United States Chemical Safety March 2012 Environmental Protection and Pollution Prevention Agency (7510P)



# Amines, C 10

- 16 

# - a lkyldimethyl,N

- o xides Registration Review : Final Work Plan March 2012Docket Number: EPA-HQ-OPP-2011-0616 www.regulations.gov



## Amines, C 1 0-16-alky ldimethy I,N -oxides Registration Review: Final Work Plan March 2012



## Case # 

## 5003

Approved By:

an Harrigan-F elly Director, Antimicrobials Division

Date:



# I I

20fl0Docket Number: EPA

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3 of 10 Amines, C 10

- 16 - a lkyldimethyl,N

- o xides Registration Review Team

Nathan Mottl Human Health & Environmental Effects

Srinivas Gowda

Seiichi Murasaki Risk Management

Lance Wormell

Philip Ross Office of General Counsel

________________________________________ S upporting documents for the Amines, C 10

- 16 - a lkyldimethyl,N

- o xides Case may be found in the registration review docket EPA

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- 0616 located on the internet at www.regulations.gov

.Docket Number: EPA

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4 of 10 This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the Agency”) for the registration review of Amines, C 10

- 16 - alkyldimethyl,N

- oxides (Case 5003 )

. The work plan includes the expected registra tion 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 Amines, C 10

- 16 - alkyldimethyl,N

- oxides 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. Introduction

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 re gistered 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 Amines, C 10

- 16 - a lkyldimethyl,N

- o xides Preliminary Work Plan (PWP) (PC Code 000439 ) was published on September 28, 2011 and the 6 0

- day comment period ended on November 29, 2011 . The Preliminary Work Plan document is available on www.regulations.gov docket number EPA

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. The first product containing alkyl dimethylamine oxides ( amines, C 10

- 16 - alkyldimethyl, N

- oxides
or ADAO ) (PC Code 000439 ) as an active ingredient was registered in the United States in 1999

. Currently, there is only one product registered with EPA. The only registered use of ADAO is as an antibacterial dishwashing detergent in residential premises. ADAO currently has an inert tolerance exemption under 40 CFR 180.9 10 for use as a surfactant in pesticide formulations. EPA does not maintain a tolerance or exemption from the requirement of a tolerance for residues for the ADAO active ingredient. During registration review, the Agency will determine if any tolerances o r exemptions from the requirement of a tolerance are needed for the registered use.

The Agency received no comments during the public comment period on the initial docket. In the PWP, the Agency solicited comm ents on specifi c 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. Comments Received on the Preliminary Work Plan

Although no comments were received on the PWP, the Agency has revisited the anticipated need for the Avian acute oral toxicity test (GLN 850.2100) and has determined that this study is not necessary to complete the risk assessments required for this regis tration review. Therefore, the study was removed while other data needs, the work plan, and timeline described in the PWP C hanges to the Final Work PlanDocket Number: EPA

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5 of 10 remain as they were presented initially. Further, this document makes final the work plan for the Amines, C 10

- 16 - alkyldimethyl,N

- oxide s registration review process.

The Agency will conduct a comprehensive ecological risk assessment, including an endangered species risk assessment, for the registered use of ADAO

. The Agency will conduct a human health risk assessment. The Agency expects to require additional data for use in conducting the registration review for ADAO

. Risk Assessments and Anticipated Data Needs

Ecological Risk Assessment Status and Anticipated Data Needs

**•** The Agency has not conducted a risk assessment that supports a complete endangered species determination for ADAO. The ecological risk assessment planned during registration review will allow the Agency to determine whether ADAO’s use has 'no effect' or 'may affect' federally listed threatened or endangered species (l isted 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 Mari ne Fisheries Services (the Services), as appropriate.

**•** The Agency anticipates the need to require the following additional ecological data for use in conducting the registration review of ADAO

. 850.5400

-- Algal Toxicity Tier I and Tier II

**•** The Agency antic ipates the need to require the following additional environmental fate data for use in conducting the registration review of ADAO

. 835.1110

-- Activated Sludge Sorption Isotherm 835.2120

-- Hydrolysis 835.2240

-- Photodegradation in water 835.3110

-- Ready Biodegradability 835.3220

-- Porous Pot Test 835.3240

-- Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units 835.3280

-- Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater 850.6800

-- Modified activated slud ge, respiration inhibition test 1

1 The results of the Activated Sludge Respiration Inhibition Test (ASRI) expected to be required will determine which of these three biodegradation tests would be anticipated to be 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 would be anticipated to be required. If the ASRI test EC 50 is great er than 20 mg/L, then the applicant would choose to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous Pot Test. If the Read y Biodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the Biodegradation in Activated Sludge or Simulation Test

– Aerobic Sew age Treatment: A. Activated Sludge Units, or the Porous Pot study would be expected to be required.Docket Number: EPA

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6 of 10 **•** F or more information , please refer to Amines, C10

- 16 alkyldimethyl, N

- oxides. Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document for Registration Review , located in the docket

. Human Health Risk Assessment Status and Anticipated Data Needs

**•** The most recent human health risk assessments for ADAO were completed in 1999 , in support of initial registration.

**•** Food and Drug Administration (FDA) worst case calculations described in "Sanitizing Solutions: Chemistry Guidelines for Food Additive Petitions" were used to estimate dietary exposure for a human health risk assessment in 1999. Acute and chronic dietary risks were assessed and found to be acceptable for all subpopulations li sted. A new indirect dietary assessment is not anticipated to be required. A drinking water risk assessment was conducted for registration because, although likely to be infrequent, dietary exposures to ADAO from drinking water may occur from residues on a cup washed with ADAO. A new drinking water assessment is not anticipated to be required. Dietary Assessment

**•** ADAO currently has an inert tolerance exemption under 40 CFR 180.910 for use as a surfactant in pesticide formulations. EPA does not maintain a tolerance or exemption from the requirement of a tolerance for residues for the ADAO active ingredient. During registration review, the Agency will determine if any tolerances or exemptions from the requirement of a tolerance are ne eded for antimicrobial uses. Tolerances and International Harmonization

**•** Occupational handler exposure is not expected with the currently registered use, and an occupational risk assessment will not be conducted during registration review. Occupational and Residential Assessment and Risk

**•** Assessments of residential risk are planned for registration review because potential exposure is expected through the dermal route resulting from the use of the dishwashing detergent.

**•** In examining aggregate exposure, EPA ta kes into account available and reliable information concerning exposures to residues in food and drinking water, non

- occupational pesticide exposures, and inert uses. An aggregate risk assessment for ADAO is expected to be needed to assess aggregate expos ures from dietary sources (food and water) and residential dermal exposures. Aggregate and Cumulative Exposure and Risk

**•** EPA does not have, at this time, available data to determine whether ADAO has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment.Docket Number: EPA

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7 of 10 **•** For the purposes of this Registration Review, EPA has assumed that ADAO does not have a common mechanism of toxicity with other substances when used as an antimicrobial as registered.

**•** The Agency antici pates the need to require the following additional human health data for use in conducting the registration review of ADAO

. Human Health Anticipated Data Needs

875.1200

-- Dermal indoor exposure 875.1600

-- Application exposure data reporting and calculations 875.1700

-- Product use information 875.2800

-- Description of human activity

**•** For more information, please refer to Summary of Human Health Effects Data for the Alkyl (C10

- C16) Dimethyl Amine Oxide (ADAO) Registration Review Decision Document. , located in the docket

.

**•** The Agency does not anticipate the need to require additional product chemistry data for the registration review at this time. Product Che mistry Anticipated Data Needs

**•** F or more information , please refer to Amines, C10

- 16 alkyldimethyl, N

- oxides. Product Chemistry, E nvironmental Fate, and Ecological Effects Scoping Document for Registration Review. , located in the docket

.

Ecological: Incidents:

**•** No ADAO ecological incidents have been reported in the Agency’s Ecological Incident Information System (EISS).

Human Health:

**•** No ADAO human poisoning incidents have been reported in OPP’s Incident Data System (IDS). Endocrine Disruptor Screening Program As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Co llectively, 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 en docrine 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 andDocket Number: EPA

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8 of 10 chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision , 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), ADAO is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). EPA has developed the EDSP to determine whether cert ain 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 emplo ys 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 syst ems. 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 t he 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 scre en 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. Amines, C 10

- 16 - alkyldimethyl, N

- oxides 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 AD AO

. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

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9 of 10 Timeline EPA has created the following estimated timeline for the completion of the Amines, C 10

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- oxides registration review: Anticipated Schedule

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

- Decision Follow

- up September 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 March 2013 . Human health and environmental fate and ecological hazard assessmen ts will be conducted for the registered use of ADAO

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10 of 10 Summary of Anticipated Data Requirements

– ADAO

The table below summarizes anticipated data needs for the Amines, C 10

- 16 - Alkyldimethyl,N

Oxides Case in this document (Final Work Plan), Amines, C10

- 16 alkyldimethyl, N

- oxides. Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document for Registration Review, and Summary of Human Health Effects Data for the Alkyl (C10

- C16) Dimethyl Amine Oxide (ADAO) Registration Review Decision Document.

Guideline Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months f rom DCI Receipt)
850.2100 Avian acute oral toxicity TGAI 12
850.5400 Algal Toxicity Tier I and Tier II TGAI 12
835.1110 Activated Sludge Sorption TGAI 12
835.2120 Hydrolysis TGAI 12
835.2240 Photodegradation in water TGAI 12
835.3110 Ready Biodegradability TGAI 12
835.3220 Porous Pot Test TGAI 12

835.3240 Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units TGAI 12

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

850.6800 Modified activated sludge, respiration inhibition test 2 TGAI 12

875.1200 Dermal indoor exposure TGAI 12
875.1600 Application exposure data TGAI 12
875.1700 Product use information TGAI 12
875.2800 Description of human activity TGAI 12

2 The results of the Activated Sludge Respiration Inhibition Test (ASRI) expected to be required will determine which of these three biodegradation tests wo uld be anticipated to be 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 would be an ticipated to be required. If the ASRI test EC 50 is greater than 20 mg/L, then the applicant would choose to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test

– Aerobic Sewage Treatment: A. Activ ated Sludge Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the Biodegrada tion in Activated Sludge or Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units, or the Porous Pot study would be expected to be required.