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Executive Summary

The Health Effects Division (HED) has evaluated the database and the most recent human health 

risk assessments for the fungicide cymoxanil. HED performed this evaluation in order to 

determine the scope of work necessary to support the established tolerances and existing 

registrations. The primary source of information for this evaluation was the most recent human 

health risk assessment ―Cymoxanil; Human Health Risk Assessment for Proposed Uses on Bulb 

Vegetables (Crop Group 3-07), Leafy Greens (Subgroup 4A), and Leaf Petioles (Subgroup 4B)”

(R. Mitkus et al., D347653, 09, July 2008).

Cymoxanil- [2-cyano-N-[(ethylamino)carbonyl]-2-(methoxyimino) acetamide] is a fungicide that 

has been registered in the United States (U.S.) for potato seed piece treatment, caneberry, hops, 

head lettuce, lychee, potato, cucurbit vegetable group, fruiting vegetable group, grape, bulb 

vegetables, subgroup 3-07A, bulb vegetables, subgroup 3-07B, leaf vegetables, subgroup 4A, 

leafy Petioles, and cilantro leaves. Cymoxanil also has been registered in Europe and Latin 

America for the control of select plant diseases in crops such as tomatoes, grapes, and potatoes. 

Cymoxanil is used to control downy mildew, and early and late blights. There are also Special 

Local Need (SLN) registrations for use on the following crops: spinach, cabbage, Swiss chard, 

and table beets when they are grown for seed. In addition, there is an SLN registration for use for 

commercial seed treatment for peas intended for export. There are currently no registered or 

proposed residential uses of cymoxanil. 

Tolerances are established for residues of cymoxanil on crops listed in 40CFR section 180.503. 

Additionally, tolerances with regional registrations are established for the states of Idaho, 

Washington and Utah. Codex has not established maximum residue limits (MRLs) but MRLs are 

established in Canada for several commodities. US and Canadian tolerances are harmonized for 

caneberry, subgroup 13A-07 and potato.

Cymoxanil is formulated as dry flowable and dust. Cymoxanil has one technical (manufacturing 

use) product containing 98.7% active ingredient; one end-use product, Curzate® 60 DF, is used 

as a tank-mix with a protectant fungicide, such as a copper product. Another cymoxanil 

containing product is Tanos®, which includes 25% cymoxanil and 25% femoxadone. The third 

registered product is Evolve®, which is a potato seed-piece treatment containing 1 % cymoxanil, 

2.5% thiophanate-methyl, and 6% mancozeb. Cymoxanil may be applied as a seed treatment to 

potato seed pieces and also to peas (export only). Seed treatments may be made using slurry or 

mist seed treatment equipment. Foliar applications may be made using ground, aerial, and 

chemigation equipment. Cymoxanil has a complete toxicology database, including studies 

relating to subchronic and developmental neurotoxicity, developmental and reproductive 

toxicity, and immunotoxicity. The Agency has granted a waiver for a 28-day inhalation toxicity

study. 

Cymoxanil has low acute toxicity via oral, dermal, inhalation, and ocular routes of exposure. It 

is a mild skin irritant and not a skin sensitizer. Systemic toxicity, as evidenced by decreased 

body weights, body weight gains, and food consumption, was observed in subchronic, chronic, 

developmental, reproductive and neurotoxicity studies across species. The dog appears to be the 

most sensitive species for cymoxanil-induced toxicity with the thymus gland identified as a 
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target organ in this species during subchronic and chronic exposures. No evidence of 

immunotoxicity was observed. Cymoxanil was not carcinogenic in rats and mice and is classified 

as ―not likely to be carcinogenic to humans‖. 

Based on toxicological considerations by the Hazard Identification Assessment Review 

Committee, HIARC (HED Doc. Date 02, Jan 2003) and updated toxicology review by RAB1 

toxicologists, recently reviewed studies, conservative residue assumptions used in the dietary 

risk assessment, and the completeness of the toxicology, residue chemistry and environmental 

fate databases, the Food Quality Protection Act ( FQPA) Safety Factor (SF) was reduced from 

10X to 1X for acute exposure, dermal exposure (short- and intermediate-term), and inhalation 

exposure (short- and intermediate-term) scenarios. The 10X FQPA SF is being retained, 

however, for chronic and long-term exposure scenarios in the form of an Uncertainty Factor 

LOAEL (UFL), due to the use of a LOAEL to extrapolate a NOAEL for the point of departure. 

In the developmental and postnatal studies for which there is increased susceptibility, the effects 

are well characterized and NOAELs were established for developmental and offspring effects. 

In addition, the doses selected for risk assessment are based on the lowest NOAELs from the 

developmental and reproductive toxicity studies, where appropriate, and are protective of any 

potential pre- and post-natal effects. Therefore, there are low levels of concern and no residual 

uncertainties for pre- and post-natal toxicity.

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

a common mechanism of toxicity, the agency has not made a common mechanism of toxicity 

finding for cymoxanil and any other substances. Cymoxanil does not appear to produce a toxic 

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

agency has assumed that cymoxanil does not have a common mechanism of toxicity with other 

substances.

In the most recent human health risk assessment (R. Mitkus et al., D347653, 09 July 2008) no 

chemical-specific data were available to assess potential exposure to occupational handlers. 

Therefore, occupational handler assessments were based primarily on surrogate unit exposures 

from the Pesticide Handler's Exposure Database (PHED) as presented in the PHED Surrogate 

Exposure Guide. Occupational handler risk estimates for the registered uses of cymoxanil did 

not exceed below HED’s level of concern for all activities (i.e. MOEs >100). However, for some

scenarios, mitigation measures were required the use of Personal Protective Equipment (PPE).

The PPE requirement is included in all active labels (i.e., coveralls, gloves, respirators). Risk 

estimates for dermal postapplication exposure were not of concern. Based on the Agency’s 

current practices, and the low likelihood of exposure, quantitative postapplication inhalation 

exposure assessments were not performed for cymoxanil. The handler dermal and inhalation, and 

dermal post application risk calculations were based on maximum application rates and assuming 

maximum area treated per day. For the purpose of cymoxanil registration review the Agency 

anticipates that if the new Occupational Pesticide Handlers Exposure Database (OPHED) or the 

revised Agricultural Re-entry Task Force (ARTF) data base were incorporated into the 

assessment, MOEs are likely to be lower (higher risk concern) than those presented in the last 

risk assessment.
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Although there are currently no uses for cymoxanil that would result in direct residential 

exposure, residential bystander exposures might occur as a result of cymoxanil aerial 

applications, volatilization, and/or transport from treated areas. HED will evaluate the need for a 

bystander assessment under registration review.

The existing residue chemistry database for cymoxanil is adequate for risk assessment purposes. 

The qualitative nature of the residue is understood. The residue of concern for tolerance 

enforcement and risk assessment includes only parent cymoxanil [2-cyano-N-[(ethylamino)

carbonyl]-2-(methoxyimino) acetamide].

The dietary exposure database is adequate to support registration review of cymoxanil. The most 

recent dietary risk estimates for cymoxanil are based on unrefined residue assumptions (01, July

2008 and 100% crop treated). The acute and chronic dietary (food and drinking water) risk 

estimates are not of concern for the existing uses of cymoxanil. Currently, there are no uses for 

cymoxanil that would result in residential exposures; therefore, aggregate risk estimates are 

equivalent to the dietary (food and water) risk estimates. A new risk assessment would be 

required for registration review only if there are any revisions to the toxicological points of 

departure, uncertainty factors, or revised drinking water estimates which would potentially lead 

to higher estimated risks.

Introduction

The Health Effects Division (HED) has evaluated the database and the most recent human health 

risk assessments for the fungicide cymoxanil. HED performed this evaluation in order to 

determine the scope of work necessary to support the established tolerances and existing 

registrations. The primary source of information for this evaluation was the most recent human 

health risk assessment (R. Mitkus et al., D347653, 09, July 2008).

The structure of cymoxanil, as well as its chemical names and other identifiers can be found in 

the chemical identity table attached to this document (Attachment 1).

Cymoxanil- [2-cyano-N-[(ethylamino)carbonyl]-2-(methoxyimino) acetamide] is a fungicide that 

has been registered in the United States (U.S.) for potato seed piece treatment, caneberry, hops, 

head lettuce, lychee, potato, cucurbit vegetable group, fruiting vegetable group, grape, bulb 

vegetables, subgroup 3-07A, bulb vegetables, subgroup 3-07B, leaf vegetables, subgroup 4A, 

leafy Petioles, and cilantro leaves. Cymoxanil also has been registered in Europe and Latin 

America for the control of select plant diseases in crops such as tomatoes, grapes, and potatoes. 

Cymoxanil is used to control downy mildew, early and late blights. It has been formulated and 

sold alone or in combination with other fungicides. There are also Special Local Need (SLN) 

registrations for use on the following crops: spinach, cabbage, Swiss chard, and table beets when 

they are grown for seed. In addition, there is a SLN registration for use for commercial seed 

treatment for peas intended for export. There are currently no registered or proposed residential 

uses of cymoxanil. 

A report of the current registrations (OPPIN,0 4, September 2011) indicates that four Section 3 

registrations that have been granted. There have been a number of Section 18 Emergency 
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Exemptions and Section 24 Special Local Needs for cymoxanil, with the last being issued in 

2003.

Hazard Identification/Toxicology

The following hazard profile was obtained from and updates the 4th Hazard Identification 

Assessment Review Committee (HIARC) report for cymoxanil (TXR# 0051440, 02, Jan 2003). 

Several studies have been added to the hazard database since that report and the last risk 

assessment for cymoxanil (DP Num: 340367, D. Rate, et. al., 17 May 2007). All submitted 

studies are summarized in tables 2.1 and 2.2 in Attachment 2. 

Cymoxanil has low acute toxicity (categories III and IV) via oral, dermal, inhalation, and ocular 

routes of exposure. It is a mild skin irritant and not a skin sensitizer. Systemic toxicity, as 

evidenced by decreased body weights, body weight gains, and food consumption, was observed 

in subchronic, chronic, developmental, reproductive and neurotoxicity studies across species. 

The dog appears to be the most sensitive species for cymoxanil-induced toxicity with the thymus 

gland identified as a target organ in this species during subchronic and chronic exposures. While 

the thymic effect in dog is suggestive of potential immunotoxicity, no evidence of 

immunotoxicity was observed following subchronic exposure of rats or mice up to 108/117 

(M/F) or 218/552 (M/F) mg/kg/day, respectively. In addition, cymoxanil was not immunotoxic 

to either mice or rats when administered in the diet for 28 days in studies designed specifically to 

assess immunotoxicity. Also, the endpoints selected for risk assessment are protective of 

potential thymic effects. 

In a 21-day dermal toxicity study in rats, no systemic toxicity was observed up to the limit dose. 

In a subchronic neurotoxicity study in rats, systemic toxicity (decreased body weight and 

decreased food efficiency in males and females, and increased incidences of testicular and 

epididymal histological effects in males) was observed at 102/137 mg/kg/day (M/F); however, 

no neurotoxicity and/or neuropathology were observed up to 224/333 mg/kg/day (M/F; highest 

dose tested). In addition, no evidence of neurotoxicity was observed in the developmental 

toxicity studies in rats or rabbits, the 2-generation reproduction study in rats, the subchronic or 

chronic dog studies, or the 18-month mouse carcinogenicity study. However, in the combined 

chronic toxicity/carcinogenicity study in rats, clinical signs of hyperactivity and aggressiveness 

in males (≥30.3 mg/kg/day), as well as retinal atrophy in both sexes (≥30.3 mg/kg/day) were 

observed.

Increased susceptibility of rats and rabbits was observed following in utero exposure to 

cymoxanil. In acceptable developmental toxicity studies in both of these species, developmental 

effects were seen at doses below those that caused maternal toxicity. In the rat developmental 

toxicity studies, skeletal anomalies, delays in skeletal ossification, and/or increases in overall 

malformations were observed at lower doses than those at which maternal toxicity was observed. 

In a rabbit developmental study, increased skeletal malformations were observed at 8 mg/kg/day 

(LOAEL), which was also below the maternal NOAEL of 32 mg/kg/day. Cleft palate was also 

observed in fetuses at 32 mg/kg/day. In the first 2-generation reproduction toxicity study (1993), 

decreased pup viability (PND 0-4) was observed at maternally toxic doses. In a second 2-

generation reproduction toxicity study (2001), decreased body weight was observed during 

lactation in both F1 and F2 offspring at a dose that was lower than that at which parental toxicity 
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was observed. The increased susceptibility of offspring observed in this study was concordant 

with the results obtained in the developmental toxicity studies. 

In a developmental neurotoxicity study, offspring toxicity – adverse effects included decreased 

pup survival, decreased pup weight and body weight gain during early lactation, increases in 

morphometric measurements (anterior/posterior cerebrum for males, cerebellar height for 

females) at PND 79-83, and decreased retention in the water maze task for adult females – was 

observed at the same dose as maternal toxicity (slight decreases in body weight, body weight 

gain during gestation, and food consumption). The LOAEL for both maternal animals and 

offspring was 100 mg/kg/day. No residual uncertainties exist in the database for pre-/post-natal 

toxicity, and the endpoints selected (increased skeletal anomalies, delays in skeletal ossification, 

and/or increases in overall malformations) for risk assessment are considered protective of 

effects observed in offspring in developmental and reproduction toxicity studies.

The Agency has granted a waiver for a 28-day inhalation toxicity study. Based on a comparison 

of inhalation and oral points of departure for a series of 89 pesticides, and on the maximum 

inhalation exposure expected from occupational and residential uses of cymoxanil, HED

concludes that a new inhalation toxicity study on cymoxanil is unlikely to result in a point of 

departure indicating risks of concern.

Cymoxanil was not carcinogenic in rats and mice and is classified as ―not likely to be 

carcinogenic to humans‖. The available studies indicate that cymoxanil is not mutagenic in 

bacteria or cultured mammalian cells. There is, however, evidence of clastogenic activity and 

induction of unscheduled DNA synthesis in vitro. In contrast, cymoxanil was neither clastogenic 

nor aneugenic in vivo in mouse bone marrow cells and did not induce a genotoxic response in rat 

somatic or germinal cells. The negative results from the in vivo mouse bone marrow 

micronucleus assay support the lack of a carcinogenic effect in long-term rat and mouse feeding 

studies.

FQPA Considerations

Adequacy of the Toxicity Database

The toxicology database for cymoxanil is adequate for assessing pre- and/or post-natal 

susceptibility. The following studies are available:

· Subchronic neurotoxicity study in rat (acceptable)

· Developmental toxicity studies in rat and rabbits (acceptable)

· 2-Generation reproduction toxicity study in rat (acceptable)

· Developmental neurotoxicity study in rat (acceptable)

Pre-and/or Postnatal Toxicity

There is an indication of increased susceptibility of rats and rabbits to in utero exposure to 

cymoxanil. In several developmental toxicity studies in the rat and rabbit, developmental 

toxicity was observed at doses that were lower than those that caused maternal toxicity. In the 
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rat developmental toxicity studies, skeletal anomalies, delays in skeletal ossification, and/or 

increases in overall malformations were observed at lower doses than those at which maternal 

toxicity was observed. However, in the developmental neurotoxicity study in rat, offspring 

toxicity was observed at the same dose as maternal toxicity, indicating increased qualitative 

susceptibility in the offspring. Other studies indicated an increase in quantitative susceptibility in 

the offspring. In one rabbit developmental study, increased skeletal anomalies were observed at 

8 mg/kg/day (LOAEL), which was below the maternal NOAEL of 32 mg/kg/day. In a second 

rabbit developmental toxicity study, an increased incidence of visceral and skeletal anomalies

was observed at 25 mg/kg bw/day; a maternal LOAEL was not observed in this study. In the 2-

generation reproduction toxicity study, decreased pup body weight was observed at a lower dose 

than that which caused toxicity in adults.

Degree of Concern Analysis and Residual Uncertainties for Pre- and/or Postnatal

Susceptibility

In the developmental and postnatal studies for which there is increased susceptibility, the effects 

are well characterized and conservative NOAELs were established for developmental and 

offspring effects. In addition, the doses selected for risk assessment are based on the lowest 

NOAELs from the developmental and reproductive toxicity studies, where appropriate, and are 

protective of any potential pre- and post-natal effects. Therefore, there are low levels of concern 

and no residual uncertainties for pre- and post-natal toxicity.

FQPA Safety Factor for Infants and Children

Based on toxicological considerations by the Hazard Identification Assessment Review 

Committee, HIARC (HED Doc. Date 02, Jan 2003) and updated toxicology review by RAB1 

toxicologists, recently reviewed studies, conservative residue assumptions used in the dietary 

risk assessment (currently no residential exposures), and the completeness of the toxicology, 

residue chemistry and environmental fate databases (evaluated by the risk assessment team), the 

FQPA Safety Factor (SF) was reduced from 10X to 1X for acute exposure, incidental oral 

exposure (short- and intermediate-term), dermal exposure (short- and intermediate-term), and 

inhalation exposure (short- and intermediate-term) scenarios. The 10X FQPA SF is being 

retained, however, for chronic and long-term exposure scenarios in the form of a UFL, due to the 

use of a LOAEL to extrapolate a NOAEL for the point of departure.

Toxicity Endpoint Selection

Acute Reference Dose (aRfD) - Females age 13-49

The acceptable developmental toxicity study in the rabbit was used to select the endpoint for 

establishing the acute RfD (aRfD) for females 13-49 years old. The aRfD is based on increased 

skeletal anomalies of the cervical and thoracic vertebrae and ribs observed in fetuses at the 

developmental LOAEL of 8 mg/kg/day. Because a clear NOAEL of 4 mg/kg/day was observed 

in the study and there are no residual uncertainties for pre-/post-natal toxicity, the FQPA safety 

factor (SF) is 1X.
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Acute Reference Dose (aRfD) - General Population

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

acute risk to the general population, including infants and children. Therefore, quantification of 

acute risk to these populations is not required.

Chronic Reference Dose (cRfD) 

The chronic toxicity study in the dog (2003) was used to select the endpoint for establishing the 

chronic RfD (cRfD). The cRfD is based on decreased absolute and relative thymus weights and 

histopathology of the thymus (thymic atrophy/involution) in males and decreased thymus 

weights in females seen at the LOAEL of 1.3/0.8 mg/kg/day (M/F). This LOAEL was the lowest 

in the database. A NOAEL was not observed in this study; therefore, the FQPA SF (10X) was 

retained for the use of a LOAEL to extrapolate a NOAEL. Although the thymic effects in dogs 

suggest potential immunotoxicity, no immunotoxicity was observed in 2 specialized welldesigned immunotoxicity studies in the rodents, and the cRfD is protective of any potential 

thymic effects. 

Incidental Oral Exposure (Short- and Intermediate-Term) 

Short-Term: A short-term incidental oral endpoint was selected from the second two-generation 

reproduction toxicity study in rats (2001). The endpoint was decreased body weight observed 

during lactation in both F1 and F2 offspring at the offspring LOAEL of 31.6/42.8 mg/kg/day 

(M/F). Because a clear offspring NOAEL of 10.5 mg/kg/day was observed in the study and 

there are no residual uncertainties for pre-/post-natal toxicity, the FQPA SF is 1X.

Intermediate-Term: An intermediate-term incidental oral endpoint was selected from the first 

two-generation reproductive toxicity study in rats (1993). The endpoint was based on reduced 

pre-mating body weight, body weight gain, and food consumption observed in P-generation 

males and decreased gestation and lactation body weight in F1 dams at the parental LOAEL of 

32.1/40.6 mg/kg/day (M/F). Because a clear parental NOAEL of 6.5 mg/kg/day was observed in 

the study and there are no residual uncertainties for pre-/post-natal toxicity, the FQPA SF is 1X.

Dermal Absorption

An upper-bound estimate of dermal absorption was calculated by comparing the maternal 

LOAEL from the oral developmental toxicity study (rat) with the NOAEL from the dermal 

toxicity study (rat): [(75 mg/kg/day ÷ 1000 mg/kg/day) x 100%] = 7.5%. The HIARC report of 

Jan. 2, 2003 incorrectly calculated this to be 2.5%.

Dermal Exposure (Short-, Intermediate- and Long-Term) 

Short-and intermediate-term dermal endpoints were selected from an acceptable developmental 

toxicity study in rabbits. Increased skeletal anomalies of the cervical and thoracic vertebrae and 

ribs were reported at the LOAEL of 8 mg/kg/day. The adverse effects observed in this study 

were considered appropriate for this exposure scenario, since they are pertinent to a portion of 
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the exposed worker population, but were not measured in the 21-day dermal study in rats. 

Because a clear developmental NOAEL of 4 mg/kg/day was observed in the study and there are 

no residual uncertainties for pre-/post-natal toxicity, the FQPA SF is 1X. Since endpoints from 

an oral study were selected for this exposure scenario, a 7.5% dermal absorption factor was used 

for route-to-route extrapolation.

The chronic toxicity study in the dog (2003) was used to select the endpoint for the long-term 

dermal exposure scenario. Decreased absolute and relative thymus weights and histopathology 

of the thymus (thymic atrophy/involution) in males and decreased thymus weights in females

were observed at the LOAEL of 1.3/0.8 mg/kg/day (M/F). A NOAEL was not observed in this 

study; therefore, the FQPA SF (10X) was retained for the use of a LOAEL to extrapolate a 

NOAEL. Since an oral endpoint was selected for this exposure scenario, a 7.5% dermal 

absorption factor was used for route-to-route extrapolation.

Inhalation Exposure (Short-, Intermediate- and Long-Term) 

Short-and intermediate-term inhalation endpoints were selected from an acceptable 

developmental toxicity study in rabbits. Increased skeletal anomalies of the cervical and thoracic 

vertebrae and ribs were reported at the LOAEL of 8 mg/kg/day. Because a clear developmental 

NOAEL of 4 mg/kg/day was observed in the study and there are no residual uncertainties for 

pre-/post-natal toxicity in the database, the FQPA SF is 1X. The adverse effects observed in the 

oral developmental toxicity study in rabbits were considered appropriate for this exposure 

scenario in the absence of route-specific data. Oral and inhalation toxicity were assumed to be 

equivalent.

The chronic toxicity study in the dog (2003) was used to select the endpoint for the long-term 

inhalation exposure scenario. Decreased absolute and relative thymus weights and 

histopathology of the thymus (thymic atrophy/involution) in males and decreased thymus 

weights in females were observed at the LOAEL of 1.3/0.8 mg/kg/day (M/F). A NOAEL was 

not observed in this study; therefore, the FQPA SF (10X) was retained for the use of a LOAEL 

to extrapolate a NOAEL. Since an oral endpoint was selected in the absence of route-specific 

data, oral and inhalation toxicity were assumed to be equivalent.

The Agency has granted a waiver for a 28-day inhalation study. Based on a comparison of 

inhalation and oral points of departure for a series of 89 pesticides, and on the maximum 

inhalation exposure expected from occupational and residential uses of cymoxanil, HED

concludes that a new inhalation toxicity study on cymoxanil is unlikely to result in a point of 

departure indicating risks of concern.
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Level of Concern for Margin of Exposure

The target MOEs for occupational and non-dietary residential exposure risk assessments are as 

follows:

Summary of Levels of Concern for Risk Assessment.

Route

Duration

Short-Term

(1-30 days)

Intermediate-Term

(1-6 Months)

Long-Term

(> 6 Months)

Occupational (Worker) Exposure

Dermal 100 100 1000

Inhalation 100 100 1000

Residential (Non-Dietary) Exposure

Oral 100 100 N/A

Dermal 100 100 1000

Inhalation 100 100 1000

Recommendation for Aggregate Exposure Risk Assessments

An aggregated exposure risk assessment is not required since there are no residential uses for 

cymoxanil at this time. 

Classification of Carcinogenic Potential

On December 2, 1997, the HIARC, in accordance with the Draft Proposed Guidelines for 

Carcinogen Risk Assessment (April 10, 1996) classified cymoxanil as ―not likely to be 

carcinogenic to humans‖ based on the lack of evidence of carcinogenicity in mice and rats at 

doses that were judged to be adequate to assess the carcinogenic potential. 

For a summary of toxicological doses and endpoints for use in human risk assessments see table

3.1, Attachment 3.

Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of cymoxanil’s most recent registration decision, EPA reviewed 

these data and selected the most sensitive endpoints for relevant risk assessment scenarios from 

the existing hazard database. However, as required by FFDCA section 408(p), cymoxanil is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 
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EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a ―naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.‖ The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Cymoxanil is 

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

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for cymoxanil. 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/.

Conclusions Regarding Hazard Identification/Toxicology

Cymoxanil has a complete database, including studies relating to subchronic and developmental

neurotoxicity, developmental and reproductive toxicity, and immunotoxicity. The Agency has

granted a waiver for a 28-day inhalation toxicity study. Based on a comparison of inhalation and 

oral points of departure for a series of 89 pesticides, and on the maximum inhalation exposure 

expected from occupational and residential uses of cymoxanil, HED concludes that a new 

inhalation toxicity study on cymoxanil is unlikely to result in a point of departure indicating risks 

of concern.

Public Health and Pesticide Epidemiology Data

The OPP Incident Data System (IDS) records incidents resulting in higher severity outcomes in 

more detail, in a module called the Main IDS module. This system stores incident data for death, 

major and moderate incidents, and it includes more details about the location, date and nature of 

the incident. Main IDS incidents involving only one pesticide are considered to provide more 

certain information about the potential effects of exposure from the pesticide. The less severe 

human incidents (minor, unknown, or no effects outcomes) are reported by registrants as counts 

called aggregate summaries and are recorded in a separate module called Aggregate IDS. 

In Aggregate IDS, from 01, January 2006 to 05, May 2011 there is one incident involving 

cymoxanil. For the Main IDS, (for the period) there were no cases that involve the active 

ingredient cymoxanil (18, October 2011, DP 395156).
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Conclusions for Public Health and Pesticide Epidemiology Data

Based on the low frequency and low severity of incident cases, there does not appear to be a 

concern at this time that would warrant further investigation. The Agency will continue to 

monitor the incident information and if a concern is triggered, additional analysis will be 

included in the cymoxanil risk assessment.

Dietary Exposure

Tolerances are currently established for residues of the fungicide cymoxanil in/on various plant 

commodities, at levels ranging from 0.05 to 4.0 ppm (as listed in 40CFR §180.503[a]). Residue 

data from field trials conducted to support the existing registrations show that, generally, 

residues of cymoxanil are relatively low. The requirements for residue analytical methods are 

fulfilled for the purpose of registration review. Adequate methods are available for enforcement 

and data collection purposes for both plant and animal commodities. The registration review 

requirements for magnitude of the residue in/on plants and milk and livestock tissues as well as 

in eggs and poultry are fulfilled. Cymoxanil is currently registered for use on potato seed piece 

treatment, caneberry , hops, head lettuce, lychee, potato, cucurbit vegetable group, fruiting 

vegetable group, grape, bulb vegetables, subgroup 3-07A, bulb vegetables, subgroup 3-07B, leaf 

vegetables, subgroup 4A, leafy petioles, and cilantro leaves. 

The most recent dietary exposure assessment for cymoxanil (D. Rate, D349396, 01 July 2008) 

evaluated acute and chronic dietary (food + drinking water) exposure using the Dietary Exposure 

Evaluation Model (DEEM-FCID, Version 2.03), which uses food consumption data from the 

USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. 

The acute analysis dated 01, July 2008 assumed 100% crop treated for all commodities, and 

DEEM 7.81 default processing factors were used for all commodities except grapes. For grape, 

tolerance level residues and 100% CT were assumed and the processing factors for grape juice 

(1.4x) and raisins (1x) derived from the grape processing study were used (DP Num: 218035 and 

219844, G. Kramer, 25, Apr 1996). The EDWC for cymoxanil in surface water and groundwater 

were calculated using the screening model FIRST (FQPA Index Reservoir Screening Tool; 

v.1.1.0; dated 8/1/2001) and the regression model SCI-GROW (Screening Concentration in 

Ground Water, v.2.3; dated 7/29/2003), respectively. Estimated drinking water concentrations 

(EDWCs) were incorporated directly into the dietary assessment using the acute concentration of 

9.3 ppb for surface water generated by FIRST model. This assessment indicates that the acute 

dietary exposure estimate (95th percentile) is below the Agency’s level of concern [<100% acute 

Population Adjusted Dose (aPAD)] for females 13-49 years old, utilizing 89% of the aPAD. 

The chronic analysis was performed for the general U.S. population and various population 

subgroups using tolerance level residues or anticipated residues and percent crop treated from 

BEAD (02, Nov 2006, J Carter) for potatoes, head lettuce, peppers, tomatoes, watermelon, 

cucumber, pumpkin, and summer and winter squash. DEEM 7.81 default processing factors 

were used for all commodities except grapes. Processing factors for grape juice (1.4x) and 

raisins (1x) were derived from grape processing data (DP Num: 218035 and 219844, G. Kramer, 

25, Apr 1996). The EDWC for cymoxanil in surface water and groundwater were calculated 

using the screening model FIRST (FQPA Index Reservoir Screening Tool; v.1.1.0; dated 
Cymoxanil Registration Review Scoping Document DP395155

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8/1/2001) and the regression model SCI-GROW (Screening Concentration in Ground Water, 

v.2.3; dated 7/29/2003), respectively. EDWCs were incorporated directly into the dietary 

assessment using the chronic concentration for surface water generated by FIRST model at 0.05 

ppb. This assessment indicated that the chronic dietary exposure estimates are below the 

Agency’s level of concern [<100% chronic Population Adjusted Dose (cPAD)] for the general 

U.S. population (48% of the cPAD) and all population subgroups. The most highly exposed 

population subgroup was children 1-2 years old utilizing 74% of the cPAD.

Since cymoxanil is classified as ―not likely to be carcinogenic to humans,‖ a cancer risk 

assessment is not needed.

Summary of Dietary Exposure and Risk for Cymoxanil. The population subgroup with the maximum estimated exposure is bolded.

Population Subgroup Acute Dietary (95th Percentile) Chronic Dietary Cancer

Exposure mg/kg/day) % aPAD Exposure (mg/kg/day) % cPAD Exposure (mg/kg/day)

General U.S. Pop. NA 0.000383 48 Not Applicable

All Infants (< 1 year) 0.000404 51

Children (1-2 years) 0.000588 74

Children (3-5 years) 0.000521 65

Children (6-12 years) 0.000348 44

Youth (13-19 years) 0.000267 33

Adults (20-49 years) 0.000401 50

Adults (50+ years) 0.000357 45

Females (13-49 years) 0.035388 89.0 0.000333 42

Conclusions for Dietary Exposure

At this time, dietary risk estimates are below HED’s level of concern (i.e., less than 100% of the 

PAD). If the points of departure, safety factors, or water concentrations for cymoxanil are 

revised, a new dietary assessment will be required during registration review and may need

additional refinement.

Residential Exposure

Although there are currently no uses for cymoxanil that would result in direct residential 

exposure, residential bystander exposures might occur as a result of cymoxanil aerial 

applications and/or transport from treated areas. 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 cymoxanil. 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. Other potential sources of residential 

exposure include volatilization of pesticides and resuspension of dusts and/or particulates that 

contain pesticides. The Agency sought expert advice and input on issues related to volatilization 

of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory 

Panel (SAP) in December 2009, and received the SAP’s final report on 02, Mar 2010 

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

process of evaluating the SAP report as well as available post-application inhalation exposure 
Cymoxanil Registration Review Scoping Document DP395155

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data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate residential

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative residential postapplication inhalation exposure assessment for cymoxanil.

Aggregate Exposure and Risk Assessment

Currently, there are no uses for cymoxanil that would result in residential exposures; therefore, 

aggregate risk estimates are equivalent to the dietary (food and water) risk estimates. During 

registration review, updated aggregate assessments may be conducted to include changes in 

toxicological endpoints, dietary exposure estimates, and any exposure estimates resulting from 

drinking water and residential uses, if applicable.

Occupational Exposure

Occupational exposure to cymoxanil is anticipated for adults who apply cymoxanil-containing 

products and from post-application exposure, or re-entry into previously treated areas. A list of 

currently registered products containing cymoxanil as an active ingredient is included in tables 

4.1 and 4.2 in Attachment 4.

Occupational Handlers

Based upon the current use patterns, potential occupational exposure scenarios include: 

1. Potato seed treatment workers (loader/applicators, sewers, baggers).

2. Mixer/loader using open-pour loading of dust and dry flowable formulations for ground

chemigation, and aerial application operations.

3. Applicator using open-cab airblast sprayers.

4. Aerial applicators (enclosed cockpit).

5. Applicator using open-cab groundboom spray equipment.

6. Flaggers supporting aerial application operations.

Occupational handler risk estimates for the registered uses of cymoxanil were below HED’s 

level of concern for all activities (i.e. MOEs >100). However, for some scenarios, mitigation 

measures were required entailing the use of Personal Protective Equipment (PPE) control for 

mixing and loading of various formulations. The PPE requirement is included in all active labels 

(i.e, coveralls, gloves, respirators). Risk estimates for dermal postapplication exposure were not 

of concern. As for the seed treatment use (potato seed piece treatment), the maximum amount of 

seed treated per day might have to be revisited since HED is currently in the process of revising 

ExpoSAC Policy 15: Amount of Seed Treated or Planted per Day (02, Mar, 2004) in efforts to 

update the daily amount of seed treated in commercial seed treatment facilities. 

Furthermore, recommended unit exposures for occupational handler assessments have generally 

been derived only from PHED. However, recently HED, the Outdoor Residential Exposure Task 

Force (ORETF) and Agricultural Handler Exposure Task Force (AHETF) have produced 

Occupational Pesticide Handlers Exposure Database (OPHED) that the Agency is using in place 
Cymoxanil Registration Review Scoping Document DP395155

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of PHED (http://www.epa.gov/pesticides/science/handler-exposure-data.html). For the purpose 

of cymoxanil registration review the Agency anticipates that if the new Occupational Pesticide 

Handlers Exposure Database (OPHED) were incorporated into the assessment, MOEs are likely 

to be lower than those presented in the last risk assessment (risk estimates will be higher). All 

applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 

CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on 

these studies.

Occupational Post-Application

It is possible for agricultural workers to have post-application exposure to pesticide residues 

during the course of typical agricultural activities. HED in conjunction with the Agricultural Reentry Task Force (ARTF) has identified a number of post-application agricultural activities that 

may occur and which may result in post-application exposures to pesticide residues. HED has 

revised the ARTF database (SOP # 3.1) and is intending to use this data base in future 

assessments. For the purpose of cymoxanil registration review the Agency anticipates that if the 

revised Agricultural Re-entry Task Force (ARTF) data base were incorporated into the 

assessment, for some scenarios risk estimates are likely to be higher than those presented in the 

last risk assessment.

Cymoxanil is classified in Acute Toxicity Category III for acute dermal toxicity and IV for eye 

irritation. It is classified in Acute Toxicity Category IV for acute inhalation toxicity and for 

dermal irritation. It is not a dermal sensitizer. Based on these acute toxicity categories, the 

restricted entry interval (REI) of 12 hours is determined to be adequate for all crops considering 

Worker Protection Standard (WPS) requirements. 

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

assessment was not performed for cymoxanil. However, there are multiple potential sources of 

post-application inhalation exposure to individuals performing post-application activities in 

previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its Federal Insecticide, 

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

received the SAP’s final report on 02, Mar, 2010 

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

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for cymoxanil.

Conclusions for Occupational Exposure

An updated occupational handler and post-application assessment may be required for any 

cymoxanil use site if new data are identified which impact exposure estimates, new points of 
Cymoxanil Registration Review Scoping Document DP395155

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departure, revised uncertainty factors, or revisions to exposure policies and procedures are made.

An updated occupational post-application assessment may be required to account for recent 

revisions to the exposure policies and procedures of the Science Advisory Council for Exposure 

(ExpoSAC) Policy 3, released on June 2011.

Tolerance Assessment and International Harmonization

 

U.S. permanent tolerances (listed in 40 CFR 180.503), and Canadian MRLs are summarized 

in table 6.1 of the attachment 6. Codex has not established MRLs in/on any commodity, and 

Mexico generally adopts US tolerances and/or Codex MRLs for export purposes. The 

tolerance expression for cymoxanil will be reviewed during registration review to ensure that 

it appropriately covers the metabolites and degradates of cymoxanil and that it specifies the 

residues to be measured for each commodity.

Environmental Justice

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

future human health risk assessments for cymoxanil, in accordance with U.S. Executive Order 

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

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office of 

Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use 

of a pesticide when conducting human health risk assessments, including, but not limited to, 

people who obtain drinking water from sources near agricultural areas, the variability of diets 

within the U.S., and people who may be exposed when harvesting crops. Should these highest 

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

that the risk estimates are based on the best available information.

Cumulative Risk Assessment

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative risks of 

chemicals sharing a common mechanism of toxicity. The Agency determined that there was 

insufficient evidence to suggest cymoxanil shares a common mechanism of toxicity with other 

chemical substances. For the purposes of this scoping action, therefore, the Agency has assumed 

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

Human Studies

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

subjects were intentionally exposed to a pesticide to determine their dermal and inhalation 

exposure. Many such studies, involving exposure to many different pesticides, comprise 

generic pesticide exposure databases such as the Pesticide Handlers Exposure Database 

(PHED) and the Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the 

studies supporting these multi-pesticide generic exposure databases, and has found no clear and 
Cymoxanil Registration Review Scoping Document DP395155

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convincing evidence that the conduct of any of them was either fundamentally unethical or 

significantly deficient relative to the ethical standards prevailing at the time the research was 

conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of 

Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued 

reliance on these studies

Data Requirements

Under current guidelines, there are no data deficiencies for cymoxanil.

References

Barcode Date Title

D349397 05, Mar 2008 CYMOXANIL-Nondietary Human Exposure/Risk Assessment fot the Use of 

Cymoxanil Leafy Greens Crop Subgroup 4A, Bulb Vegetables Crop Group3, 

Cilantro Leaves, Caneberries (Crop Subgroup 13A), and Leaf Petiole 

Vegetables, Crop Subgroup 4B

D324318 07, Feb2006 CYMOXANIL - Exposure/Risk Assessment for the Proposed Use of 

Cymoxanil on Grapes and Hops, February 7, 2006

D286768 14, June 001 CYMOXANIL - Exposure/Risk Assessment fromthe Proposed New Uses of 

Cymoxanil on Cucurbit Vegetables (Cucumber, Melon, Squash), Fruiting 

Vegetable (Tomato, Bell/Non Bell Pepper) and Head Lettuce

D347653 09, Jul 2008 CYMOXANIL; Human Health Risk Assessment for Proposed Uses on Bulb 

Vegetables (Crop Group 3-07), Leafy Greens (Subgroup 4A), and Leaf Petioles 

(Subgroup 4B)

D349396 01, Jul 2008 Cymoxanil Acute and Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessment[s] for the Section (3) Registration Action July, 

1st 2008.

NA 05, May 2011 Agricultural Transfer Coefficients (Policy 3.2), Science Advisory Council for 

Exposure (ExpoSAC)

D395156 18,Oct 2011 CYMOXANIL- Review of Human Incidents

Attachments:

Attachment 1 Chemical Identity Table

Attachment 2 Cymoxanil Toxicology Study Status

Attachment 3 Cymoxanil Endpoint Selection Table

Attachment 4 Cymoxanil Products and Use Sites

Attachment 4 Cymoxanil Toxicology Study Status

Attachment 5 Cymoxanil Toxicology Study Status

Attachment 6 International Residue Limit Status
Cymoxanil Registration Review Scoping Document DP395155

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Attachment 1 Chemical Identity Table

Chemical Identity Table

Compound

Common name Cymoxanil

Company experimental name DPX-T3217

IUPAC name 1-[(EZ)-2-cyano-2-methoxyiminoacetyl]-3-ethylurea

CAS name 2-cyano-N-[(ethylamino)carbonyl]-2-(methoxyimino) acetamide

CAS registry number 57966-95-7

N

NC

H3CO

N

H

N

H

CH3

O O
Cymoxanil Registration Review Scoping Document DP395155

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Attachment 2 Cymoxanil Toxicology Study Status

Table 2.1 Acute Toxicity of Cymoxanil Technical Grade Active Ingredient (TGAI).

Guidelin

e No.

Study Type MRID NO. Results Toxicity 

Category

81-1 Acute Oral 43616512 LD50 = 960 mg/kg III

81-2 Acute Dermal 43616513 LD50 > 2000 mg/kg III

81-3 Acute Inhalation 42706303 LC50 = >5.06 mg/L IV

81-4 Primary Eye Irritation 43616514 Non- irritant IV

81-5 Primary Skin Irritation 43616515 Mild or slight irritant IV

81-6 Dermal sensitization 43640501 Non sensitizer N/A

NA = Not applicable

Table 2.2 Toxicity Profile of Cymoxanil 

Guideline No./ 

Study Type

MRID No. (year)/ Classification/Doses Results

870.3100

90-Day oral 

Toxicity rodents 

(rat) 

43616516 (1993)

Acceptable/Guideline

0, 100, 750, 1500, or 3000 ppm, 

M: 0, 6.54, 47.6, 102, or 224 mg/kg/day

F: 0, 8, 59.9, 137, or 333 mg/kg/day

Systemic Toxicity NOAEL = 47.6 mg/kg/day in males 

and 59.9 mg/kg/day in females

Systemic Toxicity LOAEL= 102 mg/kg/day in males and 

137 mg/kg/day in females, based on decreases in body 

weights, body weight gains and food efficiency in the 

females, and body weight decreases and testicular and 

epididyal changes in males.

870.3100

90-Day oral 

Toxicity rodents 

(mouse) 

43616517 (1992)

Acceptable/Guideline

0, 50, 500, 1750, 3500, or 7000 ppm

M: 0, 8.25, 82.4, 294, 566, or 1306 mg/kg/day

F: 0, 11.3, 121, 433, 846, or 1130 mg/kg/day 

Systemic Toxicity NOAEL = 8.25 mg/kg/day in males 

and 121 mg/kg/day in females

Systemic Toxicity LOAEL= 82.4 mg/kg/day in males 

and 433 mg/kg/day in females, based on statistically 

significant dose-related decreased body weights in males 

and increased absolute liver weights in females. 

870.3150

90-Day oral 

toxicity in nonrodents (dog)

43640502 (1992)

Acceptable/Guideline

0, 100, 200 ppm (0, 3, 5 mg/kg/day) for 13 weeks, or 

250 ppm (5 mg/kg/day) for 2 weeks followed by 500 

ppm (11 mg/kg/day) for 11 weeks.

Systemic Toxicity NOAEL not established

Systemic Toxicity LOAEL= 3 mg/kg/day, based on 

decreased body weights (13%) and food consumption in 

females.

870.3200

21/28-Day dermal 

toxicity (rat)

44180705 (1996)

Acceptable/Guideline

0, 50, 500 or 1000 mg/kg/day

Systemic and Dermal Toxicity NOAEL = 1000 

mg/kg/day (HDT)

Systemic and Dermal Toxicity LOAEL was not 

established.

870.3700a

Prenatal 

developmental (rat)

43616524 (1993)

Acceptable/Guideline

0, 10, 25, 75, or 150 mg/kg/day

Maternal NOAEL = 25 mg/kg/day

Maternal LOAEL= 75 mg/kg/day, based upon reduced 

body weight, body weight change and food consumption

Developmental NOAEL = 10 mg/kg/day

Developmental LOAEL = 25 mg/kg/day, based upon 

significant increase in overall malformations, and 

generalized dose-related delay in skeletal ossification; at 75 

and 150 mg/kg/day significant decrease in fetal body 

weights; at 150 mg/kg/day increased early resorptions 

resulting in reduced litter size.

870.3700b

Prenatal 

developmental 

(rabbit)

43640503 & 43616523 (1982)

Acceptable/Guideline

0, 1, 4, 8, or 32 mg/kg/day

Maternal NOAEL 32 mg/kg/day

Maternal LOAEL was not established

Developmental NOAEL = 4 mg/kg/day

Developmental LOAEL = 8 mg/kg/day, based upon an 

increase in skeletal anomalies of the cervical and thoracic 

vertebrae and ribs; at 32 mg/kg/day, cleft palate was also 

observed.

870.3700b 43616522 (1981) Maternal NOAEL = 16 mg/kg/day
Cymoxanil Registration Review Scoping Document DP395155

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Table 2.2 Toxicity Profile of Cymoxanil 

Guideline No./ 

Study Type

MRID No. (year)/ Classification/Doses Results

Prenatal 

developmental 

(rabbit)

Unacceptable/Guideline, however, in conjunction 

with MRIDs 43616521, 43616523 & 43640503 

provides valuable information in selecting the 

maternal and developmental end-points.

0, 8, 16, or 32 mg/kg/day

Maternal LOAEL = 32 mg/kg/day, based upon increased 

incidence of clinical signs and body weight loss during first 

4 days of treatment.

Developmental NOAEL 8 mg/kg/day (not established)

Developmental LOAEL = 8 mg/kg/day, based upon an 

increase in skeletal anomalies of the cervical and thoracic 

vertebrae and ribs.

870.3700b

Prenatal 

developmental 

(rabbit)

43616521 (1980)

Unacceptable/Guideline, however, in conjunction 

with MRIDs 43616522, 43616523 & 43640503 

provides valuable information in selecting the 

maternal and developmental end-points.

0, 4, 8, or 16 mg/kg/day

Maternal NOAEL = 16 mg/kg/day (HDT)

Maternal LOAEL = not determined.

Developmental NOAEL≥16 mg/kg/day (HDT))

Developmental LOAEL = not determined.

870.3800

2-Generation 

Reproduction and 

Fertility Effects 

(rat; dietary)

43616520 (1993)

Acceptable/Non-guideline

0, 100, 500, or 1500 ppm [equal to 0/0, 6.5/7.9,

32.1/40.6, or 97.9/130 mg/kg bw/day (M/F)]

Parental NOAEL = 6.5/7.9 (M/F) mg/kg/day 

Parental LOAEL = 32.1/40.6 (M/F) mg/kg/day based on 

reduced premating body weight, body weight gain, and food 

consumption for P males; decreased gestation and lactation 

body weight for F1 females.

Offspring NOAEL = 6.5/7.9 (M/F) mg/kg/day 

Offspring LOAEL = 32.1/40.6 (M/F) mg/kg/day based on 

decreased F1 pup viability on postnatal days 0-4 and on 

significant reduction in F2b pup weight. 

870.3800

2-Generation 

Reproduction and 

Fertility Effects 

(rat; dietary)

46749810 (2001)

Acceptable/Non-guideline

0, 150, 450, or 350 ppm [equal to 0/0, 10.5/14.9, 

31.6/42.8, or 94/116.3 mg/kg bw/day (M/F)]

Parental NOAEL = 31.6/42.8 (M/F) mg/kg/day 

Parental LOAEL = 94/116.3 (M/F) mg/kg/day based on 

decreases in body weight, body weight gain, and food 

consumption in F0 and F1 generations

Reproductive NOAEL = 94/42.8 (M/F) mg/kg/day 

Reproductive LOAEL = 116.3 (F) mg/kg/day based on 

decreased mean number of corpora lutea and mean number 

of implantations and increased post-implantation loss in F1 

females (LOAEL not observed in males)

Offspring NOAEL = 10.5/14.9 (M/F) mg/kg/day 

Offspring LOAEL = 31.6/42.8 (M/F) mg/kg/day based on 

decreased body weight during lactation in both F1 and F2 

generations

870.4100

Chronic Toxicity 

(dog; dietary)

46749811 (2003) 

Acceptable/Guideline

0/0, 50/25, 100/50, or 250/100 ppm (equal to 0/0, 

1.3/0.8, 2.8/1.4, or 5.6/2.9 mg/kg bw/day) (M/F)

NOAEL not observed. 

LOAEL = 1.3/0.8 (M/F) mg/kg/day based on decreased 

absolute and relative thymus weights and histopathology of 

the thymus (thymic atrophy/involution) (M) and decreased 

thymus weights (F)

870.4200

Carcinogenicity 

rodents (mouse)

43616519 (1994)

Acceptable/Guideline

0, 30, 300, 1500, or 3000 ppm

M: 0, 4.19, 42.0, 216, or 446 mg/kg/day

F: 0, 5.83, 58.1, 298, or 582 mg/kg/day

Systemic toxicity NOAEL = 4.19 mg/kg/day for males 

and 5.83 mg/kg/day for females

Systemic toxicity LOAEL = 42 mg/kg/day for males and 

58.1 mg/kg/day for females (HDT), based upon increased 

frequency of sperm cyst/cystic dilation, tubular dilation and 

lymphoid aggregates in males and hyperplastic gastropathy 

in females. 

No evidence of carcinogenicity.

870.4300

Combined chronic 

toxicity/carcinogeni

city rodents (rat) 

43616525 (1994)

Acceptable/Guideline

0, 50, 100, 700, or 2000 ppm

M: 0, 1.98, 4.08, 30.3, or 90.1 mg/kg/day

F: 0, 2.71, 5.36, 38.4, or 126 mg/kg/day

Systemic toxicity NOAEL = 4.08 mg/kg/day for males 

and 5.36 mg/kg/day for females

Systemic toxicity LOAEL = 30.3 mg/kg/day for males 

and 38.4 mg/kg/day for females, based upon decreased 

body weight, body weight gain, and food efficiency, 

increased incidence of elongate spermatid degeneration and 

increased aggressiveness and/or hyperactivity in males and 

increased incidence of non-neoplastic lesions of the lungs, 

liver, sciatic nerve and retinal atrophy in females.

No evidence of carcinogenicity.
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Table 2.2 Toxicity Profile of Cymoxanil 

Guideline No./ 

Study Type

MRID No. (year)/ Classification/Doses Results

870.5100

Bacterial gene 

mutation assay

43616526 (1992)

Acceptable/Guideline

Salmonella typhimurium strains TA1535, TA97, 

TA98 and TA100 were exposed to Cymoxanil

Technical (96.5-97.8%) at concentrations of 10-2500 

μg/plate with or without S9 activation (both trials). 

Cytotoxicity in all strains was seen at 750 μg/plate -S9 and 

1000 μg/plate +S9. The positive controls induced the 

expected mutagenic responses in the appropriate tester 

strain. There was, however, no evidence that the test 

material induced a mutagenic effect under any test 

condition.

870.5300

In vitro mammalian 

cell gene mutation 

assay (CHO)

43616527 (1993)

Acceptable/Guideline

Chinese hamster ovary (CHO) cells were exposed to 

Cymoxanil Technical (96.5-97.8%) in dose ranges of 

5-750 μg/mL -S9 (both trials) and S9-activated doses 

of 10-1500 μg/mL (Trials 1 and 2) or 250-1500 

μg/mL (Trial 3).

Severe cytotoxicity was seen at 750 μg/mL -S9 and 1000 

μg/mL +S9. The positive controls induced the expected 

mutagenic responses. There was, however, no evidence 

that the test material was mutagenic at the HGPRT locus 

at any dose under any assay condition.

870.5375

In vitro mammalian 

chromosomal 

aberration test 

42706302 (1993)

Acceptable/Guideline

Human lymphocytes were exposed to Cymoxanil 

Technical (96.5-97.8%) in dose ranges of 100-1500 

μg/mL ± S9 activation.

Significant and dose-related clastogenic effects were seen at 

1250 and 1500 μg/mL -S9 activation and at 850, 1250 and 

1500 μg/mL +S9 activation. Cymoxanil is clastogenic 

both in the presence and absence of S9 activation. 

870.5395

Mammalian 

erythrocyte 

micronucleus test 

43616528 (1993)

Acceptable/Guideline

Groups of six male and six female CR1:CD®-

1(ICR)BR mice received single oral gavage 

administrations of 450 or 350 mg/kg Cymoxanil 

Technical (96.5-97.8%), respectively; lower doses 

(125 or 225 mg/kg) were administered to groups of 

five male and five female mice. High-dose group 

were sacrificed at 24, 48 and 72 hours postadministration; mice in the low- and mid-dose groups 

were sacrificed 24 hours post-dosing.

Death occurred in 6/18 high-dose (350 mg/kg) females. 

Other signs of compound toxicity noted in the high-dose 

males and females included abnormal gait, lethargy and 

tremors. Suggestive evidence of bone marrow cytotoxicity 

was seen in the high-dose females at the 48-hour cell harvest 

and in the high-dose males at the 24-hour harvest. The 

positive control induced the expected high yield of MPEs in 

males and females. There was, however, no evidence that 

the test material induced a clastogenic or aneugenic 

effect in either sex at any dose or sacrifice time. 

870.5550

Unscheduled DNA 

synthesis in 

mammalian cells in 

culture

42706301 (1993)

Acceptable/Guideline

Primary rat hepatocytes were exposed to Cymoxanil 

Technical (96.5-97.8%) at dose levels of 5 to 500 

μg/mL

Cytotoxicity was observed at levels 500 μg/mL. 

Cymoxanil tested positive over 5 to 500 μg/mL range.

870.5550

Unscheduled DNA 

synthesis in 

mammalian cells in 

culture

43616529(1994)

Acceptable/Guideline

Groups of five male CR1:CD®BR rats were 

administered single oral gavage doses of 500 or 1000 

mg/kg Cymoxanil Technical (96.5-97.8%) in 0.5% 

methyl cellulose. At 2 and 16 hours post-treatment 

hepatocytes and spermatocytes were scored for UDS. 

Clinical signs of toxicity noted in both treatment groups 

included death (3 of 10 rats at 1000 mg/kg; 1 of 10 rats at 

500 mg/kg), lethargy, prostrate posture, labored or rapid 

respiration, tremors, diarrhea and abnormal gait (both study 

groups). Cytotoxicity was not observed in either target 

tissue. Positive controls responded appropriately. There 

was, however, no evidence that the test material induced 

a genotoxic response in either tissue at any dose or 

sacrifice time. 

870.6200

Neurotoxicity 

screening/Subchron

ic neurotoxicity

43616516 (1993)

Acceptable/Guideline

0, 100, 750, 1500, or 3000 ppm, 

M: 0, 6.54, 47.6, 102, or 224 mg/kg/day

F: 0, 8, 59.9, 137, or 333 mg/kg/day

No effects on the functional observation battery, or motor 

activity were observed. No treatment-related gross or 

microscopic findings in the nervous system or skeletal 

muscles of the male and female rats were observed.

Subchronic systemic toxicity consisted of decreases in body 

weight/body weight gains and food efficiency in females, 

and body weight decreases and testicular and epididymal 

changes in males. 

The Subchronic systemic LOAEL = 102/137 mg/kg/day 

(M/F). The systemic NOAEL = 47.6/59.9 mg/kg/day (M/F).

The Neurotoxicity NOAEL 3000 ppm (224 mg/kg/day 

in males and 333 mg/kg/day in females; HDT). 

Neurotoxicity LOAEL was not established.
Cymoxanil Registration Review Scoping Document DP395155

Page 22 of 27

Table 2.2 Toxicity Profile of Cymoxanil 

Guideline No./ 

Study Type

MRID No. (year)/ Classification/Doses Results

870.6300

Developmental 

neurotoxicity (rat)

45377901 (2001)

Acceptable/Non-guideline

0, 5, 50 or 100 mg/kg/day

Maternal Toxicity NOAEL = 50 mg/kg/day

Maternal Toxicity LOAEL = 100 mg/kg/day, based on 

slight decrease body weight, body weight gains (17%) and 

food consumption.

Offspring NOAEL = 50 mg/kg/day

Offspring LOAEL = 100 mg/kg/day, based on decreased 

pup survival, decreased pup weight and body weight gain 

during early lactation (less than 6%), increases in 

morphometric measurements (anterior/posterior cerebrum 

for males, cerebellar height for females) at PND 79-83, and 

decreased retention in the water maze task for adult females 

(latency 158% of control levels) seen at the LOAEL of 100 

mg/kg/day.

870.7485

Metabolism and 

pharmacokinetics 

(rat)

43616530 & 43616531 (1994)

Acceptable/Guideline

[2-

14C]cymoxanil (98% a.i.) was administered to 

male and female Crl:CD/BR rats (3-5 

animals/sex/dose) by gavage as a single dose at levels 

of 2.5 or 120 mg/kg, or as a single dose (2.5 mg/kg) 

following a 14-day pretreatment with unlabeled 

cymoxanil (2.5 mg/kg/day).

Cymoxanil was readily absorbed and 86 to 94% of the 

administered dose was excreted in 96 hours. The majority 

of the administered dose was recovered in the urine (64 -

57%) with smaller amounts excreted in the feces (16 - 24%) 

and carcass (< 1%). There were no sex-related differences 

in the absorption, distribution and metabolism of cymoxanil. 

In urine about 37 - 55% of the dose was free and/or 

conjugated [14C]glycine and 2 cyano-2-methoxyiminoacetic 

acid (IN-W3595; about 7 to 33% of the dose). Intact 

cymoxanil was not isolated in urine. In feces intact 

[

14C]cymoxanil (< 1%) and IN W3595 was detected, but the 

majority of radioactivity was [14C]glycine (about 9 - 13%). 

Based on the data, the metabolic pathway involves 

hydrolysis of cymoxanil to IN W3595, which is then 

degraded to glycine, which in turn is incorporated into 

natural constituents or further metabolized.

870.7800

Immunotoxicity 

(rat; dietary)

44944601 (1999)

Acceptable/Guideline

0, 200, 400, 800, or 1600 ppm [equivalent to 0/0, 

14/16, 27/31, 54/59, or 108/117 mg/kg bw/day 

(M/F)]

NOAEL = 108/117 (M/F) mg/kg/day 

LOAEL not observed.

870.7800

Immunotoxicity 

(mouse; dietary)

44944602 (1999)

Acceptable/Guideline

0/0, 30/30, 300/300, 600/1200, or 1200/2400 ppm 

(equivalent to 0/0, 5/7, 56/71, 108/269, or 218/552 

mg/kg bw/day) (M/F)

NOAEL = 218/552 (M/F) mg/kg/day 

LOAEL not observed.
Cymoxanil Registration Review Scoping Document DP395155

Page 23 of 27

Attachment 3 Cymoxanil Endpoint Selection Table

Table3.1 Summary of Toxicological Doses and Endpoints for Cymoxanil for Use in Human Health Risk Assessments

Exposure Scenario Point of Departure Uncertainty/ FQPA 

Safety Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary (General 

population, including 

infants and children)

N/A N/A N/A 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.

Acute Dietary (Females 

13-49 years of age)

NOAEL = 4

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

aRfD = aPAD = 

0.04 mg/kg/day

Developmental toxicity (rabbit)

Offspring LOAEL = 8 mg/kg/day based 

on increased skeletal malformations of 

the cervical and thoracic vertebrae and 

ribs

Chronic Dietary (All 

populations)

NOAEL < 0.8

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF1= 10X

(includes UFL = 10X)

cRfD = cPAD = 

0.0008 mg/kg/day

Chronic toxicity (dog; 2003) LOAEL = 

1.3/0.8 mg/kg/day (M/F), based on 

decreased absolute and relative thymus 

weights and histopathology of the 

thymus (thymic atrophy/involution) in 

males and decreased thymus weights in 

females

Incidental Oral

Short-Term (1-30 days)

NOAEL = 10.5

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential LOC 

for MOE = 100

2-generation reproduction (rat; 2001) 

Offspring LOAEL = 31.6/42.8 

mg/kg/day (M/F) based on decreased 

body weight during lactation in both F1

and F2 generations

Incidental Oral

Intermediate-Term (1-6 

months)

NOAEL = 6.5

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential LOC 

for MOE = 100

2-generation reproduction (rat; 1993) 

Parental LOAEL = 32.1 mg/kg/day 

(M/F) based on reduced premating body 

weight, body weight gain, and food 

consumption for P males; and decreased 

gestation and lactation body weights for 

F1 females

Dermal

Short-Term (1-30 days)

NOAEL = 4

mg/kg/day

(Dermal absorption 

= 7.5%)2

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential/ 

Occupational LOC 

for MOE = 100

Developmental toxicity (rabbit)

Offspring LOAEL = 8 mg/kg/day based 

on increased skeletal malformations of 

the cervical and thoracic vertebrae and 

ribs

Dermal

Intermediate-Term (1-6 

months)

NOAEL = 4

mg/kg/day

(Dermal absorption 

= 7.5%)2

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential/ 

Occupational LOC 

for MOE = 100

Developmental toxicity (rabbit)

Offspring LOAEL = 8 mg/kg/day based 

on increased skeletal malformations of 

the cervical and thoracic vertebrae and 

ribs

Dermal

Long-Term (> 6 months)

NOAEL < 0.8

mg/kg/day

(Dermal absorption 

= 7.5%)2

UFA = 10X

UFH = 10X

FQPA SF1= 10X

(includes UFL = 10X)

Residential/ 

Occupational LOC 

for MOE = 1000

Chronic toxicity (dog; 2003) LOAEL = 

1.3/0.8 mg/kg/day (M/F), based on 

decreased absolute and relative thymus 

weights and histopathology of the 

thymus (thymic atrophy/involution) in 

males and decreased thymus weights in 

females

Inhalation

Short-Term (1-30 days)

NOAEL = 4

mg/kg/day

(100% inhalation 

absorption assumed)

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential/ 

Occupational LOC 

for MOE = 100

Developmental toxicity (rabbit)

Offspring LOAEL = 8 mg/kg/day based 

on increased skeletal malformations of 

the cervical and thoracic vertebrae and 

ribs

Inhalation

Intermediate-Term (1-6 

months)

NOAEL = 4

mg/kg/day

(100% inhalation 

absorption assumed)

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential/ 

Occupational LOC 

for MOE = 100

Developmental toxicity (rabbit)

Offspring LOAEL = 8 mg/kg/day based 

on increased skeletal malformations of 

the cervical and thoracic vertebrae and 

ribs

Inhalation NOAEL < 0.8 UFA = 10X Residential/ Chronic toxicity (dog; 2003) LOAEL = 
Cymoxanil Registration Review Scoping Document DP395155

Page 24 of 27

Long-Term (>6 months) mg/kg/day

(100% inhalation 

absorption assumed)

UFH = 10X

FQPA SF1= 10X

(includes UFL = 10X)

Occupational LOC 

for MOE = 1000

1.3/0.8 mg/kg/day (M/F), based on 

decreased absolute and relative thymus 

weights and histopathology of the 

thymus (thymic atrophy/involution) in 

males and decreased thymus weights in 

females

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

of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. 

LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = 

use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key date (i.e., lack of a critical study). FQPA SF = 

FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. N/A = not applicable.

The 10X FQPA SF has been retained in the form of a UFL to account for the use of a LOAEL to extrapolate a NOAEL

2An upper-bound estimate calculated as follows by comparing the maternal LOAEL from the oral developmental toxicity study (rat) with the

NOAEL from the dermal toxicity study (rat): [(75 mg/kg/day ÷ 1000 mg/kg/day) x 100%] = 7.5%; the last HIARC report of Jan. 2, 2003 

incorrectly calculated this to be 2.5%
Cymoxanil Registration Review Scoping Document DP395155

Page 25 of 27

Attachment 4. Cymoxanil Products and Use Sites

The currently registered products containing cymoxanil as an active ingredient and the use 

directions of end-products containing cymoxanil are listed in the tables below. 

Table 4.1 List of Products Containing Cymoxanil.

EPA Reg. No. Active Ingredient 

(%) Product's Name Use Site Formulation Type

264-973 1 Evolve TM Potato Seed Piece Treatment Dust

352-591 98.7 DupontTM Cymoxamil 

Technical

Manufacture of fungicides_ Dry Flowable

352-592 60 DupontTM Curzate®

Potatoes, Potato Seed Piece Treatment, 

Curcurbits, Lettuce, Spinach, Hops and 

Tomatoes 

Dry Flowable

352-604 25

DupontTM Tanos® 1 Bulb Vegetables (subgroup 3-07A)

Green onion (subgroup 3-07B)

Caneberries (subgroup13-07 A)

Curcurbit Vegetables

Grapes (East of Rocky Mountains)

Hops

Leafy vegetables (except Brassica) 

Leafy greens ((subgroup 4A)

Leaf petioles (subgroup 4B)

Peppers

Potatoes

Tomatoes 

Dry Flowable

1 Not intended for use in home plantings

 Table4.2 Use Directions of End-use Product Formulations Containing Cymoxanil.

EPA Reg. No. Application Application Rate Appl. Equipment Timing of Applications REI

264-973

Potato seed piece treatment 0.75 lb ai /100 lb 

of seed

Seed Treater Plant seed –pieces as soon 

as possible after cutting 

and treating.

48 

hours

352-592

Applications may be repeated at 14 

day intervals. There is a 7 day 

preharvest interval (PHI). 

0.15 lb ai/A Ground, Air and 

Chemigation 

Seed Treatment (except 

CA)

Crop rotation restrictions 12 

hours

352-604

Make preventive applications on a 

5- to 7-day schedule. Tanos® 

Fungicide must be tank-mixed with 

a contact fungicide which has a 

different mode of action. Do not 

alternate or tank mix with other 

Group 11 fungicides or with 

fungicides to which resistance has 

developed. In a cropping season, no 

more than 50% of the total 

applications should contain Tanos® 

Fungicide or other Group 11 

fungicides. PHI varies per crop (0 

days for caneberries up to 30 days 

for grapes. 

0.16 lb ai/A

0.16 lb ai /100 lb 

of seed 

Foliar spray

Ground (20 GPA), Aerial 

(min 5 GPA), or 

Chemigation

Crop rotation restrictions 

for some crops

12 

hours
Cymoxanil Registration Review Scoping Document DP395155

Page 26 of 27

Attachment 5 Cymoxanil Toxicology Study Status

Table 5.1. Toxicology Data Requirements

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity......................................................

870.1200 Acute Dermal Toxicity.................................................

870.1300 Acute Inhalation Toxicity.............................................

870.2400 Primary Eye Irritation...................................................

870.2500 Primary Dermal Irritation .............................................

870.2600 Dermal Sensitization ....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)..............................................

870.3150 Oral Subchronic (nonrodent)........................................

870.3200 21/28-Day Dermal........................................................

870.3250 90-Day Dermal.............................................................

870.3465 90-Day Inhalation.........................................................

yes

yes

yes

no

yes

yes

yes

yes

no

yes

870.3700a Developmental Toxicity (rodent) .................................

870.3700b Developmental Toxicity (nonrodent) ...........................

870.3800 Reproduction ................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent).............................................

870.4100b Chronic Toxicity (nonrodent).......................................

870.4200a Oncogenicity (rat).........................................................

870.4200b Oncogenicity (mouse) ..................................................

870.4300 Chronic/Oncogenicity ..................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial....................

870.5300 Mutagenicity—Gene Mutation - mammalian...............

870.5375 Mutagenicity—Structural Chromosomal Aberrations..

870.5395 Mutagenicity—Other Genotoxic Effects......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen)....................................

870.6100b 90-Day Neurotoxicity (hen) .........................................

870.6200a Acute Neurotox. Screening Battery (rat)......................

870.6200b 90 Day Neurotox. Screening Battery (rat)....................

870.6300 Develop. Neuro ............................................................

no

no

yes

yes

yes

no

no

yes

yes

yes

870.7485 General Metabolism .....................................................

870.7600 Dermal Penetration.......................................................

870.7800 Immunotoxicity in Rats.....................................

yes

no

yes

yes

no

yes
Cymoxanil Registration Review Scoping Document DP395155

Page 27 of 27

Attachement 6: International Residue Limits

Table 6.1 Summary of US and International Tolerances and Maximum Residue Limits for Cymoxanil

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.503: 

Plant: Cymoxanil- [2-cyano-N-

[(ethylamino)carbonyl]-2-

(methoxyimino) acetamide]

Livestock: N/A

2-cyano-N-[(ethylamino)carbonyl]-2-

(methoxyimino)

acetamide

None

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

US Canada Mexico2 Codex3

Caneberry, subgroup 13A-07 4.0 4.0 Blackberries, 

loganberries, 

raspberries, wild 

raspberries

Cilantro, leaves 19

Hop, dried cones 7.0

Leafy greens, subgroup 4A 19

Leaf petioles, subgroup 4B 6.0

Lychee11.0

Onion, bulb, subgroup 3-07A 0.05

Onion, green, subgroup 3-07B 1.1

Potato 0.05 0.05

Vegetable, cucurbit, group 9 0.05

Vegetable, fruiting, group 8 0.2

MRLs with No US Equivalent

Fat of cattle 0.05

Fat of goats 0.05

Fat of hogs 0.05

Fat of sheep 0.05

Meat by products of cattle 0.05

Grape 0.1

Meat by products of goats 0.05

Meat by products of hogs 0.05

Meat by products of sheep 0.05

Meat of cattle 0.05

Meat of goats 0.05

Meat of hogs 0.05

Meat of sheep 0.05

Milk 0.05

Completed: M. Negussie; 05/09/2011

1There is no U.S. registration for lychee.

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

3*

= 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 proposed have not been finalized by the CCPR and the CAC.