Pesticides; tolerances in food, animal feeds, and raw agricultural commodities: Spiromesifen,

[Federal Register: April 27, 2005 (Volume 70, Number 80)]

[Rules and Regulations]

[Page 21631-21641]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

[DOCID:fr27ap05-9]

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2005-0046; FRL-7705-1]

Spiromesifen; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

SUMMARY: This regulation establishes a tolerance for: Primary crops for the combined residues of spiromesifen (2-oxo-3-(2,4,6-trimethylphenyl)- 1-oxaspiro[4.4]non-3-en-4-yl 3,3-dimethylbutanoate) and its enol metabolite (4-hydroxy-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3- en-2-one), calculated as the parent compound equivalents; rotational crops for the inadvertent or indirect combined residues of spiromesifen (2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl 3,3- dimethylbutanoate), its enol metabolite (4-hydroxy-3-(2,4,6- trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one), and its metabolites containing the 4-hydroxymethyl moiety (4-hydroxy-3-[4-(hydroxymethyl)- 2,6-dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one), calculated as the parent compound equivalents; and livestock commodities for the combined residues of spiromesifen (2-oxo-3-(2,4,6-trimethylphenyl)-1- oxaspiro[4.4]non-3-en-4-yl 3,3-dimethylbutanoate), and its metabolites containing the enol (4-hydroxy-3-(2,4,6-trimethylphenyl)-1- oxaspiro[4.4]non-3-en-2-one) and 4-hydroxymethyl (4-hydroxy-3-[4- (hydroxymethyl)-2,6-dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one) moieties, calculated as the parent compound equivalents. Bayer CropScience requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of 1996 (FQPA).

DATES: This regulation is effective April 27, 2005. Objections and requests for hearings must be received on or before June 27, 2005.

ADDRESSES: To submit a written objection or hearing request follow the detailed instructions as provided in Unit VI. of the SUPPLEMENTARY INFORMATION. EPA has established a docket for this action under Docket identification (ID) number OPP-2005-0046. All documents in the docket are listed in the EDOCKET index at http://www.epa.gov/edocket. Although

listed in the index, some information is not publicly available, i.e., CBI or other information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, is not placed on the Internet and will be publicly available only in hard copy form. Publicly available docket materials are available either electronically in EDOCKET or in hard copy at the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 1801 S. Bell St., Arlington, VA. This docket facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The docket telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT: Thomas Harris, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: (703) 308-9423; e-mail address: harris.thomas@epa.gov.

SUPPLEMENTARY INFORMATION:

1. General Information

   1. Does this Action Apply to Me?

      You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. Potentially affected entities may include, but are not limited to:

      Crop production (NAICS 111), e.g., agricultural workers; greenhouse, nursery, and floriculture workers; farmers.

      Animal production (NAICS 112), e.g., cattle ranchers and farmers, dairy cattle farmers, livestock farmers.

      Food manufacturing (NAICS 311), e.g., agricultural workers; farmers; greenhouse, nursery, and floriculture workers; ranchers; pesticide applicators.

      Pesticide manufacturing (NAICS 32532), e.g., agricultural workers; commercial applicators; farmers; greenhouse, nursery, and floriculture workers; residential users.

      This listing is not intended to be exhaustive, but rather provides a guide

      [[Page 21632]]

      for readers regarding entities likely to be affected by this action. Other types of entities not listed in this unit could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain entities. If you have any questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT.

   2. How Can I Access Electronic Copies of this Document and Other Related Information?

      In addition to using EDOCKET (http://www.epa.gov/edocket/), you may

      access this Federal Register document electronically through the EPA Internet under the ``Federal Register'' listings at http://www.epa.gov/fedrgstr/. A frequently updated electronic version of 40 CFR part 180

      is available on E-CFR Beta Site Two athttp://www.gpoaccess.gov/ecfr/.

      To access the OPPTS Harmonized Guidelines referenced in this document, go directly to the guidelines at http://www.epa.gpo/opptsfrs/home/guidelin.htm/ .

2. Background and Statutory Findings

   In the Federal Register of July 28, 2004 (69 FR 45047) (FRL-7366- 2), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 3F6537) by Bayer CropScience, 2 T.W. Alexander Drive, Research Triangle Park, NC 27709. The petition requested that 40 CFR part 180 be amended by establishing a tolerance for the combined residues of the insecticide/miticide:

   1. Spiromesifen; butanoic acid, 3,3-dimethyl-, 2-oxo-3-(2,4,6- trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl ester [subsequently referred to as (2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3- en-4-yl 3,3-dimethylbutanoate) and its enol metabolite (4-hydroxy-3- (2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one)] in or on strawberry at 2.0 parts per million (ppm); vegetable, tuberous and corm, crop subgroup 1C, at 0.01 ppm (subsequently revised to 0.02 ppm); vegetable, leafy greens (except Brassica), crop subgroup 4A at 10 ppm (subsequently revised to vegetable, leafy greens, subgroup 4A at 12 ppm); vegetable, Brassica, head and stem, crop subgroup 5A, at 2.0 ppm; vegetable, Brassica, leafy, crop subgroup 5B at 12 ppm; vegetable, fruiting, crop group 8, at 0.30 ppm; tomato, paste at 0.60 ppm; vegetable, cucurbit, crop group 9, at 0.10 ppm; corn, field, grain, at 0.01 ppm (subsequently revised to 0.02 ppm); corn, field, forage, at 3.0 ppm; corn, field, stover, at 5.0 ppm; cotton (subsequently defined as cotton, undelinted seed) at 0.50 ppm; and cotton, gin byproducts, at 15 ppm.

   2. Spiromesifen; butanoic acid, 3,3-dimethyl-, 2-oxo-3-(2,4,6- trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl ester [subsequently referred to as (2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3- en-4-yl 3,3-dimethylbutanoate), its enol metabolite (4-hydroxy-3- (2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one), and its metabolites containing the 4-hydroxymethyl moiety (4-hydroxy-3-[4- (hydroxymethyl)-2,6-dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one)] in or on the rotational crop commodities alfalfa, forage, at 1.5 ppm; alfalfa, hay, at 3.0 ppm; wheat, grain, at 0.01 ppm (subsequently revised to 0.03 ppm); wheat, forage, at 0.20 ppm; wheat, hay, at 0.15 ppm; wheat, straw, at 0.25 ppm; wheat, bran, at 0.05 ppm (subsequently combined with wheat, shorts and defined together as ``wheat milled byproducts'' with no tolerance required); wheat, shorts, at 0.03 ppm (subsequently combined with wheat, bran and defined together as ``wheat milled byproducts'' with no tolerance required); barley, grain, at 0.02 ppm (subsequently revised to 0.03 ppm); barley, hay, at 0.25 ppm; barley, straw, at 0.25 ppm (subsequently revised to 0.15 ppm); beet, sugar, tops, at 0.20 ppm; beet, sugar, roots, at 0.02 ppm (subsequently revised to 0.03 ppm); and beet, sugar, molasses, at 0.05 ppm (tolerance subsequently not required).

   3. Spiromesifen; butanoic acid, 3,3-dimethyl-, 2-oxo-3-(2,4,6- trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl ester [subsequently referred to as 2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en- 4-yl 3,3-dimethylbutanoate), and its metabolites containing the enol (4-hydroxy-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one) and 4-hydroxymethyl (4-hydroxy-3-[4-(hydroxymethyl)-2,6-dimethylphenyl]-1- oxaspiro[4.4]non-3-en-2-one) moieties)] in or on the raw agricultural commodities cattle, fat, at 0.05 ppm; cattle, meat byproducts, at 0.05 ppm; milk at 0.01 ppm (tolerance subsequently not required); and milk, fat, at 0.03 ppm (subsequently revised to 0.10 ppm).

   Following the review of all data, tolerances are also required for the following commodities: Goat, fat at 0.05 ppm; goat meat byproducts at 0.05 ppm; sheep, fat at 0.05 ppm; sheep, meat byproducts at 0.05 ppm; horse, fat at 0.05 ppm; and horse, meat byproducts at 0.05 ppm.

   That notice included a summary of the petition prepared by Bayer CropScience, the registrant. A comment was received from a private citizen who challenged the value of using animal testing for evaluating pesticide toxicity and questioned the data gaps related to the tolerance proposal process. This commenter's objections have been addressed in prior rulemaking documents. See (69 FR 63083, 63096) (October 29, 2004).

   Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the tolerance is ``safe.'' Section 408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.'' This includes exposure through drinking water and in residential settings, but does not include occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to ``ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue. . . .''

   EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. For further discussion of the regulatory requirements of section 408 of FFDCA and a complete description of the risk assessment process, see the final rule on Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL- 5754-7).

3. Aggregate Risk Assessment and Determination of Safety

   Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the available scientific data and other relevant information in support of this action. EPA has sufficient data to assess the hazards of and to make a determination on aggregate exposure, consistent with section 408(b)(2) of FFDCA, for a tolerance for the combined residues of spiromesifen on the crops and animal commodities listed above.

   EPA's assessment of exposures and risks associated with establishing the tolerances follows.

   1. Toxicological Profile

      EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as

      [[Page 21633]]

      the relationship of the results of the studies to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. The nature of the toxic effects caused by spiromesifen are discussed in Table 1 of this unit as well as the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL) from the toxicity studies reviewed.

      Table 1.--Subchronic, Chronic, and Other Toxicity

      Guideline No.

      Study Type

      Results

      870.3050

      28-Day oral toxicity

      NOAEL was not established (mouse)

      LOAEL (M/F) = 202.6/269.6 mg/kg/day based on decreased body weight gain

      870.3050

      28-Day oral toxicity

      NOAEL was not established (mouse)

      LOAEL (M/F) = 444.3 mg/kg/day based on decreased body weight gain and increase in alkaline phosphatase ...........................................

      870.3100

      28-Day oral toxicity (rat) NOAEL = 53.4 mg/kg/day LOAEL = 536.3 mg/kg/day based on clinical signs (piloerection, reduced motility, spastic gait, discolored feces and increased reactivity when touched), decrease in body weight gain, and food consumption, hematology (thromboplastin time increase), clinical chemistry (increased aspartateaminotransferase and alanine aminotransferase), liver enzyme (increased aldrin expoxidase and epoxide hydrolase), increased spleen and lymph node cell proliferation, organ-weights (increase brain, heartand kidneys, decrease in weights in the ovaries, spleen and thymus), gross pathology (thin appearance, discolored adrenal glands and white mucous in the duodenum and jejunum), and microscopic findings (vacuolation of the superficial mucosal cells in the jejunum and duodenum, increased follicular cell hypertrophy in the thyroid, indistinct corticomedullary junction in the thymus and cytoplasmic changes in the adrenal glands)

      870.3150

      90-Day oral toxicity

      NOAEL = 9.2 mg/kg/day (nonrodent)

      LOAEL = 71 mg/kg/day (HDT) based on clinical chemistry(increased ALP) and liver histopathology

      870.3150

      90-Day oral toxicity

      NOAEL was not established (nonrodent)

      LOAEL = 98.4 mg/kg/day (HDT) based on increase in alkalinephosphatase and liver histopathology (cytoplasmic changes)

      870.3150

      90-Day oral toxicity (rat) NOAEL (M/F) = 31.7/7.7 mg/kg/day. LOAEL (F) = 36.6 mg/kg/day based on thyroid effects (increased thyroid stimulating hormone, thyroxine binding capacity and thyroid follicular cell hypertrophy), kidney effects (mineralization), and liver effect (increased ALP) LOAEL (M) = 204.0 mg/kg/day based on thyroid effect (colloidal alteration, follicular cell hypertrophy, decreased T3 and T4 and increased TBC and TSH), kidney effects (Hyalin droplets), and liver effects (increase in ALP and ALAT)

      870.3200

      21/28-Day dermal toxicity NOAEL = 1,000 mg/kg/day (HDT) (rat)

      LOAEL was not established

      870.3465

      5-Day inhalation toxicity NOAEL = 20.7 mg/kg/day (rat)

      LOAEL = 134.2 mg/kg/day based onthe clinical signs (tremors, clonic-tonic convulsions, reduced activity,bradypnea, labored breathing,vocalization, avoidance reaction,giddiness, piloerection, limp,emaciation, cyanosis, squattedposture, apathy, and salivation), andgross pathology (dark red areas orfoci in the lungs, bloated stomachsand pale liver)

      870.3465

      30-Day inhalation toxicity NOAEL >21.1 mg/kg/day (rat)

      LOAEL was not established

      870.3700

      Prenatal developmental Maternal NOAEL = 10 mg/kg/day (rat)

      Maternal LOAEL = 70 mg/kg/daybased on decreased body weight gainand reduced food consumption. Developmental NOAEL >= 500mg/kg/day (HDT) Developmental LOAEL > 500 mg/kg day

      870.3700

      Prenatal developmental Maternal NOAEL = 5 mg/kg/day (nonrodent)

      Maternal LOAEL = 35 mg/kg/day based on body weight loss and reduced food consumption Developmental NOAEL >= 250 mg/kg/day Developmental LOAEL > 250 mg/kg/day

      [[Page 21634]]

      870.3800

      Reproduction and fertility Parental/Systemic NOAEL (M/F) = 2.2/3.8 mg/ effects (rat)

      kg/day Parental/Systemic LOAEL (M/F) = 8.8/13.2 mg/ kg/day based on significantly decreased spleen weight (absolute and relative in parental females and F1 males) and significantly decreased growing ovarian follicles in females Reproductive NOAEL (M/F) = 37/64 mg/kg/day (HDT) Reproductive LOAEL = Not established Offspring NOAEL = 2.2 mg/kg/day Offspring LOAEL = 8.8 mg/kg/day based on pup body weight decrements during lactation

      870.4100

      Chronic toxicity (rat) NOAEL (M/F) = 15.9/19.3 mg/kg/day LOAEL (M/F) = 42.4/51.7 mg/kg/day based on increase in T3 hormone in males, gross pathology (enlarged liver in males, dilated uterus and discolored adrenal gland in females) and histopathology (adrenal cytoplasmic eosinophilia, metritise, thyroid colloidal alteration in female and thyroid follicular cell hypertrophy in both males and females)

      870.4100

      Chronic toxicity

      NOAEL (M/F) = 11.5/10.8 mg/kg/day (nonrodent)

      LOAEL (M/F) = 109/117 mg/kg/day based on increase in alkaline phosphatase and liver histopathology (cytoplasmic changes, inclusions and vacuoles)

      870.4200

      Carcinogenicity (rat) NOAEL (M/F) = 14.8/19.5 mg/kg/day LOAEL (M/F) = 40.0/53.5 mg/kg/day based on clinical signs (palpable masses, vaginal bleeding and pallor), gross necropsy (discolored area in the lungs, nodules/ dilation of uterus) and hispathology (osseus metaplasia and granulomatous inflammation of the lungs in the males, liver necrosis; endometritis/metritis, endometrial hyperplasia of the cervix uteria and colloidal alteration of the thyroid gland in females) and increased TSH in females. No evidence of carcinogenicity

      870.4200

      Carcinogenicity (mouse) NOAEL (M/F) = 3.3/3.8 mg/kg/day LOAEL (M/F) = 22/30 mg/kg/day based on gross (enlarged adrenal gland in males) and microscopic changes (cytoplamic eosinophilia, ceroid deposits, and diffuse fatty changes of the adrenal cortex and pancreatic amyloidosis in both sexes) No evidence of carcinogenicity

      870.5100

      Gene mutation--In Vitro Negative bacteria

      870.5300

      Cytogenetics In Vitro Negative Mammalian Gene Mutation

      870.5375

      Cytogenetics--In Vitro Negative Mammalian

      870.5395

      Cytogenetics In Vivo

      Negative Mammalian Micronucleus (mouse)

      870.6200

      Acute neurotoxicity

      NOAEL = 2,000 mg/kg/day screening battery

      LOAEL = Not established

      870.6200

      Subchronic neurotoxicity NOAEL (M/F) = 31.8/38.3 mg/kg/day. screening battery

      LOAEL (M/F) = 122.7/149.3 mg/kg/day based on decreased body weight gain and food consumption.

      870.7485

      Metabolism and

      Spiromesifen exhibits moderate absorption pharmacokinetics (rat) (approximately 43%), relatively rapid excretion primarily via the urine and feces. Approximately 39% of the administered dose was excreted in the urine and 55 to 57% in the feces with 88 to 90% of the dose being eliminated within the first 24 hours. Maximum concentration in the blood achieved within 1 to 6 hours post- dose depending upon the dose. Concentrations of residual radioactivity in the tissues were quite low at 72 hours post-dose. The test material was initially metabolized to the keto-enol by loss of the dimethylbutyric acid moiety. Both the phenyl and cyclopentyl rings were hydoxylated and the methyl groups on the phenyl ring were ultimately oxidized to a carboxylic acid. These metabolites were largely recovered in the bile and urine. The predominate moiety recovered in the feces was the unmetabolized test material.

      [[Page 21635]]

      870.7600

      Dermal penetration

      Intravenous injection resulted in excretion (nonrodent)

      of the radiolabel mainly via urine: Urine (54.32%), feces (13.08%), and cage debris/ rinse (26.57%). Excretion was rapid in that 70% of the dose was excreted within 24 hours. Dermal application of spiromesifen resulted in limited absorption after 8-hour exposure (3.3%), which a large portion was recovered from urine and cage debris/rinse showing that it is poorly absorbed through the skin layers.

      870.7800

      4-Week immunotoxicity NOAEL (M/F) = 52.8/45.7 mg/kg/day (rat)

      LOAEL (M/F) = 291.6/288.6 mg/kg/day based on mortality, clinical signs and decreased body weights, body weight gains and food consumption.

   2. Toxicological Endpoints

      The dose at which no adverse effects are observed (the NOAEL) from the toxicology study identified as appropriate for use in risk assessment is used to estimate the toxicological level of concern (LOC). However, the lowest dose at which adverse effects of concern are identified (the LOAEL) is sometimes used for risk assessment if no NOAEL was achieved in the toxicology study selected. An uncertainty factor (UF) is applied to reflect uncertainties inherent in the extrapolation from laboratory animal data to humans and in the variations in sensitivity among members of the human population as well as other unknowns. An UF of 100 is routinely used, 10X to account for interspecies differences and 10X for intraspecies differences.

      Three other types of safety or uncertainty factors may be used: ``Traditional uncertainty factors;'' the ``special FQPA safety factor;'' and the ``default FQPA safety factor.'' By the term ``traditional uncertainty factor,'' EPA is referring to those additional uncertainty factors used prior to FQPA passage to account for database deficiencies. These traditional uncertainty factors have been incorporated by the FQPA into the additional safety factor for the protection of infants and children. The term ``special FQPA safety factor'' refers to those safety factors that are deemed necessary for the protection of infants and children primarily as a result of the FQPA. The ``default FQPA safety factor'' is the additional 10X safety factor that is mandated by the statute unless it is decided that there are reliable data to choose a different additional factor (potentially a traditional uncertainty factor or a special FQPA safety factor).

      For dietary risk assessment (other than cancer) the Agency uses the UF to calculate an acute or chronic reference dose (acute RfD or chronic RfD) where the RfD is equal to the NOAEL divided by an UF of 100 to account for interspecies and intraspecies differences and any traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF). Where a special FQPA safety factor or the default FQPA safety factor is used, this additional factor is applied to the RfD by dividing the RfD by such additional factor. The acute or chronic Population Adjusted Dose (aPAD or cPAD) is a modification of the RfD to accommodate this type of safety factor.

      For non-dietary risk assessments (other than cancer) the UF is used to determine the LOC. For example, when 100 is the appropriate UF (10X to account for interspecies differences and 10X for intraspecies differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and compared to the LOC.

      The linear default risk methodology (Q*) is the primary method currently used by the Agency to quantify carcinogenic risk. The Q* approach assumes that any amount of exposure will lead to some degree of cancer risk. A Q* is calculated and used to estimate risk which represents a probability of occurrence of additional cancer cases (e.g., risk). An example of how such a probability risk is expressed would be to describe the risk as one in one hundred thousand (1 X 10-5), one in a million (1 X 10-6), or one in ten million (1 X 10-7). Under certain specific circumstances, MOE calculations will be used for the carcinogenic risk assessment. In this non-linear approach, a ``point of departure'' is identified below which carcinogenic effects are not expected. The point of departure is typically a NOAEL based on an endpoint related to cancer effects though it may be a different value derived from the dose response curve. To estimate risk, a ratio of the point of departure to exposure (MOEcancer= point of departure/exposures) is calculated.

      A summary of the toxicological endpoints for spiromesifen used for human risk assessment is shown in Table 2 of this unit:

      Table 2.-- Summary of Toxicological Dose and Endpoints for Spiromesifen for Use in Human Risk Assessment

      Dose Used in Risk Assessment,

      Special FQPA SF and 1Exposure Scenario

      Interspecies and Level of Concern for Study and Toxicological Intraspecies and any Risk Assessment

      Effect Traditional UF

      Acute dietary (females 13-49 years of Not applicable

      None

      An endpoint of concern age)

      attributable to a single dose was not identified. An aRfD was not established.

      Acute dietary (general population)

      [[Page 21636]]

      Chronic dietary (all populations) NOAEL= 2.2 mg/kg/day Special FQPA SF = 1X 2-generation UF = 100X.............. ....................... reproduction study in Chronic RfD = 0.022 mg/ ....................... rats. kg/day.

      ....................... The parental systemic LOAEL: 13.2 mg/kg/day based on significantly decreased spleen weight (absolute and relative in parental females and F1 males) and significantly decreased growing ovarian follicles in females.

      Cancer (oral, dermal, inhalation)

      Classification: ``Not likely to be carcinogenic to humans.''

   3. Exposure Assessment

      1. Dietary exposure from food and feed uses. No tolerances have previously been established for spiromesifen. Risk assessments were conducted by EPA to assess dietary exposures from spiromesifen in food as follows:

      i. Acute exposure. Acute dietary risk assessments are performed for a food-use pesticide, if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1-day or single exposure. Acute dietary exposure limits for all populations, including infants and children, were not performed because an endpoint of concern attributable to a single exposure (dose) was not identified from the oral toxicity studies.

      ii. Chronic exposure. In conducting the chronic dietary risk assessment EPA used the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCID\TM\) and the Lifeline\TM\ model version 2.0, which incorporates food consumption data as reported by respondents in the USDA 1994-1996 and 1998 Nationwide Continuing Surveys of Food Intake by Individuals (CSFII), and accumulated exposure to the chemical for each commodity. Percent crop treated and anticipated residues were not used.

      An unrefined, Tier 1 chronic dietary exposure assessment was conducted using the following:

      a. Recommended tolerances for all plant and livestock except the leafy-green and leafy-Brassica vegetable subgroups;

      b. EPA calculated residues of concern (parent and metabolites) for the leafy-green and leafy-Brassica vegetable subgroups;

      c. 100% crop treated (CT) information for all proposed uses; and

      d. Default processing factors for all commodities. The metabolism studies show that the hydroxymethyl metabolite is formed along with the enol metabolite in the leafy-green and leafy-Brassica vegetable subgroups. EPA determined that these two metabolites along with the spiromesifen should be included in the chronic dietary risk assessment for these crops. Residue data are unavailable for the 4- hydroxymethyl metabolite; to account for this metabolite in the risk assessment, the recommended tolerance levels for these crops was multiplied by a correction factor of 1.3x, where:

      1.3 = Metabolites in Risk Assessment (ppm)/Metabolites in Tolerance Expression (ppm).

      The dietary-exposure assessment was conducted for the general U.S. population and various population subgroups. This assessment concludes that the chronic dietary exposure estimates are below EPA's level of concern (There is a complete toxicity data base for spiromesifen.

      There is no evidence of increased susceptibility of rats or rabbits to in utero and/or postnatal exposure to spiromesifen. In the prenatal developmental toxicity studies in rats and rabbits and in the 2-generation reproduction study in rats, developmental toxicity to the offspring occurred at equivalent or higher doses than maternal toxicity.

      There are no neurotoxicity concerns based on acute and subchronic neurotoxicity studies.

      The dietary food exposure assessment uses proposed tolerance levels or higher residues and assumed 100% crop-treated (CT) information for all commodities. By using these screening-level assessments, chronic exposures and risks will not be underestimated. The ``higher residues'' are those that were calculated using a modifying factor to account for the lack of spiromesifen-4- hydroxymethyl residue data.

      The dietary drinking water assessment (Tier 2 estimates) uses values generated by model and associated modeling parameters which are designed to provide conservative, health protective, and high-end estimates of water concentrations.

      Residential exposure is not expected--spiromesifen will be registered for agricultural and greenhouse/ornamental uses only.

   5. Aggregate Risks and Determination of Safety

      To estimate total aggregate exposure to a pesticide from food, drinking water, and residential uses, the Agency calculates DWLOCs which are used as a point of comparison against EECs. DWLOC values are not regulatory standards for drinking water. DWLOCs are theoretical upper limits on a pesticide's concentration in drinking water in light of total aggregate exposure to a pesticide in food and residential uses. In calculating a DWLOC, the Agency determines how much of the acceptable exposure (i.e., the PAD) is available for exposure through drinking water [e.g., allowable chronic water exposure (mg/kg/day) = cPAD - (average

      [[Page 21638]]

      food + residential exposure). This allowable exposure through drinking water is used to calculate a DWLOC.

      A DWLOC will vary depending on the toxic endpoint, drinking water consumption, and body weights. Default body weights and consumption values as used by the EPA's Office of Water are used to calculate DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (adult female), and 1L/10 kg (child). Default body weights and drinking water consumption values vary on an individual basis. This variation will be taken into account in more refined screening-level and quantitative drinking water exposure assessments. Different populations will have different DWLOCs. Generally, a DWLOC is calculated for each type of risk assessment used: Acute, short-term, intermediate-term, chronic, and cancer.

      When EECs for surface water and ground water are less than the calculated DWLOCs, OPP concludes with reasonable certainty that exposures to the pesticide in drinking water (when considered along with other sources of exposure for which OPP has reliable data) would not result in unacceptable levels of aggregate human health risk at this time. Because OPP considers the aggregate risk resulting from multiple exposure pathways associated with a pesticide's uses, levels of comparison in drinking water may vary as those uses change. If new uses are added in the future, OPP will reassess the potential impacts of residues of the pesticide in drinking water as a part of the aggregate risk assessment process.

      1. Acute risk. Spiromesifen is not expected to pose an acute risk because an endpoint of concern attributable to a single exposure (dose) was not identified from the oral toxicity studies.

      2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure and the EECs from DEEM-FCID\TM\ as these were slightly higher, and thus are more conservative, than the Lifeline\TM\ estimates, EPA has concluded that exposure to spiromesifen from food will utilize 29% of the cPAD for the U.S. population, 15% of the cPAD for all infants less than 1 year old, and 37% of the cPAD for children 3-5 years old. There are no residential uses for spiromesifen that result in chronic residential exposure to spiromesifen. There is no concern regarding spiromesifen in ground water and surface water. After calculating DWLOCs and comparing them to the EECs for surface water and ground water, EPA does not expect the aggregate exposure to exceed 100% of the cPAD, as shown in Table 3 of this unit:

      Table 3.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Spiromesifen + Metabolites

      Surface Ground Population Subgroup

      cPAD mg/kg/ % cPAD Water EEC Water EEC Chronic day (Food)\1\ (ppb)

      (ppb) DWLOC (ppb)

      U.S. population

      0.022

      29

      11

      28

      545

      All Infants (