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1.0 Executive Summary

Background: Glyphosate is a nonselective Group 9 herbicide that is currently registered for preand post-emergence application to a variety of fruit, vegetable, and field crops. Tolerances are 

currently established for residues of glyphosate in/on various plant commodities (including field 

corn) at 0.2-400 ppm (40 CFR §180.364(a)) and for the combined residues of glyphosate and Nacetyl-glyphosate (expressed as glyphosate) in/on field corn, soybean, canola, aspirated grain 

fractions (AGF), and livestock commodities at 0.1-310 ppm. The Glyphosate Reregistration 

Eligibility Decision (RED) document was issued September 1993. The most recent glyphosate 

human-health risk assessment was conducted on 29-Nov-2011 (D387535, T. Bloem)

The Interregional Research Project No. 4 (IR-4) requested a Section 3 Registration modifying the 

currently registered application scenario for carrot, sweet potato, and the oilseeds (crop group (CG)

20). IR-4 also proposed translation of the wheat forage/hay tolerance to teff forage/hay and 

proposed updating the CG definitions for bulb vegetable (CG 3-07), fruiting vegetable (CG 8-10), 

citrus fruit (CG 10-10), pome fruit (CG 11-10), and berry (CG 13-07). Section 2.2.2 includes a 

summary of the petitioner proposed tolerances. 

Hazard Characterization: Glyphosate is categorized as having low acute toxicity for the oral, 

dermal, and inhalation routes, since all studies are in Toxicity Categories III or IV. It is a mild 

eye irritant (Toxicity Category III), slight skin irritant (Toxicity Category IV), and is not a 

dermal sensitizer. 

A chronic feeding/carcinogenicity study in rats found no systemic effects in any of the 

parameters examined (body weight, food consumption, clinical signs, mortality, clinical 

pathology, organ weights, and histopathology). A second chronic feeding/carcinogenicity study 

in rats tested at higher dietary levels, and a lowest-observed-adverse-effect level (LOAEL) was 

identified at 20,000 parts per million (approximately 940 mg/kg/day) based on decreased bodyweight gains in females and an increased incidence of cataracts and lens abnormalities, decreased 

urinary pH, increased absolute liver weight, and increased relative liver weight/brain weight in 

males. No evidence of carcinogenicity was found in mice or rats. In a chronic toxicity study in 

dogs, no systemic effects were found in all examined parameters. 

No significant reproductive and developmental toxic effects were found. On the basis of 

developmental studies in rats and rabbits and reproductive findings in rats, there was no evidence 

of increased susceptibility of offspring. Neurotoxicity has not been observed in any of the acute, 

subchronic, chronic, developmental, or reproductive studies performed with glyphosate. 

Since the last risk assessment, the neurotoxicity screening battery tests, and immunotoxicity 

study have been submitted. Preliminary review shows no effects up to the highest dose tested for 

both the acute and subchronic durations for the neurotoxicity studies. The preliminary review of 

the immunotoxicity study also shows no effects up to the highest dose tested. 
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Food Quality Protection Act (FQPA) Safety Factor (SF): The RAB1 risk assessment team 

recommends that the FQPA SF be reduced to 1x. This recommendation is based on the

considerations described in the subsequent sections. 

●The toxicology database for glyphosate is adequate for characterizing glyphosate toxicity and 

quantification of risk for dietary and occupational uses. The following acceptable studies are 

available for evaluation: developmental toxicity study in rats and rabbits; two-generation 

reproduction study in rats.

●There is no evidence of neurotoxicity in any of the toxicology studies conducted. 

●There is no quantitative or qualitative evidence of increased susceptibility of rat or rabbit fetuses 

to in utero exposure in developmental studies. 

●The dietary exposure analysis is conservative as it assumed tolerance level residues and 100% 

crop treated. The residential exposure analysis is also considered conservative as it is based on the 

2012 Residential SOPs.

Residential and Non-Occupational Exposure and Risk Assessment: The proposed uses are not 

anticipated to result in residential exposure. However, glyphosate is currently registered for 

application to turf (including golf courses and residential lawns) and for aquatic application, and 

residential exposure may occur as a result of these uses. These uses have been reassessed in this 

document to reflect (1) the HED’s Residential Standard Operating Procedures (SOPs; 2012), (2) 

updates to HED’s inputs for aquatic/swimmer assessments, and (3) updated body weight 

information. 

Based on the registered residential use patterns, there is a potential for short-term dermal and 

inhalation exposure to residential handlers (mixing, loading, and applying) and short-term dermal, 

inhalation, and incidental oral exposure from post-application activities. Since short- and 

intermediate-term dermal or inhalation endpoints were not selected, a quantitative exposure risk 

assessment was not completed for these routes of exposure. However, children may have shortterm post-application incidental oral exposures from hand-to-mouth behavior on treated lawns and 

swimmers (adult and children) may have short-term post-application incidental oral exposures 

from aquatic uses. Based on the soil half-life for glyphosate, intermediate-term soil ingestion was 

also considered. The resulting MOEs were all ≥1,100 and, therefore, do not exceed HED’s level 

of concern (LOC). 

Dietary (food and water) Risk Assessment: A chronic dietary risk assessment was conducted using 

the Dietary Exposure Evaluation Model - Food Consumption Intake Database (DEEM-FCID , ver. 

3.16) which incorporates consumption data from United States Department of Agriculture (USDA) 

National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA; 

2003-2008). Acute and cancer dietary risk assessments were not conducted since an appropriate 

endpoint attributable to a single dose was not identified for the general U.S. population or any 

population subgroup and glyphosate is classified as not likely to be a human carcinogen, 

respectively. The chronic analysis assumed tolerance-level residues, 100% crop treated, and DEEM 

(ver 7.81) default processing factors for all commodities, and modeled drinking water estimates 

(direct application to water scenario). The resulting chronic risk estimates (food and water) were 

≤13% chronic population adjusted dose (cPAD) and are not of concern to HED (children (1-2 years 

old) were the most highly exposed population). 
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Aggregate Risk Assessment: In accordance with the FQPA, HED must consider and aggregate 

pesticide exposures and risks from three major sources: food, drinking water, and residential 

exposures. Based on the registered/proposed agricultural and residential uses, HED conducted 

short-term (food, water, residential incidental oral), intermediate-term (food, water, residential 

incidental oral), and chronic (food and water) aggregate risk assessments. The resulting 

aggregate exposures are all less than HED’s LOC. 

Occupational Risk Assessment: Based on the proposed uses, there is the potential for 

occupational handler and post-application dermal and inhalation exposure; however, no dermal 

or inhalation points of departure (PODs) were selected for glyphosate. Therefore, a quantitative 

occupational exposure assessment was not conducted. 

Human Studies: This risk assessment relies in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide or other chemical. These data, which include 

the 2012 Residential SOPs (Lawn/Turf), 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.

2.0 HED Recommendations

Provided the petitioner submits revised Sections B and F, HED concludes that the toxicological, 

residue chemistry, and occupational/residential exposure databases support an unconditional 

registration and establishment of the tolerances listed in Table 2.2.2 for residues of glyphosate. 

2.1 Data Deficiencies

Prior to Registration: Revised Section F - See Section 2.2; Revised Section B - See Section 2.3. 

As a Condition of Registration: None.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Glyphosate is currently registered for application to a wide variety of crops. HED concludes the 

currently-available tolerance enforcement method is suitable for enforcement of the tolerances 

recommended here. 

2.2.2 Recommended Tolerances

Based on the available data, HED concludes that the tolerances listed in Table 2.2.2, for residues 

of glyphosate per se, are appropriate (40 CFR §180.364(a)(1)). With the establishment of the 

tolerances listed in Table 2.2.2, the following tolerances should be deleted: vegetables, root and 

tuber, crop group 1, except sugar beet; vegetable, bulb, group 3; vegetable, fruiting, group 8; 

fruit, citrus, group 10; fruit, pome, group 11; berry group 13; borage, seed; cotton, undelinted 
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seed; crambe, seed; flax, meal; flax, seed; jojoba seed; lesquerella, seed; meadowfoam, seed; 

mustard seed; rapeseed, seed; safflower, seed; sesame, seed; sunflower, seed; cranberry; grape; 

juneberry; kiwifruit; lingonberry; salal; and strawberry. 

There are no Canadian, Codex, or Mexican maximum residue limits for residues of glyphosate 

in/on carrot or sweet potato or for CGs 1, 3-07, 8-10, 10-10, 11-10, or 13-07; therefore, 

harmonization is not an issue for these crops or CGs. There are Codex and Canadian maximum 

residue limits for the following oilseed crops: Codex (glyphosate only) - cotton seed at 40 ppm, 

sunflower seed at 7 ppm, and canola seed at 20 ppm; Canada (combined residues of glyphosate 

and aminomethyl phosphonic acid (AMPA)) - canola seed at 10 ppm and flax at 3 ppm. 

HED recently consulted the Canadian Pesticide Management Regulatory Agency (PMRA) 

concerning the canola seed tolerance and PMRA indicated that they are willing to increase the 

canola seed tolerance to 20 ppm (D394964, T. Bloem, 15-Nov-2011). Therefore, the HEDrecommended tolerance value for canola seed will be harmonized with Canada and Codex (it is 

noted that the tolerance expressions are different). Based on the residue data and use pattern for 

the remaining oilseed crops, HED concludes that the HED-recommended 40-ppm tolerance for 

CG 20 (except canola) is appropriate; with the establishment of this tolerance the U.S. and 

Codex cottonseed tolerance will be harmonized. Based on the oilseed residue data, 

harmonization with the Canadian flax and Codex sunflower seed tolerances is not possible. 

Table 2.2.2. Tolerance Summary.

Commodity Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm) Comments

vegetables, root and tuber, group 1, except 

sugar beet 6 not recommended

Based on the magnitude of the residue following 

wiper application, HED concludes that separate 

carrot and sweet potato tolerances should be 

established. 

vegetables, root and tuber, group 1, except 

carrot, sweet potato, and sugar beet -- 0.20

Carrot -- 5.0

sweet potato -- 3.0

oilseeds, group 20 40 not recommended

In order to maintain harmonization with Canada 

and Codex and due to the introduction of 

DuPontTM Optimum® GLY Canola and the 

resulting change in the canola seed tolerance 

expression, HED concludes that maintaining the 

current canola seed tolerance is appropriate.

oilseeds, group 20, except canola -- 40

vegetable, bulb, group 3-07 0.2 0.20

HED concludes that the commodity definition 

should change and/or the tolerance value should 

be revised to reflect HED policy concerning 

significant figures. 

vegetable, fruiting, group 8-1010.1 not recommended

vegetable, fruiting, group 8-10 (except okra)1-- 0.10

fruit, citrus, group 10-10 0.5 0.50

fruit, pome, group 11-10 0.2 0.20

berry and small fruit, group 13-07 0.2 0.20

teff, forage 100 100

The proposed tolerances are adequate. 

teff, hay 100 100

1

 Tolerance are currently established in/on crop group (CG) 8 at 0.1 ppm and in/on okra at 0.5 ppm; note that okra was not 

included in CG 8 but is included in CG 8-10. 
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2.2.3 Revisions to Petitioned-For Tolerances

The commodity definitions and/or tolerance values recommended by HED in Table 2.2.2 differ 

from that proposed by the petitioner for the following reasons: (1) certain crops were excluded 

from crop group definitions due to the magnitude of the residue in these crops relative to the 

other crops in their group (carrot, sweet potato, and sugar beet; okra) or to maintain 

harmonization with Codex and Canada (canola) and (2) tolerance values were changed to 

conform with HED policy concerning significant figures (CG 3-07, CG 8-10, CG 10-10, CG 11-

10, and CG 13-07). 

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

Revised Section B specifying the following: (1) oilseeds CG 20 - both the Roundup Ultra® and 

Roundup WeatherMAX® labels should indicate that only a single harvest-aid application is 

permitted and should indicate that for canola, the harvest-aid application pertains to only those 

varieties which are not tolerant to glyphosate; (2) bulb vegetables CG 3-07 - the Roundup Ultra® 

and Roundup WeatherMAX® supplemental labels concerning application to bulb vegetables 

include statements concerning application to nonbearing ginseng and rutabaga which should be 

removed; (3) pome fruit CG 11-09 - the Roundup Ultra® and Roundup WeatherMAX® 

supplemental labels concerning application to pome fruit include statements concerning 

application to berries, citrus, and tree nuts which should be removed; and (4) berry and small 

fruit crop group 13-07 - in order to conform with the current strawberry (representative crop for 

subgroup 13-07G) label instructions, both the Roundup Ultra® and Roundup WeatherMAX® 

labels should be revised to indicate a maximum yearly application rate to subgroup 13-07G crops 

of 6.0 lb ae/acre and should indicate a 30-day plantback interval (PBI) for all nonlabeled crops 

following application to 13-07G crops (excluding cranberry).

2.3.2 Recommendations from Occupational Assessment

None.

2.3.3 Recommendations from Residential Assessment

None.
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3.0 Introduction

Glyphosate is a non-selective herbicide that acts via blocking the activity of the EPSPS enzyme. 

EPSPS is produced only by green plants and is involved in the synthesis of the amino acids

tyrosine, tryptophan, and phenylalanine.

3.1 Chemical Identity

The chemical structure and nomenclature for glyphosate is presented in Table 3.1.

Table 3.1. Test Compound Nomenclature.

Compound

Common name Glyphosate

Company experimental name DPX-B2856

IUPAC/CAS name N-(phosphonomethyl)glycine

CAS registry number 1071-83-6

3.2 Physical/Chemical Characteristics

The physicochemical properties of technical grade glyphosate are presented in Table 3.2. 

Table 3.2. Physicochemical Properties of the Technical Grade Test Compound: Glyphosate.

Melting point 189.5 ± 0.5 °C

The Pesticide Manual, 13th Edition

pH 1.9 at 20 °C

Density 1.705 g/cm3at 20 °C

Water solubility 10.5 g/L at 20 °C

Solvent solubility

acetone 0.078 g/L

methanol 0.231 g/L

hexane 0.026 g/L

ethyl acetate 0.012 g/L

dichloromethane 0.233 g/L

n-octanol 0.020 g/L

propan-2-ol 0.020 g/L

toluene 0.036 g/L

European Commission: Glyphosate 

6511/VI/99-final, 1/21/02

Vapor pressure 1.31 x 10-2 mPa at 25 °C The Pesticide Manual, 13th Edition

Dissociation constant, pKa

0.8 (1st phosphonic), 2.3 (carboxylate), 

6.0 (2nd phosphonic), and 11.0 (amine)

Knuuttila. 1979 Acta Chem. Scand. 

B 33:623-626

Octanol/water partition coefficient, Log(KOW) -3.2 (pH 2-5, 25 °C) European Commission: Glyphosate 

UV/visible absorption spectrum ε = 0.086 (295nm) 6511/VI/99-final, 1/21/02

P

O

OH

OH

N

H

HO

O
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3.3 Proposed Application Scenario

The petitioner submitted proposed supplemental labels for Roundup Ultra® and Roundup 

WeatherMAX® concerning wiper application to carrot and sweet potato and harvest-aid 

application to all oilseed crops (currently harvest-aid application is only permitted for the 

following oilseed crops: cotton, safflower, and sunflower). The petitioner also updated these 

labels to reflect the most recent commodity definitions for the following CGs: bulb vegetables 

CG 3-07; fruiting vegetables CG 8-09; citrus fruit CG 10-09; pome fruit CG 11-09; stone fruit 

CG 12-10; and berry CG 13-07. Table 3.3.1 is a summary of the proposed end-use products and 

Table 3.3.2 is a summary of the proposed application scenarios. 

HED concludes that the proposed labels are adequate provided the following are addressed 

(revised Section B is requested): (1) oilseeds CG 20 - both the Roundup Ultra® and Roundup 

WeatherMAX® labels should indicate that only a single harvest-aid application is permitted and 

should indicate that for canola, the harvest-aid application pertains to only those varieties which 

are not tolerant to glyphosate; (2) bulb vegetables CG 3-07 - the Roundup Ultra® and Roundup 

WeatherMAX® supplemental labels concerning application to bulb vegetables include 

statements concerning application to nonbearing ginseng and rutabaga which should be removed;

(3) pome fruit CG 11-09 - the Roundup Ultra® and Roundup WeatherMAX® supplemental 

labels concerning application to pome fruit include statements concerning application to berries, 

citrus, and tree nuts which should be removed; and (4) berry and small fruit crop group 13-07 -

in order to conform with the current strawberry (representative crop for subgroup 13-07G) label 

instructions, both the Roundup Ultra® and Roundup WeatherMAX® labels should be revised to 

indicate a maximum yearly application rate to subgroup 13-07G crops of 6.0 lb ae/acre and 

should indicate a 30-day PBI for all nonlabeled crops following application to 13-07G crops 

(excluding cranberry).

Table 3.3.1. Summary of Proposed End-Use Products.

Trade Name EPA Reg. No. concentration Form. Label Date Target Crops Target Pests

Roundup Ultra® 524-475

glyphosate as the 

isopropylamine salt; 

4 lbs ai/gallon; 3 lbs 

ae/gallon

water 

soluble 

liquid

not 

provided

root and tuber vegetables (CG 1)

bulb vegetable crops (CG 3-07)

fruiting vegetables (CG 8-10)

citrus (CG 10-10)

pome fruits (CG 11-10)

berry (CG 13-07)

oilseed crops (CG 20) numerous

annual and 

perennial 

grasses and 

broadleaf weeds

Roundup 

WeatherMAX® 524-537

glyphosate as the 

potassium salt; 5.5 lbs 

ai/gallon; 4.5 lbs 

ae/gallon

water 

soluble 

liquid

not 

provided

carrot

sweet potato

root and tuber vegetables (CG 1)

bulb vegetable crops (CG 3-07)

fruiting vegetables (CG 8-10)

citrus (CG 10-10)

pome fruits (CG 11-10)

berry (CG 13-07)

oilseed crops (CG 20)
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Table 3.3.2. Summary of Proposed Directions for Use.

App. Timing, 

Type, and 

Equip.

Formulation

(EPA Reg. No.)

App. Rate

(lb ae/acre)

Max. No. 

App. per 

Season

Max. Seasonal 

App. Rate

(lb ai/acre)

PHI

(days) Use Directions and Limitations

carrot

post-emergent; 

wiper or sponge 

bar applicators

Roundup 

WeatherMAX® 

(EPA Reg. No. 

524-537)

-- 2 -- 7

-Applications are to be made with a 33% solution 

of the formulated product (by volume).

-The first application can be made 60 days before 

harvest and the second application made 7 days 

before harvest. 

-Wiper contact should be a minimum of 2 inches 

above the desirable vegetation.

-Weeds should be 6 inches above the desirable 

vegetation.

-Applicators should be operated at a ground speed 

of no greater than 5 miles per hour.

-Better results may be made when two 

applications are made in opposite directions.

-Do not add a surfactant to the solution when 

using a wiper applicator.

sweet potato

post-emergent; 

wiper or sponge 

bar applicators

Roundup 

WeatherMAX® 

(EPA Reg. No. 

524-537)

-- 5 -- 7

-Applications are to be made with a 33% solution 

of the formulated product (by volume).

-RTI (retreatment interval) of 14 days.

-Wiper contact should be a minimum of 2 inches 

above the desirable vegetation.

-Weeds should be 6 inches above the desirable 

vegetation.

-Applicators should be operated at a ground speed 

of no greater than 5 miles per hour.

-Better results may be made when two 

applications are made in opposite directions.

-Do not add a surfactant to the solution when 

using a wiper applicator.

oilseed crops (CG 20)1: Borage; calendula; castor oil plant; Chinese tallow tree; crambe; cuphea; echium; euphorbia; evening primrose; 

flax seed; gold of pleasure; hare's ear mustard; jojoba; lesquerella; lunaria; meadowfoam; milkweed; mustard seed; niger seed; oil radish; 

poppy seed; rapeseed (canola varieties); rose hip; safflower; sesame; stokes aster; sunflower; sweet rocket; tallowwood; tea oil plant; 

vernonia; and cultivars, varieties, and/or hybrids of these. 

preharvest

harvest-aid 

application; 

broadcast spray; 

ground and 

aerial 

application1

Roundup 

WeatherMAX® 

(EPA Reg. No. 

524-537) 

Roundup 

Ultra® (EPA 

Reg. No. 524-

475)

safflower -

2.251

sunflower -

0.771

cotton -

1.551

all others -

1.121

not indicated

see “Use 

Direction and 

Limitations” 

column

7

-Use sufficient water volume to ensure thorough 

coverage of foliage (3-40 GPA for ground and 3-

15 GPA for aerial).

-If no harvest-aid application is made, then the 

maximum seasonal application rate is 6.0 lbs 

ae/acre. If a harvest-aid application is made, then 

the following maximum seasonal application rates 

apply: safflower - 4.50 lbs ae/acre (2.25 lbs 

ae/acre as harvest aid); sunflower - 1.54 lbs 

ae/acre (0.77 lbs ae/acre as harvest aid); cotton -

6.0 lbs ae/acre (1.55 lbs ae/acre as harvest aid); 

and all others - 2.62 lbs ae/acre (1.12 lbs ae/acre as 

harvest aid).

1

 Preplant, at-planting, pre-emergence, and post-emergence (application to row middles) application are currently permitted for 

oilseed crops and harvest-aid application to cotton, sunflower, and safflower are also currently permitted. The proposed use is to 

allow harvest-aid application to all oilseed crops (CG 20; except Buffalo gourd). Since the difference for the proposed use and 

the registered use concerns only harvest-aid application, only the application rate for harvest-aid application are included in the 

table. 
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3.4 Anticipated Exposure Pathway

Based on the toxicological database, short-/intermediate-/long-term dermal and inhalation risk 

assessments and acute dietary risk assessments are considered unnecessary (see Section 4.0). 

Since dermal and inhalation endpoints were not selected, a quantitative occupational exposure 

assessment is unnecessary. However, the proposed/registered agricultural and residential uses 

may result in chronic dietary (food and water) exposure and short-/intermediate-term incidental 

oral exposure. 

3.5 Consideration of 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.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). As a part of every 

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to 

well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the USDA under the 

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, season of the 

year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary 

exposure to smaller, specialized subgroups and exposure assessments are performed when 

conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on 

home use of pesticide products and associated risks for adult applicators and for toddlers, youths, 

and adults entering or playing on treated areas postapplication 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.

It is noted that glyphosate is registered for direct application to water with fish (0.25 ppm) and 

shellfish (3.0 ppm) tolerances established (180.364(a)(1)). Although these tolerances were 

incorporated into the dietary exposure analysis, the employed consumption database does not 

consider consumption levels associated with subsistence fishing. Making the conservative 

assumption that an adult (60-kg default body weight) will consume, on a chronic basis, 100 

grams/day of fish and 100 grams/day of shellfish, and assuming tolerance-level residues, the 

resulting exposure occupies <1% of the cPAD. Therefore, HED concludes that exposure to 

glyphosate from subsistence fishing is less than HED’s LOC. 
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4.0. Hazard Characterization and Dose-Response Assessment

4.1. Toxicology Studies Available for Analysis

The hazard database for glyphosate is complete and is adequate for endpoint selection. Since the 

last risk assessment, the neurotoxicity screening battery tests, and immunotoxicity study have 

been submitted, and are pending formal review. This hazard characterization also incorporates 

the modifications to the listing of the doses in the subchronic mouse and rat oral and rat dermal 

studies which were previously not documented correctly (TXR # 0055772, Dykstra, W. et al.,

22-Jan-1996).

4.2. Absorption, Distribution, Metabolism, & Elimination (ADME)

In the rat metabolism study, absorption was estimated to be 30-36% in males and females 

following a single 10 mg/kg oral dose. Glyphosate was excreted unchanged in the feces and 

urine (97.5% minimum). Through the oral route the urine accounted for 31.2-33.4 % of the 

administered dose in males, and 24% of the administered dose in females. The feces accounted 

for 65.9-68.1% of the administered dose in males, and 75.1% of the administered dose in 

females. The only metabolite present in the excreta was small amounts of aminomethyl 

phosphonic acid (AMPA). Less than 1% of the absorbed dose remained in the carcass, primarily 

the bone seven days post dosing. Repeated dosing did not significantly alter absorption, 

metabolism, distribution, and excretion.

4.2.1. Dermal Absorption

There is no dermal absorption study available for glyphosate.

4.3. Toxicological Effects

Glyphosate is categorized as having low acute toxicity following oral, dermal, and inhalation 

exposure, since all studies are in Toxicity Categories III or IV. It is a mild eye irritant (Toxicity 

Category III), slight skin irritant (Toxicity Category IV), and is not a dermal sensitizer. 

A chronic feeding/carcinogenicity study in rats found no systemic effects in any of the 

parameters examined (body weight, food consumption, clinical signs, mortality, clinical 

pathology, organ weights, and histopathology). A second chronic feeding/carcinogenicity study 

in rats tested at higher dietary levels, and a lowest-observed-adverse-effect level (LOAEL) was 

identified at 20,000 parts per million (approximately 940 mg/kg/day) based on decreased bodyweight gains in females and increased incidence of cataracts and lens abnormalities, decreased 

urinary pH, increased absolute liver weight, and increased relative liver weight/brain weight in 

males. No evidence of carcinogenicity was found in mice or rats. In a chronic toxicity study in 

dogs, no systemic effects were found in all examined parameters. 

No significant reproductive and developmental toxic effects were found. On the basis of 

developmental studies in rats and rabbits and reproductive findings in rats, there was no evidence 

of increased susceptibility of offspring. Neurotoxicity has not been observed in any of the acute, 

subchronic, chronic, developmental, or reproductive studies performed with glyphosate. 
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Since the last risk assessment, the neurotoxicity screening battery tests, and immunotoxicity 

study have been submitted. Preliminary review shows no effects up to the highest dose tested for 

both the acute and subchronic durations for the neurotoxicity studies. The preliminary review of 

the immunotoxicity study also shows no effects of to the highest dose tested. 

4.4. Safety Factor for Infants and Children (FQPA Safety Factor)

The RAB1 risk assessment team recommends that the FQPA SF be reduced to 1x. This 

recommendation is based on the considerations described in the subsequent sections. 

4.4.1. Completeness of the Toxicology Database

The toxicology database for glyphosate is adequate for characterizing glyphosate toxicity and 

quantification of risk for dietary and occupational uses. The following acceptable studies are 

available for evaluation:

Developmental toxicity studies in rats and rabbits

Two-generation reproduction study in rats

4.4.2. Evidence of Neurotoxicity

There is no evidence of neurotoxicity in any of the toxicology studies conducted. 

4.4.3. Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is no quantitative or qualitative evidence of increased susceptibility of rat or rabbit fetuses 

to in utero exposure in developmental studies. A focal tubular dilation of the kidneys was 

observed in an older three-generation reproductive study on rats at the 30-mg/kg/day level 

[highest dose tested (HDT)], however a two-generational reproductive study on rats did not 

observe the same effect at the 1500 mg/kg/day level (HDT), nor were any adverse reproductive 

effects observed at any dose level. A clear no-observed adverse-effect level (NOAEL) was 

established and the chronic reference dose (cRfD) was set at a level well below this effect. 

4.4.4. Residual Uncertainty in the Exposure Database

The dietary exposure analysis is conservative as it assumed tolerance level residues and 100% 

crop treated. The residential exposure analysis is also considered conservative as it is based on 

the 2012 Residential SOPs.
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4.5. Toxicity Endpoint and Point of Departure Selections

A summary of the toxicological doses and endpoints for glyphosate used in human health risk 

assessment are summarized in table 4.5.4.

4.5.1. Dose-Response Assessment

Acute Dietary Endpoint (Females age 13-49): An acute reference dose (aRfD) was not 

established for females age 13-49, based on the absence of an appropriate toxicological endpoint 

attributable to a single exposure (dose), including fetal toxicity in developmental toxicity studies. 

Acute Dietary Endpoint (General Population): An acute reference dose (aRfD) was not 

established for any population subgroup or the general population, including infants and 

children, based on the absence of an appropriate toxicological endpoint attributable to a single 

exposure (dose), including maternal toxicity in developmental toxicity studies. 

Chronic Dietary Endpoint: The developmental toxicity study in rabbits was used to select the 

endpoint for establishing the chronic RfD (cRfD) of 1.75 mg/kg bw/day which was derived from 

a maternal NOAEL of 175 mg/kg/day and a 100-fold factor that included a 10x-UF for interspecies extrapolations, 10x-UF for intra-species variations, and a 1x FQPA SF. The maternal 

LOAEL was 350 mg/kg/day based on mortality, diarrhea, soft stools, and nasal discharge. The 

NOAEL selected was the lowest observed in all of the major toxicity studies, and is the most

protective for pregnant females as well as the general population.

Incidental Oral Short- and Intermediate-Term: The developmental toxicity study in rabbits was 

chosen for the short- and intermediate-term incidental oral endpoint. The maternal NOAEL 

was175 mg/kg/day based upon mortality, diarrhea, soft stools, and nasal discharge seen at the 

LOAEL of 350 mg/kg/day. The level of concern (LOC) is 100 based upon a 100-fold factor that 

included a 10x-UF for inter-species extrapolations, 10x-UF for intra-species variations, and a 1x 

FQPA SF. The NOAEL selected was the lowest observed in all of the major toxicity studies, 

and is protective against the offspring effects observed in the 2-generation reproduction study 

seen at the offspring LOAEL of 1500 mg/kg/day (decreased body-weight gain during lactation 

for both sexes).

Dermal Absorption: There is no dermal absorption study available for glyphosate. Furthermore,

a dermal absorption factor was not calculated due to lack of dermal toxicity as well as the 

absence of any developmental effects, or any other notable effects through the oral route. 

Short-, Intermediate- and Long-Term Dermal: Short-, intermediate- and long-term dermal 

endpoints were not selected based on the absence of hazard in the 21-day dermal toxicity study 

in rabbits. Additionally, there were no developmental or reproductive toxicity concerns relevant 

to dermal endpoint selection. 

Short-, Intermediate- and Long- Term Inhalation: Short-, intermediate- and long-term inhalation 

endpoints were not selected based on the absence of hazard in the 28-day inhalation toxicity 

study in rats. Additionally, there were no developmental or reproductive toxicity concerns 

relevant to inhalation endpoint selection. 
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4.5.2. Recommendation for Combining Routes of Exposures for Risk Assessment

Based upon the common endpoints and common route of exposure, the chronic dietary endpoint 

can be aggregated to the short- and intermediate-term incidental oral endpoints.

4.5.3. Cancer Classification and Risk Assessment Recommendation

On 26-Jun-1991, the HED Carcinogenicity Peer Review Committee (CPRC) evaluated the 

weight of the evidence on glyphosate with particular emphasis on its carcinogenic potential

(October 1991, TXR# 0008898). The Committee concluded that glyphosate should be classified 

as a “Group E” chemical (evidence of non-carcinogenicity for humans), based upon lack of 

convincing carcinogenicity evidence in adequate studies in two animal species (mice and rats). 

4.5.4. Summary of PODs and Toxicity Endpoints Used in Human Risk Assessment

Table 4.5.4. Summary of Toxicological Doses and Endpoints for Glyphosate for Use in Human-Health Risk 

Assessments1.

Exposure/

Scenario POD Uncertainty/FQPA SF RfD, PAD, LOC Study and Toxicological Effects

Acute Dietary (General 

Population, including 

Infants and Children)

An endpoint of concern (effect) attributable to a single dose was not identified in the database. 

Quantification of acute risk to general population including infants and children is not required.

Chronic Dietary (All 

Populations)

NOAEL= 175 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

cPAD = cRfD = 

1.75 mg/kg/day

Developmental Toxicity Study - Rabbit: Maternal 

LOAEL = 350 mg/kg/day based on diarrhea, nasal 

discharge and death in maternal animals

Short- (1-30 days) and 

Intermediate-(1-6 months) 

Term Incidental Oral

NOAEL= 175 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

LOC (residential) 

= MOE < 100

Developmental Toxicity Study - Rabbit: Maternal 

LOAEL = 350 mg/kg/day based on diarrhea, nasal 

discharge and death in maternal animals

Short- (1-30 days), 

Intermediate (1-6 months) 

and Long- (>6 months) 

Term Dermal

None None None

Based on the lack of toxicity up to the HDT (1,000 

mg/kg/day) in the 21 day dermal toxicity study in 

rabbits and the lack of concern for developmental 

and reproductive effects, the quantification of 

dermal risks is not required.

Short- (1-30 days), 

Intermediate (1-6 months) 

and Long- (>6 months) 

Term Inhalation

None None None

Based on the lack of toxicity up to the highest 

concentration tested (0.36 mg/L) in the 28-day 

inhalation toxicity study in rats, and the physical 

characteristics of the technical (wetcake), the 

quantification of inhalation risks is not required.

Cancer (oral, dermal, 

inhalation) Classification: Group E; no evidence of carcinogenicity; risk assessment not required.

1 UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no-observed adverse-effect level, LOAEL = lowestobserved adverse-effect level, PAD = population-adjusted dose (a = acute, c = chronic) RfD = reference dose, MOE = margin of 

exposure, LOC = level of concern, HDT = highest dose tested, UFA = extrapolation from animal to human (interspecies), UFH = 

potential variation in sensitivity among members of the human population (intraspecies). 
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5.0 Dietary Exposure and Risk Assessment

5.1 Residues of Concern Summary and Rationale

Table 5.1 is a summary of the conclusion made by HED concerning the residues of concern in 

primary crops, livestock, rotational crops, and drinking water. 

Table 5.1. Residues of Concern for Tolerance Expression and Risk Assessment.

Matrix Residues Included in Risk Assessment Residues Included in Tolerance Expression

primary crops (excluding soybean and field corn) glyphosate glyphosate

soybean and field corn glyphosate and N-acetyl-glyphosate glyphosate and N-acetyl-glyphosate

livestock glyphosate and N-acetyl-glyphosate glyphosate and N-acetyl-glyphosate

rotational crops glyphosate glyphosate

drinking water glyphosate not applicable

Primary Crops: Metabolism studies conducted with non-transgenic corn, cotton, soybeans, and 

wheat were previously submitted and reviewed. Based on these data, HED concluded that the 

residue of concern in non-transgenic plants is glyphosate (Memo, R. Perfetti, 19-Oct-1992; RED, 

R. Perfetti, 27-Oct-1992; Memo, R. Perfetti, 17-Mar-1994). Metabolism studies have also been 

submitted on glyphosate-tolerant canola (RT73; D242628, T. Bloem, 30-Nov-1998) and 

glyphosate-tolerant field corn (Roundup Ready®field corn; D217539, G. Kramer, 14-Mar-1996). 

The glyphosate-tolerant canola and field corn varieties were genetically modified to express the 

EPSPS gene derived from Agrobacterium sp. (strain CP4) which codes for an EPSPS protein that 

is not inhibited by glyphosate. The glyphosate-tolerant canola and corn were also genetically 

engineered to express the oxireductase gene which converts glyphosate to the non-herbicidal 

AMPA (aminomethyl phosphonic acid). Metabolism in these varieties of transgenic canola and 

corn was essentially the same as the non-transgenic plants. Therefore, it was concluded that the 

terminal residue to be regulated, in non-transgenic plants and transgenic corn and canola 

modified to express the Agrobacterium sp. EPSPS and oxireductase genes, is glyphosate.

Subsequent to these decisions, HED approved DuPont requests permitting the commercialization 

of Optimum GAT soybean, Optimum GAT field corn, and Optimum® GLY Canola. 

These soybean, field corn, canola varieties were genetically engineered to express the gat4601 or 

gat4621 genes (derived from Bacillus licheniformis; soil bacterium) which confer tolerance to 

glyphosate via conversion of parent to the non-herbicidal N-acetyl-glyphosate. The Optimum

GAT field corn was also engineered to express the zm-hra gene (modified version of maize 

acetolactate synthase (ALS) gene) which encodes for an ALS protein which is not sensitive to 

the ALS-inhibiting herbicides. As a result of the introduction of these seed lines, HED 

concluded that the residues of concern in soybean, field corn, and canola for tolerance expression 

and risk assessment should change from glyphosate to the combined residues of glyphosate and 

N-acetyl-glyphosate (expressed in glyphosate equivalents; D346713, T. Bloem, 12-Mar-2008; 

D357880, T. Bloem, 29-Oct-2008; D361315, T. Bloem, 14-Jan-2010; D394964, T. Bloem, 15-

Nov-2011). 

Livestock: The qualitative nature of the residue in livestock following dosing with glyphosate

and AMPA is adequately understood. Studies with lactating goats and laying hens fed a mixture 

of glyphosate and AMPA indicate that the primary route of elimination was by excretion (urine 

and feces). The HED Metabolism Assessment Review Committee (MARC) determined that the 
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terminal residue to be regulated in livestock is glyphosate (Memo, R. Perfetti, 19-Oct-1992; 

RED, R. Perfetti, 27-Oct-1992; Memo, R. Perfetti, 17-Mar-1994). 

Since the Optimum GAT soybean and field corn metabolism studies resulted in significant 

residues of N-acetyl-glyphosate, DuPont submitted summaries of in vitro (rumen fluid, fertile 

hen egg, and rat liver S9 supernatant) and in vivo (rat metabolism study) studies conducted with 

the N-acetyl-glyphosate metabolite and submitted goat and hen metabolism studies conducted 

with the N-acetyl-glyphosate metabolite. Based on these data and the glyphosate metabolism 

studies, HED concluded that the residues of concern in livestock following consumption of 

glyphosate and N-acetyl-glyphosate, for tolerance expression and risk assessment purposes, are 

glyphosate and N-acetyl-glyphosate (D346713, T. Bloem, 12-Mar-2008; D361315, T. Bloem, 

14-Jan-2010). 

Rotational Crops: A confined rotational crop study has been previously submitted/reviewed

which employed an application rate of 3.71 lb ae/acre and carrot, lettuce, and barley as rotational 

crops (PBIs of 30, 119-125, and 364 days; MRIDs 415432-01 and -02, A. Abramovitch, 14-Oct1992). Glyphosate residues were <0.01 ppm in/on all rotational crops except for barley grain 

from the 125-day PBI plot which had a glyphosate residue of 0.018 ppm. Based on these data, 

HED concluded that residues in rotational crops will be insignificant provided the labels specify 

a 30-day PBI for all nonlabeled crops (D200041, G. Kramer, 12-May-1994; field rotational crop 

study has not been submitted). 

5.2 Food Residue Profile

D398861, T. Bloem, 14-Nov-2012

Magnitude of the Residue - Proposed Primary Crops: Provided a revised Section B is 

submitted, HED concludes that the proposal to update the commodity members for the following 

CGs to reflect current HED policy is acceptable and the tolerances from the old CGs may be 

translated to the new CGs: bulb vegetables CG 3-07; fruiting vegetables CG 8-09; citrus fruit 

CG 10-09; pome fruit CG 11-09; stone fruit CG 12-10; and berry CG 13-07. In addition, the 

petitioner proposed the translation of the 100-ppm cereal grain CG 16 (except field corn 

forage/stover) tolerance to teff forage and hay. Based on similar morphological, cultural 

practices, taxonomical characteristics, and application scenarios for teff and the small grains, 

HED concludes that this translation is acceptable (Chemistry Science Advisory Council 

(ChemSAC); min_542.02-May-2012).

The petitioner is also proposing the expansion of the carrot and sweet potato application scenario 

to include-over-the-top wiper application and submitted adequate carrot and sweet potato 

magnitude of the residue data depicting this application scenario. Based on these data and the 

Organization of Economic Cooperation and Development (OECD) tolerance calculation 

procedure, HED concludes that the carrot and sweet potato tolerances listed in Table 2.2.2 are 

appropriate. A revised Section F is requested. 

Finally, the petitioner is proposing the establishment of an oilseed CG 20 tolerance (40 ppm; 

glyphosate only) and is proposing harvest-aid application to all CG 20 crops. The representative 

crops for CG 20 are canola (subgroup 20A), sunflower (subgroup 20B), and cotton (subgroup 

20C) with glyphosate tolerances established in/on the seeds of these crops as follows: canola 

seed - 20 ppm (combined glyphosate and N-acetyl-glyphosate), sunflower/safflower seed - 85 

ppm (glyphosate only), and cotton seed - 40 ppm (glyphosate only). Tolerances are also 
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established in/on several other CG 20 crops as follows: borage - 0.1 ppm, crambe - 0.1 ppm, flax 

- 4.0 ppm, meadowfoam - 0.1 ppm, mustard - 0.1 ppm, safflower - 85 ppm, and sesame - 0.1 

ppm. These tolerances reflect preemergent and postemergent (row middles using shielded 

sprayers or wiper equipment) application for all as well as harvest-aid application for sunflower 

(0.77 lb ae/acre), safflower (2.25 lb ae/acre), and cotton (1.55 lb ae/acre) and over-the-top 

application to canola and cotton (glyphosate-tolerant varieties). 

Based on reevaluation of the sunflower/safflower seed harvest-aid data using the OECD 

tolerance calculation procedure and in order to maintain harmonization with the currentlyestablished Canadian (canola seed) and Codex (cotton seed and canola seed) tolerances, HED 

concludes that the oilseed tolerances listed in Table 2.2.2 are appropriate. 

Magnitude of the Residue - Livestock: HED concludes that for the following reasons the 

proposals associated with the current petition will not have a significant effect on the livestock 

dietary burdens and the currently-established livestock tolerances remain appropriate: (1) the 

additional crops included in the updated CG definitions are not considered significant feed 

commodities; (2) the proposal to extend the harvest-aid application scenario to all oil seed crops 

(CG20) will not have a significant effect on the livestock dietary burdens as harvest-aid 

application to cotton, sunflower, and safflower is currently registered; and (3) the increase in the 

carrot (carbohydrate concentrate (CC)) tolerance to will not have a significant impact on the 

livestock dietary burdens as a 30-ppm tolerance in/on the grain of several small grains (CC) is 

currently established. 

Magnitude of the Residue - Rotational Crops: HED previously concluded that a 30-day PBI 

was appropriate for all non-labeled crops (D200041, G. Kramer, 12-May-1994). Provided a 

revised Section B is submitted specifying a 30-day PBI for all non-labeled crops following 

application to 13-07G crops (excluding cranberry), the proposed labels will conform with this 

requirement. 
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5.3 Drinking Water Residue Profile

D398549, J. Hetrick, 12-Oct-2012

The available field and laboratory data indicate that glyphosate adsorbs strongly to soil and 

would not be expected to move vertically below the 6-inch soil layer. Based on unaged batch 

equilibrium studies, glyphosate and glyphosate residues are expected to be immobile with 

Kd(ads) values ranging from 62 to 175. The mechanism of adsorption is unclear; however, it is 

speculated that it may be associated with vacant phosphate sorption sites or high levels of 

metallic soil cations. The data indicate that chemical and photochemical decomposition is not a 

significant pathway of degradation of glyphosate in soil and water. However, glyphosate is 

readily degraded by soil microbes to AMPA, which is degraded to CO2, although at a slower rate 

than parent. Based on the low vapor pressure of glyphosate, volatilization from soils will not be 

an important dissipation mechanism. The low octanol/water partition coefficient suggests that 

glyphosate will have a low tendency to accumulate in fish. Based on these data, HED concluded 

that glyphosate is the only residue of concern in drinking water. 

Estimated Drinking Water Concentrations (EDWCs): In support of the current assessment, 

EFED provided the following EDWCs for glyphosate (D398549, J. Hetrick, 16-Oct-2012): 

surface source water: daily peak - 153.7 μg/L and annual average - 8.11 μg/L; ground water 

concentrations are not expected to exceed 2.03 μg/L. The surface water estimates were 

generated using the index reservoir and the direct application to water application scenario (3.75 

lbs ae/acre). The ground water estimate is based on monitoring data from the National WaterQuality Assessment Program (NAWQA). 

5.4 Dietary Risk Assessment

D398863, T. Bloem, 14-Nov-2012

A chronic dietary risk assessment was conducted using DEEM-FCID (ver. 3.16) which 

incorporates consumption data from USDA NHANES/WWEIA (2003-2008). Acute and cancer 

dietary risk assessments were not conducted since an appropriate endpoint attributable to a single 

dose was not identified for the general U.S. population or any population subgroup and 

glyphosate is classified as not likely to be a human carcinogen, respectively. The chronic 

analysis assumed tolerance-level residues, 100% crop treated, and DEEM (ver 7.81) default 

processing factors for all commodities, and modeled drinking water estimates (direct application 

to water scenario). The resulting chronic risk estimates (food and water) were ≤13% cPAD and 

are not of concern to HED (children (1-2 years old) were the most highly exposed population). 

Table 5.4 is a summary of the chronic dietary exposure estimates. 

Table 5.4. Summary of Chronic Dietary Exposure and Risk.

Population Subgroup cPAD (mg/kg/day) Exposure (mg/kg/day) %cPAD

General U.S. Population

1.75

0.088331 5.0

All Infants (< 1 year old) 0.134620 7.7

Children 1-2 years old 0.226241 13

Children 3-5 years old 0.210251 12

Children 6-12 years old 0.146472 8.4

Youth 13-19 years old 0.087318 5.0

Adults 20-49 years old 0.073213 4.2

Adults 50-99 years old 0.059852 3.4

Females 13-49 years old 0.067888 3.9

1

 The bolded %cPAD represents the population with highest risk.
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6.0 Residential (Non-Occupational) Exposure/Risk Characterization

D398862, L. Venkateshwara, 30-Oct-2012

The proposed uses are not anticipated to result in residential exposure. However, glyphosate is 

currently registered for application to turf (including golf courses and residential lawns) and for 

aquatic application, and residential exposure may occur as a result of these uses. These uses 

have been reassessed in this document to reflect (1) the HED’s Residential Standard Operating 

Procedures (SOPs; 2012), (2) updates to HED’s inputs for aquatic/swimmer assessments, and (3) 

updated body weight information. 

6.1 Residential Handler Exposure

Based on the registered residential use patterns, there is a potential for short-term dermal and 

inhalation exposures to homeowners who mix and apply products containing glyphosate 

(residential handlers). However, since short- and intermediate-term dermal or inhalation 

endpoints were not selected, a quantitative exposure risk assessment was not completed.

6.2 Post-Application Exposure

Post-application dermal and inhalation assessments were not quantitatively assessed since shortand intermediate-term dermal or inhalation endpoints were not selected. However, based on the 

registered use patterns, children 1 to <2 years old may have short-term post-application 

incidental oral exposures from hand-to-mouth behavior on treated lawns and swimmers (adults 

and children 3 to <6 years old) may have short-term post-application incidental oral exposures 

from aquatic uses. Based on the soil half-life for glyphosate, intermediate-term soil ingestion 

was also considered for children 1<2 years old. It is noted that the lifestages selected for risk 

assessment are considered protective for the exposures and risks for any other potentially 

exposed lifestages. 

Table 6.2.1 presents the post-application incidental oral MOE values calculated for children 1 to 

<2 years old after applications of glyphosate to turf. Table 6.2.2 presents the post-application 

incidental oral ingestion MOE values calculated for adults and children 3 to <6 years old after 

aquatic applications of glyphosate. The post-application MOEs are ≥1,100 and, therefore, do not 

exceed HED’s level of concern for any of the scenarios assessed. 

The incidental oral scenarios for the turf assessment (i.e., hand-to-mouth, object-to-mouth, and 

soil ingestion) should be considered inter-related and it is likely that they occur interspersed 

amongst each other across time. Combining these scenarios would be overly-conservative 

because of the conservative nature of each individual assessment. Therefore, none of the 

incidental oral scenarios were combined.
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Table 6.2.1. Post-application Incidental Oral Risk Estimates for Application of Glyphosate to Turf.

Lifestage Post-application Exposure Scenario Dose (mg/kg/day) Short-term MOEs4

Intermediate-term MOEs4

Children 1 to 

<2 year old Turf - sprays

Hand to Mouth1

0.1565 1,100 NA

Object to Mouth2

0.00481 36,000 NA

Incidental Soil Ingestion3

3.4E-04 510,000

1

 Hand-to-Mouth = Hand residue loading (mg/cm2)*fraction hand surface area mouthed/event (0.127/event)*typical surface 

area of one hand (150 cm2)*exposure time (1.5 hrs/day)*number of replenishment intervals/hr (4 intervals/hr)*(1-(1-saliva 

extraction factor (0.5)^number of hand-to-mouth contact events per hour (13.9 events/hr); Hand Residue Loading = fraction of ae 

on hands compared to total surface residue from dermal TC study (0.06)*dermal exposure (mg))/typical surface area of one hand

(150 cm2). 

2

 Object-to-Mouth = ((Object Residue (μg/cm2)*CF1 (1.0E-3 mg/μg)*Object Surface Area Mouthed/Event (10 

cm2/event))*(Exposure Time (1.5 hrs/day)*#Replenishment Intervals/hr (4))*(1-((1-Extraction by Saliva (0.48))^(#Object-toMouth Events/hr (8.8 events/hr)/#Replenishment intervals/hr))))/Body Weight (11kg).

3

 Soil Ingestion = (Soil Residue (7.0746975 μg/g) *Ingestion Rate (50 mg/kg/day) *CF(0.000001))/Body Weight (11 kg).

4

 MOE = NOAEL/Daily Dose (mg ae kg/day); Oral NOAEL = 175 mg/kg/day. LOC is for MOEs <100

Table 6.2.2. Post-Application Swimmer Risk Estimates for Aquatic Application of Glyphosate.

Exposure Scenario Application Rate

(lb ae/acre)

1

Maximum Concentration 

in water (mg/L)2

Exposure(Dose); oral 

mg/kg bw/day) 3

Short-term 

MOE4

Ingestion of water,, Adult-male

3.75 1.38

1.36E-03 129,000

Ingestion of water, Children 3 to <6 years old 1.06E-02 17,000

1

 Application rate from registered labels for aquatic weed control using glyphosate IPA salt (ex. label = EPA Reg. No. 524-343; 

max rate = 7.5 pints/A containing 4 lb acid equivalent [ae] glyphosate/gal. x 1 gal./4 pints = 3.75 lb ae/A.

2

 Maximum concentration in water (top 1 ft.) = 3.75 lb ae/A x 1A/43,560 ft2x 454,000 mg/lb x 1/ft x ft3/28.32 L = 1.38 mg/L.

3

 PDR, incidental oral exposure = concentration, Cw (mg/L) x ingestion rate, IgR (L/hr) x exposure time, ET (hrs/d) x 1/BW 

(adult-male=80 kg; children (3 to <6 years old) = 19 kg)

4

 MOE = NOAEL/PDR; short-term incidental oral NOAEL = 175 mg/kg bw/d. LOC is for MOEs <100.

6.3 Residential Risk Estimates for Use in Aggregate Assessment

Table 6.3 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for glyphosate. The recommended residential exposure for use in the adult aggregate 

assessment reflects incidental oral exposures from post-application exposure to treated aquatic 

areas. The recommended short and intermediate-term residential exposure for use in the children 

1 to <2 years old aggregate assessment reflects incidental oral exposures from post-application 

exposure to outdoor treated turf.

Table 6.3. Recommendations for the Residential Exposures for the Glyphosate Aggregate Assessment.1

Lifestage Post-application Exposure (mg/kg/day)2 Residential Post-application 

Total Exposure (mg/kg/day)

Residential Postapplication MOE3 Dermal Inhalation Oral

short-term

adult male not applicable 0.00136 0.00136 129,000

children 1-2 years old 0.1565 0.1565 1,100

intermediate term

adult male not applicable not applicable

children 1-2 years old 0.00034 0.00034 510,000

1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2

Post-application exposure represents high-end incidental oral exposure for the relevant exposure duration.

3 Residential Post-application MOE = Incidental oral NOAEL / Residential Post-application total exposure.
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6.4 Spray Drift and Residential Bystander Post-application Inhalation Exposure

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for glyphosate. The 

Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical-by-chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT® computer model 

to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic 

methods. After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risk 

estimates associated with drift.

6.5 Residential Bystander Post-Application Inhalation Exposure

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

assessment was not performed for glyphosate at this time primarily because there is no inhalation 

POD. However, volatilization of pesticides may be a source of post-application inhalation exposure 

to individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

(FIFRA) Scientific Advisory Panel (SAP) in December 2009, and 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, develop policies and 

procedures to identify 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 

developed and/or an inhalation POD is selected for glyphosate, the Agency may revisit the need for 

a quantitative post-application inhalation exposure assessment for glyphosate.
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7.0 Aggregate Risk Assessment

In accordance with the FQPA, HED must consider and aggregate pesticide exposures and risks 

from three major sources: food, drinking water, and residential exposures. Based on the 

registered/proposed agricultural and residential uses, HED conducted short- and intermediateterm (food, water, residential incidental oral) and chronic (food and water) aggregate risk 

assessments. Acute and cancer aggregate risk assessments were not conducted since an 

appropriate endpoint attributable to a single dose was not identified for the general U.S. 

population or any population subgroup and glyphosate is classified as not likely to be a human 

carcinogen, respectively. 

Short-Term Aggregate Risk Assessment: Based on the proposed/registered uses, HED 

anticipates short-term residential exposure to young children (swimmer and turf incidental oral 

ingestion) and adults (swimmer incidental oral ingestion). The short-term aggregate assessment 

combines dietary exposure with the single highest potential residential exposure.

For young children, short-term aggregate exposure includes chronic dietary (food and water) and 

incidental oral ingestion exposure resulting from the turf use (highest exposure of all possible 

scenarios). For adults, short-term aggregate exposure includes chronic dietary exposure (food 

and water) and incidental oral ingestion exposure resulting from the aquatic use (highest 

exposure of all possible scenarios). Table 7.0.1 is a summary of the short-term aggregate 

exposures and risk estimates. Since the aggregate MOEs are ≥450, short-term aggregate 

exposure to glyphosate does not exceed HED's LOC. HED notes that the lifestages selected for 

short-term aggregate risk assessment are considered protective for the exposures and risks for 

any other potentially exposed lifestage. 

Table 7.0.1. Short-Term Aggregate Exposure.

Population Exposure (mg/kg/day) Aggregate MOE2

Dietary1Incidental Oral1 Combined

General U.S. population 0.088331 0.00136 0.089691 2000

Children 1-2 years old 0.226241 0.1565 0.382741 450

1

 See Table 5.4 (dietary) and Table 6.3 (incidental oral). 

3

 Aggregate MOE = 175 mg/kg/day (short-term incidental oral NOAEL) combined exposure (mg/kg/day).

Intermediate-Term Aggregate Risk Assessment: Based on the proposed/registered uses, HED 

anticipates intermediate-term residential exposure to only young children (turf incidental oral 

ingestion). 

The intermediate-term aggregate assessment includes chronic dietary (food and water) and 

incidental oral ingestion exposure resulting from the turf use (highest exposure of all possible 

scenarios). Table 7.0.2 is a summary of the intermediate-term aggregate exposures and risk 

estimates. Since the aggregate MOE is 770, intermediate-term aggregate exposure to glyphosate 

does not exceed HED's LOC. HED notes that the lifestage selected for intermediate-term 

aggregate risk assessment is considered protective for the exposure and risk for any other 

potentially exposed lifestage. 

Table 7.0.2. Intermediate-Term Aggregate Exposure.

Population Exposure (mg/kg/day) Aggregate. MOE2

Dietary1Incidental Oral1 Combined

Children 1-2 years old 0.226241 0.00034 0.22658 770

1

 See Table 5.4 (dietary) and Table 6.3 (incidental oral). 

2

 Aggregate MOE = 175 mg/kg/day (short-term incidental oral NOAEL) combined exposure (mg/kg/day).
Glyphosate Human-Health Risk Assessment D398547

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Chronic Aggregate Risk Assessment: Because HED does not anticipate significant chronic 

residential exposure as a result of the proposed/registered glyphosate uses, aggregate chronic risk 

assessment takes into consideration dietary (food and water) exposure only. The chronic 

aggregate exposure and risk estimates do not exceed HED's LOC (≤13% cPAD; see Section 5.4). 

8.0 Cumulative Exposure/Risk Characterization

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 glyphosate and any other substances and glyphosate does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that glyphosate 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 Office of Pesticide Programs concerning common 

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

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

9.0 Occupational Exposure/Risk Characterization

Based on the proposed uses, there is the potential for occupational handler and post-application 

dermal and inhalation exposure; however, no dermal or inhalation PODs were selected for 

glyphosate. Therefore, a quantitative occupational exposure assessment was not conducted. 

10.0 References

CPRC memorandum - October 1991, TXR# 0008898

Residue chemistry summary memorandum - D394964, T. Bloem, 14-Nov-2012

EDWCs - D398549, J. Hetrick, 12-Oct-2012

Dietary exposure memorandum - D398863, T. Bloem, 14-Nov-2012

Occupational/residential exposure memorandum - D398862, L. Venkateshwara, 30-Oct-2012

Most recent human-health risk assessment - D387535, T. Bloem, 29-Nov-2011

Attachment 1: Chemical Names and Structures.

Attachment 2: Toxicity Profile Tables.

RDI: RAB1 review (14-Nov-2012)

T. Bloem:S10945:PY1:(703)-605-0217(7509P)
Glyphosate Human-Health Risk Assessment D398547

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Attachment 1: Chemical Names and Structures.

Compound Structure

Glyphosate

N-(phosphonomethyl)glycine

N-Acetyl-glyphosate

N-acetyl-N-(phosphonomethyl)glycine

AMPA

(aminomethyl)phosphonic acid

N-Acetyl-AMPA

[(acetylamino)methyl]phosphonic acid

P

O

OH

OH

N

H

HO

O

P

O

OH

OH

H2N

P

O

OH

OH

N

H

H3C

O

P

O

OH

OH

N

HO

O

H3C O
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Attachment 2: Toxicity Profile Tables.

Acute Toxicity Profile.

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

870.1100 Acute oral [rat] 41400601 LD50 > 5,000 mg/kg IV

870.1200 Acute dermal [rabbit] 41400602 LD50 > 5,000 mg/kg IV

870.1300 Acute inhalation None The requirement for an acute inhalation 

LC50 study was waived None

870.2400 Acute eye irritation [rabbit] 41400603 Corneal opacity or irritation clearing in 7 

days or less III

870.2500 Acute dermal irritation [rabbit] 41400604 Mild or slight irritant IV

870.2600 Skin sensitization [guinea pig] 41642307 Not a sensitizer None

Subchronic, Chronic, and Other Toxicity Profile.

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

Classification /Doses Results

870.3100 90-Day Oral Toxicity 

(Mice)

00036803 (1979)

Acceptable/guideline

0, 5000, 10000, 50000 ppm

(0, 944/ 1530, 1870/ 2740, 

9710/ 14800 mg/kg/day [M/F]) 

NOAEL = 1870/2740 mg/kg/day [M/F]

LOAEL = 9710/14800 mg/kg/day [M/F] based on 

decreased body weight.

870.3100 90-Day oral toxicity 

range finding (Rat)

40559401 (1987)

Acceptable/guideline

0, 1000, 5000, 20000 ppm

(0, 63, 317, 1267 mg/kg/day)

NOAEL = 1267 mg/kg/day

LOAEL = not established.

870.3150 90-Day oral toxicity 

(Rat) - Aminomethyl 

phosphoric acid -

glyphosate plant 

metabolite

00241351 (1979)

Acceptable/guideline

0, 400, 1200, 4800 mg/kg/day 

[M/F]

NOAEL = 400 mg/kg/day [M/F]

LOAEL = 1200 mg/kg/day [M/F] based on bodyweight loss and histopathological lesions of the urinary 

bladder.

870.3200 21-Day dermal toxicity 

(Rat)

00098460 (1982)

Acceptable/guideline

0, 100, 1000, 5000 mg/kg/day

NOAEL = 1000 mg/kg/day in males and females

LOAEL = 5000 mg/kg/day based on slight erythema 

and edema on intact and abraded skin of both sexes, 

and decreased food consumption in females.

870.3465 28-Day inhalation 

toxicity (rat)

00137704 (1983)

Acceptable/ guideline

0, 0.05, 0.16, 0.36 mg/L

NOAEL = 0.36 mg/L (HDT) 

LOAEL not established based on 6 hours/day, 5 

days/week for 4 weeks

870.3700a Prenatal 

developmental in 

rodents (Rat)

00046362 (1980)

Acceptable/guideline

0, 1000, 3500 mg/kg/day

Maternal NOAEL = 1000 mg/kg/day

LOAEL = 3500 mg/kg/day based on based on 

inactivity, mortality, stomach hemorrhages and reduced 

body-weight gain.

Developmental NOAEL = 1000 mg/kg/day

LOAEL = 3500 mg/kg/day based on increased 

incidence in the number of fetuses and litters with 

unossified sternebrae and decreased fetal body weight.

870.3700b Prenatal 

developmental in 

(Rabbit)

00046363 (1980)

Acceptable/guideline

0, 175, 350 mg/kg/day

Maternal NOAEL = 175 mg/kg/day

LOAEL = 350 mg/kg/day based on based on mortality, 

diarrhea, soft stools, and nasal discharge.

Developmental NOAEL = 350 mg/kg/day (HDT)

LOAEL = not established.

870.3800 Reproduction and 

fertility effects, 3-

generation (Rat)

00105995 (1981)

Acceptable/guideline

0, 10, 30 mg/kg/day

Parental/Systemic NOAEL = 30 mg/kg/day (HDT)

Reproductive NOAEL = 30 mg/kg/day (HDT)

Offspring NOAEL = 10 mg/kg/day

LOAEL = 30 mg/kg/day based on focal dilation of the 

kidney in male F3b pups.
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Subchronic, Chronic, and Other Toxicity Profile.

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

Classification /Doses Results

870.3800

Reproduction and 

fertility effects, twogeneration (Rat)

41621501 (1990)

Acceptable/guideline

0, 2000, 10,000 or 30,000 ppm

(0, 250, 500 and 1500 

mg/kg/day)

Parental/Systemic NOAEL = 500 mg/kg/day in males 

and females

LOAEL = 1500 mg/kg/day in males and females based 

on soft stools, decreased body-weight gain and food 

consumption. Focal dilation of the kidney observed at 

30 mg/kg/day in the 3-generation study was not 

observed at any dose level in this study.

Reproductive NOAEL = 1500 mg/kg/day (HDT) in 

males and females

Offspring NOAEL = 500 mg/kg/day in males and 

females

LOAEL = 1500 mg/kg/day in males and females based 

on decreased body-weight gain during lactation.

870.4100a Chronic toxicity (dog)

00153374 (1985 )

Acceptable/guideline

0, 20, 100, and 500 mg/kg/day 

[M/F]

NOAEL = 500 mg/kg/day [M/F]

LOAEL = not established.

870.4200

Combined Chronic 

Toxicity/Carcinogenici

ty (rat)

41643801, 41728701 (1990 )

Acceptable/guideline

0, 2000, 8000, 20000 ppm

0, 362/447, 940/1183 

mg/kg/day [M/F]

NOAEL = 362/447 mg/kg/day [M/F]

LOAEL = 940/1183 mg/kg/day[M/F] based on 

decreased body-weight gain in females, decreased 

urinary pH in males, increased incidence of cataracts 

and lens abnormalities in males, and increased absolute 

and relative (to brain) liver weight in males.

No evidence of carcinogenicity

870.4300

Carcinogenicity

(mouse)

41643801, 41728701 (1990 )

Acceptable/guideline

0, 1000, 5000, 30000 ppm

0, 150, 750, 4500 mg/kg/day 

[M/F]

NOAEL = 750 mg/kg/day [M/F]

LOAEL = 4500 mg/kg/day [M/F] based on significant 

decreased body-weight gain in both sexes, hepatocyte 

necrosis and interstitial nephritis in males, and 

increased incidence of proximal tubule epithelial 

basophilia and hypertrophy in the kidney of females.

No evidence of carcinogenicity

870.5265 Gene Mutation 00078620 (1978)

Acceptable/ guideline

Non-mutagenic when tested up to 1000 ug/plate, in 

presence and absence of activation in S. typhimurium

strains TA98, TA100, TA1535 and TA1537.

870.5300

Cytogenetics 00132683 (1983)

Acceptable/ guideline

Non-mutagenic at the HGPRT locus in Chinese 

hamster ovary cells tested up to cytotoxic 

concentrations or limit of solubility, in presence and 

absence of activation.

870.5385 In Vivo Cytogenetics -

Bone Marrow

00251737 (1983 )

Acceptable/guideline

0, 2000, 8000, 20000 ppm

0, 362/447, 940/1183 

mg/kg/day [M/F]

Non-mutagenic in rat bone marrow chromosome assay 

up to 1000 mg/kg in both sexes of Sprague Dawley 

rats.

870.5550

Rec - Assay and Gene 

Mutation Assay 

00078619 (1978)

Acceptable/guideline

There was no evidence of recombination in the recassay up to 2,000 ug/disk with B. subtilis H17 (rec+) 

and M45 (rec-). Negative for reverse gene mutation, 

both with and without S-9, up to 5,000 ug/plate (or 

cytotoxicity) with E.coli SP2hcrA and S. typhimuarium

TA98, TA100, TA1535, TA1537, and TA1538.

870.6200a

Acute neurotoxicity 

screening battery

44320610 (1996)

Classification: Pending

0, 500, 1000, 2000 mg/kg 

[M/F]

Preliminary NOAEL = 2000 mg/kg/day [M/F]

Preliminary LOAEL was not observed. 

870.6200b

Subchronic 

neurotoxicity 

screening battery

44320612 (1996)

Classification: Pending

0, 2000, 8000, 20000 ppm

(0, 155.5/ 166.3, 617.1/ 672.1, 

1546.5/ 1630.6 mg/kg/day 

[M/F])

Preliminary NOAEL = 1546.5/1630.6 mg/kg/day 

[M/F]

Preliminary LOAEL was not observed. 
Glyphosate Human-Health Risk Assessment D398547

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Subchronic, Chronic, and Other Toxicity Profile.

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

Classification /Doses Results

870.7485

Metabolism and 

pharmacokinetics

(rat)

40767101,40767102 (1988)

Acceptable/guideline

10 mg/kg 

Absorption was 30-36% in males and females. 

Glyphosate was excreted unchanged in the feces and 

urine (97.5% minimum). The only metabolite present 

in the excreta was AMPA. Less than 1% of the 

absorbed dose remained in the carcass, primarily bone. 

Repeat dosing did not alter metabolism, distribution, 

and excretion.

870.7800 Immunotoxicity

48934207 (2012)

Classification: Pending

0, 500, 1500, 5000 ppm 

(0, 150, 499, 1448 mg/kg/day 

[F])

Preliminary NOAEL = 1448 mg/kg/day

Preliminary LOAEL was not observed.