UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, DC 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

4/17/13 MEMORANDUM SUBJECT: Terbutryn. Drinking Water Risk Assessment (Revised) PC Code : Terbutryn: 080813 I DP Barcode No.: 41 0486 Decision No.: NA I File Symbol : 5383- RGI Regulatory Action: New Active Ingredient Registration Risk Assessment Type: Single Chemical I Case No.: 4023 TXR No. : N/A FROM:
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THRU:

Background I CAS No : 886-50-0 William J. Hazel, Ph.D., Chemist 

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# /(;)cit, ./7 / Risk Assessment and Science

# Supp~tt~h**(RASs~** Antimicrobials Division (751 OP) Stacey Grigsby Regulatory Management Branch II (RMBII) Antimicrobials Division (751 OP) Steven Weiss, Chief

# ~**~** Timothy Leighton, Team Leader I------**~** Risk Assessment and Science Support Branch (RASSB) Antimicrobials Division (751 OP)

In July 2009, Troy Chemical Corporation submitted an application to EPA requesting the registration of a product containing a new active ingredient terbutryn [2-(tertbutylamino)-4-(ethylamino)-6-(methylthio)-s-triazine] (EPA File Symbol 5383-RGI). Troy has also applied for registration of three industrial end-use products containing terbutryn: Troysan® Terbutec (5383- RGO, 99.0% terbutryn), Polyphase® 71 OS (5383- RUN, 8% terbutryn and 14% 3-iodo-2-propynyl butyl carbamate), and Troysan®V662 (5383-TBD, 48% terbutryn). The proposed uses in these applications are for material preservation ofjoint cements, stuccos, sealants, paints, primers, sealers, and industrial coatings.Dietary Exposures and Risks There are no registered food uses so dietary exposure and risk are limited to direct and indirect exposure to water including dri n king water. 1) Estimated Level of Terbutryn in Water The agency utilized conservative assumptions to estimate terbutryn levels in water. EPA calculated estimated environmental concentrations (EEC) of terbutryn in water of 9 and 18 ppb by assuming that 50% or 100%, respectively, of houses, decks, and fences in the watershed had been painted with terbutryn -preserved paint. Th ese EECs are acute (peak) figures that are most appropriate for single-day drinking water assessments in terms of duration. However, as terbutryn does not induce adverse systemic effects from a single dose, an acute dietary risk assessment is not appropriate and has not been conducted. Dietary risk due to terbutryn is only chronic**(:~6** months in duration) for which an arithmetic mean water concentration would be a more appropriate value. However, the available model for antimicrobials is not refined enough to provide average water concentrations . Therefo re, EPA used the acute (peak) value in the d ietary assessment even though it greatly overestimates chronic dietary risk due to drin king water exposure. In reality, the agency does not expect terbutryn to contaminate drin king water as a result of this use. Conservative modeling results were based on the following parameters and inputs: a) The leaching rate used was the highest reported rate; b) All (1 00%) or half (50%) of the houses in the watershed (as well as fences, decks, etc.) were painted with paint containing terbutryn. As this is a new use, no houses have yet been painted with these products. Typically, the market share increases for several years and then levels off. Both the 50% and 100% painted figures are considered conservative. c) There are 10 houses per hectare (representative of high den sity construction) and 10 hectares in the watershed, i .e., 100 houses supplying leachate to the water body. d) All leached terbutryn goes into the same water body, and it does not degrade or sorb. In reality there are always lawns and hard surfaces between the houses and water body and, as the water passes through these surfaces, part of the terbutryn will be adsorbed to the soil particles and lower concentrations will reach the water body. e) The model uses a small farm pond as the surrogate water body, which is considered to be unrealistic for drinking water. Much larger reservoirs are used for drinking water sources and, if modeled, would be expected to further reduce the water concentration. f) These calculations and the water concentration (EEC) derived from the model is an acute (peak) value, whereas the risk assessment is for ch ro nic exposure. An average water concentration would be a more appropriate value to use in the assessment but this is not available from the model.
22) Dietary Risk of Terbutryn Th e agency utilized a cPAD of 0.001 mg/kg/day (0.1 mg/kg/day + 1O Ox) from the 2-year rat feeding study (MRID 00035923) with the most sensitive endpoint. The dose of 0 .001 mg/kg/day from the 2-yr rat study is conservative, perhaps overestimating toxicity by a factor of 10-100 because of the dose spacing: the NOAEL is 0.1 mg/kg/day but the next higher doses are 15 and 150 mg/kg/day. The agency notes that the NOAEL of 12 mg/kg/day in male rats from the newer 2-yr rat study may be closer to where the true NOAEL lies because the dose spacing is much closer (1
.2, 4.0, 12, and 25 mg/kg/day)
. Terbutryn does not induce adverse systemic effects due to a single dose; therefore, an acute dietary risk assessment has not been conducted . Drinking water consumption and risk were based on a DEEM - FCID- NHANESIWWEIA (2003-2008) model run using the 18 ppb EEC level and the cPAD if 0 .001. The results indicate that , even with an extremely conservative estimate of the terbutryn level in drinking water, all infants were at 97% of the cPAD, children 1 -2 were at 54% of the cPAD, and the total U.S. population was at 38% of the cPAD. When the somewhat more refined EEC of 9 ppb is modeled, these apparent risks decline to 49%, 27%, and 19%, respective ly. 3) 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), th e Agency was directed to "ensure that there is a reasonable certainty that no harm will result to infants and chi ldren" from aggregate exposure to a pesticide chemical resi due. The law further states that in the case of threshold 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 reli able data, such margin will be safe for infants and children ." There are no existing tolerances or exemptions from tolerance for terbutryn. Dietary exposure to terbutryn is limited to drinking water through potential leaching of terbutryn from paint into surface water. As there are potential exposures to te rbutryn through drinking water that will also involve exposures of infants and children, the data on developmental, reproductive, and neurotoxic effects of terbutryn we re examined. The data on developmental and reproductive toxicity of terbutryn (two developmental toxicity studies and one multi-generation reproduction toxicity study) showed no indication of developmental or reproductive toxicity to offspring from in utero or post-natal exposure to terbutryn. Also, there are no indications of neurotoxicity of terbutryn from the available subchronic, developmental, or reproductive toxicity data . The Agency has no residual uncertainties regarding age-re lated sensitivities for women of child bearing age 3or infants and children based on the absence of sensitivity observed in the developmental and reproductive toxicity studies for terbutryn . In addition, there are no residual uncertainties regarding exposure as conservative model inputs have been used to estimate exposures to terbutryn in drinking water as discussed in section F above. For these reasons, the default 10x FQPA Safety Factor can be reduced to 1x. Aggregate Risk An aggregate risk assessment considers food, drinking water and residential sources of exposures. There are no registered food uses. For both children and adults, the adverse effects in the studies used to assess residentia l dermal and inhalation risks (decreased body weight and body weight gain) are d ifferent than the effects in the chronic toxicity study (decreased hemoglobin and e rythrocytes) used in the chronic drinking water assessment, aggregation of chronic drinking water and res idential risks is not appropriate. (U.S. EPA 2013b). The only risks that need to be aggregated are due to residential applicator exposures. These aggregate risks are add ressed in the terbutryn exposure and risk assessment. (U.S. EPA 2013c). References U.S. EPA 2013a . Memorandum: Terbutryn: Estimated Environme ntal Concentrations (EEC) for Terbutryn Used in Outdoor Paints. Memorandum from Siroos Mostaghimi to Jacqueline Campbeii - McFarlane, Product Manager. DP Barcode: 0407718. U.S. EPA 2013b. Memorandum: Terbutryn: Toxicological Review and Hazard Assessment for the Proposed Uses as a Material Preservative. Memorandum from Jonathan Chen, Ph.D . , Toxicologist to Stacey Grigsby, Prod uct Manager. DP Barcode: 04077 1 1. U .S
. EPA 20 1 3c. Memorandum : Updated Occupational and Residentia l Exposure Assessement for Terbutryn . Memorandum from Natha n Mottl, Biologist to Jacqueline Campbeii -McFarlane PM 34, DP Barcode: 0 407712.

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