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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 requesting, 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 on 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, macadamia 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, C28279 and G-28273 Residues in Milk (including Sour Milk) Using a Strong 

Cation 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” are 
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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 

had 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 additional 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 group 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 irritant, or a dermal sensitizer. 

2. Genotoxicity. Simazine was negative in 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 observed 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 developmental 

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 for 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 males 
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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 = 14.25 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 activities (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). Midand 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 adrenal 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), highdose 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 high-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 neutrophils, 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 levels 

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. No 
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non-neoplastic lesions 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 significant 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 in 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 highdose males (542 mg/kg/day) and females (652.1 mg/kg/day), and in the 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. The 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 20th, 2010) to USEPA to 

identify the most relevant ORSI that is available for simazine and to provide 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 studies) 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 Assay 
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(890.1500, MRID# 48619303), Male Pubertal Rat (890.1500, 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 (DEEMFCIDTM), 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-chloro6-ethylamino-s-triazine and 2,4-diamino-6-chloro-s-triazine. No detectable 

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) monitoring 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. The 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 Monitoring 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 Community 
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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 and 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 old, 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 exposure 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 assessments 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 Surrogate 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 nonoccupational sources of simazine. Residential handler exposure risks are 

acceptable for application of Princep® Liquid to ornamental plants using a lowpressure handwand sprayer (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 acceptable 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-
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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 that 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 

document 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 water 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 concern. 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 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 the 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.

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 = 
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300, short-term exposures from drinking water and residential exposures do not 

exceed the EPA's level of concern. Risk estimates for aggregate intermediateterm and chronic exposure are based on chronic drinking water exposures only as 

there is no residential exposure for these exposure 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 10.641 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 the 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 nonoccupational residential exposures.

F. International Tolerances

There are no Codex maximum residue levels (MRLs) established for residues of 

simazine.