UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASIDNGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

:MEMORANDUM 

DATE: November 19, 2014 

SUBJECT: Metolachlor and S-Metolachlor. Human Health Scoping Document in Support of 

Registration Review. 

PC Code: 108800 (S-Metolachlor); DP Barcode: 420468 

108801 (Metolachlor) 

Decision No.: 491501 Registration Nos.: 100-815, 11603-43, 19713-539, 

60063-17 

Petition No.: NA Regulatory Action: Registration Review 

Case No.: 0001 Risk Assessment Type: NA 

TXRNo.: NA CAS No.: 87392-12-9, 51218-45-2 

MRIDNo.: NA 40 CFR: §180.368 

FROM: 

THROUGH: 

TO: 

Jessica Kidwell, Risk Assessor ~'h · (ufl.,ve.Lf 

SueHummel,Chemist 

Ivan Nieves, ORE 

(} ~~~ 

_..../)) _· _ _... 

Risk Assessment Branch 4 U < 

Health Effects Division (7509P) 

Elissa Reaves, Ph.D., Branch Chief~'& I/ / 211'( 

R1sk Assessment Branch 4 - · 

Health Effects Division (7509P) 

Steven Snyderman, Chemical Review Manager 

Risk Management and Implementation Branch 3 

Pesticide Re-Evaluation Division (7508P) 

Attached is RED's human health risk assessment scoping document for metolachlor and 

S-metolachlor to support Registration Review. 
Metolachlor/S-Metolachlor Scoping Document D420468 

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Executive Summary 

This document summarizes the review of the Health Effects Division’s (HED’s) human health 

assessments to support the Registration Review of metolachlor and S-metolachlor. To determine 

the scope of work necessary to support Registration Review, HED has considered updates to 

Agency science policy and risk assessment methodologies and to the toxicity, exposure, and usage 

databases. The most recent HED risk assessment, which included an updated dietary and 

residential exposure assessment, was conducted for S-Metolachlor, PP#2F8115 in 2013, and 

established higher tolerances for corn forage and stover (D411153, 8/15/2013). The most current 

occupational risk assessment was conducted in 2010 (D370432; I. Nieves; 6/29/10) to include Smetolachlor new uses on sesame, melon subgroup 9A, bushberry subgroup 13-07B and lowbush 

blueberry, caneberry subgroup 13-07A, sweet sorghum, leafy brassica greens subgroup 5B, 

including turnip greens, carrot, cucumber, okra, onion bulb subgroup 3-07A, and onion green 

subgroup 3-07B. For metolachlor, the most recent risk assessment was a 2003 Revised Tolerance 

Reassessment Eligibility Decision (RED) for metolachlor and S-metolachlor (D288263). Since 

the risk assessments for either metolachlor or S-metolachlor consider uses, exposure and toxicity 

of both chemicals, the results of the most recent risk assessments, which are for S-metolachlor, 

are presented in this document and are considered reflective of metolachlor. 

Metolachlor (PC Code 108801) is a racemic broad spectrum herbicide that consists of 50% each 

of the R-enantiomer and the S-enantiomer, which is the herbicidally active isomer. S-Metolachlor 

(PC Code 108800) is an isomer enriched form of metolachlor, comprised of 88% S-isomer and 

12% R-isomer. Physical and chemical properties are presented in Attachment 1. Metolachlor and 

S-metolachlor are selective, chloroacetanilide herbicides used primarily for grassy weed control in 

many agricultural food and feed crops; residential lawns; commercial turf (including golf courses, 

sports fields, recreation areas, and sod farms); ornamental plants, trees, shrubs, and vines; hedge 

rows; and horticultural nurseries. Corn, sorghum, and soybean account for the majority of the uses 

of both metolachlor and S-metolachlor, followed by cotton, sweet corn, peanut, potato, and other 

minor field and vegetable crops. In addition, metolachlor, but not S-metolachlor is registered for 

use on tree nuts (group 14) and dill weed. S-metolachlor but not metolachlor is registered for use 

on asparagus, garden beets, sugar beets, Brassica head and stem (subgroup 5A), Brassica leafy 

greens (subgroup 5B), bushberry (subgroup 13-07B), caneberry (subgroup 13-07A), carrot, 

cilantro (coriander), cucumber, leaf petioles (subgroup 4B), melon (subgroup 9A), onion, bulb 

(subgroup 3-07A), onion, green (subgroup 3-07B), pumpkin, sesame seed, sweet sorghum, 

spinach, winter squash, sunflower, turnip greens, fruiting vegetables (metolachlor is registered for 

use on tomato only), root vegetables except sugar beets and carrots (subgroup 1B) (metolachlor is 

registered for use on potato only), and tuberous and corm vegetables (subgroup 1C). Application 

rates for metolachlor and s-metolachlor range from approximately one to four pounds active 

ingredient (a.i.) per acre. Application is typically made pre-emergence, one time per season, 

although some early post-emergence uses are registered, and layby use on peanuts, with split 

applications preemergence and postemergence.
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Two sets of toxicology data are available, one for metolachlor and one for S-metolachlor. The 

existing toxicological database is primarily comprised of studies conducted with metolachlor. 

The toxicology database for S-metolachlor consists of bridging data, which include an acute 

toxicity battery, subchronic toxicity studies in rats and dogs, developmental toxicity studies in 

rats and rabbits, a mutagenicity battery, metabolism studies and an immunotoxicity study. Based 

on a comparison of findings in the two databases by HED’s Hazard Identification Assessment 

Review Committee (HIARC) as well as the Metabolism Assessment Review Committee 

(MARC) (Dobozy, 2001), both in 2001, it was concluded that S-metolachlor is of comparable 

toxicity to the racemic mixture, metolachlor, and that studies with both chemicals can be used 

interchangeably for toxicology endpoint selection. The HIARC decision regarding toxicology 

bridging stands will not be re-evaluated in registration review. The toxicology database for Smetolachlor, when combined with the metolachlor database, is complete for risk assessment 

purposes, with the exception of a required 28-day inhalation rat study with metolachlor. 

Metolachlor was on the Endocrine Disruptor Screening Program (EDSP) List 1 and OPP has 

received all the Tier 1 assays for the EDSP which are currently under review. The endpoints, 

Points of Departure (PoDs), and uncertainty/safety factors will be reviewed at the scheduled time 

of preliminary risk assessment. 

S-Metolachlor and metolachlor have low acute toxicity following oral, dermal and inhalation 

exposures (Toxicity Categories III). Metolachlor is not irritating to the skin or eyes. 

S-metolachlor causes slight eye irritation but is non-irritating to the skin. Both are dermal 

sensitizers. In subchronic (metolachlor and S-metolachlor) and chronic (metolachlor) toxicity 

studies in dogs and rats, decreased body weight and body weight gain were the most commonly 

observed effects. No systemic toxicity was observed when metolachlor was administered 

dermally. There is no evidence of neurotoxicity. There was no qualitative or quantitative 

susceptibility seen in the developmental rat or rabbit studies with metolachlor or S-metolachlor 

or in the rat two-generation reproductive toxicity with metolachlor. The FQPA safety factor was 

reduced to 1X because there are no residual uncertainties with regard to pre- and/or postnatal 

toxicity. There was no evidence of mutagenic or cytogenetic effects in vivo or in vitro. 

Metolachlor has been classified as a “Group C, Possible Human Carcinogen” based on liver 

tumors in rats at the highest dose tested. Quantitative human cancer risk is not required. The 

chronic Reference Dose (RfD) is protective of any potential cancer effect. 

At this time, the most current risk assessments for S-metolachlor and metolachlor do not indicate 

risk estimates of concern. The dietary (food and drinking water) exposure assessment did not 

exceed the level of concern for the general U.S. population, infants, and children. There were no 

risks of concern for occupational (with label-required PPE), residential or aggregate exposure 

risk assessments.

Use Profile

Technicals for metolachlor are registered to Agan Chemical Manufacturing, LTD, Drexel 

Chemical Company, and Sipcam Agro USA, Inc. S-Metolachlor is registered by Syngenta under 

the trade names of Dual MAGNUM®, Pennant MAGNUM®, Bicep MAGNUM®, Boundary®, 

and Medal®. Syngenta does not currently hold any active end-use product registrations for 

metolachlor. 
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Metolachlor and S-metolachlor are formulated mainly as an emulsifiable concentrates. Other 

formulations include flowable concentrates, granular, pressurized liquid and ready-to-use 

formulations. Application methods for agricultural uses include primarily broadcast applications 

(includes ground and aerial), irrigation systems, and chemigation (center pivot only). A 

backpack sprayer, hose-end sprayer, or handgun application may be used by professional 

applicators for application to residential lawns or turf. Residential applications to lawns and turf 

are intended for use by professional applicators only. 

Hazard Identification/Toxicology 

Two sets of toxicology data are available, one for metolachlor and one for S-metolachlor. The 

existing toxicological database is primarily comprised of studies conducted with metolachlor. 

Based on the 2001 Hazard Identification Assessment Review Committee (HIARC) and MARC 

decisions that metolachlor and s-metolachlor are of comparable toxicity, studies of either 

chemical were used interchangeably for toxicology endpoint selection (TXR No.001469, 

D274326). Bridging toxicology data from S-metolachlor, including acute toxicity, subchronic 

toxicity studies in rats and dogs, developmental toxicity studies in rats and rabbits, mutagenicity, 

metabolism, and immunotoxicity studies are available. The toxicology database for 

S-metolachlor, when combined with the metolachlor database, is complete for risk assessment, 

with the exception of a required 28-day inhalation study in rats with metolachlor (Guideline No. 

870.3465). The Hazard Science Policy Council (HASPOC) evaluated the 2007 toxicology data 

requirements and based on a weight of evidence consideration granted a waiver for the 

neurotoxicity battery (acute and subchronic) but required a 28-day repeated exposure inhalation 

toxicity study in rats with metolachlor to assess risk via the inhalation route from occupational 

and residential uses (TXR No. 0056586). All submitted studies are detailed in the attached 

toxicology tables (See Attachment 2). 

S-Metolachlor and metolachlor have low acute toxicity following oral, dermal and inhalation 

exposures (Toxicity Categories III). Metolachlor is not irritating to the skin or eyes. 

S-metolachlor causes slight eye irritation but is non-irritating to the skin. Both are dermal 

sensitizers. In subchronic (metolachlor and S-metolachlor) and chronic (metolachlor) toxicity 

studies in dogs and rats, decreased body weight and body weight gain were the most commonly 

observed effects. No systemic toxicity was observed when metolachlor was administered 

dermally. No neurotoxicity studies with metolachlor or S-metolachlor are available. However, 

there was no evidence of neurotoxic effects in adult animals in available subchronic and chronic 

toxicity studies. Prenatal developmental studies in the rat and rabbit with both metolachlor and 

S-metolachlor revealed no evidence of a qualitative or quantitative susceptibility in fetal animals. 

A two-generation reproduction study with metolachlor in rats showed no evidence of parental or 

reproductive toxicity. The FQPA safety factor was reduced to 1X because there are no residual 

uncertainties with regard to pre- and/or postnatal toxicity. 

There was no evidence of mutagenic or cytogenetic effects in vivo or in vitro. Metolachlor has 

been classified as a Group C, possible human carcinogen based on liver tumors in rats at the 

highest dose tested. A linear risk assessment is not required. The chronic RfD is protective of any 

potential cancer effect. EPA has concluded that metolachlor does not have a common mechanism 

of carcinogenicity with acetochlor and alachlor which are structurally similar. 
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Dose Response Assessment 

Toxicological endpoints were selected for dietary/drinking water, occupational and residential 

exposure scenarios (See Attachment 3). An acute reference dose (aRfD= 3.0 mg/kg/day) for 

assessment of food and drinking water exposures was selected from a developmental toxicity 

study in rats with metolachlor (NOAEL = 300 mg/kg/day). A chronic RfD (cRfD= 0.097 

mg/kg/day) was selected from a chronic toxicity study in dogs with metolachlor (NOAEL = 9.7 

mg/kg/day). Since the Food Quality Protection Act (FQPA) Safety Factor (SF) is not retained 

(i.e., 1x), the acute and chronic Population Adjusted Doses (PADs) are equivalent to the acute 

and chronic RfDs, respectively. A short-term incidental oral point of departure (POD) (NOAEL 

= 50 mg/kg/day) was selected from a developmental toxicity study in rats with S-metolachlor. A 

POD for dermal exposure was not selected because no dermal or systemic toxicity was seen in 

rabbits following repeated dermal application at the highest dose tested for 21 days with 

metolachlor. A short-term inhalation exposure POD (NOAEL = 50 mg/kg/day) was selected 

from a developmental toxicity study in rats with S-metolachlor. An intermediate-term inhalation 

exposure POD (No Observed Adverse Effect Level (NOAEL) = 8.8 mg/kg/day) was selected 

from a subchronic toxicity study in dogs with metolachlor. For assessing risk via incidental oral 

exposure, the Level of Concern (LOC) is a target Margin of Exposure (MOE) of 100 which 

includes the conventional 10x for interspecies extrapolation and 10x for intraspecies variation. 

For assessing risk via inhalation exposure, the LOC is a target MOE of 1000 which includes the 

conventional 100 and a 10X database uncertainty factor (UFDB) for the lack of a repeated 

exposure inhalation study. 

Metolachlor is on EDSP List 1 and EPA has received all the required Tier 1 assay data. The 

Agency is currently reviewing all of the assay data for metolachlor and planning to make the 

conclusions of those reviews available in early 2015. The endpoints, PODs, and 

uncertainty/safety factors will be reviewed at the scheduled time of preliminary risk assessment. 

Conclusions: The toxicology database for S-metolachlor, when combined with the metolachlor 

database, is complete for risk assessment purposes, with the exception of a required 28-day 

inhalation study in rats with metolachlor (Guideline No. 870.3465). 

 

Residue Chemistry 

The qualitative nature of the residue of metolachlor including S-metolachlor in plants and 

livestock is adequately understood. Residues of concern in plants, livestock, and rotational crops 

include metolachlor and its metabolites, determined as the derivatives CGA-37913 and CGA49751. The residue of concern for both metolachlor and S-metolachlor includes both the Risomer and the S-isomer of metolachlor. The Agency previously concluded that the residues of 

concern for S-metolachlor are the same as for metolachlor. The residues of concern for 

metolachlor and S-metolachlor in drinking water include the parent CGA-51202 (metolachlor 

oxanilic acid (OA)), CGA40172, and CGA-77102. The text of the current tolerance expression is 

in accordance with our current guidance (S. Knizner, 5/10/2009). 

Adequate methodology is available for enforcing the established and recommended tolerances. 

PAM Vol. II, Pesticide Regulation Section 180.368, lists a gas chromatography with nitrogen-
Metolachlor/S-Metolachlor Scoping Document D420468 

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phosphorus detector (GC/NPD) method (Method I) for determining residues in/on plant 

commodities and a gas chromatography with mass selective detector (GC/MSD) method 

(Method II) for determining residues in livestock commodities. These methods determine 

residues of metolachlor and its metabolites as either CGA-37913 or CGA-49751 following acid 

hydrolysis. Adequate data are also available on the recovery of metolachlor through FDA’s 

Multiresidue Method Testing Protocols which indicate that metolachlor is completely recovered 

through Method 302. 

Syngenta has proposed a high pressure liquid chromatography with mass spectroscopy/mass 

spectroscopy (HPLC/MS/MS) enantiomer-specific method for the enforcement of the proposed 

tolerances, Method 1848-01. The method uses a chiral HPLC column to separate out the Senantiomers (SYN506357 and SYN508500) of the hydrolysis products CGA-37913 and CGA49751. This method has not been determined to be adequate for enforcement purposes because it 

monitors only a single ion transition per analyte, and because it measures only the S-isomers of 

metolachlor hydrolysis products, but could be adapted for enforcement by adding a second ion 

transition and by measuring both the R- and S-isomers. 

Several responses were made to the RED requirement for additional clarification of the 

metolachlor rotational crop study, including a new confined rotational crop study (Soderberg, 

2007). The requirement for a confined rotational crop study is satisfied. 

The label directions for use are not all supported by residue data. Discrepancies were noted for 

S-metolachlor on bulb vegetables (shorter PHI than supported by data), cotton (higher rate), 

soybeans (higher rate), and tomato (higher rate). 

Conclusions: No additional residue chemistry data are required for metolachlor/S-metolachlor 

for Registration Review, except for the cases where discrepancies have been found in the 

directions for use. In those cases, the use directions must be changed to match the residue data 

submitted or field trial data will be needed for the current directions for use. Residue chemistry 

data submitted since the RED will be reviewed and relevant tolerances will be reassessed. All 

use patterns must be examined in detail during registration review to ensure that the uses are 

properly supported by residue data. 

Dietary Exposure Including Drinking Water 

The most recent dietary exposure assessment was conducted for S-Metolachlor, PP#2F8115, 

which established higher tolerances for corn forage and stover (D411153, 8/15/2013). This 

assessment is considered to be reflective of metolachlor as well since the dietary risk assessment 

incorporates exposure and toxicity of both S-metolachlor and metolachlor. The residue of 

concern for metolachlor and S-metolachlor in plants and livestock including rotational crops for 

both tolerances and risk assessment is metolachlor, and its metabolites and degradates 

convertible to the derivatives CGA-37913 and CGA-49751. 

Environmental fate data indicate that parent metolachlor/S-metolachlor is moderately persistent 

to persistent. It is mobile to highly mobile in different soils and has been detected extensively in 

surface water and groundwater. Major degradates identified in groundwater include metolachlor 
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ethanesulfonic acid (ESA) and metolachlor oxanilic acid (OA) in both groundwater and surface 

water. Environmental Fate and Effects Division (EFED) calculated conservative, Tier I 

Estimated Drinking Water Concentrations (EDWCs) of metolachlor and S-metolachlor in ground 

water and surface water for use in the last human health risk assessment. These were 

incorporated directly into the dietary assessment.  

On August 20, 2014, the Residues of Concern Knowledge-Base Subcommittee (ROCKS) cochairs informally met with the EFED and HED metolachlor registration review teams to discuss 

potential residues of concern. Four major degradates of metolachlor were identified by the EFED 

chemical team for the drinking water assessment: metolachlor oxanilic acid (metolachlor-OA; 

CGA-51202), metolachlor ethane sulfonic acid (metolachlor ESA; CGA-354743), CGA40172, 

and CGA-77102. CGA40172, and CGA-77102 were not considered as residues of concern in 

previous drinking water assessments. For all future assessments, the ROCKS members 

recommended excluding the metolachlor-ESA from the drinking water assessment since the 

sulfonic acid is likely to be significantly less toxic than the parent compound. The ROCKS 

members also recommended including the degradates CGA-40172, and CGA-77102, in addition 

to metolachlor-OA, based on the structural similarity to parent metolachlor. It should be noted 

that the concern for CGA-40172 is diminished due to the presence of the carboxylic acid moiety, 

however, there is insufficient information to exclude from the drinking water 

assessment. Therefore, the ROCKS recommended the following degradates as residues of 

concern for drinking water: parent metolachlor, metolachlor-OA, CGA40172, and CGA-77102 

(see table below and degradates table in Attachment 1). 

Summary of Metabolites and Degradates to be included in the Risk Assessment and 

Tolerance Expression

Matrix Residues included in Risk 

Assessment 

Residues included in 

Tolerance Expression 

Plants 

Primary Field Crop 

metolachlor, and its 

metabolites and degradates 

convertible to the derivatives 

CGA-37913 and CGA-49751 

metolachlor, and its 

metabolites and degradates 

convertible to the derivatives 

CGA-37913 and CGA-49751 

Rotational Crop 

metolachlor, and its 

metabolites and degradates 

convertible to the derivatives 

CGA-37913 and CGA-49751

metolachlor, and its 

metabolites and degradates 

convertible to the derivatives 

CGA-37913 and CGA-49751

Livestock Ruminant & Poultry 

metolachlor, and its 

metabolites and degradates 

convertible to the derivatives 

CGA-37913 and CGA-49751

metolachlor, and its 

metabolites and degradates 

convertible to the derivatives 

CGA-37913 and CGA-49751

Drinking Water Metolachlor, metolachlor-OA, 

CGA-40172, and CGA-77102 Not Applicable 

For acute and non-cancer chronic exposures, EPA is concerned when estimated dietary risk 

exceeds 100% of the population adjusted dose (PAD). Metolachlor is classified as a Group C 

carcinogen; therefore, no separate dietary assessment was performed for cancer (i.e., the chronic 

dietary exposure is considered protective for cancer effects). For acute and chronic dietary 

exposures, an unrefined assessment was conducted, assuming 100% crop treated, and tolerance 
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level residues. The acute and chronic dietary risk estimates are below the Agency’s level of 

concern for the general U.S. population and all population subgroups, with the most highly 

exposed subgroups being all infants (<1 year old) at 1.5% of the acute PAD (aPAD) and 11.6% 

of the chronic PAD (cPAD). 

Conclusions: A new dietary exposure and risk assessment will likely be conducted if there are 

changes to the metolachlor/S-metolachlor toxicological PODs or UFs or significant changes to 

the EDWCs based on a new drinking water assessment. The assessment, if conducted, will use 

the newest version of the Dietary Exposure Evaluation Model (DEEM) and reflect updated 

consumption information. 

Residential Exposure 

The most recent risk assessment (“S-Metolachlor, PP#2F8115. Human Health Risk Assessment 

for the petition for higher tolerances on Corn, field, forage; Corn, sweet, forage; and Corn, 

stover”, S. Hummel, D411153, 8/15/13) reassessed residential exposure to S-metolachlor based 

on the updated Residential Standard Operating Procedures (SOPs) dated February 2012. Since 

the maximum use rates and uses are similar between S-metolachlor and metolachlor, and since 

they share the same toxicological profile, the residential exposure assessment for S-metolachlor 

is considered to be protective of metolachlor. 

S-Metolachlor is not intended for homeowner purchase or use (i.e., used by professional/ 

commercial applicators). The only potential residential risk scenario anticipated was postapplication incidental oral exposure of children playing on treated lawns. Although there is 

possibility of dermal exposure, no risks of concern were identified in the dermal toxicity study. 

 

S-Metolachlor incidental oral exposure was assumed to include hand-to-mouth exposure, objectto-mouth, and soil ingestion oral exposure. No turf transferable residue data were used. The 

maximum application rate used was 2.47 lb S-metolachlor/acre. 

The residential exposure (absorbed dose) to children 1-2 years old for combined hand-to-mouth, 

object-to-mouth, and soil ingestion oral exposure was calculated to be 0.0609 mg/kg/day 

resulting in an MOE of 820. The MOE from the residential risk scenario for exposure to Smetolachlor were above the target MOE of 100 and, therefore, this exposure scenario was not of 

concern. 

Since the estimated residential turf post-application exposure for residential turf using default 

Turf Transferable Residue (TTR) values is not minimal in comparison to the level of concern 

(i.e., the calculated MOE [820] is not greater than 10 times the level of concern [100 x 10 = 

1,000]), future refinements of this post-application exposure for metolachlor/s-metolachlor may 

be necessary due to increased use of the chemical or advances in EPA risk 

assessments. Therefore, EPA is requiring the 40CFR TTR data requirement (Guideline No. 

875.2100) to facilitate any necessary exposure assessments refinements and to further EPA’s 

general understanding of the availability of turf transferable pesticide residues. 
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Residential exposure is considered to be short-term in duration. Furthermore, since residents are 

not expected to re-enter treated areas until the spray has dried (as labeled), no inhalation 

exposure was assessed. Residential bystander exposures resulting from off-site transport (e.g., 

spray drift or volatilization) may occur as a result of applications of S-metolachlor. The potential 

for spray drift will be quantitatively evaluated for each pesticide during the Registration Review 

process which ensures that all uses for that pesticide will be considered concurrently. The 

approach is outlined in the revised (2012) SOPs for Residential Risk Assessment – Residential 

Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift. 

This document outlines the quantification of indirect non-occupational exposure to drift. In terms 

of volatilization, the agency has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine 

if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for S-metolachlor/metolachlor. 

Conclusions: The residential exposure risk assessment did not identify risks of concern in 2013 

using the updated (2012) HED’s Residential SOPs1 and policy changes for body weight 

assumptions and the most current toxicological data and PODs. However, since a TTR study and 

a 28-day inhalation toxicity study are required, the residential exposure risk assessment may be 

updated during registration review. The need for spray drift and volatilization risk assessment for 

S-metolachlor will be examined during the registration review process as well.

Aggregate Risk Assessment 

In the 2013 risk assessment, aggregate exposure assessments were performed for acute aggregate 

exposure (food + drinking water only), chronic aggregate exposure (food + drinking water only), 

and short-term exposure (residential incidental oral + dietary). A separate cancer aggregate risk 

assessment was not performed because, for S-metolachlor, the chronic reference dose is 

considered protective of cancer effects. 

No aggregate risks of concern were identified. 

Conclusions: There were no aggregate risks of concern identified in the 2013 assessment. 

During Registration Review, updated aggregate assessments may be conducted as required to 

include any significant change that might occur for toxicological PODs, FQPA and uncertainty 

factors, dietary exposure estimates or EDWCs. Emerging policies related to pesticide drift and 

volatilization assessments may dictate further changes to the existing aggregate risk assessment. 

Occupational Exposure 

S-Metolachlor and Metolachlor are registered for use on a wide variety of food and feed crops 

including: corn, cotton, grasses grown for seed, legume vegetables, peanuts, potatoes, safflower, 

sorghum, sunflower, and tomatoes. Formulations include emulsifiable and flowable concentrates, 

granular, and ready-to-use products. Application methods for agricultural uses include ground, 

 

1

 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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aerial, irrigation and chemigation. Applications to residential lawns or turf are limited to 

professional applicators using backpack, hose-end, or handgun sprayers. Based on this 

chemical’s use pattern, uses were assessed for short-/intermediate-term (i.e., 1-30 days or up to 6 

months) durations for exposure via the dermal and inhalation routes during mixing, loading, 

applying, and post-application activities. 

The most current occupational risk assessment was done in 2010 (D370432; I. Nieves; 6/29/10) 

to include S-metolachlor new uses on sesame, melon subgroup 9A, bushberry subgroup 13-07B 

and lowbush blueberry, caneberry subgroup 13-07A, sweet sorghum, leafy brassica greens 

subgroup 5B, including turnip greens, carrot, cucumber, okra, onion bulb subgroup 3-07A, and 

onion green subgroup 3-07B. Since the maximum use rates and uses are similar between Smetolachlor and metolachlor, and since they share the same toxicological profile, the 

occupational exposure assessment for S-metolachlor is considered to be protective of 

metolachlor. The 2010 assessment did not indicate risk estimates of concern to handlers with 

label-required personal protective equipment (PPE) which included long-sleeved shirt and long 

pants, shoes plus socks, and chemical-resistant gloves. 

Since there are no dermal endpoints of concern, post-application dermal exposure was not 

examined for occupational uses. Furthermore, EPA is waiving the 40CFR Dislodgeable Foliar 

Residue (DFR) data requirement as chemical-specific DFR data would not be needed to further 

refine exposure assessments nor would it add appreciably to our overall understanding of the 

availability of dislodgeable foliar pesticide residues for metolachlor/s-metolachlor. 

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for S-metolachlor at this time. However, volatilization of 

pesticides may be a potential source of post-application inhalation exposure to individuals nearby 

to pesticide applications. A study published in the Journal of Environmental Quality, Volume 38, 

September-October 2009, pages, 1785-1795, “Soil Moisture and Metolachlor Volatilization 

Observations over Three Years” demonstrated that metolachlor’s volatilization potential 

significantly increases with increasing surface soil water content. Furthermore, the Agency 

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. 

The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, developing policies and 

procedures, to identifying the need for and, subsequently, the way to incorporate post-application 

inhalation exposure into the Agency's risk assessments. If new policies or procedures are put 

into place, the Agency may revisit the need for a quantitative post-application inhalation 

exposure assessment for S-metolachlor. 

The restricted entry interval (REI) is based on the acute toxicity of S-metolachlor technical 

material which is classified as Category III and IV. Acute toxicity Category III and IV chemicals 

require a 12 hour REI. Therefore the current 24-hour labeled REI is adequate. 

Conclusions: The occupational exposure database is adequate to support the registration review 

process for S-metolachlor. Previous occupational handler and post-application exposure 
Metolachlor/S-Metolachlor Scoping Document D420468 

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assessments did not identify risks of concern. Registration review may include updated handler 

and post-application risk estimates based on current policies. 

Public Health and Pesticide Epidemiology Data 

For this evaluation, both the OPP Incident Data System (IDS) from 2006 to 2014 and the Centers 

for Disease Control and Prevention/National Institute for Occupational Safety and Health 

(CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) 

databases from 1998 to 2010 were consulted for pesticide incident data on the active ingredient 

metolachlor (pc codes: 108801, 108800) (D420801). The purpose of the database search is to 

identify potential patterns in the frequency and severity of the health effects attributed to 

metolachlor exposure. Metolachlor is included in the Agricultural Health Study (AHS), and, 

therefore, a brief summary of these results are included herein. 

Conclusion: There does not appear to be a concern at this time that would warrant further 

investigation, since there is a low frequency of reported incidents involving metolachlor reported 

to IDS from 2006-2014 and SENSOR-Pesticides from 1998-2010. Research studies within the 

AHS cohort observed an association between metolachlor and lung cancer in two separate 

evaluations. The Agency will continue to monitor the incident information and if a concern is 

triggered, additional analysis will be included in the risk assessment. 

Tolerance Assessment and International Harmonization 

U.S. permanent tolerances are established under 40 CFR §180.368 for the registered uses of 

metolachlor and S-metolachlor in/on a number of commodities. The tolerance expression is in 

accord with our current guidance. CODEX has no MRLs for metolachlor or S-metolachlor. The 

tolerance expression is compatible with the Canadian expression. The United States has a higher 

tolerance for okra (0.5 ppm vs 0.1 ppm) than Pesticide Management Regulatory Agency 

(PMRA), as well as for beet, garden, leaves (1.8 ppm vs 0.8 ppm), and beet, garden, root (0.5 

ppm vs 0.3 ppm), Brassica leafy greens (1.8 ppm vs 0.9 ppm), peppers, non-bell (0.5 ppm vs 0.1 

ppm). These should be examined during registration review to determine if numerical 

harmonization is possible. 

Conclusion: No changes to tolerances are anticipated at the current time. The tolerance 

expression is in accord with our current guidance. CODEX has no MRLs for metolachlor or Smetolachlor. The tolerance expression is compatible with the Canadian expression. The 

tolerances should be examined during registration review to determine if numerical 

harmonization is possible.

Environmental Justice 

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

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

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

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf). As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 
Metolachlor/S-Metolachlor Scoping Document D420468 

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procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the United States Department of 

Agriculture’s (USDA’s) National Health and Nutrition Examination Survey (NHANES), What 

We Eat in America (NHANES/WWEIA) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, 

specialized subgroups and exposure assessments are performed when conditions or 

circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of 

pesticide products and associated risks for adult applicators and for children, youths, and adults 

entering or playing on treated areas following application are evaluated. Further considerations 

are currently in development as OPP has committed resources and expertise to the development 

of specialized software and models that consider exposure to bystanders and farm workers as 

well as lifestyle and traditional dietary patterns among specific subgroups. 

Cumulative

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to metolachlor/S-metolachlor and any other substances. Metolachlor/S-Metolachlor does not 

appear to produce a toxic metabolite produced by other substances. Therefore, EPA has not 

assumed that metolachlor/S-metolachlor has a common mechanism of toxicity with other 

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

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

policy statements released by EPA’s OPP concerning common mechanism determinations and 

procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/. 

Human Studies

Past metolachlor/S-metolachlor 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. These data, which include studies from the Pesticide Handlers Exposure 

Database Version 1.1 (PHED 1.1); the Agricultural Re-entry Task Force (ARTF) database; and 

other registrant-submitted exposure monitoring studies, are subject to ethics review pursuant to 

40 CFR 26, have received that review, and are compliant with applicable ethics requirements. 

For certain studies that review may have included review by the Human Studies Review Board. 

Descriptions of data sources as well as guidance on their use can be found at 

http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html. 

Data Deficiencies and Risk Assessment Updates for Registration Review 

 Residue Chemistry: There are no residue chemistry data deficiencies for metolachlor/Smetolachlor, except where use patterns do not match the submitted residue data. In those 
Metolachlor/S-Metolachlor Scoping Document D420468 

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cases, the use pattern can be changed or additional field trial data can be submitted. 

Residue chemistry data submitted since the RED will be reviewed and relevant tolerances 

will be reassessed. Analytical reference standards are required to be submitted to the 

pesticide repository now and as requested by the repository staff. 

 Toxicology: A 28-day inhalation toxicity study (Guideline No. 870.3465) for metolachlor 

is a data gap. A new endpoint selection may be needed for registration review. A 10X 

database uncertainty factor will be applied only for assessing risk for inhalation scenarios 

until receipt and evaluation of the data gap. 

 ORE: A Turf Transferable Residue (TTR) study (Guideline No. 875.2100) is required for 

the residential exposure risk assessment. 

 A new dietary exposure and risk assessment will likely be conducted if there are changes 

to the metolachlor/S-metolachlor toxicological points of departure (PODs) or Uncertainty 

Factors (UFs) or significant changes to the Estimated Drinking Water Concentrations 

(EDWCs). The assessment, if conducted, will use the newest version of DEEM and 

reflect updated consumption information. 

 Updated occupational/residential exposure and risk assessments may be conducted if 

there are any significant changes to metolachlor/S-metolachlor PODs, Food Quality 

Protection Act safety factor or other uncertainty factors, standard operating procedures, 

or exposure data or assumptions. The need for spray drift and volatilization risk 

assessment for S-metolachlor will be examined during the registration review process as 

well.

 
Metolachlor/S-Metolachlor Scoping Document D420468 

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References 

Table 1. Memoranda Relevant to Registration Review.

Author Barcode Date Title

Collantes, M. D296725 4/10/2006 S-Metolachlor: Occupational Exposure 

Assessment. EPA Memorandum. 

Dapson, S and 

Rinde, E. 

TXR No. 

0011347 

11/16/1994 Carcinogenicity Peer Review of Metolachlor (4th) 

Dobozy, V. D274326 8/28/2001 Metolachlor and s-Metolachlor. Results of the 

Health Effects Division (HED) Metabolism 

Assessment Review Committee (MARC) Meeting 

Held on 14-August-2001. PC codes: 108801 and 

108800. EPA Memorandum. 

Dobozy, V. TXR No. 

0014691 

9/28/2001 Metolachlor and S-Metolachlor: Report of the 

Hazard Identification Assessment Review 

Committee (HIARC) 

EPA -- 2/2012 Residential SOPs. Available at 

http://www.epa.gov/pesticides/science/residentialexposure-sop.html 

Evans, E. and 

Recore, S 

D420801 9/16/2014 Metolachlor: Tier 1 Review of Human Incidents 

Hummel, S. D407466. 8/1/2013 S-Metolachlor. Petition for the Amendment of 

Permanent Tolerances for Residues of SMetolachlor on Corn, field, forage; Corn, sweet, 

forage; and Corn, stover. Summary of Analytical 

Chemistry and Residue Data. EPA Memorandum. 

PP#2F8115. 

Hummel, S. D411153 8/15/2013 

S-Metolachlor. Human Health Risk Assessment for 

the petition for higher tolerances on Corn, field, 

forage; Corn, sweet, forage; and Corn, stover. 

PP#2F8115 

Kinard, S. D288263 2/12/2003 Metolachlor: Revised HED Science Assessment for 

the Tolerance Reassessment Eligibility Decision, 

Including the Pending Petitions on Asparagus, 

Carrot, Horseradish, All Peppers, Rhubarb, Sugar 

Beet, Sunflower, Swiss Chard, Tomato, Spinach, 

and Grasses Grown for Seed. PP#s: 7F04897, 

9E06055, 7E04916, 2E06374, 4E04420, 8E05029, 

Kinard, S. DP Barcode 

D292881; 

Rereg. Case 

0001.D25548

8/15/2003 Revised Metolachlor and S-Metolachlor Residue 

Chemistry Chapter for the Tolerance Reassessment 

Eligibility Decision (TRED) and Registration for 

Use on Asparagus, Carrots, Cotton, Horseradish, 
Metolachlor/S-Metolachlor Scoping Document D420468 

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Table 1. Memoranda Relevant to Registration Review.

Author Barcode Date Title

4, D258813, 

D258816, 

D258825, 

D258958, 

D259117, 

D280858, 

D288570. 

Green Onions, Peppers, Rhubarb, Sugar Beet, 

Sunflower, and Swiss Chard. EPA Memorandum. 

PP#s: 7F04897, 9E06055, 7E04916, 2E06374, 

4E04420, 8E05029, and 8E05030 

Koper, C. D368735 4/22/2010 Drinking Water Assessment for S-Metolachlor and 

its Degradates Ethanesulfonic Acid (ESA) and 

Oxanilic Acid (OA) for Various Crop Uses.” EPA 

EFED Memorandum. 

Nieves, I D370432 6/29/2010 S-Metolachlor: Occupational and Residential 

Exposure/Risk Assessment of Proposed Section 3 

uses on sesame, melon subgroup 9A, bushberry 

subgroup 13-07B and lowbush blueberry, 

caneberry subgroup 13-07A, sweet sorghum, leafy 

brassica greens subgroup 5B, including turnip 

greens, carrot, cucumber, okra, onion bulb 

subgroup 3-07A, and onion green subgroup 3-07B 

Soderberg, D D341704 11/27/2007 Metolachlor: A Confined Rotational Crop Study 

with [Phenyl-14C]-Metolachlor Using Radish, 

Lettuce and Wheat. Final Report. 

Van Alstine, 

Julie 

N/A 3/20/2013 Metolachlor: Summary of Hazard and Science 

Policy Council (HASPOC) Meeting of February 

14, 2013: Recommendations on the Need for a 

Neurotoxicity Battery, a Developmental 

Neurotoxicity Study, and a Subchronic Inhalation 

Study.” EPA Memorandum. 

Attachments 

Attachment 1. Chemical Identity of Metolachlor and S-Metolachlor and Degradates 

Attachment 2. Toxicity Profile Tables 

Attachment 3. Metolachlor/S-Metolachlor Endpoints and Doses for Risk Assessment 

Attachment 4. Metolachlor and S-Metolachlor International Residue Limits Table 

 
Metolachlor/S-Metolachlor Scoping Document D420468 

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Attachment 1. Chemical Identity of Metolachlor/S-Metolachlor 

Chemical Identity and Physicochemical Properties Table 

The chemical structure and nomenclature of S-metolachlor and its regulated hydrolytic 

derivatives are presented in Table A1.1a. The chemical structure and nomenclature of 

metolachlor and its regulated hydrolytic derivatives are presented in Table A1.1b. 

Table A1.1a Nomenclature of S-Metolachlor and its Regulated Hydrolytic Derivatives. 

Parent compound 

Common name S-Metolachlor 

Company experimental name CGA-77102 (R-Metolachlor is CGA-77101) 

IUPAC name (S)-2-chloro-N-(2-ethyl-6-methyl-phenyl)-N-(2-metonym-1-methyl-ethyl)-

acetamide 

CAS name 2-chloro-N-(2-ethyl-6-methylphenyl)-N-[(1S)2-methoxy-1-methylethyl]-

acetamide 

CAS registry number 87392-12-9 

End-use product (EP) Dual Magnum® Herbicide (7.62 lb/gal EC; EPA Reg. No. 100-816) and 

Dual II Magnum® Herbicide (7.64 lb/gal EC; EPA Reg. No. 100-818) 

Regulated residue 

Common name None 

Company experimental names CGA-37913 

SYN506357 (S-enantiomer of CGA 37913) 

Chemical name 2-[(2-ethyl-6-methylphenyl) amino]-1-propanol 

H C3

CH3

N

O

CH3

Cl

H C3

O

H3C

NH

CH3

HO

CH3
Metolachlor/S-Metolachlor Scoping Document D420468 

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Table A1.1a Nomenclature of S-Metolachlor and its Regulated Hydrolytic Derivatives. 

CAS registry number 61520-53-4 

82508-08-5 (S-enantiomer) 

Regulated residue 

Common name None 

Company experimental names CGA-49751 

SYN508500 (S-enantiomer of CGA 49751) 

Chemical name 4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-morpholinone 

CAS registry number 61520-54-5 

TABLE A1.1b Metolachlor Test Compound Nomenclature.

Compound 

Common name Metolachlor 

Company experimental name Not applicable 

IUPAC name 2-chloro-N-(6-ethyl-o-tolyl)-N-[(1RS)-2-methoxy-1-methylethyl]acetamide 

or 

(aRS,1RS)-2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidide 

CAS name 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide 

CAS registry number 51218-45-2 

End-use product (EP) Stalwart® Herbicide (EPA Reg. No. 60063-34; 8 lb/gal EC) 

Compound 

Common name CGA-49751 

H3C

CH3

N

O

O

OH

H3C

H3C

N

O

Cl

CH3

O

H3C

CH3

H3C

CH3

N

O

O

OH

H3C
Metolachlor/S-Metolachlor Scoping Document D420468 

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TABLE A1.1b Metolachlor Test Compound Nomenclature.

Chemical name 4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-morpholine 

CAS registry number 61520-54-5 

Compound 

Common name CGA-37913 

Chemical name 2-[(2-ethyl-6-methylphenyl)amino]-1-propanol 

CAS registry number 61520-53-4 

H3C

NH

CH3

HO

CH3
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Table 2. Metolachlor/S-Metolachlor and Its Environmental Degradates 

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRI

Parent 

Metolachlor (CGA-24705) 

CAS Name: (R)2-Chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide CAS Number: 051218-45-2Molecular Weight: 283.80 

g/mol Chemical Formula:

C15

H22NO2Cl 

SMILES: CCC1=CC=CC(=C1N(C(C)COC)C(=O)CCl)C 

Parent structure show

S-Metolachlor (CGA-77102) 

CAS Name: (S)-2-Chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide CAS Number: 087392-12-9 Molecular Weight: 283.80 

g/mol Chemical Formula:

C15

H22NO2Cl 

SMILES: 

CCC1=CC=CC(=C1N([C@@H](C)COC)C(=O)CCl)C

Parent structure show
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Code Name/ Synonym Chemical Name Chemical Structure Study Type MRI

Transformation Products 

Metolachlor Oxanilic Acid/ Metolachlor-OA (CGA-51202) 

CAS Name: [(2-ethyl-6-methylphenyl) (2-methoxy-1-methylethyl) amino] oxo-acetic acid Molecular Weight: 389.06 g/mol 

Aqueous Photolysis 404302Aerobic Soil Metabolism 454996Aerobic Soil Metabolism 439289Aerobic Soil Metabolism 313098

A-B 

Anaerobic Soil Metabolism 

313098

A-B 

Terrestrial Field Dissipation 458480

Metolachlor ethane sulfonic acid/ MetolachlorESA (CGA-354743) 

CAS Name: Not assigned I found 2-((2-

ethyl-6-methylphenyl)(2-methoxy-1-methylethyl)amino)-2-oxoethanesulfonic acid http://sitem.herts.ac.uk/aeru/iupac/1031.htm Molecular Weight: 329 g/mol 

Aerobic Soil Metabolism 454996

Aerobic Soil Metabolism 439289Terrestrial Field Dissipation 458480

CGA-41507 CAS Name: 

Not assigned Aerobic Aquatic Metabolism 411857
Metolachlor/S-Metolachlor Scoping Document 

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Code Name/ Synonym Chemical Name Chemical Structure Study Type MRI

Molecular Weight: 157 g/mol 

Anaerobic Aquatic Metabolism 411857

CGA-40172 CAS Name: 

Not assigned (not reported) Molecular Weight: 346.03 g/mol 

Aerobic Aquatic Metabolism 411857Anaerobic Aquatic Metabolism 411857Aerobic Soil Metabolism 454996

CGA-41638 CAS Name: 

Not assigned (not reported) Molecular Weight: 346.03 g/mol 

Aqueous Photolysis 404302Aerobic Soil Metabolism 313098

A-B 

Anaerobic Soil Metabolism 

313098

A-B 

CGA-50720 CAS Name: 

Not assigned (not reported) Molecular Weight: 346.03 g/mol 

Aerobic Aquatic Metabolism 411857

Aqueous Photolysis 404302Aerobic Soil Metabolism 313098

A-B 
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Code Name/ Synonym Chemical Name Chemical Structure Study Type MRI

Anaerobic Soil Metabolism 

313098

A-B 

CGA-37913 

Anaerobic Aquatic Metabolism 411857

CGA-37735 

Aerobic Soil Metabolism 313098

A-B 

Anaerobic Soil Metabolism 

313098

A-B 

CGA-13656 

Aerobic Soil Metabolism 313098

A-B 

Anaerobic Soil Metabolism 

313098

A-B 
Metolachlor/S-Metolachlor Scoping Document 

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Code Name/ Synonym Chemical Name Chemical Structure Study Type MRICGA-46129 

Aqueous Photolysis 404302

CGA-46127 Aerobic Aquatic 

Metabolism 411857Anaerobic Aquatic Metabolism 411857

Note: Bold values denote major (> 10%) degradates. 
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Physical/Chemical Characteristics

S-Metolachlor is fairly soluble in water (0.48 g/L), and completely miscible with typical 

pesticide solvents. It has a moderately low vapor pressure (2.8 x 10-5 mm Hg). It does not 

dissociate. It has a high octanol-water partition coefficient (Log(KOW) = 3.0 at 25 C), indicating a 

potential for bioaccumulation or partitioning into human milk. Environmental fate data indicate 

that parent metolachlor/S-metolachlor is moderately persistent to persistent. It is mobile to highly 

mobile in different soils and has been detected extensively in surface water and groundwater. 

Metolachlor/S-metolachlor degradation appears to be dependent on microbially mediated and 

abiotic processes. The physical-chemical properties for S-metolachlor and metolachlor are 

tabulated in Table A1.2a and A1.2b, respectively. 

Table A1.2. Physicochemical Properties of S-Metolachlor. 

Parameter Value Reference 

Melting point/range Not applicable, liquid at room temperature MRID 47121701 

(DP#s 332846, etc., 

10/21/08, D. 

McNeilly) 

pH 7.8 at 25 oC (1% aqueous dispersion) 

Density 1.117 g/cm3 at 20 oC 

Water solubility (25°C) 0.48 g/L 

Solvent solubility (mg/L at 25°C) Completely miscible with methanol, acetone, toluene, 

n-octanol, n-hexane, ethyl acetate, and dichloromethane. 

Vapor pressure at 25°C 2.8 x 10-5 mm Hg 

Dissociation constant (pKa) No dissociation constant in pH range 2-12 

Octanol/water partition coefficient 

Log(KOW) 

3.05 at 25 oC 

UV/visible absorption spectrum Neutral: 534 L/mol•cm @ 266.4 nm 

 443 L/mol•cm @ 274.4 nm 

Acidic: 534 L/mol•cm @ 266.4 nm 

 444 L/mol•cm @ 274.4 nm 

Basic: 531 L/mol•cm @ 266.4 nm 

 411 L/mol•cm @ 274.4 nm 
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TABLE 2. Physicochemical Properties of Technical Grade Metolachlor

Parameter Value Reference1

Physical state (color) Liquid (pale yellow to light brown) TRED Product Chemistry 

Chapter (D274330) 

Boiling point 100OC at 0.001 mm mercury. RED 

pH 7-9 @ 25OC (1% aqueous dispersion) TRED Product Chemistry 

Chapter (D274330) 

Density 1.117 g/mL at 20OC TRED Product Chemistry 

Chapter (D274330) 

Water solubility 0.48 g/L @ 25OC TRED Product Chemistry 

Chapter (D274330) 

Solvent solubility Miscible in xylene, toluene, 

ethylene dichloride, and cyclohexanone. 

RED 

Vapor pressure 2.8 x 10-5 mm Hg @ 25OC TRED Product Chemistry 

Chapter (D274330) 

Octanol/water partition coefficient, 

Log(KOW) 

3.05 @ 25OC TRED Product Chemistry 

Chapter (D274330) 

 
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Attachment 2. Toxicity Profile Tables 

A.2 Toxicity Profiles 

Table A.2.1 Acute Toxicity Profile - Metolachlor 

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

870.1100 Acute oral - Rat 00015523 LD50 = 2780 mg/kg III 

870.1200 Acute dermal - Rabbit 00015526 LD50 = > 10 g/kg III 

870.1300 Acute inhalation -Rat 00015535 LC50 = > 1.75 mg/L III 

870.2400 Acute eye irritation - Rabbit 00015528 Non-irritating IV 

870.2500 Acute dermal irritation - Rabbit 00015530 Non-irritating IV 

870.2600 Skin sensitization – guinea pig 00015631 positive 

Table A.2.1 Acute Toxicity Profile – S-Metolachlor 

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

870.1100 Acute oral - Rat 43928915 LD50 = 3267 mg/kg 

(♂); 2577 mg/kg/day 

(♀); 2672 mg/kg/day 

(combined) 

III 

870.1200 Acute dermal - Rabbit 43928916 LD50 = > 2000 mg/kg III 

870.1300 Acute inhalation -Rat 43928917 LC50 = > 2.91 mg/L IV 

870.2400 Acute eye irritation - Rabbit 43928918 Slight to moderate 

conjunctival irritation 

that cleared in 48 

hours 

III 

870.2500 Acute dermal irritation - Rabbit 43928919 non-irritating IV 

870.2600 Skin sensitization – guinea pig 43928920 positive 
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Metolachlor

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral 

toxicity (rat) 

44775401 (1999) 

0, 30, 300, 3000 ppm 

(M/F: 0, 2.00/2.32, 

20.2/23.4, 210/259 

mg/kg/day) 

NOAEL for males = 3000 ppm 

LOAEL for males not established 

NOAEL for females = 300 ppm 

LOAEL for females = 3000 ppm based on 

decreased body weight/body weight gain 

Acceptable/Guideline 

870.3150 180-Day oral 

toxicity (dog) 

00032174 (1980), 

43244001 

0, 100, 300, 1000 ppm 

(M/F: 0, 2.92/2.97, 

9.71/8.77, 29.61/29.42) 

NOAEL = 300 ppm 

LOAEL = 1000 ppm based on decreased body 

weight gain 

Unacceptable/Guideline 

870.3200 21-Day dermal 

toxicity rabbits 

41833101 (1987) 

0, 10, 100 or 1000 

mg/kg/day 

Systemic NOAEL = 1000 mg/kg/day. 

Systemic LOAEL was not established 

Dermal irritation NOAEL was not established 

Dermal irritation LOAEL = 10 mg/kg/day 

based on very slight erythema, dry skin and 

fissuring (one animal) 

Acceptable/Guideline 

870.3700a Prenatal 

developmental 

toxicity in rodents 

(rat) 

00151941 (1985) 

0, 30, 100, 300 or 1000 

mg/kg/day 

Maternal toxicity NOAEL = 300 mg/kg/day. 

Maternal toxicity LOAEL = 1000 mg/kg/day 

based on an increased incidence of death, 

clinical signs of toxicity (clonic and/or toxic 

convulsions, excessive salivation, urine-stained 

abdominal fur and/or excessive lacrimation) 

and decreased body weight gain. 

Developmental toxicity NOAEL = 300 

mg/kg/day Developmental toxicity LOAEL = 

1000 mg/kg/day based on slightly decreased 

number of implantations per dam, decreased 

number of live fetuses/dam, increased number 

of resorptions/dam and significant decrease in 

mean fetal body weight 

Acceptable/Guideline 
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Metolachlor

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700b Prenatal 

developmental in 

(New Zealand 

White) rabbits 

00041283 (1980) 

0, 36, 120 or 360 

mg/kg/day 

Maternal toxicity NOAEL = 120 mg/kg/day. 

Maternal toxicity LOAEL = 360 mg/kg/day 

based on an increased incidence of clinical 

observations (persistent anorexia) and 

decreased body weight gain 

Developmental toxicity NOAEL = 360 

mg/kg/day 

Developmental toxicity LOAEL was not 

established. 

Acceptable/Guideline 

870.3800 Reproduction and 

fertility effects 

(CD albino) rats 

00080897 (1981) 

0, 30, 300 or 1000 ppm 

F0 males: 0, 2.4, 23.5, and 

75.8 mg/kg/day; F0

females: 0, 2.5, 26.0, and 

85.7 mg/kg/day; F1 males: 

0, 2.3, 23.7, and 76.6 

mg/kg/day; F1 females: 0, 

2.6, 25.7, and 84.5 

mg/kg/day metolachlor 

(95.4% ai) (dietary) 

Parental/Systemic NOAEL = 1000 ppm (F0

males/females: 75.8/85.7 mg/kg/day; F1

males/females: 76.6/84.5 mg/kg/day) highest 

dose tested. 

LOAEL = Not established 

Reproductive NOAEL = 1000 ppm (F0

males/females: 75.8/85.7 mg/kg/day; F1

males/females: 76.6/84.5 mg/kg/day) highest 

dose tested. 

LOAEL = Not established 

Offspring NOAEL = 300 ppm (F0

males/females: 23.5/26.0 mg/kg/day; F1

males/females: 23.7/25.7 mg/kg/day 

LOAEL = 1000 ppm (F0 males/females: 

75.8/85.7 mg/kg/day; F1 males/females: 

76.6/84.5 mg/kg/day based on decreased body 

weight in F1 and F2 litters. 

Acceptable/Guideline 

870.4100b Chronic toxicity 

dogs 

40980701, 41164501, 

42218601 and 42218602. 

(1989) 

0, 100, 300 or 1000 ppm 

(males: 0, 3.5, 9.7 and 

32.7 mg/kg/day, 

respectively; females: 0, 

3.6, 9.7 and 33.0 

mg/kg/day, respectively) 

for one year. 

NOAEL = 300 ppm (9.7 mg/kg/day) for 

females 

LOAEL = 1000 ppm for females (33.0 

mg/kg/day) based on decreased body weight 

gain 

NOAEL = 1000 ppm (32.7 mg/kg/day). 

LOAEL for males was not established; 

Acceptable/Guideline 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 29 of 44

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Metolachlor

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.4200 Chronic toxicity/ 

Carcinogenicity 

rat 

00129377 (1983) 

0, 30, 300 or 3000 ppm 

(0, 1.5, 15 or 150 

mg/kg/day based on 1 

ppm in food equals 0.05 

mg/kg/day) 

NOAEL = 300 ppm (15 mg/kg/day) for females 

LOAEL = 3000 ppm (150 mg/kg/day) for 

females based on slightly decreased body 

weight gain and food consumption. 

The LOAEL was not established for males. The 

NOAEL was 3000 ppm (150 mg/kg/day). 

Administration of doses up to 3000 ppm was 

associated with statistically significant 

increases in liver adenomas and combined 

adenoma/carcinoma in female rats. In male rats, 

there was a statistically significant trend but not 

pair-wise significance for liver tumors. 

Acceptable/Guideline 

870.4300 Carcinogenicity 

mice 

00117597 (1982) 

0, 300, 1000 or 3000 ppm 

(0, 45, 150 or 450 

mg/kg/day) 

NOAEL = 100 ppm (150 mg/kg/day) 

LOAEL = 3000 ppm (450 mg/kg/day) based on 

possible treatment-related deaths in females 

and decreased body weight/body weight gain in 

males and females

no evidence of carcinogenicity 

Acceptable/Guideline 

870.5100 Gene Mutation 

bacterial reverse 

mutation 

00015397 (1976) 

10, 100, 1000 and 10,000 

ug/plate 

Negative up to cytotoxic doses (1000 ug/plate) 

Acceptable/Guideline 

870.5300 Gene Mutation 

mouse lymphoma 

00158929 (1984) 

9.5-190 nL/mL without 

activation; 10.5-280 

nL/mL with activation 

No effect on the incidence of mutations in the 

presence or absence of metabolic activation 

Acceptable/Guideline 

870.5395 Cytogenetics 

micronucleus 

assay in Chinese 

hamsters 

00158925 (1984) 

0, 1250, 2500 or 5000 

mg/kg 

No effect of treatment on incidence of 

micronuclei induction 

Acceptable/Guideline 

870.5450 Cytogenetics 

dominant lethal 

assay in mice 

00015630 (1978) 

100 or 300 mg/kg 

No effect on embryonic death, pre- and postimplantation or fertility rates in mated females 

Acceptable/Guideline 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 30 of 44

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Metolachlor

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.5550 Other Effects 

DNA 

Damage/Repair in 

rat hepatocytes 

00142828 (1984) 

0.125, 0.625, 3.125 or 

15.625 nL/mL 

Negative 

Acceptable/Guideline 

870.5550 Other Effects 

DNA 

Damage/Repair in 

human fibroblasts 

00142827 

0.125, 0.625, 3.125 or 

15.625 nL/mL 

Negative 

Acceptable/Guideline 

870.5550 Other Effects 

Unscheduled 

DNA synthesis in 

rat hepatocytes 

43244003 (1994) 

1250, 2500 or 4000 mg/kg 

to males; 500, 1000 or 

1500 mg/kg to females 

Negative for induction of UDS; however, 

significant increases in percentage of cells in Sphase were observed in females dosed at 500 

mg/kg (but not at 1000 or 1500 mg/kg) and 

sacrificed at 15 hours 

Acceptable/Guideline 

870.7485 Metabolism and 

pharmacokinetics 

rodents 

MRID 00015425 (1974) 

52, 28 or 33 mg/kg to 

male rats 

Urinary metabolites of CGA 24705 (N-(2-

methoxy-1-methylethyl)-2-ethyl-6-methylchloroacetanilide) were identified following 

oral administration of 52 mg/kg, 28 mg/kg, and 

33 mg/kg to male rats. Two metabolites, each 

comprising approximately 5% of chloroform 

extractable urinary radioactivity, were 

identified from oral administration of CGA 

24705. 

The major metabolic pathway proposed from 

analysis of urinary as well as fecal metabolites 

is one of cleavage of the ether bond and 

subsequent oxidation to the carboxylic acid, as 

well as hydrolytic removal of the chlorine 

atom. Conjugation of CGA 24705 or 

metabolites with glucuronic acid or sulfate does 

not appear to occur. 

Current guideline recommendations as to dose 

levels and use of both sexes in metabolism 

studies were not followed. Thus, whether the 

metabolic pattern is altered with dose or 

repeated exposure cannot be evaluated from 

these data. 

Unacceptable/Non-guideline 

870.7485 Metabolism and 

pharmacokinetics 

40114401 (1987) Single low (1.5 mg/kg), single high (300 

mg/kg) and repeated low (1.5 mg/kg/day for 15 

days) oral doses of metolachlor were readily 
Metolachlor/S-Metolachlor Scoping Document D420468 

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Metolachlor

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

Single low (1.5 mg/kg), 

single high (300 mg/kg) 

and repeated low (1.5 

mg/kg/day for 15 days) 

absorbed and eliminated by male and female 

rats. Urinary and fecal elimination of 

radioactivity associated with orally 

administered [14C] metolachlor was essentially 

complete within 48 to 72 hours after dosing. 

Relatively low levels of radioactivity were 

present in the tissues of all animals at 7 days 

postdosing. 

Unacceptable/Non-guideline 

870.7485 Metabolism and 

pharmacokinetics 

43164201 (1992) 

low oral dose (1.5 mg/kg 

x 14 days), and a single 

high dose (300 mg/kg) 

Comparison of oral and intravenous data 

showed that of the administered dose, between 

69.6% and 93.2% was absorbed. Distribution 

data showed that the only significant sites of 

residual radioactivity at 7 days post-dose were 

residual carcass (0.9 - 2.2% of the administered 

dose) and red blood cells (0.95- 1.53 μg 

equivalents/gram in blood cells for all low dose 

male and female rats). Dosing regimen did not 

result in any apparent accumulation of residual 

radioactivity. 

Excretion data showed that urine and feces 

were both significant routes for elimination of 

metolachlor derived radioactivity 

Metabolism of metolachlor in this study was 

complex, with up to 32 metabolites identified in 

urine and/or feces. 

 Acceptable/Guideline 

 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 32 of 44

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – S-Metolachlor

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

870.3100 90-Day oral 

toxicity rodents 

43928923 (1995) 

0, 30, 300, 3000 or 10000 

ppm (0, 1.5, 15, 150 or 

500 mg/kg/day) 

NOAEL = 300 ppm 

LOAEL = 3000 ppm based on lower body 

weights/body weight gains, reduced food 

consumption and food efficiency and increased 

kidney weights in males 

Acceptable/Guideline 

870.3100 90-Day oral 

toxicity rodents 

44775402 (1999) 

0, 30, 300, 3000 ppm 

(M/F: 0, 1.90/2.13, 

20.4/23.9 and 208.0/236.0 

mg/kg/day0 

NOAEL = 3000 ppm (equivalent to 208 

mg/kg/day in males and 236 mg/kg/day in 

females 

LOAEL cannot be defined 

Unacceptable/Guideline 

870.3150 90-Day oral 

toxicity 

nonrodents 

43928922 (1995) 

0, 300, 500, 1000 or 2000 

ppm (M/F: 0, 9/10, 

15.1/17.2, 31.1/31.5 or 

62/74 mg/kg/day) 

NOAEL = 2000 ppm (M/F: 62/74 mg/kg/day) 

LOAEL = not established 

Acceptable/Non-guideline 

870.3700a Prenatal 

developmental in 

(Tif:RAI f (SPF)) 

rats 

43928925 (1995) 

0, 5, 50, 500, or 1000 

mg/kg/day S-metolachlor 

(95.6% ai) in 0.5% (w/w) 

aqueous solution of 

sodium 

carboxymethylcellulose 

(gavage) GD 6-15 

Maternal NOAEL = 50 mg/kg/day 

LOAEL = 500 mg/kg/day based on increased 

clinical signs of toxicity, decreased body 

weights and body weight gains and reduced 

food consumption and reduced food efficiency. 

Developmental NOAEL = 1000 mg/kg/day, 

highest dose tested. 

LOAEL = Not established 

Acceptable/Guideline 

870.3700b Prenatal 

developmental in 

(New Zealand 

White) rabbits 

43928924 (1995) 

0, 20, 100, or 500 

mg/kg/day S-metolachlor 

(89.6% ai (93.7% S 

isomer)) suspension in 3% 

corn starch (gavage) GD 

7-19 

Maternal NOAEL = 20 mg/kg/day 

LOAEL = 100 mg/kg/day based on clinical 

signs of toxicity. 

Developmental NOAEL = 500 mg/kg/day, 

highest dose tested. 

LOAEL = Not established 

Acceptable/Guideline 
Metolachlor/S-Metolachlor Scoping Document D420468 

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – S-Metolachlor

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

870.5100 Gene Mutation 

Salmonella & 

Escherichia/Mam

malian Microsome 

Mutagenicity Test 

43928927 (1995) 

78.13-1250.0 ug/plate 

In independently performed microbial 

mutagenicity assays, Salmonella typhimurium

TA1535, TA1537, TA98, TA100 and TA102 

and Escherichia coli WP2 uvrA were initially 

exposed to 312.5-5000.0 μg/plate CGA-77102 

technical (95.6%) in the presence and absence 

of S9 activation. For the confirmatory trial, 

doses of 78.13-1250.0 μg/plate ±S9 were 

evaluated with S. typhimurium strains TA1535, 

TA1537, TA100 and TA102; concentrations of 

312.5-5000.0 μg/plate ±S9 were examined with 

S. typhimurium TA 98 and E.coli WP2 uvrA. 

In general, doses 1250.0 μg/plate ±S9 were 

cytotoxic for S. typhimurium TA1535, TA1537, 

TA100 and TA102 and 5000.0 μg/plate ±S9 

was slightly cytotoxic for S. typhimurium TA98 

and E. coli WP2 uvrA. There was, however, no 

indication that CGA-77102 technical induced 

of a mutagenic effect in any tester strain either 

in the presence or the absence of S9 activation. 

Acceptable/Guideline 

870.5395 Cytogenetics 

Micronucleus test 

43928926 (1995) 

500, 1000 or 2000 mg/kg 

Groups of five male and five female 

Tif:MAGf(SPF) mice received single oral 

gavage administrations of 500, 1000 or 2000 

mg/kg CGA 77102 technical (95.6%). 

Toxic signs, similar to those seen in the 

preliminary range-finding studies (i.e., ataxia, 

tremors and/or hunched posture) were recorded 

for high-dose males and females throughout the 

48-hour postexposure. No bone marrow 

cytotoxicity was seen at any dose or sacrifice 

time. The positive control induced the expected 

high yield of MPEs in males and females. 

There was, however, no evidence that CGA 

77102 technical induced a clastogenic or 

aneugenic effect in either sex at any dose or 

sacrifice time. 

Acceptable/Guideline 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 34 of 44

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – S-Metolachlor

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

870.5550 Other Effects 

Unscheduled 

DNA synthesis 

43928928 (1995) 

500, 1500, 3200 

(females), 5000 (males) 

mg/kg 

CGA 77102 Technical was negative for 

genotoxicity but positive for cellular 

proliferation when tested up to overtly toxic 

and cytotoxic doses in this in vivo/in vitro rat 

hepatocyte RDS/UDS assay. 

Acceptable/Guideline 

870.7485 Metabolism and 

pharmacokinetics 

44491401 (1996) 

single dose of 0.5 (group 

B1) or 100 mg/kg (group 

D1) radiolabeled CGA77102; 100 mg/kg/day 

non-radiolabeled CGA 

77102 for 14 days 

followed by 0.5 mg/kg 

radiolabeled CGA-77102 

(Group V1); single dose 

of 0.5 or 100 mg/kg 

radiolabeled CGA-77102 

for bile-cannulation study 

In all three dose groups (B1, D1, and V1), the 

seven day combined levels of radioactivity in 

urine were 31.1 - 36.5% for males and 40.8 - 

45.5% for females; the fecal levels were 60.2 - 

62.5% for males and 48.9 - 55.0% for females. 

Only 0.1% or less was eliminated in the expired 

air. The total recovery ranged from 96.5 ± 

2.3% to 99.3 ± 0.9%. 

Irrespective of the dose and sex, there seems to 

be a biphasic plasma profile with two 

concentration maxima (Cmax); a fast rising first 

Cmax was reached at 0.25 - 1 hour post dosing 

which was succeeded by a second Cmax at 8 and 

at 12 - 24 hours following administration of the 

low and high dose, respectively. 

Acceptable/Guideline 

870.7485 Metabolism and 

pharmacokinetics 

44491402 (1996) 

single dose of 0.5 (group 

B1) or 100 mg/kg (group 

D1) radiolabeled CGA77102; 100 mg/kg/day 

non-radiolabeled CGA 

77102 for 14 days 

followed by 0.5 mg/kg 

radiolabeled CGA-77102 

(Group V1); single dose 

of 0.5 or 100 mg/kg 

radiolabeled CGA-77102 

for bile-cannulation study 

(from MRID 44491401) 

single oral low dose (0.5 

mg/kg, Group B2) of 

[Phenyl-U-14C] CGA24705 (R/S-Metolachlor, 

racemate) 

The 72 hour mean recovery of radioactivity in 

urine, feces, and carcass following 

administration of 0.5 mg/kg of [Phenyl-U-14C] 

CGA-24705 was 43.1%, 47.0%, and 7.4% in 

males and 54.0%, 39.4%, and 4.1% in females, 

respectively. In contrast, both sexes excreted 

more of the label in the feces (M:F 

59.7%:53.4%) than in the urine (M:F 

29.4%:39.8%) during the same period 

following administration of the same dose of 

[Phenyl-U-14C] CGA-77102 (the S-enantiomer) 

(MRID 44491401). 

The urinary and fecal metabolite profiles, with 

31 and 15 metabolite fractions, respectively, 

were qualitatively similar among all groups; 

however, there were large quantitative 

differences, based on the dosing formulation, 

on one hand, and the sex of the animal, on the 

other. 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 35 of 44

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – S-Metolachlor

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

 The results clearly show that the metabolite 

profile in excreta and bile fluid is very complex 

and that Metolachlor (racemate or Senantiomer) is extensively metabolized. 

Unacceptable/Guideline 

870.7800 Immunotoxicity in 

mice 

48783301 (2012) 

0, 1500, 3000 or 5000 

ppm (0, 304.3, 639.5, or 

1108.5 mg/kg/day 

NOAEL = 5000 ppm (1108.5 mg/kg/day) 

LOAEL = Not Established 

Acceptable/Guideline 

 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 36 of 44

Attachment 3. Metolachlor/S-Metolachlor Endpoints and Doses for Risk Assessment 

The points of departure, uncertainty factors, and toxicity endpoints are presented in the following 

tables. No endpoint is selected for dermal exposure scenarios. No hazard was identified at the 

maximum dermal dose tested.

Table 4.5.4.1. Summary of Toxicological Endpoints for S-metolachlor/Metolachlor for Use in Dietary 

Human Health Risk Assessments 

Exposure/Scenario Point of 

Departure 

Uncertainty/FQP

A Safety Factors 

RfD, PAD, 

LOC for Risk 

Assessment 

Study and Toxicological Effects 

Acute Dietary 

(General 

Population) 

NOAEL = 

300 

mg/kg/day 

UFA= 10x 

UFH=10x 

FQPA SF= 1x 

Acute RfD = 3.0 

mg/kg/day 

aPAD = 3.0 

mg/kg/day 

Developmental Toxicity Study - Rat 

Metolachlor (MRID 00151941) 

LOAEL = 1000 mg/kg/day based increased 

incidence of death, clinical signs (clonic 

and/or tonic convulsions, excessive 

salivation, urine-stained abdominal fur 

and/or excessive lacrimation) and 

decreased body weight gain. 

Chronic Dietary 

(All Populations) 

NOAEL = 

9.7 

mg/kg/day 

UFA= 10x 

UFH=10x 

FQPA SF= 1x 

Chronic RfD = 

0.097 

mg/kg/day 

cPAD = 

0.097mg/kg/day

One Year Chronic Toxicity – Dog; 

Metolachlor (MRIDs 40980701, 41164501, 

42218601 and 42218602) 

LOAEL = 33 mg/kg/day based decreased 

body weight gain in females 

Cancer (all routes) Metolachlor has been classified as a Group C carcinogen with risk quantitated using a nonlinear (Margin of Exposure) approach. 

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. 

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. 

UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). 

FQPA SF = FQPA Safety Factor. 

PAD = population adjusted dose (a = acute, c = chronic). 

RfD = reference dose. 

MOE = margin of exposure. 

LOC = level of concern. 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 37 of 44

Table 4.5.4.2. Summary of Toxicological Doses and Endpoints for S-METOLACHLOR for Use in 

Residential and Occupational Human Health Risk Assessments 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty 

Factors 

Level of 

Concern for 

Risk Assessment

Study and Toxicological Effects 

Incidental Oral Shortterm (1-30 days) NOAEL= 

50 mg/kg/day 

UFA= 10x 

UFH=10x Residential LOC 

for MOE = 100 

Developmental Toxicity Study - Rat 

S-Metolachlor (MRID 43928925) 

LOAEL = 500 mg/kg/day based on 

increased incidence of clinical signs, 

decreased body weight/body weight gain, 

food consumption and food efficiency seen 

at the LOAEL in maternal animals. 

Dermal Short- and 

Intermediate-Term No hazard identified 

21-day dermal toxicity study – Rabbits 

Metolachlor (MRID 41833101) 

LOAEL = Not observed 

Inhalation Short-Term 

(1-30 days) 

NOAEL= 

50 mg/kg/day 

UFA= 10x 

UFH=10x 

UFD=10x 

Occupational 

LOC for MOE = 

1000 

Developmental Toxicity Study - Rat 

S-Metolachlor (MRID 43928925) 

LOAEL = 500 mg/kg/day based on 

increased incidence of clinical signs, 

decreased body weight/body weight gain, 

food consumption and food efficiency seen 

at the LOAEL in maternal animals. 

Inhalation 

Intermediate-Term 

 (1-6 months) 

NOAEL= 

8.8 mg/kg/day 

UFA= 10x 

UFH=10x 

UFD=10x 

Occupational 

LOC for MOE = 

1000 

Subchronic Toxicity Study - Dog 

Metolachlor (MRIDs 00032174 and 

43244001) 

LOAEL = 29.4 mg/kg/day based on 

decreased body weight gain 

Cancer (all routes) Metolachlor has been classified as a Group C carcinogen with risk quantitated using a nonlinear (Margin of Exposure) approach. 

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key 

data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c 

= chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 38 of 44

Attachment 4. Metolachlor/S-Metolachlor International Residue Limits Table 

International Residue Limits 

Metolachlor (108801) and S-Metolachlor (PC Code 108800; Date of Request 6/26/14) 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR: 180.368 

(a)General (1) Tolerances are established 

for the combined residues (free and bound) 

of the herbicide metolachlor, 2-chloro-N-

(2- ethyl-6-methylphenyl)-N-(2-methoxy-1-

methylethyl)acetamide, and its metabolites, 

determined as the derivatives, 2- [(2-ethyl6- methylphenyl)amino]-1-propanol and 4-

(2-ethyl-6-methylphenyl)-2- hydroxy-5-

methyl-3-morpholinone, each expressed as 

the parent compound

2-chloro-N-(2-ethyl-6- 

methylphenyl)-N-[(1S)-2-methoxy1-methylethyl)acetamide 

and 2-chloro-N-(2-ethyl-6-

methylphenyl)-N-[(1R)-2-

methoxy-1- 

methylethyl)acetamide, including 

the metabolites 2-[(2-ethyl-6-

methylphenyl)amino]-1-propanol 

and 4-(2-ethyl-6-methylphenyl)-2- 

hydroxy-5-methyl-3-morpholinone 

 None 

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

US Canada Mexico1 Codex

Almond, hulls 0.30 

Animal feed, nongrass, group 

18 

1.0 

Cattle, fat 0.02 

Cattle, kidney 0.20 0.2 

Cattle, liver 0.05 0.05 

Cattle, meat 0.02 0.02 

Cattle, meat byproducts, 

except kidney and liver 

0.04 

Corn, field, forage 6.0 

Corn, field, grain 0.10 0.1 corn 

Corn, field, stover 6.0 

Corn, pop, grain 0.10 0.1 corn 

Corn, pop, stover 6.0 

Corn, sweet, forage 6.0 

Corn, sweet, kernel plus cob 

with husks removed 

0.10 0.1 corn 

Corn, sweet, stover 6.0 

Cotton, gin byproducts 4.0 

Cotton, undelinted seed 0.10 

Dillweed 0.50 

Egg 0.02 0.02 

Goat, fat 0.02 

Goat, kidney 0.20 

Goat, liver 0.05 

Goat, meat 0.02 0.02 

Goat, meat byproducts, 

except kidney and liver 

0.04 

Grass, forage 10 

Grass, hay 0.20 

Horse, fat 0.02 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 39 of 44

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Horse, kidney 0.20 

Horse, liver 0.05 

Horse, meat 0.02 

Horse, meat byproducts, 

except kidney and liver 

0.04 

Milk 0.02 0.02 

Nut, tree, group 14 0.10 

Okra 0.50 0.1 

Peanut 0.20 0.2 

Peanut, hay 20 

Peanut, meal 0.40 

Potato 0.20 0.2 

Poultry, fat 0.02 

Poultry, meat 0.02 0.02 

Poultry, meat byproducts 0.05 0.05 liver of poultry 

Safflower, seed 0.10 

Sheep, fat 0.02 

Sheep, kidney 0.20 

Sheep, liver 0.05 

Sheep, meat 0.02 0.02 

Sheep, meat byproducts, 

except kidney and liver 

0.04 

Sorghum, grain, forage 1.0 

Sorghum, grain, grain 0.30 

Sorghum, grain, stover 4.0 

Soybean, forage 5.0 

Soybean, hay 8.0 

Soybean, seed 0.20 0.2 dry soybeans 

Tomato 0.10 0.1 

Vegetable, foliage of legume, 

subgroup 7A, except soybean 

15.0 

Vegetable, legume, group 6 0.30 0.3 dry (beans, lima beans) 

0.3 edible podded snap beans, peas, 

succulent shelled lima beans 

0.2 dry soybeans 

 

 

40 CFR 180.368 

(2) sum of free and bound S-metolachlor, S2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-

methoxy-1-methylethyl)acetamide, its Renantiomer, and its metabolites, determined 

as the derivatives, 2-(2-ethyl-6-

methylphenyl)amino-1-propanol and 4-(2-

ethyl-6-methylphenyl)-2-hydroxy-5-

methyl-3-morpholinone, calculated as the 

stoichiometric equivalent of S-metolachlor 

Same as above None 

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

Asparagus 0.10 0.1 

Beet, garden, leaves 1.8 0.8 garden beet tops 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 40 of 44

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Beet, sugar, molasses 2.0 

Beet, sugar, roots 0.5 0.3 

Beet, sugar, tops 15.0 

Brassica, head and stem, 

subgroup 5A 

0.60 

Brassica, leafy greens, 

subgroup 5B 

1.8 0.9 bok choy Chinese cabbages, 

broccoli raab collards, kale, 

mustard greens; mustard spinach; 

rape leaves 

 

Bushberry subgroup 13-07B 0.15 

Caneberry subgroup 13-07A 0.10 

Carrot, roots 0.40 0.4 

Cattle, fat 0.02 

Cattle, kidney 0.20 0.2 

Cattle, liver 0.05 0.05 

Cattle, meat 0.02 0.02 

Cattle, meat byproducts, 

except kidney and liver 

0.04 

Cilantro, leaves 8.0 

Coriander, seed 0.13 

Corn, field, forage 40 

Corn, field, grain 0.10 0.1 corn 

Corn, field, stover 40 

Corn, pop, grain 0.10 0.1 corn 

Corn, pop, stover 40 

Corn, sweet, forage 40 

Corn, sweet, kernel plus cob 

with husks removed 

0.10 0.1 corn 

Corn, sweet, stover 40 

Cotton, gin byproducts 4.0 

Cotton, undelinted seed 0.10 

Cucumber 0.13 0.13 

Egg 0.02 0.02 

Grain, aspirated fractions 0.70 

Goat, fat 0.02 

Goat, kidney 0.20 

Goat, liver 0.05 

Goat, meat 0.02 0.02 

Goat, meat byproducts, 

except kidney and liver 

0.04 

Grass, forage 10.0 

Grass, hay 0.20 

Horse, fat 0.02 

Horse, kidney 0.20 

Horse, liver 0.05 

Horse, meat 0.02 

Horse, meat byproducts, 

except kidney and liver 

0.04 

Leaf petioles, subgroup 4B 0.10 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 41 of 44

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Melon, subgroup 9A 0.10 0.1 cantaloupe, citron melons, 

muskmelons (other than those 

listed in this item), watermelons 

 

Milk 0.02 0.02 

Okra 0.10 0.1 

Onion, bulb, subgroup 3-07A 0.10 

Onion, green, subgroup 3-

07B 

2.0 

Peanut 0.20 0.2 

Peanut, hay 20.0 

Peanut, meal 0.40 

Poultry, fat 0.02 

Poultry, meat 0.02 0.02 

Poultry, meat byproducts 0.05 0.05 liver of poultry 

Pumpkin 0.10 0.1 

Safflower, seed 0.10 

Sesame, seed 0.13 

Sheep, fat 0.02 

Sheep, kidney 0.20 

Sheep, liver 0.05 

Sheep, meat 0.02 0.02 

Sheep, meat byproducts, 

except kidney and liver 

0.04 

Sorghum, grain, forage 1.0 

Sorghum, grain, grain 0.3 

Sorghum, grain, stover 4.0 

Sorghum, sweet, stalk 4.0 

Soybean, forage 5.0 

Soybean, hay 8.0 

Soybean, seed 0.20 0.2 dry soybeans 

Spinach 0.50 

Squash, winter 0.10 0.1 

Sunflower, seed 0.50 

Sunflower, meal 1.0 

Tomato, paste 0.30 

Turnip, greens 1.8 

Vegetable, foliage of legume, 

except soybean, subgroup 7A 

15.0 

Vegetable, fruiting, group 8, 

except tabasco pepper 

0.10 0.1 African eggplants, bell peppers, 

bush tomatoes, coconas, currant 

tomatoes, eggplants, garden 

huckleberries, goji berries, 

groundcherries, martynias, 

naranjillas, nonbell peppers, okras, 

pea eggplants, pepinos, roselles, 

scarlet eggplants, sunberries, 

tomatillos, tomatoes, tree tomatoes 

 

Vegetable, legume, group 6 0.30 0.3 dry (beans, lima beans) 

0.3 edible podded snap beans, peas, 

succulent shelled lima beans 

0.2 dry soybeans 

 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 42 of 44

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Vegetable, root, except sugar 

beet, subgroup 1B, except 

carrot 

0.30 0.3 garden beet roots 

0.1 rutabaga roots 

 

Vegetable, tuberous and 

corm, subgroup 1C 

0.20 0.2 potatoes, sweet potato roots 

MRLs With NO US Equivalent 

Apples 0.1 

Apricots 0.1 

Cherries 0.1 

Meat of hogs 0.02 

Nectarines 0.1 

Peaches 0.1 

Pears 0.1 

Plums 0.1 

Strawberries 0.1 

 

Completed: M. Negussie; 07/10/14

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

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.368 (c) Tolerances with regional 

registrations 

(1) Tolerances with regional registration as defined in 

180.1(l) are established for the combined residues (free 

and bound) of the herbicide metolachlor [2-chloro-N-(2-

ethyl-6-methylphenyl)-N-(2-methoxy-1-

methylethyl)acetamide] and its metabolites, determined 

as the derivatives, 2-[2-ethyl-6-methylphenyl)amino]-1-

propanol and 4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-

methyl-3-morpholinone, each expressed as the parent 

compound, in or on the following raw agricultural 

commodities:

Same as above None 

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

US Canada Mexico1 Codex

Pepper, nonbell 0.50 0.1 

 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 43 of 44

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.368 (c) Tolerances with regional 

registrations 

(2) Compliance with the tolerance levels specified in the 

following table below is to be determined by measuring 

only the sum of free and bound S-metolachlor, S-2-

chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-

methylethyl)acetamide, its R-enantiomer, and its 

metabolites, determined as the derivatives, 2-(2-ethyl-6-

methylphenyl)amino-1-propanol and 4-(2-ethyl-6-

methylphenyl)-2-hydroxy-5-methyl-3-morpholinone, 

calculated as the stoichiometric equivalent of Smetolachlor 

 

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

US Canada Mexico1 Codex

Pepper, tabasco 0.50 

 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

(d) Indirect or inadvertent residues. 

 (1) Tolerances are established for the indirect or 

inadvertent combined residues (free and bound) of the 

herbicide metolachlor, 2-chloro-N-(2-ethyl-6- 

methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide, 

and its metabolites, determined as the derivatives, 2-[(2-

ethyl-6-methylphenyl)amino]-1-propanol and 4-(2-ethyl-6-

methylphenyl)-2- hydroxy-5-methyl-3-morpholinone, each 

expressed as the parent compound 

 None 

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

US Canada Mexico1 Codex

Animal feed, nongrass, group 

18 

1.0 

Barley, grain 0.10 

Barley, hay 0.80 

Barley, straw 0.80 

Buckwheat, grain 0.10 

Millet, forage 0.50 

Millet, grain 0.10 

Millet, hay 0.80 

Millet, straw 0.80 

Oat, forage 0.50 

Oat, grain 0.10 

Oat, hay 0.80 

Oat, straw 0.80 

Rice, grain 0.10 

Rye, forage 0.50 

Rye, grain 0.10 
Metolachlor/S-Metolachlor Scoping Document D420468 

Page 44 of 44

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Rye, straw 0.80 

Wheat, forage 0.50 

Wheat, grain 0.10 

Wheat, hay 0.80 

Wheat, straw 0.80 

40 CFR 180.368 

(2) Tolerances for are established for the indirect or 

inadvertent residues of S-metolachlor, including its 

metabolites and degradates, in or on the commodities 

identified in the following table below. Compliance with 

the tolerance levels specified in the following table below is 

to be determined by measuring only the sum of free and 

bound S-metolachlor, S-2-chloro-N-(2-ethyl-6-

methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide, its 

R-enantiomer, and its metabolites, determined as the 

derivatives, 2-(2-ethyl-6-methylphenyl)amino-1-propanol 

and 4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-

morpholinone, calculated as the stoichiometric equivalent 

of S-metolachlor 

 

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

Animal feed, nongrass, group 

18 

1.0 

Barley, grain 0.10 

Barley, hay 0.50 

Barley, straw 0.50 

Buckwheat, grain 0.10 

Millet, forage 0.50 

Millet, grain 0.10 

Millet, hay 0.50 

Millet, straw 0.50 

Oat, forage 0.50 

Oat, grain 0.10 

Oat, hay 0.50 

Oat, straw 0.50 

Rice, grain 0.10 

Rye, forage 0.50 

Rye, grain 0.10 

Rye, straw 0.50 

Wheat, forage 0.50 

Wheat, grain 0.10 

Wheat, hay 0.50 

Wheat, straw 0.50 

Completed: M. Negussie; 07/10/14 

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

.