### UNITED STATES ENVIRONM E NTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

MEMORANDUM

DATE: May 21,2014 OFFICE OF CHEM IC A L SA F E T Y

AN D POLL U TION P RE VENT I ON



### SUBJECT: PYRACLOSTROBIN

. Human Health Assessment Seeping Document in Support of Regi s tration Review.

PC Code: 0991 00

Decision No.: 487331

Petition No.: NA DP Barcode: D417742 Registration No.: NA Regulatory Action: Registration Review

Case No.: 7034 Risk Assessment Type: NA

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

40 CFR: §180.582 MRIDNo.: NA

FROM: Barry O ' Ke efe, Sen i or Biologi st

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## 0 

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Cassi Wa ll s, Senior Bi ologist

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# i**~** Steve Funk, Senior Chemist ,.(**~~** 

### _ Vincent C hen

, Toxicologist**~** 

### Risk Assessment Branch III (RA B III)

He a lt h Effects Division (7509P)

Office of Pesticide Program s

THROUGH: Christine Olinger, Branch Chief 

# /J / ( _//

Risk Assessment Branch III**(RAB~f ~**  

### Health Effects D i vision (7509P)

Office of Pesticide Program s

TO: Matthew Manupella, Chemical Review Manager

Kevin Coste ll o, Branch Chief

Risk Management and Implem entation Branch II ( RMIB2)

Pesticide Re-Evaluation Di v i s ion (PRD) (7508P)

Offic e of P est icide Programs

Executive Summary

The HED Registration Review Team has evaluated the human health assessments and databa se for the fungicide pyraclostrobin to determine whether sufficien t data are available and if any updates are needed to the human health r i sk assessme nt s to support Registration Review. Pyraclostrobin i s currently reg i ste red for use numerous agricultural crops and on residential and golf course turf

, residential ornamentals, landscape gardens, fruit trees

, nut tree s, and greenhouse

grown tomato tran sp lan ts for the home consumer market. The HED re v iew of the proposed n ew

Pa ge 1 of29

### use ofpyraclostrobin on h er b subgroup 19 A and dill is pending (EPA Not ic e of Filing: EPA-HQOPP

- 2013-0798)

. To eva lu ate t he scope of work necessary t o support Registration Review,

HED has considered t h e previously finalized human-hea l th risk assessments conduc t ed for this

chemical as well any updates to the toxicity

, exposure, and usage databas es, and cu rr ent Agency

sc i en ce po li cy and risk assessment methodologies.

The toxicology da tabas e for pyraclostrobin i s complete and no addit ional toxico l ogy studies are needed at this time. The prima r y 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 reproduct i ve toxicity, neurotoxicity

, mutagenicity

, genotoxicity, or immunotoxicity. There i s no evidence for

increased susceptibility following pre

- and/or post-na t al exposures. Based on the ava il able data,

t ox i city endpoints and points of departure (PO D s) have been selected for acute and chronic dietary, short-term incidental oral, and short

- and i n termediate

- term dermal and inhala tion

exposure scenarios. Dermal absorption is 14%

. T he Food Qualit y Protection Act (FQPA) Safety

Factor ha s been reduced to IX since the toxicity and exposu re databases are comp le te and there

are no res i dual uncertainties for pre- and post-natal toxicity.

T he residue chemistry database is sufficient to support current reg ist rations of pyraclostrobin

. The nature of the residue in plan ts and livestock h as been adequate l y defined. Adequate fie ld
trial, rotat i ona l crop, lives t ock feeding, analytical method, primary crop processing, and storage stability data are avai l able.

A new dietary exposure and aggregate risk assessment are no t anticipated during Registration

Review

.

New occupationa l and residentia l handler and post-application exposure and r i sk assessments
will not be needed during Registra t ion 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 an y

exposure from spray d rift would be l ess than exposure on t urf. Howev er
, the Agency w ill

examine the need for a volat ili zation assessment during Registration Review for pyraclostrobin

based on the potential for exposure to bystande r s from agricultural applications.

Introduction



### Pyraclostrobin be lo ngs to t he strob il urin class of fungicides (P-methoxyacrylat e class of compounds). Strobilurins are synthetic a n alogs of a natural antifunga l substance w hi ch inhibit

spore germinat i on, mycelial growt h

, and sporu l ation of the fungus on the leaf su r face.

The most recent human hea l th risk assessment for pyraclostrobin was finalized in 2013 for

numerous new uses (D405065, B. O'Keefe, 07/03/2013)

. A new use risk assessment i s pending

for pyraclostrobin use on herb subgroup 19A and dill as we ll as c r op group conversions on stone
fruit group 12-12 and t ree nut gro u p 14 -1 2. Pyraclostrobin is c u rrent l y registered fo r use on

numerous agric ult ural and orc har d crops. It 

### is also registered fo r use on golf course and

. resident i al turf a nd gardens, fruit and nut trees, as we ll as on ornamentals, in cluding 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 concentrate s
, flowable concentrate s , soluble concentrate s , granular s , water dispersible granule s , and ready

- to

use solutions. Pyraclostrobin is also formula ted 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 prim ary 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, g enotoxicity, or immunotoxicity. D evelopmental 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 chron ic dietary, short

- term incidental oral,

and short

- and intermediate

- term dermal and inhalation exposure scenarios. The d ermal absorption factor for risk assessment is 14%.

The rabbit developmental toxicity study is used for assessing risks following ac ute dietary ( f emales 13+) as well as for short

- and intermediate

- term dermal exposures. For the acute dietary endpoint ( f

emales 13+), the developmental no observable adverse effect level (NOAEL) of 5 mg/kg/day is used as the POD based on the increased res orptions/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 decrease s 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 co mbined 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 lesi ons in males at 9.2 mg/kg/day (LOAEL)

.

For assessing risk following in cident al 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 decr eased 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, a nd 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 th e 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 toxicolo gy 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 adeq uate 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 c rop 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)

- 1 H

- pyrazol

- 3

- ol (BF 500

- 5) and 1

- (4

- chloro

- 2

- hydroxy phenyl)

- 1 H

- 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 Mul t i

- residue Methods, pyraclostrobin was s uccessfully 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.

### Page 5 of 29

Adequate crop field trials and processing studies are available to support e xisting 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.

A dequate 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 Exa mination 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 ) model s . The modeled peak surface water value of 35.6 μg/L was used in the acute dietary assessment.

A somewhat refined chroni c 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 pyraclostrob in (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% o f the chronic Population Adjusted Dose (c PAD) for the general US population and 27% of the cPAD for children 1

- 2

y ea rs old , the population subgroup with the highest estimated chronic dietary exposure to pyraclostrobin. The United States Department of Agri culture ( 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 proc essing 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 pyraclostr obin (0.0356 ppm) was calculated based on a turf

scenario for surface water.

The acute dietary risk estimate s 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 foo d and

### Page 6 of 29

drinking water at the 95 th 

### 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

- 4 9 years, with an estimated exposure at the 95 th 

### 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 scenario s 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 )

. R isk estimate margins of exposure (MOEs)

range 74 0 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 childre n 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.

R esidential uses of pyraclostrobin will result in short

- te rm (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 inci dental 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 pos t

- application assessments are based upon reliable surrogate study data that are not expected to underestimate risks.

A c hemical 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 l iquid, 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 spra y 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 type s 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 f or pyraclostrobin will be examined during Registration Review

.

Conclusions: R esidential handler and conventional residential post

- application assessment s will

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

vo latilization assessment to assess post

- application residential risk fr om 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

, a nd drinking water

.

In the most recent human health risk assessment ( D 405065

, B. O’Keefe, 07 /1 3 /20 13 ), 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 8 7 % of the aPAD for the most highly exposed subgroup, females 13

- 49 years old.

A s hort

- term aggregate risk assessment , which include d 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 exp osure from the residential pathway is not anticipated based on the current pyraclostrobin use pattern. The refore, the chronic aggregate risk (food and drinking water) is equivalent to the chronic dietary (food and drinking water) exposure estimate

.

Concl usions : Aggregate exposure to pyraclostrobin is currently not of concern to HED. N ew 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 t o 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 m ade 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 (M OEs >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 p ost

- application short

- and intermediate

- term dermal and inhalation exposures are possible for workers tending treated food crops

. Chemical

- specific dislodgeable foliar residue ( DFR ) data w ere previously submitte d , reviewed, and found acceptable for use in assessing post

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

not of concern to HED. Us ing current HED SOPs, risk estimate MOE s for dermal exposure ranged from 120 to 29,000.

Labels of r egistered pyraclostrobin products require restricted entry intervals ( REI s ) 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 post

app lication exposures. Updated o ccupational handle r and post

- application exposure assessments

are not needed during R egistration R eview.

Public Health and Pesticide Epidemiology Data

The evaluation of the OPP Incident Data System (IDS) indicated that for the main IDS, from January 1, 200 9 through June 1 5 , 201 4 , 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,

D 41 7740 , 0 2/11 /201 4 ) . In the aggregate IDS

, from January 1, 200 9 to June 1 5 , 201 4 , there were 36 reported incidents involvi ng 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 o r 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

- 20 10 identified a total of 65 cases involving pyraclostrobin (pc code 099100), stemming from 28 events. Of these, 52 cas es involved a single a ctive i ngredient. Forty three cases (83%) were work

- related. Forty one of the 52 cases (79%) resulted from aerial applications. Headline Fungicide (EPA R eg

. 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 Report 1



### .

Another multiple exposure event occurred in Iowa in 20 10 tha t 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 a ctive i ngredient 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, c orn 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 g reater 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 , w ill be considered in th e registr ation 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 pat terns 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 a re 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 lifest yle 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 evalu ate 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 assessment s which have been previously conducted for pyraclostrobin rel ied 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 exposur e databases such as the Pesticide

Ha ndlers 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 ex posure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relative to the ethical standards prevailing at the time the research was

conducted. A ll applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied , and t here is no regulatory barrier to continued

reliance on these studies

.

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 N ew Uses on Sugarcane, Globe Artichoke, Belgium Endive, Persimmon, Greenhouse Grown Tomato Transplants for Home Consumer Market, and Residential Ornamentals, L andscape 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

- 1 0, 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 D2 98017 0 8 /30/200 4 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 0 9 /30/2002 Occupational and Residential Risk Assessment to Support Request for a Section 3 Registration of Pyraclostrobin on a Variety o f Crops

- Joint Review with Health Canada Incident Report

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



### Attachment s 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 Table s
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]

- N

methoxycarbanilate

CAS name methyl N

- [2

- [[[1

- (4

- chlorophenyl)

- 1 H

- 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

### Page 14 of 29 Attachment 2

TABLE 2

. Physicochemical Properties of Technical Grade Pyraclostrobin.

Parameter Value References 1 

### (MRID) Melting point/range 63.7

- 65.2oC 45118213 pH Not applicable Density 1.367 g/cm 3 

### 45118214 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, pK
a 

### None (no dissociable moieties) Octanol/water partition coefficient, Log(K OW 

### ) 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

- 1 

### cm - 1 

### ]): 2.5x10 4 

### at 205 nm;

2.4x10 4 

### at 275 nm. 1996/10955 2

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)

- 1 H

- pyrazol

- 3

- ol

500M07

BF500

- 3 Methyl

- N

- (2{[1

- (4

- chlorophenyl)

- 1 H

- 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 Mexico b 

### Codex c 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 (methyl

N

- [[[1

- (4

- chlorophenyl)

- 1H

- pyrazol

- 3

- yl]oxy]methyl] phenylcarbamate),

calculated a s the stoichiometric equivalent of pyraclostrobin methyl N

- [2

- [[[1

- (4

- chlorophenyl)

- 1 H

- pyrazol

- 3

- yl]oxy] methyl]phenyl]

- N

methoxycarbamate, including the metabolite carbamic acid, N

- [2

- [[[1

- (4

- chlorophenyl)

- 1 H

- pyrazol

3

- yl]oxy]methyl]phenyl]

- , methyl

ester Pyraclostrobin

The residue is fat

soluble.



### Commodity a 

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

US Canada Mexico b 

### Codex c 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 Marrow

stem 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 Mexico b 

### Codex c 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 1 0.3 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 Mexico b 

### Codex c 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 oilsee d, 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, pi nto 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 Mexico b 

### Codex c 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, Ch inese 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

suc culent=immature seeds)

### Page 20 of 29

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



### US Canada Mexico b 

### Codex c 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 

### Mexico b 

### Codex c 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)

- 1H

pyrazol

- 3

- ol and 1

- (4

- chloro

- 2

- hydroxyphenyl)

- 1H

- pyrazol

- 3

- ol, expressed as parent compound Ruminants: methyl N

- [2

- [[[1

- (4

- chlorophenyl)

- 1 H

- pyrazol

- 3

- yl]oxy] methyl]phenyl ]

- N

methoxycarbamate, including the

metabolites convertible to 1

- (4

- chlorophenyl)

- 1 H

pyrazol

- 3

- ol and 1

- (4

- chloro

- 2

- hydroxyphenyl)

- 1 H

pyrazol

- 3

- ol

Poultry: methyl N

- [2

- [[[1

- (4

- chlorophenyl)

- 1 H

- pyrazol

- 3

- yl]oxy] methyl]phenyl ]

- N

methoxycarbamate, including the

metabolites convertible t o 1

- (4

- chlorophenyl)

- 1 H

pyrazol

- 3

- ol and 1

- (3

- chloro

- 4

- hydroxyphenyl)

- 1 H

pyrazol

- 3

- ol Pyraclostrobin

The residue is fat

soluble.



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

US Canada Mexico b 

### Codex c
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 Mexico b 

### Codex c 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. MR Ls 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

- Occupation al Human Health Risk

Assessments

Exposure Scenario Point of

Departure (P o D) 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 OAEL =

3 0 0 mg/kg/day UF A = 10x

UF H = 10x FQPA = 1 x a RfD =

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) N OAEL =

5.0 mg/kg/day UF A = 10x

UF H = 10x FQPA = 1 x a RfD =

0.05 mg/kg/day

aPAD =

0.05 mg/kg/day Developmental Toxicity

– Ra bbi t

LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of increased resorptions.

Chronic Dietary NOAEL =

3.4 mg/kg/day UF A = 10x

UF H = 10x FQPA = 1x c RfD =

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 fore

stomach in males.

Incidental Oral

Short Term (1

- 30 days)

Intermediate Term (1

- 6 months) Oral N OAEL =

5.8 mg/kg/day UF A = 10x

UF H = 10x FQPA = 1 x 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 N OAEL =

5.0 mg/kg/day

(Dermal Absorption Rate = 14%) UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Developmental Toxicity

– Ra bbi t

LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of increased resorptions and m aternal 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%) UF A = 10x

UF H = 10x FQPA = 1 x 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 fore

stomach in males.

Inhalation

Sh ort Term (1

- 30 days)

Intermediate Term (1

- 6 months) N OAEL =

0.23 mg/kg/day

(Air

Concentration = 0.001 mg/L) UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Inhalation Toxicity

– Ra t

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

- Occupation al Human Health Risk

Assessments

Exposure Scenario Point of

Departure (P o D) 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 (P o D) = 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 fa ctor. UF A = extrapolation from animal to human (interspecies). UF H = 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 (P o D) 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 N OAEL =

5.0 mg/kg/day

(Dermal Absorption Rate = 14%) UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Developmental Toxicity

– Ra bbi t

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%) UF A = 10x

UF H = 10x FQPA = 1 x 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 fore

stomach in males.

Inhalation

Short Term (1

- 30 days)

Intermediate Term (1

- 6 months)

Long Term (>6 months) N OAEL =

0.23 mg/kg/day

(Air

Concentration = 0.001 mg/L) UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Inhalation Toxicity

– Ra t

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 (P o D) = 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. UF A = extrapolation from

anima l to human (interspecies). UF H = 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 LD 50 ≥ 5000 mg/kg IV

870.1200 Acute Dermal Toxicity 45118305 LD 50 >2000 mg/kg III

870.1300 Acute Inhalation Toxicity 45118308 0.31 mg/L < LC 50 < 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

, 5 0 0

, 150 0 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 duoden al mucosal hyperplasia

.

870.3100 90

- Day Oral Toxicity

in Rodents (Rat) 45118321 ( 1999 )

45118322 (1999)

– Dose Selection Dietary Concentration (ppm): 0, 50

, 150

, 5 0 0

, 100 0 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

B ased 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 (199 9 )

Dietary Concentration (ppm): 0, 50

, 150

, 5 0 0

, 100 0 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 = 4 0 .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

- R odents (Dog) 45118323 ( 1999 )

Dietary Concentration (ppm): 0, 100

, 200

, 4 50 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 (Ra bbi t) 4 5118324 ( 1999 )

Dose (mg/kg/day) : M: 0

, 40

, 100

, 250

F: 0

, 40

, 100

, 250

Una cceptable / G uideline

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

A cceptable / G uideline NOAEL (mg/ L ) : M = 0.001 F = 0.001 LOAEL (mg/ L ) : M = 0.030 F = 0.0 3 0 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 (19 99 ) 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 post

implantation loss and dams with t otal resorptions.

870.3800 Reproduction and

Fertility Effects (Rat) 45118327 ( 1999 )

Dietary Concentration (ppm):
0, 25

, 75

, 30 0 Dose (mg/kg/day) : M 0 : 0, 2.5

, 7.4

, 29.0

F 0 : 0, 2.6

, 7.8

, 30.4

M 1 : 0, 2.8

, 8.6

, 35.0

F 1 : 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

, 60 0 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

B ased 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 T oxicity

( Rat ) 45118329 (199 9 )

Dietary Concentration (ppm):
0, 25

, 75

, 2 0 0 Dose (mg/kg/day) : M: 0, 1.1

, 3.4

, 9.0

F: 0, 1.5

, 4.6

, 12.3

Una cceptable / Guideline

Unacceptable due to low dose selection NOAEL (mg/kg/day) : M = 9.0 F = 1 2 .3 LOAEL (mg/kg/day) : M > 9 .0 F > 12. 3

There was no evidence of carcinogenic potential

Chronic T oxicity (Dog) 45118328 (199 9 )

Dietary Concentration (ppm): 0, 100

, 200

, 4 0 0 Dose (mg/kg/day) : M: 0, 2.7

, 5.4

, 10.8

F: 0, 2.7

, 5.4

, 11.2

A cceptable / 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 (199 9 ) Dietary Concentration (ppm): 0, 25

, 75

, 2 0 0 Dose (mg/kg/day) : M: 0, 1.2

, 3.4

, 9.2

F: 0, 1.5

, 4.7

, 12.6

A cceptable / 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 th is study, there wa s no evidence of carcinogenic potential

.

Carcinogenicity ( Mouse ) 45118330 (199 9 )

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

Una cceptable / 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

A cceptable / G uideline ±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 i n 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

A cceptable / G uideline 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 i n vitro Mammalian

Chromosome

Aberration Test ( C hinese H amster
O vary 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

A cceptable / G uideline 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 clastogeni c agent under the

conditions of this study.

870.5395 Mammalian

Erythrocyte

Micronucleus Test (Mouse) 45118334 (1 998 )

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 af ter

treatment. It is therefore concluded that BAS 500 F did not induce a clastogenic effect in either sex at any

sacrifice time.

870.55 5 0 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

A cceptable / G uideline 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.

870.6 2 00 Acute N eurotoxicity

Screening Battery (Rat) 45118337 (1 999 )

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) 45118 401 (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 (19 98 )

45118404 (1999) Gavage Dose (mg/kg): Single: 5, 50 Repeated: 50

A cceptable / G uideline 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 half

life 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 ident ified 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 la rge 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 phas e 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) 4 5118402 ( 1999 )

Applied Dose (mg/ cm 2 ) : M: 0.015

, 0.075

, 0.375

Una cceptable / G uideline

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 band a ge. This material must be considered

unavailable for ab sorption.

Dermal penetration of [ 14 C

- 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/cm 2 , 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 radio activity 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 accou nted f or 0.105, 0.757 and 2.27 μg/cm 2 at mean achieved doses of 0.017, 0.087 and 0.428 mg/cm 2

. 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. Th is pattern of absorption is commonly seen with a chemical which directly damages

the stratum corneum of the skin.

870.7800 Immunotoxicity

(Mouse) 4 8830601 (1999)

Dietary Concentration (ppm): 0, 50

, 20 0

, 750 Dose (mg/kg/day):

F: 0, 13

, 50

, 1 65

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

, 20 0

, 750 Dose (mg/kg/day):

F: 0, 13

, 50

, 202

Unclassified

48830603 (2012) Dietary Concentration (ppm): 0, 50

, 20 0

, 750 Dose (mg/kg/day):

F: 0, 14

, 55

, 1 91

Unclassified