### Page 3 of 22

Introduction

HED has evaluated the existing human health risk assessments for paraquat to determine

whether sufficient data are available and whether a new human health risk assessment is needed to support Registration Review. HED has considered the most recent risk assessment s for

paraquat

, updates to its toxicity, exposure and usage data bases, and current Agency science policies and risk assessment methods.

Use Profile

Paraquat is a non

- selective herbicide currently registered for the control of weeds and grasses in agricul tural and non

- agricultural areas. It is a contact herbicide that desiccates and destroys plant cell membranes within hours of application. Paraquat is used in /on a variety of

food , feed and non

- food crops with tolerances currently established for crop and livestock food

commodities (40 CFR 180. 205 )

. It is applied to agricultural and non

- agricultural areas with

aerial

, ground , and handheld spray equipment. There are no paraquat products registered for homeowner use and no products registered for app lication to residential areas.

Hazard Identification/T oxicology

Subchronic and chronic toxicity studies in mice, rats and dogs indicate that the lung is the principal target organ for repeated exposure to paraquat . Based on a subchronic inhalation study

in rats , paraquat is severely toxic when inhaled as i ndicated by observations of increasingly severe lung effects at increased doses and an 80% mortality rate from respiratory failure in high

dose animals ( 1. 3 μ g/L ) within two weeks of a single administered dose. Prolonged oral ingestion of paraquat in chronic studies in rats, mice and dogs also led to mortality with e ffects

seen in the lung, kidney, and eyes

. The results of a two

- generation reproduction study and developmental toxicity studies in rats indicate that paraquat is not a developmental or

re productive toxicant. Required neurotoxicity studies were not available and were expressly not required for the 200 6 paraquat risk assessment ( D328653, 7/31/2006 )

. At that time, HED

determined that there was limited concern for neurotoxicity res ulting from exposure to paraquat

based on the following considerations : p araquat does not inhibit cholinesterase activity

, produce cholinergic

- like toxic signs

, or affect morphology of the central or peripheral nervous systems ; the molecular structure is not simi lar to compound classes known to have effect s on the nervous

system ; t here is no evidence of neurotoxicity based on the available toxicity data for paraquat

. HED classified paraquat as a "Group E" chemical for carcinogenicity , no evidence for carcinogenic ity to humans

, based on the absence of evidence of carcinogenicity in c hronic an d carcinog enicity studies performed in rats and mice

. The Group E classification corresponds to a designation of “Not Likely t o b e Carcinogenic t o Humans” based on the 2005 EPA Guidelines for Carcinogenic Risk Assessment

. Paraquat is highly acutely toxic via inhalation, dermal and oral routes of exposure. T he toxicology database for paraquat was deemed incomplete due to

lack of an acceptable developmental study in rabbits, but was considered adequate for hazard

characterization and FQP A assessment given the availability of four acceptable developmental

studies in rats and mice

.

### Page 4 of 22

For the 200 6 paraquat risk assessment, toxicity endpoints or points of departure ( PODs )

were selected for oral (food and drinking water) , dermal, and inhalation exposure routes. An acute dietary population adjusted dose (aPAD) was selected for the general population

, including

females 13

- 49 years old

, from the rat reproduction study based on lung effects

. A ch ronic dietary population adjusted d ose (cPAD ) w as selected from a chronic dog toxicity stud y based on lung effects. A POD for short

- and intermediate

- term dermal exposure was selected from the rat reproduction study. A POD for long term dermal exposure was selected from the chronic dog study. A dermal absorption factor of 0.3% derived from a dermal absorption study in humans

was used to convert the oral dose s to equivalent dermal dose s for the risk assessment. A POD

for inhalation exposure for all durations was selected based on the 21

- day inhalation study in

rats. The FQPA safety factor was reduced to 1 x for the following reasons: ( 1 ) there is no evidence of neurotoxicity in the registrant submitted studies ; ( 2 ) there is no indication of quantitative or qualitative increased susceptibility of rats or mice to in utero and/or pre

- /postnatal exposure to rats; ( 3 ) the dietary (food and drinking water) exposure assessments will not underestimate the potential exposures for infants and children; and ( 4 ) there are no registered residential uses of paraquat. However, a database uncertainty factor (UF DB 

### ) of 3 x was applied to the subpopulation of f

emales 1 3

- 49 years old due to lack of an acceptable developmental study in a non

- rodent species

. An uncertainty factor of 100 x (10 x for interspecies extrapolation

and 10 x for intraspecies variation) was applied for all f or dietary exposure to the general population and all subpopulations except females 13

- 49 years old. A typical uncertainty factor of 100x was applied for dermal and inhalation exposure. No toxicit y data w ere required for the

2006 assessment.

Data Requirement s

An evaluation of open literature studies on paraquat conducted by HED in 2009 indicates

that there is potential for paraquat to cause neurotoxicity in adults (D375436, 5/11/10) . Based on

that finding and new 40 CFR Part 158 requirements data requirements, HED concluded that

acute and sub chronic neurotoxicity studies would be required for paraquat for Regi stration

Review . In response, the registrant conducted a cute and subch ronic neurotoxicity studies . These

studies have been submitted to the Agency and reviewed by HED. Based on HED’s evaluation,

the submitted studies satisfy guideline requirements for n eurotoxicity data

. A developmental toxicity study in the rabbit is required for food and non

- food use pesticides under 40 CFR Part

158

. I mmunotoxic ity studies are also required under 40 CFR Part 158 as a part of the new data requirements for registration of a pesticide for food and non

- food uses

. The registrant submitted a protocol for the immunotoxicity study for HED’s review in November, 2010. HED determined

that an immunotox icity study conduct ed in accordance with the submitted protocol would satisfy the guideline data requirement for an immunotoxicity study in rats.

Conclusions

Based on HED’s re

- evaluation of the toxicity analysis conducted for the 200 6 paraquat
risk ass essment a developmental toxicity study in rabbits, and an immunotoxicity study in rats are required for Registration Review: PODs for oral , dermal and inhalation exposure are adequate but endpoints may need to be reevaluated for Registration Review based submission of

### Page 5 of 22

required toxicity data. The FQPA safety factor determin ation should be reevaluated for Registration Review based on newly required toxicity data.

Dietary and Drinking Water Exposure

The residue of concern for dietary exposure in plants and livestock is paraquat per se

. A cute and chronic d ietary and drinking water exposure assessment s w ere conducted in 200 6

usi ng the Dietary Exposure Evaluation Model DEEM

- FCIDTM ( D 327805 , 7/31/06)

. The acute dietary assessment used tolerance level residues and maximum estimates of percent crop

treated. The chronic assessment assumed tolerance level residues and 100% crop treated. Based on an evaluation of available groundwater monitoring studies, t h e Environmental Fate and Effects Division (EFED) recommended use of monitoring data reported in Virginia (1.52 μg/L) for the drinking water exposure assessment, as a high

- end, but not worst

- case value for the acute and chronic analyses. T he groundwater moni toring value was incorporated directly into the dietary assessment s

. Acute and chronic dietary and drinking water assessments
indicated that estimated risks were not of concern for the general U.S. population and all population subgroups. The acute food and water risk estimate was 3 3 % of the a PAD for the U.S. population and 66 % of the a PAD for the most highly

- exposed population subgroup (children 1

- 2 years old)

. The chronic food and water risk estimate was 8 % of the cPAD for the U.S. population and 26 % of the cPAD for the most highly

- exposed population subgroup (children 1

- 2 years old)

.

Residue chemistry data requirements included in the 200 6 assessment included crop field trial data for okra and corn aspirated grain fractions.

Data Requirements

The data base for the dietary assessment is incomplete. Crop field trial data for okra has not been submitted but is no longer required because, under new ly established crop groupings, okra is included in Crop Group 8

- 10 (Fruiting Vegetable Group ) for which adequate data are

available. However, the data requirement for aspirated grain fractions remains outstanding.

In order to bring the drinking water assessment up to date with current data, simulation models and guidance, a new drinking water exposure assessment will be conducted to support future human health dietary risk assessments of paraquat . The drinking water assessment will incorporate model estimates of paraquat in surface water and ground water. Concentrations of

paraquat in surface waters will be estimated using PRZM/EXAMS (see description above) with Index Reservoir as the receiving water body. With paraquat’s high adsorptive properties, the regular water treatment process is expected to remove almost all paraqat in the wat er. EFED is requesting the treatability study form the registrant to confirm this property. An Estimated Drinking Water Concentration (EDWC) of paraquat in groundwater will be estimated using the Tier I aquatic model SCIGROW (Screening Concentration in G round Water, version 2.3; 8/8/2003). SCIGROW is a regression model used as a screening tool to estimate pesticide concentrations found in ground water used as drinking water. The output of SCIGROW represents the concentrations that might be expected in s hallow unconfined aquifers under sandy soils, which is representative of the ground water most vulnerable to pesticide contamination

### Page 6 of 22

likely to serve as a drinking water source. The drinking water assessment will also include available surface and ground w ater monitoring data with consideration of changes in use patterns that may have occurred. States are encouraged to submit monitoring data for review.

Conclusion s

A n updated dietary risk assessment will likely be required during the registration review

process to include changes to the drinking water assessment as well as any revised points of departure (P O Ds) or uncertainty factors

. The revised assessments should be conducted using the

newest version of DEEM

- FCID which include s updated consumption inf ormation

.

Tolerances and International Harmonization

U.S. tolerances and International maximum residue levels ( MRLs ) for paraquat are not compatible for a significan t number of commodities for which tolerances have been establishe d by both entities

. U.S. and Canadian tolerances are compatible for all jointly registered

commodities. A summary of US and international tolerances and maximu m residue limits including Commodities for which U.S. tolerances differ from Codex MRLs is attached

. The

tolerance expression for paraquat needs to be reviewed and updated as necessary based on HED’s Interim Guidance on Tolerance Expressions (S. Knizner, 5/27/09 ).

Residential Exposure

There are no paraquat products registered for homeowner use and there are no products registered for app lication to residential areas. H owever, residential bystander inhalation exposures resulting from off

- site transport (e.g., spray drift ) may occur as a result of applicatio ns of paraquat dichloride . The Agency is in the process of examining its policies and refining the methods used to complete residential exposure assessments

. Therefore, the potential need for a bystander inhalation risk assessment will be examined during registration review.

Aggregate Exposure

Since there are no residential uses of paraquat, acute and chronic aggregate risks are equivalent to estimated acute and chronic dietary (food and water) risks respectively. Estimated chronic dietary risks for paraquat are not of concern based on the 200 6 risk assessment

Conclusions

T he aggregate exposure assessment is adequate. However, as previously indicated, the dietary exposure and risk assessments may need to be revised if new PODs are selected based on required toxicity data submissions.

### Page 7 of 22

Occupational Exposure

Risk assessments were conducted for occupational handler and post

- application exposure

scenarios based on registered uses. Occupational h andler exposures to paraquat are expected to
be short

- and intermediate

- term based on use patterns

. Chemical

- specific applicator biomonitoring exposure data submitted to the Agency for the 1997 RED were used to estimate dermal and inhalation exposure and risk for aerial, gro und and hand spray applications of paraquat for the 200 6 risk assessment. Standard HED unit exposure data were use to estimate risk to handlers from spot treatment and flagging scenarios. Estimated MOEs were not of concern for any of the handler and post

- application exposure scenarios assessed for the 200 6 paraquat risk assessment.

Conclusions

The occupational exposure assessment is adequate but needs to be updated to reflect current standard operating procedures. Recommended unit exposures for occup ational handler assessments have generally been derived only from PHED. However, recently both the ORETF and AHETF have produced pesticide handler exposure monitoring data that the Agency is using in place of PHED ( http://www.epa.gov/pesticides/science/handler

- exposure

- data.html ). As more reliable data become available (such as that from the AHETF and ORETF), the Agency will continue to replace existing data. Reviewers should i ncorporate new exposure monitoring data,

as necessa ry, during Registration Review. In addition, the use of chemical specific biomonitoring data to estimate exposures should be reevaluated. Based on the findings of a FIFRA Science Advisory Panel meeting h eld in January 2007, pooled passive dosimetry data may be as representative as biomonitoring data but more robust . Consequently, use of passive dosimetry data from HED’s generic pesticide exposure databases for the occupational exposure

assessment may be preferable to chemical specific data

.

Incident Report

An updated incident report was conducted for paraquat for Registration Review ( K Oo, D392273, 10/18 /11)

. In general, a moderately large number of incidents have been reported involving paraquat di chloride. There were 46 cases reported for products containing paraquat dichloride present as a single chemical only; 73 cases reported for products containing paraquat

dichloride as non

- single active chemical, and 78 cases reported in the Aggregate I cide nt D ata
S ystem

. In addition, epidemiologic findings from the Agricultural Health Study (AHS) investigated a possible link of paraquat exposure in the etiology of Parkinson’s disease. The Agency will consider these AHS findings and any other literature pe rtinent to paraquat exposure and toxicity as part of the Registration Review evaluation for paraquat.

Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Col lectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints

### Page 8 of 22

which may be susceptible to end ocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its reregistration decision

, EPA reviewed these data and

selected the mos t sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), paraquat is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, a ndrogen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if an y, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredi ents. Paraquat was included on that list and has been issued an order to conduct the Tier 1 testing. Once all required Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk assessment purposes will be exam ined and a new risk assessment performed if necessary. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our

website: http://www.epa.gov/endo/

.

C umulative

EPA does not have, at this time, available data to determine whether paraquat has a common mechanism of toxicity with other substances. EPA has not made a common mechanism of toxicity finding for paraquat and any other substances and, paraquat does not appear to produce a toxic metabolite produced by other substances which have tolerances in the U. S. Therefore, EPA has not assumed that p araquat has a common mechanism of toxicity with other

substances.

Human Studies

Past paraquat risk assessments have relied in part on human studies which have involved intentional exposure to paraquat ( MRIDs 00126096

- 00126099 (1982) . In the course of registration review EPA will reconsider these studies, as well as any other research involving intentional exposure of human subjects to paraquat or related chemicals brought to its attention.

### Page 9 of 22

If EPA decides to rely on any of these studies, EPA will ensur e that all applicable regulatory requirements are met, including but not limited to the requirements for EPA ethics review and Human Studies Review Board review of certain research involving intentional exposure of human subjects.

F uture occupational a ssessments conducted for registration review of paraquat will use

data contained in HED ’ s generic pesticide exposure databases such as Pesticide Ha ndlers Exposure Database (PHED), th e Agricultural Reentry Task Force (ARTF) Database and the

Outdoor Resident ial Exposure Task Force (ORETF) Database ). Recommended unit exposures for occupational handler assessments have generall y been derived only from PHED. However, recently both the ORETF and AHETF have produced pesticide handler exposure monitoring data that the Agency is using in place of PHED ( http://www.epa.gov/pesticides/science/handler

exposure

- data.html ). As more reliable data become available, the Agency will continue t o replace existing data and new exposure monitoring data will be incorporated into HED’s Registration Review assessments as necessary. EPA has reviewed all the studies supporting

these multi

- pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relative to the ethical standards prevailing at the time the research was conducted. A ll applicable requirements of EPA’s Rule for the Prote ction of Human Subjects of Research (40 CFR Part 26) have been satisfied , and t here is no regulatory barrier to continued reliance on

these studies

.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were con sidered

in the 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). The OPP typically considers the highest potential exposures from the legal use of a pesticide when conducting human

- health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural area s, the variability of diets within the U.S., and people who might be exposed when harvesting crops. Should these highest exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure that the risk

estimates are based on the best available information.

### Page 10 of 22

Conclusions/Future Actions Needed

T he actions needed in the future Registration Review for paraquat are listed below

.

Hazard Identification and Endpoint Selection

Rabbit developmental toxicity and immunotoxicity stud ies are required for Registration Review. PODs for oral, dermal and inhalation exposure are adequate but endpoints may need to be reevaluated for Registration Review based submission of required toxicity data.

Dietary and Drinking Water Exposure and Ri sk The dietary and drinking water exposure assessment s will likely need to be revised to include updated drinking water values and any revised points of departure (PODs) or uncertainty factors

. The revised assessments should be conducted using the newest version of DEEM

- FCID which includes updated consumption information.

Residential Exposure and Risk A residential exposure assessment is not required based on currently registered uses

. H owever, residential bystander inhalation exposures resulting from off

- site transport (e.g., spray drift ) may occur as a result of applications of paraquat dichloride . The Agency is in the process of examining its policies and refining the methods used to complete residential exposure

assessments

. Therefore, the potenti al need for a bystander inhalation risk assessment will be examined during R egistration R eview.

Aggregate Exposure and Risk The aggregate exposure assessment is adequate. However, the dietary exposure and risk assessments may need to be revised if new PODs are selected based on required toxicity data

submissions.

Occupation al Exposure and Risk The occupational exposure asse ssment is adequate but needs to be updated to reflect current standard operating procedures. In addition, the use of chemical specific biomonitoring data to estimate exposures should be reevaluated.

Incident Report In general, a moderately large number of incidents have been reported involving paraquat

dichloride. Human incident data may warrant further analysis for the risk assessment and/or risk management of paraquat dichloride

. In addition, the Agency will consider AHS and other

literature findin gs regarding a potential link between paraquat exposure and Parkinson’s disease as part of Registration Review.

### Page 11 of 22

Data Requirements

Toxicity Data Requirements

- Developmental Toxicity Study

– nonrodent (GLN 870.3700b)

- Immunotoxicity study (GLN 870.7800)

Residue Chemistry Data Requirements

- Crop Field Trials for Corn Aspirated Grain Fractions (GLN 860.1500 )

### Page 12 of 22

References

Paraquat Dichloride: Human Health Risk Assessment for Proposed Uses on Ginger and Okra

and Amended Uses on Soybeans, Wheat, Cotton, Cucurbits, Onions, and Tanier. D. Dotson, D328653, 7/31/2006.

Paraquat Dichloride. Request to Amend Uses on Cotton, Cucurbits, Onion, Soybean, Tanier, and Wheat, and Add Uses on Ginger and Okra. Summary of Analytical Chemistry and Residue

Data. D. Dotson, D 343438 , 7/31/2006

Paraquat Dichloride: Acute and Chronic Dietary Exposure Assessments for the Section 3 Registration Action on Wheat, Soybeans, Cucurbits, Cotton, Onions, Tanier, Okra, and Ginger
D. Dotson, D 327805 , 7/31/2006.

Tier 2 Drinking Water Assessment for Paraquat Dichloride, J. Angier, D311410, 3/3/06

Paraquat Dichloride: Occupational and Residential Exposure/Risk Ass essment for the New Uses

of Paraquat Dichloride on Onion (dry bulb), Ginger, Wheat, Soybean, Cotton, Cucurbits, Okra, and Tanier, S. Wang, D327807, 4/20/2006

Paraquat

- Report of the Haza rd Identification Assessment Review Committee , S. Williams

- Foy, TXR 0014110, 4/19/00

Paraquat

- Report of the FQPA Safety Factor Committee, J. Rowland, TXR 0014137, 5/4/00

Evaluation of Acute Paraquat Toxicokinetic Studies, J. Ryman, TXR 0055274, 6/30/10

Evaluation o f Acute a nd Subchronic Neurotoxicity Studies f or Paraquat

, J. Ryman , A. Assaad, TXR 0055342, 5/11/10

Evaluation Of Paraquat Brain Accumulation Data In Open Scientific Literature: Implications For

Future Risk Assessments , J. Ryman , R. Kent, TXR 0055101, 3/11/09

Paraquat dichloride : Review of Human Incidents , K. Oo, D392273, 10/18/2011

.

Paraquat: Report of the Dose Adequacy Review Team (DART)

– Concurrence with the Protocol

and Dose Selection for the Immunotoxicity Study , J. Kidwell, TXR 0055562, 12/8/10

### Page 13 of 22

Attachments

Chemical Identity

Table 1. Paraquat Nomenclature

Chemical structure

Common name Paraquat dichloride

IUPAC name 1,1’

- dimethyl

- 4,4’

- bypyridinium dichloride

CAS name 1,1’

- dimethyl

- 4,4’

- bypyridinium dichloride

CAS registry number 1910

- 42

- 5 (4685

- 14

- 7 for the cation)



### Commodities for which US and International Limits Differ

Table 2 . Commodities for which US and International Tolerances and Maximum Residue Limits Differ

Residue Definition:

US Canada Mexico Codex

40 CFR 180.205:

Plants/Livestock: paraquat (1,1′

- dimethyl

4,4′

- bipyridinium

- ion) derived from application of either the bis(methyl sulfate) or the dichloride salt (both calculated as the

cation 4,4'

- bipyridinium,
1,1'

- dimethyl

Plants/Livestock: paraquat

cation.



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

US Canada Mexico 1 

### Codex 2

Almond, hulls 0.5 0.01 (*) Asparagus 0.5

Avocado 0.05 0.01 (*) Assorted tropical and subtropical fruits

- inedible peel

Banana 0.05 0.01 (*) Assorted tropical and subtropical fruits

- inedible peel Beet, sugar, roots 0.5 0.05 Root and tuber vegetables Beet, sugar, tops 0.05 Berry group 13 0.05 0.05 0.01 (*) Berries and other

small fruits
Carrot, roots 0.05 0.05 0.05 Root and tuber vegetables
Cattle, fat 0.05 Cattle, kidney 0.5 0.05 Edible offal (mammalian)
Cattle, meat 0.05 0.005 (*) Meat from mammals other than marine mammals) Cattle, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian)

Corn, field, grain 0.1 0.1 0.03 Maize; 0.05 maize flour
Corn, field, stover 10.0 10 Maize fodder (dry)

### Page 14 of 22

Table 2 . Commodities for which US and International Tolerances and Maximum Residue Limits Differ

Residue Definition:

US Canada Mexico Codex
Cotton, undelinted seed 3.5 2 Cotton seed Cranberry 0.05 0.01 (*) Berries and other

small fruits Egg 0.01 0.005 (*)

Endive 0.05 0.07 Leafy vegetables Fruit, citrus, group 10 0.05 0.02 Citrus fruits Fruit, pome, group 11 0.05 0.05 0.01 (*) Pome fruits Fruit, stone, group 12 0.05 0. 05 0.01 (*) Stone fruits Ginger 0.1 0.05 Root and tuber vegetables Goat, kidney 0.5 0.05 Edible offal (mammalian)
Goat, meat 0.05 0.005 (*) Meat from mammals other than marine mammals) Goat, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian)

Guar, seed 0.5 0.5 Pulses

Guava 0.05 0.01 (*) Assorted tropical and subtropical fruits

- inedible peel Hog, kidney 0.5 0.05 Edible offal (mammalian) Hog, meat 0.05 0.005 (*) Meat from mammals other than marine mammals) Hog, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian)

Hop, dried cones 0.5 0.1 Hops, dry Horse, kidney 0.5 0.05 Edible offal (mammalian)
Horse, meat 0.05 0.005 (*) Meat from mammals other than marine mammals) Horse, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian)

Kiwifruit 0.05 0.01 (*) Assorted tropical and subtropical fruits

- inedible peel
Lentil, seed 0.3 0.5 Pulses

Lettuce 0.05 0.07 Leafy vegetables

Milk 0.01 0.005 (*) Nut, tree, group 14 0.05 0.05 Filberts 0.05 Tree nuts

Okra 0.05 0.05 Fruiting vegetables, other

than cucurbits

Olive 0.05 0.1 Papaya 0.05 0.01 (*) Assorted tropical and subtropical fruits

- inedible peel

Passionfruit 0.2 0.01 (*) Assorted tropical and subtropical fruits

- inedible peel Pea and bean, dried shelled, except soybean, subgroup 6C, except guar

bean 0.3 0.5 Pulses

Persimmon 0.05 0.01 (*) Assorted tropical and subtropical fruits

- inedible peel

Pistachio 0.05 0.05 Tree nuts

Potato 0.5 0.05 Root and tuber vegetables Rice, grain 0.05 0.05
Rice, straw 0.06 0.05 Rice straw and fodder, dry

### Page 15 of 22

Table 2 . Commodities for which US and International Tolerances and Maximum Residue Limits Differ

Residue Definition:

US Canada Mexico Codex Sheep, kidney 0.5 0.05 Edible offal (mammalian) Sheep, meat 0.05 0.005 (*) Meat from mammals other than marine mammals) Sheep, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian)

Sorghum, forage, forage 0.1 0.3 Sorghum straw and fodder, dry Sorghum, grain, grain 0.05 0.03 Soybean, hay 10.0 0.5 Soya bean fodder dry Soybean, seed 0.7 0.5 Pulses Turnip, greens 0.05 0.05 0.07 Leafy vegetables Turnip, roots 0.05 0.05 0.05 Root and tuber vegetables Vegetable, brassica, leafy, group 5 0.05 0.05 0.07 Leafy vegetables Vegetable, cucurbit, group 9 0.05 0.05 cucumber 0.02 Fruiting vegetables,

Cucurbits Vegetable, fruiting, group 8 0.05 0.05 Fruiting vegetables, other

than cucurbits 

### MRLs with NO US equivalent
Poultry meat 0.005 (*) Poultry, Edible offal of 0.005 (*)

Sunflower seed 2 Tea, Green, Black (black fermented and dried) 0.2



### Summary of Points of Departure

Summary of Toxicological Doses and Endpoints for Paraquat for Use in Human Health Risk Assessments

Exposure

Scenario Dose Used in Risk

Assessment, UF Special FQPA SF and

Level of Concern for

Risk Assessment Study and Toxicological Effects

Acute Dietary (females 13

- 49) NOAEL = 1.25

mg/kg/day

UF = 300

Acute RfD = 0.0125 mg/kg/day FQPA SF = 1x

aPAD = 0.0042 mg/kg/day Multi

- generation rat study LOAEL = 3.75 mg/kg/day, based on increased incidences of alveolar histiocytes

in both sexes

Acute Dietary (general population) NOAEL = 1.25

mg/kg/day

UF = 100

Acute RfD = 0.0125 mg/kg/day FQPA SF = 1x

aPAD = 0.0125 mg/kg/day Multi

- generation rat study LOAEL = 3.75 mg/kg/day, based on increased incidences of alveolar histiocytes

in both sexes

Chronic Dietary (all populations) NOAEL = 0.45

mg/kg/day

UF = 100

Chronic RfD = 0.0045 mg/kg/day FQPA SF = 1x

cPAD = 0.0045 mg/kg/day Chronic toxicity in dogs LOAEL = 0.93 mg/kg/day, based on increased severity of chronic pneumonitis and gross lung lesions in both sexes, and focal pulmonary granulomas in males

Dermal

Short

- - Intermediate

- Term NOAEL = 1.25

mg/kg/day LOC = MOE = 100

Dermal absorption Multi

- generation rat study LOAEL = 3.75 mg/kg/day, based on increased incidences of alveolar histiocytes

### Page 16 of 22

Summary of Toxicological Doses and Endpoints for Paraquat for Use in Human Health Risk Assessments

Exposure

Scenario Dose Used in Risk

Assessment, UF Special FQPA SF and

Level of Concern for

Risk Assessment Study and Toxicological Effects

(1day

– 6 months) factor = 0.3% in both sexes

Dermal Long

- Term (> 6 months) NOAEL = 0.45

mg/kg/day LOC = MOE = 100

Dermal absorption

factor = 0.3% Chronic toxicity in dogs LOAEL = 0.93 mg/kg/day, based on increased severity of chronic pneumonitis and gross lung lesions in both sexes, and focal pulmonary granulomas in males

Inhalation

Short

- through Long

- Term (1 day

- > 6 months) NOAEL = 0.01

μ g/L for respirable particles

NOAEL = 1.25 mg/kg/day for non

respirable particles LOC = MOE = 100

Inhalation absorption

factor = 100% 21

- Day inhalation toxicity study in rats (respirable particles)

LOAEL = 0.10 μ g/L, based on squamous keratinizing metaplasia and hyperplasia of the epithelium of the larynx

3

- generation reproduction study (non

respirable particles)

Cancer (oral, dermal, inhalation) Classification: Category E (evidence of non

- carcinogenicity to humans)

UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable



### International Residue Limits

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :

US Canada Mexico 1 Codex 2

40 CFR 180.205:

Plants/Livestock: paraquat (1,1′

- dimethyl

4,4′

- bipyridinium

- ion) derived from application of either the bis(methyl sulfate) or the dichloride salt (both calculated as the

cation 4,4'

- bipyridinium,
1,1'

- dimethyl

Plants/Livestock: paraquat cation.



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

US Canada Mexico 1 

### Codex 2

Acerola 0.05
Almond, hulls 0.5 0.01 (*) Animal feed, nongrass, group 18, forage 75.0

Animal feed, nongrass, group 18, hay 210.0

Artichoke, globe 0.05 Asparagus 0.5

Avocado 0.05 0.01 (*) Assorted tropical and subtropical fruits

inedible peel

### Page 17 of 22

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :

US Canada Mexico 1 Codex 2

Banana 0.05 0.01 (*) Assorted tropical and subtropical fruits

inedible peel Barley, grain 0.05 0.05 Barley, hay 3.5 Barley, straw 1.0 Beet, sugar, roots 0.5 0.05 Root and tuber vegetables Beet, sugar, tops 0.05 Berry group 13 0.05 0.05 aronia berries, blackberries, buffalo currants, Chilean guavas, currant, elderberries, European barberry, gooseberries, highbush blueberries, highbush cranberries,honeysu ckle, huckleberries, jostaberries, lingonberries, loganberries, raspberries, lowbush blueberries, native currants, raspberries, salal berries,

saskatoon berries (juneberries), sea buckthorn, wild raspberries 0.01 (*) Berries and

othe r small fruits

Cacao bean, bean 0.05
Carrot, roots 0.05 0.05 0.05 Root and tuber vegetables
Cattle, fat 0.05 Cattle, kidney 0.5 0.05 Edible offal (mammalian)
Cattle, meat 0.05 0.005 (*) Meat from

mammals other than marine mammals)
Cattle, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian) Coffee, bean, green 0.05 Corn, field, forage 3.0 Corn, field, grain 0.1 0.1 0.03 Maize; 0.05

maize flour
Corn, field, stover 10.0 10 Maize fodder (dry) Corn, pop, grain 0.1 0.1 Corn, pop, stover 10.0

### Page 18 of 22

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :

US Canada Mexico 1 Codex 2

Corn, sweet, kernel plus cob with

husks removed 0.05 0.05

Cotton, gin byproducts 110.0
Cotton, undelinted seed 3.5 2 Cotton seed Cowpea, forage 0.1 Cowpea, hay 0.4 Cranberry 0.05 0.01 (*) Berries and

other small fruits Egg 0.01 0.005 (*)

Endive 0.05 0.07 Leafy vegetables Fig 0.05 Fruit, citrus, group 10 0.05 0.02 Citrus fruits Fruit, pome, group 11 0.05 0.05 apples, asian pears, crabapples, loquats, mayhaws, pears, quinces 0.01 (*) Pome fruits

Fruit, stone, group 12 0.05 0.05 apricots, nectarines, peaches, plumcots, plums, prune plums, sweet cherries, tart

cherries 0.01 (*) Stone fruits

Ginger 0.1 0.05 Root and tuber vegetables
Goat, fat 0.05 Goat, kidney 0.5 0.05 Edible offal (mammalian)
Goat, meat 0.05 0.005 (*) Meat from

mammals other than marine mammals) Goat, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian) Grain, aspirated fractions 65.0 Grape 0.05 0.05 Grass, forage 90.0 Grass, hay 40.0
Guar, seed 0.5 0.5 Pulses

Guava 0.05 0.01 (*) Assorted tropical and subtropical fruits

inedible peel Hog, fat 0.05 Hog, kidney 0.5 0.05 Edible offal (mammalian) Hog, meat 0.05 0.005 (*) Meat from

mammals other than marine mammals) Hog, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian) Hop, dried cones 0.5 0.1 Hops, dry

### Page 19 of 22

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :

US Canada Mexico 1 Codex 2

Horse, fat 0.05 Horse, kidney 0.5 0.05 Edible offal (mammalian)
Horse, meat 0.05 0.005 (*) Meat from

mammals other than marine mammals) Horse, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian)

Kiwifruit 0.05 0.01 (*) Assorted tropical and subtropical fruits

inedible peel
Lentil, seed 0.3 0.5 Pulses

Lettuce 0.05 0.07 Leafy vegetables

Milk 0.01 0.005 (*)
Nut, tree, group 14 0.05 0.05 Filberts 0.05 Tree nuts

Okra 0.05 0.05 Fruiting vegetables, other

than cucurbits

Olive 0.05 0.1
Onion, bulb 0.1 0.1 Dry bulb onions Onion, green 0.05 0.05 Papaya 0.05 0.01 (*) Assorted tropical and subtropical fruits

inedible peel

Passionfruit 0.2 0.01 (*) Assorted tropical and subtropical fruits

inedible peel Pea and bean, dried shelled, except soybean, subgroup 6C, except guar

bean 0.3 0.5 Pulses

Pea and bean, succulent shelled, subgroup 6B 0.05 0.05 succulent shelled (blackeyed peas, broad beans, cowpeas, english

peas, garden peas, green peas, lima beans, peas, pigeon peas, southern peas)

Pea, field, hay 0.8
Pea, field, vines 0.2

Peanut 0.05 Peanut, hay 0.5 Peppermint, tops 0.5

### Page 20 of 22

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :

US Canada Mexico 1 Codex 2

Persimmon 0.05 0.01 (*) Assorted tropical and subtropical fruits

inedible peel Pineapple 0.05 Pineapple, process residue 0.25

Pistachio 0.05 0.05 Tree nuts

Potato 0.5 0.05 Root and tuber vegetables

Rhubarb 0.05 Rice, grain 0.05 0.05
Rice, straw 0.06 0.05 Rice straw and fodder, dry
Safflower, seed 0.05 Sheep, fat 0.05 Sheep, kidney 0.5 0.05 Edible offal (mammalian) Sheep, meat 0.05 0.005 (*) Meat from

mammals other than marine mammals) Sheep, meat byproducts, except kidney 0.05 0.05 Edible offal (mammalian) Sorghum, forage, forage 0.1 0.3 Sorghum straw and fodder, dry Sorghum, grain, forage 0.1 Sorghum, grain, grain 0.05 0.03 Soybean, forage 0.4 Soybean, hay 10.0 0.5 Soya bean fodder dry Soybean, hulls 4.5 Soybean, seed 0.7 0.5 Pulses Spearmint, tops 0.5 Strawberry 0.25 Sugarcane, cane 0.5 Sugarcane, molasses 3.0
Sunflower, seed 2.0 Turnip, greens 0.05 0.05 0.07 Leafy vegetables Turnip, roots 0.05 0.05 0.05 Root and tuber vegetables

### Page 21 of 22

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :

US Canada Mexico 1 Codex 2

Vegetable, brassica, leafy, group 5 0.05 0.05 bok choy Chinese cabbages, broccoli, broccoli raab, Brussels sprouts, cabbages, cauliflower, Chinese broccoli, chinese mustard cabbages, collards, kale, kohlrabi, mustard

greens, mustard spinach, napa Chinese cabbages,

rape greens 0.07 Leafy vegetables

Vegetable, cucurbit, group 9 0.05 0.05 cucumber 0.02 Fruiting vegetables,

Cucurbits Vegetable, fruiting, group 8 0.05 0.05 Fruiting vegetables, other

than cucurbits Vegetable, legume, edible podded, subgroup 6A 0.05 0.05 Edible

podded ( dwarf peas, jackbeans, moth beans, peas, pigeon peas, runner beans, snap beans,

snow peas, soybeans, sugar snap peas, sword beans, wax beans, yardlong beans)

Wheat, forage 0.5
Wheat, grain 1.1 Wheat, hay 3.5
Wheat, straw 50.0 

### MRLs with NO US equivalent
Poultry meat 0.005 (*) Poultry, Edible offal of 0.005 (*)

Sunflower seed 2 Tea, Green, Black (black fermented and dried) 0.2

Completed by: M.Negussie; 06/10/2011

c) Tolerances with regional registrations. Tolerances with regional registration as defined in §180.1(m), are established for residues of the pesticide paraquat (1,1′

- dimethyl

- 4,4′ bipyridinium ion) derived from application of either the bis(methyl sulfate) or the dichloride salt (both calculated as the cation) in or on the following food

commodities:

### Page 22 of 22 Commodity Parts per million Canada Codex 2

Cassava 0.05 0.05 Root and tuber vegetables

Pea, pigeon, seed 0.05 0.5 Pulses

Tanier 0.05 0.05 Root and tuber vegetables

Taro, corm 0.1 0.05 Root and tuber vegetables

Tyfon 0.05

Yam, true, tuber 0.05 0.05 Root and tuber vegetables

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

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as pr oposed have not been finalized by the CCPR and the CAC.