### Page 2 of 52 

## Table of Contents
1 Introduction .................................................................................................................. ........... 5

1.1 Statutory and Regulatory Authority ................................................................................. 5

1.2 Case Overview ................................................................................................................. 7

1.3 Chemical Identification and Properties ............................................................................ 7

1.4 Use/Usage Description ..................................................................................................... 9

1.4.1 Registrations ............................................................................................................. 9

1.4.2 Summary of Regist ered Uses .................................................................................. 10

1.4.3 Usage Information .................................................................................................. 12

1.5 Regulatory History ......................................................................................................... 12

1.5.1 Recent/Pending Regulatory Actions ....................................................................... 12

1.5.2 Tolerance Information ............................................................................................ 12

1.6 Incidents ..................................................................................................................... .... 12

1.6.1 Human Health ......................................................................................................... 12

1.6.2 Ecological ............................................................................................................... 14

2 Anticipated Data Needs ........................................................................................................ 14

3 Human Health Risk Assessment ........................................................................................... 17

3.1 Existing Toxicological Endpoints .................................................................................. 17

3.2 Dietary Exposure ............................................................................................................ 1 8

3.2.1 Food ........................................................................................................................ 1 8

3.2.2 Drinking Water ....................................................................................................... 19

3.3 Occupational and Residen tial (ORE) Exposures ........................................................... 19

3.3.1 ORE Exposure Assessed in the RED ...................................................................... 19

3.3.2 ORE Exposures Assessed after the RED ................................................................ 19

3.3.3 ORE Exposures that will Need to Be Assessed for Registration Review ............... 20

3.4 Aggregate and Cumulative Exposure ............................................................................. 21

3.4.1 Aggregate Exposures .............................................................................................. 21

3.4.2 Cumulative Exposures ............................................................................................ 21

4 Environmental Risk Assessment........................................................................................... 21

4.1 Environmental Conceptual M odel Exposure Pathways ................................................. 21

4.2 Ecological Effects Assessment ....................................................................................... 25

### Page 3 of 52 4.2.1 Mechanism of Action .............................................................................................. 25

4.2.2 Measures of Effect (Ecotoxicology Endpoints) ...................................................... 26

4.3 Exposure Analysis Plan .................................................................................................. 27

4.3.1 Aquatic and Terrestrial Wild life Exposure Estimates ............................................ 27

4.3.2 Down-the-Drain Analysis ....................................................................................... 27

4.4 Effects Analysis Plan ..................................................................................................... 28

5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 28

6 Guidance for Commenters .................................................................................................... 29

6.1 Preliminary Work Plan ................................................................................................... 29

6.1.1 Trade Irritants .......................................................................................................... 29

6.1.2 Water Quality .......................................................................................................... 29

6.1.3 Environmental Justice ............................................................................................. 30

6.1.4 Structure Activity Relationships ............................................................................. 31

6.1.5 Additional Information ........................................................................................... 32

7 Next Steps .................................................................................................................... ......... 32

8 References .................................................................................................................... ......... 32 Appendix A: Environmental Fate ................................................................................................ . 34 Appendix B: Toxicology Profile ................................................................................................ ... 43 Appendix C: Ecotoxicology Profile ............................................................................................. . 45

List of Tables

Table 1 - Summary of Anticipated Ri sk Assessments and Data Needs ......................................... 6 Table 2 - Anticipated Registration Review Schedule ..................................................................... 6 Table 3 - Chemical Identification Informa tion for the Chlorinated Isocyanurates ......................... 8 Table 4 – Physical and Chemical Propertie s for the Chlorinate d Isocyanurates ............................ 8 Table 5 - Distribution of Products by Specific Chlorinated Isocyanurate ...................................... 9 Table 6 – Summary of Chlorinated Is ocyanurate Antimicrobial Uses ......................................... 10 Table 7 - Incidents Reported for th e Chlorinated Isocyanurates .................................................. 13 Table 8 - Studies Anticipated as Needed for the Registration Review of the Chlorinated Isocyanurates.................................................................................................................. ............... 15 Table 9 – Existing Toxicology Endpoints .................................................................................... 17 Table 10 - Occupational Exposure Scenarios for the Chlorinated Isocyanurates ......................... 20 Table 11 – Existing Ecologi cal Effects Endpoints ....................................................................... 26

### Page 4 of 52 Table 12 Environmental Fate Data for Chlori nated Isocyanurates (di- and tri-chloro) ............... 37 Table 13 - Acute Toxicity of the Chlorinated Isocyanurates ........................................................ 43 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...................................................................................................................... ................. 46 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 ........................................................................................ ... 49 Table 18 Available Acute Endpoints from Freshwater Fish and Aquatic Inve rtebrate Ecotoxicity Studies for Sodium Dichlo ro-s-Triazinetrione .............................................................................. 49 Table 19 Available Acute Endpoints from Freshwat er Fish and Aquatic I nvertebrate Ecotoxicity Studies for Sodium Dichloro isocyanurate Dihydrate ................................................................... 50 Table 20 Available Acute Endpoints from Freshwat er Fish and Aquatic I nvertebrate Ecotoxicity Studies for Potassium Dichloroisocyanurate ................................................................................ 50 Table 21 - Available Aquatic Organism data for Isocyanuric Acid ............................................. 51

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 ................................................................... 22 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 ..................................................................................................... ........ 23 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 ..................................................................................................................... ................ 24 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 ............................................................................................ . 25

### Page 5 of 52 

## 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) and 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 needed to make a registrati on review decision. After reviewing and responding to comments and data received in the docke t during this initial comment period, the Agency will develop and commit to a Final Work Plan (FWP) and anticipated schedule for the Chlo rinated Isocyanurates Case.

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 52 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 Aquatic plants vascular and non-vascular, 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.


### 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 Phase 2: Case Development

Issue Final Work Plan 

### 2013-06 Issue Data Call-In (DCI) 

### 2014-06

### Page 7 of 52 Anticipated Activity Target Date 1 

### Completion Date
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 Case Overview The docket for the Chlorinate Isocyanurates 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 five active ingredients in this case will be referr ed to collectively as “chlorinated isocyanurates.”

The dechlorinated s -triazinetrione, isocyanuric acid (PC Code: 081402) is not being considered in this registration review. No registered pesticide products c ontain dechlorinated s

triazinetrione, isocyanuric acid as an active ingredient. Although in itially considered as part of the Chlorinated Isocyanurates case, potassium dichloro- s -triazinetrione (PC Code: 081403) was never registered by EPA in any pesticide products a nd, therefore, will not be evaluated as part of this registration review. Although the penta- s -triazinetrione (PC Code: 081406) was considered in the 1988 Registration Standar d, 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.

The chlorinated isocyanurates and triazine herbicides share a symme tric triazine ring. However, the chlorinated isocyanurates are not to be confused with agronomic herbicides that are classified

as s -triazine compounds which have alkyl side chains, and, therefor e, the chlorinated isocyanurates are not considered as part of the triazine cumulative assessment.

1.3 Chemical Identification and Properties

Table 3 presents the four ac tive ingredients to be asse ssed in Case 5069: dichloro- s -triazinetrione (PC Code: 081401); sodium dichloro- s -triazinetrione (PC Code: 081404); trichloro- s

-

1 Environmental Protection Agency, 1992. Reregistratio n Eligibility Document (RED) Chlorinated Isocyanurates http://www.epa.gov/pesticides/rer egistration/REDs/old_reds/chlorinated_isocyanurates.pdf

### Page 8 of 52 triazinetrione (PC Code: 081405); and sodium dichloro- s -triazinetrione dihydrate (PC Code: 081407). All of these substances are substituted chlo rinated 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 Dichloro- s -triazinetrione Sodium dichloro- s triazinetrione Trichloro- s -triazinetrione Sodium dichloro- s triazinetrione dihydrate

Common Name Dichloroisocyanuric acid Sodium di chloroisocyanurate Trichloroisocyanuric acid Sodium dichloroisocyanurate dihydrate

Synonyms l,3-Dichloro- s -triazine2,4,6 (l H ,3 H ,5 H ) trione 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 70; CDB 70 ACL 60; CDB 60; S.D.I.C. ACL 90 Plus; CDB 85; T.I.C.A.; TCCA. ACL 56; DICD

PC Code 081401 081404 081405 081407
CAS No. 2782-57-2 2893-78-9 87-90-1 51580-86-0
Chemical Family Halogenated triazines

Molecular Formula C3HN3O3Cl2 C3N3O3Cl2Na C3N3 O3Cl3 NaC3N3O3Cl2.2H2O

Molecular Weight 198.98 220.96 232.42 255.98

Available chlorine % Theoretical Nominal 70.0 - 71.64 60.0 - 64.48 85.0 - 91.5 55.0 % - 57.0

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 Propert ies for the Chlorinated Isocyanurates

OPPTS Guideline No./ Physical and Chemical Properties Dichloro- s triazinetrione Sodium dichloro- s triazinetrione Trichloro- s triazinetrione Sodium dichloro- s triazinetrione dihydrate

830.1550 Product identity and composition Refer to Table 1. Refer to Table 1. Refer to Table 1. Refer to Table 1.

830.6302/Color White White White White

830.6303/Physical State Crystalline solid Granular Crystalline solid Crystalline solid Crystalline solid

830.6304/Odor Chlorine 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 Stable and relatively inert when dry

### Page 9 of 52 OPPTS Guideline No./ Physical and Chemical Properties Dichloro- s triazinetrione Sodium dichloro- s triazinetrione Trichloro- s triazinetrione Sodium dichloro- s triazinetrione dihydrate

830.6314 Oxidation/Reduction: Strong Oxidizing material Strong Oxidizing material St rong Oxidizing material Strong Oxidizing material

830.7000/pH 2.6 (saturated solution) 6.1 (1% solution) 2.9 (1% solution) 6.4 (1% solution)

830.7200/Melting point 225 o C (Decomposition) 230-250 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 48 lbs/cubic ft 35 lb/cubic ft

850 – 950 kg/cubic meter

Specific gravity 2.05 g/ml at 20 o C 2.02 - 2.10 g/cc 62.56 lb/cubic ft.

830.7550 Partition coefficient ( n -octanol/water) 1.28 -0.06 0.94 -0.06

830.7840 Solubility in water 0.8 g/100 g at 25°C 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



### 1.4 Use/Usage Description

1.4.1 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

Dichloro- s -triazinetrione 081401 2 0.8 to 99.7 a Dust, Tablet/Pellet

Sodium dichloro- s -triazinetrione 081404 81 10 to 99 b Granules, Tablets/Pellets, Liquid, Impregnated Stick-On Patch

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

Sodium dichloro- s -triazinetrione dihydrate 081407 122 1.0 to 100 Granules, Tablets/Pellets, Wettable Powder, Dust, Water

soluble packaging, Liquidsolutions and emulsifiable N/A: not applicable

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%.

### Page 10 of 52 1.4.2 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.

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 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 - 600 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 3 ppm.

### Page 11 of 52 Dichloro- s -triazinetrione (PC Code : 081401), sodium dichloro- s -triazinetrione (PC Code: 081404), trichloro- s -triazinetrione (PC Code: 081405), and dichloro- s -triazinetrione dihydrate (PC Code: 081407) are all registered as disinfectants and sanitizers for use to control bacteria on indoor food and non-food contact hard surfaces a nd equipment at food processing plants, eating and food handling establishments, commercial and industrial premises, hospital and medical premises (human/veterinary), laboratories, zoos, livestock and animal living quarters, and indoor hard surfaces and contents of household/domes tic dwelling premises. Additionally sodium dichloro- s -triazinetrione and dichloro -s-triazinetrione dihydrate ar e registered for use as a virucide on hard surfaces in hospitals (human/veterinary), institutional, and zoo premises, pet kennels, animal cages, zoo premises and animal enclosures and transport vehicles, animal feeding and water equipment, locker room premis es, and shower and bathroom premises. Except for dichloro- s -triazinetrione, these chlorinated isocyanurat es are registered for use in residential, commercial, and instituti onal laundry products.

Dichloro- s -triazinetrione is registered for use to treat swimming pool water as an algaecide and bacteriocide. Sodium dichloro- s -triazinetrione, trichloro- s -triazinetrione, and dichloro- s

triazinetrione dihydrate, in addi tion to treating swimming pool wate r, are registered for use as microbiocides, microbiostats, bacteriocides, disi nfectants, sanitizers, f ungicides, and algaecides in non-food industrial water syst ems (air washer water system s, commercial/industrial water cooling systems, heat exchanger systems, coo ling towers, lakes/ponds/reservoirs (without human or wildlife use), pasteurizer water, cannery c ooling canal water, hot tub, whirl pool, and spa waters, ornamental ponds and lakes, aquaria water, ornamental fountains, sewage systems, waste water systems, sewage settling ponds, septic tanks , sewer lines (main), oil recovery drilling muds and packer fluids, and secondary oil recovery in jection water. Additionally sodium dichloro- s

triazinetrione and dichlo ro-s-triazinetrione dihydrate are regist ered 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 dichloro- s -triazinetrione dihydrate are also registered for use as a virucide and bacteriocide fo r treatment of potable water.

Formulation types include soluble concentrates both solid and flowable , ready-to-use (RTU) solutions, wettable powder, water soluble pack aging, granules, water dispersible granules, pellets, and tablets. There is a one product containing dichloro- s -triazinetrione registered only for use of impregnated patches for placement on fresh cut flowers as a bactericide for slimeforming 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.

### Page 12 of 52 1.4.3 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 disi nfectants and sanitizers (1.1 million pounds).

1.5 Regulatory History The chlorinated isocyanurates were first regist ered in the United States in 1958 for use as disinfectants, sanitizers, algicide s, and fungicides. Dichloro- s -triazinetrione was first registered in the United States in 1958; sodium dichloro- s -triazinetrione was first registered in the United States in 1968; trichlor o-s-triazinetrione was fi rst registered in the Un ited States in 1959; and sodium dichloroisocyanurate dehydrate was initially registered as a sanitizer in the United States on March 17 1964. The Agency completed a rere gistration eligibility decision document (RED) in 1992, which included a reregistration decisi on 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 ca ll-in (DCI) was issued in May 1993.

1.5.1 Recent/Pending Regulatory Actions There are currently two pending regi strations for sodium dichloro- s -triazinetrione and one pending registration for trichloro- s -triazinetrione.

1.5.2 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 Agency intends to delete the exemption for the potassium salt of dichlorois ocyanuric acid from 40 CFR 180 .940(c) because there are no registered products. The Agency intends to a dd sodium dichloroisocyanurate dihydrate (51580- 86-0) to the exempti on in 40 CFR 180.940(c).



## 1.6 Incidents

1.6.1 Human Health A total of approximately 6,500 human health incidents are listed in the OPP Incident System for the chlorinated isocyanurates for the years 1992 to the present. A summary of these incidents is given in Table 7. The severity of the incide nts range from minor effects such transient

### Page 13 of 52 respiratory irritation represented by code HD (Human Minor) to seve re 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 resulting in injuries su ch chemical burns and pulmonary edema. The labels clearly state that chloroisocyanurates should be not be handled in this manner. Less severe incidents have occurr ed when people have been exposed to irritating “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 Dichloroisocyanuric acid (081401) Food Processing 0 0 0 3 0 Pools and Spas 0 0 0 16 3 Miscellaneous and Unspecified 0 0 0 0 1 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 hydrate (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.

### Page 14 of 52 1.6.2 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.Page15of52Table 8 - Studies Anticipated as Needed for the Registration Review of the Chlorinated IsocyanuratesOCSPPGLNStudy NameTest SubstanceTime Frame(Months fromDCI Receipt)RiskAssessment(s)Data Will SupportUse Site(s) TriggeringData RequirementApplicable ExposureScenarios875.1300 Indoor Exposure, Inhalation TGAI 24Occupational andResidential HandlerAll See notes 1, 2, 3 and 4.875.1700 Product Use Information TGAI12 All All All above scenarios.875.2300 Indoor Surface Residue Dissipation TGAI 24 Residential Household floors5Toddlers playing ondisinfected floors850.4400Aquatic Plant Testing usingLemnasp., Tier IIDegradate(isocyanuric acid)12 Aquatic organisms All6850.45007Algal Toxicity Tier II –marinediatom, freshwater diatom, greenalgaeDegradate(isocyanuric acid)12 Aquatic organisms All6850.45507Algal Toxicity Tier II -CyanobacteriaDegradate(isocyanuric acid)12 Aquatic organisms All6835.31108Ready BiodegradabilityDegradate(isocyanuric acid)12Aquatic exposureand riskAll6835.32208Porous Pot TestDegradate(isocyanuric acid)12Aquatic exposureand riskAll6835.32408Simulation Test – Aerobic SewageTreatment: A. Activated SludgeUnitsDegradate(isocyanuric acid)12Aquatic exposureand riskAll6835.32808Simulation Test to Assess theBiodegradability of ChemicalsDischarged to wastewaterDegradate(isocyanuric acid)12Aquatic exposureand riskAll6835.4300 Aerobic aquatic metabolismDegradate(isocyanuric acid)12Aquatic exposureand riskAll6835.4400 Anaerobic aquatic metabolismDegradate(isocyanuric acid)12Aquatic exposureand riskAll6OECD 209 or850.33009Activated Sludge RespirationInhibition (ASRI)Degradate(isocyanuric acid)12Aquatic exposureand riskAll6860.146010Food-handling TEP 24Dietary andaggregate riskFood processing, dairy,and public eatingestablishmentsDietarySpecialStudy11Migration studies TEP 24Dietary andaggregate riskAdhesives andpulp/paper millslimicide useDietaryPage16of521Applicable Occupational Handler Exposure Scenarios: 1- Open pour liquids, granules and powder for hard surface disinfection andpool treatment; 2- Openpour granules for material preservation; 3- Mop, wipe and trigger spray for hard surface disinfection; 4- Hand wand spray disinfection of egg and food processingplants; 5- Fogging disinfection of egg and food processing plants; and 6- Brush, roller and spray application of preserved paints.2Applicable Residential Handler Exposure Scenarios: 1- Open pour liquids, granules and powder for pool treatment; 2- Mop, wipe and trigger spray for hardsurface disinfection; and 3- Brush, roller and spray application of preserved paints.3It may be possible to use proprietary surrogate exposure data if data compensation issues can be addressed.4If the labels are modified to require automatic foggers in place ofhand held foggers, then the study of hand held fogging exposures would not be expected to beneeded.5If surface residue data are not available, then the standard assumption of 100 percent transferable surface residue will be used which might overestimate the risk6Industrial Process and Water Treatment: Cooling Tower and Swimming Pools and Water Beds; Hard Surfaces Disinfectants and Sanitizers: DtD residential andindustrial; Laundry Products: DtD residential and commercial; Material Preservatives: DtD Production and In-Service.7All uses footnoted with marine diatom and freshwater diatom data formaterial preservative uses, hard surface disinfection andsanitization uses, and floricultureuse may be eligible for data waiver if green algae (Selenastrum capricornutum) NOAEC results are greater than or equal to 1 ppm. The anticipated DCI willaddress this.8EPA has published final guidelines for four biodegradation studies. The biodegradation study anticipated to be required for chlorinated isocyanurates is for thedegradate (Cyanuric acid based on an Activated Sludge Respiration Inhibition Test. The Agency anticipates codifying these studies in 40CFR 158W in the nearfuture.9The results of the Activated Sludge Respiration Inhibition Test(ASRI) expected to be required will determine which of these four biodegradation tests would beanticipated to be required. If the ASRI test EC50is less than or equal to 20 mg/L, then either the (i)Biodegradation in Activated Sludge Study or (ii) SimulationTest – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii)the Porous Pot Test would be anticipated to be required. If the ASRI test EC50is greaterthan 20 mg/L, then the 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 Sludge Units or c) the PorousPot Test. If the ReadyBiodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the antimicrobial fails the ReadyBiodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) thePorous Pot study would be expected to be required. The appropriate Test Substance to satisfy the guideline requirement is the degradate (cyanuric acid).10Residue chemistry data are anticipated to be needed to determine dietary exposure to cyanuricacid/isocyanuric acid following sanitization of food contactsurfaces of food processing plants (including dairies) and food-handling facilities(including public eating places). Protocolsubmission is recommended. Theanticipated DCI will address this.11Migration of cyanuric acid/isocyanuric acid from preserved adhesive to food and from paper/paperboard to food following the slimicide use. The anticipatedDCI will provide that a protocol must be submitted for EPA approval prior to initiating the study.

### Page 17 of 52 

## 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 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 and 15,400 mg/kg/day. Because th ese PODs are much higher than the limit dose of 1000 mg/kg/day 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 A 

### (mg/kg/day) Point of Departure (POD) Study

Acute Dietary (females 13+) NOAEL= 200 mg/kg/day UF = 100 Increased incidence of hydrocephaly at 500 mg/kg/day. Developmental Toxicity - Rat

Acute RfD =2.0 mg/kg/day Acute Dietary

(gen. Pop.) N/A No appropriate endpoint was identified for the general population
Chronic Dietary NOAEL =154 mg/kg/day 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

Chronic RfD = 1.5 mg/kg/day Incidental Oral,

Short-Term N/A No appropriate endpoint was identified for short-term incidental oral risk.
Incidental Oral, Intermediate-term NOAEL = 204 mg/kg/day Based upon hyperplasia of the urinary bladder at a dose of 672 mg/kg/day. 90-Day Oral Toxicity - Rat Short- and Intermediate-Term (Dermal) NOAEL= 200 mg/kg/day B UF = 100 C Increased incidence of hydrocephaly at 500 mg/kg/day. Developmental Toxicity - Rat
Long-Term

(Dermal) NOAEL=154 mg/kg/day 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

### Page 18 of 52 Exposure Scenario Dose A 

### (mg/kg/day) Point of Departure (POD) Study

Inhalation(Any

time point) NOAEL= 0.0032 mg/L

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

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

B Since an oral endpoint was selected for dermal risk assessments, a derm al 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.



### 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 PTAP will be assessed by comparing dietary exposure estimates expressed in mg/kg/day to the 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).

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 degrad ates and tautomeric pa ir cyanuric acid and isocyanuric acid following saniti zation of food contact surfaces of food processing plants

### Page 19 of 52 (including dairies) and food-ha ndling facilities (including pub lic 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.”

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 included the interm ediate term incident al oral NOAEL of 204 mg/kg/day and the long term N OAEL of 154 mg/kg/day. These e xposures were calculated for

### Page 20 of 52 both adult (77 kg) and child (29 kg) competitive swimmers using the SWIMODEL and assuming a chlorinated isocyanurate water concentration of 55 mg/liter, an exposure time of 3.0 hours per event, an event frequency of 150 events per ye ar, a water 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 adults and 270 for children. The combined MOEs were 160 for adults and 110 for children. All these 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 chloroisocyanurates was also measured using biomonitoring of urine to dete rmine water ingestion ra tes in a study conducted by the EPA Office of Research and Development (ORD). A pproximately 550 swimmers were included in this study and the pilot results from 53 swimmers were reported in Dufour, 2006 and incorporated into the Exposure Factors Handbook (EPA, 2011). Although the purpose of this study was to measure water ingest ion rates, the study could also be used to back calculate chloroisocyanurate exposures fo r comparison to the estimates derived from the SWIMODEL.

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 - Occupational Exposure Scenarios for the Chlorinated Isocyanurates

Scenario Exposure Route(s) Duration
Occupational Exposures Open pour liquids, 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 pour liquids, granules and powder for pool treatment Inhalation Short Term Brush and Roller Application of Preserved Paint Inhalation Short Term Swimming in Treated Pools Incidental oral Short and Intermediate Term Ingestion of treated drinking water Oral Long Term Toddlers playing on disinfected floors In cidental Oral Short and Intermediate Term

### Page 21 of 52 

## 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 threatened or endangered species (listed species) or their designated critical ha bitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.

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 on 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

### Page 22 of 52 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 2 

### . The risk assessment to be conducted as part of this registra tion review will evaluate risk from the chlorinated isocyanuric acid metabolite, isocyanuric acid.

Figure 1 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates and their Reaction Products/Deg radates from Sanitizing and Disinfecting Uses for Laundry and Hard Surfaces to Aquatic and Terrestrial Organisms

2 Na & Ca Hypochlorite Registration Review: Final Work Plan, Docket ID EPA-HQ-OPP-2012-0004-0006



### 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 disposal

### Page 23 of 52 Figure 2 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates and their Reaction Products/D egradates 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 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 Pool Treatment and Waterbed Use

WWTP microorganisms Uptake or sorption

Populatio

n Respiratio

n inhibition Disposal to sanitary drain system Stormwater drain disposal

### Page 24 of 52 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 Discharge

### Page 25 of 52 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 Drains

### Page 26 of 52 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 values 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 3 

### (HPV) chemical for which a Screening Inform ation Data Set (SIDS) Assessment Report was performed (OECD SIDS 1999 and IIHAC 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

3 http://www.epa.gov/hpv/pubs/general/hpvchemdata.htm

### Page 27 of 52 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 28 of 52 

## 4.4 Effects Analysis Plan Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database 4 

### , 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 created 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

4 http://cfpub.epa.gov/ecotox/

### Page 29 of 52 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 Guidance for Commenters

6.1 Preliminary Work Plan The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the Chlorinated Is ocyanurates registration review case.

6.1.1 Trade Irritants

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any trade irritant issues resulting fr om lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible re garding the nature of the concern.

6.1.2 Water Quality

Pesticidal use of chlorinated isoc yanurates and its degradate cyanur ic acid are not identified as a cause of impairment for any water bodies listed as impaired under sec tion 303(d) of the Clean Water Act, based on information provided at the Agency’s National Pesticides Cause of Impairment of Waters websit e (searched November 27, 2012) 5 

### . In addition, no Total Maximum Daily Loads (TMDL) have been developed for chlorinated isocyanurat es and its degradate cyanuric acid, based on information provided at th e Agency’s National Pesticide TMDL web site

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

### Page 30 of 52 (searched November 27, 2012) 6 

### . More information on impaired water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/ . The Agency invites submission of water quality data for this pesticide. To the extent possible, da ta should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: In clusion of Impaired Water Body and Other Water Quality Data in OPP’s Regist ration Review Risk Assessment and Management Process 7 

### , in order to ensure they can be used quan titatively or qualitatively in pesticide risk
assessments.

TMDL Pollutant, Chlorine: Chlorine, the degradation product of chlorinated isocyanurates, is identified as a cause of impairment, as defined under section 303(d) of th e Clean Water Act, for 335 water bodies based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_im paired_waters.tmdls?p_pollutant_id=chlorine

. Impaired Waters, Cause of Impairment: Chlorine: Chlorine is identified as a cause of impairment, as defined under section 303(d) of the Clean Water Act for 129 water bodies, based on information provided at http://ofmpub.epa.gov/tmdl_waters10/attains_ nation_cy.cause_detail?p _cause_group_name=CH LORINE

Impaired Waters, Cause of Impairm ent: Organochlorine pesticides: Organochlorine pesticides are identified as a cause of im pairment, as defined under secti on 303(d) of the Clean Water Act for 

## 3 water bodies, based on information provided at http://ofmpub.epa.gov/tmdl_waters10/attains_imp aired_waters.control?p_cause_name=organoch lorine pesticides

Impaired Waters, Cause of Impairm ent: Chlorinated pesticides: Chlorinated pesticides are identified as a cause of impairment, as defined under section 303(d) of th e Clean Water Act for 1 water body, based on information provided at http://ofmpub.epa.gov/tmdl_waters10/attains_imp aired_waters.control?p_cause_name=chlorinat ed pesticides

During registration review of chlorinated isocya nurates, the Agency will attempt to determine the contribution of chlorinated isocyanurates us ed in swimming pools, cooling towers, hard surface disinfectants, and in-can/in-container pres ervatives to chlorine in impaired water bodies.

The Agency will determine whether pesticide us e was a contributor and/or determine if use might occur in these watersheds.

6.1.3 Environmental Justice

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation,

6 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES
7 http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf

### Page 31 of 52 and enforcement of environmental laws, regulati ons, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to chlorina ted isocyanurates compared to the general population. Please comment if you are aware of any sub-populations that may have atypical, unusually high exposure compared to the general population.

6.1.4 Structure Activity Relationships EPA must rely upon information of appropriate qual ity and reliability for each decision made by the Agency. In the Office of Pesticide Program s (OPP), the evaluation process for a pesticide chemical traditionally begins with the applicant’ s submission of a set of studies conducted with the specific pesticide chemical of interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous proce ss that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant intere st in alternative techniques, i.e. , techniques other than data generation that could significantly inform the Agency’s decision-making process. Recently, OPP has made increasing use of stru cture activity relationship (SAR ) as part of its regulatory decision-making process. In the SAR process, a ch emical's molecular structure is compared to that of other chemicals for which data are availabl e. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biol ogical properties are a f unction of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured da ta on a single physical, chemical, or biological property is used to derive a model (an equatio n) to predict the valu e of that property.

Since SAR assessments and QSAR modeling are anothe r set of tools that are available to Agency scientists, OPP has begun a proce ss shift that envisions shifting from the current study-by-study approach to an approach in which the use of pr edicted data, generated us ing validated models, is considered along with information from open litera ture and studies specifically generated under Part 161 requirements. All relevant information w ould be considered as pa rt of a weight-of-theevidence evaluation.

At this time, EPA believes that for certain e ndpoints, especially physi cal/chemical and fate properties, that SAR and QSAR might be effect ively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. When considering biological prope rties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lo wer toxicity chemicals can be stream-lined, i.e. , a screening-level assessment procedure rather than multiple tiers of assessments with progressively more data requirements.

### Page 32 of 52 If stakeholders believe that submission of predic ted data can fulfill one of the data needs for the Chlorinated Isocyanurates Case, then the Agency invites submission of this information. The submitter would be expected to supply a rationale describing the utility of the information and provide documentation on the scient ific validity of the informa tion. The determination that the predicted data fulfills the data requirement woul d be at the sole discretion of the Agency. Presubmission consultation with the Agency is encouraged.

6.1.5 Additional Information

Stakeholders are also specifically asked to provid e available information a nd data that will assist the Agency in refining its risk assessments, including any species-spec ific ecological effects determinations. The Agency is interested in receiving the following information:

1. Confirmation on the following label information: A. Sites of application B. Formulations C. Application methods and equipment D. Maximum application rates E. Frequency of application, applicatio n intervals and maximum number of applications F. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non-agricultural uses ( e.g. , materials preservation) 5. Typical application interval 6. State or local use restrictions 7. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency 8. Monitoring data.



## 7 Next Steps

After the 60-day comment period closes in February 2013 the Agency will review and respond to any comments received in a timely manner, and th en issue a Final Work Plan for the Chlorinated Isocyanurates Case.



## 8 References

Ellis DD et al; Arch Environ Contam Toxicol 11: 373 - 82 (1982)

Environmental Protection Agency. High Producti on Volume Information System (HPVIS). http://www.epa.gov/hpvis/

Soto, AM et al: The E-Screen Assay as a Tool to Identify Estrogen - An Update on Estrogenic Environmental Pollutants, Environmental He alth Perspectives, Vol. 103, Supplement 7, pp 113-122, October 1995.

### Page 33 of 52 USEPA. 1985. Ambient Water Quality Crite ria for Chlorine - 1984. Office of Water Regulations and Standards Criteria and Standards Divi sion, EPA 440/5-84-030.

USEPA. 1992. Registration Eligibility Docu ment (RED): Chlorinated Isocyanurates. USEPA/Pesticides and Toxic Substa nces (H-7508W), September, 1992.

Yamasaki et al; Immature Rat Uterotrophic Assa y of 18 Chemicals and Hershberger Assay of 30 Chemicals. Toxicology 183, pp 93-115, 2003.

### Page 34 of 52 

## 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 herbic ides share a symmetric triazine ring. However, trichloro isocyanuric acid is not to be confused with agronomic herbicides that are classified as s

triazine compounds which have alkyl side chains, and therefore, it is not considered as part of the triazine cumulative assessment (See Section 4.2 above). Therefore, a total toxic residue approach, as would be used for s -triazine compounds, will not be applied to assess environmental exposure. Trichloro isocyanuric acid dechlorinates to form the cyanuric acid and isocyanuric acid metabolites. These metabolites, which are tautomers, are the compounds of potential concern based on the environmental fate data ba sed on their environmental persistence. Under anaerobic conditions (acclimated or unacclimated microorganisms) and also aerobic conditions with acclimated microorganisms, these meta bolites 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 (parent compounds) are used in water treatment to form hypochlorous acid (an oxidizing agent) when dissolved in water. Hypochlorous acid is a weak acid because it has a pKa (d issociation 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 = -log 10 

### (3.7 x 10 -8 

### ). As the pH increases above 7.4, the amount of hypochlorite ion pres ent will increase. Conversely, as the pH decreases below pH 7.4, the amount of hypoc hlorous acid present will increase. Hypochlorous acid reacts readily with ammonia, amines, sulfides, sulfites, and nitrites present in the water. Antimicrobial activity results from the oxidation reactions with

### Page 35 of 52 microbial enzyme systems. All these oxidation reactions consume residual free chlorine, with the concurrent reduction of hypochlorous 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 (1982) found that cyanuric/isocya nuric acid is not prone to abio tic 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. Mineralized 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 atrazine mineralization was obser ved. 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 data

### Page 36 of 52 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 in Section 5.1.2 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 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), or

### Page 37 of 52 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 8



### .

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, 1982 2 MRID 00056479 Cyanuric acid was stable pp. 10-12 of HPV document 1 Photodegradation in Water (835.2240) Monosodium cyanurate Rapid degradation to cyanuric acid from hydrolysis (no photodegradation)_ Hu, 1982 2 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 3 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 4 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 5 Cyanuric acid formed CO 2 and NH 3
pp. 17-18 of HPV document Bacteria isolated from corn field

8 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 38 of 52 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 6 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 7 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 8 Cyanuric acid formed CO 2 and NH 3
pp. 22-23 of HPV document

### Page 39 of 52 Test Guideline (Number) Test Substance Result Reference Comment

Unknown Cyanuric acid 100 % degradation in unknown time Sisodia et al.

, 1996 9 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 4 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 10 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 11 Mixed culture of microorganisms in laboratory test.

1. http://www.epa.gov/hpv/pubs/summaries/tricltrz/c14659rs.pdf 2. Hu, H.C.; “Photodegradation Study of Aqueous Sodium Salt Solutions of 2,4,6-Trihydroxy -1,3,5-Triazine; Unpublished Study Conducted by Center Analytical Services, Princeton Chemical Research & Development Center, Princeton, NJ 08540 for the Isocyanurate Industry Ad Hoc Committee (EPA Consortium 55643); Study No. (none), January 21, 1981. MRID 00056479. 3. Michael, P., and Cummings, I., “Cyanuric Acid Absorp tion On Soils”, Monsanto Report ES-82-SS-94, December, 1982. Method: OECD 106. 4 An Index of Refractory Organics, T. Helfgott, F. Ha rt and R. Bedard, EPA 600/2-77-174, 1977, pp. 1-7, 24-25. Process for the biological degradation of cyanuric acid, J. Zeyer, R. Hütter, and P. Mayer, UK Patent App. 2,025,919 (Jan. 30, 1980). 5 Degradation of Cyanuric Acid by Immobilized Bacteria , C. Ernst and H. Rehm, DECHEMA Biotechnol. Conf., 4(Pt. A), 1990, 577-580. Method: J. Biol. Chem. 195, 265-275 (1951). 6 Anaerobic Degradation of Cyanuric Acid, Cysteine, and Atr azine by a Facultative Anaerobi c Bacterium, J. Jessee, R. Benoit, A. Hendricks, G. Allen, and J. Neal, A ppl. and Environ. Microbiol., 1983, 45(1) 97-102. Method : J. Water Pollution Control Fed., 39, 181-187 (1967); J. Water Pollution Control Fed., 40, 306-319 (1968) 7 Ring cleavage and degradative pathway of cyanuric acid in bacteria, A. Cook, P. Beilste in, J. Grossenbacher, and R. Hütter, Biochem. J., 1985, 231, 25-30. Method : J. Water Pollution Control Fed., 39, 181-187 (1967); J. Water Pollution Control Fed., 40, 306-319 (1968) 8 Biodegradation of Cyanuric Acid, J. Sald ick, Applied Microbiology, 1974, 28(6) 1004-1008. Method: (1967) J. Water Pollut. Contr. Fed. 39:181-187; Biodegradability of organic chemicals isolated from rivers. (1963) Proc. 18th Ind. Waste Conf. Purdue Univ. 115:278-282.

### Page 40 of 52 9 Continuous Culture Biodegradation of Simazine’s Chemical Oxidation Products, S. Sisodia, A. Weber, and J. Jensen, Water Research, 1996, 30(9) 2055-2064. Method: S-triazine biodegradation was investigated as a function of continuous culture process growth rate. 10 Anderson, K.L., K.A. Wheeler, J.B. R obinson, and O.H. Tuovinen. 2002. Atrazine Mineralization Potential in Two Wetlands. Water Research 36(2002): 4785-4794. 11 Kontchou, C.Y and N. Gschwind. 1999. Biodegradation of S-Triazine Compounds by a Stable Mixed Bacterial Community. Ecotoxicology and Environmental Safety 43 (1999): 47-56.



### Hypochlorous Acid Chlorinated isocyanurates (parent compounds) are used in water treatment to form hypochlorous acid (HClO), an oxidizing agent. W hen dissolved in wa ter 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 antimicrobial 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 9 

### = 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

9 pK a = -log 10 K a

### Page 41 of 52 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 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 Dichloro- s -triazinetrione Sodium dichloro- s triazinetrione Trichloro- s -triazinetrione Sodium dichloro- s -triazinetrione dihydrate
Available Chlorine (%) 70 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

### Page 42 of 52 moieties cannot be calculated as these will depend on the environmental conditions like pH of the medium, temperature, ionic strength, etc

.

### Page 43 of 52 

## 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 44 of 52 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 45 of 52 

## Appendix C: Ecotoxicology Profile

A review of toxicity effects data for the chlorina ted isocyanurates is summarized in the following sections, with selected ecotoxicological endpoi nts for risk assessment provided in Table 1. Additional toxicity information is obt ained 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 derives freshwater and saltwater organism acute and chronic water quality cr iteria as total chlorine residual (TRC) for freshwater and total residual oxidant (TRO) for seawater . Current ambient water quality criteria for chlorine or total chlorine residual are based on the data in th e 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/L

Terrestrial - Avian acute- oral and dietary toxicity

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 (T able 14), sodium dichloroisocyanurate dihydrate (Table 15), and sodium dichloro -s-triazinetrione (Table 16). Those 10 studies categorize the chlorinated isocyanurates (TGAI) as being slightly to practically nontoxic to birds on an acuteoral basis (LD 50 

### ’s = 1021 to >2250 mg ai/kg-bw). The guideline requirement (850.2100) is satisfied. Chronic data (850.2300) are not expected to be required.

Avian dietary toxicity studies ( 850.2200) are not expected to be required for the current uses.However, 14 studies were submitted for trichloro-s-triazinetrione, sodium dichloro-striazinetrione, and sodium dichloroisocya nurate dihydrate for both mallard and northern bobwhite. Those data categori ze the chlorinated isocyanurates (TGAI) as being practically nontoxic to birds on a dietary basis (LC 50 

### ’s >5000 ppm).

### Page 46 of 52 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 Acceptable

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

98.13 LD 50 : 1766 mg/kg-bw/day Slightly toxic 256739 Acceptable

Acute – Avian Dietary 850.2200 Northern bobwhite 98 LC 50 : >5000 ppm Practically nontoxic 256739 Acceptable

Mallard 98 LC 50 : >5,000 ppm Practically nontoxic 256739 Acceptable

1 Toxicity values based on parent compound (TGAI).

### Page 47 of 52 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 : 1766 mg/kg-bw/day Slightly toxic 256739 Acceptable

98.3 LD 50 : >2250 mg/kg-bw/day Practically nontoxic 254911 Acceptable

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

100 LD 50 : 1916 mg/kg-bw/day Slightly toxic 241226 Acceptable

Acute – Avian Dietary 850.2200 Northern bobwhite 98 LC 50 : >5600 ppm Practically nontoxic 254910 Acceptable

98.3 LC 50 : >5000 ppm Practically nontoxic 256739 Acceptable

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

Mallard 100 LC 50 : >10,000 ppm Practically nontoxic 00007219 Acceptable

98 LC 50 : >5620 ppm Practically nontoxic 254909 Acceptable

98.3 LC 50 : >5000 ppm Practically nontoxic 256739 Acceptable

1 Toxicity values based on parent compound (TGAI).



### Mammals

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

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 there degradates.

### Page 48 of 52 Aquatic - Freshwater Fish and Invertebrate Toxicity

According to the Office of Water’s Ambient Water Quality Criteria for Chlorine – 1984 (AWQC, EPA 1985), the term “total residual chlorine” (TRO) refers to the sum of free chlorine and combined chlorine in fresh water. In sa ltwater, in which chlorine forms will react with bromide, “chlorine-produced oxidants” (CPO) is used to refer to the sum of the oxidative products. Therefore, the toxicity values presented in this docume nt, expressed as μg ai/L, refer to TRO for freshwater organisms and CPO for saltwater organisms.

Acute toxicity data requirements and toxicity endpoints for freshwater and saltwater fish and invertebrates are presented below. Chronic data are anticipated to be required as none are available for either fish or invertebrates.

Freshwater Fish

To assess potential acute and chr onic risks to aquatic freshwater fish, acute and chronic effects data are anticipated to be required for the TGAI . The preferred test sp ecies are rainbow trout ( Oncorhynchus mykiss ), a coldwater species, and bluegill sunfish ( Lepomis macrochirus ), a warmwater species. The 19 available studies for trout and bluegill categorize the four chlorinated isocyanurates tested as being mo stly highly toxic to freshwater fish (LC 50 

### ’s = 80 to 1720 μg ai/L). No additional acute data are neede d. Acute toxicity data for freshwater fish and invertebrates are available for trichloro- s -triazinetrione (Table 17), sodium dichloro-striazinetrione (Table 18), sodium dichlorois ocyanurate dihydrate (Tab le 19), and potassium dichloroisocyanurate (Table 20). Chronic data (early-life stage toxic ity, guideline 850.1400) are anticipated to be required.

Freshwater Invertebrates

Data are anticipated to be required to assess potential acute and chr onic risks to aquatic freshwater invertebrates. The preferred test species is Daphnia magna or Daphnia pulex

. Twelve studies have been submitted. The data categorize the four chlorinated isocyanurates tested as being highly toxic to freshwater invertebrates (LC 50 

### ’s = 110 to 800 μg ai/L). The guideline requirement for acute testing (OCSPP 850.1010) is satisfied. No additional acute data are anticipated to be needed. However, chroni c data (life stage toxic ity, guideline 850.1300) are anticipated to be required.

Estuarine and Marine Organisms

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. The preferred te st species are the sheepshead minnow ( Cyprinodon variegatus ), Eastern oyster ( Crassostrea virginica ), and mysid shrimp ( Mysidopsis bahia ). No data have been submitted for the TGAI. Data submitted to support sodium hypochlorite, which

### Page 49 of 52 also generates hypochlorous acid, indicates 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 generated using sodium hypochlorite formulations and do not support the TGAI. Howe ver, data are available in the AWQC (EPA 1985) indicating that CPO is highly to very hi ghly toxic to estuar ine/marine fish and invertebrates (Table 17). No additional acute data are needed. However, chronic data for fish (early life stage toxicity, guideline 850.1400) an d invertebrate (life st age toxicity, guideline 850.1350) are required.

Table 17 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate Ecotoxicity Studies for Tr ichloro-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 26195 Acceptable

100 96-hr LC 50 : 370 μg ai/L Highly toxic 26193 Acceptable

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

Bluegill 100 96-hr LC 50 : 200 μg ai/L Highly toxic 00150965 Acceptable

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

100 96-hr LC 50 : 620 μg ai/L Highly toxic 26194 Supplemental

Acute – Freshwater Invertebrate

850.1010 Waterflea 92.8 48-hr EC 50 : 170 μg ai/L Highly toxic 00150967 Acceptable

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

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

NR 48-hr EC 50 : 250 μg ai/L Highly toxic 00019766 Supplemental



### 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 TN1038 Acceptable

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

### Page 50 of 52 Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & Status

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

Bluegill 100 96-hr LC 50 : 1720 μg ai/L Moderately toxic TN1039 Acceptable

100 96-hr LC 50 : 810 μg ai/L Highly toxic TN368 Supplemental

63 96-hr LC 50 : 283 μg ai/L Highly toxic 251231 Supplemental

57 96-hr LC 50 : 2400 μg ai/L Moderately toxic TN1030 Acceptable

Acute – Freshwater Invertebrate

850.1010 Waterflea 98 48-hr EC 50 : 110 μg ai/L Highly toxic 255593 Acceptable

98.3 48-hr EC 50 : 280 μg ai/L Highly toxic 256739 Acceptable

55.63 48-hr EC 50 : 199 μg ai/L Highly toxic 00007241 Supplemental

NR 48-hr EC 50 : 220 μg ai/L Highly toxic 00019310 Supplemental



### 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 & Status

Acute – Freshwater Fish 850.1075 Rainbow

trout 98 96-hr LC 50 : 250 μg ai/L Highly toxic 256739 Acceptable
Bluegill 98 96-hr LC 50 : 460μg ai/L Highly toxic 00150950 Acceptable
Acute – Freshwater Invertebrate

850.1010 Waterflea 98 48-hr EC 50 : 460 μg ai/L Highly toxic 00150950 Acceptable



### Table 20 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate Ecotoxicity Studies for Pota ssium Dichloroisocyanurate

Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & Status

Acute – Freshwater Fish 850.1075 Rainbow

trout 100 96-hr LC 50 : 316 μg ai/L Highly toxic 00019316 Acceptable

50 96-hr LC 50 : 750 μg ai/L Highly toxic TN0679 Supplemental

### Page 51 of 52 Study Type Species Test material

(% ai) Toxicity Toxicity Classification MRID & Status

Bluegill 100 96-hr LC 50 : 490 μg ai/L Highly toxic 00019316 Supplemental

Brook trout 100 96-hr LC 50 : 278 μg ai/L Highly toxic TN01107 Supplemental

Acute – Freshwater Invertebrate

850.1010 Waterflea 100 48-hr EC 50 : 170 μg ai/L Highly toxic 234257 Acceptable

50 48-hr EC 50 : 660 μg ai/L Highly toxic TN0868 Acceptable

NR 48-hr EC 50 : 170 μg ai/L Highly toxic 00019311 Supplemental



### Aquatic Plants

Aquatic plant-growth data are anticipated to be required to support the industrial processes and water systems uses. Data are anticipated to be required for one vascular species, Lemna sp. (OCSPP 850.4400), three algal species (O CSPP 850.4500), and cyanobacteria (OCSPP 850.4550). No data have been submitted.

Isocyanuric acid Toxicity

No effects data on cyanurate/isocyanuric acid has been submitted to the OPP for review in support of pesticide registration. The Agency recognizes that is ocyanuric acid is an EPA high production volume 10 

### (HPV) chemical for which a Screening Information Data Set (SIDS) Assessment Report was performed (OECD SIDS 1999 and IIHAC 2003). Values found in these sources have been listed in the table below and consist of freshwater fi sh and invertebrate and green algae data. While some critical elements of these studies 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 estuarine/marine fish and invertebrate acute and chronic values and the median effect concentration (EC 50 

### ) and maximum allowable toxicant con centration (MATC; geometric mean of the NOAEC and LOAEC) for green algae. These values are also listed in Table 21.

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 / Acceptable Model

Rainbow trout Acute 96-h LC 50 >2100 mg/L b IIHAC 2003 b / Unacceptable c
Bluegill Acute 96-h LC 50 >1000 mg/L b IIHAC 2003 b / Unacceptable c

10 http://www.epa.gov/hpv/pubs/general/hpvchemdata.htm

### Page 52 of 52 Receptor

Group Test Material a Surrogate Species Risk Scenario Toxicity Endpoint Reference/ Study Classification
Fathead minnow Acute 96-h LC 50 >1000 mg/L b IIHAC 2003 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 / Acceptable Model

Freshwater invertebrates isocyanuric acid Daphnid Acute 48-h EC 50 = 24.6 mg/L ECOSAR v1.1 a / Acceptable Model Daphnid Chronic MATC = 1.49 mg/L ECOSAR v1.1 a / Acceptable Model

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 fish Isocyanuric acid Generic Acute 96-h LC 50 = 46.9 mg/L ECOSAR v1.1 a / Acceptable Model Generic Chronic MATC = 2.45 mg/L ECOSAR v1.1 a / Acceptable Model

Estuarine/marine

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

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

EC 50 96-h EC 50 = 712 mg/L b IIHAC 2003 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 estima tions for aromatic triazines.
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.