Federal Register / Vol. 63, No. 144 / Tuesday, July 28, 1998 / Notices 40273
Name Case No.
Ben Salamoni Trucking Service Inc ...... RK272±01697 Clarke Oil Well Servicing Inc ...... RK272±01871 Excel Specialty Products ...... RK272±04762 Leggett & Platt, Incorporated ...... RF272±4705 National Beverages, Inc...... RK272±04677 Personnel Security Hearing ...... VSO±0206 Petrolane Gas Service Ltd. Partnership ...... RF340±00169 Texaco Refining and Marketing, Inc...... RR340±0001 The Brindle Excavating Co., Inc...... RK272±01477 Weinberg Chemical & Supply Company ...... RK272±04716 200 Varick Street Associates ...... RK272±04603
[FR Doc. 98–20128 Filed 7–27–98; 8:45 am] DATES: Comments, identified by the claimed confidential by marking any BILLING CODE 6450±01±P docket control number PF–816, must be part or all of that information as received on or before August 27, 1998. ‘‘Confidential Business Information’’ ADDRESSES: By mail submit written (CBI). CBI should not be submitted comments to: Public Information and through e-mail. Information marked as ENVIRONMENTAL PROTECTION Records Integrity Branch, Information CBI will not be disclosed except in AGENCY Resources and Services Division accordance with procedures set forth in (7502C), Office of Pesticides Programs, 40 CFR part 2. A copy of the comment [PF±816; FRL±5799±3] Environmental Protection Agency, 401 that does not contain CBI must be M St., SW., Washington, DC 20460. In submitted for inclusion in the public Notice of Filing of Pesticide Petitions person bring comments to: Rm. 1132, record. Information not marked CM #2, 1921 Jefferson Davis Highway, confidential may be disclosed publicly AGENCY: Environmental Protection Arlington, VA. by EPA without prior notice. All written Agency (EPA). Comments and data may also be comments will be available for public ACTION: Notice. submitted electronically to: opp- inspection in Rm. 1132 at the address [email protected]. Follow the given above, from 8:30 a.m. to 4 p.m., SUMMARY: This notice announces the instructions under ‘‘SUPPLEMENTARY Monday through Friday, excluding legal initial filing of pesticide petitions INFORMATION.’’ No confidential holidays. proposing the establishment of business information should be regulations for residues of certain submitted through e-mail. FOR FURTHER INFORMATION CONTACT: The pesticide chemicals in or on various Information submitted as a comment product manager listed in the table food commodities. concerning this document may be below:
Product Manager Office location/telephone number Address
Bipin Gandhi (PM 21) .... Rm. 707A, CM #2, 703±308±8380, e-mail:[email protected]. 1921 Jefferson Davis Hwy, Ar- lington, VA. Cynthia Giles-Parker Rm. 247, CM #2, 703±305±7740, e-mail:[email protected]. 1921 Jefferson Davis (PM 22). Hwy.,Arlington, VA.
SUPPLEMENTARY INFORMATION: EPA has including printed, paper versions of may be filed online at many Federal received pesticide petitions as follows electronic comments, which does not Depository Libraries. proposing the establishment and/or include any information claimed as CBI, amendment of regulations for residues is available for inspection from 8:30 List of Subjects of certain pesticide chemicals in or on a.m. to 4 p.m., Monday through Friday, Environmental protection, various food commodities under section excluding legal holidays. The official Agricultural commodities, Food 408 of the Federal Food, Drug, and record is located at the address in additives, Feed additives, Pesticides and Comestic Act (FFDCA), 21 U.S.C. 346a. ‘‘ADDRESSES’’ at the beginning of this pests, Reporting and recordkeeping EPA has determined that these petitions document. contain data or information regarding Electronic comments can be sent requirements. the elements set forth in section directly to EPA at: Dated:July 9, 1998. 408(d)(2); however, EPA has not fully [email protected] evaluated the sufficiency of the James Jones, submitted data at this time or whether Electronic comments must be Director, Registration Division, Office of the data supports granting of the submitted as an ASCII file avoiding the Pesticide Programs. petition. Additional data may be needed use of special characters and any form before EPA rules on the petition. of encryption. Comments and data will Summaries of Petitions The official record for this notice of also be accepted on disks in Petitioner summaries of the pesticide filing, as well as the public version, has Wordperfect 5.1 file format or ASCII file been established for this notice of filing format. All comments and data in petitions are printed below as required under docket control number [PF–816] electronic form must be identified by by section 408(d)(3) of the FFDCA. The (including comments and data the docket number (insert docket summaries of the petitions were submitted electronically as described number) and appropriate petition prepared by the petitioners and below). A public version of this record, number. Electronic comments on notice 40274 Federal Register / Vol. 63, No. 144 / Tuesday, July 28, 1998 / Notices represent the views of the petitioners. with methyl thioglycolate. The effects on the fertility, fecundity, or EPA is publishing the petition derivative is partitioned into toluene, health and survival of swine dams and summaries verbatim without editing which is analyzed by gas their offspring at an arsanilic acid feed them in any way. The petition summary chromatography (GC) and an electron concentration of 100 ppm. Furthermore, announces the availability of a capture detector (ECD). The anticipated at the 100 ppm arsanilic acid feeding description of the analytical methods Limit of Quantitation (LOQ) is 0.05 level, no gross abnormalities or adverse available to EPA for the detection and ppm. Method development for the effects were found on organ weights or measurement of the pesticide chemical metabolite residues will ensue as the pathology. To the contrary, arsanilic residues or an explanation of why no metabolites are identified. acid in the diet improved the overall such method is needed. 3. Magnitude of residues. Field health, improved weight gain, and residue trials are currently in progress at increased survival of swine. 1. Fleming Laboratories, Inc. several sites in Florida. Mature No developmental effects were found PP 4G4276 grapefruit samples have been harvested in rats exposed in utero to arsanilic acid from trees treated with 6.25 lbs Pro- at levels up to and including that which EPA has received a pesticide petition Gen(r) per acre and are being stored produced overt maternal toxicity. (PP 4G4276) from Fleming Laboratories, until residue analytical method Arsanilic acid was administered orally Inc., P.O.Box 34384, Charlotte, NC development is complete. However, by gavage to pregnant rats at nominal 28234 proposing pursuant to section based on the data from the plant dose levels of up to 60 mg/kg/day. 408(d) of the Federal Food, Drug, and metabolism study, total residues of Reduced body weight gains early in the Cosmetic Act, 21 U.S.C. 346a(d), to arsanilic acid in grapefruit are expected treatment period, reduced food amend 40 CFR part 180 by establishing to be less than 0.5 ppm. consumption, and the presence clinical a tolerance for residues of (4- signs (60 mg/kg/day group) were B. Toxicological Profile methylphenyl)arsonic acid in or on the considered evidence of maternal raw agricultural commodity fresh 1. Acute toxicity. Pro-Gen(r)/arsanilic toxicity. No developmental toxicity was market grapefruit grown only in Florida acid is only moderately acutely toxic to apparent at any dose level. A no at 0.5 parts per million (ppm). EPA has mammals. The rat acute oral LD50 values observable effect level (NOEL) for determined that the petition contains were 1,411 mg/kg for males, 976 (646- maternal effects (reduced food data or information regarding the 2883) mg/kg for females and 1,461 mg/ consumption) was considered to be less elements set forth in section 408(d)(2) of kg for males and females combined. A than 6 mg/kg/day (based on a 60.0% of the FFDCA; however, EPA has not fully study with New Zealand white rabbits target concentration analysis of the 10 evaluated the sufficiency of the established acute dermal LD50 values of mg/kg/day formulation used during the submitted data at this time or whether 922 mg/kg for males, 909 (445-1972) first 5 days of dose administration). The the data supports granting of the mg/kg for females and 921 (577-1402) NOEL for maternal clinical signs was 30 petition. Additional data may be needed mg/kg for males and females combined. mg/kg/day. The NOEL for before EPA rules on the petition. Arsanilic acid has caused minimal signs developmental toxicity of rats was 60 A. Residue Chemistry of toxicity in rats following a 4 hour mg/kg/day. inhalation exposure to a measured No developmental effects were noted 1. Plant metabolism. A plant atmospheric concentration of 5.35 mg/l. in rabbits exposed in utero to arsanilic metabolism study is being conducted at The acute inhalation LC50 is greater than acid (100%) at levels up to and the proposed use rate of 6.22 lbs active 5.35 mg/l. Arsanilic acid is slightly including that which produced overt ingredient (6.25 lbs product) per acre irritant to rabbit eyes and is not irritant maternal toxicity. Arsanilic acid (Pro- and has revealed approximately 0.46 to rabbit skin. Gen(r)) was administered orally by ppm total radioactive residue (TRR) in Arsanilic acid is not considered a skin gavage to pregnant rabbits at nominal whole fruit, of which 0.13 ppm or sensitizer. Arsanilic acid does not cause dose levels up to 6 mg/kg/day. Maternal 29.2% of the TRR was parent sensitization in guinea pigs. effects were observed only in the 6 mg/ compound. Four of the 11 metabolites Additionally, arsanilic acid has been kg/day dosed dams and were limited to isolated from whole fruit exceed 10% of manufactured and used since the 1940’s reductions in mean body weight gain the TRR. Metabolite characterization as a medicinal feed additive for poultry and food consumption. No maternal and identification is still in progress. and swine with no reported incidents of effects were apparent at dose levels of 2. Analytical method. A High hypersensitivity among workers. 1 and 3 mg/kg/day. No developmental Performance Liquid Chromatography 2. Genotoxicty. Arsanilic acid is not toxicity was expressed at any dose level. (HPLC) method is available to verify the mutagenic to five strains of Salmonella The NOEL for maternal effects was 3 certified limits of arsanilic acid in the typhimurium. In the mouse mg/kg/day. The NOEL for end-use product. micronucleus test, arsanilic acid (99.6% developmental toxicity was 6 mg/kg/ Currently there is no validated purity) was devoid of micronucleus day. method for determining any of the inducing potential in the bone marrow 4. Subchronic toxicity. No mortality residues of arsanilic acid in/on of male and female CD-1 mice when occurred during a 91-day feeding study grapefruit. However, method tested to maximum tolerated doses. in which male and female rats were fed development is partially complete for an Arsanilic acid was determined to be nominal concentrations of up to 750 analytical method to determine residues weakly mutagenic in mouse lymphoma ppm arsanilic acid in the diet. Some of (4-aminophenyl)arsonic acid, per se, L51178Y cells in the presence of S9 signs of toxicity (behavior, locomotion the active ingredient of Pro-Gen(r), in or mix, when tested at concentrations and excreta) were observed at feeding on whole grapefruit. In principle, a 50 extending into the toxic range. However, levels of 375 ppm and above. No gram sample of grapefruit is extracted evidence of mutagenicity in the absence definite treatment effects were observed by homogenization with water. The of S9 mix was inconclusive. in animals receiving 50 ppm arsanilic extract is centrifuged, filtered, 3. Reproductive and developmental acid in the diet. The NOEL was concentrated by rotary evaporation, toxicity. A review of three studies determined to be 50 ppm (3.77 mg/kg/ cleaned up on a florisil column, detailing the effects of arsanilic acid on day for males and 4.76 mg/kg/day for buffered to pH 4.5, then derivatized reproduction in swine found no adverse females). Federal Register / Vol. 63, No. 144 / Tuesday, July 28, 1998 / Notices 40275
No mortality occurred during a 90-day 6. Animal metabolism. Arsanilic acid acid have shown no effect on the time- feeding study in which male and female uniformly labeled with 14C in the to-mating or on mating and fertility beagles were fed arsanilic acid at up to benzene ring was used to determine the indices. Radiolabelled [14C]-arsanilic 200 ppm in diet. No ophthalmoscopic metabolic fate of arsanilic acid fed to acid fed to chickens (laying hens) had abnormalities were observed at any pigs and chickens. Arsanilic acid was no effect on the ability of the hens to level. Clinical signs of toxicity were well absorbed by both species. Urine produce eggs. Multigeneration observed in some dogs receiving 200 was the predominant route of excretion. reproduction studies in swine, ppm arsanilic acid in diet. While there The bile was a minor (<5% of the dose) developmental toxicity studies in rats was no observable indication of toxicity route of excretion in pigs (was not and rabbits, chronic studies in rats plus in animals receiving up to 100 ppm measured in chickens). Arsanilic acid long term medicinal use in animal arsanilic acid in the diet, microscopic and two other metabolites, N- husbandry amply demonstrates that evaluation of the kidneys revealed dose- acetylarsanilic acid and (4- related abnormalities. The NOEL for acetamidophenyl)dimethylarsine oxide, arsanilic acid does not affect the estrous female beagle dogs was 50 ppm (1.7 mg/ were identified in the pig urine. In pigs, cycle, mating behavior, male or female kg/day). The NOEL for male beagle dogs somewhere between 17-39% of the fertility, or male or female reproductive was 25 ppm (0.7 mg/kg/day). urinary 14C metabolites was excreted as tracts. 5. Chronic toxicity. Arsanilic acid is arsanilic acid, 15-29% as N- C. Aggregate Exposure not carcinogenic to rats. Arsanilic acid acetylarsanilic acid and <5% as (4- is approved by the FDA for use as a acetamidophenyl)dimethylarsine oxide. 1. Dietary exposure—Food— i. From medicinal feed supplement for swine Only 2-5% of the radio-labeled arsanilic medicinal feed additive use. Arsanilic and poultry at concentrations up to acid dose remained in the carcass or acid has been utilized under FDA 0.01% of the ration and has been liver of pigs while less than 1% approval as a medicinal feed additive in extensively used in commercial rations remained in the chicken carcasses (liver pig, chicken and turkey feeds since the since the 1940’s. included). There was no evidence of any 1940’s. However, the feed additive Arsanilic acid was fed to rats (two biotransformation of arsanilic acid in tolerances established by the FDA are separate studies) at concentration levels chickens. The study authors also note expressed in terms of total residues of of 100, 500 and 1,000 ppm in the diet that the results of this study corroborate combined arsenic (calculated as As) for 106 to 116-weeks. In both studies, earlier research showing that chickens instead of as arsanilic acid (21 CFR the presence of arsanilic acid in the diet rapidly excrete arsanilic acid with no was reported to have caused no gross biotransformation. 558.62 and 556.60). Because arsanilic abnormalities or adverse effects on 7. Metabolite toxicology. There is no acid may be the sole dietary contributor organ weights, pathology, incidence of known information about the toxicity of that necessitates the feed additive tumors or health of rats. any of the currently identified tolerances for arsenic, these tolerances Long term feeding of 0.01% arsanilic metabolites of arsanilic acid. can be converted to total arsanilic acid acid in pig feed for up to 51 months 8. Endocrine disruption. Arsanilic equivalents by using a conversion factor during a multigeneration study resulted acid is not considered to be an of 2.9, the ratio of the molecular weight in increased survival and overall endocrine disruptor. Several studies in of arsanilic acid (217.04) to that of its improved health of arsanilic acid- which different species were arsenic content (74.92). treated pigs. administered high levels of arsanilic
Total Residues as Total Residues as Arsenic (ppm) Arsanilic Acid Commodity (ppm)
0.5 ...... 1.45 eggs, chicken 0.5 ...... 1.45 muscle, chicken 2.0 ...... 5.8 edible by-products, chicken 0.5 ...... 1.45 eggs, turkey 0.5 ...... 1.45 muscle, turkey 2.0 ...... 5.8 edible by-products, turkey 2.0 ...... 5.8 liver, swine 2.0 ...... 5,8 kidney, swine 0.5 ...... 1.45 muscle, swine 0.5 ...... 1.45 by-products, swine
ii. From proposed use on fresh market temporary tolerances proposed for the livestock consumption of Pro-Gen(r) grapefruit grown only in Florida. In the processed commodities, grapefruit juice, under the auspices of the proposed EUP. amended petition for a Saleable dried grapefruit pulp or grapefruit citrus 2. Drinking water. No exposure to Experimental Use Permit, the following oil. arsanilic acid is expected from temporary tolerance is proposed for iii. From livestock consumption of consumption of drinking water. total residues of arsanilic acid expressed treated grapefruit and/or processed Arsanilic acid is not proposed for as arsanilic acid, per se, in or on fresh products. Under the amended petition application to sources of drinking water. market grapefruit. for Experimental Use Permits (EUP), Additionally, hydrolysis, soil 0.5 ppm in/on grapefruit (whole fruit) treated fruit may not be fed to livestock. metabolism and soil adsorption/ Because the treated fruit are The amended EUP also restricts desorption studies have shown that prohibited from being processed under livestock grazing or consumption of arsanilic acid is stable to environmental the amended Experimental Use Permit, forage or hay from Pro-Gen(r) treated degradation and binds tightly and no dietary exposure is anticipated from orchards. Therefore, no dietary exposure irreversibly to the organic and mineral the processed commodities nor are any to arsanilic acid is anticipated from fractions of soils. Any arsanilic acid that 40276 Federal Register / Vol. 63, No. 144 / Tuesday, July 28, 1998 / Notices might be excreted by poultry or swine structure (containing a phenyl ring) proposed for pesticide-bearing crop or administered arsanilic acid for from these other straight-chained animal commodities that may be medicinal purposes will be tightly organic arsenical herbicides, it is consumed by humans. To conduct the bound to soil if incorporated in to the reasonable to assume that arsanilic acid risk assessment for arsanilic acid under soil as a fertilizer. Consequently, will have a unique mode of action the tenets of the proposed amended potential exposure of surface and/or compared to the straight chain Experimental Use Permit for Florida- ground water to arsanilic acid will be herbicides. The proposed use of grown, fresh market fruit only, one minimized. arsanilic acid as a plant growth needs to know how much grapefruit 3. Non-dietary exposure. There are no regulator further illustrates the would typically be consumed by known sources of non-dietary exposure differences when comparing arsanilic humans and the amount of arsanilic to arsanilic acid, outside of occupational acid to these herbicides. acid residues in or on the fruit. exposure in the manufacturing and Therefore, for cumulative exposure Additionally, human exposure from packaging of Pro-Gen(r)/arsanilic acid in considerations, Fleming Laboratories consumption of swine and poultry its current usage in animal husbandry, believes it is appropriate to consider products from medicinally treated or in its proposed use in Florida fresh only the potential risks of arsanilic acid animals must be considered. market grapefruit production. There is noted in the discussion of aggregate For estimating grapefruit dietary little concern that children would be exposure (above). consumption, EPA’s Total Diet Study, exposed to non-dietary sources of which is used to calculate exposure and arsanilic acid. E. Safety Determination dietary risk for pesticides, reveals that U.S. population. The Acceptable 25-30 year-old men have the highest D. Cumulative Effects Daily Intake (ADI) is the amount of consumption of grapefruit compared to For cumulative exposure pesticide residue that can be ‘‘safely’’ all other age and sex groupings. considerations, Fleming Laboratories ingested by humans and still be Consumption rates in this group are believes it is appropriate to consider protective of the health of all segments listed as 4.3 grams of grapefruit per day. only the potential risks of arsanilic acid of the population. An ADI must be Consumption of whole grapefruit (4.3 noted in the discussion of aggregate established for any pesticide that results grams/day) contributes to less than exposure (above), based on the current in a residue on crops used for human 0.08% of the total diet in this age and approaches used by the FDA and EPA consumption. The ADI, sometimes sex category. for regulating organic arsenical referred to as the Reference Dose (RfD), Dietary exposure from grapefruit compounds in animal husbandry and is a mathematically derived figure based consumption will be reduced by the crop production. on the NOEL of a chronic or subchronic limited use of Pro-Gen(r) to grapefruit Arsanilic acid is an organic arsenical toxicity study and safety or uncertainty grown in Florida. According to the compound. FDA regulations have factors. Uncertainty factors are used to Florida Citrus Summary 1993-94, established feed additive tolerances, compensate for inter- and intra-species Florida produced 816,800 tons of expressed as ppm total combined differences, type of study, etc. when grapefruit in 1993-1994, which was arsenic, for the following medicinal extrapolating from toxicity data (animal 66.10% of the total U.S. production of organoarsenical compounds, arsanilic or human) to human risk assessments. grapefruit. This means that grapefruit acid, arsanilate sodium, nitarsone, For arsanilic acid, the ADI will be grown in Florida would contribute to carbarsone, and roxarsone. based on the results of the dog less than 0.053% (i.e. 0.08% of diet x Although FDA has authorized the use subchronic feeding study. The ADI is 66.1% of grapefruit = 0.053%) of the of these compounds as medicinal feed equal to the NOEL times a safety or total diet for the highest consumers of additives, only one of these uncertainty factor (UF). It is customary grapefruit, 25-30 year-old men. organoarsenicals may be used at a time to use a UF of 100 fold (100x) to account For estimating the dietary as the sole source of organic arsenic in for the species differences from dog to consumption of swine and poultry the feed. Therefore, there is no exposure human, as well as for extrapolating from products, EPA’s Total Diet Study reveals from multiple organic arsenicals in a subchronic study to chronic exposure that 25-30 year-old men have the animal feeds. of humans. Assuming that EPA concurs highest consumption of pork (39.5 With regards to crop protection, the with an uncertainty factor of 100x, the grams/day) and poultry (chicken plus only known organic arsenicals ADI based on the most sensitive NOEL turkey; 28.7 grams/day). (Gram servings registered in the U.S. are the herbicides: can be calculated as follows: of pork, chicken and turkey kidneys and cacodylic acid, a cotton defoliant; and NOEL = 25 ppm arsanilic acid in diet livers were not included). While 60-65 disodium or monosodium of dogs = 0.75 mg/kg/day year old men have the highest methanearsonic acid, contact herbicides Then the ADI or RfD = 0.75 mg/kg/ consumption of eggs, the 25-30 year-old used in cotton and citrus production. day x (1/100) = 0.0075 mg/kg/day men have the second highest With regard to residue tolerances for Based on EPA’s total diet survey, consumption rate (31 grams/day). Total these herbicides, residues of cacodylic sensitive populations, such as infants, consumption of pork, poultry and eggs acid are regulated discretely for that have little or no intake of grapefruit or accounts for 3.23% of the diet of 25-20 compound under 40 CFR 180.311. grapefruit juice. Therefore the ADI is year-old men. In comparison, the same While, residues of disodium and based on consumption of grapefruit and commodities comprise 3.1% of the diet monosodium methanearsonic acid are grapefruit juice by 70 kg adult humans. of 2 year-old children, 2.7 % for females regulated simultaneously as Therefore, if the ADI is 0.0075 mg/kg/ 14-16 years-old, 2.9% for males 14-16 methanearsonic acid under 40 CFR day, a 70 kg adult could safely consume years-old and 2.8% for 25-30 year-old 180.289. Since these compounds are 0.525 mg arsanilic acid /day (0.0075 mg/ women. regulated discretely, it can be assumed kg/day x 70 kg). For conducting a dietary risk that EPA considers them to have assessment and to provide conservative distinct metabolic pathways and modes F. Dietary Risk Assessment estimates: (1) the total consumption of of action. The dietary risk assessment evaluates fruit has been adjusted up from an Since arsanilic acid has a how much of the ADI would be ‘‘used estimated 4.3 grams to 5 grams considerably different chemical up’’ when residue tolerances are grapefruit consumed per day (2); total Federal Register / Vol. 63, No. 144 / Tuesday, July 28, 1998 / Notices 40277 residues of arsanilic acid in or on whole Total residues of 5.8 ppm arsanilic No. 85637-75-8) when used as an inert fruit are considered to be 0.5 ppm, acid = 5.8 mg total arsanilic acid ingredient in pesticide formulations based on the proposed temporary residues /kg food applied to growing crops or to raw tolerance for total residues of Pro-Gen(r) (Amount of kidneys and liver agricultural commodities after harvest in or on treated grapefruit (3); the total consumed) x (residue level) = 0.0028 kg or to animals. EPA has determined that consumption of pork, poultry and eggs total arsanilic acid /day x 5.8 mg/kg = the petition contains data or information has been adjusted from the estimated 0.016 mg total arsanilic acid/day in pork regarding the elements set forth in 39.5 grams/day to 40 grams/day; and (4) and poultry kidneys and liver. section 408(d)(2) of the FFDCA; total FDA allowed residues of arsanilic Total dietary intake of total arsanilic however, EPA has not fully evaluated acid in pork or poultry products (with acid = 0.00166 + 0.058 + 0.016 = the sufficiency of the submitted data at the exception of kidneys and liver) is 0.07566 mg total arsanilic acid residues this time or whether the data supports 1.45 ppm. Since the estimated gram per day granting of the petition. Additional data quantities of pork and poultry organ This estimate of total dietary intake may be needed before EPA rules on the meats (kidneys and livers) were not represents only 14% of the allowable petition. provided using the estimated daily daily consumption of 0.525 mg arsanilic A. Residue Chemistry consumption of 2.8 g beef liver provides acid/day for a 70 kg adult, established an extremely conservative estimate for by a NOEL of 25 ppm and an ADI of Magnitude of residues. No residue pork and poultry livers with FDA 0.0075 mg/kg/day. The estimated chemistry data or environmental fate allowed arsanilic acid residues of 5.8 dietary intake of total arsanilic acid data are presented in the petition as the ppm. residues from Pro-Gen(r)-treated fresh Agency does not generally require some If it is assumed that all grapefruit in market grapefruit is only 0.03% of the or all of the listed studies to rule on the Florida are treated with Pro-Gen(r), ADI of 0.0075 mg/kg/day. exemption from the requirement of a which results in total arsanilic acid Infants and children. Based on EPA’s tolerance for an inert ingredient. residue levels of 0.5 ppm in fruit, and total diet survey, sensitive populations, B. Toxicological Profile a 70 kg adult consumes 5 grams of such as infants, have little or no intake grapefruit per day of which 66.1% is of grapefruit or grapefruit juice. 1. Acute toxicity. ICI believes from Florida, then the total dietary Therefore, the proposed use of Pro- sufficient information was submitted in intake per day can be calculated as Gen(r) on Florida grapefruit will pose no the petition to assess the hazards of follows: additional risk of adverse effects to oxirane, methyl-,polymer with oxirane, 5 grams/day grapefruit consumed = infants or children beyond that which mono[2-(2-butoxyethoxy)ethyl]ether. No 0.005 kg/day grapefruit consumed already exists from consumption of toxicology data were presented in the 0.005 kg/day grapefruit x 0.661 = poultry and swine products from petition as the Agency does not 0.00331 kg/day Florida fresh market animals medicinally treated with generally require some or all of the grapefruit consumed arsanilic acid. Even so, it is appropriate listed studies to rule on the exemption Total residues of 0.5 ppm arsanilic to consider the results of the from the requirement of a tolerance for acid = 0.5 mg total arsanilic acid developmental, reproductive, and an inert ingredient. Based on this residues /kg food chronic studies. The available data polymer conforming to the definition of (Amount of Florida fruit consumed) x clearly show that there is no increased a polymer and meeting the criteria of a (residue level) = 0.00331 kg fruit/day x risk to neonates or young when arsanilic polymer under 40 CFR 723.250 ICI 0.5 mg total arsanilic acid residues /kg acid is ingested. Therefore, Fleming believes there are no concerns for risks fruit = 0.00166 mg total arsanilic acid/ Laboratories concludes that associated with toxicity. day in grapefruit An additional safety factor for the 2. Endocrine disruption. ICI has no If it is assumed that all swine and protection of infants and children is not information to suggest that oxirane, poultry received arsanilic acid-treated, needed and methyl-, polymer with oxirane, mono[2- then the total dietary intake per day of The ADI or RfD of 0.0075 mg/kg/day (2- butoxyethoxy)ethyl]ether will have arsanilic acid from pork and poultry is appropriate for assessing arsanilic an effect on the immune and endocrine products except organ meats, can be acid risks to infants and children. systems. EPA is not requiring calculated as follows: information on the endocrine effects of 40 grams/day pork, poultry and eggs G. International Tolerances this substance at this time; Congress has consumed = 0.04 kg/day animal The Applicant is not aware of any allowed 3-years after August 3, 1996, for products consumed international tolerances or Codes the Agency to implement a screening X total residues of 1.45 ppm arsanilic Maximum Residue Limits (MRLs) for program with respect to endocrine acid = 1.45 mg total arsanilic acid arsanilic acid on any crop or livestock effects. residues /kg food commodities. (Cynthia Giles-Parker) (Amount of pork, poultry and eggs C. Cumulative Effects consumed) x (residue level) = 0.04 kg/ 2. ICI Surfactants ICI believes sufficient information day x 1.45 mg total arsanilic acid PP 8E4965 was submitted in the petition to assess residues /kg food = 0.058 mg total the hazards of oxirane, methyl-,polymer arsanilic acid/day in pork, poultry and EPA has received a pesticide petition with oxirane, mono[2-(2- eggs. (PP 8E4965) from ICI Surfactants, 3411 butoxyethoxy)ethyl]ether. Based on this If it is assumed that all swine and Silverside Road, Wilmington, DE, polymer conforming to the definition of poultry received arsanilic acid-treated, proposing pursuant to section 408(d) of a polymer and meeting the criteria of a then the total dietary intake per day of the Federal Food, Drug, and Cosmetic polymer under 40 CFR 723.250 ICI arsanilic acid from pork and poultry Act, 21 U.S.C. 346a(d), to amend 40 CFR believes there are no concerns for risks kidneys and liver can be calculated as 180.1001(c) and (e) to establish an associated with cumulative effects. follows: exemption from the requirement of a 2.8 grams/day pork and poultry tolerance for oxirane, methyl-, polymer D. Safety Determination organs consumed = 0.0028 kg/day with oxirane, mono[2-(2- 1. U.S. population. ICI believes organs consumed butoxyethoxy)ethyl]ether (CAS Registry sufficient information was submitted in 40278 Federal Register / Vol. 63, No. 144 / Tuesday, July 28, 1998 / Notices the petition to assess the hazards of that the residue is in the low parts per In-vivo structural chromosomal oxirane, methyl-,polymer with oxirane, billion (ppb) range at harvest and that aberration assay: Negative mono[2-(2-butoxyethoxy)ethyl]ether. the residue is primarily associated with In-vivo micronucleus aberration assay: Based on this polymer conforming to the skin. CPPU does not translocate any Negative the definition of a polymer and meeting significant distance in the plant, not 3. Reproductive and developmental the criteria of a polymer under 40 CFR moving from the leaves to the fruit nor toxicity. Results of these studies 723.250 ICI believes there are no from the fruit to the leaves. The use indicate that CPPU is not a reproductive concerns for risks associated with any level of 10 to 20 grams of CPPU per acre toxicant, developmental toxicant, or a potential exposure to adults. assures that only low residues will teratogen. 2. Infants and children. ICI believes occur. Residue analysis on grapes and Teratology in rats: NOAEL (maternal) sufficient information was submitted in kiwis confirm the radiolabel findings. In = 100 mg/kg/day; no observed adverse the petition to assess the hazards of grapes and kiwis the residue level was effect level (NOAEL) (fetal/ oxirane, methyl-,polymer with oxirane, below the level of quantification (LOQ) development) = 200 mg/kg/day mono[2-(2-butoxyethoxy)ethyl]ether. in all cases and generally below the Teratology in rabbits: NOAEL Based on this polymer conforming to level of validated detection. The LOQ in (maternal) = 25 mg/kg/day; NOAEL the definition of a polymer and meeting whole grape was 0.01 ppm; the level of (fetal/development) = 100 mg/kg/day the criteria of a polymer under 40 CFR detection (LOD) was 0.003 ppm. In 2-Generation reproduction in rats: 723.250 ICI believes there are no grape juice, the LOQ was 0.002 ppm and NOAEL (parental) = 150 ppm; NOAEL concerns for risks associated with any the LOD was 0.0007 ppm (0.7 ppb). In (reproductive) = 2,000 ppm (115 mg/kg/ potential exposure to infants and raisins the LOQ was 0.01 ppm and the day - males) (205 mg/kg/day - females). children. (Bipin Gandhi) LOD was 0.003 ppm. 4. Subchronic toxicity. No treatment- 3. KIM-C1, LLC 2. Analytical method. The analytical related adverse effects were noted in method extracted the parent material PP 7G4906 subchronic toxicity studies at the and analyzed it using HPLC analysis highest doses tested. EPA has received a pesticide petition with UV fluorescence at wavelength 265 28 - Day dietary in rats: NOEL 1,000 (PP 7G4906) from KIM-C1, LLC, 6333 nm. ppm East Liberty Avenue, Fresno, CA 93727 3. Magnitude of residues. The 13 - Week dietary in rats: NOEL 200 proposing pursuant to section 408(d) of magnitude of the residues in the crops ppm the Federal Food, Drug, and Cosmetic are anticipated to be below the level of 28 - Day dietary in dogs: NOEL 2,500 Act, 21 U.S.C. 346a(d), to amend 40 CFR quantification which, based on whole ppm part 180 by establishing a tolerance for fruit, will be 0.01 ppm. 13 - Week Dietary in dogs: NOAEL residues of N-(2-chloro-4-pyridinyl)-N- 500 ppm 13 - Week dietary in mice: phenylurea in or on the raw agricultural B. Toxicological Profile NOAEL 3,500 ppm. commodities grape, kiwi, almond, apple, blueberries, cranberries, figs, 1. Acute toxicity. Based on EPA 5. Chronic toxicity 1-year chronic plums, pears, and olives at 0.01 parts criteria, CPPU would be placed in EPA toxicity in dogs: not required for EUP; per million (ppm). EPA has determined toxicity Category III generally, while the Test initiated. that the petition contains data or dermal irritation results would be 18 -month chronic toxicity and information regarding the elements set placed in EPA Category IV. carconogeniscity in mice: not required forth in section 408(d)(2) of the FFDCA; for EUP will be initiated section 3 reg. Acute Oral 81-1 LD 4.9 gr/kg however, EPA has not fully evaluated 50 24-month chronic toxicity and Acute Dermal 81-2 LD50 >2000 mg/ carcinogenicity in rats: NOAEL 150 ppm the sufficiency of the submitted data at kg this time or whether the data supports (8 mg/kg/day); NOAEL 7,500 ppm (435 Acute Inhalation 81-3 LC50 >3.0 mg/l mg/kg/day). granting of the petition. Additional data (the higest may be needed before EPA rules on the conc achiev- 6. Animal metabolism. Study will be petition. able) completed prior to section 3 registration Eye Irritation 81-4 Mildly irritating; requirement. (Not required for an A. Residue Chemistry No corneal or Experiment Use Permit.) 1. Plant metabolism. The qualitative iridial irritation 7. Metabolite toxicology. Metabolites nature of the residues of CPPU in noted occur at levels below 0.1 ppm and Dermal Irritation 81-5 Non-irritating almonds, apples, blueberries, therefore are below levels required to be Skin Sensitization 81-6 Non-sensitizing cranberries, figs, grapes, kiwis, olives, assayed in animal testing. The 14C pears and plums are adequately radiolabel plant studies show understood. Three 14C radiolabeled 2. Genotoxicity. The results from a metabolites to be glucosides of the plant metabolism studies conducted in battery of three genetic toxicity tests parent material. apples, grapes and kiwis shows CPPU with CPPU show that this compound is 8. Endocrine disruption. Collective leaves the same residue pattern in all not mutagenic or genotoxic. weights and histopathological findings three crops, representing three unrelated Gene mutation - Ames: Slightly from the 2-generation rat reproductive botanical species. These studies show Positive study, as well as from the subchronic Federal Register / Vol. 63, No. 144 / Tuesday, July 28, 1998 / Notices 40279 and chronic toxicity studies in two or C. Aggregate Exposure estimated residue levels with results more animal species, demonstrate no from treatment of the indicated crops. apparent effects on the endocrine 1. Dietary exposure—Food. A The table below shows the Theoretical system. There is no information reference dose (RfD) was calculated Maximum Residue Concentrations available which suggests that CPPU using the most sensitive species data (TMRC) of CPPU on or in the listed would be associated with endocrine available from the toxicological testing. crops requested in this EUP request. effects. This RfD 0.08 mg/kg/day/based on a Theoretical Maximum Residue temporary tolerance of 0.01 ppm, was Concentrations for CPPU for the crops used to calculate the impact of the listed in the EUP request.
Total Exposure All-Apples All+Apples mg/kg body wt/ day Percent of RfD
General U.S. Populations, all seasons ...... 0.000005 0.000011 0.000016 0.02 Non-nursing infants ...... 0.000029 0.000064 0.000093 0.12 Children 1 to 6-years of age ...... 0.000010 0.000048 0.000058 0.07 Children 7 to 12-years of age ...... 0.000005 0.000017 0.000022 0.03
The anticipated use rate of 17 grams safe and efficacious use and, yet, not represents only slightly more than 1% of CPPU per acre applied once per year subject any segment of the public to a of the estimated safe level for the most yielding residue levels in the very low health risk. sensitive segment of the population, ppb range indicates that less than 1% of 2. Dietary exposure - drinking water. non-nursing infants. the reference dose would be consumed The very low use rate of CPPU i.e. 17 2. Infants and children. No in aggregate with all of these crops. The grams or less per acre, if used constantly developmental, reproductive or crop contributing greatest to the percent for 20-years, would apply only 3/4 of a fetotoxic effects have been associated of the reference dose related to the most pound of CPPU per acre during that 20- with CPPU. The calculation of safety sensitive of the population i.e. all year period. Computer modeling, using margins with respect to these segments nursing infants (less than 1-year old), the conservative pesticide root zone of the population were taken into non-nursing infants (less than 1-year model (PRZM) means of analysis has consideration in the TMRC estimates old), children (1 to 6 years old) would shown that no CPPU would reach with respect to the risk associated with represent 1/10th of 1% of the reference ground water, even in sandy loam soils. the percentage of the reference dose dose. Making the same risk exposure The results of this risk analysis being consumed. supported an unambiguous conclusion calculations, it is shown that no F. International Tolerances significant impact on reducing the RfD of ‘‘essentially zero risk to ground by using blueberries, cranberries, water’’ even under reasonable worst There is no Codex maximum residue cranberry juice, grapes-raisins, pears, case assumptions. Concentrations are level established for CPPU. However, pears dried, cherries, cherries dried, not predicted to exceed 15 to 20 ppb of CPPU is registered for use on grapes and cherry juice, plums (Damsons), plums as CPPU in the soil in the upper soil other crops in Japan, Chile, Mexico, and prunes (dried), plum/prune juice, figs, horizons, even following yearly South Africa. (Cynthia Giles-Parker) kiwifruit, grapes-wine and sherry, applications for as long as 30 years. No [FR Doc. 98–20145 Filed 7–27–98; 8:45 am] cranberry juice concentrate, pear nectar secondary exposure is anticipated as a BILLING CODE 6560±50±F in aggregate. Combining the RfD result of contamination of drinking consumption from the large group of water. crops with that of the apples would 3. Non-dietary exposure. No non- ENVIRONMENTAL PROTECTION exceed 1% of the reference dose only dietary exposure is expected since AGENCY CPPU is not anticipated to be found in slightly if the total acreage of all of these [FRL±6131±5] crops were treated. The intention of this the drinking water. It does not experimental use permit is not to treat translocate in plants and thus secondary Notice of Proposed NPDES General all of the various crops listed; the table exposure through plants growing in soil Permit for Discharges From Ready- below shows the requested acreage of receiving CPPU is not anticipated. The Mixed Concrete Plants, Concrete each crop. extremely low application rates will not Products Plants and Their Associated result in significant buildup in the Facilities in Texas (TXG110000) Acreage % Total environment. Crop Requested Acreage AGENCY: Environmental Protection D. Cumulative Effects Agency (EPA). Grape 3,500 0.53 There are no cumulative effects ACTION: Notice of draft NPDES general Kiwi 1,000 14.08 expected since CPPU is not taken up by permit. Almond 50 0.01 plants from the soil. It slowly degrades Apple 50 0.14 to mineral end points. Its low use rate SUMMARY: EPA Region 6 is proposing to Blueberries 50 issue a general NPDES permit Cranberries 50 is not conducive to buildup in the Figs 50 0.40 environment. authorizing discharges of facility waste water and contact storm water from Plums 50 0.03 E. Safety Determination Pears 50 0.15 ready-mixed concrete plants, concrete Olives 50 0.05 1. U.S. population. As pointed out products plants and their associated above in dietary exposure-food the facilities in Texas. This permit covers This program would permit percentage of the reference dose facilities having Standard Industrial development of requisite data to assure consumed by treating the subject crops Classification (SIC) Codes 3273