United States Chemical Safety March 2012

Environmental Protection and Pollution Prevention

Agency (7510P)

Amines, C10-16-alkyldimethyl,N-oxides

Registration Review:

Final Work Plan

March 2012
Docket 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 

20fl0 
Docket Number: EPA-HQ-OPP-2011-0616

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Amines, C10-16-alkyldimethyl,N-oxides Registration Review Team

Nathan Mottl

Human Health & Environmental Effects

Srinivas Gowda

Seiichi Murasaki

Risk Management

Lance Wormell

Philip Ross

Office of General Counsel

________________________________________

Supporting documents for the Amines, C10-16-alkyldimethyl,N-oxides Case may be found in the 

registration review docket EPA-HQ-OPP-2011-0616 located on the internet at

www.regulations.gov.
Docket Number: EPA-HQ-OPP-2011-0616

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

Agency”) for the registration review of Amines, C10-16-alkyldimethyl,N-oxides (Case 5003). 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 Amines, C10-16-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 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 Amines, C10-16-alkyldimethyl,N-oxides Preliminary Work Plan (PWP) (PC Code 000439) 

was published on September 28, 2011 and the 60-day comment period ended on November 29, 

2011. The Preliminary Work Plan document is available on www.regulations.gov docket number 

EPA-HQ-OPP-2011-0616.

The first product containing alkyl dimethylamine oxides (amines, C10-16-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 180.910 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 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 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.

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 registration review. Therefore, the 

study was removed while other data needs, the work plan, and timeline described in the PWP 

Changes to the Final Work Plan 
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remain as they were presented initially. Further, this document makes final the work plan for the 

Amines, C10-16-alkyldimethyl,N-oxides 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 (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.

• 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 anticipates 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 sludge, respiration inhibition test1

 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 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 would be anticipated to be required. If the ASRI test 

EC50 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. Activated 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 

Biodegradation in Activated Sludge or Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or 

the Porous Pot study would be expected to be required.
Docket Number: EPA-HQ-OPP-2011-0616

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• For 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 listed. 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 needed 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 takes 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 exposures 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.
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• 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 anticipates 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 Chemistry Anticipated Data Needs

• For 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.

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. 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 
Docket Number: EPA-HQ-OPP-2011-0616

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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 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. Amines, C10-16-

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 ADAO.

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/.
Docket Number: EPA-HQ-OPP-2011-0616

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Timeline

EPA has created the following estimated timeline for the completion of the Amines, C10-16-

alkyldimethyl,N-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 assessments will be 

conducted for the registered use of ADAO. 
Docket Number: EPA-HQ-OPP-2011-0616

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Summary of Anticipated Data Requirements – ADAO

The table below summarizes anticipated data needs for the Amines, C10-16-Alkyldimethyl,NOxides 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 from 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 would be anticipated to be 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 would be anticipated to be required. If the ASRI test 

EC50 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. Activated 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 

Biodegradation in Activated Sludge or Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or 

the Porous Pot study would be expected to be required.