United States Chemical Safety March 2011 Environmental Protection and Pollution Prevention Agency (7510P)



# Chlorhexidine Derivatives Summary Document Registration Review: Initial Docket March 2011Docket Number: EPA-HQ-OPP-2011-0069

www

. regulations

. gov



### Chlorhexidine Derivatives Summary Document Registration Review: Initial Docket March 201 1



## Case # 

## 3038

20f21 arrigan-Farrelly irector, Antimicrobials Divi

Date: 

# Z 

# p<£/2JJIIDocket Number: EPA

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### Table of Contents

Chlorhexidine Derivatives Registration Review Team .................................................................. 4 I. Preliminary Work Plan

-- Chlorhexidine Derivatives ................................................................. 5 II. Fact Sheet ................................................................................................................................. 12 III. Summary of An ticipated Data Requirements – Chlorhexidine Derivatives ........................... 16 IV. Appendix A: Use Patterns – Chlorhexidine D erivatives ....................................................... 18

________________________________________
Please Note

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

1. Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Chlorhexidine Derivatives Registration Review Decision Document. March 11, 2011

2. Chlorhexidine Derivatives (Chlorhexidine Diacetate and Chlorhexidine Digluconate): Human Health Assessment Scoping Document in Support of Registration Review. March 1, 2011

Additional supporting documents for the Chlorhexidine Derivatives Case may be found in the registration review docket EPA

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.Docket Number: EPA

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4 of 20 Chlorhexidine Derivatives Registration Review Team

Michelle Centra Human Health & Environmental Effects

Timothy Dole Srinivas Gowda

Rebecca von dem Hagen Risk Management

Lance Wormell

Philip Ross Office of General CounselDocket Number: EPA

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5 of 20 I. Preliminary Work Plan

-- Chlorhexidine Derivatives

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United States generally must be registered by the U.S. Environmental Protection Agency (USEPA, EPA, or the Agency) based on sc ientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess risk evolves and as pol icies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided at Introduction:

http://www.epa.gov/oppsrrd1/registration_review/

. 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. The Agency will consider 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 what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period, the Agency will develop and commit to a final work plan and schedule for the chlorhexidine d erivatives c ase.
The chlorhexidine derivatives case (Case Number 3038) includes three active ingredients, chlorhexidine diactetate (PC Code 045502), chlorhexidine digluconate (PC Code 045504) and chlorhexidine dihydrochloride (PC Code 481700). Chlorhexidine diacetate is registered for use as hard surface

- treatment disinfectants, sanitizer s, bactericides and virucides. Chlorhexidine diacetate is also registered to control bacteria in agricultural premises and equipment and to control certain viruses in animal premises and equipment, egg handling and packing equipment, and meat processing plants. Chlorhexidine digluconate is registered for use as a disinfectant for hard, non-porous surfaces (wheelchairs, metal bed frames, exteriors of toilets, countertops, metal surfaces, imaging equipment surfaces, glass, acrylic, and porcelain) in hospitals, restrooms, sch ools, offices, gyms, and homes. Chlorhexidine digluconate is also registered for use to control microbial contamination in dental unit waterlines. When EPA created the schedule for evaluating chemicals under the registration review pro gram, chlorhexidine dihydrochloride (PC Code 481700) was identified as being part of the chlorhexidine derivatives registration review

case. After further review, the Agency has determined that there are no registered pesticide products containing chlorhexidine dihydrochloride as an active ingredient (AI) and, thus, chlorhexidine dihydrochloride is not subject to evaluation under registration review and will be removed from Case 3038.

The first product containing chlorhexidine diacetate was registered in the United States in 1955. T here are currently five registered chlorhexidine diactetate products and two registeredDocket Number: EPA

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6 of 20 chl orhexidine digluconate products. The Agency completed a Reregistration Eligibility Decision (RED) for chlorhexidine diacetate in 1996 . Because the first product containing chlorhexidine digluconate was registered after November 1, 1984, a RED was not completed for chlorhexidine digluconate. Documents associated with the registration review of chlorhexidine derivatives can be viewed at www.regulations.gov in docket EPA

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The Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species risk assessment, for all uses of chlorhexidine derivatives. The Agency anticipates the need to conduct a human health risk assessment. The Agency anticipates needing additional data to conduct the registration review for chlorhexidine derivatives. Anticipated Risk Assessment and Data Needs:

Ecological Risk:

**•** No ecological risk assessment has been performed for chlorhexidine derivatives.

**•** The Agency has not conducted a risk assessment that supports a complete endangered species determination for chlorhexidine derivatives. The ecological risk assessment planned during registration review will allow the Agency to determine whether chlorhexidine derivatives’ uses have '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, th e 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 the registration review of chlorhexidine derivatives.

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 the registration review of chlorhexidine derivatives

.
835.2120

-- Hydrolysis 835.2240

-- Photodegradation in water 850.6800

-- Modified Activated Sludge Respiration Inhibition 835.1110

-- Activated Sludge Sorption Isotherm 835.3110 – Ready Biodegradability

**•** F or more information
, please refer to Summa ry of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Chlorhexidine Derivatives Registration Review Decision Document , located in the docket.Docket Number: EPA

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7 of 20 Human Health Risk:

**•** The most recent human health risk assessment for chlorhexidine diacetate was c onducted in support of the 1996 RED. The most recent human health risk assessment for chlorhexidine digluconate was completed in 2010 in support of its use in dental unit waterlines

.

**•** The Agency anticipates conducting residential and occupational exposure risk assessments for chlorhexidine derivatives based on current use patterns.

**•** The Agency anticipates conducting dietary and aggregate risk assessments for the registration revi ew of chlorhexidine derivatives.

**•** EPA does not have, at this time, available data to determine whether chlorhexidine derivatives have a common mechanism of toxicity with other substances or how to include these pesticides in a cumulative risk assessment. For the purposes of this Registration Review, EPA has assumed that chlorhexidine derivatives do not have a common mechanism of toxicity with other substances when used as an antimicrobial as registered

.

**•** The Agency anticipates the need to require the following additional human health data to conduct the registration review of chlorhexidine derivatives.

870.3465

-- 90- day inhalation toxicity (rat) 870.5100

-- Bacterial reverse mutation assay 870.5395

-- Mammalian erthrocyte micronucleus test 875.1200

-- Dermal indoor exposure 875.1400

-- Inhalation indoor exposure 875.1600

-- Application exposure data reporting and calculations 875.1700

-- Product use information 875.2300

-- Indoor surface residue dissipation

**•** The Agency has identified one product that is registered "for dipping teats as an aid in controlling bacteria that causes mastitis." EPA will examine this use as part of the registration review process.

**•** F or more information
, please refer to Chlorhexidine Derivatives (Chlorhexidine Diacetate and Chlorhexidine Digluconate): Human Health Assessment Scoping Document in Support of 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 at this time.Docket Number: EPA

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8 of 20 **•** F or more information
, please refer to Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Chlorhexidine Derivatives Registration Review Decision Document , located in the docket.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. A s part of the 1996 chlorhexidine diacetate reregistration decision and the 2010 chlorhexidine digluconate registration , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard databa se. However, as required by FFDCA section 408(p), chlorhexidine derivatives are subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). EPA has developed the EDSP to determine whether certain substances (including pest icide 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 m aking 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 throu gh 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
te sting 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.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. 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. Chlorhexidine derivatives were not among the group of 58 pesticide a ctive ingredients on the initial 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 assays for chlorhexidine derivatives

. For furthe r 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 screening battery, please visit our website: http://www.epa.gov/endo/.Docket Number: EPA

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9 of 20 Timeline

EPA has created the followin g estimated timeline for the completion of the chlorhexidine derivatives registration review:

Registration Review for Calcium Oxide

– Projected Registration Review Timeline Activities Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Docket March 2011 Close Public Comment Period for Docket May 2011 Phase 2: Case Development Develop Final Work Plan (FWP) September 2011 Issue DCI September 2012 Data Submission September 2014 Open Public Comment Period for Preliminary Risk Assessments March 2016 Close Public Comment Period for Preliminary Risk Assessments June 2016 Phase 3: Registration Review Decision Open Public Comment Period for Proposed Reg. Review Decision September 201 7 Close Public Comment Period for Proposed Reg. Review Decision December 201 7 Final Decision and Begin Post

- Decision Follow

- up 2017 Total (years) 6

Guidance for Commenters:

The public is invited to comment on EPA’s P reliminary 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 plan for the chlorhexidine derivatives registration review case.

Trade Irritants

Thr ough the registration review process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any trade irritant issues resulting from lack of Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the concern.

Water Quality

Chlorhexidine derivatives are n ot identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=88 5. In a ddition, no Total Maximum Daily Loads (TMDL) have been developed for chlorhexidineDocket Number: EPA

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10 of 20 derivatives , based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id =885&p_pollutant_group_name=PESTIC IDES.

More information on impaired water 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 conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process (see: http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm ), in order to ensure the data can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, 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 their location, cultural practices, or other factors, may have atypical, unusually high exposure to chlorhexidine derivatives compared to the general population. Please comment if you are aware of any sub -populations that may have atypical, unusually high exposure compared to the general population.

St

ructure Activity Relationships

EPA must rely upon information of appropriate quality and reliability for each decision made by the Agency. In the Office of Pesticide Programs (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 use of the results of such testing (measured data) is a logical, scientifically rigorous process 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 alternative techniques, i.e., techniques other than data generation that could significantly inform th e Agency’s decision

- making process. Recently, OPP has made increasing use of structure activity relationship (SAR) as part of its regulatory decision

- making process. In the SAR process, a chemical's molecular structure is compared to that of other chemic als for which data are available. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biological properties are a function 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 data on a single physical, chemical, or biological property is used to derive a model (an equation) to predict the value of that property.

Since SAR assessments and QSAR modeling are another set of tools that are available to Agency scientists, OPP has begun a process shift that envisions shifting from the current study- by

- study approach to an approach in which the use of predicted data, generated using validated models, isDocket Number: EPA

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11 of 20 considered along with information from open literature and studies specifically generated underPart 161 requirements. All relevant information would be considered as part of a weight-of-theevidence evaluation.

At this time, EPA believes that for certain endpoints, especially physical/chemical and fate properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements for many antimicrobial pesticide chem icals. When considering biological properties, 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 be cause 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 predicted data can fulfill one of the data needs for the chlorhexidine d erivatives case, then the Agency invites submission of this information. The submitter would be expected to supply a rationale describing the utility of the information and provide documenta tion on the scientific validity of the information. The determination that thepredicted data fulfills the data requirement would be at the sole discretion of the Agency. Presubmission consultation with the Agency is encouraged.

Additional Information

S takeholders are also specifically asked to provide available information and data that will assist the Agency in refining its risk assessments , including any species

- specific 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, application 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- agricultural uses (e.g., materials preservation) 5. Typical application interval 6. State or local use restrictions 7. Ecological incidents (non- target plant damage 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 May 2011, the Agency will review and respond to any comments received in a timely manner , and then issue a Final Work Plan for the chlorhexidine d erivatives c ase.Docket Number: EPA

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12 of 20 II. Fact Sheet

Background Information:

**•** Active Ingredient s : chlorhexidine diacetate & chlorhexidine digluconate

**•** C ase number: 3038

**•** PC Codes : 045502 & 045504

**•** CAS numbers : 56-95-1 & 18472-51-0

**•** Technical registrants: Fort Dodge Animal Health and The Procter & Gamble Company

**•** First approved for use in a registered product: 1955

**•** When EPA created the schedule for evaluating chemicals under the registration review program, chlorhexidine dihydrochloride (PC Code 481700) was identified as being part of the chlorhexidine derivatives registration review case. After further review, the Agency has determined that there are no registered pesticide products containing chlorhexidine dihydrochloride as an active ingredient (AI) and, thus, chlorhexidine dihydrochloride is not subject to evaluation under registration review and will be removed from Case 3038.

**•** There are no tolerances or exemptions from requirements of a tolerance established for chlorh exidine derivatives used as a pesticide.

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

**•** Antimicrobials Division Product Manager (PM): Marshall Swindell
, swindell.marshall@epa.gov

**•** Chemical Structur e:

Chlorhexidine diacetate Chlorhexidine digluconate

Use & Usage Information: (For additional details, please refer to the Appendix A: Registered Antimicrobial Uses of Chlorhexidine Derivatives)

**•** Chlorhexidine diacetate is registered for use as hard surface

- treatment disinfectants, sanitizers, bactericides and virucides. Chlorhexidine diacetate is also registered to control bacteria in agricultural premises and equipment and to control certain viruses in animal premises and equipment, egg handling and packing equipment, and meat processing plants.Docket Number: EPA

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13 of 20 **•** Chlorhexidine digluconate is registered for use as a disinfectant for hard, non-porous surfaces (wheelchairs, metal bed frames, exteriors of toilets, cou ntertops, metal surfaces, imaging equipment surfaces, glass, acrylic, and porcelain) in hospitals, restrooms, schools, offices, gyms, and homes. Chlorhexidine digluconate is also registered for use to control microbial contamination in dental unit wate rlines.

Recent/Pending Regulatory Actions :

**•** There are no recent or pending regulatory actions for these chemicals

. Ecological Risk Assessment Status:

Please refer to Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Chlorhexidine Derivatives Registration Review Decision Document , located in the docket, for a detailed discussion of the ecological risk assessments.

**•** Based on ecotoxicity studies submitted to the Agency, chlorhexidine diacetate was found to be slightly tox ic to practically nontoxic to avian species, moderately toxic to cold water fish, and highly toxic to warm water fish and aquatic invertebrates. Chlorhexidine digluconate is slightly toxic to avian species and highly toxic to cold water fish, warm water fish and aquatic invertebrates.

**•** An environmental fate assessment has not been completed due to the lack of data on the chlorhexidine derivatives.

Human Health Risk Assessment Status:
The following are key findings of the recent human health risk assessments for Chlorhexidine derivatives

. Please refer to Chlorhexidine Derivatives (Chlorhexidine Diacetate and Chlorhexidine Digluconate): Human Health Assessment Scoping Document in Support of Registration Review , located in the docket, for a detailed discussion of the human health risk
assessment.

Hazard Characterization:

**•** Chlorhexidine diacetate is of mild to moderate toxicity via the oral, dermal and inhalation exposure routes. Chlorhexidine diacetate is also a severe eye irritant.

**•** Chlorhexidine digluconate is mildly toxic via the oral, dermal and inhalati on routes of exposure and a mild eye and dermal irritant.

Dietary (Food and Water):

**•** A dietary risk assessment was not conducted for the 1996 RED because at that time, the U.S. Department of Agriculture and the EPA agreed that disinfectants, when applied to federally inspected meat, poultry, egg, and rabbit processing plants, did not present dietary exposure risks (USDA, FSIS publication# 1419, “List of Proprietary Substances and Nonfood Compounds”). This publication was no longer updated after 1998 and thisDocket Number: EPA

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14 of 20 policy is now referred to as a “former” guideline or “former requirement;” therefore, the Agency anticipates conducting a dietary risk assessment for the registration review of chlorhexidine derivatives.

Residential:

**•** A residential risk assessment has not been conducted for chlorhexidine derivatives.

**•** T he Agency determined residential exposure was not expected for the dental unit waterlines use of chlorhexidine digluconate when it was initially registered in 2010

. Aggregate:

**•** The Agency has not conducted an aggregate risk assessment for chlorhexidine derivatives.

Occupational:

**•** An occupational risk assessment was conducted for chlorhexidine diacetate in the 1996 RED based on potential exposures from its use as a non-porous, hard surface disinfectant in various agricultural and veterinary settings.

**•** Risks exceeded EPA’s level of concern for the wet mist fogging use scenario assessed in the Chlorhexidine Diacetate RED. This ex ceedance was addressed by label language requiring ventilation prior to re- entry into the treated area. The Agency determined all registered uses of chlorhexidine diacetate were eligible for reregistration.

**•** The most recent human health risk assessment f or chlorhexidine digluconate was conducted in 2010. Due to the small amount of product used per treatment, the high dilution of the active ingredient in the product, and the method of application, the Agency determined that the occupational exposures would be minimal in compari son to the toxicology endpoints; therefore, an occupational risk assessment was not completed.

Cumulative:

**•** EPA does not have, at this time, available data to determine whether chlorhexidine derivatives have a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. For the purposes of this Registration Review, EPA has assumed that chlorhexidine derivatives does not have a common mechanism of toxicity with other substances when used as an antimicrobial as registered.

Incidents:

Ecological:

**•** There were seven animal incidents associated with chlorhexidine exposure reported in the OPP Incident Data System (IDS)

. There were seven domestic animal incidents reportedDocket Number: EPA

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15 of 20 involving cats and dogs exposure to chlorhexidine diacetate from pesticidal uses . For cats, the symptoms following exposure to a chlorhexidine diacetate solution were skin redness, inflammation at the site of exposure, weakness, central nerve system signs, apnea, respiratory arrest, comatose -like state and death. For dogs, the symptoms after chlorhexidine exposure were facial paralysis and deafness.

Human Health:

**•** There were three human incidents assoc iated with chlorhexidine exposure reported in the OPP Incident Data System (IDS). The three human incidents reported to be associated with chlorhexidine exposure from pesticidal uses included: (1) tracheal edema in a

wom a n following her visit to a veterin arian’s office where a chlorhexidine solution had been used, (2) severe cold-like symptoms that progressed to bronchitis in a woman running a cattery housing six cats who used a chlorhexidine solution to disinfect cages, and (3) dermal sensitization sympto ms occurring in one person after dermal exposure to a chlorhexidine cleaning solution.

Tolerances and International Harmonization:

**•** There are no tolerances or exemptions from requirements of a tolerance established for either chlorhexidine derivatives us ed as a pesticide.

Data Call- In Status:

**•** There are currently no outstanding Data Call -In data requirements for the chlorohexidine derivatives case.

Labels:
Registered products, including EPA registration numbers are provided in Table 1 below. For future reference, during registration review a list of product registration 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 – Chlorhexidine Derivatives

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

1117-30 Fort Dodge Nolvasan Solution Fort Dodge Animal Health Soluble Concentrate 2

1117-48 Fort Dodge Nolvasan S Fort Dodge Animal Health Soluble Concentrate 2

1117-62 Chlorhexidine Diacetate Fort Dodge Animal Health Technical 99.3

3573

- 74 Cougar The Procter & Gamble Soluble 0.01Docket Number: EPA

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16 of 20 Company Concentrate

3573-94 Chlor hexidine Diacetate The Procter & Gamble Company Technical 99.3

70467-3 BioSURF Micrylium Laboratories Liquid Spray 0.2

85298-2 Mint -A- Kleen ® Anodia Systems Ready

- to

- use Liquid 0.12

III. Summary of Anticipated Data Requirements – Chlorhexidine Derivatives

The table below summarizes anticipated data needs for the chlorhexidine d erivatives c ase in Section I of this document (Preliminary Work Plan), Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Chlorhexidine Derivatives Registration Review Decision Document , and Chlorhexidine Derivatives (Chlorhexidine Diacetate and Chlorhexidine Digluconate): Human Health Assessment Scoping Document in Support of Registration Review

. Table 2. Summary of Anticipated Data Requirements – Chlorhexidine D erivatives

Active Ingredient Guideline Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in Months
from DCI Receipt)
045502 or 045504 835.2120 Hydrolysis TGAI 12

045502 or 045504 835.2240 Photodegradation in water TGAI 12

045502 or 045504 850.6800 Modified Activated Sludge Respiration Inhibition TGAI 12

045502 or 045504 835.1110 Activated Sludge Sorption Isotherm TGAI 12

045502 or 045504 835.3110 Ready Biodegradability TGAI 12

045502 or 045504 850.5400 Aquatic growth, Tier II green algae TGAI 12

045502 or 045504 870.3465 28

- day Inhalation Toxicity TGAI 24

045502 or 045504 870.5100 Bacterial Reverse Mutation Test TGAI 8

045502 or 045504 870.5395 Mammalian Erythrocyte Micronucleus Test TGAI 8

045502 and 045504 875.1200 Dermal Exposure

- Indoor TGAI 24

045502 and 045504 875.1400 Inhalation Exposure

- Indoor TGAI 24Docket Number: EPA

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17 of 20 Active Ingredient Guideline Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in Months
from DCI Receipt)
045502 and 045504 875.1600 Data Reporting and Calculations TGAI 24

045502 and 045504 875.1700 Product Use Information TGAI 12IV. Appendix A : Registered Antimicrobial Uses of Chlorhexidine D erivatives

PC Code EPA Reg Numbe r used for Max. Appl. Rate Formulation % Active Ingred ient in End Use Formu lation Use Category Use Site Treatment Site/Surfaces Method of Application Max Applicat ion/Use Rate Use Limitations

045502 1117

- 30 Soluble Concentrate 2.0 Food handling/s torage establishm
ents premises and equipment Meat Processi
ng Establis hments Barns, pens, stalls, chutes, halters, ropes and other types of equipment used in feeding, handling and restraining animals, as well as forks, shovels and scrapers used for removing litter and

manure. wipe, mop, spray or wet mist fogging. 3 oz. per gallon of water 10 min
contact time Thoroughly scrub all treated feed racks, mangers, troughs, automatic feeder s, fountains and waterers with soap or detergent, and rinse with potable water before

reuse.

045502 1117

- 30 Soluble Concentrate 2.0 Food handling/s torage establishm
ents premises and equipment Poultry Processi
ng Establis hments Barns, pens, stalls, chutes, halters, ropes and other types of equipment used in feeding, handling and restraining animals, as well as forks, shovels and scrapers used for removing litter and

manure. wipe, mop, spray or wet mist fogging. 3 oz. per gallon of water 10 min
contact time Thoroughly scrub all treated feed racks, mangers, troughs, automatic feeders, fountains and waterers with soap or detergent, and rinse with potable water before

reuse.

045502 1117

- 30 Soluble Concentrate 2.0 Food handling/s torage establishm
ents premises and equipment Rabbit Processi
ng Establis hments Barns, pens, stalls, chutes, halters, ropes and other types of equipment used in feeding, handling and restraining animals, as well as forks, shovels and scrapers used for removing litter and

manure. wipe, mop
, spray or wet mist fogging. 3 oz. per gallon of water 10 min
contact time Thoroughly scrub all treated feed racks, mangers, troughs, automatic feeders, fountains and waterers with soap or detergent, and rinse with potable water before

reuse.Docket Number: EPA

- HQ

- OPP -2011-0069 www.regulations.gov

19 of 20

045502 1117

- 30 Soluble Concentrate 2.0 Agricultur al premises and equipment Egg Processi
ng Establis hments Barns, pens, stalls, chutes, halters, ropes and other types of equipment used in feeding, handling and restraining animals, as well as forks, shovels and scrapers used for removing litter and

manure. wipe, mop, spray or wet mist fogging. 3 oz. per gallon of water 10 min
contact time Thoroughly scrub all treated feed racks, mangers, troughs, automatic feeders, fountains and waterers with soap or detergent, and rinse with potable water before

reuse.

045502 1117

- 30 Soluble Concentrate 2.0 Agricultur al premises and equipment Farm premise

s Barns, pens, stalls, chutes, halters, ropes and other types of equipment used in feeding, handling and restraining animals,

as well as forks, shovels and scrapers used for removing litter and

manure. wipe, mop, spray or wet mist fogging. 3 oz. per gallon of water 10 min
contact time Thoroughly scrub all treated feed racks, mangers, troughs, automatic feeders, fountains and watere rs with soap or detergent, and rinse with potable water before

reuse.

045502 1117

- 30 Soluble Concentrate 2.0 Agricultur al premises and equipment Dairy Cattle (lactatin g) Teats Dip 32 oz per 90 oz of
water

045502 1117

- 30 Soluble Concentrate 2.0 Residentia l and public

access premises Veterin
ary premise

s Barns, pens, stalls, chutes, halters, ropes and other types of equipment used in feeding, handling and restraining animals, as well as forks, shovels and scrapers used for removing litter and

manur e. wipe, mop, spray or wet mist fogging. 3 oz. per gallon of water 10 min
contact time Thoroughly scrub all treated feed racks, mangers, troughs, automatic feeders, fountains and waterers with soap or detergent, and rinse with potable water before

reuse.

045502 1117

- 48 Soluble Concentrate 2.0 Agricultur al premises and equipment Farm premise

s Barns, pens, stalls, chutes, halters, ropes and other types of equipment used in feeding, handling and restraining animals, as well as forks, shovels and scrapers used for wipe, mop,
or spray 3 oz. per gallon of water 10 min

con tact time Thoroughly scrub all treated feed racks, mangers, troughs, automatic feeders, fountains and waterers with soap or detergent, and rinse with potable water before

reuse.Docket Number: EPA

- HQ

- OPP -2011-0069 www.regulations.gov

20 of 20 removing litter and

manure.

045502 1117

- 48 Soluble Concentrate 2.0 Residentia l and public

access premises Veterin
ary premise

s Barns, pens, stalls, chutes, halters, ropes and other types of equipment used in feeding, handling and restraining animals, as well as forks, shovels and scrapers used for removing litter and

manure. wipe, mop,
or spray 3 oz. p er gallon of water 10 min
contact time Thoroughly scrub all treated feed racks, mangers, troughs, automatic feeders, fountains and waterers with soap or detergent, and rinse with potable water before

reuse.

045502 1117

- 62 Technical Chemical 99.3 This product is a manufacture use product for formulation use only.

045502 3573

- 74 Soluble Concentrate .01 Residentia l and public

access premises Househ old/dom estic dwellin
gs Household floors Spray 5 minutes
contact time Do not use on unfinished, oiled or waxed wood floors.

045502 3573

- 94 Technical Chemical 99.3 This product is a manufacture use product for formulation use only.

045504 70467

- 3 Ready

- to

- Use Solution .2 Medical premises and equipment Hospital equipm ent and surfaces hard non

- porus surfaces such as countertops, wheelchairs, toilet exteriors, metal bed frames, medial equipment exteriors Spray coat use site with light mist, 60 second
contact time