UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

Date: June 4, 2013 

SUBJECT: Atrazine, Propazine, and Simazine. Human Health Risk Scoping Document in 

Support of Registration Review. 

PC Code: 080803,080808,080807 

Decision No.: 472844 

DP Barcode: D407489 

Registration No.: NA 

Petition No.: NA Regulatory Action: Registration Review 

Risk Assessment Type: Scoping Case No.: 0062, 0230, 0070 

TXRNo.:NA CAS No.: 1912-24-9, 139-40-2, 122-34-9 

MRIDNo.: NA 40 CFR: 180.220, 180.243, 180.213 

FROM: William Donovan, PhD, Risk 

Seyed Tadayon, Chemist~~~~-# 

John Liccione, PhD, Toxicologist 

Risk Assessment Branch V (RA 

Health Effects Division (HED) (7509P) 

Office of Pesticide Programs 

THROUGH: Michael S. Metzger, Chief If( J p1 jJ )/}/ / . Risk Assessment Branch V Vvfflv1 /f · / ~ 

Health Effects Division (750 P) 

Office of Pesticide Programs 

TO: Monica Wait, Chemical Review Manager 

Molly Clayton, Chemical Review Manager 

Risk Management and Implementation Branch III (RMIB3) 

Pesticide Re-Evaluation Division (PRO) 

Office of Pesticide Programs (7508P) 

Attached is Health Effects Division's (BED's) human health risk assessment status update 

(scoping document) for the herbicides atrazine, propazine, and simazine, as part of the 

registration review process. 

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Executive Summary 

The HED Atrazine, Propazine, and Simazine Registration Review Team has evaluated the status 

of the human health risk assessments for these triazine herbicides to determine the scope of work 

necessary to support Registration Review. These herbicides are being considered together in this 

seeping document because of their shared chloro metabolites, hazard identification, and hazard 

characterization. The most recent human-health risk assessment for atrazine was conducted in 

2002 (D272009, C. Eiden, 4/1 6/2002); for propazine in 2005 (D336673, J. Morales et al., 

12/13/2005); for simazine in 2006 (D325433, D. Soderberg et al., 1112/2006); and for the 

triazine cumulative assessment in 2006 (D317976, C. Eiden, 3/28/2006). HED has considered 

whether updates are needed to these assessments based on current Agency science policy and 

risk assessment methodologies; and after reviewing the toxicity, exposure and usage databases of 

these triazine herbicides. Between 2009 and 2011, the agency held five meetings of the FIFRA 

Scientific Advisory Panel (SAP) on topics related to non-cancer and cancer effects of atrazine 

and its chloro-triazine metabolites (http://www.epa.gov/scipoly/sap/meetings/index.htm). To 

support this seeping document, HED has updated the literature search for recent publications 

relevant to the human health risk assessment related to experimental toxicology and 

epidemiology studies. The Agency's issue papers

1 and respective SAP reports2 will be used to 

inform updates to the hazard assessment for atrazine, propazine, and simazine. 

In accordance with the 2007 revised 40 CFR Part 158 Toxicology data requirements, the 

neurotoxicity battery (acute and subchronic neurotoxicity studies) and an inhalation study are 

required for triazines. However, based on a weight-of-evidence (WOE) approach, considering 

all the available triazine hazard and exposure information, the HED Hazard and Science Policy 

Council (HASPOC) concluded that at this time no new dermal, inhalation, or neurotoxicity 

studies are required for atrazine, propazine, or simazine (K. Rury, in preparation). 

Residue chemistry studies submitted in response to previous data call-in requests for atrazine and 

simazine are currently in review. These reviews will be completed as part of the registration 

review risk assessments for the single chemicals as appropriate. 

The current tolerance expressions for atrazine, propazine, and simazine should be modified in 

accordance with the current policy on tolerance definitions (S. Knizner, 5/27/09). See the 

Tolerance Assessment section for the recommended language. 

In registration review, occupational exposure assessments will be updated to incorporate current 

occupational exposure policies, currently registered maximum application rates, and any changes 

to the toxicological endpoints. Similarly, residential exposure assessments will be updated to 

incorporate HED's 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment, currently registered maximum application rates, and any changes to the 

toxicological endpoints. 

Also in registration review, updated risk estimates for exposures to residues of atrazine, 

propazine, and simazine and their chlorinated metabolites in drinking water will be determined 

1 Issue paper citations. 2 Sap report citations. 

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for standard populations receiving their drinking water from community water systems (CWS), 

using the most recent results from on-going surface and ground water monitoring data programs. 

Introduction

Atrazine, propazine, and simazine are selective triazine herbicides that, for the purpose of this 

memo, are referred to collectively as the “chlorotriazine herbicides”. These herbicides are being 

considered together in this scoping document because of their shared chloro metabolites, hazard 

identification, and hazard characterization. They control a wide variety of broadleaf weeds and 

some grassy weeds. 

The chlorotriazine herbicides may be grouped together based on a common toxicity end-point

(neuroendocrine and neuroendocrine-related developmental and reproductive effects) and a 

known mechanism of toxicity for this endpoint. These three chemicals and their three major 

chloro metabolites, desethyl-s-atrazine (DEA), desisopropyl-s-atrazine (DIA), and 

diaminochlorotriazine (DACT), constitute the triazine common mechanism group (CMG). For 

the purpose of this memo, these six compounds are referred to collectively as the “CMG 

triazines”, which can cause a disruption of the hypothalamic-pituitary-gonadal (HPG) axis in the 

rats by alteration of levels of luteinizing hormone (LH). The grouping of the CMG triazines

based on a common mechanism of action was presented to the FIFRA SAP in 2000. The SAP 

agreed with the Agency’s conclusion that there is sufficient evidence to support the proposed 

grouping for the neuroendocrine and neuroendocrine-related effects (USEPA, 2000). 

Refer to Attachment 1 for relevant nomenclature and physical properties of the chlorotriazine 

herbicides, and the chemical structures of the CMG triazines.

Use Profile

Atrazine is registered for the control of broadleaf weeds and some grassy weeds. Atrazine is used 

on corn (field, pop, and sweet), sorghum, sugarcane, wheat (application to wheat stubble on 

fallow land following harvest), guava, macadamia nuts, hay, pasture, fallow, forestry or 

woodlands, conifers, woody ornamentals, Christmas trees, sod, and residential and recreational 

turf (parks, golf courses). Most atrazine use on lawns is in Florida and the Southeast. 

Propazine is registered in the U.S. for indoor greenhouse uses and on sorghum (predominantly 

used in TX). 

Simazine is registered for use in/on a variety of food and feed crops in the United States. 

Simazine is also used on ornamental plants, Christmas tree farms, nursery stock, building 

perimeters, non-agricultural areas, shelterbelt plantings, home lawns, golf courses, and turfgrass 

grown commercially for sod, as well as in forestry.

Atrazine is formulated for occupational use as liquid, wettable powder, dry flowable,

and granular products. In several formulations, atrazine is combined with other active 

ingredients, usually herbicides, and it is also formulated with fertilizer. Simazine is 
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formulated as wettable powders, emulsifiable concentrates, and flowable

concentrates. Propazine is formulated for occupational use as a liquid product.

Hazard Identification/Toxicology

For the purpose of estimating risks, the CMG triazines are assumed to be equivalent in toxicity to 

atrazine. This health-protective assumption is based on the evaluation of endocrine-related data 

on the chlorotriazine herbicides demonstrating either equal potency or potency less than atrazine,

and minimizes the possibility of underestimating risk3.

The CMG triazines exhibit low acute toxicity via oral, dermal, and inhalation routes of exposure 

(Category III or IV), and are not dermal sensitizers. 

As a result of their common mechanism of toxicity, exposure to the CMG triazines results in 

reproductive and developmental effects that are considered relevant to humans. These effects 

form the basis of the regulatory endpoint selection for triazines. The toxic mode of action 

involves central nervous system (CNS) toxicity (suppression of the luteinizing hormone surge 

prior to ovulation resulting in prolonged estrus in adult female rats (demonstrated with atrazine 

and simazine)), and developmental delays (delayed vaginal opening and preputial separation in 

developing rats (studied in atrazine but not simazine)). These neuroendocrine effects are 

considered the primary toxicological effects of regulatory concern. 

In recent years, numerous governmental and academic research groups have published 

experimental toxicology and epidemiologic studies evaluating the toxicity profile and/or mode of 

action (MOA) of atrazine. These new studies have considered a variety of adverse outcomes

such as reproductive toxicity in males and females, adverse birth outcomes, hormone disruption, 

neurotoxicity, immunotoxicity, respiratory health, effects on the mammary gland, and 

carcinogenicity. To consider the extent to which these new studies may influence the Agency’s 

human health risk characterization for atrazine, OPP in collaboration with the Office of Research 

and Development (ORD) has evaluated the new research on atrazine and its chloro-s-triazines 

metabolites (DEA, DIA, and DACT). Between 2009 and 2011, the agency held five meetings of 

the FIFRA Scientific Advisory Panel (SAP) on topics related to non-cancer and cancer effects of 

atrazine and its chlorinated metabolites of concern 

(http://www.epa.gov/scipoly/sap/meetings/index.htm). 

The February 2010 SAP meeting (public docket EPA-HQ-OPP-2009-0851) focused on a number 

of broad scientific issues related to the use of epidemiology and human incident data in risk 

assessment known as the draft Framework. The “Framework” delineated OPP’s proposed 

method of identifying, evaluating, and synthesizing epidemiology data within the regulatory 

review process, and also described issues related to the integration of both toxicology and 

epidemiology to inform hazard identification, characterization and exposure-response 

assessment. At this meeting, EPA also presented a case study of the preliminary evaluation and 

 

3 USEPA (2006). Triazine Cumulative Risk Assessment. HED Human Health Risk Assessment in Support of the 

Reregistration Eligibility Decisions for Atrazine, Simazine and Propazine. PC Codes: 080808, 080803, 080807. DP 

317976. May 28, 2006
Page 5 of 29

synthesis of epidemiology studies concerning atrazine exposure in relation to adverse birth 

outcomes. The FIFRA SAPs consideration of the “Framework” as well as the case study 

provided useful advice to consider as OPP works to incorporate epidemiology data in risk 

assessment. The materials prepared and presented at this meeting have informed the review of 

numerous epidemiology studies on atrazine. 

The April and September 2010 SAP meetings (public dockets EPA-HQ-OPP-2010-0125 and 

EPA-HQ-OPP-2010-0481 respectively) included a review of numerous atrazine in vivo and in 

vitro experimental toxicology studies as well as epidemiology evaluations concerning the noncancer health effects of atrazine. The focus of these reviews were studies published between 

2003 and January 2010; EPA had previously summarized the experimental and observational

literature on this topic in the 2002 human health risk assessment and June 2003 FIFRA SAP on 

atrazine, respectively. Based on these analyses, the agency concluded and the SAP concurred 

that attenuation of the LH surge continues to be the most sensitive effect (i.e., occurs at the 

lowest dose) identified to date in the atrazine database. Perturbations of LH signal a disruption 

of the hormonal environment in the individual and serve as a sentinel effect used to establish a 

point of departure (PoD) for the risk assessment that would be health protective for the other 

effects noted in the database. These other effects occur at higher doses than the LH surge 

attenuation and include delays in puberty onset, disruption of estrous cycles, and suppression of 

suckling-induced prolactin release in the lactating dams, leading to prostatitis in young adult rats; 

they provide insight into the temporal relationship between atrazine exposure and adverse health 

outcomes. Concerning the epidemiology evidence, EPA concluded and the SAP concurred that 

while the evidence of a possible association between atrazine exposure and non-cancer health 

outcomes such as male and female reproductive health effects (e.g., semen quality and menstrual 

cycle irregularities) and adverse birth outcomes (e.g., preterm birth and birth malformations) 

could plausibly be related to the herbicide’s influence on the hypothalamic-pituitary-gonadal 

(HPG) axis observed in the toxicology data, the strength of the epidemiologic evidence was 

insufficient to conclude a causal association may exist. Limitations in the epidemiology database 

were significant including inadequate characterization of atrazine exposure. In addition, while 

the observational data qualitatively support the experimental studies, the Agency will rely upon 

toxicology studies to perform hazard identification and characterization as well as dose-response 

assessment for non-cancer effects in the upcoming human health risk assessment.

At the September 2010 and July 2011 SAP meetings (public dockets EPA-HQ-OPP-2010-0481 

and EPA-HQ-OPP-2011-0399 respectively), the Agency proposed a range of exposure durations 

relevant for the toxic effects of 4-28 days. A single value was not proposed due to uncertainties 

in the duration required to elicit toxic effects, particularly in humans. The SAP commented in the 

December 2010 report that “the imprecision in the Agency’s proposed sampling frequency seems 

justified. This may be about as precise an estimate as can be obtained when starting with the 

experimental animal data and the exposure requirements for LH surge suppression...” 

The CNS mechanism of toxicity also results in mammary tumors specific to female SpragueDawley rats exposed to chlorotriazine herbicides; however, the particular cascade of events 

leading to tumor formation is species, strain and sex specific, and is not considered to be 

operative in humans. Consequently, atrazine has been classified as “Not Likely to be 

Carcinogenic to Humans”, as described in the June 2000 Scientific Advisory Panel (SAP) report. 

This classification also pertains to propazine and simazine. At the April 2010 SAP (public 
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docket EPA-HQ-OPP-2010-0125), the Agency reviewed new experimental toxicology studies on 

cancer published since the last atrazine risk assessment in 2003. The Agency concluded, and the 

SAP concurred, that the new experimental toxicology studies on cancer did not alter or 

contradict the major key events in the neuroendocrine MOA leading to mammary gland tumors 

in the rat or the conclusion that the MOA leading to mammary gland tumors in the rat is not 

relevant to humans. In July 2011 (public docket EPA-HQ-OPP-2011-0399), EPA presented its 

review of the cancer epidemiology studies for atrazine published since 2003. In this meeting, 

EPA concluded the epidemiology evidence are not strong enough to warrant a change to its 

current cancer classification for atrazine, although SAP panel members urged the Agency to 

continue to follow the published cancer epidemiology literature with regard to ovarian, thyroid 

and possibly lymphohematopoietic cancers specifically. The SAP stated that although studies of 

these anatomical cancer endpoints are inconclusive at this time, Panel members believed the data 

were suggestive of a possible association and warrant close evaluation in future assessments. 

During registration review, EPA will perform an up to date atrazine/triazine cancer epidemiology 

literature review in support of the human health risk assessment in consideration of the Panel’s 

advice. 

Per the 2007 revised 40 CFR Part 158 Toxicology data requirements, the neurotoxicity battery 

(acute and subchronic neurotoxicity studies) and an immunotoxicity study are all required for the 

chlorotriazine herbicides. However, HASPOC (meeting of 2/14/13) determined that acute and 

subchronic neurotoxicity studies are not required because the available data for the chlorotriazine

herbicides indicate that the neuroendocrine effects described above will be more sensitive than 

any potential apical neurotoxicity effects seen in adult animals in the neurotoxicity studies. In an 

immunotoxicity study in rats with atrazine, there was no evidence of immunosuppression at the 

highest dose tested. Although a few recent studies in the published literature suggest a potential 

for atrazine to affect the immune system at high doses, the available data do not indicate 

atrazine-induced immunotoxicity is a more sensitive endpoint than the atrazine-induced effects 

on neuroendocrine function, e.g., attenuation of LH surge in female Sprague -Dawley rats. Thus, 

based on the atrazine immunotoxicity data, studies for propazine and simazine are not necessary. 

The points of departure (PoDs) and toxicity endpoints from the most recent risk assessments are 

summarized in Attachment 3, Table 3.1. The toxicity endpoints and PoDs for risk assessment 

were selected for acute and chronic dietary, and short- and intermediate-term dermal, incidental 

oral, and inhalation scenarios. Toxicity endpoints for the chlorotriazine herbicides will be reevaluated after consideration of recent studies in the published literature. With respect to the 

endpoint selection and relevant duration(s) of exposure, the agency plans to update the information 

contained in Attachment 3, Table 3.1 based on the SAP reviews from 2010 and 2011. 

There are no toxicology data gaps for the chlorotriazine herbicides (Attachment 4).

Residue Chemistry

In response to data call-ins for the atrazine RED (GDCI-080803-25114 and GDCI-080803-

20871), a field accumulation in rotational crops study was submitted (MRID 47377502 and

Amended Final Report MRID 48487001). The final study report is currently in review; once 

complete, recommendations regarding the need for inadvertent tolerances on rotational crops at 

the desired plant-back intervals (PBIs) will be made. 
Page 7 of 29

In response to a data call in for the simazine RED (GDCI-080807-26426), and as part of a 

simazine new use petition (PP#2F8006), crop field trial, storage stability, field accumulation in 

rotational crops, and analytical method studies have been submitted (MRID 485777-01 thru -09; 

486822-01 thru -03; 488047-01 and 489601-01). These studies are currently in review. Data 

Evaluation Records (DERs) with classifications will be issued upon review completion.

No new residue chemistry studies were required for propazine during reregistration, and no 

recent data have been submitted. 

Dietary Exposure (food)

The 2006 triazine cumulative assessment indicated that negligible atrazine, propazine, and 

simazine exposures occur through foods. Thus, food related exposures to atrazine, propazine and 

simazine were set to zero for the aggregate and cumulative triazine dietary assessments. The 

rationale for this decision was based on the use patterns for these herbicides involving preemergent uses as soil directed sprays and the lack of detections in the monitoring and crop field 

trial databases. This decision will be re-evaluated in registration review, taking into account the 

most recent food monitoring and crop field trial data.

Dietary Exposure (water)

Atrazine

The occurrence of atrazine in the environment prompted the EPA’s Office of Water (OW) to 

regulate atrazine under the Safe Drinking Water Act (SDWA), and in 1991 OW established a 

Maximum Contaminant Level (MCL) of 3 parts per billion (ppb) for atrazine. Under the 

SDWA, atrazine has been subject to compliance monitoring. Consequently, there are extensive 

water (surface and ground) monitoring data available for atrazine: more than for any other 

pesticide. Thus, the 2002 atrazine drinking water exposure assessment was based only on 

monitoring data. As comparisons show higher total residue levels in surface water than in 

ground water, the 2002 dietary exposure assessments were based on surface water monitoring 

data, which are protective for residues in ground water.
Page 8 of 29

Screening-level exposure assessments were conducted for maximum one day (acute), 90-day 

average (intermediate-term), and annual average (chronic) exposures to residues of atrazine and 

its chlorinated metabolites in Community Water System (CWS) data collected from 1993-2001, 

for a total of 3670 systems. For acute exposures to the relevant population subgroup, females 

13-49 years, the maximum concentration of atrazine and its chlorinated metabolites measured in 

any CWS gave risk estimates below HED’s level of concern. Based on screening criteria used,

29 CWS (out of the pool of 3670 systems) were identified for probabilistic assessment for the 

intermediate-term exposure scenario. This analysis demonstrated that 90-day average exposures 

to atrazine and its chlorinated metabolites exceeded HED’s level of concern for infants in all 29 

CWS. Risk estimates for these CWS ranged from 1.0 – 6.7 times the LOC. For the chronic 

analysis, eleven of these systems had annual average concentrations of atrazine and its 

chlorinated metabolites that exceeded HED’s level of concern for children. 

As a result of the potential risk concerns identified, further refinements in the form of targeted, 

intensive monitoring data were requested. As part of the 2003 Interim Reregistration Eligibility 

Decision (IRED) for atrazine, a Memorandum of Agreement was developed for monitoring CWS 

in the United States. This monitoring program measures for the presence of the CMG triazines 

by determining total chlorinated triazine levels. An analysis of the most recent results from this 

monitoring program will be included as part of the registration review risk assessments. 

Simazine

Monitoring data are also available for simazine. In 2006, the monitoring data were considered 

adequate to evaluate water exposures in most major simazine use areas in the United States 

(Mid-West and Mid-Atlantic States, and Washington State), but inadequate for California and

Florida. Thus, PRZM/EXAMS modeling results were used to assess simazine water exposures 

in areas lacking sufficient monitoring data. For acute exposures to the relevant population 

subgroup, females 13-49 years, the maximum concentration of simazine and its chlorinated 

metabolites measured in any CWS was below HED’s level of concern, as were the peak water 

concentrations from all modeling scenarios. 

For intermediate-term water exposures, consideration of both monitoring data and modeling 

estimates resulted in the identification of scenarios where HED’s level of concern was exceeded. 

Specifically, from the monitoring data, two CWS from the Midwest (Defiance City, OH and 

Hillsboro, IL) were identified with exceedances for infants and children based on 90-day average 

simazine concentrations at these two locations. Based on 90-day average concentrations from 

PRZM/EXAMS modeling, several simazine application scenarios exceeded HED’s level of 

concern: almond uses (aerial applications only) in California, Georgia peach and nut uses (aerial 

and ground applications), and citrus uses in Florida (aerial and ground applications). However,

upon further review of the monitoring data, the Agency concluded that the maximum 90-day 

average concentration is lower than previously calculated, and no concentrations for this CWS 

are of concern to the Agency.

For chronic water exposures, annual average concentrations of simazine and its two chlorinated 
Page 9 of 29

metabolites were determined from the monitoring data and modeling results. This analysis 

showed no chronic exposure risk issues from any of the CWS monitoring data. 

Propazine

As no suitable water monitoring data were available for propazine, PRZM/EXAMS water 

modeling results were used for the dietary exposure assessment. No risk concerns were 

identified.

Cumulative Water Assessment

In the 2006 cumulative water assessment, CMG triazine residues in drinking water sources were

considered the only contributor to dietary exposure. A combination of monitoring and modeling 

data was used to assess the risk from potential exposures to CMG triazine residues in water. 

Based on chlorotriazine herbicide usage information provided by the Biological and Economic 

Affects Division (BEAD), the following drinking water exposure scenarios were assessed since 

they were considered representative of high-end exposures to the CMG triazines: 1) Mid-West 

using monitoring data, 2) California using modeling data, and 3) Florida using modeling data. 

Data from a pool of 118 CWS using surface water monitored from 2002-2004 for the CMG 

triazines were used for the cumulative drinking water assessment in the Mid-West. The 118 

CWS were ranked from high to low for peak concentrations (from 90-day rolling average 

exposures) of total CMG triazines. The 15 highest CWS were further analyzed using

probabilistic modeling, which showed no risk levels exceeded EPA’s level of concern for the 

four most vulnerable and sensitive population subgroups identified: infants < 1 year old, 

children 1-2 years old, females 13-49 years old, and males 20-49 years old.

Risk estimates for the California and Florida scenarios were based on PRZM/EXAMS modeling 

data, modified by a cumulative adjustment factor (CAF) to account for portions of the simulated 

watershed that are not treated with atrazine and/or simazine. Modeled 90-day average exposures 

were utilized to determine risk estimates for the same four population subgroups discussed 

above. No risk concern for any population subgroup was found. 

For the Florida and California drinking water exposure scenarios, PRZM/EXAMS modeling 

estimates were used in previous assessments. As part of registration review, the Agency will

determine if any updates to the water modeling estimates are appropriate, or if there are 

sufficient monitoring data available for these states. 

Residential Exposure

Registered residential uses for atrazine and simazine (no residential use for propazine) include 

application to residential turfgrass, ornamentals, and recreational turf areas. The duration of 

exposure is expected to be short-term (1-30 days) only; intermediate- and long-term exposures 

are not anticipated. The level of concern (LOC) for risk estimates is a margin of exposure 

(MOE) of less than 100 for short-term dermal, inhalation and oral exposure. Existing residential 

handler and post-application exposure and risk assessments do not show risk estimates of 

concern.
Page 10 of 29

Turf Transferable Residue (TTR): There are several TTR studies available for atrazine and 

simazine that will be used to assess residential post-application scenarios. 

There is sufficient information available to assess residential exposure. Previous residential 

exposure assessments for atrazine and simazine did not identify any scenarios that exceeded 

HED’s level of concern. However, as new residential SOPs containing additional turf scenarios 

have recently been finalized, the residential exposure assessments for atrazine and simazine will 

be updated in the registration review risk assessments. Any changes to toxicity endpoints and/or 

safety factors will also be included in these updates.

Aggregate Risk Assessment

Aggregate risk assessments evaluate the combined risk from dietary exposure (food and water) 

and any non-occupational (residential) uses. Separate assessments may be conducted to include 

relevant exposure durations: acute, chronic, short-, intermediate-, and long-term. Separate 

aggregate risk assessments have been conducted for atrazine, simazine, propazine, and the 

CMG triazines. 

For atrazine and simazine, acute aggregate risk estimates were the same as those for the acute 

drinking water assessment. Exposures from residential turf uses were aggregated with dietary 

exposures for a short-term aggregate risk assessment. No intermediate-term nor long-term 

exposures to atrazine or simazine are expected for residential uses. Thus, a quantitative 

intermediate-term assessment is not required, and chronic aggregate risk estimates were the 

same as those for the chronic drinking water assessments. 

Since there are no registered residential uses of propazine, its aggregate assessment consists of 

the dietary exposure (water only) assessment. 

During registration review, updated aggregate assessments may be conducted to include any 

updates to toxicological endpoints, dietary exposure estimates, and changes to residential SOPs.

Occupational Exposure

The chlorotriazine herbicides are registered for uses on agricultural crops and non-crop areas. The 

durations of exposure are expected to be short-term (1-30 days) and intermediate-term (1-6 

months); long-term exposures are not anticipated. The Agency’s LOC for short- and 

intermediate-term dermal and inhalation risk estimates is 100; i.e., MOEs below 100 are of 

concern to the Agency. Occupational handler and post-application exposure and risk 

assessments were conducted on the registered occupational (agricultural and non-crop) uses, 

resulting in risk estimates that are not of concern for the majority of scenarios. For those 

scenarios with risk estimates below 100 that exceeded HED’s level of concern, risk mitigation 

steps were taken (i.e., reduction in application rate). As a result of risk mitigation, new 

supplemental labels were created for some atrazine and simazine products. 

The current HED policy incorporates new scenarios that were not previously assessed (e.g. 

handheld equipment for turf and ornamentals); all relevant occupational exposure scenarios will 
Page 11 of 29

be considered when the registration review risk assessments are prepared.

Dislodgeable Foliar Residue (DFR): There are several DFR studies available for the 

chlorotriazine herbicides; these will be considered in assessing postapplication risk for re-entry 

scenarios. 

There is sufficient information available to assess occupational handler and post-application 

exposures. In registration review, an up-to-date quantitative occupational risk assessment may 

be required to account for current registered application rates, unit exposures, transfer 

coefficients (TCs), and toxicity endpoints and safety factors. 

Endocrine Disruptor Screening Program

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal 

Food, Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

different taxonomic groups. As part of its most recent registration decision, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), atrazine, simazine 

and propazine are subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Atrazine and

simazine are among the group of 58 pesticide active ingredients on the initial list to be screened 

under the EDSP. Once all required Tier 1 assays have been received and reviewed, the endpoints 
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and safety factors used for risk assessment purposes will be examined and a new risk assessment 

performed if necessary. Propazine was not included in the initial list. Accordingly, as part of 

registration review, EPA will issue future EDSP orders/data call-ins, requiring the submission of 

EDSP screening assays for propazine. For further information on the status of the EDSP, the 

policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 

screening battery, please visit our website: http://www.epa.gov/endo/.

Public Health and Pesticide Epidemiology Data

The April and September 2010 SAP meetings (public dockets EPA-HQ-OPP-2010-0125 and 

EPA-HQ-OPP-2010-0481 respectively) included a review of epidemiology evaluations 

concerning the non-cancer health effects of atrazine. EPA concluded, and the SAP concurred,

that while the evidence of a possible association between atrazine exposure and non-cancer 

health outcomes such as male and female reproductive health effects (e.g., semen quality and 

menstrual cycle irregularities) and adverse birth outcomes (e.g., preterm birth and birth 

malformations) could plausibly be related to the herbicide’s influence on the hypothalamicpituitary-gonadal (HPG) axis observed in the toxicology data, the strength of the epidemiologic 

evidence was insufficient to conclude a causal association may exist. Significant limitations in 

the epidemiology database were noted, including inadequate characterization of atrazine 

exposure.

In the July 2011 SAP meeting (public docket EPA-HQ-OPP-2011-0399), EPA concluded the 

epidemiology evidence are not strong enough to warrant a change to its current cancer 

classification for atrazine, although SAP panel members urged the Agency to continue to follow 

the published cancer epidemiology literature with regard to ovarian, thyroid and possibly 

lymphohematopoietic cancers. The SAP stated that although studies of these anatomical cancer 

endpoints are inconclusive at this time, the data were suggestive of a possible association and 

warrant close evaluation in future assessments. EPA will perform up to date atrazine/triazine 

cancer epidemiology literature reviews in support of the human-health risk assessment in 

consideration of the Panel’s advice. 

Based on the low frequency and severity of incident cases reported for atrazine, propazine and

simazine to both the OPP Incident Data System (IDS) and the National Institute for Occupational 

Safety and Health Sentinel Event Notification System for Occupational Risk – Pesticides 

(NIOSH SENSOR-Pesticides), there does not appear to be a concern at this time that would 

warrant further investigation (D407491, S. Recore, 1/22/13). The Agency will continue to 

monitor the incident information and if a concern is triggered, additional analysis will be also be 

included at that time.

Tolerance Assessment and International Harmonization

A summary of US tolerances for residues of atrazine, propazine, and simazine may be found in 

Attachment 2. No Codex Maximum Residue Limits (MRLs) have been established for atrazine, 

propazine, or simazine in/on any commodity. Mexico generally adopts US tolerances and/or 

Codex MRLs for export purposes. Canada has established MRLs for atrazine that are 

harmonized with US tolerances except for meat, milk, poultry and egg (MMPE) commodities. 
Page 13 of 29

For MMPE commodities, either the US tolerance is less than the Canadian MRL, or no US 

tolerance has been established.

Tolerances are established under 40 CFR §180.220 for the combined residues of atrazine and 

its three chlorinated metabolites in/on a variety of crops and livestock commodities. HED 

recommends that the residue definition for the tolerance expression for atrazine be modified in 

accordance with current policy on tolerance definitions (S. Knizner, 5/27/09), to read:

“Tolerances are established for residues of the herbicide atrazine, including its 

metabolites and degradates, in or on the commodities in the table below. Compliance 

with the tolerance levels specified below is to be determined by measuring only the sum 

of atrazine,6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, its desethyl

metabolite 2-amino-4-chloro-6-isopropylamino-s-triazine (G-30033) (DEA), its 

desisopropyl metabolite 2-amino-4-chloro-6-ethylamino-s-triazine (G-28279) (DIA), and 

its diamino metabolite 2,4-diamino-6-chloro-s-triazine (G-28273) (DACT), calculated as 

the stoichiometric equivalent of atrazine, in or on the commodity.”

Tolerances are established under 40 CFR §180.243 for residues of propazine in/on sorghum

commodities. HED recommends that the residue definition for the tolerance expression for 

propazine be modified in accordance with current policy on tolerance definitions, to read:

“Tolerances are established for residues of the herbicide propazine, including its 

metabolites and degradates, in or on the commodities in the table below. Compliance 

with the tolerance levels specified below is to be determined by measuring only the sum 

of propazine, 6-chloro-N,N’-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, its

desisopropyl metabolite 2-amino-4-chloro-6-isopropylamino-s-triazine (G-30033) 

(DEA), and its diamino metabolite 2,4-diamino-6-chloro-s-triazine (G-28273) (DACT),

calculated as the stoichiometric equivalent of propazine, in or on the commodity.”

Tolerances are established under 40 CFR §180.213 for the combined residues of simazine and 

its two chlorinated metabolites in/on a variety of crops and livestock commodities. HED 

recommends that the residue definition for the tolerance expression for simazine be modified in

accordance with current policy on tolerance definitions, to read:

“Tolerances are established for residues of the herbicide simazine, including its 

metabolites and degradates, in or on the commodities in the table below. Compliance 

with the tolerance levels specified below is to be determined by measuring only the sum 

of simazine, 6-chloro-N,N’-diethyl-1,3,5-triazine-2,4-diamine, its desethyl metabolite 2-

amino-4-chloro-6-ethylamino-s-triazine (G-28279) (DIA), and its diamino metabolite 

2,4-diamino-6-chloro-s-triazine (G-28273) (DACT), calculated as the stoichiometric 

equivalent of simazine, in or on the commodity.

Environmental Justice
Page 14 of 29

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with US Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf).

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used 

in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed 

and categorized by subgroups based on age, season of the year, ethnic group, and region of the 

country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups 

and exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

Cumulative 

For information regarding EPA’s efforts to determine which chemicals have a common 

mechanism of toxicity, and how to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/. 

In assessing cumulative risks, EPA evaluates the potential for people to be exposed to more than 

one pesticide at a time from a group with an identified common mechanism of toxicity. These 

cumulative assessments consider exposures from all relevant pathways and routes of exposure to 

all chemicals in a common mechanism group. The Agency incorporates regional exposures from 

residential and drinking water sources since this is the most appropriate way to account for the 

considerable variation in potential exposures across the country. EPA's cumulative assessments, 

therefore, estimate actual exposures and potential risks resulting from current uses of these 

pesticides in different parts of the country.

EPA followed a cumulative risk approach based on a common mechanism of toxicity for the 

CMG triazines. In the most recent cumulative risk assessment, issued on June 21, 2006, the 

agency evaluated water-only for the Midwest, California and Florida using a 90-day rolling 

average approach based on attenuation of LH from an atrazine study as the toxicity endpoint, and 

also evaluated multi-pathway exposure from water and residential turf exposure in Florida using 

a 28-day rolling average, and a 28-day pubertal atrazine study in rats. Thus, risk estimates from 

residential turf and drinking water exposures to atrazine and simazine were summed for Florida 
Page 15 of 29

only.

Results of probabilistic modeling demonstrated that cumulative risks were below HED’s level of 

concern for the most vulnerable and sensitive population subgroups at the 99.9th percentile of 

exposure. The majority of the cumulative exposure was from residential dermal exposure. 

Additional information and supporting documentation for the 2006 triazine cumulative 

assessment can be found in the public docket EPA-HQ-OPP-2005-0481.

The 2006 cumulative risk assessment for the CMG triazines demonstrated no risk levels 

exceeding HED’s level of concern. EPA anticipates updating the cumulative risk assessment 

during registration review to take into consideration recent monitoring and exposure data and 

any changes to toxicity endpoints and models or assessment methodologies. -

Human Studies

Past chlorotriazine herbicide risk assessments rely in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide or other chemical to determine their 

dermal and inhalation exposure. Many such studies, involving exposure to many different 

pesticides, comprise generic pesticide exposure databases such as the Pesticide Handlers 

Exposure Database (PHED) and the Agricultural Reentry Task Force (ARTF) Database. EPA 

has reviewed all the studies supporting these multi-pesticide generic exposure databases, and 

has found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards prevailing at 

the time the research was conducted. All applicable requirements of EPA’s Rule for the 

Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is 

no regulatory barrier to continued reliance on these studies.

Data Requirements

As shown in References below, the most recent human health risk assessments for atrazine, 

propazine, and simazine were conducted between 2002 and 2007. Provided the submitted 

residue chemistry data are found to be acceptable, there are no outstanding data gaps associated 

with the toxicology, exposure and residue chemistry requirements. 

References

Memoranda Relevant to Registration Review of Triazines

Author Barcode 

(DP#)

Date Title

Risk Assessments

C. Eiden D272009 4/16/2002 Atrazine. HED’s Revised Human Health Risk Assessment for the 

Reregistration Eligibility Decision (RED).

C. Eiden D317976 3/28/2006 Cumulative Risk from Triazine Pesticides

J. Morales et 

al.

D323271 12/13/2005 Propazine. Revised HED Risk Assessment for the Tolerance 

Reassessment Eligibility Decision Document (TRED) Which 

Includes a New Use on Grain Sorghum. 
Page 16 of 29

Memoranda Relevant to Registration Review of Triazines

Author Barcode 

(DP#)

Date Title

D. Soderberg 

et al.

D325433 1/12/2006 Simazine. Revised HED Chapter of the Reregistration Eligibility

decision Document (RED); Revised for Public Comments and to 

Correct SWLOC Values.

Incident Reports

S. Recore & E. 

Evans

D407491 1/22/2013 Atrazine, Propazine, and Simazine: Review of Human Incidents

Residue Chemistry

C. Eiden & D. 

Soderberg

D272006 4/16/2002 Atrazine. HED Product and Residue Chemistry Chapters.

J. Morales D308537 8/31/2005 Propazine. Residue Chemistry Summary for the Tolerance 

Reassessment Eligibility Decision Document (TRED) and a 

Proposal To Reinstate Food/Feed Use on Grain Sorghum.

D. Soderberg D326105 2/1/2006 SIMAZINE: Residue Chemistry Chapter for the RED, Revised to 

repair some inconsistencies in Table 11 compared to the rest of the 

text in the Chapter.

Occupational Residential Exposure

Gary Bangs D282457 4/25/2002 ATRAZINE: Revised Occupational and Residential

Exposure Assessment and Recommendations for the

Reregistration Eligibility Decision Document

Steven Weiss D316475 05/31/2005 SIMAZINE: Occupational and Residential Exposure

Assessment and Recommendations for the

Reregistration Eligibility Decision Document

Steven Weiss D308535 08/31/2005 PROPAZINE: Occupational and Residential Exposure

Assessments for the Proposed Sorghum Use and the

Existing Greenhouse Uses Updated with New Toxicity

Endpoints

Attachments

1. Chemical Identity Tables

2. Tolerance Summary Tables

3. Endpoint Selection Table

4. Toxicology Data Requirements
Page 17 of 29

Attachment 1

Chemical Identity Tables

TABLE 1.1. Atrazine Nomenclature.

Compound

Common name Atrazine

Company experimental name G-30027

IUPAC name 6-Chloro-N-ethyl-N-isopropyl-[1,3,5]triazine-2,4-diamine

CAS name 6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine

CAS registry number 1912-24-9

End-use product (EP) AAtrex® 4L

TABLE 1.2 Physicochemical Properties of Atrazine.

Parameter Value References

Melting point/range 176.0o C MRID 00142160, 00164822, 

43337901, 230302, Ciba 

Analytical Test #AG-87, 

Syngenta Study #1744-02

pH 7.0 at 25o C

Relative Density (20oC) 0.37 g/cm3

Water solubility (20oC) 0.033 g/L

Solvent solubility (g/100 mL at 20oC) Solvent grams/100 mL solvent

Acetone 3.2

Octanol 0.92

Ethanol 1.11

Toluene 0.42

Hexane 0.01

Vapor pressure 2.89 x 10-7 mm Hg

Dissociation constant, pKa PKa = 1.60 @ 20o C

Octanol/water partition coefficient, 

Log(KOW)

481 (log Pow = 2.68) at 25o C

Table 1.3 Propazine Nomenclature.

Compound

Common name Propazine

Company experimental name Not available

IUPAC name 6-chloro-N

2

,N

4

-di-isopropyl-1,3,5-triazine-2,4-diamine

CAS name 6-chloro-N,N’-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine

CAS # 139-40-2
Page 18 of 29

TABLE 1.4 Physicochemical Properties of Propazine. 

Parameter Value Reference1

Melting point 217.7 C RD D219079, 9/26/95, S. 

Malak

pH 5.66

Density 0.46 g/mL

Water solubility 3.8 ppm at 25 C

Solvent solubility (at 25°C) 14,252 ppm in acetone

4,696 ppm in 1-octanol

Vapor pressure 2.9 x 10-8 mm Hg at 20 C

2.98 x 10-5 Torr at 45 C

Product Chemistry Chapter 

of the Propazine 

Reregistration Standard, 

5/19/87

RD D219079, 9/26/95, S. 

Malak

Dissociation constant (pKa) Not applicable; practically insoluble in water RD D219079, 9/26/95, S. 

Malak Octanol/water partition coefficient Log(KOW) P = 1234.7

Log P = 3.08

TABLE 1.5 Simazine Nomenclature.

Chemical Structure

Empirical Formula C7N5H12Cl

Common name Simazine

Company experimental name G27692

IUPAC name 6-chloro-N

2

,N4-diethyl-1,3,5-triazine-2,4-diamine

Other Systematic 2-chloro-4,6-bis(ethylamino)-s-triazine

CAS name 6-chloro-N,N’-diethyl-1,3,5-triazine-2,4-diamine

CAS Registry Number 122-34-9

End-use product/EP Amizine, Gesapun, Primatol S, Princep, 

Chemical Class triazine herbicide

TABLE 1.6 Physicochemical Properties of Simazine.

Parameter Value Reference
Page 19 of 29

TABLE 1.6 Physicochemical Properties of Simazine.

Parameter Value Reference

Molecular Weight 201.7

Melting point/range 225-227 C Simazine Registration Standard 1989

pH 6 - 7 Simazine Registration Standard 1989

Density (specific gravity) 1.21 at 20 C Simazine Registration Standard 1989

Water solubility (20 C) 5 ug/g Simazine Registration Standard 1989

Solvent solubility (temperature not specified) 400 ppm in methanol at 20 C

3 ppm in n-pentane at 25 C

300 ppm in diethyl ether at 25 C

900 ppm in chloroform at 20 C

100 mg/20 mL in tetrahydrofuran

Simazine Registration Standard 1989

Table 1.7. Structures of Chlorotriazine Metabolites

Metabolite Structure

G30033

Desethyl Atrazine 

(DEA)

G28279

Desisopropyl Atrazine 

(DIA)

GG28273

Diamino chlorotriazine

(DACT)
Page 20 of 29

Attachment 2

Tolerance/MRL Table

Atrazine (PC Code 080803)

Table2.1 Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR § 180.220 

(a) General: combined residues of 

the herbicide atrazine (2-chloro-4-

ethylamino-6-isopropylamino-striazine) and its chlorinated 

metabolites 2-amino-4-chloro-6-

isopropylamino-s-triazine, 2-amino4-chloro-6-ethylamino-s-triazine, 

and 2,4-diamino-6-chloro-s-triazine

6-chloro-N-ethyl-N'-(1-

methylethyl)-1,3,5-

triazine-2,4-diamine, 

including the metabolites 

1,3,5-triazine-2,4-

diamine, 6-chloro-; 1,3,5-

triazine-2,4-diamine, 6-

chloro-N-ethyl- and 

1,3,5-triazine-2,4-

diamine, 6-chloro-N-(1-

methylethyl)-

None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Cattle, fat 0.02 0.04

Cattle, meat 0.02 0.04

Cattle, meat byproducts 0.02 0.04

Corn, field, forage 1.5

Corn, field, grain 0.20 0.2

Corn, field, stover 0.5

Corn, pop, forage 1.5

Corn, pop, grain 0.20 0.2

Corn, pop, stover 0.5

Corn, sweet, forage 15

Corn, sweet, kernel plus cob 

with husks removed

0.20 0.2

Corn, sweet, stover 2.0

Goat, fat 0.02 0.04

Goat, meat 0.02 0.04

Goat, meat byproducts 0.02 0.04

Grass, forage 4.0

Grass, hay 4.0

Guava 0.05

Horse, fat 0.02 0.04

Horse, meat 0.02 0.04

Horse, meat byproducts 0.02 0.04

Milk 0.02 0.04

Nut, macadamia 0.20

Sheep, fat 0.02 0.04

Sheep, meat 0.02 0.04

Sheep, meat byproducts 0.02 0.04

Sorghum, forage, forage 0.25

Sorghum, grain, forage 0.25

Sorghum, grain, grain 0.20
Page 21 of 29

Table2.1 Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Sorghum, grain, stover 0.50

Sugarcane, cane 0.20

Wheat, forage 1.5

Wheat, grain 0.10

Wheat, hay 5.0

Wheat, straw 0.50

MRLs With No US Equivalent

Eggs 0.04

Fat of Hogs 0.04

Meat of hogs 0.04

Meat byproducts of hogs 0.04

Fat of poultry 0.04

Meat of poultry 0.04

Meat byproducts of poultry 0.04

Completed: M. Negussie; 10/30/2012

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

(d) Indirect or inadvertent residues. Tolerances are established for indirect or inadvertent residues of 

atrazine, 2-chloro-4-ethylamino-6-isopropylamino-s-triazine, in or on the following raw agricultural 

commodity when present therein as a result of application of atrazine to the growing crops in paragraph 

(a) of this section:

Commodity Parts per million

Vegetable, leafy, except brassica, group 4 0.25
Page 22 of 29

Propazine (PC Code 080808)

Table 2.3 Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR § 180.243

(a) General: the sum of propazine, 

2-chloro-4,6-bis(isopropylamino)- s

-triazine, and its two chlorinated 

degradates, 2-amino-4-chloro-6-

isopropylamino- s -triazine and 2,4-

diamino-6-chloro- s -triazine, 

calculated as the stoichiometric 

equivalent of propazine

None None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Sorghum, grain, forage 0.25

Sorghum, grain, grain 0.25

Sorghum, grain, stover 0.25

Completed: M. Negussie; 10/30/2012

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Page 23 of 29

Simazine (PC Code 080807)

Table2.2 Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR § 180.213 

(a) General: combined residues of 

the herbicide simazine (2-chloro4,6-bis(ethylamino)-s-triazine) and 

its two chlorinated degradates (2-

amino-4-chloro-6-ethylamino-striazine and 2,4-diamino-6-chloro-striazine)

None None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex2

Almond 0.25

Almond, hulls 0.25

Apple 0.20

Avocado 0.20

Blackberry 0.20

Blueberry 0.20

Cattle, meat 0.03

Cattle, meat byproducts 0.03

Cherry 0.25

Corn, field, forage 0.20

Corn, field, grain 0.20

Corn, field, stover 0.25

Corn, pop, grain 0.20

Corn, pop, stover 0.25

Corn, sweet, forage 0.20

Corn, sweet, kernel plus cob 

with husks removed

0.25

Corn, sweet, stover 0.25

Cranberry 0.25

Currant 0.25

Egg 0.03

Goat, meat 0.03

Goat, meat byproducts 0.03

Grape 0.20

Grapefruit 0.25

Hazelnut 0.20

Horse, meat 0.03

Horse, meat byproducts 0.03

Lemon 0.25

Loganberry 0.20

Milk 0.03

Nut, macadamia 0.25

Olive 0.20

Orange 0.25

Peach 0.20

Pear 0.25

Pecan 0.20
Page 24 of 29

Table2.2 Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Plum 0.20

Raspberry 0.20

Sheep, meat 0.03

Sheep, meat byproducts 0.03

Strawberry 0.25

Walnut 0.2

Completed: M. Negussie; 10/30/2012

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Page 25 of 29

Attachment 3

Summary of Endpoints, Points of Departure, and Toxicology Data Requirements for 

Atrazine, Propazine, and Simazine.

Table 3.1 Summary of Toxicological Doses and Endpoints for Atrazine, Propazine, and Simazine Used in the Most Recent

Human-Health Risk Assessments.

Exposure Scenario Dose used in Risk 

Assessment, UF

FQPA SF and Level of Concern for 

Risk Assessment

Study and Toxicological Effects

Atrazine Acute Dietary 

(females 13-49)

Developmental

NOAEL = 10 

mg/kg/day

UF = 100

Acute RfD = 0.1

mg/kg/day

1X for hazard-based

concerns. 3X for exposure-based

concerns if atrazine monitoring

data used; 1X otherwise. 

aPAD = aRfD/FQPA SF

aPAD = 0.1 mg/kg/day (modeling)

aPAD = 0.033 mg/kg/day (monitoring)

Developmental toxicity study in rat & rabbit 

(weight of evidence from four studies) w/ 

atrazine.

Delayed ossification of certain cranial bones

in fetuses (LOAEL = 70 mg/kg/day).

Decreased body weight gain in adult

(LOAEL = 70 mg/kg/day).

Propazine Acute Dietary 

(females 13-49)

Developmental 

NOAEL =

10 mg/kg/day

UF = 100

Acute RfD = 0.1 

mg/kg/day

1X for hazard-based

concerns. 3X for exposure-based

concerns if propazine monitoring

data used; 1X otherwise. 

aPAD = aRfD/FQPA SF

aPAD = 0.1 mg/kg/day (modeling)

aPAD = 0.033 mg/kg/day (monitoring)

Development study in rats w/ propazine

LOAEL = 100 mg/kg/day

based on decreased ossification

Simazine Acute Dietary 

(females 13-49)

Developmental 

NOAEL = 30 

mg/kg/day

UF = 100

Acute RfD = 0.3 

mg/kg/day

1X for hazard-based

concerns. 3X for exposure-based

concerns if simazine monitoring

data used; 1X otherwise. 

aPAD = aRfD/FQPA SF

aPAD = 0.3 mg/kg/day (modeling)

aPAD = 0.1 mg/kg/day (monitoring)

Development study in rats w/ simazine

LOAEL = 300 mg/kg/day based on 

increased incidence of unossified teeth, 

head, centra vertebrae, sternabrae, and also 

on rudimentary ribs

Acute Dietary (general 

population)

No toxic effect attributable to a single dose was identified for the general population 

Chronic Dietary (all 

populations)

NOAEL = 1.8 

mg/kg/day

UF = 100

Chronic RfD = 0.018 

mg/kg/day

10Xfor residual hazard-based and 

exposure-based uncertainties

cPAD = cRfD/FQPA SF

cPAD = 0.0018 mg/kg/day

6-month LH surge study in rat w/ 

Atrazine

LOAEL = 3.65 mg/kg/day based on estrous 

cycle alterations and LH surge suppression 

Incidental Oral Short-Term NOAEL = 6.25 

mg/kg/day

UF = 100

3X for residual hazard-based concerns

LOC is an MOE of 300 for Residential 

Exposure

28-day Pubertal study in rats w/ Atrazine

LOAEL = 12.5 mg/kg/day based on delayed 

preputial separation

Incidental Oral IntermediateTerm NOAEL = 1.8 

mg/kg/day

UF = 100

3X for residual hazard-based concerns

LOC is an MOE of 300 for Residential 

Exposure

6-month LH surge study in rat w/ 

Atrazine

LOAEL = 3.65 mg/kg/day based on estrous 

cycle alterations and LH surge suppression

Dermal short-term NOAEL = 6.25 

mg/kg/day

UF = 100

3X for residual hazard-based concerns

LOC is an MOE of 300 for Residential 

Exposure

LOC is an MOE of 100 for 

Occupational Exposure

28-day Pubertal study in rats w/ Atrazine

LOAEL = 12.5 mg/kg/day based on delayed 

preputial separation

Dermal intermediate and longterm NOAEL = 1.8 

mg/kg/day

3X for residual hazard-based concerns

LOC is an MOE of 300 for Residential 

6-month LH surge study in rat w/ 

Atrazine
Page 26 of 29

Table 3.1 Summary of Toxicological Doses and Endpoints for Atrazine, Propazine, and Simazine Used in the Most Recent

Human-Health Risk Assessments.

Exposure Scenario Dose used in Risk 

Assessment, UF

FQPA SF and Level of Concern for 

Risk Assessment

Study and Toxicological Effects

UF = 100

Exposure

LOC is an MOE of 100 for 

Occupational Exposure

LOAEL = 3.65 mg/kg/day based on estrous 

cycle alterations and LH surge suppression

Inhalation short-term NOAEL = 6.25 

mg/kg/day

UF = 100

3X for residual hazard-based concerns

LOC is an MOE of 300 for Residential 

Exposure

LOC is an MOE of 100 for 

Occupational Exposure

28-day Pubertal study in rats w/ Atrazine

LOAEL = 12.5 mg/kg/day based on delayed 

preputial separation

Inhalation intermediate and 

long-term 

NOAEL = 1.8 

mg/kg/day

UF = 100

3X for residual hazard-based concerns

LOC is an MOE of 300 for Residential 

Exposure

LOC is an MOE of 100 for 

Occupational Exposure)

6-month LH surge study in rat w/ 

Atrazine

LOAEL = 3.65 mg/kg/day based on estrous 

cycle alterations and LH surge suppression

Dermal absorption = 6% (based on human data for atrazine)

Cancer (oral, dermal, 

inhalation)

Classification: Atrazine, propazine, and simazine are classified as “not likely to be carcinogenic to 

humans.”

UF = uncertainty factor, FQPA SF = Special 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, 

MOE = margin of exposure, LOC = level of concern
Page 27 of 29

Attachment 4

Toxicology Data Requirements

The requirements (40 CFR 180.220) for food uses of atrazine are in Table 4.1. Use of the new guideline numbers 

does not imply that the new guideline protocols were used.

Table 4.1 Summary of Toxicological Data Requirements for Atrazine

Test

Technical

Required Satisfied

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (nonrodent)

870.3200 21-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation*

yes

yes

yes

yes

yes

yes

yes

waived

waived

waived

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (nonrodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (nonrodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial

870.5300 Mutagenicity—Gene Mutation - mammalian

870.5385 Mutagenicity—Mammalian Bone Marrow 

 Chromosome Aberration Aberrations

870.5550 Mutagenicity—Unscheduled DNA Synthesis

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90-Day Neurotoxicity Screening Battery (rat)

870.6300 Developmental Neurotoxicity

yes

yes

yes

waived

waived

yes

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

yes

CR

yes

yes

yes

yes
Page 28 of 29

The requirements (40 CFR 180.243) for food uses of propazine are in Table 4.2. Use of the new guideline numbers 

does not imply that the new guideline protocols were used.

Table 4.2 Summary of Toxicological Data Requirements for Propazine 

Test

Technical

Required Satisfied

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (nonrodent)

870.3200 21-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation*

yes

yes

yes

yes

yes

yes

yes

waived

waived

waived

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (nonrodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (nonrodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial

870.5300 Mutagenicity—Gene Mutation - mammalian

870.5385 Mutagenicity—Mammalian Bone Marrow 

 Chromosome Aberration Aberrations

870.5550 Mutagenicity—Unscheduled DNA Synthesis

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90-Day Neurotoxicity Screening Battery (rat)

870.6300 Developmental Neurotoxicity

yes

yes

yes

waived

waived

yes

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

yes

CR

yes

yes

yes

yes
Page 29 of 29

The requirements (40 CFR 180.213) for food uses of simazine are in Table 4.3. Use of the new guideline numbers 

does not imply that the new guideline protocols were used.

Table 4.3 Summary of Toxicological Data Requirements for Simazine 

Test

Technical

Required Satisfied

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (nonrodent)

870.3200 21-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation*

yes

yes

yes

yes

yes

yes

yes

waived

waived

waived

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (nonrodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (nonrodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial

870.5300 Mutagenicity—Gene Mutation - mammalian

870.5385 Mutagenicity—Mammalian Bone Marrow 

 Chromosome Aberration Aberrations

870.5550 Mutagenicity—Unscheduled DNA Synthesis

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90-Day Neurotoxicity Screening Battery (rat)

870.6300 Developmental Neurotoxicity

yes

yes

yes

waived

waived

yes

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

yes

CR

yes

yes

yes

yes