United States Chemical Safety March 2012

Environmental Protection and Pollution Prevention

Agency (7510P)

Methyloxazolidines

Summary Document:

Registration Review: Initial Docket

March 2012
Docket 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 

20f18 
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TABLE OF CONTENTS

Methyloxazolidines Registration Review Team..................................................................4

I. Preliminary Work Plan .....................................................................................................5

II. Fact Sheet ......................................................................................................................13

III. Summary of Anticipated Data Requirements..............................................................18

IV. Appendix A..................................................................................................................20

________________________________________

Please Note

This Preliminary Work Plan 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-HQ-OPP-2012-0007 located on the internet at

www.regulations.gov.
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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 Counsel
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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 standard 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 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. 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 will develop and commit to a final work plan and 

schedule for the Methyloxazolidines Case.

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 products registered with EPA. 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. 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. 124-68-5) 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 active 

ingredient will be evaluated under Registration Review Case 0556. EPA’s formaldehyde RED is 
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available in the formaldehyde public docket at http://www.regulations.gov in docket number 

EPA-HQ-OPP-2008-0121.

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-HQ-OPP-2012-0007. Below is a summary of the issues 

relevant to this registration review case.

The Agency anticipates the need to conduct a comprehensive ecological risk assessment, 

including an endangered 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-

Dimethyloxazolidine.

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 ecological 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 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 the registration review of 4,4-Dimethyloxazolidine.

850.68001

850.2100

-- Activated Sludge Respiration Inhibition test

1,2

850.1075

-- Avian acute oral toxicity test

1,3

850.1400

-- 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

850.10751 -- Fish acute toxicity (freshwater)

850.10351 -- 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 sunfish). 5 Results needed using Daphnia magna.
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850.10551 -- Bivalve acute tox larval (embryo/larval)

850.13501,6

850.4225

-- Mysid chronic tox - aquatic invertebrate life-cycle (saltwater)

1 -- Seedling emergence, Tier II

850.44001 -- Aquatic plant toxicology test using Lemna spp.

850.54001 -- Algal Toxicity Tier II

• The Agency anticipates the need to require the following additional environmental fate 

data for use in the registration review of 4,4-Dimethyloxazolidine.

835.1110 -- Activated Sludge Sorption Isotherm

835.43001 -- Aerobic aquatic metabolism

835.44001 -- Anaerobic aquatic metabolism

835.31101,7

835.3220

-- Ready Biodegradability

1,7 -- Porous Pot Test

835.32801,7 -- Simulation Tests to Assess the Biodegradability of Chemicals 

Discharged to Wastewater

835.32401,7 -- Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge 

Units

• For 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 health data 

for use in the registration review of 4,4-Dimethyloxazolidine.

870.34658

870.4300

-- 90-day inhalation toxicity (rat)

8 -- Combined chronic toxicity/carcinogenicity

875.11008,9

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 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.

8 Measurements of DMO, AMP, and HCHO are anticipated as being needed. 9 Exposure studies are anticipated as being needed for following scenarios: open-pour liquids for material 

preservation or oil-field treatments; application of preserved paints using brush/roller or airless sprayer; use of 

treated metalworking fluids; and trigger 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 scenarios can be waived
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875.16008,9 -- Application exposure data reporting and calculations

875.23008,10,11

875.2500

-- Indoor surface residue dissipation

8,12

875.1700 -- Product use information

-- Small Chamber Emissions

Special Study8-- Nature of Residue on Surfaces

Special Study8-- Migration Study

• For 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.

• For 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 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 reregistration decision for DMO, 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), 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 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 

 10 Study is anticipated as being needed for following scenario: post-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% would be expected to be 

used.

12 Study is anticipated as being needed for the following scenario: post-application inhalation exposure to treated 

paints.
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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. 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 timeline 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 2017

Open Public Comment Period for Preliminary Risk Assessments March 2019

Close Public Comment Period for Preliminary Risk Assessments April 2019

Phase 3: Registration Review Decision

Open Public Comment Period for Proposed Reg. Review Decision September 2019

Close Public Comment Period for Proposed Reg. Review Decision November 2019

Final Decision and Begin Post-Decision Follow-up 2020

Total (years) 8

The public is invited to comment on EPA’s Preliminary Work Plan 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:
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Through the registration review 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 of 

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 impairment 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 impaired 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 (see: 

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 assessments.

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 policies. 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 compared 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 information 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 conducted 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: 
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Today, there is significant interest in alternative techniques, i.e., techniques other than data 

generation that could significantly inform the Agency’s decision-making 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 available. 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 property. 

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 data, 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-theevidence 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 case, 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 information. 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 following 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 

applications
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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 case. 
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II. Fact Sheet

• Active Ingredient: 4,4-Dimethyloxazolidine

Background Information:

• Case number: 3095

• PC Code: 114801

• CAS number: 51200-87-4

• Technical registrants: Dow Chemical, International 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

• Antimicrobials 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 (AMP, 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 patterns 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 database 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 risk 
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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 degradates 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 (mouse 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-administered 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 mg/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 for 
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dermal irritation was 1 mg/kg/day. 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, since 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 risk 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 exposure 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) using 

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 examining aggregate exposure, EPA takes into account the available and reliable 

information concerning exposures to residues in food and drinking water, and nonoccupational pesticide exposures. If the results of the environmental fate data that are 

anticipated to 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:

• Dimethyloxazolidine, 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 

needed for use in estimating occupational exposure to DMO or its metabolites during 
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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 

preservation 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 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 4,4-Dimethyloxazolidine does not have a 

common mechanism of toxicity with other 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.
Docket Number: EPA-HQ-OPP-2012-0007

www.regulations.gov

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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 68
Docket Number: EPA-HQ-OPP-2012-0007

www.regulations.gov

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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)

850.680013 Activated Sludge Respiration Inhibition test AMP 24

850.210013,14 Avian acute oral toxicity test AMP 12

850.107513,15 Fish acute toxicity (freshwater) AMP 12

850.140013,16 Fish early-life stage toxicity test 

(freshwater) AMP 12

850.101013,17 Aquatic invertebrate acute toxicity, 

freshwater daphnids AMP 12

850.130013,17 Daphnid chronic toxicity test AMP 12

850.107513 Fish acute toxicity (freshwater) AMP 12

850.103513 Mysid acute toxicity test AMP 12

850.105513 Bivalve acute tox larval (embryo/larval) AMP 12

850.135013,18 Mysid chronic tox - aquatic invertebrate lifecycle (saltwater) AMP 12

850.422513 Seedling emergence, Tier II AMP 12

850.440013 Aquatic plant toxicology test using Lemna

spp.

AMP 12

850.540013 Algal Toxicity Tier II AMP 12

835.1110 Activated Sludge Sorption Isotherm TGAI 24

835.430013 Aerobic aquatic metabolism AMP 24

835.440013 Anaerobic aquatic metabolism AMP 24

835.311013,19 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-HQ-OPP-2012-0007

www.regulations.gov

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835.322013,19 Porous Pot Test AMP 24

835.328013,19

Simulation Tests to Assess the 

Biodegradability of Chemicals Discharged 

to Wastewater

AMP 24

835.324013,19 Simulation Test – Aerobic Sewage 

Treatment: A. Activated Sludge Units AMP 24

870.346520 90-day inhalation toxicity (rat) DMO, AMP, & HCHO 24

870.430020 Combined chronic toxicity/carcinogenicity DMO, AMP, & HCHO 48

875.110020,21 Dermal outdoor exposure DMO, AMP, & HCHO 24

875.130020,21 Inhalation outdoor exposure DMO, AMP, & HCHO 24

875.160020,21 Application exposure data reporting and 

calculations DMO, AMP, & HCHO 24

875.230020,22,23 Indoor surface residue dissipation DMO, AMP, & HCHO 24

875.250020,24 Small Chamber Emissions DMO, AMP, & HCHO 24

875.1700 Product use information DMO, AMP, & HCHO 12

Special Study20 Nature of Residue on Surfaces DMO, AMP, & HCHO 24

Special Study20 Migration Study DMO, AMP, & HCHO 24

 19 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.

20 Measurements of DMO, AMP, and HCHO are anticipated as being needed. 21 Exposure studies are anticipated as being needed for following scenarios: open-pour liquids for material 

preservation or oil-field treatments; application of preserved paints using brush/roller or airless sprayer; use of

treated metalworking fluids; and trigger 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 scenarios can be waived 22 Study is anticipated as being needed for following scenario: post-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% would be expected to be 

used.

24 Study is anticipated as being needed for the following scenario: post-application inhalation exposure to treated 

paints.
Docket Number: EPA-HQ-OPP-2012-0007

www.regulations.gov

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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 preservative / 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 jointcements. 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.