Chlorine Dioxide Occupational and Residential Exposure Assessment Case 4023 Timothy Leighton, Ph. D. Office of Pesticide Programs Antimicrobials Division U. S. Environmental Protection Agency 1200 Pennsylvania Avenue, NW Washington, DC 20460 April 5, 2006 Page 2 of 58 TABLE OF CONTENTS 1.0 INTRODUCTION...................................................................................................................................... 6 1.1 Purpose................................................................................................................................................. 6 1.2 Criteria for Conducting Exposure Assessments...................................................................................... 6 1.3 Chemical Identification ......................................................................................................................... 6 1.4 Physical/ Chemical Properties ................................................................................................................ 7 2.0 USE INFORMATION................................................................................................................................ 7 2.1 Formulation Types and Percent Active Ingredient.................................................................................. 7 2.2 Summary of Use Pattern and Formulations ............................................................................................ 8 3.0 SUMMARY OF TOXICITY CONCERNS RELATING TO EXPOSURES............................................... 15 3.1 Acute Toxicology................................................................................................................................ 15 3.2 Summary of Toxicity Concerns Relating to Exposures......................................................................... 16 3.3 FQPA Considerations.......................................................................................................................... 17 4.0 RESIDENTIAL AND PUBLIC ACCESS PREMISES .............................................................................. 18 4.1 Summary of Registered Uses............................................................................................................... 18 4.2 Dietary Exposure/ Risk Pathway ( Place holder) .................................................................................... 18 4.3 Drinking Water Exposure/ Risk Pathway ( Place holder)........................................................................ 18 4.4 Residential Exposure/ Risk Pathway..................................................................................................... 18 4.4.1 Residential Handler Exposure........................................................................................................ 18 4.4.2 Residential Post Application Exposure........................................................................................... 23 <IP_ADDRESS> Hard Surface/ Floor ................................................................................................................... 24 <IP_ADDRESS> Ventilation Systems .................................................................................................................. 30 <IP_ADDRESS> Continuous Release ( Gas) Deodorizer ...................................................................................... 31 <IP_ADDRESS> Swimming Pools & Spas........................................................................................................... 33 4.4.3 Data Limitations/ Uncertainties....................................................................................................... 33 5.0 RESIDENTIAL AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION ................. 34 6.0 OCCUPATIONAL EXPOSURE AND RISK............................................................................................ 34 6.1 Occupational Handlers ........................................................................................................................ 34 6.2 Occupational Post Application Exposure ............................................................................................. 44 6.3 Data Limitations/ Uncertainties ............................................................................................................ 49 7.0 REFERENCES........................................................................................................................................ 51 APPENDIX A: Summary of CMA data and PHED............................................................................................... 53 APPENDIX B: Input/ Output from E FAST/ CEM................................................................................................. 56 Page 3 of 58 EXECUTIVE SUMMARY This document contains the occupational and residential exposure assessment for industrial, commercial, residential, and agricultural premises and equipment uses of chlorine dioxide. Both sodium chlorite and sodium chlorate are used as a precursor in the generation of chlorine dioxide. The handler exposures to sodium chlorite are also included in this document because the same toxicological endpoints are used for both chlorine dioxide and sodium chlorite. The handler exposures to sodium chlorate itself are assessed in a separate document ( USEPA, 2005b).

Chlorine dioxide, sodium chlorite, and sodium chlorate are active ingredients in numerous products used in the control of bacteria, fungi, and algal slimes. In addition, they are used as material preservatives and as disinfectants. At this time, these products are intended for agricultural premises and equipment, commercial, industrial, medical and residential use. The agricultural uses include the disinfection of hard surfaces and equipment ( such as hatching facilities and mushroom houses) and water systems ( such as chiller water and humidification water in poultry houses). Commercial, industrial, and medical uses include disinfection of heating ventilating and air conditioning ( HVAC) systems, hard surfaces ( e. g., floors, walls, and laboratory equipment), water systems, pulp/ paper mills, and food rinses. Residential uses include disinfection of hard surfaces ( e. g., floors, bathrooms), and HVAC systems. Concentrations of chlorine dioxide and sodium chlorite in products range from 0.1% to 80%. Most formulations are in liquid form. However, chlorine dioxide and sodium chlorite are also available as tablets, ready to use solutions, dusts, and sachets. The application rates used in this assessment were the maximum application rates recommended on the product labels.

Acute toxicity categories for chlorine dioxide include Category III for oral and dermal and Category II for inhalation. The toxicological endpoints selected to assess chlorine dioxide and sodium chlorite risks include short and intermediate term dermal and ingestion exposure. The short and intermediate term NOAEL for both the dermal and oral routes is 3 mg/ kg/ day. For the dermal route, 100 percent dermal absorption is assumed. The oral NOAEL is based on depression of serum T4 levels in pups from dosed maternal rats and delays in development of locomotor and exploratory behavior activities. For the oral and dermal route of exposure, an uncertainty factor or " target" margin of exposure ( MOE) of 100 is based on 10x for differences among humans ( intraspecies variability) and 10x for differences between the test animals and humans ( interspecies extrapolation). Thus, MOEs of greater than 100 are above the Agency's target MOE for oral and dermal routes for occupational and residential uses.

The inhalation route of exposure to chlorine dioxide is assessed for three distinct subpopulations: ( 1) occupational exposures ( 8 hours/ day, 5 days/ week), ( 2) one time exposures for residential uses ( e. g., HVAC systems, mopping floors, etc), and ( 3) long term exposure for continuous release products in the home ( 24 hours/ day, 7 days/ week). Several animal studies were used to develop reference concentrations ( RfCs). The effects seen at various concentrations include rhinorrhea, altered respiration, respiratory infection, bronchial inflammation, alveolar congestion and hemorrhage, vascular congestion, and peribronchiolar edema. Readers are referred to USEPA ( 2005a) for a detailed review of the effects seen at specific concentrations and exposure durations along with the derivation of the RfC. In summary, the occupational RfC Page 4 of 58 is determined to be 0.003 ppm and represents an 8 hour time weighted average ( TWA). The one time residential exposure scenario is represented by the RfC of 0.05 ppm and the RfC for long term, continuous exposure is 0.00007 ppm. The RfC methodology incorporates the uncertainty factors into the concentration. For inhalation, the RfC is compared directly to the air concentration of interest. Inhalation risks are of concern if the air concentrations people are exposed to exceed the RfC.

The exposure scenarios selected as representative uses of chlorine dioxide to be assessed in the risk assessment are presented in the table at the end of this section. These scenarios were based on examination of product labels describing uses for the product. Several different sources of handler exposure data were used to assess occupational and residential chlorine dioxide risks. Data from both the proprietary Chemical Manufacturers Association ( CMA) antimicrobial exposure study and the Pesticide Handlers Exposure Database ( PHED) were used. In addition, chemical specific data were available to assess inhalation exposures for the following uses: HVAC, carpet, automobiles, and OSHA's Integrated Management Information System ( IMIS) for various industrial uses.

Residential Risks For residential dermal exposures, the calculated MOEs for handlers are less then the target MOE of 100 for the swimming pool & spa application scenarios ( i. e., for placing tablets into swimming pools/ spas, the dermal MOE = 46). Note: The risk may be over stated because the dermal absorption was assumed to be 100 percent due to the lack of a dermal absorption study or dermal route specific toxicity study. If the applicator wears gloves, the dermal risk would be mitigated ( i. e. MOE is 500) The inhalation exposures to the handlers are not of concern.

The calculated dermal and incidental oral MOEs for post application exposure were not of concern for all scenarios. The post application inhalation MOEs were not of concern except for dust applications to carpets. Although the inhalation risks were indeterminate for the carpet use, additional monitoring data are warranted based on the air concentration measurements available 3 to 4 hours post treatment.

One product has been identified that is registered as a continuous release of chlorine dioxide gas in homes. The product is packaged as a pouch or sachet. A bounding estimate of air concentration is presented based on the application rate and the label referenced longevity of the pouches/ sachets. The theoretical constant air concentration would be 0.52 ppm assuming no air exchange and no build up of chlorine dioxide over time because of the short half life. The RfC for long term continuous exposure is 0.00007 ppm. Therefore, the theoretical concentration from the product's release is of concern. Before any refinements to these air concentration estimates are attempted, it should be determined if the product's efficacy can be maintained at the RfC of ~ 0.00007 ppm.

Occupational Risks For occupational dermal exposures, calculated MOEs less than the target dermal MOE of Page 5 of 58 100 were found for the following handler scenarios: Agricultural Premises and Equipment ° application to hard surfaces via low pressure hand wand ( MOE = 31) ° application to hard surfaces via mopping ( MOE = 70) ° foam applicator to animal transport vehicles/ tractor trailer ( MOE = 8)

Food Handling, Commercial/ Institutional, and Medical Premises and Equipment ° application to hard surfaces via mopping ( MOE = 66 for commercial and 3 for medical)

Inhalation exposures/ risks were not assessed separately for the handlers. Instead, the occupational inhalation handler exposures are combined as part of the full work day for handler/ bystanders to be comparable to EPA's inhalation toxicological endpoint which is based on an 8 hour TWA. For the peak, short term exposures to chlorine dioxide gas experienced during mixing/ loading and/ or system leaks/ failures, EPA will rely on the American Conference of Governmental Industrial Hygienists ( ACGIH) Short term Exposure Limit ( STEL) and Immediately Dangerous to Life or health ( IDLH) to mitigate risks.

For most of the bystander/ post application occupational scenarios, dermal exposures are not expected to occur or are expected to be negligible based on the relatively low application rates and chemical properties ( e. g., volatility and short ½ life) of chlorine dioxide, sodium chlorite and sodium chlorate. However, the inhalation risks for the bystander/ post application occupational exposures are of concern using the EPA's selected inhalation toxicological endpoint ( RfC). The occupational RfC, 0.003 ppm, is below the limit of detection for chlorine dioxide. Based on OSHA's IMIS data available for chlorine dioxide, all air concentration measurements, even those that were nondetect, are above the RfC. Reconciliation of the EPA risk based RfC and current OSHA standards will be made during the regulatory decision phase of the Reregistration Eligibility Decision ( RED) for chlorine dioxide.

There are a number of uncertainties associated with this assessment ( see Sections 4.4.3 and 6.3). In general, conservative values were used in cases where data were lacking. Assessments for these scenarios should be considered as screening level.

Use Scenarios Based on Product Labels for Chlorine Dioxide, Sodium Chlorite and Sodium Chlorate Use Site Scenario Agricultural Premises and Equipment Low pressure hand wand, fog, mop, spray, foaming wand for hard surfaces Fogging ( e. g., egg houses) Food Handling, Commercial/ Institutional, Medical Mop and spray on hard surfaces Fruit & vegetable dip Residential and Public Access Trigger pump sprayer and mop to hard surfaces HVAC reentry Solid tablets for swimming pools and spas Continuous release deodorizer Page 6 of 58 Use Scenarios Based on Product Labels for Chlorine Dioxide, Sodium Chlorite and Sodium Chlorate Use Site Scenario Human Drinking Water Systems Metering pump for potable water and storage systems Material Preservatives Metal working fluids ( MWF)

Industrial Processes and Water Systems Metering pump to pulp and paper white water systems Liquid pour to oil systems Swimming Pools and Aquatic Areas Liquid pour to non potable water systems ( e. g., retention ponds and decorative fountains)

Tablets in the circulation systems of swimming pools & spas HVAC Systems Spray and fog of ventilation systems ( e. g., duct work)

1.0 INTRODUCTION 1.1 Purpose In this document, EPA presents the results of its review of the potential human health effects of occupational and residential exposure to chlorine dioxide, including the releases of chlorine dioxide from sodium chlorite and sodium chlorate applications. This information is for use in EPA's development of the chlorine dioxide Reregistration Eligibility Decision ( RED) document.

1.2 Criteria for Conducting Exposure Assessments An occupational exposure assessment is required for an active ingredient if ( 1) certain toxicological criteria are triggered and ( 2) there is potential exposure to handlers ( mixers, loaders, applicators, etc.) during use or to persons entering treated sites after application is complete. For chlorine dioxide, both criterions are met. Note: The toxicity of sodium chlorite has been assumed to be equivalent to that of chlorine dioxide.

1.3 Chemical Identification Three chemicals are considered in this document: chlorine dioxide, sodium chlorite, and sodium chlorate. Products containing chlorine dioxide or sodium chlorite have been included in this risk assessment. Risks/ exposures to sodium chlorate itself have been assessed in a separate document: " Sodium Chlorate: Occupational and Residential Exposure Assessment of Antimicrobial Uses for the Reregistration Eligibility Decision Document" ( USEPA, 2005). However, risks to chlorine dioxide released from sodium chlorate applications are included in the scope of this document. Table 1.1 presents the chemical identification information for the three chemicals. Page 7 of 58 Table 1.1. Chemical Identification Information for Chlorine Dioxide, Sodium Chlorite, and Sodium Chlorate Chlorine Dioxide Sodium Chlorite Sodium Chlorate OPP Chemical Code 020503 020502 073301 CAS Number 10049 04 4 7758 19 2 7775 09 9 Molecular Formula ClO2 NaClO2 NaClO3 1.4 Physical/ Chemical Properties Table 1.2 shows physical/ chemical characteristics that have been reported for chlorine dioxide and sodium chlorite.

Table 1.2. Physical/ Chemical Properties of Chlorine Dioxide and Sodium Chlorite Property Chlorine Dioxide Sodium Chlorite Molecular Weight 67.45 g/ mol 90.45 g/ mol Color Yellow to Reddish Yellow White Melting Point  59oC 180 200oC ( decomposes)

Boiling Point 11oC n/ a Odor Strongly pungent, chlorine like n/ a Physical State Gas at room temperature Solid Density 1.64 g/ ml at 0oC ( liquid) 1.614 g/ ml at 10o C ( liquid) 2.468 g/ ml ( as a solid)

Vapor Pressure 490 mm Hg ( 0oC) > 760 mm Hg ( 25oC) n/ a Stability Unstable, estimated half life in water ~ 25 minutes n/ a Solubility ( water) 3.01 g/ L at 25oC and 34.5 mmHg 390 g/ L at 30oC References: ATSDR 2004 and Gates 1998 2.0 USE INFORMATION 2.1 Formulation Types and Percent Active Ingredient Concentrations of chlorine dioxide and sodium chlorite in products range from 0.1% to 80%. Most formulations are in liquid form. However, chlorine dioxide and sodium chlorite are also available as tablets, wettable powders, and water soluble packets. Registered uses include use as a fruit/ vegetable rinse, potable water treatment, hard surface disinfectant, disinfectant of ventilation systems, foggers, material preservatives ( e. g., water based cutting oils), industrial systems ( e. g., water cooling towers), and non potable water systems. Page 8 of 58 2.2 Summary of Use Pattern and Formulations Chlorine dioxide and sodium chlorite are active ingredients in numerous products used in the control of bacteria, fungi, and algal slimes. In addition, chlorine dioxide and sodium chlorite are used as material preservatives and as disinfectants. At this time, products containing chlorine dioxide and sodium chlorite are intended for agricultural, commercial, industrial, medical, and residential use. The agricultural uses include the disinfection of hard surfaces and equipment ( such as hatching facilities and mushroom houses) and water systems ( such as chiller water and humidification water in poultry houses). Commercial, industrial, and medical uses include disinfection of ventilation systems, hard surfaces ( e. g., floors, walls, and laboratory equipment), water systems, pulp/ paper mills, and food rinses. Residential uses include disinfection of hard surfaces ( e. g., floors, bathrooms), and ventilation systems along with a pool/ spa water circulation system treatment.

The Agency determines potential exposures to handlers of the product by considering exposure scenarios from the various application methods that are plausible, given the label uses. Based on review of the product labels and the various uses identified, several potential exposure scenarios were chosen for this risk assessment. Those scenarios, the methods of application, and the maximum application rates are provided in Tables 2.1 through 2.3. Tables of use scenarios are provided for chlorine dioxide, sodium chlorite, and sodium chlorate. Representative uses were chosen from all of the uses for all three chemicals, based on application method, rate and potential exposures. After review of the labels, it was determined that sodium chlorite and chlorine dioxide labels represent the highest application rates that produce chlorine dioxide. Application rates were determined in pounds active ingredient per gallon ( lb ai/ gal). It is assumed that rates of sodium chlorite produce equivalent rates of chlorine dioxide ( e. g., 0.08 lb ai/ gal of sodium chlorite solution equals 0.08 lb ai/ gal of chlorine dioxide). The density of chlorine dioxide in liquid form ( 1.642 g/ cm3 or 13.7 lb/ gal) was used to determine the lbs ai/ gal. It was assumed that a 100% active ingredient solution would contain 13.7 lb ai/ gal. This ratio was then used to determine the lb ai/ gal for other products, by multiplying the % ai provided on the label by a factor of 0.137 ( 13.7/ 100). For some of the sodium chlorite labels, the application rate was not provided in terms of lbs ai/ gal. Therefore, a ratio of lbs ai/ gal to % ai was used from another label ( 0.1032; EPA Reg. 1757 96). This ratio was multiplied by the % ai to estimate the lbs ai/ gal. Page 9 of 58 Table 2.1. Use Scenarios and Methods of Application Based on Product Labels for Chlorine Dioxide Uses Representative Exposure EPA Reg. # Associated with Maximum Exposure Application Rate Associated with Maximum Exposure ( lb a. i./ gallon) Residual Chlorine Dioxide Level ( ppm)

Use Site Category I ( Agricultural Premises and Equipment) a $ Low pressure hand wand 0.014 1000 $ fog ( 1 hour REIb) 0.014 1000 $ mop $ spray 0.018 1250 $ dip ( e. g., litter boxes) Liquid concentrate 9150 2 0.014 1000 $ shampoo Liquid concentrate 9804 1 0.008 500 Application to hard surfaces ( e. g., animal rearing and confinement facilities; horticulture uses; mushroom facilities)

$ foaming wand ( animal transport vehicles; agricultural storage facilities; containers, trailers, rail cars, vessels) Liquid concentrate 9150 11 0.025 not provided chiller water $ liquid pour Liquid concentrate 9150 2 0.001 40 Water systems humidification water in poultry houses $ mist or fog ( 1 hour REI) Liquid concentrate 9150 2 0.001 40 Use Site Categories II ( Food Handling), III ( Commercial/ Institutional), and V ( Medical)

Application to hard surfaces with food contact in Food processing plants; Hospitals ( e. g., water bath incubators, autoclaves); Public places ( e. g., restaurants, hotel/ motel rooms); Medical/ Dental offices $ spray 9150 2 Liquid Concentrate 0.014 1000 Page 10 of 58 Table 2.1. Use Scenarios and Methods of Application Based on Product Labels for Chlorine Dioxide Uses Representative Exposure EPA Reg. # Associated with Maximum Exposure Application Rate Associated with Maximum Exposure ( lb a. i./ gallon) Residual Chlorine Dioxide Level ( ppm)

Application to hard surfaces without food contact in Food processing plants; Hospitals ( e. g., water bath incubators, autoclaves); Public places ( e. g., restaurants, hotel/ motel rooms); Medical/ Dental offices $ mop or spray 9150 10 active Liquid concentrate ( 10589 3 transferred) 0.019 not provided Canner retort and pasteurizer cooling water $ liquid pour; chemical feed pump or injector 9804 1 Liquid concentrate 0.00007 5 Humidification water on stored potatoes $ mist or fog ( 1 hour REI after fogging) 9804 5 Liquid concentrate 0.003 200 Water systems Potable water, ice made from potable water $ liquid pour 9804 5 Liquid concentrate 0.017 not provided Ventilation systems ( HVAC) Ventilation systems ( HVAC)

$ spray or fog ( 1hour REI after fogging) 9804 1 Liquid concentrate 0.007 500 Fruit/ Vegetable rinses $ dip Liquid concentrate 9150 2 0.002 not provided Use Site Category IV ( Residential & Public Access) Application to hard surfaces ( e. g., floors, carpet, bedding, furniture) $ Pump trigger 9804 3 Liquid concentrate 0.002 not provided Evaporative cooler $ liquid pour 9150 11 Liquid concentrate 0.0007 not provided Ventilation systems ( HVAC) $ Handler not assessed, only post application ( 1 hour REI after fogging) 9804 1 Liquid concentrate 0.007 500 ppm Decorative pools, fountains, and water displays $ liquid pour 9150 11 Liquid concentrate 0.0001 not provided Continuous release deodorizer Handler not assessed, only post application inhalation 70060 12 Pouch/ Sachet NA not provided Use Site Category VI ( Human Drinking Water Systems) Water Treatment and water storage systems $ liquid pour and/ or metering pump 9804 1 Liquid concentrate 0.008 ( to treat water storage system of aircraft, boats, RVs, offshore oil rigs) 500 Page 11 of 58 Table 2.1. Use Scenarios and Methods of Application Based on Product Labels for Chlorine Dioxide Uses Representative Exposure EPA Reg. # Associated with Maximum Exposure Application Rate Associated with Maximum Exposure ( lb a. i./ gallon) Residual Chlorine Dioxide Level ( ppm)

0.00007 ( to treat stored potable water) 5 Use Site Category VII ( Material Preservatives) Industrial application to water based cutting oils ( MWF) $ liquid pour and/ or metering pump 9150 2 Liquid concentrate ( 5% ai assume density 8 lb/ gal) batch method: 0.0001 ( per week)

continuous method: 8E 7 ( per day)

badly contaminated systems: 4E 6 ( slug dose) not provided Use Site Category VIII ( Industrial Processes and Water Systems) Application to hard surfaces ( e. g., evaporative cooler) $ liquid pour and/ or metering pump 9150 11 Liquid concentrate 0.0007 not provided Water filtration systems, sand beds, gravel beds, charcoal filters ( e. g., to control mollusks) $ liquid pour and/ or metering pump 9150 2 Liquid concentrate 0.03 2000 9150 2 Liquid concentrate 3.1 lb ai/ 100 tons paper produced not provided Paper mill systems $ liquid pour and/ or metering pump 9804 1 Liquid concentrate 0.00007 5 Oil wells $ liquid pour and/ or metering pump 9150 2 Liquid concentrate 0.069 5000 Use Site Categories XI and XII ( Swimming Pools and Aquatic Areas)

Non potable water systems ( e. g., retention basins and ponds, decorative pools and fountains) $ liquid pour and/ or metering pump 9150 11 Liquid concentrate 0.00001 ( 18 fl oz x 0.72% ai per 100 gallons water) 10 Use Site Category XIII ( HVAC) Ventilation systems $ spray or fog ( 1hour REI after fogging) 9804 1 Liquid concentrate 0.007 500 a Applications are made in agricultural settings including, but not limited to, mushroom houses, poultry facilities, animal facilities, and hatching facilities. b REI = Reentry Interval Page 12 of 58 Table 2.2. Use Scenarios and Methods of Application Based on Product Labels for Sodium Chlorite Uses Representative Exposure EPA Reg. # Associated with Maximum Exposure Application Rate Associated with Maximum Exposure ( lb a. i./ gallon) Residual Chlorine Dioxide Level ( ppm)

Use Site Category I ( Agricultural Premises and Equipment) a $ low pressure hand wand 74602 02 Liquid concentrate 70060 18 tablet 0.015 0.002 1000 100 $ high pressure hand wand 74602 02 Liquid concentrate 0.0003 20 $ spray or fog ( 1 hour REI after fogging) 74602 02 Liquid concentrate 0.0083 500 Application to hard surfaces ( e. g., Animal rearing and confinement facilities; Horticulture uses; Mushroom facilities)

$ shampoo 74602 02 Liquid concentrate 0.008 500 Water supply ( e. g., drinking water, humidification water in poultry houses) $ liquid pour 74602 02 Liquid concentrate ° .0006 40 Use Site Categories II ( Food Handling), III ( Commercial/ Institutional), and V ( Medical)

$ foam 21164 8 Liquid concentrate 0.002 Not provided Application to hard surfaces with food contact in Food processing plants; Hospitals ( e. g., water bath incubators, autoclaves); Public places ( e. g., restaurants, hotel/ motel rooms); Medical/ Dental offices $ spray or dip 74602 02 Liquid concentrate 0.003 200 $ spray $ mop $ sponge $ immersion 70060 19 tablet 0.005 200 $ sprayer or dilution device 74986 1 WP 100 $ spray $ mist $ sponge 21164 3 Liquid concentrate 0.08 Not provided $ fog/ mist ( 15 min REI) 21164 3 Liquid concentrate 0.007 Not provided $ RTU packet 70060 12 RTU packet ** Not provided Application to hard surfaces without food contact in Food processing plants; Hospitals ( e. g., water bath incubators, autoclaves); Public places ( e. g., restaurants, hotel/ motel rooms); Medical/ Dental offices ( cont.)

$ RTU packet 70060 13 RTU packet 0.04 lb ai ( 20 lb ai/ day) Not provided Water systems ( e. g., potable water) $ liquid pour 9150 7 Liquid concentrate 0.002 150 Page 13 of 58 Table 2.2. Use Scenarios and Methods of Application Based on Product Labels for Sodium Chlorite Uses Representative Exposure EPA Reg. # Associated with Maximum Exposure Application Rate Associated with Maximum Exposure ( lb a. i./ gallon) Residual Chlorine Dioxide Level ( ppm) 70060 16 tablet 0.000004 Not provided Fruit/ vegetable rinse $ dip 74602 02 Liquid concentrate 0.011 1200 Air Deodorizer $ fog ( 15 min REI) 74602 3 Liquid concentrate 0.007 Not provided Carpet deodorizer $ duster 70060 4 Dust 0.0001 lb ai/ ft2 Not provided Use Site Category IV ( Residential & Public Access)

Application to hard surfaces ( e. g., bathrooms, laundry rooms, trash cans) $ RTU packet 70060 12 RTU packet ** Not provided Room/ Surface deodorizer $ spray, sponge 74602 02 Liquid concentrate 0.004 Not provided Carpet deodorizer $ duster 70060 4 Dust 0.0001 lb ai/ ft2 Not provided Residential and Industrial Ion Exchange Resin Beds $ tablet 70060 19 tablet 0.003 lb ai/ ft3 Not provided Use Site Category VI ( Human Drinking Water Systems)

$ sprayer or dilution device 74986 1 ( potable water systems) WP Not provided 100 5382 46 ( potable water systems) Liquid concentrate 0.00008 5 $ liquid pour and/ or metering pump 74602 02 ( aircraft, boats, RVs, offshore oil rigs) Liquid concentrate 0.008 500 Water Treatment and water storage systems $ tablet 70060 22 ( emergency disinfection of drinking water) tablet 0.0002 Not provided Use Site Category VII ( Material Preservatives)

Pulp/ Paper products Polymers Emulsions Adhesives Pigment slurries $ liquid pour and/ or metering pump 74655 2 Liquid concentrate Not provided 1000 Use Site Category VIII ( Industrial Processes and Water Systems)

Water cooling systems ( e. g., commercial and industrial $ tablet 70060 16 tablet 0.000004 Not provided Page 14 of 58 Table 2.2. Use Scenarios and Methods of Application Based on Product Labels for Sodium Chlorite Uses Representative Exposure EPA Reg. # Associated with Maximum Exposure Application Rate Associated with Maximum Exposure ( lb a. i./ gallon) Residual Chlorine Dioxide Level ( ppm) recirculation cooling water systems, once through cooling water systems) $ water soluble packet 72874 1 WSP ( bag) 0.0002 Not provided Recycle wash water systems $

tabletcanister feed or tank addition 70060 16 tablet 0.00009 Not provided Oil field secondary recovery operations $ liquid pour and/ or metering pump 21164 3 Liquid concentrate 0.007 Not provided Paper mills $ liquid pou and/ or metering pump 74602 3 Liquid concentrate 0.0001 lb ai/ gal white water ( 3.44 lb ai/ 100 ton paper produced) Not provided Use Site Category XI ( Swimming Pools)

Swimming pools & Spas ( place 2 tablets in skimmer and 2 tablets in hair/ lint basket to clean pool circulation system) $ tablet 70060 20 tablet 4 tablet / 10,000 gal ( Pool tablet is 100 g x 4 tablets x 20% ai = 80 g ai/ 10,000 gal = 1.8E 5 lb ai/ gal) Not provided Use Site Category XII ( Aquatic Areas)

$ liquid pour and/ or metering pump 53345 23 Liquid concentrate Not provided 2 Water Treatment and water storage systems ( e. g., municipal water, nonpotable water used with cut flowers) $ sprayer or dilution device 74986 1 WP Not provided 100 ** Label lists various application rates: refrigerator: 0.006 lb ai; shoes: 0.0006 lb ai; hamper: 0.01 lb ai/ ft2; basement: 0.0002 lb ai/ ft2; gym locker: 0.0002 lb ai/ ft3; cars: 0.006 lb ai; boats: 0.0002 lb ai/ ft3; athletic bag: 0.0003 lb ai/ ft3; trash can: 0.006 lb ai; trash bag: 0.006 lb ai; diaper pail: 0.002 lb ai; litter box/ pet area: 0.0001 lb ai Page 15 of 58 Table 2.3. Use Scenarios and Methods of Application Based on Product Labels for Sodium Chloratea Uses Representative Exposure EPA Reg. # Associated with Maximum Exposure Application Rate Associated with Maximum Exposure ( lb a. i./ gallon) Residual Chlorine Dioxide Level ( ppm)

Use Site Categories I ( Agricultural), II ( Food Handling), III ( Commercial/ Institutional), VIII ( Industrial Processes and water systems), XII ( Aquatic areas) Agricultural water uses 49620 4  a 2 Pasteurizer./ Cannery/ Retort 49620 4  a 0.4 Cooling towers; wastewater 10707 32  a 800 Pulp and Paper 53345 17/ 18  a 4000 Gas/ oil injection 49620 4  a 3000 Water systems Ultrasonic tank water and photo processing was water 49620 4  a 5 Aquatic areas ( e. g., lakes and reservoirs) 49650 4  a 5 a Table developed from Table 2 of the Sodium Chlorate ORE Document; application rates were not provided 3.0 SUMMARY OF TOXICITY CONCERNS RELATING TO EXPOSURES 3.1 Acute Toxicology Chlorine dioxide ( CAS No. 10049 04 4) is used as a disinfectant in a variety of sites, including drinking water, swimming pools, fruits and vegetables, and household uses. Sodium chlorite and sodium chlorate products release chlorine dioxide and are included in this assessment as well.

Table 3.1 presents the acute toxicity categories as outlined in the toxicity memorandum dated February 15, 2005 ( USEPA, 2005a).

Table 3.1. Acute Toxicity Categories for Chlorine Dioxide Study Type Toxicity Categorya Acute Oral Toxicity II Acute Dermal Toxicity III Acute Inhalation Toxicity II Primary Eye Irritation III Primary Dermal Irritation II Dermal Sensitization No acceptable sensitization study available a The available acute studies are all graded as acceptable. An acceptable dermal sensitization study is not available in the database. Page 16 of 58 3.2 Summary of Toxicity Concerns Relating to Exposures Chlorine Dioxide/ Sodium Chlorite  Report of the Hazard Identification Assessment Review Committee and the Antimicrobials Division Toxicity Endpoint Selection Committee ( USEPA 2005a) indicates that there are toxicological endpoints of concern for chlorine dioxide. The endpoints and associated uncertainty factors used in assessing the risks for chlorine dioxide are presented in Table 3.2. These endpoints have also been identified for sodium chlorite. Since the same endpoints have been identified for both chemicals, this risk assessment examines products causing the greater exposure if a similar use scenario is found for both chlorine dioxide and sodium chlorite. The reader is referred to USEPA ( 2005a) for the derivation of the riskbased inhalation RfC values. Page 17 of 58 Table 3.2. Toxicological Endpoints Selected for Chlorine Dioxide ( and Representative of Sodium Chlorite).

Exposure Scenario Dose Used in Risk Assessment ( mg/ kg/ day) UF/ MOE for Risk Assessment Study and Toxicological Effects Acute Dietary An acute dietary endpoint was not identified in the data base for chlorine dioxide.

Chronic Dietary NOAEL = 3 mg/ kg/ day UF = 100 ( 10x inter species extrapolation, 10x intra species variation)

FPQA = 1 Chronic PAD = 0.03 mg/ kg/ day Developmental Toxicity  Rat ( Orme et al., 1985) based on depression of serum T4 levels in pups from dosed maternal rats and delays in development of locomotor and exploratory behavior activity at 14 mg/ kg/ day Two generation reproduction toxicity study ( CMA, 1996)  decreases in absolute brain and liver weight, and lowered auditory startle amplitude at LOAEL of 6 mg/ kg/ day Incidental Oral ( short and intermediate  term) NOAEL = 3 mg/ kg/ day MOE = 100 See summary for dietary assessment Dermal ( All Durationsa) NOAEL= 3 mg/ kg/ day MOE = 100 See summary for dietary assessment [ Assume 100% dermal absorption]

see ADTC endpoint selection document for explanation of NOAEL/ LOAEL values and effects ( USEPA 2005a) Occupational ` RfC' = 0.009 mg/ m3 ( 0.003 ppm) b Homeowner short term ` RfC' = 0.14 mg/ m3 ( 0.05 ppm) b Inhalation toxicity studies Rat: Homeowner short term: Dalhamn, 1957 [ LOAEL of 28 mg/ m3 ( 10 ppm)]

Occupational exposure: Paulet and Debrousses, 1970, 1972 using LOAEL of 1.0 ppm ( 2.8 mg/ m3); Dalhamn, 1957 using NOAEL of 0.1 ppm ( 0.28 mg/ m3). Inhalation Homeowner long term: Agency RfC methodology used to derive a RfC value of 2 x 10 4 mg/ m3 or 0.00007 ppm ( USEPA, 2000) ( Paulet and Debrousses, 1970, 1972) selected as cocritical studies ( USEPA, 2005a)

aBased on the use of an oral endpoint for dermal risk assessments and the lack of a dermal absorption study, a dermal absorption value of 100% as default will be used. Short term is 1 to 30 days; Intermediate term is 1 to 6 months; and long term is greater than 6 months. bunit conversion: ppm = ( mg/ m3 x 24.45) / mw. For chlorine dioxide 1 ppm = 2.8 mg/ m3 3.3 FQPA Considerations The endpoint selected for both dietary and non dietary exposures was based upon adverse effects observed in offspring from developmental and reproductive toxicity data. Consistent with the approach used by the EPA's Office of Water for use of chlorine dioxide as a drinking Page 18 of 58 water disinfectant ( Federal Register Vol. 63, No. 61, pages 15673 15692, March 31, 1998) and the updated guidance on selection of a safety factor under FQPA, the endpoint selected for assessment of risk from dietary and non dietary exposure to chlorine dioxide is felt to be protective of potentially susceptible populations including children, based upon the selection of an endpoint and effects observed in offspring and the use of an NOAEL value based on those effects. Therefore it can be concluded that an additional safety factor under FQPA is not necessary in this case for dietary and/ or residential risk assessments, and that the traditional uncertainty factor ( MOE) of 100 for intraspecies and interspecies variation will support the safety standard of ` reasonable certainty of no harm' as required by the FQPA statute for food use pesticides ( USEPA 2005).

4.0 RESIDENTIAL AND PUBLIC ACCESS PREMISES 4.1 Summary of Registered Uses Chlorine dioxide and/ or sodium chlorite products are used by homeowners as disinfectants as well as to control mold and mildew. For this assessment, household cleaning products have been grouped together to be represented by the higher application rate from the chlorine dioxide and sodium chlorite products. For example, EPA Reg. No. 9804 3 is representative of products that are used in the home to clean floors, bathroom surfaces, shower stalls, laundry rooms, and hampers.

Sodium chlorite is also used for homeowner treatments of circulation systems in swimming pools and spas. The pool and spa product, EPA Reg. No. 70060 20, is formulated as a solid tablet. In addition, chlorine dioxide has a registered use for HVAC systems. Applications to residential heating, ventilating, air conditioning ( HVAC) systems are not generally performed by the homeowner, but rather a commercial applicator ( e. g., EPA Reg. No. 9804 1). Therefore, homeowner based HVAC applications are not presented; only potential exposures during post application activities. Finally, there is a continuous release product packaged as a sachet that releases chlorine dioxide as a gas over time in homes, automobiles, etc.

4.2 Dietary Exposure/ Risk Pathway   Place holder for risk assessment document 4.3 Drinking Water Exposure/ Risk Pathway   Place holder for risk assessment.

4.4 Residential Exposure/ Risk Pathway 4.4.1 Residential Handler Exposure EPA has estimated both the potential dermal and inhalation routes of exposure for residential handlers. The dermal and inhalation exposures are presented in separate sections below. Page 19 of 58 <IP_ADDRESS> Residential Handler Dermal Exposure and Risk The following equations were used to calculate potential dermal doses and risks to handlers:

Daily Exposure: E = UE * AR * AT Where: E = amount ( mg ai/ day) deposited on the surface of the skin that is available for dermal absorption; UE = unit exposure value ( mg ai/ lb ai) derived from August 1998 PHED data or from CMA data; AR = normalized application rate based on a logical unit treatment, such as acres, square feet, gallons, or cubic feet. Maximum values are generally used ( lb ai/ A, lb ai/ sq ft, lb ai/ gal, lb ai/ cu ft); and AT = normalized application area based on a logical unit treatment such as acres ( A/ day), square feet ( sq ft/ day), gallons per day ( gal/ day), or cubic feet ( cu ft/ day).

Daily Dose: ADD = E * ( ABS / BW)

Where: ADD = absorbed dose received from exposure to a pesticide in a given scenario; in the case of chlorine dioxide, the dermal absorption is defaulted to 100% because of the lack of data. ( mg pesticide active ingredient/ kg body weight/ day); E = amount ( mg ai/ day) deposited on the surface of the skin that is available for dermal absorption; ABS = a measure of the amount of chemical that crosses a biological boundary such as the skin (% of the total available absorbed); and BW = body weight determined to represent the population of interest in a risk assessment ( kg).

Margins of Exposure: MOE = ( NOAEL or LOAEL) / ADD Where:

MOE = margin of exposure, value used to represent risk; NOAEL or LOAEL = dose level in a toxicity study, where no observed adverse effects ( NOAEL) or where the lowest observed adverse effects ( LOAEL) occurred in the study; and ADD = average daily dose or the absorbed dose received from exposure to a pesticide in a given scenario ( mg pesticide active ingredient/ kg body weight/ day).

A series of assumptions and exposure factors served as the basis for completing the handler risk assessment for each use site category. Each general assumption and factor is Page 20 of 58 detailed below. Assumptions specific to the use site category are listed in each separate section below. The general assumptions and factors used in the risk calculations include:

$ Chlorine dioxide is a widely used disinfectant and has a large number of use patterns. As a result, AD has patterned this risk assessment on a series of likely representative scenarios for each use site that are believed by AD to represent the vast majority of chlorine dioxide uses.

$ The toxicological endpoint of concern for dermal risks is from a reproductive study; therefore the average body weight of an adult female handler ( i. e., 60 kg) was used to complete the dermal risk assessment.

$ Exposure factors used to calculate daily exposures to handlers are based on applicable data, if available. For lack of appropriate data, values from a scenario deemed similar enough by the assessor might be used.

$ The maximum application rates allowed by the representative labels were used in the development of the risk estimates ( see Tables 2.1, 2.2, and 2.3).

Those assumptions specific to the residential handler assessment are as follows:

$ Unit Exposure Values: Dermal unit exposure values were taken from the proprietary Chemical Manufacturers Association ( CMA) antimicrobial exposure study ( MRID 42587501) or from the Pesticide Handler Exposure Database ( PHED, 1998). o For mopping, the CMA dermal unit exposure value for ungloved mopping was used ( 71.6 mg/ lb ai). This value is based on data collected from six replicates mopping floors and receiving exposure via contact with the mop or with the bucket. o For trigger pump sprays, the PHED dermal unit exposure value for ungloved, short pants, and short sleeved clothing scenario for aerosol spraying ( 220 mg/ lb ai) was used as a surrogate for the trigger pump. This value is based on data collected from 30 dermal and 15 hand replicates who applied the spray on surfaces ( only 15 hand replicates available because ½ the test subjects wore chemical resistant gloves). o For solid place ( tablets), the CMA dermal unit exposure value for placing solids, such as tablets, is 10.8 mg/ lb ai ( ungloved). This value is based on only one replicate. The value for the dermal exposure when wearing gloves is reduced to 0.142mg/ lb a. i. This value is also based on only one replicate ( metal working fluid). Page 21 of 58 $ Amount handled/ treated: The amounts handled/ treated were estimated based on information from various sources, including the Standard Operating Procedures ( SOPs) for Residential Exposure Assessments ( 2000). In certain cases, no standard values are available for some scenarios. Assumptions for these scenarios are based on AD estimates and could be further refined from input from affected sectors. The following assumptions were made:

o Trigger pump sprayers: 0.5 liters or 0.13 gal/ day o Mopping: 1 gal/ event o Swimming pools: 20,000 gallons Two scenarios ( mopping and spraying) were examined for residential cleaning purposes in this risk assessment and one scenario for the pool/ spa application. Table 4.1 provides the label information that is representative of the high end residential cleaning and pool/ spa treatment scenarios for chlorine dioxide as well as sodium chlorite. For use in residential cleaning, sodium chlorite was identified for the high end exposure. Sodium chlorite has the only swimming pool and spa use on the labels reviewed for this assessment.

Table 4.1. Exposure Scenarios Associated with Residential Exposure Assessed in this Document Representative Use Application Method EPA Registration Number Application Rate ( lb ai/ gal) Exposure Scenario Assessed Application to hard surfaces $ mop $

triggerpump sprayer 9804 3 ( chlorine dioxide) 0.002 lb ai/ gal Short term Adult Handler ( dermal and inhalation)

Application to swimming pools and spas $ place solid ( tablets) 70060 20 ( Sodium Chlorite) 2 tablets in skimmer and 2 tablets in hair/ lint basket to clean pool circulation system per 10,000 gallons of water. 100 g x 4 tablets x 20% ai = 80 g ai/ 10,000 gal = 1.8E 5 lb ai/ gallon Short term Adult Handler ( dermal and inhalation)

The results of the MOE analysis for these scenarios are presented in Table 4.2. Although the dermal endpoint represents short, intermediate, and long term durations, the exposure duration of most homeowner applications of cleaning products and pools are believed to be best represented by the short term duration. The toxicological endpoint is based on an oral study and no dermal absorption value is available. Therefore 100% dermal absorption was assumed for chlorine dioxide and/ or chlorite ion residues. The dermal MOEs for the general use on floors, etc., are above the target MOE of 100, and therefore, are not of concern ( i. e., the short term dermal MOEs for applications to hard surfaces are 3,200 for the trigger pump sprayer and 1,300 for the mopping). The short term dermal MOE for pool and/ or spa treatments is 46 without the use of gloves and the MOE is 500 with the use of gloves. Page 22 of 58 Table 4.2. Calculation of Short term Dermal MOEs for Residential Handlers Exposure Scenario Application Ratea ( lb ai/ gal) Amount Handled/ Treated Dailyb ( gal) Baseline Dermal Unit Exposurec ( mg/ lb ai) Baseline Dermal Dosed, e ( mg/ kg/ day) Baseline Dermal MOEf ( Target MOE = 100)

Mopping ( CMA data) hard surfaces 0.002 1 71.6 0.0024 1300 Trigger pump sprayer ( Aerosol can PHED data used as surrogate) hard surfaces 0.002 0.13 220 0.00095 3200 Solid Place ( Tablets) Pools & Spa water circulation systems 1.8E 5 ( 4 tablets / 10,000 gal. Pool tablet is 100 g x 4 tablets x 20% ai = 80 g ai/ 10,000 gal = 1.8E 5 lb ai/ gal) 20,000 10.8 ( no gloves) 0.065 ( no gloves) 46 ( no gloves)

0.412 ( gloves) 0.006 ( gloves) 500 ( gloves)

a Application rates are the maximum application rates determined from EPA registered labels for chlorine dioxide, sodium chlorite, and sodium chlorate. b Amount handled/ treated per day values are based on AD estimates. c Dermal unit exposures are from CMA and PHED. d Baseline dermal: Long sleeve shirt, long pants, no gloves for mopping and short pants, short sleeved shirt, and no gloves for spraying. e Dermal dose ( mg/ kg/ day) = [ unit exposure ( mg/ lb ai) * dermal absorption ( 1.0) * appl. rate ( lb ai/ gallon) * gallons handled / body weight ( 60 kg). f MOE = NOAEL ( mg/ kg/ day) / Daily Dose [ Where short and intermediate term dermal NOAEL = 3 mg/ kg/ day]. Target MOE is 100.

<IP_ADDRESS> Residential Handler Inhalation Exposure and Risk The potential inhalation of chlorine dioxide may occur from off gassing during application of the aqueous solution. Chlorine dioxide has the potential to generate a gas during the residential uses of mopping and spraying. However, it is unlikely that levels of concern for chlorine dioxide would be generated outdoors while treating swimming pools & spas with tablets placed into water.

Of the three inhalation toxicological endpoints selected, the short term homeowner ( i. e., not a continuous exposure) best represents the inhalation exposure duration of residential handlers. The short term residential RfC is 0.05 ppm.

To determine the potential inhalation handler exposure resulting from the vapor of chlorine dioxide as a general purpose cleaner, the model EFAST ( Exposure and Fate Assessment Screening Tool) was used to estimate the air concentration. OPPT/ EETD has developed the model, EFAST, to estimate air concentrations. More information and access to the EFAST model is available at http:// www. epa. gov/ opptintr/ exposure/. In summary, EFAST Version 1.1 Page 23 of 58 bases its air concentration estimates on physical/ chemical properties. The air concentration estimates for the chlorine dioxide are based on the model's standard input parameters. The following information is presented in the EFAST model:

".... it is assumed to contact the target surface, and to subsequently volatilize at a rate that depends upon the chemical's molecular weight and vapor pressure."

The molecular weight of chlorine dioxide is 67.45 g/ mol and the vapor pressure is > 760 mm Hg at 25 degrees C. EFAST estimates a peak air concentration as well as a daily air concentration. The peak air concentration estimate "... is the highest instantaneous air concentration that is modeled during the exposure event." This peak air concentration is instantaneous and at the source of the treatment solution. The peak concentration is not a useful measurement for comparison to the inhalation RfC selected.

EFAST was used to model the air concentration from general purpose cleaners using an application rate of 0.002 lb ai/ gal ( i. e., weight fraction = 0.00024). The peak instantaneous air concentration is 0.265 mg/ m3 ( 0.09 ppm) and the average daily TWA air concentration is determined to be 0.00794 mg/ m3 ( 0.003 ppm).

The inhalation endpoint ( RfC) for one time applications is 0.05 ppm. Based on the average daily air concentration ( representing both application and post application), the handler inhalation exposures of chlorine dioxide are not of concern ( i. e., the average air concentration estimated by EFAST of 0.003 ppm is below the RfC of 0.05 ppm).

4.4.2 Residential Post Application Exposure Typically, most products used in a residential setting result in exposures occurring over short term time duration ( 1   30 days). If the products are used on a routine basis ( i. e., once a week) and the active ingredient has a long indoor half life, exposures may occur over an intermediate term time duration ( 30 days   6 months). However, AD does not have residue dissipation data or reliable use pattern data including the frequency and duration of use of antimicrobial products used in the residential setting. Therefore, even though AD does not believe that the use patterns of many residential products result in intermediate term exposure, they are assessed to provide an upper bound estimate of exposure ( e. g., day care centers). Note: For chlorine dioxide the dermal and oral endpoints and durations are identical.

For the purposes of this screening level assessment, post application scenarios have been developed that encompass multiple products, but still represent a high end scenario for all products represented. Four scenarios have been considered: ( 1) exposure to residue from hard floors that have been cleaned with a solution containing chlorine dioxide, ( 2) exposure to chlorine dioxide used to clean residential HVAC systems, ( 3) exposure to a continuous release ( gas) deodorizer, and ( 4) swimming. Page 24 of 58 <IP_ADDRESS> Hard Surface/ Floor Dermal Exposure to Children from Treated Floors Exposure Calculations There is the potential for dermal exposure to toddlers crawling on hard floors after mopping with chlorine dioxide products and to carpets after application with a formulated dust product. The hard floor scenario was selected because it represents the higher amount of residue transferred ( i. e., 5% residue transfer assumed for carpets and 10% for hard surfaces). Exposures and MOEs were calculated for children contacting treated hard surface floors in residential homes ( short term exposure) and in commercial daycare centers ( intermediate term exposure). To determine toddler exposure to floor residues ( mopping), the following equation was used:

PDD = AR x DTF x DRF x CF1 x CF2 x SA BW where, PDD = Potential daily dose; AR = Application rate ( lb/ ft2); DTF = Dermal transfer factor ( fraction, unitless); DRF = Disinfectant fraction remaining on floor ( unitless); CF1 = Conversion factor ( 4.54x105 mg/ lb); CF2 = Conversion factor ( 10.8 ft2/ m2); SA = Surface area of the body which is in contact with floor ( m2); and BW = Body weight ( kg)

Assumptions   Toddlers ( 3 years old) were used to represent the 1 to 6 year old age group. A body surface area of 0.657 m2 and a body weight of 15 kg was been assumed, which are the median values for 3 year olds ( USEPA, 1997).   Generic household cleaners are commercially available in a large range of concentrations. It is assumed that one gallon of diluted treatment solution is used to treat 1000 ft2 of floor. The maximum application rate on the chlorine dioxide and/ or sodium chlorite product labels for application to hard surfaces which are believed to encompass floors where children may play was 0.002 lb ai/ gal. Therefore, the application rate used in the post application scenarios was 0.000002 lb ai/ ft2.   No transferable residue data were available that could be used to estimate the transfer of chlorine dioxide or chlorite ion from the floor to skin. Therefore, it is assumed that 10% of the deposition rate is available for dermal transfer ( USEPA, 2000, and 2001). This is a very conservative estimate for chlorine dioxide as it has a very high vapor pressure and volatility will affect the amount of residue deposited.   No data could be found regarding the quantity of dilute treatment solution left on the floor after treatment. It has been assumed that 25% of the treatment solution remains Page 25 of 58 on the floor after the final mopping ( i. e., some solution remains in the mop itself and some in the bucket).   It was assumed that the exposed toddler plays regularly on the treated floor. In a residential home, short term exposure duration is most likely since homeowners are expected to clean the floor only intermittently. In a commercial daycare center, intermediate term exposure duration is likely since it is expected that the floors are cleaned on a routine basis.

Results The calculations of the short and intermediate term dermal doses and MOEs are shown in Table 4.3. The dermal MOEs for the residential settings ( short term MOE) and institutional settings ( intermediate term MOE) are identical because the endpoints and uncertainty factors are the same for both durations. The estimated dermal MOE of 280 is not of concern ( i. e., above the target MOE of 100).

Table 4.3. Short and Intermediate term Post Application Dermal Exposures and MOEs for Children Contacting Treated Floors Exposure scenario Application rate ( lb ai/ sq ft) Product remaining after mopping Percent trans. residue Body area in contact with floor ( m2) Potential daily dosea ( mg/ kg/ day) Dermal MOEb Hard surfaces  residential and daycare settings 2x10 6 25% 10% 0.657 0.017 280 a Potential daily dose ( mg/ kg/ day) = [( Application rate, lb ai/ ft2)*( conversion factor, 454 g/ lb)*( conversion factor, 1,000 mg/ g) * ( conversion factor, 1 ft2/ 0.093 m2) * ( product remaining after mopping, 25%) * ( dermal transfer factor, 10%) * ( body surface area in contact with floor, 0.657 m2)] / ( body weight, 15 kg) b Dermal MOE = NOAEL ( mg/ kg/ day) / Potential daily dose ( mg/ kg/ day) [ Where short and intermediate term dermal NOAEL ( derived from an oral study and 100% dermal absorption is assumed) is 3 mg/ kg/ day. Target MOE = 100.

Child Incidental Ingestion Exposure to Treated Floors Exposure Calculations In addition to dermal exposure, toddlers crawling on treated hard floors will also be exposed to chlorine dioxide or chlorite ion residues via incidental oral exposure through hand tomouth activity. To calculate incidental ingestion exposure to these chemicals due to hand tomouth transfer, the methodologies established in the Standard Operating Procedures ( SOPs) for Residential Exposure Assessments ( USEPA 2000 and 2001) were used. These use assumptions are similar to those used in calculating dermal exposures for toddlers crawling on treated hard floors. Because the incidental oral endpoints and uncertainty factors are identical for short and intermediate term durations, scenarios for children at day care centers are not listed separately. Exposures were calculated for children contacting treated floors in residential homes using the following equations for hand to mouth transfer of pesticide residues to toddlers:

PDD = SR x DTF x SA x EF x ET x SE x CF1 Page 26 of 58 BW where: PDD = Potential daily dose ( mg/ kg/ day); SR = Indoor surface residue ( µ g/ cm2); DTF = Dermal transfer factor ( unitless fraction); SA = Surface area of the hands that contact both the treated area, and the individuals mouth ( cm2/ event); EF = Frequency of hand to mouth events ( events/ hr); SE = Saliva extraction efficiency ( unitless fraction); ET = Exposure time ( 4 hrs/ day); CF1 = Unit conversion factor ( 0.001 mg/ µ g); and BW = Body weight ( 15 kg)

And SR= AR x DRF x CF2 x CF3 where: SR = Surface residue ( µ g/ cm2); AR = Application rate ( lb ai/ ft2); DRF = Disinfection fraction remaining on floor ( unitless); CF2 = Unit conversion factor ( 4.54x108 µ g/ lb); and CF3 = Unit conversion factor ( 1.08x10 3 ft2/ cm2)

Assumptions   Toddlers ( 3 years old) were used to represent the 1 to 6 year old age group and are assumed to weigh 15 kg, the median for male and female toddlers ( USEPA, 2000 and 2001).   Based on HED's Residential SOP, it was assumed that the surface area used for each hand to mouth event is 20 cm2. For short term exposures, it is assumed that the frequency of hand to mouth events is 20 events per hour ( 90th percentile) ( USEPA 2001). A separate assessment at the intermediate term duration is not necessary, as the shortterm assessment is more conservative because the frequency of hand to mouth events for the intermediate term exposure duration is less than the short term and because the toxicological endpoints and uncertainty factors are the same for both durations.   The exposure time was 4 hours a day ( USEPA, 2000 and 2001).   The saliva extraction efficiency was 50% ( USEPA, 2000 and 2001).   The labels did not provide information on the volume of disinfectant to be used for cleaning surfaces such as floors. It was assumed that the diluted treatment solution was applied at a rate of 1 gallon per 1,000 sq. ft. The maximum application rate on the product labels for application to hard surfaces is 0.002 lb ai/ gal ( EPA Reg. No. 9804 3). Therefore, the application rate used in the post application scenario was 0.000002 lb ai/ ft2.   No data could be found regarding the quantity of dilute treatment solution left on the floor after treatment. It has been assumed that 25% of the treatment solution remains on Page 27 of 58 the floor after the final mopping ( i. e., some solution remains in the mop itself and some in the bucket).   No transferable residue data were available that could be used to estimate the transfer of chlorine dioxide and chlorite ion from the floor to skin. Therefore, it was assumed that 10% of the deposition rate is available for dermal transfer ( USEPA, 2000 and 2001).

Results The calculation of the short term oral doses and the oral MOEs are shown in Table 4.4. The oral MOE is 2,300 and is above the target MOE of 100.

For the short term exposures, it was necessary to determine the total MOE since the toxicity effects are the same for the dermal and oral routes. The short term total MOE for children contacting treated floors ( dermal + oral routes) is 250 which is greater than the target MOE of 100, and therefore is not of concern. The total MOE was estimated using the following equation: Total MOE = 1 / (( 1/ MOEdermal) + ( 1/ MOEoral)) where, MOEdermal = 280 and MOEoral = 2,300.

Table 4.4. ST Incidental Oral Post Application Exposures and MOEs for Children Contacting Treated Floors Exposure Scenario Appl. Rate ( lb ai/ sq ft) Product Remaining after Mopping Surface Residuea ( µ g/ cm2) Percent transferable residue Surface area mouthed ( cm2/ event) Exposure Frequency ( events/ hr) Saliva Extraction Factor Exp. Time ( hrs/ day) Potential Daily Doseb ( mg/ kg/ day) Oral MOEc Hard surfaces  residential setting 2x10 6 25% 0.245 10% 20 20 50% 4 0.0013 2,300 a Surface residue ( µ g/ cm2) = ( application rate, lb ai/ ft2)*( disinfectant fraction remaining on floor, 0.25)*( conversion factor to convert lb to µ g, 4.54E+ 08 µ g/ lb)*( conversion factor to convert ft2 to cm2, 1.08E 03 ft2/ cm2) b Potential daily dose ( mg/ kg/ day) = [( surface residue, µ g/ cm2)*( transferable residue, 0.10)*( exposure time, 4 hrs/ day)*( surface area of hands, 20 cm2/ event)*( frequency of hand to mouth activity, 20 events/ hr)*( extraction by saliva, 50 %)*( conversion factor to convert µ g to mg, 0.001 mg/ µ g)]/ ( body weight, 15 kg) c MOE = NOAEL ( mg/ kg/ day) / potential daily dose ( mg/ kg/ day) [ Where short term oral NOAEL = 3 mg/ kg/ day]. Target MOE = 100.

Child Inhalation Exposure after the Treatment of Floors Chlorine dioxide can potentially be released into the air as a gas/ vapor after it is applied as an aqueous solution to hard surfaces such as floors. At this time there are no air concentration data available to assess the release of chlorine dioxide during or after mopping floors. There are, however, air concentration measurements available after the application of chlorine dioxide as a dust treatment on carpets ( Speronello 2005). Although there are limitations to this study ( e. g., not conducted under Good Laboratory Practices ( GLPs), minimal information is available in the study report, and the study did not monitor aqueous applications), it is the only data source available at this time. In addition, the results are directly applicable to the carpet dust application of chlorine dioxide ( e. g., EPA Reg. No. 58300 16). Finally, a theoretical approach to estimating chlorine dioxide air concentration is also presented below based on dilution and ventilation Page 28 of 58 equations.

Monitoring Data:

Speronello ( 2005) measured chlorine dioxide air concentrations in a 10ft x 10ft x 8ft room. Chlorine dioxide, formulated as Sanitizer 71 powder, was applied to a carpet at application rates of 0.5 gram/ ft2, 1.5 gram/ ft2, and 2.5 gram/ ft2. The limit of detection for the sampling was 0.01 ppm. Samples were collected at 1, 36, and 60 inches above the carpet. The room was reportedly ventilated at 35 and 135 cfm, however, the study indicates that the configuration of the inlet/ outlet exhaust was such that minimal ventilation actually occurred. One experiment per application rate was monitored at the 135 cfm ventilation rate and it appears that a similar sampling schedule was used for the experiments at the 35 cfm ventilation rate. Raw data tables were not provided but the data were presented graphically. It is unclear for what durations samples were collected and time weighted averages ( TWAs) were not reported. The results indicate that at the lower ventilation rate ( i. e., 35 cfm) the peak concentration of chlorine dioxide was measured at 0.3 ppm for all application rates. For the 135 cfm ventilation experiment, peak air concentrations were measured as 0.1 ppm, 0.3 ppm, and 0.5 ppm for the 0.5, 1.5, and 2.5 gram/ ft2 rates, respectively. Air samples were nondetect ( i. e., less then 0.01 ppm) after 3 to 4 hours.

To determine the inhalation risks associated with chlorine dioxide vapors as a result of the carpet dust applications, the appropriate exposure duration and frequency need to be compared to an inhalation toxicity endpoint of similar duration and frequency. Carpet and/ or mopping hard surface floor treatments are believed to be intermittent in frequency. Therefore, the short term, single exposure inhalation endpoint for residents, 0.05 ppm, is the appropriate endpoint to use in this exposure scenario.

The air concentration data available in this study are peak measurements with the sampling time not reported. The peak concentrations measured in the first 3 or 4 hours after application ( up to 0.5 ppm) exceed the level of concern ( i. e., RfC of 0.05 ppm) by an order of magnitude. However, the peak air concentrations for chlorine dioxide decrease below the level of concern after 3 or 4 hours, most likely earlier. Actual inhalation risk concerns are indeterminate because the air concentrations in the room available for children to breathe are only measured in the study as peak concentrations which are not directly comparable to the time weighted average ( TWA) toxicity value. These data do, however, indicate that additional study information and/ or a new study are warranted to provide a reasonable certainty of no harm for children ( or adults) in rooms treated with chlorine dioxide.

Dilution Ventilation Approach:

In the dilution and ventilation approach to determining air concentrations in a room, the application rate from EPA Reg. No. 9804 3 is used ( USEPA 2005c). As a bounding estimate, it is conservatively assumed that the concentration in the dilute cleaning solution is immediately released as the initial air concentration in the room. From this initial air concentration, the ventilation rate of the room and the half life of chlorine dioxide in an aqueous solution are used to estimate the air concentration in the room every 30 minutes. The results are a bounding Page 29 of 58 estimate of the maximum air concentration in the room. Actual results will be lower as the initial concentration of chlorine dioxide in the air would not be equal to that of what is in the treatment solution. Furthermore, the half life of chlorine dioxide in an aqueous solution was used ( i. e., 30 minutes). The half life of chlorine dioxide in air is expected to be much lower. The half life in the aqueous solution was used because the gas would be released over time in the room rather then immediately as assumed.

The initial concentration of chlorine dioxide in the aqueous solution is 0.6 ppm derived from the application rate of EPA Reg. No. 9804.3. This product is mixed as a 0.1% ai solution of 24 oz of product per gallon of water and it is assumed that 1 gallon of a treatment solution is used to mop the floor which is equivalent to 681 mg chorine dioxide ( i. e., [ 8 lb/ gal density x 0.001 ClO2 x 1 ga/ 128 fl oz] x 24 fl oz product/ gal x 1 gallon mopping solution = 0.0015 lb ai of treatment solution or 681 mg ai.). Assuming all of the 681 mg of chlorine dioxide is released into a 1,800 ft2 house ( volume = 1,800 ft2 x 8 ft ceiling = 14,400 ft3 or 408 m3) the air concentration would be 0.6 ppm ( i. e., 681 mg ai/ 408 m3 = 1.7 mg/ m3 or 0.6 ppm). Note: The area of a house was used to estimate the volume of the house, not the total surface area of the house mopped.

The dilution ventilation equation is as follows:

t = Vr/ Q ln [ Ci/ C]

Where: t = time required in minutes C = desired concentration of the disinfectant ( 0.05 ppm) Ci = initial concentration of the disinfectant Vr = volume of area/ room in ft3 Q = air flow into room, in ft3/ min.

Note: The above equation does not include the half life factor for chlorine dioxide. To account for the half life the following equation is used to estimate C/ Ci :

C/ Ci = e   ( t/ 0.693 x Q/ Vr)( ln2/ t0.5)

Where: C, Ci, t, Q and Vr have the same meanings as outlined above while the factor ln2/ t0.5 represents the assumption of first order decay for chlorine dioxide gas. t0.50 is the half life of chlorine dioxide. It is assumed that it takes longer for chlorine dioxide to breakdown from aqueous solution than when it is in gaseous state. The most cited literature for the half life of chlorine dioxide from an aqueous solution states it to be 30 minutes.

Table 4.5 summarizes the concentrations for chlorine dioxide for every 30 minutes. The results indicate that for an assumed room ventilation rate of 43.2 ft3/ minute, the bounding estimate of chlorine dioxide in the air is below the inhalation level of concern of 0.05 ppm at 1.5 hours after treatment. Based on this conservative bounding estimate, the inhalation of chlorine dioxide during off gassing from the treatment solution used to mop floors does not appear to be a risk of concern if there is no reentry during the first hour after treatment ( i. e., 1 hr REI). To Page 30 of 58 accurately determine the initial concentration of chlorine dioxide in the air after mopping, air monitoring data would be needed.

Table 4.5 Bounding Estimate of Chlorine Dioxide over Time ( Mopping). Time ( minutes) Time ( hours) Chlorine Dioxide ( ppm) 0 0 0.6 30 0.5 0.27 60 1 0.13 90 1.5 0.057 120 2 0.026 180 3 0.0055 240 4 0.0011 300 5 0.0002 360 6 0.00005 420 7 0.00001 480 8 0.000002 540 9 0.0000005 8 hour TWA starting 0 hrs after treatment 0.08 8 hour TWA starting 1 hr after treatment 0.02 <IP_ADDRESS> Heating Ventilating and Air Conditioning ( HVAC) Systems There is one product registered for use in cleaning HVAC systems. This product, OXINE ( EPA Reg. No. 9804 1), is a registered sanitizer for residential/ commercial/ institutional HVAC systems. It is formulated at 2 percent chlorine dioxide. Label use directions indicate that the product is mixed at a rate of 3.24 fluid ounces product per gallon of water with an activator to activate the chlorine dioxide ( 500 ppm ClO2). The aqueous chlorine dioxide solution is then sprayed or fogged into closed and sealed duct work. After application, the label directions indicate that the "  area should be opened and aired for one ( 1) hour before repopulating." It is assumed that dermal post application exposures are negligible for applications to HVAC systems. This assumption is supported by the deposition samples discussed below ( BCI 2002). However, it is assumed that post application inhalation exposure can occur when people reenter a building after application.

BCI ( 2002) monitored a chlorine dioxide treatment of a HVAC system in a 2250 ft2 residence. The application was performed at the maximum labeled rate ( i. e., aqueous solution of 500 ppm). The ambient air in the house was monitored for chlorine dioxide gas during and after the application. Deposition of the chlorite ion was measured using 1 ft2 glass plates on the floor of each room. Results of the study indicated that the deposition samples were all nondetect ( LOD not reported). The air concentrations monitored indicated a maximum instantaneous reading of 0.02 ppm and the average of the readings was below the detection limit of 0.01 ppm.

The short term inhalation RfC for chlorine dioxide is 0.05 ppm. According to the label, the frequency of HVAC system treatments is to " treat as required". The frequency of residential ( and/ or commercial/ intuitional) HVAC treatments is expected to be minimal ( one treatment per year may be an overestimate). In addition, the half life of chlorine dioxide is rapid. Page 31 of 58 Therefore, inhalation exposure is expected to be limited to short term durations. The maximum value monitored by BCI ( 2002) during application and/ or reentry was 0.02 ppm, below the RfC value of 0.05 ppm. Therefore, there are no inhalation risks of concern. <IP_ADDRESS> Continuous Release ( Gas) Deodorizer Product Use in Homes:

One product has been identified that is registered as a continuous release of chlorine dioxide gas in homes ( EPA Reg. No. 70060 12). The product is packaged as a pouch or sachet. The product states that it "  controls odor causing bacteria, mold and mildew and chemical odors in confined spaces " and is for use in households, hospitals, and institutions. The product is packaged in 5, 10, 20, 50, 100, and 200 gram pouches/ sachets. Household uses include refrigerators, shoes, closets, laundry hampers, cupboards, cabinets, drawers, diaper pails, pet areas, and basements. Other use sites of this product outside the home include gym lockers, automobiles, boat cabins, and trash cans.

No monitoring data are available to determine the air concentrations in the home. Therefore, a bounding estimate of air concentration is presented based on the application rate and the label referenced longevity of the pouches/ sachets. According to the label, the basement rate is 200 grams of product per 500 ft2 of basement area for up to 2 months of treatment. A 500 ft2 basement area is assumed to be equivalent to a volume of 4,000 ft3 or 113 m3 ( i. e., 500 ft2 x 8 ft ceiling). A linear release of the chlorine dioxide gas is assumed. Based on the rapid half life of chlorine dioxide (~ 30 minutes for aqueous solution and reportedly shorter in air), it is assumed that a gas build up will not occur. The theoretical constant air concentration would be 0.52 ppm assuming no air exchange and no build up of chlorine dioxide over time because of the short half life ( i. e., label rate of 200 grams of 5% ai product/ 500ft2 for 2 months, assuming an 8 ft ceiling). The RfC for long term continuous exposure is 0.00007 ppm. Therefore, the theoretical concentration from the product's release is of concern. This bounding estimate of exposure can be refined by determining residential ventilation rates, identifying sensitive analytical detection methods ( current sampling techniques do not have the capability of monitoring to a level of 0.00007 ppm), collecting monitoring data, and determining the number of hours an individual is exposed in treatment areas. However, before any refinements to these air concentration estimates are attempted, it should be determined if the product's efficacy can be maintained at the RfC of ~ 0.00007 ppm.

Product Use in Automobiles:

There are data available to assess the use of the continuous release deodorizer product in automobiles ( e. g., EPA Reg. No. 70060 12). Two studies were submitted that measured chlorine dioxide air concentrations in automobiles ( Wood and Gallo 1997, and Speronello 1998).

Wood and Gallo ( 1997) measured chlorine dioxide in a total of 16 automobiles ( 8 cars parked outside and 8 cars parked inside a garage). Cars were parked in inside and outside parking lots to account for sunlight degradation of chlorine dioxide. The study author indicated that "  approximately half the chlorine dioxide released was consumed by sunlight". Cars parked outside were treated with 5, 15, 25, and 50 gram sachets while cars parked inside were Page 32 of 58 treated with 5 and 25 gram sachets. An Interscan Digital Chlorine Dioxide Analyzer was used to measure chlorine dioxide inside the cars ( LOD appears to be 0.01 ppm). To sample chlorine dioxide in the cars, tubes were inserted through the weather stripping of the doors to preclude dilution by opening the doors. Each car was sampled from 1 to 4 days. Samples were taken for some cars at 2, 4, 8, and 24 hours after placement of sachets and other cars at 24, 27, 29, 33, and 50 hours after placement of sachets and finally, some at 1, 2, 4, 8, 48, and 96 hours after placement of sachets. Duplicate and triplicate readings were recorded at each sampling interval at various locations in the cars ( i. e., floor, bench, or face for a total of 2 or 3 samples per interval). It appears that reported air concentrations represent instantaneous measurements.

The maximum reported single reading for outdoor cars was 0.19 ppm for the 50 gram sachet and also 0.19 ppm for the indoor car with a 25 gram sachet. The maximum and average readings for all sampling intervals are reported in Table 4.6. Although some of the maximum single reading values of chlorine dioxide exceed the short term residential inhalation toxicity of concern ( i. e., level of concern is a RfC of 0.05 ppm), these maximum single readings are not meaningful to determine risk concerns when compared to the short term inhalation RfC selected in this document. It is more appropriate to compare the peak measurements to the ACGIH STEL which is based on a 15 minute average. The highest maximum single reading of 0.19 ppm from this study does not exceed the STEL of 0.3 ppm. The average of all of the instantaneous readings is below the RfC and the STEL. In conclusion, the data presented by Wood and Gallo ( 1997) indicate that the concentration of chlorine dioxide remains below the STEL and the average of the single measurements does not exceed the RfC of 0.05 ppm. However, a more appropriate measurement would have been to sample over a period of time that is representative of the duration people spend in cars to obtain a time weighted average ( TWA).

Table 4.6. Maximum and Average Chlorine Dioxide Measurements in Automobiles. Weight of Chlorine Dioxide Sachets Chlorine Dioxide Reading ( ppm) 5 grams 15 grams 25 grams 50 grams Cars Parked Outdoors Maximum single reading 0.01 0.06 0.1 0.19 Average of all readings 0.0005 0.009 0.011 0.029 Cars Parked Indoors Maximum single reading 0.008 0.19 Average of all readings 0.002 Not Sampled 0.008 Not Sampled LOD = 0.01 ppm. " Average of all readings" represents the average where nondetects are counted as zero.

Speronello ( 1998) provided limited additional information on chlorine dioxide measurements inside of automobiles. Two cars using different application rates were monitored in this study ( problems were encountered with the 3rd car and this experiment was discontinued). One car was treated with a 20 gram sachet and the other car was treated with three 20 gram sachets. Air concentrations in this study were measured with an INTERSCAN Digital Compact Portable Analyzer ( model 4335DG). This device recorded chlorine dioxide measurements at 10 second intervals for 5 minutes. Sampling intervals were 0, 1, 2, 4, 6, 8, 24, 101, 149, and 192 hours after initial placement of the sachet. All of the 5 minute samples in the car treated with 20 grams of chlorine dioxide are below the detection limit of 0.05 ppm. The results from the car Page 33 of 58 with the exaggerated application rate indicated a maximum chlorine dioxide concentration of 0.091 ppm. However, the text did not indicate if this was a 5 minute sample or peak 10 second interval within the 5 minute measurement. It also appears that some of the data tables in Speronello ( 1998) are missing from the experiment identified as " Run 3". The data table for " Run 3" only includes the 10 second measurements for the 0 hours after treatment interval. The results of this second study do not raise any additional concerns for peak measurements, however, the data are of limited use to determine a TWA concentration over the time period people spend in cars.

<IP_ADDRESS> Swimming Pools & Spas Sodium chlorite is used to treat circulation systems in swimming pools & spas ( EPA Reg. No. 70060 20). The use directions for treating the circulation systems include the following types of statements:

  Do not add this product through any automatic dispensing device;   Apply product when no persons are in the pool;   For pools leave pump off for 6 to 12 hours before resuming pumping and then wait at least 8 hours before allowing swimmers to enter pool;   Frequency of application is once every 3   4 weeks for pools and once every 4   6 weeks for spas; and   For spas wait approximately 30 minutes before reusing spa.

Based on the intended use of the product, swimming in pools or spas treated with chlorine dioxide is not assessed quantitatively. When use directions are properly followed, dermal, incidental oral, and inhalation exposures to chlorine dioxide residual levels after the cleaning of the circulation systems are expected to be minimal.

4.4.3 Data Limitations/ Uncertainties There are several data limitations and uncertainties associated with the residential handler and post application exposure assessments. These include:

° The exposure factors used to calculate daily exposures to handlers are based on applicable data, if available. For lack of appropriate data, values from a scenario deemed similar enough by the assessor were used. ° Surrogate dermal unit exposure values were taken from the proprietary Chemical Manufacturers Association ( CMA) antimicrobial exposure study ( MRID 42587501) or from the Pesticide Handler Exposure Database ( PHED, 1998). See Appendix A for summaries of these data sources. ° The amounts handled/ treated were estimated based on information from various sources, including the Draft Standard Operating Procedures ( SOPs) for Residential Exposure Assessments ( 2000) and the Draft SOPs for Occupational Exposure Assessments ( 2003). In certain cases, no standard values were available for some scenarios. Assumptions for these scenarios were based on AD estimates and could be further refined from input from affected sectors. Page 34 of 58 ° The full study report for the HVAC monitoring ( BCI 2002) needs to be submitted. ° The two studies submitted to support the use in automobiles appear to provide instantaneous readings of chlorine dioxide levels rather than TWA. 5.0 RESIDENTIAL AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION The aggregate risk assessment will be conducted in the overall risk assessment for chlorine dioxide. The non dietary uses that may co occur for consideration in the aggregate assessment include the dermal and incidental oral post application exposures to children playing on treated floors and handler dermal exposures for adults.

6.0 OCCUPATIONAL EXPOSURE AND RISK 6.1 Occupational Handlers 6.1.1 Dermal Handler Exposures Potential occupational handler exposure can occur in various use sites, including agricultural premises, food handling, commercial and institutional premises, medical premises, human drinking water systems, industrial processes and water systems, application to material preservatives, and swimming pools and other aquatic areas. Table 6.1 provides the representative use scenarios that were assessed in this risk assessment.

Table 6.1. Exposure Scenarios Associated with Occupational Exposure Assessed in this Document Representative Use Application Method EPA Registration Number ( chemical associated with use) Application Rate ( lb ai/ gal) Exposure Scenario Assessed Use Site Category I ( Agricultural Premises and Equipment) a $

lowpressure hand wand 74602 2 ( Sodium Chlorite) ( Application rate from label, 2.5 fl oz/ gal)*( 1 gal/ 128 oz)*( 0.75 lb ai/ gal) = 0.015 $

triggerpump sprayer $ fogger ( 1 hour REI after fogging) 74602 2 ( Sodium Chlorite) ( Application rate from label, 2.5 fl oz/ gal)*( 1 gal/ 128 oz)*( 0.75 lb ai/ gal) = 0.015 $ mop 9150 2 ( Chlorine Dioxide) ( Application rate from label, 3.25 fl oz/ gal)*( 1 gal/ 128 oz)*( 0.69 lb ai/ gal) = 0.018 Application to hard surfaces and equipment $ foaming wand 9150 11 ( Chlorine Dioxide) ( Application rate from label, 0.25 gal of product* 0.10 lb ai/ gal) = 0.025 lb ai/ gal.) Apply at rate of 4 to 6 gallons/ minute to inside/ outside of animal trucks/ equipment. Short and Intermediateterm ( ST and IT) Adult Handler ( dermal and inhalation) and Adult Bystander and Post Application ( dermal and inhalation) Page 35 of 58 Table 6.1. Exposure Scenarios Associated with Occupational Exposure Assessed in this Document Representative Use Application Method EPA Registration Number ( chemical associated with use) Application Rate ( lb ai/ gal) Exposure Scenario Assessed   ULV fogger ( e. g., Dramm fogger) 74602 2 ( Sodium Chlorite) ( Egg house label rate, 1 gal product x 5% ClO2) per 50 gal = 0.0083)

Use Site Categories II ( Food Handling), III ( Commercial/ Institutional), and V ( Medical)

$ mop 9150 10 active ( 10589 3 transferred) ( Chlorine Dioxide) ( Application rate from label, 5 oz/ gal)*( 1 gal/ 128 oz)*( 0.49 lb ai/ gal) = 0.019 Application to hard surfaces and equipment without food contact $

triggerpump sprayer 21164 3 ( Sodium Chlorite) ( Application rate from label, 12 fl oz/ gal)*( 1 gal/ 128 oz)*( 0.86 lb ai/ gal) = 0.08 Application to foods ( Fruit/ vegetable rinse) $ dip 74602 2 ( Sodium Chlorite) ( Application rate from label, 1.9 oz/ gal)*( 1 gal/ 128 oz)*( 0.75 lb ai/ gal) = 0.011 ST/ IT Adult Handler ( dermal and inhalation) and Adult Post Application/ Bystander ( dermal and inhalation)

Use Site Category VI ( Human Drinking Water Systems)

Application to water systems ( Water Treatment and water storage systems) $ metering pump 9804 1 ( Chlorine Dioxide) ( Application rate from label, 3.25 fl oz/ gal)*( 1 gal/ 128 oz)*( 0.27 lb ai/ gal) = 0.007 ST/ IT Adult Handler; Potential for inhalation exposure unknown at this time.

Use Site Category VII ( Material Preservatives)

Applications to MWFs $ liquid pour 9150 2 ( Chlorine Dioxide) batch method: 0.0001 ( per week)

continuous method: 8E 7 ( per day)

badly contaminated systems: 4E 6 ( slug dose) ST/ IT Adult Handler ( dermal and inhalation) and Long term Dermal and Inhalation for Machinists.

Use Site Category VIII ( Industrial Processes and Water Systems) Application to pulp and paper white water systems $ metering pump 74602 3 ( Sodium Chlorite) ( Application rate from label, 15 gal/ 100,000 gal white water to be treated or 4 gal/ 100 tons paper produced)*( 0.86 lb ai/ gal) = 0.0001 lb ai/ gal white water or 3.44 lb ai/ 100 ton paper produced ST/ IT Adult Handler ( dermal and inhalation) and Adult Bystander ( inhalation)

Application to oil systems ( oil wells during secondary recovery operations) $ liquid pour 9150 2 ( Chlorine Dioxide) ( Application rate from label, 1 gal/ 10 gal)*( 0.69 lb ai/ gal) = 0.069. Label indicates to portion 1 part of this solution to 150 parts reinjection water. ST/ IT Adult Handler ( dermal and inhalation) and Adult Bystander ( inhalation) Page 36 of 58 Table 6.1. Exposure Scenarios Associated with Occupational Exposure Assessed in this Document Representative Use Application Method EPA Registration Number ( chemical associated with use) Application Rate ( lb ai/ gal) Exposure Scenario Assessed Use Site Category XI ( Swimming Pools)

Application to public swimming pool circulation water systems ( Swimming pools) $ solid place ( tablets) 70060 20 ( Sodium chlorite) 4 tablet / 10,000 gal ( Pool tablet is 100 g x 4 tablets x 20% ai = 80 g ai/ 10,000 gal = 1.8E 5 lb ai/ gal) Short term Adult Handler ( dermal and inhalation)

Use Site Category XII ( Aquatic Areas)

Non potable water systems ( e. g., retention basins and ponds, decorative pools and fountains) $ liquid pour 9150 11 ( Chlorine Dioxide) 0.00001 ( 18 fl oz x 0.72% ai per 100 gallons water) ST/ IT Adult Handler ( dermal and inhalation)

Use Site Category XIII ( HVAC)

Application to ventilation systems ( HVAC) $ airless sprayer $ fogger ( 1hour REI after fogging) 9804 1 ( Chlorine Dioxide) ( Application rate from label, 3.25 fl oz/ gal)*( 1 gal/ 128 oz)*( 0.27 lb ai/ gal) = 0.007 ST/ IT Adult Handler ( dermal and inhalation) and Short term Child and Adult Post Application ( inhalation)

The following assumptions and unit exposure values were used in the risk assessment:

$ Unit Exposure Values: Dermal unit exposure values were taken from the proprietary Chemical Manufacturers Association ( CMA) antimicrobial exposure study ( MRID 42587501) or from the Pesticide Handler Exposure Database ( PHED, 1998). o For low pressure hand wand, the CMA dermal unit exposure value for ungloved use of a low pressure spray was used ( 191 mg/ lb ai). This value is based on data collected from eight replicates that hand sprayed carpet using 200 psi, and then used a push broom rake to raise the carpet nap. The time required to perform this activity took between 33 to 141 minutes. o For fogging, it is assumed that most of the exposure to the handler will be due to preparing the fogger and that the handler leaves the room immediately after fogging commences. Therefore, the CMA dermal unit exposure value for ungloved pouring was used ( 50.3 mg/ lb ai). This value is based on data collected from one replicate that transferred the pesticide from a large container to a smaller measuring or pouring container. The time required to perform this activity took between 5 to 78 minutes. o For mopping, the CMA dermal unit exposure value for ungloved mopping was used ( 71.6 mg/ lb ai). This value is based on data collected from six replicates mopping floors and receiving exposure via contact with the mop or with the bucket. Page 37 of 58 o For airless sprayer, PHED dermal unit exposure values for ungloved ( 38 mg/ lb ai) and gloved ( 14.3 mg/ lb ai) were used. These values are based on data collected from 15 replicates who applied a house stain to the outside of a house. The airless sprayer was used to represent the spraying of HVAC duct work. In addition to airless sprayers, duct work applications would include ULV foggers, robotic spraying systems, and various electric sprayers. o For foam applicator, the CMA dermal unit exposure value for smaller applications ungloved use of a low pressure spray was used ( 191 mg/ lb ai). This value is based on data collected from eight replicates that hand sprayed carpet using 200 psi, and then used a push broom rake to raise the carpet nap. The time required to perform this activity took between 33 to 141 minutes. Assume PHED airless sprayer equipment as a surrogate for large applications such as to animal transport vehicles. o For metering pump into human drinking water systems and industrial processes and water systems, the unit exposure value from the CMA dermal unit exposure value for gloved metering pump of a preservative is used ( 0.00629 mg/ lb ai). This value is based on data collected from two replicates. o For liquid pour, the CMA preservative dermal unit exposure value for a gloved worker was used. The dermal unit exposure is 0.135 mg/ lb a. i. and is based on 2 replicates. Although this unit exposure is based on minimal replicates, the exposure value is similar to the one found in PHED for a similar scenarios o For place solid ( tablets) into public swimming pool water circulation systems, the unit exposure value from the CMA dermal unit exposure for ungloved use is 10.8 mg/ lb ai and 0.412 mg/ lb ai for gloved use, only one replicate of each. o For trigger pump sprays, the PHED dermal unit exposure value for the aerosol sprays were also used as a surrogate for the trigger pump. The PHED dermal unit exposure values for ungloved ( 190 mg/ lb ai) and gloved ( 81 mg/ lb ai) were used. These values are based on data collected from 15 replicates in which the aerosol spray was applied on surfaces.

$ Amount handled/ treated: The amounts handled/ treated were calculated based on AD estimates and could be further refined with input from affected sectors. The following assumptions were made: o Low pressure hand wand: 2 gal/ day o Trigger pump sprayers: 1 liter/ day ( 0.26 gal/ day) o Airless sprayer for the HVAC use is assumed to be 5 gallons for one worker. This value is assumed to be representative of either a commercial applicator treating multiple residential homes or a work day treating a commercial building ( 5 gal) o Mopping: it was assumed that two gallons of solution are used in the food handling and commercial/ institutional/ industrial setting and 45 gallons are used in the medical setting. The reason for this assumption specific to medical premises is because in hospitals, a janitor cleans approximately 28 rooms a day and must change the cleaning water every three rooms ( Helwig 2003) o Fogger ( e. g., HVAC): 1 quart assumed for a single work day ( 0.25 gal) Page 38 of 58 o Foam: for application to animal transport vehicles, label directed 4 to 6 gallons per minute and assume applied for 10 minutes. Additional information on this use scenario is warranted. o Water storage systems: 34,000 gal/ day ( estimated storage capacity of water system for 100 people; based on Occupational SOPs, assumption of 170,000 gal/ day for population of < 500 people) o Pulp and Paper process water: 500 tons/ day o Oil systems ( oil wells): The following use was used to estimate the amount of ai handled per day during oil well activities. Biocide is typically added directly to drilling rig mud tanks via open pouring. Over a 3 to 6 week period, while a 13,000 ft well is being drilled, 1 to 2 drums ( 1 drum = 42 gallons) of biocide may be used if microbiological problems are encountered. Therefore, the shortterm exposure assessment used 5.6 gallons for the amount of biocide handled per day by the drilling rig worker [ i. e., ( 2 drums x 42 gal/ drum) / ( 5 days/ week x 3 weeks) = 5.6 gal/ day]. The intermediate term exposure assessment used 2.8 gallons for the amount of biocide handled per day by the drilling rig worker [ i. e., ( 2 drums x 42 gal/ drum) / ( 5 days/ week x 6 weeks) = 2.8 gal/ day]. However, since the volume of water being treated in secondary recovery operations is so large ( i. e., 1,000 barrels per day, 42 gal/ barrel, closed metering system), the available CMA data can not be reliably extrapolated because they are based on activities that handle much lower volumes and possibly different techniques. Therefore, it was assumed that if the open pour handling activities for the other oil well operations resulted in MOEs that are not of concern, then the MOEs for the closed system chemical metering into secondary recovery operations would also be not of concern. AD requests that confirmatory data be conducted to show that this is accurate. o Retention ponds/ fountains: 10,000 gallons o Public swimming pool: 200,000 gallons $ To calculate the dermal exposure for a worker treating fruits and vegetables, the Consumer Exposure Pathway of the Exposure and Fate Assessment Tool ( CEM/ E FAST) was used. CEM calculates conservative estimates of inhalation and dermal exposures to consumer products. Because CEM does not include a scenario similar to treating fruits and vegetables via dip/ rinse, a new user defined scenario was created ( using the category " products that contact skin directly ( dermal), potential dose"). Surrogate exposure factor values have been extracted from E FAST defaults provided in the CEM help manual. Assumptions and input values for the model are listed in Table 6.3.

The calculated dermal MOEs are shown in Table 6.2. Table 6.3 provides the CEM model inputs and results for the fruit and vegetable rinse scenario. Calculated dermal MOEs less than the target MOE of 100 were found for the following scenarios: Page 39 of 58 Agricultural Premises and Equipment ° application to hard surfaces via low pressure hand wand ( MOE = 31) ° application to hard surfaces via mopping ( MOE = 70) ° foam applicator to animal transport vehicles/ tractor trailer ( MOE = 8)

Food Handling, Commercial/ Institutional, and Medical Premises and Equipment ° application to hard surfaces via mopping ( MOE = 66 for commercial and 3 for medical)

In addition to the above handler assessments, the dermal exposure to machinists contacting chlorine dioxide when used as a material preservative in metal working fluid ( MWF) is presented below. There is a potential for dermal and inhalation exposure when a worker handles treated metalworking fluids. Because of the high vapor pressure of chlorine dioxide, the inhalation route of exposure is not assessed in the typical manner ( i. e., using the OSHA PEL for oil mist x percent concentration in solution). See Sections 6.1.2 and 6.2 for discussion of the inhalation route.

The dermal route of exposure to machinists occurs after the chemical has been incorporated into the metalworking fluid and a machinist is using/ handling this treated endproduct Short, intermediate, and long term exposure estimates were derived using the 2 hand immersion model from ChemSTEER. The model is available at www. epa. gov/ opptintr/ exposure/ docs/ chemsteer. htm. The 2 hand immersion equation is as follows:

PDR = SA x % a. i. x FT x FQ BW where:

PDR = Potential dose rate ( mg/ kg/ day); SA = Surface area of both hands ( cm2); % a. i. = Fraction active ingredient in treated metalworking fluid ( unitless) FT = Film thickness of metal fluid on hands ( mg/ cm2) FQ = Frequency of events ( event/ day); BW = Body weight ( kg)

Assumptions   The surface of area of both hands is 840 cm2 ( US EPA 1997)   The body weight of an adult female is 60 kg ( US EPA 1997)   The percent active ingredient in treated metalworking fluid for continuous operations ( label specified " continuous" rate selected because this is a long term duration) is 8E 7 lb ai/ gallon or 0.00001 % ( EPA Registration No. 9150 2). Three rates are listed on the product's label which contains 5% chlorine dioxide: ( 1) Batch Method is 32 fl oz product/ 1,000 gallons water based cutting oils; ( 2) Continuous Method is 2 gallons product/ 1,000,000 gallons water based cutting oils ( 2 gal x 8 lb/ gal x 0.05 ai / 1,000,000 gallons cutting oil = 8E 7 lb ai/ gal); and ( 3) Badly Contaminated Systems is 10 gallons product/ 1,000,000 gallons water Page 40 of 58 based cutting oils. [ To convert to % ai = 8E 7 lbai/ gal x 454 g/ 1 L x 1000 mg / 1 g x 1 gal/ 3.79 L = 0.1 mg/ L / 10,000 = 0.00001% ai]   For short, intermediate and long term durations, the film thickness on the hands is 1.75 mg/ cm2, which was extracted from the document entitled, " A Laboratory Method to Determine the Retention of Liquids on the Surface of Hands." The film thickness is based on a machinist immersing both hands in metalworking fluid and then partially cleaning hands with a rag. The film thickness was chosen because the dermal endpoint for short, intermediate and long term durations is based on systemic effects ( USEPA, 1991).

The results of the dermal exposure/ risk to machinists working with fluids treated with chlorine dioxide and/ or sodium chlorite are presented in Table 6.4. The short, intermediate, and long term dermal MOE is 14,000, and therefore, not of concern. Page 41 of 58 Table 6.2. Short and Intermediate Term Dermal and Inhalation Exposures/ Risks to Occupational Handlers from the Use of Chlorine Dioxide Dermal Unit Exposuresc ( mg/ lb ai) Baseline Attired PPE ( with gloves) e Exposure Scenario Application Ratea ( lb ai/ gal) Area Treated Dailyb ( gal) Baseline PPE with gloves Dermal Dosef ( mg/ kg/

day) Dermal MOEg Dermal Dosef ( mg/ kg/

day) Dermal MOEg Agricultural Premises and Equipment Low Pressure Hand Wand (

CMAdisinfectant hard surfaces 0.015 2 191 NA 0.096 31 No Data No Data Liquid Pour ( CMA Data for cooling tower)  fogger scenario hard surfaces 0.015 0.188 50.3 10.1 0.0024 1,300 0.00047 6,300 Trigger pump Sprayer ( PHED data for aerosol can used as surrogate) hard surfaces 0.015 0.26 190 81 0.012 240 0.0053 570 Mopping ( CMA data) hard surfaces 0.018 2 71.6 NA 0.043 70 No Data No Data Foam Wand Applicator ( using PHED airless sprayer) animal transport vehicles 0.025 6 gal/ min x 10 min =

60 gallons 38 14.3 0.95 3 0.36 8 Food Handling, Commercial/ Institutional, and Medical Premises and Equipment 2 0.045 66 Mopping ( CMA data) hard surfaces 0.019 45 71.6 NA 1.0 3 No Data No Data Trigger pump Sprayer ( PHED data for aerosol can is used as surrogate) hard surfaces 0.08 0.26 190 81 0.066 46 0.028 110 Human Drinking Water Systems Metering Pump ( CMA) water and storage systems 0.007 34000 NA 0.00629 No Data No Data 0.025 120 Material Preservatives Liquid Pour ( CMA) MWF 0.0001 ( Batch Method) 300 NA 0.184 No Data No Data 0.000092 33,000 Industrial Processes and Water Systems Metering Pump ( CMA data for pulp & paper) paper and pulp white water systems 0.0344 lb ai/ ton paper 500 tons paper NA 0.00454 No Data No Data 0.0013 2,300 2.8 0.00043 6,900 Liquid Pour ( CMA data for preservative) oil systems 0.069 5.6 NA 0.135 No Data No Data 0.00087 3,500 Page 42 of 58 Table 6.2. Short and Intermediate Term Dermal and Inhalation Exposures/ Risks to Occupational Handlers from the Use of Chlorine Dioxide Dermal Unit Exposuresc ( mg/ lb ai) Baseline Attired PPE ( with gloves) e Exposure Scenario Application Ratea ( lb ai/ gal) Area Treated Dailyb ( gal) Baseline PPE with gloves Dermal Dosef ( mg/ kg/

day) Dermal MOEg Dermal Dosef ( mg/ kg/

day) Dermal MOEg Swimming Pools and Aquatic Areas Liquid Pour ( CMA data) retention ponds/ fountain 0.00001 10,000 NA 0.135 No Data No Data 0.0045 670 Solid Place ( CMA) public pools 1.8E 5 200,000 10.8 0.412 0.65 5 0.025 120 HVAC Systems Airless Sprayer ( PHED data) HVAC 0.007 5 38 14.3 0.022 140 0.0083 360 Liquid Pour ( CMA data)  fogger scenario HVAC 0.007 0.25 50.3 10.1 0.0015 2,000 0.00029 10,000 a Application rates are the maximum application rates determined from EPA registered labels for chlorine dioxide, sodium chlorite, and sodium chlorate.

b Amount handled per day values are based on Residential SOPs, industry sources, and AD estimates.

c Dermal unit exposures are from CMA and PHED studies.

d Baseline dermal: Long sleeve shirt, long pants, and no gloves.

e PPE dermal with gloves: baseline dermal plus chemical resistant gloves.

f Dermal dose ( mg/ kg/ day) = [ unit exposure ( mg/ lb ai) * dermal absorption ( 1.0) * Appl. rate * amount handled / Body weight ( 60 kg).

g MOE = NOAEL ( mg/ kg/ day) / daily dose [ Where short and intermediate term dermal NOAEL = 3 mg/ kg/ day]. Target MOE is 100. Page 43 of 58 Table 6.3. E FAST/ CEM Model Inputs and Results for the Fruit/ Vegetable Rinse Scenario Parameter Value Rationale Inputs Weight Fraction of Chemical in Product 0.073 Based on maximum use rate listed on product label Hand Surface Area/ Body Weight Ratio 15.6 cm2/ kg Derived from both hands being immersed in the dip solution ( EFAST default value for general purpose cleaner scenario, Versar, 1988)

Film Thickness 0.00214 cm Assumed to be the initial thickness of water uptake on hands from handling a rag ( E FAST default value for general purpose cleaner scenario, Versar, 1988)

Density of Formulation 0.032 g/ cm3 Based on information from label ( 0.27 lb ai/ gal = 0.032 g/ cm3)

Dilution Fraction 0.015 Derived from information on product label ( 1.9 oz/ gal = 0.015 gal/ gal)

Frequency of Events per Year 130 event/ yr Assumed 5 days/ week for 50 weeks/ yr Number of Years of Use 57 yrs Assumed to be total number of years between the ages of 18 and 75 Amount Retained on Skin 0.000001 g/ cm2 Derived from product of the film thickness on the skin's surface and the density of the formulation and the dilution factor Calculated Results Potential Dermal Dose Rate 1.14e 03 mg/ kg day ADRpot output from model ( see Appendix B)

Calculated MOE 2600 MOE = NOAEL / Daily Dose [ Where dermal NOAEL = 3 mg/ kg/ day].

Table 6.4. Short, Intermediate, and Long Term Risks Associated with Post Application Exposure to Metalworking Fluids treated with Chlorine Dioxide ( Machinist)

Dermal Inputs Continuous Feed Method % a. i.

( EPA Reg. No. 9150 2) Hand Surface Area ( cm2) Film thickness ( mg/ cm2) Frequency ( event/ day) Daily Dermal Dose ( mg/ kg/ day) ( a) ST/ IT/ LT Dermal MOE ( Target MOE = 100) ( b)

0.00001 840 1.75 1 0.00025 12,000 a Dermal daily dose ( mg/ kg/ day) = [(% active ingredient * hand surface area* dermal absorption factor ( 100% for all durations)* film thickness ( mg/ cm2)* frequency ( event/ day)] / body weight ( 60 kg). b Dermal MOE = NOAEL ( mg/ kg/ day) / daily dose ( mg/ kg/ day) [ Where: ST/ IT/ LT NOAEL = 3 mg/ kg/ day from an oral study assuming 100% dermal absorption]. Page 44 of 58 6.1.2 Inhalation Handler Exposures Inhalation exposure to the release of chlorine dioxide gas during the mixing/ loading/ application of products producing chlorine dioxide may occur. Because the inhalation toxicological endpoint is based on an 8 hour TWA, the assessment of handler inhalation exposures is assessed as a combination of activities throughout a work day. The assessment of inhalation exposure is presented in the post application/ bystander section ( Section 6.2).

As indicated above, EPA has selected an 8 hour TWA inhalation endpoint. EPA does not provide a separate endpoint for short term exposures to handlers. Short term releases of chlorine dioxide are of concern for accidental releases/ leaks and/ or when applicators are in close proximity to open solutions of chlorine dioxide. EPA assumes that the ACGIH 15 minute short term exposure limit ( STEL) of 0.3 ppm as well as the immediately dangerous to life or health ( IDLH) limit of 5 ppm will be adhered to in the industries using chlorine dioxide.

6.2 Occupational Post Application/ Bystander Exposure 6.2.1 Dermal Post Application/ Bystander Exposures No information is available to assess post application/ bystander dermal exposure to uses in agricultural premises as well as food handling, commercial/ institutional and medical premises; human drinking water facilities; industrial processes; and retention ponds. However, dermal post application exposure to chlorine dioxide is expected to be less than that of the dermal contact of children playing on treated floor surfaces. Therefore, the dermal exposure route is not believed to be of concern in these industries.

6.2.2 Inhalation Post Application/ Bystander Exposures Non Fogging Uses There is the potential for the off gassing of chlorine dioxide during some applications that are not totally enclosed ( e. g., spray aqueous solution, mopping, pouring, etc). Although no occupational air monitoring data have been submitted to assess the inhalation route, EPA has obtained air concentration measurements from OSHA. OSHA maintains a data base known as the Integrated Management Information System ( IMIS). The IMIS entries for chlorine dioxide are available for 7 industry Standard Industrial Classification ( SIC) codes. Specific uses such as applicators, bystanders and the activities involved are not available. The SIC codes representing the chlorine dioxide data in IMIS used in this assessment include:

  SIC 0723 Crop preparation services for market;   SIC 1629 Heavy construction;   SIC 2611 Pulp mills;   SIC 2621 Paper mills;   SIC 2819 Industrial inorganic chemicals;   SIC 2836 Biological products; and Page 45 of 58   SIC 3999 Manufacturing industries.

The data selected for this analysis include only those samples that are reported as 8 hour TWA measurements from personal air samplers. Other samples, such as peaks concentrations and/ or area monitors, have been omitted. The chlorine dioxide sampling and analytical procedures used in the collection of the data in IMIS are available at http:// www. osha. gov/ dts/ sltc/ methods/ inorganic/ id202/ id202. html. The quantitative LOD from this method is 0.004 ppm for a 4 hour sample ( the recommended sampling time). The reported full 8 hour work shift samples are based on two 4 hour samples collected in sequence. The inhalation endpoint selected by EPA is 0.003 ppm, just below the OSHA LOD for an 8 hour TWA air sample [ i. e., ( 0.5 x 0.004 ppm per 4 hrs) + ( 0.5 x 0.004 ppm per 4 hrs)= 0.004 ppm per 8 hours].

The summary results of the 33 observations taken from 8 hour TWA personal air samplers for chlorine dioxide are provided below in Table 6.5. All values, including ½ LOD are above the EPA selected inhalation reference concentration ( RfC) of 0.003 ppm, and therefore, are of concern. Of the 33 TWA measurements available, 21 of those measurements were below the LOD of 0.004 ppm. In addition, of the 33 TWA measurements, only 3 were at or above the OSHA PEL of 0.1 ppm. For nondetected samples, 1/ 2 the detection limit for an 8 hour sample was used to determine the summary.

Table 6.5. Chlorine Dioxide 8 hour TWA for Personal Air Samplers from OSHA's IMIS Data Base. Statistic Chlorine Dioxide 8 hr TWA ( ppm) MOE Arithmetic mean ± std 0.034 ± 0.096 50th% tile 0.004 ( 1/ 2 8 hr LOD) 75th% tile 0.008 90th% tile 0.032 Maximum 0.42 Number of Observations 33 Number of Nondetects 21 te: The inhalation endpoint is expressed as the RfC. Because the uncertainty factors are included in the RfC a separate MOE is not needed. The occupational RfC of 0.003 ppm is compared directly to the air concentration monitored for the worker. Air concentrations above the RfC are of concern. All values, including the LOD, are above the RfC.

Fogging Uses The fogging use of chlorine dioxide is unique such that no persons are present during the actual application/ fogging. There is also a greater potential for chlorine dioxide gas formation from fogging then an aqueous based application such as mopping. Therefore, a separate assessment is presented for foggers that indicate potential inhalation exposure and reentry recommendations. The air concentration in a fogged area should be below the occupational RfC of 0.003 ppm before the room is entered by persons not wearing respiratory protection. In the fogging assessment below, EPA Reg. No. 74602 2 is used to illustrate potential air concentrations. Page 46 of 58 Concentrations of chlorine dioxide were estimated for buildings after fogging applications. Air concentrations were calculated using the Multi Chamber Concentration and Exposure Model ( MCCEM v1.2). MCCEM estimates average and peak indoor air concentrations of chemicals released from products or materials in houses, apartments, townhouses, or other residences. Although the data libraries contained in MCCEM are limited to residential settings, the model can be used to assess other indoor environments. MCCEM has the capability to estimate inhalation exposures to chemicals, calculated as single day doses, chronic average daily doses, or lifetime average daily doses.

The product, EPA Reg # 74602 2 ( sodium chlorite with a 5% chlorine dioxide equivalent) has a maximum application rate for egg houses of 0.0083 lb ai/ gal ( 1000 ppm chlorine dioxide treatment solution). This particular product specifically lists a Dramm fogger for the application ( i. e., ultra low volume ( ULV)). According to the registrant, the Dramm fogger for chlorine dioxide applications uses 2.5 ounces of the diluted product per 225,000 cubic feet ( USEPA 2006), and the label states to run the fogger for five minutes. Note: This labeled rate should be added to all chlorine dioxide fogger uses. If other registrants require a higher application rate, these rates need to be brought to EPA's attention during the development of the chlorine dioxide RED.

Model input assumptions for MCCEM and the calculated exposures are presented in Tables 6.6 and 6.7 for 0.18 ACH and 4 ACH, respectively. The following assumptions were made:

  The area being fogged is a one chamber barn with dimensions of 300 ft x 50 ft x10 ft ( AD standard assumption).   Two different air exchange rates ( kACH) were used in the calculations: 0.18 air exchange per hour ( ACH) ( MCCEM default based on a poorly vented residential home) and 4 ACH based on the rate for a poultry barn ( Jacobson, 2005).   The half life of chlorine dioxide is 30 minutes ( 0.5 hours) in an aqueous solution ( believed to be less in air but reliable data are not available). Using the equation t kdecay e C C   = 0 0 2 1 , and substituting 0.5 hours for " t", the rate of decay is calculated to be 1.386/ hr.   Both air exchange and chemical decay can be modeled as first order processes for a wellmixed single chamber ( i. e., the rate of chemical loss that can be attributed to either of these processes is proportional to the quantity of chemical in the chamber). Therefore, the two rates ( kACH and kdecay) can be added together to form a single loss rate ( kloss= kACH+ kdecay), such that t kloss e C t C   = 0 ) ( . This value was used for the " Air Exchange Rate" in the MCCEM model to account not only for the air exchange, but also the decay.   Fogging occurs instantaneously, so that the entire mass of product is mixed homogeneously with the indoor air as soon as fogging commences.

The initial concentrations of chlorine dioxide, as indicated in Tables 6.6 and 6.7, is 0.0116 mg/ m3 or 0.004 ppm. Using an ACH of 0.18, an 8 hr TWA of less than 0.003 ppm ( 0.0084 mg/ m3) is expected with no REI. Using an ACH of 4/ hr, an 8 hr TWA of less than 0.003 ppm ( 0.0084 mg/ m3) is expected without an REI. A detailed report is presented in Appendix C, including hourly air concentrations. Although there appears to be no inhalation risks of concern, Page 47 of 58 a 1 hour REI would be prudent. Moreover, potential label language to assure proper ventilation if rates above that used in this assessment are identified for existing products include:  ten air exchanges, or  2 hours of mechanical ventilation ( i. e., fans), or  4 hours of passive ventilation ( i. e., windows, vents), or  11 hours of no ventilation followed by 1 hour of mechanical ventilation, or  11 hours of no ventilation followed by 2 hours of passive ventilation, or  24 hours of no ventilation Table 6.6. Short and Intermediate Term Inhalation Risks Associated with Post Application Exposure to Chlorine Dioxide After Fogging 0.18 ACH Parametera Value Rationale Dimensions 300x50x10 ft, 15,000 ft2 floor area, 150,000 ft3 ( 4,248 m3) volume EPA assumption Air Changes per Hour ( ACH)* 1.566/ hr Value used in MCCEM is actually the ACH rate ( 0.18/ hr) plus the decay rate ( 1.386/ hr) a Activity Pattern* 8 hour Time Weighted Average ( TWA) starting immediately, 1 hour, and 12 hours after fogging Based on product =

s reentry interval ( EPA Reg# 74602 2)

Application Rate 0.0083 lb ai/ gal Product label Use Rate 2.5 oz/ 225,000 ft3 Manufacturer's specifications Amount Applied to Room 1.16x10 5 g/ m3 ( Use rate) x ( Application rate) Concentration in Room after Fogging ( initial concentration rate at time 0)* 0.0116 mg/ m3 Amount applied to room MCCEM Output Average Concentration over 8 hrs ( mg/ m3) 0 hr re entry: 0.00109 Average of MCCEMcalculated air concentrations from Hour 0 to Hour 8 Average Concentration over 8 hrs ( mg/ m3) 1 hr re entry: 0.000227 Average of MCCEMcalculated air concentrations from Hour 1 to Hour 9 Occupational RfC ( i. e., level of concern) 8 hour TWA 0.0084( mg/ m3) Level of concern not exceeded * Used as MCCEM input. Default values from MCCEM were used for all inputs not listed in the table above a Half life of chlorine dioxide = 30 minutes ( 0.5 hr). Using the equation t kdecay e C C   = 0 0 2 1 and substituting 0.5 hours for " t", the rate of decay is calculated to be 1.386/ hr. Page 48 of 58 Table 6.7. Short and Intermediate Term Inhalation Risks Associated with Post application Exposure to Chlorine Dioxide After Fogging 4 ACH Parametera Value Rationale Dimensions 300x50x10 ft, 15,000 ft2 floor area, 150,000 ft3 ( 4,248 m3) volume EPA assumption Air Changes per Hour ( ACH)* 5.386/ hr Value used in MCCEM is actually the ACH rate ( 4.0/ hr) plus the decay rate ( 1.386/ hr) a Activity Pattern* 8 hour Time Weight Average ( TWA) starting immediately, 30 minutes, and 1 hour after fogging Based on product =

s reentry interval ( EPA Reg# 74602 2)

Application Rate 0.0083 lb ai/ gal Product label Use Rate 2.5 oz/ 225,000 ft3 Manufacturer's specifications Amount Applied to Room 1.16x10 5 g/ m3 ( Use rate) x ( Application rate) Concentration in Room after Fogging ( initial concentration rate at time 0)* 0.0116 mg/ m3 Amount applied to room MCCEM Output Average Concentration over 8 hrs ( mg/ m3) 0 hr re entry: 0.000475 Average of MCCEMcalculated air concentrations from Hour 0 to Hour 8 Average Concentration over 8 hrs ( mg/ m3) 1 hr re entry: 2.18x10 6 Average of MCCEMcalculated air concentrations from Hour 1 to Hour 9 Occupational RfC ( i. e., level of concern) 8 hour TWA 0.0084( mg/ m3) Level of concern not exceeded * Used as MCCEM input. Default values from MCCEM were used for all inputs not listed in the table above a Half life of chlorine dioxide = 30 minutes ( 0.5 hr). Using the equation t kdecay e C C   = 0 0 2 1 and substituting 0.5 hours for " t", the rate of decay is calculated to be 1.386/ hr.

In a second fogging example, EPA Reg. No. 21164 3 allows chlorine dioxide fogging and misting applications while workers are in the room if the level of chlorine dioxide does not exceed the TLV TWA of 0.1 ppm. The use directions are as follows:

"  may be added to the plant misting or fogging systems to deodorize and to control odor causing bacteria, mold and mildew in food processing plants, dairies, bottling plants, poultry, meat and fish plants and animal facilities such as poultry houses, swine pens, calf barns and kennels. If the TLV TWA is to be exceeded, turn off air handlers and Page 49 of 58 vacate people and livestock from the rooms to be fogged or misted. Ventilate for 15 minutes prior to reentry. Note   Be careful not to add concentrated acid solutions to undiluted DURA KLOR as high concentrations of chlorine dioxide gas may evolve. The concentration of chlorine dioxide in the diluted DURA KLOR solution should not be allowed to exceed 0.5 ppm "

The occupational RfC of 0.003 ppm could be exceeded based on these use directions ( i. e., workers do not need to leave treatment area unless the TLV TWA of 0.1 ppm is exceeded).

EPA's Risk based RfC versus OSHA PEL It is also important to note that the OSHA PEL for chlorine dioxide is 0.1 ppm. Air concentrations above the PEL are assumed to be mitigated at each facility. Facilities using chlorine dioxide are not required to mitigate inhalation exposures until the air concentration reaches 0.1 ppm. Based on the occupational inhalation toxicological endpoint selected for chlorine dioxide ( i. e., RfC of 0.003 ppm), levels at or near the PEL are of concern. In fact, the capability ( i. e., LOD) of the OSHA sampling method is insufficient for the occupational RfC presented in this document. Reconciliation of the EPA risk based RfC and the current OSHA standards will be made during the regulatory decision phase of the Reregistration Eligibility Decision ( RED) for chlorine dioxide. The various cited chlorine dioxide levels from other organizations are reported in Table 6.8 for review by regulatory managers.

Table 6.8 Chlorine Dioxide Regulatory Levels. Organization Time/ Duration Description Air Concentration ( ppm) OSHA 8 hour TWA PEL 0.1 8 hour TWA TLV 0.1 ACGIH 15 minutes STEL 0.3 10 hour TWA REL 0.1 NIOSH 30 minutes ( escape) IDLH 5 8 hour TWA RfC  Occupational 0.003 " Short term" RfC   Residential for single exposures 0.05 EPA Continuous ( 24/ 7) RfC   Residential 0.00007 6.3 Data Limitations/ Uncertainties There are several data limitations and uncertainties associated with the occupational handler and post application exposure assessments. These include:

$ The exposure factors used to calculate daily exposures to handlers are based on applicable data, if available. For lack of appropriate data, values from a scenario deemed similar enough by the assessor were used.

$ The inhalation toxicological endpoints of concern for the occupational and long term residential scenarios/ durations are below the limit of detection for chlorine dioxide.

$ Specific application techniques and/ or worker activities are not available in OSHA's IMIS data base. Page 50 of 58 $ Surrogate dermal unit exposure values were taken from the proprietary Chemical Manufacturers Association ( CMA) antimicrobial exposure study ( MRID 42587501) or from the Pesticide Handler Exposure Database ( PHED, 1998). See Appendix A for summaries of these data sources. o The amounts handled/ treated were estimated based on information from various sources, including the Draft Standard Operating Procedures ( SOPs) for Residential Exposure Assessments ( 2000) and the Draft SOPs for Occupational Exposure Assessments ( 2003). In certain cases, no standard values are available for some scenarios. Assumptions for these scenarios are based on AD estimates and could be further refined from input from affected sectors. Page 51 of 58 7.0 REFERENCES 42587501 Popendorf, W.; Selim, M.; Kross, B. ( 1992) Chemical Manufacturers Association Antimicrobial Exposure Assessment Study: Second Replacement to MRID 41761201: Lab Project Number: Q626. Unpublished study prepared by The University of Iowa. 316 p.

ATSDR. 2004. Agency for Toxic Substances and Disease Registry ( ATSDR) Toxicological Profile For Chlorine Dioxide and Sodium Chlorite, US Department of Health and Human Services. September 2004.

BCI, 2002. ( Need to get full citation for the HVAC air monitoring study.)

Gates, Don. 1998. The Chlorine Dioxide HANDBOOK. AWWA Publishers.

Helwig, D. ( 2003) Personal Communication between D. Helwig ( Johnson Diversy, Inc) and K. Riley ( Versar, Inc.), November 11, 2003.

Oak Ridge National Laboratory. 2005. Risk Assessment Information System. http:// risk. lsd. ornl. gov/ tox/ tox_ values. shtml PHED Surrogate Exposure Guide. 1998. Estimates of Worker Exposure from the Pesticide Handler Exposure Database Version 1.1. August, 1998.

Speronello, Barry. 1998. Worst Case Release Study for Automotive Deodorizing Products. Engelhard Corporation, Iselin, NJ. Completed date March 12, 1998.

Speronello, Barry. 2005. Chlorine Dioxide Concentration Over a Carpet Treated with Sanitizer 71 Powder. Engelhard Corporation, Iselin, NJ. Completed date January 18, 2005.

U. S. EPA. 1991. Chemical Engineering Branch Manual for the Preparation of Engineering Assessments. Prepared for the OPPT by IT Environmental Programs, Inc.

USEPA. 1992. Dermal Exposure Assessment: Principles and Applications. Interim Report. Office of Research and Development, Washington, D. C. January 1992. EPA/ 600/ 8 91/ 011B.

USEPA. 1997. Exposure Factors Handbook. Volume I II. Office of Research and Development. Washington, D. C. EPA/ 600/ P 95/ 002Fa.

USEPA. 2000. Residential SOPs. EPA Office of Pesticide Programs  Human Health Division. Dated April 5, 2000.

USEPA. 2001. HED Science Advisory Council for Exposure. Policy Update, November 12. Recommended Revisions to the Standard Operating Procedures ( SOPs) for Residential Exposure Assessment, February 22, 2001. Page 52 of 58 USEPA. 2005a. Chlorine Dioxide/ Sodium Chlorite  Report of the Hazard Identification Assessment Review Committee ( HIARC) and the Antimicrobials Division Toxicity Endpoint Selection Committee ( ADTC). Dated March 29, 2005.

USEPA. 2005b. Sodium Chlorate: Occupational and Residential Exposure Assessment of Antimicrobial Uses for the Reregistration Eligibility Decision Document. PC Code 073301, RED Case No. 4049, DP Barcode D3112200.

USEPA. 2005c. Exposure Determination from a Indoor Disinfectant ( One Time) Use of Chlorine Dioxide. Dated July 20, 2005.

USEPA. 2006. Personal communication between Tim Leighton ( EPA) and Ken Howlett ( Verox). January 27, 2006.

Versar, Inc. 1988. Standard Scenarios for Estimating Exposure to Chemical Substances During Use of Consumer Products.

Wood, Richard and Gallo, Vanessa. 1997. Aseptrol Automotive Field Testing: Chlorine Dioxide Air Levels Inside Vehicle. Engelhard Corporation, Iselin, NJ. Completed date November 14, 1997. Page 53 of 58 APPENDIX A: Summary of CMA data and PHED Page 54 of 58 Chemical Manufacturers Association ( CMA) Data: In response to an EPA Data Call In Notice, a study was undertaken by the Institute of Agricultural Medicine and Occupational Health of The University of Iowa under contract to the Chemical Manufacturers Association. In order to meet the requirements of Subdivision U of the Pesticide Assessment Guidelines ( superseded by Series 875.1000 875.1600 of the Pesticide Assessment Guidelines), handler exposure data are required from the chemical manufacturer specifically registering the antimicrobial pesticide. The applicator exposure study must comply with the assessment guidelines for " Applicator Exposure Monitoring" in Subdivision U and the " Occupational and Residential Exposure Test Guidelines" in Series 875. For this purpose, CMA submitted a study on 28 February, 1990, entitled " Antimicrobial Exposure Assessment Study ( amended on December 8, 1992)" which was conducted by William Popendorf, et al. It was evaluated and accepted by Occupational and Residential Exposure Branch ( OREB) of Health Effect Division ( HED), Office of Pesticides Program ( OPP) of EPA in 1990. The purpose of this CMA study was to characterize exposure to antimicrobial chemicals in order to support pesticide reregistrations ( CMA, 1992). The unit exposures presented in the most recent EPA evaluation of the CMA database ( U. S. EPA, 1999) were used in this assessment.

The Agency determined that the CMA study had fulfilled the basic requirements of Subdivision U  Applicator Exposure Monitoring. The advantages of CMA data over other " surrogate data sets" is that the chemicals and the job functions of mixer/ loader/ applicator were defined based on common application methods used for antimicrobial pesticides. A few of the deficiencies in the CMA data are noted below:

!

The inhalation concentrations were typically below the detection limits, so the unit exposures for the inhalation exposure route could not be accurately calculated.

!

QA/ QC problems including lack of either/ or field fortification, laboratory recoveries, and storage stability information.

!

Data have an insufficient amount of replicates.

The Pesticide Handlers Exposure Database ( PHED): The Pesticide Handlers Exposure Database ( PHED) has been developed by a Task Force consisting of representatives from Health Canada, the U. S. Environmental Protection Agency ( EPA), and the American Crop Protection Association ( ACPA). PHED provides generic pesticide worker ( i. e., mixer/ loader and applicator) exposure estimates. The dermal and inhalation exposure estimates generated by PHED are based on actual field monitoring data, which are reported generically ( i. e., chemical specific names not reported) in PHED. It has been the Agency's policy to use " surrogate" or " generic" exposure data for pesticide applicators in certain circumstances because it is believed that the physical parameters ( e. g., packaging type) or application technique ( e. g., aerosol can), not the chemical properties of the pesticide, attribute to exposure levels. [ Note: Vapor pressures for the chemicals in PHED are in the range of E 5 to E 7 mm Hg.] Chemical specific properties are accounted for by correcting the exposure data for study specific field and laboratory recovery values as specified by the PHED grading criteria.