**EPA Registration**  **Division contact: Susan Lewis**  **, (703) 30 5** 
**- 7090** 

**Interregional Research Project Number 4 (IR** 
**- 4)**  **5E8349** EPA has received a pesticide petition **( 5E8349**  **)** from **IR**
**- 4**  **, 500 College Road**  **East, S uite 201W, Princeton, New Jerse** **y, 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 by

establishing a tolerance for residues of **f luazinam**  **, including its metabolites and degradates,**  in or on the raw agricultural commodity **m ayhaw**  at **2.0** parts per million (ppm) , **cabbage at 3.0 ppm ,**  **cucurbit vegetables, squash/cucumber**  **subgroup 9 B**  **at 0. 0**  **5 ppm**  **, vegetable, b rassica leafy, group 5, except cabbage**  **at 0.01 ppm, and v**  **egetable, tuberous and corm, subgroup 1C at 0.02 ppm**  **. Upon approval of the aforementioned tolerances, IR** 
**- 4 requests to remove the established tolerances**  **for fluazinam on vegetable, brassica leafy, group 5 of 0.01 ppm and potato at 0.02 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 Plant metabolism. **The residue of concern is best defined as the parent, fluazinam in most crops and as the parent, fluazinam and its metabolite, AMGT, in fruit crops**  **(grape and blu eberry).**  **The metabolism of fluazinam in plants (potatoes, peanuts, apples and wine grapes) is adequately understood for the purposes of these**  **tolerances. The metabolism of fluazinam in peanut and potato involves initial reduction of**  **the nitro groups, hydrolysis of the trifluoromethyl group as well as replacement of chlorine by glutathione with subsequent reactions along the**  **glutathione pathway. Following replacement of the deactivating NO2 and Cl groups with activating groups such a**  **s OH, NH2 and sulfhydryl, ring cleavage occurs. Parent fluazinam is then rapidly degraded to form CO2 and carbon fragments**  **which are incorporated into natural products such as glucose, fructose, sucrose, oils and protein. Thus, parent fluazinam is either**  **not found or barely detectable in peanuts and potatoes. Fluazinam parent was the major identifiable residue in both**  **the grape and apple metabolism studies. However, minor levels of AMGT (less than 5% of the total radioactive residue) were also formed in**  **grapes and apples. In grape and apple metabolism studies, following reduction of the nitro groups and**  **replacement of chlorine with a sulfur containing side**
**- chain such as glutathione (as**  **occurred in peanuts and potatoes), glucose is attached to the thiola ctic acid**  **conjugate of AMPA to form the metabolite known as AMGT. This metabolite was not found in**  **the peanut or potatoes metabolism studies. It is analogous to the cysteine conjugate of AMPA found in rats. Identifiable residues in**  **plant metabolism studies either closely resemble fluazinam in structure or are the result**  **of re**
**- incorporation of the fluazinam carbon pool into natural products.**  **Ruminant and poultry metabolism studies demonstrated that the transmittal of**2

**residues fr om the feed of goats and hens through to meat, milk, and eggs was low.**  **Total 14C residues were below 1 ppm in all tissues, milk and eggs. Identifiable residues were less than 2% of the administered dose in all matrices, except for**  **chicken fat and liver .**  **The major metabolite found in animal tissues and milk w ere**  **DAPA, AMPA, and their sulfam ate conjugates. Parent Fluazinam was only**  **detected in very small amounts .**  2. Analytical method. **An analytical method using LC** 
**- MS/MS**  **for the determination of fluazina**  **m and AMGT**  **residues on cabbag**  **e , squash**  **and cucumbers**  **has been developed and validated. The method involves solvent extraction followed by liquid** 
**- liquid partitioning and concentration prior to a final purifica** **tion . The**  **method has been successfully validat ed by an independent laboratory using peanut**  **nutmeat as the matrix. The limit of quantitation (LOQ) of the method is 0.0 1**  **ppm for both fluazinam and AMGT**  **in these**  **crops .**  3. Magnitude of residues. **Cabbage . A total of**  **8 field trials were conducted on**  **cabb age**  **. Treatment 2 of each field site consisted of**  **one application applied as 0.055**  **lb. a.i./1000 plants in a plant base drench at the time of transplanting followed by**  **six (6** **) foliar applications at the target rate of approximately 0. 5**  **lb .**  **a.i./A, applied**  **at 7 (** **+ 1) day intervals**  **. C**  **abbages were harvested**  **approximately 7**  **days after the last application.**  **One decline trial was included with sampling at 0**  **, 3**  **, 7**  **, 9, 14**  **and 21**  **days after the last application. The results show that**  **the maximum Fluazinam residue**  **in cabbage**  **following a total foliar**  **application of approximately**  **3 lb**  **. a.i./A/season with an average PHI of**  **7 days,**  **was 1.**  **7 ppm. The**  **mean fluazinam residue was 0.**  **64 ppm**  **. Residues**  **generally declined over time.**  **Only one residue of**  **AMGT above the LOQ**  **( 0.01**  **ppm )**  **at 0.011 ppm was observed .**  **Squash . A total of**  **6 field trials were conducted on**  **summer squash . Treatment**  **2 of each field site consisted of**  **one soil directed and four (4 )**  **foliar applications at the**  **target rate of approximately 0. 78**  **lb .**  **a.i./A, appl** **ied at 7**  **( +**  **1) day intervals. Squash**  **were harvested 6 to**  **7 days after the last application. The results show that**  **the maximum Fluazinam residue**  **in summer squash following a total**  **application of**  **approximately 3.9**  **lb a.i./A/season with an average PHI of**  **7 d**  **ays, was**  **0.0 16**  **ppm .**  **The mean fluazinam residue was 0.01**  **1 ppm**  **. No residues of AMGT above the LOQ of 0.01 ppm were observed in any sample.**  **Cucumber. A total of**  **6 field trials were conducted on**  **cucumbers . Treatment**  **2 of each field site consisted of**  **one soil directed**  **at transplanting and four (4**  **) foliar**  **applications at the target rate of approximately 0. 78**  **lb .**  **a.i./A, applied at 7 (** **+ 2**  **) day intervals**  **, for a total of 3.9 lb. a.i./A .**  **(Two sites received more than the target amount: 4.6 and 5.7 lb. a.i./A.)**  **Cucumbers were harvested**  **6 to 7 days after the last**  **applicati on.**  **The results show that the maximum Fluazinam residue**  **in cucumbers following a total**  **application of approximately**  **3.9**

**– 5.7**  **lb a.i./A/season with an**  **average PHI of 7**  **days, was**  **0.0 32**  **ppm. Th**  **e mean fluazinam residue was 0.01**  **3 ppm**  **. No residues of AMGT above the LOQ of 0.01 ppm were observed in any sample.**  B. Toxicological Profile3

1. Acute toxicity. **A battery of acute toxicity studies was conducted which placed technical fl**  **uazinam in Toxi city Category IV for**  **acute oral LD50 and**  **dermal irritation,**  **and Category II**  **I for**  **dermal LD50, inhalation LC50 and eye irritation.**  **Technical fluazinam showed potential for dermal sensitization. In an acute neurotoxicity study, the NO**  **A EL for neurotoxicity**  **was 2000 mg/kg bw (the highest dose tested) and the NO**  **A EL for systemic effects was 50 mg/kg bw.**  2. Genotoxicty. **A battery of tests has been conducted to assess the genotoxic potential of technical fluazinam. Assays conducted included two gene mutation t**  **ests in bacteria, a chromosomal aberration test in mammalian cells, a mouse**  **micronucleus test and a DNA repair test in bacteria. Technical fluazinam did not elicit a genotoxic response**  **in any of the studies conducted .**  3. Reproductive and developmental toxicity. **In a two**
**- generation reproductive**  **toxicity study, the NOAEL**  **for reproductive effects was 100 ppm (10. 6**  **mg/kg bw/day). The**  **NOAEL for parental toxicity was 20 ppm (**  **1.9 mg/kg bw/day).**  **In a rat developmental study, there were no developmental effe cts observed at**  **non -**  **maternally toxic doses. The developmental NOAEL**  **was 50 mg/kg bw/day and the**  **LOAEL was 250 mg/kg bw/day, base**  **d upon decreased mean fetal body weight**  **and other evidence suggestive of delayed fetal development related to maternal toxicity**  **. The maternal NOAEL**  **was shown to be 50 mg/kg bw/day. In a rabbit developmental study, there were no developmental effects observed at**  **non -**  **maternally toxic doses. The developmental NOAEL**  **was 7 mg/kg bw/day and the**  **LOAEL was 12 mg/kg bw/day, based on**  **increased incidence of total litter loss and possible slightly increased incidences of fetal findings at this dose. It was**  **concluded that the m aternal**  **NOAEL was 4 mg/kg bw/day**  **.** 4. Subchronic toxicity. **The NOAEL**  **for the 13**
**- week feeding study in rats was**  **50 ppm ( 3.8**  **mg/kg bw/day in males, 4.3**  **mg/kg bw/day in females**  **). The LOAEL**  **was 500 ppm ( 38**  **mg/kg bw/day in males, 44**  **mg /kg bw/day**  **in females ), based on**  **periacinar hepatocellular hypertrophy and sinusoidal chronic inflammation in males, increased liver wei**  **ghts in males and increased lung weights in females. In a 13** 
**- week dog study, the**  **NOAEL was 10 mg/kg bw/day. The**  **LOAEL was 100**  **mg/kg bw/day, based on ocular change observed ophthalmoscopically and liver effects consisting of increased relative liver to**  **body weight, bile duct hyperplasia with or without cholangiofibrosis and increased plasma phosphatase levels.**  **In a 21**
**- day dermal study, the**  **NOAEL for systemic effects was 10 mg/kg bw/day.**  **The LOAEL**  **was 100 mg/kg bw/day, based on hepatocelluar hypertr ophy and**  **increases in AST and cholesterol levels. In a subchronic neurotoxicity study, no effects considered to be indicative of**  **neurotoxicity were observed at the highest dose tested, 3000 ppm (233 mg/kg bw/day in males,**  **2 80**  **mg/kg bw/day in females**  **). The**  **NOAEL for systemic toxicity (body**  **weight differences) was 1000 ppm (74 mg/kg bw/day). In a developmental neurotoxicity study in rats, fluazinam was administered by**  **gavage to female rats from Day 6 after mating to Day 20 of lactation and addition**  **ally to their offspring from Day 7 of age to Day 20 or 21 of age. The author** 4

**concluded that the ma**  **ternal NOAEL**  **was 2 mg/kg bw/day based on reduced body weights and lower food intake. No effects were seen on the microscopic structure of**  **the nervous system of the dams at any dose level (maximum dose of 50 mg/kg**  **bw/day). The NOAEL for behavior and nervous system of the dams was >**  **50 mg/kg bw/day** **, the highest dose tested . No adverse effect of treatment at any dose level was**  **seen on number of implantations, l itter size or offspring survival. Signs of general**  **toxicity in the offspring were evident based on lower Day 1 body weights and lower weight gains at 10 and 50 mg/kg bw/day through weaning. The**  **NOAEL for general**  **toxicity to offspring was 2 mg/kg bw/day. There was no evidence of developmental**  **neurotoxicity in the offspring. The NOAEL for the functional and morphological development of the nervous system in the offspring was**  **> 50 mg/kg bw/day** **, the highest dose tested**  **. There was no increased sensitivity of the fetus or young rat**  **pups to fl uazinam as compared to the dams**  **.** 5. Chronic toxicity. **Fluazinam was not carcinogenic in rats. A NOAEL**  **of 10 ppm (** **Males: 0.**  **38 mg/kg bw/day**  **; Females: 0.**  **47 mg/kg bw/day** **) of fluazinam was established based on the following**  **effects at 1000 and/or 100 ppm: lower food consumption and efficiency of food utilization, slight anemia, elevated cholesterol,**  **increased liver weights, an increased number of macroscopic liver and testes lesions and an increased incidence of microscopical** **ly observed lung, liver, pancreas, lymph node and testes lesions.**  **An additional study was conducted to further define the NOAEL**  **for long**
**- term**  **effects in the rat. In the second study, a NOAEL**  **of 50 ppm (2.2 mg/kg bw/day) was established based on liver**  **and testes effects. Two long** 
**- term feeding studies were conducted in mice. In the first, the**  **NOAEL for all effects was 10 ppm (** **Males: 1.1 mg/kg bw/day**  **; Females: 1.2 mg** **/kg bw/day )**  **and the LOAEL**  **was 100 ppm ( Males: 10.7**  **mg/kg bw/day ; Females: 11.7**  **mg/kg bw/day** **) based on the treatment**
**- related effects observed in the liver.**  **A second oncogenicity study in mice was conducted at 1000, 3000 and 7000 ppm to ensure that an MTD dose was studied. Findings included increased female**  **mo rtality, reduced body weigh**  **t gains, increased brain weights and/or liver weights. An impurity in the test material used in this study resulted in vacuolation of the**  **white matter of the brain and cervical spinal cord in treated animals. A statistically significant higher incidence o**  **f hepatocellular adenomas was observed in the 3000 ppm dose males. Hepatocellular adenomas are common tumors in male mice.**  **There was no dose relationship in the induction of the adenoma and no increase in hepatocellular carcinomas. It**  **was concluded that**  **fluazinam is not carcinogenic in the mouse.**  **In a chronic dog study, the NOAEL**  **was determined to be 1 mg/kg bw/day. The LOAEL**  **was 10 mg/kg bw/day based on generalized, nonspecific toxicity. No ocular effects were observed ophthalmosco**  **pally at any do se in this study**  **.** 6. Animal metabolism. **After an oral dose of fluazinam the median peak time for blood concentration of radiolabel activity for both sexes was 6 hours. The major**  **route of excretion was the feces with urine contributing as a minor route. Less than**  **1% of the administered dose was found in the terminated animals. The highest concentration**  **in tissues was found in the liver. There were no major differences** 5

**related to sex or dose level in the findings. It was concluded that fluazinam is meta** **bolized by both reduction and glutathione and glucuronide conjugation and further metabolism**  **.** 7. Metabolite toxicology

. **The same metabolic processes occur in plants and animals but metabolism in plants is more extensive than in animals. All of the major**  **identified metabolites in both plants and animals retain the phenylpyridinylamine structure. Many of the metabolites resulting from fluazinam are similar in plants**  **and animals and, therefore, have already been evaluated toxicologically. Because of t** **he rapid and complete elimination (in animals) and re**
**- incorporation**  **(in plants) of fluazinam, the toxicity of metabolites is expected to be similar to but lower than the toxicity of the parent compound. The residue of concern is parent**  **fluazinam only in m ost crops and parent fluazinam plus its minor metabolite**  **AMGT on/in fruit crops such as grape and blueberry .**  8. Endocrine disruption

. **The toxicological profile of fluazinam shows no evidence of physiological effects characteristic of the disruption of th**  **e hormone estrogen in mammalian chronic studies or in mammalian or avian reproduction**  **studies. It is therefore considered that there is an adequate level of safety over the reference dose for possible endocrine effects and that an additional safety facto**  **r for possible endocrine effects is not warranted**  **.** C. Aggregate Exposure 1. Dietary exposure. **Potential dietary exposures from food were estimated using the pr**  **oposed tolerances for all crops ,**  **using the Dietary Exposure Evaluation**  **Model**
**- Food Consumption**  **Intake Database (DEEM**
**- FCID**  **TM )** **/Calendex Version 4.02/10.00 Release**  **and percent cr op treated of 100%**  **. The following raw agricultural commoditie**  **s were included: apple; carrot; brassica (cole) leafy**  **vegetables (Group 5) including turnip greens and cabbage at**  **the proposed increased tolerance level;**  **bean (Groups 6A, 6B and 6C); bushberry (Group 13** 
**- 07B); ginseng;**  **head lettuce; leaf lettuce**  **; bulb onion (Crop 3** 
**- 07A)**  **; peanut; vegetable, tuberous and**  **corm, subgroup 1C; pepper/eggplant subgroup 8**
**- 10B;**  **cucurbit vegeta bles,**  **melon subgroup 9A**  **and squash/cucumber subgroup 9B; soybeans;**  **imported wine grapes and sherry**  **; and resulting secondary residues in meat and milk** **. For acute dietary exposure, the acute population adjusted dose (aPAD) was based on the NO**  **A EL of**  **50 mg/kg bw/day from an acute rat neurotoxicity study.**  **For females 13**
**- 49 years of**  **age, the NOAEL of 7 mg/kg bw/day from the rabbit developmental toxicity study was used for acute dietary exposure.**  **For chronic dietary exposure, the chronic population adjusted do**  **se (cPAD) was based on the NO A** **EL from the mouse**  **carcinogenicity study (1**  **.1 mg/kg bw/day). An uncertainty factor of 100 was used in**  **both cases since the results of a DNT study confirmed there was no increased sensitivity of the fetus or young rat pups to f**  **luazinam as compared to the dams and the FQPA uncertainty factor could be reduced to one (1)**  **.** i. Food. **Acute Risk Tier 1 acute dietary exposure analyses were conducted for fluazinam to determine the exposure contribution of**  **the above mentioned**6

**commoditie s to the diet and to ascertain the acute risk potential. The estimates were**  **based on: proposed tolerance level residues for all the crops; apple, peanut and potato processing studies; market share assumptions of 100% crop treated;**  **screening**
**- level acute ED**  **WC of 218 ppb for water**  **; and consumption data from**  **NHANES/WWEIA (** **2005**
**- 6, 2007** 
**- 8, and 2009** 
**- 10 cycles**  **) continuing survey of food intake.**  **Even using all of the worst**
**- case exposure scenarios listed above, the Tier 1 95th**  **percentile acute dietary exposure ( per capita)**  **fr om** **food and drinking water for the**  **U.S. population was estimated to be 0.0**  **2 6340**  **mg/kg bw/day or 5.27**  **% of the aPAD.**  **The highest acute exposure estimate (95th percentile) was observed in the females 13** 
**- 49 yrs.**  **subpopulation: 0.01 9739**  **mg/kg bw/d ay. This corresponds to**  **28.2 %**  **of the aPAD.**  **Chronic Risk Tier 1 dietary exposure analyses were conducted for fluazinam to determine the exposure**  **contribution of th e above mentioned**  **commodities to the diet and to ascertain the chronic risk potential. T**  **he estimates were based on: proposed tolerance level residues for all the crops; apple, peanut and potato processing**  **studies; market share assumptions of 100% crop treated; screening** 
**- level chronic**  **EDWC of 37**  **ppb; and consumption data from**  **NHANES/WWEIA (** **200 5** 
**- 6, 2007** 
**- 8,**  **and 2009**
**- 10 cycles**  **) continuing survey of food intake.**  **Even using all of the worst**
**- case exposure scenarios listed above, the Tier 1**  **chronic dietary exposure estimates resulted in an estimated exposure for the U.S. population of 0.00**  **2375 mg/** **kg bw/day. This exposure corresponds to 21.6**  **% of the cPAD of 0.011mg/kg bw/day. The highest exposure estimate was calculated for the**  **non -**  **nursing infants population subgroup. This exposure was determined to be**  **0.00 7247**  **mg/kg bw/day (**  **65.9 % of the cPAD)**  **mo st**  **of which was due to the water contribution**  **. It can be concluded that acute or long** 
**- term dietary exposure to fluazinam**  **through residues on treat ed apple, carrot,**  **brassica (cole) leafy vegetables (Group 5) including turnip greens, bean (Groups 6A, 6B**  **and 6C), bushberry (Group 13**
**- 07B),**  **ginseng, head lettuce, leaf lettuce, bulb onion (Crop 3**
**- 07A), peanut,**  **tuberous and corm, subgroup 1C**  **, pepper/eggplant subgroup 8** 
**- 10B,**  **cucurbit vegetables, melon subgroup 9A and squash/cucumber subgroup 9B,**  **soybeans, impo**  **rted wine grapes and sherry**  **and resulting secondary residues in meat and milk should not be of**  **cause for concern.** ii. Drinking water

. **Since fluazinam is intended for application outdoors to field grown crops, the potential exists for parent and** **/ or metabo**  **lites to reach ground or surface water that may be used for drinking water. The potential estimated**  **drinking water concentrations (EDWCs) associated with the application of fluazinam to**  **cabbage, mayhaw, squash/cucumber subgroup**  **9B ,**  **or tuberous and**  **corm, s ubgroup 1C**  **, is less than the maximum values estimated for**  **turf . Thus, the**  **mo re conservative**  **screening**
**- level acute EDWC (218 ppb) and chronic EDWC**  **(37 ppb)**  **for turf**  **were incorporated into the DEEM** 
**- FCID model to estimate dietary**  **exposure .**  2. Non

- dietary e

xposure . **A registration**  **f or the use of**  **fluazinam on golf** 7

**courses has been approved**  **. Applications are to be made by golf course workers**  **only , thus no residential handler exposure is expected**  **. However,**  **post -**  **application dermal exposure from contact with the**  **treated turf on golf courses may occur. Thus, post** 
**- application dermal exposure was calculated for adults**  **and for youth**  **playing golf**

**, using the general US population subgroup and**  **youth , 13** 
**- 19 years**  **subgroup . T**  **he Margins of Exposure (MOE) for both the**  **ad ults (21,800) and**  **the youth**  **(14,300) were well above the acceptable MOE of 100.** D. Cumulative Effects **Fluazinam is a phenylpyridinylamine fungicide. Since there are no other members of this class of fungicides, it is considered unlikely that fluazin**  **am would have a common mechanism of toxicity with any other pesticide in use at this time**  **.** E. Safety Determination 1. U.S. population. **Dietary and**  **post -**  **application dermal**  **exposure from**  **recreational contact**  **with treated**  **turf on**  **golf courses**  **will be**  **the r**  **outes of**  **exposure to**  **the U.S.**  **population. Am** **ple margins**  **of safety**  **have been**  **demonstrated for**  **both situations.**  **For the**  **general U.S.**  **population, the**  **chronic aggregate**  **risk assessment**  **is based**  **on exposure**  **from food**  **a nd**  **drinking water**  **only, since**  **no residenti**  **al uses**  **exist. A**  **s noted**  **above, the**  **chronic dietary**  **exposure to**  **fluazinam represents**  **21.6 %**  **of the**  **cPAD for**  **the overall**  **U.S. population,**  **using the**  **conservativ e**  **Tier I**  **assumptions .**  **A cancer**  **dietary assessment**  **was not**  **conducted because**  **this product**  **has been**  **c lassified**  **as “**  **suggestive evidence**  **of carcinogenicity,**  **but not**  **sufficient to**  **assess human carcinogenic potential .”**  **An acute**  **aggregate risk**  **assessment is**  **required for**  **the general**  **population and**  **for the**  **subgroup of**  **females 13** 
**- 49**  **years old.**  **For both**  **of these**  **population s**  **, the**  **acute dietary**  **(food and**  **drinking water)**  **risk assessment**  **represents acute**  **aggregate risk**  **since the**  **dietary route**  **alone is**  **relevant for**  **acute exposure**  **and risk**  **assessment. As**  **noted above, the acute dietary**  **exposure to**  **fluazinam is estimated**  **to be**  **5.27 % o**  **f t he**  **aPAD for**  **the overall**  **U.S. population,**  **and 28.2**  **% of**  **the aPAD**  **for the**  **subgroup of**  **females 13** 
**- 49**  **years old.**  **These values**  **were presented**  **above and**  **are below**  **the Agency’**  **s level of concern.**  **Short**
**- term**  **and intermediate** 
**- term**  **aggregate risks**  **i nclude**  **chronic dietary**  **and short** 
**- term**  **residen tial**  **sources of**  **exposure. Since**  **Fluazinam is**  **proposed for**  **use on**  **golf courses**  **there is**  **potential for**  **post -**  **application exposure**  **to adults**  **and youths**  **from playing**  **golf. T**  **he US**  **general population**  **was chosen**  **as the**  **representative short** 
**- term**  **population for**  **adults, while**  **the dietary**  **subpopulation youths**  **aged 13**  **to 19**  **was chosen**  **to match**  **with the**  **youth golfer**  **residential exposure.**  **The d**  **ietary (food**  **and drinking**  **water) exposure**  **was based**  **on the**  **Tier I**  **chronic exposure**  **assessment as**  **noted above**  **but converted**  **to an**  **MOE .**  **This was aggregated**  **with the**  **appropriate post**
**- application residential golfer MOE to yield the following aggregate**  **short/intermediate**
**- term**  **MOEs: US**  **general population**  **MOE =**  **1811; youths,**  **13**
**- 19** 8

**= 2779.**  **T he**  **se aggregate**  **risks are**  **well above**  **100 for**  **all populations,**  **indicating acceptable risks for both adults and youth.**  **Based on this information, it can be concluded that there is reasonable certainty that no**  **harm will**  **result from**  **acute ,**  **short/intermediate t**  **erm or**  **chronic exposure**  **to fluazinam**  **.** 2. Infants and children

. **Data from developmental toxicity studies in the rat and rabbit, a 2** 
**- generation reproduction study and a developmental neurotoxicity**  **study were considered. These studies, that**  **were described earlier, demonstrated no**  **increased sensitivity of rats or rabbits to in utero or gavage exposure of pups to fluazinam. In addition, the multigeneration reproductive toxicity study did not**  **identify any increased sensitivity of rats to in utero or postnatal exposure. For all**  **four studies, parental NOAEL**  **s were lower than or equivalent to the developmental or offspring**  **NOAEL s. It is concluded that the standard margin of safety will**  **protect the safety of infants and children and that an additional FQPA safety factor**  **is not warranted. The dietary exposure of fluazinam to infants and children is estimated to be**  **less than any level of concern**  **. The proposed tolerances plus drinking water input**  **will utilize**  **20. 3**  **% of the aPAD**  **for the “Children (1** 
**- 2 years)”**  **subg ro**  **up, and**  **53.6 % of**  **the cPAD**  **for the “Children (1** 
**- 2 years)”**  **subgroup. The**  **non -**  **nursing infants population subgroup**  **utilizes 65.9**  **% of the cPAD. (These were the most sensitive**  **infant/child subgroups .**  **) Thus, it can be concluded that there is reasonable certai**  **nty that no harm will result to infants and children from acute or chronic exposure to**  **fluazinam .**  F. International Tolerances **There are presently no Codex maximum residue levels (MRLs) established for residues of fluazinam on any crop.**  **The Canadian est**  **ablished MRLs for brassicas (crop group 5A & 5B), bushberries (crop group 13B), dry beans, lima**  **beans, snap beans, and the Mexican MRLs for beans and potatoes are similar to the**  **tolerances established for these crops in the USA .**