UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: May 21,2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: PYRACLOSTROBIN. Human Health Assessment Seeping Document in Support of 

Registration Review. 

PC Code: 0991 00 

Decision No.: 487331 

Petition No.: NA 

DP Barcode: D417742 

Registration No.: NA 

Regulatory Action: Registration Review 

Risk Assessment Type: NA Case No.: 7034 

TXRNo.:NA CAS No.: 175013-18-0 

MRIDNo.: NA 40 CFR: §180.582 

FROM: Barry O'Keefe, Senior Biologist /3~ 0 fJ0 ;h 

Steve 

Cassi 

Funk, 

Walls, 

Senior 

Senior 

Chemist 

Biologist 

,.( 

/::P"~ ~~ i ~ 

_ 

Risk 

Vincent 

Assessment 

Chen, Toxicologist 

Branch III (RA

~ 

B III) 

Health Effects Division (7509P) 

Office of Pesticide Programs 

THROUGH: Christine Olinger, Branch Chief /J / ( _// 

Risk 

Health 

Assessment 

Effects Division 

Branch 

(7509P) 

III (RAB~f ~ 

Office of Pesticide Programs 

TO: Matthew Manupella, Chemical Review Manager 

Kevin Costello, Branch Chief 

Risk Management and Implementation Branch II (RMIB2) 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Office of Pesticide Programs 

Executive Summary 

The HED Registration Review Team has evaluated the human health assessments and database 

for the fungicide pyraclostrobin to determine whether sufficient data are available and if any 

updates are needed to the human health risk assessments to support Registration Review. 

Pyraclostrobin is currently registered for use numerous agricultural crops and on residential and 

golf course turf, residential ornamentals, landscape gardens, fruit trees, nut trees, and greenhouse 

grown tomato transplants for the home consumer market. The HED review of the proposed new 

Page 1 of29 
use ofpyraclostrobin on herb subgroup 19A and dill is pending (EPA Notice of Filing: EPA-HQOPP-2013-0798). To evaluate the scope of work necessary to support Registration Review, 

HED has considered the previously finalized human-health risk assessments conducted for this 

chemical as well any updates to the toxicity, exposure, and usage databases, and current Agency 

science policy and risk assessment methodologies. 

The toxicology database for pyraclostrobin is complete and no additional toxicology studies are 

needed at this time. The primary effects were decreases in body weight, body weight gain, and 

food consumption, and diarrhea observed in multiple species. Pyraclostrobin is classified as 

"Not likely to be Carcinogenic to Humans." There are no concerns for reproductive toxicity, 

neurotoxicity, mutagenicity, genotoxicity, or immunotoxicity. There is no evidence for 

increased susceptibility following pre- and/or post-natal exposures. Based on the available data, 

toxicity endpoints and points of departure (PODs) have been selected for acute and chronic 

dietary, short-term incidental oral, and short- and intermediate-term dermal and inhalation 

exposure scenarios. Dermal absorption is 14%. The Food Quality Protection Act (FQPA) Safety 

Factor has been reduced to IX since the toxicity and exposure databases are complete and there 

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

The residue chemistry database is sufficient to support current registrations of pyraclostrobin. 

The nature of the residue in plants and livestock has been adequately defined. Adequate field 

trial, rotational crop, livestock feeding, analytical method, primary crop processing, and storage 

stability data are available. 

A new dietary exposure and aggregate risk assessment are not anticipated during Registration 

Review. 

New occupational and residential handler and post-application exposure and risk assessments 

will not be needed during Registration Review. An assessment of spray drift is not needed, 

because pyraclostrobin is currently registered for use on residential turf at an application rate (0.5 

lb ai/A) greater than those for agricultural crops (0.2 lb ai/A maximum) and therefore any 

exposure from spray drift would be less than exposure on turf. However, the Agency will 

examine the need for a volatilization assessment during Registration Review for pyraclostrobin 

based on the potential for exposure to bystanders from agricultural applications. 

Introduction 

Pyraclostrobin belongs to the strobilurin class of fungicides (P-methoxyacrylate class of 

compounds). Strobilurins are synthetic analogs of a natural antifungal substance which inhibit 

spore germination, mycelial growth, and sporulation of the fungus on the leaf surface. 

The most recent human health risk assessment for pyraclostrobin was finalized in 2013 for 

numerous new uses (D405065, B. O'Keefe, 07/03/2013). A new use risk assessment is pending 

for pyraclostrobin use on herb subgroup 19A and dill as well as crop group conversions on stone 

fruit group 12-12 and tree nut group 14-12. Pyraclostrobin is currently registered for use on 

numerous agricultural and orchard crops. It is also registered for use on golf course and 

. residential turf and gardens, fruit and nut trees, as well as on ornamentals, including shmbs and 

Page 2 of29 
Page 3 of 29

bushes, and on tomato plants meant to be transplanted into home gardens. Homeowners may 

apply pyraclostrobin to residential gardens and turf, as well as fruit and nut trees. Pyraclostrobin 

end use products are formulated into the following formulation types: emulsifiable concentrates, 

flowable concentrates, soluble concentrates, granulars, water dispersible granules, and ready-touse solutions. Pyraclostrobin is also formulated into products with other fungicides or 

insecticides. Applications can be made with ground, aerial, airblast, chemigation, hand held, or 

seed treatment equipment. Refer to Attachment 1 (Table 1) for the chemical identity of 

pyraclostrobin. 

Hazard Identification/Toxicology

The toxicological data base for pyraclostrobin is complete and adequate for risk assessment. All 

toxicity data requirements for conventional pesticide registration under the current 40 CFR 

§158.500 have been satisfied.

The primary effects were diarrhea and decreased body weight, body weight gain, and food 

consumption. Pyraclostrobin was classified as “Not likely to be Carcinogenic to Humans.” 

There are no concerns for reproductive susceptibility, neurotoxicity, mutagenicity, genotoxicity, 

or immunotoxicity. Developmental toxicity occurred at doses greater than or equal to those 

doses causing maternal toxicity. Based on the available data, toxicity endpoints and points of 

departure (PODs) have been selected for acute and chronic dietary, short-term incidental oral, 

and short- and intermediate-term dermal and inhalation exposure scenarios. The dermal 

absorption factor for risk assessment is 14%. 

The rabbit developmental toxicity study is used for assessing risks following acute dietary 

(females 13+) as well as for short- and intermediate-term dermal exposures. For the acute 

dietary endpoint (females 13+), the developmental no observable adverse effect level (NOAEL) 

of 5 mg/kg/day is used as the POD based on the increased resorptions/post-implantation loss at 

10 mg/kg/day (LOAEL, lowest observable adverse effect level); these effects are assumed to 

occur following a single in utero exposure. The same POD from the rabbit developmental study 

is used for assessing risk following short- and intermediate-term dermal exposures. The 

endpoint of concern is the maternal toxicity characterized as decreases in body weight gain, food 

intake and food efficiency at 10 mg/kg/day. The developmental toxicity is not a concern for 

dermal exposures since the developmental effects were seen in the presence of maternal toxicity. 

The dermal toxicity study is not used for risk assessment since the doses tested were deemed to 

be inadequate and the study unacceptable. 

The combined chronic toxicity/carcinogenicity study in rats is used for assessing risk via chronic 

dietary exposures. The POD is 3.4 mg/kg/day based on decreased body weight/gain and kidney 

tubular casts/atrophy in both sexes and liver necrosis and stomach lesions in males at 9.2 

mg/kg/day (LOAEL). 

For assessing risk following incidental oral exposures inn infants and children, the POD of 5.8 

mg/kg/day based on increased incidence of diarrhea, clinical chemistry changes, duodenum 

mucosal hypertrophy, and decreased body weight and food intake/efficiency at 12.9 mg/kg/day

(LOAEL) in a subchronic toxicity study in dogs.
Page 4 of 29

The short- and intermediate-term inhalation exposures are based on the 28-day inhalation 

toxicity study in rats which had dose-dependent adverse findings in the respiratory system and 

duodenum. The study’s oral equivalents NOAEL/LOAEL are 0.23/6.92 mg/kg/day 

(corresponding to study’s air concentration of 0.001/0.03 mg/L air). The findings are well 

characterized in that the severity, frequency, and location (e.g., along the respiratory tract) are 

dose-dependent ranging from no effects at the NOAEL of 0.001 mg/L air to severe respiratory 

effects and death at the highest dose of 0.3 mg/L air.

Pyraclostrobin has moderate to low acute toxicity via the oral (Toxicity Category IV), dermal 

(Toxicity Category III), and inhalation (Toxicity Category II) routes of exposure. Pyraclostrobin 

is not a dermal sensitizer, but was determined to produce a low acute dermal and eye irritation

(Toxicity Category III).

Refer to Attachment 5 for a summary of the toxicity endpoints and points of departure for 

pyraclostrobin. Refer to Attachment 6 for the complete toxicity profiles tables for 

pyraclostrobin. 

The Food Quality Protection Act (FQPA) Safety Factor has been reduced to 1X because the 

toxicity database is complete, there is no concern for susceptibility in infants and young children, 

there are no neurotoxicity concerns, and there are no residual uncertainties regarding exposure.

Conclusions: The toxicology database of pyraclostrobin is complete. Therefore, the PODs and 

endpoints of concern, and the safety/uncertainty factors are unlikely to change during 

Registration Review. 

Dietary Exposure

The residue chemistry data and drinking water data are adequate to assess dietary exposure and 

sufficient to support current registrations. The nature of the residue in plants and livestock has 

been defined. For purposes of tolerance and dietary risk assessments, the residues of concern in 

plant and rotational crop commodities include pyraclostrobin and desmethoxy metabolite (BF 

500-3). The residues of concern in livestock commodities include pyraclostrobin and its 

metabolites convertible to 1-(4-chlorophenyl)-1H-pyrazol-3-ol (BF 500-5) and 1-(4-chloro-2-

hydroxyphenyl)-1H-pyrazol-3-ol (BF 500-8).

There are adequate residue analytical methods for tolerance enforcement. The analytical 

methods for plant commodities are liquid chromatography with tandem mass spectrometry 

(LC/MS/MS) and high pressure liquid chromatography with ultraviolet detector (HPLC/UV), 

while the ,. The analytical methods for livestock commodities use gas chromatography with 

mass spectrometry (GC/MS). and LC/MS/MS. For the FDA Multi-residue Methods, 

pyraclostrobin was successfully evaluated through several of the FDA protocols (complete 

recovery through protocols D and E), while recovery of metabolite BF 500-3 was unsuccessful in 

all protocols.
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Adequate crop field trials and processing studies are available to support existing uses. 

Adequate confined, limited and extensive field rotational crop studies are available supporting 

the existing tolerances for indirect residues of pyraclostrobin in rotational crops. These data 

support the 14-day plant-back interval currently specified for crops without pyraclostrobin uses. 

Adequate storage stability data are available to support storage durations for pyraclostrobin in/on 

plant commodities and livestock commodities. 

The most recent dietary (food and drinking water) exposure assessment was conducted in 2013 

(D410739, S. Funk, 04/17/2013) using the Dietary Exposure Evaluation Model (DEEM-FCID, 

Version 3.16), which uses 2003 – 2008 food consumption data from the U.S. Department of 

Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA). Estimated drinking water concentrations (EDWCs) in surface water were 

generated using the Pesticide Root Zone Model and Exposure Analysis Modeling System 

(PRZM-EXAMS) model. Ground water EDWCs were generated using the Screening 

Concentration in Ground Water (SCI-GROW) and Pesticide Root Zone Model – Ground Water 

(PRZM-GW) models. The modeled peak surface water value of 35.6 μg/L was used in the acute 

dietary assessment. 

A somewhat refined chronic dietary analysis was conducted in order to compensate for exposure 

resulting from residential uses in the aggregate assessment. The chronic dietary analysis 

included tolerance-level or average field trial residues, average percent crop treated estimates

(2012) when available, and empirical processing factors. Screening level estimates of 

agricultural uses of pyraclostrobin were provided previously by the Biological & Economic 

Analysis Division (BEAD). Experimentally derived processing factors were used for fruit juices, 

tomato, sugarcane, and wheat commodities. For all other processed commodities, DEEM default 

processing factors were assumed. The estimated drinking water concentration for pyraclostrobin 

(0.0023 ppm) was calculated based on a turf scenario for surface water. The chronic dietary 

(food and drinking water) exposure estimates were below the Agency’s level of concern for all 

population subgroups. The dietary exposure estimates utilized 8% of the chronic Population 

Adjusted Dose (cPAD) for the general US population and 27% of the cPAD for children 1-2 

years old, the population subgroup with the highest estimated chronic dietary exposure to 

pyraclostrobin. The United States Department of Agriculture (USDA) Pesticide Data Program 

(PDP) monitoring data on over 10,000 samples per year (2010-2012) of some twenty food 

commodities show pyraclostrobin detection rates of 3 – 7% with maximum residues <10% - 20% 

of the respective tolerances.

A slightly refined acute dietary exposure assessment was performed for pyraclostrobin. The 

analysis used tolerance-level residues or highest field trial residues, 100% crop treated, and 

empirical or default processing factors. Experimentally derived processing factors were used for 

fruit juices, tomato, sugarcane, and wheat commodities. For all other processed commodities, 

DEEM default processing factors were assumed. EDWCs were also used. The estimated acute 

drinking water concentration for pyraclostrobin (0.0356 ppm) was calculated based on a turf 

scenario for surface water. 

The acute dietary risk estimates do not exceed the Agency’s level of concern (< 100% of the 

aPAD) for the U.S. population and all subgroups. Combined dietary exposure from food and 
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drinking water at the 95th percentile of exposure for the U.S. population is equivalent to 1.5% of 

the acute Population Adjusted Dose (aPAD). The population subgroup with the highest 

estimated acute dietary exposure to pyraclostrobin is females 13-49 years, with an estimated 

exposure at the 95th percentile of 87% of the aPAD.

Conclusions: A new dietary exposure assessment is not anticipated to be needed during 

Registration Review unless there are changes to the drinking water exposure estimates that need 

to be incorporated. If the drinking water exposure estimates do not change, a dietary exposure 

assessment will not be conducted. 

Residential Exposure

Pyraclostrobin is registered for use on residential gardens, fruit and nut trees, turf and on tomato 

plants meant to be transplanted in residential settings. Residential handler and post-application 

exposures are expected.

Residential Handlers

HED has determined that residential handlers are likely to be exposed to pyraclostrobin residues 

via dermal and inhalation routes during handling activities, i.e. mixing, loading, and applying 

pesticide. HED expects the duration of residential handler exposure to only be short-term (1-30 

days). All of the potential residential handler exposure scenarios for the registered uses of 

pyraclostrobin were assessed in previous human health risk assessments using the Revised 

Residential Standard Operating Procedures (SOPs); no risks of concern were identified (all 

MOEs >100; with level of concern (LOC) = 100). Risk estimate margins of exposure (MOEs) 

range 740 to 24,000 for dermal exposures and 590 to 3,900,000 for inhalation exposures. 

Residential Post-Application 

HED has determined that there is potential for post-application exposure to adults and children 

from the residential uses of pyraclostrobin. Potential routes of exposure include dermal and 

inhalation for adults and children, and incidental oral ingestion for children 1 to <2 years of age. 

Residential uses of pyraclostrobin will result in short-term (1 to 30 days) post-application 

exposures. Incidental oral hand-to-mouth exposures to children 1 to <2 years of age from use on 

turf are likely to occur. These exposure scenarios were all assessed in previous human-health 

risk assessments; no risks of concern were identified (LOC = 100), with MOEs ranging from 130 

to 3,400,000 for combined dermal and incidental oral exposures to children 1 to <2 years old, 

490 to 2,800 for dermal exposures to children 6 to <11 years old, 3,300 to 13,000 for dermal 

exposures to youths 11 to 16 years old, and 260 to 13,000 for dermal exposures to adults. The 

residential post-application assessments are based upon reliable surrogate study data that are not 

expected to underestimate risks. 

A chemical specific turf transferrable residue (TTR) study (MRID 45118725) is available and 

was used in the most recent risk assessment. Although the study uses an emulsifiable 

concentrate, and the current registered formulation of pyraclostrobin on golf course turf is a 

water dispersible granule, HED has determined that there is no statistical difference between 

residues resulting from liquid, wettable powder (applied as a spray), or water dispersible granular 
Page 7 of 29

(applied as a spray) applications; therefore, data from the emulsifiable concentrate can be used as 

a surrogate to support the water dispersible granule formulation. 

An assessment of spray drift is not needed, because pyraclostrobin is currently registered for use 

on residential turf at an application rate (0.5 lb ai/A) greater than those for agricultural crops (0.2 

lb ai/A maximum) and therefore any exposure from spray drift would be less than exposure on 

turf. Residential exposures resulting from off-site transport (e.g., volatilization) may occur as a 

result of pyraclostrobin applications to agricultural fields. The Agency is in the process of 

evaluating these types of exposures and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate these post-application exposures 

into the Agency's risk assessments. The need for a volatilization risk assessment for 

pyraclostrobin will be examined during Registration Review.

Conclusions: Residential handler and conventional residential post-application assessments will 

not be conducted during Registration Review; however, the Agency will examine the need for a 

volatilization assessment to assess post-application residential risk from pyraclostrobin during 

Registration Review. 

Aggregate Risk Assessment

Aggregate assessments consider exposures from food, drinking water, and residential uses. 

Since there are residential uses of pyraclostrobin, aggregate risk for all exposure durations 

consists of residential handler and post-application exposures, food, and drinking water. 

In the most recent human health risk assessment (D405065, B. O’Keefe, 07/13/2013), an acute 

aggregate risk assessment, which is equivalent to the acute dietary risk assessment, was not of 

concern. The food and drinking water exposure estimates are 1.5% of the acute population 

adjusted dose (aPAD) for the general U.S. population, and 87% of the aPAD for the most highly 

exposed subgroup, females 13-49 years old.

A short-term aggregate risk assessment, which included dermal, inhalation, and incidental oral 

exposures combined with background chronic dietary (food and drinking water) exposures, 

resulted in MOEs ranging from 120 to 1,500 (LOC = 100). The greatest adult non-cancer 

aggregate exposure risk estimate is not of concern to HED; the MOE is 230, which is greater 

than the LOC of 100. The aggregate MOE for children 1-2 years old, including incidental oral 

exposures from treated turf, is 120, which is above the LOC of 100, and is not of concern to 

HED.

Chronic exposure from the residential pathway is not anticipated based on the current 

pyraclostrobin use pattern. Therefore, the chronic aggregate risk (food and drinking water) is 

equivalent to the chronic dietary (food and drinking water) exposure estimate.

Conclusions: Aggregate exposure to pyraclostrobin is currently not of concern to HED. New 

aggregate assessments are not needed during Registration Review, unless changes in uses, 

procedures, or estimated drinking water concentrations (EDWCs) occur. 
Page 8 of 29

Occupational Exposure

Pyraclostrobin is registered for use on numerous agricultural use sites. It is also registered for 

occupational use on several non-agricultural use sites. There is potential for short- and 

intermediate-term occupational exposure to pyraclostrobin during handling (mixing, loading, and 

applying) and post-application activities.

Occupational Handlers

Previous occupational handler exposure and risk assessments for pyraclostrobin were conducted 

at the maximum application rate, assumed the maximum area treated per day for all the 

registered agricultural use sites. The registered pyraclostrobin labels require occupational 

handlers to wear long-sleeved shirts, long pants, shoes, socks, and chemical resistant gloves. 

Applications can be made with ground, aerial, airblast, chemigation, or seed treatment 

equipment. All current exposure estimates at baseline personal protective equipment (PPE) 

(single layer clothing, no gloves, and no respirator) or label specified PPE were not of concern 

(MOEs >100). Using current HED SOPs, handler risk estimate MOEs ranged from 270 to 

16,000 for dermal exposures and 140 to 8,500 for inhalation exposures. Therefore, an updated 

occupational handler risk assessment is not needed during Registration Review.

Occupational Post-Application

Occupational post-application short- and intermediate-term dermal and inhalation exposures are 

possible for workers tending treated food crops. Chemical-specific dislodgeable foliar residue 

(DFR) data were previously submitted, reviewed, and found acceptable for use in assessing postapplication exposure (D269670, K. O’Rourke, 09/30/2002). Pyraclostrobin DFR studies were 

conducted on peaches, peanuts, strawberries, and grapes. All post-application scenarios for all 

crops resulted in MOEs greater than 100 on day 0 (12 hours after application), and therefore, are 

not of concern to HED. Using current HED SOPs, risk estimate MOEs for dermal exposure 

ranged from 120 to 29,000.

Labels of registered pyraclostrobin products require restricted entry intervals (REIs) of 12 hours, 

which is adequate to protect agricultural workers from post-application exposures to 

pyraclostrobin.

Conclusions: There is sufficient information available to assess occupational handler and postapplication exposures. Updated occupational handler and post-application exposure assessments 

are not needed during Registration Review. 

Public Health and Pesticide Epidemiology Data

The evaluation of the OPP Incident Data System (IDS) indicated that for the main IDS, from 

January 1, 2009 through June 15, 2014, there were 5 incidents reported for single chemical 

pyraclostrobin only in the database. There were 9 additional incidents reported involving more 

than one chemical. One incident was classified as no or unknown effects, one incident was 

classified as minor severity and the rest were classified as moderate severity (S. Recore, 

D417740, 02/11/2014). In the aggregate IDS, from January 1, 2009 to June 15, 2014, there were 

36 reported incidents involving pyraclostrobin. These reports were classified as minor severity. 
Page 9 of 29

Overall, there are few incidents involving pyraclostrobin reported to IDS. Because these 

aggregate results fall within the categories reported as counts (which includes minor, unknown or 

no effects), there is no unique report that provides details about the incident and single chemical 

incidents are not distinguished from multiple chemical incidents; however, a high frequency of 

incidents indicates there is a high potential for exposure and vice versa.

The evaluation of the Sentinel Event Notification System for Occupational Risk (SENSOR) 

Pesticides database from 1998-2010 identified a total of 65 cases involving pyraclostrobin (pc 

code 099100), stemming from 28 events. Of these, 52 cases involved a single active ingredient. 

Forty three cases (83%) were work-related. Forty one of the 52 cases (79%) resulted from aerial 

applications. Headline Fungicide (EPA Reg. No. 7969-186) is the product implicated in 42 of 

the 52 cases, including one multiple exposure agricultural drift event that occurred in Iowa in 

2007 and led to 27 cases of pesticide illness. This event was documented in the CDC’s 

Morbidity and Mortality Weekly Report1. 

Another multiple exposure event occurred in Iowa in 2010 that resulted in four case reports. The 

event narrative states, “18 people were [over] sprayed by a crop-duster while detasseling. Four

people went to the ER, the rest were decontaminated on-site. Headline Fungicide was the 

product used.”2

Of the 52 single active ingredient pyraclostrobin cases, four were moderate in severity and 48 

were low in severity. Respiratory symptoms were the most frequently reported (63%) health 

effects involving pyraclostrobin cases.

Pyraclostrobin is not included in the Agricultural Health Study (AHS), and therefore, the AHS 

does not provide information for this report. 

Based on the low frequency and severity of incident cases reported for pyraclostrobin in both 

IDS and SENSOR-Pesticides, compared to other pesticides, 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 risk assessment.

Tolerance Assessment and International Harmonization

There are numerous pyraclostrobin maximum residue limits (MRLs)/tolerances both for Canada 

and Codex. The US and Canada residue definitions are effectively harmonized, but differ from 

the Codex definition. The latter is parent only. The Canada/US tolerances are harmonized for 

banana, strawberry, Brassica head and stem vegetables subgroup 5A, Brassica leafy greens 

subgroup 5B, citrus oil, sweet corn, citrus fruit group 10-10, pome fruit group 11-10, grapes, 

raisins, hops, tree nut group 14, oat grain, oilseed group 20, pea and bean dried shelled subgroup 

6C, peanut, peanut oil, peppermint tops, rye grain, soybean, spearmint tops, bulb vegetables 

 

1 MMWR January 4, 2008/ 56 (51); 1343-1345

2 The other 14 cases may not have met the SENSOR case definition (two or more symptoms) and are therefore not 

included as cases.
Page 10 of 29

group 3-07, cucurbit vegetables group 9, leafy vegetables group 4, root vegetables subgroup 1B, 

and tuberous and corm vegetables subgroup 1C. The US and Canadian tolerances are also 

harmonized for livestock commodities (meat, milk, poultry, eggs). The US and Canadian 

tolerances differ for the following commodities: barley grain, succulent shelled bean, sugar beet 

root, bushberry subgroup 13-07B, caneberry subgroup 13-07A, corn grain, popcorn grain, stone 

fruit group 12, mango, papaya, succulent pea, persimmon, pistachio, fruiting vegetable group 8-

10, and legume vegetable edible podded subgroup 6A. With the exception of succulent pea and 

wheat grain, the US tolerances are greater than the corresponding Canada tolerances. The 

possibility for harmonization will be discussed during registration review.

The US and Codex numerical tolerance/MRL values agree for only a few commodities: sugar 

beet roots, strawberry, blueberries, citrus fruits, grapes, lentil (dry), cucurbit fruiting vegetables. 

None of the livestock commodity values are harmonized.

Environmental Justice

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

registration review, in accordance with US Executive Order 12898, "Federal Actions to Address 

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

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

assessment, OPP considers a large variety of consumer subgroups according to well-established 

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

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

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

Extensive data on food consumption patterns are compiled under the NHANES/WWEIA and are 

used in pesticide risk assessments for all registered food uses of a pesticide. These data are 

analyzed and categorized by subgroups based on age and ethnic group. Additionally, OPP is 

able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas post-application are 

evaluated. Further considerations are currently in development as OPP has committed resources 

and expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

Cumulative 

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

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

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

metabolite produced by other substances. For information regarding EPA’s efforts to determine 

which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of 

such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs 

concerning common mechanism determinations and procedures for cumulating effects from 
Page 11 of 29

substances found to have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/.

Human Studies

The risk assessments which have been previously conducted for pyraclostrobin relied 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), the Outdoor Residential Exposure Task Force (ORETF), 

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

supporting these multi-pesticide generic exposure databases, and has found no clear and 

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

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

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

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

reliance on these studies.

Data Deficiencies

No additional toxicity, residue chemistry, or occupational and residential exposure data are 

needed to support the registered uses of pyraclostrobin at this time.
Page 12 of 29

References

Memoranda Relevant to Registration Review of Pyraclostrobin

Author DP/TXR# Date Title

Risk Assessment

B. O’Keefe D405065 07/03/2013 Pyraclostrobin – Human Health Risk Assessment for a Section 3 

Registration of New Uses on Sugarcane, Globe Artichoke, Belgium 

Endive, Persimmon, Greenhouse Grown Tomato Transplants for 

Home Consumer Market, and Residential Ornamentals, Landscape 

Gardens, Fruit Trees, and Nut Trees; Plus Crop Group 

Expansions/Revisions for Bulb Vegetable Group 3-07, Fruiting 

Vegetable Group 8-10, Citrus Fruit Group 10-10, Pome Fruit Group 

11-10, Berry Subgroups 13-07A, B, F, and G, and Oilseed Group 

20.

Residue Chemistry

S. Funk D410737 04/30/2013 Pyraclostrobin: Petition for the Establishment of Permanent 

Tolerances and Registration for Use on Belgium Endive, 

Persimmon, and Globe Artichoke. Request for Crop Group 

Expansions/Revisions for Bulb Vegetable Group 3-07, Fruiting 

Vegetable 8-10, Citrus Fruit Group 10-10, Pome Fruit Group 11-

10, Berry Subgroups 13-07A, B, F, and G, and Oilseed Group 20. 

Summary of Analytical Chemistry and Residue Data.

S. Funk D403449 04/16/2013 Pyraclostrobin: Request for the Use on Sugarcane. Summary of 

Analytical Chemistry and Residue Data.

Dietary Exposure Assessment

S. Funk D410739 04/17/2013 Pyraclostrobin. Acute and Chronic Aggregate Dietary (Food and 

Drinking Water) Exposure and Risk Assessments to Support New 

Uses on Sugarcane, Persimmon, Globe Artichoke, and Belgium 

Endive

Occupational Residential Exposure

C. Walls D403449 04/30/2013 Pyraclostrobin. Occupational and Residential Exposure Assessment 

for proposed new uses of pyraclostrobin on sugarcane, globe 

artichoke, Belgium endive, persimmon, greenhouse grown tomato 

transplants grown for home consumer market, and residential 

ornamentals, landscape gardens, fruit trees and nut trees.

K. O’Rourke D298017 08/30/2004 Occupational and Residential Risk Assessment to Support Request 

for a Section 3 Registration of Pyraclostrobin on a Variety of Crops 

and Residential Turf

K. O’Rourke D269670 09/30/2002 Occupational and Residential Risk Assessment to Support Request 

for a Section 3 Registration of Pyraclostrobin on a Variety of Crops 

- Joint Review with Health Canada

Incident Report

S. Recore D417740 02/11/2014 Revised: Pyraclostrobin: Tier I Review of Human Incidents

Attachments

1. Chemical Identity Table

2. Physicochemical Properties of Technical Grade Pyraclostrobin Table

3. Structure and Names of Regulated Pyraclostrobin Metabolites Table

4. Tolerance/MRL Summary Table

5. Endpoint Selection Tables

6. Toxicity Profile Tables
Page 13 of 29

Attachment 1

Chemical Identity Table

TABLE 1. Chemical Identity of Pyraclostrobin

Compound

Common name Pyraclostrobin

Company experimental 

name BAS 500 F

IUPAC name methyl 2-[1-(4-chlorophenyl)pyrazol-3-yloxymethyl]-Nmethoxycarbanilate

CAS name methyl N-[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-

yl]oxy]methyl]phenyl]-N-methoxycarbamate

CAS registry number 175013-18-0

Chemical Class Strobilurin

End-use product (EP) Headline® EC Fungicide, EPA Reg. No. 7969-186.

Cabrio® EG fungicide, EPA Reg. No. 7969-187

Pristine® fungicide, EPA Reg. No. 7969-199

Headline® SC fungicide, EPA Reg. No 7969-289

N

N

Cl

O

N O

H3C

O

OCH3
Page 14 of 29

Attachment 2

TABLE 2. Physicochemical Properties of Technical Grade Pyraclostrobin.

Parameter Value References1(MRID)

Melting point/range 63.7-65.2oC 45118213

pH Not applicable

Density 1.367 g/cm345118214

Water solubility at 20 oC 1.9 ± 0.17 mg/L (deionized water, 

pH 5.8)

45118233

Solvent solubility n-heptane (0.37 g/100mL); 2-

propanol (3.0 g/100mL); 1-octanol 

(2.42 g/100mL); olive oil (2.80 

g/100m/L); methanol (10.08 

g/100mL); >50 g/100mL in 

acetone, ethyl acetate , acetonitrile, 

dichloromethane and toluene.

45118228

Vapor pressure 2.6 x 10-10 hPa at 20 oC 45118214

Dissociation constant, pKa None (no dissociable moieties)

Octanol/water partition 

coefficient, Log(KOW) at room 

temperature

3.990 mean log Pow; Pow is 9772 

45118215

UV/visible absorption 

spectrum

The structural identity of BAS 500 

F was confirmed by NMR and MS 

spectra. UV molecular extinction (e 

[1 mol-1cm-1]): 2.5x104at 205 nm; 

2.4x104at 275 nm.

1996/109552

1 Product Chemistry data were reviewed by the Registration Division (DP# 269848 and DP# 

274191, 5/3/01, 5/15/01, and 6/7/01, S. Malak). 

2 BASF Document Number.
Page 15 of 29

Attachment 3

TABLE 3. Structure and Names of Regulated Pyraclostrobin Metabolites

Structure Name

500M04

BF500-5

1-(4-chlorophenyl)-1H-pyrazol-3-ol

500M07

BF500-3

Methyl -N-(2{[1-(4-chlorophenyl)-1H-pyrazol-3-yl] 

oxymethyl}phenyl) carbamate

500M85

BF500-8

1-(4-chloro-2-hydroxyphenyl)-1-H-pyrazol-3-ol
Page 16 of 29

Attachment 4

Tolerance/MRL Table

Table 4. Summary of US and International Tolerances and Maximum Residue Limits 

US Canada Mexicob Codexc

Residue Definition

40CFR§180.582

Plant: the sum of pyraclostrobin 

(carbamic acid, [2-[[[ 1-(4-

chlorophenyl)-1H-pyrazol-3-yl]oxy] 

methyl]phenyl]methoxy-, methyl ester) 

and its desmethoxy metabolite (methylN-[[[1-(4-chlorophenyl)-1H-pyrazol-3-

yl]oxy]methyl] phenylcarbamate), 

calculated as the stoichiometric 

equivalent of pyraclostrobin

methyl N-[2-[[[1-(4-

chlorophenyl)-1H-pyrazol-3-

yl]oxy]

methyl]phenyl]-Nmethoxycarbamate, including the

metabolite carbamic acid, N-[2-

[[[1-(4-chlorophenyl)-1H-pyrazol3-yl]oxy]methyl]phenyl]-, methyl 

ester

Pyraclostrobin

The residue is fat 

soluble.

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

US Canada Mexicob Codexc

Alfalfa, forage 10

Alfalfa, hay 30 30 alfalfa fodder

Almond, hulls 7.0

Apple, wet pomace 8.0

Artichoke, globe 3.0 2

Avocado 0.6

Banana 0.04 0.04 0.02 (*)

Barley, grain 1.4 0.4 1

Barley, hay 25

Barley, straw 6.0 30 straw and fodder 

(dry) of cereal grains

Bean, succulent shelled 0.5 0.35 succulent shelled (broad 

beans, lima beans)

Beet, sugar, dried pulp 1.0

Beet, sugar, roots 0.2 0.15 0.2 sugar beet

Beet, sugar, tops 8.0

Berry, low growing, 

subgroup 13-07G, except 

cranberry

1.2 1.2 strawberries 4 blueberries

1.5 strawberry

Brassica, head and stem, 

subgroup 5A

5.0 5 broccoli, brussels sprouts, 

cabbage, cauliflower, Chinese 

broccoli, Chinese mustard 

cabbages, kohlrabi, napa Chinese 

cabbages 

0.3 brussels sprouts

0.2 cabbage head

0.1 flowerhead brassicas 

(includes croccoli: 

broccoli, Chinese and 

cauliflower) 

Brassica, leafy greens, 

subgroup 5B

16.0 16 bok choy Chinese cabbages, 

broccoli raab, collards, kale, 

mustard greens, mustard spinach, 

rape leaves

1 kale (including among 

others: collards, curly 

kale, scotch kale, 

thousand-headed kale; 

not including Marrowstem kele)

Bushberry subgroup 13-07B 4.0 3.5 blueberries, currants,

elderberries, huckleberries, 

jostaberries, Juneberries 

(Saskatoon berries)

4 blueberries
Page 17 of 29

Table 4. Summary of US and International Tolerances and Maximum Residue Limits 

US Canada Mexicob Codexc

Caneberry subgroup 13-07A 4.0 3.5 blackberries, loganberries, 

raspberries

3 blackberries, 

raspberries, red, black

Canistel 0.6

Citrus, dried pulp 12.5

Citrus, oil 9.0 9 10 citrus oil. edible 

(proposed) 

10 orange oil, edible 

Coffee, green bean 10.3 0.3 coffee beans

Corn, field, forage 5.0

Corn, field, grain 0.1 0.04 0.02 (*) maize

Corn, field, refined oil 0.2

Corn, field, stover 17.0 30 straw and fodder 

(dry) of cereal grains

Corn, pop, grain 0.1 0.04

Corn, pop, stover 17.0 30 straw and fodder 

(dry) of cereal grains

Corn, sweet, forage 5.0

Corn, sweet, kernel plus cob 

with husks removed

0.04 0.04

Corn, sweet, stover 23.0 30 straw and fodder 

(dry) of cereal grains

Cotton, gin byproducts 30

Endive, belgium 4.0

Fruit, citrus, group 10-10 2.0 2 calamondin, citrus citron, citrus 

hybrids, grapefruits, kumquats, 

lemons, limes, oranges, pummelos, 

tangerines, Satsuma mandarins

2 citrus fruits

Fruit, pome, group 11-10 1.5 1.5 apples, Asian pears, 

crabapples, loquats, mayhaws, 

pears, quinces

0.5 apple

Fruit, small vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

2.0 2 grapes 2 grapes

Fruit, stone, group 12 2.5 0.7 apricots, fresh prune plums, 

nectarines, peaches, plumcots, 

plums, sweet cherries, tart cherries 

3 cherries 

0.3 nectarine, peach

0.8plums (including 

prunes)

Grain, aspirated fractions 2.5

Grape, raisin 7.0 7 raisins 5 Dried grapes 

(=currants, raisins and 

sultanas)

Grass, forage 10

Grass, hay 4.5

Grass, seed screenings 27

Grass, straw 14

Hop, dried cones 23.0 23 hops (dried) 15 hops, dry

Mango 0.6 0.1 0.05 (*)
Page 18 of 29

Table 4. Summary of US and International Tolerances and Maximum Residue Limits 

US Canada Mexicob Codexc

Nut, tree, group 14 0.04 0.04 almond nuts, beechnut, black 

walnut, Brazil nut, butternut, 

cashew nuts, chestnut, chinquapin 

nuts, Enflish walnut, hazelnut 

(filbert), hickory nut, macadamia 

nut, pecan nuts 

0.5 pistachio nut

0.02 (*) tree nuts, 

(except pistachio nuts), 

peanut whole

Oat, grain 1.2 1.2 1

Oat, hay 18

Oat, straw 15 30 straw and fodder 

(dry) of cereal grains

Oilseed group 20 0.45 0.45 seeds (borage , calendula, 

cuphea, echium, flax, gold of 

pleasure, hare's ear, jojoba, 

milkweed, mustard (condiment 

and oil type), niger seed, oil radish, 

poppy, rapeseed (canola), 

safflower, sesame, tallowwood, tea 

oil plant

0.4 oilseed, except 

peanut

Papaya 0.6 0.1 0.15

Pea, succulent 0.2 0.35 succulent shelled (blackeyed 

peas, English peas, garden peas, 

green peas, peas, pigeon peas, 

southern peas

0.02 (*) peas (pods and 

succulent=immature 

seeds)

Pea and bean, dried shelled, 

except soybean, subgroup 6C

0.5 0.5 Dry (adzuki beans, beans, 

blackeyed peas, broad beans, 

catjang seeds, chickpeas, field 

peas, guar seeds, kidney beans, 

lablab beans, lentils, lima beans, 

moth beans, mung beans, navy 

beans, pigeon peas, pink beans, 

pinto beans, rice beans, southern 

peas, tepary beans, urd beans); 

grain lupin

0.04 soybeans

0.2 beans (dry)

0.5 lentil (dry)

0.3 peas (dry)

Peanut 0.05 0.05 0.02 (*) peaunt whole

Peanut, refined oil 0.1 0.1 peanut oil (refined)

Peppermint, tops 8.0 8

Persimmon 3.0

Pistachio 0.7 0.5 pistachio nuts 1 pistachio nuts

Radish, tops 16 20 radish leaves 

(including radish tops)

Rye, grain 0.04 0.04 0.2

Rye, straw 0.5 30 straw and fodder 

(dry) of cereal grains

Sapodilla 0.6

Sapote, black 0.6

Sapote, mamey 0.6

Sorghum, grain, forage 5.0

Sorghum, grain, grain 0.60 0.5

Sorghum, grain, stover 0.80 30 straw and fodder 

(dry) of cereal grains
Page 19 of 29

Table 4. Summary of US and International Tolerances and Maximum Residue Limits 

US Canada Mexicob Codexc

Soybean, forage 11

Soybean, hay 14

Soybean, hulls 0.06

Soybean, seed 0.04 0.04 dry soybeans 0.05 soya bean (dry)

Spearmint, tops 8.0 8

Star apple 0.6

Sugarcane, cane 0.20

Vegetable, bulb, group 3-07 0.9 0.9 Chinese onion, dry bulb onion, 

garlic, green onion, leeks, potato 

oinion, shallots, tree onion tops, 

Welsh onion tops

0.15 garlic

0.7 leek

1.5 onion, bulb

1.5 spring onion

Vegetable, cucurbit, group 9 0.5 0.5 balsam apples, balsam pears, 

cantaloupes, chayote fruit, Chinese 

cucumbers, Chinese waxgourds, 

citron melons, cucumbers, edible 

gourds, muskmelons (other than 

those listed in this item) pumpkins, 

summer squash, watermelons, west 

Indian gherkins, winter squash

0.2 cantaloupes

0.5 fruiting vegetables, 

Cucurbits

Vegetable, foliage of legume, 

except soybean, subgroup 7A

25.0

Vegetable, fruiting, group 8-

10

1.4 1 bell peppers, eggplants, ground 

cherries, nonbell peppers, pepper 

hybrids, pepinos, tomatillos, 

tomatoes

0.3 egg plant,

tomato

0.5 peppers

Vegetable, leafy, except 

brassica, group 4

29.0 29 Amaranth, arugula, cardoon, 

celery, celtuce, Chinese celery, 

corn salad, dandelion leaves, dock, 

edible leaved chrysanthemum, 

endives, fresh chervil leaves, fresh 

Florence fennel leaves and stalks, 

fresh parsley leaves, garden cress, 

garden purslane , garland 

chrysanthemum, head lettuce, leaf 

lettuce, Malabar spinach, New 

Zealand spinach, orach, radicchio, 

rhubarb, spinach, swiss chard, 

upland cress, winter purslane

2 lettuce, head

Vegetable, leaves of root and 

tuber, group 2, except sugar 

beet

16.0 20 radish leaves 

(including radish tops)

Vegetable, legume, edible 

podded, subgroup 6A

0.5 0.4 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);

0.02 (*) peas (pods and 

succulent=immature 

seeds)
Page 20 of 29

Table 4. Summary of US and International Tolerances and Maximum Residue Limits 

US Canada Mexicob Codexc

Vegetable, root, except sugar 

beet, subgroup 1B

0.4 0.4 Roots (black salsify, carrot, 

celeriac, chicory, edible burdock, 

garden beet, ginseng, horseradish, 

oriental radish, parsnip, rutabaga, 

salsify, skirret, Spanish salsify, 

turnip, turnip-rooted chervil, 

turnip-rooted parsley

0.5 carrot, radish 

Vegetable, tuberous and 

corm, subgroup 1C

0.04 0.04 arracacha, arrowroot, cassava 

roots, chayote roots, Chinese 

artichokes, chufa, edible canna, 

ginger roots, Jerusalem artichokes, 

lerens, potatoes, sweet potato 

roots, tanier corms, taro corms, 

true yam tubers, turmeric roots, 

yam bean roots

0.02 (*) potato

Vegetables, foliage of 

legume, group 7

25 30 pea hay or pea fodder 

(dry)

Wheat, grain 0.02 0.2 0.2 wheat, triticale

Wheat, hay 6.0

Wheat, straw 8.5 30 straw and fodder 

(dry) of cereal grains

40CFR§180.582 Canada Mexicob Codexc

Livestock: fungicide pyraclostrobin 

carbamic acid, [2-[[[1-(4-

chlorophenyl)-1H-pyrazol-3-

yl]oxy]methyl]phenyl]methoxy-, 

methyl ester and its metabolites 

convertible to 1-(4-chlorophenyl)-1Hpyrazol-3-ol and 1-(4-chloro-2-

hydroxyphenyl)-1H-pyrazol-3-ol, 

expressed as parent compound

Ruminants: methyl N-[2-[[[1-(4-

chlorophenyl)-1H-pyrazol-3-

yl]oxy]

methyl]phenyl]-Nmethoxycarbamate, including the

metabolites convertible to 1-(4-

chlorophenyl)-1Hpyrazol-3-ol and 1-(4-chloro-2-

hydroxyphenyl)-1Hpyrazol-3-ol

Poultry: methyl N-[2-[[[1-(4-

chlorophenyl)-1H-pyrazol-3-

yl]oxy]

methyl]phenyl]-Nmethoxycarbamate, including the

metabolites convertible to 1-(4-

chlorophenyl)-1Hpyrazol-3-ol and 1-(3-chloro-4-

hydroxyphenyl)-1Hpyrazol-3-ol

Pyraclostrobin

The residue is fat 

soluble.

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

US Canada Mexicob Codexc

Cattle, fat 0.1 0.1

Cattle, liver 1.5 1.5 0.05 (*) edible offal 

(mammalian)

Cattle, meat 0.1 0.1 0.5 (fat) meat from 

mammals other than 

marine mammals)
Page 21 of 29

Table 4. Summary of US and International Tolerances and Maximum Residue Limits 

US Canada Mexicob Codexc

Cattle, meat byproducts, 

except liver

0.2 0.2 meat byproducts of cattle 

(except liver)

0.05 (*) edible offal 

(mammalian)

Goat, fat 0.1 0.1

Goat, liver 1.5 1.5 0.05 (*) edible offal 

(mammalian)

Goat, meat 0.1 0.1 0.5 (fat) meat from 

mammals other than 

marine mammals)

Goat, meat byproducts, 

except liver

0.2 0.2 meat byproducts of goats 

(except liver)

0.05 (*) edible offal 

(mammalian)

Hog, fat 0.1 0.1

Hog, liver 1.5 1.5 0.05 (*) edible offal 

(mammalian)

Hog, meat 0.1 0.1 0.5 (fat) meat from 

mammals other than 

marine mammals)

Hog, meat byproducts, except 

liver

0.2 0.2 meat byproducts of hogs 

(except liver)

0.05 (*) edible offal 

(mammalian)

Horse, fat 0.1 0.1

Horse, liver 0.1 1.5 0.05 (*) edible offal 

(mammalian)

Horse, meat 0.1 0.1 0.5 (fat) meat from 

mammals other than 

marine mammals)

Horse, meat byproducts, 

except liver

0.2 0.2 meat byproducts of horses 

(except liver)

0.05 (*) edible offal 

(mammalian)

Milk 0.1 0.1 0.03

Poultry, eggs 0.10 0.1 0.05 (*) eggs

Poultry, fat 0.10 -

Poultry, meat 0.10 0.1 0.05 (*) (fat)

Poultry, meat byproducts 0.10 0.1 0.05 (*) poultry edible 

offal of

Sheep, fat 0.1 0.1

Sheep, liver 1.5 1.5 0.05 (*) edible offal 

(mammalian)

Sheep, meat 0.1 0.1 0.5 (fat) meat from 

mammals other than 

marine mammals)

Sheep, meat byproducts, 

except liver

0.2 0.2 meat byproducts of sheep 

(except liver)

0.05 (*) edible offal 

(mammalian)

MRLs with NO US Equivalent

Peanut fodder 50

Spelt 0.2

Completed: M. Negussie; 01/09/2014

a

Includes all commodities with current US tolerances.

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

c * = 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.
Page 22 of 29

Attachment 5

Summary of Toxicity Endpoints and Points of Departure of Pyraclostrobin

Table 5.1. Summary of Toxicological Doses and Endpoints for use in Dietary and Non-Occupational Human Health Risk 

Assessments

Exposure Scenario Point of 

Departure (PoD)

Uncertainty / 

FQPA Safety 

Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary

General population 

(including infants and 

children)

NOAEL = 

300 mg/kg/day

UFA = 10x

UFH = 10x

FQPA = 1x

aRfD =

3.0 mg/kg/day

aPAD = 

3.0 mg/kg/day

Acute Neurotoxicity – Rat

LOAEL = 1000 mg/kg/day based on 

decreased body weight gain in males.

Acute Dietary,

Females (13-49 years 

old)

NOAEL = 

5.0 mg/kg/day

UFA = 10x

UFH = 10x

FQPA = 1x

aRfD =

0.05 mg/kg/day

aPAD = 

0.05 mg/kg/day

Developmental Toxicity – Rabbit

LOAEL = 10.0 mg/kg/day based on 

developmental toxicity findings of 

increased resorptions.

Chronic Dietary NOAEL = 

3.4 mg/kg/day

UFA = 10x

UFH = 10x

FQPA = 1x

cRfD = 

0.034 mg/kg/day

cPAD = 

0.034 mg/kg/day

Carcinogenicity – Rat

LOAEL = 9.2 mg/kg/day based on 

decreased body weight/body weight 

gain, kidney tubular casts and atrophy 

in both sexes; increased incidence of

liver necrosis and erosion/ulceration of 

the glandular- stomach and forestomach in males.

Incidental Oral

Short Term 

(1-30 days)

Intermediate Term

(1-6 months)

Oral NOAEL = 

5.8 mg/kg/day

UFA = 10x

UFH = 10x

FQPA = 1x

Residential LOC 

for MOE = 100

Subchronic Toxicity – Dog

LOAEL = 12.9 mg/kg/day based on 

increased incidence of diarrhea, 

clinical chemistry changes, duodenum 

mucosal hypertrophy, and decreased 

body weight and food 

intake/efficiency.

Dermal 

Short Term 

(1-30 days)

Intermediate Term

(1-6 months)

Oral NOAEL = 

5.0 mg/kg/day

(Dermal 

Absorption Rate 

= 14%)

UFA = 10x

UFH = 10x

FQPA = 1x

Residential LOC 

for MOE = 100

Developmental Toxicity – Rabbit

LOAEL = 10.0 mg/kg/day based on 

developmental toxicity findings of 

increased resorptions and maternal 

toxicity based on decreased body 

weight gain and decreased food 

intake/efficiency.

Dermal

Long Term

(>6 months)

Oral NOAEL =

3.4 mg/kg/day

(Dermal 

Absorption Rat = 

14%)

UFA = 10x

UFH = 10x

FQPA = 1x

Residential LOC 

for MOE = 100

Carcinogenicity – Rat

LOAEL = 9.2 mg/kg/day based on 

decreased body weight/body weight 

gain, kidney tubular casts and atrophy 

in both sexes; increased incidence of

liver necrosis and erosion/ulceration of 

the glandular- stomach and forestomach in males.

Inhalation 

Short Term 

(1-30 days)

Intermediate Term

(1-6 months)

NOAEL = 

0.23 mg/kg/day

(Air 

Concentration = 

0.001 mg/L)

UFA = 10x

UFH = 10x

FQPA = 1x

Residential LOC 

for MOE = 100

Inhalation Toxicity – Rat

LOAEL = 6.9 mg/kg/day (air 

concentration = 0.03 mg/L) based on 

duodenum mucosal hyperplasia and 

respiratory system findings including 

alveolar histiocytosis and olfactory 
Page 23 of 29

Table 5.1. Summary of Toxicological Doses and Endpoints for use in Dietary and Non-Occupational Human Health Risk 

Assessments

Exposure Scenario Point of 

Departure (PoD)

Uncertainty / 

FQPA Safety 

Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Long Term

(>6 months)

atrophy/necrosis in nasal tissue.

Cancer (oral, dermal, 

and inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor 

increases in two adequate rodent carcinogenicity studies.

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

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no 

observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from 

animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies).

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

of exposure. LOC = level of concern. N/A = not applicable.

Table 5.2. Summary of Toxicological Doses and Endpoints for use in Occupational Human Health Risk Assessments

Exposure Scenario Point of 

Departure (PoD)

Uncertainty /

FQPA Safety 

Factors

Level of 

Concern for 

Risk Assessment

Study and Toxicological Effects

Dermal 

Short Term 

(1-30 days)

Intermediate Term

(1-6 months)

Oral NOAEL = 

5.0 mg/kg/day

(Dermal 

Absorption Rate 

= 14%)

UFA = 10x

UFH = 10x

FQPA = 1x

Residential LOC 

for MOE = 100

Developmental Toxicity – Rabbit

LOAEL = 10.0 mg/kg/day based on 

developmental toxicity findings of 

increased resorptions and maternal 

toxicity based on decreased body 

weight gain and decreased food 

intake/efficiency.

Dermal

Long Term

(>6 months)

Oral NOAEL =

3.4 mg/kg/day

(Dermal 

Absorption Rat = 

14%)

UFA = 10x

UFH = 10x

FQPA = 1x

Residential LOC 

for MOE = 100

Carcinogenicity – Rat

LOAEL = 9.2 mg/kg/day based on 

decreased body weight/body weight 

gain, kidney tubular casts and atrophy 

in both sexes; increased incidence of

liver necrosis and erosion/ulceration of 

the glandular- stomach and forestomach in males.

Inhalation 

Short Term 

(1-30 days)

Intermediate Term

(1-6 months)

Long Term

(>6 months)

NOAEL = 

0.23 mg/kg/day

(Air 

Concentration = 

0.001 mg/L)

UFA = 10x

UFH = 10x

FQPA = 1x

Residential LOC 

for MOE = 100

Inhalation Toxicity – Rat

LOAEL = 6.9 mg/kg/day (air 

concentration = 0.03 mg/L) based on 

duodenum mucosal hyperplasia and 

respiratory system findings including 

alveolar histiocytosis and olfactory 

atrophy/necrosis in nasal tissue.

Cancer (oral) Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor 

increases in two adequate rodent carcinogenicity studies.

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

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no 

observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from 

animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies).

FQPA SF = FQPA Safety Factor. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
Page 24 of 29

Attachment 6

Toxicity Profile for Pyraclostrobin

Table 6.1. Acute Toxicity Profile

Guideline Study Type MRID Results

Toxicity

Category

870.1100 Acute Oral Toxicity 45118302 LD50 ≥ 5000 mg/kg IV

870.1200 Acute Dermal Toxicity 45118305 LD50 >2000 mg/kg III

870.1300 Acute Inhalation Toxicity 45118308 0.31 mg/L < LC50 < 1.07 mg/L II

870.2400 Acute Eye Irritation 45118311

Minimal Eye Irritation

Maximum Average Score (MAS): 4.6 / 110

24 hr Maximum Irritation Score (MIS): 6.3 / 110

III

870.2500 Acute Dermal Irritation 45118314

Moderate Skin Irritation

Maximum Average Score (MAS): 2.2 / 8.0

24 h Maximum Irritation Score (MIS): 2.7 / 8.0

III

870.2600 Dermal Sensitization 45118317 Not a dermal sensitizer N/A

Table 6.2. Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

870.3050 Repeated Dose 

28-Day Oral Toxicity 

in Rodents (Rat)

45118322 (1999)

Dietary Concentration (ppm):

0, 20, 100, 500, 1500

Dose (mg/kg/day):

M: 0, 1.8, 9.0, 42.3, 120.2

F: 0, 2.0, 9.6, 46.6, 126.3

Acceptable / Guideline

NOAEL (mg/kg/day): M = 9.0 F = 9.6

LOAEL (mg/kg/day): M = 42.3 F = 46.6

Based on changes in hematology parameters, increased 

spleen weight (both absolute and relative), and 

histopathology in the spleen and liver, in addition to 

increased duodenal mucosal hyperplasia.

870.3100 90-Day Oral Toxicity 

in Rodents (Rat)

45118321 (1999)

45118322 (1999) – Dose Selection

Dietary Concentration (ppm):

0, 50, 150, 500, 1000 1500

Dose (mg/kg/day):

M: 0, 3.5, 10.7, 34.7, 68.8, 105.8

F: 0, 4.2, 12.6, 40.8, 79.7, 118.9

Acceptable / Guideline

NOAEL (mg/kg/day): M = 10.7 F = 12.6

LOAEL (mg/kg/day): M = 34.7 F = 40.8

Based on decreased body weights/body weight gains 

(males), decreased food consumption, increased relative 

liver weight and absolute and relative spleen weight in 

females, and histopathology of the duodenum, spleen 

and liver.

90-Day Oral Toxicity 

in Rodents (Mouse)

45118320 (1999)

Dietary Concentration (ppm):

0, 50, 150, 500, 1000 1500

Dose (mg/kg/day):

M: 0, 9.2, 30.4, 119.4, 274.4, 475.5

F: 0, 12.9, 40.4, 162.0, 374.1, 634.8

Acceptable / Guideline

NOAEL (mg/kg/day): M = 9.2 F = 12.9

LOAEL (mg/kg/day): M = 30.4 F = 40.4

Based on decreased body weights/body weight gains 

(males), changes in clinical chemistry (increased urea 

and decreased triglycerides), and increased incidences in 

females of lymph node apoptosis, thymus atropy, and 

ulcer/erosion in the glandular stomach.

870.3150 90-Day Oral Toxicity 

in Non-Rodents (Dog)

45118323 (1999) 

Dietary Concentration (ppm):

0, 100, 200, 450

Dose (mg/kg/day):

M: 0, 2.8, 5.8, 12.9

F: 0, 3.0, 6.2, 13.6

Acceptable / Guideline

NOAEL (mg/kg/day): M = 5.8 F = 6.2

LOAEL (mg/kg/day): M = 12.9 F = 13.6

Based on an increased incidence of diarrhea, clinical 

chemistry changes and mucosal hypertrophy of the 

duodenum (both sexes) and body weight loss, decreased 

food intake and decreased food efficiency (females 

only).
Page 25 of 29

Table 6.2. Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

870.3200 21/28-Day

Dermal Toxicity 

(Rabbit)

45118324 (1999)

Dose (mg/kg/day):

M: 0, 40, 100, 250

F: 0, 40, 100, 250

Unacceptable / Guideline

Unacceptable due to the lack of systemic 

effects at the highest dose tested (250 

mg/kg/day); the limit dose is 1000 

mg/kg/day.

Dermal

NOAEL (mg/kg/day): M = 40 F = 40

LOAEL (mg/kg/day): M = 100 F = 100

Based on scale formation, hyperkeratosis, and epidermal 

thickening at the site of application.

Systemic

NOAEL (mg/kg/day): M = 250 F = 250

LOAEL (mg/kg/day): M > 250 F > 250

870.3465 28-Day 

Inhalation Toxicity

(Rat)

46638801 (2005)

Applied Dose (mg/L):

M: 0, 0.001, 0.030, 0.300

F: 0, 0.001, 0.030, 0.300

Acceptable / Guideline

NOAEL (mg/L): M = 0.001 F = 0.001

LOAEL (mg/L): M = 0.030 F = 0.030

Based on findings of hyperplasia in the duodenum, 

alveolar histiocytosis in the lungs, and olfactory 

atrophy/necrosis in the nasal tissues.

870.3700 Prenatal 

Developmental 

Toxicity Study (Rat)

45118325 (1999) 

Gavage Dose (mg/kg/day):

F: 0, 10, 25, 50

Acceptable / Guideline

Maternal

NOAEL (mg/kg/day) = 10

LOAEL (mg/kg/day) = 25

Based on decreased body weights and body weight gains 

and reduced food consumption and reduced food 

efficiency.

Developmental

NOAEL (mg/kg/day) = 25

LOAEL (mg/kg/day) = 50

Based on increased incidence of dilated renal pelvis and 

cervical ribs.

Prenatal 

Developmental 

Toxicity Study 

(Rabbit)

45118326 (1999)

45437001 (2001)

Gavage Dose (mg/kg/day):

F: 0, 1, 3, 5, 10, 20

Acceptable / Guideline

Maternal

NOAEL (mg/kg/day) = 5

LOAEL (mg/kg/day) = 10

Based on body weight gains, reduced food consumption 

and reduced food efficiency.

Developmental

NOAEL (mg/kg/day) = 5

LOAEL (mg/kg/day) = 10

Based on increased resorptions per litter, increased postimplantation loss and dams with total resorptions.

870.3800 Reproduction and 

Fertility Effects 

(Rat)

45118327 (1999) 

Dietary Concentration (ppm):

0, 25, 75, 300

Dose (mg/kg/day):

M0: 0, 2.5, 7.4, 29.0

F0: 0, 2.6, 7.8, 30.4

M1: 0, 2.8, 8.6, 35.0

F1: 0, 3.0, 9.0, 36.0

Acceptable / Guideline

Parental

NOAEL (mg/kg/day): M = 29.0 F = 30.4

LOAEL (mg/kg/day): M > 29.0 F > 30.4

Reproductive

NOAEL (mg/kg/day): M = 29.0 F = 30.4

LOAEL (mg/kg/day): M > 29.0 F > 30.4

Offspring

NOAEL (mg/kg/day): M = 29.0 F = 30.4

LOAEL (mg/kg/day): M > 29.0 F > 30.4
Page 26 of 29

Table 6.2. Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

45596210 (2002) 

Dietary Concentration (ppm):

0, 200, 400, 600

Dose (mg/kg/day):

M: 0, 20.5, 39.9, 59.1

F: 0, 21.3, 42.5, 60.4

Acceptable / Non-Guideline

One-Generation Study

Parental

NOAEL (mg/kg/day): M = 20.5 F = 42.5

LOAEL (mg/kg/day): M = 39.9 F = 60.4

Based on reduced body weights and body weight gains.

Reproductive

NOAEL (mg/kg/day): M < 20.5 F < 21.3

LOAEL (mg/kg/day): M ≤ 20.5 F ≤ 21.3

Offspring

NOAEL (mg/kg/day): M ≥ 59.1 F ≥ 60.4

LOAEL (mg/kg/day): M > 59.1 F > 60.4

Based on a reduced pup body weights and body weight 

gains (a threshold body weight effect).

870.4100 Chronic Toxicity 

(Rat)

45118329 (1999)

Dietary Concentration (ppm):

0, 25, 75, 200

Dose (mg/kg/day):

M: 0, 1.1, 3.4, 9.0

F: 0, 1.5, 4.6, 12.3

Unacceptable / Guideline

Unacceptable due to low dose selection

NOAEL (mg/kg/day): M = 9.0 F = 12.3

LOAEL (mg/kg/day): M > 9.0 F > 12.3

There was no evidence of carcinogenic potential

Chronic Toxicity 

(Dog)

45118328 (1999)

Dietary Concentration (ppm):

0, 100, 200, 400

Dose (mg/kg/day):

M: 0, 2.7, 5.4, 10.8

F: 0, 2.7, 5.4, 11.2

Acceptable / Guideline

NOAEL (mg/kg/day): M = 5.4 F = 5.4

LOAEL (mg/kg/day): M = 10.8 F = 11.2

Based on an increased incidence of diarrhea and clinical 

chemistry changes (both sexes) and decreased body 

weight gain, decreased food intake and decreased food 

efficiency (females only).

870.4200 Carcinogenicity (Rat) 45118331 (1999)

Dietary Concentration (ppm):

0, 25, 75, 200

Dose (mg/kg/day):

M: 0, 1.2, 3.4, 9.2

F: 0, 1.5, 4.7, 12.6

Acceptable / Guideline

NOAEL (mg/kg/day): M = 3.4 F = 4.7

LOAEL (mg/kg/day): M = 9.2 F = 12.6

Based on differences in body weight and body weight 

gains, increased incidences of kidney tubular casts and 

atrophy in males and females, and in males, an increased 

incidence of necrosis of the liver, gross and microscopic 

evidence of erosion/ulcer of the glandular stomach and 

an increased incidence of acanthosis and ulcers of the 

forestomach.

Under the conditions of this study, there was no 

evidence of carcinogenic potential.

Carcinogenicity 

(Mouse)

45118330 (1999)

Dietary Concentration (ppm):

M: 0, 10, 30, 120

F: 0, 10, 30, 120, 180

Dose (mg/kg/day):

M: 0, 1.4, 4.1, 17.2

F: 0, 1.6, 4.8, 20.5, 32.8

Unacceptable / Guideline

Unacceptable due to low dose selection

NOAEL (mg/kg/day): M ≥ 17.2 F ≥ 32.8

LOAEL (mg/kg/day): M > 17.2 F > 32.8

Under the conditions of this study, there was no 

evidence of carcinogenic potential.
Page 27 of 29

Table 6.2. Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

870.5100 Bacterial Reverse 

Mutation Test

(Salmonella 

typhimurium)

45118332 (1997)

Applied Dose (μg/plate):

S9: 0, 20, 100, 500, 2500,

5000

Acceptable / Guideline

±S9: Negative up to 2500 μg/plate in the absence of 

cytotoxicity with precipitation above this concentration.

There was no evidence of treatment-induced mutant 

colonies above background levels.

870.5300 in vitro Mammalian 

Cell Gene Mutation 

Test

(Mouse Lymphoma 

Cells)

45118335 (1998)

Applied Dose (μg/mL):

S9: 0.625, 1.25, 2.5, 5.0, 10.0,

20.0

S9: 3, 4, 5, 6, 7,

8

S9: 1.25, 2.5, 5.0, 10.0, 20.0

Acceptable / Guideline

BAS 500 F was tested up to cytotoxic and solubility 

limit concentrations. The positive controls induced the 

appropriate response. There was no evidence of induced 

mutant colonies over background.

870.5375 in vitro Mammalian 

Chromosome 

Aberration Test

(Chinese Hamster 

Ovary cells)

45118333 (1999)

Applied Dose (μg/mL):

S9: 0, 6.25, 12.5, 25.0

+S9: 0, 3.125, 6.25, 12.5

S9: 0, 0.005, 0.010, 0.050, 0.100

Acceptable / Guideline

BAS 500 F was tested up to preciptating concentrations.

Positive controls induced the appropriate response.

There was no evidence of an increase in the number of

structural or numerical chromosomal aberrations 

induced over background. It is therefore concluded that 

BAS 500 F is not a clastogenic agent under the 

conditions of this study.

870.5395 Mammalian 

Erythrocyte 

Micronucleus Test

(Mouse)

45118334 (1998)

Gavage Dose (mg/kg/day):

M: 0, 75, 150, 300

F: 0, 75, 150, 300

Acceptable / Guideline

There was no significant increase in the frequency of 

micronucleated polychromatic erythrocytes in bone 

marrow at any dose level tested, at any time after

treatment. It is therefore concluded that BAS 500 F did 

not induce a clastogenic effect in either sex at any 

sacrifice time.

870.5550 Unscheduled DNA 

Synthesis in 

Mammalian Cells in 

Culture

(Rat Hepatocytes)

45118336 (1998)

Applied Dose (μg/mL):

Run 1: 0.01, 0.03, 0.1, 0.3, 1.0

Run 2: 0.004, 0.02, 0.5

Acceptable / Guideline

BAS 500 F was tested up to cytotoxic concentrations.

The positive controls induced the appropriate response.

There was no evidence that BAS 500 F induced 

unscheduled DNA synthesis, as determined by net 

nuclear silver grain counts.

870.6200 Acute Neurotoxicity 

Screening Battery

(Rat)

45118337 (1999)

Gavage Dose (mg/kg/day):

M: 0, 100, 300, 1000

F: 0, 100, 300, 1000

Acceptable / Guideline

Neurotoxicity

NOAEL (mg/kg/day): M = 1000 F = 1000

LOAEL (mg/kg/day): M > 1000 F > 1000

Systemic

NOAEL (mg/kg/day): M = 300 F = 1000

LOAEL (mg/kg/day): M = 1000 F > 1000

For males, based on 33% decreased body weight gain (p 

 0.01) on days 0-7; no similar effect was detected on 

days 0-14.

90-Day Neurotoxicity 

Screening Battery

(Rat)

45118401 (1999)

Dietary Concentration (ppm):

0, 50, 250, M: 750

F: 1500

Dose (mg/kg/day):

M: 0, 3.5, 16.9, 49.9

F: 0, 4.0, 20.4, 111.9

Acceptable / Guideline

Neurotoxicity

NOAEL (mg/kg/day): M = 49.9 F = 111.9

LOAEL (mg/kg/day): M > 49.9 F > 111.9

Systemic

NOAEL (mg/kg/day): M = 16.9 F = 20.4

LOAEL (mg/kg/day): M = 49.9 F = 111.9

Based on decreased body weight gain, food intake and 

food efficiency (both sexes) and decreased water intake 

(males only).
Page 28 of 29

Table 6.2. Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

870.7485 Metabolism and 

Pharmacokinetics 

(Rat)

45118403 (1998)

45118404 (1999)

Gavage Dose (mg/kg):

Single: 5, 50

Repeated: 50

Acceptable / Guideline

Nearly 35% of an oral dose of pyraclostrobin is 

absorbed with urinary and fecal excretions accounting 

for about 15% and 85%, respectively, and bile 

elimination accounted for about 30%. Two peak plasma 

concentrations were reached at 0.5-1 and 8 hours with 

lower plasma concentrations in males than females (by 

16-38%) during the early peak phase. Elimination was 

biphasic at a low dose with plasma half lives of nearly 

10/35 hours and monophasic at a high dose with a halflife of nearly 20 hours.

Tissue distribution was fast, peaking at 0.5 hours, and 

was slightly higher among females. Some of the highest 

concentrations were found in the liver, thyroid, kidney, 

lung, adrenal glands, and pancreas but all levels dropped 

by more than 20-fold within 72 hours. 

About 33 metabolites were identified in urine, feces, and 

bile with no sex- or dose-related differences but the 

position of the label seemed to alter the profile, 

particularly in the urine. Desmethoxy pyraclostrobin 

(500M07) is one of the major metabolites in rat and is 

also found in large amounts in plants (BF 500-3) and 

livestock (500M07). The rat metabolic pathway included 

phase-I reactions such as N-demethoxylation, various 

hydroxylations, and cleavage of the ether bond with 

subsequent oxidation; these reactions were followed by 

phase II glucuronidation and sulfation.
Page 29 of 29

Table 6.2. Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

870.7600 Dermal Penetration 

(Rat)

45118402 (1999)

Applied Dose (mg/cm2):

M: 0.015, 0.075, 0.375

Unacceptable / Guideline

Unacceptable because the actual dose was 

indeterminate due to material retained on 

the dressings being unavailable for 

absorption. 

The HIARC calculated and recommended a dermal 

penetration rate of 14%. (TXR#0051553: 10 FEB 2003)

In all three doses the largest portion of the dose was 

found in the Dressings (72.38-84.36%, 78.51-81.58% 

and 76.38-80.24% for the respective doses) The 

dressings consisted of silicone ring, nylon mesh cover 

and porous bandage. This material must be considered 

unavailable for absorption.

Dermal penetration of [14C-tolyl]-pyraclostrobin was 

low for all dose groups and time intervals (0.44-2.60%).

After an 8-hour exposure period, absorbed radioactivity 

accounted for 0.65%, 0.86% and 0.50% of the applied 

dose at nominal doses of 0.015, 0.075 and 0.375 

mg/cm2, respectively. After removal of the test 

substance and washing the site, absorption continued -

an additional 0.93-1.74% of the dose in each dose group 

over the next 64 hours; however, there was no 

concomitant decrease in radioactivity in the skin.

The percent of the dose absorbed was not dose 

dependent; however, the actual amount of the test 

material absorbed did increase with increasing dose 

level. Immediately following the 8-hour exposure 

period, absorbed radioactivity accounted for 0.105, 

0.757 and 2.27 μg/cm2at mean achieved doses of 0.017, 

0.087 and 0.428 mg/cm2. Comparing the increases from 

the low to high-dose groups, the amount of actual 

absorption increased by 21.6x compared to the 25.2x 

increase in the dose level. This pattern of absorption is 

commonly seen with a chemical which directly damages 

the stratum corneum of the skin.

870.7800 Immunotoxicity

(Mouse)

48830601 (1999)

Dietary Concentration (ppm):

0, 50, 200, 750

Dose (mg/kg/day):

F: 0, 13, 50, 165

Unclassified

Preliminary review of the studies does not indicate any 

immunotoxicity or systemic toxicity below 165 

mg/kg/day.

48830602 (2012)

Dietary Concentration (ppm):

0, 50, 200, 750

Dose (mg/kg/day):

F: 0, 13, 50, 202

Unclassified

48830603 (2012)

Dietary Concentration (ppm):

0, 50, 200, 750

Dose (mg/kg/day):

F: 0, 14, 55, 191

Unclassified