*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

1 of 43 EO12866_BPA-Testing_ANPRM_2010-12-10.doc EO 12866 Review Draft as submitted.

BILLING CODE 6560–50–P ENVIRONMENTAL PRO TECTION AGENCY 40 CFR Part 799 [EPA–HQ–OPPT–2010–0812; FRL– XXXX

– X ] RIN 2070-AJ83 Testing of Bisphenol A

AGENCY: Environmental Protection Agency (EPA). ACTION: Advance notice of proposed rulemaking. SUMMARY : Bisphenol A (BPA, CASRN 80- 05-7), a high production volume chemical, is a reproductive, developmental, a nd systemic toxicant in animal studies and is weakly estrogenic. EPA is providing this advance notice of proposed rulemaking to request comment on requiring toxi city testing to determine the potential for BPA to cause endocrine-related and other adverse effects in envir onmental organisms at low concentrations. EPA is also seeking comment on requiring environmental testing consisting of sampling and monitoring for BP A in surface water, ground water, drinking water, soil, sediment, sludge, and landfill le achate in the vicinity of expected BPA releases to determine whether environmenta l organisms may currently be exposed to concentrations of BPA in the environment that are at or above levels of concern for adverse effects, including endocrine-related effects.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

2 of 43 DATES: Comments must be recei ved on or before [ insert date [ 60 ] days after date of publication in the Federal Register ]. ADDRESSES: Submit your comments, identified by docket identification (ID) number EPA–HQ–OPPT–2010–0812, by one of the following methods:

• Federal eRulemaking Portal : http://www.regulations.gov . Follow the on-line instructions for submitting comments.

• Mail : Document Control Office (7407M), Office of Pollution Prevention and Toxics (OPPT), Environmental Protect ion Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001.

• Hand Delivery : OPPT Document Control Office (DCO), EPA East Bldg., Rm. 6428, 1201 Constitution Ave., NW., Washington, DC. Attention: Docket ID Number EPA–HQ–OPPT–2010–0812. The DCO is open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The te lephone number for the DCO is (202) 564–8930. Such deliveries are only accepted during the DCO’s normal hours of operation, and special arrangements should be made for deliveries of boxed information.
Instructions : Direct your comments to doc ket ID number EPA–HQ–OPPT– 2010–0812. EPA's policy is that all comments received will be included in the docket without change and may be made available on-line at http://www.regulations.gov , including any personal information provided, unless the comment includes information claimed to be Confidential Business Info rmation (CBI) or other information whose disclosure is restricted by st atute. Do not submit informati on that you consider to be CBI or otherwise protected through regulations.gov or e-mail. The regulations.gov website is an “anonymous access” system, which means EP A will not know your identity or contact*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

3 of 43 information unless you provide it in the body of your comment. If you send an e-mail comment directly to EPA without going through regulations.gov, your e-mail address will be automatically captured and included as part of the comment that is placed in the docket and made available on the Internet. If you submit an electronic comment, EPA recommends that you include your name and other contact information in the body of your comment and with any disk or CD-ROM you submit. If EPA cannot read your comment due to technical difficulties and cannot contact you for clarification, EPA may not be able to consider your comment. El ectronic files should a void the use of special characters, any form of encryption, and be free of any defects or viruses.
Docket : All documents in the docket are list ed in the docket index available at http://www.regulations.gov . Although listed in the index, some information is not publicly available, e.g., CBI or other information whose disclosure is re stricted by statute. Certain other material, such as copyrighted material, will be publicly available only in hard copy. Publicly available docket mate rials are available electronically at http://www.regulations.gov , or, if only available in hard copy, at the OPPT Docket. The OPPT Docket is located in the EPA Docket Center (EPA/DC) at Rm. 3334, EPA West Bldg., 1301 Constitution Ave., NW., Washington, DC. The EPA/DC Public Reading Room hours of operation are 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. The telephone number of the EPA/DC Public Reading Room is (202) 566–1744, and the telephone number for the OPPT Docket is (202) 566–0280. Docket visitors are required to show photographic id entification, pass through a metal detector, and sign the EPA visitor log. All visitor bags are proce ssed through an X-ray machine*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

4 of 43 and subject to search. Visitors will be provi ded an EPA/DC badge that must be visible at all times in the building a nd returned upon departure. FOR FURTHER INFORMATION CONTACT: For technical information contact : Mary Dominiak, Chemical Control Division (7405M) , Office of Pollution Prevention and Toxics, Environmental Protectio n Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001; telephone number: 202-564-8104; e-mail address: dominiak.mary @epa.gov

. For general information contact : The TSCA-Hotline, ABVI-Goodwill, 422 South Clinton Ave., Rochester, NY 14620; telephon e number: (202) 554–1404; e-mail address: TSCA-Hotline@epa.gov

. SUPPLEMENTARY INFORMATION: I. General Information A. Does this Action Apply to Me? You may be potentially affected by this action if you manufac ture (identified by statute to include import) or process BPA (CASRN 80-05-7) . BPA is listed on the TSCA Inventory under the name phenol, 4,4’-(1-methyl ethylidene)bis-. Potentially affected entities may include, but are not limited to: • Chemical manufacturers (includi ng importers) (NAICS codes 325, 32411, e.g., chemical manufacturing and petr oleum refineries) of BPA. • Plastics material and resin ma nufacturers (NAICS code 325211, e.g., manufacturers and processors of BPA-base d polycarbonate plastics and epoxy resins).*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

5 of 43 • Foundries (NAICS codes 331512, 331524, 331528, e.g. steel investment foundries, aluminum foundries, and other non-ferrous foundries, except die-casting) using BPA in casting sands. • Paint and coating manufacturers (NAI CS code 325510), e.g. manufacturers of epoxy-based paints and other coating products that may contain BPA. • Paper recyclers (NAICS codes 322110, 322121, 3222, e.g. pulp mills, paper (except newsprint) mills, and converted pape r product manufacturers) that may process waste thermal paper containing BPA. • Materials recovery facilities (NAICS code 562920, e.g. facilities separating and sorting recyclable materials), that may handle thermal paper, polycarbonates, or food and beverage cans lined with BPA-based epoxy coatings. • Custom compounders of purchased re sins (NAICS code 325991, e.g. facilities where resins are made from recycled poly carbonate plastics) that may contain BPA. This listing is not intended to be exha ustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in this unit could also be affected. The North American I ndustrial Classification System (NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain en tities. If you have a ny questions regarding the applicability of this action to a particul ar entity, consult the technical person listed under FOR FURTHER INFORMATION CONTACT

. B. What Should I Consider as I Prepare My Comments for EPA?
1. Submitting CBI . Do not submit this information to EPA through regulations.gov or e-mail. Clearly mark the pa rt or all of the information that you claim*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

6 of 43 to be CBI. For CBI information in a disk or CD-ROM that you mail to EPA, mark the outside of the disk or CD-ROM as CBI and then identify electronically within the disk or CD-ROM the specific information that is clai med as CBI. In addition to one complete version of the comment that includes inform ation claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public docket. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2.
2. Tips for preparing your comments . When submitting comments, remember to: i. Identify the document by docket ID nu mber and other identifying information (subject heading, Federal Register date and page number). ii. Follow directions. The Agency may ask you to respond to specific questions or organize comments by referencing a Code of Federal Regulations (C FR) part or section number. iii. Explain why you agree or disagree; suggest alternatives and substitute language for your requested changes. iv. Describe any assumptions and provid e any technical information and/or data that you used. v. If you estimate potential costs or bu rdens, explain how you arrived at your estimate in sufficient detail to allow for it to be reproduced. vi. Provide specific examples to illustra te your concerns and suggest alternatives. vii. Explain your views as clearly as possible, avoidi ng the use of profanity or personal threats.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

7 of 43 viii. Make sure to submit your comments by the comment period deadline identified. II. Background A. What Action is the Agency Taking? As a follow-up to the BPA Action Plan released on March 29, 2010 (Ref. 1), EPA is issuing this advance notice of propos ed rulemaking to solicit public input on the necessity for and best approach to obtain environmental effects, exposure, and pathway information relevant to a determination th at BPA either does or does not present an unreasonable risk of injury to the environment. In particular, EPA requests comment on: 1. Whether EPA should propose requiring sp ecific toxicity testing to more fully characterize the effects of BPA on environmen tal organisms at low concentrations; and 2. Whether EPA should propose requiring environmental tes ting consisting of sampling and monitoring, particularly in the vi cinity of reported rel eases of BPA into the environment, and what design and protoc ol it should use for such sampling and monitoring, in order to id entify potential sources and pathways of exposure and determine the extent to which environmental organisms may be exposed to BPA concentrations of concern as determined by existing data and by a dditional studies that are either already underway or would be conducted under a proposed test rule. B. What Testing Is EPA Considering in this ANPRM? In this ANPRM, EPA is considering requiring both toxicity testing for environmental organisms exposed to BPA and environmental testing consisting of sampling and monitoring in the vicinity of reported BPA releases to measure its environmental presence. The toxicity test ing is being proposed to resolve existing*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

8 of 43 uncertainties concerning the potential for BPA to elicit adverse effects in ecologically relevant species, including endocrine-related impacts that could occur at low doses. The environmental testing is being proposed to resolve existing uncer tainties concerning potential sources of and pathways leading to environmental exposures and to determine whether or not the concentrations to which organisms currently may be exposed in the environment are at or above levels of con cern for adverse effects, including endocrinerelated effects. On May 17, 1985, EPA published a Proposed Rule (50 FR 20691) to require human health and environmental testing in response to the Interagency Testing Committee's (ITC's) designation of BPA for priority consideration for health and environmental effects. EPA proposed standa rd freshwater and marine acute fish and aquatic invertebrate toxicity te sts, and freshwater aquatic plan t toxicity tests. Test results were submitted in response to the proposal fo r freshwater and marine acute fish, acute aquatic invertebrate, and al gal toxicity. EPA’s Final Rule (51 FR 33047), published September 18, 1986, terminated the test rule pr ocess for environmental effects testing for bisphenol A. At the time, EPA determined th at the test data were adequate and that chronic freshwater organism tes ting was not needed because the LC 50 values for the standard acute aquatic organism toxicity te sts were greater than 1.0 ppm (1 mg/L), and the ratio of 48-hour to 96-hour LC 50 values were not greater than two. Since the 1986 Final Rule, however, several studies on BPA have raised concerns about its environmental effects at concentrat ions less than 1.0 ppm (1 mg/L). 1. What Is Currently Known About the Environmental Hazard of BPA?*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

9 of 43 The toxicity of BPA has been studied ex tensively, as indicat ed in the multiple studies cited in the Action Plan (Ref. 1) . There is general agreement among multiple reviewers that BPA is a repr oductive and developmental toxi cant at doses in animal studies of > 50 mg/kg-bw/day (delayed puberty in ma le and female rats and male mice; discussed in Ref. 2-9); > 235 mg/kg-bw/day (reduced fetal or birth weight or growth early in life, effects on testis of male rats; Ref. 9); and > 500 mg/kg-bw/day (possible decreased fertility in mice, altered estrous cycl ing in female rats, and reduced survival of fetuses; Ref. 9). Systemic effects (reduction in body weight, change s in relative organ weights, and increases in liver toxicity; Ref. 2-8) were obs erved at doses above 5 mg/kgbw/day (identified as a no observed advers e effect level (NOAEL); lowest observed adverse effect level (LOAEL) of 50 mg/kg- bw/day). There are reports of endocrinerelated low-dose effects on puberty and neurolog ical development (brain, behavior; Ref. 9) at doses in animal studies as low as 2 μ g/kg-bw/day. There is disagreement about whether effects seen at doses in animals less than 1 mg/kg/day are meaningful and relevant to humans. The Food and Drug Ad ministration (FDA), together with the National Institute of Environmental Health Sciences (NIEHS) and the Centers for Disease Control and Prevention (CDC), is e ngaging in additional re search to better determine and evaluate the potential human h ealth consequences of exposures to BPA, including exposures at low doses (Ref. 10). EPA is working with FDA, NIEHS, and CDC on this ongoing research, and is not proposing an y additional testing specifically in regard to human health issues at this time. Many studies have been conducted to determine potential effects of BPA exposure on invertebrates, fish, amphibians, reptiles, birds, and wild mammals, and a*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

10 of 43 review is provided by Crain et al. (Ref. 11). In general, studies have shown that BPA can affect growth, reproduction and development in aquatic organisms. Evidence of sublethal effects mediated through either endocri ne or non-endocrine related mechanisms in fish, amphibians, reptiles, and invertebrate aquatic organisms has been reported at potentially environmentally relevant exposure levels lower than those required for acute toxicity. There is a widespread variation in reported values for thes e sub-lethal effects, but many fall in the range of 1 μg/L to 1 mg/L . (Ref. 6; also, see in dividual studies noted in Table 2). The ecological hazard for BPA has been evaluated in three different risk assessments performed by the European Union (EU), Canada, and Japan (Refs. 7, 6, and 8), as summarized in Table 1 below. The different methodologies, endpoints and study results used by each country to derive thei r ecological values highlight the significant uncertainty in the estimated hazard values. Japan concluded that “the current exposure levels of BPA will not pose unacceptable risks to the local populations of aquatic life, particularly fish” (Ref. 8). In contrast, the EU concluded that although the predicted exposure concentrations were significantly belo w its hazard values, there was a need for further information and/or testing on such organisms as freshwater snails (Ref. 7). Canada used a study (Ref. 12) that re ported reduced sperm quality and delayed ovulation in brown trout at a very low concentration in wa ter (1.75 μg/L). Other effects such as the induction of intersex (or test es-ova in males and females), decreased spermatogenesis, induction of vitellogenin, delayed or ceased ovulat ion, or histological liver changes 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*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

11 of 43 assessment guidance for evaluating some of thes e endocrine-related e ffects at the time of these assessments, the EU and Japan set ecotoxicological hazard values based on conventional effects (mortality and reproductive effects) from standardized studies. In contrast, Canada concluded in its hazard char acterization that “[c]ons idered together, the data provide strong evidence that bisphenol A is capable of eliciting adverse effects: (1) following prolonged exposure at levels below those usually seen to elicit effects in standard toxicity tests (i.e ., tests based on recognized methods which evaluate endpoints such as survival, reproduc tion and growth); (2) following brief low-dose exposure, particularly at sensitive developmental stages, with effects apparent later in the life cycle; (3) on filial generations follo wing parental exposure; and (4 ) using more than one mode of action.” (Ref. 6). Canada concluded that BPA concentrations in water have the potential to cause adverse effects on populations of pelagic organisms in Cana da and concentrations in biota have the potential to cau se adverse effects in populations of wildlife in Canada, but that there is a low risk of direct adverse effects to sediment organisms and to avian wildlife species in Canada. In the conclusion of its risk asse ssment, Canada stated that it is considered appropriate to apply a precau tionary approach when characterizing risk, observing “it is concluded that bisphenol A is entering the environment in a quantity or concentration or under conditi ons that have or may have an immediate or long-term harmful effect on the environment or its biological dive rsity.” (Ref. 6). Table 1: Summary of Bisphenol A Ecological Values Country Predicted No Effect Concentrations 1 (μg/L) Endpoints European 1.5 The predicted no effect concentration (PNEC) for aquatic*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

12 of 43 Table 1: Summary of Bisphenol A Ecological Values Country Predicted No Effect Concentrations 1 (μg/L) Endpoints Union organisms (derived by using a st atistical 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 arrive at a value of 7.5 μg/L, which is divided by an uncertainty factor of 5, resulting in a PNEC of 1.5 μg/L (Ref. 7). 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 brow n trout study (Lahnsteiner et al, 2005) and applying an uncertainty factor of 10 (Ref. 6). Japan 1.6 The PNEC was derived by using the 16 μg/L no effect concentration (NOEC) for egg ha tchability 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 (Ref. 8). 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 concentration to PNEC is less than one, the risk is generally considered acceptable. As noted in the table, countries use different approaches for genera ting PNECs, and the precise values may differ even when based on the same studies.

EPA considers that the uncertainty de monstrated by these divergent opinions concerning interpretation of the results of existing environmental toxicity studies, particularly studies addressi ng potential effects at low leve ls of exposure, may indicate further testing is necessary to resolve the question of whether or not BPA presents an unreasonable risk of injury to the environment on the basis of those effects. This is due to the combination of the existence of meas ured values, as discussed in Unit II.B.4 and shown in Table 3, for BPA in U.S. surface wate rs at a mean concentration range of up to 1.78 μg/L (ppb) and a single maximum concen tration of 12 μg/L (ppb); in ground water at a mean concentration range of up to 1.9 μg/L (ppb) and a maximum concentration of 2.55 μg/L (ppb); and in freshwater sediment s at a median concentration of 0.6 μg/kg*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

13 of 43 (ppb) dry weight and a maximum concentra tion of 140 μg/kg (ppb) (See Table 3), and the existence of many hazard studies describing a variety of effects in aquatic organisms at some of these concentrations (See Table 2), leaving little or no room for a reasonable or acceptable margin of exposure. There are two principal, initial questions that need to be answered in order to assess the potential for BPA to harm the environment in the U.S.:

a. What additional hazard information is need ed to fully characterize the effects of BPA in environmental organisms at low doses and potentially environmentally relevant concentrations; and b. What levels of BPA are present in the e nvironment, particularly in areas where environmental exposures are likely to be highest (e.g., near BPA manufacturing facilities, polycarbon ate and epoxy resin manufacturi ng and processing facilities, foundries, landfills, wastewat er treatment plants (WWT Ps) and other locations associated with uses and/or releases of BPA)? 2. What Additional Hazard Information is Needed on the Effects of BPA on Environmental Organisms? EPA performed a literature search to identify relevant scientific information to assess the acute and chronic toxicity of BPA to envir onmental organisms from 2007 1 to the present. A total of 645 articles were found (Ref. 13), of which 31 were found to be of some relevance (Ref. 14). Since thorough anal yses of acute and ch ronic toxicity for “conventional endpoints” (which generally a ddress immediate effects on survival or reproduction) had already been conducted fo r BPA by Canada, the European Union, and

1 The starting date of 2007 was used to allow for some overlap between the thorough searches done by Canada, the EU and Japan*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

14 of 43 Japan (Ref. 6-8), EPA performed a more detailed evaluation of the scientific literature for sub-lethal effects at lower c oncentrations (< 100 μg/L). Thes e sub-lethal effects in both vertebrates and invertebrates could be me diated either through endocrine or nonendocrine-related mechanisms. There are many studies indicating such sub-lethal effects from BPA exposures at levels that, based on the information discussed in Unit II.B.4, appear to be potentially environmentally rele vant concentrations because they may occur in the environment. Some of thes e studies are included in Table 2. Table 2. Summary of Reported Hazard Effects of BPA at

Potentially Environmentally Relevant Concentrations

Test Organism Endpoint Effect Conc. (μg/L) References (Listed in Ref. 14) Amphibians Xenopus laevis (African clawed frog) Inhibited metamorphosis via T3 pathways 22.8 Heimeier et al., 2009 Xenopus laevis High ratio of females to males-1st study 23 Levy et al., 2004 Xenopus laevis High ratio of females to males-2nd study only at 23 Levy et al., 2004
Avian Gallus domesticus (chicken) Delayed development of wattle, comb and testes 2 Furuya et al., 2006

Gallus domesticus Inhibited development of seminiferous tubuli and spermatogenesis 20 Furuya et al., 2006
Fish Dicentrarchus labrax (seabass) Increased vitellogenin production 10 Correia et al., 2007 Misgurnus anguillicaudatus ( Chinese loach) Increased vitellogenin production 10 Lv et al., 2007 Orizias latipes (medaka) Egg hatchability delayed 13 only Yokota et al., 2000

Orizias latipes Loss of testicular structure, increased fibrotic tissue; decreased 50 Metcalfe et al., 2001*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

15 of 43 Table 2. Summary of Reported Hazard Effects of BPA at

Potentially Environmentally Relevant Concentrations

Test Organism Endpoint Effect Conc. (μg/L) References (Listed in Ref. 14) sperm cells. Orizias latipes Vitellogenin production 10 Kashiwada et al., 2002 Orizias latipes Increased female proteins (i.e. vitellogenin) 10 Tabata et al., 2001 Orizias latipes Decreased egg hatching in 2nd generation 2 only Japanese MOE, 2006 Orizias latipes Increased male hepatosomatic index 49.7 Japanese MOE, 2006 Pimephales promelas (fathead minnow) Increased vitellogenin production 52.8 Rhodes et al., 2007- unpublished Xiphophorus helleri (swordtail fish) Reduced sword tail length 20 Kwak et al., 2001 Cyprinus carpio (carp) Oviduct formation in males 32 Bowmer & Gimeno, 2001., unpublished

Cyprinus carpio Altered sex steroid levels; alterations in testes structure; oocyte atresi a 1 Mandich et al., 2007

Invertebrates Bellamya purificata (snail) Enzyme activities in gills and digestive glands 1 Li et al., 2008 Marisa cornuarietis (ramshorn snail) Superfeminization 1 Oehlmann et al., 2000
Marisa cornuarietis Increased egg and clutch production per female 0.25 at 20 degrees C Oehlmann et al., 2006
Marisa cornuarietis Increased egg production 0.25 at 27 degrees C Oehlmann et al., 2006
Marisa cornuarietis Increased clutch production 5 at 27 degrees C Oehlmann et al., 2006 Potamopyrgus antipodarum (snail) Increased growth/embryo production 5 only Jobling et al., 2004 Potamopyrgus antipodarum Unshelled embryos 30 Duft et al., 2003 Potamopyrgus antipodarum Increased embryo production 1 Duft et al., 2003*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

16 of 43 Table 2. Summary of Reported Hazard Effects of BPA at

Potentially Environmentally Relevant Concentrations

Test Organism Endpoint Effect Conc. (μg/L) References (Listed in Ref. 14)

Nucella lapillus (marine snail) Superfeminization; reduced sperm/penis length/prostrate gland in males 1 Oehlmann et al., 2000
Acartia tonsa (copepod) Increased egg production 20 (day 10 only) Andersen et al., 1999 Tigriopus japonicus (intertidal copepod) Delayed development (Parent) 0.1 Marcial et al., 2003 Tigriopus japonicus Delayed development (F1) 0.01 Marcial et al., 2003 Chironomus riparius Delayed emergence (2nd generation) 0.078 Watts et al., 2001 Chironomus riparius Mouthpart deformities 0.01 Watts et al., 2002

There is debate in the scientific literat ure on how best to inte rpret these low-dose, sub-lethal effects of BPA and other chemicals on envir onmental organisms. EPA is concerned that these sub-lethal effects may be having a detrimental effect on populations of aquatic organisms over time based on the reported increased susceptibility of subsequent generations exposed to BPA in mu ltigeneration invertebrate and fish studies. For example, in the intertidal copepod ( Tigriopus japonicus ), delayed development was reported in the first generati on at 0.1 μg/L, but at a 10-fold lower concentration of 0.01 μg/L in the next generation (Ref. 15). In the freshwater midge ( Chironomus riparius ), the first generation did not have a significant de lay in emergence time from the egg, but in the second generation emergence was delayed at 0.08 μg/L (Ref. 16). Egg hatchability decreased in fathead minnows ( Pimephales promelas ) at 640 μg/L in the first (F1) generation, then at 160 μg/L in the sec ond (F2) generation (Ref. 17). Although the mechanisms of action leading to effects may be different for vertebrate and invertebrate*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

17 of 43 organisms, this suggests the potential for increasing developmental and reproductive effects in populations of a quatic organisms that have re peated exposures to BPA for generations, even at very low concentrations. Testing with BPA has been extensive at sub-lethal concentrat ions, but the studies with effects across multiple sp ecies generally have flaws a ssociated with them, including lack of analytical monitoring, small sample size, inadequate re plication, or use of inappropriate statistical analys es leading to incorrect conclu sions of study results. Studies in ramshorn snails, for example, resulted in superfeminization at very low concentrations in one lab (Ref. 18), but those results were not found in studies by other researchers (Ref. 19-21). In addition, in some studies, BPA demonstrated effects at very low concentrations, but no effects were observed at the higher test concentrations. For example, tadpoles exposed to 2.3, 23 a nd 230 μg/L of BPA (Ref. 22) before metamorphosis had an increased female to male ratio at 23 μg/L only. These types of anomalous responses have been reported acro ss multiple species of fish and invertebrates for BPA and are characteristic of endocrine- active chemicals. They suggest inhibition of reproduction and development at low concentrations and overcompensation by the organism at higher concentrations in response to a toxicant (Ref. 23). It is difficult to interpret this inform ation in a regulatory context, because the scientific methods employed in individual acad emic settings to test a hypothesis are not necessarily geared toward meeting or establ ishing generally applicable guidelines for evaluating ecotoxicity and setti ng corresponding regulatory limits or controls. In terms of environmental toxicity, EPA considers the curr ently available research as evidence that*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

18 of 43 BPA has the potential to interact with th e estrogen hormone system. There is some evidence that BPA is also active via the thyr oid hormone pathway in amphibians and fish (Ref. 24, 25). More recent evidence indicates th at BPA also acts as an androgen receptor antagonist in both mammals and fish (Ref. 26). There are currently efforts underway by the EPA Office of Science Coordination and Policy (OSCP) through the Endocrine Disruptor Screening Program (EDSP) and the Organization for Economic Cooperation and Development (OECD) Endocrine Disr upter Testing and Assessment Work Group (EDTAWG), among others, to determine the best approach to evaluate and assess such effects. (Ref. 27-29). EPA is inviting comment on the need to further determine the hazard of BPA to various ecological species. The purpose of further testing would be to produce high quality data to identify and establish a dos e-response that could be used for risk assessment purposes for any adverse reproductiv e or developmental effects in different species that might result from the interacti ons identified through the available research. 3. What are the Issues for Comment Concerning Toxicity Testing? EPA invites comment on whether and what testing should be required to further describe the hazard of BPA to various ecologi cal species to resolve the low dose effects issue. EPA particularly invites comment on th e following, for which little or no clarifying hazard information appears to be currently av ailable or for which much of the available data have been derived from studies of ques tionable quality or uncer tain interpretation:

a. Effects of BPA on fish in long-term test s, including those that encompass multiple generations.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

19 of 43 b. Effects of BPA on amphibians at sensitive life stages, specifically metamorphosis (thyroid effects) and sexual development/differentiation (hypothalamic-pituitarygonadal axis effects).

c. Effects of BPA on birds over multiple generations. d. Effects of BPA on aquatic invertebrate species EPA further invites comment on the availa bility of current te st guidelines that could help address these issues. This ma y include, for example, considering the recommendations for Aquatic Life Criteri a For Contaminants Of Emerging Concern (Ref. 30). Additionally EPA is inviting the pub lic to describe and define where they believe there are data gaps concerning the e nvironmental toxicity of BPA, especially at low concentrations, or whether and on what basis they believe the current data are sufficient to determine whether BPA does or does not present an unreasonable risk of injury to the environment.
4. What Levels of BPA Are Present in the U.S. Environment? BPA is present in the environment as a result of direct releases from manufacturing or processing facilities (R ef. 31). BPA also may be present in the environment as a result of fugitive emissions during processing and handling, release of unreacted monomer from products (Ref. 9), or possibly from degradation of products under certain conditions. In addition, although no environmental studies on thermal paper have been done in the U.S., based on information from EPA’s review of European and Japanese studies, the use of unconjugated BP A in thermal paper also may contribute to environmental releases of BPA from paper ma nufacturing and recycling plants and to the presence of BPA in the stream of recycled paper used in toilet pa per, paper tableware,*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

20 of 43 and other products, and may contribute to the presence of BPA in landfills because paper products are a major contributor to the U. S. solid waste stream (Ref. 32-37). Recent studies also indicate therma l paper may contribute directly to human exposure to BPA through dermal contact. In one U.S. study, for example, pregnant women who worked as cashiers, who presumably had frequent contac t with thermal paper used in cash register receipts, had the highest urinary BPA concentr ations compared with pregnant women in other occupations (Ref. 38). According to the Toxics Release Invent ory (TRI) Database, to tal release of BPA in the U.S. in 2007 was 1,132,062 pounds, with releases of 122,965 pounds to air, 6,246 pounds to water, 14,972 pounds released on-si te to land, and 684,638 pounds transferred off-site to land. An additional 32,928 pounds were reported as off-site water transfer to Publicly Owned Treatment Works (POTWs ), with another 2,759,705 pounds transferred to incineration (Ref. 31). Some information is available for BPA concentrations in U.S. water and other environmental media (see Table 3, providing valu es from the U.S. studies cited in this discussion). Most environmental monitoring resu lts show that the concentrations of BPA in surface water bodies are lower than 1 μ g/L (ppb), mainly due to its partitioning and biodegradability properties (Ref . 39). BPA was detected at a median concentration of
0.14 μ g/L (ppb) and a maximum concentration of 12 μ g/L (ppb) in 41.2% of 85 samples collected from U.S. streams in 1999 and 2000 (Ref. 40). The maximum concentration of
12 μ g/L (ppb) was much higher th an any of the other sample s reported in the study; the next highest concentration reported was 5.2 μ g/L (ppb), and as indicated by the median concentration of 0.14 μ g/L (ppb), BPA concentration in other U.S. waters was much*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

21 of 43 lower. A recent review of reports of BPA in surface water found that BPA was reported in 26 studies in North America (2 in Canada and 24 in the United St ates) with detection in 80 percent (852 of 1068) of surface water samples. The median concentration reported was 0.081 μg/L (ppb) and the 95 th percentile concentrati on was 0.47 μg/L (ppb) (Ref. 41). Two studies have addresse d individual wastewater tr eatment plants (WWTPs) in two different parts of the U.S. In 2001 and 2002, BPA was not detected above the detection limit of 0.0001 μ g/L (ppb) in Louisiana in effl uent from a WWTP, in samples collected from surface waters in Louisiana, or in drinking water at various stages of treatment at plants in Louisiana (Ref. 42). A 2008 study sampled BPA in treated wastewater from the East Bay Municipal Uti lities WWTP in Oakland, California, and in a variety of locations that discharge to this WWTP (Ref. 43). This study reported detecting (limit of detection = 0.25 μg/L (ppb )) BPA in two of three treated wastewater samples at 0.38 and 0.31 μg/L (ppb). It also reported detecting BPA in wastewater generated by a pharmaceutical manufacturer (0 .295 μg/L (ppb)), an industrial laundry (21.5 μg/L (ppb)), and a paper produ cts manufacturer (0.753 μg/L (ppb)). While U.S. studies on wastewater are limited to only two state locations, a Canadian study published in 2000 reported BP A concentrations ranging from 49.9 to 0.031 μg/L (ppb) in sewage influent and effluent (generally < 1 μg/L (ppb) in the influent and < 0.3 μg/L (ppb) in the effluent) and from 36.7 to 0.104 μg/g (ppm) in raw and digested sewage sludge from multiple WWTPs in Canada (Ref. 44). The same authors reported that BPA contamination was detected in 100 percent of sewage samples from 31 WWTPs across Canada with concentrations ranging fr om 0.080 to 4.98 μg/L (ppb)*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

22 of 43 (median 0.329 μg/L (ppb)) for the influent and from 0.010 to 1.08 μg/L (ppb)(median 0.136 μg/L (ppb)) for the effluent (Ref. 45). Ba sed on comparison of influent and effluent levels, they estimated that BPA in the in fluent was removed by the sewage treatment process with a median reduction rate of 68 pe rcent. BPA was detected in sludge samples at concentrations ranging from 0.033 to 36.7 μg/g (ppm), on a dry weight basis. The authors also reported a wide range of BPA in wastewater discharges from industrial facilities in the Toronto area, with concentrations rangi ng from 0.23 to 149.2 μg/L (ppb). Higher BPA levels in wastewater were associ ated with facilities producing chemicals and chemical products and packaging and paper products, and with commercial dry cleaning establishments. BPA concentrations in pulp and paper mill sludge ranged from < 0.02 (below detection limit) to 3.33 μg/g (ppm), with a median value of 0.076 μg/g (ppm), on a dry weight basis (Ref. 45). EPA notes that U.S. wastewater treatment conditions and industrial and commercial discharges may di ffer from what was found in Canada, but considers this Canadian st udy to be informative. Municipal wastewater treatment produces solid byproducts, commonly referred to as sewage sludge. After additional treatment to meet regulatory standards for pathogen, nutrient, and metal content, this treated sewa ge sludge, now classified as biosolids, may be disposed of by land application; biosolids may also be incinerated or disposed of in landfills. A U.S. study published in 2006 meas ured BPA in nine treated biosolids products from WWTPs in seven states a nd found that all contained between 1,090 and 14,400 μg/kg (ppb) (median 4,690 μg/kg (ppb)) (Ref. 46). A 2008 study reported BPA in treated biosolids from a municipal U.S. WWTP at 4,600 μg/kg (ppb) and reported 81 μg/kg (ppb) in soil that received the land-appl ied biosolids (Ref. 47). That study detected*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

23 of 43 BPA at 81 μg/kg (ppb) in earthworms living in treated soil. The au thors also reported detecting 147 μg/kg (ppb) in a nearby “contro l” soil that did not receive treatment with biosolids. That anomalous result was not explained. In 2000, the U.S. Geological Survey (USG S) collected samples from 47 ambient groundwater sites (not drinking water wells) in 18 states and analyzed them for 65 organic wastewater contaminants. BPA was detected in 29.8% of the sampled groundwater sites, with a mean detected concentration of 1.78 μ g/L (ppb) and a range of
1.06 to 2.55 μ g/L (ppb). BPA was among the top five most frequently detected organic compounds in this study (Ref. 48, 49). In the summer of 2001, the USGS collected samples from 74 sources of raw, untreated, drinking water in 25 states and 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 groundwater and 49 su rface water sources of drinking water serving populations ranging from one family to more than 8 million people. BPA was detected in 9.5% of th ese samples at a reporting level of 1 μ g/L (ppb). The maximum concentration measured in these samples was 1.9 μ g/L (ppb) (Ref. 48, 50). Landfill leachate from one U.S. study re ported maximum BPA concentrations of
1.7 μ g/L (ppb) in landfill leachate and 1.4 μ g/L (ppb) in the receiving groundwater plume at a landfill on Cape Cod that was known to be leaking (Ref. 51). Data for other landfill sites in the United States were not available, and this single point is not representative of the country. Landfill leachate from othe r countries contained more than 500 μ g/L (ppb) of BPA (Ref. 39). Studies conduc ted at Japanese landfills re sulted in maximum untreated*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

24 of 43 leachate concentrations of 17,200 μ g/L (ppb) and treated leacha te concentrations of 5.1
μ g/L (ppb) (Ref. 11). Wilson et al. (Ref. 52) reported that BP A concentrations in soil samples taken from outdoor play areas of homes and daycare centers ra nged from 4-14 ppb dry weight, with means of 6-7 ppb dry weight. Kleck a et al. (Ref. 41) reported a median concentration of 0.6 ppb BPA in North Amer ican freshwater sediments, including nondetected samples; BPA concentrations in samples from the United States ranged from 1.4 to 140 ppb dry weight. Levels in U.S. ma rine sediments were reported to have a median of 3.5 ppb of BPA and to range from 1.5 to 5 ppb dry weight (Ref. 53).
Table 3: U.S. Reported Environmental Concentrations of BPA Location Mean or Range of Means (ppb) Range (ppb) References

Surface Water <0.0001 to 0.14* <0.0001 to 12 Barnes et al. (2008a) (Ref. 48) Boyd et al. (2003) (Ref. 42) Boyd et al. (2004) (Ref. 54) Focazio et al. (2008) (Ref. 50) Klecka et al. (2009) (Ref. 41) Kolpin et al. (2002) (Ref. 40) Staples et al. (2000) (Ref. 55) Zhang et al. (2007) (Ref. 56)

Groundwater NR** to 1.78 † <0.003 to 2.55 Barnes et al. (2008a) (Ref. 48) Barnes et al. (2008b) (Ref. 49) Focazio et al. (2008) (Ref. 50) Rudel et al. (1998) (Ref. 51) Drinking Water <0.0001 <0.0001 to 0.42 Boyd et al. (2003) (Ref. 42) Stackelberg et al . (2004) (Ref. 57)

Wastewater <0.0001 <0.0001 to 25 Boyd et al. (2003) (Ref. 42) Drewes et al. (2005) (Ref. 58) Jackson and Sutton (2008) (Ref. 43) Rudel et al. (1998) (Ref. 51) Tsai (2006) (Ref. 39) Soils 6 to 7 4 to 147 Kinney et al. (2008) (Ref. 47) Wilson et al. (2003) (Ref. 52) Sediment, Fresh 0.6* †† 1.4 to 140 †† Klecka et al. (2009) (Ref. 41) Sediment, Marine 3.5* 1.5 to 5.0 Stuart et al. (2005) (Ref. 53)*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

25 of 43 Table 3: U.S. Reported Environmental Concentrations of BPA Location Mean or Range of Means (ppb) Range (ppb) References
Biosolids 4600 to 4690* 1090-14,400 Kinney et al. (2006) (Ref. 46) Kinney et al. (2008) (Ref. 47) * Value is median ** Not Reported † Mean of values above Reporting Limit (1 ppb) †† Median value includes nondetected values below the MDL, while the reported range includes only detected values.
Although there is disagreement in interp reting some of the effects observed in studies performed to date with BPA, as described in Unit II.B.1 and 2, a comparison of the range of the effect levels observed in many studies and the predicted no effect concentration (PNEC) values used in three international regulatory risk assessments (0.175 to 1.6 μg/L, Table 1) with measured concentrations in some U.S. waters and sediments, which included values as high as 12 μg/L (ppb) (surface water), 2.55 μg/L (ppb) (ground water), and 140 ppb sediment (f reshwater sediment) (Table 2), indicate possible risk of injury to a quatic organisms. The single avai lable measurement of BPA in leachate from one U.S. landfill site is not suffi cient to represent or characterize the United States as a whole, and landf ill leachate data from other countries suggest that BPA concentrations in leachate may be significan tly higher than concentrations in surface water bodies. The direct exposure pathway from wastewater to envi ronmental organisms, along with the widespread dete ction of BPA in WWTP sludges, further suggest that land application of WWTP sludges may be a signif icant environmental exposure pathway that needs to be better understood. Although most currently available environm ental monitoring results show that the concentrations of BPA in U.S. water bodi es are lower than 1 μg/L (ppb) (median*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

26 of 43 concentration of 0.14 μg/L (ppb )), these environmental measur ements represent isolated snapshots in time. Because these results come from a variety of studies designed for very different purposes and conditions (for exam ple, laboratory analytical development contrasted with field monitoring), the data are not readily comp arable and cannot be assembled into a nationally or regionally repr esentative picture. Part icularly in light of the corresponding uncertainties described in Unit II.B.1 and 2 con cerning potential BPA hazards at low doses, the existing data do not allow EPA to determine how many areas may exceed potential concentrations of concern, how often or how long such concentrations may be exceeded, or the source s or pathways leading to BPA presence in the environment from manufacturing, proces sing, distribution in commerce, use, or disposal that may result in human and envir onmental exposures. EPA considers that these existing data would not be sufficient to dete rmine whether or not an unreasonable risk exists. To help resolve these uncertain ties, EPA is considering requiring that manufacturers and processors of BPA c onduct environmental testing consisting of targeted sampling and monitoring of surface water, groundwater, sediment, soil, landfill leachate, and drinking water on and adjacent to their properties, specifically in the vicinity of manufacturing fac ilities and such processing facil ities as foundries, WWTPs, paper and plastics recycling f acilities, and other sources of BPA releases as identified through TRI reporting and other information. Th ese test data could also help guide development of effective risk management actions if it should be determined that activities involving BPA present an unreasonabl e risk of injury to aquatic or other environmental systems.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

27 of 43 Fully understanding exposure pathways and in particular the magnitude, frequency, and duration of exposure could requ ire a nationwide survey of the occurrence of the chemical in environmental media a ssociated with production, processing, use, disposal and recycling faciliti es. However, at this time, EPA is proposing that selected monitoring of a more limited scope be c onducted to help identify the most likely locations of high exposure and the sources and pathways of exposure, to determine whether BPA may be present in those locations at concentrations that pose a risk of concern to aquatic or other systems. Mon itoring of aquatic sites and sediments near releases (effluents and sludge) from manufact uring and processing s ites (including on-site WWTPs) reporting high releases under TRI or associated wi th high releases identified from other information, as well as monitoring of sites that receive runoff from landfills, would be included. EPA believes these targeted monitoring data may provide information relevant both to the characterization of e nvironmental risk and to the potential focus of future risk management activities such as those under sec tion 6 of TSCA, if the data indicate such activities are warranted. EPA also considers th ese data would further inform the issue of potential human exposure levels attributable to sources other than the direct food contact uses believed to be the principal source of human exposure, which are regulated by the
FDA. In order to be useful to an investiga tion of potential envir onmental risks posed by BPA, environmental testing must be repres entative and of known quality. To accomplish this, data should be collect ed using approved or recogni zed sampling, preparation, and*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

28 of 43 analytical techniques. Appropriate quality a ssurance and quality controls also should be incorporated in the protocols for collection and analyses. Potential methodologies and protocol s for use in monitoring programs may include ASTM D7574-09 Standard Test Method for Determination of Bisphenol A in Environmental Waters by Liquid Chromat ography/Tandem Mass Spectrometry (Ref. 59); ASTM D5730-04 Standard Guide for Site Ch aracterization for Environmental Purposes With Emphasis on Soil, Rock, the Vados e Zone and Ground Water (Ref. 60); EPA Method 8270D (SW-846), Semivol atile Organic Compounds by Gas Chromatography/Mass Spectrometry (GC/MS), Revision 4 (Ref. 61); and other methods cited and described in such publications as Ba rnes et al. (2008) (Ref. 48) and Focazio et al. (2008) (Ref. 50). 5. What are the Issues for Comment Concer ning Environmental Testing Consisting of Sampling and Monitoring? EPA particularly invites comment on:

a. The extent and type of environmental testing that may be sufficient to characterize the environmental presence of BPA. b. The extent and type of environmental tes ting that may be sufficient to understand sources of and exposure from the high c oncentrations of BPA found in treated biosolids from WWTPs.

c. Whether environmental testing should be conducted now, or should be tiered to occur after the uncertaintie s associated with the hazards of BPA at low concentrations in the environment have been resolved.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

29 of 43 d. The locations where such environmental testing should be un dertaken, such as manufacturing, processing, recycling, f oundry, and other use, treatment, and disposal sites identified with BPA releases reported under TRI or other information.

e. The media (e.g., soil, sediment, sludge, WW TP influent and effluent, landfill leachate, drinking water, surface water, gr ound water) to be sampled at each such site. f. Which parties should be required to conduc t the testing and/or be potentially responsible for providing reimbursement to those who conduct specific tests.
g. The appropriate methods and protocols to use in such a e nvironmental testing
program. h. Whether and what additional environmen tal testing activities may be necessary to understand and characterize non- food-contact uses, sources, and environmental pathways that may contri bute to human exposure to BPA. i. Other information that may provide in sight into sources and pathways of environmental and human exposure to BP A released into the environment. j. The cost and economic feasibility of such environmental testing, for the different types of sites. B. What is the Agency's Aut hority for Taking this Action? EPA is issuing this advance notice of proposed rulemaking on certain toxicity testing and on certain environmental testi ng consisting of sampling and monitoring for the chemical substance BPA under TSCA section 4(a)(15 U.S.C. § 2603(a)).*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

30 of 43 Section 2(b)(1) of TSCA (15 U.S.C. § 2601(b)) states that it is the policy of the United States that “adequate data should be developed with respect to the effect of chemical substances and mixtures on h ealth and the environment and that the development of such data should be the re sponsibility of those who manufacture [which is defined by statue to include import] and those who process such chemical substances and mixtures[.]” To implement this policy, TSCA subsection 4(a)(1) provides that EPA shall require by rule that manu facturers or processors or bot h of chemical substances and mixtures conduct testing if th e Administrator finds that: (A)(i) the manufacture, distribution in comm erce, processing, use, or disposal of a chemical substance or mixture, or that any co mbination of such activ ities, may present an unreasonable risk of injury to health or the environment, (ii) there are insufficient data and ex perience upon which the effects of such manufacture, distribution in co mmerce, processing, use, or di sposal of such substance or mixture or any combination of such activ ities on health or the environment can reasonably be determined or predicted, and (iii) testing of such substances or mixtur e with respect to such effects is necessary to develop such data; or (B)(i) a chemical substance or mixture is or will be produced in substantial quantities, and (I) it enters or may reasonably be anticipated to enter the environment in substantial quantities or (II) there is or may be significant or substantial human exposure to such substance or mixture, (ii) there are insufficient data and experience upon which the effects of the manufacture, distribution in co mmerce, processing, use, or di sposal of such substance or*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

31 of 43 mixture or of any combination of such act ivities on health or the environment can reasonably be determined or predicted, and (iii) testing of such substance or mixture with respect to such effects is necessary to develop such data and (C) in the case of a mixture, the e ffects which the mixt ure’s manufacture, distribution in commerce, processing, use or disposal or any combination of such activities may have on health or the envi ronment may not be reasonably and more efficiently determined or predicted by test ing the chemical substances which comprise the mixture[.] (15 U.S.C. § 2603(a)). If EPA makes these findings for a chemical substance or mixture, the Administrator shall require th at testing be conducted on th at chemical substance or mixture. The purpose of the testing would be to develop data with respect to the health and environmental effects for which there is an insufficiency of data and experience, and which are relevant to a determination that the manufacture, distribution in commerce, processing, use, or disposal of the substan ce or mixture, or any combination of such activities, does or does not present an unreasonable risk of injury to health or the environment. Id. Once the Administrator has made the re levant findings under TSCA section 4(a), EPA may require any health or environmen tal effects testing for which data are insufficient and which are necessary to devel op the data. EPA need not limit the scope of testing required to the factual basis for the se ction 4(a)(1)(A)(i) or (B)(i) findings as long as EPA also finds that there are insufficient data and experience upon which the effects of the manufacture, distribution in commerce, pro cessing, use, or disposal of such substance*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

32 of 43 or mixture or of any combination of such activities on health or the environment can reasonably be determined or predicted, and that testing is necessary to develop such data. This approach is explained in more detail in EPA’s TSCA section 4(a)(1)(B) Final Statement of Policy published in the Fe deral Register at 58 FR 28736, 28738-28739, May 14, 1993 (B Policy). Authority for requiring sampling and m onitoring for a chemical substance or mixture can be found within TSCA section 4. Se ction 4(a) authorizes EPA to require the development of data “which are relevant to a determination that the manufacture, distribution in commerce, proces sing, use, or disposal of su ch substance or mixture, or that any combination of such activities, does or does not present an unreasonable risk of injury to health and the environment.” The extent to which such activities may affect health or the environment is dependent in part upon the human and environmental exposures to the chemical substance occasio ned by those activities. As an example, section 4(a)(2)(A) specifically addresses testing for persistenc e of a substance. Testing to identify where and in what concentrations a chemical substance or mixture may become present in the environment contributes to an understanding of human and environmental exposures resulting from those activities. III. References 1. EPA. 2010. Bisphenol A Acti on Plan. Available online at http://www.regulations.gov/search/R egs/home.html#documentDetail?R=0900006480ad7
e0c 2. EPA. 1993. Integrated Risk Information System (IRIS) (1993). Accessed at http://www.epa.gov/ncea/iris/subst/0356.htm.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

33 of 43 3. FDA. 2008. U. S. Food and Drug Administration. Draft Assessment of Bisphenol A for Use in Food Contact Applications. http://www.fda.gov/ohrms/ dockets/AC/08/briefing/2008- 0038b1_01_02_FDA%20BPA%20Draft%20Assessment .pdf; peer review report and additional information available at http://www.fda.gov/Food/FoodIngr edientsPackaging/ucm166145.htm. 4. European Food and Safety Authority (EFSA). 2006. Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food . Summary Opinion of the Scientific Panel on food a dditives, flavourings, processing aids and materials in contact w ith food (AFC) related to 2,2-BIS(4-HYDROXYPHENYL) PROPANE. Question number EFSA-Q-2005-100 November. 5. European Food and Safety Authority (EFSA). 2008. Scientific Opinion of the Panel on Food additives, Flavourings, Proce ssing aids and Materials in Contact with Food (AFC) on a request from the Commission on the toxicokinetics of Bisphenol A. The EFSA Journal (2008) 759, 1-10. 6. Canada. 2008. Environment Canada, Health Canada. Screening Assessment for the Challenge Phenol, 4,4' (1-methyleth ylidene)bis- (Bisphenol A) CAS 80-05-7 . October 2008. http://www.ec.gc.ca/substances/ese/e ng/challenge/batch2/ batch2_80-05-7_en.pdf
7. EU. 2008. European Union Updated Risk Assessment Report. Bisphenol A,
CAS No: 80-05-7 . Institute for Health and Consum er Protection, European Chemicals Bureau, European Commission Joint Research Centre, 3rd Priority List, Luxembourg: Office for Official Publications of the European Communities.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

34 of 43 8. AIST (Japan’s National Institut e of Advanced Indus trial Science and Technology). 2007. AIST Risk Assessment Document Series 4. Bisphenol A. 9. NTP/CERHR. 2008. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bis phenol A. US Department of Health and Human Services. National Toxicology Program . Center for the Evaluation of Risks to Human Reproduction. http://cerhr.nieh s.nih.gov/evals/bisphenol/bisphenol.pdf 10. FDA. 2010. U.S. Food and Drug Admi nistration. Update on Bisphenol A for Use in Food Contact Applications: January 2010. Accessed at http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm197739.htm

. 11. Crain, D.A.; Eriksen, M.; Iguchi, T.; Jobling, S.; Laufer, H.; LeBlanc, G.A.; Guillette, Jr., L.J. 2007. An ecological assessment of Bisphenol A: evidence from comparative biology. Repr od. Toxicology (24): 225-239. 12. Lahnsteiner, F.; Berger, B.; Kletzl, M.: Weismann, T. 2005. Effect of Bisphenol A on Maturation and Quality of Semen and Eggs in the Brown Trout, Salmo trutta f. fario

. Aquatic Tox. 75: 213-224. 13. Reference to RAD bibliographical list of 645 articles found; list will appear in docket. 14. Reference to RAD bibliographical li st of 31 articles d eemed relevant; list will appear in docket. 15. Marcial, H.S.; Hagiwara, A.; Sne ll, T.W. 2003. Estrogenic compounds affect development of harpacticoid copepod Tigriopus Japonicus

. Env. Tox. and Chem

. 22(12), 3025–3030.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

35 of 43 16. Watts, M.M.; Pascoe, D.; Carroll, K. 2001. Chronic exposure to 17 α ethinylestradiol and bisphenol A-effect s on development and reproduction in the freshwater invertebrate Chironomus riparius (Diptera: Chironomidae). Aquat. Tox. 55,
113–124. 17. Sumpter, J.P.; Tyler, C.R.; Sherazi, A. 2001. Bisphenol-A: Multigeneration study with the fathead minnow ( Pimephales promelas ). Brunel University (unpublished; part of study published as Sohoni et al , 2001). 18. Oehlmann, J.; Schulte-Oehlmann, U.; Werner, K.; Jagnytsch, O.; Lutz, I.; Kresten, K.; Wollenberger, L.; Santos, E. M.; Paull, G.C.; Van Look, K.J.W.; Tyler, C.R. 2008. A Critical Analysis of the Biol ogical Impacts of Plasticizers on Wildlife. Philos. Trans. R. Soc ., B: Biol. Sci. 364(1526): 2047–2062. 19. Forbes, V.E.; Selck, H.; Palmqvist , A.; Aufderheide, J.; Warbritton, R.; Pounds, N.; Thompson, R.; van der Hoeven, N.; Caspers, N. 2007. Does bisphenol A induce superfeminization in Marisa cornuarietis ? Part I: Intra- and inter-laboratory variability in test endpoints. Ecotox. and Env. Safe . 66, 309–318. 20. Forbes, V.E.; Aufderheide, J.; Warbritton, R.; Thompson, R.; van der Hoeven, N.; Caspers, N. 2007. Does bisphenol A induce superfeminization in Marisa
cornuarietis ? Part I: Intra- and inter-laborator y variability in test endpoints. Ecotox. and Env. Safe . 66, 319–325. 21. Forbes, V.E; Aufderheide, J.; Warb ritton, R.; Thompson, R.; van der Hoeven, N.; Caspers, N. 2008. Effects of bisphe nol A on fecundity, egg hatchability, and juvenile growth of Maris Cornuarietis

. Env. Tox. and Chem . 27 (11), 2332–2340.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

36 of 43 22. Levy, G.; Lutz, I.; Krüger, A.; Kloas, W. 2004. Bisphenol A induces feminization in Xenopus laevis tadpoles. Environ. Res. 94, 102-111. 23. Calabrese, E.J.; Baldwin, L.A. 2 003. Hormesis at the National Toxicology Program (NTP): evidence of hormetic dos e responses in NTP dose-range studies. Nonlinearity Biol. Toxicol. Med. 1, 455–467. 24. Heimeier, R.A.; Das, B.; Buchholz, D.R.; Shi, Y. 2009. The Xenoestrogen Bisphenol A inhibits postembryonic vert ebrate development by antagonizing gene regulation by thyroid hormone. Endocrinology , 150, 2964-2973. 25. Ramakrishnan, S.; Wayne, N.L. 2008. Impact of bisphenol-A on early embryonic development and reproductive maturation. Reproductive Toxicology 25, 177–
183. 26. Ankley, G.T., K.M. Jensen, M.D. Kahl, E.J. Durhan, E.A. Makynen, J.E. Cavallin, D. Martinovic, L.C. Wehmas, N.D. Mueller and D.L. Villeneuve. 2010. Use of chemical mixtures to differentiate mechanisms of endocrine action in a small fish model. Aquat. Toxicol. 99, 389-396. 27. EPA. Endocrine Disruptor Screeni ng Program; Policies and Procedures for Initial Screening. 74 Fed.Reg. 17560. April 15, 2009. 28. EPA. Endocrine Disruptor Scre ening Program website. Accessed at http://www.epa.gov/scipoly/oscpendo/

. 29. Organization for Economic Co-ope ration and Development Environment Directorate. Endocrine Disruptor Testing and Assessment. Accessed at http://www.oecd.org/document/62/0,3343,en_2649_34377_2348606_1_1_1_1,00.html*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

37 of 43 30. EPA. 2008. Aquatic Life Criteria for Contaminants of Emerging Concern (Part 1) & Illustration of Reco mmendations using Data for 17 α -Ethinylestradiol (EE2). USEPA Office of Water, Washington, DC. 31. EPA. 2009a. Toxic Release Inventor y. 2007 Public Data Release, Released March 14, 2009. http://www.epa.gov/tri/tridata/index.htm#pdr 32. European Union. 2010. Risk Assessment Report, 4,4'-Isopropylidenediphenol (Bisphenol-A), CAS No: 80-05-7, (February 2010). 33. Vinggaard, A.M.: Körner, W.; Lund, K.H.; Bolz, U.; Petersen, J.H. 2000. Identification and quantification of estrogeni c compounds in recycled and virgin paper for household use as determined by an in vitro yeast estrogen screen and chemical analysis. Chem Res Toxicol. 13(12):1214-22. 34. Gehring, M.; Vogel, D.; Tennhardt, L.; Weltin, D.; Bilitewski, B. Undated. Bisphenol A contamination of wastepaper, ellulose and recycled paper products. http://rcswww.urz.tu-dresden.de/~ge hring/deutsch/dt/vortr/040929ge.pdf 35. Ozaki, A.; Yamaguchi, Y.; Fujita, T.; Kuroda, K.; Endo, G. 2004. Chemical analysis and genotoxicological safety assessment of paper and paperboard used for food packaging. Food Chem Toxicol. 42(8):1323-37. 36. Fukazawa, H.; Hoshino, K.; Shiozawa, T.; Matsushita, H.; Terao, Y. 2001. Identification and quantification of chlori nated bisphenol A in wastewater from wastepaper recycling plants. Chemosphere . 44(5):973-9. 37. Terasaki, M.; Shiraishi, F.; Fuka zawa, H.; Makino, M. 2007. Occurrence and estrogenicity of phenolics in paper-recycling process water: pollutants originating from thermal paper in waste paper. Environ Toxicol Chem. 26(11):2356-66.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

38 of 43 38. Braun J.M., Kalkbrenner A.E., Cala fat A.M., Bernert J.T., Ye X., et al. 2010 Variability and Predictors of Urinary Bi sphenol A Concentrations during Pregnancy. Environ Health Perspect doi:10.1289/ehp.1002366.39. Tsai, W. 2006. Human Health Risk on Environmental Exposure to BisphenolA: A Review. Journal of Environmental Science and Health Part C, 24:225-255. 40. Kolpin, D.W.; Furlong, E.T.; Meyer, M.T.; Thurman, E.M.; Zaugg, S.D.; Barber, L.B.; Buxton, H.T. 2002. Pharmaceu ticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: a national survey. Environ Sci Technol 36:1202–1211. 41. Klecka, G.M.; Staples, C.A.; Clark, K.E.; van der Hoeven, N.; Thomas, D.E.; Hentges, S.G. 2009. Exposure Analysis of Bisphenol A in Surface Water Systems in North America and Europe. Environ. Sci. Technol . 2009, 43(16):6145–6150. 42. Boyd G.R.; Reemtsma, H.; Grimm, D.A.; Mitra, S. 2003. Pharmaceuticals and personal care products (PPCPs) in surface an d treated waters of Louisiana, U.S.A. and Ontario, Canada. Sci Total Environ 311: 135-149. 43. Jackson, J.; Sutton, R. 2008. Sources of endocrine-disrupting chemicals in an urban wastewater, Oakland, CA. Sci. Total Env ., vol. 405:153-160. 44. Lee, H-B; Peart, T.E. 2000. Determin ation of bisphenol A in sewage effluent and sludge by solid-phase and supercritical fluid extraction and gas chromatography/mass spectrometry. J AOAC Int. vol. 83:290-7. 45. Lee, H-B; Peart, T.F. 2000. Bis phenol A contamination in Canadian municipal and industrial wast ewater and sludge samples. Water Quality Res. J Canada. vol. 35: 283-298.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

39 of 43 46. Kinney, C.A.; Furlong, E.T.; Zaugg, S.D.; Burkhardt, M.R.; Werner, S.L.; Cahill, J.D.; Jorgensen, G.R. 2006. Survey of Organic Wastewater Contaminants in Biosolids Destined for Land Application. Environ. Sci. Technol. Vol. 40:7207–7215. 47. Kinney, C.A; Furlong, E.T.; Kolpi n, D.W.; Burkhardt, M.R.; Zaugg, S.D.; Werner, S.L.; Bossio, J.P.; Benotti, M.J. 2008. Bioaccumulation of pharmaceuticals and other anthropogenic waste indicators in earthwo rms from agricultural soil amended with biosolid or swine manure. Environ. Sci. Technol. 2008, vol. 42: 1863–1870. 48. Barnes, K.K.; Kolpin, D.W.; Fo cazio, M.J.; Furlong, E.T.; Meyer, M.T.; Zaugg, S.D.; Haack, S.K.; Barber, L.B.; Thurman, E.M. 2008a. U. S. Geological Survey. Water-Quality Data for Pharm aceuticals and Other Organic Wastewater Contaminants in Ground Water and in Untreat ed Drinking Water Sources in the United States, 2000-01. Available at : http://pubs.usgs.gov/of/2008/1293/

. 49. Barnes, K.K.; Kolpin, D.W.; Furlong, E.T.; Zaugg, S.D.; Meyer, M.T.; Barber, L.B. 2008b. A National Reconnaissa nce of Pharmaceuticals and Other Organic Wastewater Contaminants in the United States: (I) Groundwater. Sci.Total Enviro . 402 (2–3), 192–200. 50. Focazio, M.J.; Kolpin, D.W.; Barnes, K.K.; Furlong, E.T.; Meyer, M.T.; Zaugg, S.D.; Barber, L.B.; Thurman, E.M. 2008. A National Reconnaissance for Pharmaceuticals and Other Organic Wastewater Contaminants in the United States—(II) Untreated Drinking Water Sources. Sci. Total Environ . 402(2–3), 201–216. 51. Rudel, R.A.; Melly, S.J.; Geno, P.W.; Sun, G.; Brody, J.G. 1998. Identification of Alkylphenols and Other Estr ogenic Phenolic Com pounds in Wastewater, Septage, and Groundwater on Cape Cod, MA. Environ. Sci. Technol 32:861-9.*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

40 of 43 52. Wilson, N.K.; Chuang, J.C.; Lyu, C.; Menton, R.; Morgan, M.K. 2003. Aggregate exposures of nine preschool children to persistent organi c pollutants at day care and home. J. Expo. Anal. Environ. Epidemiol. 13:187-202. 53. Stuart, J.D.; Capulong, C.P.; Launer, K.D.; Pan, X. 2005. Analyses of phenolic endocrine disrupting chemicals in marine samples by both gas and liquid chromatography-mass spectrometry. J. Chromatogr. A. 1079:136-145. 54. Boyd, G.R.; Palmerib, J.M.; Gr imm, D.A. 2004. Pharmaceuticals and Personal Care Products (PPCPs) and Endoc rine Disrupting Chemicals (EDCs) in Stormwater Canals and Bayou St. John in New Orleans, Louisiana, USA. Sci. Total
Environ. 333:137-48. 55. Staples, C.A.; Dorn, P.B.; Klecka, G.M.; O’Block, S.T.; Branson, D.R.; Harris, L.R. 2000. Bisphenol A Concentra tions in Receiving Waters Near U.S. Manufacturing and Processing Facilities. Chemosphere 40:521-525. 56. Zhang, S.; Zhang, Q.; Darisaw, S. ; Ehie, O.; Wang, G. 2007. Simultaneous Quantification of Polycyclic Aromatic Hydr ocarbons (PAHs), Polychlorinated Biphenyls (PCBs), and Pharmaceuticals and Personal Care Products (PPCPs) in Mississippi River Water, in New Orleans, Louisiana, USA. Chemosphere 66:1057-69. 57. Stackelberg, P.E.; Furlong, E.T.; Meyer, M.T.; Zaugg, S.D.; Henderson, A.K.; Reissman, D.B. 2004. Persistence of Phar maceutical Compounds and Other Organic Wastewater Contaminants in a Conven tional Drinking-Water-Treatment Plant. Sci. Total
Environ. 329:99-113. 58. Drewes, J.E.; Hemming, J.; Ladenburge r, S.J.; Schauer, J.; Sonzogni, W. 2005. An Assessment of Endocrine Disrupti ng Activity Changes during Wastewater*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

41 of 43 Treatment through the Use of Bioassays and Chemical Measurements. Water Environ.
Res. 77:12–23. 59. ASTM. 2009. ASTM International. ASTM D7574-09 Standard Test Method for Determination of Bisphenol A in Environmental Waters by Liquid Chromatography/Tandem Mass Spectrometry. http://www.astm.org/Standards/D7574.htm

. 60. ASTM. 2004. ASTM International. AS TM D5730-04 Standard Guide for Site Characterization for Environmental Purposes With Emphasis on Soil, Rock, the Vadose Zone and Ground Water. http:// www.astm.org/Standards/D5730.htm

. 61. USEPA. 1998. U.S. Environmenta l Protection Agency. EPA Method 8270D (SW-846), Semivolatile Organic Com pounds by Gas Chromatography/Mass Spectrometry (GC/MS), Revision 4. http://www.epa.gov/sam/pdfs/EPA-8270d.pdf

. IV. Statutory and Executive Order Reviews Under Executive Order 12866, entitled “Regulatory Planning and Review” (58 FR 51735, October 4, 1993), this action was su bmitted to the Office of Management and Budget (OMB) for review. Any changes made to this document in response to OMB comments received by EPA during that review have been documented in the docket as required by the Executive Order. Since this document does not impose or propose any requirements, and instead seeks comments and suggestions for the Agen cy to consider in possibly developing a subsequent proposed rule, the various other review requirements that apply when an agency imposes requirements do not apply to this action. Nevertheless, as part of your*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

42 of 43 comments on this notice, you may include a ny comments or information that you have regarding this action. In particular, any comments or informa tion that would help the Agency to assess the potential impact of a rule on small entiti es pursuant to the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.); to consider voluntary consensus st andards pursuant to section 12(d) of the National Technol ogy Transfer and Advancement Act of 1995 (NTTAA) (15 U.S.C. 272 note); to consider environmental health or safety effects on children pursuant to Executive Order 13045, en titled “Protection of Children from Environmental Health Risks and Safety Ri sks” (62 FR 19885, April 23, 1997); or to consider human health or environmental e ffects on minority or low-income populations pursuant to Executive Order 12898, entitled “Fed eral Actions to Address Environmental Justice in Minority Populations and Low-In come Populations” (59 FR 7629, February 16, 1994). The Agency will consider such comments during the development of any subsequent proposed rule as it takes appropriate steps to address any applicable requirements. List of Subjects in 40 CFR Part 799 Environmental protection, Bisphenol A, BPA, Chemical testing, Chemicals, Hazardous substances, Reports and recordkeeping requirements.

Dated: ____________________*** EO 12866 Review Draft – Do Not Cite, Quote or Release During Review ***

43 of 43 __________________________________________

Assistant Administrator, Office of Chemical Safety and Pollution Prevention.