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 2010 

 

 

Docket 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 ..................................................................... 20 

 
Docket Number: EPA-HQ-OPP-2009-0546 

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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 Peroxy Compounds. The work plan includes the 

expected registration review timeline. The 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. The 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 years 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 registration 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 that 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 three active ingredients: hydrogen 

peroxide, peroxyacetic acid, and potassium peroxymonosulfate sulfate. The Peroxy 

Compounds Preliminary Work Plan was entered 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 Received 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 Compounds registration review process. 

In the Preliminary Work Plan, the Agency 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 requesting 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 registration review and makes its registration review decisions. 

TOXICITY DATA NEEDS 

Comment: There are no data available to change 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 the 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 occupational and residential risk assessments. 

EPA traditionally develops toxicity endpoints for risk assessments using a No 

Observed Adverse Effect Level (NOAEL) and /or Lowest Observed Adverse Effect 

Level (LOAEL) (U.S. EPA 2009) that are based 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 toxicological endpoint that can be used to 

develop a human health risk assessment. The Agency determined that the EU data 

provides the most acceptable hazard characterization and dose response data which can 

be utilized to develop a toxicological endpoint. In addition, EPA developed uncertainty 

factors to apply to the EU LOAEL 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 the toxicological data and uncertainty factors 

used to develop the toxicological determination 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 purposes. 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, 4th ed. Van Nostrand Reinhold, New 

York (1996). 

• Stellman, J.M.; Hydrogen Peroxide. In: Encyclopedia of Occupational Health and 

Safety, 4th 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 sprays can generate vapors, aerosols or mists that can 

potentially be hazardous to applicators, bystanders, or people reentering a sprayed area. 

OSHA has set a PEL at 1.0 ppm (1.4 mg/m3

) for hydrogen peroxide and the EU data 

LOAEL is 2.9 mg/m3. EPA provided the following comment on the EU endpoints in a 

previous review (“Hydrogen Peroxide – Interim Inhalation 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 that the effects were 

treatment related due to the absence of a relationship with exposure concentration and the 

low incidence, and hence EU identify the 2.9 mg/m3 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/m3 should be 

identified as LOAEL of the study given the fact that hydrogen peroxide and/or its 

immediate degradation products (reactive oxygen 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 effects on the lung, and make a dose-dependent 

determination. 

Although there is not a considerable difference between the 2.9 mg/m3 value reported 

from the EU and the 1.4 mg/m3 OSHA PEL value, 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 uncertainty factors and to evaluate the 

products to see if the application concentrations are greater than 3% and can result in an 

inhalation exposure. The Agency anticipates that those vapors, fogs, mists, aerosols that 

have hydrogen peroxide concentration >3% will need to be quantitatively assessed in risk 

assessments using Agency selected toxicological endpoints. 

Comment: There is no need for a 90-day Inhalation Toxicity Study because observed 

effects in the existing 28-day range finding study were related to acute toxicity and 

cumulative effects are not anticipated. Negotiations are in progress between the task 

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force and the European Chemical Industry Council (CEFIC) to obtain 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 fumigants, the Agency developed an interim 

toxicity endpoint using the 28-day inhalation range finding study. 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 submission of these data. The Agency believes 

the task force should submit the available inhalation 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 generate 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 another inhalation study. However, without the 

submission of the complete EU data set, the EPA 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 preliminary understanding is that EPA is concerned with inhalation 

exposures resulting from mechanically generated aerosol applications, including foggers 

and automated sprayers, and potentially residues from application of peroxygen products 

in HVAC systems. The listing of uses mentioned above will be a starting point for 

developing these descriptions.

Response: The Agency anticipates that end-use products 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 assessments 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 during application is not 

likely to be significant, because sensory irritation of the eyes and upper respiratory tract 

at the anticipated airborne concentrations cannot be tolerated. 

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

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

Please refer to Agency waiver guidance (EPA, 2002): 

“An active ingredient which causes severe irritation 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 essential 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 category II). Using the current waiver criteria 

the Agency does not believe that enough rationale exists for waiver and expects to require 

the registrant to submit the complete EU study or if this is not possible submit a new 

inhalation study to clear up any 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 generate significant fine droplet mist or fog. 

Applications by such means principally applies 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 evaporation. In these circumstances, fine droplets 

(those that might be in a respirable 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 insignificant in comparison with the vapor 

concentration resulting from evaporation from the sprayed surfaces.

It would be helpful for the Agency to quantitatively define the 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 particles 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 instructions for use that require 

the worker to wear personal protective equipment including eye protection, respirators, 

and skin protection as well. Similarly, some of the mixing operations would require 

appropriate equipment according to the Material 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 requirements 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 engineering considerations of ventilation of the 

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space with fresh air. A similar approach may 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 Decision Document”, dated September 1, 2009, 

that “Formulations of Peroxy Compounds are usually highly diluted as labeled products 

(usually maximum dilution is 3%), and formulations containing hydrogen peroxide are 

commonly sold in the marketplace as antiseptics. The Food and Drug Administration 

(FDA) designated hydrogen peroxide as generally regarded as safe (GRAS). Hydrogen 

peroxide is found in the human body and naturally breaks down as a result of detoxifying 

enzymes found in cells (eg., catalase, 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%) concentrations of Peroxy Compounds for trigger sprays, 

mopping, or wiping and will only qualitatively 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, ENVIRONMENTAL FATE AND ECOLOGICAL 

EFFECTS

Comment: The PCTF appears to believe that the Agency has already completed a risk 

assessment for Peroxy Compounds, and that it views Peroxy Compounds like 

conventional pesticides in terms of stability, metabolism, environmental fate, 

biodegradation, and exposure and risk concerns. 

Response: The registration review PWP and supporting scoping documents are not risk 

assessments, but a summary of the information/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 national and international organizations’ 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 pesticide. Sometimes a simple chemical, because 

of the high application rates, may result in risk concerns; or a use pattern may show a 

high level of exposure, which may result in risk concerns, and therefore, the Agency has 

to take into account not only the physical/chemical properties 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 organic 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 environmental database that it possesses and 

reviewed the studies, most of which were open literature or done by European 

Agencies, and expects to need new environmental 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 similar approach was adopted for the third 

chemical in this case, potassium peroxymonosulfate 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 identified by the Agency in the scoping document 

and this FWP. Once a DCI is issued, registrants 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 include 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 Registration 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 additional documents which PCTF has provided 

in its reference database for the Peroxy Compounds case and consider them when 

conducting the risk assessment 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 explosive mixture with organic materials 

when the peroxide is highly concentrated. At the concentration level 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 alcohol, 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 chemistry database on Peroxy Compounds. 

Activated Sludge Sorption Isotherm

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Comment: As Peroxy Compounds are rapidly biodegradable, 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 classified 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-reared 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 well-known chemistry of these two Peroxy 

Compounds. 

Response: Once the DCI is issued, the Agency will 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 and 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 MRID#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 Toxicological Endpoints for Risk Assessment 

for uses as a fumigant in sealed room enclosures 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. Mottl, 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 Inhalation Toxicity 

Studies. Memorandum from M.Stasikowski, Director 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 anticipate 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 needed to complete a risk 

assessment. 

Antimicrobial Considerations

The following discussion of risk, exposure and data needs applies only to 

antimicrobial products containing Peroxy Compounds.

A Reregistration Eligibility Decision (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 hydrogen peroxide by the Agency in 2006 for 

uses of Peroxy Compounds as fumigants, the 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 inhalation study” - CEFIC Peroxygen Sector Group, 2002) cited in a 

European Union (EU) risk assessment for hydrogen peroxide (see 

http://ecb.jrc.ec.europa.eu/DOCUMENTS/ExistingChemicals/RISK_ASSESSMENT/REPORT/hydrogenperoxidereport022.pdf). 

 

 The summary report was sufficient to establish 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 for the registration review risk assessments. 

Therefore, the Agency anticipates needing 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 result in dietary exposure via drinking water. Such sites include 

Human Water Systems (Bottled Water Containers, Water Filters, Drinking Water 

Coolers, Ice Making Machines, Chemigation Systems Connected to Public Water 

Systems and Dental Unit Water Lines), and Industrial Processes and Water Systems (Air 

Washer Water Systems, Evaporative Condenser Water Systems, Commercial/Industrial 

Cooling Water [Recirculating], Commercial/Industrial Cooling Water, etc.). 

According to the Federal Register: May 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 exposure assessment is required for an active 

ingredient if (1) certain toxicological criteria are triggered and (2) there is potential 

exposure to handlers (mixers, loaders, applicators, etc.) during use. The Agency believes 

potential occupational and residential inhalation exposures can occur when spraying, 

misting, applying fumigants, and/or fogging 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 Inhalation Toxicity Study 

Occupational and Residential Exposure:

o (GLN 875.1400) Inhalation Indoor Exposure 

o (GLN 875.1600) Data Reporting 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 Reporting and Calculations 

 Once the Agency receives and reviews these toxicological studies, if they are 

required, additional occupational, dietary and aggregate assessments may be needed. 

Further information is available in “Summary of Human Health Effects Data for the 

Peroxy Compounds Registration Review Decision Document,” dated September 1, 2009. 

Anticipated Physical/ Chemical Property Data Needs 

The Agency’s database for product chemistry is nearly complete; the agency 

anticipates needing only the following product 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 Data for the Peroxy Compounds Registration 

Review Summary Document”, dated September 2, 2009. 

Environmental Fate 

The Agency has determined that the reactivity of hydrogen peroxide and 

peroxyacetic acid is similar and hence they will 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 hydrogen peroxide and 

peroxyacetic acid degrade into chemicals that are not environmentally harmful: hydrogen 

peroxide into water and oxygen, and peroxyacetic 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 are 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 environmental fate and transport test guidelines, which 

were developed for organic compounds only, cannot be used to conduct 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 known 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 this 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 stated above, potassium peroxymonosulfate sulfate 

has two indoor-use registrations and is not expected to persist in the environment. 

However, similar to the environmental fate risk assessment needs above, the same 

outdoor use scenarios for hydrogen peroxide and peroxyacetic acid are expected to 

trigger acute and chronic data needs. 

The Agency has not conducted a risk assessment that supports a complete 

endangered species determination. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether Peroxy Compounds’ 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 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 following data in order to conduct a complete 

environmental fate and ecotoxicity assessment, 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 sludge sorption isotherm 

o (GLN 835.3110) ready biodegradability 

Ecological Risk Assessment Data Needs: 

o (GLN 850.4400) Aquatic plant toxicity using Lemna spp 

o (GLN 850.5400) Algal toxicity, 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 

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Endocrine Disruptor Screening Program 

As required under FFDCA section 408(p), EPA has developed the Endocrine 

Disruptor Screening Program (EDSP) to determine whether 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 other such endocrine effects as 

the Administrator may designate.” The EDSP 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 substance 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 interact with E, A, or T hormonal systems will 

proceed to the next stage of the EDSP where EPA will determine which, if any, of the 

Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to 

identify any adverse endocrine related effects caused by the substance, and establish a 

dose-response relationship between the 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 contains 58 pesticide active ingredients and 9 

inert ingredients. This list of chemicals was selected based on the potential for human 

exposure through pathways such as food and water, residential activity, and certain postapplication agricultural scenarios. This list should not be construed as a list of known or 

likely endocrine disruptors. 

None of the Peroxy Compounds are among the group of 58 pesticide active 

ingredients on the initial list to be screened under the EDSP. Under FFDCA sec. 408(p) 

the Agency must screen all pesticide chemicals. 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 

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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. 

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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 

LC50 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. 

LD50 Median Lethal Dose. A statistically derived 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 Identification (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 

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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 

Q1* 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 (Registrations 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