United States Chemi cal Safety June 2012 Environmental Protection and Pollution Prevention Agency (7510P)



# Bis (trichloromethyl) sulfone Registration Review: Final Work Plan June 2012Docket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

3 of 14 Bis (trichloromethyl) sulfon e Registration Review Team

Human Health & Environmental Effects William Hazel Srinivas Gowda

Risk Management Seiichi Murasaki Lance Wormell

Office of General Counsel Philip Ross

________________________________________ Supporting documents for the Bis (trichlorome thyl) sulfone Case may be found in the registration review docket EPA-HQ-OPP-2011-0614 located on the internet at www.regulations.gov

.Docket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

4 of 14 Introduction

This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the Agency”) for the registration review of Bis (tri chloromethyl) sulfone (Case 2055). The work plan includes the expected registration review time line. The work plan also addresses public comments received concerning the Preliminary Wo rk Plan (PWP) in the Summary Document which was posted in the Bis (trichloromethyl) su lfone registration review docket, and any other comments concerning the initial docket postings. The Summary Do cument provided information on what EPA knows about the pesticide and what additional risk analyses and data or information the Agency believes are needed to make a registration review decision.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. Changes in science, public policy an d pesticide use practices will occur over time. The registration review program is intended to ma ke sure that, as the ability to assess risk evolves and as policies and practi ces change, all registered pestic ides continue to meet that statutory standard. The public pha se of registration review begins when the initial docket is opened for each case. Information on this program is provided at: http://www.epa.gov/oppsrrd1/ registration_review/.

The Bis (trichloromethyl) sulfone Prelimin ary Work Plan (PWP) (PC Code 035601) was published on December 21, 2011 and the 60-day comment period ended on February 21, 2012.The Preliminary Work Plan document is available on www.regulations.gov docket number EPAHQ-OPP-2011-0614.

The first product containing bis (trichloromet hyl) sulfone (BTS) (PC C ode 035601) as an active ingredient was registered in the United Stat es in 1967. Currently, th ere are nine products containing BTS as an active ingr edient registered with EPA. Products containing the organosulfur compound BTS are registered for use to cont rol algae, slime-forming bacteria, and fungi in industrial process water systems such as pulp and papermill process water systems, recirculating cooling towers, and secondary oil-recovery in jection water systems. Additionally, products containing BTS are registered for use as a mate rial preservative in household and construction materials including paints, coa tings, and fuels. There are no tolerances, exemptions from tolerances, or tolerance petitions for BTS. BTS is approved by FDA as an indirect food additive at 21 CFR 176.300 for use as a paper slimicide, at 21 CFR 175.105 to preserve food-packaging adhesives, and at 21 CFR 176.180 to preserve coati ngs to be used on paper and paperboard in contact with dry foods.

The Agency completed a Reregistration Eligibil ity Decision (RED) for bis (trichloromethyl) sulfone in 1995.

Comments Received on the Preliminary Work Plan

The Agency received one comment during the p ublic comment period on the initial docket, described below. In the PWP, the Agency soli cited comments on specific topics: environmentalDocket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

5 of 14 justice, water body impairment, trade irritants, an d structure activity relati onships. No comments or information were received during the public comment period con cerning these issues.

Comment : We wish to comment on the multigeneration reproduction and fertility effects requirement (870.3800). PCRM foun d a study that analyzed th e effects of BTS and its reversibility in male rats.

Xu Y et al . 1998. Studies on the antifertility eff ect of bis-trichloromethyl sulfone and its reversibility in male rats. Yao Xue Xue Bao 33(1):1-4.

While we recognize that this study is sex speci fic we urge the Agency to review this study. If it provides no additional information to aid in the risk assessment process then we suggest the registrant use the [Organisation for Economic Cooperation and Development (OECD) Technical Guidance] 443 Extended One-Generation Reproductive Toxicity Study (EOGRTS) instead of the EPA guideline. This will allow the registrants to conduct one extended study saving many animal s lives while gaining the same results. The TG is currently availa ble on the OCED web site.

Response : The Agency encourages the registra nts to submit relevant studies and applicable waivers in response to the data call-in associated w ith this registration review. At that time, the Agency will review the in formation to determine if the reproductive toxicity data requirement is ade quately met or can be waived.

The Agency agrees with PCRM that an extended one-generation reproductive and fertility effects study will provide the Agency with sufficient information to support the human health risk assessment planned for the BTS registration review. The Agency will accept a multigeneration or an extended one-g eneration reproductive and fertility effects study.

The comment received during the initial public co mment period did not affect the data needs, work plan and timeline described in the PWP and th ey remain as they were presented initially in the PWP. Further, this document makes final the work plan for the Bis (trichloromethyl) sulfone registration review process.

Risk Assessments and Anticipated Data Needs

The Agency will conduct a comprehensive ecologi cal risk assessment, including an endangered species risk assessment, for all uses of bis (t richloromethyl) sulfone. The Agency will conduct a human health risk assessment. The Agency e xpects to require additi onal data for use in conducting the registration review fo r bis (trichloromethyl) sulfone.

Ecological Risk Asse ssment Status and Anticipated Data Needs

• The Agency has not conducted a risk asse ssment that supports a complete endangered species determination for bis (trichloromethyl) sulfone.

• The Agency anticipates the need to require th e following additional ecological data for use in conducting the registration review of bis (trichloromethyl) sulfone.Docket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

6 of 14 850.1010 – Freshwater inverteb rate acute toxicity, Daphnia magna 1 850.1035 – Estuarine/marine inve rtebrate acute toxicity 1 850.1055 – Embryo larvae study using Mercenaria mercenaria 2 850.1075 – Freshwater fish acute toxicity 3 850.1300 – Aquatic invertebrate life-cycle, freshwater Daphnia magna 1 850.1350 – Aquatic invertebrate life-cycle, saltwater Americamysis bahia 2 850.1400 – Fish early-life stage toxic ity test, freshwater species 4 850.4225 – Seedling emergence (Tier II) with rice 2 850.4400 – Aquatic plant toxicity test using Lemna spp. 1 850.5400 – Algal Toxicity (Tier II) 5 850.6800 or OECD 209 – Activated sludge respiration inhibition test 2

• The Agency anticipates the need to require th e following additional environmental fate data for use in conducting the registration revi ew of bis (trichlo romethyl) sulfone.

835.1110 – Activated Sludge Sorption Isotherm 6 835.3110 – Ready Biodegradability 6 835.3220 – Porous Pot Test 6 835.3240 – Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units 6 835.3280 – Simulation Tests to Assess the Biodegra dability of Chemicals Discharged to Wastewater 6

• For more information, please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in support of Registrati on Review of Bis (trichloromethyl) sulfone (BTS) , located in the docket.

1 Results for studies conducted with both the TGAI and the major degradate, pentachlorodimethylsulfone, must be submitted to satisfy this requirement.
2 Results for a study conducted with the major degradate, pentachlorodimethylsulfone, must be submitted to satisfy this requirement.
3 Results for studies conducted with the TGAI for both (i) coldwater and (ii) warmwater species, as well as results for a study with the major degradate, pentachlorodimethylsulfone, and (iii) the most TGAI-sensitive species, must be submitted to satisfy this requirement.
4 Results for studies conducted using the most TGAI-sens itive species with both the TGAI and the major degradate, pentachlorodimethylsulfone, must be submitted to satisfy this requirement.
5 Results for studies conducted with the TGAI for (i) the freshwater green alga, Selenastrum capricornutum , (ii) the freshwater diatom, Navicula pelliculosa , (iii) the marine diatom, Skeletonema costatum , and (iv) the cyanobacteria species Anabaena flos-aquae as well as results for a study with the ma jor degradate, pentachlorodimethylsulfone, and (v) the most TGAI-sensitive species, must be submitted to satisfy this requirement.
6 The results of the Activated Sludge Respiration In hibition Test (ASRI) determine which of these three biodegradation tests would be anticipated to be required. If the ASRI test EC 50 is less than or equal to 20 mg/L, then either the (i) Biodegradation in Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test would be anticipated to be required. If the ASRI test EC 50 is greater than 20 mg/L, then the applicant would choose to conduct either: (i) Ready Biodegradability or (ii) Biodegradation in Activated Sludge or Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or the Porous Pot Test. If the antimicrobial passes the ready biodegradability study, then no further testing would be expected to be required. If, however, the antimicr obial fails the ready biodegradability study, then the (i) Biodegradation in Activated Sludge or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or (iii) the Porous Pot study would be expected to be re quired. Results for studies co nducted with both the TGAI and the major degradate, pentachlorodimethylsulfone, must be submitted to satisfy this requirement.Docket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

7 of 14 Human Health Risk Assessment Status and Anticipated Data Needs

• The most recent human health risk assessmen ts for bis (trichloromethyl) sulfone were completed in 1995, in support of the RED.

Dietary Assessment

• Dietary (food) exposure to BTS could potentially occur sin ce products containing BTS are registered for use to inhibit slime-forming bact eria and fungi in paper process water systems when producing paper and paperboard that ma y be used for food c ontact. Also, products containing BTS are registered for use to pres erve a number of paper-making chemicals as well as paper and paperboard coatings, adhe sives, dispersed pigments, etc. The FDA regulates BTS as an indirect food additive at 21 CFR 176.300 for use as a paper slimicide, at 21 CFR 175.105 to preserve food-packaging adhe sives, and at 21 CF R 176.180 to preserve coatings to be used on paper and paperboard in contact with dry f oods. Migration of BTS from paper packaging to the food contents is li kely to occur. Therefor e, a migration study is expected to be needed as is a di etary (food source) risk assessment.

Tolerances and Intern ational Harmonization

• There are no tolerances, exemptions from tolera nces, or tolerance petitions for BTS. BTS is approved by FDA as an indirect food addi tive at 21 CFR 176.300 for use as a paper slimicide, at 21 CFR 175.105 to preserve f ood-packaging adhesives, and at 21 CFR 176.180 to preserve coatings to be used on paper and paperboard in contact with dry foods.

Occupational and Residen tial Assessment and Risk

• The product labels instruct the handler to w ear protective eyewear (goggles, face shield, or safety glasses), rubber gloves, and protective clothing when BTS produc ts are added to pulp and paper water systems, other industrial water systems, and different materials during the manufacturing process. However, open-pour loading is permissibl e in most cases since labels do not indicate the type of loading and mi xing equipment to be used (Note: The only exception is Verichem's 20% EP (EPA Re g. No. 67869-32), which requires a meter-pump system or a closed loading/application system be used to load and apply the product to oil recovery drilling muds/packer fluids, comme rcial/industrial water cooling systems, evaporative condenser water systems, and heat exchanger systems). During open-pour activities, dermal and inhalati on exposure of workers to BTS is expected. Worker inhalation exposure is likely to result from both gaseous and aerosolized parent compound due to the relatively high vapor pressure of BTS (1.1 x 10-3 mmHg). Detailed product use and human activity information as well as dermal and inha lation exposure studies ar e anticipated to be needed for use in determining more real istic estimates of occupational exposure.

• Products containing BTS are registered for use to preserve a number of construction and household materials for use in th e home and/or in commercial, institutional, and industrial settings resulting in residen tial and other non-occupational exposures. Of the preserved materials, paints are expected to result in the high est residential exposure. Both dermal and inhalation exposures of homeowner handler s and bystanders (inc luding children) areDocket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

8 of 14 expected. Children may be exposed to BTS th rough post-application e xposure as well as incidental oral exposure from pl aying with toys made of treate d plastic. Data are anticipated to be needed for use in estimating exposure s associated with residential paint use.

Aggregate and Cumulative Exposure and Risk

• In examining aggregate exposure, EPA take s into account the available and reliable information concerning exposures to pesticide re sidues in food and drinking water, as well as non-occupational pesticide exposures. Dietary exposure may occur based on the registered uses of BTS as a paper chemical preservative and use as a slimicide during the manufacture of paper and paperboard that may contact f ood. The extent to which residues of BTS may reach drinking water will be determined upon re view of the anticipated environmental fate data. Additionally, exposure of adults and children to BTS in residential and other nonoccupational settings is likely to occur from the use of preserved materials to be represented by preserved paint. Thus, the Agency intends to assess potential aggregate risk from exposures via food, in the home, and possibly via drinking water.

• EPA does not have, at this time, available data to determine whether bis (trichloromethyl) sulfone has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment.

• For the purposes of this Registration Review, EPA has assumed that bis (trichloromethyl) sulfone does not have a common me chanism of toxicity with othe r substances when used as an antimicrobial as registered.

Human Health Anticipated Data Needs

• The Agency anticipates the need to require the following additional human health data for use in conducting the registration revi ew of bis (trichloromethyl) sulfone.

870.3465 – 90-day inhalation toxicity (rat) 870.3800 – Reproduction and fertility e ffects (multigeneration) - rat 870.4100 – Chronic oral toxicity - rat 870.4200 – Carcinogenicity (rat and mouse, preferred) 870.7485 – Rat Metabolism Study 875.1100 – Dermal outdoor exposure 875.1200 – Dermal indoor exposure 875.1300 – Inhalation outdoor exposur e (HSRB costs not included) 875.1400 – Inhalation indoor exposure 875.1600 – Application exposure data reporting and calculations 875.1700 – Product use information 875.2300 – Indoor surface residue dissipation 875.2500 – Inhalation exposure 875.2700 – Product use information 875.2800 – Description of human activity 875.2900 – Data reporting and calculationsDocket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

9 of 14 Special Study – Migration Studies 7

• For more information, please refer to Bis(trichloromethyl)sulfone: Human Health Effects Scoping Document for the Re gistration Review Decision , located in the docket.

Product Chemistry Anticipated Data Needs

• The Agency does not anticipate the need to re quire additional product chemistry data for the registration review at this time.

• For more information, please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in support of Registrati on Review of Bis (trichloromethyl) sulfone (BTS) , located in the docket.

Incidents:

Ecological:

• No bis (trichloromethyl) sulfone ecological incidents have been reported in the Agency’s Ecological Incident Information System (EISS).

Human Health:

• No bis (trichloromethyl) sulfone human poisoni ng incidents have been reported in OPP’s Incident Data System (IDS).

Endangered Species

The Agency has not conducted a risk assessmen t that supports a complete endangered species determination for bis (trichloromethyl) sulfone . The ecological risk assessment planned during registration review will allow th e Agency to determine whether bis (trichloromethyl) sulfone’s use has 'no effect' or 'may affect ' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Mari ne Fisheries Services (the Services), as appropriate.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology,

7 Migration of BTS from paper packaging to the food contents is likely to occur; therefore, registrants would be expected to be required to conduct a food migration study . Registrants will be expected to be required to submit a protocol for EPA review prior to initiating the study.Docket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

10 of 14 organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its reregistration decision for bis (trichloromethyl) sulfone, EPA reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. Ho wever, as required by FFDCA section 408(p), bis (trichloromethyl) sulfone is subj ect to the endocrine screening pa rt of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Bis (trichloromethyl) sulfone is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of regi stration review, EPA will issue future EDSP orders/data call-ins, requiring th e submission of EDSP screening a ssays for bis (trichloromethyl) sulfone. For further information on the status of th e EDSP, the policies and pr ocedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/.

Timeline

EPA has created the following estimated timeline for the completion of the Bis (trichloromethyl) sulfone registration review:

Anticipated Schedule Activities Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Docket Completed December 2011 Close Public Comment Peri od for Docket Completed February 2012 Phase 2: Case Development Develop Final Work Plan (FWP) Completed June 2012Docket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

11 of 14 Issue DCI June 2013 Data Submission June 2015 Open Public Comment Period for Prelim inary Risk Assessments December 2016
Close Public Comment Period for Prelim inary Risk Assessments January 2017 Phase 3: Registration Review Decision Open Public Comment Period for Pro posed Reg. Review Decision June 2017 Close Public Comment Period for Pro posed Reg. Review Decision August 2017 Final Decision and Begin Post-Decision Follow-up December 2017 Total (years) 6

Next Steps

A DCI will be developed regarding the data needs listed under the “Risk Assessments and Anticipated Data Needs” section of this document. The Agency expects to issue the DCI in June 2013. Human health and environmental fate and ecological hazard assessments will be conducted for all uses.Docket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

12 of 14 Summary of Anticipated Data Requirem ents – bis (trichloromethyl) sulfone

The table below summarizes anticipated data needs for the Bis (trichloromethyl) sulfone Case in this document (Final Work Plan), Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in support of Regist ration Review of Bis(trichloromethyl)sulfone, and Bis(trichloromethyl)sulfone: Human Health Ef fects Scoping Document for the Registration Review Decision.

Guideline Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months

from DCI Receipt)

850.1010 Freshwater invertebrate acute toxicity, Daphnia magna TGAI and the major degradate, pentachlorodimethylsulfone 24

850.1035 Estuarine/marine invertebrate acute toxicity TGAI and the major degradate, pentachlorodimethylsulfone 24

850.1055 Embryo larvae study using Mercenaria mercenaria Major degradate, pentachlorodimethylsulfone 24

850.1075 Freshwater fish acute toxicity 8 TGAI and the major degradate, pentachlorodimethylsulfone 24

850.1300 Aquatic invertebrate life-cycle, freshwater Daphnia magna TGAI and the major degradate, pentachlorodimethylsulfone 24

850.1350 Aquatic invertebrate life-cycle, saltwater Americamysis bahia Major degradate, pentachlorodimethylsulfone 24

850.1400 Fish early-life stage toxicity test, freshwater species 9 TGAI and the major degradate, pentachlorodimethylsulfone 24

850.4225 Seedling emergence (Tier II) with rice Major degradate, pentachlorodimethylsulfone 24

850.4400 Aquatic plant toxicity test using Lemna spp. TGAI and the major degradate, pentachlorodimethylsulfone 24

850.5400 Algal Toxicity (Tier II) 10 TGAI and the major degradate, pentachlorodimethylsulfone 24

850.6800 or OECD 209 Activated sludge respiration inhibition test TGAI and the major degradate, pentachlorodimethylsulfone 24

835.1110 Activated Sludge Sorption TGAI and the major degradate, 24

8 Results for studies conducted with the TGAI for both (i) coldwater and (ii) warmwater species, as well as results for a study with the major degradate, pentachlorodimethylsulfone, and (iii) the most TGAI-sensitive species, must be submitted to satisfy this requirement.
9 Results for studies conducted using the most TGAI-sens itive species with both the TGAI and the major degradate, pentachlorodimethylsulfone, must be submitted to satisfy this requirement.
10 Results for studies conducted with the TGAI for (i) the freshwater green alga, Selenastrum capricornutum , (ii) the freshwater diatom, Navicula pelliculosa , (iii) the marine diatom, Skeletonema costatum , and (iv) the cyanobacteria species Anabaena flos-aquae as well as results for a study with the ma jor degradate, pentachlorodimethylsulfone, and (v) the most TGAI-sensitive species, must be submitted to satisfy this requirement.Docket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

13 of 14 Isotherm 11 pentachlorodimethylsulfone

835.3110 Ready Biodegradability 11 TGAI and the major degradate, pentachlorodimethylsulfone 24

835.3220 Porous Pot Test 11 TGAI and the major degradate, pentachlorodimethylsulfone 24

835.3240 Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units 11 TGAI and the major degradate, pentachlorodimethylsulfone 24

835.3280 Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater 11 TGAI and the major degradate, pentachlorodimethylsulfone 24

870.3465 90-day inhalation toxicity (rat) TGAI 24

870.3800 Reproduction and fertility effects (multigeneration) – rat TGAI 48

870.4100 Chronic oral toxicity – rat TGAI 48

870.4200 Carcinogenicity (rat and mouse, preferred) TGAI 48

870.7485 Rat Metabolism Study TGAI 24
875.1100 Dermal outdoor exposure TGAI 24
875.1200 Dermal indoor exposure TGAI 24

875.1300 Inhalation outdoor exposure (HSRB costs not included) TGAI 24

875.1400 Inhalation indoor exposure TGAI 24

875.1600 Application exposure data reporting and calculations TGAI 12

875.1700 Product use information TGAI 12

875.2300 Indoor surface resi due dissipation TGAI 24
875.2500 Inhalation exposure TGAI 24

875.2700 Product use information TGAI 12

11 The results of the Activated Sludge Respiration In hibition Test (ASRI) determine which of these three biodegradation tests would be anticipated to be required. If the ASRI test EC50 is less than or equal to 20 mg/L, then either the (i) Biodegradation in Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test would be anticipated to be required. If the ASRI test EC50 is greater than 20 mg/L, then the applicant would choose to conduct either: (i) Ready Biodegradability or (ii) Biodegradation in Activated Sludge or Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or the Porous Pot Test. If the antimicrobial passes the ready biodegradability study, then no further testing would be expected to be required. If, however, the antimicr obial fails the ready biodegradability study, then the (i) Biodegradation in Activated Sludge or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or (iii) the Porous Pot study would be expected to be required.Docket Number: EPA-HQ-OPP-2011-0614 www.regulations.gov

14 of 14 875.2800 Description of human activity TGAI 12
875.2900 Data reporting and calculations TGAI 12
Special Study Migration Studies 12 TGAI 24

12 Migration of BTS from paper packaging to the food contents is likely to occur; therefore, registrants would be expected to be required to conduct a food migration study . Registrants will be expected to be required to submit a protocol for EPA review prior to initiating the study.