1 of 20 United States Chemical Safety September 2011 Environmental Protection and Pollution Prevention Agency (7510P)



# Glycine, N-(Hydroxymethyl)-Monosodium Salt (SHMG) Summary Document Registration Review: Initial Docket September 2011Docket Number: EPA-HQ-OPP-2011-06 1 5 www.regulations.gov



### Glycine, N-(Hydroxymethyl)-Monosodium Salt (SHMG) Summary Document Registration Review: Initial Docket Se p tember 2011

Case # 5030

Approved By:

n Harrigan

- F elly irector, Antimicrobials Divis i on

Date:



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20f20Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

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### TABLE OF CONTENTS

SHMG Registration Review Team ................................................................................................. 4 I. Preliminary Work Plan -- SHMG .............................................................................................. .. 5 II. Fact Sheet ................................................................................................................ ................. 14 III. Summary of Anticipated Data Requirements – SHMG .......................................................... 18 IV. Appendix A: Use Patterns – SHMG .................................................................20

________________________________________
Please Note

This Preliminary Work Plan and Fact Sheet su mmarize the Environmental Protection Agency's current position based on the following documents:

1. Summary of Product Chemistry, Environmenta l Fate, and Ecotoxicity Data for the Glycine, N-(hydroxymethyl)-monosodium salt Re gistration Review Decision Document. August 11, 2011

2. Glycine, N-(hydroxymethyl)-, monosodium sa lt. Human Health Scoping Document for the Registration Review. September 13, 2011

Additional supporting documents for the Glycine, N-(Hydroxym ethyl)-Monosodium Salt Case may be found in the registration review docket EPA-HQ-OPP-2011-0615 located on the internet
at

www.regulations.gov

.Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

4 of 20 SHMG Registration Review Team

Human Health & Environmental Effects William Hazel Srinivas Gowda

Risk Management Rebecca von dem Hagen Lance Wormell

Office of General Counsel Philip RossDocket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

5 of 20 I. Preliminary Work Plan -- SHMG

Introduction:

The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the U.S. Environmental Protection Agency (USEPA, EPA, or the Agency ) based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The regist ration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet th e statutory standard of no unreas onable 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 program, the Agency periodically reevaluates pesticides to make sure that as change occurs , products in the marketpl ace can be used safely. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

. 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. The Agency will consid er benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state whatit knows about the pesticide and what additional risk analyses and data or information it belie ves are needed to make a registration review decision. After reviewing and responding to co mments and data received in the docket during this initial comment period, the Agency will de velop and commit to a final work plan and schedule for the Glycine, N-(Hydr oxymethyl)-Monosodium Salt Case.

The first product containing Glycine, N-( hydroxymethyl)-, monosodium salt (PC Code 128972), also known as sodium hydroxymethyl glycinate or SHMG, as an activ e ingredient was registered in the United States in 1997. Currently, there is only one product containing SHMG registered with EPA. This product, Suttocide A 50% Solutio n, is a biocidal agent registered for use to inhibit the growth of bacteria and fungi. It is registered for use as a material preservative in liquid soaps, fabric cleaning and care pr oducts, water based cleaning pr oducts, waterborne coatings and polishes, water based adhesives, printing supplies, and textile emulsions. SHMG can also be used as a preservative in cosmetics. Cosmetic uses are not regulated by EPA.

SHMG’s mechanism of antimicrobi al action appears to be largel y or wholly vi a release of formaldehyde (HCHO). In a 2002 “Opinion,” The EU’s Scientific Committee on Cosmetic and Non-food Products Intended for Consumers (SCC NFP) indicated that, in aqueous solution, SHMG is rapidly decomposed to formaldehyde and sodium glycinate. Glycine/sodium glycinate is the simplest amino acid, is naturally occurring in humans, is one of the basic 20 components of protein, and is not of toxicol ogical concern. Formaldehyde is being evaluated as an active ingredient separately under regi stration review Case 0556. EPA anticipates the need to require additional data on SHMG for use in assessing risk from the parent compound (i.e., SHMG) and/or formaldehyde.Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

6 of 20 SHMG is not registered for use in products that may come in direct contact with food. No tolerance or tolerance exemption has been establis hed in food as a result of use as a direct or indirect food additive, as an active i ngredient, or as an inert ingredient.

EPA did not complete a reregistration eligibil ity decision (RED) for SHMG because the first pesticide product containing SHMG was regist ered after November 1, 1984. Documents associated with the registration review of SHMG can be viewed at www.regulations.gov in docket EPA-HQ-OPP-2011-0615. Below is a summary of the issues relevant to this registration review case.

Anticipated Risk Assessment and Data Needs:

The Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species risk assessment, for all uses of SHMG. The Agency anticipates the need to conduct a human hea lth risk assessment. The Agency anticipates needing additional data for use in conducting the registration review for SHMG.

Ecological Risk:

 No ecological risk assessment has been performed for SHMG.

 The Agency has not conducted a risk asse ssment that supports a complete endangered species determination for SHMG. The eco logical risk assessment planned during registration review will allow the Agency to determine whether SHMG’s use has 'no effect' or 'may affect' federall y listed threatened or endange red 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 cr itical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.

 The Agency anticipates the need to require the following additional ecological data for use in the registrati on review of SHMG.

850.5400 -- Algal Toxicity Tier II using freshwater green alga, Selenastrum capricornutum

 The Agency anticipates the need to require the following additional environmental fate data for use in the regi stration review of SHMG.

835.1110 -- Activated Sludge Sorption Isotherm 835.2120 -- Hydrolysis 835.2240 -- Photodegradation in Water 850.6800 -- Modified Activated Sludge , Respiration Inhibition Test 1

1 Based on the results of any required Activated Sludge Respiration Inhibition Test (ASRI), registrants may be able to request that EPA waive the requirements for add itional biodegradation tests. If the ASRI test EC 50 is less than or equal to 20 mg/L, registrants would need to perform one of 835.3220, 835.3240, or 835.3280. If the ASRI test EC 50 is greater than 20 mg/L, registrants would need to perform either (i) 835.3110 or (ii) one of 835.3220, 835.3240, orDocket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

7 of 20 835.3110 -- Ready Biodegradability 835.3220 -- Porous Pot Test 835.3240 -- Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units 835.3280 -- Simulation Tests to Assess the Biodeg radability of Chemicals Discharged to Wastewater

 For more information, please refer to Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Gl ycine, N-(hydroxymethyl)-monosodium salt Registration Review Decision Document , located in the docket.

Human Health Risk:

 The Agency did not perform a quantitative human health risk assessment at the time of the initial registration based on the low likelihood of exposur e and the absence of adverse systemic effects in available toxicity studies.

 Dietary (food) exposure is not expected becau se the SHMG product cannot be used to preserve materials that may come in direct contact with food.

 Due to the potential for dietary (drinking wate r) exposure from the ma terial preservative use of SHMG, the Agency intends to determ ine the need for a drinking water assessment upon the submission and review of the environmen tal fate data anticipated to be needed for this registration review.

 To determine the conditions under which resi dential and occupationa l exposure to the parent compound and/or formal dehyde are likely to occur from the use of SHMG as a preservative, the Agency anticipates re quiring detailed use and other information, presented below, to clarify the conditions, ra tes, and magnitude of formaldehyde release from SHMG under various conditions and in various materials.

 The Agency anticipates conducti ng residential risk assessmen ts on adult applicator/user dermal and inhalation exposure and postappl ication dermal and inhalation exposure to adults and children.

 The Agency anticipates conducting occupationa l risk assessments on handler dermal and inhalation exposure during direct -pour activities, handler dermal and inhalation exposure to SHMG and inhalation risk to formalde hyde resulting from use or application of preserved water-based materials, and bystande r inhalation risk to formaldehyde resulting from preservation of wa ter-based materials.

 The Agency has not conducted an aggr egate risk assessment for SHMG.

835.3280. If the antimicrobial reaches pass levels for 835.3110 (i.e., 70% removal of dissolved organic carbon (DOC) and 60% removal of theoretical oxygen demand (ThOD) or theoretical carbon dioxide (ThCO 2 ) production for respirometric methods) in a 10-day window within the 28-day period of the test, registrants would be able to request that EPA waive the requirements for additional bi odegradation tests. If the antimicrobial does not pass 835.3110, the registrants would need to perform one of 835.3220, 835.3240, or 835.3280.Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

8 of 20  In examining aggregate exposure, EPA take s into account the available and reliable information concerning exposures to resi dues in food and drinking water, and nonoccupational pesticide exposures. If the result s of the environmental fate data indicate that a drinking water assessment is necessary, then the Agency anticipates the need to conduct an aggregate assessment for residentia l and dietary exposure to SHMG. In the absence of the environmental fate data, the Agency would assume that dietary exposure occurs and; therefore, would anticipate the n eed to perform an aggregate risk assessment. The Agency anticipates performing an a ggregate assessment for all non-occupational sources of formaldehyde.

 The Agency anticipates the need to require the following additional human health data for use in the registra tion review of SHMG.

870.3250 -- 90-day dermal toxicity 2 870.3465 -- 90-day inhalati on toxicity (rat) 2 870.3800 -- Reproduction and fertility e ffects (multigeneration) - rat 875.1700 -- Product use information 875.2700 -- Product use information 875.2800 -- Description of human activity 875.1100 -- Dermal outdoor exposure 875.1200 -- Dermal indoor exposure 875.1300 -- Inhalation outdoor exposure 3 875.1400 -- Inhalation indoor exposure 3 875.1600 -- Application exposure data reporting and calculations 875.2900 -- Data reporti ng and calculations

 The Agency does not anticipate the need to require additional toxicity data on formaldehyde through the SH MG registration review.

 Past SHMG risk assessments have relied in part on two human studies that involved intentional exposure to SHMG (both studies are combined in a single data volume, MRID 43514301). In the course of registration review , EPA will reconsider these studies, as well as consider any other research involving intentional exposure of human subjects to

2 If the environmental fate studies that are expected to be required demonstrate that SHMG rapidly and completely degrades to formaldehyde and glycine, registrants may request that EPA waive the requirement for Guideline 870.3250 and Guideline 870.3465.
3 If the inhalation indoor (875.1400) and outdoor (875.1300) exposure data are required as anticipated, the DCI would provide that the registrant may elect to submit small chamber studies demonstrating formaldehyde air emission rates and any available Industrial Hygiene air sampling data (explained below). Based on the results of the small chamber studies, the Agency may de termine that the inhalation indoor and outdoor exposure data expected to be required would no longer be necessary. The DCI would provide that, if the registrant elects to perform such small chamber studies , a protocol will need to be submitted for review and approval by the Agency prior to initiation. The Agency also anticipates the need to require that available Industrial Hygiene air sampling data from commercial facilities manufacturing, storing, or using large quantities of bulk or end-products made from preserved materials be submitted, especially for paper mills, facilities manufacturing preserved liquid materials, and other manufacturing facilities where SHMG is used as part of the inhalation indoor (875.1400) and outdoor (875.1300) exposure studies expect ed to be required.Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

9 of 20 SHMG brought to its attention. If EPA determ ines that the two pr eviously-identified intentional exposure human studies (or any ad ditional intentional exposure human studies brought to EPA’s attention) are sufficiently soun d from a scientific pe rspective to warrant inclusion in future risk assessments, EPA w ill consider the ethical acceptability of the studies. Before reaching a final decision to rely on any such studies, EPA will ensure that all applicable regulatory requirements ar e met, including but not limited to the requirements for EPA ethics re view and Human Studies Review Board review of certain research involving intentional exposure of human subjects.

 For more information, please refer to Glycine, N-(hydroxymethyl)-, monosodium salt. Human Health Scoping Document for the Registration Review , located in the docket.

Product Chemistry:

 The Agency does not anticipate the need to require additional product chemistry data for this registration review case at this time.

 For more information, please refer to Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Gl ycine, N-(hydroxymethyl)-monosodium salt Registration Review Decision Document , located in the docket.

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, 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. A human health risk assessment identifying the most sensitive endpoints has not been conducted for the SHMG Case. As required by FFDCA section 408(p), SHMG is subject to the endocrine screeni ng part of the Endocrine Disrup tor 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.Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

10 of 20 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 activ e ingredients and 9 inert ingred ients. SHMG is not among the group of 58 pesticide active ingredients on the in itial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP screening assa ys for SHMG. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 scr eening battery, please visit our website: http://www.epa.gov/endo/.

Timeline

EPA has created the following estimated timelin e for the completion of the SHMG registration review:

Anticipated Schedule

Activities Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Docket September 2011 Close Public Comment Period for Docket November 2011 Phase 2: Case Development Develop Final Work Plan (FWP) March 2012 Issue DCI March 2013 Data Submission March 2015 Open Public Comment Period for Prelim inary Risk Assessments September 2016
Close Public Comment Period for Prelim inary Risk Assessments October 2016 Phase 3: Registration Review Decision Open Public Comment Period for Propos ed Reg. Review Decision March 2017 Close Public Comment Period for Pro posed Reg. Review Decision May 2017 Final Decision and Begin Post-Decision Follow-up 2017 Total (years) 6

Guidance for Commenters:

The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work pl an for the SHMG registration review case.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any tr ade irritant issues resulting from lack ofDocket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

11 of 20 Maximum Residue Limits (MRLs) or disparitie s between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the na ture of the concern.

Water Quality:

SHMG is not identified as a cau se of impairment for any wate r bodies listed as impaired under section 303(d) of the Clean Water Ac t, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation_cy.cause_detail_303d?p_cause_group_id=88 5. In addition, no Total Maximum Daily Loads (T MDL) have been developed for SHMG, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation.tmdl_pollutant_de tail?p_pollutant_group_id =885&p_pollutant_group_name=PESTICIDES.

More information on impaired wate r bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/ . The Agency invites submission of water quality data for this pesticide. To the extent possible, data should co nform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclus ion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Revi ew Risk Assessment and Management Process (see: http://www.epa.gov/oppsrrd1/regist ration_review/water_quality_sop.htm ), in order to ensure the data can be used quantitatively or qual itatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to SHMG compared to the gene ral population. Please comment if you are aware of any sub-populatio ns that may have atypical, unusually high exposure compared to th e general population.

Structure Activity Relationships:

EPA must rely upon information of appropriate qual ity and reliability for each decision made by the Agency. In the Office of Pesticide Program s (OPP), the evaluation process for a pesticide chemical traditionally begins with the applicant’ s submission of a set of studies conducted with the specific pesticide chemical of interest. The us e of the results of such testing (measured data) is a logical, scientifically rigorous proce ss that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant interest in alternat ive techniques, i.e., tech niques other than data generation that could significantly inform the Agency’s decision-making process. Recently, OPP has made increasing use of stru cture activity relationship (SAR ) as part of its regulatory decision-making process. In the SAR process, a ch emical's molecular structure is compared to that of other chemicals for which data are availabl e. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties.Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

12 of 20 Thus, the chemical’s physical, chemical, and biol ogical properties are a f unction of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured da ta on a single physical, chemical, or biological property is used to derive a model (an equatio n) to predict the valu e of that property.

Since SAR assessments and QSAR modeling are anothe r set of tools that are available to Agency scientists, OPP has begun a proce ss shift that envisions shifting from the current study-by-study approach to an approach in which the use of pr edicted data, generated us ing validated models, is considered along with information from open litera ture and studies specifically generated under Part 161 requirements. All relevant information w ould be considered as pa rt of a weight-of-theevidence evaluation.

At this time, EPA believes that for certain e ndpoints, especially physi cal/chemical and fate properties, that SAR and QSAR might be effect ively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. When considering biological prope rties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a screening-level assessment procedure rather than multiple tiers of assessments with progressively more data requirements.

If stakeholders believe that submission of predic ted data can fulfill one of the data needs for the SHMG Case, then the Agency invites submissi on of this information. The submitter would be expected to supply a rationale describing th e utility of the information and provide documentation on the scientific va lidity of the information. The de termination that the predicted data fulfills the data requirement would be at the sole discretion of the Agency. Pre-submission consultation with the Agency is encouraged.

Additional Information:

Stakeholders are also specifically asked to provid e available information a nd data that will assist the Agency in refining its risk assessments, including any species-spec ific ecological effects determinations. The Agency is interested in receiving the following information:

1. Confirmation on the following label information:

a. Sites of application b. Formulations

c. Application methods and equipment d. Maximum application rates

e. Frequency of application, applicatio n intervals and maximum number of applications f. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non-agricultura l uses (e.g., materials preservation) 5. Typical application interval 6. State or local use restrictionsDocket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

13 of 20 7. Ecological incidents (non-target plant dama ge and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency 8. Monitoring data

Next Steps:

After the 60-day comment period closes in N ovember 2011, the Agency will review and respond to any comments received in a timely manner, a nd then issue a Final Work Plan for the SHMG

case.Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

14 of 20 II. Fact Sheet

Background Information:

 Active Ingredient: Glycine, N-( hydroxymethyl)-, monosodium salt

 Other Names: SHMG, sodium hydroxymethyl glycinate, Sodium hydroxymethylamino
acetate

 Case number: 5030

 PC Code: 128972

 CAS number: 70161-44-3

 Technical registrants: no regist ered manufacturi ng-use products

 First approved for use in a registered product: 1997

 There are no tolerances or exemp tions from tolerances for SHMG.

 Antimicrobials Division Chemical Review Manager (CRM): Rebecca von dem Hagen, vondem-hagen.rebecca@epa.gov

 Antimicrobials Division Product Ma nager (PM): Marshall Swindell, swindell.marshall@epa.gov

 Chemical Structure:

Use & Usage Information:

 Suttocide A 50% Solution, the only regist ered SHMG product (EPA Reg. No. 57978-4), is a biocidal agent registered for use to inhi bit the growth of bact eria and fungi. It is registered for use as a material preservative in liquid soaps, fabric cleaning and care products, water based cleaning products, waterb orne coatings and polishes, water based adhesives, printing supplies and textile emulsions.

 SHMG can also be used as a preservative in cosmetics. Cosmetic uses are not regulated by EPA.

Recent/Pending Regulatory Actions:

 There are no recent or pending regulatory actions for SHMG.

Ecological Risk Assessment Status:

Please refer to Summary of Product Chemistry, Environm ental Fate, and Ecotoxicity Data for the Glycine, N-(hydroxymethyl)-monosodium sa lt Registration Review Decision Document.

, located in the docket, for a detailed discus sion of the ecological risk assessments.

 No ecological risk assessment has been conducted on SHMG.Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

15 of 20  SHMG is practically nontoxic to avian species on an acute oral and subacute dietary basis, practically nontoxic to mammals on an acu te oral basis, and practically nontoxic to warm/cold freshwater fish a nd aquatic invertebrates.

 Formaldehyde degradate: 37% ai formaldehyde is slightly toxic to avian species on an acute oral basis and practical ly non-toxic on a subacute diet ary basis, technical grade formaldehyde (37% a.i.) is moderately toxic to mammals on an acute oral basis and 37% ai formaldehyde is slightly to practically nontox ic to freshwater fish and slightly toxic to freshwater invertebrates.

 The Agency has not conducted a risk asse ssment for SHMG that supports a complete endangered species effects determination fo r SHMG. The ecological risk assessment planned during registration review will allow the Agency to determine whether SHMG's use has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their designated critical ha bitats. 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 Marine Fisheries Services (the Services), as appropriate.

Human Health Risk Assessment Status:

Please refer to Glycine, N-(hydroxymethyl)-, monosodi um salt. Human Health Scoping Document for the Registration Review , located in the docket, for a detailed discussion of the human health risk assessment.

 The Agency did not perform a quantitative human health risk assessment at the time of the initial registration based on the low likelihood of exposur e and the absence of adverse systemic effects in available toxicity studies.

 In a 2002 “Opinion,” The EU’s Scientific Committee on Cosmetic and Non-food Products Intended for Consumers (SCCNFP) indicated that, in aqueous solution, SHMG is rapidly decomposed to formaldehyde and s odium glycinate. Glycine/sodium glycinate is the simplest amino acid, is naturally occurring in humans, is one of the basic 20 components of protein, and is not of toxicological concern.

Hazard Characterization:

 SHMG exhibits slight acute oral and dermal toxicity (Toxicity Category III), no dermal irritation (Toxicity Category IV), low acute inhalation toxicity (Toxicity Category IV) and moderate eye irritation (Toxicity Category II) in animal testing. SHMG is also a severe gastrointestinal irritant.

 Two human dermal sensitizati on studies that involved in tentional exposure to SHMG were submitted in 1993 (both studies are comb ined in a single data volume, MRID 43514301). SHMG did not cause dermal sensitizati on in humans at either 0.5 or 1% ai in water in the repeat-dose patch tests. In the course of registration review, EPA will reconsider these studies, as well as consider any other re search involving intentionalDocket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

16 of 20 exposure of human subjects to SHMG brought to its attention. If EPA determines that the two previously-identified intentional e xposure human studies (or any additional intentional exposure human studies brought to EPA’s attention) are sufficiently sound from a scientific perspective to warrant inclusion in future risk assessments, EPA will consider the ethical acceptability of the studi es. Before reaching a final decision to rely on any such studies, EPA will ensure that all ap plicable regulatory requirements are met, including but not limited to the requirement s for EPA ethics review and Human Studies Review Board review of certain research involving intentiona l exposure of human subjects.

Dietary (Food and Water):

 SHMG product labeling prohibits use in products that may come in direct contact with food.

 The Agency did not complete a dietary risk assessment for th e initial registration of the only SHMG product.

Residential:

 The Agency has not conducted a resi dential risk assessment for SHMG.

Aggregate:

 An aggregate risk assessment ha s not been conducted for SHMG.

 In examining aggregate exposure, EPA take s into account the available and reliable information concerning exposures to resi dues in food and drinking water, and nonoccupational pesticide exposures. If the result s of the environmental fate data indicate that a drinking water assessment is necessary, then the Agency anticipates the need to conduct an aggregate assessment for residentia l and dietary exposure to SHMG. In the absence of the environmental fate data, the Agency would assume that dietary exposure occurs and; therefore, would anticipate the n eed to perform an aggregate risk assessment. The Agency anticipates performing an a ggregate assessment for all non-occupational sources of formaldehyde.

Occupational:

 The Agency has not conducted a quantitativ e occupational risk assessment for SHMG.

Cumulative:

 Unlike other pesticides for which EPA has fo llowed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to SHMG and any other substan ces and SHMG does not appear to produce a toxic metabolite produced by other substances . For the purposes of this registration review, therefore, EPA ha s not assumed that SHMG has a common mechanism ofDocket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

17 of 20 toxicity with other s ubstances. For the purposes of this action, therefore, EPA has not assumed that SHMG has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures fo r cumulating effects from substances found to have a common mechan ism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

Incidents:

Ecological:

 No SHMG ecological incidents have been repo rted in the Agency’s Ecological Incident Information System (EIIS).

Human Health:

 No SHMG human poisoning incidents have been reported in the OPP incident database.

Tolerances and International Harmonization:

 There are no tolerances or exemp tions from tolerances for SHMG.

Data Call-In Status:

 A Data Call-In has never been issued for SHMG.

Labels:

Registered products, including EP A registration numbers are provi ded in Table 1 below. For future reference, during registra tion review a list of product regi stration numbers will be included in the docket. Product registration labels may be obtained from the Pesticide Product Label System (PPLS) website at: http ://oaspub.epa.gov/pestlabl/ppls.home

. Table 1. Registered Products – SHMG

Registration # Registration Name Company Name Formulation Type % A.I.

57978-4 Suttocide A 50% Solution ISP Chemicals, LLC Ready-to-Use Solution 50Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

18 of 20 III. Summary of Anticipated Data Requirements – SHMG

The table below summarizes anticipated data needs for the SHMG Case in Section I of this document (Preliminary Work Plan), Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Glycine, N-(hydro xymethyl)-monosodium salt Registration Review Decision Document. , and Glycine, N-(hydroxymethyl)-, monosodium salt. Human Health Scoping Document for the Registration Review.

Table 2. Summary of Anticipated Data Requirements – SHMG

Guideline Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months from DCI Receipt)
870.3250 90-day dermal toxicity 4 TGAI 24
870.3800 90-day inhalation toxicity (rat) 4 TGAI 24

870.3800 Reproduction and fertility effects (multigeneration) - rat TGAI 24

875.1700 Product use information TGAI 12

875.2700 Product use information TGAI 12
875.2800 Description of human activity TGAI 12
875.1100 Dermal outdoor exposure TGAI 24
875.1200 Dermal indoor exposure TGAI 24
875.1300 Inhalation outdoor exposure 5 TGAI 24
875.1400 Inhalation indoor exposure 5 TGAI 24

875.1600 Application exposure data reporting and calculations TGAI 24

875.2900 Data reporting and calculations TGAI 24

4 If the environmental fate studies that are expected to be demonstrate that SHMG rapidly and completely degrades to formaldehyde and glycine, registrants may request that EPA waive the requirement for Guideline 870.3250 and Guideline 870.3465.
5 If the inhalation indoor (875.1400) and outdoor (875.1300) exposure data are required as anticipated, the DCI would provide that the registrant may elect to submit small chamber studies demonstrating formaldehyde air emission rates and any available Industrial Hygiene air sampling data (explained below). Based on the results of the small chamber studies, the Agency may de termine that the inhalation indoor and outdoor exposure data expected to be required would no longer be necessary. The DCI would provide that, if the registrant elects to perform such small chamber studies , a protocol will need to be submitted for review and approval by the Agency prior to initiation. The Agency also anticipates the need to require that available Industrial Hygiene air sampling data from commercial facilities manufacturing, storing, or using large quantities of bulk or end-products made from preserved materials be submitted, especially for paper mills, facilities manufacturing preserved liquid materials, and other manufacturing facilities where SHMG is used as part of the inhalation indoor (875.1400) and outdoor (875.1300) exposure studies expect ed to be required.Docket Number: EPA-HQ-OPP-2011-0615 www.regulations.gov

19 of 20 850.5400 Algal Toxicity Tier II using freshwater green alga, Selenastrum capricornutum TGAI 12

835.1110 Activated Sludge Sorption TGAI 12
835.2120 Hydrolysis TGAI 12
835.2240 Photodegradation in water TGAI 12
835.3110 Ready Biodegradability TGAI 12

835.3220 Porous Pot Test TGAI 12

835.3240 Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units TGAI 12

835.3280 Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater TGAI 12

850.6800 Modified activated sludge, respiration inhibition test 6 TGAI 12

6 Based on the results of any required Activated Sludge Respiration Inhibition Test (ASRI), registrants may be able to request that EPA waive the requirements for add itional biodegradation tests. If the ASRI test EC 50 is less than or equal to 20 mg/L, registrants would need to perform one of 835.3220, 835.3240, or 835.3280. If the ASRI test EC 50 is greater than 20 mg/L, registrants would need to perform either (i) 835.3110 or (ii) one of 835.3220, 835.3240, or 835.3280. If the antimicrobial reaches pass levels for 835.3110 (i.e., 70% removal of dissolved organic carbon (DOC) and 60% removal of theoretical oxygen demand (ThOD) or theoretical carbon dioxide (ThCO 2 ) production for respirometric methods) in a 10-day window within the 28-day period of the test, registrants would be able to request that EPA waive the requirements for additional bi odegradation tests. If the antimicrobial does not pass 835.3110, the registrants would need to perform one of 835.3220, 835.3240, or 835.3280.20 of 20IV. Appendix A: Use Patterns – SHMGEPA RegNumberused forMax.Appl.RateFormulation % ActiveIngredientin End UseFormulationUseCategoryUse Site TreatmentSite/SurfacesMethod ofApplicationMaxApplication/UseRateUseLimitations57978-4SolubleConcentrate 50.0MaterialsPreservativeAqueouscompositionsLiquid Soaps,fabric cleaning andcare products, waterbased cleaningproductsNotspecified onlabel2-10 gallons per1000 gallons ofproduct beingtreated (1000-5000 ppm)For non fooduseapplicationsonly57978-4SolubleConcentrate 50.0MaterialsPreservativeAqueouscompositionsWaterbornecoatings, polishesWater basedadhesivesNotspecified onlabel2-10 gallons per1000 gallons ofproduct beingtreated (1000-5000 ppm)For non fooduseapplicationsonly57978-4SolubleConcentrate 50.0MaterialsPreservativeAqueouscompositionsPrinting suppliesTextile emulsionsNotspecified onlabel2-10 gallons per1000 gallons ofproduct beingtreated (1000-5000 ppm)For non fooduseapplicationsonly