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 2012

Docket Number: EPA-HQ-OPP-2011-0952

www.regulations.gov

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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

________________________________________

Supporting 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-HQ-OPP-2011-0952

www.regulations.gov

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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 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

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/.

The Tri-N Butyl Tetradecyl Phosphonium Chloride Preliminary Work Plan (PWP) (PC Code 

128824) was published on December 21, 2011 and the 60-day comment period ended on 

February 21, 2012. The Preliminary Work Plan document is available on www.regulations.gov

docket number EPA-HQ-OPP-2011-0952.

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 well 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 public comment period on the initial docket, 

described below. 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.

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-HQ-OPP-2011-0952

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Response: 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 registration 

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 test1

835.1110 -- Activated Sludge Sorption Isotherm1

 

1 The results of the Activated Sludge Respiration Inhibition Test (ASRI) determine which of these three 

biodegradation tests are required. If the ASRI test EC50 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 EC50 is greater than 20 mg/L, then the 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 study, 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-HQ-OPP-2011-0952

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835.3110 -- Ready Biodegradability1

835.3280 -- Simulation Tests to Assess the Biodegradability of Chemicals Discharged 

to Wastewater1

For 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.

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 water 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 water 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 directly 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 breaks 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 exposures for closed mixing/loading systems.
Docket Number: EPA-HQ-OPP-2011-0952

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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 

exposures 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 risks 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 substances 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 this time.

For 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 Incident 

Information System (EIIS).

Human Health:
Docket Number: EPA-HQ-OPP-2011-0952

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No TTPC human poisoning incidents have been reported in the OPP Incident 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 '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 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 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. 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 for TTPC. For further information on the 
Docket Number: EPA-HQ-OPP-2011-0952

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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 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 assessments will be 

conducted for all uses. 
Docket Number: EPA-HQ-OPP-2011-0952

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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, Environmental 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 Registration 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 Biodegradability1TGAI 12

835.3220 Porous Pot Test1TGAI 12

835.3280

Simulation Test to Assess the 

Biodegradibility of Chemicals 

Dsicharged to Wastewater1

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

Fish 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 EC50 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 EC50 is greater than 20 mg/L, then the 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 study, 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.