Page 2 of 80 

### Table of Contents
1 Introduction .................................................................................................................. ........... 5
1.1 Statutory and Regulatory Authority ................................................................................. 5

1.2 Updates to the Work Plan ................................................................................................. 7
1.3 Case Overview ................................................................................................................. 8
1.4 Chemical Identification and Properties ............................................................................ 9
1.5 Use/Usage Description ................................................................................................... 11
1.5.1 Registrations ........................................................................................................... 11
1.5.2 Summary of Regist ered Uses .................................................................................. 11
1.5.3 Usage Information .................................................................................................. 13
1.6 Regulatory History ......................................................................................................... 14
1.6.1 Recent/Pending Regulatory Actions ....................................................................... 14
1.6.2 Tolerance Information ............................................................................................ 14

1.7 Incidents ..................................................................................................................... .... 14
1.7.1 Human Health ......................................................................................................... 14

1.7.2 Ecological ............................................................................................................... 15

2 Anticipated Data Needs ........................................................................................................ 15
3 Human Health Risk Assessment ........................................................................................... 19
3.1 Existing Toxicological Endpoints .................................................................................. 19
3.2 Dietary Exposure ............................................................................................................ 2 0
3.2.1 Food ........................................................................................................................ 2 0
3.2.2 Drinking Water ....................................................................................................... 21
3.3 Occupational and Residen tial (ORE) Exposures ........................................................... 21
3.3.1 ORE Exposure Assessed in the RED ...................................................................... 21
3.3.2 ORE Exposures Assessed after the RED ................................................................ 22
3.3.3 ORE Exposures that will Need to Be Assessed for Registration Review ............... 22
3.4 Aggregate and Cumulative Exposure ............................................................................. 23
3.4.1 Aggregate Exposures .............................................................................................. 23
3.4.2 Cumulative Exposures ............................................................................................ 23

4 Environmental Risk Assessment........................................................................................... 23

4.1 Environmental Conceptual M odel Exposure Pathways ................................................. 23Page 3 of 80 4.2 Ecological Effects Assessment ....................................................................................... 28

4.2.1 Mechanism of Action .............................................................................................. 28

4.2.2 Measures of Effect (Ecotoxicology Endpoints) ...................................................... 29
4.3 Exposure Analysis Plan .................................................................................................. 30
4.3.1 Aquatic and Terrestrial Wild life Exposure Estimates ............................................ 30
4.3.2 Down-the-Drain Analysis ....................................................................................... 30

4.4 Effects Analysis Plan ..................................................................................................... 31
5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 31

6 Next Steps .................................................................................................................... ......... 32

7 References .................................................................................................................... ......... 32 Appendix A: Environmental Fate ................................................................................................ . 35 Appendix B: Toxicology Profile ................................................................................................ ... 44 Appendix C: Ecotoxicology Profile ............................................................................................. . 46 Appendix D: ECOSAR Version 1.1 Results Page for Isocyanuric Acid ...................................... 56 Appendix E: Response to the 60-Day Public Co mments on the Chlorinated Isocyanurates ........ 58

List of Tables
Table 1 - Summary of Anticipated Ri sk Assessments and Data Needs ......................................... 6 Table 2 - Anticipated Registration Review Schedule ..................................................................... 7 Table 3 - Chemical Identification Informa tion for the Chlorinated Isocyanurates ......................... 9 Table 4 – Physical and Chemical Propertie s for the Chlorinate d Isocyanurates .......................... 10 Table 5 - Distribution of Products by Specific Chlorinated Isocyanurate .................................... 11 Table 6 – Summary of Chlorinated Is ocyanurate Antimicrobial Uses ......................................... 12 Table 7 - Incidents Reported for th e Chlorinated Isocyanurates .................................................. 15 Table 8 - Studies Anticipated as Needed for the Registration Review of the Chlorinated Isocyanurates.................................................................................................................. ............... 16 Table 9 – Existing Toxicology Endpoints .................................................................................... 19 Table 10 - ORE Scenarios for the Chlorinated Isocyanurates ...................................................... 22 Table 11 – Existing Ecologi cal Effects Endpoints ....................................................................... 29 Table 12 Environmental Fate Data for Chlori nated Isocyanurates (di- and tri-chloro) ............... 38 Table 13 - Acute Toxicity of the Chlorinated Isocyanurates ........................................................ 44 Table 14 Available Endpoints from Avian Ecotoxic ity Studies for Trichlor o-s-triazinetrione ... 46 Table 15 Available Endpoints fr om Avian Ecotoxicity Studies fo r Sodium Dichloroisocyanurate Dihydrate...................................................................................................................... ................. 47Page 4 of 80 Table 16 Available Endpoints from Avian Ecotoxicity Studies for Sodium Dichloro- s

Triazinetrione ................................................................................................................ ................ 47 Table 17 Available Acute Endpoints from Freshwat er Fish and Aquatic I nvertebrate Ecotoxicity Studies for Trichloro- s -triazinetrione ........................................................................................... 50 Table 18 Available Acute Endpoints from Freshwater Fish and Aquatic Inve rtebrate Ecotoxicity Studies for Sodium Dichlo ro-s-Triazinetrione .............................................................................. 51 Table 19 Available Acute Endpoints from Freshwat er Fish and Aquatic I nvertebrate Ecotoxicity Studies for Sodium Dichloro isocyanurate Dihydrate ................................................................... 51 Table 20 Available Avian Acute Toxici ty Studies for Isocyanuric Acid .................................... 53 Table 21 - Available Aquatic Organism data for Isocyanuric Acid ............................................. 53

List of Figures
Figure 1 Conceptual Model for Ecological Exposu re and Effects of Chlo rinated Isocyanurates and their Reaction Products/Degradates from Sa nitizing and Disinfecting Uses for Laundry and Hard Surfaces to Aquatic and Terrestrial Organisms ................................................................... 25 Figure 2 Conceptual Model for Ecological Exposu re and Effects of Chlo rinated Isocyanurates and their Reaction Products/Degr adates from Swimming Pool a nd Water Bed Uses to Aquatic and Terrestrial Organisms ..................................................................................................... ........ 26 Figure 3 Conceptual Model for Ecological Exposu re and Effects of Chlo rinated Isocyanurates and their Reaction/Degradates from Cooling Wa ter Tower Uses to Aquatic and Terrestrial Organisms ..................................................................................................................... ................ 27 Figure 4 Conceptual Model for Ecological Exposu re and Effects of Chlo rinated Isocyanurates and their Reaction/Degradates from the Use and Disposal of In-Can or In-Container Material Preservatives to Aquatic Organisms ............................................................................................ . 28Page 5 of 80 

### 1 Introduction

1.1 Statutory and Regulatory Authority The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates 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 ri sks to human health or the environment when used as directed on product labeling. The regist ration 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 th e statutory standard of no unreas onable 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 marketpl ace can be used safely. Information on this program is provided at http://www.epa.gov/oppsrrd 1/registration_review/.
The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registration review begin at 40 CFR 155.40. 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 need ed to make a registra tion review decision. The Chlorinated Isocyanurates Preliminary Work Plan (PWP) was published on December 21, 2012, and the 60-day comment period ended on February 21, 2013.
Documents associated with this registration re view can be viewed at www.regulations.gov in docket EPA-HQ-OPP-2012-0794. Below is a summary of the issues relevant to this registration review case.Page 6 of 80 Table 1 - Summary of Anticipated Risk Assessments and Data Needs

Risk Assessment Assessment Necessary to Support Registration Review Date of Most Recent Assessment Type of Assessment Required (New/Updated) Data Needed

Dietary (food) Yes None New Food-handling, Migration Studies 1 Dietary (drinking water) Yes 3/26/2001 Updated None Occupational Handler (Inhalation Exposure) Yes None New Inhalation Indoor Exposure Data 2
Residential Handler (Inhalation Exposure) Yes None New Inhalation Indoor Exposure Data 3 Residental Post Application, Swimming Pools (Incidental Oral Exposure) Yes 2/26/2001 Updated None

Residental Post Application, Disinfected Floors (Incidental Oral Exposure) Yes None New Surface Residue Data

Aggregate Exposures Yes None New None Cumulative Exposures No None None None

Ecological Yes None 4 New Isocyanuric acid/cyanuric acid acute and chronic data for freshwater fish and invertebrates and estuarine/marine fish and invertebrates, Aquatic plants vascular and non-vascular, Vegetative vigor and seedling emergence tests with rice, ASRI, Aquatic metabolism, WWTP biodegradation study 1. Residue chemistry data are anticipated as needed to determine dietary expos ure to cyanuric acid/isocyanuric acid following sanitization of food contact surfaces of food processing plants (including dairies) and food- handling facilities (including pub lic eating places), adhesive preservation, and slimicide use in the pulp slurry to make paper/ paperboard for food contact. 2. Indoor exposure data are an ticipated as needed for the fo llowing occupational handler scenarios: 1- Open pour liquids, granules and powder for hard surface disinfection and pool treatmen t; 2- Open pour granules for material preservation; 3- Mop, wipe and trigger spray for hard surface disinfection; 4- Hand wand spray disinfection of egg and food processing plants; 5- Fogging disinfection of egg and food processing plants; and 6- Brush, roller and spray app lication of preserved paints. 3. Indoor exposure data are needed for th e following residential handler scenarios: 1- Open pour liquids, granules and powder for pool treatment; 2- Mop, wipe and trigger spray for hard surface disinfection; and 3- Brush, roller and spray application of preserved paints.

4. A hazards assessment was done in the 1992 RED, but no risk assessment was conducted.Page 7 of 80 Table 2 - Anticipated Registration Review Schedule Anticipated Activity Target Date 1 Completion Date Phase 1: Opening the Docket Open Docket and 60-Day Public Comment for Preliminary Work Plan 2012-12 2012-12-19

Close Public Comment Period 2013-02 2013-02-21 Phase 2: Case Development
Issue Final Work Plan 2013-06 2013-06-28 Issue Data Call-In (DCI) 2014-06
Receive Data to be Considered in Risk Assessment 2016-06 Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2017-12

Close Public Comment Period 2018-01 Phase 3: Registration Review Decision and Implementation Open 60-Day Public Comment Period for Proposed Decision 2018-06
Close Public Comment Period 2018-08
Issue Final Decision 2018-12 Begin Post-Decision Follow-up 2018 Total (years) 6

1 The anticipated sc hedule will be revise d as necessary ( e.g. , on any need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case).



### 1.2 Updates to the Work Plan Since the publication of the PWP, the agency has made the following updates:

 Added the following anticipa ted ecotoxicity data requirements for the degradate isocyanuric acid/cyanuric aci d because of high uncertain ty in the ECOSAR model results:

o 850.1010 Aquatic invertebrates, acute, freshwater

o 850.1025 or 850.1055 Estuarine/marine acute mollusk (shell deposition or embryo/larvae test)

o 850.1075 Fish acute, freshwater (warm and cold water species)

o 850.1075 Fish acute, estuarine/marine

o 850.1300 Freshwater inverteb rate life cycle

o 850.1350 Estuarine/marine invertebrate life cycle

o 850.1400 Fish early life-stage, freshwat er or estuarine/ marine species

o 850.4100 Seedling emergence, Tier II – dose response, rice

o 850.4150 Vegetative vigor, Tier II – dose response, ricePage 8 of 80  Added the following anticipated fate data re quirement for the isocyanuric acid/cyanuric acid to the table because it was omitted in error

o 835.1230 or OECD 106 Batch Equilibrium

 Added references.

 Deleted references to dichloro-s-triazinetr ione in Tables 3, 4, 5, and 7 throughout the document because the chemical is not included in this registration review.

 Removed ingestion of treated drinking wate r from ORE scenarios (Table 10) because potential exposure from that rout e is addressed in section 3.2.2.

 Updated Appendix C to address duplicate test results, and additional results found in the agency’s files

 Added Appendix D to document the ECOSAR version 1.1. isocyanuric acid/cyanuric acid ecotoxicity modeling results

 Corrected formatting and typographical errors

 Added Appendix E to document public comments received and the agency’s responses.



### 1.3 Case Overview The docket for the Chlorinate Isocyanurate Case (Case 0569) has been established at http://www.regulations.gov in docket num ber EPA-HQ-OPP-2012-0794. Except where otherwise noted, the three active ingredients [sodium dichloro- s -triazinetrione (PC Code: 081404); trichloro- s -triazinetrione (PC Code: 081405); and sodium dichloro- s -triazinetrione dihydrate (PC Code: 081407)] in this case will be referred to collectively as “chlorinated isocyanurates.” Dechlorinated s -triazinetrione, also called cyanur ic acid or isocyanuric acid (CAS Number 108-80-5), is a major degradate of these three chlorinated isocyanurates and has the PC Code 081402. Information on this degradate will be used in conducting both the human health and ecological risk assessment of the chlo rinated isocyanurates, but there are no registered pesticide products containing d echlorinated-s-triazinetrione as the active ingredient, and therefore it is not consider ed as part of the case.
There were products incorrectly identified in the PWP as dichlo ro-s-triazinetrione, which have since been reclassified as sodium dichloro-s-t riazinetrione. Dichloro-s-t riazinetrione (081401) is not being considered in this registration revi ew. There are currently, no registered pesticide products containing dichloro-s-t riazinetrione as an active in gredient. Although initially considered as part of the Chlorinated Isocyanur ates case the only registration for potassium dichloro- s -triazinetrione (PC Code: 081403) was cancel led in 1993 and, therefore, will not be evaluated as part of this regi stration review. Although the penta- s -triazinetrione (PC Code: 081406) was considered in the 1988 Registratio n Standard, it was not included in the 1992 Reregistration Eligibility Document 1 and is not included in this registration review action since no registered products remain with the Agency. Therefore, the three active ingredients to be

1 Environmental Protection Agency, 1992. Reregistratio n Eligibility Document (RED) Chlorinated Isocyanurates http://www.epa.gov/pesticides/rer egistration/REDs/old_reds/chlorinated_isocyanurates.pdfPage 9 of 80 assessed in Case 5069 are: sodium dichloro- s -triazinetrione (PC Code: 081404); trichloro- s

triazinetrione (PC Code: 081405); and sodium dichloro- s -triazinetrione dihydrate (PC Code: 081407).
The chlorinated isocyanurates and triazine herbicides share a symme tric triazine ring. However, the agronomic herbicides that are classified as s -triazine compounds have alkyl side chains. The chlorinated isocyanurates are not considered as part of the triazine cumulative assessment.
As discussed in Appendix A, Environmental Fate, chlorinated isocyanurates are converted in the environment to the tautomer paired degradates , isocyanuric acid/cyanuric acid. The agency anticipates evaluating potential ri sk and hazards for chlorinated isocyanurates based on exposure to chlorine residual and on the paired tautomer degradates for human health and ecological effects. Risks from hypochlorous acid for coo ling towers and water process system uses are discussed under the sodium and calcium hypochlorite case 2

.

1.4 Chemical Identification and Properties
Table 3 presents the three activ e ingredients to be assessed in Case 5069: sodium dichloro- s

triazinetrione (PC Code: 081404); trichloro- s -triazinetrione (PC Code: 081405); and sodium dichloro- s -triazinetrione dihydrate (P C Code: 081407). All of these substances are substituted chlorinated salts or acids of isocyanuric acid ((CNOH) 3 ) and act as chlorine releasers, they are hereinafter collectively referred to in this document as chlorinated isocyanurates.

Table 3 - Chemical Identification Inform ation for the Chlorinated Isocyanurates

Chemical Name Sodium dichloro- s triazinetrione Trichloro- s -triazinetrione Sodium dichloro- s -triazinetrione dihydrate

Common Name Sodium dichloroisocyanurate Trichloroisocyanuric acid Sodium dichloroisocyanurate dihydrate

Synonyms l,3-Dichloro-s-triazine-2,4,6 (l H ,3 H ,5 H ) trione sodium salt 1,3,5-trichloro-s-triazine2,4,6 (l H ,3 H ,5 H ) Trione 1,3-Dichloro-s-triazine-2,4,6 (1 H ,3 H ,5 H ) trione sodium salt dihydrate
Trade Names ACL 60; CDB 60; S.D.I.C. ACL 90 Plus; CDB 85; T.I.C.A.; TCCA. ACL 56; DICD

PC Code 081404 081405 081407 CAS Number 2893-78-9 87-90-1 51580-86-0 Chemical Family Halogenated triazines Molecular Formula C 3 N 3 O 3 Cl 2 Na C 3 N 3 O 3 Cl 3 NaC 3 N 3 O 3 Cl 2 ·2H 2 O

Molecular Weight 220.96 232.42 255.98

Available chlorine % Theoretical Nominal 60.0 - 64.48 89.5 - 91 .5 55.0 % - 57.0

2 Na & Ca Hypochlorite Registration Review: Final Work Plan, Docket ID EPA-HQ-OPP-2012-0004-0006Page 10 of 80 Chemical Name Sodium dichloro- s triazinetrione Trichloro- s -triazinetrione Sodium dichloro- s -triazinetrione dihydrate Molecular Structures:

The chlorinated isocyanurates product chemistry rele vant to risk assessment is presented in Table 4 and details of the fate propert ies are discussed in Appendix A.
Table 4 – Physical and Chemical Prop erties for the Chlorinated Isocyanurates

OPPTS Guideline Number/ Physical and Chemical Properties Sodium dichloro- s triazinetrione Trichloro- s triazinetrione Sodium dichloro- s triazinetrione dihydrate

830.1550 Product identity and composition Refer to Table 3. Refer to Table 3. Refer to Table 3.

830.6302/Color White White White
830.6303/Physical State Granular Crystalline solid Crystalline solid Crystalline solid

830.6304/Odor Chlorine Chlorine Chlorine
830.6313 Stability to sunlight, normal and elevated temperature, metals/metal ions Stable and relatively inert when dry Stable and relatively inert when dry Stable and relatively inert when dry

830.6314 Oxidation/Reduction: Strong oxidizing material Strong oxidizing material Strong oxidizing material

830.7000/pH 6.1 (1 percent (%) solution) 2.9 (1% solution) 6.4 (1% solution)

830.7200/Melting point 230-250 degrees Celsius ( o C) (Decomposition) 225-230 o C (Decomposition) 240 o C (Decomposes) 830.7200/Boiling point Not applicable (substances are all solids)

830.7300 Density 35 pound per cubic foot (lb/cubic ft)

850 – 950 kilogram per cubic meter (kg/cubic meter)

Specific gravity 2.05 gram per milliliter (g/ml) at 20

o C 2.02 - 2.10 grams per cubic centimeter (g/cc) 62.56 lb/cubic ft.

830.7550 Partition coefficient ( n -octanol/water) -0.06 0.94 -0.06Page 11 of 80 OPPTS Guideline Number/ Physical and Chemical Properties Sodium dichloro- s triazinetrione Trichloro- s triazinetrione Sodium dichloro- s triazinetrione dihydrate

830.7840 Solubility in water 24.8 g/100g at 26.8 o C 1.2 g/100g at 25 o C 26.2 g/l00 ml at 25°C

830.7950 Vapor pressure Very low, impossible to measure Source: From the 1988 Chlorinated Isocyanurates Registration Standa rd and 1992 Registration Eligibility Document (RED)

1.5 Use/Usage Description
1.5.1 Registrations There are 451 registered products that contain chlorinated isoc yanurates. The distribution of products by specific isocyanurate is presented in Table 5. Most of the products are formulated as solid granules or tablets and a few products are formulated as liquids.
Table 5 - Distribution of Products by Specific Chlorinated Isocyanurate

Chemical Name PC Code Number of Products Percent a.i. Formulations

Sodium dichloro- s -triazinetrione 081404 84 10 to 99 b Granules, Tablets/Pellets, Impregnated Stick-On Patch

Trichloro- s -triazinetrione 081405 246 1.9 to 100 c Granule, Tablets/Pellets, Water soluble packaging, soluble powder

Sodium dichloro- s -triazinetrione dihydrate 081407 122 1.0 to 100 Granules, Tablets/Pellets, Soluble Powder, Dust, Water soluble packaging N/A: not applicable a.i.: active ingredient

a One product also contains trichloro-s-triazinetrio ne as an active at a decl ared content of 66.96%

b Two products also contain trichloro-s-triazinetrione as an active: one with 44.6% and one with 70.54%.

c Two products also contain sodium dichloro- s -triazinetrione as an active at d eclared content of 18.19 and 14.5% and one product also contains dichloro- s -triazinetrione as an active at a declared content of 53.2%.

1.5.2 Summary of Registered Uses The chlorinated isocyanurates are registered for use as disinfectants, sanitizers, microbiocides, microbiostats, bacteriocides, bacteriostats, s limicides, algaecides, fungicides, fungistats, tuberculocides and virucides as summarized in Ta ble 6. Application rates are provided in terms of the theoretical amount of available chlorine based on molecular weight ratios. For products that contain more than one chlorinated isocyanura te, the reported availabl e chlorine application rate is expressed as the total chlorine produced from all chlorina ted isocyanurates in the product.Page 12 of 80 Table 6 – Summary of Chlorinated Isocyanurate Antimicrobial Uses

Use Site Application Rate (In Terms of Available Chlorine) Hard Surface Disinfection and Sanitization (Many Labels) Agriculture/Farm Structure and Equipment 100 to 971 parts per million (ppm) Animal Housing (poultry, swine, zoos and farms) 97 to 1,300 ppm Commercial, Institutional, Industrial Premise and Equipment 117 to 6,846 ppm Dairy Farm Milk Handling Facilities and Equipment 97 to 572 ppm Eating Establishments (Including Utensils) 100 to 150 ppm Egg Handling Equipment and Washing 97 to 300 ppm, 13,000 ppm Food Processing Plant Premise and Equipment (includes dairy/cheese, poultry, meat and seafood) 101 to 4,900 ppm Household/Domestic Dwellings (Includes floors) 100 to 4,720 ppm Laundry Premises and Equipment 113 to 457 ppm Medical/Veterinary Premise and Equipment 100 to 937 ppm Mushroom Houses 102 to 644 ppm Laundry Sanitizer, Deodorizer, and Destainer Laundry (Commercial, Industrial, Ins titutional) 60 to 200 ppm per load Oil Production (Many Labels) Secondary Oil Recovery Injection Water 0.5 to 10 ppm Oil Recovery Drilling Muds and Packer Fluids 0.5 to 10 ppm Water Treatment (Many Labels) Commercial and Industrial Cooling Water Systems (includes once through and recirculating cooling towers) 0.5 to 10 ppm Drinking Water (Emergency, public and individual systems) 1 0.2 - 500 ppm Ornamental Ponds 0.5 to 20 ppm Pasteurizer Water Systems 0.5 to 10 ppm Sewage Treatment 0.2 to 3 ppm Swimming Pools and SPAs 2 0.5 to 8 ppm Waterbed Water 16 ppm In-Can Material Preservative (Label #935-71 Only) Adhesives, Water Based 71 to 2,280 ppm Emulsions (Vinyl Acrylic, Acrylic and PVA) 71 to 2,280 ppm Joint Compounds 142 to 2,280 ppm Paints, Interior (Vinyl Acrylic, Acrylic and PVA) 285 to 1,140 ppm Pigment Dispersions 142 to 2,280 ppm Floriculture (Labels #72992-12 and #72992-16) Water Conditioner for Flower Cuttings (Tablet or Label) 17 to 78 ppm

1 Higher rates are for emergency treatments after floods. Maintenance rate is 0.2 ppm.

2 Higher rates are for shock and winterizing treatments. Water cannot be entered until level is below 4 ppm.

Sodium dichloro- s -triazinetrione (PC Code: 081404), trichloro- s -triazinetrione (PC Code: 081405), and sodium dichloro- s -triazinetrione dihydrate (PC Code : 081407) are all registered as disinfectants and sanitizers for use to control bacteria on indo or food and non-food contact hard surfaces and equipment at food processing plan ts, eating and food handling establishments, commercial and industrial premises, hospital and medical premises (human/veterinary), laboratories, zoos, livestock and animal living qua rters, and indoor hard surfaces and contents of household/domestic dwelling premises. Additionally sodium dichloro- s -triazinetrione andPage 13 of 80 sodium dichloro-s-triazinetrione di hydrate are registered for use as a virucide on hard surfaces in hospitals (human/veterinary), institutional, a nd zoo premises, pet kennels, animal cages, zoo premises and animal enclosures and transport vehicles, animal feeding and water equipment, locker room premises, and shower and bathroom premises. These chlorinated isocyanurates are registered for use in residential, commer cial, and institutiona l laundry products.

Sodium dichloro- s -triazinetrione, trichloro- s -triazinetrione, and sodium dichloro- s -triazinetrione dihydrate, in addition to treati ng swimming pool water, are register ed for use as microbiocides, microbiostats, bacteriocides, disinfectants, sa nitizers, fungicides, a nd algaecides in non-food industrial water systems (air wash er water systems, commercial/i ndustrial water cooling systems, heat exchanger systems, cooling towers, lakes/ ponds/reservoirs (without human or wildlife use), pasteurizer water, cannery cooling canal water, hot tub, whirl pool, and spa waters, ornamental ponds and lakes, aquaria water, ornamental fount ains, sewage systems, waste water systems, sewage settling ponds, septic tanks , sewer lines (main), oil recove ry drilling muds and packer fluids, and secondary oil recovery injecti on water. Additionally sodium dichloro- s -triazinetrione and sodium dichloro-s-triazinetr ione dihydrate are regi stered for use as a virucide for the treatment of water used in spas, immersion ultras onic tank water, whirlpool bath water, and shoe baths. Sodium dichloro- s -triazinetrione, trichloro- s -triazinetrione, and sodium dichloro- s

triazinetrione dihydrate are also re gistered for use as a virucide a nd bacteriocide for treatment of potable water.
Formulation types include soluble concentrates both solid and flowable, wettable powder, water soluble packaging, granules, water dispersible gr anules, pellets, and tablets. There is a one product containing sodium dichloro- s -triazinetrione registered only for use of impregnated patches for placement on fresh cut flowers as a bactericide for slime-forming bacteria.

The labels indicate that the ch loroisocyanurates can be applie d to industrial water treatment systems and materials being preserved using bot h open pour and closed systems, applied to swimming pools and spas using open pour systems, applied to various hard surfaces using sprayers, foamers, mops and wipes, and applie d to food processing equipment and systems using immersion and circulate in place methods. So me labels, such as EPA Reg. Nos.1677-91 and 66570-2, also indicate that fogging can be used for applications in da iry, beverage and food processing plants.

1.5.3 Usage Information According to the Kline Biocides Report fo r 2004/2005 (Kline, 2006), the estimated U.S. consumption of chloroisocyanurates for 2004 was 195 million pounds. This consumption was distributed among recreational water (188.5 m illion pounds), cooling water (5.2 million pounds) and household, industrial and institutional disinf ectants and sanitizers (1.1 million pounds). According to a more recent report (Chemical Economics Report, 2012), “The global market for chlorinated isocyanurates is forecast to grow at an average annual rate of almost 3.5%”.Page 14 of 80 1.6 Regulatory History The chlorinated isocyanurates were first regist ered in the United States in 1958 for use as disinfectants, sanitizers, algicides, and fungicides. Sodium dichloro- s -triazinetrione was first registered in the United States in 1968; trichloro-s-triazinetri one was first registered in the United States in 1959; and sodium dichloroisocya nurate dihydrate was ini tially registered as a sanitizer in the United States on March 17 1964. The Agency completed a reregistration eligibility decision do cument (RED) in 1992, which include d a reregistration decision on all current uses except the material preservative uses, and all of the existing uses at that time were found to be eligible for registration. The post- RED data call-in (DCI) was issued in May 1993.

1.6.1 Recent/Pending Regulatory Actions There is currently one pending registration for sodium dichloro- s -triazinetrione, one pending registration for trichloro- s -triazinetrione and one for sodium dichloro- s -triazinetrione dihydrate.

1.6.2 Tolerance Information A tolerance exemption has been es tablished for sodium dichloroisoc yanurate used as a sanitizer on food contact surfaces of public eating places, dairy processing equipment, and food processing equipment and utensils [40 CFR 180.940( a)]. Tolerance exemptions have also been established for trichloroisocyanuric acid and dichloroisocyanuric acid and its sodium and potassium salts used as sanitizers on food c ontact surfaces of food processing equipment and utensils [40 CFR 180.940(c)]. A ll these sanitizers must be us ed such that the final use concentration of di- and trichloroisocya nuric acid chemicals does not exceed 100 ppm determined as total available chlorine. The Agen cy intends to add sodium dichloroisocyanurate dihydrate (51580-86-0) to the exemption in 40 CFR 180.940(c).



### 1.7 Incidents
1.7.1 Human Health A total of approximately 6,500 human health incide nts are listed in the Office of Pesticide Programs (OPP) Incident System for the chlori nated isocyanurates for the years 1992 to the present. A summary of these incidents is given in Table 7. The severity of the incidents range from minor effects such as transient respir atory irritation represented by code HD (Human Minor) to severe effects such as injuries and death represented by codes HB (Human Major) and HA (Human Fatality).
Approximately 4,900 of the incidents involved th e swimming pool uses. The most severe incidents were caused by label misuses such as premixing the chlorois ocyanurate pool products with small amounts of water or incompatible ch emicals such as bleach. These two actions caused explosions and the release of chlorine gas re sulting in injuries such as chemical burns and pulmonary edema. The labels clearly state that chloroisocyanurates should not be handled in this manner. Less severe incidents have occurred when people have been exposed to irritatingPage 15 of 80 “fumes” when opening containers or when produc ts fell out of floating dispensing containers ( i.e. , floaters) causing excessi ve dosing of the pool.
Approximately 680 incidents are associated with the food processing uses where chloroisocyanurate is used to tr eat beverage or milkshake machines. Two major (HB) incidents occurred when a person drank what he or she beli eved to be ice tea from an unlabeled container containing chloroisocyanurate sanitizer solution and when a person drank a milkshake from a milkshake machine that had not been pr operly rinsed following treatment with chloroisocyanurate.
Another 750 minor (HD) incidents are associat ed with the toilet bowl cleaning and hard surface disinfection uses and 7 minor incidents ar e associated with the industrial uses.
Table 7 - Incidents Reported for the Chlorinated Isocyanurates

Product Type Number of Incidents 1 HA HB HC HD HE Sodium dichloroisocyanurate (081404) Food Processing 0 0 0 1 0 Industrial Uses – Cooling Water, Paper Mills, Material Preservation 0 0 0 3 0 Pools and Spas 0 9 1 1014 26 Miscellaneous and Unspecified 0 0 0 8 0 Trichloro-isocyanuric Acid (081405) Toilet Bowl 0 0 0 78 0 Industrial Uses – Cooling Water, Paper Mills, Material Preservation 0 0 0 2 1 Pools and Spas 3 19 0 3425 49 Miscellaneous and Unspecified 2 0 0 0 19 3 Sodium dichloro-isocyanurate dihydrate (081407) Food Processing 0 2 0 675 2 Hard Surface Disinfection 1 0 0 671 80 Industrial Uses – Cooling Water, Paper Mills, Material Preservation 0 0 0 4 0 Pools and Spas 1 4 0 402 26 Miscellaneous and Unspecified 0 1 0 0 0

1 HA = Human Fatality, HB = Human Major, HC = Human Moderate, HD = Human Minor, HE = Human Unspecified
2 Two of the HD incidents involved the misuse of an industrial product in a swimming pool.

1.7.2 Ecological
No chlorinated isocyanurate ecological incide nts have been reported in the Agency’s OPP Incident Data System (IDS).



### 2 Anticipated Data Needs

Table 8 presents a summary of the data anticipate d as being needed to su pport this registration review.Page 16 of 80 Table 8 - Studies Anticipated as Needed for the Registration Review of the Chlorinated Isocyanurates

OCSPP GLN Study Name Test Substance Time Frame (Months

from DCI Receipt) Risk Assessment(s)

Data Will Support Use Site(s) Triggering Data

Requirement Applicable Exposure Scenarios

875.1300 Indoor Exposure, Inhalation Degradate (isocyanuric acid) 24 Occupational and Residential

Handler All See notes 1, 2, 3 and 4.

875.1700 Product Use Information TGAI 12 All All All above scenarios.

875.2300 Indoor Surface Residue Dissipation TGAI 24 Residential Household floors 5 Toddlers playing on disinfected floors

850.1010 Aquatic invertebrates, acute, freshwater Degradate (isocyanuric acid) 24 Aquatic organisms All 6 Transport to the aquatic environment

850.1025 or

850.1055 Estuarine/marine acute mollusk (shell deposition or embryo/larvae test) Degradate (isocyanuric acid) 12 Aquatic organisms All 6 Transport to the aquatic environment

850.1075 Fish acute, freshwater (warm and cold water species 7 ) Degradate (isocyanuric acid) 18 Aquatic organisms All 6 Transport to the aquatic environment

850.1075 Fish acute, estuarine/marine Degradate (isocyanuric acid) 18 Aquatic organisms All 6 Transport to the aquatic environment

850.1300 Freshwater invertebrate life cycle Degradate (isocyanuric acid) 12 Aquatic organisms All 6 Transport to the aquatic environment

850.1350 Estuarine/marine invertebrate life cycle Degradate (isocyanuric acid) 12 Aquatic organisms All 6 Transport to the aquatic environment

850.1400 8 Fish early life-stage, freshwater or estuarine/marine species Degradate (isocyanuric acid) 12 Aquatic organisms All 6 Transport to the aquatic environment

850.4100 9 Seedling emergence, Tier II – dose response, rice Degradate (isocyanuric acid) 12 Aquatic/Terrestrial exposure and risk All 6 except in-can material preservatives and floriculture patch Transport to the aquatic environment

850.4150 9 Vegetative vigor, Tier II – dose response, rice Degradate (isocyanuric acid) 12 Aquatic/Terrestrial organism exposure and risk All 6 except in-can material preservatives and floriculture patch Transport to the aquatic environment

850.4400 10 Aquatic Plant Testing using Lemna sp., Tier II Degradate (isocyanuric acid) 12 Aquatic organisms All 6 Transport to the aquatic environment

850.4500 11 Algal Toxicity Tier II –marine diatom, freshwater diatom, green algae Degradate (isocyanuric acid) 12 Aquatic organisms All 6 Transport to the aquatic environment

850.4550 11 Algal Toxicity Tier II - Cyanobacteria Degradate (isocyanuric acid) 12 Aquatic organisms All 6 Transport to the aquatic environmentPage 17 of 80 OCSPP GLN Study Name Test Substance Time Frame (Months

from DCI Receipt) Risk Assessment(s)

Data Will Support Use Site(s) Triggering Data

Requirement Applicable Exposure Scenarios

835.1230 (or OECD 106) Batch Equilibrium Degradate (isocyanuric acid) 12 Aquatic exposure and risk All 6 Transport and fate to the aquatic environment

835.3110 12 Ready Biodegradability Degradate (isocyanuric acid) 12 Aquatic exposure and risk All 6 Transport to wastewater treatment plant and aquatic environment

835.3220 12 Porous Pot Test Degradate (isocyanuric acid) 12 Aquatic exposure and risk All 6 Transport to wastewater treatment plant and aquatic environment

835.3240 12 Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units Degradate (isocyanuric acid) 12 Aquatic exposure and risk All 6 Transport to wastewater treatment plant and aquatic environment

835.3280 12 Simulation Test to Assess the Biodegradability of Chemicals Discharged to wastewater Degradate (isocyanuric acid) 12 Aquatic exposure and risk All 6 Transport to wastewater treatment plant and aquatic environment

835.4300 Aerobic aquatic metabolism Degradate (isocyanuric acid) 12 Aquatic exposure and risk All 6 Transport to the aquatic environment

835.4400 Anaerobic aquatic metabolism Degradate (isocyanuric acid) 12 Aquatic exposure and risk All 6 Transport to the aquatic environment

OECD 209 or

850.3300 13 Activated Sludge Respiration Inhibition (ASRI) Degradate (isocyanuric acid) 12 Aquatic exposure and risk All 6 Transport to wastewater treatment plant and aquatic environment

860.1460 14 Food-handling TEP 24 Dietary and aggregate risk Food processing, dairy, and public eating establishments Dietary

Special Study 15 Migration studies TEP 24 Dietary and aggregate risk Adhesives and pulp/paper mill

slimicide use Dietary

OCSPP: Office of Chemical Safety and Pollution Prevention; GLN: guid eline number, DCI: data call-in

1 Applicable Occupational Handler Exposure Scenarios: 1- Open pour liquids, granules and powder for hard surface disinfection and pool treatment; 2- Open pour granules for material preservation; 3- Mop, wipe and trigger spray for hard surface disinfection; 4- Hand wand spray disinfect ion of egg and food proce ssing plants; 5- Fogging disinfection of egg and food processing plants; and 6- Brush, roller and spray application of preserved paints.

2 Applicable Residential Handler Exposure Scenarios: 1- Open pour liquids, granules and powder for pool treatment; 2- Mop, wipe and trigger spray for hard surface disinfection; and 3- Brush, ro ller and spray application of preserved paints.

3 It may be possible to use proprietary surrogate exposure data if data compensation issues can be addressed.

4 If the labels are modified to require automatic foggers in place of hand held foggers, th en the study of hand held fogging exposures would not be expected to be needed.

5 If surface residue data are not available, then the standa rd assumption of 100 percent transferable surface residue will be used which might overestimate th e risk. For Hard Surface Flooring, only.Page 18 of 80 6 Industrial Process and Water Treat ment: Cooling Tower and Swimming P ools and Water Beds; Hard Surfaces Disinfectants and Sanitizers: Down-the -Drain (DtD) residential and industrial; Laundry Products: DtD residential and commercial; Material Preservativ es: DtD Production and In-Service.

7 Except for the industrial processes and water system uses , testing of a second freshwater species (cold or warm water) may be waived if isocyanuric acid is not stable and the median lethal concentration (LC 50 ) in the first species tested is >1 ppm.

8 Expected to be required for the more acutely sensitive of the freshwater and estuarine/marine fish species tested.

9 Data may be waived for uses where environmental exposu re concentrations will be less than the aquatic plant growth Tier II (850.4400, 850.4500, and 850.4550) no observable adverse effect concentration (NOAEC) values.

10 Except for industrial process and water treatment uses, a us e may be eligible for data waiver if the aquatic plant NOAEC results are all greater than or equal to 1 ppm.

11 All uses footnoted with marine diat om and freshwater diatom data for material preservative uses, hard surface disinfection and sanitization uses, and floriculture use may be eligible for data waiver if green algae ( Selenastrum capricornutum ) NOAEC results are greater than or equal to 1 ppm. The anticipated DCI will address this.

12 EPA has published final guidelines for four biodegradation studies. The biodegradation study anticipated to be required for chlorinated isocyanurates is for the degr adate (Isocyanuric acid base d on an Activated Sludge Respiration Inhibition Test).

13 The results of the Activated Sludge Respiration Inhibitio n Test (ASRI) expected to be required will determine which of these four biodegradation tests would be an ticipated to be required. If the ASRI test EC 50 is less than or equal to 20 milligrams per liter (mg/L), then either th e (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test would be anticipated to be required. If the ASRI test EC 50 is greater than 20 mg/L, then th e DCI expected to be issued would provide that the registrant would choose to conduct either : (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludg e Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted an d passes, then no further testing would be expected to be required. If, however, th e antimicrobial fails the Read y Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study would be expected to be required. The appropriate Test Substance to satisfy the guideline requirement is the degradate (isocyanuric acid).

14 Residue chemistry data are anticipated to be needed to determine dietary exposure to cyanuric acid/isocyanuric acid following sanitization of food contact surfaces of food processing plants (including dairies) and food-handling facilities (including public eating places ). Protocol subm ission is recommended. The an ticipated DCI will address this.

15 Migration of cyanuric acid/isocyanuric acid from preserved adhesive to food and from paper/paperboard to food following the slimicide use. The anticipated DCI will prov ide that a protocol must be submitted for EPA approval prior to initiating the study.Page 19 of 80 

### 3 Human Health Risk Assessment

The Agency anticipates the need to conduct a hu man health risk assessment for the chlorinated isocyanurates. The Agency expects to require additional data for use in conducting the registration review.



### 3.1 Existing Toxicological Endpoints EPA anticipates the need to revise the existing t oxicological endpoints as pa rt of this registration review. Table 9 presents the existing toxicologi cal points of departure (POD) for the chlorinated isocyanurates. The existing PODs were es tablished by the EPA Hazard Identification Assessment Review Committee (HIARC) in 2001 based on the toxicity database for the isocyanuric acids. It should be noted that the PODs for derm al exposure are based on oral studies and are used with a dermal absorption fa ctor of 1 percent to account for route to route extrapolation. Because the PODs for dermal exposure are the oral NOAELs of 200 milligrams per kilogram per day (mg/kg/day) and 154 mg/kg/day and the dermal absorption is 1 percent, the dermal equivalent PODs are 20,000 mg/kg/day a nd 15,400 mg/kg/day. Because these PODs are much higher than the limit dose of 1000 mg/kg/da y for dermal toxicity studies, the dermal toxicity is very low and does not need to be assessed. See Appendix B for additional information.

Table 9 – Existing Toxicology Endpoints Exposure Scenario Dose (mg/kg/day) Point of Departure (POD) Study (MRID)

Acute Dietary (females 13+) NOAEL= 200 mg/kg/day A

UF = 100 Increased incidence of hydrocephaly at 500 mg/kg/day. Developmental Toxicity – Rabbit (42054101)
Acute RfD =2.0 mg/kg/day Acute Dietary (general Population) N/A No appropriate endpoint was identified for the general population

Chronic Dietary NOAEL =154 mg/kg/day A

UF = 100 D ecreased survival in male rats and lesions of the urinary tract and heart at the next highest dose of 502 mg/kg/day. Chronic Toxicity / Carcinogenicity- Rat (00126362)
Chronic RfD = 1.5 mg/kg/day
Incidental Oral,

Short-Term N/A No appropriate POD was identified for short-term incidental oral risk.

Incidental Oral, Intermediate-term NOAEL = 204 mg/kg/day A Based upon hyperplasia of the urinary bladder at a dose of 672 mg/kg/day. 90-Day Oral Toxicity – Rat (00063477) Short- and Intermediate-Term (Dermal) NOAEL= 200 mg/kg/day A,B

UF = 100 C Increased incidence of hydrocephaly at 500 mg/kg/day. Developmental Toxicity – Rabbit (42054101)Page 20 of 80 Exposure Scenario Dose (mg/kg/day) Point of Departure (POD) Study (MRID)

Long-Term

(Dermal) NOAEL=154 mg/kg/day A,B

UF = 100 C Decreased survival in male rats and lesions of the urinary tract and heart at the next highest dose of 502 mg/kg/day. Chronic Toxicity/ Carcinogenicity –Rat (00126362)

Inhalation(Any

time point) NOAEL= 0.0032 mg/L D

UF = 100 C Based on increased incidence of clinical signs, decreased body weight, and increased relative lung weight at the next highest dose level. 28-Day Inhalation Toxicity – Rat

(00132438)
Abbreviations: MRID = Master Record Identification; UF = Un certainty factor, NOAEL = No Observed Adverse Effect Level, RfD = Reference Dose

A These PODs are based on toxicity studies of isocyanuric acid as discussed in the HIARC report of 1/25/2001.

B Since an oral POD was selected for dermal risk a ssessments, a dermal absorption value of 1.0 percent ( i.e. a dermal absorption factor of 0.01) should be used in route-to-route extrapolations. This value is based on available data as discussed in an OPP Memorandum of 20 March 1980 from Robert Zendzian, Ph. D. to James Skaptason.

C The HIARC report lists uncertainty factors (UF) of 100 for occupational dermal and inhalation exposure. The HIARC report does not list UFs for residential exposure.

D . This NOAEL is from a study where the test substance was sodium dichloro- s -triazinetrione.

3.2 Dietary Exposure The Agency anticipates the need to conduct a dietary assessment. Uses of chlorinated isocyanurates that may result in dietary exposur es include food proces sing plants including dairies and food-handling facilities including pub lic eating places, emergency drinking water, and individual and public drinking water systems including tanks, wells, re servoirs, and basins.
Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which reflects the reference dose (RfD), either acute or chronic, that has been adjusted to account for the FQPA Safety Factor (SF). This calculation is perf ormed for each population subgroup for which an endpoint exists. A risk estimate th at is less than 100% of the ac ute or chronic PAD is not of concern. Acute dietary risk for Chlorinated Isoc yanurates will be assess ed by comparing dietary exposure estimates expressed in mg/kg/day to th e acute Population Adjusted Dose (aPAD) and chronic Population Adjusted Dose (cPAD).

3.2.1 Food Human dietary exposure to chlorinated isocyanurate residues may occur as a result of their use to sanitize food contact surfaces of food processi ng plants including dairies and food-handling facilities including public eating pl aces. After treatment, most product labels state that food contact surfaces should be drained and that they should not receive a potable water rinse prior to reuse. However, some product labels state that a potable water rinse should be made after treatment. This issue will be addressed during the risk assessment stage of this registration review. Chlorinated isocyanurates are also used to preserve adhesives and as slimicides during production of paper/paperboard which may be used for food-contact purposes (labels are silent re: whether food contact is prohibited).Page 21 of 80 The Agency did not conduct a dietary risk assessment to support the 1992 RED for the Chlorinated Isocyanurates because, at that time, the uses noted above were under the purview of the Food and Drug Administration. Also, FQPA had not yet become law meaning that aggregate risk assessments were not conducted. Residue ch emistry data are expected to be needed to determine dietary exposure to the stable, tautom eric degradate pair of cyanuric acid and isocyanuric acid following saniti zation of food contact surfaces of food processing plants (including dairies) and food-ha ndling facilities (inc luding public eating places), adhesive preservation, and slimicide use in the pulp slurry to make paper/paper board for food contact.

The acute and chronic assessments to be conduc ted during registration review will estimate dietary exposure to chlorinate d isocyanurates and the degradat e cyanurate/isocyanurate for all population subgroups.

3.2.2 Drinking Water The chlorinated isocyanurates are registered fo r emergency drinking water treatment as well as routine (non-emergency) treatment of individu al and public drinking water systems including tanks, wells, reservoirs, and basins. While the ch lorinated isocyanurate ac tive ingredients are not persistent, contamination of drinking water by the degradate cyanurate/isocyanurate may occur as a result of discharge of waste water from paper and paperboard mills, down-the-drain from swimming pools or food-handling establishments , or run-off from livestock premises.
Chlorinated isocyanurates degrade rapidly to cyanurate/isocyanurat e and hypochlorous acid. Both parent compounds and cyanurate/isocyanurate are highly water-soluble and weakly sorbed to soil, sediment, and sludge. The routine wate r treatment use was assessed in response to a registrant proposal that EPA a pprove these uses on four of th eir product labels (T. McMahon, 3/26/01, D270655). Estimated exposures were compar ed to the cPAD value of 1.5 mg/kg/day as determined by the HIARC (report dated 1/25/01). Ch ronic dietary risks were reported to be 2% of the cPAD for adults and 6% of the cPAD for children.

The acute and chronic assessments to be conduc ted during registration review will estimate drinking water exposure to the degradate cyanur ate/isocyanurate for all population subgroups.

3.3 Occupational and Residential (ORE) Exposures
3.3.1 ORE Exposure Assessed in the RED Occupational and Residential (O RE) Exposures were not assesse d in the RED because “the chlorinated isocyanurates did not appear to induce significant acute (except eye irritation), subchronic or chronic toxicity ba sed on available information”. Th e RED further stated that “the toxicity data indicate that these compounds do not meet the Ag ency's toxicity criteria for the requirement of post-application re-entry and/ or mixer/loader/applicator exposure monitoring data. Accordingly, occupational a nd residential exposure data ar e not required to support the reregistration of the ch lorinated isocyanurates.”Page 22 of 80 3.3.2 ORE Exposures Assessed after the RED The dermal and incidental oral exposures of pe rsons swimming in pools tr eated with chlorinated isocyanurates were assessed in D270656 of 2/26/2001 using the endpoints established by the HIARC. These endpoints includ ed the intermediate term in cidental oral NOAEL of 204 mg/kg/day and the long term N OAEL of 154 mg/kg/day. These e xposures were calculated for both adult (77 kg) and child (29 kg) competitive swimmers using the SWIMODEL and assuming an isocyanuric acid concentra tion of 55 mg/liter, an exposure tim e of 3.0 hours per event, an event frequency of 150 events per year, a wate r ingestion rate of 0.05 liters per hour and a permeability coefficient of 1.5 x 10 -5 cm/hr. The oral MOEs were 270 for adults and 240 for children and the dermal MOEs were 720 for adu lts and 270 for children. The combined MOEs were 160 for adults and 110 for children. All thes e MOEs were considered to be not of concern because they exceeded the target MOE of 100.
The exposures to persons swimmi ng in public pools treated with chlorinated isocyanurates are also measured using biomonitoring of urine to determine water ingestion rates in a study conducted by the EPA Office of Research and Development (ORD). Approximately 550 swimmers were included in this study and the p ilot results from 53 swimmers were reported in Dufour, 2006 and incorporated into th e Exposure Factors Handbook (EPA, 2011).

3.3.3 ORE Exposures that will Need to Be Assessed for Registration Review Because endpoints of concern were identified af ter the RED for incidental oral and inhalation exposures, occupational and residential exposure s will need to be assessed for registration review. Although endpoints were also selected for dermal exposure, dermal exposures will not need to be assessed for reasons previously di scussed in Section 3.1. A listing of the exposure scenarios that need to be assessed is included in Table 10

.
Table 10 - ORE Scenarios for th e Chlorinated Isocyanurates

Scenario Exposure Route(s) Duration
Occupational Exposures Open pour granules and powder for hard surface disinfection and pool treatment Inhalation Short and Intermediate Term Open pour granules for material preserva tion Inhalation Short and Intermediate Term Mop, wipe and trigger spray application for disinfection (Medical and CII prem ise and equipment) Inhalation Short and Intermediate Term Hand wand spray application for disinfection (animal housing, food processing plants) Inhalation Short and Intermediate Term Fog application for disinfection (egg and food processing plants) Inhalation Short and Intermediate Term Brush, Roller and Spray Application of Preserved Paint Inhalation Short and Intermediate Term Residential Exposures Mop, wipe and trigger spray application for disinfection (Household/domestic dwellings, includes floors) Inhalation Short and Intermediate Term Open and pour granules and powder for pool treatment Inhalation Short TermPage 23 of 80 Brush and Roller Application of Preserved Paint Inhalation Short Term Swimming in Treated Pools Incidental oral Short and Intermediate Term Toddlers playing on disinfected floors In cidental Oral Short and Intermediate Term



### 3.4 Aggregate and Cumulative Exposure
3.4.1 Aggregate Exposures
Upon a reevaluation and selection of toxicological endpoints, comb ined with the human health exposure assessments expected as a part of this registration review cas e, aggregate exposures will need to be assessed. This assessment will likely include dietary exposures and residential exposures.

3.4.2 Cumulative Exposures
With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common me chanism of toxicity, EPA has not made a common mechanism of toxicity finding as to the chlorinated isocyanurates and any other substances and the chlorinated isocyanurates do not appear to produce a toxic metabolite produced by other substances. For the purposes of this registration review, therefore, EPA has not assumed that the chlorinated isocyanurates have a common mech anism of toxicity with other substances. For information regarding EPA’s ef forts to determine which chemicals have a common mechanism of toxicity and to evaluate th e cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs at http://www.epa.gov/pesticides/cumulative/.



### 4 Environmental Risk Assessment The Agency has not conducted a risk assessmen t that supports a complete endangered species determination for the chlorinated isocyanurates . The ecological risk assessment planned during registration review will allow the Agency to determine whether the use of chlorinated isocyanurates has 'no effect' or 'may affect' federally listed th reatened 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.

4.1 Environmental Conceptual Model Exposure Pathways Based on the chemical/physical properties and en vironmental fate studies (Appendix A) and the uses in Table 6, the Agency has developed concep tual models for the environmental exposure to the chlorinated isocyanurates and their major meta bolites/degradates. For all uses, the Agency assumes that environmental exposures may occur, especially from the cyanuric/isocyanuric acid metabolites, but bioconcentration will not be si gnificant because of their low log Kow (log P) and high water solubility values. This environmental exposure is expected to be of shorter duration in the presence of acclimated micr oorganisms or anaerobic conditions, based onPage 24 of 80 literature references (Zeyer et al. , 1980, Ernst and Rehm, 1990, Jessee et al. , 1983, Cook et al.
, 1985, Saldick et al. , 1974). The ultimate breakdown produc ts of cyanuric acid are carbon dioxide (CO 2 ) and ammonia (NH 3 ), both of which can be released into air or incorporated into microbial biomass. Figure 1 below contains the conceptual model for the use of disinfection and sanitizing products including cleaning products for floors and laundry additives ( e.g. , pre-wash cycle sanitizers, cleansers) which go down the dr ain after use. Figure 2 below contains the conceptual model for swimming pools and wate rbed water uses. Figure 3 contains the conceptual model for cooling towers. Figure 4 contains the conceptual model for in-can preservatives.
The use of chlorinated isocyanurat es in industrial processes and wa ter systems has a potential to expose aquatic organisms to hypochlorous acid and cyanuric/isocyanuric acid. However, hypochlorous acid has a finding of “ no effect” for cooling towers and water process system uses and therefore is not of concer n for chlorinated isocyanurates 3 . The risk assessment to be conducted as part of this registra tion review will evaluate risk from the chlorinated isocyanuric acid metabolite, isocyanuric acid.

3 Na & Ca Hypochlorite Registration Review: Final Work Plan, Docket ID EPA-HQ-OPP-2012-0004-0006Page 25 of 80 Figure 1 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates and their Reaction Products/D egradates from Sanitizing and Disinfecting Uses for Laundry and Hard Surfaces to Aquatic and Terrestrial Organisms

Stressor

Source

Receptors and Exposure Routes

Attribute Change(s) Individual organisms Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae Reduction in prey Modification of PCEs related to prey availability Habitat integrity Reduction in primary productivity Reduced cover Community change Modification of PCEs related to habitat Surface Water/Sediment

Aquatic Animals Invertebrates Vertebrates Exposure Media

Ingestion Ingestion Uptake/gills

or integument

Aquatic Plants Non

‐ vascular Vascular Uptake or sorption/cell, roots, leaves,

Piscivorous* Invertebrates Vertebrates Phytoplanktivore/ Herbivore Invertebrates Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc.) Ingestion Waste Water Treatment Plant (WWTP)

Key Most likely

exposure pathway contributing to risk Low likelihood of contributing to risk Disinfection and Sanitizing Products: cleaning products for floors and laundry additives (e.g., pre

‐ wash cycle sanitizers, cleansers)

WWTP microorganisms Uptake or sorption

Population Respiration inhibition Down

‐ the

‐ drain disposalPage 26 of 80 Figure 2 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates and their Reaction Products /Degradates from Swimming Pool and Water Bed Uses to Aquatic and Terrestrial Organisms

Stressor

Source

Receptors and Exposure Routes

Attribute Change(s) Individual organisms Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae Reduction in prey Modification of PCEs related to prey availability Habitat integrity Reduction in primary productivity Reduced cover Community change Modification of PCEs related to habitat Aquatic Animals Invertebrates Vertebrates Exposure Media

Ingestion Ingestion Uptake/gills

or integument
Aquatic Plants Non

‐ vascular Vascular Uptake or sorption/cell, roots, leaves,

Piscivorous* Invertebrates Vertebrates Phytoplanktivore/ Herbivore Invertebrates Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc.) Ingestion Waste Water Treatment Plant (WWTP)

Key Most likely

exposure pathway contributing to risk Low likelihood of contributing to risk Pool Treatment and Waterbed Use

WWTP microorganisms Uptake or sorption

Population Respiration inhibition Disposal of Water to sanitary drain system Stormwater drain disposal

Surface Water/SedimentPage 27 of 80 Figure 3 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates and their Reaction/Degradates from Cooling Water Tower Uses to Aquatic and Terrestrial Organisms

Stressor

Source

Receptors and Exposure Routes

Attribute Change(s) Individual organisms Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae Reduction in prey Modification of PCEs related
to prey availability Habitat integrity Reduction in primary productivity Reduced cover Community change Modification of PCEs related to habitat Surface Water/Sediment

Aquatic Animals Invertebrates Vertebrates Exposure Media

Ingestion Ingestion Uptake/gills

or integument

Aquatic Plants Non

‐ vascular Vascular Uptake or sorption/cell, roots, leaves,

Piscivorous* Invertebrates Vertebrates Phytoplanktivore/ Herbivore Invertebrates Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc.) Ingestion Waste Water Treatment Plant (WWTP)

Key Most likely

exposure pathway contributing to risk Low likelihood of contributing to risk Cooling Tower (Once Through and Recirculating)

WWTP microorganisms Uptake or sorption

Population Respiration inhibition Direct DischargePage 28 of 80 Figure 4 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates and their Reaction/Degradates fr om the Use and Disposal of In-Can or InContainer Material Preservat ives to Aquatic Organisms

4.2 Ecological Effects Assessment Ecological effects data are used as measures of di rect and indirect effect s to biological receptors. Acute and chronic toxicity data from studies submitted by pesticide registrants along with the available open literature obtained from ECOTOX w ill be used to evaluate the potential direct and indirect effects of the chlorina ted isocyanurates and their degrad ates to aquatic and terrestrial receptors. Data discussed herein are from regi strant-submitted data and from the EPA Office of Water’s Ambient Water Quality Criteria for Chlorine - 1984 (EPA 1985).

4.2.1 Mechanism of Action
In the aquatic environment, toxic action of ch lorinated isocyanurates is largely due to the formation of hypochlorous acid when chlorine reacts with water. Adverse effects of hypochlorous acid are due mainly to its corrosive ac tion. Acute necrosis ma y occur. Fish gillsStressor

Source

Receptors and Exposure Routes

Attribute Change(s) Individual organisms Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae Reduction in prey Modification of PCEs related
to prey availability Habitat integrity Reduction in primary productivity Reduced cover Community change Modification of PCEs related to habitat Aquatic Animals Invertebrates Vertebrates Exposure Media

Ingestion Ingestion Uptake/gills

or integument

Aquatic Plants Non

‐ vascular Vascular Uptake or sorption by

cells, roots, leaves,

Piscivorous* Invertebrates Vertebrates Phytoplanktivore/ Herbivore Invertebrates Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc.) Ingestion Waste Water Treatment Plant (WWTP)

Key Most likely

exposure pathway contributing to risk Low likelihood of contributing to risk In

‐ Surface Use of In

‐ Can or In

‐ Container Material Preservatives

WWTP microorganisms Uptake or sorption

Population Respiration inhibition Down

‐ the

‐ drain disposal of waste water from paint roller, brush, and tray rinsate

Surface Water/ Sediment Leaching from Exterior Facades and Structures to Storm DrainsPage 29 of 80 structure may be damaged; gill necrosis can lead to respirat ory problems and asphyxiation. The protective slime coating on fish also may be removed due to corrosive action.

4.2.2 Measures of Effect (Ecotoxicology Endpoints) Current selected ecotoxicologica l endpoints for conducting the risk assessment are provided in Table 11. All available ecotoxicity endpoints from studies submitted by registrants are tabulated separately for each isocyanurate in Appendix C. Available information on water quality criteria for chlorine residual is also discussed in Appe ndix C. The Ambient Water Quality criteria for Chlorine – 1984 document contains a review of public literature on effect s of chlorine (total residual chlorine (TRC) for freshwater spec ies and chlorine produced oxidants (CPO) for estuarine/marine species) and derives freshwater and saltwater organism acute and chronic water quality criteria. Curren t ambient water quality criteria (EPA , 2012) for chlorine are based on the 1986 Water Quality Document (EPA, 1986) which contained slight data updates to the 1984 document. OPP uses the most sensitive toxicity va lues for assessing risk to each receptor group. The endpoints that are expected to be used for the chlorinate d isocyanurates ecological risk assessment are presented in Table 11. Data ga ps also are indicated. No effects data on cyanurate/isocyanuric acid have been submitted to the OPP for review in support of pesticide registration. The Agency recognizes that isoc yanuric acid is an EPA high production volume 4 (HPV) chemical for which a Screening Inform ation Data Set (SIDS) Assessment Report was performed (OECD SIDS 1999 and IIAHC 2003). Values found in these sources have been listed in Appendix C and consist of fres hwater fish and invertebrate a nd green algae data. While some critical elements of these studi es are identified in the HPV SIDS files, there is insufficient information available on the studies for AD to review the studies for purposes of a risk assessment. ECOSAR v1.1 was used to estimate freshwater and estuar ine/marine fish and invertebrate acute and chronic values a nd the median effect concentration (EC 50 ) and maximum allowable toxicant concentra tion (MATC; geometric mean of the NOAEC and LOAEC) for green algae.
Table 11 – Existing Ecological Effects Endpoints
Receptor

Group Test Material a Surrogate Species Risk Scenario Toxicity Endpoint Reference

Freshwater fish TRC Rainbow trout Acute 96-h LC 50 = 80 μg ai/L MRID 00150966 Chronic AWQ criteria = 11 ug/l EPA 2012 b isocyanuric acid Generic Acute 96-h LC 50 = 72.0 mg/L ECOSAR v 1.1 Rainbow trout Chronic MATC = 1.85 mg/L ECOSAR v1.1

Freshwater invertebrates TRC Waterflea Acute 48-h EC 50 = 110 μg/L MRID 255593 Chronic AWQ criteria = 11 ug/L EPA 2012 b isocyanuric acid Waterflea Acute 48-h EC 50 = 34.65 mg/L ECOSAR v1.1 Chronic NOEC = 1.49 mg/L ECOSAR v 1.1

Estuarine/marine fish CPO Atlantic silverside Acute LC 50 = 37 μg/L EPA 1985 Chronic AWQ criteria = 7.5 ug/L EPA 2012 b Isocyanuric Generic fish Acute 96-h LC 50 = 46.9 mg/L ECOSAR v1.1

4 http://www.epa.gov/hpv/pubs/general/hpvchemdata.htmPage 30 of 80 Receptor

Group Test Material a Surrogate Species Risk Scenario Toxicity Endpoint Reference
acid Chronic MATC = 2.46 mg/L ECOSAR v1.1

Estuarine/marine

invertebrates CPO Eastern oyster Acute EC 50 = 26 μg/L EPA 1985 Chronic AWQ criteria = 7.5 ug/L c EPA 2012 b Isocyanuric acid Mysid Acute 96-h LC 50 = 6.97 mg/L ECOSAR v1.1 Chronic MATC = 4.82 mg/L ECOSAR v1.1

Algae TRC 4 spp. EC 50 Not required NOAEL Not required isocyanuric acid Green algae EC 50 96-h EC 50 = 0.114 mg/L b ECOSAR v1.1 NOAEL MATC = 0.057 mg/L b ECOSAR v1.1

Aquatic vascular plants TRC Lemna EC 50 Not required NOAEL Isocyanuric acid EC 50 Data required NOAEL

Birds Trichloro-striazinetrione Mallard Acute LD 50 = 1021 mg ai/kg-bw MRID 00126521 Chronic Not required

Mammals Chlorinated isocyanurates Lab. rat Acute LD 50 = 787 mg/kg-bw MRID 00150959 Chronic >1000 mg/kg-bw/day See Section 4.1.3 isocyanuric acid Lab. rat Acute LD 50 = 7700 mg/kg-bw OECD SIDS 1999

Nontarget insects Isocyanuric acid Honey bee Acute Not required

a TRC (total residual chlorine) refers to the sum of free chlo rine and combined chlorine in fresh water; in saltwater, in which chlorine forms will react w ith bromide, CPO (chlorin e-produced oxidants) refe rs to the sum of the oxidative products.

b Office of Water Aquatic Water Criteria value (http://water.epa.gov/scitech/swguidance/standards/handbook/index.cfm )



### 4.3 Exposure Analysis Plan
4.3.1 Aquatic and Terrestrial W ildlife Exposure Estimates In order to address the risk hypot hesis, the potential for adverse effects on the environment will be estimated. For down-the-drain (DtD) risk estim ates, an approach that estimates the number of days a concentration-of-concern (COC) is exceeded, also referre d to as a probabilistic dilution model (PDM) approach, is used to assess risk to aquatic organisms. The environmental fate and effects data anticipated to be needed to conduc t a more refined DtD asse ssment are provided as part of the work plan.
This analysis plan will be re visited and may be revised dependi ng upon a full review of the data available in the open literature and the inform ation submitted by the public in response to the opening of the Registration Review docket.

4.3.2 Down-the-Drain Analysis Data received in response to the data call-in expe cted to be issued as part of this registration review will allow the Agency to esti mate potential down-the-drain exposure.Page 31 of 80 

### 4.4 Effects Analysis Plan Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database 5 , which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. Th e ECOTOX database will be searched when the risk assessment for chlorinated isocyanurates is pr epared. At that time, op en literature studies will be reviewed that potentially provide data fo r missing or modeled endpoint values or provide a value more sensitive than what is available in-house.

Data from an ECOTOX run for ch lorinated isocyanurates and thei r degradates will be evaluated for possible quantitative and/or qualitative incl usion in the risk assessment in support of Registration Review. Data are obtained from registrant-submitted studies or from literature studies identified by ECOTOX. Th e ECOTOX database provides more ecological effects data in an attempt to bridge existing data gaps and uncertainties. ECOTOX is a source for locating single chemical toxicity data and potential chem ical mixture toxicity data for aquatic life, terrestrial plants, and wildlife. ECOTOX was creat ed and is maintained by the USEPA, Office of Research and Development, and the National Health and Environmental Effects Research Laboratory's Mid-Contin ent Ecology Division.



### 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of a 2001, registrati on action for chlorinate d isocyanurates, EPA reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), chlorinated isocyanurates are subject to the endo crine screening part of the Endocrine Disruptor Screening Program (EDSP).
EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal

5 http://cfpub.epa.gov/ecotox/Page 32 of 80 systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.
Under FFDCA section 408(p), the Agency must scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide ac tive ingredients and 9 inert ingredients. The chlorinated isocyanurates are not among the group of 58 pesticid e active ingredients on th e 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 subm ission of EDSP screening assays for the chlorinated isocyanurates. For further informati on on the status of the EDSP, the policies and procedures, the list of 67 chem icals, future lists, the test gui delines and the Tier 1 screening battery, please visit our webs ite: http://www.epa.gov/endo/.



### 6 Next Steps

EPA will issue a DCI for the Chlorinated Isocyanurates Case.



### 7 References

Anderson, K.L., K.A. Wheeler, J.B. Robins on, and O.H. Tuovinen. 2002. Atrazine Mineralization Potential in Two We tlands. Water Research 36: 4785-4794.

Cook, A., P. Beilstein, J. Grossenbacher, and R. Hütter. 1985. Ring cleavage and degradative pathway of cyanuric acid in bacteria, Biochem. J., 1985, 231, 25-30.
Dufour, A, O. Evans, T. Behymer, and R. Cantú. 2006. Water ingestion during swimming activities in a pool: a pilot study. Journal of Water & Health, 4, 425-430.

Ellis DD et al . 1982. Arch Environ Contam Toxicol 11: 373 - 82.
Ernst, C., and H. Rehm. 1990. Degradation of Cyanuric Acid by Immobilized Bacteria, , DECHEMA Biotechnol. Conf., 4(Pt. A), 577-580.
Helfgott, T., F. Hart and R. Bedard. 1977. An Index of Refractory Organics, EPA 600/2-77- 174,, pp. 1-7, 24-25.
Hu, H.C. 1981a. Hydrolysis Study of Aqueous Sodium Salt Solutions of 2,4,6-Trihydroxy-1,3,5- triazine. (Unpublished study received Ja n 26, 1981 under unknown admin. no.; prepared by FMC Corp., submitted by Monsanto Co., Washington, D.C.; CDL:244259-A). MRID 00056478Page 33 of 80 Hu, H.C.; 1981b. Photodegradation Study of Aqueous Sodium Salt Solutions of 2,4,6- Trihydroxy -1,3,5-Triazine; Unpublished St udy Conducted by Center Analytical Services, Princeton Chemical Research & Development Center, Princeton, NJ 08540 for the Isocyanurate Industry Ad Hoc Co mmittee (EPA Consortium 55643); Study No. (none), January 21, 1981. MRID 00056479.

IHS Chemical Economics Handbook. 2012. Chlori nated Isocyanurates. IHS Chemical

Jessee, J., R. Benoit, A., Hendricks, G. Allen, and J. Neal. 1983. Anaerobic Degradation of Cyanuric Acid, Cysteine, and Atrazine by a Facultative An aerobic Bacterium, Appl. and Environ. Microbiol. 45(1) 97-102.
Kontchou, C.Y and N. Gschwind. 1999. Biodegrad ation of S-Triazine Compounds by a Stable Mixed Bacterial Community. Ecotoxicol ogy and Environmental Safety 43: 47-56.
Michael, P., and Cummings, I. 1982. Cyanuric Acid Absorption On Soils, Monsanto Report ES82-SS-94. Method: OECD 106.
Saldick, J. 1974. Biodegradation of Cyanur ic Acid, Applied Microbiology 28(6) 1004-1008.

Sisodia,, S., A. Weber, and J. Jensen, 1996. Continuous Culture Biodegradation of Simazine’s Chemical Oxidation Products, Water Research 30(9) 2055-2064.

Soto, AM et al . 1995. The E-Screen Assay as a Tool to Identify Estrogen - An Update on Estrogenic Environmental Poll utants, Environmental Hea lth Perspectives, Vol. 103, Supplement 7, pp 113-122.
United States Environmental Protection Ag ency (USEPA). High Production Volume Information System (HPVIS). http://www.epa.gov/hpvis/
USEPA. 1988. Guidance for the Reregistration of Pesticide Products Containing Chlorinated Isocyanurates as the Active Ingr edient, 540/RS-88-077, PB88-220660. 83 pp. http://nepis.epa.gov/Exe/ZyNET.EXE?ZyAc tionL=Register&User=anonymous&Passwor d=anonymous&Client=EPA&Init=1
USEPA. 1985. Ambient Water Quality Crite ria for Chlorine - 1984. Office of Water Regulations and Standards Criteria a nd Standards Division, EPA 440/5-84-030. http://water.epa.gov/scitech /swguidance/standards/upl oad/2001_10_12_criteria_ambient wqc_chlorine1984.pdf
USEPA. 1992. Registration Eligibility Docu ment (RED): Chlorinated Isocyanurates. USEPA/Pesticides and Toxic Substa nces (H-7508W), September, 1992. http://www.epa.gov/oppsrrd1/REDs/old_r eds/chlorinated_isocyanurates.pdfPage 34 of 80 Yamasaki et al . 2003. Immature Rat Uterotrophic A ssay of 18 Chemicals and Hershberger Assay of 30 Chemicals. Toxicology 183, pp 93-115, 2003.
Zeyer, J., R. Hütter, and P. Mayer. 1980. Pr ocess for the biological degradation of cyanuric acid, UK Patent App. 2,025,919 (Jan. 30, 1980).Page 35 of 80 

### Appendix A: Environmental Fate

The Agency has reviewed environmental fate da ta submitted in support of registration review from submitted OCSPP 835 laboratory studies, the EPI-WEB 4.0 program, and the open literature. Many of these litera ture sources were included in the High Production Volume (HPV) submissions ( http://www.epa.gov/hpv/pubs/summa ries/tricltrz/c14659rs.pdf ). These data sources indicate that the parent compounds tric hloro- and dichloro isocyanurates readily dechlorinate in water to form the active i ngredient hypochlorous acid and the degradates cyanuric/isocyanuric acid (symmetrical triazine ring tautomers with readil y-interchangeable keto or enol groups depending on pH). Cyanuric and isocyanuric aci ds are highly water soluble, weakly sorbed, and will be in the water phase in both soil and waste water treatment plants (WWTPs). Cyanuric/isocyanuric acids degr adates do not degrade under abiotic conditions (presence of water and/or light without microorga nisms). However, cyanuric/isocyanuric acid is generally more degradable under anaerobic co nditions in the presence of microorganisms (acclimated or unacclimated) or when acclimat ed microorganisms are present under aerobic conditions. The ultimate breakdown products of cyanuric acid are CO 2 and NH 3 , both of which can be released into air or incorporated into microbial biomass. The environmental fate properties of trichloro isocyanuric acid and its metabolites are summa rized in Table 12.
Cyanuric/Isocyanuric Acids
Trichloro isocyanuric acid and triazine herbicid es share a symmetric triazine ring. However, the agronomic herbicides that are classified as s -triazine compounds have alkyl side chains. Trichloro isocyanuric acid is not considered as part of the tr iazine cumulative assessment (See Section 4.2). Therefore, a total toxic residue approac h, as would be used for s -triazine compounds, will not be applied to assess environm ental exposure. Trichloro isocyanuric acid dechlorinates to form the cyanuric acid and is ocyanuric acid metabolites. These metabolites, which are tautomers, are the compounds of pot ential concern based on the environmental fate data based on their environmental persistence. Under anaerobic condi tions (acclimated or unacclimated microorganisms) and also aerobic conditions with acclimated microorganisms, these metabolites can be further degraded into CO 2 and NH 3 , both of which can be released into air or incorporated into microbial biomass.
Chlorinated isocyanurates (paren t compounds) are used in water treatment to form hypochlorous acid (an oxidizing agent) when dissolved in wate r. Hypochlorous acid is a weak acid because it has a pKa (dissociat ion constant) of 3.7 x 10 -8 ) at 25 o C. Based on this pKa, 50% will be in hypochlorous acid form (HOCl) and 50% will be in hypochlorite ion (-OCl) form at pH 7.4 (pH = -log10 (3.7 x 10 -8 ). As the pH increases above 7.4, the amount of hypochlorite ion present will increase. Conversely, as the pH decreases below pH 7.4, the amount of hypochlorous acid present will increase. Hypochlorous acid reacts readily with ammoni a, amines, sulfides, sulfites, and nitrites present in the water. Antimicrobial activity results from the oxidation reactions with microbial enzyme systems. All these oxidation reactions consume residual freePage 36 of 80 chlorine, with the concurrent reduction of hypoc hlorous acid/hypochlorite to chloride anions. However, the release of hypochlorous acid is reversible and it can reattach to the cyanuric/isocyanuric acid if additional free hypochlorous acid is added.
The chlorinated isocyanurate degradates, cyan uric acid and isocyanuric acid (dechlorinated parent compound) exist in a pH-dependent equili brium. These two acids are keto/enol tautomers which interconvert readily depending on the pH of the environment. The cyanuric acid (enol form with three hydroxyl groups (-OH) attached to triazine ring) is the primary form found at lower pH values, while the isocyanuric acid (keto form, with three oxygens double-bonded with triazine ring) would be found at higher pH values. The pKa va lues for cyanuric acid are 6.88, 11.4, and 13.5 (http://www.drugfuture.com/ chemdata/cyanuri c-acid.html ).
Hu (1981a.b) found that cyanuric/isocyanuric acid is not prone to abiotic degradation (hydrolysis or direct photolysis in water). Microbial degradation of cyanuric /isocyanuric acid was variable and depended on the level of oxygenation and the presence of acclimated microorganisms. Cyanuric/isocyanuric acid degrad es more quickly under anaerobic conditions than under aerobic conditions. Degradation under aerobic conditions, however, is accelerated in the presence of acclimated microorganisms.

There are data available on the metabolism of the triazine ring from studies conducted with trichloro isocyanuric acid a nd from studies with the s -triazine herbicide atrazine, which like cyanuric/isocyanuric acid, contains a symmetric triazine ring. Mi neralized cyanuric/isocyanuric acid forms CO 2 and NH 3 which can enter the air or microbi al biomass (Saldick, 1974; Ernst and Rehm, 1990; Jessee et al. , 1983; Cook et al. , 1985; Zeyer et al. , 1980). In artificial and natural wetlands and in river water draining atrazine-treated corn fields, de gradation of atrazine occurred by acclimated microorganisms (Anderson et al. , 2002). Most atrazine (60-81 %) was ultimately degraded (mineralized) to CO 2 and NH 3 . The remaining applied atrazine was present in the form of cyanuric acid. However, in a Cedar Bog wetland with no previous exposure of microorganisms to atrazine, very limited atrazi ne mineralization was obs erved. In a laboratory biodegradation study (Kontchou and Gschwind, 1999), most s -triazine herbicides were readily metabolized to cyanuric acid, which did not readil y degrade. These results indicate that the microorganisms in this study were not acclimated to cyanuric acid. Therefore, if atrazine mineralizes in a stream with acclimated microorganisms, then cyanuric acid would also be expected to mineralize because they both share a symmetric triazine ring.
Bioconcentration of the cyanuric/isocyanic acid metabolites in mammals, fish, or non-target aquatic organisms is not expected to be significant. This conclusion is based on the relatively low Log Kow (1.95), which is less th an the level of concern (3.0). Also, these metabolites have a water solubility of approximate ly 2,000 mg/l (ppm) [EPI-WEB 4.0].
There are some outstanding environmental fa te data requirements for the degradate cyanuric/isocyanuric acid to suppor t Registration Review, and the an ticipated need for these dataPage 37 of 80 is based on the unknown relevance of the WWTP degr adation results in the HPV document. The Agency expects to require the registrant to s ubmit these studies on the fate of trichloro- and dichloro- cyanuric acid degradates on sewage treatment to satisf y the relevant data requirements listed below. They can be submitted to OPP for review to meet the data requirements.
Trichloro- and di-chloro- isocya nuric acids (parent compounds) de grade rapidly by hydrolysis to form cyanuric and isocyanuric acids (CAS 108-80-5), which ar e stable in the absence of microorganisms and under most aerobic conditions in the presence of microorganisms. Because of this rapid hydrolysis to cy anuric acid, photodegradation of parent compounds in water (a competing environmental dissipation route) is not a significant route of degradation. The Agency's in-house database does not have any ac ceptable environmental fate and transport data on cyanuric acid. These data are anticipated to be required to assess environmental fate for the registered use patterns that may potentially enter waste water treatment plants (WWTPs) and subsequently be discharged to aquatic environmen ts. An examination of the chemical structure, open literature from Science Direct (Ande rson, 2002; Kontchou and Gschwind, 1999, Table 12), and a review of information in a Robust Summary in the HPV documentation ( http://www.epa.gov/hpv/pubs/su mmaries/tricltrz/c14659rs.pdf , Table 12) indicates that a high percentage (up to 100 %) of cyanuric acid ma y be removed either by aerobic WWTPs using acclimated microorganisms or WWTPs using anaer obic conditions (acclimated or unacclimated microorganisms). The primary removal mechanism was attributed to mineralization because (1) there was no evidence of sorption to sludge base d on the low log Kow (1.95) and water solubility (2,000 mg/l) and (2) the study auth ors reported the release of CO 2 and ammonia (NH 3 ) or the incorporation of these substances into microbial biomass.
To be able to give merit to this claim of mi neralization, the Agency would need to review and evaluate the primary references cited in the HPV documentation. Without reviewing and evaluating these primary references and reaching the same conclusions as those presented, the Agency anticipates needing environmental fate data from tests including the st udies listed below.

o Anaerobic aquatic metabolism for the de gradate cyanuric acid (GLN 835.4400);

o Aerobic aquatic metabolism for the de gradate cyanuric acid (GLN 835.4300);

o Activated Sludge Respiration Inhibition (ASRI, OECD 209) or Modified ASRI test (850.3300)

o Ready biodegradability (GLN 835.3110), or Porous Pot Test (GLN 835.3220), orPage 38 of 80 Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater (GLN 835.3280), or Simulation Test – Ae robic Sewage Treatment: A. Activated Sludge Units (GLN 835.3240) for cyanuric acid 6

.

Table 12 Environmental Fate Data for Chlorinated Isocyanurates (di- and tri-chloro)

Test Guideline (Number) Test Substance Result Reference Comment

Hydrolysis (835.2120) Isocyanuric acid and sodium isocyanurate Rapid degradation to cyanuric acid Hu, 1981a MRID 00056478 Cyanuric acid was stable Not mentioned in HPV document 1 Photodegradation in Water (835.2240) Monosodium cyanurate Rapid degradation to cyanuric acid from hydrolysis (no photodegradation)_ Hu, 1981b MRID 00056479 Cyanuric acid was stable pp. 10-12 of HPV document 1 Batch Equilibrium (835.1230, OECD 106) Cyanuric acid Average K oc of 51 ml/g Michael and Cummings, 1982 Similar to OECD 106

Unknown Cyanuric acid Aerobic Conditions

Degrades slowly under aerobic conditions. Some microorganisms can degrade cyanuric acid if acclimated and organic nutrients are present

Anaerobic conditions

Readily biodegradable Zeyer et al. , 1980 Cyanuric acid formed CO 2 and NH 3 p. 15 of HPV document

Unknown Cyanuric acid Aerobic conditions

30 and 15 % degradation of cyanuric acid in 48 h for Pseudomonas sp . And Achromobacter sp

. Ernst and Rehm. 1990 Cyanuric acid formed CO 2 and NH 3 pp. 17-18 of HPV document Bacteria isolated from corn field

6 The results of the Activated Sludge Respiration Inhib ition Test (ASRI) determine which of these biodegradation tests are required. If the ASRI test EC 50 is less than or equal to 20 mg/L, then either the Biodegradation in Activated Sludge Study or the Porous Pot Test is required. If the ASRI test EC 50 is greater than 20 mg /L, then the applicant must choose either: (i) Ready Biodegradability or (ii) Biodegradation in Activated Sludge or the Porous Pot Test. If the antimicrobial passes the ready biodegradability study, then no further testing is required. If, however, the antimicrobial fails the ready biodegradability study, then th e Biodegradation in Activated Sludge or the Porous Pot study is required.Page 39 of 80 Test Guideline (Number) Test Substance Result Reference Comment

Unknown Cyanuric acid Aerobic conditions

58 % degradation of cyanuric acid in 8 days in FeS medium under aerobic conditions

Anaerobic conditions

100 % degradation of cyanuric acid in 4 days under anaerobic conditions in cysteine medium Jessee et al. , 1983 Unknown bacterium from acclimated bottom sediment downstream of WWTP in Illinois that treats wastewater from trichloro isocyanuric acid manufacturing facility

Cyanuric acid formed CO 2 and NH 3

pp. 19-20 of HPV document Unknown Cyanuric acid Anaerobic conditions

100 % degradation of triazine ring when additional source of nitrogen was present

No cell growth in absence of additional nitrogen source Cook et al. , 1985 Pseudomonas NRRL B12227 and B-12228 and Klebsiella pneumoniae Cyanuric acid formed CO 2 and NH 3

pp. 21-22

Unknown Cyanuric acid Aerobic conditions

100% degradation after 8 h (aerated activated sludge, 2.5 mg/l O 2 )

42% degradation after 9 h (aerated activated sludge, 8.7 mg/l O 2 )

0 % degradation (highly aerobic system, O 2 concentration not specified)

Anaerobic conditions

25-50% degradation in 48 h and 100 % in 72 h (sewage)

95-98 % degradation in 72 h (nutrient broth)

52-100 % degradation in 9-23 days (6 soils and muds) Saldick, 1974 Cyanuric acid formed CO 2 and NH 3 pp. 22-23 of HPV documentPage 40 of 80 Test Guideline (Number) Test Substance Result Reference Comment

Unknown Cyanuric acid 100 % degradation in unknown time Sisodia et al.
, 1996 Degradation of cyanuric acid occurs in absence ofnitrogen when triazineacclimated bacteria are present Cyanuric acid formed CO 2 and NH 3 pp. 24-25 of HPV document Unknown Cyanuric acid BOD 5 and COD of 6.5 and 11 mg/l Unknown reference, possibly Zeyer et al. , 1980 p. 15 of HPV document

Aerobic Aquatic Metabolism (835.4300) Atrazine 70-80 % of atrazine mineralization in constructed wetland fed by river draining treated corn fields

Wetland water demonstrated 60-80 % of atrazine mineralization in one month

75-81 % mineralization in river water samples containing acclimated microorganisms

Cedar bog did not demonstrate mineralization of atrazine because microorganisms were not adapted Anderson et al.
, 2002 Atrazine acid totally mineralized in the river and constructed wetland that contained microorganisms that are acclimated to degradation of triazine rings from herbicides.

Atrazine did not mineralize in wetland without acclimated microorganisms.

Atrazine formed CO 2 and NH 3

None Numerous triazine herbicides Cyanuric acid was end product (degradate) of S-triazines that reached WWTPs and was not degraded significantly Kontchou and Gschwind, 1998 Mixed culture of microorganisms in laboratory test.

1. HPV, http://www.epa. gov/hpv/pubs/summaries/tricltrz/c14659rs.pdf
Hypochlorous Acid Chlorinated isocyanurates (parent compounds) are used in water treatment to form hypochlorous acid (HClO), an oxidizing agent. W hen dissolved in water the chlorinated isocyanurates rapidly hydrolyze to release free chlorine and a co mplex series of equilibria of chlorinated and non-chlorinated is ocyanurates. The concentration of each entity depends on the concentration of total availabl e chlorine (free available chlo rine plus “reservoir” or bound chlorine), total isocyanurate c oncentration, and pH. It is HClO which is the active disinfection moiety for all hypochlorites in aqueous medium and is the most effective form of what is called free chlorine residual, which is chlorine available to kill microorganisms. The trichloro form has three chlorine molecules which can be released, and the dichloro has two. HClO is a weak acid and depending upon pH can fu rther breakdown or disa ssociate into a proton or hydrogen ion and a hypochlorite ion (ClO - ), the reaction is reversible. The antimicrobialPage 41 of 80 activity of chlorine compounds depends prim arily on HClO which can rapidly cross cell membranes. While ClO - has some disinfection potential it requires longer contact time.
HClO
ு௬௣௢௖௛௟௢௥௢௨௦ ௔௖௜ௗ ር
ۛ ۛ ሮ H ൅

ு௬ௗ௥௢௚௘௡ ௜௢௡ ൅ ClO
‐
ு௬௣௢௖௛௟௢௥௜௧௘ ௜௢௡

o The acid dissociation constant (K diss or K a ) of HClO is 3.4 x 10 -8 (or pK a 7 = 7.7). Hence at any given time, the concentration of HClO is not very high; however, as it gets used up—more HClO is formed and so on. It also means that at pH 7.7, the ratio of HClO to ClO - is 50:50, while at pH 7.2, 70% is HClO and 30% is ClO -

.

o A literature report (Connell, 1996) estimated the changes due to protolysis (hydrolysis) of a so lution containing ClO - . The graphical data is converted into the numerical data on the percent of HClO and ClO - from pH 4 to 11 as shown in the table below. In dilute aqueous soluti ons these reactions oc curs in seconds or even in less time. This is typical of inorganic reactions. pH Percent HClO Percent ClO 4.0 100 6.3 95 5 7.2 70 30 7.7 50 50 8.0 21 79 11 100

o Disinfection is more efficient at lower pH than at higher pH because HClO is a more efficient disinfectant than ClO - , and as indicated above there is a higher proportion of HClO at lower pH than at higher pH values.

 It is ClO - and/or HClO moieties that are the active antimicrobial portion of the chlorinated isocyanurates.

 Available chlorine (AC) is a measure of the equivalent weights of oxidizing agents, with chlorine gas as a basis— i.e. , normalizes chlorine-containing compounds to allow comparison of oxidizing potential. The c oncentration of hypochlorite (or any other oxidizing disinfectant) may be expressed as available ch lorine by determining the electrochemical equivalent amount of elemental chlorine (Cl 2 ) to that compound (USEPA 1986).

o A mole of chlorine gas reacts with water to form a mole of HClO and a mole of protons (or hydrogen ions) and a mole of chloride ions. The oxidation state of chlorine is 0 in chlorine gas, +1 in HClO and -1 in Cl - ; therefore chlorine is both oxidized and reduced in this reaction. Cl 2 ஼௛௟௢௥௜௡௘, ௚௔௦ ൅ H 2 O

ௐ௔௧௘௥ ሱ ۛ

ሮ HClO
ு௬௣௢௖௛௟௢௥௢௨௦ ௔௖௜ௗ ൅ H ൅

ு௬ௗ௥௢௚௘௡ ௜௢௡ ൅ Cl
‐

஼௛௟௢௥௜ௗ௘ ௜௢௡

o Elemental Cl 2 oxidizing potential : one mole of elemental chlorine is capable of reacting with two electrons to from in ert chloride, as s hown in the reaction

7 pK a = -log 10 K aPage 42 of 80 equation below (USEPA, 1986). The AC is 70.91 grams per mole (identical to the molecular weight of Cl 2 ). Cl 2
஼௛௟௢௥௜௡௘ ൅ 2݁ ି

ா௟௘௖௧௥௢௡௦ ൌ 2Cl
‐

஼௛௟௢௥௜ௗ௘ ௜௢௡

o ClO - oxidizing potential : one mole of ClO - may react with two electrons to form chloride, as shown in the reaction eq uation below. Hence, one mole of hypochlorite is equivalent (electrochemica lly) to one mole of elemental chlorine, and may be said to contain 70.91 grams of AC (identical to the molecular weight of Cl 2 ) (USEPA, 1986). ClO ି
ு௬௣௢௖௛௟௢௥௜ௗ௘ ൅ 2݁ ି

ா௟௘௖௧௥௢௡௦ ൅ 2H ൅

ு௬ௗ௥௢௚௘௡ ௜௢௡ ൌ Cl
‐

஼௛௟௢௥௜ௗ௘ ௜௢௡ ൅ 2H 2 O

ௐ௔௧௘௥

o The free available chlorine as a percen t by weight for each of the chlorinated isocyanurates in this registra tion review is theoretically:

Chemical Name Sodium dichloro- s -triazinetrione Trichloro- s -triazinetrione Sodium dichloro- s -triazinetrione dihydrate

Available Chlorine (%) 63 90 56

 Chlorine in addition to provi ding disinfection or oxidation of microorganisms can be consumed by oxidation or subs titution reactions with inor ganic substances such as ammonia, iron, manganese, sulfides a nd some other organic substances ( e.g. , phenols).

 In the surface water and wa stewater streams possible tr ansformation products like chlorine, HOCl, ClO 3 - may be present, but the determ ination of exact amounts of these moieties cannot be calculated as these will depend on the environmental conditions like pH of the medium, temperature, ionic strength, etc

.



### Appendix A References

Anderson, K.L., K.A. Wheeler, J.B. Robins on, and O.H. Tuovinen. 2002. Atrazine Mineralization Potential in Two We tlands. Water Research 36: 4785-4794.

Cook, A., P. Beilstein, J. Grossenbacher, and R. Hütter. 1985. Ring cleavage and degradative pathway of cyanuric acid in bacteria, Biochem. J., 1985, 231, 25-30.
Ernst, C., and H. Rehm. 1990. Degradation of Cyanuric Acid by Immobilized Bacteria, , DECHEMA Biotechnol. Conf., 4(Pt. A), 577-580.
Hu, H.C. (1981a) Hydrolysis Study of Aqueous Sodium Salt Solutions of 2,4,6-Trihydroxy1,3,5-triazine. (Unpublished study receive d Jan 26, 1981 under unknown admin. no.; prepared by FMC Corp., submitted by Mons anto Co., Washington, D.C.; CDL:244259- A). MRID 00056478Page 43 of 80 Hu, H.C. (1981b) Photodegradation Study of Aqueous Sodium salt Solutions of 2,4,6- Trihydroxy-1,3,5-triazine. (Unpublished study received Jan 26, 1981 under unknown admin. no.; prepared by FMC Corp., subm itted by Monsanto Co., Washington, D.C.; CDL: 244259-B). MRID 00056479

Jessee, J., R. Benoit, A., Hendricks, G. Allen, and J. Neal. 1983. Anaerobic Degradation of Cyanuric Acid, Cysteine, and Atrazine by a Facultative An aerobic Bacterium, Appl. and Environ. Microbiol. 45(1) 97-102.
Kontchou, C.Y and N. Gschwind. 1999. Biodegrad ation of S-Triazine Compounds by a Stable Mixed Bacterial Community. Ecotoxicol ogy and Environmental Safety 43: 47-56.
Michael, P., and Cummings, I. 1982. Cyanuric Acid Absorption On Soils, Monsanto Report ES82-SS-94. Method: OECD 106.
Saldick, J. 1974. Biodegradation of Cyanur ic Acid, Applied Microbiology 28(6) 1004-1008.

Sisodia,, S., A. Weber, and J. Jensen, 1996. Continuous Culture Biodegradation of Simazine’s Chemical Oxidation Products, Water Research 30(9) 2055-2064.
Zeyer, J., R. Hütter, and P. Mayer. 1980. Pr ocess for the biological degradation of cyanuric acid, , UK Patent App. 2,025,919 (Jan. 30, 1980).Page 44 of 80 

### Appendix B: Toxicology Profile
Hazard/Toxicity

The most recent review of the toxicity data for the chlorinated isocyanurates was included in the HIARC report of January 25, 2001. This report al so re-affirmed the conclusion from the RED that toxicology data on isocyanur ic acid would support assessment of hazard from exposure to the chlorinated derivatives. In RED, which wa s written in 1992, the Agency stated that for purposes of hazard assessment, the isocyanurates could be divided into three groups for acute toxicity testing (isocyanuric ac id, dichloroisocyanurates, and tric hloroisocyanurates), while for subchronic, chronic, developmental, mutage nicity, and metabolism testing, the Agency determined that isocyanuric acid could repres ent all of the chlorina ted isocyanurates. The Agency justified this approach at that time, statin g that “since the chronic effects of chlorine for humans are well known, EPA determined that isocya nuric acid can represent all the chlorinated isocyanurates for the purpose of conducting metabo lism, subchronic, chronic, developmental, and mutagenicity studies.”

No additional studies have been submitted to th e Agency and no public literature was found that was dated after the HIARC report was written. 

### Acute Toxicity for Product Labeling

The acute toxicity profile for isocyanuric acid, as repr esented by data on the chlorinated isocyanurate compound trichloro-s-tr iazinetrione, is listed in Ta ble 13. The acute toxicity is minimal by the oral, dermal, and inhalation routes of exposures, (Toxicity Category III for oral and dermal, Toxicity Category IV for inhalatio n). However, the isocyanurates demonstrate significant irritation to the skin and eyes (Toxici ty Category I) and are also dermal sensitizers.
Table 13 - Acute Toxicity of the Chlorinated Isocyanurates

Guideline No. Study Type MRIDs # Results Toxicity Category 81-1 Acute Oral 00150959 LD 50 = 787 mg/kg (M) and 868 mg/kg (F) III 81-2 Acute Dermal 42180403 LD 50 > 2000 mg/kg III 81-3 Acute Inhalation LC 50 > 200 mg/L IV 81-4 Primary Eye Irritation 00019754 severe eye irritant I 81-5 Primary Skin Irritation 00019754 severe dermal irritant I 81-6 Dermal Sensitization 00144720 dermal sensitizer 81-8 Acute Neurotoxicity N/A N/A



### Subchronic Toxicity

In subchronic toxicity te sts (MRIDs #0063477 and MRID #00124782) , the dose levels in rats and mice at which toxicity is manifested are c onsidered high (LOAELs of 672 mg/kg/day in rats,Page 45 of 80 LOAEL > 1994 mg/kg/day in mice). There were no reported signs of t oxicity after 13-week administration of the test chemical to mice, and in rats, toxicity was manifested in the urinary bladder as hyperplasia of the urinary bl adder epithelium, a known toxic response to isocyanurates at high dose levels as a result of pr ecipitation of the chemical in the bladder.


### Developmental and Repr oductive Toxicity

In developmental toxicity tests, isocyanuric acid at doses up to 500 mg/kg/day in rabbits (MRID #42054101) and 5000 mg/kg/day in rats (MRID #00105168) caused no significant maternal or developmental toxicity.
In reproductive toxicity testing, isocyanuric aci d produced calculi in the urinary bladder in parental rats of the F2 generation at doses approximating a limit dose of 1000 mg/kg/day, while there were no reported reproductive or fertility effects in offspr ing of any generation at doses up to and including a limit dose of 1000 mg /kg/day (MRID #00150286). In one study with monosodium isocyanurate in rabbits (MRID #42054101) , increased fetal and litter incidence of hydrocephaly was observed in offspring at a dose of 500 mg/kg/day, a dose which was not maternally toxic. The weight of the evidence suggests no developmental or reproductive toxicity from exposure to isocyanuric acid, but the resu lts of the single rabbit study must also be considered. 

### Chronic Toxicity and Carcinogenicity

Isocyanuric acid has been adequately tested for chronic toxicity and carc inogenicity in studies with rats (MRID #00126362) and mice (MRID #00126361). In both of these studies, isocyanuric acid was found to be devoid of carci nogenic effects. Alt hough epithelial hyperplasia was observed in the rat study, this is known to be a result of calculi formation in male rat bladder as a result of precipitation of the test chemical in urine at high doses and as a result of the pH of rodent urine. 

### Mutagenicity

The negative results of carcinog enicity testing are supported by the results of mutagenicity testing (MRIDs #0094883, #0091031 and #0094882) of isocya nuric acid that shows the chemical to be negative in all mutagenicity assays submitted to the Agency.Page 46 of 80 

### Appendix C: Ecotoxicology Profile

 A review of toxicity effects data for th e chlorinated isocyanurates is summarized in the following sections, with selected ecotoxicological endpoints for risk assessment provided in Table #11. As discussed in the fate section, the chlorinated isocyanurates in aqueous so lution will release chlorine forming hypochlorous acid and the isoc yanuric acid/cyanuric acid degradate. Therefore for aquatic organisms, toxicity informa tion on both the chlorinated isocyanurates or chlorine as surrogate and the isocyanuric acid degradate is used to assess risks.

Terrestrial - Avian acute- oral and dietary toxicity-Chlorinated Isocyanurates
An acute oral toxicity study using the tec hnical grade of the activ e ingredient (parent compounds, i.e. TGAI) is anticipated to be required to establish the toxicity of the chlorinated isocyanurates to birds. The preferred test species is either the mallard ( Anas platyrhynchos ) or the northern bobwhite ( Colinus virginianus ). Data for both mallard and northern bobwhite have been submitted for trichloro- s -triazinetrione (Table 14), sodi um dichloroisocyanurate dihydrate (Table 15), and sodium dichloro- s -triazinetrione (Table 16). Those 7 studies categorize the chlorinated isocyanurates as bei ng slightly to practically nontoxi c to birds on an acute-oral basis (LD 50 ’s = 1021 to >2250 mg ai/kg-bw). The data requirement (850.2100) is satisfied. Chronic data (850.2300) are not exp ected to be required.
Avian dietary toxicity studies ( 850.2200) are not expected to be required for the current uses. However, a total of 12 studies were submitted for trichloro- s -triazinetrione, sodium dichloro- s

triazinetrione, and sodium dichloroisocya nurate dihydrate for both mallard and northern bobwhite. Those data categorize th e chlorinated isocyanurates as being practically non-toxic to birds on a dietary basis (LC 50 ’s >5000 ppm).
Table 14 Available Endpoints from Avia n Ecotoxicity Studies for Trichloro-striazinetrione

Study Type Species Test material

(% ai) Toxicity 1 Toxicity Classification MRID & Status

Acute – Avian Oral 850.2100 Northern bobwhite 92 LD 50 : 1674 mg/kg-bw/day Slightly toxic 00150962 Acceptable

99 LD 50 : >2250 mg/kg-bw/day Practically nontoxic 00144303 Supplemental

Mallard 100 LD 50 : 1890 mg/kg-bw/day Slightly toxic 00132603 Supplemental

100 LD 50 : 1021 mg/kg-bw/day Slightly toxic 00126521 Acceptable Acute – Avian Dietary 850.2200 Northern bobwhite 100 LC 50 : 7235 ppm Practically nontoxic 0019380 & 00132427 AcceptablePage 47 of 80 Study Type Species Test material

(% ai) Toxicity 1 Toxicity Classification MRID & Status

92 LC 50 : >5000 ppm Practically nontoxic 00150964 Acceptable

99 LC 50 : >5000 ppm Practically nontoxic 00144302 Supplemental

Mallard 100 LC 50 : >10,000 ppm Practically nontoxic 00132426 Acceptable

92 LC 50 : >5000 ppm Practically nontoxic 00150963 Supplemental

99 LC 50 : >5620 ppm Practically nontoxic 00144301 Supplemental

1 Toxicity values based on parent compound (TGAI).
Table 15 Available Endpoints from Av ian Ecotoxicity Studies for Sodium Dichloroisocyanurate Dihydrate

Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & Status

Acute – Avian Oral 850.2100 Northern bobwhite 98.3 LD 50 : 1766 mg/kg-bw/day Slightly toxic 00150947 Acceptable

Acute – Avian Dietary 850.2200 Northern bobwhite 98 LC 50 : >5000 ppm Practically nontoxic 00150949 Acceptable

Mallard 98 LC 50 : >5,000 ppm Practically nontoxic 00150948 Acceptable

1 Toxicity values based on parent compound (TGAI).

Table 16 Available Endpoints from Avian Ecotoxicity Studies for Sodium Dichloro- sTriazinetrione

Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & Status

Acute – Avian Oral 850.2100 Northern bobwhite 98 LD 50 : >2250 mg/kg-bw/day Practically nontoxic 00144306 Acceptable

Mallard 100 LD 50 : 1915 mg/kg-bw/day Slightly toxic 00125993 Supplemental 2

Acute – Avian Dietary 850.2200 Northern bobwhite 98 LC 50 : >5600 ppm Practically nontoxic 001444305 Acceptable

100 LC 50 : >10,000 ppm Practically nontoxic 0019608 Acceptable

Mallard 100 LC 50 : >10,000 ppm Practically nontoxic 00007219 AcceptablePage 48 of 80 Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & Status

98 LC 50 : >5620 ppm Practically nontoxic 00144304 Acceptable

1 Toxicity values based on parent compound (TGAI).

2 This study was reviewed twice, once in 1980 when it was classified as “Acceptable” and a second time in 1987 when it was classified as “Supplemental”. The Supplement al classification was due to the presence of regurgitation in the two highest doses.

Terrestrial Mammals-Chlorinated Isocyanurates
The chlorinated isocyanurates are slightly toxic to mammals on an acute basis (LD 50 = 787 to 868 mg/kg-bw; MRID 00150959 (see Appendix B)). Developmental and repr oductive toxicity is not expected from exposure to the degradate, is ocyanuric acid (see Append ix B). In reproductive toxicity testing with rats, isocyanuric acid produ ced no reported reproductive or fertility effects in offspring of any generation at doses up to and including a limit dose of 1000 mg/kg-bw/day (MRID #00150286). In one study with monosodi um isocyanurate in rabbits (MRID #42054101), increased fetal and litter incidence of hydrocephaly was observed in offspring at a dose of 500 mg/kg-bw/day, a dose whic h was not maternally toxic.
Nontarget Terrestrial Insects-Chlorinated Isocyanurates
Data are not expected to be required for the ch lorinated isocyanurate uses because exposure is unlikely given the use pattern and fate of the chlorinated isocyanurates and their degradates.
Aquatic - Fish and Invertebrate Toxici ty-Chlorinated Isocyanurates/Chlorine
In addition to the chlorinated isocyanurate ecoto xicity data discussed he re, additional chlorine toxicity information was obtained from the EPA Office of Water’s Ambient Water Quality Criteria for Chlorine - 1984 (EPA 1985). The document contains a review of public literature on effects of chlorine and based on the data deri ves freshwater and saltwater organism acute and chronic water quality criteria as total chlori ne residual (TRC) for fr eshwater and chlorineproduced oxidants (CPO) for seawater. Current ambient water quality criteria for freshwater TRC and seawater CPO are based on the data in the 1984 document and the method for deriving water quality standards discussed in a 1986 Water Quality Document (USEPA, 1986).

 Freshwater Criterion Maximu m Concentration = 19 μg/L;

 Freshwater Criterion Continuous Concentration = 11 μg/L;

 Saltwater Criterion Maximum Concentration = 13 μg/L; and

 Saltwater Criterion Continuous Concentration = 7.5 μg/LPage 49 of 80 According to the Office of Water’s Ambient Water Quality Criteria for Chlorine – 1984 (AWQC, EPA 1985), the term “total residual chlorine” (TRC) refers to the sum of free and combined chlorine in fresh water. In saltwat er, in which chlorine will react with bromide, “chlorine-produced oxidants” (CPO) is used to refer to the sum of the free and combined chlorine and bromine oxidative products. Therefor e, the toxicity values presented in the AWQC document, expressed as μg/L, refer to TRC fo r freshwater organisms and CPO for saltwater organisms.
Acute toxicity data on chlorinated isocyanur ates for freshwater and saltwater fish and invertebrates are presented below. Howeve r, unlike the AWQC document unless specified otherwise in the tables, there data are expr essed as ug ai/L, and not as TRC or CPO. Additionally, while these studies are marked acceptable, they were conducted under static conditions rather than flow -through and are based on nomina l rather than measured concentrations. For purposes of a hazard assess ment, they were considered acceptable. For assessment of risk tests using flow-through, measur ed concentrations from the AWQC Chlorine document are used.

Freshwater Fish
To assess potential acute and chr onic risks to aquatic freshwater fish, acute and chronic effects data for chlorinated isocyanurates are used. The preferred test spec ies are rainbow trout ( Oncorhynchus mykiss ), a coldwater species, and bluegill sunfish ( Lepomis macrochirus ), a warmwater species. Acute toxicity data for fr eshwater fish and invertebrates are available for trichloro- s -triazinetrione (Table 17), sodium dichlo ro-s-triazinetrione (Table 18), and sodium dichloroisocyanur ate dihydrate ( 1 While these studies are deemed acceptable, they were conducted under static conditions rather than fl ow-through and are based on nominal rather than measured concentrations. For purposes of a hazar d assessment, they are considered acceptable.

Table 19). The 11 high purity grad e test material studies (>90% ai) available for trout and bluegill categorize the three chlo rinated isocyanurates tested as being very highly toxic to moderately toxic to freshwater fish (LC 50 ’s = 80 to 1720 μg ai/L). As discussed previously these studies were conducted under static conditions and, given the test material rapid reactivity and dissipation, likely underestimate toxicity as compared to flow-through conditions. However, with the availability of chlorine toxicity st udies from the AWQC docum ents no additional acute or chronic data are anticipated to be required.

Freshwater Invertebrates
To assess potential acute and chroni c risks to aquatic freshwater inve rtebrates. The preferred test species is Daphnia magna or Daphnia pulex acute and chronic effects data chlorinated isocyanurates are anticipated to be used. Five acute studies with high purity grade test material (>90% ai) have been submitted. The data categorize the three chlorinated isocyanurates tested as being highly toxic to fres hwater invertebrates (LC 50 ’s = 110 to 800 μg ai/L). As discussedPage 50 of 80 previously these studies were c onducted under static conditions and, given the test material rapid reactivity and dissipation, likely underestimate toxicity as compar ed to flow-through conditions. However, with the availability of chlorine toxicity studies from the AWQC documents no additional acute or chronic data are anticipated to be required for chlorinated isocyanurates .

Estuarine and Marine Fish and Invertebrates -Chlorinated Isocyanurates/Chlorine
TGAI data are required to assess acute and chronic risks to estuarine/marine fish and invertebrates potentially exposed from use of chlorinated isocya nurates in industrial processes and water systems. Acute testing with one fi sh, one shrimp (Mysidae or Penaeidae), and one mollusk are used. The preferred test speci es are the Silverside spp., Eastern oyster ( Crassostrea virginica ), and mysid shrimp ( Americamysis bahia formerly called Mysidopsis bahia ). No data have been submitted for the TGAI. Data submitted to support sodium hypochlorite, which also generates hypochlorous acid, indica te that hypochlorous acid (11.43- 12.96% ai) is highly to very highly toxic to estuarine/marine fish (LC 50 ’s = 50 and 380 μg ai/L) and invertebrates (LC 50 ’s = 160 and 200 μg ai/L). Those data were genera ted using sodium hypochlorite formulations and do not support the TGAI. However, data are av ailable in the AWQC (E PA 1985) indicating that CPO is highly to very highly toxic to estuarine/ma rine fish and invertebrates (Table 17). No additional acute or chronic data for fish a nd invertebrates are anticipated as required.
Table 17 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate Ecotoxicity Studies for Trichloro- s -triazinetrione

Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & Status

Acute – Freshwater Fish 850.1075 Rainbow trout 100 96-hr LC 50 : 330 μg ai/L Highly toxic 00026195 Acceptable 1

100 96-hr LC 50 : 370 μg ai/L Highly toxic 00026193 Acceptable 1

92 96-hr LC 50 : 80 μg ai/L Very highly toxic 00150966 Acceptable 1

Bluegill 92 96-hr LC 50 : 200 μg ai/L Highly toxic 00150965 Supplemental

100 96-hr LC 50 : 620 μg ai/L Highly toxic 00026194 Supplemental

Acute – Freshwater Invertebrate

850.1010 Waterflea 92.8 48-hr EC 50 : 170 μg ai/L Highly toxic 00150867 Acceptable 1

100 48-hr EC 50 : 800 μg ai/L Highly toxic 00154329 Acceptable 1

98 48-hr EC 50 : 640 μg ai/L Highly toxic 00150967 Acceptable 1

NR 48-hr EC 50 : 250 μg ai/L Highly toxic 00019766 & 00019383 SupplementalPage 51 of 80 1 While these studies are deemed acceptable, they were conducted under static conditions rather than flow-through and are based on nominal rather than measured concentrations. For purposes of a hazard assessment, they are considered acceptable.

Table 18 Available Acute Endpoints from Fr eshwater Fish and Aquatic Invertebrate Ecotoxicity Studies for Sodium Dichloro-s-Triazinetrione

Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & Status

Acute – Freshwater Fish 850.1075 Rainbow trout 100 96-hr LC 50 : 358 μg ai/L Highly toxic McCann, 1976a (TN** 1038) Acceptable 1

98.3 96-hr LC 50 : 250 μg ai/L Highly toxic 256739 Acceptable 1

63 96-hr LC 50 : 240 μg ai/L Highly toxic 00019523 Supplemental

Bluegill 100 96-hr LC 50 : 810 μg ai/L Highly toxic McCann, 1971a (TN 368) Supplemental

63 96-hr LC 50 : 283 μg ai/L Highly toxic 00019523 & 00130832 Supplemental

57 96-hr LC 50 : 2400 μg/L Moderately toxic 00026194 (McCann, 1976b);TN 1030) Acceptable 1

7 96-hr LC 50 : 9800 μg/L Moderately toxic 00026192 (McCann, 1971b; TN 361) Supplemental Acute – Freshwater Invertebrate

850.1010 Waterflea 98 48-hr EC 50 : 110 μg ai/L Highly toxic 00154328 Acceptable 1

55.63 48-hr EC 50 : 199 μg ai/L Highly toxic 00007241 Supplemental
** TN = test number
1 While these studies are deemed acceptable, they were conducted under static conditions rather than flow-through and are based on nominal rather than measured concentrations. For purposes of a hazard assessment, they are considered acceptable.

Table 19 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate Ecotoxicity Studies for Sodium Dichloroisocyanurate Dihydrate

Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & StatusPage 52 of 80 Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & Status

Acute – Freshwater Fish 850.1075 Rainbow trout 98 96-hr LC 50 : 250 μg ai/L Highly toxic 00150951 Acceptable 1

71/12 3 96-hr LC 50 : 620 μg/L Highly toxic McCann, 1975a (TN 2 0800) Supplemental

71/12 3 96-hr LC 50 : 655 μg/L Highly toxic McCann, 1975b (TN 0799) Supplemental

Bluegill 98 96-hr LC 50 : 460μg ai/L Highly toxic 00150950 Acceptable

100 96-hr LC 50 : 1,720 μg ai/L Moderately toxic McCann, 1976c (TN 1039) Acceptable 1
Acute – Freshwater Invertebrate

850.1010 Waterflea 98.3 48-hr EC 50 : 280 μg ai/L Highly toxic 00150952 Acceptable 1

1 While these studies are deemed acceptable, they were conducted under static conditions rather than flow-through and are based on nominal rather than measured concentrations. For purposes of a hazard assessment, they are considered acceptable.

2 TN = test number

3 Multi-ai formulation containing 71% sodium dichloro- s -triazinetrione dihydrate and 12% simazine. Toxicity result expressed as μg formulation/L. Aquatic Plants-Chlorinated Isocyanurates/Chlorine

Data on chlorinate isocyanurates or chlorine ar e anticipated to be re quired for one vascular species, Lemna sp. (OCSPP 850.4400), three algal species (OCSPP 850.4500), and cyanobacteria (OCSPP 850.4550) are used to asse ss risk to aquatic plants. No data for chlorinated isocyanurates have been submitte d. However, there are data in the AWQC documents (1985, 1986) that adequately addresses e ffects for aquatic plants from chlorine so no additional testing of chlorinated isocyanur ates are required.
Isocyanuric acid Toxicity
Except for two subacute avian dietary studies with a salt of cy anuric acid, monosodium cyanurate, and an acute test w ith a freshwater invertebrate, D. magna , no effects data on cyanurate/isocyanuric acid has been submitted to the OPP for review in support of pesticide registration. The Agency recognizes that isoc yanuric acid is an EPA high production volume 8 (HPV) chemical for which a Screening Inform ation Data Set (SIDS) Assessment Report was performed (OECD SIDS 1999 and IIAHC 2003). Values found in these sources have been listed in the table below and consist of freshwater fish and invertebrate and gr een algae data. While some critical elements of these studies are identified in the HPV SIDS files, there is insufficient

8 http://www.epa.gov/chemrtk/index.htmPage 53 of 80 information available on the studies for AD to review the studies for purposes of a risk assessment. ECOSAR v1.1 was used to estimate freshwater and estuar ine/marine fish and invertebrate acute and chronic values a nd the median effect concentration (EC 50 ) and maximum allowable toxicant concentra tion (MATC; geometric mean of the NOAEC and LOAEC) for green algae. These values are also listed in Table 21. Isocyanuric ac id/cyanuric acid was not part of the training set for this model and sensi tivity as compared to data in the HPV summaries indicates the potential for the model in this case to significantly overestimate sensitivity Data are anticipated to be required for one vascular aquatic plant species, Lemna sp. (OCSPP 850.4400), three algal species (OCSPP 850.4500), and cy anobacteria (OCSPP 850.4550). Acute and chronic freshwater and estuarine/marine fish a nd invertebrate data a nd seedling emergence and vegetative vigor.
Table 20 Available Avian Acute Toxicity Studies for Isocyanuric Acid

Study Type Species Test material (% Purity) Toxicity Toxicity Classification MRID & Status

Acute – Avian Dietary 850.2200 Northern bobwhite Monosodium cyanurate 90.8-92.3% LC 50 : >10,000 ppm Practically non-toxic 00019604 Acceptable

Mallard Monosodium cyanurate 90.8-92.3% LC 50 : >10,000 ppm Practically non-toxic 00019605 Acceptable

Table 21 - Available Aquatic Organi sm data for Isocyanuric Acid
Receptor

Group Test Material a Surrogate Species Risk Scenario Toxicity Endpoint Reference/ Study Classification

Freshwater fish isocyanuric acid Generic fish Acute 96-h LC 50 = 72.0 mg/L ECOSAR v1.1 a

Rainbow trout Acute 96-h LC 50 >2100 mg/L b IIAHC 2004 b / Unacceptable c Bluegill Acute 96-h LC 50 >1000 mg/L b IIAHC 2004 b / Unacceptable c Fathead minnow Acute 96-h LC 50 >1000 mg/L b IIAHC 2004 b / Unacceptable c Japanese medaka Acute 96-h LC 50 >100 mg/L OECD SIDS 1999/ Unacceptable c Generic fish Chronic MATC = 1.85 mg/L ECOSAR v1.1 a

Freshwater invertebrates isocyanuric acid Daphnid Acute 48-h EC 50 = 24.6 mg/L ECOSAR v1.1 a

Daphnid Chronic MATC = 1.49 mg/L ECOSAR v1.1 a

D. magna Acute 48-hr EC 50 >1000 mg/L (static test, nominal) MRID 00132442 Supplemental

Waterflea Acute 48-h EC 50 = 1000 mg/L b OECD SIDS 1999 b / Unacceptable c Chronic NOEC = 65,900 μg/L b Estuarine/marine Isocyanuric Generic Acute 96-h LC 50 = 46.9 mg/L ECOSAR v1.1 aPage 54 of 80 Receptor

Group Test Material a Surrogate Species Risk Scenario Toxicity Endpoint Reference/ Study Classification fish acid Generic Chronic MATC = 2.45 mg/L ECOSAR v1.1 a Estuarine/marine

invertebrates Isocyanuric acid Mysid Acute 96-h LC 50 = 6.98 mg/L ECOSAR v1.1 a Mysid Chronic MATC = 4.82 mg/L ECOSAR v1.1 a

Algae isocyanuric acid Green algae EC 50 96-h EC 50 = 0.114 mg/L ECOSAR v1.1 a NOAEL MATC = 0.057 mg/L ECOSAR v1.1 a / Acceptable Model

EC 50 96-h EC 50 = 712 mg/L b IIAHC 2004 b / Unacceptable c EC 50 72-h EC 50 = 620 mg/L b OECD SIDS 1999 b / Unacceptable c NOAEL 62.5 mg/L b MATC (maximum allowable toxicant concentration) = geometric mean of the NOEC and LOEC

a ECOSAR v1.1 class specific estimations for aromatic triazines. Isocyanuric acid/cyanuric acid was not part of the training set for the ECOSAR model and values appear to potentially overestimate sensitivity. b While some critical elements of these studies are identified in the HPV SIDS f iles, there is insufficient information available on the studies for AD to review the studies for pur poses of a risk assessment. These studies would need to be submitted for review by AD for incorporation in a risk assessment.

c Study value is from a secondary source; the original study is not available. There is insufficient information available on the study to allow AD to conduct a revi ew for determination of acceptability for use in a risk assessment.

Appendix C REFERENCES
Isocyanurate Industry Ad Hoc Committee, “R obust summaries for sodium dichloro-striazinetrione (CAS No. 2893-78- 9) and sodium dichloro-s-t riazinetrione dihydrate (CAS No. 51580-86-0)”, revised May 20, 2004.
Isocyanurate Industry Ad Hoc Committee, “Robust summaries for trichloro-s-triazinetrione (CAS No. 87-90-1)”, revised May 20, 2004.
McCann, J.A. 1971a. CDB-63 (Sodium dichloro- s -triazinetrione 100%): Toxicity to Bluegill: Test No. 368. (U.S. Environmental Protec tion Agency, Pesticides Regulation Div., Agricultural Research Center, Animal Biology Laboratory, unpublished report.)
McCann, J.A. 1971b. Perf Perf Chlor (Sodium dichloro- s -triazinetrione 7%, Inert 93.7%): Toxicity to Bluegill: Test No. 361. (U.S. E nvironmental Protection Agency, Pesticides Regulation Div., Agricultural Research Ce nter, Animal Biology Laboratory, unpublished report.)
McCann, J.A. 1975a. Algimycin T (Sodium dichloro- s -triazinetrione dihydr ate 71.5%; Simazine 2-chloro-4, 6-bis ethylamino-s- triazine 12.0%; Inert 16.5%): T oxicity to Rainbow Trout|: Test No. 800. (U.S. Environmental Protec tion Agency, Pesticides Regulation Div., Agricultural Research Center, Animal Biology Laboratory, unpublished report.)
McCann, J.A. 1975b. Algimycin T (Sodium dichloro- s -triazinetrione dihydr ate 71.5%; Simazine 2-chloro-4, 6-bis ethylamino-s- triazine 12.0%; Inert 16.5%): T oxicity to Rainbow Trout|:Page 55 of 80 Test No. 799. (U.S. Environmental Protec tion Agency, Pesticides Regulation Div., Agricultural Research Center, Animal Biology Laboratory, unpublished report.)
McCann, J.A. 1976a. Cu-Chlor Concentrate (Sodium dichloro- s -triazinetrione 100%): Toxicity to Rainbow Trout|: Test No. 1038. (U.S. Envi ronmental Protection Agency, Pesticides Regulation Div., Agricultural Research Ce nter, Animal Biology Laboratory, unpublished report.)
McCann, J.A. 1976b. Utiken Shock Treatment (Sodium dichloro- s -triazinetrione 57%, Inert 43%): Toxicity to Bluegill|: Test No. 1030. (U.S. Environmental Protection Agency, Pesticides Regulation Div., Agricultural Re search Center, Animal Biology Laboratory, unpublished report.)
McCann, J.A. 1976c. Arco Super shock Granular (Sodium dichloro- s -triazinetrione 100%) Toxicity to Bluegill|: Test No. 1039. (U.S. Environmental Protection Agency, Pesticides Regulation Div., Agricultural Research Ce nter, Animal Biology Laboratory, unpublished report.)Page 56 of 80 

### Appendix D: ECOSAR Version 1.1 Resu lts Page for Isocyanuric Acid

SMILES : N1C(=O)NC(=O)NC1(=O) CHEM : 1,3,5-Triazine-2,4,6(1H,3H,5H)-trione CAS Num: 000108-80-5 ChemID1: MOL FOR: C3 H3 N3 O3 MOL WT : 129.08 Log Kow: 1.952 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value - for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: 360.00 (deg C, PhysProp DB exp value for Wat Sol est) Wat Sol: 2.768 (mg/L, EPISuite WSKowwin v1.43 Estimate) Wat Sol: (User Entered) Wat Sol: 2000 (mg/L, PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: 1.952 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 2000 (mg/L, PhysProp DB exp value)

------------------------------------------------ Available Measured Data from ECOSAR Training Set

------------------------------------------------

No Data Available

-------------------------------------- ECOSAR v1.1 Class-specific Estimations

-------------------------------------- Triazines, Aromatic Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Triazines, Aromatic : Fish 96-hr LC50 72.039 Triazines, Aromatic : Daphnid 48-hr LC50 34.650 Triazines, Aromatic : Green Algae 96-hr EC50 0.114 Triazines, Aromatic : Fish ChV 1.852 Triazines, Aromatic : Daphnid ChV 1.491 Triazines, Aromatic : Green Algae ChV 0.057 Triazines, Aromatic : Fish (SW) 96-hr LC50 46.900 Triazines, Aromatic : Mysid (SW) 96-hr LC50 6.987 Triazines, Aromatic : Fish (SW) ChV 2.456 Triazines, Aromatic : Mysid (SW) ChV 4.820

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96-hr LC50 116.978 (Baseline Toxicity) : Daphnid 48-hr LC50 61.332 : Green Algae 96-hr EC50 56.868 : Fish ChV 11.375 : Daphnid ChV 6.371 : Green Algae ChV 12.545

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.Page 57 of 80 ------------------------------ Class Specific LogKow Cut-Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut-offs presented below, then no effects at saturation are expected for those endpoints.

Triazines, Aromatic:

------------------- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

------------------------------------------------------------------------------Page 58 of 80 

### Appendix E: Response to the 60-Day Public Comments on the Chlorinated Isocyanurates
The Office of Pesticide Programs' Antimicrobi al Division (AD) has reviewed the public comments received concerning the Preliminar y Work Plan (PWP) for the Chlorinated Isocyanurates Registration Review, Case# 0569 (Docket ID Number EPA- HQ- OPP- 2012- 0794).

Comments were received from the Isocyanurates Industry Ad Hoc Committee (IIAHC), a consortium (consortium numbe r 55643) of 12 manufacturers worldwide of the chlorinated isocyanurates. The following are the responses to each one of IIAHC’s, comments in their letter dated February 11, 2013, which may be seen in the docket for this case:

The first five comments were determined to be the most critical issues requiring a response per IIAHC letter.

Comment 1. The PWP indicates in several places that the Agency needs to review several references cited in the HPV Summaries, whic h was produced and submitted to the EPA by the IIAHC. The PWP also cites other needs for data, part icularly ecotox data (acu te toxicity to fish, algae, fish juvenile growth, Daphnia magna re production) which the IIAHC or its individual members own. The IIAHC and members thereof also own several new studies (chironomid, earthworm, phyto-toxicity, skin sensitizer, physi cal/chemical properties, acute inhalation on isocyanuric acid, new Ames test, and others) not specifically requested by the PWP, but which could be of considerable intere st to EPA’s review of the chlo rinated isocyanurates. Further, twelve studies were submitted to the EPA in No vember, 2007. No DERs have been received to date, and the IIAHC believes that these studies, and the other studies mentioned above, should all be reviewed prior to the issuance of a DCI.
The IIAHC would be happy to meet with the EP A and review any and all additional studies which the EPA might require for performing the Registration Review. The IIAHC and members thereof would be happy to submit those studies re quired by the EPA for the Registration Review.
Agency's Response: Regarding studies submitted to the Agency in November, 2007, upon further review of the Agency’s files the following studies have been located, and will be reviewed prior to issuing any GDCI, and if found to be acceptable for use in a risk assessment will be used in lieu of mode led values, where appropriate.

MRID Citation Reference 47302305 Skin sensitization in the guinea pi g – Magnusson and Kligman maximization method (NaDCC dihydrate). 47302306 Vryenhoef, H.; Hill, J. (2007) Monosodium Salt of Cyanuric Acid: Navicula pelliculosa : Algal Inhibition Test. Project Number: 2255/0001. Unpublished study prepared by Safepharm Laboratories, Ltd. 52 p. 47302307 Sewell, I.; Mullee, D. (2007) M onosodium Salt of Cyanuric Acid: DaphniaPage 59 of 80 MRID Citation Reference
magna Reproduction Test. Project Number: 2255/0002. Unpublished study prepared by Safepharm Laboratories, Ltd. 70 p. 47302308 Sewell, I.; Mullee, D. (2007) Monosodium Salt of Cyanuric Acid: Fish, Juvenile Growth Test - 28 Days. Project Number: 2255/0003. Unpublished study prepared by Safepharm Laboratories, Ltd. 63 p. 47302309 Goodband, T.; Mullee, D. (2007) MonosodiumSalt of Cyanuric Acid: SedimentWater Chironomid Toxicity Test Using Spiked Sediment. Project Number: 2255/0004. Unpublished study prepared by Sa fepharm Laboratories, Ltd. 57 p. 47302310 Goodband, T. (2007) Monosodium Salt of Cyanuric Acid: Acute Toxicity to Earthworms ( Eisenia foetida ). Project Number: 2255/0005. Unpublished study prepared by Safepharm Laboratories, Ltd. 35 p. 47302311 Clarke, N. (2007) Monosodium Salt of Cyanuric Acid: Assessment of the Inhibitory Effect on the Respiration of Activated Sewage Sludge. Project Number: 2255/0006. Unpublished study prepar ed by Safepharm Laboratories, Ltd. 29 p. 47302312 Cyanuric acid: Physical and chemical characteriscs: Partition coefficient (nOctanol/Water). 41943101 Murphy, D.; Peters, G. (1991) Sodium o-Nitrophenolate: A 96-Hour FlowThrough Acute Toxicity Test with the Rainbow Trout ( Oncorhynchus mykiss ). Unpublished study prepared by Wildlife International, Ltd. 38 p.

Comment 2. We do not agree with the conclusion that trichloro-s-triazine trione or sodium dichloro-s-triazinetrione are dermal sensitizers.
The study cited is MRID 00144720, J. Mappes, “D ermal sensitization test performed on Na trichloroisocyanurate”, Bioa ssay Systems Corp., Project 1200 66, Oct 1984. There are several issues with this study which indicate that the study may not be acceptable or that the stated conclusion is incorrect:

 The 1987 DER concluded that it is a "very mild sensitizer." However, the original data review in 1984 by James Wilson of the EPA agr eed with the study conclusion that it is not a sensitizer.

 There were too few animals used in the st udy and the inductions and challenges occurred at different times than in the current protoc ol. A minimum of 20 treatment animals (versus 10 in the Mappes study) is recommended for the Buehler method. This may have been a contributing factor to the equi vocal nature of the response, which was borderline at worst.

 The product was applied in a dry, pure form during the initial expos ures and during the challenge. However, the study reported no ir ritation during the initial exposure, even though the product is a severe dermal irritant (when wet), see Tabl e 13 of the PWP. A slight amount of moisture pr esent during the challenge could have been the cause of the observed minor irritation.
Performing a skin sensitizat ion test with a severe dermal irrita nt is inherently difficult. The test substance should be tested at a c oncentration where it is not irri tating. Plus, the severity of thePage 60 of 80 dermal irritation produced by either trichloro-s-triazinetr ione or sodium dichloro-s-triazinetrione is strikingly different for dry product versus wet product, with wet material being much more irritating.
More recent studies which fully meet EPA guide lines, on both trichloro- s-triazinetrione and sodium dichloro-s-triazinetrione dihydrate, have concluded that the product is not a sensitizer:

 D. Allen, Safepharm Laboratories Ltd. ( 2000) ACL 90XG Chlorinating Composition: skin sensitization in th e guinea pig - Magnusson and Kligman maximization method, Project 1402/006, 22 pp.

 D. Allen, Safepharm Laboratories Ltd. ( 2000) ACL 90 Chlorinating Tablets: skin sensitization in the guinea pig - Magnu sson and Kligman maximization method, Project 1402/007, 22 pp.

 D. Allen, Safepharm Laboratories Ltd. (2000) ACL 56G Chlorinating Composition: skin sensitization in the guinea pig - Magnu sson and Kligman maximization method, Project 1402/005, 22 pp. MRID 47202305

These studies substantiate IIAHC ’s recommendation that these chlorinated isocyanurates should not be classified as skin sensitizers. These IIAHC-owned studies were referenced in the HPV summaries. One has been submitted to the EPA. The IIAHC would be happy to discuss and submit the other two studies, as required.
Agency's Response: The agency will review all available studies during registration review and use a weight of evidence appro ach to determine if the chlorinated isocyanurates are dermal sensitizers. The above mentioned studies should be submitted by IIAHC so they can be included in the review.

Comment 3. Tables 1 and 8 are intended to summarize all of the data requirements. However, additional potential data requirements are scatte red throughout the PWP and are not included in these summary tables. For example, in Appendix A, Page 36, the PWP indicates that the Agency needs to review several primary references cited in the HPV Summaries. However, Tables 1 and 8 list some but not all of the re quired data. The Final Work Plan should clarify the anticipated data requirements.
Also, pages 48-49 indicate that numerous aquatic toxicity data requireme nts, including chronic data (850.1400 Fish Early-Life Stage Toxicity Test for freshwater and for marine fish, 850.1300 - Daphnid Chronic Toxicity Test for freshwat er invertebrates, and 850.1350 - Mysid Chronic Toxicity Test for marine inverteb rates), are anticipated to be re quired. However, these studies are not included in either Table 1 or Table 8. The Fi nal Work Plan should specify whether such data are required or not.

The IIAHC would like to meet with EPA to disc uss and further clarify the data requirements.Page 61 of 80 Agency's Response: The chronic fish and aquatic inverteb rate studies are anticipated to be required as indicated in Appendix C. Tables 1 and 8 have been re vised to include those expected requirements. Additionally, Tables 1 and 8 have been revised to include any missing environmental fate requirements.

Comment 4. It is clear that the ECOS AR v1.1 model used to estimat e the toxicity endpoints for isocyanuric acid in Tables 11 and 21 provides valu es which are completely incompatible with the values from experimental studies. Despite this, the results from the model in Table 21 have been selected for use in Table 11 over the experimental data because EPA did not have copies of the studies. As noted above, the IIAHC is willing to submit any and all studies referenced in the HPV Summaries, if required. Th e IIAHC and members thereof al so own additional test data which can be provided for Agency review.

In contrast to the ECOSAR calcula tions, all of our ecotoxicity experimental data have shown that isocyanuric acid has very low toxicity to aqua tic organisms. The PWP provides no details on how the ECOSAR calculation was accomplished. The results from the ECOSAR model should be dropped from the environmental risk assessm ents, as they do not provide any realistic estimate of the true toxicity of isoc yanuric acid to aquatic organisms.
Agency's Response: The difference in sensitivity betw een ECOSAR modeled data and HPV data has been noted in the document. The Agency will use submitted experimental ecotoxicity data, which upon review have been found to be “Acceptable” for use in a risk assessment 9 over modeled ecotoxicity data ( i.e ., ECOSAR results). If the IIAHC or other interest ed parties are aware of experimental data that may be able to be used to replace the modeled values, these studies should be submitted for review and consid eration in the risk assessment. The ECOSAR calculations are added as Appendix D.

Comment 5. The re-entry level for swimming pools is gi ven as 3 ppm chlorine. This is true for many labels, but some labels (EPA Reg. Nos. 1258-1338, 5185-100, 5185-144 and 88896-3) have recently been approved with a re-entry le vel of 4 ppm chlorine (“Reentry into treated swimming pools is prohibited above levels of 4 ppm chlorine due to risk of body injury.”). Furthermore, the EPA has agreed that a re-ent ry level of 4 ppm chlo rine is acceptable at a November 16, 2011 meeting betw een representatives of the IIAHC and the OCSPP, Antimicrobial Division. The Final Work Plan should indicate that the accepta ble re-entry level is 4 ppm chlorine.
Agency's Response: The ppm level for re-entry into swimming pools has been changed to 4ppm in the FWP.

9 U.S. EPA. 2004. Overview of the Ecological Risk Assess ment Process in the Office of Pesticide Programs. Office of Prevention, Pesticides, and Toxic Substances. Office of Pesticide Programs. Washington, D.C. January 23, 2004. Support Document 1: Study Classification used by EFED in Data Evaluation Records (DERs) http://www.epa.gov/oppfead1/endanger /consultation/ecorisk-overview.pdfPage 62 of 80 

### A dd i t i on a l C o mm e n t s on t h e P W P

Comment 6. We are surprised that the PWP does not include a specific request for Nontarget Plant Protection Data, incl uding 850.4225 Seedling Emergence Tier II and 850.4250 Vegetative Vigor Tier II, as these were required in the May 16, 2012 DCI for NaBr, due to its once-through industrial water systems uses. Existing labels for the chlorinated isocyanu rates allow for similar uses. The IIAHC is currently performing such a st udy and would be willing to submit this data to the EPA, if EPA requires this data.
Agency's Response: Seedling emergence data for semi-aquatic plants (850.4100, rice) might be useful for the risk assessment. However, the st udy is needed only if the risk quotient from any aquatic plant growth Tier II study (850.4400, 850.4500, or 850.4550) exceeds a level of concern for aquatic plants. The agency has updated Tables 1 and 8 to reflect this anticipated requirement. Vegetative vigor data (850.4150, rice) is expected to be required fo r uses in which spray drift or irrigation using contaminated water may be a concern.

Comment 7. The second sentence states that five activ e ingredients are included in this case but they are not named or listed here. The five active ingredients appear to be four listed in Table 3 and potassium dichloro-s- triazinetrione, as mentioned in paragraph 2 on page 7.
Agency's Response: The Case Overview has been updated to reflect that there are 3 active ingredients which have product registra tions for chlorinated isocyanurates.

Comment 8. The third sentence incorrectly states that potassium dichloro-s-triazinetrione was never registered by EPA in any pesticide products. In fact, EPA Reg. No. 524-105 was registered from 1975 to 1993.
Agency's Response: The Agency acknowledges th is fact and has made the correction to the FWP.

Comment 9. The entry for the Available Chlorine cont ent for trichloro-s-triazinetrione is questionable. We suggest that the range for products containing 99% or more trichloro-striazinetrione should be 89.5 - 91.5%.
Agency's Response: The Agency concurs and the appropriate change has been made to Table 3 in the FWP.
Comment 10. (a) The first line of Table 4 (four instances ) mistakenly refers to Table 1 for product identity and composition. These re ferences actually refer to Table 3. (b) Table 4 does not identify the source/date of the information pr ovided. This document, as with others in the past, will be used as a refere nce source and it is essential to document the source of data. (c)
The IIAHC has recently generated new GLP data for several physical/c hemical properties of trichloro-s- triazinetri one, sodium dichloro-s-triazinetrione and sodium dichloro-s-triazinetrionePage 63 of 80 dihydrate, including better values for pH, melting point, density and solubility in water. The IIAHC would be willing to submit th e relevant studies, if required.
Agency's Response: (a) The Agency concurs with these comments and the FWP has been changed accordingly.
(b) The agency concurs with these comments and th e FWP has been changed to insert the source of data, 1988 Registration Standard and 1992 RED.
(c) The IIAHC should submit the above mentioned st udies be submitted so they can be included in the review.

Comment 11. Table 5 indicates that th ere are two active produc ts based on dichloro-striazinetrione. To the best of our knowledge , no company currently sells a product based on dichloro-s-triazinetrione and no manufacturer has a Manufactu ring Use label registered for dichloro-s-triazinetrione.
NPIRS lists two products under PC Code 081401: 5185-497 (Bio-Lab Wonder Tab) and 6466- 12 (Fitzpatrick Bros. Kitchen Klenzer). However, 5185-497 is improperly classified in NPIRS as the label indicates that this product contains 66.7% sodium dichloro-s-triazinetrione (PC Code 081404), not dichloro-s-triazinet rione. BioLab (IIAHC memb er) confirms that 5185-497 contains sodium dichloro-s- triazinetrione. NPIRS does not list a product containing 99.7% dichloro-s-triazinetrione. Fitz patrick Bros. has confirmed that 6466-12 (Kitchen Klenzer, last label revision 2003) actually cont ains 0.8% sodium dichloro-s-tri azinetrione, not dichloro-striazinetrione, therefore, th is product is mislabeled.
Agency's Response: The FWP has been updated to reflect th at only three activ e ingredients are contained in registered pestic ides and are to be assessed in Case 5069: sodium dichloro- s

triazinetrione (PC Code: 081404); trichloro- s -triazinetrione (PC Code: 081405); and sodium dichloro- s -triazinetrione dihydr ate (PC Code: 081407).

Comment 12. Table 5 indicates that some formulations are liquids or liquid-solutions. Liquid formulations of the chlorinated isocyanurates are not sufficiently stable to package and market as finished products. Therefore, we believe that all of the formulations listed in Table 5 as Liquid formulations or Liquid- soluti ons are misclassified. Although th e NPIRS database lists a number of products classified as “sol utions-ready to use”, these products are all actually solid formulations (e.g., tablets or granules).
EPA currently defines formulations based on stan dard agricultural pesticide terminology. This can cause confusion for antimicrobial formulatio ns, which have inheren tly different physical properties and use patterns than th e agricultural pesticide formulations. This is especially true for solid formulations, as the agricultural pest icide terminology implies certain properties which normally do not apply to the antimicrobial form ulations. In partic ular for Table 5, for agricultural pesticide formulati ons “wettable powders” are dr y, finely ground solids that are usually mixed with water to form a suspension for application as a spray. In many cases, thePage 64 of 80 product has very low solubility in water. In contrast, tr ichlor-s-triazinetrione, sodium dichloro-striazinetrione and sodium dichlo ro-s-triazinetrione dihydrate powde rs are “soluble powders”, that is, they are fully soluble in water. They are eith er added directly to the water system, where they dissolve completely, or are pr e-dissolved in water and then added to the water system.
Agency's Response: The Agency concurs with this comment and the FWP has been changed to indicate that the wettable powde rs are actually soluble powders a nd that no liquid formulations are registered

. Comment 13. The IIAHC requests a copy of the fu ll list of chlorinated isocyanurate products/uses derived from labels which was rece ntly prepared by EPA’s contractor. This list would be very useful in se veral situations for our unders tanding of the Work Plan.
Agency's Response: This information could be obtained through a Freedom of Information Act (FOIA) request.

Comment 14. The 600 ppm Maximum Application Rate list ed for the Drinking Water use site is incorrect. The correct value is 500 ppm.
Agency's Response: The Agency concurs with this comment and the FWP has been changed accordingly.

Comment 15. Page 10, Table 6 – This corresponds to co mment #5 in this response to comments appendix (See Critical Issue #5).
Agency's Response: The Agency concurs with this comm ent and the FWP has been updated.

Comment 16. To the best of our knowledge, no comp any currently sells a product based on dichloro-s-triazinetrione.
Agency's Response: The Agency concurs with this comm ent and the FWP has been updated.

Comment 17. There are four instances where “sodium dichloro-s-triazinetrione dihydrate” is incorrectly written as “dichlor o-s-triazinetrione dihydrate”.
Agency's Response: The Agency concurs with this comm ent and the FWP has been updated.

Comment 18. There is one instance where “sodium dich loro-s-triazinetrione” is incorrectly written as “dichloro-s- triazinetrione”.
See comment above on Table 5 concerning liquid form ulations. We believe that all formulations classified as “ready-to-use solutions” are inaccurate.
See comment above on Table 5 concerning ag ricultural pesticide terminology. The PWP indicates that some chlorinated isocyanurate formul ations are “water dispersible granules”. For agricultural pesticide formulati ons, “water dispersible granules” normally comprise a small percentage of active ingredient adsorbed onto an inert carrier. Water dispersible granules must bePage 65 of 80 mixed with water, where the granules break apar t into fine particles, forming a suspension or slurry, which is then applied by spraying. This suspension requires constant agitation to keep the particles suspended in water. In contrast, trichlor-s-triazinetrione, sodium dichloro-striazinetrione and sodium dichlo ro-s-triazinetrione dihydrate granul es are “soluble granules”, that is, they are fully soluble in water. They are eith er added directly to the water system, where they dissolve completely, or are pre-di ssolved in water and then adde d to the water system. We do not know of any chlorinated isocyanurate formul ation where the active ingredient is adsorbed onto a granular carrier. Therefore, we believe that “water dispersible granules” is not an accurate formulation type descriptor for a ny chlorinated isocyanurate product.
Agency's Response: The Agency concurs with this comm ent and the FWP has been updated.

Comment 19. SRI International, “Chl orinated isocyanurates”, Chemical Economics Handbook, Feb 2012 (page 14) provides more recent information on the estimated U.S. consumption than the 2006 Kline report. It estimated that the U. S. consumption in 2011 was less than 4% higher than in 2004.
Agency's Response: The agency concurs with these comments and the FWP be changed accordingly.

Comment 20. In the second sentence, “dehydrate” is inco rrect. The correct term is “dihydrate”.
Agency's Response: The agency concurs with this comm ent and the FWP has been updated.

Comment 21. In the 3rd sentence, “such transien t” should be “suc h as transient”.
Agency's Response: The agency concurs with this comm ent and the FWP has been updated.

Comment 22. In the 3rd sentence, “such chemical burns” should be “such as chemical burns”. In the 4th sentence, “should be not be” is more correctly written as “should not be”.
Agency's Response: The agency concurs with this comment and the FWP has been updated.

Comment 23. “Sodium dichloro-isocyanur ate hydrate” is incorrect . The correct name is “Sodium dichloro- isocyanurate dihydrate”.
Agency's Response: The agency concurs with this comm ent and the FWP has been updated.

Comment 23b. If there are no dichloro-s-triazinetri one products on the ma rket, the dichloros-triazinetrione incidents are probably not lis ted properly.
Agency's Response: The agency concurs with this comment and the FWP has been updated.

Comment 24 . Page 15, Table 8, Indoor Exposure, Inhalation and Page 6, Table 1

Table 8 indicates that the test substance for th e required indoor exposure studies should be the TGAI. However, the exposure studies already performed by the AEATF or currently beingPage 66 of 80 planned by the AEATF normally use a surrogate compound to minimize risk to the human test subjects. For example, the mop study (M RID 48210201) with its supplement (MRID 48724801) used DDAC as the test substance. The Final Work Plan should clearly state that the use of a surrogate compounds in the expos ure studies will be acceptable.
Agency's Response: The Agency concurs with this comm ent and the FWP has been updated.

Comment 25. There is no data requirement for derm al exposure data, even though the AEATF studies contain such data, and such data are relevant to an informed risk assessment.
Agency's Response: The Agency does not concur with th is comment at this time. Although dermal points of departure (PODs) for systemic eff ects were selected as listed in Table 9 of the PWP, these PODs are from oral exposure studies and when adjusted for dermal absorption yield dermal equivalent PODs of gr eater than 1000 mg/kg/day. This means that systemic dermal toxicity is very low and does not need to be assessed. Dermal irritation may need to be addressed because acute tests indicate Tox I.

Comment 26. Page 15, Table 8, Residential Post Appli cation, Disinfected Floors, Incidental Oral Exposure and Page 6, Table 1

OCSPP GLN 875.2300 is not listed on th e EPA website for EPA test me thods. It only exists in draft form.
The chlorinated isocyanurates provi de available chlorine, therefor e, these would only be used on hard surface flooring, such as vi nyl tile or ceramic tile. Thes e products would not be used on carpets, since the carpets would potentially be bl eached and thus permanently discolored. The Final Work Plan should clarify that the desire d Indoor Surface Residue Di ssipation data is for hard surface flooring only. The IIAHC is willing to work with EPA on clarifying label language, if needed.
Simple worst-case calculations can be used and would indicate minimal exposure from disinfected floors, much less than the expected exposure from other uses such as swimming pools or drinking water. Woul d a worst-case calculation fulf ill this data requirement?
Agency's Response: The Agency concurs with these comment s and is aware that the guideline exists only in draft form and w ill assist in the development of st udy protocols. The Agency will also consider exposure calculations submitted as waiver requests and determine their impact on whether data are need or not.
The FWP has been changed to indicate that th e Surface Residue Study is only needed for hard surface flooring only.

Comment 27. For clarity, all abbreviations should be e xplained when first used. In Footnote 6, “DtD” means “Down the Drain”.Page 67 of 80 Agency's Response: The Agency concurs with this comment and the FWP has been updated.

Comment 28. Footnote 7 to Table 8 indicate s that some uses may be eligible for data waiver if Selenastrum capricornutum NOAEC results are greater than 1 ppm. The HPV Summaries included a study (T. Hollister (1978) Acute Toxic ity of Cyanuric Acid (BN-78-1384330-1) to the Fresh-Water Alga Selenastrum capricornutum ; EG&G Bionomics, Report No. BP-78-9-137; Study No. H74-500) which found that the 96 hr NOAEC for Selenastrum capricornutum was greater than 100 ppm. This study is owned by O ccidental Chemical Corp. (IIAHC member) but has not been submitted to the EPA. Shikoku In ternational Corp. (IIAHC member) also owns data on algae which also shows that the NOAEC is greater than 100 ppm.
The IIAHC also has algal ( Navicula pelliculosa and Skeletonema costatum , a marine algae) toxicity data on the monosodium salt of isocya nuric acid. We would be happy to submit these studies, if required.
Agency's Response: The agency will review the Selanastrum study when it is submitted by IIAHC to fulfill the anticipated data requirement in Table 8. Results from that study, if acceptable, will determine if the additional waiver is accepted. A waiver request for the other plant data may be submitted at the same time, based on the >1 ppm results.

Comment 29. A petition submitted to the U.S. FDA by Occidental Chemical Corp. (IIAHC member) calculated the potential human exposure to isocyanuric acid due to use of a sodium dichloro-s-triazinetrione base d product in pulp/paper slimicide use. Using worst case assumptions, the estimated daily intake of isocyanuric acid was considerably lower than the chronic RfD in Table 9. Based on these results and other data submitted, FDA approved this product (EPA Reg. No. 935-71) for this use. See Food Contact Substance Notification (FCN) 000495, effective June 18, 2005. FCN’s are listed on the FDA’s website at: http://www.fda.gov/Food/FoodIngredientsPac kaging/FoodContactSubs tancesFCS/ucm116567.ht

m. Use of the chlorinated isocyanurates for pres ervation of adhesives is on EPA Reg. No. 935-71 only. This product has not been approved by the FDA for preservation of food-contact adhesives. As use for food-contact adhesives is not contemplated, the request ed data on this use should not be required.
Agency's Response: Regarding the pulp and paper slimicid e use, EPA is required to conduct aggregate risk assessments which essentially comb ine all sources of exposure to all pesticides that have cyanuric acid/isoc yanuric acid as a degradate including food, drinking water, residential, FDA-regulated uses, etc. The risk due to one chlorinated isocyanurate used as a slimicide cannot be considered in isolation. Howe ver, if actual residue data were submitted to FDA, the same data should be submitted to EPA as should the approach used to estimate dietary intake.Page 68 of 80 Regarding adhesive preservation, as the use appears on a FIFRA-approved pesticide label, it is the agency’s position that either the associated risk must be included in th e aggregate risk or the label should be revised to stat e that the adhesive preservati on use is for nonfood contact only.

Comment 30. The HIARC report (2001) does not appear to be publically available. The IIAHC requests a copy for review.
Agency's Response: The HIARC report (2001) will be pl aced in the docket at EPA-HQ-OPP2012-0794.

Comment 31. For clarity, all abbreviations should be e xplained when first used. For example, UF = uncertainty factor and RfD = refere nce dose. (see http://www.epa.gov/risk/doseresponse.htm)
Table 9 does not reference the original reports for the data, but refers to the HIARC report, which does not appear to be publically available. Since it is unclear whic h reports Table 9 refers to, it is difficult to comment on some of the conclusions in the Table.
Two entries in Table 9 incorrectly reference a Developmental Toxicity study with rats. Appendix B (page 44) indicates that this data is from D. Rodwell ( 1990) Teratology study in rabbits with monosodium isocyanurate, Sp ringborn Laboratories Inc., Study 3222.1, MRID 42054101, which was done on rabbits, not rats. Th is correction was made in T. McMahon, 3/26/01, D270655 (cited in section 3.2.2). Anot her study on rats, MRID 105168, resulted in a higher NOAEL, so it is not rele vant to a toxicology endpoint.
Footnote A indicates that the endpoints in Table 9 are for isocyanuric acid. However, the last entry (Inhalation) in Table 9 is for the active ingredient (sodium dichloro-s-triazinetrione dihydrate). This data appears to be from G. Rusch, Bio/dynamics (1979) A four week inhalation toxicity study of sodium dich loro-s-triazinetrione dihydrate in the rat, Project No. 78-7154, MRID 28525, 97495 or 132438, which was refe renced by T. McMahon, 3/26/01, D270655. Therefore, Footnote A is confusing as the inhala tion endpoint is for a different material than isocyanuric acid.

The IIAHC now has a four-hour acute inha lation study on isocyanuric acid, which found no deaths at 5.25 mg/L. The IIAHC is willi ng to submit this report, if required.
Agency's Response: The agency concurs with the comments regarding Table 9 and has revised Table 9 as appropriate.

Comment 32. The table indicates that th e chronic RfD is 1.5 mg/kg/day, which is based on the NOAEL of 154 mg/kg/day from th e 2-year rat study and an UF of 100. However, MRID 44834403, which was submitted to the EPA, indicates that this value is overly conservative. In particular, this report indicat es that the UF should be le ss than 100. The normal UF of 100 comprises a factor of 10 for intra-human variatio n and a safety factor of 10 for extrapolatingPage 69 of 80 from rat to human. However, this report concluded that for the specific effects seen in the 2-year rat study, the rat is more sensitive than humans. In particular, the rat is more susceptible to the formation and retention of urin ary calculi, formed by precipita tion of isocyanuric acid/sodium isocyanurate in the kidneys at high doses. The rat is inherently more susc eptible than humans due to physiological differences. Therefore, the repo rt concluded that a safety factor of 10 for interspecies extrapolation is unr easonable and should be reduced.

The IIAHC recommends that the EPA reconsider the calculation of the chronic RfD, using a smaller UF than 100.
Agency's Response: The Agency will reevaluate the toxici ty database and endpoints during the risk assessment phase of registration review a nd will consider the findings of MRID 44834403 at that time.

Comment 33. The reference to “PTAP” is incorrect. This should refer to isocyanuric acid.
Agency's Response: The Agency concurs with this comment and the FWP has been updated.

Comment 34. The last paragraph indicates that “resid ue chemistry data are expected to be needed to determine dietary exposure”. However, the exact nature of the needed data is not clearly identified in Table 1 or Table 8. The II AHC would like to meet with the EPA to discuss what, if any, data will be required.
Agency's Response: Tables 1 and 8 both have the follo wing as does the text at 3.2.1:

 Residue chemistry data are anticipated to be needed to determine dietary exposure to cyanuric acid/isocyanuric acid following sani tization of food contact surfaces of food processing plants (including da iries) and food-handling faci lities (including public eating places). Protocol submission is recommended. The anticipated DCI will address this.

 Migration of cyanuric acid/isocyanuric acid from preserved adhesive to food and from paper/paperboard to food following the slimic ide use. The anticipated DCI will provide that a protocol must be submitted for EP A approval prior to initiating the study.

Comment 35. The third sentence says that “Residue chem istry data are expected to be needed to determine dietary exposure to the stable degrad ates and tautomeric pa ir cyanuric acid and isocyanuric acid following ...”. This sentence imp lies that degradates other than isocyanuric acid/cyanuric acid will be evalua ted. There are no other “degra dates” other than isocyanuric acid/cyanuric acid.
Agency's Response: The agency agrees that there are no other “degradates” other than isocyanuric acid/cyanuric acid. Th e sentence has been modified to “Residue chemistry data are expected to be needed to determine dietary expos ure to the stable, tautom eric degradate pair of cyanuric acid and isocyanuric acid following...” to clarify Cyanuric acid and isocyanuric acid are meant to be described as being both stable degradates and a tautomeric pair.Page 70 of 80 Comment 36. Section 3.2.2 Paragraph 1 states: “...contamination of drinking water by the degradate cyanurate/isocyanurate may occur as a re sult of discharge from paper and paperboard mills, down-the-drain from swimming pools or f ood-handling establishments, or run-off from livestock premises.” We disagree that these disc harges lead to any significant contamination of drinking water. Many of these discharges wi ll go through a WWTP before discharge to the environment and any surface water used for drinki ng water will be treated at a drinking water plant. Either process could remove most of th e isocyanuric acid from the water. In addition, biodegradation of the isocyanuric acid after bein g released to the environment and the large dilution expected upon discharge would result in isocyanuric aci d concentrations much lower than the concentrations resulting from direct treatment of drinking water.
Furthermore, published data (L. Wise, E. Walte rs (1917) Isolation of CYA from soil, J of Agricultural Research, 10, 85-91) indicate that is ocyanuric acid is formed by natural processes, resulting in a natural isocyanuric acid level in soil up to 6 ppm. Once treated and diluted, the discharges described above will result in average levels in soil and natural bodies of water much lower than the natural level.
Agency's Response: The Agency acknowledged in its Pre liminary Work Plan (beginning on page 36) that,
“An examination of the chemical structure, op en literature from Scien ce Direct (Anderson, 2002: Kontchou and Gschwind, 1999, Table 12) and a review of informa tion in a Robust Summary in the HPV documentation (http://www.epa.gov/hpv/pubs /summaries/tricltrz/c14659re.pdf-, Table 12) indicates that a high percen tage (up to 100%) of cyanuric acid may be removed either by aerobic WWTPs using acclimated microorganism s or WWTPs using anaerobic conditions (acclimated or unacclimated microorganisms). The primary removal mechanism was attributed to mineralization because (1) there was no evid ence of sorption to sludge based on the low log Kow (1.95) and water solubility (2,000 mg/L) and (2) the study authors re ported the release of CO 2 and NH 3 or the incorporation of these s ubstances into microbial biomass.”
To be able to give merit to this claim of mi neralization, the Agency would need to review and evaluate the primary references cited in the HPV documentation. These fate data correspond to anticipated data requirements listed in Table 8 a nd the IIAHC and its members are encouraged to submit this data for these requirements.
If fate data submitted to meet these anticipated data requirements are found to be acceptable and support rapid mineralization, the agency would be able to agree with th e commenter that postWWTP discharges from paper and paperboard mills and down-the-drain from swimming pools or food-handling establishments would not be expect ed to result in releases of cyanuric acid to surface water downstream of these establishments and there would be no potential for cyanuric acid to enter drinking water inta kes downstream of these sources. For run-off from livestock premises that would not undergo wastewater treatment, however, additional evidence of removalPage 71 of 80 in the surface water environment such as that provided by the anaerobic aquatic and aerobic aquatic metabolism studies would be required to de monstrate that there would be no potential for surface water downstream of these locations to c ontain cyanuric acid that could enter drinking water intakes downstream of livestock premises.
Depending on the outcome of the review and evalua tion of the primary references cited in the HPV documentation and/or review of the necessary environmental fate data listed above, the need to reassess human dietary exposure to cyanuric acid will be determined.

Comment 37. The PWP references a number of publica tions, without providing a full citation. For example, this section refers to “Dufour, 2006” but does not list this reference in section 8. The full citation is:
A. Dufour, O. Evans, T. Behymer, R. Cant ú (2006) Water ingestion during swimming activities in a pool: a pilot study, Journal of Water & Health, 4, 425-430.
The Dufour results and other input indicate that previous calculat ions of exposure to isocyanuric acid in swimming pools (S. Mostaghimi, “Review of non-dietary exposure and risk assessment for cyanuric acid applied to swimming pool s”, U.S. EPA Letter, DP No. D270656, Mar 26, 2001.) may have overestimated the amount of water ingested while swimming.
The second line on page 20 says “...assuming a chlorinated isocyanurate concentration of 55 mg/liter...”. This is obviously incorrect and “chl orinated isocyanurate” should be “isocyanuric acid”.
In paragraph 2, the last sentence discusses usi ng the Dufour study, which “...could be used to back calculate chloroisocyanurate exposures for comparisons to the estimates derived from the SWIMODEL”.
Here “chloroisocyanurate” should be “isocyanuric acid”. Also, it is not clear if EPA intends to conduct this comparison and what implications it may have on SWIMODEL if results are not consistent.
The exposure calculation in SWIMODEL has been refined since 2001. We assume the Agency will use the most recent versi on (version 3) of SWIMODEL at http://www.epa.gov/oppad001/swimodel.htm for cal culating potential swimmer exposures.
Agency's Response: The Agency concurs with the commen t regarding the Dufour study and the full citation for the study will be added to the reference list. The Agency concurs with comment regardi ng the second line on page 20 and the phrase “chlorinated isocyanurante concentration of 55 mg/li ter” has been changed to “isocyanuric acid concentration of 55 mg/liter”. The Agency concurs with the comments regarding the SWIMODEL and will use the most recent version when calculating swimmer exposures.Page 72 of 80 Comment 38. Occupational and residential exposure da ta is being generated by the AEATF, with full cooperation of the EPA. It is important that the Work Plan and DCI requests for data be consistent with the studies being performed by the AEATF. We look forward to working with both EPA and the AEATF to produce the studies re quired. Some members of the IIAHC are also members of the AEATF and are actively work ing with the AEATF Protocol Committee to develop the protocol for th e upcoming Pour Solid study.
Table 10 indicates that the exposure scenario fo r ingestion of treated drinking water consider long term exposure. While this is true, remember th at isocyanuric acid is rapidly eliminated from the body (elimination half-life is about 4 hr) and that it is not metabolized and does not accumulate. Thus, isocyanuric acid ingested during one day is essentially completely eliminated by the next day’s exposure so there are no cumulative effects from daily exposure.
Agency's Response : The agency concurs with the co mment regarding the AEATF exposure data that are under development.
The title of Table 10 has been changed to “ORE Scenarios for the Chlorinated Isocyanurates” and that the “Ingestion of treated drinking water” scenario be deleted since it is not an ORE scenario. Note, however, that dietary exposure to cyanuric acid via drin king water is addressed at 3.2.2.

Comment 39. We generally agree with the discussion he re, however, a number of papers have been published recently which contain additional da ta on the biodegradation of isocyanuric acid. The IIAHC would be happy to submit a review and a reference list.
Agency's Response: The Agency will review studies\information submitted by IIAHC for isocyanuric acid as part of Registration Review.

Comment 40. What kind of model will be used for thes e calculations? We would like to know how the model determines what percentage of th e isocyanuric acid in the WWTP influent is released to the surface water and sediment, the basis for this assumption, and how these data will be used in the risk assessments. This path way triggers ecotoxicity and potentially additional environmental data needs with down-the-drain and sanitary drain system disposals if the substance is not fully degraded or consumed by the WWTP process.
Agency's Response: The down-the-drain model will be used for the calculations of isocyanuric acid exposure to WWTPs. Specific model assump tions are provided in the Final Work Plan.

Comment 41. The IIAHC and its members anticipate submitting additional environmental toxicity and ecological effects data to support the planned risk assessments.
Agency's Response: The Agency will consider the studies when submitted by IIAHC.

Comment 42. In sentence 10, “IIHAC” should have been written as “IIAHC”.Page 73 of 80 Agency's Response : The correction has been made to the FWP.

Comment 43. The Final Work Plan should make it clear that the environmental risk assessments will only be done on isocyanuric acid.
Agency's Response : Added statement to Section 1.2 Overvi ew Case regarding what the risk assessment will evaluate. Risks from both the chlorine residual and tautomer degradates need to be addressed. Where these risks have been pr eviously assessed and updated methods, and new policies do not change exposure, effects, and risk conclusions, a new risk assessment will not be performed.

Comment 44. The IIAHC has a number of ecotox studies which have been or could be submitted. These studies will be of better quality than most open literature studies identified through ECOTOX.
Agency's Response: The agency will consider any relevant studies submitted by the IIAHC. Per OPP policy for Registration Review risk assessmen ts, relevant open litera ture studies identified through ECOTOX also will be considered: www.epa.gov/pesticides/science/efed/policy/ policy_guidance/team_authors/endangered_species _reregistration_workgroup/esa_ evaluation_open_literature.htm

Comment 45. Most of the internet links provided in this section have been changed, for example:
http://www.epa.gov/owow/tmdl/ is now http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/index.cfm.
http://ofmpub.epa.gov/tmdl_waters10/attains_ nation_cy.cause_detail?p _cause_group_name=CH LORINE is now http://iaspub.epa.gov/tmdl_waters10/attains_ nation_cy.cause_detail_303d?p_cause_group_id=27 7 (which indicates only 40 water bodies impaired by chlorine)
Footnotes 6 and 7 - the web-pages given are no longer correct. The causes of impairment are listed at:
http://iaspub.epa.gov/waters10/attains_nati on_cy.control?p_report_type=T#causes_303d
The sections on organochlorine pesticides and chlorinated pestic ides are not relevant to the chlorinated isocyanurates

.
The IIAHC would like to discuss these issues to determine the extent of EPA’s concerns for impaired waters.
Agency's Response: 1) (a) The first link has not changed and the agency tested the link and it leads to the correct page whereas the one suggested to take its pl ace leads to an Error 404 page and the agency will keep the original link in the FWP. (b) The agency agrees the second link is no longer correct and has tested and replaced that link in the FWP with the one provided in thePage 74 of 80 comment. (c) The agency checked the links in f ootnotes 6 and 7 of Section 6.1.2 and these linked to the correct web site pages. The link provide d by the commenter is a general impairment and TMDL page and was added to the first paragraph, third sent ence of Section 6.1.2. 2) The agency is open to discussion with regards to impaired waters.

Comment 46. Regarding Section 6.1.5 additional informa tion corresponds to comment #1 in this response to comment appendix. The IIAHC and members thereof will be providing additional data to assist EPA’s risk asse ssments, see Critical Issue #1.
Agency's Response: The agency thanks IIAHC and its me mbers for any additional information that will assist the agency in refining its ri sk assessment. (See the Agency’s response to Comment 1.)

Comment 47. The text states that EPA has no envir onmental fate data on isocyanuric acid. Instead, EPA cites scientific literature cited by the HPV Summaries for environmental fate data on isocyanuric acid. IIAHC can provide copies of the references in the HPV Summaries. In addition, the IIAHC can provide many additi onal published papers on biodegradation of isocyanuric acid.
Agency's Response: Tables 1 and 8 provide generic antici pated data requirements; it does not list specific studies. These tables have been updated to include a ll anticipated environmental fate data requirements. The IIAHC can choose to su bmit HPV studies or any other relevant source for those data listed in Table 12. The agency wi ll review and consider any relevant studies submitted by the IIAHC.

Comment 48. The PWP indicates that the Agency needs to review several primary references cited in the HPV Summaries. The IIAHC will be happy to submit these. Otherwise, the PWP does not specify exactly wh at data are required.
The first partial paragraph refers to Secti on 5.1.2 which supposedly includes relevant data requirements; however, the PWP does not contain a section 5.1.2.
Agency’s Response: The reference to Section 5.1.2 has been removed. The FWP has been updated to identify the type of fa te data anticipated to be required (see Comment #47). If IIAHC submits studies that were referenced in HPV Summaries which meet these anticipated data needs, those data will be reviewed for use in the risk assessment. Alternatively, if IIAHC has access to other studies which would fulfill th e anticipated data requirements, IIAHC should submit them for agency consideration.

Comment 49. The MRID cited for the hydrolysis study by Hu is incorrect; the correct reference is MRID 00056478. Also, Footnote 2 is not the corre ct citation for the hydrolysis study. The correct citation is:

 H. Hu (1981) Hydrolysis study of aqueous sodium salt solutions of 2,4,6-trihydroxy1,3,5-triazine. Princeton Chemical Resear ch and Development Centre. MRID 00056478.Page 75 of 80 Agency's Response: There are two references for Hu, one is for the hydrolysis study and the other is for the photolysis study. The MRIDs and footnotes have been corrected in the FWP.

Comment 50. The statement “In surface waters and wast ewater streams, possible transformation products like chlorine, HOCl, ClO3 - may be present...” is inconsis tent with the three previous bullet points.
Agency's Response: The Agency does not concur with the comment because some residual chlorine may still be present even though hypochlorite is highly reactive.

Comment 51. The IIAHC has not submitted additional subchronic, chronic, developmental, mutagenicity, and metabolism studies to the EP A since the HIARC report in 2001. However, the IIAHC has recently obtained a new Ames test study, which was performed according to the current protocol. The results of the new study agr ee with previous results (no mutagenic effects), so the conclusions of the HIARC study are unchanged. The IIAHC is willing to submit this report, if required.
Agency's Response: The Agency will review all available studies during registration review and use a weight of evidence approach to determine if the chlorinated isocyanurates are mutagenic. IIAHC should submit that the above mentioned st udy be submitted so it can be considered by the
agency.

Comment 52. It should be noted that the IIAHC has also submitted MRID 43819301 which investigated the friability of these products. This relates to the potential attrition of these products into inhalable size part icles during transportation and ha ndling. The study measured the percent by weight of product less th an 11 microns in size and less than 53 microns in size after transportation or after vibration.
For granular products, this study found that less than 0.1% by we ight of the product is smaller than 11 microns and less than 0.2% by weight is smaller than 53 microns. Vibration of the granular products did not appear to make any difference in these percentages. For tablets which had undergone vibration, this st udy found that less than 0.2% by we ight of the product is smaller than 11 microns and less than 0.6% by weight is smaller than 53 microns (in the inhalable size range). This study demonstrated that the products are not friable. Therefore, only a very small percentage of the product is small enough to be in haled if the product was re leased into the air.
We have also attempted an acute inhalation study on trichloro-s-triazinetri one particles in the 45 - 75 micron size range. These particles could not be aerosolized sufficiently to conduct the test, so that even if the product is re leased to the air, only the very small percentage smaller than about 50 microns could be suspended in air. Thus , the potential for inhalation exposure to these products is limited to less than 1% by weight of the product.Page 76 of 80 Based on the physical form of these products, as defined by the studies cited above, the inhalation exposure to particles of toxicological concern and the consequent inhalation risk to these products are low.
Agency's Response: The agency will consider this inform ation during registration review in its effort to characterize inhalation exposures.

Comment 53. IIAHC agrees with the rankings listed fo r eye irritation (Cat egory I) and skin irritation (Category I) ar e correct, particularly for wet mate rial. However, the study cited, MRID 00019754 (B. Brett (1976) Acute Toxicity Studies with Brom-O-Rings, IBT No. 601-08105) is inappropriate for either endpoint. This formulatio n contains both trichlor o-s-triazinetrione and another material which may affect the study resu lts. Therefore, this study is not directly applicable to pure trichloro-s- triazinetrione. Furthermore, this study was performed by IBT (EPA does not accept studies from IBT) and was not run under GLP.
The IIAHC recommends referencing the follo wing study performed on pure trichloro-striazinetrione for Primary Eye Irritation:

 G. Wnorowski, Product Safety Labs (1995) ACL-90, primary eye irritation, Project ID 3450. MRID 43592601
The IIAHC recommends referencing one of the following studies performed on pure trichloro-striazinetrione for Primary Skin Irritation:

 J. Gargus, Hazleton Laboratories America (1984) Primary dermal irritation study in rabbits, trichloro- s-triazinetrione”, Project 2291-103. MR ID 150961 (also see HPV Summary)

 J. Lemen, Hazleton Laboratori es (1988) Primary dermal irritation study in rabbits (Biocare 90), Project HLA 2514-102. MRID 40835803

 R. Shapiro, Product Safety Labs (1990) EPA acute dermal irritation test, trichloroisocyanuric, Project T-292. MRID 42180404
Agency's Response: The Agency will review all available studies during registration review and use a weight of evidence approach to determin e the acute toxicity cate gories. RASSB will reevaluate MRID 00019754 and determine if it shoul d still be used for this determination

Comment 54. IIAHC does not agree with the conclusion that trichloro-s-triazine trione or sodium dichloro-s-triazinetrione are dermal sensitizers, and recommend that this be corrected to “not sensitizers”. See Critical Issue #2.
Agency's Response: The Agency will review all available studies during registration review and use a weight of evidence appro ach to determine if the chlorinated isocyanurates are dermal sensitizers. IIAHC should submit the above menti oned studies so they can be considered by the
agency.Page 77 of 80 Comment 55. The third sentence on page 45 defines “total chlorine residual” (TRC) for freshwater and “total residual ox idant” (TRO) for seawater while the first paragraph on page 48 defines “total residual chlorine” (TRO) as the su m of free chlorine and combined chlorine in fresh water, and “chlorine-produc ed oxidants” (CPO) as the sum of the oxidative products in seawater. These definitions are inconsistent , even though both reference the same source document. It appears that “TRO” on page 48 should really be “TRC”.
Agency's Response: The correction has been made in the FWP.

Comment 56. Given the conceptual models in Figures 1-4, we are surprised that this review does not discuss terrestrial organisms (such as earthworms) or sediment organisms (such as chironomid). The IIAHC owns studies on the toxi city of isocyanuric acid to earthworms and chironomid. We would like to meet with the Ag ency and review the data which could be submitted, if required.

In addition, this review does not cover terrestrial plants and th e PWP does not include a request for Nontarget Plant Protecti on Data, including 850.4225 Seed ling Emergence Tier II and 850.4250 Vegetative Vigor Tier II. We are surprised that these stud ies are not required, as these were required in the May 16, 2012 DCI for Na Br, due to the once-through industrial water system uses for NaBr. The IIAHC is currently performing such a study a nd would be willing to submit this data, if required.
Agency's Response: AD does not require earthworm toxicity studies and does not assess risk to earthworms. AD will consider any sediment-toxicity data that IIAHC wishes to submit for isocyanuric acid but, based on the physica l/chemical information, the major exposure compartment is expected to be water rather than sediment and so sediment data are not anticipated as being required. AD assesses risk to “semi-aqua tic”-terrestrial plants using vegetative vigor and seedling emergence studies on rice (see Agency’s response to Comment 6).

Comment 57. What use causes exposure of birds to th e chlorinated isocya nurates to be of concern? In contrast, pa ge 47, last paragraph, indi cates that there is no co ncern for exposure of insects to chlorinated isocyanurates.
Agency's Response: The avian acute oral study is required for all antimicrobial pesticides to determine whether a label precau tionary-hazards statement is n eeded for wildlife (see 40 CFR §156.85 Non-target organisms). If a use results in an antimicrobial and/or its major transformation product(s) reaching surface water or the terrestrial environment, then exposure and risk to wildlife via the dietar y route is assessed. As discusse d in Section 4.1, in the case of chlorinated isocyanurates, while several of the us e patterns are expected to reach surface water, bioconcentration and ther efore the dietary exposure route fo r wildlife is not considered an environmental concern which is why the conceptual models show this pathway as dashed lines. Testing with terrestrial insects (honey bee) is required fo r antimicrobial use patterns where exposure is likely such as applications to crops and wood-preservative uses.Page 78 of 80 Comment 58. Both Tables 15 and 16 have a Footnote 1, but no reference to the footnote. The footnote should refer to “Toxicity”, the head ing in column 4, as was done in Table 14.
Several MRIDs given in Tables 15 and 16 are no t listed in NPIRS. The numbers listed are Accession Numbers, rather than MRIDs. Th e following tables list the proper MRIDs:
Table 15 (sodium dichloro-s-triazinetrione dihydrate)

N umber liste d Correct MRID 256739 acute - avian oral, Bobwhite* 150947 256739 acute - avian dietar y , Bobwhite150949 256739 acute - avian dietar y , Mallar d 150948 * This is a duplicate of 150947
Table 16 (sodium dichloro-s-triazinetrione)

N umber liste d Correct MRID 254911 00144306 254910 00144305 254909 00144304 In addition, the three studies listed in Tabl e 16 with Accession No. 256739 are duplicates of studies in Table 15 and are incorrectly listed. Accession No. 256739 was submitted by 3V Sigma S.P.A. (IIAHC member) which only perf ormed avian toxicity studies on sodium dichloroisocyanur ate dihydrate.
Agency's Response: The footnote has been corrected. Th e duplicates in Table 16 has been removed, additional duplicates were found in these tables and also removed. Three studies for isocyanuric acid, two with birds and one with a freshwater invert ebrate, were found and added to this appendix.

Comment 59. At the end of the sentence, “there de gradates” should be read as “their degradates”.
Agency's Response: That correction has been made in the FWP.

Comment 60. This heading should be “Aquatic - Fish and Invertebrate Toxicity ” as this section covers not only freshwater fish and invertebra tes but also estuarine and marine organisms.
Agency's Response: That correction has been made in the FWP.

Comment 61. This section indicates that chronic toxicity da ta for freshwater fish (guideline 850.1400 Fish Early-Life Stage Toxicity Test) an d freshwater inverteb rates (guideline 850.1300 - Daphnid Chronic Toxicity Test) are anticipated to be required. Howe ver, it is not clear from the PWP whether chronic toxicity data on the active ingredient or on the degr adate, isocyanuric acid, is required. We recommend th at the required chronic data should be on the degradate, isocyanuric acid, as the acute data for the active i ngredients already indicate very high toxicity.Page 79 of 80 The IIAHC owns a 28 day juvenile fish growth study and a Daphnia magna reproduction test on the monosodium salt of cyanuric acid, which will at least partially meet these requirements. These studies have been submitted to EPA, but ha ve not been reviewed in conjunction with any action.

We are not familiar with the TN numbers used here to refer to studies

. Agency's Response : The Agency agrees that the chronic studies s hould be conducted using isocyanuric acid, and that will be stated in the FWP. Data indicated in response to comment #1 will be reviewed before a DCI is issued.

Comment 62. This section indicates that chronic toxicity data fo r marine fish (guideline 850.1400 - Fish Early-Life Stage Toxicity Test) and marine invertebrates (guideline 850.1350 - Mysid Chronic Toxicity Test) are “anticipated to be required”. Ho wever, it is not clear from the PWP whether chronic data on the active ingredient or on the degradate, isocyanuric acid, are required. We recommend that the required chronic data should be on the degradate, isocyanuric acid, as the acute data for the active ingredie nts already indicate very high toxicity.

Occidental Chemical Cor p. (IIAHC member) owns data on the acu te toxicity of isocyanuric acid and of sodium dichloro-s-triazinetrione to In land Silversides (Menidia beryllina) and Mysid shrimp, which can be submitted, if required. Other IIAHC members may also have some relevant data.
Agency's Response: See previous comment regarding the te st material for chronic studies.

Comment 63. The website given for HPV data, http://www.epa.gov/hpv/pubs/general/hpvchemdata.html , has been moved. The current web address for the HPV Challenge is http://www.epa.gov/chemrtk/index.htm.
Agency's Response: That correction has been made in the FWP.

Comment 64. On Page 51, Table 21 which corresponds to comment #4 in this response to comments appendix (See Critical Issue #4.)
Agency's Response: See response to comment #4. The agency will use actual data in lieu of the ECOSAR calculations for isocya nuric acid if IIAHC submits acceptable studies for evaluation.

Comment 65. The table has several references to “IIHAC 2003” which refers to the HPV Summaries for trichloro-s- triazi netrione, sodium dichloro-s-triaz inetrione and sodium dichloros-triazinetrione dihydrate, but doesn’t provide a full reference. The full references are:

 Isocyanurate Industry Ad Hoc Committee, “R obust summaries for sodium dichloro-striazinetrione (CAS No. 2893-78- 9) and sodium dichloro-s-t riazinetrione dihydrate (CAS No. 51580-86-0)”, revised May 20, 2004.

 Isocyanurate Industry Ad Hoc Committee, “Robust summaries for trichloro-striazinetrione (CAS No. 87-90-1)”, revised May 20, 2004.Page 80 of 80 Note that the IIAHC did not submit a separate HPV Summary for isocyanuric acid; the data for isocyanuric acid was included in the HPV Summaries for the active ingredients. However, the HPV Information System (HPVIS) lists some ofthis data separately for 1,3,5-Triazine2,4,6(1H,3H,5H)-trione (isocyanuric acid, CAS Number 108-80-5) and for 1,3,5-Triazine2,4,6(1H,3H,5H)-trione, monosodium salt (monosodium isocyanurate, CA S Number 2624-17-1).

The references in the table to “IIHAC 2003” s hould be to “IIAHC 2004”. “IIHAC” is incorrect and should be “IIAHC”, for the Isocyanurate Industry Ad Hoc Committee. They should refer to the revised HPV Summaries submitted in 2004, rath er than the original submissions in 2003.

Footnote c indicates that several studies in the HPV Summaries are not available to the EPA. The IIAHC is willing to submit these studies, including the acute toxicity studies on isocyanuric acid and rainbow trout (Salmo Gairdneri), fathead minnows ( Pimephales promelas ), bluegill sunfish (Lepomis macrochirus), and fresh-water algae ( Selenastrum Capricornutum ).
The OECD SIDS 1999 summary provides the results of several other studies which have not been submitted to the EPA. The SIDS summary i ndicates that the Japanese medaka fish, water flea (Daphnia magna) and green algae ( Selenastrum capricornutum ) data were obtained by the Environment Agency of Japan based on OECD Test Guidelines and GLP.
Agency's Response : The citations have been corrected and references added to the FWP. As indicated in previous responses to comments, the Agency will review any data submitted to fulfill anticipated data requirements.

FIFRA Endangered Species Task Force (FESTF): FESTF provided a list of Member Companies that could rely on data submitted by the Ta sk Force in their lette r dated February 11, 2013.
California Stormwater Quality Association: Commended the agency on their improved examination of surface water quality risks for chlo rinated isocyanurates in their letter dated February 12, 2013.

TriTAC: Commended the agency on their improved examination of surface water quality risks for chlorinated isocyanurates in th eir letter dated February 12, 2013.
California Stormwater Quality Association: Commended the agency on their improved examination of surface water quality risks for chlo rinated isocyanurates in their letter dated February 12, 2013.
Physicians Committee for Responsible Medicine (PCRM): PCRM commended the Agency for their holistic approach to risk assessment.