United States Chemical Safety March 2011

Environmental Protection and Pollution Prevention

Agency (7510P)

 

Chlorhexidine Derivatives 

Summary Document 

Registration Review: Initial Docket

March 2011 
Docket 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<£/2JJII 
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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 Anticipated Data Requirements – Chlorhexidine Derivatives ........................... 16

IV. Appendix A: Use Patterns – Chlorhexidine Derivatives ....................................................... 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-HQ-OPP-2011-0069 located on the internet at

www.regulations.gov. 
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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 Counsel
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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 scientific 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 policies 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 derivatives case.

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, 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. 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, 

schools, 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 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. 

The first product containing chlorhexidine diacetate was registered in the United States in 1955. 

There are currently five registered chlorhexidine diactetate products and two registered 
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chlorhexidine 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-HQ-OPP-2011-0069. Below is a summary of 

the issues relevant to the registration review case. 

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, the Agency will consult with the U.S. Fish and Wildlife Service and/or 

National Marine Fisheries Services (the Services), as appropriate.

• The Agency anticipates the need to require the following additional ecological data for 

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

• For 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.
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Human Health Risk: 

• The most recent human health risk assessment for chlorhexidine diacetate was conducted 

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 review 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. 

• For 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.
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• For 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. As 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 database. 

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 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. 

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 active 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 further information on the status of the EDSP, the policies and procedures, the 

list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit 

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

EPA has created the following 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 2017

Close Public Comment Period for Proposed Reg. Review Decision December 2017

Final Decision and Begin Post-Decision Follow-up 2017

Total (years) 6

Guidance for Commenters:

The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the chlorhexidine derivatives registration 

review case.

Trade Irritants

Through 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 not 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 addition, no Total Maximum Daily Loads (TMDL) have been developed for chlorhexidine 
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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=PESTICIDES.

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. 

Structure 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 the 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 chemicals 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, is 
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considered along with information from open literature and studies specifically generated under 

Part 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 chemicals. 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 because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a 

screening-level assessment procedure rather than multiple tiers of assessments with progressively 

more data requirements.

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the 

chlorhexidine derivatives 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 documentation on the scientific validity of the information. The determination that the 

predicted data fulfills the data requirement would be at the sole discretion of the Agency. Presubmission consultation with the Agency is encouraged. 

Additional Information

Stakeholders 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 derivatives case. 
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II. Fact Sheet

Background Information:

• Active Ingredients: chlorhexidine diacetate & chlorhexidine digluconate 

• Case 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 

chlorhexidine 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 Structure:

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. 
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• 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, 

schools, offices, gyms, and homes. Chlorhexidine digluconate is also registered for use 

to control microbial contamination in dental unit waterlines. 

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 toxic 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 inhalation 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 this 
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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. 

• The 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 exceedance 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 for 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 comparison 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 reported 
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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 associated 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 

woman following her visit to a veterinarian’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 symptoms 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 used 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 0.01
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Company Concentrate

3573-94 Chlorhexidine 

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 derivatives case 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 Derivatives

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 24
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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 12
IV. Appendix A: Registered Antimicrobial Uses of Chlorhexidine Derivatives

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 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

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 waterers 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 

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 1117-48 

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 

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

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. 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 1117-62 

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