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## Executive Summary

Carfentrazone-ethyl is a post-emergent herbic ide of the phenyl tri azolinone group used for

control of broadleaf weeds. It acts as an inhibitor of protoporphyrinoge n oxidase, which results in disruption of the cell membrane and desiccati on of susceptible plant species. Carfentrazoneethyl is registered for use on numerous agricultural crops, turf (including golf courses and residential lawns), and aquatic areas. The mo st recent HED human-health risk assessment on carfentrazone-ethyl was conducted in Ju ly of 2006 (Memo, 7/14/06, M. Clock-Rust et al

., D328332).

HED has evaluated the status of the human-h ealth assessments for carfentrazone-ethyl to

determine whether sufficient data are availabl e and whether any updates are needed to support Registration Review. HED has c onsidered the most recent human-health risk assessments for carfentrazone-ethyl with respect to its toxicit y, exposure, and usage databases, and the most updated Agency science policy and risk assessm ent methodologies to determine the scope of work necessary to support Registration Review.

The toxicity database for carfentrazone-ethyl is adequate to support th e existing registrations, with the exception of an immunot oxicity study, which is now require d as a part of 40 CFR Part

158.

The registrant has adequately addressed all de ficiencies identified in previous HED residue chemistry reviews. However, as part of the re gistration review HED is requesting revisions to some of the currently-registered labels and currently-established to lerances and identified issues concerning the livestock/fish/sh ellfish tolerance enforcement method (see Data Requirements Section for details). Provided these deficiencies are adequately addressed, the residue chemistry database will be considered adequate to support the resulti ng registrations.

Conservative acute and chronic di etary risk assessments were pr eviously conducted and resulted in exposure less than HED’s leve l of concern (LOC). Depending on the registrant response to the requested label changes and EFED’s registration review anal ysis concerning residues in drinking water, a revised dietar y exposure analysis may be ne cessary. HED notes that the currently registered labels incl ude application scenarios which we re not addressed in the residue estimates incorporated into the previous diet ary exposure analysis. However, based on the available residue data, the conser vative nature of the previous analysis, and the carfentrazone screening-level usage analysis (S LUA) data, HED concludes that in corporation of these uses in the dietary analysis will not likely result in exposure gr eater than HED's LOC.

New occupational exposure assessments will be necessary to support Registration Review. Several occupational handler scen arios have not been previously assessed (o r are not covered by already assessed uses). A revised residential expo sure assessment will need to be performed to

include residential handler scen arios and updated residential post- application scenarios. A new aggregate exposure assessment will be necessary to support Registration Review in light of the requirements for a new residential exposure assessment.

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## Hazard Identification/Toxicology

Carfentrazone-ethyl acts as an inhibitor of protoporphyrinogen oxidase, which results in disruption of the cell membrane a nd desiccation of susceptible pl ant species. In plants, this inhibition interferes with the chlorophyll biosyn thetic pathway. In mammals, this inhibition interferes with the heme biosynthetic pathwa y and results in increased porphyrin levels. Carfentrazone-ethyl has low acute oral, dermal, and inhalation toxicity (Toxicity Categories III and IV). It is minimally irritating to the eyes , non-irritating to the sk in, and is not a skin

sensitizer.

Following oral administration in the rat, carfentr azone-ethyl was rapidly absorbed as measured indirectly by the rapid excreti on of radioactivity (>85%) within the first 24 hours after dosing in both sexes. The urine contained the majority of the administered dose (72-87%); feces contained a lesser amount (10-26%). Extensive metabolism was indicated by only a small amount of the parent (0.06-2.8%) found in the feces; no parent was found in th e urine by 48 hours. There was no evidence suggestive of bioaccumulation; the total mean percentage of the administered dose found in all tissues and carcasses assayed wa s very low (0.09%, 0.08%), with the highest concentration found in the residual carcasses (0.0 8%) of both sexes. No difference in metabolic profile was observed between the sexes.

The subchronic toxicity studies in rats, mice, and dogs demonstrated that the primary effects of carfentrazone-ethyl were on hematological para meters (decreased mean corpuscular hemoglobin and mean corpuscular volume), increased urinar y porphyrin excretion, incr eased liver weights, and histopathology findings including hepatic pi gment deposition, hepatocytomegaly, single-cell necrosis, and individual mitosis. The chronic toxicity studies in rats and dogs demonstrated increased urinary porphyrin, and microscopic examin ation showed hepatoxicity in rats and mice. Fluorescence microscopy on liver sec tions also revealed red fluores cent granules consistent with porphyrin deposits in rats and mice.

There was no evidence of increased susceptibility in the prenatal developmental toxicity studies (rats and rabbits) or the multigeneration reproductiv e toxicity study in rats . Carfentrazone-ethyl induced a significant increase in litter incidences of wavy and thickened ribs in rats at a dose higher than the dose that caused maternal effects (staining of the abdominogenital area and of the cage pan liner). The rabbit prenatal developmenta l toxicity study did not yield any evidence of treatment-related prenatal developmental toxi city; no lowest-observed adverse-effect level (LOAEL) was identified. The offspring effect s from the 2-generation reproduction study were based on decreased pup body weight in both sexes of the F2 generati on at the highest dose tested (343 mg/kg/day) and at which maternal toxicity [i.e., decreased body-wei ght gains, increased liver weights, liver and bile duct histopathology, and reductions in the mean cell volume (F0 and F1 males, F1 females), mean cell hemoglobin (F 0 and F1 males, F1 females), hematocrit (F1 males), and hemoglobin (F1 ma les)] was also observed.

Acute and subchronic neurotoxicity studies are available for carfent razone-ethyl. Clinical signs (i.e., salivation) and mild decrea ses in motor activity were noted at day 0 only in an acute neurotoxicity study, while no signs of neurotoxicity were reported in a subchronic neurotoxicity study at the highest dose tested (1,178 mg/kg/day for males a nd 1,434 mg/kg/day for females).

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## In a 21-day dermal toxicity study, carfentrazone-ethyl failed to induce any type of dermal or systemic toxicity up to th e limit dose of 1,000 mg/kg/day.

The mutagenic test battery demonstrated that carfentrazone-ethyl is not mutagenic. In carcinogenicity studies in mice and rats, there was no indica tion of increased incidence of neoplasms and spontaneous tumor formation at the doses tested.

The HED Hazard Identification Assessment Review Committee (HIARC) met on 11-March1998 (HED Doc. No. 012550) and 8-March-2001 (HED Doc. No. 014567) to evaluate the carfentrazone-ethyl toxicity database and to sel ect toxicological endpoints for dietary, as well as occupational/residential risk assessments. The carfentrazone-ethyl toxi cological database was deemed sufficient to evaluate exposures from the proposed/registered applications. The HIARC requested a 28-day inhalation toxi city study as a condition of re gistration. However, based on low volatility and low inhalation toxicity (Toxi city Category IV) for carfentrazone-ethyl and since the inhalation margins of exposure (MOEs) associated with requested applications were >1,000, a waiver of the 28-day i nhalation toxicity study for th e proposed uses was deemed acceptable [HED Standard Operating Procedure (SOP) 2002.01: Guidance: Waiver Criteria for Multiple-Exposure Inhalation Toxicity Studies , 15-Aug-2002]. However, the Agency is currently reevaluating the inhala tion waiver criteria and based on this analysis, an inhalation study may be required in the future.

The Food Quality Protection Act (FQPA) Safety F actor (SF) of 1X used in the carfentrazoneethyl 2006 risk assessment (Memo, 7/14/06, M. Clock-Rust et al ., D328332) was based on policy developed in 2002. The FQPA policy was revised and updated in 2008 (see Hot Sheet #30). Under the current policy, previous uncertainty factors, which were utilized independently, are now components of the FQPA SF. In future risk assessments of carfentrazone-ethyl, the FQPA SF will need to be updated based upon changes in policy as well as submission of studies as a part of new data requirements in the 40 CF R Part 158 for conventional pesticide registration.

The most recent risk assessment for carfent razone-ethyl (Memo, 7/14/06, M. Clock-Rust et al

., D328332) provided a hazard characte rization and dose-response a ssessment for carfentrazoneethyl. A detailed listing of the e ndpoints, doses and uncertainty f actors selected for that risk assessment may be found in Table 4 of this document.

Immunotoxicity

An immunotoxicity study is required as a part of new data requirements in the 40 CFR Part 158 for conventional pesticide registration. Because the immune system is highly complex, studies not specifically conducted to assess immunotoxic endpoints are in adequate to characterize a pesticide’s potential immunotoxicity. While da ta from hematology, lymphoid organ weights, and histopathology in routine chroni c or subchronic toxicity studies may offer useful information on potential immunotoxic effects, these e ndpoints alone are insufficient to predict immunotoxicity. In the absence of required studies, EPA may use a database uncertainty factor of up to 10X. An immunotoxicity study on carfentrazone-ethyl s hould be conducted (see attachment). Once all data have been rece ived and reviewed, th e carfentrazone-ethyl Registration Review Team reco mmends that the points of depa rture and SFs used for risk assessment purposes be reexamined and a new risk assessment done, if necessary.

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## Endocrine Disruption

As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered ap proach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 scr eening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticid e active ingredients and 9 inert ingredients.

This list of chemicals was selected based on th e potential for human exposure through pathways such as food and water, residen tial activity, and certain post-applic ation agricultural scenarios.

This list should not be construed as a lis t of known or likely e ndocrine disruptors.

Carfentrazone-ethyl was not among the group of 58 pesticide active ingredie nts on the initial list

to be screened under the EDSP. Under FFDCA sec. 408(p) the Agen cy must screen all pesticide chemicals. Accordingly, EPA anticipates issuin g future EDSP test orders/data call-ins for all pesticide active ingredients.

Conclusions The toxicity database for carfentrazone-ethyl is adequate to support exis ting registrations and registration review; however, as specified in the new 40 CFR Pa rt 158 data requirements, an immunotoxicity study is required, an d depending on the outcome of the Agency’s reevaluation of the inhalation waiver criteria, an inhalation study may also be re quired In addition, the toxicity endpoint/dose selection along with the FQPA SF may need to be re-evaluated according to current policy for future actions.

Residue Chemistry

HED reviewed and carfentrazone-ethyl is currently registered for applic ation to crop groups 1-17 and 19 as well as the following crops: acerola , atemoya, avocado, banana, birida, borage, cacao, cactus, canistel, canola, cherimoya, coconut, coffee, cotton, crambe, custard apple, date, feijoa, fig, flax, grape, guava, hops, horseradish, ilm a, jaboticaba, juneberry, kava, kiwifruit, lingonberry, longan, lychee, mango, mustard, noni, o live, palm heart, papaya, passionfruit, pawpaw, peanut, persimmon, pistachio, pomegra nate, pulasan, pummelo, rambutan, safflower, salal, sapodilla, black sapote, mamey sapote, sours op, Spanish lime, star apple, starfruit, stevia, strawberry, strawberrypear, sugar apple, sugarcane, sunflower, t ea, ti, vanilla, wassaba, and wax jambu. Broadcast application to surface water is also registered. As a result of these

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## registrations, crop/livestock/fish/shellfish toleran ces are established for the combined residues of carfentrazone-ethyl and carfent razone-chloropropionic acid at 0.05-10 ppm (40 CFR 180.515).

Use Directions: The following is a summary of the a pplication scenarios evaluated by HED for the above listed crops: (1) cereal grain, soybean (feeding forage and hay to livestock is prohibited), and cotton - preplant, foliar, and harvest-aid applicatio n; (2) peanut and sugarcane - preplant, postemergent-banded (between rows), a nd harvest-aid application; (3) vegetables, herbs and spices, canola, sunflower, sweet sorghum, stra wberry, ti, prickly pear cactus, strawberrypear, wasabi, stevia, and kava - preplant and posteme rgent-banded (between rows) application; (4) potato - preplant and harvest-aid application; (5) tree, vine, a nd bush crops; tobacco; and hops - soil-directed application and appl ication directed to the base of the plant; and (6) grass and horseradish - foliar application. Carfentrazone-ethyl is also registered for soil-directed application to cranberry (EPA Reg. No. 279-3308 and 279-3309); HED has not reviewed a petition concerning applicat ion of carfentrazone-ethyl to cran berry and a cranbe rry tolerance is not currently established. It is noted that as part of an IR-4 reduced field trial proposal, HED concluded that the berries crop group 13 residue da ta may be translated to cranberry provided the application scenarios were similar (D280458, T. Bloem, 24-Jan-2002); note that the IR-4 reduced field trial proposal was not a request for registration.

Based on the master label report provided by PRD a nd a review of the current ly registered labels and the application scenarios reviewed by HED, HED requests that the labels be revised as follows: (1) labels with instructions for app lication to soybean should include a restriction prohibiting the feeding of soybean forage and hay to livestock; (2) labels should restrict harvestaid application to only the following crops: cer eal grains, soybean, cotton, peanut, sugarcane, and potato; (3) labels should indicate the follo wing rotational crop rest rictions: seasonal application rate of <0.031 lb ai/ acre - rotate to a registered crop at anytime and to all other crops 12 months after application; seas onal application rate of >0.031 lb ai/acre - rotate to only a registered crop; and (4) instructions for appli cation to cranberry should be removed from all

labels.

Residues of Concern: The petitioner has submitted sufficient information to determine the nature of the residue in/on the registered prim ary crops, livestock, and dr inking water (see Table 5 for a summary of the residues of concern). Based on the confined rotational crop study (0.031 lb ai/acre; field rotational crop study has not been submitted), the Metabolism Assessment Review Committee (MARC) determined that carfentrazone-ethyl and F8426-ClPAc are of concern in rotational crops; the MARC also expre ssed concern for residues of the benzoic acid compounds if the levels found are similar to or greater than the parent and F8426-ClPAc. Therefore, the MARC decision memorandum did not include a definitive statement relating to

the residues of concern in rotati onal crops for tolerance enforcement and risk assessment. Based on the confined rotational crop study, the applica tion rates evaluated by HE D for the registered crops, and the following HED-recommended rotationa l crop restrictions, residues in rotational crops are anticipated to be insignificant: seasonal application rate of <0.031 lb ai/acre - rotate to a registered crop at anytime a nd to all other crops 12 months after applicati on; seasonal application rate of >0.031 lb ai/acre - rotate to only a registered crop.

Analytical Enforcement Methods: An adequate method is available for enforcing the currently established crop tolerances (D245908, J. Stokes, 20-May-199 8; D260428, T. Bloem, 23-Nov1999). The proposed livestock enforcement method P-3151M has been radiovalidated and

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## undergone a successful independent laboratory valid ation (ILV). HED forw arded this method to the Analytical Chemistry Laboratory (ACL) fo r a petition method validation (PMV; D305152, T. Bloem, 12-Jul-2004). Provided the ACL dete rmined that method P-3151M was acceptable,

HED concluded that method P-3151M would be appropriate for enforcement of the

livestock/fish/shellfis h tolerances (D294823, T. Bloem, 15-Jul-2004). To date, HED has not received information from ACL concerning th e adequacy of method P-3151M for tolerance enforcement. The procedure to determine if an analytical method is appropriate for tolerance enforcement has changed such that a laboratory trial by EPA is no longer required. As part of the registration review process, HED will eval uate method P-3151M using this procedure and make a determination concerning the appropriatene ss of this method for tolerance enforcement.

If the method is found to be unsuitable for toleran ce enforcement, then the registrant will need to proposed and validate a new method.

Magnitude of the Residue - Primary Crops, Livestock, Fish, and Shellfish: Provided the labels are revised as indicated above, the submitted magn itude of the residue studies are adequate and to support the registered applications scenarios. HED notes that the HED recommended banana tolerance was 0.10 ppm while the currently established banana tolerance is 0.20 ppm. In addition, HED previously recommen ded that the following establishe d tolerances be deleted: cotton hulls, meal, and oil (D303274, T. Bloem, 19-May-2004); barley flour, barley bran, millet flour, oat flour, rye flour, rye bran, wheat bra n, wheat flour, wheat middlings, wheat shorts, and wheat germ (D351363, T. Bloem, T. Bloem, 14- May-2008); and caneberry subgroup 13A (berry crop group 13 tolerance has been establis hed at the same level; D296322, T. Bloem et al. , 21-Jul2004). Also, the cereal grain forage , hay, stover, and straw tolerances need to be altered as there are conflicting commodity definiti ons and/or tolerance levels.

Conclusions The registrant has adequately addressed all de ficiencies identified in previous HED residue chemistry reviews. However, HED as identified th e following issues during registration review.

● The registrant should revise the labels as follows: (1) labels with instructions for application to soybean should include a restriction prohibiti ng the feeding of soybean forage and hay to livestock; (2) labels should restrict harvest-aid application to only the fo llowing crops: cereal grains, soybean, cotton, peanut, sugarcane, and potato; (3) labels shoul d indicate the following rotational crop restrictions: season al application rate of <0.031 lb ai/acre - rotate to a registered crop at anytime and to all other crops 12 months af ter application; seasonal application rate of

>0.031 lb ai/acre - rotate to onl y a registered crop; and (4) in structions for application to cranberry should be removed from all labels.

● As part of the registration review process, HED will evaluate method P-3151M to determine the suitability of this method for enforcement of the livestock/fish/shellfis h tolerances. If the

method is found to be unsuitable for tolerance en forcement, then the registrant will need to proposed and validate a new method.

● The banana tolerance should be lowered to 0.1 0 ppm and the following currently-established

tolerances should be deleted: cotton hulls, cotton meal, cotton o il, barley flour, barley bran, millet flour, oat flour, rye flour, rye bran, wh eat bran, wheat flour, wheat middlings, wheat shorts, wheat germ, and caneberry subgroup 13A. Al so, the cereal grain forage, hay, stover, and

straw tolerances need to be altered as ther e are conflicting commodity definitions and/or

tolerance levels. Fina lly, the tolerance expression should be updated as follows to conform to

current standards: Tolerances are established for residues of carfentrazone-ethyl, including its

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## metabolites and degradates, in or on the commod ities listed below. Compliance with the following tolerance levels is to be determined by measuring carfentrazone -ethyl (ethyl alpha-2- dichloro-5-[4-(difluoromethyl )-4,5-dihydro-3-methyl-5-oxo-1 H -1,2,4-triazol-1-yl]-4- fluorobenzenepropanoate) and its metabolite ca rfentrazone-chloropropio nic acid (alpha, 2- dichloro-5-[4-difluoromethyl )-4,5-dihydro-3-methyl-5-oxo-1 H -1,2,4-triazol-1-yl]-4- fluorobenzenepropanoic acid).

Dietary Exposure

Acute and chronic dietary risk assessments were previously conducted using the Dietary Exposure Evaluation Model - Food Consumption Intake Database (DEEM-FCIDTM, ver. 2.03; D328829, T. Bloem, 14-Jun-2006). DEEM-FCID inco rporates food consumption data from the USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII; 1994-1996 and 1998). The acute and chronic analyses a ssumed 100% crop treated, DEEM (ver. 7.81) default processing factors, and modeled (Pestic ide Root Zone Model/Exposur e Analysis Modeling System; PRZM/EXAMS) drinking water estimates resulting from the caneberry application rate (yielded the highest drinking water concentr ations). Tolerance level resi dues were assumed for livestock, fish, shellfish, cereal grain, and cotton commodities. Since the residues of concern for risk assessment for the remaining commodities includes compounds which are not included in the tolerance expression, the acute a nd chronic analyses did not empl oy tolerance-level residues for these commodities. However, the residues used in the risk assessment for these commodities are considered conservative estimates of expect ed residues following treat ment at the maximum labeled rate. The resulting acute ( ≤ 1% aPAD; children 1-2 years old were the most highly exposed subgroup) and chronic ( ≤ 89% cPAD; children 1-2 years old were the most highly exposed subgroup) exposure estimates ar e less than HED’s level of concern.

Conclusions Depending on the registrant response to the requ ested label changes and EFED’s registration review analysis concerning resi dues in drinking water, a revise d dietary exposure analysis may be necessary. HED notes that the currently regist ered labels include application scenarios which

were not addressed in the residu e estimates incorporated into the previous dietary exposure analysis. Based on the available residue data, th e conservative nature of the previous analysis, and the carfentrazone SLUA data, HED concludes that incorporation of these uses in the dietary analysis will not likely resu lt in exposure greater than HED's LOC.

Residential Exposure

Carfentrazone-ethyl is registered for use on lawn s and turf, including golf courses and residential lawns. It is also registered for aquatic appli cations. The residential s cenarios that have been assessed previously for carfentrazone-ethyl include only postapplica tion scenarios for the residential lawn use and the aquatic use (see Tabl e 6). The currently registered residential use patterns, maximum application rates and fo rmulations are provided in Table 7.

Residential Handlers

HED has determined that residential handlers ar e likely to be exposed to carfentrazone-ethyl

residues via dermal and inhalation routes duri ng mixing, loading, and applying activities from the residential lawn use. HED expects the dura tion of these exposures to be short-term (1-30 days) due to the infrequent use pattern associat ed with the carfentraz one-ethyl products. No

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## residential handler scenarios have been assessedpreviously by HED. In the 2006 carfentrazoneethyl risk assessment (D328332), it was stated that the label for review only allowed for application by Professional Lawn Care Operators to residentia l lawns and to golf courses; therefore, exposure to homeowne rs was not expected. However, a review of the currently registered carfentrazone-ethyl product labels indi cated that there are registered labels for home lawn use that do not restrict app lication to professionals only.

Residential Post-Application HED has determined that there is potential for post-application exposure to adults and children from the turf and aquatic uses of carfentr azone-ethyl. In the Ju ly 2006 risk assessment (D328332), a residential post-application exposur e assessment was conducted that assessed incidental oral exposure to children from the home lawn use, as well as inhalation and ingestion exposure to adult and child swimme rs from the aquatic use. No chemical-specific data were available; therefore, the Re sidential SOPs, as well as HED’s Swimmer Exposure Assessment Model (SWIMODEL) V 1.0 (W. Dang and Vers ar, 27-MAR-1999), were used to estimate

exposure.

All residential incidental oral exposure and ri sk estimates for the home lawn use were below HED’s LOC (MOEs ≥ 100) at an application ra te of 0.031 lb ai/A. A ll incidental oral and inhalation exposure and risk estimates for th e aquatic uses were below HED’s LOC (MOEs

≥ 100) at an application rate of 0.2 lb ai/A.

During review of the previous carfentrazone-ethyl risk assessments and review of the currently registered carfentrazone-ethyl la bels, it was noted that the 2006 assessment used an application rate of 0.03 lb ai/A for the home lawn use, wh ereas a label review fo r carfentrazone-ethyl revealed a higher registered application rate for home lawns (0.04 lb ai/A).

Based on the Agency's current practices, a qua ntitative postapplication inhalation exposure assessment has not been performed for carfentrazone -ethyl at this time. However, volatilization of pesticides may be a potential source of postapplication inhalation exposure to individuals nearby to pesticide applications. The Agency s ought expert advice and input on issues related to volatilization of pes ticides from its Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/ meetings/2009/120109meeting.html ). The Agency is in the process of ev aluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, s ubsequently, the way to in corporate postapplication inhalation exposure into the Agency 's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need fo r a quantitative postapplic ation inhalation exposure assessment for carfentrazone-ethyl.

Conclusions

There is sufficient information available to asse ss residential exposure. A revised residential assessment will need to be performed to incl ude residential handler scenarios and updated residential post-application scenar ios (higher turf/home lawn applic ation rate). HED is currently revising its Residential SOPs, in cluding those used to determine exposure associated with home lawn treatments. Reviewers should incorporate new guidance from the updated SOPs to refine exposure estimates.

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## Aggregate Risk Assessment

Aggregate exposure risk assessments were perf ormed for the acute, chronic, and short-term exposure scenarios. Since the use pattern was not expected to result in exposure of more than a 30-day duration, longer-term aggregate assessments were not performed. A cancer aggregate risk assessment was not performed because ca rfentrazone-ethyl is not carcinogenic.

Dietary (food and drinking water) and residential post-applicati on residential exposures were considered because there is a potential for indivi duals to be exposed concurrently through these routes. All potential exposure pa thways were assessed in the a ggregate risk assessment. The acute and chronic aggregate risk assessments were conducted taking into account exposure estimates from dietary consumption of carfentra zone-ethyl (food and drinking water). For the short-term aggregate risk assessment, estimates of the residential exposure and dietary (food and drinking water) exposures were used. For carfent razone-ethyl, the turf and aquatic residential scenario estimates were aggregated with the chronic dietary (food) to provide a worst-case estimate of short-term aggregate risk for the U. S. population and children 1- 2 years old (the child population subgroup with the highest estimat ed chronic dietary food exposure).

The most recent aggregate exposure assessment was conducted in July of 2006 (Memo, 7/14/06,

M. Clock-Rust et al ., D328332). Acute and chronic aggregat e risks are made up only of dietary sources; therefore, the exposure estimates provided in the diet ary exposure analysis represent acute and chronic aggregate exposur es, respectively, and are not of concern to HED. Short-term aggregate exposures to carfentr azone-ethyl were not of conc ern to HED [i.e., MOEs were ≥ LOC = 100] (see Table 8).

Conclusions

There is sufficient information available to a ssess aggregate exposure. A revised aggregate assessment will need to be performed, which will incorporate the revised residential exposures.

Occupational Exposure

As mentioned previously, carfentr azone-ethyl is registered for use on several agricultural crops, non-crop use sites, turf (including golf courses, ornamental lawns and turf, and home lawns), and aquatic areas.

Occupational Handlers No chemical-specific data were available with which to assess potential exposure to pesticide handlers. Therefore, occupational handler asse ssments were based primarily on surrogate unit exposures from the Pesticide Handler's Exposure Database (PHED) as presented in the PHED Surrogate Exposure Guide and from the Outdoor Residential Exposure Task Force (ORETF).

The risk calculations were based on maximum application rates and assuming maximum area treated per day. Handler's exposure and risk were calculated at two levels of mitigation: baseline (long pants, a long-sleeved shirt, no chemical-re sistant gloves, and no re spirator) and personalprotective equipment (PPE; baseline clothing with chemical-resista nt gloves and/ or respirator, when necessary). The occupational handler scenarios that have been previously assessed are listed in Table 9. The currently registered occ upational use patterns, ma ximum application rates and formulations are provided in Table 10.

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## The most recent occupational handler exposur e assessment was conducted in July of 2006 (Memo, 7/14/06, M. Clock-Rust et al ., D328332). Provided that commercial pesticide handlers used label-prescribed PPE (i.e., long pants, l ong-sleeved shir t, shoes + socks and protective gloves), all assessed MOEs were not of concern to HED (i.e., MOEs were ≥ LOC = 100).

The following items were noted during review of the previous carfentrazone-ethyl risk assessments and review of the currently re gistered carfentrazone -ethyl product labels:

• The flagger scenario for all uses that allo w for aerial application was only previously assessed at a rate of 0.016 lb ai/A, but a re view of carfentrazone-ethyl product labels indicates higher rates are registered for aerial applications.

• For certain crops/use sites, there are hi gher application rates allowed on currently registered labels than have been assessed previously.

• For scenarios that allow for spot treatmen ts (indicating use of handheld equipment), mixer/loader/applicator exposures from us e of handheld equipment have not been assessed previously (or have not been a ssessed using maximum allowable rates/area treated and/or appropr iate unit exposures).

Conclusions

There is sufficient information available to a ssess occupational handler exposure. Several occupational handler scenarios need to be assess ed, which have not been assessed previously, or need to be reassessed based on higher application rates or area treated.

Occupational Post-Application An appropriate endpoint attribut able to exposure through the de rmal route for carfentrazoneethyl was not identified. Theref ore, dermal postapplication exposure assessments have not been performed for carfentrazone-ethyl.

Based on the Agency's current practices, a quant itative occupational post- application inhalation exposure assessment has not been performed fo r carfentrazone-ethyl. However, there aremultiple potential sources of post-application inhalation exposure to individuals performing postapplication activities in previously treated fiel ds. These potential sour ces include volatilization of pesticides and resuspension of dusts and/or pa rticulates that contain pesticides. The Agency sought expert advice and input on is sues related to volatilization of pesticides from its FIFRA SAP in December 2009. The Agency received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SA P/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report as well as available postapplica tion inhalation exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and procedures, to identify the need for and, s ubsequently, the way to incorporate occupational post-application inhalation exposur e into the Agency's risk asse ssments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post-application inhalation exposure assessment for carfentrazone-ethyl.

Conclusions

There is sufficient information available to a ssess occupational posta pplication exposure. Currently, since there are no dermal points of departure for carfentrazone-ethyl, a dermal postapplication exposure assessment is not necessar y. Based on the Agency's current practices, a quantitative occupational post-application inhala tion exposure assessment has not been performed for carfentrazone-ethyl; however, if new policies or procedures are put into place, the Agency may revisit the need for a qu antitative occupational post-applicati on inhalation exposure assessment.

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## Public Health and Pesticide Epidemiology Data

A summary report listing incidents re ported to EPA for carfentrazone-ethyl will be provided for the docket. The reported incidents will be screened in more detail during the development of the Final Work Plan for carfentrazone-ethyl.

The OPP Incident Data System (IDS) was util ized for poisoning incident data on the active ingredient carfentrazone-ethyl (Memo, S. Reco re, D382672, 11/30/10). IDS records incidents of generally high severity in more detail, in softwa re called the main IDS. This system stores incident data for death, major and moderate in cidents, and it includes more details about the location, date and nature of the incident. Th e less-severe human inci dents are reported by registrants as counts, which are called aggreg ate summaries and are recorded in separate software. For IDS aggregate summaries, from January 1, 2002 to May 27, 2010, there are 37 cases reported for carfentrazone-ethyl. Because it falls within the categories reported as counts (which includes minor, unknown, or no effects), ther e is no unique report that provides details about the incident, and single-chemical incident s are not distinguished from multiple-chemical incidents. For the main IDS, from January 1, 2002 to October 7, 2010, there is one case reported for single-chemical carfentrazone-ethyl only in th e database. For this incident, the symptoms were unknown or not specified.

Conclusions Based on the low frequency and severity of incide nt cases, there does not appear to be a concern at this time that would warrant further investig ation. The Agency will co ntinue to monitor the

incident information and if a con cern is triggered, additional analysis will be included in the risk

assessment.

Tolerance Assessment and International Harmonization

U.S. permanent tolerances and Canadian, Mexica n, and Codex maximum residue limits (MRLs) are

summarized in Table 3. The U.S. and Canadian carfentrazone-ethyl residue definitions are

harmonized and the numerical values are also ha rmonized for milk (0.05 ppm) and sorghum grain (0.25 ppm). For the remaining commodities for which both the U.S. and Canada have tolerances/ MRLs, the U.S. tolerance is expressed with tw o significant figures (0.10 ppm or 0.80 ppm), while the Canadian MRL is expressed with one significa nt figure (0.1 or 0.8 ppm). It is noted that Mexico adopts U.S. tolerances and/or Codex MRLs for its export purposes. Since there are no carfentrazone-ethyl Codex MRLs, the U.S. toleran ces and Mexican MRLs should be harmonized.

Environmental Justice

Potential areas of environmental ju stice concerns, to the extent po ssible, were considered in the human-health risk assessment, in accordance w ith U.S. Executive Order 12898, “Federal Actions

to Address Environmental Just ice in Minority Populations an d Low-Income Populations,” (http://www.hss.energy.gov/nuclearsafety/env/ guidance/justice/e o12898.pdf). The OPP typically considers the highest potential exposures from the le gal use of a pesticide when conducting human-health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diet s within the U.S., and people who may be exposed when harvesting crop s. Should these highest exposures indicate potential risks of concern, OPP further refines th e risk assessments to ensure that the risk

estimates are based on the best available information.

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## Human Studies

Past carfentrazone-ethyl risk asse ssments rely in part on data fr om studies in which adult human subjects were intentionally exposed to a pest icide to determine their dermal and inhalation exposure. Many such studies, i nvolving exposure to many different pesticides, comprise generic pesticide exposure databases such as PHED a nd the Outdoor Residential Exposure Task Force (ORETF). EPA has reviewed all the studies in these multi-pesticide gene ric exposure databases, and on the basis of available evidence has found them to have been neither fundamentally unethical nor significantly deficien t relative to standards of et hical research conduct prevailing when they were conducted. There is no regulator y barrier to continued reliance on these studies, and all applicable requirements of EPA’s Rule fo r the Protection of Huma n Subjects of research (40 CFR Pat 26) have been satisfied.

Deficiencies or Data Requirements

Toxicology

• An immunotoxicity study is now requir ed as a part of revised CFR 158.340.

Residue Chemistry

• The registrant should revise the labels as follows : (1) labels with inst ructions for application to soybean should include a rest riction prohibiting the feeding of soybean forage and hay to livestock; (2) labels should restrict harvest-aid application to only the fo llowing crops: cereal grains, soybean, cotton, peanut, sugarcane, and potato; (3) labels should indicate the following rotational crop restric tions: seasonal application rate of <0.031 lb ai/acre - rotate to a registered crop at anytime and to all ot her crops 12 months afte r application; seasonal application rate of >0.031 lb ai/ acre - rotate to only a registered crop; and (4) instructions for application to cranberry should be removed from all labels.

• As part of the registration review process, HED will evaluate method P-3151M to determine the suitability of this method for enforcement of the livestock/fish/shellfis h tolerances. If the

method is found to be unsuitable for tolerance en forcement, then the registrant will need to proposed and validate a new method.

• The banana tolerance should be lowered to 0.10 ppm and the following currently-established

tolerances should be deleted: cotton hulls, cotton meal, cotton o il, barley flour, barley bran, millet flour, oat flour, rye flour, rye bran, wh eat bran, wheat flour, wheat middlings, wheat shorts, wheat germ, and caneberry subgroup 13A. Also, the cereal grain forage, hay, stover, and straw tolerances need to be altered as there are conflicting commodity definitions and/or

tolerance levels. Fina lly, the tolerance expression should be updated as follows to conform

to current standards: Tolerances are esta blished for residues of carfentrazone-ethyl, including its metabolites and de gradates, in or on the commoditi es listed below. Compliance with the following tolerance levels is to be determined by measuri ng carfentrazone-ethyl (ethyl alpha-2-dichloro-5-[4-(difl uoromethyl)-4,5-dihydro- 3-methyl-5-oxo-1 H-1,2,4-triazol1-yl]-4-fluorobenzenepropanoate) and its meta bolite carfentrazone-chloropropionic acid (alpha, 2-dichloro-5-[4-difluorom ethyl)-4,5-dihydro-3-methyl-5-oxo-1 H -1,2,4-triazol-1-yl]- 4-fluorobenzenepropanoic acid).

ORE

• None.

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## References

Referenced Memoranda.

Author DP Barcode Date Title
B. Madden D232457 27-Jan-1997 New Chemical Screen for Carfentrazone (F8426) - 128712. Toxicology and Residue Chemistry Data Requirements for a Permanent Tolerance for Use of

Carfentrazone on Field Co rn, Wheat and Soybeans.

José J. Morales et al. D236431 15-Jul-1997 CARFENTRAZONE-ETHYL - 128712. Health

Effects Division Risk Char acterization Document for Use of Carfentrazone-ethyl (F8426 50 DF) in/on Corn and Wheat (PP#6G4615).

José J. Morales et al. D233587 24-Jul-1998 CARFENTRAZONE-ETHYL - 128712: Health

Effects Division Risk Char acterization Document for the First Food Use of Carfentrazone-ethyl in/on Corn, Soybeans, and Wheat.

Tom Bloem et al. D258880, D258882, and

D241256 25-May2000 PP#s 7F04795 - Human Health Risk Assessment for the Application of Carfentrazone-Ethyl to Cereal Grains. DP Barcodes: D258880, D258882, and

D241256. Submission #: S533492. Case: 288204. Chemical #: 128712. EPA Registration Number: 279- 3194 (AimTM and SharkTM).

Tom Bloem et al. D266146, D271183,

and D270508 5-Apr-2001 PP#s 0F06151 (cotton), 0E06183 (caneberry), and 002217-IGE (turfgrass) - Carfentrazone-Ethyl in/on Cotton, Caneberry and Turfgrass. Health Effects Division (HED) Risk Asse ssment. PC Code 128712. DP Barcodes D266146, D271183, and D270508. Case 293003, 293206, and 069065. Submissions S579800, S589462, and S588204.

Tom Bloem et al. D296322 and

D305499 21-Jul-2004 Carfentrazone-Ethyl (PC Code 128712) - Human Health Risk Assessment for Proposed Aquatic Application of Carfentrazone-Ethyl and the Application of Carfentrazone-Ethyl to Numerous Fruit and Vegetable Crops. D296322 and D305499. Mary Clock-Rust et al. D328332,

D322956 14-Jul-2006 Carfentrazone-Ethyl. Section 3 Request for Use on Cereal Grain, Peanut, Soybean and Sugarcane as a

Harvest-Aid. Health Effects Division (HED) HumanHealth Risk Assessment. Tim Leighton D246199 3-Jun-1998 OCCUPATIONAL AND RESIDENTIAL

EXPOSURE ASSESSMENT AND

RECOMMENDATIONS FO R CARFENTRAZONEETHYL (ID No. 7F4795; Chemical No. 128712) DP

Barcode D246199. J. Troy Swackhammer D273969 5-Apr-2001 Occupational, Residential, and Non-Occupational Exposure Risk Assessment/Characterization for the

Use of Carfentrazone-Eth yl for Postermergence Control of Broadleaf Weeds in Cotton and Turfgrass

and for Control of Primocanes in Caneberries. PC

Code: 128712 DP Barcode: D273969.J. Troy Swackhammer D277894 28-Sep-2001 Update to Occupational, Residential, and NonOccupational Exposure Risk

Assessment/Characterization for the Use of Carfentrazone-Ethyl on Turfgrass. PC Code: 128712;

DP Barcode: D277894.

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## Referenced Memoranda.

Author DP Barcode Date Title

M. Dow D297385 31-Dec2003 CARFENTRAZONE-ETHYL - Exposure/Risk Assessment for Proposed Uses of Carfentrazone-ethyl on Numerous Tree Fruits and Nuts, Vegetables, Grapes, Tobacco, Potato, Berries, Grass, Hops and for Aquatic Weed Control. Mark I. Dow D329138,

D329139 30- May2006 CARFENTRAZONE-ETHYL - Exposure/Risk Assessment for Proposed Uses of Carfentrazone-ethyl as a Harvest Aid on Sugarcane, Peanut, Cereal Grains, Sorghum and Soybean.

J. Stokes TXR No.

0012659 19-Jun-1998 Carfentrazone-ethyl. Decisions of the Metabolism Assessment Review Committee (MARC).

T. Bloem D294823 15-Jul-2004 Carfentrazone-e thyl. Petition for Tolerances on Fish and Shellfish. Summary of Analytical Chemistry and

Residue Data.J. Stokes D245908 20-May1998 Carfentrazone-ethyl in/on Corn, Soybeans, and

Wheat. Petition Method Validation Results.

T. Bloem D260428 23-Nov1999 Analytical methodology and petition methodvalidation for the quantification of carfentrazoneethyl residues in/on corn, wheat, and soybeans. T. Bloem D305152 12-Jul-2004 Carfentrazone-ethyl in Livestock Commodities. Request Petition Method Validation (PMV).T. Bloem D303274 19-May2004 Carfentrazone-Ethyl in/on Cotton. Review ofInformation Submitted by the Petitioner (29-May2003) Addressing the Residue Chemistry Deficiencies Identified in D278800 (T. Bloem, 15-Nov-2001).T. Bloem D351363 14-May2008 Review of Amendment (dated 21-Feb-2008) Submitted in Response to Residue Chemistry Deficiencies Identified in D328830 (T. Bloem, 26- Apr-2006) Concerning the Harvest-Aid Application of Carfentrazone-Ethyl to Cereal Grains and Soybean. T. Bloem D280458 24-Jan-2002 Carfentrazone-ethyl in/on Various Commodities. Interregional Research Project No. 4 (IR-4) Reduced Residue Chemistry Data Set Proposal. T. Bloem D328829 14-Jun-2006 Carfentrazone-Ethyl - Acute and Chronic Dietary Exposure Assessments.

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## Attachments

Attachment 1: Chemical Identity Table ....................................................................................... 17 Attachment 2: Physicochemical Properties Table ..................................................................... 178 Attachment 3: Tolerance Summary Table ................................................................................... 19 Attachment 4: Endpoint Selection Table ..................................................................................... 2 4 Attachment 5: Residue Chemistry Tables .................................................................................... 25

Attachment 6: Resident ial Exposure Tables ................................................................................ 26

Attachment 7: Adult and Child Aggregate Risk Estimates ......................................................... 27 Attachment 8: Occupational Exposure Tables ............................................................................. 28

Attachment 9: DCI Table ...................................................................................................... ....... 38

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## Attachment 1: Chemical Identity Table

Table 1. Chemical Identity.

Chemical Structure

N F Cl

N N O

CHF 2

CH 3 Et O Cl

O

Common name carfentrazone-ethyl

Company experimental name F8426

IUPAC name ethyl ( RS )-2-chloro-3-{2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1 H -1,2,4- triazol-1-yl]-4-fluorophenyl}propionic acid

CAS name ethyl α ,2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1 H -1,2,4-triazol-1-yl]-4- fluorobenzenepropanoic acid

CAS # 128639-02-1

Chemical Structure

N F Cl

N N O

CHF 2

CH 3 HO Cl

O

Common name carfentrazone-chloropropionic acid

Company experimental name F8426-Cl-PAc

CAS name α ,2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1 H -1,2,4-triazol-1-yl]-4- fluorobenzenepropanoic acid

### Carfentrazone Human-Health Assessment Scoping Document D382666

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## Attachment 2: Physicoc hemical Properties Table

Table 2. Physicochemical Properties of the Technical Grade Test Compound.

Melting point -22.1 ° C

pH not available

Density 1.46 g/mL at 20 ° C

Water solubility (20°C) 12 mg/L

Solvent solubility ( μ g/L at 20°C) acetone - >2000; toluene - 900; di chloromethane - >2000; hexane - 30; ethanol - >2000; ethyl acetate - >2000

Vapor pressure 1.2 x 10 -7 mm Hg (25 ° C); 5.4 x 10 -8 mm Hg (20 ° C)

Dissociation constant (pK

a ) no dissociation constant

Octanol/water partition coefficient Log(K OW ) log K

ow = 3.36

UV/visible absorption spectrum not available

### Carfentrazone Human-Health Assessment Scoping Document D382666

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## Attachment 3: Tolerance Summary Table

Table 3. Summary of US and Internationa l Tolerances and Maximum Residue Limits.

US Canada Mexico 1 

### Codex 2



### Residue Definition:

40CFR180.515 carfentrazone-ethyl (ethyl- α -2-dichloro-5-[- 4-(difluoromethyl)-4,5-dihydro-3-methyl-5-

oxo-1 H -1,2,4-triazol-1-yl]-4-fluorobenzenepropanoate) and its metabolite: carfentrazonechloropropionic acid (alpha, 2-dichloro-5-[-4- difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1

H

-1,2,4-triazol-1-yl]-4- fluorobenzenepropanoic acid) ethyl α , 2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl5-oxo-1 H -1,2,4-triazol-1-yl]-4- fluorobenzenepropanoate, including the

metabolite α , 2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl5-oxo-1 H -1,2,4-triazol-1-yl]-4- fluorobenzenepropanoic acid None

Commodity Tolerance (ppm) /M aximum Residue Limit (mg/kg) Commodity US Canada Mexico Codex

Acerola 0.10
Almond, hulls 0.20 Atemoya 0.10

Avocado 0.10

Banana 0.20 Barley, bran 0.80 Barley, flour 0.80

Berry group 13 0.10 0.1 blackberries, blueberries, currant, elderberries, goosebe rries, huckleberries, loganberries, raspberries

Birida 0.10 Borage 0.10 Cacao bean, bean 0.10

Cactus 0.10

Caneberry subgroup 13A 0.1 0.1 blackberries, loganberries, raspberries

Canistel 0.10 Canola 0.10 0.1 rapeseed (canola)
Cattle, fat 0.10 0.1 Cattle, meat 0.10 0.1 Cattle, meat byproduc ts 0.10 0.1 Cherimoya 0.10

Coconut 0.10 Coffee, bean, green 0.10 Corn, field, forage 0.20 Corn, sweet, forage 0.20 Corn, sweet, kernel plus cob

with husk removed 0.10 0.1

Cotton, gin byproducts 10 Cotton, undelinted seed 0.20
Cotton, hulls 0.60
Cotton, meal 0.35
Cotton, refined oil 1.0
Crambe, seed 0.10 Custard apple 0.10
Date, dried fruit 0.10 Feijoa 0.10 Fig 0.10

Fish 0.30
Flax, seed 0.10 0.1 flaxseed Fruit, citrus, group 10 0.10

Fruit, pome, group 11 0.10 0.1 apples, crabapples, loquats, mayhaws, priental pears, pears, quinces

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### Table 3. Summary of US and Internationa l Tolerances and Maximum Residue Limits.

US Canada Mexico 1 

### Codex 2

Fruit, stone, group 12 0.10 0.1 apricots, nectarines, peaches, plumcots, plums, pr une plums, sweet cherries, tart cherries
Goat, fat 0.10 0.1
Goat, meat 0.10 0.1 Goat, meat byproducts 0.10 0.1 Grain, aspirated grain fractions 1.8 Grain, cereal, forage, fodder and straw group 16, except corn and sorghum; forage 1.0

Grain, cereal, forage, fodder and straw, group 16, hay 0.30

Grain, cereal, forage, fodder and straw, group 16, stover 0.30

Grain, cereal, forage, fodder and straw, group 16, except rice; straw 0.10

Grain, cereal, group 15 0.10 0.1 barley, buckwheat, field corn, oats, pearl millet, proso m illet, popcorn grain, rye, teosinte, triticale, wheat, wild rice

Grain, cereal, group 15 (except rice grain and sorghum grain) 0.10 0.1 barley, buckwheat, field corn, oats, pearl millet, proso m illet, popcorn grain, rye, sweet corn kernel plus cob with husks removed, teosin te, triticale, wheat,

wild rice Grain, cereal, stover 0.80
Grain, cereal, straw 3.0 Grape 0.10 0.1 Grass, forage 5.0 Grass, hay 8.0

Guava 0.10 Herbs and spices group 19 2.0 0.1 mustard seeds (oilseed type) Hog, fat 0.10 Hog, meat 0.10 Hog, meat byproducts 0.10 Hop, dried cones 0.10
Horse, fat 0.10 0.1
Horse, meat 0.10 0.1 Horse, meat byproducts 0.10 0.1

Horseradish 0.10 0.1 Horseradish roots

Ilama 0.10

Jaboticaba 0.10 Juneberry 0.10
Kava, roots 0.10

Kiwifruit 0.10 Lingonberry 0.10 0.1 Longan 0.10 Lychee 0.10 Mango 0.10

Milk 0.05 0.05
Millet, flour 0.80
Mustard, seed 0.10 0.1

Noni 0.10 Nut, tree, group 14 0.10 Oat, flour 0.80

Okra 0.10

Olive 0.10

Palm heart 0.10 Palm heart, leaves 0.10 Papaya 0.10

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### Table 3. Summary of US and Internationa l Tolerances and Maximum Residue Limits.

US Canada Mexico 1 

### Codex 2

Passionfruit 0.10 Pawpaw 0.10

Peanut 0.10 Peanut, hay 0.10

Persimmon 0.10

Pistachio 0.10 Pomegranate 0.10 Poultry, meat byproducts 0.10

Pulasan 0.10

Pummelo 0.10

Rambutan 0.10 Rapeseed, forage 0.10 Rapeseed, seed 0.10 Rice, grain 1.3
Rice, hulls 3.5
Rice, straw 1.0 Rye, bran 0.80 Rye, flour 0.80 Safflower, seed 0.10 0.1 safflower seeds

Salal 0.10 0.1 Sapodilla 0.10 Sapote, black 0.10 Sapote, mamey 0.10 Sheep, fat 0.10 0.1 Sheep, meat 0.10 0.1 Sheep, meat byproducts 0.10 0.1

Shellfish 0.30 Sorghum, forage 0.20 Sorghum, grain 0.25 0.25 Sorghum, sweet 0.10 Soursop 0.10 Soybean, seed 0.10 Spanish lime 0.10 Star apple 0.10

Starfruit 0.10

Stevia 0.10 Strawberry 0.10 0.1 Strawberrypear 0.10 Sugar apple 0.10 Sugarcane 0.15 Sunflower, seed 0.10 0.1 sunflower seeds
Tea, dried 0.10
Ti, leaves 0.10
Ti, roots 0.10

Vanilla 0.10

Vegetable, Brassica, leafy, group 5 0.10 0.1 bok choy Chinese cabbages, broccoli, broccoli raab, Brussels sprouts, cabbages, cauliflower, Chinese broccoli, 21nglish mustard cabbages, collards,, kale, kohlrabi, mustard greens, mustard spinach, napa Chinese cabbages, rape

greens

Vegetable, bulb, group 3 0.10 0.1 chinese onions, dry bulb onions, garlic, great-headed garlic, green onions, leeks, potato onions, shallots, tree onion tops, welsh onion tops,

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### Table 3. Summary of US and Internationa l Tolerances and Maximum Residue Limits.

US Canada Mexico 1 

### Codex 2

Vegetable, cucurbit, group 9 0.10 0.1 balsam appl es, 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 Vegetable, foliage of legume, except soybean, subgroup 7A 0.10

Vegetable, fruiting, group 8 0.10 0.1 bell peppers, eggplants. Ground cherry, non-bell peppers, pepinos, pepper hybrids, tomatillos, tomatoes

Vegetable, leafy, except Brassica, group 4 0.10 0.1 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 pursiane , garland chrysanthemum, head lettuce, leaf lettuce, New Zealand spinach, orach leaves, radicchio, rhubarb, spinach, swiss chard, upland cress, vine spinach, winter purslane Vegetable, leaves of root and tuber, group 2 0.10

Vegetable, legume, group 6 0.10 0.1 Dry (adzuki beans, beans, blackeyed peas, broad beans, catjang seeds, chickpeas, cowpea seed, 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, soybeans, tepary beans, urd beans); 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); grain lupin; succulent shelled ( blackeyed peas, broad beans, cowp eas, english peas, garden peas, green peas, lima beans, peas, pigeon peas, southern peas, soybeans, tepary beans, urd

Vegetable, root and tuber, group 1 0.10 0.1 arracacha, ar rowroot, black salsify roots, carrot roots, cassava roots, celeriac roots, chayote roots, chicory roots, Chinese artichokes, chufa, edible burdock roots, edible canna, garden beet roots, ginger roots, ginseng roots, Jerusalem artichokes, lerens, oriental radish roots, parsnip roots, potatoes, radish roots, rutabaga roots, salsify roots, skirret roots, Spanish salsify roots, sugar beet roots, sweet potato roots, tanier corms, taro corms, true yam tubers, turmeric roots, turnip roots, turnip-rooted chervil roots, turnip-rooted parsley roots, yam bean roots
Wasaba, roots 0.10 Wax jambu 0.10

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### Table 3. Summary of US and Internationa l Tolerances and Maximum Residue Limits.

US Canada Mexico 1 

### Codex 2

Wheat, bran 0.80 Wheat, flour 0.80 Wheat, germ 0.80 Wheat, middlings 0.80
Wheat, shorts 0.80 

### MRLs with no US equivalent
Barley milling fractions 0.8 Buckwheat milling fractions 0.8 Millet milling fractions 0.8 Oat milling fractions 0.8 Rye milling fractions 0.8 Triticale milling fractions 0.8 Wheat milling fractions 0.8
Completed: M. Negussie; 08/09/2010 1. Mexico adopts US tolerances and/ or Codex MRLs for its export purposes. 2. * = absent at the limit of quantitation; Po = postharvest treatment, such as treatme nt of stored grains. PoP = processed po stharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measur ed on the fat portion of the sample. MRLs i ndicated as proposed have not been finalized by the CCPR and the CAC.



## Section 18 emergency exemptions. Time-limited tolerances are established for combined residues

of the herbicide carfentrazone-e thyl and its chloropr opionic acid metabolite in connection with use of the pesticide under secti on 18 emergency exemptions granted by EPA. These tolerances have expired and were revoked on the da tes specified in th e following table.

Commodity Parts per million Expiration/Revocation Date

Hop, dried cones 0.30 6/30/05

Tomato, paste 0.60 6/30/07

Tomato, puree 0.60 6/30/07

Vegetable, fruiting, group 8 0.10 6/30/07

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## Attachment 4: Endpoint Selection Table

Table 4. Summary of Toxicological Doses and Endpoints for Carfentrazone-ethyl from the July 2006 Human-Health

Risk Assessment a



### . Exposure

Scenario Dose Used in Risk Assessment, UF FQPA SF and LOC for Risk

Assessment Study and Toxicological Effects

Acute Dietary - all populations NOAEL = 500 mg/kg/day FQPA SF = 1x
aPAD = 5 mg/kg/day 

### Acute Neurotoxicity-Rat; Clinical observations (salivation) and decreased motor activity.

Chronic Dietary – all populations NOAEL = 3.0 mg/kg/day FQPA SF = 1x cPAD = 0.03 mg/kg/day 

### Chronic Toxicity-Rat; observations of liver histopathology and total urinary porphyrin.

Short-term Incidental

Oral (1-30 Days) NOAEL = 500 mg/kg/day FQPA SF = 1x

LOC for MOEs >100 

### Acute Neurotoxicity-Rat; Clinical observations (salivation) and decreased motor activity.

Intermediate-term

Incidental Oral
(1-6 months) NOAEL = 50 mg/kg/day FQPA SF = 1x

LOC for MOEs >100 

### Subchronic Toxicity-Dog; decreased bodyweight gain, increased porphyrin levels.

Dermal
(Any Time Period) 

### No systemic toxicity was seen at the limit-dose (1000 mg/kg/day) in a 21-day dermal toxicity study in rats; therefore, these risk assessments are not required.

Short-term Inhalation (1-30 days) NOAEL = 500 mg/kg/day FQPA SF = 1x

LOC for MOEs >100 

### Acute Neurotoxicity-Rat; Clinical observations (salivation) and decreased motor activity.

Intermediate-term

Inhalation (1-6 Months) NOAEL = 50 mg/kg/day FQPA SF = 1x

LOC for MOEs >100 

### Subchronic Toxicity-Dog; decreased bodyweight gain, increased porphyrin levels.

Long-term Inhalation
(more than 6 months) 

### NOAEL = 3 mg/kg/day FQPA SF = 1x

LOC for MOEs >100 

### Chronic Toxicity-Rat; observations of liver histopathology and total urinary porphyrin.

Cancer Classification: Not likely to be carci nogen; cancer risk assessment is not required.

a. Memo, 7/14/06, M. Clock-Rust et al ., D328332

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

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## Attachment 5: Residue Chemistry Tables

Table 5. Residues of Concern in Cr ops, Livestock, and Fish/Shellfish.

Matrix Tolerance Expression Re sidues for Risk Assessment

cereal grain and cotton 1,3 carfentrazone-ethyl and F8426-ClPAc carfentrazone-ethyl and F8426-ClPAc

remaining registered crops 2,3 carfentrazone-ethyl and F8426-ClPAc carfentrazone-ethyl, F8426-ClPAc, 3-OH-F8426- ClPAc, 3-OH-F8426-BAc, F8426-BAc, and Me-3-

OH-F8426-BAc

livestock/fish/shellfish 4 carfentrazone-ethyl and F8426-ClPAc carfentrazone-ethyl and F8426-ClPAc

rotational crops See text above.

drinking water 5 -- carfentrazone-ethyl, F8426-ClPAc, and F8426-CAc

1 The residues of concern for risk assessment are based on the registered foliar application scenario for these crops and the corn, wheat, and soybean metabolism studies; see the MARC decision memora ndum (J. Stokes, 19-Jun-1998) and D328332 (M. Clock-Rust et al. , 14-Jul-2006) for further information.

2 The residues of concern for risk assessment are based on the so il-directed applications; the co rn, wheat, soybean, and radish metabolism studies; and the confined rotational crop study; see the MARC deci sion memorandum (J. Stokes, 19-Jun-1998) and D328332 (M. Clock-Rust et al. , 14-Jul-2006) for further information.

3 HED notes that if a future foliar regist ration is requested for a crops other than a cereal grain or a le gume vegetable, then the

residues of concern for risk assessmen t will be carfentrazone-ethyl, F8426-Cl PAc, 3-OH-F8426-ClPAc, 3-OH-F8426-BAc, and F8426-BAc (residues for tolerance enfor cement will be carfentraz one-ethyl and F8426-ClPAc); this decision is based on the soybean, wheat, corn, and radish metabolism studies.

4 See MARC decision memorandum (J. Stokes, 19-Jun-1998) and D294823 (T. Bloem, 15-Ju l-2004) for further information.

5 See MARC decision memorandum (J. Stokes, 19-Jun-1998) for further information.

### Carfentrazone Human-Health Assessment Scoping Document D382666

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## Attachment 6: Residential Exposure Tables

Table 6. Residential Scenarios That Have Been Assessed.

Scenario Application rate (lb ai/A) Area treated (acres)

Mixer/Loader/Applicator: None previously assessed

Postapplication

Hand-to-mouth incidental oral for toddlers 0.03 N/A

Inhalation/Incidental Ingestion for swimmers 0.2 NA

Table 7. Summary of Registered Residential Use Patt erns, Formulations, and Maximum Application Rates for Carfentrazone-ethyl.

Crop / Site Formulation 1 

### Equipment Max App Rate Scenario Covered?

M/L/A Postapp
Residential Handler and post-application

Residential lawns DF Handheld equipment 0.03 lb ai/A N Y

Liquid Handheld equipment 0.04 lb ai/A N N RTU Trigger-pump 0.015 lb ai/A N Y Residential post-application only (PCO applied)

Golf course turf EC/liquid Ground; Handheld equipment 0.09 lb ai/A

N/A N/A 2 

### DF (water soluble bags) Ground; Handheld equipment 0.12 lb ai/A

1. EC = emulsifiable concentrate; DF = dry flowable; RTU = ready-to-use. 2. Typically only dermal posta pplication exposure would be assessed and ther e is no dermal point of departure for carfentrazone-ethyl.

### Carfentrazone Human-Health Assessment Scoping Document D382666

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## Attachment 7: Adult and Child Aggregate Risk Estimates

Acute and chronic aggregate exposure assessments include food and water exposure (acute and chronic residential exposure is not anticipated). The acute and chronic dietary exposure analysis incorporated drinking water direc tly, and therefore, the acute and chronic dietary risk estimates represent acute and chronic aggregate risk fo r carfentrazone-ethyl. The acute and chronic exposure estimates are below HED’s LOC. Inte rmediate-term (1-6 months), non-dietary postapplication exposure to carfentr azone-ethyl is considered unli kely based on the use pattern. Therefore, an intermediate-term aggreg ate risk assessment was not performed.

Short-term aggregate exposures were conducte d by combining chronic dietary, inhalation, and incidental oral exposures. Short-term aggregate exposure to carfentrazone-e thyl, as a result of all registered and proposed uses, is less than HED’s LOC.

Table 8. Short-Term Aggregate Risk for Carfentrazone-ethyl.

Population Subgroup NOAEL (mg/kg/day) Target

MOE Average

Food Exposure (mg/kg/day) Dietary

MOE 1 Residential Exposure 2
(mg/kg/day) Combined Exposure (food + residential) Aggregate

MOE 3
(food + residential)
General U.S. Population 500 100 0. 009177 54,000 0.0001051 0.0093 54,000 All Infants < 1 year old 500 100 0.015951 31,000 0.0009545 0.017 30,000 Children 1-2 years old 500 100 0. 026621 19,000 0.0009545 0.028 18,000 Children 3-5 years old 500 100 0. 021464 23,000 0.0002539 0.022 23,000 Children 6-12 years old 500 100 0.013265 38,000 0.0002539 0.014 37,000 Youth 13-19 years old 500 100 0.008021 62,000 0.0002539 0.0083 60,000 Adults 20-49 years old 500 100 0.007154 70,000 0.0001051 0.0073 69,000 Adults 50+ years old 500 100 0.006730 74,000 0.0001051 0.0068 73,000 Females 13-49 years old 500 100 0. 006948 72,000 0.0001051 0.0071 71,000
1. Dietary MOE = NOAEL/exposure. 2. Residential Exposure = total residential exposure. 3. Aggregate MOE = (NOAEL ÷ (Avg Food Exposure + Residential Exposure)).

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## Attachment 8: Occupational Exposure Tables

Table 9. Occupational Scenarios That Have Been Assessed.

Scenario Application rate (lb ai/A) Area treated (acres)

Mixer/Loader

(1) Liquids for aerial application 0.03 1200

0.075 350

(2) Wettable powders for aerial application 0.03 1200

0.075 350 (3) Dry flowable for aerial application 0.016 1200

Applicator

(4) Aerial sprays 0.03 1200

0.016 1200

(5) Groundboom sprays 0.03 200

0.016 200

0.1 80

Flagger

(6) Aerial applications 0.016 350

Mixer/Loader/Applicator

(7) High pressure handwand (aquatic sites) 0.2 50 (8) Backpack (aquatic sites) 0.2 2 (9) Handgun (lawns) 0.03 5Carfentrazone Human-Health Assessment Scoping Document D382666Page 29 of 39Table 10. Summary of Registered Occupational Use Patterns, Formulations and MaximumApplication Rates for Carfentrazone-ethyl.Crop / Use SiteFormula-tionApplication EquipmentMaximumapplicationrate (lb ai/A)Scenario Covered?NotesMixer/loaderApplicatorFlaggerMixer/loader/applicatorArtichoke (Jerusalem) EC/Liquid Aerial; Groundboom 0.0625 Y YNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.Artichoke (Globe) EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.AvocadoEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNBerry (caneberry,blackberry, boysenberry,black raspberry, redraspberry, cranberry)EC/LiquidAerial; Groundboom;Handheld equipment0.1NNNNHigher rate on labels than has been assessedpreviously. Spot treatments allowed on labelsfor liquid formulations – not assessed.DF Aerial; Groundboom 0.1NNNN/ABorage seedEC/Liquid Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNBushberry (blueberry,currant, elderberry,gooseberry, huckleberry)EC/Liquid Aerial; Groundboom 0.096NNNN/AHigher rate on labelsfor liquid formulationthan has been assessedpreviously. Flaggerpreviously assessed at 0.016 lb ai/A rate.Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNCanolaEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNBarley (small grains)EC/LiquidAerial; Groundboom;Handheld equipment0.0625 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.031 YYNN/ABuckwheatEC/LiquidAerial; Groundboom;Handheld equipment0.064 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.064 YYNN/ACorn (field corn, seedcorn, popcorn, cornsilage, sweet corn)EC/LiquidAerial; Groundboom;Handheld equipment0.064NNNNHigh acreage crop not assessed at highest rateallowed on label. Spot treatments allowed onlabels for liquid formulations – not assessed.DF Aerial; Groundboom 0.064NNNN/ACarfentrazone Human-Health Assessment Scoping Document D382666Page 30 of 39Table 10. Summary of Registered Occupational Use Patterns, Formulations and MaximumApplication Rates for Carfentrazone-ethyl.Crop / Use SiteFormula-tionApplication EquipmentMaximumapplicationrate (lb ai/A)Scenario Covered?NotesMixer/loaderApplicatorFlaggerMixer/loader/applicatorMillet (proso and pearl;small grains)EC/LiquidAerial; Groundboom;Handheld equipment0.0625 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.031 YYNN/AOats (small grains)EC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNRiceEC/Liquid Aerial; Groundboom 0.064NNNN/AHigh acreage crop not assessed at highest rateallowed on label. Flagger previously assessedat 0.016 lb ai/A rate. Higher rate allowed onlabels.DF Aerial; Groundboom 0.2NNNRye (small grains)EC/LiquidAerial; Groundboom;Handheld equipment0.0625 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.031 YYNN/ASorghum (grain orforage)EC/LiquidAerial; Groundboom;Handheld equipment0.064 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.016 YYNN/ATeosinte (small grains)EC/Liquid Aerial; Groundboom 0.4NNNN/AHigher rate on labelsfor liquid formulationthan has been assessedpreviously. Flaggerpreviously assessed at 0.016 lb ai/A rate.Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNTriticale (small grains)EC/LiquidAerial; Groundboom;Handheld equipment0.0625 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.031 YYNN/AWheat (small grains)EC/LiquidAerial; Groundboom;Handheld equipment0.0625NNNNHigh acreage crop not assessed at highest rateallowed on label for liquid formulation.Flagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.031 YYNN/ACotton EC/LiquidAerial; Groundboom;Handheld equipment0.064NNNNHigh acreage crop not assessed at highest rateallowed on label. Flagger previously assessedCarfentrazone Human-Health Assessment Scoping Document D382666Page 31 of 39Table 10. Summary of Registered Occupational Use Patterns, Formulations and MaximumApplication Rates for Carfentrazone-ethyl.Crop / Use SiteFormula-tionApplication EquipmentMaximumapplicationrate (lb ai/A)Scenario Covered?NotesMixer/loaderApplicatorFlaggerMixer/loader/applicatorDF Aerial; Groundboom 0.064NNNN/Aat 0.016 lb ai/A rate. Higher rate allowed onlabels. Spot treatments allowed on labels forliquid formulations – not assessed.Crambe seedEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNFallow systemsEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNFlax seedEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNGrape (raisin, table,wine)EC/Liquid Aerial; Groundboom 0.034 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNGrassesEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNHerbs and spicesEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNHopsEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNHorseradishEC/Liquid Aerial; Groundboom 0.034 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNMustard seedEC/Liquid Aerial; Groundboom 0.031 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.031 YYNN/AOkraEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNPastures EC/Liquid Aerial; Groundboom 0.04 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.PeanutsEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNRapeseedEC/Liquid Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNSafflower seedEC/Liquid Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNCarfentrazone Human-Health Assessment Scoping Document D382666Page 32 of 39Table 10. Summary of Registered Occupational Use Patterns, Formulations and MaximumApplication Rates for Carfentrazone-ethyl.Crop / Use SiteFormula-tionApplication EquipmentMaximumapplicationrate (lb ai/A)Scenario Covered?NotesMixer/loaderApplicatorFlaggerMixer/loader/applicatorSoybeansEC/LiquidAerial; Groundboom;Handheld equipment0.064NNNNHigh acreage crop not assessed at highest rateallowed on label for liquid formulation.Flagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.023 YYNN/AStrawberryEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNSugarcaneEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNSunflower seedEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNTobaccoEC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.024 YYNCitrus (calamondin,citron, chironja, tangelo,tangot, grapefruit,kumquat, lemon, lime,mandarin, orange,pumello)EC/LiquidAerial; Groundboom;Handheld equipment0.031 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.031 YYNN/APome fruits (apple,crabapple, loquat,mayhaw, pear, quince)EC/LiquidAerial; Groundboom;Handheld equipment0.031 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.031 YYNN/AStone fruits (apricot,cherry, nectarine, peach,plum, plumcot, prune)EC/LiquidAerial; Groundboom;Handheld equipment0.031 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidformulations – not assessed.DF Aerial; Groundboom 0.031 YYNN/ANuts (almond, beech nut,brazil nut, butternut,cashew, chestnut,EC/LiquidAerial; Groundboom;Handheld equipment0.031 YYNNFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels. Spottreatments allowed on labels for liquidCarfentrazone Human-Health Assessment Scoping Document D382666Page 33 of 39Table 10. Summary of Registered Occupational Use Patterns, Formulations and MaximumApplication Rates for Carfentrazone-ethyl.Crop / Use SiteFormula-tionApplication EquipmentMaximumapplicationrate (lb ai/A)Scenario Covered?NotesMixer/loaderApplicatorFlaggerMixer/loader/applicatorchinquapin, filbert,hickory nut, macadamianut, pecan, walnut)DF Aerial; Groundboom 0.031 YYNN/Aformulations – not assessed.Tropical fruits (acerola,atemoya, biriba, blacksapote, canistel,cherimoya, custard apple,feijoa, guava, jaboticaba,llama, longan, lychee,mango, papaya, passionfruit, pawpaw, pulasan,rambutan, sapodilla,soursop Spanish lime,star apple, sugar apple,wax jambu)EC/Liquid Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNBananaEC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNCacaoEC/Liquid Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNCocoa beans EC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.CoconutEC/Liquid Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNCoffeeEC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNDateEC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNFigEC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNGuayuleEC/Liquid Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNIndian MulberryEC/Liquid Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNKiwiEC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNCarfentrazone Human-Health Assessment Scoping Document D382666Page 34 of 39Table 10. Summary of Registered Occupational Use Patterns, Formulations and MaximumApplication Rates for Carfentrazone-ethyl.Crop / Use SiteFormula-tionApplication EquipmentMaximumapplicationrate (lb ai/A)Scenario Covered?NotesMixer/loaderApplicatorFlaggerMixer/loader/applicatorOliveEC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNPalm heartEC/Liquid Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNPersimmonEC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNPomegranateEC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNTeaEC/Liquid Aerial; Groundboom 0.0625 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.031 YYNVanilla DF Aerial; Groundboom 0.031 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.PotatoEC/Liquid Aerial; Groundboom 0.09NNNN/AHigher rate allowed onlabel than has beenassessed. Flagger previously assessed at 0.016lb ai/A rate. Higher rate allowed on labels.DF Aerial; Groundboom 0.09NNNVegetable, root andtuber; tuberous and corm(beets, carrots, ginger,horseradish, parsnip,radish, sugar beets, yams,sweet potatoes, turnips)EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNVegetable, leaves of rootand tuber (beets, carrots,radish, sugar beets,turnip tops, chicory)EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNVegetable, bulb (chive,dry bulb onions, garlic,onions, leek, scallions,shallots)EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNVegetable, leafy(arugula, celery, celeriac,cress, endive, fennel,lettuce, parsley, purslane,rhubarb, spinach,radicchio, Swiss chard)EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNCarfentrazone Human-Health Assessment Scoping Document D382666Page 35 of 39Table 10. Summary of Registered Occupational Use Patterns, Formulations and MaximumApplication Rates for Carfentrazone-ethyl.Crop / Use SiteFormula-tionApplication EquipmentMaximumapplicationrate (lb ai/A)Scenario Covered?NotesMixer/loaderApplicatorFlaggerMixer/loader/applicatorVegetable,Brassica(broccoli, Brusselssprout, cabbage, Chinesecabbage, cauliflower,collards, kale, kohlrabi,greens, mustard greens,mustard spinach, rapegreens)EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNVegetable, legume (blackeyed peas, chick pea,edible peas, endamame,kidney beans, lentil, limabeans, pinto beans, snapbeans, succulent shelledpeas, wax beans)EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNVegetables, foliage oflegume (beans, cowpeas,catjang, endamame, guar,lentil, lupin, peas)EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNVegetable, fruiting(eggplant, groundcherry,pepino, pepper,tomatillo, tomato)EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNVegetable, cucurbit(cucumber, cantaloupe,melons, gherkin, gourd,pumpkin, summer andwinter squash,watermelon)EC/Liquid Aerial; Groundboom 0.064 YYNN/AFlagger previously assessed at 0.016 lb ai/Arate. Higher rate allowed on labels.DF Aerial; Groundboom 0.064 YYNAquatic sites EC/LiquidAerial; Boat-mountedboom; Handheldequipment0.2 lb ai/A or0.54 lb ai/AftNNNNHigher acreage typically assessed for aquaticuse sites than has been assessed previously.Site preparation EC/LiquidAerial; Groundboom;Handheld equipment0.09NNNNHigher application rate allowed on label thanhas been previously assessed.Airports EC/LiquidGroundboom; Handheldequipment0.09NYN/ANLabels indicate application used to “trim andedge around objects and landscape features inCarfentrazone Human-Health Assessment Scoping Document D382666Page 36 of 39Table 10. Summary of Registered Occupational Use Patterns, Formulations and MaximumApplication Rates for Carfentrazone-ethyl.Crop / Use SiteFormula-tionApplication EquipmentMaximumapplicationrate (lb ai/A)Scenario Covered?NotesMixer/loaderApplicatorFlaggerMixer/loader/applicatorBuffer strips EC/LiquidGroundboom; Handheldequipment0.04 Y YN/ANnon-crop sites” – Handheld equipmentapplications not assessed previously. Forcertain use sites, higher application rateallowed on labels thanassessed previously.Conservation reserveprogramEC/LiquidGroundboom; Handheldequipment0.04 Y YN/ANGolf coursesEC/LiquidGroundboom; Handheldequipment0.09NYN/ANDF (watersolublebags)0.12NY N/ANHabitat Restoration andManagement AreasEC/LiquidGroundboom; Handheldequipment0.09NYN/ANHighways and Roadsides EC/LiquidGroundboom; Handheldequipment0.09NYN/ANIndustrial Plant Sites EC/LiquidGroundboom; Handheldequipment0.09NYN/ANLumberyards EC/LiquidGroundboom; Handheldequipment0.09NYN/ANMine reclamation projectsitesEC/LiquidGroundboom; Handheldequipment0.04NYN/ANParking Areas EC/LiquidGroundboom; Handheldequipment0.09NYN/ANPavement cracks EC/LiquidGroundboom; Handheldequipment0.09NYN/ANParks EC/LiquidGroundboom; Handheldequipment0.09NYN/ANResidential, commercial,and public landscapesEC/LiquidGroundboom; Handheldequipment0.09NYN/ANPetroleum tank farms EC/LiquidGroundboom; Handheldequipment0.09NYN/ANPipeline, power,telephone and utilityROWEC/LiquidGroundboom; Handheldequipment0.09NYN/ANPumping installations EC/LiquidGroundboom; Handheldequipment0.09NYN/ANRailroads EC/LiquidGroundboom; Handheldequipment0.09NYN/ANCarfentrazone Human-Health Assessment Scoping Document D382666Page 37 of 39Table 10. Summary of Registered Occupational Use Patterns, Formulations and MaximumApplication Rates for Carfentrazone-ethyl.Crop / Use SiteFormula-tionApplication EquipmentMaximumapplicationrate (lb ai/A)Scenario Covered?NotesMixer/loaderApplicatorFlaggerMixer/loader/applicatorSchools EC/LiquidGroundboom; Handheldequipment0.09NYN/ANStorage areas EC/LiquidGroundboom; Handheldequipment0.09NYN/ANElectrical substations EC/LiquidGroundboom; Handheldequipment0.09NYN/ANFencerows EC/LiquidGroundboom; Handheldequipment0.09NYN/ANEdge of landscape beds EC/LiquidGroundboom; Handheldequipment0.09NYN/ANFarmyards EC/LiquidGroundboom; Handheldequipment0.04 YYN/ANTurfgrass renovation(excluding commercialsod farms)EC/LiquidGroundboom; Handheldequipment0.09NYN/ANSod production EC/LiquidGroundboom; Handheldequipment0.04 YYN/ANContainer and Fieldgrown ornamentalsEC/liquidGroundboom; Handheldequipment0.04 Y Y N/ANHandheld equipment applications not assessedpreviously.Christmas tree farms EC/liquidGroundboom; Handheldequipment0.04 Y Y N/ANHandheld equipment applications not assessedpreviously.Ornamental Lawns andTurfDFGroundboom; Handheldequipment0.04 Y Y N/ANHigher unit exposure for handheld equipmentscenario (handgun) than previously assessed.Other handheld equipment not previouslyassessed.Residential lawnsDF Handheld equipment 0.03 N/A N/A N/ANHandheld equipment applications not assessedpreviously.LiquidHandheld equipment 0.04 N/A N/A N/ANRTU Trigger-pump 0.015 N/A N/A N/ANa. DF = dry flowable; EC = emulsifiable concentrateb. N/A = not applicable; Y = yes; N= no; M/L/A = mixer/loader/applicator

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## Attachment 9: DCI Table

Guideline Number: 870.7800 Study Title : Immunotoxicity Rationale for Requiring the Data



## This is a new data requirement under 40 CFR Part 158 as a part of the data requirements for registration of a pesticid e (food and non-food uses).

The Immunotoxicity Test Guideline (OPPTS 870 .7800) prescribes functional immunotoxicity testing and is designed to evaluate the potenti al of a repeated chemical exposure to produce adverse effects (i.e., suppression ) on the immune system. Immunos uppression is a deficit in the ability of the immune system to respond to a chal lenge of bacterial or vi ral infections such as tuberculosis (TB), Severe Acqui red Respiratory Syndrome (SARS) , or neoplasia. Because the immune system is highly complex, studies assessing functional immunotoxic endpoints are helpful in fully characterizing a pesticide’s poten tial immunotoxicity. Thes e data will be used in combination with data from hematology, lymphoid organ weights, and histopathology in

routine chronic or subchronic toxi city studies to characterize pot ential immunotoxic effects.

Practical Utility of the Data

How will the data be used?



## These animal studies can be used to select endpoi nts and doses for use in risk assessment of all exposure scenarios and are cons idered a primary data source for reliable reference dose calculation. For example, animal studies have de monstrated that immunotoxicity in rodents is

one of the more sensitive manifestations of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) among developmental, reproductive, and endocrinol ogic toxicities. Additionally, the EPA has established an oral reference dose (RfD) fo r tributyltin oxide (TBTO) based on observed immunotoxicity in animal studies (IRIS, 1997).

How could the data impact the Agency's future decision-making?



## If the immunotoxicity study shows th at the test material poses eith er a greater or a diminished risk than that given in the in terim decision’s conclusion, the risk assessments for the test material may need to be revised to reflect the magnitude of potential ri sk derived from the new

data.

If the Agency does not have this data, a 10X da tabase uncertainty factor may be applied for conducting a risk assessment from the available studies.

### Carfentrazone Human-Health Assessment Scoping Document D382666

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### Guideline Number: 870.3465 Study Title: 28-Day Inhalation Toxicity Study Rationale for Requiring the Data



## The HED HIARC requested a 28-day inhalation toxi city study as a condition of registration. However, based on low volatility and low inha lation toxicity (Toxicity Category IV) for carfentrazone-ethyl and since the inhalation marg ins of exposure (MOEs) were >1,000, a waiver of the 28-day inhalation toxic ity study was deemed acceptable [HED Standard Operating Procedure (SOP) 2002.01: Guidance: Waiver Criter ia for Multiple-Exposure Inhalation Toxicity Studies, 15-Aug-2002]. However, the Agency is currently reevaluating the inhalation waiver criteria and based on this analysis, an inhalation study may be required in the

future. Practical Utility of the Data

How will the data be used? Repeated-exposure inhalation toxici ty studies provide critical scientific information needed to characterize potential hazard to the human population on the e ffects of a pesticide from inhalation exposure. Since epidemiologic da ta on the effects of inhalation exposure to chlorfenapyr are unavailable and therefore inadequate to characterize a pesticide’s potential effects in humans, animal studies are used as th e most sensitive endpoint for risk assessment. These animal studies can be used to select endpoi nts and doses for use in risk assessment of all exposure scenarios and are cons idered a primary data source for reliable reference dose

calculation.

How could the data impact the Ag ency's future decision-making? If the inhalation study shows that the test material poses either a greater or a diminished risk than that using the biomonitoring data in conjun ction with the oral e ndpoint, then the risk assessments for the test material may need to be revised to reflect the magn itude of potential risk derived from the new data. If the Agency does not have this data, a 10X database uncertainty factor may be applied for conducting a risk assesment from the available studies.