Docket Number: EPA-HQ-OPP-2009-0546 www.regulations.gov

United States Prevention, Pesticides March 2010
Environmental Protection and Toxic Substances Agency (7510P)



# Peroxy Compounds Final Work Plan Registration Review

March 2010Docket Number: EPA-HQ-OPP-2009-0546 www.regulations.gov



### TABLE OF CONTENTS

Peroxy Compounds Registration Review Team ............................................................. 4

I. Introduction ............................................................................................................... 5

II. Summary of Comments Received on Preliminary Work Plan ............................. 5

III. Risk Assessment and Data Needs .......................................................................... 13

IV. Timeline ................................................................................................................... 18

V. Glossary of Terms & Abbreviations ..................................................................... 20Docket Number: EPA-HQ-OPP-2009-0546 www.regulations.gov

Peroxy Compounds Registration Review Team

Human Health & Environmental Effects Nathan Mottl (AD) Najm Shamim (AD) Miachel Rexrode (BPPD)

Risk Management Eliza Blair (AD) Lance Wormell (AD) Andrew Bryceland (BPPD)

Office of General Counsel Philip Ross

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I. Introduction:

This is the Environmental Protection Agency’s (EPA or “the Agency”) Final Work Plan for the registration review of Pe roxy Compounds. The work plan includes the expected registration review timeline. Th e work plan also addresses public comments received concerning the Preliminary Work Plan in the Summary Document which was posted in the Peroxy Compounds registration review docket, and any other comments concerning the initial docket postings. Th e Summary Document 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 Review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 year s to determine whether it continues to meet the FIFRA standard for registration. Changes in science, public policy and pesticide use practices will occur over time. The registrati on review program is intended to make sure that, as the ability to assess risk evolve s and as policies and practices change, all registered pesticides continue to meet th at statutory standard . The public phase 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 Peroxy Compounds case includes th ree active ingred ients: hydrogen peroxide, peroxyacetic acid, and potassium peroxymonosulfate sulfate. The Peroxy Compounds Preliminary Work Plan was entere d into the docket for this registration review on September 23, 2009. The 90-day comment period ended on December 22, 2009. The Preliminary Work Plan document is available on www.regulations.gov , docket number EPA-HQ-OPP-2009-0546.

II. Summary of Comments Receive d on Preliminary Work Plan:

EPA received several comments from the Peroxy Compounds Task Force (PCTF) during the public comment period on the initial docket as described below. In addition, the Agency received one comment from the FIFRA Endangered Species Task Force (FESTF). The anticipated data needs, work plan and timeline described in the Preliminary Work Plan remain as they were presented initially. This document makes final the work plan for the Peroxy Co mpounds registration review process.

In the Preliminary Work Plan, the Agen cy solicited comments on three specific topics: environmental justice, water body impairment, and trade irritants. No comments or information were received during the comment period concerning these issues.

Comment : The FIFRA Endangered Species Task Force (FESTF) submitted a comment noting that it has data that will assist the Agency in conducting an endangered species risk assessment for Peroxy Compounds, and requ esting that any technical registrant for Peroxy Compounds who is not a member of the FESTF (or a company having met its data compensation obligations) be asked to provide a formal offer-to-pay to FESTF for

reliance on their data.

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Response : The Agency thanks FESTF for its comment and will consider this information as it conducts the registrati on review and makes its regi stration review decisions.

TOXICITY DATA NEEDS

Comment: There are no data available to ch ange EPA’s conclusions about the risk profile of the substances for the traditional uses of the compounds. The registrant points out that an Occupational Safety and Health Administration Permissible Exposure Limit (PEL) for hydrogen peroxide exists, and that occupational exposure limits for hydrogen peroxide around the world are uniform at th e 1 ppm level. OSHA review of the 28-day study conducted in the European Union (EU) resulted in no change in PEL.

Response: The Occupational Safety and Health Administration (OSHA) developed Permissible Exposure Limits (PELs) for hydrogen peroxide to regulate industrial worker’s exposure to hydrogen peroxide vapor or mist. The Office of Pesticide Programs considers PEL information but does not solely rely on this information to develop a toxicological endpoint for occupationa l and residential risk assessments.

EPA traditionally develops toxicity e ndpoints for risk assessments using a No Observed Adverse Effect Level (NOAEL) a nd /or Lowest Observed Adverse Effect Level (LOAEL) (U.S. EPA 2009) that are base d on dose response curves that are usually developed using animal studies. In addition, EPA traditionally applies safety/uncertainty factors to the NOAEL/LOAEL to develop a toxi cological endpoint that can be used to develop a human health risk assessment. The Agency determined that the EU data provides the most acceptable hazard characte rization and dose response data which can be utilized to develop a t oxicological endpoint. In addi tion, EPA developed uncertainty factors to apply to the EU LO AEL in order to develop a toxicological endpoint. However, in response to the comment, EPA will review the OSHA PEL information again during the registration review process and look at th e toxicological data and uncertainty factors used to develop the toxicological determ ination of the OSHA PEL and see how this information compares to the EU risk assessment information. However, at this time EPA believes it should not solely rely on the OSHA’s PEL data to establish toxicity endpoints for risk assessment for the regulatory purpos es. EPA has already determined that OSHA used the following studies to develop its PEL:

• Oberst, F.W. Comstock, C.C.; Hackley, E.B. Inhalation Toxicity of Ninety Percent Hydrogen Peroxide Vapor- Acute, Subacute, and Chronic Exposure to Laboratory Animals.Arch. Ind. Hyg. Occup. Med. 10:319-327 (1954).

• Hathway, G.J.; Proctor, N.H.; Hughes, J. P. Hydrogen Peroxide. In: Proctor and Hughes Chemical Hazards of the Workplace, 4 th ed. Van Nostrand Reinhold, New York (1996).

• Stellman, J.M.; Hydrogen Peroxide. In: En cyclopedia of Occupational Health and Safety, 4 th ed., Chap 104, p. 349. International Labour Office, Geneva (1998).

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The Agency is reviewing the Stellman (1998) study. However, the Agency does

not have the other studies.

The Agency believes that fogging, fumigating, and spraying with Peroxy Compounds using pressurized spra ys can generate vapors, aerosols or mists that can potentially be hazardous to applicators, bys tanders, or people reen tering a sprayed area. OSHA has set a PEL at 1.0 ppm (1.4 mg/m 3 ) for hydrogen peroxide and the EU data LOAEL is 2.9 mg/m3. EPA provided the follo wing comment on the EU endpoints in a previous review (“Hydrogen Peroxide – Interim Inhalati on Toxicological Endpoints for Risk Assessment for uses as a fumigant in sealed room enclosures and vehicles”, June 2006).

“Comments about Study/Endpoint: The EU believed the nasal localization of the primary injury by peroxide is what can be expected from a water soluble oxidant vapor. As regards pathology in the lungs, the authors of the study considered it unlikely t hat the effects were

treatment related due to the absence of a re lationship with exposure concentration and the low incidence, and hence EU identify the 2.9 mg/m 3 as the NOAEL of the study. Since the study report is not available to the Agency, RASSB can not assess the severity of the pathological effects identified in the study. However, the findings were consistent and persistent throughout all treatment groups. RASSB believes 2.9 mg/m 3 should be

identified as LOAEL of the study given the fact that hydrogen peroxide and/or its immediate degradation products (reactive o xygen species) are strong oxidants and can cause airway inflammation (D324625).”

Note without the full EU submittal, the Agency applied the following uncertainty

recommendations ( 3x for LOAEL to NOAEL, 10x for intra-species, and 10x for inter species) and developed a target MOE of 300 for short-term and intermediate-term inhalation assessments in the past (D324625). At this point, the Agency still does not

have a full dataset from the EU document. The full dataset will allow the Agency to assess the severity of the pathological e ffects on the lung, and make a dose-dependent

determination.

Although there is not a consid erable difference between th e 2.9 mg/m3 value reported from the EU and the 1.4 mg/m3 OSHA PEL valu e, there is a considerable difference when an additional 300 uncertainty factor is applied to the LOAEL for regulatory purposes using the standard EPA paradigm discussed in the second paragraph. The key considerations for EPA at this point will be selecting an appropriate inhalation endpoint based on supportable data and supportable unc ertainty factors and to evaluate the products to see if the ap plication concentrations are greate r than 3% and can result in an inhalation exposure. The Agency anticipates that those vapors, fogs, mists, aerosols that have hydrogen peroxide concentr ation >3% will need to be qu antitatively assessed in risk assessments using Agency sele cted toxicological endpoints.

Comment: There is no need for a 90-day Inha lation Toxicity Study because observed effects in the existing 28-day range finding study were rela ted to acute toxicity and cumulative effects are not anticipated. Nego tiations are in progress between the task

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force and the European Chemical Industry C ouncil (CEFIC) to obtai n access to the 28- day range finding study (see “CEFIC 2002” in References) for submission to EPA.

Response: In a previous registration action for hydrogen peroxides by the Agency in 2006 for uses of Peroxy Compounds as fumiga nts, the Agency developed an interim toxicity endpoint using the 28-day inhalation range finding st udy. However, at the time of the assessment, the Agency did not have a complete submission of this study. The Agency still does not have the complete subm ission of these data. The Agency believes

the task force should submit the available inhala tion toxicology data. If the task force can provide a full submission of this data to EPA, then EPA will initiate a comprehensive review of the complete submission and genera te a data evaluation record (DER) of the study. In the event that the review of the complete submission indicates the study is acceptable then the EPA would not need anot her inhalation study. However, without the submission of the complete EU data set, the EP A still anticipates that there is a need for a 90-day Inhalation Toxicity Study as per guideline number 870.3465.

HUMAN EXPOSURE DATA NEEDS

Comment on the Description of Human Activity (GLN) 875.2800 : The PCTF will work

with EPA to describe the human activities associated with inhalation exposures of concern. The PCTF’s preliminar y understanding is that EPA is concerned with inhalation exposures resulting from mechanically genera ted aerosol applications, including foggers and automated sprayers, and potentially resi dues from application of peroxygen products in HVAC systems. The listing of uses men tioned above will be a starting point for developing these descriptions.

Response: The Agency anticipates that end-use pr oducts that produce vapors, fogs, mists, and/or aerosols that have hydrogen peroxide concentration in excess of 3% will need to be quantitatively assessed in risk assessmen ts using Agency selected toxicological endpoints.

Comment on Human Exposures #1 : It is not clear what, if any, concerns EPA has about human exposures during uses that apply the products by mists, fogging, or other mechanically generated aerosols. Exposures to the applicators duri ng application is not likely to be significant, because sensory irrita tion of the eyes and upper respiratory tract at the anticipated airborne con centrations cannot be tolerated.

Response #1: The Agency does not believe it ha s enough toxicological dose response

data to make a clear determination ab out the hazards of this chemical.

Please refer to Agency wa iver guidance (EPA, 2002):

“An active ingredient which causes severe irri tation or corrosion of the skin or eye will also damage the sensitive respiratory mucosa if inhaled. Waivers should be granted for active ingredients which are corrosive (pH <2 or >11.5) or severely irritating. Waivers should not be granted for active ingredients which are slight to moderate irritants. Inhalation toxicity

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studies of irritants can quantify the sensitivity of this route and characterize portal-of-entry

effects. This information is ess ential in an inhalation risk assessment.”

According to the acute inhalation data in the Human Health Scoping Document, hydrogen peroxide and peroxyacetic acid exposures through the inhalation route are moderately irritating to the lungs (toxicity cat egory II). Using the cu rrent waiver criteria the Agency does not believe that enough rationale exists for waiver and expects to require the registrant to submit the complete EU st udy or if this is not possible submit a new inhalation study to clear up a ny uncertainties whether the irritation and pathological damage of this chemical to the lung tissue is related to the treatment related issues (e.g. dose response issues).

Comment on Human Exposures #2: Application of aerosol sprays of dilute ready-to-use liquids and Use Dilution solutions by hand actuated and low pressure mechanically driven sprayers for many uses do not genera te significant fine droplet mist or fog. Applications by such means principally app lies product as droplets with sufficient fine droplet mist or fog. Application by such means principally applies product as droplets with sufficient size so that their persistence as airborne droplets is a matter of seconds to about a minute because of settling and evaporati on. In these circumstances, fine droplets (those that might be in a resp irable range of 10 micrometers or less) typically amount to much less than a few tenths of a percent of the sprayed liquid volume, and so, their contribution to inhalation exposure is in significant in compar ison with the vapor concentration resulting from evaporation from the sprayed surfaces.

It would be helpful for the Agency to qua ntitatively define th e terms fog, mist, and aerosol preferably by droplet size and concentration.

Response #2: As per the Agency’s (EPA, 2002) waiver guidance, “An aerosol for a product formulation or application method can be considered essentially non-inhalable provided 99% of the particle s are >100 μm in diameter. Although aerosols that meet these criteria are candidates for waivers, it is the responsibility of the registrant to provide

data on aerosol size distribution.”

Comment on Human Exposures #3: Many products have instructi ons for use that require the worker to wear personal protective equi pment including eye protection, respirators, and skin protection as well. Similarly, some of the mixing operations would require appropriate equipment according to the Mate rial Safety Data Sheets (MSDS) of the product. OSHA standards require the use of PPE where the PPE can mitigate a potential hazard. Clearly with the peroxygen compounds, exposures of the kind that concern EPA would be subject to the PPE requi rements in occupational settings.

For non-occupational exposures, the PCTF will work with EPA to assess and document the potential exposures for the risk assessment. EPA has used risk assessment standards in the Worker Protection Standard ( 40 C.F.R. Part 170) that defines reentry time limits for greenhouse applications based on engineer ing considerations of ventilation of the

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space with fresh air. A similar approach ma y be suited to the HVAC applications and mechanical indoor fogging and misting applications.

Response #3: The Agency stated in “Summary of Human Health Effects Data for the Peroxy Compounds Registration Review Deci sion Document”, dated September 1, 2009, that “Formulations of Peroxy Compounds are usually highly diluted as labeled products (usually maximum dilution is 3%), and fo rmulations containing hydrogen peroxide are commonly sold in the marketplace as antiseptics. The Food and Drug Administration (FDA) designated hydrogen peroxide as gene rally regarded as safe (GRAS). Hydrogen peroxide is found in the human body and natura lly breaks down as a result of detoxifying enzymes found in cells (eg., catal ase, glutathione peroxidase).”

As a result the Agency also does not anticipate that it will need additional applicator data using diluted (e.g. less than 3%) concentra tions of Peroxy Compounds for trigger sprays, mopping, or wiping and will only qual itatively assess uses >3%.

Until a risk assessment has been completed, the Agency cannot comment on potential label changes such as PPE or reentry intervals.

PRODUCT CHEMISTRY, ENVIRO NMENTAL FATE AND ECOLOGICAL

EFFECTS

Comment: The PCTF appears to believe that the Agency has already completed a risk assessment for Peroxy Compounds, and th at it views Peroxy Compounds like conventional pesticides in terms of st ability, metabolism, environmental fate, biodegradation, and exposur e and risk concerns.

Response: The registration review PWP and sup porting scoping documents are not risk assessments, but a summary of the informati on/documents/data currently available and possible information that the Agency will need to support risk assessment.

The Agency, however, would consider any additional data that may be available (published literature, other na tional and international organi zations’ databases, etc.) The Agency takes into account the unique physical/chemical characteristics of each

antimicrobial when it conducts the risk assessment. The data requirements of antimicrobials are based not only on the physical /chemical characteristics, but also on the use pattern and application rates of the pest icide. Sometimes a simple chemical, because of the high application rates, may result in risk concer ns; or a use pattern may show a high level of exposure, which may result in ri sk concerns, and therefore, the Agency has to take into account not only the physical/chemical propertie s but also the application rates as well as the possibility of high levels of exposure of a pesticide when it is applied

as an antimicrobial.

o The Agency has indicated only one product chemistry data gap: solubility in organic solvents. The Agency does recognize because of the nature of a chemical, it may not be soluble at all in any organi c solvent, but then it may be sparingly

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soluble in some organic solvent. The registrants may submit rationale for why they believe this study is unneeded at the time of the data call-in.

o The Agency has looked into the environm ental database that it possesses and reviewed the studies, most of which we re open literature or done by European Agencies, and expects to need new envir onmental fate data for hydrogen peroxide and peroxyacetic acid at the time of risk assessment. Irrespective of the fact the uses are indoor or outdoor, the possibility of antimicrobials’ presence in the waste water streams exists, and thus the Agency would like to make sure that such peroxides do not end up in the drinking water or sludge as biosolids which may then be applied to agricultural lands. A si milar approach was adopted for the third chemical in this case, potassium peroxy monosulfate sulfate, but no chemistry or environmental fate data are expected to be needed for the potassium peroxymonosulfate risk assessment.

o Ecological effects data gaps are identifi ed by the Agency in the scoping document and this FWP. Once a DCI is issued, regi strants may request a waiver for any or

all of the studies.

Comment: Under Section V of their comment letter, PCTF has referenced a few European Documents which are risk assessment documents on the Peroxy Compounds. PCTF recommends that the Agency should incl ude the assessments and their conclusions in its risk assessment for the Peroxy Compounds.

Response: The Preliminary Work Plan and “Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for Hydrogen peroxide, Peroxyacetic acid, and Potassium Peroxymonosulfate for Registra tion Review”, dated September 2, 2009, do

include some of the indicated fate studies in an environmental fate data table and summary. The Agency will include the addi tional documents which PCTF has provided in its reference database for the Peroxy Compounds case and consider them when conducting the risk assessme nt of Peroxy Compounds.

Comment: Solubility in organic compounds of hydrogen peroxide and peroxyacetic acid should not be required as it forms an unstable explosive mixture with organic materials.

Response: Hydrogen peroxide does produce an e xplosive mixture with organic materials when the peroxide is highly concentrated. At the concentration leve l in end-use products, mixing of peroxide and organic solvents will not produce explosive mixtures. Previous work on solubility of hydrogen peroxide with organic solvents has shown that hydrogen peroxide is soluble in ethyl acetate, amyl acetate, isobutyl alc ohol, acetophenone, etc; however, many of these solvents are no longer in use. The Agency needs a Solubility in Organic Compounds study using solvents such as methanol, ethanol, acetone, hexane, or benzene to complete its product chemis try database on Peroxy Compounds.

Activated Sludge Sorption Isotherm

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Comment: As Peroxy Compounds are rapidly biodegr adable, this study is not feasible. A waiver is requested.

Response: The Agency believes the registrants are able to conduct this study and that the information from this study is required to conduct a risk assessment. Once the DCI is issued, the Agency will consider any formal request for a waiver.

Ready Biodegradability

Comment: The PCTF has existing data that it can provide it to the Agency.

Response: The Agency encourages the PCTF and all stakeholders to submit any studies that might assist the Agency in conducting risk assessments.

Estuarine/Marine Shrimp

Comment: Additional Studies have been submitted to the Agency and these studies have been assigned MRIDs. The submitted studies should satisfy the data requirement.

Response: The Agency will evaluate the studies prior to conducting the risk assessments and, if appropriate, will consider waiving this data requirement.

Aquatic Invertebrate Life Cycle

Comment: EPA has received a study on Daphnia 21-day life cycle study using peroxyacetic acid and has classifi ed this study as supplemental.

Response: The Agency will make the correction in its database to remove the data gap.

Fish Early Life Stage

Comment: A study has been completed for this category and submitted by CEFIC to EU. Also, FDA has approved hydrogen peroxide as a new animal drug to control various fungal and bacterial diseases in freshwater-rea red finfish eggs and finfish species in 2007. This approval was sought and obtained by USGS’s Upper Midwest Environmental Science Center. A summary of the testing program has been submitted to EPA through

the EPA docket.

Response: The Agency cannot rely on a summary of a study and encourages the PCTF to submit the complete study

.

Whole Sediment, Acute Invertebrate, Fresh Water and Whole Sediment, acute Invertebrate, Marine Water

Comment: A waiver is requested based on the we ll-known chemistry of these two Peroxy Compounds.

Response: Once the DCI is issued, the Agency w ill consider any formal request for a

waiver.

Avian Oral

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Comment: This study on hydrogen peroxide has been submitted and reviewed by EPA

and classified as ‘core’.

Response: The Agency will make the appropriate changes in its database

.

Aquatic Plant, Toxicity using Lemna spp, and Algal Toxicity, Two species: Anabaena flos-aquae and Navicula pelliculosa

Comment: Studies were conducted a nd provided to the Agency on these scenarios.

Response: The Agency will make the appropriate changes in its database. The Agency requests that the PCTF provide the correct MR ID#s since those referenced in the PCTF’s response appear to be inaccurate.

Modified Activated Sludge Respiration Inhibition

Comment: A study exists that, if taken into account, will negate the requirement for this

data.

Response: The Agency encourages the PCTF and all stakeholders to submit any studies that might assist the Agency in conducting risk assessments.

References:

Hydrogen Peroxide – Interim Inhalation Toxi cological Endpoints for Risk Assessment for uses as a fumigant in sealed room encl osures and vehicles. Memorandum from J. Tao, Senior Toxicologist, U.S. EPA to Marshall Swindell, Product Manager, U.S. EPA. June,

2006.

CEFIC 2002. Hydrogen Peroxide: 28-day Inhalation Study in Rats. CTL/MR0211/Technical Toxicology/Report. Central Toxicology Laboratory, Alderley Park Macclesfield. CEFIC Peroxygen Sector Group (cited in EU Risk Assessment Report: hydrogen peroxide. 2003).

“Summary of the Human Effects Data for the Peroxy Compounds Registration Review

Decision Document”. Memorandum from N. Mot tl, Biologist, U.S. EPA to E. Blair, Chemical Review Manager, U.S. EPA. September, 2009.

U.S. EPA 2009. Revised Risk Assessment Methods for Worker, Children of Workers, in Agricultural Fields and Pesticide with Non Food Uses. December 2009. Docket #: EPAHQ-OPP-2009-0889-002.

U.S. EPA 2002. Guidance. Waiver Criteria for Multiple-Exposure I nhalation Toxicity Studies. Memorandum from M.Stasikowski, Di rector HED, U.S. EPA to HED Staff. August 2002.

III. Risk Assessment and Data Needs:

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Biochemical Considerations

The Agency has reviewed the database for biochemical pesticide products containing Peroxy Compounds and does not antic ipate needing additional human health or environmental fate and ecotoxicity data for these products for the registration review of this case. An endangered species risk assessment will be performed for biochemical pesticide products at the same time as the antimicrobials assessment. However, additional data for antimicrobial Peroxy Compounds products will be ne eded to complete a risk

assessment.

Antimicrobial Considerations

The following discussion of risk, exposure and data needs applies only to antimicrobial products co ntaining Peroxy Compounds.

A Reregistration Eligibility Decisi on (RED) was completed for Peroxy Compounds in 1993. Since then, data has been submitted to the Agency and reviewed. However, to complete registration review, additional data are needed to conduct the human health and ecological risk assessments.

Human Health Risk

Toxicity

In a previous registration action for hydr ogen peroxide by the Agency in 2006 for uses of Peroxy Compounds as fumigants, th e Agency developed an interim toxicity endpoint using a 28-Day Inhalation Toxicity Study in Rats (see “Hydrogen Peroxide – Interim Inhalation Toxicological Endpoints for Risk Assessment for uses as a fumigant in sealed room enclosures and vehicles”, dated June 5, 2006). However, the study submission on which the interim endpoint was based was only a summary of an industry study (“28-day rats inhalati on study” - CEFIC Peroxygen Se ctor Group, 2002) cited in a European Union (EU) risk assessment for hydrogen peroxide (see http://ecb.jrc.ec.europa .eu/DOCUMENTS/ExistingChemicals/RISK_ASSESSMENT/REPO RT/hydrogenperoxidereport022.pdf ).

The summary report was sufficient to es tablish an interim endpoint for Peroxy Compounds; however, the full study report for this study, or an equivalent study, is needed to establish a long-term endpoint fo r the registration review risk assessments. Therefore, the Agency anticipates ne eding a 90-day inhalation study to support development of a long-term endpoint for the human health risk assessment.

Dietary and Drinking Water Exposure

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Certain registered outdoor Peroxy Compounds use sites or those often directly discharged are likely to resu lt in dietary exposure via drinki ng water. Such sites include Human Water Systems (Bottled Water Cont ainers, Water Filters, Drinking Water Coolers, Ice Making Machines, Chemigati on Systems Connected to Public Water Systems and Dental Unit Water Lines), and I ndustrial Processes and Water Systems (Air Washer Water Systems, Evaporative Condens er Water Systems, Commercial/Industrial Cooling Water [Recirculating], Commercia l/Industrial Cooling Water, etc.).

According to the Federal Register: Ma y 6, 1998 (Volume 63, Number 87), pages 24955-24963,

“Although the proposed food contact uses for hydrogen peroxide acid may result in transfer of minor amounts of residues to potential drinking water sources, no risk assessment is warranted because of: (i) the rapid degradation of hydrogen peroxide into oxygen, and water, and (ii) these degradates are not of toxicological

concern. Information from the EPA Office of Water also indicates that when used for potable water disinfection, no residues of hydrogen peroxide acid are present by the time the water is pumped through a distribution system.”

Therefore, the Agency does not anticipate that a quantitative drinking water risk assessment will be needed in this registration review.

Occupational and Residential Exposure

An occupational and/or residential exposur e assessment is required for an active ingredient if (1) certain toxi cological criteria are triggere d and (2) there is potential exposure to handlers (mixers, loaders, applicat ors, etc.) during use. The Agency believes potential occupational and residential inhala tion exposures can occur when spraying, misting, applying fumigants, and/or foggi ng in the following use categories:

• agricultural premises and equipment

• food handling premises

• commercial, institutional, and industrial premises

• residential and public access premises

• medical premises and equipment

Anticipated Human Health Data Needs

Human Health Toxicity:

o (GLN 870.3465) 90-day Inhala tion Toxicity Study

Occupational and Residential Exposure:

o (GLN 875.1400) Inhalation Indoor Exposure

o (GLN 875.1600) Data Reporti ng and Calculations

o (GLN 875.1700) Product Use Information

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o (GLN 875.2500) Inhalation Exposure

o (GLN 875.2800) Description of Human Activity

o (GLN 875.2900) Data Reporti ng and Calculations

Once the Agency receives and reviews th ese toxicological studies, if they are required, additional occupational, dietary and aggregate assessments may be needed.

Further information is available in “Summa ry of Human Health Effects Data for the Peroxy Compounds Registration Review Deci sion Document,” dated September 1, 2009.

Anticipated Physical/ Chemic al Property Data Needs

The Agency’s database for product chemis try is nearly complete; the agency anticipates needing only the following pr oduct chemistry study for all three active ingredients in order to complete a risk assessment for the Peroxy Compounds case:

o (GLN 830.7860) Solubility in Organic Compounds

Further information is available in “Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Da ta for the Peroxy Compounds Registration Review Summary Document”, dated September 2, 2009.

Environmental Fate

The Agency has determined that th e reactivity of hydrogen peroxide and peroxyacetic acid is similar and hence they wi ll be treated as interchangeable for the purposes of the environmental fate and ecotoxicity risk assessment.

Much of the Agency’s database on hydrogen peroxide and peroxyacetic acid has been drawn from the open literature. Moreoever, both hydrog en peroxide and peroxyacetic acid degrade into chemicals that are not e nvironmentally harmful: hydrogen peroxide into water and oxygen, and peroxyace tic acid into water and acetic acid, which ultimately degrades into carbon dioxide and water.

Both hydrogen peroxide and peroxyacetic acid are widely used as indoor disinfectants and sanitizers. However, there ar e some outdoor uses that are likely to give rise to high exposure: once- through cooling towers, wastewater treatment plants and

ballast water.

Potassium peroxymonosulfate sulfate has two indoor-use registrations. This chemical is an inorganic salt and environmenta l fate and transport test guidelines, which were developed for organic compounds only, cannot be used to c onduct the studies and obtain fate and transport parameters. In addition, it is a salt which contains a peroxy functional group which makes it very reactive, and it readily oxidizes/ breaks down in an aqueous medium. Moreover, it will produce kno wn ions which are already present in the

environmental media like water and soils. In the presence of sodium chloride it produces hypochlorous ion which also acts as a disinfectant. At th is time the Agency does not

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believe that additional environmental fate and transport data will be needed to assess potassium peroxymonosulfate.

Ecological Risk

Environmental fate and ecological risk assessments have not been conducted for the active ingredients in this case. As stat ed above, potassium pe roxymonosulfate sulfate has two indoor-use registrations and is not expected to persist in the environment. However, similar to the environmental fa te risk assessment needs above, the same outdoor use scenarios for hydrogen peroxide and peroxyacetic acid are expected to trigger acute and ch ronic data needs.

The Agency has not conducted a risk assessment that supports a complete endangered species determination. The eco logical risk assessment planned during registration review will allow the Agency to determine whether Peroxy Compounds’ use has “no effect” or “may affect” federally lis ted threatened or endangered species (listed species) or their designated critical habita ts. 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 Service (the Services ), as appropriate.

Anticipated Environmental Fate and Ecological Data Needs for Hydrogen Peroxide and Peroxyacetic Acid

The Agency anticipates needing the followi ng data in order to conduct a complete environmental fate and ecotoxicity asse ssment, including an endangered species

assessment for all uses:

Environmental Fate Risk Assessment Data Needs :

o (GLN 850.6800) modified activated sludge respiration inhibition

o (GLN 835.1110) activated sl udge sorption isotherm

o (GLN 835.3110) ready biodegradability

Ecological Risk Assessment Data Needs :

o (GLN 850.4400) Aquatic pl ant toxicity using Lemna spp

o (GLN 850.5400) Algal t oxicity, two species: Anabaena flos-aquae and Navicula pelliculosa

o (GLN 850.1035) Estuarine/marine shrimp

o Acute effects monitoring data from a harbor where ballast water is released. Depending on the results of this monitoring data, the following studies may also be needed:

• 850.1735-Whole sediment, acute invertebrates, fresh water

• 850.1740-Whole sediment, acute invertebrates, marine

• 850.1400-Fish early life stage

14Docket Number: EPA-HQ-OPP-2009-0546 www.regulations.gov

Endocrine Disruptor Screening Program

As required under FFDCA section 408(p) , EPA has developed the Endocrine Disruptor Screening Program (EDSP) to dete rmine whether certain substances (including pesticide active and other ingred ients) may have an effect in humans or wildlife similar to an effect produced by a “natur ally occurring estrogen, or othe r such endocrine effects as the Administrator may designate.” The ED SP employs a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substa nce to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to inte ract with E, A, or T hormonal systems will proceed to the next stage of the EDSP wher e EPA will determine which, if any, of the Tier 2 tests are necessary based on the avai lable data. Tier 2 te sting is designed to identify any adverse endocrine related eff ects caused by the substance, and establish a dose-response relationship between th e dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which c ontains 58 pesticide ac tive ingredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathways such as food and wa ter, residential activity, and certain postapplication agricultural s cenarios. This list should not be construed as a list of known or likely endocrine disruptors.

None of the Peroxy Compounds are am ong the group of 58 pesticide active ingredients on the initi al list to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemi cals. Accordingly, EPA anticipates issuing

future EDSP test orders/data call-ins for all pesticide active ingredients.

For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our

website: http://www.epa.gov/endo/

.

IV. Timeline:

EPA has created the following estimated timeline for the completion of the Peroxy Compounds registration review.



### Registration Review for Peroxy Compounds Projected Registration Review Timeline

Activities Time

Opening Docket
Open Docket Completed September 2009

Close Public Comment Period Completed December 2009
Case Development

15Docket Number: EPA-HQ-OPP-2009-0546 www.regulations.gov



### Registration Review for Peroxy Compounds Projected Registration Review Timeline

Activities Time

Final Work Plan March 2010

Issue DCI September 2010

Data Submission September 2011
Preliminary Risk Assessment September 2013

Close Public Comment Period December 2013

Registration Review Decision
Proposed Registration Review Decision March 2014

Public Comment Period June 2014 Final Registration Review Decision & Begin Post-Decision Follow-up 2014 Total (years) 4

Next Steps:

A Data Call-In (DCI) will be developed regarding the data gaps listed under the

“Risk Assessment and Data Needs” section. Also, human health and ecological risk

assessments will be conducted for all uses.

16Docket Number: EPA-HQ-OPP-2009-0546 www.regulations.gov

V. GLOSSARY of TERMS & ABBREVIATIONS

ai Active Ingredient AR Anticipated Residue ASTM American Society for Testing and Materials

AWPA American Wood Preserver’s Association

CFR Code of Federal Regulations cPAD Chronic Population Adjusted Dose

CSF Confidential Statement of Formula CSFII USDA Continuing Surveys for Food Intake by Individuals

DCI Data Call-In DEEM Dietary Exposure Evaluation Model DFR Dislodgeable Foliar Residue DNT Developmental Neurotoxicity DWLOC Drinking Water Level of Comparison

EC Emulsifiable Concentrate Formulation EDWC Estimated Drinking Water Concentration

EEC Estimated Environmental Concentration EPA Environmental Protection Agency

EUP End-Use Product FDA Food and Drug Administration FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FFDCA Federal Food, Drug, and Cosmetic Act FQPA Food Quality Protection Act FOB Functional Observation Battery GENEEC Tier I Surface Water Computer Model

IR Index Reservoir

LC 50 Median Lethal Concentration. A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD 50 Median Lethal Dose. A statistically deri ved single dose that can be expected to

cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.

LOC Level of Concern

LOAEL Lowest Observed Adverse Effect Level μg/g Micrograms Per Gram μg/L Micrograms Per Liter mg/kg/day Milligram Per Kilogram Per Day mg/L Milligrams Per Liter MOE Margin of Exposure

MRID Master Record Identifi cation (number). EPA's system of recording and tracking

submitted studies. MUP Manufacturing-Use Product

NA Not Applicable NAWQA USGS National Ambient Water Quality Assessment NPDES National Pollutant Discharge Elimination System

NR Not Required

NOAEL No Observed Adverse Effect Level

OPP EPA Office of Pesticide Programs OPPTS EPA Office of Prevention, Pesticides and Toxic Substances PAD Population Adjusted Dose PAIRA Pure Active Ingredient Radiolabelled PCA Percent Crop Area

17Docket Number: EPA-HQ-OPP-2009-0546 www.regulations.gov

18 PDP USDA Pesticide Data Program PHED Pesticide Handler's Exposure Data

PHI Preharvest Interval ppb Parts Per Billion

PPE Personal Protective Equipment

ppm Parts Per Million PRZM/EXAMS Tier II Surface Water Computer Model Q 1 * The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer

Risk Model RAC Raw Agriculture Commodity RASSB Risk Assessment and Science Support Branch RED Reregistration Eligibility Decision

REI Restricted Entry Interval

RfD Reference Dose RQ Risk Quotient SCI-GROW Tier I Ground Water Computer Model

SAP Science Advisory Panel SF Safety Factor

SLN Special Local Need (Registrati ons Under Section 24©) of FIFRA) TGAI Technical Grade Active Ingredient

TEP Typical End-Use Product USDA United States Department of Agriculture UF Uncertainty Factor

WPS Worker Protection Standard