Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

United States Prevent ion, Pesticides March 2010
Environmental Protection and Toxic Substances Agency (7510P)



## 1-(3-chloroally)-3,5,7-triaza-1-azoniaadamantane (CTAC) Summary Document: Registration ReviewDocket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov



### TABLE OF CONTENTS

CTAC Registration Review Team Members.............................................. 1 I. Preliminary Work Plan..................................................................... 2

II. Fact Sheet.................................................................................... 13 III. Glossary of Terms and Abbreviations................................................ 17 IV. Appendix A................................................................................. 19Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

1-(3-chloroally)-3,5,7-triaza-1-azoniaadaman tane (CTAC) Registration Review

Team

Human Health & Environmental Effects Timothy Dole

Srinivas Gowda

Risk Management

K. Avivah Jakob

Lance Wormell

Office of General Counsel Philip Ross

1Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

I. PRELIMINARY WORK PLAN - 1-(3-chloroally)-3,5,7-triaza-1-

azoniaadamantane

Introduction

The Food Quality Protection Act (FQPA) of 1996 mandated a re gistration review program. All pesticides distributed or sold in the United States generally must be registered by the U.S. Environmental Protec tion 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 di rected on product labe ling. 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 pestic ide use practices will occur over time. Through the registration review program, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided at http://www.epa.gov/oppsrr d1/registration_review/

.

The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and R odenticide Act (FIFRA) and will review each registered pesticide every 15 years to determ ine whether it continues to meet the FIFRA standard for registration. The Agency will c onsider benefits information and data as required by FIFRA. The public phase of regi stration 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 registrati on review decision. After reviewing and responding to comments and data received in the docket during th is initial comment period, the Agency will develop and commit to a final work plan and schedule for the registration review of 1- (3-chloroally)-3,5,7-triaza-1- azoniaadamantane (CTAC).

The chemical name for this registration revi ew case is 1-(3-chl oroally)-3,5,7-triaza-1- azoniaadamantane chloride (CTAC). CTAC can be in the form of a cis or trans isomer. The CTAC registration review case consists of two active ingredients: PC Code 017901,

Trade Name Dowicil TM 75, which contains a mixture of th e cis and trans isomers and PC Code 017902, Trade Name Dowicil TM 150, which contains primarily the cis isomer of CTAC. Because both active ingr edients contain the cis isom er of CTAC and one also contains the trans isomer of CTAC, the Agency will use the name CTAC when referring

to both of these ac tive ingredients.

CTAC is registered as a mi crobiocide/microbiostat for use as a materials preservative in pesticide formulations, adhesives, cons truction materials, latex emulsions, metal working fluids, paints, coatings and inks. It is also registered for use in household, institutional and industrial cleaning and laundr y products. Additional use sites include oil production (packer fluids, re-circulated muds and underground strata), pulp and paper (coatings, finishes and printing colors) and te xtiles (finishing and spinning fluids).

2Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

CTAC is also used as a preservative in cosmetics and personal care products and is known by the name Dowicil R 200 when used in these item s (examples of personal care products include but are not limited to mo isturizers, lotions, shampoos, conditioners, soaps, body washes, etc.). These cosmetic and personal care produc t uses are regulated by the Food and Drug Administration (FDA).

CTAC was first registered in the United St ates in 1964. A Reregistration Eligibility Decision (RED) for CTAC was issued in 1995. The RED can be located at: http://www.epa.gov/pesticides/reregistration/status.htm

.

Formaldehyde

CTAC is a formaldehyde (HCHO) releasing biocide. Therefore, this registration review case also addresses pot ential exposure to HCHO resul ting from the use of CTAC. However, this registration review case doe s not address possible aggregate risks from HCHO. When the HCHO registration review case is at the stage in which a risk assessment is conducted, aggregate risks from HCHO derived from the use of CTAC will be considered at that time. The Agency issued a Reregistration Eligibility Decision (RED) document for formaldehyde in 2008 to address potential risks associated with formaldehyde. The formaldehyde RED did not include potential exposure to HCHO resulting from the use of products contai ning CTAC as an active ingredient. .

The Office of Pesticide Programs (OPP) developed the formaldehyde inhalation noncancer toxicological endpoint used in the 2008 formaldehyde RED through the established reregistration process, which includes stakeholder consultation and public comment. However, the result has not been subjected to an inter-agency review or external peer review. Because of time c onstraints imposed by statutory deadline, OPP

could not consider all availa ble peer reviewed science (for example, the intentional human dosing toxicity studies). Thus , this value (10 ppb residential and 100ppb occupational) should be considered an interim value, developed solely for the purposes of the RED and subject to future revision and subsequent peer revi ew and should not be used in other contexts as EPA's opinion of the best available science on the non-cancer effects of formaldehyde.

The Agency has formed a work group that is charged with developing a harmonized

non-cancer hazard characterization document fo r formaldehyde. The Agency intends to

use this non-cancer information when a ssessing the risks associated with the antimicrobial uses of CTAC and other formaldehyde releasers. In the near term, the

antimicrobial uses will also be assessed for cancer risks in the same manner as presented in the formaldehyde RED (i.e., a range of cancer risks using the Chemical Industry Institute of Toxicology [CIIT] model and th e existing Integrated Risk Information System [IRIS] unit risk). Once the IRIS upda te of the formaldehyde cancer unit risk is available, the Agency will adopt that value in our risk assessments. The formaldehyde

risk assessments are available on EPA’s Pe sticide Docket at: www.regulations.gov. The docket number is EPA-HQ-OPP-2008-0121.

3Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

Risk Assessment Status & Anticipa ted Risk Assessment and Data Needs

Human Health Risk Assessment Status

The Agency has reviewed the hazard and exposure databases for the CTAC registration review case. As a result of this review, EPA believes risk assessments are needed to ensure that the CTAC registration review case meets the FIFRA and FFDCA standards. Because CTAC releases formaldehyde it will al so be necessary to assess formaldehyde exposures. The Agency will complete the human health risk assessments presented

below.

• Dietary (Food) Risk Assessment - Indirect dietary (food) exposure resulting from the use of CTAC in food packaging materials.

• Residential Handler Risk Assessment - Dermal and inhalation exposure to CTAC and inhalation exposure to form aldehyde during the use of treated paints and general purpose cleaners. Residential inhalation exposure to formaldehyde during the use of CT AC treated laundry detergents.

• Residential Post-Application Risk Assessment - Incidental oral and incidental dermal exposure from wearing clothing made from textiles treated with finishing fluids preserved with CTAC.

• Occupational Handler Risk Assessment - Occupational dermal and inhalation exposure to CTAC and inhalation expos ure to formaldehyde during the open pour addition of CTAC pow der for materials preser vation, oil products, pulp and paper production and textile pro duction. Occupational dermal and inhalation exposure to CTAC and inhala tion exposure to formaldehyde during

the use of CTAC treated metal work ing fluids and preserved paints.

Dietary and Drinking Wa ter Exposure and Risk

Dietary Food Exposure

CTAC is FDA-approved for use as an indi rect food additive in adhesives and components of coatings (21 CFR 175.015); pa per and paperboard board components (21 CFR 176.170 & 21 CFR 176.180); and polyurethane resins in contact with bulk quantities of dry foods (21 CFR 177.1680). Thes e uses may result in indirect dietary food exposure. However, they were not asse ssed in the 1995 CTAC RE D. Therefore, an indirect dietary (food) exposure risk assessment is needed in support of this registration

review.

Dietary Drinking Water Exposure

The registered uses of CTAC are not likely to result in contamination of surface water and ground water and as a result drinking wate r exposure is not expected. However, the need for a dietary drinking water exposure assessment for CTAC will be determined upon review of environmental fate data, wh ich the Agency anticipates requiring. The Agency anticipates that environmental fate da ta will be useful to determine if CTAC can

4Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

pass through waste-water treatment faciliti es into drinking water or migrate into residential groundwater wells as a result of its current use patterns. Therefore, the need for a dietary drinking water assessment will be revisited upon submission and review of the environmental fate data that are anticipated as being needed.

Tolerances

CTAC is permitted for use as an inert i ngredient in non-food use pesticide products (40CFR Part 180). CTAC is also exempt from the requirement of a tolerance when used as an inert ingredient as a preservative at 0.14% by weight (wt) or less of pesticide formulations (40 CFR 180.920).

There are no tolerances or exemptions from tolerances for the use of CTAC as an active ingredient and no registered food uses . As previously mentioned, CTAC is FDAapproved for use as an indirect food additive in adhesives and components of coatings, paper and paperboard component s and polyurethane resins in contact with bulk quantities of dry foods.

It is noted that exemptions and regulati ons for food additives under Section 409 of the Federal Food, Drug, and Cosmetic Act (FFDCA) do not relieve the registrant of meeting

the standard under Section 408 as amended by the Food Quality Protection Act (FQPA), when the active ingredient is subject to re gulation as a food-us e pesticide under the Federal Insecticide, Fungicide, and Rode nticide Act (FIFRA). Under Section 408, a determination of safety for residues of a pes ticide that may be in food is required, and as defined in Section 408(b)(2)(A)(ii), “that there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical resi due, including all anticipated dietary exposures and all other exposures for which there is reliable information.” EPA will be performing risk assessments to determine if tolerances or exemptions from tolerances will be needed to support th e existing registered uses of CTAC.

Aggregate and Cumulative Exposure and Risk

In examining aggregate exposure, EPA take s into account the available and reliable information concerning exposures to pesticid e residues in food and drinking water, as well as non-occupational pesticide exposures. An aggregate risk assessment may be

needed for CTAC if it is determined that drinking water exposure could occur based on

the environmental fate data. This assessmen t would consist of the aggregation of the indirect dietary food exposure from CTAC residues in treated food packaging and the exposure that would occur from CT AC residues in drinking water. If it is determined that an aggregate assessment is needed, the need for including residential incidental oral, dermal and inhalation exposures in the aggreg ate assessment will be determined when the toxicity data that are anticipated as bei ng required are completed and added to the database for use in endpoint selection. Ther efore, the need for an aggregate assessment will be revisited upon submission and review of the environmental fate data and human toxicology data that are antic ipated as being required.

5Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

Section 408(b)(2)(D)(v) of FFDCA require s that, when considering whether to establish, modify, or revoke a tolerance, th e Agency consider “available information” concerning the cumulative effects of a part icular pesticide's residues and “other

substances that have a common mechanism of toxicity.” EPA has not yet determined

whether CTAC has a common mechanism with other compounds; consequently, a cumulative assessment will not be performed at this time.

It should be noted that this registra tion review case does not address aggregate exposure from HCHO. When th e HCHO registration review case is at the point at which a risk assessment is to be conducted, a ggregate exposure from HCHO will be assessed

and the need for a cumulative HCHO assessment also will be addressed at that time.

Occupational and Residential Exposure and Risk

The Agency reviewed all available data associated with CTAC and has determined that the currently registered uses of CTAC may result in residential and occupational exposure. Therefore, the Agency will conduct residential (handler and post-application) and occupational (handler) risk assessme nts to assess possible dermal, inhalation, incidental oral and incidental dermal expos ure to CTAC and possibl e inhalation exposure

to HCHO.

Dermal exposure may possibly lead to de rmal sensitization. Du ring its review the Agency has identified dermal sensitization in open literature studies. This literature may be reviewed during the registration review process. If the Ag ency decides to rely on this open literature study, the Agency will make su re it meets all applicable standards that apply to human study ethics. Formaldehyde has been identified as one of the major allergens in the cosmetic related allergic c ontact dermatitis (Groot,et al, 1988 and Storrs, et al. 1989). Although the indi viduals involved in these inci dents may have been exposed to different types of allergens, the Agency cannot rule out the possi bility that CTAC may be related to the cosmetic related allergic co ntact dermatitis. It is also not known if the contact dermatitis is due to exposure to the CTAC parent or if it is due to exposure to the formaldehyde released by the parent. In a patch test study (Zug et. al., 2009) of 4,454 patients who had suspected contact dermatitis, 10.3% had positive reactions to Quaternium 15 and 9% had positive reactions to formaldehyde. Quaternium 15 was among the 4 most positive allergens with th e top three being nickel sulfate (19.0%), balsam of Peru (11.9%) and fragrance mix (11.5%).

Anticipated Human Health Data Needs

The Agency anticipates that the following toxicity and exposure data will be needed to conduct residential (handler and post-application) and oc cupational (handl er) exposure risk assessments for the regi stered uses of CTAC.

6Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

Anticipated Toxicity Data Needs

• (GLN 870.3250) 90-Day Oral Toxicity- rodent and non-rodent

• (GLN 870.3700) Developmenta l Toxicity- non-rodent

• (GLN 870.3465) 90-Day Inhalation- rat

• (GLN 870.3800) Reproductive Study- oral

• (GLN 870.4100) Chronic Oral- rodent *

• (GLN 870.4200) Carcinogenicity *

* A combined chronic toxicity/carcinogenic ity study (OPPT 870.4300) can fulfill both the chronic oral and carcinogenicity data requirements.

Anticipated Residential and Occupa tional Handler Exposure Data Needs

• (GLN 875.1200) Dermal Exposure

• (GLN 875.1400) Inhalation Exposure

• (GLN 875.1600) Data Re porting/Calculations

• (GLN 875.1700) Product Use Information

• (Non-Guideline Study) Textile Leaching Study

Anticipated Physical/Chemical Property Data Needs

All product chemistry data requirements have been fulfilled for CTAC. Therefore, it is anticipated that additional product chemis try data will not be needed for CTAC.

Environmental Fate and Ecologi cal Risk Assessment Status

The Agency reviewed the environmental fate and ecological hazard databases for CTAC. Based on its review, EPA believes risk assessments are needed to ensure that the CTAC registration review case meets the FIFRA standards. The Agency will complete the environmental fate and ecological hazard risk assessments presented below. Further information and detailed justifications for the studies that are expected to be required are available in the document titled “Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the CTAC Regist ration Review Decision Document,” dated March 23, 2010.

• Environmental fate

• Ecological hazard

• Endangered species assessment

Environmental fate and ecological risk assessments have not been conducted for

CTAC. The use of CTAC as a materials preservative could potentially result in environmental exposure. These uses may re sult in waste water treatment plant (WWTP) discharges into terrestrial and aquatic environments. Therefore, the Agency will conduct environmental fate and ecological risk a ssessments to assess environmental exposure resulting from possible discharges into terres trial and aquatic environments. The Agency also anticipates that environmental fate a nd ecological data will be needed to conduct

these assessments.

7Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

Anticipated Environmental Fate and Ecological Data Needs

The Agency anticipates conducting envi ronmental fate and ecological risk

assessments for CTAC based on its use as a ma terials preservative. The use of CTAC as a materials preservative could potentially re sult in CTAC passing through waste water treatment plants (WWTPs), which may then be discharged into terrestrial and/or aquatic environments. Therefore, the Agency anticipates needing environmental fate and ecological toxicity data for CTAC and/or any of its major degradation products that are of potential concern. The environmental fate a nd ecological toxicity data listed below are anticipated as being needed to conduct environmental fate and ecological risk

assessments.

Anticipated Environmental Fate Data Needs

• (GLN 835.1110) Activated Sludge Sorption Isotherm

• (GLN 835.2240) Photodeg radation in Water

• (GLN 835.3110) Ready Biodegradability

Anticipated Ecological Data Needs

• (GLN 850.4225) Seedling Emergence, Ti er II dose response study on rice

( Oryza sativa )

• (GLN 850.4250) Vegetative Vigor, Tier II dose response study on rice ( Oryza

sativa )

• (GLN 850.4400) Aquatic Plant Growth (aquatic vascular plant t oxicity), Tier II dose response study on floating macrophyte ( Lemna gibba )

• (GLN 850.5400) Aquatic Plant Growth (alg al toxicity), Tier II dose response

studies on Anabaena flos-aquae (blue-green cyanobacteria) , Navicula pelliculosa (freshwater diatom), and Skeletonema costatum (marine diatom)

Endangered Species

The Agency has not conducted a risk asse ssment that supports a complete endangered species determination. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of CTAC 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 habita t, the Agency will consult with the U.S. Fish

and Wildlife Service and/or National Marine Fisheries Se rvice (the Services), as appropriate.

Incidents

No CTAC specific incidents have been reported in the OPP Incident Data System (IDS). CTAC (as Quaternium-15) has been used as a preservative in cosmetics and it has been reported as one of the potential causes of allergic contact dermatitis in consumers of cosmetics (Groot,et al, 1988; Storrs, et al. 1989; and O'Reilly and Murphy, 1996).

8Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

Timeline

The EPA has created the following estimated timeline for the completion of the CTAC registration review case. The Agency anticipates requiring additional data and conducting residential, occ upational and ecological exposure assessments for this registration review case.

Anticipated Schedule
Registration Review for CTAC Projected Registration Review Timeline

Activities Time

Opening Docket Open Public Comment Period for CTAC Docket March 2010

Close Public Comment Period May 2010 Case Development Develop Final Work Plan (FWP) September 2010

Issue Final DCI September 2011

Data Submission September 2015 Open Public Comment Period for Preliminary Risk Assessments March 2016

Close Public Comment Period June 2016 Registration Review Decision Open Public Comment Period for Proposed RR Decision September 2016

Close Public Comment Period December 2016

Final Decision 2017 Total (years) 7 years

Guidance for Commenters

The public is invited to comment on the Ag ency’s preliminary registration review work plan and rationale. The Agency will consider all comments as well as any

additional information or data provided in a timely manner pr ior to issuing a final work plan (FWP) for the CTAC case.

Trade Irritants

Through the registration review process, th e 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 Li mits (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.

9Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

Water Quality

CTAC 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/attain s_nation_cy.cause_detail_303d?p_cause_grou p_id=885 . In addition, no Total Maximum Daily Loads (TMDL) have been developed for CTAC, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attain s_nation.tmdl_pollutant _detail?p_pollutant_gr oup_id=885&p_pollutant_group_name=PESTICIDES . 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 Im paired Water Body and Other Water Quality Data in OPP’s Registration Review Risk A ssessment and Management Process (see: http://www.epa.gov/oppsrrd1/regist ration_review/water_quality_sop.htm ) in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice

The EPA seeks to achieve environmental just ice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcemen t of environmental laws, regulations, and policies. To help address potential envir onmental 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 factor s, may have atypical, unusually high exposure to CTAC, compared to the general populati on. Please comment if you are aware of any sub-populations that may have atypical, unusua lly high exposure compared to the general population.

Structure Activity Relationships

EPA must rely upon information of appropr iate 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 appli cant’s submission of a

set of studies conducted with th e 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 environmen tal fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant interest in altern ative techniques, i.e., techniques other than data generation that could significantly info rm the Agency’s decision-making process. Recently, OPP has made increasing use of struct ure activity relationshi p (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 ma ke predictive judgments about a chemical’s

10Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

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 re ferred to as QSAR. To develop a QSAR, a selected set of measured data on a single phys ical, chemical, or bi ological property is used to derive a model (an equation) to predict the value of that property.

Since SAR assessments and QSAR modeli ng 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 appro ach to an approach in which the use of predicted data, generated using validated models, is cons idered along with information from open literature and studies specifi cally 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 cert ain 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 c onsidering biological properties, at this time, EPA believes that SAR and QSAR can be most effectively

utilized in the evaluation of ch emicals that exhibit lower toxi city 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 screen ing-level assessment pr ocedure rather than multiple tiers of assessments with pr ogressively more data requirements.

If stakeholders believe that submission of da ta may affect this registration review case for CTAC, then the Agency invites submission of this information. The submitter would be expected to supply a rati onale describing the utility of the information and provide

documentation on the scientific validity of the information. The determination that the predicted data fulfills a data requirement would be at the sole discretion of the Agency.

Pre-submission consultation with the Agency is encouraged.

Endocrine Disruptor Screening Program

As required under FFDCA section 408(p) , EPA has developed the Endocrine Disruptor Screening Program (EDSP) to dete rmine whether certain substances (including pesticide active and other ingred ients) may have an effect in humans or wildlife similar to an effect produced by a “natur ally occurring estrogen, or othe r such endocrine effects as the Administrator may designate.” The ED SP 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 substa nce 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 inte ract with E, A, or T hormonal systems will proceed to the next stage of the EDSP wher e EPA will determine which, if any, of the Tier 2 tests are necessary based on the avai lable data. Tier 2 te sting is designed to identify any adverse endocrine related eff ects caused by the substance, and establish a quantitative relationship between the dose and the E, A, or T effect.

11Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

Between October 2009 and February 2010, EPA i ssued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active i ngredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathways such as food and wa ter, residential activity, and certain postapplication agricultural s cenarios. This list should not be construed as a list of known or likely endocrine disruptors.

CTAC is not among the group of 58 pesticide ac tive ingredients on the initial list to

be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen allpesticide chemicals. Accordingly, EPA anticipates issuing future EDSP orders/data callins for all Registration Review cases, includ ing those for which EPA has already opened a Registration Review docket for a pesticide active ingredient.

For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and th e Tier 1 screening ba ttery, please visit our

website: http://www.epa.gov/endo/

.

Additional Information

Stakeholders are also specifically asked to provide available information and data in the following areas:

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, app lication intervals and maximum number of applications

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 mo rtalities) not already reported to the Agency

8. Monitoring data

9. Structure Activity Relationships

Next Steps

After the 60-day comment period closes in May 2010, the Agency will review and respond to any comments received in a timely manner and then issue a Final Work Plan (FWP) for CTAC.

12Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

II. FACT SHEET

Background Information

• Active Ingredient: 1-(3-chloroally)-3, 5,7-triaza-1-azoniaad amantane (CTAC)

• Case Number: 3069

• PC Codes: 017901 (Cis/Trans CTAC, Dowicil TM 75); 017902 (Cis CTAC,

Dowicil 150 TM )

• CAS Registry Numbers: 4080-31-3 (Dowicil 75 TM ); 51229-78-8 (Dowicil 150 TM )

• Technical Registrant: The Dow Chemical Company

• First approved for use in a registered product: 1964

• Antimicrobials Division Chemical Revi ew Manager (CRM): K. Avivah Jakob, jakob.kathryn@epa.gov

• Antimicrobials Division Acting Product Manager (PM): Jacqueline CampbellMcFarlane,Campbell-Mcfarlane.Jacqueline@epa.gov

Chemical Identity/Structure

• Empirical Formula: C 9 H 16 N 4 Cl 2

Trans-Form Cis-Form

Use & Usage Information For additional usage information and use de tails please refer to “Appendix A: Use and Usage Information for 1-(3-chloroally )-3,5,7-triaza-1-azoniaadamantane (PC Codes 017901, 017902),” in this document.

• There are two end-use products (EP).

• CTAC is registered for use as a microbiocide/microbiostat.

• Antimicrobial Use Sites : Materials preservative in pesticide formulations, adhesives, construction materials, latex emulsions, metal working fluids, paints, coatings and inks, oil production (pac ker fluids, re-circulated muds and underground strata), pulp a nd paper (coatings, finishes and printing colors) and textiles (finishing and spinning fluids ); use in household, institutional and industrial cleaning and laundry products.

• CTAC is a formaldehyde (HCHO) releasing biocide.

13Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

• There are no tolerances or exemptions from tolerances for the use of CTAC as an active ingredient and no registered food uses.

• CTAC is FDA-approved for use as an indi rect food additive in adhesives and components of coatings, paper and pa perboard components and polyurethane

resins in contact with bul k quantities of dry foods.

Earlier Regulatory Actions

• Dowicil CTAC R Reregistration Eligibility Decision (RED) Document, 1995 http://www.epa.gov/pesticides/reregistration/status.htm

Human Health Risk Assessment Status

The Agency will conduct residential and o ccupational exposure risk assessments as well as an indirect dietary (food) exposure risk assessment for CTAC. The Agency will also conduct residential and occupational exposure risk assessments to assess exposure to formaldehyde during the use of CTAC. The need for an aggregate exposure assessment will be revisited upon submission and review of the environmental fate data and human toxicology data that are antic ipated as being required. Prior to conducting the risk assessments, the Agency anticipates requiring additional data. Further information and detailed justifications for the studies that ar e expected to be required are available in the document titled “Summary of Human Health Effects Data for the CTAC Registration Review,” dated March 23, 2010.

Product Chemistry Database Status

The Agency has reviewed the product chemistry database for the CTAC registration review case and an ticipates that no additional product chemistry data will be needed for registration review. Further info rmation is available in the “Summary of Product Chemistry, Environmental Fate, and Ec otoxicity Data for the CTAC Registration Review Decision Document,” dated March 23, 2010.

Ecological Risk Assessment Status

The Agency will conduct environmental fa te and ecological risk assessments for CTAC. Prior to conducting the risk asse ssments, the Agency anticipates requiring

additional data. Further information and deta iled justifications for the studies that are expected to be required are available in the document titled, “Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the CTAC Registration Review Decision Document,” dated March 23, 2010.

The Agency has not conducted a risk asse ssment that supports a complete endangered species determination. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of CTAC 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 habita t, the Agency will consult with the U.S. Fish

14Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

and Wildlife Service and/or National Marine Fisheries Se rvice (the Services), as appropriate.

Tolerances

There are no tolerances or exemptions from tolerances for CTAC as an active ingredient and no registered food uses. EP A will be performing risk assessments to determine if tolerances or exemptions from tolerances will be needed to support the existing registered uses of CTAC. As prev iously mentioned, CTAC is FDA-approved for

use as an indirect food additive in adhesi ves and components of coatings, paper and paperboard components and polyur ethane resins in contact with bulk quantities of dry

foods.

CTAC is permitted for use as an inert i ngredient in non-food use pesticide products (40CFR Part 180). Also, as an inert ingredie nt CTAC is exempt from the requirement of a tolerance when used as a preservative at 0.14% by weight (wt) or less of pesticide formulations (40 CFR 180.920).

Data Call-In Status

• In March of 1992, EPA issued a GDCI (gener ic data call-in) for cis/trans-CTAC (Dowicil TM 75) for product chemistry data, eco logical effects and environmental fate data. The data requirments for this GDCI have been satisfied.

• In September of 1993, EPA issued a GDCI for cis/trans-CTAC (Dowicil TM 75) for human toxicity data, human exposure data, product chemistry data, ecological

effects data and environmental fate data. The data requirments for this DCI have

been satisfied.

• In July of 1995, EPA issued a PDCI (product data all-in) for cis/trans-CTAC (Dowicil TM 75) for human toxicity and exposur e data, and product chemistry data. The data requirements for this PDCI have been satisfied.

• In March of 2002, EPA issued a GDCI for cis-CTAC (Dowicil 150 TM ) for product use information. The data requirements for this GDCI have been satisfied.

• In July of 1995, EPA issued a PDCI for cis-CTAC (Dowicil 150 TM ) for product use data and human toxicity data. The data requirements for this PDCI have been

satisfied.

• The Agency anticipates issuing a data call-in (DCI) for CTAC to support the registration review risk assessment processes.

15Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

Labels

There are two registered products that are a part of the CTAC registration review case. A list of product registration numbers is below. Product registration labels may be obtained from the Pesticide Product Label System (PPLS) website at: http://oaspub.epa.gov/pestlabl/ppls.home

.

Table #1. Registered Active Products of CTAC

Registration Number Product Name Company Name

464-327 Dowicil TM 150 The Dow Chemical Company

464-403 Dowicil TM 75 The Dow Chemical company

16Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

III. GLOSSARY of TERMS & ABBREVIATIONS

AI Active Ingredient AR Anticipated Residue ASTM American Society for Testing and Materials

AWPA American Wood Preserver’s Association

CBI Confidential Business Information

CFR Code of Federal Regulations cPAD Chronic Population Adjusted Dose

CSF Confidential Statement of Formula CSFII USDA Continuing Surveys for Food Intake by Individuals

DCI Data Call-In DEEM Dietary Exposure Evaluation Model DFR Dislodgeable Foliar Residue DNT Developmental Neurotoxicity DWLOC Drinking Water Level of Comparison

EC Emulsifiable Concentrate Formulation EDWC Estimated Drinking Water Concentration

EEC Estimated Environmental Concentration

EP End use Product EPA Environmental Protection Agency

EUP End-Use Product FDA Food and Drug Administration FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FFDCA Federal Food, Drug, and Cosmetic Act FQPA Food Quality Protection Act FOB Functional Observation Battery GENEEC Tier I Surface Water Computer Model

IR Index Reservoir

LC 50 Median Lethal Concentration. A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD 50 Median Lethal Dose. A statistically deri ved single dose that can be expected to

cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.

LOC Level of Concern

LOAEL Lowest Observed Adverse Effect Level μg/g Micrograms Per Gram μg/L Micrograms Per Liter mg/kg/day Milligram Per Kilogram Per Day mg/L Milligrams Per Liter MOE Margin of Exposure

MRID Master Record Identifi cation (number). EPA's system of recording and tracking

submitted studies. MUP Manufacturing-Use Product

NA Not Applicable NAWQA USGS National Ambient Water Quality Assessment NPDES National Pollutant Discharge Elimination System

NR Not Required

NOAEL No Observed Adverse Effect Level

OPP EPA Office of Pesticide Programs OPPTS EPA Office of Prevention, Pesticides and Toxic Substances PAD Population Adjusted Dose

17Docket Number: EPA–HQ–OPP–2010–0004 www.regulations.gov

18 PAIRA Pure Active Ingredient Radiolabelled PCA Percent Crop Area

PDP USDA Pesticide Data Program PHED Pesticide Handler's Exposure Data

PHI Preharvest Interval phr Pounds Per Hundred ppb Parts Per Billion

PPE Personal Protective Equipment

ppm Parts Per Million PRZM/EXAMS Tier II Surface Water Computer Model Q 1 * The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer

Risk Model RAC Raw Agriculture Commodity RED Reregistration Eligibility Decision

REI Restricted Entry Interval

RfD Reference Dose RQ Risk Quotient RTU Ready to Use SCI-GROW Tier I Ground Water Computer Model

SAP Science Advisory Panel SF Safety Factor

SLN Special Local Need (Registrati ons Under Section 24©) of FIFRA) TGAI Technical Grade Active Ingredient

TEP Typical End-Use Product USDA United States Department of Agriculture UF Uncertainty Factor

WPS Worker Protection StandardDocket Number: EPA–HQ–OPP–2010–0004www.regulations.govAppendix A: Use and Usage Information for1-(3-chloroally)-3,5,7-triaza-1-azoniaadamantane (CTAC)(PC Codes 017901, 017902)Use SiteFormulationMethod ofApplicationApplication Rate/ No. ofapplicationsUse LimitationsCis/Trans-CTAC (PC Code 017901)Materials PreservativesIndoor Non-foodAdhesives, Industrial (non-foodcontact)FormulationIntermediate464-403PourAdd 0.07 - 0.66% productpreservative by wt of theformulation. Add at a suitablepoint in the mfg. process.For use in the following types ofadhesives:Starch Based (corn, tapioca,sago, potato): Add 0.13% -0.27%.Protein-Derived (animal gluessuch as hide, bone, fish, bloodand gelatin): Add 0.13 - 0.66%.Natural Gums (Arabic, guar andtragacanth): Add 0.07 - 0.27%.Natural Rubber Latex: Add 0.07- 0.2%.Polyvinyl Acetate Emulsions:Add 0.07 - 0.2%.Synthetic Gums (e.g.METHOCEL* methylcellulosegums) and Other SyntheticBased Adhesives: Add 0.07 -0.2%Highly concentrated gumsdo not readily supportbacterial or fungi growth; consequently, higherconcentrations product are required in the lessconcentrated gum solutions.Synthetic adhesives formulations sometimesincorporate natural substances such as starches orproteinaceous materials. To preserve theseformulations, use the level of preservativerecommended for the adhesive containing only thenatural material.19Docket Number: EPA–HQ–OPP–2010–0004www.regulations.govUse SiteFormulationMethod ofApplicationApplication Rate/ No. ofUse LimitationsapplicationsIndoor Non-foodCaulkscaulking, grouting,spackling compounds, jointcements, constructionadhesives, tape jointcompounds, concreteadmixes and sealingcoatingsMetalworking cutting fluidsSpecialty productsLatex emulsionsPaint, coatings & inksPapermaking (Non-foodcontact)Pulp and paperTextilesTextile finishing andspinning fluidsJanitorial products (incontainer)Household, institutional andindustrial cleaning & laundryproductsAdd 0.015 - 0.3% product by wtof the formulation.Product is incompatible with casein in both liquid anddry systems and with some types of amine modifiedclays.Indoor/Outdoor Non-foodDispersions/Emulsions/Solutions/SuspensionsPacker fluids, recirculatingmuds and undergroundstrataFor use with closed deliverysystems only. Add 0.03 - 0.05%product by wt of mud or packerfluid. Add .0025 - .005 % by wtunderground water flooding.Add at a suitable point in theclosed delivery system.20Docket Number: EPA–HQ–OPP–2010–0004www.regulations.govUse SiteFormulationMethod ofApplicationApplication Rate/ No. ofapplicationsUse LimitationsIndoor/Outdoor Non-foodCoatings: Industrial,Household institutional &industrial polishes andwaxesAdd 0.07 - 0.2% product by wtof the formulation. Add at asuitable point during the mfg.process.Indoor FoodPapermaking (Food contact)Add 0.13 – 0.27% product by wtof the formulation. Add as anaqueous solution.Cis-CTAC (PC CODE 017902)Materials PreservativesIndoor non-foodJanitorial productsDetergentsFloor wax emulsions andfloor polishesSpecialty productsLaundry StarchInksLatex emulsionsCaulksConstruction materials(caulking. grouting, andspackling compounds)Metalworking Cutting FluidsPaintsPulp & paperTextilesAdd 0.03 - 0.2% product wt ofthe formulation.Indoor FoodPapermaking (Food contact)Soluble ConcentratePour464-327Add 0.1 - 0.2% product wt of theformulation. Add as an aqueoussolution.21Docket Number: EPA–HQ–OPP–2010–0004www.regulations.govUse SiteFormulationMethod ofApplicationApplication Rate/ No. ofapplicationsUse LimitationsIndoor non-foodAdhesives, Industrial (non-foodcontact)Add 0.06 - 0.5% product by wtto the formulation.For use in the following types ofadhesives:Starch Based (corn, tapioca,sago. potato): Add 0.1 - 02%product by wt.Protein-derived (animal gluessuch as hide, bone, fish, blood,and gelatin): Add 0.1 - 0.5%product by wt.Natural gums (Arabic, guar, andtragacanth): Add 0.05 - 02%product by wt.Natural Rubber Latex: Add 0.05- .2% product by wt.Polyvinyl Acetate Emulsions:Add 0.05 - 0.15 product by wt.Synthetic gums and OtherSynthetic-based Adhesives:Add 0.05 - 0.15% product by wt.Synthetic adhesive formulations sometimes incorporatenatural substances such asstarches or proteinaceousmaterials. To preserve these formulations, use the levelof antimicrobial recommended for the adhesivecontaining only the natural material.22