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



# IPBC (Troysan KK-108A) Registration Review: Final Work Plan December 2011Docket 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[12Docket Number: EPA-HQ-OPP-2011-0420 www.regulations.gov

3 of 12 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 www.regulations.gov

4 of 12 Introduction

This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the Agency”) for the registration review of IP BC (Troysan KK-108A) (Case 2725). The work plan includes the expected registration review time line. The work plan also addresses public comments received concerning the Preliminary Wo rk 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 Do cument 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 revi ew 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 th e FIFRA standard for registration. Changes in science, public policy an d pesticide use practices will occur over time. The registration review program is intended to ma ke sure that, as the ability to assess risk evolves and as policies and practi ces change, all registered pestic ides continue to meet that statutory standard. The public pha se 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 ingr edient. Currently registered pesticide products contain IPBC as an active ingredie nt. 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. Th e wood preservative uses include spray, dip and pressure treatment applications for new lumber, millwork and joinery and brush and spray applications for existing above gr ound structures such as decks. The industrial preservative uses include metal working fluids, adhesives, caulks, sealants, plastics, te xtiles, paper coatings, canvas, cordage, and inks. Additional preservative uses include household, consumer, industrial, institutional and janitorial produc ts such as air fresheners, di sh detergents, laundry products, surface cleaners, floor care products and fabric ca re 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 publis hed 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.Docket Number: EPA-HQ-OPP-2011-0420 www.regulations.gov

5 of 12 Comments Received on the Preliminary Work Plan

The Agency received one submission of comm ents 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 Chem ical Co., Thor-Actichem, and Troy Chemical Corp. on the anticipated toxicology data requi rements for IPBC outlined in the PWP. A summary of the submission and the Agency’s res ponse 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 Comme nts Associated with Toxicology Data Requirements dated November 8, 2011.

In the PWP, the Agency solicited comments on sp ecific topics: environmental justice, water body impairment, trade irritants, and structur e activity relationships. No comments or information were received during the public comment period concerning these issues.

Comparative Cholinesterase Assa y with Thyroid Measurements Comment: The registrants believe that based on existing data and the absence of guidelines, a Comparative Cholinesterase A ssay with Thyroid Measurements should not be required for the registration review of IP BC. 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 cau se mild to modest inhibition of plasma cholinestersase activity which ha s been shown to be complete ly reversible. Many studies have investigated the effects of IPBC on c holinesterase inhibiti on. Plasma, erythrocyte and brain cholinesterase activity were ev aluated 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 ava ilable (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 addi tional data on this t oxicological endpoint it should provide specific guidance on study pa rameters and conduct in order that registrants can properly addre ss the Agency’s concerns.”

Response: The Agency continues to anticipat e the need to require a Comparative Cholinesterase Assay (CCA) with thyr oid hormone measurements because:

1. Several studies conducted with IPBC have shown inhibition of cholinesterase. 2. There are no data on the comparative sens itivity of juvenile vs. adults to the cholinesterase inhibition potential of IPBC. 3. IPBC has been observed to a ffect the thyroid gland.

Also, iodine uptake in the developing fetus is critical in development. The Agency expects to require comparative thyroid meas urements 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 Comme nts Associated with Toxicology Data Requirements . A protocol is expected to be required to be submitted for review andDocket Number: EPA-HQ-OPP-2011-0420 www.regulations.gov

6 of 12 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 sh ould be sufficient information available to the Agency to assess this compound’s sensitiza tion potential. If the need for this data is the assessment of occupational exposure fr om Metalworking fluids and textile uses, registrants would propose to l ook specifically at these uses in order to address this requirement.”

Response : Although there are some registration data and literature info rmation available on the dermal sensitization potential of IPBC, a dermal sensitization study that can be used for a quantitative dermal sensitization ri sk assessment is not av ailable. The study anticipated as needed in this Work Plan would require measurements of dermal sensitization potential of the technical IPBC at different leve ls of exposure. The Agency anticipates conducting a quantitat ive dermal sensitization ri sk assessment only when the registered use involving direct dermal contact is considered the primary route of exposure and the final product cannot be labeled w ith warning language (e.g., textile use for clothing). If the guideline dermal sensitizati on study can demonstrat e the technical grade IPBC is not a dermal sensitizer and/or the di rect dermal contact us es are discontinued by deletion from the registrations and labels, the registrants ma y request that EPA waive any such study requirement imposed for the dermal sensitization risk assessment.

The comments received during the initial public co mment period did not affect the data needs, work plan and timeline described in the PWP and th ey remain as they were presented initially in the PWP. Further, this document makes fina l the work plan for the IPBC (Troysan KK-108A) registration review process.

Anticipated Risk Assessments and Anticipated Data Needs

The Agency anticipates conducting a comprehens ive ecological risk assessment, including an endangered species risk assessment, for all us es of IPBC. The Agen cy also anticipates conducting a human health risk assessment. The Agen cy anticipates requiri ng additional data for use in conducting the regist ration 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 th e following additional ecological data for use in conducting the registrati on review of IPBC.

850.1350 -- Mysid chronic tox - aquatic inve rtebrate life-cycle (saltwater) 850.1400 -- Fish early-life stage to xicity test (freshwater) 850.3020 -- Honey bee acute contact toxicity 850.3030 -- Honey bee toxicity of residues on foliage 850.4400 -- Aquatic plant toxicology te st using Lemna spp., Tier IDocket Number: EPA-HQ-OPP-2011-0420 www.regulations.gov

7 of 12 850.5400 -- Algal Toxicity Tier I and Tier II

 The Agency anticipates the need to require th e following additional environmental fate data for use in conducting the regi stration review of IPBC.

850.6800 -- Modified activated sludge , respiration inhibition test 835.2240 -- Photodegradation in water Special Study -- Leachability of w ood 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-propyny l 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 de tergent which is considered to be a food use; therefore, the Agency anticipates conducting a di etary assessment of th is and other uses of IPBC.

Tolerances and Intern ational Harmonization

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

Occupational and Residen tial Assessment and Risk

 An occupational assessment has not been perf ormed for IPBC. Assessm ents of occupational risk are planned for registration review b ecause occupational exposure can occur for the handlers applying wood preservatives to lumber using the dip or spray treatment and for machinists using IPBC-preser ved metal working fluids.

 A residential assessment has not been performe d for IPBC. Assessments of residential risk are planned for registration re view because inhalation exposure can occur for residential applicators of paints or stai ns containing IPBC. Incidental oral exposure can occur from household items and toys made of plastics preser ved 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 informationDocket Number: EPA-HQ-OPP-2011-0420 www.regulations.gov

8 of 12 concerning exposures to pesticide residues in food and drinking water, as well as nonoccupational (i.e. residential) pesticide exposures. An aggr egate risk assessment may be needed for IPBC if it is determined that a dr inking 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 residentia l 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 regist ration review of IPBC.

Special Study – Residues from dish detergent 875.1100 – Dermal indoor exposure (Open pour powders 1 , open pour liquids 1 , spray and dip treatment, pressure treatment, br ush/roller painting, metal working fluids, and sponges and wipes) 875.1200 – Dermal outdoor exposure (Airless sprayer painting) 875.1300 – Inhalation indoor exposure (Open pour powders 1 , open pour liquids 1 , spray and dip treatment, pressure treatme nt, brush/roller painting, metal working fluids, and sponges and wipes) 875.1400 – Inhalation outdoor exposur e (Airless sprayer painting) 875.1600 – Data reporting indoor exposure (Open pour powders 1 , open pour liquids 1

, spray and dip treatment, pressure tr eatment, 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 Cholinestera se Assay with thyroid measurements Special Study – Dermal sensitization study 2

 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.Docket Number: EPA-HQ-OPP-2011-0420 www.regulations.gov

9 of 12  The Agency does not anticipate the need to re quire 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-propyny l butylcarbamate (IPBC) Registration Review Decision Document , located in the docket.

Incidents

Ecological:

 No IPBC ecological incidents have been re ported 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 irrita tion and systemic effects were reported in these incidents. Skin irritation and skin sensitizat ion-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 effect s include nausea/vomitting, headache, fatigue, vertigo, and fever.

Endangered Species

The Agency has not conducted a risk assessmen t that supports a complete endangered species determination for IPBC. The ecological risk as sessment 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 sp ecies (listed species) or their de signated critical habitats. When an assessment concludes that a pesticide’s use 'm ay affect' a listed species or its designated critical habitat, the Agency will consult with th e 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 num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its reregistration decision for IPBC, EPA reviewed these data and selected the most sensitive endpoi nts for relevant risk assessment scenarios from the existing hazard database. However, as required by FFD CA section 408(p), IPBC is subject to the endocrine screening part of the Endocrine Disruptor Screenin g Program (EDSP).Docket Number: EPA-HQ-OPP-2011-0420 www.regulations.gov

10 of 12 EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide activ e ingredients and 9 inert ingr edients. IPBC is not among the group of 58 pesticide active ingredients on the in itial 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 assa ys 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 scr eening 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 Peri od 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 Pre liminary Risk Assessments July 2016 Phase 3: Registration Review Decision Open Public Comment Period for Propos ed Reg. Review Decision December 2016 Close Public Comment Period for Proposed Reg. Review Decision February 2017Docket Number: EPA-HQ-OPP-2011-0420 www.regulations.gov

11 of 12 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 doc ument. The Agency expects to issue the DCI in December 2012. Human health and environmental fa te 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 Anticipate d 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 powders 3 , open pour liquids 3 , 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 powders 3 , open pour liquids 3 , 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 www.regulations.gov

12 of 12 and wipes)

875.1400 Inhalation outdoor exposure (Airless sprayer painting) TGAI 24

875.1600 Data reporting indoor exposure (open pour powders 3 , open pour liquids 3 , 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 pr eservatives in water
contact TGAI 12

Special Study Leachability of IP BC 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 Leachin g on Textiles TGAI 12

Special Study Comparative Cholinesterase Assay with Thyroid Measurements TGAI 24

Special Study Dermal Sensitization Study 4 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.