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


# Methyloxazolidines Summary Document: Registration Review : Initial Docket March 2012Docket Number: EPA-HQ-OPP-2012-0007 www.regulations.gov



### Methyloxazolidines Summary Document Registration Review: Initial Docket March 2012
Case # 3095

Approved By:

J an Harrigan-Farre y

irector, Antimicrobials Division

Date:



### I I



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### TABLE OF CONTENTS Methyloxazolidines Registration Review Team

................................ ................................ .. 4 I. Preliminary Work Plan

................................ ................................ ................................ ..... 5 II. Fact Sheet

................................ ................................ ................................ ...................... 1 3 III. Summary of Anticipated Data Requirements

................................ .............................. 1 8 IV. Appendix A

................................ ................................ ................................ .................. 20

________________________________________ Please Note This Preliminary Work P lan and Fact Sheet summarize the Environmental Protection Agency's current position based on the following documents:
1. Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Methyloxazolidines

. March 16, 2012 2. Methyloxazolidines. Human Health Scoping Document for the Registration Review

. March 16, 2012 Additional supporting documents for the Methyloxazolidines Case may be found in the registration review docket EPA

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4 of 20 Methyloxazolidines Registration Review Team

William Hazel Human Health & Environmental Effects Jenny Tao Timothy Dole Jonathan Chen Srinivas Gowda James Breithaupt Zoё Layton

Seiichi Murasaki Risk Management
Lance Wormell
Philip Ross Office of General CounselDocket Number: EPA

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5 of 20 I. Preliminary Work Plan
-- Methyloxazolidines

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program

. All pesticides distributed or sold in the United States generally must be registered by the U.S. Environmental Protection Agency (USEPA, EPA, or the Agency) based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling

. 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 the statutory stan dard of no unreasonable adverse effects to human health or the environment

. Changes in science, public policy, and pesticide use practices will occur over time

. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely

. Information on this program is provided at Introduction:

http://www.epa.gov/oppsrrd1/registration_review/

. The Agency is implement ing 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 regist ration

. The Agency will consider benefits information and data as required by FIFRA

. The public phase of registration review begins when the initial docket is opened for each case

. The docket is the Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registration review decision

. After reviewing and responding to comments and data received in the docket during this initial comment period, the Agency wil l develop and commit to a final work plan and schedule for the Methyloxazolidines C ase. The Methyloxazolidines Case (Case 3095) contains two active ingredients, 4,4

- dimethyloxazolidine (DMO) (PC Code 114801) and 3,4,4

- trimethyloxazolidine (PC Code 114802). DMO is the only active ingredient in the case with registered products. 3,4,4

- trimethyloxazolidine was not supported during reregistration and, because no currently registered products contain 3,4,4

- trimethyloxazolidine as an active ingredient, will not be addressed in this registration review. The first product containing 4,4

- Dimethyloxazolidine as an active ingredient was registered in the United States in 1982

. Currently , there are six product s registered with EPA. DMO is registered for use as a mate rial preservative for protection against microbial deterioration and as a microbiocide and bacteriostat additive in industrial processes and water systems. EPA does not maintain a tolerance or exemption from the requirement of a tolerance for residues for DMO. During registration review, the Agency will determine if any tolerances or exemptions from the requirement of a tolerance are needed for registered uses. DMO is rapidly hydrolyzed to formaldehyde (HCHO) and 2

- amino

- 2

- methyl

- 1

- propanol (AMP, CAS No. 12 4

- 68

- 5) in water

. Because EPA believes that DMO releases formaldehyde (HCHO) under certain conditions , this Registration Review also addresses potential risks associated with formaldehyde exposure from DMO use. Products containing formaldehyde as an activ e ingredient will be evaluated under Registration Review Case 0556. EPA ’s formaldehyde RED isDocket Number: EPA

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6 of 20 available in the formaldehyde public docket at http://www.regulations.gov in docket number EPA

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- 0121. The Agency completed a Reregistration Eligibility Decision (RED) for 4,4

- Dimethyloxazolidine in 1996

. Documents associated with the registration review of Methyloxazolidines can be viewed at www.regulations.gov in docket EPA

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. Below is a summary of the issues relevant to th is registration review case.

The Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endang ered species risk assessment, for all uses of 4,4

- Dimethyloxazolidine. The Agency anticipates the need to conduct a human health risk assessment. The Agency anticipates needing additional data for use in conducting the registration review for 4,4

- Dimethylo xazolidine. Anticipated Risk Assessment and Data Needs:

Ecological Risk:

**•** No ecological risk assessment has been performed for 4,4

- Dimethyloxazolidine

.

**•** The Agency has not conducted a risk assessment that supports a complete endangered species determination for 4,4

- Dimethyloxazolidine

. The ecologica l risk assessment planned during registration review will allow the Agency to determine whether 4,4

- Dimethyloxazolidine ’s use has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical ha bitats. 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 the registration review of 4,4

- Dimethyloxazolidine.
850.6800 1 850.2100 -- A ctivated S ludge R espiration I nhibition test 1 , 2 850.1075 -- Avian acute oral toxicity test 1 , 3 850.140 0 -- Fish acute toxicity (freshwater) 1 , 4 850.1010 -- Fish early

- life stage toxicity test (freshwater) 1 , 5 850.1300 -- Aquatic invertebrate acute toxicity, freshwater daphnids 1 , 5

-- Daphnid chronic toxicity test 850.1075 1

-- Fish acute toxicity (freshwater) 850.1 035 1

-- Mysid acute toxicity test

1 Results needed for the major degradate of concern, AMP. 2 Results needed using bobwhite quail. 3 Results needed using most sensitive species (i.e., bluegill sunfish)

. 4 Results needed using same species as used in acute toxicity test (i.e., bluegill sunfi sh). 5 Results needed using Daphnia magna

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7 of 20 850.1055 1

-- Bivalve acute tox larval (embryo/larval) 850.1350 1 , 6 850.4225 -- Mysid chronic tox

- aquatic inverteb rate life

- cycle (saltwater) 1

-- Seedling emergence, Tier II 850.4400 1

-- Aquatic plant toxicolo gy test using Lemna spp. 850.5400 1

-- Algal Toxicity Tier II

**•** The Agency anticipates the need to require the following additional environmental fate data for use in the registration rev iew of 4,4

- Dimethyloxazolidine.
835.1110

-- Activated Sludge Sorption Isotherm 835.4300 1

-- Aerobic aquatic metabolism 835.4400 1

-- Anaerobic aquatic metabolism 835.3110 1 , 7 835.3220 -- Ready Biodegradability 1 , 7

-- Porous Pot Test 835.3280 1 , 7

-- Simulation Tests to Assess the Biodegrad ability of Chemicals Discharged to Wastewater 83 5.3240 1 , 7

-- Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units

**•** F or more information , please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Methyloxazolidines , located in the docket

. Human Health Risk:

**•** No human health risk assessment has been performed for 4,4

- Dimethyloxazolidine

.

**•** The Agency anticipates the need to require the following additional human h ealth data for use in the registration review of 4,4

- Dimethyloxazolidine.
870.3465 8 870.4300 -- 90

- day inhalation toxicity (rat) 8

-- Combined chronic toxicity/carcinogenicity 875.1100 8 , 9 875.1300 -- Dermal outdoor exposure 8 , 9

-- Inhalation outdoor exposure

6 Results needed using Americamysis bahia

. 7 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 anticipat ed 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 Sl udge 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. 8 M easure ments of DMO , AMP, and HCHO are anticipated as being needed

. 9 E x posure studies are anticipated as being needed for following scenarios: o pen
- pour liquids for material preservation or oil

- field treatments; a pplication of preserved paints using brush/roller or airless sprayer; u se of treated metalworking fluids; and t rigger sprayer, wipe, and mop appl ication of preserved cleaners. If labels are amended to require closed mixing/loading, then any required exposure study for open
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8 of 20 875.1600 8 , 9

-- Application exposure data reporting and calculations 875.2300 8 , 10 , 11 875.2500 -- Indoor surface residue dissipation 8 , 12 875.1700

-- Product use information -- Small Chamber Emissions
S pecial S tudy 8

-- Nature of Residue on Surfaces S pecial S tudy 8

-- Migration Study

**•** F or more information , please refer to Methyloxazolidines. Human Health Scoping Document for the Registration Review , located in the docket

. Product Chemistry:

**•** The Agency does not anticipate the need to require additional product chemistry data for this registration review case at this time because all product chemistry data requirements have been satisfied for DMO

.

**•** F or more information , please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Methyloxazolidines , located in the docket

.

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chem icals

. 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 suscepti ble 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 e valuates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups

. As part of its reregistration decision for DMO , EPA reviewed these data and selected the most sensitive endpoints for relevan t risk assessment scenarios from the existing hazard database

. However, as required by FFDCA section 408(p), DMO is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). Endocrine Disruptor Screening Program

EPA has developed the EDSP to determine whethe r 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) hormona l

10 Study is anticipated as being needed for following scenario: p ost

- application exposure to floors and carpets cleaned with preserved household cleaners

. 11 If this anticipated study is required but is not conducted, a default transfer factor of 100% w ould be expected to be used. 12 S tud y is anticipated as being needed for the following scenario: p ost

- ap plication inhalation exposure to treated paints

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9 of 20 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 base d 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 mus t 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. DMO 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 DMO

. 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/

.

EPA has created the following estimated tim eline for the completion of the Methyloxazolidines registration review: Timeline

Anticipated Schedule Activities Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Docket March 2012 Close Public Comment Period for Docket May 2012 Phase 2: Case Development Develop Final Work Plan (FWP) September 2012 Issue DCI September 2013 Data Submission September 201 7 Open Public Comment Period for Preliminary Risk Assessments March 201 9 Close Public Comment Period for Preliminary Risk Assessments April 201 9 Phase 3: Registration Review Decision Open Public Comment Period for Proposed Reg. Review Decision September 201 9 Close Public Comment Period for Proposed Reg. Review Decision November 201 9 Final Decision and Begin Post

- Decision Follow

- up 20 20 Total (years) 8

The public is invited to comment on EPA’s P reliminary W ork P lan and rationale

. The Agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the Methyloxazolidines Registration Review case. Guidance for Commenters:Docket Number: EPA

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10 of 20 Through the registration revi ew process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution

. Growers and other stakeholders are asked to comment on any trade irritant issues resulting from lack o f Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the concern. Trade Irritants:

4,4

- Dimethyloxazolidine is not identified as a cause of im pairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=88 5. In addition, no Total Maximum Daily Loads (TMDL) have been developed for 4,4

- Dimethyloxazolidine , based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id =885&p_pollutant_group_name=PESTICIDES. Water Quality:

More information on impaire d water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/

. The Agency invites submission of water quality data for this pesticide

. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process (s ee: http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm ), in order to ensure the data can be used quantitatively or qualitatively in pesticide risk assess ments.

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and poli cies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to 4 ,4

- Dimethyloxazolidine compare d to the general population. Please comment if you are aware of any sub

- populations that may have atypical, unusually high exposure compared to the general population. Environmental Justice:

EPA must rely upon info rmation of appropriate quality and reliability for each decision made by the Agency

. In the Office of Pesticide Programs (OPP), the evaluation process for a pesticide chemical traditionally begins with the applicant’s submission of a set of studies conduct ed with the specific pesticide chemical of interest

. The use of the results of such testing (measured data) is a logical, scientifically rigorous process that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species. Structure Activity Relationships:Docket Number: EPA

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11 of 20 Today, there is significant interest in alternative techniques, i.e., techniques other than data generation that could significantly inform the Agency’s decision

- makin g process
. Recently, OPP has made increasing use of structure activity relationship (SAR) as part of its regulatory decision

- making process

. In the SAR process, a chemical's molecular structure is compared to that of other chemicals for which data are avai lable

. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties

. Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly related to) the chemical’s molecular structure

. Quantitative SAR is referred to as QSAR

. To develop a QSAR, a selected set of measured data on a single physical, chemical, or biological property is used to derive a model (an equation) to predict the value of that prop erty

. Since SAR assessments and QSAR modeling are another set of tools that are available to Agency scientists, OPP has begun a process shift that envisions shifting from the current study

- by

- study approach to an approach in which the use of predicted dat a, generated using validated models, is considered along with information from open literature and studies specifically generated under Part 161 requirements

. All relevant information would be considered as part of a weight

- of

- the

evidence evaluation

. At this time, EPA believes that for certain endpoints, especially physical/chemical and fate properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals

. When considering biological properties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters

. This is appropriate because the risk assessment for lower toxicity chemicals can be stream

- lined, i.e., a screening

- level assessment procedure rather than multiple tiers of assessments with progressively more data requirements. If stakeholders believe that submission of predicted data can fulfill one of the data needs for the Methyloxazolidines c ase, then the Agency invites submission of this information

. The submitter would be expected to supply a rationale describing the utility of the information and provide documentation on the scientific validity of the infor mation

. The determination that the predicted data fulfills the data requirement would be at the sole discretion of the Agency

. Pre

- submission consultation with the Agency is encouraged.

Stakeholders are also specifically asked to provide available information and data that will assist the Agency in refining its risk assessments , including any species

- specific ecological effects determinations. The Agency is interested in receiving the fol lowing information: Additional Information:

1. Confirmation on the following label information: a. Sites of application b. Formulations c. Application methods and equipment d. Maximum application rates e. Frequency of application, application intervals and maximum number of applicationsDocket Number: EPA

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12 of 20 f. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non

- agricultural uses (e.g., materials preservation) 5. Typical application interval 6. State or local use restrictions 7. Ecological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency 8. Monitoring data Next Steps:
After the 60

- day comment period closes in May 2012 , the Agency will review and respond to any comments received in a timely manner , and then issue a Final Work Plan for the Methyloxazolidines c ase
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13 of 20 II. Fact Sheet

**•** Active Ingredient: 4,4

- Dimethyloxazolidine Background Information:

**•** C ase number: 3095

**•** PC Code: 114801

**•** CAS number : 51200

- 87

- 4

**•** Technical registrants: Dow Chemical, Internati onal Specialty Products, Troy Chemical

**•** First approved for use in a registered product: 1982

**•** There are no tolerances or exemptions from tolerances for DMO.

**•** Antimicrobials Division Chemical Review Manager (CRM): Seiichi Murasaki , murasaki.seiichi@epa.gov

**•** Ant imicrobials Division Product Manager (PM): Marshall Swindell , swindell.marshall@epa.gov

**•** Chemical Structure:

**•** DMO is registered for use as a material preservative for protection against microbial deterioration and as a microbiocide and bacteriostat additive in industrial processes and water systems. Use & Usage Information:

**•** There are no pending regulatory actions for DMO. Recent/Pending Regulatory Actions :

Please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Methyloxazolidines , located in the docket, for a detailed discussion of the ecological risk assessments. Ecological Risk Assessment Status:

**•** DMO degrades rapidly by hydrolysis to form 2

- amino

- 2

- methyl

- 1

- propanol (AM P, CAS No. 124

- 68

- 5), which is stable to abiotic degradation processes. The Agency does not have acceptable environmental fate and transport data on AMP. These data are expected to be needed for use in assessing environmental fate for the registered use p atterns that may potentially enter waste water treatment plants (WWTPs) and subsequently be discharged to aquatic environments. With the exception of one avian oral toxicity study on a waterfowl species (OCSPP Guideline 850.2100), the ecotoxicological data base is adequate to characterize the hazards from acute toxicity of DMO to nontarget terrestrial and aquatic organisms. However, there is a lack of data for assessing risk from the major degradate, AMP. Since potential exposure to nontarget organisms will occur in the form of the major degradates AMP and formaldehyde, a quantitative ecological riskDocket Number: EPA

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14 of 20 assessment, focusing on the degradates rather than the parent, is expected to be conducted for use patterns which result in discharges of the parent or degradat es of concern to aquatic systems (e.g., metalworking fluids, industrial water process systems, oil well treatment and drilling muds, and consumer product uses).

The following are key findings of the recent human health risk assessments for Methyloxazolidines . Please refer to Methyloxazolidines. Human Health Scoping Document for the Registration Review , located in the docket, for a detailed discussion of the human health risk assessment. Human Health Risk Assessment Status:

Hazard Characterization:

**•** Based on acute toxicity data, DMO is corrosive to the eyes (Toxicity Category I), slightly irritating to the skin (Toxicity Category IV), and it is not a dermal sensitizer. Acute oral, dermal, and inhalation toxicities are classified as Toxicity Category III.

**•** Both chronic dietary (food and drinking water) exposure and long

- term occupational exposure (metal workers) scenarios are expected based on the currently

- approved DMO uses. No chronic toxicity studies are available for DMO to be used for assessment of potential chronic exposure concerns.

**•** A study to determine the carcinogenic potential of DMO has not been conducted. Cancer studies are typically required to characterize the hazard associated with dietary, residential, and/or occupational exposure extending over a chronic or long

- term duration (>6 months or as long as a lifetime). The Agency believes that a carcinogenicity study is necessary to evaluate the potential carcinogenicity of DMO, based on the following evidence:

o Positive results in mutagenicity assays (mo use lymphoma assay and structural chromosome aberration). o Potential indirect food

- contact and drinking water exposures to DMO are expected. o The metabolism study indicates that HCHO was rapidly released when DMO was administered orally. Of the orally

- admin istered radioactivity, AMP in the excreta accounted for about 90%. HCHO is classified as “Group B1; probable human carcinogen”. Although EPA has an acceptable cancer study for HCHO, it is via the inhalation route of exposure. o No carcinogenicity studies are available for DMO or its metabolites HCHO or AMP to assess carcinogenic potential via the oral route of exposure.

**•** Results from a 90

- day dermal toxicity study in rats (MRID 43322601) indicated the systemic LOAEL for males was 100 mg/kg/day based on decreased body weight gain; a systemic LOAEL was not established for females (>100 mg/kg/day). The systemic NOAEL was 30 m g/kg/day for males and ≥100 mg/kg/day for females. The LOAEL for dermal irritation was 30 mg/kg/day based on microscopic changes, including inflammation, ulceration, and acanthosis in both males and females and the NOAEL forDocket Number: EPA

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15 of 20 dermal irritation was 1 mg/kg/d ay. If the dermal irritation endpoint from this study is chosen for dermal risk assessment, the NOAEL dose will need to be converted to the equivalent μg/cm2 dose.
Dietary (Food and Water):

**•** Dietary (food) exposure to DMO or AMP could potentially occur, si nce materials preserved with DMO could potentially contact food directly or be used to manufacture food contact materials, leading to exposure to the parent compound and AMP. Dietary (food) risk assessments are expected to be necessary unless all use sites on all product labels are limited to nonfood contact.

**•** Material preservative uses of dimethyloxazolidine may lead to contamination of human and livestock drinking water through the discharge of waste water. Dimethyloxazolidine and/or its degradates could potentially pass through wastewater treatment plants (WWTPs). The contaminating substance is expected to be largely AMP (the stable hydrolytic and metabolic product of the parent compound). The Agency will determine the need for a dietary drinking water r isk assessment following the submission and review of environmental fate data that are anticipated to be required

. Residential:

**•** Detailed use information and results from small chamber studies are anticipated as needed for use in estimating residential expo sure to DMO or its metabolites from materials preserved or treated with DMO (e.g., liquid soaps, fabric cleaning and care products, water

- based cleaning products, paints, adhesives, printing supplies, polishes, and textile emulsions). Scenarios expected to be needed to be assessed include: (1) u sing treated surface cleaners and laundry detergents, (2) painting with treated paints (Airless spray and brush/roller), and (3) toddlers playing on floors cleaned with treated surface cleaners. Aggregate:

**•** In examini ng aggregate exposure, EPA takes into account the available and reliable information concerning exposures to residues in food and drinking water, and non

occupational pesticide exposures. If the results of the environmental fate data that are anticipated t o be required indicate that a drinking water assessment is necessary, then the Agency anticipates the need to conduct an aggregate assessment for residential and dietary exposure to DMO and its residues of concern (AMP and HCHO). Occupational:

**•** Dimethylox azolidine, AMP, and HCHO all pose potential worker dermal and inhalation exposure concerns during open

- pour activities, painting, and metal

- working. Detailed use information and results from exposure and small chamber studies are anticipated as being neede d for use in estimat ing occupational exposure to DMO or its metabolites duringDocket Number: EPA

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16 of 20 manufacture of preserved materials and treatment and use of other liquids. Scenarios expected to be needed to be assessed include: (1) open
- pour liquids during material preserva tion and oil field treatments, (2) using treated metal

- working fluids, and (3) painting with treated paints (Airless spray and brush/roller). Cumulative:

**•** EPA does not have, at this time, available data to determine whether 4,4

- Dimethyloxazolidine has a com mon 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 4,4

- Dimethyloxazolidine does not have a common mechanism of toxicity with o ther substances when used as an antimicrobial as registered.

Ecological: Incidents:

**•** No 4,4

- Dimethyloxazolidine ecological incidents have been reported in OPP’s Ecological Incident Information System (EIIS)

. Human Health:

**•** No 4,4

- Dimethyloxazolidine human poisoning incidents have been reported in the OPP Incident Data System (IDS)

. Tolerances and International Harmonization:

**•** EPA does not maintain a tolerance or exemption from the requirement of a tolerance for residues for DMO. During registration review, the Agency will determine if any tolerances or exemptions from the requirement of a tolerance are needed for registered uses.

**•** There are no outstanding data call

- in (DCI) requirements for DMO. Data Call
- In Status:

Labels: Registered products, including EPA registration numbers are provided in Table 1 below

. For future reference, during registration review a list of product registration numbers will be included in the docket. Product registration labels may be obtained from the Pesticide Product Label System (PPLS) website at: http://oaspub.epa.gov/pestlabl/ppls.home

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17 of 20 Table 1
. Registered Products

– Methyloxazolidines Registration # Registration Name Company Name Formulation Type % A.I.

464

- 660 Bioban CS

- 1135 Antimicrobial Agent The Dow Chemical Co. Ready

- to

- Use Solution 78

464

- 664 Bioban CS

- 40l Preservative The Dow Chemical Co. Ready

- to

- Use Solution 38
1529

- 32 Nuosept 101 Preservative International Specialty Products Ready

- to

- Use Solution 77 1529

- 37 Nuosept 166 Preservative International Specialty Products Soluble Concentrate 65.63
5383

- 82 Troysan 192 II Troy Chemical Corp Ready

- to

- Use Solution 73.7
5383

- 90 Troysan 186 Formula II Troy Chemical Corp Soluble Concentrate 68Docket Number: EPA

- HQ

- OPP

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- 0007 www.regulations.gov

18 of 20 III. Summary of Anticipated Data Requirements

– Methyloxazolidines
The table below summarizes anticipated data needs for the Methyloxazolidines Case in Section I of this document (Preliminary Work Plan), Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Methyloxazolidines , and Methyloxazolidines. Human Health Scoping Document for the Registration Review
. Table 2. Summary of Anticipated Data Requirements

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

from DCI Receipt) 850.6800 13 Activated Sludge Respiration Inhibition test AMP 24 850.2100 13 , 14 Avian acute oral toxicity test AMP 12 850.1075 13 , 15 Fish acute toxicity (freshwater) AMP 12

850.1400 13 , 16 Fish early

- life stage toxicity test (freshwater) AMP 12

850.1010 13 , 17 Aquatic invertebrate acute toxicity, freshwater daphnids AMP 12

850.1300 13 , 17 Daphnid chronic toxicity test AMP 12 850.1075 13 Fish acute toxicity (freshwater) AMP 12 850.1035 13 Mysid acute toxicity test AMP 12 850.1055 13 Bivalve acute tox larval (embryo/larval) AMP 12

850.1350 13 , 18 Mysid chronic tox

- aquatic invertebrate life

cycle (saltwater) AMP 12

850.4225 13 Seedling emergence, Tier II AMP 12

850.4400 13 Aquatic plant toxicology test using Lemna spp. AMP 12

850.5400 13 Algal Toxicity Tier II AMP 12 835.1110 Activated Sludge Sorption Isotherm TGAI 24 835.4300 13 Aerobic aquatic metabolism AMP 24 835.4400 13 Anaerobic aquatic metabolism AMP 24 835.3110 13 , 19 Ready Biodegradability AMP 24

13 Results needed for the major degradate of concern, AMP. 14 Results needed using bobwhite quail. 15 Results needed using most sensitive species (i.e., bluegill sunfish)

. 16 Results needed using same species as used in acute toxicity test (i.e., bluegill sunfish). 17 Results needed using Daphnia magna

. 18 Results needed using Americamysis bahia

.Docket Number: EPA

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- 2012

- 0007 www.regulations.gov

19 of 20 835.3220 13 , 19 Porous Pot Test AMP 24

835.3280 13 , 19 Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater AMP 24

835.3240 13 , 19 Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units AMP 24

870.3 465 20 90

- day inhalation toxicity (rat) DMO, AMP, & HCHO 24 870.4300 20 Combined chronic toxicity/carcinogenicity DMO, AMP, & HCHO 48 875.1100 20 , 21 Dermal outdoor exposure DMO, AMP, & HCHO 24 875.1300 20 , 21 Inhalation outdoor exposure DMO, AMP, & HCHO 24

875.1600 20 , 21 Application exposure data reporting and c alculations DMO, AMP, & HCHO 24

875.2300 20 , 22 , 23 Indoor surface residue dissipation DMO, AMP, & HCHO 24 875.2500 20 , 24 Small Chamber Emissions DMO, AMP, & HCHO 24 875.1700 Product use information DMO, AMP, & HCHO 12 S pecial S tudy 20 Nature of Residue on Surfaces DMO, AMP, & HCHO 24 S pecial S tudy 20 Migration Study DMO, AMP, & HCHO 24

19 The results of the Activated Sludge Respiration Inhibition Test (ASRI) expected to be required will determine whic h 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 T est

– 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 Bio degradability 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. 20 M easure ments of DMO , AMP, and HCHO are anticipated as being needed

. 21 E x posure studies are anticipated as being needed for following scenarios: o pen
- pour liquids for material preservation or oil

- field treatments; a pplication of preserved paints using brush/roller or airless sprayer; u se of treated metalworking fluids; and t rigger sprayer, wipe, and mop application of preserved cleaners. If labels are amended to require closed mixing/loading, then any required exposure study for open
- pour scenario s can be waived 22 Study is anticipated as bei ng needed for following scenario: p ost

- application exposure to floors and carpets cleaned with preserved household cleaners

. 23 If this anticipated study is required but is not conducted, a default transfer factor of 100% w ould be expected to be used. 24 S tud y is anticipated as being needed for the following scenario: p ost

- application inhalation exposure to treated paints

.Docket Number: EPA

- HQ

- OPP

- 2012

- 0007 www.regulations.gov

20 of 20 IV. Appendix A : Use Patterns

– Methyloxazolidines Treatment Site Reg. # Method of Application Application / Use Rate Industrial processes and water systems / Oil and gas production Drilling muds and workover and completion fluids 464

- 660 Open pour, metered 21

- 42 gallons per 1000 barrels. (500

- 1000ppm) Drilling muds and workover and completion fluids 5383

- 82 Open pour, metered 85.33

- 42.67 gallons per 2000 barrels. (500

- 1000ppm) Oilfield water systems such as drilling muds and workover and completion fluids 464

- 664 metered 0.86

- 25.6 gallons per 2000 barrels. (10

- 300ppm) Oilfield and gas water injection water systems 464

- 660 Open pour, metered 2.1

- 10.5 gallons per 1000 barrels (5

- 250ppm). 2

- 8 hours per day, 1

- 4 days per week. Oilfield and gas water injection water systems 5383

- 82 Open pour, metered 0.43

- 12.8 gallons per 2000 barrels (5

- 150ppm). 2

- 8 hours per day, 1

- 4 days per week. Material pr eservative / Adhesives Non

- food contact adhesives 464

- 660 metered 0.1

- 0.5 lb. per 100 lb of formulation. Non

- food contact adhesives 5383

- 82 metered 0.1

- 0.5 lb. per 100 lb of formulation. Material preservative / Consumer, household and institutional products Dishwashing liquids, surface cleaners, laundry cleaners, and polishes 464

- 660 Open pour, metered 0.04

- 0.2lb. Per 100 lb slurry (400

- 2000ppm) Material preservative / Lubricants and mold release agents Die

- cast applications and mold release agents in plastic manufacturing. Diluted or concentrated. 464

- 660 Open pour, metered 1.0

- 2.0 pints per 100 gallons of fluid.(1000

- 2000ppm) Material preservative / Metalworking fluids Diluted or concentrated metalworking fluids 464

- 660 Open pour, metered 1.0

- 2.0 pints per 100 gallons of fluid.(1000

- 2000ppm) Diluted or concentrated metalworking fluids 5383

- 82 Open pour, metered 1.0

- 2.0 pints per 100 gallons of fluid.(1000

- 2000ppm) Material preservative / Mineral slurries Mineral slurries 464

- 660 Open pour, metered 0.04

- 0.2lb. Per 100 lb slurry (400

- 2000ppm) Material preservative / Surfactants Anionic, nonionic amphoteric and cationic surfactants 464

- 660 Open pour, metered 0.04

- 0.2lb. Per 100 lb slurry (400

- 2000ppm) Material preservative / Water based systems Caulks, sealants, grouts, spackling, ready

- mixed wallboard compounds, resin emulsions, latex paints, adhesives, inks, dispersed colors and ready

- mixed joint cements. Non

- food contact 5383

- 90 metered 0.1

- 0.3% by weight Caulks, sealants, grouts, spackling, ready

- mixed wallboard compounds, resin emulsions, latex paints, adhesives, inks, dispersed colors and ready

- mixed joint cements. 1529

- 32 metered 0.05 to 0.5% by weight

Caulks, sealants, grouts, spackling, ready

- mixed wallboard compounds , resin emulsions, latex paints, adhesives, inks, dispersed colors and ready

- mixed joint cements. 1529

- 37 metered 0.05 to 0.5% by weight

Material preservative / Water based systems such as latex paints and ink and resin emulsions Latex paint, ink and resin emulsions. 464

- 660 metered 0.1

- 0.2 lb. per 100 lb of formulation. Latex paint, ink and resin emulsions. 5383

- 82 metered 0.1

- 0.5 lb. per 100 lb of formulation.