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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA Registration Division contact: Kable Bo Davis, 703 - 306 - 0415 Syngenta Crop Protection, LLC [ 2F8006 ] EPA has received a pesticide petition ( [ 2F8006 ] ) from Syngenta Crop Protection , LLC, P.O. Box 18300, Greensboro, NC 27419

- 8300 request ing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of Simazine: 6

- chloro

- N, N ’

- diethyl

- 1,3,5

- triazine

- 2,4

- diamine in or o n the raw agricultural commodities: citrus fruits (Crop Group 10) at 0. 05 parts per million (ppm ) ; pome fruits (Crop Group 11 ) , at 0. 03 ppm ; stone fruits (Crop Group 12 ) , at 0. 10 ppm ; tree nuts (Crop Group 14 , except almond hull ) , at 0.07 ppm and amending a tolerance for residues in or on almond hull to 3.0 ppm . Also, the purpose of this petition is to remove individual tolerances for simazine herbicide in the following commodities: [apple, hazelnut, peach, pecan, plum and walnut (established tolerances at 0.20 ppm)] and [almond, cherry, grapefruit, lemon, macadam ia nut, orange and pear (established tolerances at 0.25 ppm)]. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d ) ( 2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry
1. Plant metabolism. The nature of the residue in plants is adequately understood. HED has determined that the residue for tolerance expression for currently registered plant uses, and the residue of concern in plants, is simazine and its 2 chlorometabolites: G

- 28279 and G

- 28273. 2. Analytical method. Analytical methods, AG

- 539 , “Determination of Simazine, G

- 28279, and G

- 28273 Residues in Vegetables, Fruit, Grains, and Crop Fractions using Capillary Gas Chromatography , ” AG

- 497, “Determination of Simazine, C

28279 and G

- 28273 Residues in Milk (including Sour Milk) Using a Strong Ca tion Exchange Column Isolation and Cleanup” and AG

- 540, “Determination of Simazine, Atrazine, G

- 30033, G

- 28279 and G

- 28273 Residues in Beef Tissues, Poultry Tissues and Poultry Eggs Using Capillary Gas Chromatography ” are2 available for enforcement purposes with limits of detection that allows monitoring of food with residues at or above the levels set in these tolerances. The analytical methods have undergone successful independent laboratory validations. For data submitted with this petition, the method used was based on the Syngenta Crop Protection Method entitled, “Analytical Method GRM052.01A for the Determination of Simazine, G28273, and G28279 in Crops. Final Determination by LC

- MS/MS”, effective date: May 11, 2010. This method was validated and ha d a Limit of Detection (LOD) of 0.40 pg and Limit of Quantitation (LOQ) of 0.01 ppm. Both study method and validation reports will be submitted with this data package. 3. Magnitude of residues. Additional field trials have been conducted reflecting the use of simazine at the maximum labeled use rate to support the requested crop group tolerance for citrus fruits, pome fruits, stone fruits, and tree nuts. The number and location of these addition al field trials , along with others submitted previously by Syngenta , are sufficient to be in accordance with OPPTS Test Guidelines 860.1500 and to support a request from EPA (Data Call

- in request). Complete residue data to support the requested crop grou p tolerances are included with this petition

. B. Toxicological Profile 1. Acute toxicity. The acute toxicity database for simazine is considered complete for acute oral, acute dermal, acute inhalation, dermal and eye irritation, and dermal sensitization . Simazine has a low order of toxicity via the oral (Category IV), dermal (Category III), and inhalation (Category III) routes of exposure. It is not an eye or skin irr itant, or a dermal sensitizer. 2. Genotoxic i ty. Simazine was negative i n a bacterial (Salmonella typhimurium) assay, in a mammalian cytogenetic assay (bone marrow micronucleus), and in an unscheduled DNA synthesis assay in rat hepatocytes

. 3. Reproductive and developmental toxicity. Available developmental toxicity data provided no indication of increased susceptibility (quantitative or qualitative) of rats or rabbits to in utero and/or postnatal exposure to simazine. Developmental effects (skeletal variations) in the rat were observe d in the presence of maternal toxicity (decreased body weight/body weight gain and food utilization at 300 mg/kg/day). No malformations were reported. In the rabbit, maternal effects occurred at doses (75 mg/kg/day) lower than those associated with develop mental effects (decreased fetal weight and increased skeletal variations at 200 mg/kg/day). No treatment

- related offspring toxicity was reported in a two

- generation reproduction study in the rat. The parental LOAEL is 100 ppm (5.61 and 7.04 mg/kg/day fo r males and females, respectively), based on decreased body weight and body weight gain. The NOAEL is 10 ppm (0.56 and 0.7 mg/kg/day for males3 and females, respectively). The NOAEL for offspring toxicity is 500 ppm (HDT

- 28.9 and 35.0 mg/kg/day for males and females). 4. Subchronic toxicity. In rats, decreased body weight gain, reduced food consumption, and decreased white blood cell count (males) and blood urea nitrogen (female) were noted in rats administered simazine in the diet for 90 days (LOAEL = 1 4.25 mg/kg/day; NOAEL = not identified). Effects overall were similar to atrazine. Differences in LOAELs and NOAELs may be attributed to dose spacing. Dogs administered simazine (65.2/64.3 mg/kg/day), males/females) in the diet for 90 days exhibited decreased body weight/body weight gain, decreased food consumption, increased relative brain and liver weights, decreased heart weight, decreased testes weight (males), decreased serum glutamate oxaloacetate (SGOT) and reduced alkaline phosphatase activiti es (females). The NOAEL was 6.9/8.2 mg/kg/day in males/females. 5. Chronic toxicity. In a 12

- month dietary study in the dog, decreased body weight gains were noted in males administered 42.9 mg/kg/day (HDT) simazine, and in females administered 3.64 mg/kg/day (MDT) and 44.9 mg/kg/day (HDT). Mid

and high

- dose females displayed decreased levels of red blood cell counts, hemoglobin, and hematocrit. Platelet counts were increased in high

- dose males and females. Adrenal weight , adrenal/brain weight ratio, and adrenal/body weight ratio were significantly increased in the high

- dose females, whereas adrenal/brain ratio was increased in the high

- dose males. The LOAEL in males is 42.9 mg/kg/day based on decreased body weight gains, increased platelet counts, and increased adrenal/brain weight ratio; the NOAEL is 3.41 mg/kg/day. The LOAEL in females is 3.64 mg/kg/day based on decreased body weight gain, hematological effects (decreased levels of red blood cell counts, hemoglobin and hematocrit) and increased adren al weight, adrenal/brain weight ratio, and adrenal/body weight ratio. The NOAEL in females is 0.76 mg/kg/day. In a 104

- week dietary study in rats treated with simazine, decreased body weights and body weight gains were evident in mid

- dose females (5.3 mg/ kg/day), high

dose females (63.1 mg/kg/day), and high

- dose males (45.8 mg/kg/day). Food consumption was reduced in the high

- dose animals. Mortality was increased in the high

- dose females. Treatment

- related hematological effects observed in the mid

- and hig h

- dose females included decreased red blood cell counts, decreased hemoglobin and hematocrit levels, increased mean corpuscular hemoglobin, increased mean corpuscular hemoglobin concentration, increased white blood cell counts, increased percent neutrophil s, and decreased lymphocyte count. Hematological changes in males included increased mean corpuscular hemoglobin concentration (high

- dose) and decreased leukocyte counts (mid

- and high

- dose). Females receiving the high dose exhibited decreased glucose level s and increased alkaline phosphatase activity. Organ weight changes in high

- dose females included increased heart, kidney and liver weights. In high

- dose males, increased liver and testes weights and decreased heart weights were noted. No4

non - neoplastic le sions were observed in males. In the high

- dose females, liver hematopoiesis, splenic hematopoiesis and cystic mammary glandular hyperplasia were significantly increased. A reevaluation of selected tissues subsequent to the original study revealed a signifi cant increase after 24 months exposure to the high dose in ovarian atrophy and Sertoli cell hyperplasia. The LOAEL in females is 5.3 mg/kg/day based on hematological changes and decreased body weight gain. The NOAEL in females is 0.5 mg/kg/day. The LOAEL i n males is 4.2 mg/kg/day based on decreased leukocyte counts. The NOAEL in males is 0.41 mg/kg/day. Effects overall were similar to atrazine. Differences in LOAELs and NOAELs may be attributed to dose spacing. In a carcinogenicity study, male and female mice administered simazine (131.5 mg/kg/day

- males; 160 mg/kg/day

- females) in the diet exhibited decreased body weights and body weight gains. Food consumption was decreased in the high

dose males (542 mg/kg/day) and females (652.1 mg/kg/day), and in th e mid

- dose males. Water consumption tended to be decreased in the mid

- and high

- dose males and females. There were no apparent treatment

- related effects on hematology, clinical chemistry, organ weights and pathology. The LOAEL (131.5 mg/kg/day

- males; 160 mg/kg/day

- females) is based on decreased body weights and body weight gains. The NOAEL is 5.3 mg/kg/day for males, and 6.2 mg/kg/day for females. 6. Animal metabolism. The nature of simazine residues in livestock is adequately understood based on the available goat and poultry metabolism studies. HED has determined that the residue for the tolerance expression, and the residue of concern in livestock and poultry, is simazine and its 2 chlorometabolites: G

- 28279 and G

- 28273. 7. Metabolite toxicology

. T he toxicity of G

- 28279 and G

- 28273 are taken to be the same as the parent. 8. Endocrine disruption

. USEPA developed a Tier 1 Screening (TIS) battery of eleven separate assays to identify potential endocrine

- modulating chemicals. A series of guidelines for TIS assays was published, and on December 10, 2009, USEPA sent the test orders (DCI#EDSP

- 080807) for the TIS to registrants of simazine. The Agency has also indicated that “other scientifically relevant information” (ORSI) is functionally equivalent to the information obtained from the Tier 1 assays may be utilized in lieu of conducting the Tier 1 assays. Syngenta submitted a proposal ( MRID# 48104901 , May 20 th , 2010) to USEPA to identify the most relevant ORSI that is available for simazine and to prov ide the justification for waivers of all eleven EDSP Tier 1 assays. USEPA agreed to waiver 5 studies (Test Order EDSP

- 080807

- 130, 131 and 132, December 16, 2010 ). The additional six studies required to fulfill the outstanding data requirements have (4 st udies) or will (two studies) be submitted by July 2012: Androgen Receptor Binding (890.1150 , MRID# 48619301 ), Estrogen Receptor transcriptional activation (890.1300 , MRID# 48619302 ), Hershberger Assay5 (890.1500 , MRID# 48619303 ), Male Pubertal Rat (890.150 0 , MRID# 48619304 ); Amphibian Morphometric Assay ( 890.1100); and Fish Short

- term Repro (890.1350)

.
C. Aggregate Exposure 1. Dietary exposure. Acute, short

- term, and chronic exposure evaluations were made for simazine using the Dietary Exposure Evaluation Model (DEEM

FCID TM ), version 2.16 from Exponent for all current uses, including additional residue data generated in response to a Data Call

- In (DCI) for citrus fruit (Crop Group 10), pome fruit (Crop Group 11), stone fruit (Crop Group 12), and tree nuts (Crop Group 14). Percent crop treated (%CT) values were estimated based upon economic, pest, and competitive pressures. Food consumption data for these assessments was taken from the USDA’s Continuing Survey of Food Intake by Individuals (CSFII ) with the 1994

- 96 consumption databases and the Supplemental CSFII children’s survey (1998) consumption database. Simazine is a pre - emergent herbicide applied mostly in pre

- plant broadcast or pre

- plant banded treatments (where pesticide is applied to the field in bands or rows) to soil. Residues of concern in food include parent simazine (2

- chloro

- 4,6

- bis(ethylamino)

- s - triazine) plus its two chlorinated degradates, 2

- amino

- 4

- chloro

6

- ethylamino

- s - triazine and 2,4

- diamino

- 6

- chloro

- s - triazine. No detectab le quantities of simazine and its chloro

- degradates are expected in raw agricultural commodities. Existing field trial data, the United States Department of Agriculture’s (USDA) Pesticide Data Program (PDP), and the Food and Drug Administration’s (FDA) mo nitoring data indicate non

- detectable residues (less than 0.05 ppm) of simazine. Dietary exposure to simazine from food is estimated to be essentially zero, resulting in a risk estimate of 0% of the aRfD and cRfD which is not of concern to the EPA. i. Food. Acute Exposure. Estimated acute dietary risk from food for females 13

- 49 years old (the only population subgroup for which an acute endpoint has been established) is 0% of the aRfD (0.1 mg/kg

- bw/day). Chronic Exposure. Estimated chronic dietary risk from food for all population subgroups is 0% of the cRfD (0.0018 mg/kg

- bw/day). Cancer

. Simazine has been classified as not likely to be carcinogenic in humans. Therefore, no cancer risk assessment was performed for simazine. ii. Drinking water
. T he Estimated Drinking Water Concentrations (EDWCs) of simazine (expressed as simazine total chlorotriazine; simazine TCT) were taken from 2006

- 2010 water monitoring data from four programs: Simazine Confirmatory Monitoring Program (SCMP), Atrazine Monitori ng Program (AMP), Simazine Monitoring Program (SMP), and Stewardship Voluntary Monitoring Program (SVMP). These water monitoring programs collected finished water samples primarily using surface water sources from Community6 Water Systems across the United States. Based on these monitoring data, the maximum concentration of simazine TCT detected was used as the peak (acute) drinking water EDWC and the maximum 90

- day rolling average of simazine TCT was used as the chronic drinking water EDWC. The acute a nd chronic EDWCs were determined to be 33.860 ppb and 10.641 ppb, respectively. These EDWCs represent both surface water and ground water. Acute Exposure from Drinking Water. The acute EDWC of 33.860 ppb was compared against the acute drinking water level of comparison (DWLOC) of 9000 ppb for females 13

- 49 years old. The acute DWLOC was not exceeded. Since EPA generally has no concern for exposures below the DWLOC, Syngenta believes that there is a reasonable certainty that no harm will result from acute drinking water exposure to residues arising from the current and proposed uses for simazine. Chronic Exposure from Drinking Water. The chronic EDWC of 10.641 ppb was compared against the chronic DWLOC of 37.5 ppb for infants and children <1 year o ld, the most sensitive subpopulation. The chronic DWLOC was not exceeded. Since the EPA generally has no concern for exposures below the DWLOC, Syngenta believes that there is a reasonable certainty that no harm will result from chronic drinking water ex posure to residues arising from the current and proposed uses for simazine. 2. Non

- dietary exposure

. Residential exposure risk assessments were performed for simazine uses on turf and ornamentals (Princep® Liquid). The Syngenta residential risk assessmen ts were conducted based on the maximum label rates of 2 lb a.i./A for turf grass and 0.12 lb a.i./gal for ornamental plants. Residential handler exposure risks were calculated using exposure data from the Occupational Pesticide Handler Unit Exposure Surro gate Reference Table. Post

- application dermal exposure risks were refined based on a simazine chemical

- specific transferable turf residue study. Toddler hand

- to

- mouth oral exposure risk was refined using a hand

- press study performed using atrazine. A short

- term NOAEL of 6.25 mg/kg

- bw/day, from a 28

- day pubertal study in rats with atrazine, was selected for assessment of dermal, inhalation, and non

- dietary incidental oral exposure risk . Exposures of greater than 30 days ( i.e. intermediate term) are not anticipated for dermal, incidental oral, or inhalation routes of exposure from non

occupational sources of simazine. Residential handler exposure risks are acceptable for application of Princep® Liquid to ornamental plants using a low

pressure handwand s prayer (MOE = 4,501,029) and for application to turf using a backpack sprayer (MOE = 428,922) or low

- pressure handwand sprayer (MOE = 5,293,750). Post

- application dermal exposure risks due to re

- entering lawn turf grass treated with Princep® Liquid are a cceptable for adults (MOE = 788) and toddlers (MOE = 471). Post

- application dermal exposure risks due to re

- entering golf course turf grass treated with Princep® Liquid are acceptable for adults (MOE = 1,633) and youths (MOE = 910). Post application non

- dietary oral exposure risks from simazine are also acceptable (MOE = 442) for children re

-7 entering lawn turf grass following treatment with Princep® Liquid. Since the residential MOEs are above the Benchmark MOE of 300 there is a reasonable certainty tha t no harm will result from exposures arising from residential uses of simazine

. D. Cumulative Effects The EPA has completed its cumulative risk assessment for the chlorinated triazine class of pesticides and has concluded that with the mitigation measures in the 2006 RED for simazine and in the 2003 IRED for atrazine, the cumulative risks associated with these pesticides are below the EPA’s level of concern. The EPA has determined that, with label amendments and changes as specified in this docume nt and the 2006 RED for simazine and 2003 IRED for atrazine, there is a reasonable certainty that no harm will result to the general U.S. population, infants, children, or other major identifiable subgroups of consumers, from the use of simazine, atrazine, and propazine. The cumulative risk assessment and supporting documents are available in the public docket EPA

- HQ

- OPP

- 2005

- 0481. E. Safety Determination 1. U.S. population. Simazine dietary exposures from food are estimated to be zero, with aggregate exposures to simazine being limited to the drinking water and/or residential exposure pathways. In the acute risk assessments, females 13 to 49 years (the only population subgroup of concern) had an acute DWLOC of 9,000 ppb. Using Syngenta's extensive wa ter monitoring data, the maximum peak concentration of simazine TCT was 33.860 ppb. Since the maximum peak concentration from monitoring data does not exceed the acute DWLOC, acute drinking water exposure to simazine TCT is below the EPA’s level of concer n. In the chronic risk assessments, the chronic DWLOC for the general U.S. population was 204 ppb. Based on monitoring data, the maximum 90

- day rolling average concentration of simazine TCT was 10.641 ppb. Since the maximum 90

- day rolling average concen tration from monitoring data does not exceed the chronic DWLOC, chronic drinking water exposure to simazine TCT is below the EPA’s level of concern. Based on the completeness and reliability of the toxicity data supporting these petitions, Syngenta believ es that there is a reasonable certainty that no harm will result from aggregate exposure to residues arising from all current and proposed simazine uses, including anticipated dietary exposure from water, and all other types of non

- occupational residential exposures . 2. Infants and children

. Simazine dietary exposures from food are estimated to be zero, with aggregate exposures to simazine being limited to the drinking water and/or residential exposure pathways. No acute endpoint has been established for infants and children. Aggregate short

- term exposures were based on short

- term exposures from drinking water and from the post

- application dermal (MOE = 910) and non

- dietary oral exposures (MOE = 442). Since the Benchmark MOE =8 300, short

- term exposures f rom drinking water and residential exposures do not exceed the EPA's level of concern. Risk estimates for aggregate intermediate

term and chronic exposure are based on chronic drinking water exposures only as there is no residential exposure for these exp osure durations. In the chronic risk assessments, infants <1 year were the most sensitive subgroup, with a chronic DWLOC of 37.5 ppb. Using Syngenta's extensive water monitoring data, the maximum 90

- day rolling average concentration of simazine TCT was 1 0.641 ppb. Since the maximum 90

- day rolling average concentration from monitoring data does not exceed the chronic DWLOC, chronic drinking water exposure to simazine TCT is below the EPA’s level of concern. Based on the completeness and reliability of th e toxicity data supporting these petitions, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure to residues arising from all current and proposed simazine uses, including anticipated dietary exposure from water, and all other types of non

occupational residential exposures. F. International Tolerances There are no Codex maximum residue levels (MRLs) established for residues of simazine.