Interregional Research Project Number 4

Petition #4E8306

	EPA has received a pesticide petition (4E8306) from Interregional Research Project Number 4 at 500 College Road East, Suite 201W, Princeton, NJ 08540 proposing, 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 180.377 as follows:

   By establishing a tolerance for the combined residues of diflubenzuron (N-[[(4-chlorophenyl)amino]carbonyl]-2,6-difluorobenzamide) and its metabolites 4-chlorophenlyurea and 4-chloroaniline in or on the raw agricultural commodities: Carrot, roots at 0.2 parts per million (ppm); Peach subgroup 12-12B at 0.5 ppm; Plum subgroup 12-12C at 0.5 ppm; Plum, prune, dried at 0.5 ppm; Nut, tree, group 14-12 at 0.2 ppm; and Pepper/Eggplant subgroup 8-10 B at 1.0 ppm.
   
By establishing a regional tolerance for the combined residues of diflubenzuron and its metabolites 4-chlorophenlyurea and 4-chloroaniline in or on the raw agricultural commodities: Alfalfa, forage at 6 ppm; Alfalfa, hay at 20 ppm; and Alfalfa, seed at 0.9 ppm.
   
By establishing a tolerance for residues of diflubenzuron in or on the raw agricultural commodities: Cottonseed subgroup 20C at 0.2 ppm; Egg at 0.15 ppm; Poultry, fat at 0.15 ppm; and Poultry, meat byproducts at 0.06 ppm.
   
Upon the approval of the aforementioned tolerances, to remove established tolerances for the combined residues of diflubenzuron and its metabolites 4-chlorophenlyurea and 4-chloroaniline in or on the raw agricultural commodities: Fruit, stone, group 12, except cherry at 0.07 ppm; Nut, tree, group 14 at 0.06 ppm; Pistachio at 0.06 ppm; and Pepper at 1.0 ppm.
   
   Upon the approval of the aforementioned tolerances, to remove established tolerances of diflubenzuron (N-[[(4-chlorophenyl)amino]carbonyl]-2,6- difluorobenzamide) in or on the raw agricultural commodities: Cotton, undelinted seed at 0.2 ppm; Egg at 0.05 ppm; Poultry, fat at 0.05 ppm; and Poultry, meat byproducts at 0.05 ppm.

   EPA has determined that the petition contains data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; 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. The nature of the residue in plants is adequately understood.  In plants, the metabolism of diflubenzuron was investigated in soybeans, citrus, mushroom, and rice.  The main component of residues in rice was CPU; levels of PCA were negligible to non-detectable.  The main component of the residues in soybeans and oranges was the parent diflubenzuron. A considerable portion of the residues were bound. Diflubenzuron showed very limited absorption and translocation in plants with most of the residues remaining on the surface. The Agency has concluded that the residues of concern are diflubenzuron and its metabolites CPU and PCA.

	2. Analytical method. Adequate enforcement analytical methods for determining diflubenzuron and its metabolites, 4-chlorophenlyurea and 4-chloroaniline in/on appropriate raw agricultural commodities and processed commodities are available for the established and proposed tolerances.  

      3. 	Magnitude of residues.  Appropriate residue field trials have been conducted to support the use of diflubenzuron on the crops proposed in this petition. Field trials were conducted on alfalfa, peaches, plums, and carrots. The crops were treated according to the proposed label, were sampled and the residues reported in these field trials support the proposed tolerances. The analytical data demonstrated that residues in crops are not expected to exceed the proposed tolerance levels.
      
B. Toxicological Profile

      1. 	Acute toxicity.  Studies for diflubenzuron technical indicate the acute oral toxicity in rats and mice is >4,640 mg/kg, and the acute dermal toxicity in rats is >10,000 mg/kg.  The acute inhalation LC50 in rats is >35 mg/l (6 hours). Diflubenzuron technical is not an eye or skin irritant to rabbits, and is not a dermal sensitizer in guinea pigs.
      
      In an acute neurotoxicity study, diflubenzuron was administered to rats as a single dose via oral gavage. Three treatment groups of 10 male and 10 female rats were administered the test article at dose levels of 500, 1000, and 2000 mg/kg. There were no test article-related effects on any parameter examined. There were no lesions in any of the examined neural tissues that indicated a test article-related effect. Under the conditions of this study, where male and female rats received a single oral (gavage) dose of diflubenzuron at 0, 500, 1000 and 2000 mg/kg, the No Observed Effect Level (NOEL) was 2,000 mg/kg, the highest dose tested. No signs of systemic or neurotoxicity were evident.
      
      2. 	Genotoxicity.  Diflubenzuron did not show any mutagenic activity in point mutation assays employing S. typhimurium, S. cerevisiae, or L5178Y Mouse Lymphoma cells.  Diflubenzuron did not induce chromosomal aberrations in Chinese Hamster Ovary cells and did not induce unscheduled DNA synthesis in human WI-38 cells.  Diflubenzuron was also negative in Mouse Micronucleus and Mouse Dominant Lethal assays and it did not induce cell transformation in Balb/3T3 cells.

      3. 	Reproductive and developmental toxicity.  In a rat developmental toxicity study, diflubenzuron was administered by oral gavage to pregnant female rats at dosage levels of 0, 1, 2 and 4 mg/kg/day. No treatment related effects were seen. A subsequent study was conducted in pregnant Sprague Dawley rats at a dose of 0 and 1,000 mg/kg/day. No maternal toxicity was observed. The incidence of fetuses with skeletal abnormalities was slightly increased in the treated group, but was within historical background range. The NOEL for maternal and developmental toxicity in rats was greater than 1,000 mg/kg/day. 

      Diflubenzuron was also administered by oral gavage to pregnant New Zealand White rabbits at dosage levels of 0, 1, 2 and 4 mg/kg/day. No treatment related effects were seen. A subsequent study was conducted in pregnant rabbits at a dose of 0 and 1,000 mg/kg/day. No maternal or developmental toxicity was seen. The NOEL for maternal and developmental toxicity in rabbits was greater than 1,000 mg/kg/day.

      In a rat reproduction study, diflubenzuron was fed to two generations of male and female rats at dietary concentrations of 0, 10, 20, 40, and 160 ppm. No effects were seen on parental body weight gain and there were no reproductive effects. In a subsequent study, diflubenzuron was fed to two generations of male and female rats at dietary concentrations of 500, 5,000 and 50,000 ppm.  Systemic adult toxicity was seen at all dosage levels.  No effects were seen on reproductive  parameters, however, litter and mean pup weights of F1 offspring were reduced at 50,000 ppm.  The NOEL for reproductive toxicity in rats was 50,000 ppm (2.5 g/kg/day), and for pre-weaning development it was 5,000 ppm (250 mg/kg/day).	
      
      4. 	Subchronic toxicity. To assess subchronic toxicity, a four-week inhalation study and a three-week dermal study were conducted.  In the inhalation study rats were exposed nose only to 10, 30 or 100 mg/m[3] for 6 hours per day, 5 days per week for 4 weeks.  Treatment related findings were a slight reduction in erythrocytes, hemoglobin and hematocrit in male and female rats at a concentration of 100 mg/m[3] and an increase in total bilirubin in high dose female rats.  There was no effect on methemoglobin concentration at any dose level.  The NOEL for subchronic inhalation toxicity was 30 mg/m[3]. 

      In the dermal toxicity study, diflubenzuron was applied to the backs of male and female CD rats for three weeks at dose levels of 20, 500 and 1,000 mg/kg/day. Hematology evaluation showed reductions in red blood cell (RBC), hemoglobin (Hgb) and hematocrit values at 500 and 1,000 mg/kg/day.  An increased incidence of polychromasia, hypochromasia and anisocytosis was seen at 500 and 1,000 mg/kg/day.  An increase in methemoglobin and sulfhemoglobin values was seen at 1,000 mg/kg/day.  The NOEL for systemic toxicity was 20 mg/kg/day. Also, a dermal absorption factor of 0.5% for systemic absorption, was derived from a study where rats were dosed with either 0.005 or 0.05 mg/cm[2] of [[14]C] diflubenzuron technical. This value can be used for converting dermal exposure to oral equivalents.
      
      In an immunotoxicity study, diflubenzuron was fed to mice at concentrations of 0, 80, 400, 2,000 and 10,000 ppm for 28 days.  There was no observed effect of diflubenzuron, at any dose tested on the anti-SRBC IgM response.  The immunotoxicity NOAEL for this study was the highest dose tested dose concentration of 10,000 ppm.
      
      In a subchronic neurotoxicity study, diflubenzuron was administered to rats daily for 90 or 91 days via oral gavage. Three treatment groups of 10 male and 10 female rats were administered the test article at dose levels of 100, 300, or 1,000 mg/kg/day. There were no adverse test article-related effects on any parameter examined. There were no lesions in any of the examined neural tissues that indicated a test article-related effect. The only test article-related minor finding noted in both sexes at >= 300 mg/kg/day was minimal to mild reductions in erythrocyte mass. These changes were not adverse at these magnitudes. Under the conditions of this study, the No Observed Adverse Effect Level (NOAEL) was 1000 mg/kg/day, the highest dose level tested. No adverse signs of systemic toxicity or any evidence of neurotoxicity were evident.

      5. 	Chronic toxicity.  Diflubenzuron was given by capsule to male and female Beagle dogs for one year at dose levels of 0, 2, 10, 50 and 250 mg/kg/day.  Body weight gain was slightly reduced in females at 250 mg/kg/day.  Absolute liver and spleen weights were increased in males given 50 and 250 mg/kg/day.  A reduction in hemoglobin and mean corpuscular hemoglobin concentration, with an elevation in reticulocyte count, was seen at 50 and 250 mg/kg/day.  Methemoglobin and sulfhemoglobin values were increased at doses of 10 mg/kg/day and greater.  Histopathological findings were limited to pigmented macrophages and Kupffer cells in the liver at doses of 50 and 250 mg/kg/day. The NOEL for chronic toxicity in dogs was 2 mg/kg/day.
 
      Diflubenzuron was fed to male and female Sprague Dawley rats for two years at dose levels of  0, 156, 625, 2,500 and 10,000 ppm. Methemoglobin values were elevated in female rats at all dose levels and in male rats at the two highest dose levels.  Sulfhemoglobin was elevated in females, only, at dose levels of 2,500 and 10,000 ppm.  Mean corpuscular volume (MCV) and reticulocyte counts were increased in high dose females. Spleen and liver weights were elevated at the two highest doses.  Histopathological examination demonstrated an increase in hemosiderosis of the liver and spleen, bone marrow and erythroid hyperplasia and areas of cellular alteration in the liver.  In another study diflubenzuron was administered to male and female CD rats for two years at dose levels of 0, 10, 20, 40 and 160 ppm. Elevated methemoglobin levels were seen in high dose males and females.  No additional effects, including carcinogenic findings, were observed.  The NOEL for chronic toxicity in rats was 40 ppm (2 mg/kg/day).

      A ninety-one week oncogenicity study in CFLP mice was conducted at doses of 0, 16, 80, 400, 2,000 and 10,000 ppm.  There was no increase in tumor incidence as a result of diflubenzuron administration.  Target organ effects included: increased methemoglobin and sulfhemoglobin values, Heinz bodies, increased liver and spleen weight, hepatocyte enlargement and vacuolation, extramedullary hemopoiesis in the liver and spleen, siderocytosis in the spleen and pigmented Kupffer cells.  A NOEL for these effects was 16 ppm (2 mg/kg/day).  

      Diflubenzuron was fed to male and female Sprague Dawley rats for two years at dose levels of 0, 156, 625, 2,500 and 10,000 ppm.  Methemoglobin values were elevated in female rats at all dose levels and in male rats at the two highest dose levels.  Blood sulfhemoglobin was elevated in females, only, at dose levels of 2,500 and 10,000 ppm.  MCV and reticulocyte counts were increased in high dose females. Spleen and liver weights were elevated at the two highest doses.  Histopathological examination demonstrated an increase in hemosiderosis of the liver and spleen, bone marrow and erythroid hyperplasia and areas of cellular alteration in the liver. There was no increase in tumor formation.  In another study diflubenzuron was administered to male and female CD rats for two years at dose levels of 0, 10, 20, 40 and 160 ppm. Elevated methemoglobin levels were seen in high dose males and females.  No additional effects, including carcinogenic findings, were observed.

      6. 	Animal metabolism. The qualitative nature of the residues in livestock is adequately understood based on data from ruminant and poultry metabolism studies. The Agency has concluded that the residues of concern are diflubenzuron and its metabolites CPU and PCA.
      
      DFB in rats at a single dose of 100 mg/kg and 5 mg/kg single and multiple oral doses depicted limited absorption from the gastrointestinal tract.  No major difference was observed between the single and multiple doses.  In single dose  treatments, after 7 days,  20% and 3% of the applied dose 5 and 100 mg/kg, respectively were excreted in urine, while 79% and 98% of the applied dose 5 and 100 mg/kg, respectively, were eliminated in the feces.  Very little bioaccumulation in the tissues was observed.  In the feces, only unchanged parent compound was detected.  Several metabolites were observed in the urine which are, among others, 2-6-difluorobenzoic acid (DFBA), 2,6-diflurophippuric acid, 2-6-difluorobenzamide (DFBAM), and  2-hydroxydiflubenzuron (2-HDFB).  An unresolved peak that was characterized as p-chloroaniline (PCA) and/or p-chlorophenylurea (CPU) was  found.  This latter peak accounted for about 2% of the administered dose (5 mg/kg).  To resolve if PCA and CPU are indeed metabolites of DFB, rats were administered a single oral dose, 100 mg/kg of 14C DFB.  The major metabolites identified in rat urine were 4-chloroaniline-2-sulfate, accounting  for almost 50% of the total radioactive residue (TRR) in the urine and N-(4-chlorophenyl)oxamic acid which accounted  for about 15% of the (TRR).  Neither CPU, PCA nor their N-hydroxylderivatives  were found in rat urine at a limit of detection of 23 parts per billion (ppb).  As in the previous study, DFB was the only residue found in the feces.

      7. 	Metabolite toxicology. NCI/NTP conducted chronic feeding and gavage studies with p-chloroaniline (PCA), a minor potential metabolite of diflubenzuron, in Fischer 344 rats and B6C3F1 mice.
      
      PCA was administered in the diet to Fischer 344/N rats at dietary concentrations of 250 and 500 ppm for 78 weeks, followed by a 24 week observation period.  A slight body weight depression was seen in high dose females rats compared to controls.  Survival was reduced in high dose males compared to controls.  In male rats there was a slight increase in uncommon fibromas or fibrosarcomas of the spleen, which was not statistically significant.  Non-neoplastic proliferative and chronic inflammatory lesions were found in spleens of treated rats. It was concluded that, under the conditions of the assay, sufficient evidence was not found to establish the carcinogenicity of PCA for Fischer 344/N rats.

      PCA was administered 5 days/week by oral gavage, as a hydrochloride salt in water, to male and female F344/N rats at doses of 0, 2, 6 or 18 mg/kg/day.  Mean body weights of dosed rats were generally within 5% of those of controls throughout the study.  High dose animals generally showed mild hemolytic anemia and dose-related methemoglobinemia.  Non-neoplastic lesions seen were bone marrow hyperplasia, hepatic hemosiderosis and splenic fibrosis, suggesting treatment related effects on the hematopoietic system.  Adrenal medullary hyperplasia was observed in high dose female rats.  The incidence of uncommon sarcomas of the spleen was significantly increased in high dose male rats.  A marginal increase in pheochromocytomas of the adrenal gland was seen in high dose male and female rats.  It was concluded that, under the conditions of this 2 year gavage study, there was clear evidence of carcinogenic activity of PCA hydrochloride for male Fischer 344/N rats and equivocal evidence of carcinogenic activity of PCA hydrochloride for female Fischer 344/N rats.
                                    
      PCA was administered in the diet to B6C3F6 mice at dietary concentrations of 2,500 and 5,000 ppm for 78 weeks followed by a 13-week observation period.  A body weight depression was seen in treated mice of both sexes, compared to controls. An increased incidence of hemangiomas and hemangiosarcomas in spleen, kidney, liver and other sites was seen in treated mice of both sexes; however this increase was not statistically significant compared to controls.  Non-neoplastic proliferative and chronic inflammatory lesions were found in spleens of treated mice.  The evidence was considered insufficient to conclusively relate the hemangiomatous tumors in mice to compound administration.  It was concluded that, under the conditions of the assay, sufficient evidence was not found to establish the carcinogenicity of PCA for B6C3F1 mice.
      
      PCA hydrochloride was administered 5 days/week by oral gavage to male and female B6C3F1 mice at doses of 0, 3, 10, or 30 mg/kg/day.  Mean body weights of high dose male and female mice were generally within 5% of those of controls throughout the study.  The incidence of hepatocellular adenomas or carcinomas (combined) was increased in a non-dose-dependent manner in treated male mice. Metastasis of carcinoma to the lung was seen in the high dose group.  An increased incidence of hemangiosarcomas of the liver or spleen was seen in high dose male mice. It was concluded that, under the conditions of this 2-year gavage study, there was some evidence of carcinogenic activity of PCA hydrochloride for male B6C3F1 mice and no evidence of carcinogenic activity of PCA hydrochloride for female B6C3F1 mice. 
      
      In addition to PCA, 4-chlorophenylurea (CPU) is also a potential minor metabolite of diflubenzuron.  By association with Monuron, the EPA had assumed that CPU has oncogenic potential with the same carcinogenic potency (q1*) as Monuron. 
      
      8. Endocrine disruption.  Diflubenzuron is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call ins, requiring the submission of EDSP screening assays for dilubenzuron.

C. Aggregate Exposure

      1.  Dietary exposure. An evaluation of chronic dietary exposure, including drinking water, has been performed for the U.S. population and various population subgroups including infants and children.  No toxic effects attributable to a single (i.e., acute) exposure to diflubenzuron have been identified; therefore, an acute reference dose (RfD) has not been established for diflubenzuron and an acute dietary exposure assessment has not been conducted.
     
      i. 	Food. The dietary exposure from diflubenzuron was estimated based on replicating the diflubenzuron, CPU, and PCA residue files included in EPA's December 12, 2013 risk assessment and then incorporating all of the IR-4 requests outlined above. Tolerance level residues and 100% crop treated were assumed for all of the proposed commodities. Residues in meat, milk and egg products were obtained from extrapolation of metabolism study data to anticipated livestock dietary burdens.  
     
     A chronic dietary exposure assessment was conducted on diflubenzuron using DEEM-FCID[TM] Version 3.16, which incorporates consumption data from the Center for Disease Control and Prevention (CDC) NHANES (National Health and Nutrition Examination Survey) 2-day food consumption data for 2003-2008. The chronic dietary exposure to the US Population (total) was estimated to be 10.3% (0.002069 mg/kg/day) of the cPAD of 0.02 mg/kg/day. The most highly exposed subpopulation, children 1-2 years, had an estimated total exposure of 39.3% (0.007858 mg/kg/day) of the cPAD. The total chronic dietary exposure associated with current and proposed uses of diflubenzuron has been demonstrated to be less than the cPAD (0.02 mg/kg/day) and are therefore not of concern. Using updated percent crop treated estimates on all crops would further refine the exposure estimate. Use of percent crop treated information for all crops and switching to average residues rather than tolerances would further refine the exposure downward.  
     
     Cancer risk assessments were conducted for CPU and PCA for the current and proposed uses. The cancer risks are estimated to be 0.000033 mg/kg/day (4.96 x 10E-7) for CPU and 0.000010 mg/kg/day (1.15 x 10E-6) for PCA. As per EPA's January 31, 2014 FR Notice for diflubenzuron (Volume 79, No. 21, page 5299), "...cancer risk assessment should generally not be assumed to exceed the benchmark level of concern of the range of 10E-6 until the calculated value exceeds approximately 3 x 10E-6."  It goes on to say that, "This is particularly the case where some conservatism is maintained in the exposure assessment", and concludes that this is the case for the PCA and CPU cancer risk assessments. 

		ii. Drinking water. For drinking water, PRZM/EXAMS 5.0 (PE5) surface water modeling was conducted for diflubenzuron and CPU for the proposed uses on alfalfa, peach, plum, and carrot, following EPA's December 12, 2013 diflubenzuron risk assessment. Ground water modeling was conducted for these crops with SCI-GROW.  In addition, to update EPA's previous PE3 surface water modeling for CPU, which was driven by peppers, surface water modeling on peppers was completed using PE5.  Revised PE5 surface modeling did not need to be conducted for diflubenzuron since EPA used PE5 in their latest assessment and found citrus resulted in the highest surface water residues.  The maximum drinking water concentrations were generated from the surface water modeling and these were used in the risk assessments.  The drinking water value used in the chronic non-cancer diflubenzuron risk assessment is 1.2 ppb (combines CPU value of 0.925 ppb on peppers and diflubenzuron value of 0.260 ppb on citrus/peach) from updated PE5 water modeling, while the drinking water value used in the cancer CPU risk assessment is 0.64 ppb (from Florida peppers) from updated PE5 water modeling on peppers. As per EPA, 2013, water modeling was not conducted for PCA since, as per EPA's December 12, 2013 diflubenzuron risk assessment, "...[it] is only a minor metabolite of DFB in the environment...[and] will thus not be considered in the risk assessment for PCA". 
      
      2. 	Non-dietary exposure. Diflubenzuron is a restricted use pesticide based on its toxicity to aquatic invertebrates. This restricted use classification makes it unavailable for use by homeowners except in a tablet containing 2.0% of the active ingredient for use in outdoor water containers. Tablets are a form of engineering control which require minimal handling and significantly reduce exposures. Given the effects in the 21-day dermal toxicity study were only observed at the limit dose (1,000 mg/kg/day) and the dermal absorption is extremely low (0.5%), a residential exposure assessment is not necessary.  Professional applications to outdoor trees and ornamentals in residential areas may expose people in residential locations, parks, or forests treated with diflubenzuron. Based on very low residues detected in forestry dissipation studies, a low dermal absorption rate, and extremely low dermal and inhalation toxicity, these uses are expected to result in insignificant risk, and are therefore not included in the aggregate risk assessment.

D. Cumulative Effects

     The registrant has considered the potential for cumulative effects of diflubenzuron and other substances with a common mechanism of toxicity.  The mammalian toxicity of diflubenzuron is well defined.  Chemtura is not aware of any other pesticide product registered in the United States that could be metabolized to p-chloroaniline. For this reason, consideration of potential cumulative effects of residues from pesticidal substances with a common mechanism of action as diflubenzuron is not appropriate. Thus, only the potential exposures to diflubenzuron were considered in the exposure assessments generated in support of this petition.

E. Safety Determination

      1. 	U.S. population. Based on the available toxicology and exposure database for diflubenzuron, the registrant has determined that the total non-occupational aggregate exposure from diflubenzuron would occur from food and drinking water routes only.  Based on the 0.02 mg/kg/day cPAD (chronic population adjusted dose) derived from the dog chronic NOEL of 2 mg/kg/day and a 100-fold safety factor, chronic aggregate exposure (including food and drinking water) for the U.S. population (total) is equivalent to 10.3% of the cPAD. 
     
     
     For PCA, the total non-occupational aggregate exposure would occur from the dietary route. EPA has determined the Q* as 0.112 and using this Q*, the theoretical risk to the U.S. population (total) from dietary exposure to diflubenzuron-derived PCA was estimated at 1.15 x 10[-][6].  


     For CPU, total aggregate exposure could occur from food (milk) and drinking water. The EPA has determined the Q* is 1.52 x 10-2 and using this Q*,  the theoretical risk to the U.S. population (total) from chronic aggregate exposure (including food and drinking water) to CPU was estimated to be 4.96 x 10[-7]. 

	These cancer risks are well below 3 x 10E-6, which is the acceptable level for conservative assessments such as those conducted in support of this petition (see FR Volume 79, No. 21, Pages 5294-5300, January 31, 2014).

      2. 	Infants and children. The dietary exposure of diflubenzuron was calculated as 0.002681 mg/kg/day for all infants. This value corresponds to 13.4% of the cPAD for diflubenzuron.  The dietary exposure from diflubenzuron in children 1-2 was determined as 0.006601 mg/kg/day and 0.007858 mg/kg/day. This value corresponds to 39.3% of the cPAD.  Aggregate exposure from food and drinking water does not exceed the level of concern. 

          As previously discussed, the NOEL's for maternal and developmental toxicity in rats and rabbits were greater than 1,000 mg/kg/day, and the NOEL for reproductive toxicity was greater than 5,000 mg/kg/day.  Therefore, based on the completeness and reliability of the toxicity data and the conservative exposure assessment, the registrant concludes that there is reasonable certainty that no harm will result in infants and children from aggregate exposure to residues of diflubenzuron and its conversion products containing the p-chloroaniline moiety.

F. International Tolerances
     
     Codex MRLs have been established for diflubenzuron per se on many commodities including : barley (0.05 ppm), citrus fruit (0.5 ppm), edible offal (mammalian (0.1 ppm), eggs (0.05 ppm), hay or fodder (dry) of grasses (3 ppm), meat (from mammals other than marine mammals) (0.01 ppm), milks (0.02 ppm), mushrooms (0.3 ppm), mustard greens (10 ppm), nectarines (0.5 ppm), oats (0.05 ppm), peaches (0.5 ppm), peanuts (0.1 ppm), peanut fodder (40 ppm), peppers chili (3 ppm), peppers chili dried (20 ppm), peppers sweet including pimento or pimiento (0.7 ppm), plums including prunes (0.5 ppm), pome fruits (5 ppm), poultry meat (0.05 ppm), rice (0.01 ppm), rice straw and fodder (dry; 0.7 ppm), Straw and fodder (dry) of cereal grains (1.5 ppm), tree nuts (0.2 ppm), triticale (0.05 ppm), Wheat (0.05 ppm). MRLs have been established for diflubenzuron in the EU for citrus (1.0 ppm), pome fruit (5 ppm), apricot (1 ppm), strawberry (2 ppm), grapes (1 ppm), and brassica vegetables (1 ppm). 

