Docket Number: EP**A~HQ~OPP~2011 ~0952**  www .regulations.gov



## Tri-N Butyl Tetradecyl Phosphonium Chloride (TTPC) Amended Final Work Plan Registration Review

Case Number: 5111

Approved 

### By:

Acting Director, Antimicrobials Division

Date:

\.Docket Number: EPA-HQ-OPP-2011-0952 www.regulations.gov

2 Tri-N Butyl Tetradecyl Phosphonium Ch loride AMENDED FI NAL WORK PLAN

Introduction

This document amends the Final Work Plan (FWP) for the registration review of tri-N butyl tetradecyl phosphonium chloride (TTPC)

. Since the publicat i on of the June 2012 Final Work Plan, the Agency has determined that certain data requirements identified to support the registration r e view of TTPC in the Preliminary Work Plan were inadvertently omitted in the FWP. This document amends the June 2012 FWP to include the following studies among the data identified as needed for registration review:

• 850.1075: Acute fish toxicity (estuarine/marine)

• 850.1300: Aquatic invertebrate lif e-cycle test (freshwater)

• Non-guideline study: Chronic sediment toxicity test (freshwater invertebrate- Hyallela
azteca )

• 850.4400: Aquatic Plant Test using Lemna sp., Tier II

• 850.4500/850.4550: Algal Toxicity Tier II

• 830.7550: Octanol/water partition coefficient determination

Unless otherwise stated by the Agency, all other elements of the Agency's June 2012 TTPC FWP remain unchanged.Docket Number: EPA-HQ-OPP-2011-0952 www.regulations.gov

3 Summary of Data Requirements

A summary table of the data re quired to support the registration review of TTPC is presented below.

Data Requirements for the Regi stration Review of TTPC

Guideline Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months

from DCI receipt) 835.1230 Absorption/Desorption TGAI 12 835.4300 Aerobic aquatic metabolism TGAI 12 835.4400 Anaerobic aquatic metabolism TGAI 12 850.1075 1 Acute fish toxicity (estuarine/marine) TGAI 12 850.1300 Aquatic invertebrate life-cycle test (freshwater) TGAI 12 850.1400 2 Fish early-life stage toxicity test, freshwater species TGAI 12

N/G 3 Chronic sediment toxicity test (freshwater invertebrate- Hyallela azteca ) TGAI 12 850.4400 Aquatic Plant Test using Lemna sp., Tier II TGAI 12

850.4500 4 Algal Toxicity Tier II -- marine diatom, freshwater diatom, green algae TGAI 12

850.4550 4 Algal Toxicity Tier II – Cyanobacteria TGAI 12 830.7550 5 Octanol/water partition coefficient determination TGAI 12 850.3300 6 Activated Sludge Respiration Inhibition TGAI 12 835.1110 7 Activated Sludge Sorption Isotherm TGAI 12 835.3110 8 Ready Biodegradability TGAI 12 835.3220 8 Porous Pot Test TGAI 12

835.3240 8 Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units TGAI 12

835.3280 8 Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater TGAI 12

1 Results from a study using one estuarine/marine fish species must be submitted to satisfy this requirement.
2 Results from a study using the acutely sensitive Bluegill sunfish ( Lepomis macrochirus ), must be submitted to satisfy this requirement.
3 The anticipated DCI will provide that a protocol must be submitted for review and approval by the Agency prior to initiating this study.
4 Results for studies conducted with TTPC for (i) the freshwater green alga, Selenastrum capricornutum , (ii) the freshwater diatom, Navicula pelliculosa , (iii) the marine diatom, Skeletonema costatum , and (iv) the cyanobacteria species Anabaena flos-aquae , must be submitted to satisfy this requirement. Final 850 guidelines for the algal testing were posted in June 2012 after posting of the FWP. The Public Draft OPPT S 850.5400 Algal Toxicity guideline was split into two separate guidelines and renu mbered with the cyanobacteria species separated into OCSPP 850.4550 and the other three species under OCSPP 850.4500.
5 Modified to measure TTPC ion pair and cation concentrations at equilibrium.
6 EPA has a published final guideline for this study. The Agency anticipates codifying this study in 40 CFR 158(W) in the near future. OECD Test Guide line 209 can also be used as guidance for this study, available online at http://www.oecd-ilibrary.org/content/book/9789264070080-en

. 7 EPA has a published final guideline for this study. The Agency anticipates codifying this study in 40 CFR 158(W) in the near future.
8 EPA has published final guidelines for four biodegradation studies. The biodegradation study required for TTPC is based on results of an Activated Sludge Respiration Inhi bition test. The Agency anticip ates codifying these studies in 40 CFR 158(W) in the near future.United States Chemical Safety June 2012 Environmental Protection and Pollution Prevention Agency (7510P)



# Tri

- N Butyl Tetradecyl Phosphonium Chloride

Registration Review : Final Work Plan June 2012Docket Number: EPA

- HQ

- OPP

- 2011

- 0952

www.regulations.gov

3 of 10 Tri

- N Butyl Tetradecyl Phosphonium Chloride Registration Review Team

Human Health & Environmental Effects Nathan Mottl Michelle Centra Jonathan Chen Srinivas Gowda William Erickson Najm Shamim

Risk Management Wanda Henson Lance Wormell

Office of General Counsel Philip Ross

________________________________________ S upporting documents for the Tri

- N Butyl Tetradecyl Phosphonium Chloride Case may be found in the registration review docket EPA

- HQ

- OPP

- 2011

- 0952 located on the internet at www.regulations.gov

.Docket Number: EPA

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4 of 10 Introduction

This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the Agency”) for the registration review of Tri

- n butyl tetradecyl phosphonium chloride (Case 5111 )

. 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 Tri

- n butyl tetradecyl phosphonium chloride

r egistration 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 need ed 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 d etermine 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 evol ves and as policies and practices change, all registered pesticides continue to meet that statutory standard. The public phase of registration review begins when the initial docket is opened for each case. Information on this program is provided at: http:/ /www.epa.gov/oppsrrd1/registration_review/.

The Tri

- N Butyl Tetradecyl Phosphonium Chloride Preliminary Work Plan (PWP) (PC Code 128824 ) was published on December 21, 2011 and the 6 0

- day comment period ended on February 21, 2012 . The Preliminary Work Plan document is available on www.regulations.gov docket number EPA

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. The first product containing Tri

- n butyl tetradecyl phosponium chloride ( TTPC ) (PC Code 128824 ) as an active ingredient was registered in the United States in 2006

. Currently, there are three products containing TTPC registered with EPA. It is used in industrial processes and water systems such as commercial and industrial cooling towers, evaporative condensers, heat exchange water systems, evaporative coolers, dairy sweetwater systems, industrial process water systems, brewery pasteurizers, can warmers, hydrostatic sterilizers and retorts, air washing systems equipped with a mist eliminator, and industrial air scrubbing systems as w ell as enhanced oil recovery Systems. There are no pesticide tolerances or exemptions from the requirement of tolerance for TTPC established by either EPA or FDA.

Comments Received on the Preliminary Work Plan

The Agency received one comment during the pub lic comment period on the initial docket, described below. In the PWP, the Agency solicited comments on specifi c topics: environmental justice, water body impairment

, trade irritants , and structure activity relationships

. No comments or information were re ceived during the public comment period concerning these issues.

Comment: BWA Water Additives disagreed with the anticipated schedule for TTPC. Ten of the twenty

- one anticipated studies require 24 months instead of the proposed 12 months to complete.Docket Number: EPA

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5 of 10 Res ponse: The Agency has revised the schedule to reflect the 24

- month timeframes. The updated schedule is presented in this FWP.

The comment received during the initial public comment period did not affect the data needs and work plan 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 Tri

- n butyl tetradecyl phosphonium chloride registration review process.

Risk Assessments and Anticipated Data Needs

The Agency will conduct a comprehensive ecological risk assessment, including an endangered species risk assessment, for all uses of TTPC. The Agency will not conduct a human health risk
assessment. The Agency expects to require additional data for use in conducting the registra tion review for TTPC.

Ecological Risk Assessment Status and Anticipated Data Needs

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

. The Agency anticipates the need to require the following additional ecological data for use in conducting the registration review of TTPC.

850.1400

-- Fish early

- life stage toxicity test (freshwater) 850.1300

-- Daphnid chronic toxicity test 850.4400

-- Aquatic plant toxicology test using Lemna spp., Tier I 850 .5400

-- Algal Toxicity Tier I and Tier II 850.1735

-- Whole sediment acute toxicity invertebrates (freshwater) Special Study

- Sediment chronic toxicity test, freshwater invertebrate

The Agency anticipates the need to require the following additional environmental fate data for use in conducting the registration review of TTPC.

835.4300

-- Aerobic aquatic metabolism 835.4400

-- Anaerobic aquatic metabolism 835.1240

-- Leaching and adsorption/desorption 850.6800

-- Modified activated sludge, respiration inhibition test 1
835.1110

-- Activated Sludge Sorption Isotherm 1

1 The results of the Activated Sludge Respiration Inhibition Test (ASRI) determine which of these three biodegradation tests are required. If the ASRI test EC 50 is less than or equal to 20 mg/L, then either the Biodegradation in Activated Sludge Study or Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or the Porous Pot Test is required. If the ASRI test EC 50 is greater than 20 mg/L, then th e applicant must choose either: (i) Ready Biodegradability or (ii) Biodegradation in Activated Sludge or Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or the Porous Pot Test. If the antimicrobial passes the ready biodegradability s tudy, then no further testing is required. If, however, the antimicrobial fails the ready biodegradability study, then the Biodegradation in Activated Sludge or Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units, or the Porous Pot study is required.Docket Number: EPA

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6 of 10

835.3110

-- Ready Biodegradability 1
835.3280

-- Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater 1

F or more information

, please refer to Product Chemistr y, Environmental Fate, and Ecological Effects Scoping Document in Support of the Registration Review of Tri

- n

- butyl tetradecyl phosphonium chloride , located in the docket

.
Human Health Risk Assessment Status and Anticipated Data Needs

The Agency reviewed the existing human healthy toxicology and exposure data from its initial registration in 2007 and the existing open literature.

Dietary Assessment

According to the existing labels, TTPC may be used as a slimacide for pulp, paper and paperboard mills and wa ter systems; however, the label restricts the use to nonfood applications and TTPC was not cleared for any indirect food contact use by FDA. As a result, no dietary exposure assessment is anticipated to be needed.

Although it is expected that drinking wat er exposures are likely to be infrequent, dietary exposures via drinking water may occur in the event of a down

- the

- drain discharge. The contaminated water could pass through wastewater treatment facilities into the drinking water or may be discharged dire ctly to surface water which is later treated. However, at this time there are no available environmental fate data to determine whether TTPC can pass through wastewater treatment facilities into drinking water or migrate into residential groundwater wells as a result of its current use patterns. Upon receipt and review of the environmental fate data the Agency anticipates requiring, the Agency will determine the need for a down

- the

- drain drinking water assessment.

Tolerances and International Harmonization

There are no pesticide tolerances or exemptions from the requirement of tolerance for TTPC established by either EPA or FDA.

Occupational and Residential Assessment and Risk

The end

- use products contain 5 to 50% active ingredient (a.i.), the labels of which explicitly states that the biocide is to be metered into water via a fully closed system. Labeling also requires PPE such as coveralls worn over long

- sleeved shirt, goggles, face shield, chemical resistant gloves and footwear in case of leaks or bre aks in the closed delivery system.

The Agency did an open literature search and did not identify any relevant exposure studies in the existing literature that could be used to supplement the existing Agency exposure database. There are minimal potential e xposures for closed mixing/loading systems.Docket Number: EPA

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7 of 10 The labels for TTPC are for industrial applications and no consumer products are treated. Therefore, no residential assessments will be needed.

Aggregate and Cumulative Exposure and Risk

In examining aggregate exposure, EPA takes into account the available and reliable information concerning exposures to pesticide residues in food and drinking water as well as nonoccupational pesticide exposures. There are no dietary (food) or residential/public access
exposure s associated with the registered uses of TTPC. There is the potential for drinking water exposures due to discharges from cooling towers, enhanced oil recovery systems, and a variety of industrial water systems. However, the need to assess potential risk s due to TTPC residues in drinking water will be based upon the outcome of the environmental fate studies anticipated to be needed.

EPA does not have, at this time, available data to determine whether TTPC has a common mechanism of toxicity with other sub stances or how to include this pesticide in a cumulative risk assessment.

For the purposes of this Registration Review, EPA has assumed that TTPC does not have a common mechanism of toxicity with other substances when used as an antimicrobial as registered

.
Human Health Anticipated Data Needs

The Agency does not anticipate the need to require additional human health data for the registration review at this time.

For more information, please refer to Tributyl Tertradecyl Phosphonium Chloride (TTPC): Human Health Risk Assessment Scoping Document in Support of Registration Review

, located in the docket

. Product Chemistry Anticipated Data Needs

The Agency does not anticipate the need to require additional product chemistry data for the registration review at t his time.

F or more information

, please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of the Registration Review of Tri

- n

- butyl tetradecyl phosphonium chloride

, located in the docket

.
Incidents:

Ecological:

No TTPC ecological incidents have been reported in the Agency’s Ecological I ncident Information System (EIIS)

.
Human Health:Docket Number: EPA

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8 of 10 No TTPC human poisoning incidents have been reported in the OPP I ncident Data System (IDS)

. Endangered Species

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

. The ecological risk assessment planned during registration review will allow the Agency to determine whether TTPC ’s use has 'no effect' or 'm ay 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 consu lt 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 fro m 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 whi ch 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 most recent registration decision for TTPC , 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), TTPC is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has develo ped 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 Admini strator 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 FFDC A 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. TTPC 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 fo r TTPC

. For further information on theDocket Number: EPA

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www.regulations.gov

9 of 10 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 creat ed the following estimated timeline for the completion of the Tri

- n butyl tetradecyl phosphonium chloride registration review:

Anticipated Schedule Activities Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Docket Completed December 2011 Close Public Comment Period for Docket Completed February 2012 Phase 2: Case Development Develop Final Work Plan (FWP) Completed June 2012 Issue DCI June 2013 Data Submission June 2015 Open Public Comment Period for Preliminary Risk Assessments December 2016 Close Public Comment Period for Preliminary Risk Assessments January 2017 Phase 3: Registration Review Decision Open Public Comment Period for Proposed Reg. Review Decision June 2017 Close Public Comment Period for Proposed Reg. Review Decision August 2017 Final Decision and Begin Post

- Decision Follow

- up December 2017 Total (years) 6

Next Steps

A DCI will be developed regarding the data needs listed under the “Risk Assessments and Anticipated Data Needs” section of this document. The Agency expects to issue the DCI in June 2013 . Human health and environmental fate and ecological hazard assessment s will be conducted for all uses.Docket Number: EPA

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10 of 10 Summary of Anticipated Data Requirements

– TTPC

The table below summarizes anticipated data needs for the Tri

- N Butyl Tetradecyl Phosphonium Chloride Case in this document (Final Work Plan), Product Chemistry, Enviro nmental Fate, and Ecological Effects Scoping Document in Support of the Registration Review of Tri

- n

- butyl tetradecyl phosphonium chloride

, and Tributyl Tertradecyl Phosphonium Chloride (TTPC): Human Health Risk Assessment Scoping Document in Support of Re gistration Review

.

Guideline Number Anticipated Data Requirement Test Material Estimated Timeframe

(Measured in months from DCI Receipt)

835.1110 Activated Sludge Sorption Isothem TGAI 24

835.3110 Ready Biodegradability 1 TGAI 12

835.3220 Porous Pot Test 1 TGAI 12

835.3280 Simulation Test to Assess the

Biodegradibility of Chemicals Dsicharged to Wastewater 1 TGAI 12

835.3240 Simulation Test

– Aerobic Sewage

Treatment: A. Activated Sludge Units TGAI 12

835.4300 Aerobic aquatic metabolism TGAI 24

835.4400 Anaerobic aquatic metabolism TGAI 24

835.1240 Adsorption/Desorption TGAI 24

850.6800 Modified Activated Sludge Respiration

Inhibition TGAI 24

850.1400 F ish early

- life stage toxicity test,

freshwater species (most acutely sensitive Blue gill sunfish, Lepomis macrochirus ) TGAI 24

1 The results of the Activated Sludge Respiration Inhibition Test (ASRI) determine which of these three biodegradation tests are required. If the ASRI test EC 50 is less than or equal to 20 mg/L, then either the Biodegradation in Activated Sludge Study or Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or the Porous Pot Test is required. If the ASRI test EC 50 is greater than 20 mg/L, then the applicant must choose either: (i) Ready Biodegradability or (ii) Biodegradati on in Activated Sludge or Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or the Porous Pot Test. If the antimicrobial passes the ready biodegradability study, then no further testing is required. If, however, the antimicrobial fail s the ready biodegradability study, then the Biodegradation in Activated Sludge or Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units, or the Porous Pot study is required.