TRICHLOROMELAMINE RISK ASSESSMENT FOR THE REREGISTRATION ELIGIBILITY DECISION September 15, 2005 Case 3144 PC Code 077101 Office of Pesticide Programs Antimicrobials Division U. S. Environmental Protection Agency 1200 Pennsylvania Avenue, NW Washington, DC 20460 Page 2 of 38 1.0 EXECUTIVE SUMMARY Trichloromelamine ( 1,3,5 triazine N, N', N' trichloro 2,4,6 triamino) is a pesticide that has been formulated for use in food contact surface sanitizing and disinfecting products, as well as in a fruit and vegetable disinfectant. Trichloromelamine is expected to rapidly break down into hypochlorous acid and melamine in the presence of organic material ( EPA, 1988).

Based on a review of acute toxicity studies, EPA has determined that trichloromelamine should be classified in toxicity category I for primary eye irritation, in category II for acute inhalation and oral toxicity and primary skin irritation, and in category III for acute dermal toxicity.

Based on the available hazard information on trichloromelamine and the use pattern for this chemical, the Agency has performed a quantitative risk assessment for this chemical. A screening level assessment was performed to determine potential exposure to workers who use the chemical to treat food utensils, food surfaces, fruits, and vegetables; restaurant/ bar and mess hall patrons who ingest residues left on treated food utensils, fruits, and vegetables; and individuals as a result of transfer of residues of trichloromelamine from countertops to food ( indirect food contact). The total aggregate MOEs for restaurant workers washing countertops and washing utensils were calculated to be 240 and 3200, respectively. The total combined mixer/ loader and applicator MOE for Army mess hall workers washing mess kits or washing fruits and vegetables was calculated to be 170. For restaurant patrons, the aggregate acute and chronic dietary risks calculated ranged from 6.77% of the aPAD for adult males to 53.7% of the cPAD for a 15kg child. For Army mess hall patrons, the aggregate dietary risks were calculated to be between 6.20% aPAD ( adult male) and 21.3% cPAD ( adult female). The aggregate risks to adults from dietary exposure and from cleaning countertops ( calculated using the aggregate risk index [ ARI] method) were 1.89 ( male) and 1.83 ( female) ( EPA, 2001). ARI values greater than or equal to 1 indicate no risk of concern.

Although there is not enough information regarding melamine ( a metabolite of trichloromelamine) toxicity for an ecological hazard assessment, evidence suggests that melamine may be chronically toxic to fish and invertebrates, causing adverse effects on reproduction and embryonic development. Because use of trichloromelamine is limited to use as a food and food contact surface sanitizer in homes, restaurants, and similar establishments, trichloromelamine ( or the degradate melamine, as a result of use of the parent chemical) is not expected to enter the environment and risk to terrestrial and aquatic organisms is not expected due to the lack of exposure.

Taking into consideration all available information on trichloromelamine, there is a reasonable certainty that no harm will occur to the general public or any population subgroup from aggregate exposure. Page 3 of 38 2.0 USE INFORMATION The tolerance exemption being reassessed in this document, the 40 CFR location of the established tolerance exemption, and the use pattern of the chemical as an active ingredient are listed in Table 1.

Table 1. Tolerance Exemptions Being Reassessed in this Document Tolerance Exemption Expression CAS No. 40 CFRa PC Code Use Pattern ( Pesticidal) List Classification Trichloromelamine ( 1,3,5 triazine, N, N'N"  trichloro 2,4,6 triamino) 7673 09 8 180.940 ( c) 077101 Food contact surface sanitizing solutions ( for use on food processing equipment and utensils) Algicide, Disinfectant, Microbiocide/ microbiostat for slime forming bacteria, fungi, and algae, Sanitizer a Residues of chemicals listed in 40 CFR § 180.940 are exempted from the requirement of a tolerance when used in accordance with good manufacturing practice as ingredients in an antimicrobial pesticide formulation, provided that the substance is applied on a semipermanent or permanent food contact surface ( other than being applied on food packaging) with adequate draining before contact with food. The chemicals listed in subsection ( c) are exempted from the requirement of a tolerance when applied to food processing equipment and utensils. For trichloromelamine, 40 CFR states that for ready for use products, the end use concentration should not exceed 200 ppm as total available chlorine.

2.1 Active and Inert Uses According to the EPA's Office of Pesticide Programs Information Network ( OPPIN) database, trichlormelamine is registered as an active ingredient in six end use products and two technical grade products ( one product specified as manufacturing use only). All of the end use products are listed for use as a sanitizer or disinfectant ( PC Code 077101). EPA's OPPIN database does not identify trichloromelamine as an inert ingredient in any registered products.

Uses listed on labels include use on utensils, glasses, and hard surfaces in eating establishments and industrial and institutional food service areas, as well as in food processing facilities and on food dispensing equipment. In addition, it can be used on non food contact surfaces in hospitals ( non critical areas), nursing homes ( non critical areas), and schools. One trichloromelamine product is registered for use as a disinfectant for mess gear as well as fresh fruits and vegetables. The use involves thoroughly washing the fresh fruits and vegetables in the trichloromelamine use solution. After washing, the fruits and vegetables are immersed in a freshly prepared solution. According to the label, the immersion is followed by a potable water rinse of the fruits and vegetables.

2.2 FDA Approved Uses Melamine, a metabolite of trichloromelamine, is cleared by the FDA for use as an adhesive for food packaging material ( 21 CFR § 175.105). Page 4 of 38 3.0 PHYSICAL AND CHEMICAL PROPERTIES The physical/ chemical data for trichloromelamine are presented in Table 2. Figure 1 represents the molecular structure of trichloromelamine. Sources for these data include the submitted guideline studies ( MRIDs 42131101, 42283401, 42385101, 43350301, 43350302, 43350303, and 43395401), European Inventory of Existing Commercial Substances ( ECB, 2004) and a Material Safety Data Sheet ( H& S, 2004). Vapor pressure information was found in EPI Suite, a modeling program which is a screening level predictive tool used to estimate physical and chemical properties of chemicals ( EPA, 2005).

Table 2. Physical/ Chemical Properties of Trichloromelamine Property Value Molecular Formula C3H3Cl3N6 Molecular Weight 229.46 Physical State Cream colored powder Melting Point Above 300 E C Solubility in Water 0.064 g/ 100 mL at 20 E C.

pH 4.7 ( 5% slurry H2O)

Density/ Specific Gravity 0.34 g/ cm3 Log Kow  0.38 Vapor Density NA Vapor Pressure 7.1 x 10 5 mm Hg at 25 E C Dissociation Constant NA Estimated Henry's Law Constant 1.3x10 9 atm/ m3 mole at 25 E C Estimated Soil Sorption Coefficient ( KOC) 150 Stability Oxidizing agent, with highly available chlorine content Flammability Auto ignition occurs at 320 E F Explodability Does not explode Storage Stability Corrosive to metals NA = Not Available Page 5 of 38 Figure 1. Molecular Structure of Trichloromelamine 4.0 HAZARD ASSESSMENT 4.1 Hazard Profile Table 3 summarizes the available toxicology data for trichloromelamine. Trichloromelamine instantaneously breaks down into hypochlorous acid and melamine in the presence of organic material ( EPA, 1988). Trichloromelamine in the presence of water will produce a small amount of unreacted trichloromelamine, hypochlorous acid, and melamine. Melamine is relatively stable and would be expected to remain as a residue on food and food contact surfaces ( EPA, 2004b). Chronic toxicity studies are not required for trichloromelamine based on its rapid degradation.

Table 3. Summary of Toxicity Data for Trichloromelamine Guideline No. Study Type MRID #( s) Results Toxicity Category Acute Toxicity 81 1 Acute Oral 43165701 LD50 = 398 mg/ kg II 81 2 Acute Dermal 43159901 LD50 > 2000 mg/ kg III 81 3 Acute Inhalation 43368501 LC50 = 0.4 mg/ L, males and 0.780 mg/ L, females II 81 4 Primary Eye Irritation 43159902 Severe conjunctival irritation I 81 5 Primary Skin Irritation 43159903 Severe irritant II 81 6 Dermal Sensitization 43159904 No sensitization reactions for group treated with 0.1% [ w/ v] solution NA N H Cl N N H Cl N N H Cl N Page 6 of 38 Guideline No. Study Type MRID #( s) Results Toxicity Category Subchronic Toxicity 82 1( a) 90 day Oral Study ( Rodent) 43064301 NOAEL = 30 mg/ kg/ day LOAEL = 150 mg/ kg/ day, based on the observation of histological lesions ( engorgement of small blood vessels of the adrenal gland, brain, kidneys, liver, lung, and pituitary gland). NA Developmental Toxicity Systemic Toxicity NOAEL < 30 mg/ kg/ day and LOAEL   30 mg/ kg/ day, based on depressions in mean maternal body weights and decreased mean feed consumption values. NA 43614301 ( Rabbit)

Developmental toxicity NOAEL $ 120 mg/ kg/ day NA Maternal NOAEL < 62.5 mg/ kg/ day and LOAEL   62.5 mg/ kg/ day, based on clinical signs at several or all dose levels ( alopecia, gasping, altered respiration, salivation, lethargy, chromodacryorrhea), reduction in body weight gains, and statistically significant trends for decreased food consumption at all dose levels. NA 83 3 Developmental Toxicity 43614302 ( Rat)

Developmental toxicity NOAEL = 500 mg/ kg/ day NA Mutagenicity Studies 84 2( a) 84 2( b) 84 2( c) Gene Mutation 42148801, 42021801, 42021701 Positive result at 25 Fg/ plate for TA98 and at 50 Fg/ plate in Chinese hamster ovary cells, both with and without metabolic activation. Negative result in primary rat hepatocytes. NA Notes: LC = Lethal Concentration; LD = Lethal Dose; LOAEL = Lowest Observed Adverse Effects Level; NA = Not Applicable; NOAEL = No Observed Adverse Effects Level 4.1.1 Acute Toxcity EPA reviewed an acute oral toxicity study in rats ( MRID 43165701). In this study, rats ( 5/ sex/ dose) were administered 100, 300 or 500 mg/ kg of trichloromelamine by gavage in aqueous suspension. The acute oral LD50 values were 413 mg/ kg for males and 387 mg/ kg for females; the combined LD50 value was 398 mg/ kg. Clinical signs observed included hypoactivity, staggered gait, prostration, absence of righting reflex, mydriasis, hunched posture, dyspnea and soft stool. This study is classified acceptable. Page 7 of 38 EPA reviewed an acute dermal toxicity study in rabbits ( MRID 43159901). In this study, the test chemical ( 93% a. i.) was applied to the intact skin of rabbits at 2000 mg/ kg for a period of 24 hours. The test material produced severe dermal irritation, including " severe erythema and edema, marked atonis and coriaceousness, and slight desquamation and fissuring. Eschar, exfoliation and possible necrotic areas were also seen." No systemic toxicity was observed. This study is classified acceptable.

EPA reviewed an acute inhalation toxicity study in rats ( MRID 43368501). In this study, rats were exposed to aerosol concentrations of powdered trichloromelamine ( 100% a. i.) for 4 hours. The test material caused " breathing difficulties, wet and stained fur, decreased activity, head tilt, weakness, cold to touch, and pale skin. [ The] majority of these signs disappeared by the end of the first week in the surviving rats; no clinical signs were seen at termination.... In rats that died, gross necropsy was indicative of respiratory failure; principal gross lesions were uncollapsed and mottled lungs." This study is classified acceptable.

EPA reviewed a primary eye irritation study on rabbits ( MRID 43159902). The test chemical, 0.05 g ( 95% a. i.), was placed into the conjunctival sac of rabbits ( 3/ sex). The chemical produced " severe conjunctival irritation that included petite hemorrhaging, blanching, redstained discharge, and possible necrotic areas." This study is classified acceptable.

EPA reviewed a primary dermal irritation study on rabbits ( MRID 43159903). The technical grade of the test chemical ( 95.1% a. i.) was applied to the intact skin under semioccluded conditions. The chemical produced " moderate severe to severe erythema; slight to severe edema; subcutaneous hemorrhaging; blanching; possible necrotic areas; exfoliation; and possible scar tissue." Irritation continued to be present at Day 21 of observation. This study is classified acceptable.

EPA reviewed a dermal sensitization study on rabbits ( MRID 43159904). Guinea pigs received dermal applications of the test chemical ( 95.1% a. i.) as a 50% ( first induction dose) and 25% ( second and third induction doses) w/ v mixture in mineral oil. Fourteen days after the last induction, the animals were challenged at a concentration of 1%. No irritation was observed in any of the animals. This study is classified acceptable.

4.1.2 Subchronic Toxicity EPA reviewed a 90 day subchronic oral toxicity study in rats ( MRID 43064301). In this study, trichloromelamine ( 92.07% a. i.) was dissolved in 0.08% Triton X 100 and administered by gavage at doses at doses of 30, 150, and 300 mg/ kg/ day to groups of 10 male and female rats per dose. " Histopathology revealed engorgement of the small blood vessels of the adrenal gland, brain, kidneys, liver, lung, and pituitary gland as well as pulmonary edema in rats that died during the study at 150 and 300 mg/ kg/ day." A NOAEL of 30 mg/ kg/ day and a LOAEL of 150 mg/ kg/ day were established, based on histopathological lesions. This study is classified acceptable. Page 8 of 38 4.1.3 Developmental Toxicity Studies EPA reviewed a rabbit developmental toxicity study ( MRID 43614301). In this study, pregnant rabbits were administered 30, 60, 90, or 120 mg/ kg/ day ( 16 rabbits/ dose group) of the test chemical by gavage on gestation days 6 through 19. On gestation day 30, the animals were sacrificed and gross necropsies performed. " Administration of [ the test chemical] produced dose related depressions in mean maternal body weights during gestation days 7 19 ( statistically significant) and generally throughout the dosing period.... Mean feed consumption values were significantly decreased for gestation days 7 9, 9 12, and 7 19." No evidence of developmental effects was observed. A systemic toxicity NOAEL < 20 mg/ kg/ day and LOAEL   30 mg/ kg/ day and a developmental NOAEL   120 mg/ kg/ day were established. This study is classified acceptable.

EPA reviewed a rat developmental study ( MRID 43614302). In this study, rats were administered 0, 62.5, 250, or 500 mg/ kg/ day ( 25 sperm positive rats/ dose group) of the test chemical by gavage on gestation days 6 through 15. On gestation day 20, the animals were sacrificed and gross necropsies performed. The study found " clinical signs at several or all dose levels ( alopecia, gasping, altered respiration, salivation, lethargy, chromodacryorrhea), reduction in body weight gains at two top doses during gestation days 6 9, and statistically significant trends... for decreased food consumption at all dose levels." No evidence of developmental effects was observed. A maternal NOAEL < 62.5 mg/ kg/ day and LOAEL   62.5 mg/ kg/ day and a developmental NOAEL of 500 mg/ kg/ day were established. This study is classified acceptable. 4.1.4 Mutagenicity Studies EPA reviewed three gene mutation studies ( MRIDs 42148801, 42021801, and 42021701). These studies were classified as acceptable by EPA. In these studies, cells were exposed to the test chemical. The cells used included salmonella, S. typhimurium stains TA98, TA100, TA1535, TA 1537, and TA1538, Chinese hamster ovary cells, and primary rat hepatocytes. Tests with and without metabolic activation were used for all cells except primary rat hepatocytes, which used only tests without metabolic activation. Positive results were seen at concentrations of 25 µ g/ plate for TA98 and TA100, both with and without the metabolic activation. Positive results were seen at concentrations of 50 µ g/ mL in Chinese hamster cells. " The aberrations observed [ a high frequency of complex arrangements such as triradial and quadriradials] were typical of a chemical clastogen rarely seen in untreated control cultures [ of Chinese hamster cells]." There were no indications of mutagenic response in the strains TA1535, TA1537, or TA1538. No mutagenic response was observed in the primary rat hepatocytes. These studies are classified acceptable.

4.1.5 Melamine Studies Trichloromelamine is expected to rapidly break down into hypochlorous acid and melamine ( EPA, 1994). A number of toxicity studies have been performed to characterize the hazard of melamine. Page 9 of 38 Based on a review of a number of acute toxicity studies ( EPA, 1983), the FDA concluded and EPA concurred that:

1. Oral LD50 values were 3,161 and 3,828 mg/ kg for male and female rats, respectively. Melamine can be classified as a moderate to slight weak acute toxicant. 2. Melamine caused little or no irritation when dermally applied to guinea pigs. 3. Mild transient irritation was produced when dry melamine was instilled into the eyes of rabbits. 4. Melamine is absorbed rapidly and distributed in the body tissue waters, and rapidly eliminated in the urine unchanged after oral dosing. 5. The weight of evidence is not sufficient to reasonably anticipate that melamine will cause serious or irreversible chronic health effects. 6. For the mice tested, the incidence effecters were greater in the males than in the females. 7. Melamine is not mutagenic in the Salmonella/ mammalian microsomal assay.

The FDA Cancer Committee reviewed a number of melamine studies ( EPA, 1984). The committee, based on these studies, concluded that " melamine is associated with an increase in the incidence of urinary bladder neoplasms in male rats. Melamine is also associated with the production of bladder calculi in male rats."

The Health Effects Division Carcinogenicity Peer Review Committee ( PRC) concluded that it was unlikely that melamine is a carcinogenic hazard to humans from the pesticidal usage of a pesticide product ( Cyromazine) ( Cyromazine is a pesticide whose main metabolite is melamine; Cyromazine is a developmental toxicant in rabbits) ( EPA, 1988). They noted that " humans are not likely to be exposed to the high doses of melamine that produce the urinary tract toxicity that precedes and seems to lead to the carcinogenic response in rats" ( EPA, 1993). This conclusion is based on the review of a number of studies, including a mouse carcinogenicity study in which no evidence of tumors were found due to exposure to melamine at the highest dose tested ( 4,500 ppm).

4.1.6 Dietary Studies FDA cleared trichloromelamine as an indirect food additive ( 21 CFR 178.1010( b)( 10)) and, therefore, no dietary exposure assessment was required ( EPA, 1988). However, one product label notes that the product can be used as a fruit and vegetable wash ( Reg. No. 40510 1). In addition, indirect food contact sanitizers are now under the jurisdiction of the Office of Pesticide Programs ( OPP). A dietary exposure assessment was conducted based on FDA guidelines ( Refer to Tables 9  13).

4.2 FQPA Considerations Under the Food Quality Protection Act ( FQPA), P. L. 104 170, which was promulgated in 1996 as an amendment to the Federal Insecticide, Fungicide, and Rodenticide Act ( FIFRA) and the Federal Food, Drug and Cosmetic Act ( FFDCA), the Agency was directed to " ensure that there is a reasonable certainty that no harm will result to infants and children" from aggregate exposure to a pesticide chemical residue. The law further states that in the case of threshold Page 10 of 38 effects, for purposes of providing this reasonable certainty of no harm, " an additional tenfold margin of safety for the pesticide chemical residue and other sources of exposure shall be applied for infants and children to take into account potential pre and post natal toxicity and completeness of the data with respect to exposure and toxicity to infants and children. Notwithstanding such requirement for an additional margin of safety, the Administrator may use a different margin of safety for the pesticide residue only if, on the basis of reliable data, such margin will be safe for infants and children."

Trichloromelamine will not cause an FQPA concern since there is no evidence from the available toxicology data that it will induce neurotoxic effects. Prenatal toxicity studies, in both the rat and rabbit, did not provide quantitative or qualitative evidence of increased susceptibility to fetus following in utero exposure.

4.3 Dose Response Assessment The doses and toxicological endpoints selected for various exposure scenarios are summarized in Table 4 below.

Table 4. Doses and Toxicological Endpoints Used in Exposure Scenarios Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SFa and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( General Population including infants and children) NOAEL = 30 mg/ kg/ day UF = 100 Acute RfD = 0.3 mg/ kg/ day FQPA SF = 1 aPAD = acute RfD FQPA SF = 0.3 mg/ kg/ day 90 Day Oral Rodent Study ( MRID 43064301)

LOAEL = 150 mg/ kg/ day A NOAEL of 30 mg/ kg/ day was determined, based on histopathological lesions ( engorgement of small blood vessels of the adrenal gland, brain, kidneys, liver, lung, and pituitary gland) observed at the next highest dose of 150 mg/ kg/ day.

Acute Dietary ( Females 13+ years of age) Endpoint for this population was not identified in the database Chronic Dietary ( All populations) NOAEL = 30 mg/ kg/ day UF = 300b Chronic RfD = 0.1 mg/ kg/ day FQPA SF = 1 cPAD = chronic RfD FQPA SF = 0.1 mg/ kg/ day 90 Day Oral Rodent Study ( MRID 43064301)

LOAEL = 150 mg/ kg/ day A NOAEL of 30 mg/ kg/ day was determined, based on histopathological lesions ( engorgement of small blood vessels of the adrenal gland, brain, kidneys, liver, lung, and pituitary gland) observed at the next highest dose of 150 mg/ kg/ day. Page 11 of 38 Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SFa and Level of Concern for Risk Assessment Study and Toxicological Effects Short Term Incidental Oral ( 1 30 days) NOAEL= 30 mg/ kg/ day UF = 100 Target MOE = 100 Occupational = NA See Chronic Dietary Endpoint Intermediate Term Incidental Oral ( 1 6 months) NOAEL= 30 mg/ kg/ day UF = 100 Target MOE = 100 Occupational = NA See Chronic Dietary Endpoint Short Term and Intermediate Term Dermal Exposure Oral Study NOAEL= 30 mg/ kg/ day UF = 100 Dermal Absorption= 100% Target MOE = 100 See Chronic Dietary Endpoint Short Term and Intermediate Term Inhalation Exposure No appropriate route specific study was available. The oral endpoint of 30 mg/ kg with a Margin of Exposure of 100 ( 10x inter species extrapolation, 10x intra species variation) is used. An additional 10x route to route extrapolation is used to determine if a confirmatory inhalation toxicity study is warranted.

Notes: UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose ( a = acute, c = chronic) RfD = reference dose ( NOAEL/ UF), MOE = margin of exposure a The developmental toxicity studies both showed a lack of effects in offspring up to and including the highest doses tested in both studies, and the LOAELs for both studies were based on general systemic effects that were not considered severe. Both studies were well designed and provided an adequate dose response for trichloromelamine. Therefore, the FQPA Safety Factor is removed.

b UF of 300 includes a 10x interspecies extrapolation, 10x intraspecies variation, and 3x extrapolation from subchronic study to chronic endpoint. The Agency considers the NOAEL of 30 mg/ kg/ day to be conservative, as residues of trichloromelamine are likely to disappear quickly based on the chemistry of trichloromelamine, and chronic exposure is likely to be very low.

4.4 Endocrine Disruption EPA is required under the Federal Food Drug and Cosmetic Act ( FFDCA), as amended by FQPA, to develop a screening program to determine whether certain substances ( including all pesticide active and other ingredients) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC), EPA determined that there was scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA, and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA has authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP). Page 12 of 38 When the appropriate screening and/ or testing protocols being considered under the Agency's EDSP have been developed, trichloromelamine may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption.

5.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION A review of the EPA Pesticide Product Database ( EPA, 2004c) showed that there are eight trichloromelamine products with currently active registrations. With the exception of the technical grade products, the concentrations of trichloromelamine in these products ranged from 9.5% to 19.3%, and the listed uses for these products include use as a surface sanitizer, including on food surfaces, and as a fruit and vegetable wash. The product with the highest concentration of trichloromelamine ( Reg. No. 40510 1, 19.3% a. i.) appears to be exclusively for use of the Department of the United States Army. The product with the second highest concentration of trichloromelamine ( Reg. No. 8160 1, 18% a. i.), as diluted per label directions, is to be used on food contact surfaces in restaurants and bars, homes, and other institutional and commercial sites. In addition, another product ( Reg. No. 65169 1, 18.7% a. i.) is used in restaurants and bars on food contact surfaces as well as to sanitize glassware and utensils. Because the uses, concentrations, and exposed individuals associated with these three products will be different, all of these labels were considered in the exposure assessment.

The Army label ( Reg. No. 40510 1) states that the product can be used " for disinfection of mess gear, fresh fruits, and vegetables." The labels for the latter products selected for examination state that the product is a food contact sanitizer for use on hard, non porous inanimate surfaces in homes, offices, schools, bars, and restaurants, as well as bar and restaurant glassware and utensils. Although there are non food contact uses, as well as other food contact use sites ( i. e. food processing plants) on other labels, the concentration of active ingredient in those products ( once diluted according to label directions) are lower than that for Reg. No. 8160 1. It is assumed that exposure from the restaurant use that was assessed, which includes infants and children with chronic exposure, represents the high end exposure and is, therefore, representative of these other uses, excluding to sanitize glassware and utensils.

Based on the information provided on the labels, the following scenarios were chosen for consideration in this human health risk assessment:

$ Dermal/ inhalation exposure due to ungloved workers in the Army using the product to disinfect mess kits, fruits, and vegetables ( 19.3% a. i. product);

$ Dermal/ inhalation exposure due to ungloved workers at restaurants/ bars using the product to sanitize surfaces and food utensils ( 18.7% product);

$ Dietary exposure due to ingestion of residues left on treated food utensils and due to ingestion of residues from washed fruits and vegetables ( 19.3% product); and,

$ Dietary exposure due to ingestion of residues left on treated food utensils and due to ingestion of residues that were transferred to food when prepared on treated surfaces ( 18.7% and 18% products, respectively). Page 13 of 38 5.1 Occupational Exposure Assessment 5.1.1 Inhalation and Dermal Exposure for Army Workers Estimates of inhalation and dermal risk were calculated for ungloved occupational workers in the army using the product to disinfect mess kits, fruits, and vegetables. To disinfect mess kits, the label ( Reg. No. 40510 1) for the 19.3% product states that 4.77 oz. of the chemical powder is to be poured into a 25 gallon container of water ( i. e., 0.0276% a. i. in the diluted solution) and that two containers ( 25 gallons each) should be prepared ( 4.77 oz. product/ packet x 2 packets x 19.3% a. i. x 1 lb./ 16 ozs. = 0.115 lbs a. i. in diluted solution). Mess kits that have been washed are to be rinsed twice  once in the first container, and then again in the second  and then allowed to air dry. The 50 gallons used should be sufficient to treat 100 mess kits.

To disinfect fruits and vegetables, the label for the 19.3% product states that 4.77 oz of the chemical powder is to be poured into a 20 gallon container of water ( i. e., 0.0344% a. i. in the diluted solution), and that two containers ( 20 gallons each) should be prepared. Unpeeled fruits and vegetables, with bruised leaves removed, are to be washed thoroughly in the first container, then are to be completely immersed in the second container and allowed to soak for 10 minutes. After the soaking time, the product is to be rinsed with potable water.

This exposure scenario can be divided into three parts:

$ The worker opening the packets and pouring two 4.77 oz. packets of the chemical into water,

$ The worker dipping mess kits into the diluted solution, and $ The worker dipping fruits and vegetables.

To calculate the risks associated with this type of exposure, the following assumptions were used:

$ It is assumed, for this assessment, that two 4.77 oz. packets are sufficient for the needs of an individual worker in a kitchen per day, either washing mess kits or washing fruits and vegetables.

$ To model opening the packet and pouring the contents, surrogate data from the Chemical Manufacturers Association ( MRID 42587501) were used. CMA data exists for ` solid pour' scenarios, which entails a worker transferring powder from large shipping containers to smaller containers for measuring and pouring. The quantities of powder used in the CMA studies are much greater than the quantities of trichloromelamine that will be used in this scenario. However, for lack of better data, the CMA data were used.

$ To calculate the inhalation exposure associated with standing over the containers and washing mess kits, fruits, and vegetables, surrogate data from CMA were used. CMA data exist for ` wiping' scenarios, which entails a worker applying a chemical to surfaces and then wiping them. Although the representativeness of the CMA scenario for wiping is uncertain, no better surrogate data currently exists. Page 14 of 38 $ To calculate the dermal exposure for a worker treating mess kits, fruits, and vegetables, the DERMAL model was used. According to the Standard Operating Procedures ( SOPs) for Residential Exposure Assessments, " The DERMAL model was developed by EPA's Office of Pollution Prevention and Toxics ( OPPT) to support the assessment of new chemicals under Premanufacture Chemicals under the Toxic Substance Control Act. DERMAL is used primarily in screening level assessments of dermal exposure to the components of consumer products" ( U. S. EPA, 1997). The DERMAL model calculates exposures to wet surfaces for the whole day. In actual practice, it is unlikely that workers would have their hands wet with the dilute trichloromelamine solution for the entire day. The DERMAL model requires that a weight fraction be used as a user input. Other inputs include surface area to body weight ratio ( SA/ BW) and the amount of chemical retained on skin.

The calculations and results for exposures and risks to Army workers are shown in Tables 5  7. As all MOEs are greater than the target MOE of 100, no risks of concern are identified for the tasks conducted in mess halls. However, as the inhalation MOE of 660 for either washing mess kits or fruits and vegetables falls below the MOE of 1000, when the additional route toroute extrapolation uncertainty factor is applied, an inhalation study would be required to confirm these findings.

The combined MOE for both dermal and inhalation exposure for both the opening and pouring of packets and washing mess kits is 160, as is the combined MOE for the opening and pouring of packets and washing fruits and vegetables ( Table 7). As a conservative measure, it is assumed that, because this is potentially a small scale process, one person could mix the solution and use it immediately after. These combined risks are greater than the target MOE of 100 and, therefore, not of concern. Page 15 of 38 Table 5. Inhalation and Dermal Exposure Calculations for Opening and Pouring Packet and Inhalation Exposure Calculations for Standing Over Containers While Washing Mess Kits, Fruits, and Vegetables ( 19.3% a. i. Product)

Exposure Scenario Clothing and PPE Parameters Dermal Unit Exposurea ( mg/ lb a. i.) Inhalation Unit Exposurea ( mg/ lb a. i.) Daily Amount Usedb ( lb a. i.) Daily Dermal Dosec ( mg/ kg/ day) Daily Inhalation Dosec ( mg/ kg/ day) MOE Opening and Pouring Two Packets ( Solid Pour of Powder) 76.2 0.0412 0.115 0.125 6.77x10 5 Dermal = 240 Inhalation = 440,000 Exposure For Washing Mess Kits or Fruits and Vegetables ( Wiping) Long sleeved shirt and pants, no gloves NAd 27.7 0.115 NAd 4.55x10 2 Inhalation = 660 a Unit Exposure data from CMA.

b 4.77 oz. product/ packet x 2 packets x 19.3% a. i. x 1 lb./ 16 ozs. = 0.115 lbs a. i. in diluted solution ( Reg No. 40510 1)

c Daily dose = Daily Amt. Used ( lb a. i.) * Unit Exposure ( mg/ lb a. i.) / 70 kg body weight.

d Not Applicable. For the washing of mess kits, fruits, and vegetables, dermal doses were calculated using a different method. These calculations are shown in Table 5.

NOAEL = 30 mg/ kg/ day; MOE = NOAEL/ Exposure Dermal absorption is assumed to be 100%

Target MOE= 100 Page 16 of 38 Table 6. Dermal Exposure Calculations for Washing Mess Kits and Fruits and Vegetables ( 19.3% a. i. Product)

Value Parameter Mess Kits Fruits and Vegetables Rationale Weight Fraction of Chemical in Product 2.76x10 4 3.45x10 4 Based on maximum use rate listed on product label Skin Surface Area/ Body Weight Ratio 18.8 cm2/ kg High end ratio ( 90th percentile) default value for hands ( DERMAL model)

Film Thickness 2.14x10 3 cm Default value ( DERMAL model) for cleaning products Density of Formulation 1.040 g/ cm3 Default value ( DERMAL model) for cleaning products Dilution Fraction 1.000 Default value ( DERMAL model)

Calculated Results Potential Dermal Dose Rate 0.0058 mg/ kg/ day 0.0072 mg/ kg/ day Dermal MOE 5200 4200 DERMAL Model Results Divided by 2 ( Half day Exposure)

Target MOE = 100 Weight Fraction = % a. i.* ( oz. product used/ gallons water used for dilution) * ( 1/ density of water), where: 2 Packets of 4.77 oz each were diluted in two 20 ( fruits and vegetables) or two 25 ( mess kits) gallon containers ( one packet per container) of water ( EPA Reg. No. 40510 1). Density of Water = 133.5 oz./ gal Table 7. Combined Exposure and Risk for Opening and Pouring plus Washing Mess Kits or Fruits and Vegetables Exposure Scenario Daily Dermal Dose ( mg/ kg/ day) Daily Inhalation Dose ( mg/ kg/ day) Dermal MOE Inhalation MOE Aggregate MOE Opening and Pouring Two Packets ( Solid Pour of Powder) & Washing Mess Kits 0.131 4.56x10 2 230 660 170 Opening and Pouring Two Packets ( Solid Pour of Powder) & Washing Fruits and Vegetables 0.132 4.56x10 2 230 660 170 5.1.2 Inhalation and Dermal Exposure for Commercial/ Institutional Workers Estimates of inhalation and dermal risk were calculated for ungloved workers at restaurants/ bars using the product to sanitize surfaces. The label for the 18.7% product ( Reg. No. 65169 1) states that one 0.25 oz. packet of the chemical powder is to be poured into three gallons of water ( i. e., 0.0117% a. i. in the diluted solution). Glassware that has been washed with soap and water is immersed into this solution for at least two minutes and then allowed to air dry. Alternatively, the solution can be used to wipe surfaces such as countertops. Page 17 of 38 This exposure scenario can be divided into three parts:

$ The worker opening the packet and pouring the contents into the water,

$ The worker dipping food utensils into the diluted solution, and $ The worker using the diluted solution to wipe countertops.

To calculate the risks associated with this type of exposure, the following assumptions were used:

$ The label states that additional quantities should be used if the diluted solution falls below 100 ppm available chlorine. It is assumed, for this occupational assessment, that the available chlorine does not fall over the course of a day, and that 0.25 oz. in three gallons of water for each activity ( sanitizing utensils and wiping countertops) is sufficient for the needs of one worker in a restaurant per day.

$ To model opening the packet and pouring the contents, surrogate data from the Chemical Manufacturers Association ( MRID 42587501) were used. CMA data exists for ` solid pour' scenarios, which entails a worker transferring powder from large shipping containers to smaller containers for measuring and pouring. The quantities of powder used in the CMA studies are much greater than the quantities of trichloromelamine that will be used in this scenario. However, for lack of better data, the CMA data were used.

$ To model the worker treating food utensils, the DERMAL model was used. According to the Standard Operating Procedures ( SOPs) for Residential Exposure Assessments, " The Dermal model was developed by EPA's Office of Pollution Prevention and Toxics ( OPPT) to support the assessment of new chemicals under Premanufacture Chemicals under the Toxic Substance Control Act. DERMAL is used primarily in screening level assessments of dermal exposure to the components of consumer products" ( U. S. EPA, 1997). The DERMAL model calculates exposures to wet surfaces for the whole day. In actual practice, it is unlikely that workers would have their hands wet with the dilute trichloromelamine solution for the entire day. The DERMAL model requires that a weight fraction be used as a user input. Other inputs include surface area to body weight ratio ( SA/ BW) and the amount of chemical retained on skin.

$ For inhalation exposure, it is assumed that the pathway through which the chemical is inhaled when standing over a bucket of solution is similar to the pathway when using the chemical as a wiping agent. The amount of exposure is assumed to be the same from that calculated for wiping since the same amount of solution is used in treating food utensils and wiping ( 3 gallons).

$ To model the wiping of surfaces with the diluted solution, surrogate data from the Chemical Manufacturers Association ( MRID 42587501) were used.

The calculations and results are shown in Tables 8  10. As all MOEs are greater than the target MOE of 100, no risks of concern are identified for the tasks conducted in restaurants and Page 18 of 38 bars. The combined MOE for both dermal and inhalation exposure for both the opening and pouring of packets and wiping countertops is 240, and the combined MOE for the opening and pouring of packets and washing utensils is 2500 ( Table 10). As a conservative measure, it is assumed that, because this is potentially a small scale process, one person could mix the solution and use it immediately after. The combined risks from these exposures are below the Agency's level of concern. Page 19 of 38 Table 8. Exposure Calculations for Opening and Pouring Packet and Wiping Countertops Exposure Scenario Clothing and PPE Parameters Dermal Unit Exposurea ( mg/ lb a. i.) Inhalation Unit Exposurea ( mg/ lb a. i.) Daily Amount Usedb ( lb a. i.) Daily Dermal Dosec ( mg/ kg/ day) Daily Inhalation Dosec ( mg/ kg/ day) MOE Opening and Pouring Packet ( Solid Pour) 76.2 0.0412 0.00292 3.18x10 3 1.72x10 6 Dermal = 9400 Inhal.= 1.7x107 Wiping Countertops ( Wiping) Long sleeved shirt and pants,

no gloves 2870 27.7 0.00292 1.20x10 1 1.16x10 3 Dermal = 250 Inhal. = 26,000 a Unit Exposure data from CMA.

b 0.25 oz. product/ packet x 18.7% a. i. x 1 lb./ 16 ozs. = 0.00292 lbs a. i. in diluted solution ( Reg. No. 65169 1)

c Daily dose = Daily Amount Used ( lb a. i.) * Unit Exposure ( mg/ lb a. i.) / 70 kg body weight MOE= NOAEL/ Exposure; NOAEL = 30 mg/ kg/ day.

Dermal absorption is assumed to be 100%.

Target MOE= 100 Page 20 of 38 Table 9. Exposure Calculations for Treating Food Utensils Parameter Value Rationale Weight Fraction of Chemical in Product 1.17x10 4 Based on maximum use rate listed on product label Skin Surface Area/ Body Weight Ratio 18.8 cm2/ kg High end ratio ( 90th percentile) default value for hands ( DERMAL model)

Film Thickness 2.14x10 3 cm Default value ( DERMAL model) for cleaning products Density of Formulation 1.040 g/ cm3 Default value ( DERMAL model) for cleaning products Dilution Fraction 1.000 Default value ( DERMAL model)

Calculated Results Potential Dermal Dose Rate 4.88x10 3 mg/ kg/ day Dermal MOE 6100 DERMAL model Inhalation Dose Rate 1.16x10 3 mg/ kg/ day Inhalation MOE 26,000 Same as the inhalation dose rate for wiping Target MOE = 100 Weight Fraction = % a. i.* ( oz. product used/ gallons water used for dilution) * ( 1/ density of water), where: 0.25 oz. was diluted in 3 gallons of water ( EPA Reg. No. 65169 1) Density of Water = 133.5 oz./ gal Table 10. Combined Exposure and Risk for Opening and Pouring plus Wiping Countertops or Treating Utensils Exposure Scenario Daily Dermal Dose ( mg/ kg/ day) Daily Inhalation Dose ( mg/ kg/ day) Dermal MOE Inhalation MOE Aggregate MOE Opening and Pouring Packet ( Solid Pour) & Wiping Countertops 1.23x10 1 1.16x10 3 240 26,000 240 Opening and Pouring Packet ( Solid Pour) & Treating Utensils 8.06x10 3 1.16x10 3 3700 26,000 3200 5.2 Residential Exposure Assessment A separate residential risk assessment was not performed, as the assessment for occupational handlers in restaurants is considered to be a conservative and protective surrogate for residential uses. Since a higher application rate is found on the label used to calculate occupational risks, these values are used to represent residential risks in the aggregate assessment and are an overestimate of the residential exposures and risks. These values are not being refined because the assessment shows no risks of concern. Page 21 of 38 5.3 Dietary Exposure Assessment 5.3.1 Dietary Assessment for Army Mess Hall Patrons Patrons of a mess hall using the chemical may have dietary exposure to the chemical via two routes:

$ The diluted solution of this chemical is used as a " last tank" for washing mess kits. That is to say, mess kits that have been washed with soap and water are then dipped in the solution, air dried, and then reused. Patrons of the mess hall may ingest residues of the chemical left on plates, forks, glasses, and other food utensils.

$ The diluted solution of this chemical is used as a disinfectant on fruits and vegetables, which are washed in the solution and then soaked in the solution for 10 minutes and rinsed with potable water.

These two assessments have been performed separately, and then combined to determine a total dietary intake associated with patrons of a mess hall that uses the chemical for mess kits, fruits, and vegetables.

To calculate the EDI associated with use of a trichloromelamine product as a mess kit disinfectant, a number of assumptions have been made based on the FDA guidelines ( FDA, 2003).

$ When a surface is treated with a disinfectant, a quantity of the disinfectant remains on the surface. The FDA recommended worst case concentration for this quantity is 1 mg of solution per square centimeter of treated surface area. In the absence of any other data, this value has been used.

$ The FDA suggests that, as a worst case scenario, all food that an individual consumes will come into contact with 4000 cm2 of sanitized non porous food contact surfaces. This contact area represents all the surface area from silverware, china, and glass used by a person who regularly eats three meals per day at an institutional or public facility.

$ FDA calculations assume that 100% of the active material present on food contact surfaces will migrate. This represents a worst case scenario.

For calculating exposure associated with use of a trichloromelamine product as a fruit and vegetable disinfectant, the following assumptions were used:

$ The following equation was used to calculate the EDI:

  = i i i Q C EDI Page 22 of 38 Where:

EDI = Estimated Daily Intake of trichloromelamine associated with ingestion of washed fruits and vegetables ( mg/ day), i = Type of fruit or vegetable, Ci = Concentration of chemical residue on food type i ( mg/ kg), and Qi = Quantity of food type i eaten by a person per day ( kg/ day).

$ Ideally, to determine Ci, data from a study showing the amount of trichloromelamine absorbed would be used. This study would replicate the conditions described in the product label and would consider a variety of fruits and vegetables, including foods with a variety of skin textures, surface area/ volume ratios, and chemical compositions. No such study was available. Instead, data were used from an EPA review of the use of sodium lauryl sulfate ( SLS) on fruits and vegetables as a disinfectant ( EPA, 2000). Fruits and vegetables were to be sprayed with enough SLS solution to ` cover' them, rubbed for 30 seconds, and then rinsed with water. Use of the SLS product differs from the use specified for the trichloromelamine product. The SLS solution is sprayed on foods and rubbed for 30 seconds. For the trichloromelamine product, foods are washed in a container of the solution, and then soaked for 10 minutes in another container of the solution. SLS also differs chemically from trichloromelamine, and it is not clear that the absorption kinetics of SLS on fruits and vegetables would be similar to those of trichloromelamine. However, for lack of better data, this review was used. SLS residue data were collected for the following foods: apples, pears, cherries, grapes, cucumbers, squash, peppers, tomatoes, potatoes, spinach, and strawberries. These foods were sprayed with the SLS product, rubbed for 30 seconds, then rinsed with water for 10 seconds ( 20 seconds for grapes). EPA noted a number of concerns with this study, including the fact that the rinse times used were excessively long, and that the analytical method used in the study was not adequately validated. The food concentrations in the SLS study were reported in terms of ppm SLS. Values of ppm trichloromelamine were determined by dividing the weight fraction of the trichloromelamine dilute solution ( 0.0345% a. i.) by the weight fraction of the SLS product ( reported in MRID 45012316 as 0.2% SLS), and then multiplying by the SLS concentrations reported.

$ Values of Qi were determined using data from the Continuing Survey of Food Intakes by Individuals ( CSFII). Data were available both for adult food consumption ( Wilson et al., 1997) and for children ( USDA, 1999). For the purposes of this assessment, two populations were examined: adult males ( 20 and older) and adult females ( 20 and older). It is assumed that children are not eating at mess halls. Data regarding consumption of fruit juices and dried fruits have not been used. Mean consumption rates were used for each population. The dietary intake for fruits and vegetables is limited to subset of the general population, specifically members of the army; since this subpopulation is not representative of the general population, the 90th percentile was not used to calculate dietary risk. It has been assumed that all vegetables consumed have been washed using the product. This is a conservative assumption; people may also obtain fruits and vegetables from unwashed sources, including canned or frozen foods. Page 23 of 38 The calculations of the estimated daily intakes are shown in Tables 11 13. Summary calculations for all dietary exposures are presented at the end of this section. The total dietary exposure from eating fruits and vegetables and using mess kits treated with trichloromelamine is:

0.00282 mg/ kg/ day + 1.104 mg/ day / 70 kg = 0.0186 mg/ kg/ day ( adult male) 0.00290 mg/ kg/ day + 1.104 mg/ day / 60 kg = 0.0213 mg/ kg/ day ( adult female) Page 24 of 38 Table 11. Calculations of EDI for Adult Males ( Age 20 Years and Older) Consuming Washed Fruits and Vegetables ( 19.3% Product)

Food Concentrationa ( mg a. i./ kg food) Food Ingestedb ( g food/ day) Active Ingredient Ingestedc ( mg/ day) EDId ( mg/ kg/ day)

Applese 0.0345 17 0.000586 0.0000083 Bananase 0.0345 19 0.000656 0.0000094 Melons and Berriesf 0.552 17 0.00938 0.000134 Other fruitsf 0.552 20 0.011 0.000157 Potatoes 0.138 79 0.0109 0.000156 Dark Green Vegetablesg 1.73 14 0.0242 0.000346 Deep Yellow Vegetablesh 0.069 8 0.000552 0.0000079 Tomatoes 0.0518 37 0.00191 0.0000273 Lettuce, Lettuce Based Saladsg 1.73 20 0.0345 0.000493 Green Beansi 0.138 9 0.00124 0.0000177 Corn, Green Peas, Lima Beansi 0.138 16 0.00221 0.0000316 Other Vegetablesg 1.73 58 0.10034 0.00143 Total: 314 0.197 0.00282 a Values of ppm Trichloromelamine were determined by dividing the weight fraction of the trichloromelamine dilute solution ( 0.0334% a. i.) by the weight fraction of the SLS product ( reported in MRID 45012316 as 0.2% SLS), and then multiplying by the SLS concentrations reported in EPA ( 2000). The types of foods examined in the SLS study did not match exactly those types examined in CSFII. See footnotes for individual food types for more information. b Sources: Wilson et al., 1997; USDA, 1999. c Active Ingredient Ingested ( mg/ day) = Concentration ( mg a. i./ kg food) * Food Ingested ( g food/ day) / ( 1000 g/ kg) d Estimated Daily Intake ( mg/ kg/ day) = Active Ingredient Ingested ( mg/ day) / Adult Male Body Weight ( 70 kg) e Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for apples and pears ( one category) were used to determine concentrations for apples and bananas. f Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for strawberries were used to determine concentrations for melons, berries and other fruits. The SLS concentrations for strawberries were the highest reported for fruits, and therefore the use of this number for other fruits is most likely conservative. g Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for spinach were used to determine concentrations for dark green vegetables, lettuce, and other vegetables. The SLS concentrations for spinach were the highest reported for vegetables, and therefore the use of this number for other vegetables is most likely conservative. h Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for cucumbers, melons, and squash ( one category) were used to determine concentrations for deep yellow vegetables. i Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for potatoes were used to determine concentrations for green beans, corn, green peas, and lima beans. Page 25 of 38 Table 12. Calculations of EDI for Adult Females ( Age 20 Years and Older) Consuming Washed Fruits and Vegetables ( 19.3% Product)

Food Concentrationa ( mg a. i./ kg food) Food Ingestedb ( g food/ day) Active Ingredientc Ingested ( mg/ day) EDId ( mg/ kg/ day)

Applese 0.0345 17 0.000587 9.8x10 6 Bananase 0.0345 17 0.000587 9.8x10 6 Melons and Berriesf 0.552 18 0.00994 0.00017 Other fruitsf 0.552 20 0.0110 0.00018 Potatoes 0.138 51 0.00704 0.00012 Dark Green Vegetablesg 1.73 14 0.0242 0.000400 Deep Yellow Vegetablesh 0.069 10 0.000690 0.0000100 Tomatoes 0.0518 28 0.00145 0.0000200 Lettuce, Lettuce Based Saladsg 1.73 17 0.0293 0.000490 Green Beansi 0.138 8 0.00110 0.0000200 Corn, Green Peas, Lima Beansi 0.138 11 0.00152 0.0000300 Other Vegetablesg 1.73 50 0.0863 0.00144 Total: 261 0.174 0.0029 a Values of ppm Trichloromelamine were determined by dividing the weight fraction of the trichloromelamine dilute solution ( 0.0334% a. i.) by the weight fraction of the SLS product ( reported in MRID 45012316 as 0.2% SLS), and then multiplying by the SLS concentrations reported in EPA ( 2000). The types of foods examined in the SLS study did not match exactly those types examined in CSFII. See footnotes for individual food types for more information. b Sources: Wilson et al., 1997; USDA, 1999. c Active Ingredient Ingested ( mg/ day) = Concentration ( mg a. i./ kg food) * Food Ingested ( g food/ day) / ( 1000 g/ kg) d Estimated Daily Intake ( mg/ kg/ day) = Active Ingredient Ingested ( mg/ day) / Adult Female Body Weight ( 60 kg) e Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for apples and pears ( one category) were used to determine concentrations for apples and bananas. f Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for strawberries were used to determine concentrations for melons, berries and other fruits. The SLS concentrations for strawberries were the highest reported for fruits, and therefore the use of this number for other fruits is most likely conservative. g Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for spinach were used to determine concentrations for dark green vegetables, lettuce, and other vegetables. The SLS concentrations for spinach were the highest reported for vegetables, and therefore the use of this number for other vegetables is most likely conservative. h Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for cucumbers, melons, and squash ( one category) were used to determine concentrations for deep yellow vegetables. i Because the food types from EPA ( 2000) did not exactly match those from CSFII, SLS concentrations for potatoes were used to determine concentrations for green beans, corn, green peas, and lima beans. Page 26 of 38 Table 13. Calculations of EDI for Use of Trichloromelamine Products on Mess Kits ( 19.3% a. i. Product)

Parameter Value Rationale Residual Solution on Surface 1 mg/ cm2 FDA worst case assumption Area of Treated Surface 4,000 cm2 100% and 50% of FDA worst case assumption for food utensils Percent Active Ingredient 0.0276% Diluted Solution concentration, based on maximum concentration listed on product label ( 4.77 oz in 25 gal water)

Calculated Results Estimated Daily Intake 1.104 mg/ person/ day EDI = ( Resid. Solution) * (% a. i.) / 100 * ( Surface Area)

5.3.2 Dietary Assessment for Restaurant/ Bar Patrons Patrons of a restaurant/ bar using the chemical may have dietary exposure to the chemical via two routes:

$ The diluted solution of this chemical is used as a " last tank" for washing food utensils. That is to say, food utensils that have been washed with soap and water are then dipped in the solution, air dried, and then reused. Patrons of the restaurant/ bar may ingest residues of the chemical left on plates, forks, glasses, and other food utensils. This analysis is based on EPA Reg. No. 65169 1.

$ The diluted solution of this chemical is used as a sanitizer on food contact surfaces, such as countertops. The diluted solution is wiped across surfaces, which are then allowed to air dry. The residues on these food preparation surfaces may be transferred to food, which is then ingested by the patrons. For purposes of this assessment, use of trichloromelamine as a food contact sanitizer in restaurants will also be representative of trichloromelamine exposures in the home. The food contact surface analysis is based on EPA Reg. No. 8160 1.

These two assessments have been performed separately, and then combined to determine a total dietary intake associated with patrons of a restaurant that uses the chemical for both food utensils and food preparation surfaces.

To calculate the EDI associated with use of a trichloromelamine product as a food utensil sanitizer, a number of assumptions have been made based on the FDA guidelines ( FDA, 2003).

$ When a surface is treated with a disinfectant, a quantity of the disinfectant remains on the surface. The FDA recommended worst case concentration for this quantity is 1 mg of solution per square centimeter of treated surface area. In the absence of any other data, this value has been used. Page 27 of 38 $ The FDA suggests that, as a worst case scenario, all food that an individual consumes will come into contact with 4000 cm2 of sanitized non porous food contact surfaces. This contact area represents all the surface area from silverware, china, and glass used by a person who regularly eats three meals per day at an institutional or public facility.

$ FDA calculations assume that 100% of the active material present on food contact surfaces will migrate. This represents a worst case scenario.

For use of a trichloromelamine product as a countertop disinfectant, the same assumptions as listed above were used, and one additional assumption was added:

$ The amount of countertop surface area that comes in contact with food should be much smaller than the amount of food utensil area that comes into contact with food. As a conservative estimate, it is assumed that 50% of the FDA value, or 2000 cm2 of treated surface area, comes into contact with an individual's food per day.

For both assessments, the product with highest percent of the active ingredient in solution ( as diluted per label instructions) was used to estimate the worst case scenario. However, two labels ( Reg. Nos. 6198 3 and 70627 26) state that additional quantities should be used if the diluted solution falls below 100 ppm available chlorine and list the amount of product required to achieve 200 ppm available chlorine. Although the Agency does not believe that these higher concentrations will be used often, as a conservative measure, they are assessed as an acute exposure.

The calculation of the estimated daily intakes is shown in Table 14. The total amount of dietary intake associated with a restaurant using a trichloromelamine product as both a food utensil sanitizer and a countertop disinfectant is 1.42 mg/ day ( acute exposure) and 0.806 ( chronic exposure). Hence, the total dietary exposure is:

1.42 mg/ 70 kg/ p/ d = 0.0203 mg/ kg/ day ( adult male, acute exposure) 1.42 mg/ 60kg/ p/ d = 0.0237 mg/ kg/ day ( adult female, acute exposure) 1.42 mg/ 15 kg/ p/ d = 0.0948 mg/ kg/ day ( child, acute exposure)

0.806 mg/ 70 kg/ p/ d = 0.0115 mg/ kg/ day ( adult male, chronic exposure) 0.806 mg/ 60kg/ p/ d = 0.0134 mg/ kg/ day ( adult female, chronic exposure) 0.806 mg/ 15 kg/ p/ d = 0.0537 mg/ kg/ day ( child, chronic exposure) Page 28 of 38 Table 14. Calculations of EDI for Use of Trichloromelamine Products in Restaurants Value Parameter Food Utensil Countertop Rationale Residual Solution on Surface 1 mg/ cm2 FDA worst case assumption Area of Treated Surface 4,000 cm2 2,000 cm2 100% and 50% of FDA worst case assumption for food utensils Percent Active Ingredient ( acute exposure) 0.0237% 0.0237% Diluted solution concentration, based on maximum concentration listed on product label ( Reg. No. 6198 3)

Percent Active Ingredient ( chronic exposure) 0.0117% 0.0169% Diluted solution concentration, based on maximum concentration listed on product label ( Reg. No. 65169 1 for utensils and Reg. No. 8160 1 for countertops)

Calculated Results Estimated Daily Intake ( Acute) 0.948 mg/ person/ day 0.474 mg/ person/ day EDI = ( Resid. Solution) * (% a. i.) / 100 * ( Surface Area)

Estimated Daily Intake ( Chronic) 0.468 mg/ person/ day 0.338 mg/ person/ day EDI = ( Resid. Solution) * (% a. i.) / 100 * ( Surface Area)

Table 15 summarizes the dietary exposure and risks for trichloromelamine. As the % PAD does not exceed 100%, the dietary risks from both acute and chronic exposure to trichloromelamine fall below the Agency's level of concern.

Table 15. Summary of Dietary Exposure and Risk Population EDIa ( mg/ kg/ day) % PADb Army Fruits/ Vegetables Mess Kits Total Acute Chronic Adult Males 0.00282 0.0158 0.0186 6.20% 18.6%

Adult Females 0.00290 0.0184 0.0213 7.10% 21.3%

Restaurant/ Bar ( Acute)

Food Utensil Countertop Total Acute Adult Males 0.0135 0.00677 0.0203 6.77%

Adult Females 0.0158 0.0079 0.0237 7.90%

Children 0.0632 0.0316 0.0948 31.6%

Restaurant/ Bar ( Chronic)

Food Utensil Countertop Total Chronic Adult Males 0.00669 0.00483 0.0115 11.5%

Adult Females 0.00780 0.00563 0.0134 13.4%

Children 0.0312 0.0225 0.0537 53.7% EDI= Estimated Daily Intake; PAD= Population Adjusted Dose ( acute or chronic) a EDI= Intake ( mg/ person/ day)/ BW ( adult male= 70kg, adult female= 60kg, and child= 15kg) b % PAD = EDI/ aPAD or cPAD * 100, where aPAD= 0.3 mg/ kg/ day and cPAD= 0.1 mg/ kg/ day Page 29 of 38 6.0 AGGREGATE RISK ASSESSMENT In accordance with the policy of the Office of Pesticide Programs ( OPP), aggregate risk assessments are typically considered for acute and chronic dietary exposure ( which includes diet + drinking water exposure) and for short, intermediate, and long term exposures, which usually include the dietary exposure and any residential exposures that can be thought of as reasonably occurring together. These aggregate assessments can be performed for both non cancer and cancer as needed. In the case of trichloromelamine, a cancer aggregate assessment is not needed, as it has been determined by the Health Effects Division that " humans are not likely to be exposed to the high doses of melamine that produce the urinary tract toxicity that precedes and seems to lead to the carcinogenic response in rats." For non cancer aggregate assessment, there is no need for an acute and chronic dietary aggregate assessment, as the uses of trichloromelamine have been determined to have no impact on surface or ground water and the dietary risk calculations estimated in this chapter will characterize the total dietary risk of trichloromelamine. In the case of short, intermediate, and long term aggregate assessments, the following aggregate assessments were performed for adults exposed to trichloromelamine: dietary exposure from eating food that has come into contact with treated surfaces, utensils, and glassware; dermal and inhalation exposure from opening and pouring of the trichloromelamine product in residential settings; and dermal and inhalation exposure from wiping the countertop in residential settings. No aggregate assessment was performed for children as they are not likely to have non dietary exposures. Further, the residential exposure scenarios associated with trichloromelamine uses do not involve long term exposures, only short and intermediate term exposures.

For the short and intermediate term aggregate risk assessment, the oral, dermal, and inhalation exposures were combined, due to the common endpoint ( all from the subchronic study) defining the toxicity by these routes. The values used for dermal and inhalation exposures are derived from a label ( Reg. No. 65169 1) intended mainly for use in occupational settings. However, as this product had the highest use rates ( Section 5.1.2) and the mixing/ loading and application on food contact surfaces in restaurants is assumed to be representative of hard surface uses in homes, these values are used here and are a slight overestimate of the residential exposures and risks. These values are not being refined because the assessment shows no risks of concern. Aggregate MOE calculations were performed using the Aggregate Risk Index method ( EPA, 2001). As shown in Table 16, no aggregate risks of concern were identified for either males or females, as the ARI value is above 1 for both. Page 30 of 38 Table 16. Summary of Short and Intermediate Term ( ST/ IT) Aggregate Exposure and Risk Calculations Population Chronic Food Exposure mg/ kg/ day ( MOE) Opening and Pouring Inhalation Exposure mg/ kg/ day ( MOE) Opening and Pouring Dermal Exposure mg/ kg/ day ( MOE) Wiping Inhalation Exposure mg/ kg/ day ( MOE) Wiping Dermal Exposure mg/ kg/ day ( MOE) Aggregate Risk Index Adult Males 0.0115 ( 2610) 1.72x10 6 ( 1.7x107) 3.18x10 3 ( 9400) 1.16x10 3 ( 26,000) 1.20x10 1 ( 250) 1.89 Adult Females 0.0134 ( 2240) 1.72x10 6 ( 1.7x107) 3.18x10 3 ( 9400) 1.16x10 3 ( 26,000) 1.20x10 1 ( 250) 1.83 ARI = 1/ (( UF1/ MOE1) + ( UF2/ MOE2) + ( UF3/ MOE3) +  ), where the UF = 300 for chronic dietary exposure and 100 for inhalation and dermal exposures.

7.0 CUMULATIVE EXPOSURE FQPA ( 1996) stipulates that when determining the safety of a pesticide chemical, EPA shall base its assessment of the risk posed by the chemical on, among other things, available information concerning the cumulative effects to human health that may result from dietary, residential, or other non occupational exposure to other substances that have a common mechanism of toxicity. The reason for consideration of other substances is due to the possibility that low level exposures to multiple chemical substances that cause a common toxic effect by a common mechanism could lead to the same adverse health effect as would a higher level of exposure to any of the other substances individually. A person exposed to a pesticide at a level that is considered safe may in fact experience harm if that person is also exposed to other substances that cause a common toxic effect by a mechanism common with that of the subject pesticide, even if the individual exposure levels to the other substances are also considered safe.

AD did not perform a cumulative risk assessment as part of this RED for trichloromelamine because AD has not yet initiated a review to determine if there are any other chemical substances that have a mechanism of toxicity common with that of trichloromelamine. For purposes of this RED, EPA has assumed that trichloromelamine does not have a common mechanism of toxicity with other substances.

On this basis, the Registrant must submit, upon EPA's request and according to a schedule determined by the Agency, such information as the Agency directs to be submitted in order to evaluate issues related to whether trichloromelamine shares a common mechanism of toxicity with any other substance and, if so, whether any tolerances for trichloromelamine need to be modified or revoked. If AD identifies other substances that share a common mechanism of toxicity with trichloromelamine, AD will perform aggregate exposure assessments on each chemical and will begin to conduct a cumulative risk assessment.

The Health Effects Division, Office of Pesticide Programs, has recently developed a framework proposed for conducting cumulative risk assessments on substances that have a common mechanism of toxicity. This guidance was issued for public comment on January 16, 2002 ( 67 FR 2210 2214) and is available from the OPP Website at: Page 31 of 38 http:// www. epa. gov/ pesticides/ trac/ science/ cumulative_ guidance. pdf. In the guidance, it is stated that a cumulative risk assessment of substances that cause a common toxic effect by a common mechanism will not be conducted until an aggregate exposure assessment of each substance has been completed.

Before undertaking a cumulative risk assessment, AD will follow procedures for identifying chemicals that have a common mechanism of toxicity as set forth in the " Guidance for Identifying Pesticide Chemicals and Other Substances that Have a Common Mechanism of Toxicity" ( 64 FR 5795 5796, February 5, 1999).

8.0 ECOTOXICOLOGY AND ENVIRONMENTAL RISK ASSESSMENT 8.1 Ecological Hazard Information regarding the potential ecotoxicity of trichloromelamine is shown in Table 17. Because the use of trichloromelamine is limited to use as a food surface disinfectant in restaurants and similar establishments, trichloromelamine is not expected to enter the environment and risk to terrestrial and aquatic organisms is not expected due to the lack of exposure.

Although the information currently available regarding melamine toxicity is insufficient for a hazard assessment, an Agency memorandum notes that there is sufficient evidence to conclude that melamine may be chronically toxic to fish and invertebrates, causing adverse effects on reproduction and embryonic development. It was noted that melamine may be more toxic, chronically, than the data reviewed indicate ( EPA, 1983).

FDA conducted a review of a number of acute toxicity studies for melamine ( EPA, 1983). The FDA concluded that, although there is insufficient evidence to determine the potential environmental toxicity of melamine, there is basis for concern, due to the structureactivity relationship ( SAR) of melamine to meta phenylenediamine, and the readily available studies on melamine's reproductive effects on embryonic development to fish and invertebrates. Based on SARs of melamine to meta phenylenediamine, the 96 hour EC50 for melamine for green algae is expected to be 2.4 mg/ L. The LC50 for daphnids is expected to be 5.9 mg/ L, and the MATC is expected to range between 0.05 and 0.09 mg/ L. Page 32 of 38 Table 17. Summary of Ecotoxicity Data ( Trichloromelamine)

Endpoint Type Species Results Reference/ MRID#

Acute Avian Oral Bobwhite quail ( Colinus virginianus) LD50 > 5,000 mg/ kg NOEC = 5,000 mg/ kg 42250801 Acute Avain Diet Bobwhite quail ( Colinus virginianus) LD50 > 2,150 mg/ kg 42280801 Acute Avain Diet Mallard duck ( Anas platyrhynchos) LC50 > 5,000 mg/ kg NOEC = 2,500 mg/ kg 42247401 Acute Fish Toxicity Bluegill sunfish ( Lepomis macrochirus) LC50 = 4.5 mg/ L NOEC = 1.0 mg/ L 41934901 Acute Fish Toxicity Rainbow Trout LC50 = 4.0 mg a. i./ L NOEC = 0.56 mg a. i./ L 42010601 Acute Aquatic Invertebrate Toxicity Daphnia EC50 = 0.80 mg ai/ L NOEC = 0.32 mg ai/ L 42020801 8.2 Environmental Fate According to EPA's EPI Suite database used by OPPTS, a linear model on biodegradability predicts that trichloromelamine has a high probability of biodegrading in water within hours. The half life in air for trichloromelamine, as determined through mediation of the hydroxy radical in the atmosphere, is about 16 days ( based on a 12 hour day), and it appears to be moderately persistent in the atmosphere ( EPA, 2005).

The half life of trichloromelamine in soils has been estimated to be about 38 days and 150 days in sediments. With an estimated Koc of 150, it is likely to be immobile and persistent in soils and sediments and may not pose a concern for groundwater contamination. However, as trichloromelamine is immobile, it may pose a concern for surface water contamination due to soil erosion. Because use of trichloromelamine is limited to use as a food and food contact surface sanitizer in restaurants and similar establishments, and in Army mess halls, trichloromelamine is not expected to enter the environment and exposure to soil and water should be minimal.

8.3 Environmental Exposure and Risk Characterization Environmental exposure modeling was not conducted for trichloromelamine. The use patterns are not likely to result in significant outdoor exposure. The uses of trichloromelamine considered in this RED make it unlikely that any appreciable exposure to terrestrial or aquatic organisms would occur. However, the high toxicity of trichloromelamine to freshwater organisms is of concern in the event of a spill or misuse of the product. Product labeling should indicate that the chemical is toxic to aquatic invertebrates, and, if more than 50 pounds or 5 gallons of product is sold in one package, that discharge into water should not occur except in accordance with NPDES requirements. Page 33 of 38 8.4 Listed Species Considerations Section 7 of the Endangered Species Act, 16 U. S. C. Section 1536( a)( 2), requires all federal agencies to consult with the National Marine Fisheries Service ( NMFS) for marine and anadromous listed species, or the United States Fish and Wildlife Services ( FWS) for listed wildlife and freshwater organisms, if they are proposing an " action" that may affect listed species or their designated habitat. Each federal agency is required under the Act to insure that any action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a listed species or result in the destruction or adverse modification of designated critical habitat. To jeopardize the continued existence of a listed species means " to engage in an action that reasonably would be expected, directly or indirectly, to reduce appreciably the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of the species." 50 C. F. R. § 402.02.

To facilitate compliance with the requirements of the Endangered Species Act subsection ( a)( 2) the Environmental Protection Agency, Office of Pesticide Programs has established procedures to evaluate whether a proposed registration action may directly or indirectly reduce appreciably the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of any listed species ( EPA 2004a). After the Agency's screening level risk assessment is performed, if any of the Agency's Listed Species LOC Criteria are exceeded for either direct or indirect effects, a determination is made to identify if any listed or candidate species may co occur in the area of the proposed pesticide use. If determined that listed or candidate species may be present in the proposed use areas, further biological assessment is undertaken. The extent to which listed species may be at risk then determines the need for the development of a more comprehensive consultation package as required by the Endangered Species Act.

For certain use categories, the Agency assumes there will be minimal environmental exposure, and only a minimal toxicity data set is required ( Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs U. S. Environmental Protection Agency  Endangered and Threatened Species Effects Determinations, 1/ 23/ 04, Appendix A, Section IIB, pg. 81). Chemicals in these categories therefore do not undergo a full screening level risk assessment, and are considered to fall under a " no effect" determination. Due to the low likelihood of exposure and low toxicity of trichloromelamine, the Agency expects no effects to listed species or critical habitat and therefore makes a " No Effect" determination for this chemical. Page 34 of 38 7.0 REFERENCES Submitted Studies:

MRID Citation 41934901 Bowman, J. ( 1986) Acute Toxicity of Trichloromelamine to Bluegill Sunfish ( Lepomis macrochirus): Lab Project Number: 34811. Unpublished study prepared by ABC Labs, Inc. 17 p.

42010601 Bowman, J. ( 1986) Acute Oral Toxicity Trichloromelamine to Rainbow Trout ( Salmo gairdneri): Lab Project Number: 34812. Unpublished study prepared by Analytical Bio chemistry Laboratories, Inc. 17 p.

42020801 Burgess, D.; Frazier, S.; Schoen, L. ( 1991) Acute Toxicity Trichloromelamine to Daphnia magna: Lab Project Number: 34813. Unpublished study prepared by ABC Laboratories, Inc. 15 p.

42021701 Cifone, M. ( 1986) Evaluation of Trichloromelamine in the Rat Hepatocyte Unscheduled DNA Synthesis Assay: Lab Project Number: 20991 Unpublished study prepared by Hazleton Laboratories America, Inc. 25 p.

42021801 Ivett, J. ( 1986) Clastogenic Evaluation of Trichloromelamine in an In Vitro Cytogenic Assay Measuring Chromosomal Aberration Freq uencies in Chinese Hamster Ovary ( CHO) Cells: Lab Project Number : 20990. Unpublished study prepared by Hazelton Laboratories America, Inc. 33 p.

42131101 Leifheit, B. ( 1990) Product Chemistry for Trichloromelamine, Technical Grade. Unpublished study prepared by Drackett Co. 8 p.

42148801 Jagannath, D. ( 1987) Evaluation of Trichloromelamine, (...) in Ames Salmonella/ Microsome Reverse Mutation Assay: Lab Project Number: 20988. Unpublished study prepared by Hazleton Labs., America, Inc. 26 p.

42247401 Fletcher, D.; Pedersen, C. ( 1988) Trichloromelamine: 8 Day Acute Dietary LC50 Study in Mallard Ducklings: Lab Project Number: 88 DC 109. Unpublished study prepared by Bio Life Associates, Ltd. 26 p.

42250801 Fletcher, D.; Pedersen, C. ( 1988) Trichloromelamine: 21 Day Acute Dietary LD50 Study in Bobwhite Quail: Lab Project Number: BLAL 88 QD 109. Unpublished study prepared by Bio Life Assocs. 31 p.

42280801 Fletcher, D.; Pedersen, C. ( 1988) Trichloromelamine: 8 Day Acute Dietary LC50 Study in Bobwhite Quail: Lab Project Number: BLAL 88 QC 110. Unpublished study prepared by Bio Life Associates, Ltd. 25 p. Page 35 of 38 42283401 DBK Incorporated ( 1992) Trichloromelamine & DBK Food Contact Sanitizer: Product Chemistry Data. Unpublished study. 35 p.

42385101 Schneder, D. ( 1992) Trichloromelamine Efficacy Data " Replacement Study": Lab Project Number: TCM EFF. Unpublished study prepared by H & S Chemical Co. Inc. 25 p.

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.

43064301 Michie, M. ( 1989) Trichloromelamine 90 Day Subchronic Study in Rats: Lab Project Number: 75 51 0743 88: 40 0743 88. Unpublished study prepared by U. S. Army Environmental Hygiene Agency. 1177 p.

43159901 Glaza, S. ( 1994) Acute Dermal Toxicity Study in Trichloromelamine ( TCM), # 14468W46 in Rabbits: Final Report: Lab Project Number: HWI 31102386: TP3016. Unpublished study prepared by Hazleton Wisconsin, Inc. 31 p.

43159902 Glaza, S. ( 1994) Primary Eye Irritation Study of Trichloromelamine ( TCM), # 14468W46 in Rabbits: Final Report: Lab Project Number: HWI 31102388: TP3015. Unpublished study prepared by Hazleton Wisconsin, Inc. 26 p.

43159903 Glaza, S. ( 1994) Primary Dermal Irritation Study of Trichloromelamine ( TCM), # 14468W46 in Rabbits: Final Report: Lab Project Number: HWI 31102387: TP3014. Unpublished study prepared by Hazleton Wisconsin, Inc. 24 p.

43159904 Glaza, S. ( 1994) Dermal Sensitization Study of Trichloromelamine ( TCM), # 14468W46 in Guinea Pigs Closed Patch Technique: Final Report: Lab Project Number: HWI 31102389: TP2008. Unpublished study prepared by Hazleton Wisconsin, Inc. 38 p.

43165701 Glaza, S. ( 1994) Acute Oral Toxicity Study of Trichloromelamine ( TCM), # 14468W46 in Rats: Final Report: Lab Project Number: HWI/ 31102385. Unpublished study prepared by Hazleton Wisconsin, Inc. 44 p.

43350301 Schneider, D. ( 1994) Trichloromelamine Series 61 3: Product Chemistry: Lab Project Number: TCM 61 3. Unpublished study prepared by H& S Chemical Co., Inc. 5 p.

43350302 Schneider, D. ( 1994) Trichloromelamine Series 62 1,2: Product Chemistry: Lab Project Number: TCM 62 1,2. Unpublished study prepared by H& S Chemical Co., Inc. 6 p. Page 36 of 38 43350303 Schneider, D. ( 1994) Trichloromelamine Series 63 9, 10, 11: Product Chemistry: Lab Project Number: TCM 63 9, 10, 11. Unpublished study prepared by H& S Chemical Co., Inc. 8 p.

43368501 Viau, A. ( 1994) An Evaluation of the Acute Toxicity of Inhaled Trichloromelamine Dry Powder Formulation in the Albino Rat: Lab Project Number: 90906. Unpublished study prepared by Bio Research Lab., Ltd. 190 p.

43395401 Lee, H. ( 1994) Physical and Chemical Characteristics of Trichloromelamine: Lab Project Number: 7673/ 09/ 08/ A1: 233A1. Unpublished study prepared by S. C. Johnson & Son, Inc. 17 p.

43614301 Tyl, R.; Marr, M.; Myers, C. ( 1995) Developmental Toxicity Evaluation of Trichloromelamine Administered by Gavage to New Zealand White Rabbits: Final Report: Lab Project Number: 65C 5742 300/ 400. Unpublished study prepared by Research Triangle Institute. 215 p.

43614302 Tyl, R.; Marr, M.; Myers, C. ( 1995) Developmental Toxicity Evaluation of Trichloromelamine Administered by Gavage to CD ( Sprague Dawley) Rats: Final Report: Lab Project Number: 65C 5742 100/ 200. Unpublished study prepared by Research Triangle Institute. 246 p.

45012316 Walls, C.; Watters, J. ( 1999) Exposure and Risk Assessments for Sodium Lauryl Sulfate: Lab Project Number: 99 02: 99 01. Unpublished study prepared by Novigen Sciences, Inc. 153 p.

Memos, Open Literature, and Websites:

Environmental Protection Agency, 1983. Meeting with FDA Toxicology Department concerning their evaluation of pituitary tumor incidence in male Fischer 344 rats and bone marrow leukemia incidence in female F 344 rats in the 30 month melamine study submitted by American Cyanamin ( 1983). Memorandum from Stephanie April, Toxicology Branch, to Tim Gardner, Registration Division. December 14, 1983.

Environmental Protection Agency, 1984. Melamine Studies. Memorandum from Stephanie April, Toxicology Branch, to James Davis, Pesticide and Toxic Substances. May 2, 1984.

Environmental Protection Agency, 1988. Data waiver request for Trichloromelamine; EPA I. D. No. 8029 5; Proj. No. 8 0169A; Caswell No. 877. Memorandum from James Rowe, Toxicology Branch, HED, to Quang Bui, Section Head of Section V, Toxicology Branch, HED. July 6, 1988.

Environmental Protection Agency, 1993. Carcinogenicity Peer Review of Melamine. Memorandum from Stephen C. Dapson, Senior Pharmacologist, HED, and Esther Rinde, Page 37 of 38 Manager of Carcinogenicity Peer Review Committee, HED, to Phil Hutton, Insecticide Rodenticide Branch, Registration Division. July 21, 1993.

Environmental Protection Agency, 1994. Trichloromelamine: Review of Acute Toxicity Studies Submitted in Response to DCI. Memorandum from Jess Rowland, Toxicologist, HED, to K. Davis and B. Alder, Product Managers, Reregistration Division. July 21, 1994.

Environmental Protection Agency, 1997. Standard Operating Procedures ( SOPs) for Residential Exposure Assessments. Prepared for the Office of Pesticide Programs, Health Effects Division. Contract No. 68 Environmental Protection Agency, 2000. Review of the Proctor & Gamble Submission for Registration of the Product, FIT, to Wash Fruits and Vegetables. Memorandum from Robert Quick, Chemist, RASSB, to Velma Noble, Product Manager Team, RMB I. DP Barcode D262976.

Environmental Protection Agency, 2001. " General Principles for Performing Aggregate Exposure and Risk Assessments." US Environmental Protection Agency, Office of Pesticide Programs. November 28, 2001. http:// www. epa. gov/ pesticides/ trac/ science/ aggregate. pdf.

Environmental Protection Agency, 2004a. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs U. S. Environmental Protection Agency  Endangered and Threatened Species Effects Determinations, Appendix A, Section IIB, pg. 81. US Environmental Protection Agency. January 24, 2004. http:// www. epa. gov/ oppfead1/ endanger/ consultation/ ecorisk overview. pdf.

Environmental Protection Agency, 2004b. Residue Chemistry Comments on the Trichloromelamine Preliminary Risk Assessment. Electronic Correspondence from Robert Quick, Chemist, RASSB, to L. Bailey, Senior Environmental Scientist, Antimicrobial Division, Immediate Office. August 24, 2004.

Environmental Protection Agency, 2004c. USEPA/ OPP Pesticide Products Database Query  Updated Weekly. http:// www. cdpr. ca. gov/ docs/ epa/ m2. htm Accessed July, 2004.

Environmental Protection Agency, 2005. Estimation Program Interface ( EPI) Suite. http:// www. epa. gov/ oppt/ exposure/ docs/ episuite. htm. Accessed 2005.

European Chemicals Bureau, 2004. European Inventory of Existing Commercial Substances. http:// ecb. jrc. it/ EINECS# 231 648 4. Accessed 2004.

FDA, 2003. " Sanitizing Solutions: Chemistry Guidelines for Food Additive Petitions." January, 1993. http:// www. cfsan. fda. gov/~ dms/ opa cg3a. html. Last accessed June 9, 2003. Page 38 of 38 H& S Chemical Co., Inc, 2004. Material Safety Data Sheet. http:// www. hschem. com/ tccmmsds. html Accessed 2004.

US Department of Agriculture, Agricultural Resarch Service, 1999. Food and Nutrient Intakes by Children 1994 96, 1998. Online. ARS Food Surveys Research Group, available on the " Products" page at < hhtp:// www. barc. usda. gov/ bhnrc/ foodsurvey/ home. htm>. Last accessed July 28, 2004.

Wilson JW, CW Enns, JD Goldman, KS Tippett, JH Mickle, LE Cleveland, and PS Chahil, 1997. Data tables: Combined results from USDA's 1994 and 1995 Continuing Survey of Food Intakes by Individuals and 1994 and 1995 Diet and Health Knowledge Survey, [ Onlise]. ARS Food Surveys Research Group. Available ( under " Releases"): < http:// www. barc. usda. gov/ bhnrc/ foodsurvey/ home. htm>. Last accessed July 28, 2004.