Prometryn Registration Review Human-Health Assessment ~coping Document ·--·---

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 28-FEB-201 3 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Prometryn. Human-Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 080805 

Decision No.: l/121C.> 

Petition No.: NIA 

DP Barcode: D407422 

Registration No.: N/A 

Regulatory Action: Registration Review Scoping Document 

Risk Assessment Type: N/ A Case No.: 467 

TXRNo.: N/A CAS No.: 7287-19-6 

MRID No.: N/ A 40 CFR: § 180.222 

FROM: Kelly 

Anwar 

M. 

Y. 

Lo

Dunbar, 

we, Senior 

Ph.D.Environme,J armacntal olo Scientist~i {k1'1/ fj , t/t·/c_,/ 

. ~ 

Sarah J. Levy, Chemist bvt :?\ f 

Risk Assessment Branch 1 (RAB 1) 

Health Effects Division (HED, 7509P) 

THROUGH: Charles W. Smith III, Acting Branch Chiee:::: C )~5. "'> 

George 

RAB 1/HED 

F. Kramer, 

(7509P) 

Ph.D., Senior Cherni~.....,- ~ 

TO: Christina Schletema, Chemical Review Manager 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Attached is HED's human-health risk assessment scoping document for prometryn to support 

registration review. 

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______ Pr~me!!Y._~ ~e~J.~trat_i_~~_Re-:~~ Human-Health Assessment Scoping D~cume~ --- _ ____ _ 

Executive Summary 

Prometryn [2,4-bis(isopropylamino )-6-methylthio-s-triazine] is a substituted thiomethyl triazine 

herbicide (Group 5) registered in the U.S. for the control of weeds in a number of agricultural 

crops, such as celery, cotton, dill, pigeon peas, carrot, celeriac, cilantro, okra, parsley, and leaf 

petioles (crop subgroup 4B). There are no residential uses registered for prometryn. There are 

currently six prometryn containing end-use products sold under the following names: Caparol® 

4L (100-620), SuprenlM Herbicide (100-1163), Prometryne 4L Herbicide (two different 

Registrants: 9779-297 and 34704-692), Prometryn 4L Herbicide (66222-15), and Cotton-Pro® 

( 66222-116). In addition, there are several Special Local Need (SLN) labels, which include 

applications to carrots, celery, cotton, dill, parsnip, and parsley. 

The Prometryn Reregistration Eligibility Decision (RED) document was issued in 1996, at which 

time prometryn was registered for use on celery, cotton, dill, and pigeon peas (Memo, J. Redden 

et al., 16-MAR-1 995). In 1998, a tolerance without a US registration was issued for the use of 

prometryn on carrots (Memo, W. Wassell et al., D224645, 20-JAN-1998). In 2009, a humanhealth risk assessment was conducted for registration of prometryn on carrots in the US, as well 

as new food use registrations on celeriac, cilantro, okra, parsley, and leaf petioles (crop subgroup 

4B) (Memo, W. Wassell et al., D367830, 05-AUG-2009). There is one pending Pesticide 

Registration Improvement Extension Act (PRIA) action (petition #2E8052) for new food uses on 

snap beans and dill. 

HED has evaluated the status of the human-health assessments for prometryn to determine 

whether sufficient data are available and whether any updates are needed to support Registration 

Review. HED has considered all available data and human-health risk assessments for 

prometryn with respect to its toxicity, exposure, and usage databases, and the most updated 

Agency science policy and risk assessment methodologies to determine the scope of work 

necessary to support Registration Review. 

The toxicity database for prometryn is nearly complete at the present time with the exception of 

the neurotoxicity battery as required by the 2007 revised 40 CFR §158 Toxicology Data 

Requirements. These studies have been submitted to the Agency and will be reviewed during the 

pending PRIA action for new food uses on snap beans and dill. HED's Hazard and Science 

Policy Council (HASPOC) has determined that an inhalation toxicity study is required for 

prometryn at this time. Prometryn demonstrated minimal acute toxicity via the oral, dermal, and 

inhalation routes (Toxicity Category III or IV). It is mildly irritating to the eyes and slightly 

irritating to the skin and is a non-sensitizer of the skin. Effects in the subchronic and chronic 

oral studies in mice, dogs, and rats primarily occurred at the highest doses tested. No evidence 

of toxicity was observed in the dermal toxicity study in rabbits for prometryn. In rats and 

rabbits, fetal effects occurred at doses where maternal toxicity was seen. Parental and offspring 

effects occurred at similar doses, and there were no reproductive effects. In accordance with the 

1986 EPA Carcinogen Risk Assessment Guidelines, Prometryn is classified as a Group E 

chemical (Evidence of non-carcinogenicity for humans) based on the lack of evidence for 

carcinogenicity in mice or rats. During Registration Review, HED will reevaluate the points of 

departure (PODs) and uncertainty factors (Ufs) for the dietary and occupational exposure 

assessments. 

Adequate metabolism (crops, livestock, and rotational crops) and magnitude of the residue data 

are available to support the currently registered uses of prometryn, except for a metabolism study 

in a root crop. In the 2009 human-health assessment, two data gaps were identified: a 

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magnitude of residue study in carrots and a metabolism study in carrots (or other root crop). 

Since then, a magnitude of residue study in carrots has been submitted, along with a metabolism 

study in rice. These studies will be reviewed as part of the pending PRIA action for new food 

uses on snap beans and dill. After preliminary review of the metabolism in rice study, it appears 

that the metabolism in rice presents a different metabolic profile than the celery and cotton 

profiles; therefore, HED is still requesting a root crop metabolism study. HED is also requesting 

a ruminant feeding study at this time since the livestock dietary burden could change 

significantly pending the results of the root crop metabolism study. Based on available data, 

HED concluded that the residue of concern in cotton and celery, rotational crops, and livestock, 

for purposes of tolerance enforcement and risk assessment, is prometryn per se. Adequate 

methods are available for enforcement of the currently established tolerances. 

The dietary-exposure database is adequate to support current registration requirements. The 

most recent dietary-exposure assessment was performed in the August 2009 human-health risk 

assessment conducted by HED. As part of Registration Review, a revised dietary risk 

assessment may be necessary to reflect potential revised estimated drinking water concentrations 

(EDWCs), the most recent dietary exposure models, and/or revised toxicological PODs.

There is sufficient information available to assess occupational and residential exposure and risk 

from the registered uses. There are no residential uses currently registered for prometryn; 

therefore, a quantitative residential exposure/risk assessment is not necessary during Registration 

Review. Based on existing registrations, the previous assessments identified most of the 

anticipated occupational handler and post-application exposure scenarios with the exception of 

handler scenarios associated with a dry-flowable (DF) formulation. These scenarios may be 

included in Registration Review. Additionally, all occupational scenarios may need to be 

reassessed to address updates to HED’s exposure policies, including updates to default exposure 

data and assumptions for body weights. 

The following data deficiencies were identified for prometryn:

Toxicology: 

o 870.6200: Acute Neurotoxicity Study1.

o 870.6200: Subchronic Neurotoxicity Study1.

o 870.7800: Immunotoxicity Study1.

o 870.3465 : 90-day Inhalation study2.

Residue Chemistry: 

o 860.1300: Metabolism Study in Carrots (or other root crop)3.

o 860.1500: Magnitude of the Residue in Carrots1.

o 860.1480: Magnitude of the Residue Study in Ruminants.

Dietary Exposure: None.

Occupational/Residential Exposure: 

o 875.2100: Dislodgeable Foliar Residue (DFR) study.

 

1 These data have been submitted to the Agency and will be reviewed during the pending PRIA action for new food 

uses on snap beans and dill.

2

28-day inhalation study will be sufficient.

3 This study was required as conditional data per the 2009 HED risk assessment and has not been fulfilled at this 

time.
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EPA anticipates conducting the following risk assessment updates during Registration Review:

Toxicology: 

o Reevaluation of the toxicity endpoint/dose selection, along with the Food Quality 

Protection Act (FQPA) Safety Factor (SF) may be required.

Residue Chemistry: 

o The tolerance expression for prometryn in 40 CFR §180.222 needs to be updated

as follows to reflect current Agency policy: “Tolerances are established for 

residues of the herbicide prometryn, 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 prometryn (N,N'-bis(1-

methylethyl)-6-(methylthio)-1,3,5-triazine-2,4-diamine).....”

Dietary Exposure: 

o Revised dietary risk assessment may be necessary to reflect the potential revised 

EDWCs, dietary exposure models, and/or toxicological PODs.

Occupational/Residential Exposure: 

o Revised occupational handler and post-application risk assessment may be 

necessary based on the most recent exposure data and Agency policies, and 

should include an assessment of all registered formulations.

1.0 Introduction

Prometryn [2,4-bis(isopropylamino)-6-methylthio-s-triazine] is a substituted thiomethyl triazine 

herbicide (Group 5) registered in the U.S. for the control of weeds in a number of agricultural 

crops, such as celery, cotton, dill, pigeon peas, carrot, celeriac, cilantro, okra, parsley, and leaf 

petioles (crop subgroup 4B). There are no residential uses registered for prometryn. There are 

currently six end-use products sold under the following names: Caparol®4L (100-620), 

SuprendTM Herbicide (100-1163), Prometryne 4L Herbicide (two different Registrants: 9779-297 

and 34704-692), Prometryn 4L Herbicide (66222-15), and Cotton-Pro®(66222-116). In 

addition, there are several SLN labels, which include applications to carrots, celery, cotton, dill, 

parsnip, and parsley. All products are liquid formulations and contain prometryn as the sole 

active ingredient, except for SuprendTM Herbicide, which is a DF formulation and contains 

another active ingredient, trifloxysulfuron-sodium. This memo only evaluates the status of the 

human-health assessments for prometryn.

The Prometryn RED document was issued in 1996, at which time prometryn was registered for 

use on celery, cotton, dill, and pigeon peas (Memo, J. Redden et al., 16-MAR-1995). In 1998, a 

tolerance without an U.S. registration was issued for the use of prometryn on carrots (Memo, W. 

Wassell et al., D224645, 20-JAN-1998). The most recent human-health risk assessment was 

conducted in 2009 in support of registration of prometryn on carrots, as well as celeriac, cilantro, 

okra, parsley, and leaf petioles (crop subgroup 4B) (Memo, W. Wassell et al., D367830, 05-

AUG-2009). 

2.0 Hazard Identification/Toxicology

Prometryn is a substituted thiomethyl triazine herbicide that acts by inhibiting photosynthesis at 

photosystem II. For a summary of the acute, subchronic, and chronic toxicity profile, see 

Attachment 2. For a summary of the relevant toxicological endpoints used in risk assessment, 

see Attachment 3.
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In the rat metabolism study for prometryn, absorption from the gastrointestinal (GI) tract was not 

directly measured. However, based upon the urinary excretion profile, it can be estimated that 

47.06-53.3% of the 10-mg/kg single oral dose was absorbed. Because no bile duct ligation 

experiment was performed, it cannot be reasonably estimated how much of the fraction from 

feces was absorbed from the GI tract. Prometryn is distributed primarily to the blood, spleen, 

and lungs. There was a dose-dependent increase in tissue levels at 168 hours post dosing. 

Prometryn is extensively metabolized in rats, with <2% of recovered material representing the 

parent compound. Prometryn is excreted predominantly in the urine (47.06-53.3%) and feces 

(33.13-45.48%) out to 168 hours post dosing. These values were similar following 14 days of 

repeated low dosing, and for the high-dose group (500 mg/kg) at 168 hours. Greater than 90% of 

the radiolabel in the urine and feces was excreted by both sexes in the low dose groups by 24 

hours. Seventy-two hours were required for urinary and fecal excretion to be greater than 90% 

complete for the high-dose animals, suggesting saturation of either absorption or excretion. 

Prometryn demonstrated minimal acute toxicity via the oral, dermal, and inhalation routes 

(Toxicity Category III or IV). It is mildly irritating to the eyes and slightly irritating to the skin 

and is a non-sensitizer of the skin.

The only subchronic oral feeding study available for prometryn is a 28-day feeding study in 

mice. In this study, prometryn caused decreased body weight and/or mortality at doses that 

exceeded the limit dose (1000 mg/kg/day). Regarding chronic oral exposure, effects primarily 

occurred only at the highest doses tested for dogs, rats, and mice. Effects in the dog included 

degenerative hepatic changes, renal tubule degeneration, and bone marrow atrophy. In a 

combined chronic toxicity/carcinogenicity study in rats, effects included decreased body weight 

and body-weight gains and renal toxicity (mineralized concretions). In a carcinogenicity study in 

mice, the sole effect was decreased body-weight gain.

In the developmental and reproductive studies for prometryn, effects were observed primarily at 

the highest doses tested. Furthermore, fetal and offspring effects were observed at the same 

doses as maternal/parental toxicity. In rats, decreased body weight and food consumption and 

clinical signs of toxicity were observed in dams, and decreased fetal body weight and incomplete 

ossification of sternebrae and metacarpals were observed at the same dose in offspring. In 

rabbits, decreased food consumption and an increased incidence of resorptions, abortions, and 

post-implantation loss were observed in maternal animals and led to a decreased number of 

viable litters and live fetuses. In the two-generation rat reproductive study, decreased food 

consumption, body weight, and body-weight gain were observed in parental animals, and 

decreased body weights were observed in offspring at the same dose. There was no evidence of 

toxicity to the reproductive organs in the study.

No evidence of local or systemic toxicity was observed in a 21-day dermal toxicity study in 

rabbits. There was no evidence of carcinogenicity in either mice or rats, and prometryn was nongenotoxic or mutagenic. In accordance with the 1986 EPA Carcinogen Risk Assessment

Guidelines, Prometryn is classified as a Group E chemical (Evidence of non-carcinogenicity for 

humans); therefore, EPA is not likely to re-evaluate the carcinogenicity of prometryn. 

In the last risk assessment, three toxicity data gaps were identified: (1) an immunotoxicity study, 

(2) an acute neurotoxicity study, and (3) a subchronic neurotoxicity study. A 28-day dietary 

immunotoxicity study in female mice has been submitted to the Agency. Upon preliminary 

review, it was determined that prometryn caused a transient decrease in body weights, as well as 

a decrease in antibody formation response at the highest dose tested. The neurotoxicity 

screening battery tests have been conducted and will be reviewed during the pending PRIA 
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action for new food uses on snap beans and dill. The HED HASPOC has determined that a 

subchronic repeated dose inhalation study for prometryn is needed based on weight of evidence 

considerations, including the available toxicity data and the potential for exposure to prometryn 

via the inhalation route.

Conclusions: The toxicity database for prometryn is complete at the present time as required by 

the 2007 revised 40CFR Toxicology Data Requirements. HED’s HASPOC has determined that 

an inhalation toxicity study is required for prometryn at this time based on weight of evidence 

considerations, including the available toxicity data and the potential for exposure to prometryn 

via the inhalation route. During registration review, the endpoints, doses, and safety factors used 

in the most recent human health risk assessments should be reconsidered based on current HED 

policy, recently submitted studies, and any other outstanding data. 

3.0 Residue Chemistry

Tolerances are established for residues of prometryn per se in/on carrots, celeriac, cilantro, 

cotton, leaf petioles (crop subgroup 4B), okra, parsley, and pigeon peas at 0.05-9.0 ppm (40 CFR 

§ 180.222). Additionally, a permanent tolerance with regional registration is established under 

40 CFR §180.222(c) for residues of prometryn per se in/on dill at 0.3 ppm. Tolerances are also 

established for indirect or inadvertent residues of prometryn per se in/on the forage and straw of 

barley, oat, rye, triticale, and wheat at 0.3 ppm and the hay of barley, oat, rye, triticale, and wheat 

at 1.0 ppm.

The petitioner submitted adequate celery and cotton metabolism studies for prometryn, with 

these data indicating that metabolism proceeds via N-dealkylation and hydrolysis of prometryn. 

These data are sufficient for all registered crops, excluding carrot and celeriac. In the most 

recent assessment, a root crop metabolism study was requested as a condition of registration 

(Memo, W. Wassell et al., D367830, 05-AUG-2009). The petitioner has not submitted a root 

crop metabolism study, therefore, this conditional data is still considered outstanding. A

metabolism study in/on rice was recently submitted to the Agency, along with justification to 

explain why this study was submitted instead of the requested metabolism study in/on a root 

crop. HED is in the process of reviewing these data in conjunction with the pending PRIA action 

for new uses on snap beans and dill. However, after preliminary review, it appears that the rice 

metabolism study presents a different metabolic profile than the celery and cotton profiles; 

therefore, HED is still requesting a root crop metabolism study. 

The nature of the residue in livestock is adequately understood based on acceptable poultry and 

ruminant metabolism studies. The residue of concern (and that which should be regulated) in 

livestock is the parent, prometryn per se. As in plant commodities, the metabolism of prometryn 

in livestock involves N-dealkylation along with hydrolysis and/or amino acid conjugation. 

The 1994 Residue Chemistry Chapter concluded that residues of prometryn per se in meat and 

milk can be classified under Category 3 of 40 CFR §180.6(a); that is, there is no reasonable 

expectation of finite residues in meat and milk. Thus, no tolerances were required, and ruminant 

feeding studies were not required at that time. HED tentatively concluded in the 2009 

assessment (Memo, W. Wassell et al., D367830, 05-AUG-2009) that the Category 3 situation is 

still applicable with the carrot registration as long as a metabolism study was submitted in/on a 

root crop. HED is requesting a ruminant feeding study at this time since the livestock dietary 

burden could change significantly pending the results of the root crop metabolism study and this 

study requirement has not been fulfilled.
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The nature of the residue in rotational crops is also adequately understood. The metabolism of 

prometryn in rotational crops is similar to that of the primary crops and involves dealkylation, 

oxidation, hydroxylation, deamination, and conjugation. The residue of concern in rotational 

crops is prometryn per se.

Excluding carrot, adequate crop field trial and processing data are available. Previously, three 

additional carrot trials were requested in several regions reflecting application according to the 

maximum proposed use pattern, including use of a surfactant; with one of the trials generating 

residue-decline data. These data have been submitted, and HED is in the process of reviewing 

these data in conjunction with the pending PRIA action. HED notes that if the review of a future 

root crop metabolism study may indicate a major metabolite which was not monitored, then 

additional carrot field trial data could be required. 

There are no outstanding issues related to the use directions and/or tolerances. Adequate 

methods are available for enforcement of all currently established tolerances. In addition, the 

FDA PESTDATA database (dated 06/05) indicates that prometryn is completely recovered 

(>80% recovery) using the multiresidue method (MRM) in the Pesticide Analytical Manual, 

volume I (PAM, Vol. I) Section 302 and partially recovered (22-87% recovery) using Sections 

303 and 304, with the recovery varying depending upon the choice of Florisil system used. 

Conclusions: A metabolism study in/on a root crop is still required per the 2009 risk assessment. 

HED is requesting a ruminant feeding study at this time since the livestock dietary burden could 

change significantly pending the results of the root crop metabolism study. A carrot magnitude 

of the residue study (MRID 48727501) has been received by the Agency and will be reviewed as 

part of the pending PRIA action. Depending on the conclusions concerning the residues of 

concern in root crops, additional carrot and celeriac field trial data may be requested.

4.0 Dietary Exposure

HED has previously conducted acute and chronic dietary exposure analyses, which considered 

all currently registered uses (Memo, W. Wassell et al., D367830, 05-AUG-2009). The analyses 

were conducted using the Dietary Exposure Evaluation Model – Food Consumption Intake 

Database (DEEM-FCIDTM, ver. 2.03), which incorporates the food consumption data from the 

United States Department of Agriculture (USDA) Continuing Surveys of Food Intakes by 

Individuals (CSFII; 1994-1996 and 1998) and assumed tolerance-level residues and 100% crop 

treated. Dietary risk estimates were determined considering exposures from food plus drinking 

water using EDWCs for surface water sources provided by the Environmental Fate and Effects 

Division (EFED; Memo, S. Termes, 06/19/2009; D357096). In the 2009 risk assessment, 

EDWCs of 0.1579 ppm and 0.3774 ppm were incorporated directly in the acute and chronic 

analysis, respectively into the food categories “water, direct, all sources” and “water, indirect, all 

sources.” 

The residues of concern in drinking water identified in the 2009 EFED memo indicated that 

EDWCs were modeled for parent only. Recently, EFED provided information regarding the 

degradation products of prometryn (Memo, M. Ruhman and N. Mastrota, 01/08/2013, D408043), 

which indicated that the only major degradate of prometryn identified in the submitted 

environmental fate studies was hydroxypropazine (GS-11526). This transformation product 

accounted for 27% of the maximum percent applied radioactivity in the aerobic soil study. It

also accounted for 16-18% in the aerobic aquatic study and 15-31% in the terrestrial field 

dissipation study. All other transformation products identified in these studies were <7% of the 
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% applied radioactivity. Since there is limited information regarding the toxicity of 

hydroxypropazine, HED has taken a conservative approach and determined that the residues of 

concern for prometryn drinking water estimates should be parent plus hydroxypropazine (GS11526). Updated drinking water estimates will be calculated as part of the pending PRIA action. 

In the 2009 assessment, the resulting acute food plus water exposure estimates were not of 

concern to HED (<100% acute population-adjusted dose (aPAD)) at the 95th percentile of the 

exposure distribution for females 13 to 49 years old (only subgroup of interest). Specifically, the 

resulting acute exposure estimate for this subgroup was 16% of the aPAD. The resulting chronic 

exposure estimates were also not of concern to HED (<100% chronic PAD). The most highly 

exposed population subgroup was all infants (<1 year old) utilizing 30% of the chronic PAD 

(cPAD).

Conclusions: The dietary-exposure database is adequate to support current registration 

requirements. In the most recent risk assessment, neither acute nor chronic dietary exposures 

were of concern to HED. However, as part of Registration Review, revised dietary exposure 

analyses may be required to reflect the most recent dietary exposure models, potential revised 

EDWCs, and/or changes to the toxicological PODs.

5.0 Residential Exposure

The registered uses for prometryn are not expected to result in residential exposure; therefore, a 

quantitative residential exposure assessment has not been conducted and would not be required 

for Registration Review.

Spray Drift

Residential exposures resulting from off-site transport (e.g., spray drift or volatilization) may 

occur as a result of applications of prometryn. The Agency is in the process of evaluating these 

types of exposures and may, as appropriate, develop policies and procedures to identify the need 

for and, subsequently, the way to incorporate these post-application exposures into the Agency's 

risk assessments. The need for spray drift and volatilization risk assessment for prometryn will 

be examined during registration review.

Conclusions: There are no residential uses currently registered for prometryn; therefore, a 

quantitative residential exposure/risk assessment is not necessary during Registration Review.

6.0 Aggregate-Risk Assessment

The most recent aggregate-risk assessment was performed in conjunction with the August 2009 

human-health risk assessment conducted by HED (Memo, W. Wassell et al., D367830, 05-AUG2009). Since there are no residential uses for prometryn, only acute and chronic aggregate 

assessments were conducted, which only took into consideration dietary food plus water 

exposures. Neither the acute nor chronic aggregate risk assessments showed risks of concern

(aPAD for females 13 to 49 years old (only subgroup of interest) = 16% and cPAD for most 

highly exposed population subgroup (all infants <1 year old) = 30%). 

Conclusions: A new aggregate risk assessment may be required during Registration Review to 

incorporate potential changes to the prometryn toxicological PODs and dietary assessment. 

7.0 Occupational Exposure
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Occupational handler and post-application exposures are expected based on the registered

agricultural uses of prometryn. Attachment 4 provides a summary of the occupational use 

pattern. The current registrations include several SLN registrations. Current formulations 

include one dry flowable product and several liquid products. The application rates range from 

0.75 - 4 lb ai/A, and applications can be made either pre- or post-emergence. Most labels appear 

to restrict over-the-top sprays or allow them only up to an early crop stage (i.e., when few leaves 

are present). 

Occupational Handlers

There is the potential for dermal and inhalation exposure to occupational handlers from the 

currently registered use pattern of prometryn. In all past risk assessments, no chemical-specific 

data were available with which to assess potential exposure to pesticide handlers; therefore, 

occupational handler assessments were based primarily on surrogate unit exposures from the 

Pesticide Handlers Exposure Database (PHED). Previous risk calculations were based on the 

maximum application rates and assumed maximum area treated per day or gallons handled. 

Handler's exposure and risk were calculated at baseline (long pants, a long-sleeved shirt, no 

chemical-resistant gloves, and no respirator) and with personal protective equipment (PPE) when 

necessary (e.g., chemical-resistant gloves, respirators, and engineering controls). 

In the 1995 RED, which assessed the uses on celery, cotton, dill, and pigeon peas, occupational 

handler scenarios were assessed for wettable powder and liquid formulations at rates ranging 

from 0.8 - 3.2 lb ai/A. The mixer/loader scenarios for aerial (liquids and wettable powder) and 

groundboom (wettable powder) applications resulted in risks of concern. Currently, there are no 

wettable powder formulations registered for prometryn, and all but one of the liquid formulation 

product labels require some type of respirator and an apron as required PPE for mixer/loaders of 

aerial applications. In the 2009 assessment, which assessed the uses on carrots, celeriac, cilantro, 

okra, parsley, and leaf petioles (crop subgroup 4B), occupational handler scenarios were assessed 

for liquid formulations at rates ranging from 3.2 - 4 lb ai/A. None of the scenarios resulted in 

risks of concern as long as handlers wore protective gloves. Gloves are currently required as 

PPE on all registered prometryn labels.

Based on existing registrations, the previous assessments identified most of the anticipated 

occupational handler exposure scenarios with the exception of those associated with a DF

formulation. These scenarios may be included in Registration Review. Additionally, all 

occupational handler scenarios may need to be reassessed to address updates to HED’s exposure 

policies, including updates to default exposure data used for handler scenarios and assumptions 

for body weights. 

Occupational Post-Application

There may be the potential for post-application dermal exposure to workers following 

applications of prometryn to agricultural crops. As noted above, applications can be made either 

pre- or post-emergence, but most labels appear to restrict over-the-top sprays or allow them only 

up to an early crop stage (i.e., when few leaves are present). Therefore, any post-application 

exposure is expected only for early season activities (i.e., scouting, irrigation). 

In the 1995 RED, similar conclusions were made as to the diminished potential for postapplication exposure except for applications to celery, which could be made over the crop. It 

was noted that celery is often thinned by hand and, therefore, there could be potential postapplication dermal exposure. A quantitative assessment was not conducted since no data were 
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available; however, the RED required a DFR study on celery and determined that entry to treated 

areas should not be permitted immediately following application. The RED established a 24-

hour restricted-entry interval (REI) for celery and a 12-hour REI for all other crops. 

In the 2009 risk assessment for prometryn, early season post-application activities were assessed 

for celeriac and the leafy petioles crop group. No risk estimates of concern were identified and a 

12-hour REI was proposed. 

Since the previous reviews, there have been several updates to HED’s exposure policies, 

including updates to post-application transfer coefficients, transferable residue assumptions, and 

assumptions for body weights. Thus, these scenarios may need to be updated in the Registration 

Review assessment to be sure they are assessed using current policies and recommended 

exposure data.

In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are 

required when a pesticide has occupational uses that could result in post-application dermal 

exposure. HED analyzed a number of DFR studies and selected a new default value for the 

fraction of the application rate available to be dislodged after a foliar application (FAR). This 

default value is 25%. Of the analyzed DFR studies, the maximum FAR value seen was 89% or 

3.6 times higher than the default residue transfer value. Therefore, HED has decided that a 

calculated MOE of approximately four times higher than the level of concern (e.g., an MOE > 

400 if the LOC = 100) using the default dislodged residue values would provide an adequate 

margin of safety for any potentially higher residues seen in a chemical-specific DFR study. This

policy is described in Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and 

Dislodgeable Foliar Residue (DFR) Studies (Memo, J. Housenger, 12/12/12). A new DFR study 

for prometryn is required since estimated dermal MOEs for occupational workers exposed to 

treated foliage are not greater than 400.

Conclusions: The occupational exposure database is adequate to support the Registration 

Review process for prometryn. Previous occupational handler exposure assessments did identify 

risks of concern and additional PPE is currently required on some labels. Registration Review 

may include updated risk estimates based on revised surrogate unit exposures. Previous 

occupational post-application exposure assessments did not identify risks of concern; 

applications are mostly pre-emergent or early season post-emergent. Registration Review may 

include updated post-application risk estimates based on revisions to ExpoSAC Policy 3. 

Additional DFR data are necessary based on existing and anticipated occupational postapplication risk estimates.

8.0 Public Health and Pesticide Epidemiology Data

The Agency has reviewed the available incident data for prometryn (Memo, S. Recore and E. 

Evans, D406671, 13-NOV-2012) and concludes that based on the low frequency and severity of 

incident cases reported for prometryn, there does not appear to be a concern at this time that 

would warrant further investigation. The Agency will continue to monitor the incident 

information and if a concern is triggered, additional analysis will be included in the risk 

assessment.

9.0 Tolerance Assessment and International Harmonization
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U.S. permanent tolerances (listed in 40 CFR 180.222) are summarized in Attachment 5. There 

are no Codex or Mexican maximum residue limits (MRLs) in/on the registered crops. 

 

10.0 Environmental Justice

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

most recent prometryn human-health risk assessment, in accordance with U.S. Executive Order 

12898, “Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations,” 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The OPP 

typically considers the highest potential exposures from the legal use of a pesticide when 

conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and

people who may be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information.

11.0 Cumulative

Prometryn is a triazine, and certain triazine pesticides were identified as a common-mechanism 

group (CMG) by the Agency in a 2002 paper entitled, “The Grouping of a Series of Triazine 

Pesticides Based on a Common Mechanism of Toxicity.

4

” However, prometryn was excluded 

from the triazine CMG because it does not share the toxicity profile of the CMG triazines. 

Therefore, for the purposes of the prometryn registration review, EPA is assuming that

prometryn does not have a common mechanism of toxicity with other substances. 

12.0 Endocrine Disruption

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), prometryn is 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 

 

4

http://www.epa.gov/oppsrrd1/REDs/triazine_cumulative_risk.pdf
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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. Prometryn is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of Registration Review, EPA will issue future EDSP orders/data 

call-ins, requiring the submission of EDSP screening assays for prometryn. 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/.

13.0 Human Studies

Past prometryn risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. 

Many such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as PHED, the Outdoor Residential Exposure Task Force (ORETF)

Database, 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.

14.0 Risk Assessment Updates, Data Deficiencies, and Label Revisions

The following data deficiencies were identified for prometryn:

Toxicology: 

o 870.6200: Acute Neurotoxicity Study5.

o 870.6200: Subchronic Neurotoxicity Study4.

o 870.7800: Immunotoxicity Study4.

o 870.3465 : 90-day Inhalation study6.

Residue Chemistry: 

o 860.1300: Metabolism Study in Carrots (or other root crop)7.

o 860.1500: Magnitude of the Residue in Carrots4.

o 860.1480: Magnitude of the Residue Study in Ruminants.

Dietary Exposure: None.

 

5 These data have been submitted to the Agency and will be reviewed during the pending PRIA action for new food 

uses on snap beans and dill.

6

28-day inhalation study will be sufficient.

7 This study was required as conditional data per the 2009 HED risk assessment and has not been fulfilled at this 

time.
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Occupational/Residential Exposure: 

o 875.2100: DFR study.

EPA anticipates conducting the following risk assessment updates during Registration Review:

Toxicology: 

o Reevaluation of the toxicity endpoint/dose selection, along with the FQPA SF 

may be required.

Residue Chemistry: 

o The tolerance expression for prometryn in 40 CFR §180.222 needs to be updated 

as follows to reflect current Agency policy: “Tolerances are established for 

residues of the herbicide prometryn, 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 prometryn (N,N'-bis(1-

methylethyl)-6-(methylthio)-1,3,5-triazine-2,4-diamine).....”

Dietary Exposure: 

o Revised dietary risk assessment may be necessary to reflect the potential revised 

EDWCs, dietary exposure models, and/or toxicological PODs.

Occupational/Residential Exposure: 

o Revised occupational handler and post-application risk assessment may be

necessary based on the most recent exposure data and Agency policies, and 

should include an assessment of all registered formulations.

15.0 References

Table 3. Memoranda Relevant to Registration Review.

Author Barcode Date Title

J. Redden N/A 16-MAR-1995

The HED Chapter of the Reregistration Eligibility Decision 

Document (RED) for Prometryn, Case #0467 (Pesticide 

Chemical Code 080805; Reg. Group A).

J. Redden N/A 27-JUL-1995

The 2nd revised Mixer/Loader Exposure Assessment for 

the Reregistration Eligibility Decision Document (RED) for 

Prometryn, Case #0467 (Pesticide Chemical Code 080805).

W. Wassell et al. D237148, 

D224645 20-JAN-1998

PP#6E4691. Prometryn in or on Carrots. Tolerance with 

no U.S. Registration. U.S. Harmonization of Pesticide 

Tolerances with Canada.

W. Wassell et al. D367830 05-AUG-2009

Prometryn. Section 3 Registration Request to Add New 

Uses on Carrot, Celeriac, Cilantro, Okra, Parsley, and Leaf 

Petioles (Crop Subgroup 4B). Human-Health Risk 

Assessment.

W. Wassell D382622 22-DEC-2010

Prometryn (080805). Section 3 Registration Request to Add 

New Uses on Carrot, Celeriac, Cilantro, Okra, Parsley, and 

Leaf Petioles (Crop Subgroup 4B). Response (Dated 

09/03/2010) to Conditions of Registration.

Attachments: 

Attachment 1: Chemical Identity Table.

Attachment 2: Prometryn Acute, Subchronic, and Chronic Toxicity Profile

Attachment 3: Prometryn Endpoint Selection Tables.
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Attachment 4: Summary of Occupational Registered Uses Pulled From LUIS Report 

(dated 8/22/12).

Attachment 5: Prometryn International Residue Limit Status Sheet.

cc: K. Lowe (RAB1), S. Levy (RAB1), A. Dunbar (RAB1)

RDI: RAB1 (11/16/12), D. Vogel (11/16/12), J. Rowland (11/16/12)

K.Lowe:S10947:PY-S:(703)347-8989:7509P:RAB1
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Attachment 1: Chemical Identity Table.

Prometryn Nomenclature.

Chemical structure

Common name Prometryn

Company experimental name G-34161

IUPAC name N,N'-diisopropyl-6-(methylthio)-1,3,5-triazine-2,4-diamine

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

CAS registry number 7287-19-6

Physicochemical Properties of Prometryn.

Parameter Value Reference

Melting range 118-120 C DP# 207139, 12/8/94, C. Swartz

pH 6.7 at 20oC (saturated solution) RCB# 2907, 12/4/87, G. Makhijani

Density 1.16 g/mL at 20oC

Water solubility 33 ppm at 20oC DP# 207139, 12/8/94, C. Swartz

Solvent solubility 10-30 g/100 mL in acetone,

dichloromethane, methanol, 

octanol, and toluene at 20oC

Vapor pressure 8.54 x 10-7 mm Hg at 25oC DP#s 196116 & 196123, 4/25/94, K. 

Dockter

Dissociation constant, pKa 4.09 at 20oC RCB# 2907, 12/4/87, G. Makhijani

Octanol/water partition 

coefficient

KOW = 2140 at 25oC DP#s 196116 & 196123, 4/25/94, K. 

Dockter

UV/visible absorption spectrum Not available

N

N

N

HN

N

H

S

H3C

CH3

CH3

CH3

CH3
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Attachment 2: Prometryn Acute, Subchronic, and Chronic Toxicity Profile

Acute Toxicity Profile – Prometryn.

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 00060314

LD50 = 1802 (1265-

2568)/

2076 (1654-2607) 

mg/kg (M/F)

III

870.1200 Acute dermal (rat) 00060647 LD50 >3170 mg/kg III

870.1300 Acute inhalation (rat) 42325503 LC50 = 4.96 mg/L IV

870.2400 Primary eye irritation (rabbit) 40776601 Mild Irritation III

870.2500 Primary dermal irritation (rabbit) 00060317 Slight Irritation IV

870.2600 Dermal sensitization (Guinea pig) 00256682 Not a sensitizer N/A

Subchronic and Chronic Toxicity and Genotoxicity Profile – Prometryn.

Guideline 

No. Study Type MRID No./ Classification /Doses Results

870.3100 28-Day oral toxicity 

(mouse)

40457 515

Acceptable/non-guideline

0, 30, 100, 300, 600, 1,000, 

3,000, 10,000, or 30,000 ppm

NOAEL = 3000 ppm (~450 mg/kg/day).

LOAEL = 10000 ppm (~1500 mg/kg/day) based on 

decreased body weight.

870.3200 21-Day dermal 

toxicity (rabbit)

40573702

Acceptable/guideline

0, 10, 100, or 1000 mg/kg 

bw/day (limit dose)

NOAEL = 1000 mg/kg/day.

LOAEL not established.

870.3700a Prenatal 

developmental (rat)

404574517

Acceptable/guideline

0, 10, 50, or 250 mg/kg 

bw/day

Maternal NOAEL = 50 mg/kg/day.

LOAEL = 250 mg/kg/day based on salivation and 

decreases in body-weight and food consumption.

Developmental NOAEL = 50 mg/kg/day

LOAEL = 250 mg/kg/day based on decreased fetal 

body-weight and incomplete ossification of 

sternebrae & metacarpals.

870.3700b Prenatal 

developmental 

(rabbit)

00157995

Acceptable/guideline

0, 2, 12, or 72 mg/kg bw/day

Maternal NOAEL = 12 mg/kg/day.

LOAEL = 72 mg/kg/day based on decreased food 

consumption and increased incidence of resorptions, 

abortions, and post-implantation loss leading to 

decreased number of viable litters and live fetuses.

Developmental NOAEL = 12 mg/kg/day.

LOAEL = 72 mg/kg/day based on increased 

incidence of resorptions, abortions, and postimplantation loss leading to decreased number of 

viable litters and live fetuses.

870.3800 2-gen. reproduction 

and fertility effects

(rat)

41445101

Acceptable/guideline

0, 10, 750, or 1500 ppm (0/0, 

0.6/0.7, 47.8/53.6, or 

96.7/105.6 mg/kg bw/day 

[M/F])

Parental NOAEL = 10 ppm (0.6/0.7 mg/kg/day 

[M/F]).

LOAEL = 750 ppm (47.8/53.6 mg/kg/day [M/F]) 

based on decreased food consumption, body weight 

& body-weight gain.

Reproductive NOAEL = 750 ppm (47.8/53.6 

mg/kg/day [M/F]).

LOAEL not observed.

Offspring NOAEL = 10 ppm (0.6/0.7 mg/kg/day 

[M/F]).

LOAEL = 750 ppm (47.8/53.6 mg/kg/day [M/F]) 

based on decreased pup weight.

870.4100 Chronic toxicity (2-

year; dog)

00042794

Acceptable/guideline

0, 15, 150, or 1500 ppm (0.0, 

0.375, 3.75, or 37.50 

mg/kg/d) 

NOAEL = 150 ppm (3.75 mg/kg/day).

LOAEL = 1500 ppm (37.5 mg/kg/day) based on 

degenerative hepatic changes, renal tubule 

degeneration, and bone marrow atrophy.
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Subchronic and Chronic Toxicity and Genotoxicity Profile – Prometryn.

Guideline 

No. Study Type MRID No./ Classification /Doses Results

870.4300 Combined Chronic 

Toxicity/

Carcinogenicity

(rat)

41901201

Acceptable/guideline

0, 10, 100, 750 or 1500 ppm 

(males: 0, 0.38, 3.90, 29.45, 

or 60.88 mg/kg/d; females: 0, 

0.49, 4.91, 37.25, or 80.62 

mg/kg/d) 

NOAEL = 750 ppm (29.45/37.25 mg/kg/day [M/F]).

LOAEL = 1500 ppm (60.88/80.62 mg/kg/day [M/F]) 

based on decreased body weight and body-weight 

gains (both sexes) and renal lesions (mineralized 

concretions) (M).

No evidence of oncogenicity.

870.4200 Carcinogenicity

(mouse)

40466201

Acceptable/guideline

0, 10, 1000, or 3000 ppm (0, 

1, 100, or 300 mg/kg/d)

NOAEL = 1000 ppm (100 mg/kg/day).

LOAEL = 3000 ppm (300 mg/kg/day) based on 

decreased body-weight gain (F).

No evidence of oncogenicity.

870.5100 Bacterial Gene 

Mutation

40457518

Acceptable/guideline

Up to 1000-2000 ug/plate

Negative

870.5100 Bacterial Gene 

Mutation

40457519

Acceptable/guideline

Up to 1000 ug/plate

Negative

870.5385 In vivo bone marrow 

chromosomal 

aberration assay 

(Chinese hamster)

40457520

Acceptable/guideline

Up to 5000 mg/kg bw

Negative

870.5550 In vitro UDS assay 

(rat hepatocytes)

40457522

Acceptable/guideline

Up to 156.25 ug/ml

Negative

870.7485 Metabolism and 

pharmacokinetics

(rat)

41255901

Acceptable/guideline

0.46 or 467 mg/kg bw 

(single)

0.46 mg/kg bw (repeat)

Prometryn is distributed in blood > spleen > lungs 

(the three highest tissues measured). Distribution is 

not dosage-dependent. It is extensively metabolized 

with <2% of recovered 14C radioactivity representing 

the parent compound. Twenty-eight metabolites 

were identified in the urine, and 28 in the feces. Ten 

metabolites were identified in both urine and feces. 

Prometryn is excreted predominantly in the urine and 

feces, with slightly higher concentrations in the 

urine. The 7-day recovery of 14C radioactivity 

averaged 95% for all dosing groups.

870.7485 Immunotoxicity 

(mice)

48936501

Classification: Pending

0, 500, 2000, 5000 ppm

(0, 105.8, 413.1, 1044.5 

mg/kg/day)

Preliminary NOAEL = 413.1 mg/kg/day.

Preliminary LOAEL = 1044.5 mg/kg/day based upon 

a reduced humoral immune response using the sheep 

red blood cell assay.
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Attachment 3: Prometryn Endpoint Selection Tables.

Summary of Toxicological Doses and Endpoints for Prometryn for Use in Dietary Human-Health Risk 

Assessments. 

Exposure 

Scenario Point of Departure Uncertainty/FQPA Safety Factors

RfD, PAD, LOC for 

Risk Assessment

Study and Relevant 

Toxicological Effects

Acute Dietary 

(Females 13+)

NOAEL = 12

mg/kg/day

UFA = 10X

UFH = 10X

UFFQPA = 1X 

aRfD = aPAD = 0.12 

mg/kg/day

Developmental toxicity (rabbit)

LOAEL = 72 mg/kg based on 

increased incidence of resorptions, 

abortions, and post-implantation 

loss leading to decreased number 

of viable litters and live fetuses.

Chronic Dietary 

(All populations)

NOAEL = 3.75

mg/kg/day

UFA = 10X

UFH = 10X

UFFQPA = 1X

cRfD = cPAD = 0.04 

mg/kg/day

Chronic toxicity (dog; dietary)

LOAEL = 37.5 mg/kg/day based 

on degenerative hepatic changes, 

renal tubule degeneration, and 

bone marrow atrophy.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Group E: Evidence of non-carcinogenicity for humans.”

Abbreviations: UF = uncertainty factor, UFA = extrapolation from animal to human (interspecies), UFH = potential variation in sensitivity among 

members of the human population (intraspecies), UFFQPA = FQPA Safety Factor, NOAEL = no-observed adverse-effect level, LOAEL = lowestobserved adverse-effect level, RfD = reference dose (a = acute, c = chronic), PAD = population-adjusted dose.

Summary of Toxicological Doses and Endpoints for Prometryn for Use in Occupational Human-Health Risk 

Assessments.

Exposure 

Scenario Point of Departure Uncertainty Factors

Level of Concern 

for Risk Assessment Study and Toxicological Effects

Dermal

Short- and 

IntermediateTerm (1-30 

days and 1-6 

months)

NOAEL = 12

mg/kg/day 

Dermal-absorption 

factor = 15%

UFA = 10X

UFH = 10X

Occupational LOC 

for MOE <100

Developmental toxicity (rabbit)

LOAEL = 72 mg/kg based on increased 

incidence of resorptions, abortions, and 

post-implantation loss leading to 

decreased number of viable litters and 

live fetuses.

Dermal

Long-Term (>6 

months)

NOAEL = 3.75

mg/kg/day

Dermal-absorption 

factor = 15%

UFA = 10X

UFH = 10X

Occupational LOC 

for MOE <100

Chronic toxicity (dog; dietary)

LOAEL = 37.5 mg/kg/day based on 

degenerative hepatic changes, renal 

tubule degeneration, and bone marrow 

atrophy.

Inhalation

Short- and 

IntermediateTerm (1-30 

days and 1-6 

months)

NOAEL = 12

mg/kg/day 

100% inhalation 

assumed

UFA = 10X

UFH = 10X

Occupational LOC 

for MOE <100

Developmental toxicity (rabbit)

LOAEL = 72 mg/kg based on increased 

incidence of resorptions, abortions, and 

post-implantation loss leading to 

decreased number of viable litters and 

live fetuses.

Inhalation

Long-Term (>6 

months)

NOAEL = 3.75

mg/kg/day

100% inhalation 

assumed

UFA = 10X

UFH = 10X

Occupational LOC 

for MOE <100

Chronic toxicity (dog; dietary)

LOAEL = 37.5 mg/kg/day based on 

degenerative hepatic changes, renal 

tubule degeneration, and bone marrow 

atrophy.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Group E: Evidence of non-carcinogenicity for humans”

Abbreviations: UF = uncertainty factor, UFA = extrapolation from animal to human (interspecies), UFH = potential variation in sensitivity among 

members of the human population (intraspecies), UFFQPA = FQPA Safety Factor, NOAEL = no-observed adverse-effect level, LOAEL = lowestobserved adverse-effect level, MOE = margin of exposure, LOC = level of concern.
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Attachment 4: Summary of Occupational Registered Uses Pulled From LUIS Report 

(dated 8/22/12).

Formulation Use Site Application 

Equipment Application Timing Max App Rate REI Comments

Liquid 

Carrot 

(including 

tops)

Groundboom

Postemergence. Apply 

after crop has 3-5 true 

leaves.

1 lb ai/A

12 hr

SLN use. 

Used on 

carrot seed. 

Preemergence and 

postemergence (make 

through 6-leaf stage of 

carrot development).

2 lb ai/A

Liquid Celeriac

Groundboom Postemergence. Up to the 

6- to 8-leaf stage. 4 lb ai/A

Groundboom 12 hr

and 

Chemigation

Transplant. Apply after the 

crop has 6-8 leaves. 2 lb ai/A

Liquid Celery

Groundboom

Post-transplant. 2-6 weeks 

after transplant 3.2 lb ai/A 24 hr

Pre- and Post-transplant. 2-

6 weeks after transplant 2 lb ai/A 12 hr SLN use

Groundboom 

and 

Chemigation

Preemergence 1.6 lb ai/A 12 hr

Seed bed. Applications 

may be made over the crop 

after the crop has 2-5 true 

leaves.

0.8 lb ai/A 12 hr

Liquid Cilantro Groundboom Post-plant, preemergence 1.6 lb ai/A 12 hr

Liquid 

Cotton

Groundboom Preplant 1 lb ai/A 12 hr SLN use.

Aerial, 

Groundboom, 

Chemigation

Preemergence 2.8 lb ai/A 12 hr

Groundboom

Postemergence. Do not 

allow contact of spray with 

cotton leaves, or injury may 

occur. Direct spray to base 

of cotton plants.

1.6 lb ai/A 12 hr

Dry 

Flowable Groundboom Postemergence (avoid contact with cotton leaves) 1.2 lb ai/A 12 hr

Liquid Dill Groundboom

Postemergence. Apply 

after crop has 3-5 true 

leaves.

1 lb ai/A 12 hr

SLN use. 

Used on dill 

seed. 

Preemergence and 

Postemergence 1.6 lb ai/A 12 hr

Liquid Fennel

Groundboom 

and 

Chemigation

Post-transplant. 2-6 weeks 

after transplant 2 lb ai/A 12 hr

Groundboom Preemergence and Postplant 1.6 lb ai/A 12 hr

Groundboom 

and 

Chemigation

Preemergence 1.6 lb ai/A 12 hr SLN use. 

Groundboom

and 

Chemigation

Seed bed. Applications 

may be made over the crop 

after the crop has 2-5 true 

leaves.

0.8 lb ai/A 12 hr
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Formulation Use Site Application 

Equipment Application Timing Max App Rate REI Comments

Liquid 

Leafy petioles 

crops (cardoon, 

celery, chinese 

celery, celtuce, 

florence 

fennel, 

rhubarb, Swiss

chard)

Groundboom Post-transplant. 2-6 weeks 

after transplant 3.2 lb ai/A 12 hr

Groundboom 

and 

Chemigation

Preemergence 1.6 lb ai/A 12 hr

Groundboom 

and 

Chemigation

Postemergence. Apps can 

be made over the top of the 

crop when celery has 2-5 

true leaves.

1 lb ai/A 12 hr

Groundboom

Seed bed. Applications 

may be made over the crop 

after the crop has 2-5 true 

leaves.

0.8 lb ai/A 12 hr

Liquid Okra Groundboom

Preemergence. After 

planting before crop 

emergence for 1 app. 

1.5 lb ai/A 12 hr

Postemergence. Directed 

spray when plants at 7-9 

leaf stage.

0.75 lb ai/A 12 hr

Liquid Parsnip Groundboom

Postemergence. Apply 

after crop has 3-5 true 

leaves.

1 lb ai/A 12 hr

SLN use. 

Used on 

parsnip seed. 

Liquid Parsley Groundboom

Postemergence. Apply 

after crop has 3-5 true 

leaves.

1 lb ai/A 12 hr

SLN use. 

Used on 

parsley seed. 

Preemergence. Before crop 

emergence.

2 lb ai/A 12 hr

Liquid Pigeon peas Groundboom Preemergence. Before crop 

emergence.

3 lb ai/A 12 hr

Liquid Rhubarb Groundboom Dormant. Before leaves 

have emerged from crown. 2 lb ai/A 12 hr
Prometryn Registration Review Human-Health Assessment Scoping Document

_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ __________________________

Page 21 of 21

Attachment 5: Prometryn International Residue Limit Status Sheet.

Prometryn (080805); current as of 11/5/12

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.222:

Prometryn (2,4-bis(isopropylamino)-6-

methylthio-s –triazine)

None None

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

US Canada Mexico1 Codex

General Tolerances

Carrot, roots 0.45

Celeriac, roots 0.05

Celeriac, tops 0.20

Cilantro, leaves 3.5

Coriander, dried leaves 9.0

Cotton, gin byproducts 1.0

Cotton, undelinted seed 0.25

Leaf petioles subgroup 4B 0.50

Okra 0.05

Parsley, dried leaves 1.5

Parsley, leaves 0.60

Pea, pigeon, seed 0.25

Tolerances with regional registration

Dill 0.3

Indirect or inadvertent residues

Barley, forage 0.3

Barley, hay 1.0

Barley, straw 0.3

Oat, forage 0.3

Oat, hay 1.0

Oat, straw 0.3

Rye, forage 0.3

Rye, hay 1.0

Rye, straw 0.3

Triticale, forage 0.3

Triticale, hay 1.0

Triticale, straw 0.3

Wheat, forage 0.3

Wheat, hay 1.0

Wheat, straw 0.3

Completed: M. Negussie; 11/06/2012

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