “[c]onsidered together, the data provide strong evidence that bis phenol A is capable of e liciting adverse eff (1) following prolonged exposure at levels below t hose usually seen to elic it effects in standa toxicity tests (i.e., tests based on recognized methods which evaluate endpoints such as survival, reproduction and growth); (2) following brief lo w-dose exposure, particularly at sensitive developmental stages, with effects apparent la ter in the life cycle; (3) on filial generations following parental exposure; and (4) using more than one mode of action.” (Canada, 2008). ve effects)

ects:
rd

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

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 (EC, 2008).

6 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.

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Table 3: Summary of Bisphenol A Ecological Hazard Values

Predicted No

Effect Country Endpoints Concentrations 1
(μg/L)

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. Based on the criteria set forth in EPA’s policy statement on Category for Persistent,
Bioaccumulative, and Toxic New Chemical Substances (64 Fed. Reg. 60194, November 4, 1999), BPA is expected to have low persistence (P 1) and low bioaccumulation potential (B1). (EC, 2003, 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 is present in the environment as a result of direct releases fr om manufacturing or processing facilities (USEPA, 2009a). BPA may also be present in the environment as a result of fugitive emissions during processing and hand ling, or release of unreacted monomer from products (NTP-CERHR, 2008). Accord ing to the Toxics Release I nventory (TRI) Database, total

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release of BPA in 2007 was 1,132,062 pounds 7 , with releases of 122,965 pounds to air, 6,246 pounds to water (direct), 14,972 pounds released on-site to land, and 684,638 pounds transferred off-site to land (USEPA, 2009a). 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, so il and dust), and use of consumer products. Given the tendency of young child ren to put inappropriate objects into their mouths, there is some minor pot ential for children to be exposed to BPA through their mouthing or accidental ingestion of consum er products. Dietary intake appear s to be the primary source of human exposure. However, food packaging and f ood 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; processi ng; industrial uses; commercial uses; selected consumer uses; inge stion of BPA in drinking water, including drinking water contaminated by wa stewater releases to surface water, drinking water drawn from ground water contaminated by leachate from la ndfills, and drinking water distributed through BPA-based water pipes; and inci dental ingestion of BPA from contact with consumer products. OPPT used release data, modeling, and informa tion available in peer-re viewed articles and government publications to obtain information on exposure to BPA.

Very little information is available on e xposure from consumer products. While noting that the primary intake for children six m onths and older came through food, Miyamoto and Kotake (2006) also estimated exposure to BPA fo r Japanese 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. Current information posted by the HHS indicates that most plastic toys that children put in their mouths do not contain BPA 4 . No studies were identif ied measuring potential exposures to adults or children from contact with other consumer products.

Limited information is available for BPA concentrations in U.S. water and other environmental media (Table 4, providing values from all of the studies cited in this discussion). Most environmental monitoring resu lts show that the concentrati ons of BPA in water bodies are

lower than 1 μ g/L, mainly due to its partitioning and bi odegradability 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 U.S. streams in 1999 and 2000 (Kolpin et al., 2002).

The maximum concentration of 12 μ g/L is an outlier; the BPA con centration in other U.S. 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 wastewat er treatment plant in Louisiana, and concentrations were not quantifiable in samp les collected from surface waters in Louisiana and in drinking water at various stages of treatment at plants in Louisiana (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., 2008a-b). 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

7 This total does not include off-site water transfer to POTWs (Publicly Owned Treat ment Works) wastewater treatment facilities (32,928 pounds) or transf er to incineration (2,759,705 pounds).

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et al., 2008b). BPA was among the top five most frequently detected organic compounds (Barnes, et al., 2008a).

In the summer of 2001, the U.S. Geological Survey 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 (Barnes, et al., 2008a; 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). Data for other landfill sites in the United States were not available, and this single point may not be representative of the country. 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). Studies conducted at Japanese

landfills resulted in maximum untreat ed leachate concen trations of 17,200 μ g/L and treated

leachate concentrations of 5.1 μ g/L (Crain et al., 2007).

Soil concentrations reported by NTP-CERHR (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 dry weight. Klecka et al. (2009) reported a median concentration of 0.6 ppb BPA in North American freshwater sediments, including nondetected samples; BPA concentrations in samples from the United Stat es ranged from 1.4 to 140 ppb dry weight. U.S. marine sediments were reported to have a medi an 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

11U.S. Environmental Protection Agency 3/29/2010

E-FAST2 8 modeling of BPA releases in the 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 also 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 (FDA, 2008). Human exposures from food contact uses are consiste ntly estimated by researchers to be higher than exposures from a ll 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)

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

Inhalation 0.7 – 2.7 b USE 1: Polycarbonates Dermal (solids) 0.31 – 3,100 c

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

Inhalation 0 d USE 3: Flame Retardants 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 has been evaluated as a chemical of potential concern by some U.S. agencies and

other countries sin ce the early 1980’s.

8 Information on E-FAST2 can be found at http://www.epa.gov/opptintr/exposure/pubs/efastdl.htm

.

12U.S. Environmental Protection Agency 3/29/2010

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 Fed. Reg. 21001, June 4, 1987). That 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 Environment and Public Works Committee Print 99-169, so there was no separate discussion of the justification for placing BPA

on the initial TRI list.

In 2009, the EPA Office of Water considered BPA during its development of the third Candidate Contaminant List (CCL3) of substances 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 heal th concern because its measured presence in water was well below potential effect levels in gu ideline studies, and thus did not appear on the final CCL3 list. The notice publishing the fi nal CCL3 list (74 Fed. Reg. 51850, October 8, 2009) does not specifically address BPA, but suppor ting materials available on the EPA website describe the process and criteria used in the de velopment of the list, including the information on BPA (USEPA, 2009b).

Connecticut, Minnesota, Wisconsin, Washi ngton, Chicago and Suffolk County, N.Y., have banned the sale of polycarbonate baby bottles, food containers and cups that contain BPA. The Connecticut ban also applies to infant formula cans and all reusable food and beverage containers. The Suffolk County ban (County of Suffo lk, 2009) went into effect in July 2009. The Minnesota ban (Minnesota, 2009) went into e ffect on 1/1/2010, and the Chicago ban (Chicago, 2009) on 1/31/2010. The Wisconsin ban (Wisconsin 2010) will go into effect on 6/15/2010, and the Connecticut ban (Connecticut, 2009) will ta ke effect on 10/1/2011. The Washington state ban (Washington, 2010) will take e ffect on 7/1/2010 concerning food and drink containers for children three years old and under, and will ban BPA in sports water bottles effective 7/1/2012. Similar bills banning BPA in children’s food a nd drink containers passed both houses in Maryland (Maryland, 2010) in February 2010, and if they are signed in to law by the governor,

would take effect on 1/1/2012. Calif ornia bill (California, 2009) to ban the use of BPA in baby bottles and cups and infant formula cans failed to pass in September 2009 and was moved to the inactive file. A similar bill failed to pa ss in Oregon (Oregon, 2010) in February 2010.

International Regulatory Reviews and Actions

Numerous foreign governmental bodies and review panels have conducted human health risk assessments for BPA in the recent past . Japan (AIST, 2007), the European Union (EC, 2008), and the European Food Safety Administrati on (EFSA, 2008) all concluded within the past three years that the novel studies indicating low dose, endocrine-re lated effects were insufficient for the purposes of hazard evaluation/risk asse ssment. Using hazard values derived by dividing the doses used in standardized animal studies by the respective uncertainty factors applied by the different regulatory bodies, these regulatory bodies concluded that expected exposures even from

13U.S. Environmental Protection Agency 3/29/2010

food contact uses, the largest expected source of exposure, did not present concern for risk to

human health.

In contrast, on June 26, 2009, Canada became th e first country to take regulatory action against BPA. Canada announced that it was m oving forward with proposed regulations to prohibit the advertisement, sale and importati on of polycarbonate plas tic baby bottles that contain BPA, to reduce newborn and infant expo sure to this substance. In announcing this decision, Canada noted “The Government has conc luded that exposure levels for newborns and infants up to 18 months of age are below those that could cause health effects. However, due to the uncertainty raised in some studies relating to the potential effects of low levels of BPA, the Government wants to further limit exposure.” (Canada, 2009).

Ecological risk for BPA has been evaluate d by the European Union (EC, 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. Based on a novel low-dose study (Lahnsteiner et al., 2005), Canada concluded that BPA concentrations in water have the pot ential to cause adverse effects on populations of pelagic organisms in Canada and concentrations in biota have the potential to cause adverse effects in populations of wildlife in Canada, but that there is a lo w risk of direct adverse effects to sediment organisms and to avian wildlife spec ies in Canada. In the conclusion of its risk assessment, Canada stated 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 concentration orunder conditions that have or may have an immediate or longterm harmful effect on the environm ent or its biological diversity.”

In August 2009, Taiwan designated BPA as a Class 4 toxic substance under the Toxic Chemical Substances Control Act (Taiwan, 2009). A Class 4 toxic substance is defined as a

substance for which there is c oncern of pollution of the enviro nment or the endangerment of

human health. Handlers of Class 4 substances are required to k eep and report records of the toxicity, production, release, and use of those chemicals, but th e chemicals are not subject to other restrictions on handling, transportation, or use (Taiwan, 2007). Cl ass 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 regu latory controls. Similarly, environmental concentrations of BPA, apart from isolated hot sp ots, are estimated generally to be lower than the

levels associated with effects in standardized toxicological studies done according to established guidelines. The complicating f actor, however, is the uncertain ty surrounding the meaning and

14U.S. Environmental Protection Agency 3/29/2010

relevance both to humans and the environment of the effects seen in some novel low-dose studies, because some concentrations are simila r to levels associated with observed effects reported in those studies.

Reproductive and developmental toxicity are the most sensitive e ffects observed in the guideline studies, and some novel studies suggest the potential fo r endocrine-related effects at much lower levels than the effect levels identified in the standardized studies. Accordingly, BPA exposures raise particular quest ions concerning children’s healt h. Children may be exposed to BPA before birth through their mo thers’ exposures, and directly through the use of BPA in food packaging materials and child feeding products (such as baby bottles, sippy cups, and spoons) within FDA jurisdiction. FDA is conducting furthe r studies on potential health risks to both children and adults from exposure to BPA in food contact materials (FDA, 2010), and HHS has provided recommendations on how parents and families can reduce their potential exposure to BPA while this investigation continues 4 . Children and adults may also be exposed to a lesser extent through contact with other consumer products and through contac t with environmental media (e.g., air and water). Children’ s exposures are greater than a dults’ due to increased intakes of food, water, and air per pound of body weight.

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 Human 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 (NIEHS, 2009). Including these Recovery Act funds, NIEHS is invest ing approximately $30 million 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 in cluding behavior, obesity, diab etes, reproductive disorders, development of prostate, breast and uterine cancer, asthma, cardiovascular diseases and transgenerational or epigenetic effects.

Given that human exposures from TSCA us es of BPA are minor compared with human exposures from uses under FDA jurisdiction, EPA considers that FDA has the lead in making human health judgments on BPA. EPA does not consider that action under TSCA would be warranted at this time on the basis of potential human health concerns from exposures through

TSCA uses of BPA.

EPA has jurisdiction over environmental exposures to BPA. Although there is disagreement in interpreting the novel low-dose st udies and some of the effects observed in the many aquatic toxicity studies performed thus far with BPA, a compar ison 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

15U.S. Environmental Protection Agency 3/29/2010

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. Additional informati on would help to resolve these uncertainties.

16U.S. Environmental Protection Agency 3/29/2010

IX. Next Steps

In conducting this review of bisphenol A, EPA considered a number of potential actions, including regulatory actions under TSCA sections 4, 5 and 6; cooperative activities with other federal agencies; and voluntary actions through 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 lo w-dose studies, EPA intends to:

1. Consider initiating ru lemaking under section 5(b)(4) of the Toxic Substances Control Act (TSCA) to identify BPA on the Concern Li st as a substance that may present an unreasonable risk of injury to the environment on the basis of its potential for longterm adverse effects on growth, reproduction and development in aquatic species at concentrations similar to those found in the environment. A notice of proposed rulemaking is intended to publish in autumn, 2010.

2. Consider initiating rulemaki ng under section 4(a) of TS CA to develop data with respect to environmental effects relevant to a further determination that BPA either does or does not present an unreasonable risk of injury to the environment. This may include testing or monitoring data in the vi cinity of landfills, manufacturing facilities, or similar locations to determine the poten tial for BPA to enter the environment, including surface water, ground water, and drinking water, at levels of potential concern particularly for environmental organisms, pregnant women, and children. EPA anticipates publishing an advance not ice of proposed rulemaking in late 2010.

3. Initiate collaborative alte rnatives assessment activiti es under its Design for the Environment (DfE) program to encourage reductions in BPA manufacturing and use

to facilitate reductions in environmental releases and subseque nt exposures. One of these activities, intended to be initiated in April 2010, will address thermal and carbonless paper coatings, a use where preferab le alternatives to BPA may be readily available. This DfE alternatives 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 BPA, which would be expected to be more available for exposure than BPA bound into resin or plas tic. Popular uses of this paper include airline tickets, event and cinema tickets, labels, and point of sale applications (receipts). While there is little concern for dermal absorption of BPA, free BPA can readily be transferred to sk in and residues on hands can be ingested. Use of BPA in paper also may contribute to the presence of BPA in the stream of recycled paper used in toilet paper, paper tableware, and other products, and may contribute to the presence of BPA in landfills since paper products are a major solid waste stream. Additionally, EPA intends to in itiate alternatives analys es for BPA used in foundry castings since foundries are accountable for large releases of BPA as reported under TRI, and for BPA-based materials lining water and waste water pipes since this application may have a potential for human and environmental exposure.

17U.S. Environmental Protection Agency 3/29/2010

EPA does not intend to initiate regulatory acti on under TSCA at this time on the basis of human health. EPA remains committed to protecti ng human health, but notes that most human exposure, including exposure to children, co mes through food packaging materials under the jurisdiction of the Food and Dr ug Administration (FDA). FDA, t ogether with the Centers for Disease Control and Prevention (CDC) and the National Institute of Environmental Health Sciences (NIEHS), is investing in important new health studies in both animals and humans to better determine and evaluate the potential he alth consequences of BPA exposures. EPA will continue to coordinate closely with FDA, CDC, and NIEHS on this activity. To the extent that FDA may identify health concer ns from BPA in food contact ma terials, EPA will work with FDA to identify and assess potential substitutes. Levels of exposure that may be identified by the ongoing review as being of concern to human hea lth, including children’s health, will affect the

extent to which EPA would take additional actio n to address potential risks to human health resulting 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 ot her sub-populations thr ough exposure from TSCA

uses.

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