UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

MEMORANDUM



### Date : 09-MA Y-2013 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: Ametryn

. Human-Health Assessment Scoping Document in Support of Registration Review.

DP Barcode: 0407652 Registration No. : N/ A PC Code: 080801 Decision No. : 473109 Petition No.: N/ A Risk Assessment Type : N/ A TXRNo .: N/A Regulatory Action : Registration Review Scoping Document Case No

. : 2010 CAS No.: 834-12-8 MRID No. : N/ A 40 CFR: § 180.258

FROM: Kelly M. Lowe, Senior Environmenta l Scientist

## ~ Chester E

. Rodriguez, Ph.D.,

### Toxi~l ·

### ~GJ-~1.:~~~~**d-.'~** Sarah J. Levy, Chemist

### ~ Risk Assessment Branch 1 (RABl) Health Effects Division (HED, 7509P)



### THROUGH: Dana M

. Vogel, Acting Branch Chief George F. Kramer, P h.D

., Senior Chemist RAB l /HED (7509P)



### TO: Molly Clayton, Chemical Review Manager Pesticide Re-Evaluation Division (PRD) (7508P) 

# ___ . ...**.**

Attac hed is HED's human-health risk assessment scoping document for ametryn to support Registration Review.

Page 1 of21**~etryn** Re gis trati on**.Y ie** **~ uma~-** **ealth** Assessm!nt**Sc~pi g** **ocum nt**  

### Executive Summary

Ametryn, N-eth yl-N'

- (1

- m e thylethyl)-6-(m e thylthio )

- 1 ,3 ,5

- triazine- 2,4

- diamin e, is a selective methylthiotriazine herbi c id e r eg i stere d for u se on com, pineapple, and s u garca n e. There are no

re s id en tial or non-agricultural u ses regi ste r ed for ametryn

. There i s currently one end-use produ ct (EUP) containing ametryn as th e act iv e ingred ie nt (ai) s old under the name Evik ® DF (100-786). The final HED c hapter of th e a metryn Reregi stratio n Eligibility Decision ( RED) docum e nt was issued in 2005 (Memo, W. Donovan et al., 15

- JUN

- 2005). There is one pendin g Special Local Needs (SLN) regi s tration for ametryn (HI120004) for application to s ugarcan e (same r ate as Section 3 regi str ation with revi se d spr ay dri ft language)

, which was receiv e d in Oct ober of 2012.

HED ha s eva luated the s tatus of the human

- health asse ssme nt s for ametryn to determine whether sufficient data are available and whether any updates are ne e ded to support Re g istration R ev iew. HED ha s co nsidered all available data and human-health ri s k assessments for ametryn with respect to it s toxicity, exposure, and usage databases

, and the most upda ted Agency science policy a nd ri s k asses s m ent methodologie s to determine the sco p e of w or k n e ce ss ary to s upp ort R egistration Re v i ew.

The available toxicity database for ametryn indicates that th e liver is a targ e t organ of toxicity and th e d og i s the most se n s itive specie s

. In a dog chronic

- toxicity study, r e port e d effect s includ ed hi s topatholo gica l fi nding s con s i ste nt with d egenerat i ve liver l es i ons. In the rat , hi sto patholo g i cal finding s we re report ed in th e kidney

, te stes, li v er , and pancrea s, but at higher admini s tered doses compared to the dog. Prenatal de velopmen t al toxicity s tudies in rats a nd rabbit s and a rat reproductive toxicity s tudy do not indicat e i n c r ease d pre- or po s tnatal susceptibility following ametryn exposure. Neither prenatal developmental toxicity study

rev ea l e d offspring effect s a nd the rat reproductive toxici ty s tudy only s how e d body-weight de c r ements at the same do se as s im ilar maternal toxicit y. In the fina l HED c h apter of the

am e tr yn RED (Me mo , W. Dono van et al

, 15

- JUN -200 5

, 0 3 1 6695), it wa s determined that do sing in a rat carcinogenicity s tud y wa s a d e quate for carci no gen icity as s e ss ment. Th e re s ult s indicated that that th e re wa s no indication of treatment

- relat ed increased in c id ence of tumor s in the absence of excessive body

- weight lo ss. In a mouse carcinogenicity st udy

, there was also no indication of treatm e nt-r e lated tumors at any dose. Th e r efore, a quantitativ e ca n ce r risk

asse ss ment was deem e d not n ecessary. In ac ut e toxicit y st udi es, ametryn wa s clas s ified a s ha v in g l ow ac ut e toxicit y v i a b y th e oral

, dermal

, and inhalation rout es (Tox i c it y Category III o r IV ). It wa s found to ca u se mild eye irritation, but it was neither a dermal irr itant nor a derm al

se n s iti ze r. The current toxicity databa se for ametryn lack s a 28- day inhalation toxicity, neurotoxicity (acute and s ubchronic), and immunotoxicity s tudies accordin g to the 2007 revi se d 40 CFR data requirem e nt s

. The HED' s Ha zar d and Scien ce Po l icy Council ( HASPOC) ha s determined that th e n e urotoxicity stu di es are n o t requir ed at this t ime ; howev e r , a 28-day inhalati on toxicity s tudy a nd an immunotoxi c it y s tudy are required.

Th e re s idue chemistry database is adequ ate to s upport current Registration Review requirem ents

. Adequ a t e metabolism (crops, livestock

, and ro t ational crops)

, s torage stability, magnitude of th e

re s idu e, a nd proce ssing d a t a are available to s upport the r eg i s tered uses. Adequate method s are available for enforcem e nt of the current ly e s tablished tol e r a n ces.

The di e tary-exposure d atabase i s adequate to su pport current registration r equ irement s. Th e l ast ri sk asse ss ment provid ed c hronic dietary (food only) expo s ur e es timate s th a t are below HED' s level of concern (LOC) for th e general U.S. population and all population s ub gro ups (M emo, W.
Page 2 of21Ametryn Registration Review Human

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Page 3 of 21 

### Donovan, 24

- MAY

- 2005; D316934). C hronic dietary (food only) risk estimates were less than <1.0% of the c hronic population

- adjusted dose (c PAD )

. As part of Registration Review, a revised dietary exposure analys i s will be requi red to reflect current Agency policy (incorporating both food and water exposures ) , the most recent dietary

- exposure models, and any potential changes to the toxicological points of departure ( PODs )

.

There is sufficient information available to assess o ccupational and residential exposure and risk from the registered uses. There are no residential uses currently registered for a metryn ; therefore, a quantitative residential exposure/risk assessment is not necessary during Registration Review. The previo us occupational handler assessment covered the relevant exposure scenarios and did not result in risk estimates of concern. Revised occupational handler assessments will be required during Registration Review to include revised surrogate unit exposures fo r occupational handlers 1 

### . An occupational post

- application assessment was not conducted previously based on (1) the use directions to avoid contacting foliage and (2) the timing of applications (early season). A quantitative occupational post

- application assessment will not be necessary during Registration Review.

The following data deficiencies were identified for a metryn :

Toxicology:

o 870.7800: Immunotoxicity Study

o 870.3465: 90

- day Inhalation study 2 

### Residue Chemistry:

o None

. Dietary Exposure:

o None

. Occupational/Residential Exposure:

o None.

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

Toxicology:

o Reevaluate toxicity endpoint/dose selection, along with the Food Quality Protection Act (FQPA) Safety Factor (SF) , based on submitted studies and any outstanding data needs

. Residue Chemistr y:

o The tolerance expression should be changed to conform to current HED policy (see S ection 9.0 of this document for details). Dietary Exposure:

o A r evised dietary risk assessment will be necessary to reflect current Agency policy ( incorporating both foo d and water exposures )

, the most recent dietary exposure models, and any potential changes to the toxicological PODs. Occupational/Residential Exposure:

o A r evised occupational handler risk assessment will be necessary to reflect the

1 O utlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table ” available at http://www.epa.gov/pesticides/science/handler

- exposure

- data.html
2 28

- day inhalation stu dy will be sufficient.Ametryn Registration Review Human

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Page 4 of 21 

### most recent occupati onal handler surrogate exposure data 3 

### and current Agency policies. Aggregate Exposure:

o A revised aggregate exposure assessment will be necessary to reflect the latest Agency policy [ the drinking water level of comparison (DWLOC) approach has been superseded ]
, a new dietary assessment (incorporating both food and water exposures) , and any potential changes to the ametryn toxicological PODs.

1.0 Introduction

Ametryn is a selective methylthiotriazine herbicide registered for use on corn, pineapple, and sugarcane. There are no residential uses registered for ametryn. There is currently one EUP with ametryn as the ai

, Evik ® 

### DF (100

- 786). This produc t is a dry

- flowable (DF) formulation containing 78.9 % ai . The final HED chapter of the ametryn RED document was issued in 2005 (Memo, W. Donovan et al

. , 15

- JUN

- 2005 , D316695 ). This is the most recent human

- health risk assessment for ametryn. There is one pending SLN registration for ametryn (HI120004 ;

su garcane ), which was received in October of 2012. This memo only evaluates the status of the human

- health assessments for a metryn

.

2.0 Hazard Characterization/Assessment

Ametryn is a methylthiotriazine herbicide . It is a member of the triazine family of herbicides and its mode of action involves inhibition of photosynthesis. Some of the toxic effects reported in mammals involving body

- weight decrements are consistent with a similar metabolism

disrupting mode of action.

Toxicity Database Based on the n ew guidelines as specified in 40 CFR Part 158 requirements, the following studies are currently missing in the ametryn toxicity database: neurotoxicity (acute and subchronic), immunotoxicity, and potentially a 28

- day inhalation toxicity study. The HASPOC met on January 17, 2013 (TXR #0056557) to decide on the missing studies for ametryn. In the case of the missing neurotoxicity studies, the committee determined that the acute and subchronic neurotoxicity studies are not required at this time. In the abs ence of an acute neurotoxicity study (870.6200), the rat prenatal developmental toxicity study where maternal clinical signs

, consisting of ptosis and salivation

, were observed after approximately two days of dosing will be used for the acute dietary endpo int of the general U.S. population. With regard to the immunotoxicity requirement, EPA’s Office of Pesticide Programs ( OPP ) has published the findings of an independent retrospective analysis of 170 immunotoxicity studies submitted to the Agency. The ret rospective analysis suggests that the submitted immunotoxicity studies have not yet resulted in PODs that are lower than the PODs selected from other available guideline experimental toxicology studies. As a result, the currently available immunotoxicity studies have not impacted the Agency’s risk assessments. HED is in the process of developing a guidance document on data waiver considerations. In the interim, HED recommends that immunotoxicity studies continue to be required for registration and regist ration review chemicals. Lastly , the committee determined that a 28

- day rat inhalation toxicity study (870.3465) was required for ametryn. The decision was primarily based on the low margin of exposure (MOE) estimates when an oral POD is used for assessi ng occupational inhalation risk.

3 O utlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table ” available at http://www.epa.gov/pesticides/science/handler

- exposure

- data.htmlAmetryn Registration Review Human

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Page 5 of 21 

### Adsorption, Distribution, Metabolism, and Excretion (ADME) In rats, radiolabeled ametryn was readily absorbed into the systemic circulation when administered as a single dose or multiple doses via oral gavage to rats. Bas ed on the amount of radioactivity collected in urine (the primary clearance pathway), the fraction absorbed was estimated at 50

- 60%. There was extensive metabolism of ametryn to hydrophilic residues. The radiolabel was widely distributed, although tissue levels were relatively low

. Based on urinary and fecal excretion profiles, excretion primarily occurred in the first 48 hours.

Toxicological Effects In acute toxicity studies, ametryn was classified as having low acute toxicity via by the oral, dermal, and inhalation routes ( Toxicity Category III or IV). It was found to cause mild eye irritation, but it was neither a dermal irritant nor a dermal sensitizer.

The available toxicity database for ametryn indicates that the liver is a target organ of toxic ity and the dog is the most sensitive species. In a dog chronic toxicity study, reported effects were histopathological findings indicative of degenerative liver lesions including inflammation (granulomatous, purulent, and lymphocytic), isolated cellular necrosis, endogenous pigment deposition, vacuolar degeneration, and bile duct hyperplasia. At higher dose levels, there were also clinical signs consisting of ataxia, cachexia, coma, convulsions, hypersensitivity to touch, hypoactivity, hypotonia, pallor, tremors, and unkempt appearance. In the rat, toxicity reported at higher administered levels of ametryn compared to the dog, consisted of body weight and body

weight gain decreases and histopathological lesions in the kidney (mineralization in the renal pelvis), testes (interstitial hyperplasia), pituitary (hyperplasia), liver (hyperplasia), and pancreas (hyperplasia).

Prenatal developmental toxicity studies in rats and rabbits and a rat reproductive toxicity study do not indicate increased pre

- or postn atal susceptibility following ametryn exposure. Maternal effects in the rat study were limited to ptosis and salivation, while in rabbits, maternal effects were based on decreased body weight, feed consumption, and increased liver weight. Neither prenata l developmental toxicity study revealed offspring effects. In a rat two

- generation reproductive toxicity study, offspring body weight and body

- weight gain decrements were reported at the same dose as similar maternal effects (i.e., decreased body weight/ body

- weight gain and feed efficiency).

In a rat carcinogenicity study, at the highest average daily doses tested of 145.3 and 176.1 mg/kg/day for males and females, respectively, there was a significant increase in tumors in the testes, epididymis, and th yroid in males and both the liver and mammary gland in females. However, these effects were accompanied by excessive decrements in body weight and body

weight gain. At the next lower dose of 500 ppm, there was no effect on body weight reported, and there were no tumors seen

. In 2004, the HED Cancer Assessment Review Committee (CARC) evaluated the study findings and determined that the data was inadequate for assessment of human carcinogenic potential and requested for a new rat carcinogenicity study to b e conducted (TXR# 0052862). In 2005, HED conducted a re

- analysis of the body

- weight data for the 500 ppm group in conjunction with a more recent 90

- day subchronic study (MRID# 46467501) submitted by the registrant

. The results indicated that there was a consistently lower body weight of 3

- 7% for males for most of the duration and a comparable body

- weight decrease for females for most of the first 90 days of dosing. Since the body

- weight decrements at 500 ppm were now deemed adequate for carcinogenicity a ssessment and there was no indication of
treatment

- related increased incidence of tumors at this lower dose, a quantitative risk assessment was deemed not necessary and a new rat carcinogenicity study not required (D316605, W.Ametryn Registration Review Human

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Page 6 of 21 

### Donovan et al., 15

- JUN

- 2005 ). The decision for not requiring a new rat carcinogenicity study was supported by additional information from closely related s

- triazines: prometryn and terbutryn. The cancer studies with these structurally related chemicals support the notion that eithe r tumor are not seen at all at dose tested (prometryn) or are seen (terbutryn) at doses where body weight is drastically affected. The Agency’s Science Advisory Panel (SAP) evaluated the carcinogenicity data for terbutryn and determined that quantitative cancer risk assessment was not required (SAP meeting, 23

- DEC

- 1 987). In a mouse carcinogenicity study, there were no
treatment

- related tumors seen in males or females at any dose.

In the last HED chapter of the ametryn RED (Memo, W. Donovan et al

. , 15

- JUN

- 2005, D316695), a forward gene

- mutation assay in mammalian cell cultures was noted as a missing data requirement. Since then, a mouse lymphoma cells/mammalian activation gene forward mutation assay has been submitted and reviewed by the Agency. The resu lts of the study are in agreement with other genotoxicity assays indicating that there is no evidence of genotoxicity for ametryn.

Ametryn was not included in the cumulative risk assessment performed for triazines that included atrazine, simazine, and pro pazine because it does not cause the same carcinogenic profile as these chlorotriazines, and there is no mechanistic information that would support including it in this group.

There is no dermal penetration study or inhalation toxicity study based on repe ated exposures to ametryn. In the last risk assessment, a dermal

- absorption factor of 6% was indirectly estimated based on the no

- observed adverse

- effect level (NOAEL) of the rabbit prenatal developmental toxicity study and that from a 21

- day rabbit derma l toxicity study. The rabbit developmental toxicity study based on oral exposure was also used for assessing short

- and intermediate

- term occupational inhalation endpoints.

Conclusions: Based on the new guidelines as specified in 40 CFR Part 158 requirements, the following studies are currently missing in the ametryn toxicity database: neurotoxicity (acute and subchronic), immunotoxicity, and a 28

- day inhalation toxicity study. The HASPOC determined that while the neurotoxicity studies (acute an d subchronic) are not needed at this time, a 28

- day rat inhalation toxicity study (870.3465) is required for ametryn. HED is in the process of developing a guidance document on data waiver considerations for immunotoxicity studies. In the interim, HED re commends that immunotoxicity studies continue to be required for registration and registration review chemicals. During Registration Review , the endpoints, doses, and safety factors used in the most recent human

- health risk assessments should be reconside red based on current HED policy, recently submitted studies, and any other outstanding data.

3.0 Residue Chemistry

Permanent tolerances are established for residues of ametryn per se in/on field corn grain and stover, pop corn grain and stover, pineapple, and sugarcane commodities at 0.50 ppm, as well as a tolerance for corn forage at 0.1 ppm [40 CFR §180.258]. There are currently no tolerances for ametryn residues in livestock commo dities or for inadvertent residues in rotational crops.

The nature of the residue in primary crops and livestock is adequately understood based on the available corn, sugarcane, banana, goat, and hen metabolism studies. In plants, ametryn is extensively metabolized by N

- dealkylation and desulfation (oxidation/hydroxylation) to a varietyAmetryn Registration Review Human

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Page 7 of 21 

### of triazine ring containing metabolites. The metabolism of ametryn in livestock also involves N

dealkylation of the isopropyl and ethyl side chains, as well as modificati on at the 6

- position, followed by conjugation, with the triazine ring structure remaining intact. The regulated residues in plant commodities consist of ametryn per se . The residues of concern for tolerance enforcement and risk assessment (food only) als o consist of ametryn per se

. Adequate field trial data are available to support the use of ametryn on corn (field and pop), pineapples, and sugarcane. An adequate number of trials were conducted in the appropriate geographical regions using the appropria te formulation applied at the maximum use rate. These studies are also supported by adequate storage stability data. The available processing studies for corn, pineapple, and sugarcane are adequate and indicate that residues of ametryn and its three thio methyl metabolites are not likely to be quantifiable ( 0.02 ppm) in corn, pineapple, or sugarcane processed fractions derived from crops treated at the maximum labeled rates.

Adequate methods are available for enforcing tolerances and/or collecting data on ametryn residues in/on plant and livestock commodities. Two gas chromatography (GC) methods are available for enforcing tolerances of ametryn in plant commodities and are listed as Methods I and A in the Pesticide Analytical Method Volume II (PAM II; S ection 180.258). Method I is a GC/microcoulometric (MC) detection method for determining ametryn per se , with a limit of quantitation (LOQ) of 0.05 ppm. Method A is a GC/flame

- photometric detection (sulfur mode, FPD

- S) method for determining residues of ametryn and its three thiomethyl metabolites (GS

11354, GS

- 11355, and GS

- 26831), with a LOQ of 0.05 ppm for parent and 0.1 ppm for each metabolite.

Considering the data from the available livestock metabolism and feeding studies and the calculated maximum theoretical dietary burdens (MTDBs) of 0.15

- 0.18 ppm for cattle and 0.04 ppm for poultry and swine, HED concludes that there is no reasonable expectation of quantifiable residues of ametryn occurring in livestock commodities [40 CFR §180.6(a)(3)]. Theref ore, tolerances for livestock commodities are not required at the present time.

An adequate confined rotational crop study is available and indicates that the metabolism in rotational crops is similar to the primary crops. Adequate field rotational crop studies are also available and indicate that the labeled plant back intervals are appropriate and rotational crop tolerances are not required.

Conclusions: The residue chemistry database is adequate to support current R egistration Review data requirements. Adequate metabolism (crops, livestock, and rotational crops), storage stability, magnitude of the residue and processing data are available to support the registered uses. Adequate methods are available for enforcement of the currently esta blished tolerances.

4.0 Dietary Exposure

In the 2005 chronic dietary exposure assessment for the ametryn RED, HED conducted chronic dietary exposure analyses for all currently registered food uses of ametryn (Memo, W. Donovan, D316934 , 24

- MAY

- 2005). A cute dietary exposure analyses were not conducted since no acute endpo int was chosen for ametryn. The chronic dietary analyses were conducted using both the Dietary Exposure Evaluation Model

– Food Consumption Intake Database (DEEM

- FCID, ver. 2.0) model, as well as the Lifeline (ver. 2.0) model. Both models incorporated 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 averageAmetryn Registration Review Human

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Page 8 of 21 

### residue levels from applicable field trials, percent crop treated information, and DEEM (ver. 7.76) default processing factors. The chronic dietary assessments from both models show dietary (food only) risk estimates were less than 1.0% of the cPAD and were belo w HED’s LOC (i.e., <100% of the cPAD)

.

In the 2005 HED chapter of the ametryn RED (Memo, W. Donovan et al. , 15

- JUN

- 2005, D316695) , exposure to ametryn in drinking water was also assessed. Water models were used to assess potential exposure to ametryn f rom consumption of contaminated drinking water. Estimated drinking water concentrations (EDWCs) for ametryn were generated using the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) for surface water and the Screening Concentration in Ground Water (SCI

- GROW) 2 model for groundwater. The ametryn EDWCs were not incorporated into the dietary exposure assessment in the RED, but were compared to calculate d DWLOCs for the aggregate assessment (see Section 6 bel ow). Potential contaminants of concern considered in the drinking water exposure assessment were parent ametryn and the degradates 2

- amino

- 4

- isopropylamino

- 6

- methylthio

- s

- triazine (GS

11354), 2

- ethylamino

- 4

- amino

- 6

- methylthio

- s

- triazine (GS

- 11355), NOA

- 42 3271, and NOA

428383. Based on input from EFED on the environmental transformation products of ametryn, HED does not anticipate any changes to the residues of concern identified for ametryn. The modeled EDWCs for ametryn were 14 ppb for surface water and 1.4 ppb for groundwater. It is unlikely that updated drinking water estimates will be required during Registration Review.

Conclusions: The dietary

- exposure database is adequate to support current R egistration Review requirements. The chronic die tary assessments from both models show dietary (food only) risk estimates were less than 1.0% of the cPAD and were, therefore, below HED’s LOC (i.e., <100% of the cPAD) . As part of Registration Review, revised dietary exposure analyses will be required to reflect current Agency policy (incorporating both food + water exposures )

, the most recent dietary exposure models, and any potential changes to the toxicological PODs

.

5.0 Residential Exposure

The registered uses for a metryn are not expected to resul t in residential exposure; therefore, a quantitative residential exposure assessment has not been conducted and will 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 a metryn

. The Agency is in the process of evaluating these types of exposures and may, as appropriate, develop policies a nd 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 a metryn will be examined during R egistrat ion R eview

.

Conclusions : There are no residential uses currently registered for a metryn ; 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 2005 HED chapter of the ametryn RED conducted by HED ( Memo, W. Donovan et al

. , 15

- JUN

- 2005, D316695 ). Since there were no registered residential uses for a metryn or an acute endpoint , onlyAmetryn Registration Review Human

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Page 9 of 21 

### a chronic aggregate assessment was conducted utilizing the DWLOC approach . DWLOCs represent aggregate exposure from food and drinking water , and were compared to the modeled EDWCs for surface and ground water to determine whether aggregate chronic risks wer e of concern. All EDWCs were less than HED’s calculated chronic DWLOCs. Therefore, chronic aggregate exposures to ametryn in food and drinking water were not of concern from a risk perspective.

Conclusions : A new aggregate risk assessment will be req uired during Registration Review to incorporate the latest Agency policy (the DWLOC approach has been superseded )

, a new dietary assessment (incorporating both food and water exposures), and any potential changes to the

a metryn toxicological PODs

.

7 .0 Occupational Exposure

Occupational handler and post

- application exposures are expected b ased on the registered agricultural uses of a metryn

. Attachment 4 provides a summary of the occupational use pattern. The current registered formulation is a DF prod uct , with a pplication rates ranging from 1.2

- 2.4 pounds active ingredient per acre ( lb ai/A )

. Occupational Handlers There is the potential for dermal and inhalation exposure to occupational handlers from the currently registered use pattern of a metryn . 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 Handler s Exposure Database (PHED). Previous risk calculations were based on the maximum application rates and assuming maximum area treated per day. 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 2005 HED chapter of the ametryn RED (Memo, W. Donovan et al. , 15

- JUN

- 2005, D316695)

, occupational handler scenarios were assessed for DF formulations at rates ranging from 1.2

- 2.4 lb ai/A. A total MOE (dermal + inhalation) was presented along with route

- specific MOEs. None of the scenarios assessed resulted in risk estimates of concern (i.e., all MOEs ≥ 100 ; total MOEs (dermal + inhalation) ranged from 230 to 57,000 ). Based on existing registrations, the previous assessments identified all of the anticipated occupat ional handler exposure scenarios

. The occupational handler scenarios ma y 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 a metryn to agricultural crops. However, the labels indicate that most applications are to be made as directed sprays, avoiding the crop foliage. For sugarcane, the product label appears to allow for over

- the

- top applications, but based on crop profile information for sugarcane, weed control is most important during the early growth stages, when the crop height is low and there is minimal foliage 4 

### . Therefore, it is not anticipated that there will be s ignificant worker exposure to foliar residues following applications.

4 Weed Management in Sugarcane. D.C. Odero and J.A. Dusky. http://edis.ifas.ufl.edu/wg004Ametryn Registration Review Human

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Page 10 of 21 

### The 2005 HED chapter of the ametryn RED (Memo, W. Donovan et al. , 15

- JUN

- 2005, D316695) came to a similar conclusion noting th e following: (1) ametryn product labeling specifies applic ation as either a directed spray at weeds or as a preemergent broadcast spray, (2) the label includes instructions to avoid application to the crop foliage, (3) the label specifies the last ametryn application be made 30 and 160 days prior to harvesting fo r corn and pineapples, respectively, and (4) the label specifies “Avoid wetting sugarcane foliage, or injury may occur” for sugarcane, and also recommends against application after “close

- in”

- when the sugarcane grows over the planting beds prior to harve sting. For these reasons, HED did not anticipate any foliar residues on the ametryn treated crops, and did not quantitatively assess post

- application occupational exposures.

Conclusions: The occupational exposure database is adequate to support the Re gistration Review process for a metryn

. The previous occupational handler assessment covered the relevant exposure scenarios and did not result in risk estimates of concern. Revised occupational handler assessments will be required during Registration R ev iew to include revised surrogate unit
exposures for occupational handlers 5



### . An occupational post

- application assessment was not conducted previously based on (1) the use directions to avoid contacting foliage and (2) the timing of applications (early season)

. A quantitative occupational post

- application assessment will not be necessary during Registration Review.

8.0 Public Health and Pesticide Epidemiology Data

The Agency has reviewed the available incident data for a metryn ( Memo, S. Recore and E. Evans
, D 407648 , 31

- JAN

- 2013 ) and concludes that based on the low frequency and severity of incident cases reported for a metryn , there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue t o 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

The tolerance expression should be changed to conform to current HED p olicy. Specifically, the tolerance expression for 40 CFR §180.258(a) should be as follows:

"Tolerances are established for residues of the herbicide ametryn, including its metabolites and degradates, in or on the commodities listed in the following table . Compliance with the tolerance levels specified in the table is to be determined by measuring only ametryn, N

- ethyl

- N′

- (1

- methylethyl)

- 6

- (methylthio)

- 1,3,5

- triazine

- 2,4

- diamine), in or on the following commodities."

U.S. permanent tolerances (listed in 40 CFR § 180.258) are summarized in Attachment 5. There are no Codex or Mexican maximum residue limits (MRLs) in/on the U.S. registered crops.

10 .0 Environmental Justice

Potential areas of environmental justice co ncerns, to the extent possible, were considered in the
most recent Ametryn human

- health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions to Address Environmental Justice in Minority Populations and Low

-

5 O utlined in the “Occupational Pesticide Handler Unit Exposure Surrogat e Reference Table ” available at http://www.epa.gov/pesticides/science/handler

- exposure

- data.htmlAmetryn Registration Review Human

- Health Assessment Scoping Document

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Page 11 of 21 

### Income Populations 6 

### .” 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 variabil ity 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 availab le information.

11.0 Cumulative

Ametryn 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 Mechanis m of Toxicity. 7 

### ” However, a metryn was excluded from the triazine CMG because it does not share the toxicity profile of the CMG triazines. For the purposes of this action, therefore, EPA has assumed that a metryn does not have a common mechanism of toxicit y 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 fr om 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 that 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 haz ard 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 sensit ive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), a metryn is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has develop ed 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 Adminis trator 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 t he 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

. Ametryn is not

6 h ttp://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf
7 http://www.epa.gov/oppsrrd1/REDs/triazine_cumulative_risk.pdfAmetryn Registration Review Human

- Health Assessment Scoping Document

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Page 12 of 21 

### among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of Registration R eview, EPA will issue future EDSP orders/data call

- ins, requiring the submission of EDSP screenin g assays for a metryn

. 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/

.

1 3 .0 Human Studies

Past a metryn 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.

1 4 .0 Risk Assessment Updates, Data Deficiencies, and Label Revisions

The following data deficiencies were identified for ametryn:

Toxicology:

o 870.7800: Immunotoxicity Study

o 870.3465: 90

- day Inhalation study 8 

### Residue Chemistry:

o None

. Dietary Exposure:

o None. Occupational/Residential Exposure:

o None.

EPA anticipates c onducting the following risk assessment updates during Registration Review:

Toxicology:

o Reevaluate toxicity endpoint/dose selection, along with the FQPA SF, based on submitted studies and any outstanding data. Residue Chemistry:

o The tolerance expressio n should be changed to conform to current HED policy (see S ection 9.0 of this document for details). Dietary Exposure:

o A r evised dietary risk assessment will be necessary to reflect current Agency policy ( incorporating both food and water exposures)

, the most recent dietary exposure models, and any potential changes to the toxicological PODs. Occupational/Residential Exposure:

8 28

- day inhalation study will be sufficient.Ametryn Registration Review Human

- Health Assessment Scoping Document

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Page 13 of 21 

### o Revised occupational handler risk assessment s will be necessary to reflect the
most recent occupational handler surrogate exposure data 9 

### and current Agency policies. Aggregate Exposure:

o A revised aggregate exposure assessment will be necessary incorporating the latest Agency policy (the DWLOC approach has been superseded), a new dietary assessment (incorporating both food and water exposures) , and any potential changes to the ametryn toxicological PODs.

9 O utlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table ” available at http://www.epa.gov/pesticides/science/handler

- exposure

- data.htmlAmetryn Registration Review Human

- Health Assessment Scoping Document

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Page 14 of 21 

### 1 5 .0 References

Table 1 . Memoranda Relevant to Registration Review 1

. Autho r Barcode Date Title

W. Donovan et al

. D316695 15

- JUN

- 2005 Revised Memo to Incorporate Responses to Phase 3 Public Comments. Ametryn: HED Chapter of the Reregistration Eligibility Decision Document (RED). PC Code: 080801, Case #: 2010, DP Barcode: D316695.

R. Travaglini D 318295 13

- JUN

- 2005 Corrected Ametryn ORE Chapter to Incorporate Responses to Phase 3 Public Comments

- Ametryn. HED Occupational and Residential Exposure Chapter of the Reregistration Eligibility Decision Document.
1. This table only includes references to final versions. Previous versions of these documents are available, but have been sup erseded.



### Attachments:

Attachment 1: Chemical Identity Table. Attachment 2: Ametryn Acute, Subchronic, and Chronic Toxicity Profile Attachment 3: Ametryn Endpoint Selection Tables. Attachment 4: Summary of Occupational Registered Uses Pulled From LUIS Report (dated 8/22/12). Attachment 5: Ametryn International Residue Limit Status Sheet.

cc: K. Lowe (RAB1), S. Levy (RAB1), C. Rodriguez (RAB1) RDI: RAB1 ( 2/20 / 13 ), D. Vogel ( 2/20/13 ), J. Rowland ( 2/20/13 ) K.Lowe :S109 4 7:PY

- S:(703)3 47

- 8989 :7509P:RAB1Ametryn Registration Review Human

- Health Assessment Scoping Document

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Page 15 of 21 

### Attachment 1: Chemical Identity Table

.

Chemical Structure and Nomenclature for Ametryn and its Thiomethyl Metabolites.

Chemical structure

Common name Ametryn
Molecular Formula C 9 H 17 N 5 S Molecular Weight 227.35
IUPAC name N 2

- ethyl

- N

4

- isopropyl

- 6

- methylthio

- 1,3,5

- triazine

- 2,4

- diamine
CAS name N

- ethyl

- N

- (1

- methylethyl)

- 6

- (methylthio)

- 1,3,5

- triazine

- 2,4

- diamine
CAS # 834

- 12

- 8
PC Code 080801 Food/Feed Site Registration Field Corn, Pineapple, and Sugarcane Chemical structure

Common name NA Company experimental name GS

- 11354; CG

- 3 IUPAC name NA CAS name N

- isopropyl

- 6

- (methylthio)

- 1,3,5

- triazine

- 2,4

- diamine CAS registry number 4147

- 57

- 3 Chemical structure

Common name NA Company experimental name GS

- 11355; CG

- 4 IUPAC name NA CAS name N

- ethyl

- 6

- (methylthio)

- 1,3,5

- triazine

- 2,4

- diamine CAS registry number 4147

- 58

- 4 Chemical structure

Common name NA Company experimental name GS

- 26831; CG

- 2 IUPAC name NA CAS name 6

- (methylthio)

- 1,3,5

- triazine

- 2,4

- diamine CAS registry number 5397

- 01

- 3Ametryn Registration Review Human

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Page 16 of 21 Physicochemical Properties of Ametryn

. Parameter Value Reference Melting point 84.5

- 86 C MRID 40877301; Ametryn PC RED Chapter pH 8

- 9 at 20 C (1% solution in water) Density, bulk density, or specific gravity 0.373 g/mL at 20 C

Water solubility 0.020 g/100 mL at 20 C Solvent solubility 56.9 g/100 mL in acetone 61.4 g/100/mL in methylene chloride 51.6 g/100 mL in methanol 46.0 g/100 mL in toluene 24.2 g/100 mL in n

- octanol 1.4 g/100 mL in n

- hexane Vapor pressure 2.74 x 10 - 6 mm Hg at 25 C Dissociation constant, pK a 4.02 at 20 C Octanol/water partition coefficient K OW = 423 (log P = 2.63)

UV/visible absorption spectrum λ max = 223 nmAmetryn Registration Review Human

- Health Assessment Scoping Document

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Page 17 of 21 

### Attachment 2: Ametryn Acute, Subchronic, and Chronic Toxicity Profile

Acute Toxicity Profile

– Ametryn

. Guideline Study Type MRID(s) Results Tox Cat

870.1100 Acute oral

- rat 40995814 LD 50 = 1356 (1164

- 1581 ) mg/kg (M) LD 50 = 1009 (829

- 1229) mg/kg (F) III

870.1200 Acute dermal

- rabbit 40995815 LD 50 >2020 mg/kg III 870.1300 Acute inhalation

- rat 42470902 LC 50 >5.03 mg/L IV

870.2400 Acute eye irritation

- rabbit 40995817 No corneal involvement, mild conjunctiva irritation (redness, chemosis

, and discharge) reversed by 72 hours in washed eyes. III

870.2500 Acute dermal irritation

- rabbit 40995818 Essentially non

- irritating. IV 870.2600 Skin sensitization

- guinea pig 40995819 Not a sensitizer

.

Subchronic, Chronic , and Other Toxicity Profile

– Ametryn

. Guideline No./Study Type MRID No. (year)/

Classification/Doses Results

870.3100 90

- Day oral toxicity

- rat Old study. Refer to chronic dosing.

870.3150 90

- Day oral toxicity

- dog Old study

. Refer to chronic dosing.

870.3200 21

- Day dermal toxicity

- rabbit 41067902 (1989), Acceptable/Non

- Guideline 0, 10, 100

, or 1000 mg/kg/day NOAEL = 100 mg/kg/day

. LOAEL = 1000 mg/kg/day based primarily on body

- weight gain effects and decreased food consumption.

Note: Study is non

- guideline because on 5/sex/dose group were used. 870.3250 90

- Day dermal toxicity (species) No study.

870.3465 90

- Day inhalation toxicity (species) No study.

870.3700a Prenatal developmental in rats. 00153215 (1985) Acceptable/Guideline 0, 5, 50

, or 250 mg/kg/day Maternal NOAEL = 5 mg/kg/day

. LOAEL = 50 mg/kg/day based on ptosis and salivation. Developmental NOAEL and LOAEL >250 mg/kg/day. No effects at highest dose tested. 870.3700b Prenatal developmental in rabbits 00153214 (1985) Acceptable/Guideline 0, 1, 10

, or 60 mg/kg/day Materna l NOAEL = 10 mg/kg/day

. LOAEL = 60 mg/kg/day based on body

- weight loss, deceased feed consumption and increased liver weight. Developmenta l NOAEL and LOAEL >60 mg/kg/day. No effects at highest dose te sted. 870.3800 Reproduction and fertility effects (species) 40349905 (1987) Acceptable/Guideline 0, 1.3, 13

, or 131 mg/kg/day in males (approximately). 0, 1.2, 12

, or 117 mg/kg/day in females (approximately). Parental/Systemic NOAEL = 13 mg/kg/day

. LOAEL = 131 mg/kg/day based on decreased body weight and weight

- gain and decreased feed efficiency. Reproductive NOAEL and LOAEL >131 mg/kg/day. No effects at highest dose tested. Offspring NOAEL = 13 mg/kg/day

. LOAEL = 131 mg/kg/day based on decreased pup weights and weight gain in the F 2 generation. 870.4100a Chronic toxicity Refer to 870.4300 combined chronic feeding/carcinogenicity study in rats below.

870.4100b Chronic toxicity (dog) 40349902 (1987) Acceptable/Guideline 0, 0.71, 7.2, 70, 103

, and 83 mg/kg/day in males and 0, 0.84, 8.1, 74, 112

, and 92 mg/kg/day in females. NOAEL = 7.2 mg/kg/day

. LOAEL = 70 mg/kg/day based on degenerative liver lesions.Ametryn Registration Review Human

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Page 18 of 21 Subchronic, Chronic , and Other Toxicity Profile

– Ametryn

. Guideline No./Study Type MRID No. (year)/

Classification/Doses Results

870.4300 Carcinogenicity (mouse) 40349904 (1981) “CORE MINIMUM” 0, 1.5, 150

, or 300 mg/kg/day. NOAEL and LOAEL >300 mg/kg/day. No effects at highest dose tested. No evidence of carcinogenicity.

Note: Marked decreases in body weight at 3000 ppm justify selection of 2000 ppm (i.e. about 300 mg/kg/day) as an acceptable dose. 870.4300. Chronic Feeding/ Carcinogenicity (rat) 40349906 (1987), 41184201 (1987) and 403 82001 (1987) Acceptable/Guideline 0, 2, 21

, or 145 mg/kg/day for males and 0, 2.5, 26

, or 176 mg/kg/day for females. NOAEL = 21 mg/kg/ day. LOAEL = 145 mg/kg/day based on based on decreased body weight and weight gain in both sexes and histopathological lesions in the kidney, testes, and pituitary in male rats and in the liver and pancreas in male and female rats.

Gene Mutation 870.5100. Ames test, bacterial mutation. 40995829 and 41189701 (1984) Acceptable/Guideline 0, 20, 80, 320, 1280

, or 5120 μg/mL. No evidence of mutagenicity in Salmonella strains TA98, TA 100, TA 1535 and TA 1537 up to levels causing cytotoxicity.

Cytogenetics 8 70.5395. Mouse micronucleus test. 41067903 (1989) Acceptable/Guideline 1. 800 mg/kg, harvest at 16, 24, and 48 hours. 2. 200, 400, or 800 mg/kg: harvest at 24 hours. Negative for increased MPCEs up to clinical toxicity (death).

Other Effects 870.5550. Unscheduled DNA synthesis in rat hepatocytes. 41067904 (1989) Acceptable/Guideline. 1. 0.1 to 100 μg/mL 2. 0.137 to 33.3 μg/mL Negative for increases UDS up to cytotoxicity.

870.6200a Acute neurotoxicity screening battery No study.

870.6200b Subchronic neurotoxicity screening battery No study.

870.6300 Developmental neurotoxicity No study.

870.7485 Metabolism and pharmacokinetics (species) 41463301, 41463302, 41463303 (all 1990) Acceptable. Ametryn is readily absorbed by rats aft er a single or multiple oral doses of 0.5 or 200 mg/kg. It is widely distributed, being found in all tissues and organs tested although in low levels. It is metabolized to several polar products, 13 of which were identified

. It is excreted mainly throug h the urine (50

- 61%) within 48 hours with the feces being the other major route (30

- 42%). No significant differences in pharmacokinetic parameters were seen among dosing groups (singular oral high and low, multiple low) or between sexes. 870.7600 Dermal penetration (species) No study.

Special studies No studies.Ametryn Registration Review Human

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Page 19 of 21 

### Attachment 3: Ametryn Endpoint Selection Tables.

Summary of Toxicological Doses and Endpoints for Ametryn Use d in the 2005 RED

. Exposure Scenario Dose Used in Risk

Assessment, UF Special FQPA SF*

and Level of Concern for Risk Assessment Study and Toxicological Effects

Acute Dietary (females 13

- 49) & (general population) No selection

Chronic Dietary (all populations) NOAEL = 7.2 mg/kg/day

UF = 100 1X

cRfD = cPAD = 0.072 mg/kg/day Dog chronic feeding study with

indications of degenerative and inflammatory liver effects at LOAEL

of 70 mg/kg/day. Incidental Oral Short

- Term (1

- 30 days) & Intermediate

- Term (1

- 6 months) NOAEL = 10 mg/kg/day

MOE = 100 1X Rabbit developmental toxicity. Body weight and deceased feed consumption and increased liver weight at the LOAEL of 60 mg/kg/day. Dermal Short

- Term (1

- 30 days) & Intermediate

- Term (1

- 6 months) NOAEL = 100 mg/kg/day

MOE = 100 1X Rabbit 21

- day dermal toxicity study. Body

- weight gain decrease at 1000

mg/kg/day.

Dermal Long

- Term (> 6 months) Same as for cRfD . MOE = 100 . Dermal

- absorption factor of 6% recommended.

Inhalation Short

- Term (1

- 30 days) & Intermediate

- Term (1

- 6 months) Same as for incidental oral. MOE = 100. Assume 100% absorption following inhalation.

Inhalation Long

- Term (> 6 months) Same as for cRfD . MOE = 100. Assume 100% absorption following inhalation.

Cancer (oral, dermal, inhalation) No quantitative carcinogenicity ris k assessment is required.

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, NA = not applicableAmetryn Registration Review Human

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Page 20 of 21 

### Attachment 4: Summary of Occupational Uses Based on Registered Label

.

Evik ® 

### 80WDG (EPA Reg. #100

- 786; 12

- 15

- 09)

Crop Application

equipment Applic.

Rate (lb ai/A) Max. No.

Applic. per Season Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Corn (field corn, popcorn) Groundboom 1.6 1 1.6 30 No aerial or chemigation applications. Apply as a postemergence directed spray to weeds after the smallest corn is at least 12 inches high. Do not spray over top of corn. Do not apply within 3 weeks of tasseling.

Pineapple Groundboom 1.6 2 3.2 160 No aerial or chemigation applications. Use only in Hawaii . Apply immediately after planting or after previous crop harvest and before weeds
emerge.

Sugarcane Aerial and

Groundboom FL: 1.2 2 FL: 2.4

NS Apply as broadcast spray or directed to the base of the plant. Avoid wetting
sugarcane foliage. Make applications prior to close

in 1

.

Groundboom LA, TX:

1.2 2 LA, TX: 2.4 Apply broadcast or band over the top of the plant or as a directed spray. Do not apply over the top of plant after April 10, or after plant exceeds 20 inches in heig ht. Make final application before close

- in.

Groundboom HI: 2.4 3 HI: 7.2 Apply before weeds or sugarcane emerge. May apply up to 30 days prior to close

- in or at close

- in, if needed.
1. Weed control is most critical early in the season prior to sugarcane canopy closure over the row middles.Ametryn Registration Review Human

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Page 21 of 21 

### Attachment 5: Ametryn International Residue Limit Status Sheet.

Ametryn (080801); current as of 12/19/12

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 Codex 40 CFR 180.258: Plant: ametryn (2

- ethylamino)

- 4

- (isopropylamino)

- 6

- (methylthio)

- s

- triazine) Livestock: NA None None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 1 Codex Banana 0.25 Corn, field, forage 0.1 Corn, field, grain 0.05 Corn, field, stover 0.05 Corn, pop, grain 0.05 Corn, pop, stover 0.05 Corn, sweet, forage 0.5 Corn, sweet, kernel plus cob with husk removed 0.25

Corn, sweet, stover 0.5 Pineapple 0.05 Sugarcane, cane 0.05

Completed: M. Negussie; 12/19/2012

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