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**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER**  **EPA Registration**  **Division contact: Cynthia Giles**  **- Parker; Acting Product Manager,**  **Team 20; (703) 305 -**  **7740 TEMPLATE:**  KIM
- C1, LLC 2F8055 EPA has received a pesticide petition ( 2F8055 ) from KIM
- C
- 1, LL C , 2547 West Shaw Avenue, Suite 116, Fresno, CA 93711 request ing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 1. by establishing a temporary tolerance for residues of N
- (2
- chloro
- 4
- py

ridinyl
- N’
- phen yl urea (forchlorfenuron) in or on the raw agricultural commodity almond, cherry (sweet), fig, pear, pistachio, plum/prune at 0.01 parts per million (ppm). EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully

evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry

1. Plant metabolism. One plant metabolism study on each of three crops, including grapes, kiwi fruit and apple fruit, were conducted. Based on all three studies the residue of concern was defined as forchlorfenuron parent compound. 2. Analytical method. Two anal yt ical methods, both based on high performance liquid chromatograph y (HP LC) procedures have been developed. The first meth od used a visible ultraviolet (UV) detector, while the second method used a mass spectrophotometer (MS) detector. Since the MS detector is capable of both qualitative as well as quantitative measurement, it is the preferred method. The level of quantific ation (LOQ) in all of the crops (i.e., almond, cherry , fig, pear, pistachio and plum/prune) is 0.01 ppm.2 3. Magnitude of residues. Ten f ield magnitude of residue trials with florchlorfenuron were conducted in five counties in California during the 2006 growing season. This included residue trials on sweet cherry , fig, pear, pistachio and plum/prune. In addition, three almond trials were conducted in three counties in California during the 2005 and 2006 growing seasons. Applications on almonds were mad e at 11.4 grams a.i./A while applications on the other five crops were made at 10 grams a.i./A. Treatments were made with the shortest possible interval between application and harvest to maximize the residue level. A ll commodities were anal yz ed for pare nt compound
. The validated limit of quantification (LOQ) for forchlorfenuron was set at 0.01 ppm. The limit of detection (L OD) was defined as 1/3 of the LOQ or 0.003 ppm for each matrix. Residues of forchlorfenuron were < LOQ (0.01 ppm) on all cherry , f ig , pear, pistachio and plum/prune matrices. No residues of forchlorfenuron were found in the almond nut in shell samples (<0.01). Non
- detectable to l ow levels of forchlorfenuron were found in almond hulls, with the highest level being 0.0841 ppm (0.0935 ppm corrected for concurrent mean procedural recovery). B. Toxicological Profile 1. Acute toxicity. Acute toxicity

endpoints for forchlorfenuron technical are as follows: **Guideline No./Study Type Results**  **Toxicity Category** 870.1100 Acute Oral

– Rat LD50 (mg/kg bw): M = 4904; F = 4899; Combined = 4918 III
870.1200 Acute Dermal

– Rabbit LD50 (mg/kg bw): M = >2000; F = >2000 III
870.1300 Acute Inhalation

– Rat LC50 (mg/L): M = >3.0; F = >3.0 IV 870.2400 Primary Eye Irritation
- Rabbit Mild ey e irrit ant III 870.2500 Primary Skin Irritation

– Rabbit Non
- irritant IV 870.2600 Dermal Sensitization

– Guinea Pig Non
- sensitizer N/A

2. Genotoxicty. The genotoxic potential of forchlorfenuron was studied in vitro in bacteria and mammalian cells and in vivo in the unscheduled DNA s ynthesis test. The test sy stems assay ed did not show any evidence of genotoxicity except in the bacterial mutagenicity

assay , strain TA1535, without metabolic activation. The weight of evidence indicates that forchlorfenuron does not possess3 significant genotoxicity

concerns. 3. Reproductive	and	developmental	toxicity. A developmental toxicity study was conducted with forchlorfenuron using rats gavaged with levels of 0, 100, 200 and 400 mg/kg/day . The maternal and developmental N OAE Ls were 200 mg/kg/day based on reduced body weights, body weight gain, food consumption, and an increased incidence of alopecia in dams. There were no developmental effects. A developmental toxicity study was conducted with forchlorfenuron using rabbi ts gavaged with doses of 0, 25, 50 and 100 mg/kg/day . Maternal toxicity (decreased bod y weight and body weight gains) were observed at 50 mg/kg/day

and above. The maternal NOAEL was 25 mg/kg/day and the developmental NOAEL was 100 mg/kg/day . There were no developmental effects. A two generation reproduction study was conducted in rats in which forchlorfenuron was administered in the diet at levels of 0, 150, 2,000 and 7,500 ppm
. There were no adverse effects of forchlorfenuron on reproductive success. Parental toxicity consisted of clinical signs, inhibition of body weight gain, reduced food consumption, and macroscopic and microscopic effects in the kidney . Reproductive toxicity in the highest dose consisted of slightly reduced live litter sizes in the F 2 litters. In the pups, body weights and survival (late lactation period) were reduced and at the high dose, pup mortality and emaciation were increased. The parental, pup and reproductive NOAELs were 150 ppm, 150 ppm and 2,000 ppm, respectivel y. 4. Subchronic toxicity. Forchlorfenuron was tested in rats in a 3
- month study at dietary levels of 0, 200, 1,000 and 5,000 ppm Observations were decreased body weight, body weight gain and food efficiency. The NOAEL for males was 5,000 ppm (400 mg/kg/day) and in females was 1,000 ppm (84 mg/kg/day). Forchlorfenuron was tested in a 13
- week dietary toxicity study in mice conducted at dose levels of 0, 900, 1,800, 3,500 and 7,000 ppm. Effects included decreased body weight and food consumption, increas ed relative liver weight and l ymphocy tic cell infiltration in the kidneys. The NOAEL was 3,500 ppm (609 mg/kg/day in males and 788 mg/kg/day in females). A 13
- week dietary

toxicity study was conducted with forchlorfenuron in beagle dogs at dose levels of 0, 50, 500 and 5,000 ppm. Effects included decreased bod y weight gain, food consumption, and food efficiency . The4 NOAEL for both sexes was 500 ppm (16.8 mg/kg/day in males and 19.1 mg/kg/day

in females). 5. Chronic toxicity. In a 104
- week combined chronic/oncogenicity study in rats, forchlorfenuron was administered in the diet at dose levels of 0, 150, 2,000 and 7,500 ppm. Findings were decreased body weight and body

histopathological effects in the kidney . No oncogenicity was found. The NOAELf or this study

was 150 ppm (7 mg/kg/day

in males and 9 mg/kg/day in females). Forchlorfenuron was administered in the diet to mice for 78
- weeks at dose levels of 0, 10, and 1,000 mg/kg/day . Observations were decreased body weight, bod y weight gain, food consumption, increased kidney weights and incidence of chronic kidney histopathological lesions. The NOAEL for both sexes was 10 mg/kg/day . No oncogenicit y was found. In a 12
- month study , forchlorfenuron was administered in the diet given to dogs at dose levels of 0, 150, 3,000 and 7,500 ppm. Observations included reduced bod y weight, body weight gain, food consumption, and various hematology

changes. The NOAEL for both sexes was 3,000 ppm (87 mg/kg/day

in males and 91 mg/kg/day in females). 6. An imal metabolism. A rat metabolism study

indicated that forchlorfenuron is almost completely absorbed and most of the 14 C
- forchlorfenuron
- derived radioactivity is rapidly eliminated primarily

via the urine. The majority of the metabolism of forchlorfe nuron was via hydrox yl ation of the phenyl ring. The sulfate conjugate of the h ydrox yl forchlrofenuron was the major metabolite excreted in the urine, accounting for as much as approximately 96% of the urinary radioactivity . Tissue residues accounted f or less than 1% of the administered dose at 168 hours post
- dosing. 7. Metabolite toxicology
. Metabolites occur at levels below 0.1 ppm and, therefore, are below levels required to be assay ed in animal testing. Nevertheless, the toxicity of sulfate con jugate (and an y other animal metabolites) was assessed during the conduct of the CPPU required mammalian toxicity studies.
8. Endocrine disruption
. No special studies to investigate the potential for endocrine effects of forchlorfenuron have been perform ed. However, a large, detailed toxicology5 data base exists for the compound with studies in all required categories. In cluded are acute, sub
- chronic, chronic, developmental and reproductive toxicology

studies, with detailed histology and histopathology

o f numerous tissues, including endocrine organs, following repeated or long
- term exposures. These studies are considered capable of revealing endocrine effects. The results of all of these studies show no evidence of an y endocrine
mediated effects and no pathology of the endocrine organs. Consequentl y, it is concluded that forchlorfenuron does not possess estrogenic or endocrine disrupting properties.
C. Aggregate Exposure 1. Dietary exposure. A dietary exposure assessment was conducted looking at a number of crops including almond, fig, pear and prune (as well as apples, blueberries, grapes and kiwifruit). This assessment was conducted in connection with a previous EUP that was obtained for development of efficacy data on the above listed crops. The f

ollowing information was published by EPA in FR, Vol. 69, No. 67, pp. 18375
- 18380, 4/7/04. i. Food. A reference dose (RfD) was calculated using the most sensitive species data available from the toxicological testing. The calculated RfD of 0.08 mg/kg/da y was used to calculate the impact of the estimated residue with results from treatment of the total acreage of all crops included in the prior EUP. Making the same risk exposure calculations, it was shown that there was no significant impact on reducing the RfD b y using almonds, apples, blueberries, figs, grapes, kiwifruit, pears and plums in aggregate. ii. Drinking water
. EPA stated the following in FR Vol. 73, No. 159, pp. 47841
- 47847, under “Forchlorfenuron; Permanent and Time
- Limited Pesticide Toleran ces” wherein EPA established permanent tolerances for residues of forchlorfenuron in or on bushberry subgroup 13
- 07B and time
- limited tolerances under Petition No. 7F7246 for use on almond, cherry (sweet), fig, pear, pistachio and plum/prune (see FR pp. 47 844);

“ The Agency

used screening level water exposure models in the dietary exposure anal ys is and risk assessment for forchlorfenuron in drinking water. Forchlorfenuron is persistent and moderately mobile in soils. Forchlorfenuron is also a substituted urea plant growth regulator that is essentially

stable to all routes of dissipation except sensitized photodegradation in water. Based on the Pesticide Root Zone Model /6 Exposure Analy sis Modeling Sy stem (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI
- GROW) models, the Estimated Environmental Concentrations (EECs) of forchlorfenuron from the newl y proposed use on bushberries and the uses on almonds, sweet cherries, figs, pears, plums and pistachios under the EUP will not exceed the EECs from the grape and kiwi uses previously assessed by

the Agency

in document titled Drinking W

ater Assessment for Forchlorfenuron for Grape and Kiwi Uses. Therefore, the Agency has incorporated the drinking water EEC from the grape and kiwi anal ys i s directl y into this dietary assessment. For chronic dietary

risk assessment, the water concentration of value 0.003 ppb was used to assess the contribution to drinking water. ”
2. Non

- dietary exposure
. EPA noted the following in FR Vol. 73, No. 159, 8/ 15/08 in the notice establishing the prior temporary tolerances under PP 7F7246 in almonds, sweet cherries, figs, pears, plums and pistachios in regard to non
- dietary exposure: “The term ‘‘residential exposure’’ is used in this document to refer to non occupational, non - dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Forchlorfenuron is not registered for an y specific use patterns that would result in residential exposure. ” D. Cumulative Effects EPA noted the following in FR Vol. 73, No. 159, 8/15/08 in the FR Notice establishing prior temporary tolerances under PP 7F7246 in almonds, sweet cherries, figs, pears, plums and pistachios in regard to cumulative effects:

“ Sect ion 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify , or revoke a tolerance, the Agency consider ‘‘available information’’ concerning the cumulative effects of a particular pesticide’s residues and ‘‘other substances th at have a common mechanism of toxicity .’’ EPA has not made a common mechanism of toxicity finding as to forchlorfenuron and any other substances and forchlorfenuron does not appear to produce a toxic metabolite produced b y other substances. For the purpos es of this tolerance action, therefore, EPA has not assumed that forchlorfenuron has a common mechanism of toxicity with other substances. ” E. Safety Determination7 EPA noted the following in FR Vol. 73, No. 159, 8/15/08 in the notice establishing prior temporary tolerances under PP 7F7246 in almond, sweet cherry , fig, pear, pistachio and plum/prune relative to the Agency ’s conclusions regarding the safet y of the proposed uses under the proposed temporary tolerances for forchlorfenuron (which are the same tolerance levels proposed in this Petition):

“ EPA has determined that reliable data show the safet y of infants and children would be adequatel y protected if the FQPA SF were reduced to 1X. That decision is based on the following findings: i. The toxicity database for forchlorfenuron is complete. ii. There is no indication that forchlorfenuron is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity
. iii. There is no evidence that forchlorfe nuron results in increased susceptibility

in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2

–generation reproduction study
. iv. There are no residual uncertainties identified in the exposure databases. EPA made cons ervative (protective) assumptions in the ground and surface water modeling used to assess exposure to forchlorfenuron in drinking water. EPA used similarly conservative assumptions to assess exposure to forchlorfenuron residues in food. These assessments will not underestimate the exposure and risks posed b y forchlorfenuron. EPA determines whether acute and chronic pesticide exposures are safe b y comparing aggregate exposure estimates to the aPAD and cPAD. The aPAD and cPAD represent the highest safe expo sures, taking into account all a ppropriate SFs. EPA calculates the aPAD and cPAD by dividing the POD by all applicable UFs. For linear cancer risks, EPA calculates the probability

of additional cancer cases given the estimated aggregate exposure. Short
- ter

m, intermediate
- term, and chronic
- term risks are evaluated b y comparing the estimated aggregate food, water, and residential exposure to the POD to ensure that the margin of exposure (MOE) called for b y the product of all applicable UFs is not exceeded. 1. Acute risk. An acute aggregate risk assessment takes into account exposure estimates from acute dietary consumption of food and drinking water. No adverse effect resulting from a single
- oral exposure was identified and no acute dietary endpoint was select ed. Therefore, forchlorfenuron is not expected to pose an acute risk. 2. Chronic risk . Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to forchlorfenuron from food and water will utilize <1% of the cPAD for the general U.S. population and all subpopulations. There are no residential uses for forchlorfenuron.8 3. Short

- term and intermediate

- term risk . Short
- term and Intermediate
term aggregate exposure takes into account short
- term and inter mediate
term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Forchlorfenuron is not registered for an y use patterns that would result in short
- term and intermediate
- term residential exposure. Th erefore, the short
- term and intermediate
- term aggregate risk, individually is the sum of the risk from exposure to forchlorfenuron through food and water, which has already been addressed, and will not be greater than the chronic aggregate risk. 4. Aggrega te cancer risk for U.S. population . Since forchlorfenuron has been classified as not likely to be carcinogenic, aggregate cancer risk is not a concern. 5. Determination of safety

- U.S. population and Infants &Children. Based on these risk assessments, EPA concludes that there is a reasonable certaint y that no harm will result to the general population or to infants and children from aggregate exposure to forchlorfenuron residues. F. International Tolerances The following international tolerances exist f or forchlorfenuron: Australia: An MRLof 0.01 ppm has been established for grapes and as a temporary

MRL level for blueberries, mango and plum/prune. European Union: Forchlorfenuron MRLs are set for table grapes and kiwifruit at 0.05 ppm. However, a new E U MRL of 0.01 ppm is proposed because sufficient trials are available showing residues below 0.01 ppm Is rael: An MRL of 0.01 ppm has been established for table grapes, wine grapes and kiwifruit. Japan: An MRLof 0.01 has been set for almonds. Mexico: Has d eferred to the U.S. Tolerances. Therefore, all forchlorfenuron tolerances established in the U.S. apply to Mexico.