Docket Number EPA-HQ-OPP-2013

- 0598 www.regulations.gov



## Sodium Metabisulfite and Sulfur Dioxide Preliminary Work Plan Registration Review: Initial Docket Case Numbers 7019 and 4056
September 2013

Approved By:

## G~~**)cu.e~..** 

## P**v~~'UA** 

# ,:) "") Richard P. Keigw in, Jr., Director Pesticide Re-evaluation Division

Date Susan Lewis, Acting Director Antimicrob i als Division

Date

### Inorganic Sulfites Preliminary Work Plan - Table of Contents
Overview Anticipated Data Needs Statutory and Regulatory Authority Chemical Facts Use and Usage Information Recent Actions 3 4 5 6 7 9 Anticipated Risk Assessments for Registration Review 10 Timeline 12 Next Steps 12 Appendix -Additional Considerations in the Inorganic Sulfites Registration Review 13

References: Thi s Preliminary Wo rk Plan summarizes the Environmental Protecti on Agency's current position based on the following documents : 1. Registration Review: Preliminary Problem Formulation for Ecological Risk, Environmental Fate, Endangered Species, and Drinking Water Assessments for Sulfur Dioxide (PC Code 077601) and Sodium Metabisulfite (PC Code 111409). Geoffrey Sinclair and L a rry Liu. Ju ly 23, 2013. 2. Inorganic Sulfites. Human Health Assessment Scoping Document in Support of Registration Review

. l deliz Negron-Encarnacion, Ronnie Bever, and Alexandra LaMay. September 1 1, 2013. 3. Inorganic**Sulfite~** (Sulfur Dioxide and Sodium Bisulfite): Review of Human Incidents. Elizabeth Evans and Sha:nna Recore. May 15, 2013. 4. BEAD Chemical Profile for Registration Review: .Sodium metabisulfite. Michelle Ranville, Carl Chen, and Katherine Stebbins. December 7, 20 1 0.
5. BEAD Chemical Profile for Registration Review: Sulfur Dioxide (07760I). Tara Chandgoyal, Rafae l Prieto, and Stephen Smearman. April 11, 20 13.
6

. Sodium Metabisulfite Appendix A

. October 30, 2009.
7. Sulfur Dioxide Appendix A. February 5, 2013. These and other supporting documents for the inorganic sulfites registrati on review case may be found in the docket EPA- H Q-OPP-20 1 3-0598 at http://www.regulations.gov.

2OVERVIEW The docket for sodium metab i sulfite and sulfur dioxide is now open, initiating the first public comment period for this registrati on review (docket number E PA- H Q-OPP-20 13-0598). Both sodium metabisulfite and sulfur dioxide are registered for use as commodity f umigants

. Sodium metabisulfite products are formulated as an anh ydrous powder contained in sem i-sealed pads which are added to containers holding grapes prior to s hipping ; the pads absorb moisture and release lo w le vels of sulfur dioxide to inhibit the growt h ofthe fungus Botrytis cinere a. Sodium metabisulfite is also registered for use in enhanced packaging stickers to control mold and odor during shipping of clothing, purses, and other commod ities. Sulfur dioxide products are formulated as gas and as compressed liquid that converts to gas upon relea se for post

- harvest grape fumigation in cold-storage warehouses , trucks, vans, trail ers, and rail cars (also fo r control of Botrytis cinerea). Sulfur diox ide i s al so registered for use in the fumigation of barrels and corks used in wine production . There are no regi s tered res identia l uses of either active ingredient. This Prelim inary Work Plan (PWP) document explains what EPA's Office of Pesticide Program s knows about sodium metabisulfite and sulfur dioxide , hi g hlighting anticipated data and assessment needs , identifying the types of information that would be especially useful to the Agency in conducting the review , and pro v idin g an antic ipated timeline for completing the re g i stration review for sod ium metabisulfite and sulfur dioxide. The registrati on review process was designed to include a public participation component to so licit input f rom interested stakeho lders . The Agency in tends, by sharing this info rmati on in the docket, to inform th e public of what it know s about sodium metabisulfite and sulfur dioxide and what t y pes of new data or other information would be helpful for the Age ncy to receive as it moves toward a decision o n sodium metabisulfite and sulfur dioxide. The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional information that will help the Agency's decision-making process for these chemicals. In addition to general areas on which persons may wis h to comment, there are some areas identified in the PWP and Appendix about which the Agency specifically seeks comments and information. Interested stakeholders could include : environmental non-profit or intere st groups; pesticide manufacturer s; agricu ltural labor or commodity groups ; commercial , instituti ona l, residential , and other users of pesticides ; or the public at large. The Preliminary Work Plan begins by listing the anticipated data needs for sodium metabisulfite and sulfur dioxide. Next, it discusses the statutory and regulatory authority for R eg istration Review

. Then the d ocu ment provides chemical fact s, use and usage information, recent actions , the anticipated risk assessments, and a project ed registration review timeline for so dium metabisulfite and s ul fur dioxide. Finally, the Appendix to this document includes identification and discuss i on of some areas that are considered generall y in Registrati on Review along with some ad ditional chemical case-specific information.

3ANTICIPATED DATA NEEDS Table 1 below summarizes anticipat ed data needs for sodium metabisulfite and sulfur dioxide

. For addi tio nal discussion of the anticipated data needs, see the Registration Review : Preliminary Problem Formulation for Ecological Risk, Environmental Fate, Endangered Species, and Drinking Water Assessments for Sulfur Dioxide (PC Code 077601) and Sodium Metabisulfite (PC Code 111409) and Inorganic Sulfites. Human Health Assessment Scoping Document in Support of Registration Review

. Table 1: Anticipated Data Needs for Sodium Metabisulfite and Sulfur Dioxide Registration Review Estimated Guideline Timeframe Number Study T itle Test Material (Mo nths from receipt of DCI)
860.1500 Crop field trial s- post-harvest fumigation 1 Sulfur dioxide, 24 TEP 875.1400 Applicator

- inhalation indoo r exposu re Sulfur dioxide, 24 TEP 875 .1700 Product use in format ion Sulfur dioxide, 12 TEP 875.2500 Post application

- inhalation indoor exposure Su lfur dioxide, 24 TEP Non- Avi an acute inhalation toxic ity study with Su lfur dioxide, 24 guideline bobwhite qua il TGA I

Non

- Honeybee acute vapor phase Sulfur dioxide, 24 gu id el in e TGAI

Non- Vegetative vigor vapor phase Sulfur dioxide, 12 g uideline TEP

Non- Monitoring data on fum igated commodities (from Sodium metabisulfite, 24 g uid el i ne sod ium metabisulfite pads) TEP TGAJ = techmcal grade active mgredient; TEP = typ1cal end-use product Additional information needs: Current labels do not have clear app li cation information such as maximum single application rate, maximum number of applications per year, and minimum app li cation interval. Additional information on typical number of applications and application intervals in storage and shipping would also be helpful. Some sodium metabisulfite labels specify that grapes can be fumigated with gaseous sulfur dio x ide and then subsequently transported with sodium metabisulfite pads. Other l abels do not specify if use of sulfur dioxide gas and sodium me tabisulfite pads can be combined. In the absence of clear lab el inf ormation, the Agency will make conservative assumptions in the risk assessment. In addition, the RED required lab el language regarding

1 I n li eu of data, modified application parameters may be proposed on the sulfur dioxide product labels. 4limits on the concentration of sulfur dioxide released into the atmosphere during aeration

- this language does not appear on some of the sulfur dioxide end-use product labels. During registration review , th e Agency will work with registrants to re v i se the sodium metabisulfite and sulfur dioxide product labels. STATUTORY AND REGULATORY AUTHORITY The Food Quality Pro tection Act (FQPA) of 19 9 6 mandated a registration review program. All pesticides distributed or sold in the United Stat es (U .S. ) generally must be registered by the Environmental Protection Agency (EPA or the Agency) , based on scientific data showing that they will not cause unreasonab le risks to human health or the environment when used as directed on product labeling. The registration revi ew program i s intended to make sure that, as the ability to assess ri sk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review p rogram , the Agency periodically reevaluates pesticides to make sure that as change occurs , products in the marketplace can be used safely. Information on this program is provided on EPA ' s website. 2
The Agency is implementing the registrati on review program pursuant to Sec tion 3(g) of the Federal Insectic ide , Fungicide, and Rodenticide Act (FIFRA), and will review each registered pesticide every 15 years to detennine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CFR 155.40. The Agency will consider benefits information and data as requ i red by FIFRA

. The public phase of reg istration review begins when the initial docket is opened for each case. The docket is the Agency's opportunity to state what it knows about the pesticide and what additional risk analyse s and data or information it believ es are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period , the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of sodi um metabisulfite and sulfur dioxide.

2 http :// www.epa.gov/ opps rr d 1 / registration_review/ 

### 5CHEMICAL FACTS Ta bles 2 and 3 provide a summary of the chemica l facts for sodium metabisulfite and sulfur dioxide.
Table 2: Ch em ical Facts for Sodium Metabisulfite PC code 1 11409 Case Number 7019 CAS Number 7681

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- 4 Year firs t registered 1989 Pesticide Type Fungicide Chemical class Inorganic Rere gis tration Eligibi li ty May 2007 Decisi on (RED) To lerance Reassessment Not applicable E lig ibility Deci sion (TRE D) Cumulative group Sodium metabisu lfite has not been identified as a member of a cumulative group that shares a common mechanism of toxicity

. 40 CFR Citation To lerances are established in 40 CFR 

### § 180.444 under sulfur d i oxide. Dual

- use In addition to its conventi onal use in packaging for stored grapes , sodiu m metabisulfite is embedded in packaging stickers to inhibit odor causing bacteria and mo ld/mildew growth in commercial goods s uch as footwear, clothing, luggage, handbags , purses, wallets , furniture, and the like

. Non

-pesticida l uses Sodium metabisulfite is used as a preservative and an tioxidant in food and in wine and beer making. It is also u sed in photography, in tree stump removal , in wastewater treatment, in water desalination, and in te sting for si ckl e cell anemia. Pes tici de Re-e valuation Khue Nguyen, ngu yen.khue @ epa . gov, 703-347-0248 Division, Chemical Review Manager Antimicrobial D ivision, Jaclyn Pyne, pyne .jaclyn @epa.gov, 703-347-0213 Chemical Review Manager Registration Division , Tony Kish, kish.tony@e pa. gov, 703-308-94 4 3 Product Manager
Table 3: Chemical Facts for Sulfur Dioxide PC code 077601 Case Number 4056 CAS Number 7446-09-5 Year first registered 1948 Pes tici de Type Fungicide

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### Table 3: Chemica l Facts for Sulfur Dioxide Chemical class I norganic Reregistration E ligibility May 2007 Decision (RED ) To lerance Reassessment Not app licab le Eligibility Decision (TRED) Cumulative group Sulfur dioxi de has not been identified as a member of a cumulative group that s h ares a co mmon mechanism of tox ici ty
. 40 CFR C itatio n To leranc es for s ul fur dioxide are establishe d in 40 CFR 

### § 180.444. Dual -use Sulfur diox i de i s regis tered for conve ntion a l pesticidaJ uses only and has no registered antimicrobial or biope sticidal uses. Non-pesticidal uses Su lfur dioxide is used in foods (especially dried fruits) as a preservative and in beverages (especially wine) as an antioxidant and preservative. It is also used as a reducing agent in municipal wastewater treatment to treat c hl or in ated wastewater prior to release. Pesticide Re-evaluation Khue Ng uyen , nguyen.khue(ci'cpa.gov, 703-347

- 0248 Di vis io n , C hemica l Review Manager Reg istrat io n Di v i s ion, Tony Kish , kish.tonvt@cpa.gov, 703-308-9443 Product Manager

USE AND USAGE INFORMATION Tables 4 a nd 5 su mmari ze the use and usage information fo r sodium metabisulfite and sulfur dio xide. Pl ease see th e BEAD Chemical Profile for R egistration Review: Sod ium metabi s ulfit e a nd BEAD Chem ical Profile for Registration Review: Sulfur Dioxide (077601) in the registration review docket for more details.


### Table 4: Sodium Metabisulfite Pesticidal Use and Usage Information Summary of Use Registered for use for postharvest treatment of grapes to treat Botrytis cinerea which causes gray mold. A lso registered for use as an antibacterial and antifungal agent in clothing, leather goods, and other commercial products. Use Sites Grapes, clothes storage , furniture , athletic equipment, carpets, leather products , human bedd ing , human clothi n g, and human footwear. Summary of Usage Th e Agenc y only has usage information for Cali fornia , which acco unt s for about 90% of national grape producti on . Approximately l ,759 lbs of sodium metabisulfite were applied to domestic grapes in Calif ornia in 2008. Many grapes imported from Central and South America use sod ium metabisulfite pads; the Agency lack definitive usage inf o rm ati on on imported grapes. The

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### Table 4 : Sodium Metabisulfite Pesticidal Use and Usage Information Agency also l acks usage information for sodi um metabisulfite 's anti microbial use as packag i ng stic kers. Formulation Type(s) Semi -sealed pads/b ags and stickers i mpregnated with sodium metabisulfite. Applicati on Me th od(s) Pads/bags are placed inside containers of fresh grapes and release sulfur dioxide as moisture is absorbed; stickers are placed in commercial goods Technical Registrant(s) There are no technical registrants; end-use product registrants are: Imal LTDA, Productos Quimicos y A li menticios OSKU S .A. , Quimetal Indu str ial S.A., Grapetek (PTY) LTD , Embalajes Proem LTDA., Insumos Frutico l as S

. A. Infruta, Ma t eriales de Embalaje S

. A., Quimas S.A., and Micro -P ak LTD No. of Registrations 12 Restricted Use No


### Table 5: Sulfur Dioxide Pesticidal Use and Usage Information Summary of Use Re gistered for use for post-harvest fumigation of grapes h eld in cold storage, fumigation trailers, railcars, transport vehicles, and warehouses to treat Botrytis cinerea which causes gray mold. Also registered for use in combinati on with carbon d ioxide to treat for black w i dow spider on grapes in warehouse settings. Use Sites Grapes in railroad boxcars, trucks, truck trai l ers, transport vehicles, warehouses, storage rooms, and fruit storage rooms; wine barrels and corks Summary of Usage The Agency only has usage i nformation for Ca li fornia , which accounts fo r about 90% of national grape production. Approximately 89,578 lb s of sulfur dioxide were used on domesti c wine and non-wine grapes in California in 2010. Use seems to be increasing. In 201 1 , about 62,481 lbs of su l fur dioxide were used on domestic table grapes and 69,290 lb s were used on domestic wine grape . Many grapes imported from Central and So uth America are tre ated w i th sulfur diox i de; the Agency lack definitive usage information on imported graQ_es. Formul ati o n Type(s) Pressurized gas conta iners; pressurized li quid containers Application Method(s) Pressurized containers release sulfur dioxide as a gas Te chnical Registrant(s) There are no technical registrants; end -us e product registrants are: Sierra Chemical Co., Snowden Enterprises, Inc., and Seaco Technologies, Inc. No. of Registrations 3 Restricted Use No 

### Guidance for Commenters: Additional areas of use and usage related information requested for this registra tion review, and of parti cu l ar interest to EPA, are described below.



### 8• The Agency has limited use and usage data o n sodium metabisulfite and s ulfur dio xide 

### from the California Department of Pe sticide Regulation. The Agency seeks other known u ses of sodium metab i sulfi te and su l fur d ioxide in sta tes other than C alifornia and in o th er countrie s from which grape commod ities are imp orted into the USA. • The Agency seek s usage information on so dium metabisulfite use as an antimicrobial in packaging st ickers. • Certain sodium metabisulfite and sulfur dioxide labels are unclear w ith respect to application parameters such as the size of the treated area , retreatment intervals , or maximum annual application rates. Without further informati o n , EPA expects to use conservative ass umptions to approxim ate these parameters in order to conduct a quantitative risk assessment. However , th e Agency will work with registrants to clarify information on product labels. • Confirmation of the following label information : s ites of app lication ; formulations; app li cation methods and equipment ; maximum app li cati on rates and application intervals ; PP E r equ irements. • State or local use restrictions. • Foreign technical registrants not listed above who supply technical sodium metabi sulfite and sulfur dioxide to the US market.

RECENT ACTIONS In June 2013 , the Agency received a petition for an exemption from a requirement of a toleranc e for residues of sodium metabisulfite when used as a pesticide inert ingredi ent (78 FR 33788). A new use for sod ium metabisulfite formulated as e nhanced packaging stickers was added in March 2013. In September 2011, the Agency established a 10 ppm time-limited tolerance for residues of sulfur diox ide in or o n figs. T his was related to an emergency exem p tion which was granted for use of su lfur dioxide to control grey mo ld on Ca lifornia figs. T his tolerance expires on December 31 ,20 14 (76 FR 56644).



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### ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW The most recent comprehensive human health risk assessment for sodium me tabisulfite and sulfur dioxide was completed in 2007 in preparation for the Reregistration Eligibility Decision. The most recent ecological and environment al fate risk assessment was complet ed in 2007 for the same purpose. Findings and conclusions from these ri sk assessments are summarized in the Registration Review: Preliminary Problem Formulationfor Ecological Ris k , Environmental Fate , Endangered Species , and Drinking Water Assessments for Sulfur Dioxide (PC Code 077601) and Sodium Metabisulfite (PC Code 111409) and Inorganic Sulfites. Human Health Assessment Scoping Document in Support of Registration Review. During registration review, the Agency anticipates the need to conduct a comprehensive ecological risk assessment, inc luding an endangered species assessment, for a ll uses of sodium metabisulfite and sulfur dioxide. For human health, EPA anticipates the need to conduct a new bystander exposure assessment and occupational handler risk assessment during regis tration review. EPA also intends to work with FDA to determine residue levels in various foods and appropriate methods for assuring safe levels of sulfite residues from pesticidal applications in foods. If toxicological endpoints or points of departure are revised based on the data that are anticipated to be required for registration review, they will be considered in the new assessments, as well as any changes to the standard operating procedures or default exposure assumptions. Table 6 below summarizes the anticipated registration review risk assessments based on the EFED Problem Formulation and HED Scoping Document. 

### Table 6: Anticipated Risk Assessments for Sodium Metabisulfite and Sulfur Dioxide Registration Review Type of Risk Assessment Conduct? Notes Ecological and Environmental Fate Comprehensive ecological y (species to be assessed include terrestrial and aquatic organisms), including endangered species Incidents Will check for No ecological incidents have been identified updates involving either sod ium metabisulfite or sulfur dioxide. 

### Human Health D ietary Food y The Agency will work with FDA to determine pesticidal residue level s in foods and appropriate methods for assuring safe levels in dietary consumption. Drinking water N The Agency does not have any drinking water concerns for sodium metabisulfite and sulfur dioxide. Occupati o na l

1 0Handlers (mixers, loaders , 

### y There is potential for occupational applicator applicato rs) inhalation exposure to sulfur dioxide during fumigation. Post-applica t ion 

### y Potent ia l exposure due to off-gass ing are anticipated to be assessed for workers conducting post

app li cation activities near treatment operations. Residential Handlers N Sodium metabisulfite and sulfur dioxide are not Post-application N registe red for residential use ; therefore, residential handler and residential po s t-application assessment s are not applicable. Bystander 

### y There is potential for by stander exposure from offgassing during grape fumiga tions which involv e the release of high levels of su[fur dioxide during aeration. Other Aggregate N Evaluates the combined risk from dietary and residential exposures. An aggregate assessment would include only the dietary exposure scenarios , for which quantification of risks is not appropriate s in ce exposure is primarily through i nhal ation. Cumulative N Sodium metabisu lfi te and su lfur dioxide have not bee n identified as members of a cumulative group that share a common mechanism of toxicity. Tolerances N There are currently no estab li s h ed Codex, Canadian , and/ or Mexican MRL s for su lfur dioxide i n/o n g rape s, therefore tolerance harmonization is not applicabl e . Incidents Will check for For a discussion of reported human incidents for updates sod ium metabisulfite and sulf ur dioxide, see page 11 of the Scoping Document and the Inorganic Su(fites (Sulfur Dioxide and Sodium Bisulfite): Revie w of Human Incidents. Guidance for Commenters: Additional ecological information requested for this registration revi ew, and of particular interest to EPA , is described below.

• Ecotoxicity data from the published literature. • Information on the maximum application rate, the maximum number of applications, and/ or the mi nimum application interval as well as the typical number of applications and application intervals. • Ecological incidents ( non-target plant damage and avian, fish , reptilian , amphibian and mammalian mortalities ) not already reported to the Agency.



### 11Add itional human health information re quested for thi s registration review, and of particular interest to EPA , is described below.

• The Age ncy requests re levant published toxicity data fo r sulfur d i oxide. T h e Age n cy recommends that registrants present a we i ght-of-evidence r ati onale summarizing why use of pub li shed data w ill suffice for endpoint selection to determine ri sks from exposure to sulfur dioxide gas through inhalation.

TIMELINE EPA has created t h e fo ll ow ing estimated timeline for the completion of the sodium metabisu lfite and sulfur d ioxide registration review in T able 7 below . Table 7: Projected Sodium Metabisulfite and Sulfur Dioxide Registration Review Timeline Activities Estimated Date Openi ng the Doc ket Open D ocket and 60-day Public Comment Period 20 1 3

- September C lose Public Comment 2013 -November Case Development Fina l Wor k Plan 2014

- February Issue DCI 2014 Ap ril

- June Data Submission 2016 April

- June 60-day Public Comment Period for Draft Risk Assessmentsj 2017 Oc tober

- December Reg istration Review Decision 60-day Pub lic Comment Period for Proposed Regis tration 2018 Apr il - June Review Decision Regis tration Review Decision and Begin Post-Decision 2019 Fo ll ow- up To tal (years) 6

NEXT STEPS After the 60

- day public comment p eriod closes, the Agency w ill review and respond to any comments
.received in a timely manner and then issue a Final Work Plan for the registration review of sodium meta b isulfite and sulfur dioxide.

3 T he regulations govern i ng Registration Rev iew generally require the Agency to provide a public comment period of at least 30 calendar days for draft risk assessments; see 40 CFR Part l55.53(c). For conventional pestic ides , the Agency plans to provide a 60 calendar day pub lic comment period generally for draft r isk as s essments. 12

### Appendix- Additional Areas Considered in the Sodium Meta bisulfite and Sulfur Dioxide Registration Review PUBLIC COMMENTS AND FEEDBACK: Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments, data s ubmissions , or re fe rence to sources of additional information could be of particular use. Environm e ntal Justice: EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of rac e , co lor, national origin, or income , in the development, implementation, and enforcement of environmental law s, regulations, and policies. To help address potential environmental justice issues, th e Agency seeks information on any groups or segments of the population who , as a result of their location , cultural practices, or other factors , may have atypical, unusually high exposure to sodium metabisulfite or su lfur dioxide compared to the general population. Please comment if you are aware of any sub-populations that may have atypical , unusually high exposure compared to the general population. ENDANGERED SPECIES: A risk assessment that supports a complete endangered species determination has not been conducted for sodium metabisulfite and s ulfur dioxide: The eco logical risk assessment planned during registration revi ew will allow the Agency to determine whether us e of sod ium metabisulfite and sulfur dioxide have "no effect" or "may a ffect" federally listed threatened or endangered species (listed species) or their designated criti c al habitats. When an assessment concludes that a pes ticide ' s use " may affect " a listed specjes or its designated critical habitat , the Agency will consult with the U.S. Fi sh and Wildlife Service and/ or National Marine Fisheries Service (the Services), as appropriate. ENDOCRINE DISRUPTOR SCREENING PROGRAM: As required by FIFRA and FFDCA , EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively , these stud ie s include acute, subchronic and chronic toxicity, includin g assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoint s which may be susceptible to endocrine influence, including effec ts on endocrine target organ histopathology , organ weights , estrus c y clicity , sexual maturation, fertility , pregnancy rates , reproductive loss , and sex ratios in offspring. For ecological hazard assessments , EPA evaluates acute tests and chronic stu dies that assess growt h, developmental and reproductive

- effects in different taxonomic groups. As part of its most rec ent registration decision for sodi urn metabisulfite and sulfur dioxide, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p) , sodium metabisulfite and sulfur dioxide are subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

13EPA has developed the EDSP to determine whether certa in substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a "naturally occurr i ng estrogen , or other such endocrine effects as the Administrator may designate ." The EDSP employs a two

-tiered approach to making the statutoril y required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals t hat go through Ti er 

### 1 screening and are found to have the potential to interact w ith E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the avai l able data. T i er 2 testing is designed to identify any adverse endocrine

- re l ated ef f ects caused by the substance, and establ ish a dose-response relationship between the dose and theE , A, or T effect. U nder FFDCA section 408(p ), the Agency must screen all pesticide chemicals. Between Oc to ber 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemica l s, which contains 58 pesticide acti ve i ngredi ents and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 4 and includes some pesticides scheduled for Registration Review and chemicals found in water. For further information on the status of the EDSP, the policies and procedures, the lis ts of chemicals, future lists , the test guidelines and the Tier 1 screening battery , please visit our website. 5 · In the interim, EPA is making no human health or environmental safety findings associated with the EDSP screening of sodium metabisulfite and sulfur dioxide. Before completing this Registration Review , the Agency will make an EDSP FFDCA section 408(p) determ i nation. HUMAN STUDIES: The Agency is aware that inorganic sulfites studies involving human subjects are available i n the scientific literature. The 2007 RED referenced regulatory levels established by other agencies which are based on studies that involved intentional exposure of human subjects. In addition,

· OPP may be coordinating w ith other agencies on the human health risk assessment for sodium metabisulfite and sulfur dioxide. 

### If after considering any of these studies and/or any submitted by the reg i strants, the EPA dec i des to re ly on one or more of them, the Agency wi ll ensure tha t all regulatory requirements are met, including EPA ethics reviews or Human Studies Review Board reviews of any data from research involving i ntentional exposure of human subjects.

4 See http: //www.regulat ions.gov/#!docume ntD etaii;D=EPA -HQ-OPPT -2009-0477-0074 for the final second list of chemicals. 5 http: //www.epa.gov/endo /

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