United States Chemical Safety December 2011 

Environmental Protection and Pollution Prevention 

Agency (7510P) 

 

IPBC (Troysan KK-108A) 

Registration Review: 

Final Work Plan 

December 2011 

 
Docket Number: EPA-HQ-OPP-2011-0420 

www.regulations.gov 

IPBC (Troysan KK-I08A) 

Registration Review: 

Final Work Plan 

December 2011 

Case # 2725 

Approved By: 

n Harrigan-Farre ly 

irector, Antimicrobials Division 

Date: 

§ /"30/2/JII I I 

20[12 
Docket Number: EPA-HQ-OPP-2011-0420 

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IPBC (Troysan KK-108A) Registration Review Team

Human Health & Environmental Effects

Timothy Dole 

Srinivas Gowda 

Risk Management

Rebecca von dem Hagen 

Lance Wormell 

Office of General Counsel

Philip Ross 

________________________________________ 

Supporting documents for the IPBC (Troysan KK-108a) Case may be found in the registration 

review docket EPA-HQ-OPP-2011-0420 located on the internet at www.regulations.gov. 
Docket Number: EPA-HQ-OPP-2011-0420 

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Introduction

This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the 

Agency”) for the registration review of IPBC (Troysan KK-108A) (Case 2725). The work plan 

includes the expected registration review timeline. The work plan also addresses public 

comments received concerning the Preliminary Work Plan (PWP) in the Summary Document 

which was posted in the IPBC (Troysan KK-108A) 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/. 

Troysan KK-108A is a trade name that refers to a specific product, which itself is no longer 

registered, but contained IPBC as an active ingredient. Currently registered pesticide products 

contain IPBC as an active ingredient. Although the previous name for this registration review 

case is Troysan KK-108A, henceforth this case will be referred to by its chemical name, 

iodopropynylbutylcarbamate (IPBC). 

The first product containing IPBC (PC Code 107801) as an active ingredient was registered in 

the United States in 1975. Currently, there are 106 products containing IPBC that are registered 

with EPA. Products containing IPBC are registered for use as wood preservatives, industrial 

preservatives and as dry film mildewcides. The wood preservative uses include spray, dip and 

pressure treatment applications for new lumber, millwork and joinery and brush and spray 

applications for existing above ground structures such as decks. The industrial preservative uses 

include metal working fluids, adhesives, caulks, sealants, plastics, textiles, paper coatings, 

canvas, cordage, and inks. Additional preservative uses include household, consumer, industrial, 

institutional and janitorial products such as air fresheners, dish detergents, laundry products, 

surface cleaners, floor care products and fabric care products. Products containing IPBC are also 

registered for use as dry film mildewcides in paints and stains. No tolerances or exemptions 

from tolerances have been established for IPBC 

The IPBC Preliminary Work Plan was published on June 29, 2011 and the 60-day comment 

period ended on August 29, 2011. The Preliminary Work Plan and supporting documents are 

available on www.regulations.gov in docket number EPA-HQ-OPP-2011-0420. 

 
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Comments Received on the Preliminary Work Plan

The Agency received one submission of comments during the public comment period on the 

initial docket. The comments were submitted jointly by Arch Chemicals Inc, International 

Specialty products, Lanxess Corp, The Dow Chemical Co., Thor-Actichem, and Troy Chemical 

Corp. on the anticipated toxicology data requirements for IPBC outlined in the PWP. A 

summary of the submission and the Agency’s response is given below. The complete Agency 

response is available in the docket in the document titled IPBC (Troysan KK-108A), 2725 

Registration Review Case: Response to Comments Associated with Toxicology Data 

Requirements dated November 8, 2011. 

In the PWP, the Agency solicited comments on specific topics: environmental justice, water 

body impairment, trade irritants, and structure activity relationships. No comments or 

information were received during the public comment period concerning these issues. 

Comparative Cholinesterase Assay with Thyroid Measurements 

Comment: The registrants believe that based on existing data and the absence of 

guidelines, a Comparative Cholinesterase Assay with Thyroid Measurements should not 

be required for the registration review of IPBC. The commenters state that “IPBC study 

results have shown only minor findings of fleeting or questionable decreases in 

cholinesterase activity in a number of animal and human studies due to sub-chronic and 

chronic exposure” and “overall, IPBC can cause mild to modest inhibition of plasma 

cholinestersase activity which has been shown to be completely reversible. Many studies 

have investigated the effects of IPBC on cholinesterase inhibition. Plasma, erythrocyte 

and brain cholinesterase activity were evaluated from multiple in-vitro and in-vivo 

animal studies with the overall conclusion that inhibition of cholinesterase was not 

observed. Based upon the data currently available (animal and human studies) IPBC is 

not the typical carbamate and additional data should not be necessary. In lieu of this 

information, if the Agency still requests additional data on this toxicological endpoint it 

should provide specific guidance on study parameters and conduct in order that 

registrants can properly address the Agency’s concerns.” 

Response: The Agency continues to anticipate the need to require a Comparative 

Cholinesterase Assay (CCA) with thyroid hormone measurements because: 

1. Several studies conducted with IPBC have shown inhibition of cholinesterase. 

2. There are no data on the comparative sensitivity of juvenile vs. adults to the 

cholinesterase inhibition potential of IPBC. 

3. IPBC has been observed to affect the thyroid gland. 

Also, iodine uptake in the developing fetus is critical in development. The Agency 

expects to require comparative thyroid measurements in the pregnant females and the 

developing fetus to determine potential susceptibility. 

Agency guidance on the study design is available in IPBC (Troysan KK-108A), 2725 

Registration Review Case: Response to Comments Associated with Toxicology Data 

Requirements. A protocol is expected to be required to be submitted for review and 
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approval by the Agency prior to initiating this study; EPA will be available to discuss 

appropriate study design with the registrants. 

Dermal Sensitization Threshold Quantification 

Comment: The registrants comment that “there should be sufficient information available 

to the Agency to assess this compound’s sensitization potential. If the need for this data is 

the assessment of occupational exposure from Metalworking fluids and textile uses, 

registrants would propose to look specifically at these uses in order to address this 

requirement.”

Response: Although there are some registration data and literature information available 

on the dermal sensitization potential of IPBC, a dermal sensitization study that can be 

used for a quantitative dermal sensitization risk assessment is not available. The study 

anticipated as needed in this Work Plan would require measurements of dermal 

sensitization potential of the technical IPBC at different levels of exposure. The Agency 

anticipates conducting a quantitative dermal sensitization risk assessment only when the 

registered use involving direct dermal contact is considered the primary route of exposure 

and the final product cannot be labeled with warning language (e.g., textile use for 

clothing). If the guideline dermal sensitization study can demonstrate the technical grade 

IPBC is not a dermal sensitizer and/or the direct dermal contact uses are discontinued by 

deletion from the registrations and labels, the registrants may request that EPA waive any 

such study requirement imposed for the dermal sensitization risk assessment. The comments received during the initial public comment period did not affect the data needs, 

work plan and timeline described in the PWP and they remain as they were presented initially in 

the PWP. Further, this document makes final the work plan for the IPBC (Troysan KK-108A) 

registration review process. 

Anticipated Risk Assessments and Anticipated Data Needs

The Agency anticipates conducting a comprehensive ecological risk assessment, including an 

endangered species risk assessment, for all uses of IPBC. The Agency also anticipates 

conducting a human health risk assessment. The Agency anticipates requiring additional data for 

use in conducting the registration review for IPBC. 

Ecological Risk Assessment Status and Data Needs 

 No ecological risk assessment has been performed for IPBC. 

 The Agency anticipates the need to require the following additional ecological data for use in 

conducting the registration review of IPBC. 

850.1350 -- Mysid chronic tox - aquatic invertebrate life-cycle (saltwater) 

850.1400 -- Fish early-life stage toxicity test (freshwater) 

850.3020 -- Honey bee acute contact toxicity 

850.3030 -- Honey bee toxicity of residues on foliage 

850.4400 -- Aquatic plant toxicology test using Lemna spp., Tier I 
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850.5400 -- Algal Toxicity Tier I and Tier II 

 The Agency anticipates the need to require the following additional environmental fate data 

for use in conducting the registration review of IPBC. 

850.6800 -- Modified activated sludge, respiration inhibition test 

835.2240 -- Photodegradation in water 

Special Study -- Leachability of wood preservatives in water contact 

Special Study -- Leachability of IPBC from shingles 

 For more information, please refer to Summary of Product Chemistry, Environmental Fate, 

and Ecotoxicity Data for the 3-Iodo-2-propynyl butylcarbamate (IPBC) Registration Review 

Decision Document, located in the docket. 

Human Health Risk Assessment Status and Data Needs 

 No human health risk assessment has been performed for IPBC. 

Dietary Assessment

 A dietary assessment has not been performed for IPBC. 

 IPBC is currently registered for use in dish detergent which is considered to be a food use; 

therefore, the Agency anticipates conducting a dietary assessment of this and other uses of 

IPBC. 

Tolerances and International Harmonization

 No tolerances or exemptions from tolerances have been established for IPBC. 

Occupational and Residential Assessment and Risk

 An occupational assessment has not been performed for IPBC. Assessments of occupational 

risk are planned for registration review because occupational exposure can occur for the 

handlers applying wood preservatives to lumber using the dip or spray treatment and for 

machinists using IPBC-preserved metal working fluids. 

 A residential assessment has not been performed for IPBC. Assessments of residential risk 

are planned for registration review because inhalation exposure can occur for residential 

applicators of paints or stains containing IPBC. Incidental oral exposure can occur from 

household items and toys made of plastics preserved with IPBC. Incidental oral and dermal 

exposures can occur from floors cleaned with IPBC-treated household cleaners, textiles, and 

leather products. 

Aggregate and Cumulative Exposure and Risk

 The Agency has not conducted an aggregate risk assessment for IPBC. In examining 

aggregate exposure, EPA takes into account the available and reliable information 
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concerning exposures to pesticide residues in food and drinking water, as well as nonoccupational (i.e. residential) pesticide exposures. An aggregate risk assessment may be 

needed for IPBC if it is determined that a drinking water exposure could occur based on the 

environmental fate data. This assessment might also need to include dietary exposures from 

the dishwashing detergent use and residential exposures from the wood treatment, floor 

cleaners, plastics, paints, leathers and textile uses. 

 EPA does not have, at this time, available data to determine whether IPBC has 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 IPBC 

does not have a common mechanism of toxicity with other substances when used as an 

antimicrobial as registered. 

Human Health Data Needs

 The Agency anticipates the need to require the following additional human health data for 

use in conducting the registration review of IPBC. 

Special Study – Residues from dish detergent 

875.1100 – Dermal indoor exposure (Open pour powders1

, open pour liquids1, spray and 

dip treatment, pressure treatment, brush/roller painting, metal working 

fluids, and sponges and wipes) 

875.1200 – Dermal outdoor exposure (Airless sprayer painting) 

875.1300 – Inhalation indoor exposure (Open pour powders1

, open pour liquids1, spray 

and dip treatment, pressure treatment, brush/roller painting, metal 

working fluids, and sponges and wipes) 

875.1400 – Inhalation outdoor exposure (Airless sprayer painting) 

875.1600 – Data reporting indoor exposure (Open pour powders1

, open pour liquids1, 

spray and dip treatment, pressure treatment, brush/roller painting, metal 

working fluids, sponges and wipes, and airless sprayer painting) 

875.1700 – Product use information 

Special Study – Leaching on plastics 

Special Study – Leaching on leather 

Special Study – Leaching on textiles 

875.2300 – Surface residue dissipation (Household floors and treated wood) 

Special Study – Comparative Cholinesterase Assay with thyroid measurements 

Special Study – Dermal sensitization study2

 For more information, please refer to Summary of Human Health Effects Data for IPBC 

Registration Review, located in the docket. 

Product Chemistry Data Needs 

 

1

 If the labels are amended to require closed mixing and loading for liquid products and water soluble packaging for 

powder products, then the registrants may request that the Agency waive exposure studies that are anticipated to be 

required for the open loading/mixing scenarios. 

2

 The Agency anticipates the need to require a quantitative dermal sensitization study measuring dermal sensitization 

potential of the technical IPBC at different levels of exposure. 
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 The Agency does not anticipate the need to require additional product chemistry data for the 

registration review at this time. 

 For more information, please refer to Summary of Product Chemistry, Environmental Fate, 

and Ecotoxicity Data for the 3-Iodo-2-propynyl butylcarbamate (IPBC) Registration Review 

Decision Document, located in the docket. 

Incidents

Ecological: 

 No IPBC ecological incidents have been reported in the OPP incident database. 

Human Health: 

 Twenty-seven human incidents associated with IPBC exposure have been reported in the 

OPP incident database . Both local skin irritation and systemic effects were reported in these 

incidents. Skin irritation and skin sensitization-like symptoms were the primary effects, 

including rash, swelling, itching, burning and/or tingling sensation, blister, 

erythema/flushing, and hives. In some cases, chest tightness and respiratory problems were 

reported. Other reported systemic effects include nausea/vomitting, headache, fatigue, 

vertigo, and fever. 

Endangered Species

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

determination for IPBC. The ecological risk assessment planned during registration review will 

allow the Agency to determine whether the use of IPBC 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 Services (the Services), as appropriate. 

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 its reregistration decision for IPBC, 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), IPBC is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 
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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. IPBC is 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 IPBC. 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/. 

Timeline

EPA has created the following estimated timeline for the completion of the IPBC registration 

review: 

Anticipated Schedule

Activities Estimated Month/Year

Phase 1: Opening the docket 

Open Public Comment Period for Docket Completed 

June 2011

Close Public Comment Period for Docket Completed 

August 2011 

Phase 2: Case Development 

Develop Final Work Plan (FWP) Completed 

December 2011 

Issue DCI December 2012 

Data Submission December 2014 

Open Public Comment Period for Preliminary Risk Assessments June 2016 

Close Public Comment Period for Preliminary Risk Assessments July 2016 

Phase 3: Registration Review Decision 

Open Public Comment Period for Proposed Reg. Review Decision December 2016 

Close Public Comment Period for Proposed Reg. Review Decision February 2017 
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Final Decision and Begin Post-Decision Follow-up June 2017 

Total (years) 6 

Next Steps

A DCI will be developed regarding the data needs listed under the “Anticipated Risk 

Assessments and Data Needs” section of this document. The Agency expects to issue the DCI in 

December 2012. Human health and environmental fate and ecological hazard assessments will 

be conducted for all uses. 

Summary of Anticipated Data Requirements – IPBC

The table below summarizes anticipated data needs for the registration review of IPBC. 

Table 1. Summary of Anticipated Data Requirements – IPBC 

Guideline 

Number Anticipated Data Requirement Test Material

Estimated Timeframe 

(Measured in months 

from DCI Receipt) 

835.2240 Photodegradation in water TGAI 12 

850.1350 Mysid Chronic Toxicity Test TGAI 12 

850.1400 Fish early-life stage toxicity test TGAI 12 

850.3020 Honeybee Acute Contact Toxicity TGAI 12 

850.3030 Honey Bee Toxicity of Residues on Foliage TGAI 12 

850.4400 Aquatic Plant Toxicity Test Using Lemna 

gibba, Tier II 

TGAI 12 

850.5400 Algal Toxicity Test, Tier II TGAI 12 

850.6800 Modified activated sludge respiration 

inhibition 

TGAI 12 

875.1100 

Dermal indoor exposure (open pour 

powders3

, open pour liquids3, spray and dip 

treatment, pressure treatment, brush/roller 

painting, metal working fluids, and sponges 

and wipes) 

TGAI 

24 

875.1200 Dermal outdoor exposure (Airless sprayer 

painting) 

TGAI 24 

875.1300 

Inhalation indoor exposure (open pour 

powders3

, open pour liquids3, spray and dip 

treatment, pressure treatment, brush/roller 

painting, metal working fluids, and sponges 

TGAI

24 

 

3

 If the labels are amended to require closed mixing and loading for liquid products and water soluble packaging for 

powder products, then the Agency would not expect to need exposure studies for the open loading/mixing scenarios. 
Docket Number: EPA-HQ-OPP-2011-0420 

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and wipes) 

875.1400 Inhalation outdoor exposure (Airless sprayer 

painting) 

TGAI 24 

875.1600 

Data reporting indoor exposure (open pour 

powders3

, open pour liquids3, spray and dip 

treatment, pressure treatment, brush/roller 

painting, metal working fluids, sponges and 

wipes, and airless sprayer painting) 

TGAI

24 

875.1700 Product use information TGAI 12 

875.2300 Surface residue dissipation TGAI 12 

Special Study Leachability of wood preservatives in water 

contact 

TGAI 12 

Special Study Leachability of IPBC from shingles TGAI 12 

Special Study Residues from dish detergent TGAI 12 

Special Study Leaching on plastics TGAI 12 

Special Study Leaching on leather TGAI 12 

Special Study Leaching on Textiles TGAI 12 

Special Study Comparative Cholinesterase Assay with 

Thyroid Measurements 

TGAI 24 

Special Study Dermal Sensitization Study4 TGAI 24 

 

3 If the labels are amended to require closed mixing and loading for liquid products and water soluble packaging for 

powder products, then the Agency would not expect to need exposure studies for the open loading/mixing scenarios. 

4

 The Agency anticipates the need to require a quantitative dermal sensitization study conducted with varying 

concentrations of the technical grade product.