Pesticides; tolerances in food, animal feeds, and raw agricultural commodities: Cyazofamid,
[Federal Register: September 30, 2004 (Volume 69, Number 189)]
[Rules and Regulations]
[Page 58290-58299]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30se04-13]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2004-0211; FRL-7367-4]
Cyazofamid; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes a tolerance for the combined residues of cyazofamid and its metabolite CCIM in or on potatoes, tomatoes, cucurbits, and imported wine. ISK Biosciences Corporation requested this tolerance 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 September 30, 2004. Objections and requests for hearings must be received on or before November 29, 2004.
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 ID number OPP-2004-0211. All documents in the docket are listed in the EDOCKET index athttp://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: Janet Whitehurst, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,Washington, DC 20460- 0001; telephone number: (703) 305-6129; e-mail address:whitehurst.janet@epa.gov.
SUPPLEMENTARY INFORMATION:
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General Information
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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 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.
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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 at E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/.
To access the OPPTS Harmonized Guidelines referenced in this document, go directly to the guidelines athttp://www.epa.gpo/opptsfrs/home/guidelin.htm/ .
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Background and Statutory Findings
In the Federal Register of May 7, 2003 (68 FR 24463) (FRL-7305-7), EPA issued a notice pursuant to section 408(d)(3) of the FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 1F06305) by ISK Biosciences Corporation, Concord, OH. That notice included a summary of the petition prepared by ISK Biosciences Corporation, the registrant. There were no comments received in response to the notice of filing.
The petition requested that 40 CFR part 180 be amended by establishing tolerances for combined residues of the fungicide cyazofamid, 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H- imidazole-1-sulfonamide and its metabolite CCIM, 4-chloro-5-(4- methylphenyl)-1H-imidazole-2-carbonitrile, expressed as cyazofamid, in or on cucurbit vegetables (Group 9) at 0.10 parts per million (ppm), potato at 0.01 ppm, tomato at 0.20 ppm, and grape wine at 1.0 ppm.
Following review of the residue and metabolism data, EPA has made several minor changes to the proposed tolerances. For cucurbits and potatoes, EPA expanded the tolerance expression to cover both cyazofamid and its metabolite CCIM, which is also a residue of concern. This expansion of the toleranceexpression necessitated a raising of the tolerance level for potatoes from 0.01 ppm to 0.02 ppm. No change in the tolerance values was needed for tomatoes. Finally, residue and processing data for grape wine showed that residues might slightly exceed 1.0
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ppm; accordingly, the tolerance for grape wine was raised to 1.5 ppm.
Section 408(b)(2)(A)(i) of the 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).
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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 combined residues of cyazofamid on cucurbits at 0.10 ppm, potatoes at 0.01 ppm, tomatoes at 0.2 ppm, and wine grape at 1.0 ppm. EPA's assessment of exposures and risks associated with establishing the tolerance follows.
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Toxicological Profile
EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as 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 cyazofamid 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.--Toxicity Profile of Cyazofamid [IKF-916] Technical
Guideline No.
Study Type
Results
870.3100
90-day oral toxicity in NOAEL = 29.5 [M] mg/kg/day rats
LOAEL = 295 [M] mg/kg/day based on increased number of ``basophilic kidney tubules,'' and increased urinary volume, pH, and protein.
870.3150
90-Day oral toxicity in NOAEL = 1,000 [M/F] mg/kg/day dogs
LOAEL = not observed.
870.3200
28-Day dermal toxicity in NOAEL = 1,000 [M/F] mg/kg/day rats
LOAEL = not observed.
870.3700
Prenatal developmental in Maternal NOAEL = 1,000 mg/kg/day rats
LOAEL = not observed Developmental NOAEL = 100 mg/kg/day LOAEL = 1,000 mg/kg/day based on increased incidence of bent ribs.
870.3700
Prenatal developmental in Maternal NOAEL = 1,000 mg/kg/day rabbits
LOAEL = not observed Developmental NOAEL = 1,000 mg/kg/day LOAEL = not observed
870.3800
Reproduction and fertility Parental/Systemic NOAEL = 1,114/1,416 [M/F] effects in rats
mg/kg/day LOAEL = not observed Reproductive NOAEL = 1,114/1,416 [M/F] mg/ kg/day LOAEL = not observed Offspring NOAEL = 1,114/1,416 [M/F] mg/kg/ day LOAEL = not observed
870.4100
Chronic toxicity in rats NOAEL = 171/ 856 [M/F] mg/kg/day LOAEL = not observed.
870.4100
Chronic toxicity in dogs NOAEL = 200 [M/F] mg/kg/day LOAEL = 1,000 [M/F] mg/kg/day based on increased cysts in parathyroids in both sexes and increased pituitary cysts in females.
870.4200
Carcinogenicity rats
NOAEL = 171/ 856 [M/F] mg/kg/day LOAEL = not observed. No evidence of carcinogenicity
870.4300
Carcinogenicity mice
NOAEL = 94.8 [M] mg/kg/day LOAEL = 985 [M] mg/kg/day based on increased incidence of skin lesions including hair loss, body sores, dermatitis, ulceration, and acanthosis. No evidence of carcinogenicity
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870.5100
Gene Mutation
Negative S9 up to 5,000 [mu]g/ Bacterial reverse mutation plate by standard plate and tube assay.
preincubation (not cytotoxic but there was precipitation at >= 1,500 [mu]g/plate.
870.5300
Gene Mutation
Negative S9 up to cytotoxic Mammalian cell culture.... and precipitating concentration of 100 [mu]g/mL
870.5375
Cytogenetics
Negative S9 for clastogenic/ Chromosomal aberrations... aneugenic activity up to cytotoxic and precipitating 200 [mu]g/mL
870.5395
Cytogenetics
Negative up to the highest dose tested Micronucleus test on mouse (limit dose) 2,000 mg/kg
870.5500
Other Effects
Negative S9 up to limit of Bacterial DNA repair test solubility at 8,000 [mu]g/disc (Rec-assay).
870.7485
Metabolism and
There was rapid absorption (irrespective of pharmacokinetics in rats dose tcmax = 0.25-0.5 hrs) and rapid elimination at the low dose (t[frac12] 4.4- 5.8 hrs) while there was saturated absorption with prolonged elimination (t[frac12] of 7.6-11.6 hrs) at the high- dose. The extent of absorption (as per cent of administered dose) was highly dose- dependent being nearly 75% at the low dose and only about 5% at the high dose. Both the urine and feces were major routes of excretion at the low dose with most of the urinary radioactivity being a metabolite named CCBA (4-(4-chloro-2-cyanoimidazol-5- yl)benzoic acid). The biliary elimination was highly variable at the low dose (12- 39% of the administered low dose) and negligible (-\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
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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 cyazofamid used for human risk assessment is shown in Table 2 of this unit:
Table 2.--Summary of Toxicological Dose and Endpoints for Cyazofamid
Special FQPA SF* and Exposure Scenario
Dose Used in Risk Level of Concern for Study and Toxicological Assessment, UF
Risk Assessment
Effects
Acute Dietary (Females 13-50 years of NOAEL = 100 mg/kg
FQPA SF = 1X
Rat Prenatal age)
UF = 100............... aPAD = acute RfD / FQPA Developmental Toxicity Acute RfD = 1.0 mg/kg.. SF = 1.0 mg/kg.
(MRID 45408933) LOAEL = 1,000 mg/kg based on developmental toxicity findings of increased incidence of bent ribs.
Acute Dietary (General population NOAEL = NA
FQPA SF = NA
Not Required. No including infants and children) UF = NA................ aPAD = acute RfD / FQPA adverse effects were Acute RfD = NA......... SF = NA.
observed which could be attributed to a single-dose exposure.
Chronic Dietary (All populations) NOAEL= 94.8 mg/kg/day FQPA SF = 1X
18-Month Mouse Oral UF = 100............... cPAD = chronic RfD / Carcinogenicity (MRID Chronic RfD = 0.95 mg/ FQPA SF = 0.95 mg/kg/ 45408932) kg/day.
day.
LOAEL = 985 mg/kg/day based on increased skin lesions.
Short- (1-30 days) and Intermediate- NOAEL= NA
Residential LOC for MOE NA Term (1 to 6 months) Incidental Oral No Residential Uses.... = NA Occupational = NA......
Short- (1-30 days) and Intermediate- Oral study NOAEL = 100 Residential LOC for MOE Rat Prenatal Term (1 to 6 months) Dermal
mg/kg/day
= NA
Developmental Toxicity (dermal absorption rate Occupational LOC for (MRID 45408933) = 37%).
MOE = 100.
LOAEL = 1,000 mg/kg based on developmental toxicity findings of increased incidence of bent ribs.
Long-Term Dermal (>6 months)
Oral study NOAEL = 94.8 Residential LOC for MOE 18-Month Mouse Oral mg/kg/day
= NA
Carcinogenicity (MRID (dermal absorption rate Occupational LOC for 45408932) = 37%).
MOE = 100.
LOAEL = 985 mg/kg/day based on increased skin lesions.
Short- (1-30 days) and Intermediate- Oral study NOAEL = 100 Residential LOC for MOE Rat Prenatal Term (1 to 6 months) Inhalation
mg/kg/day
= NA
Developmental Toxicity Occupational LOC for (MRID 45408933) MOE = 100.
LOAEL = 1,000 mg/kg based on developmental toxicity findings of increased incidence of bent ribs.
Long-Term Inhalation (>6 months) Oral study NOAEL = 94.8 Residential LOC for MOE 18-Month Mouse Oral mg/kg/day
= NA
Carcinogenicity (MRID Occupational LOC for 45408932) MOE = 100.
LOAEL = 985 mg/kg/day based on increased skin lesions.
Cancer (oral, dermal, inhalation) Not Applicable
NA
NA
UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no-observed-adverse-effect-level, LOAEL = lowest-observed-adverse-effect-level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable
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Exposure Assessment
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Dietary exposure from food and feed uses. Permanent and temporary tolerances for residues of cyazofamid and its metabolites are not currently established. Risk assessments were conducted by EPA to assess dietary exposures from the proposed uses of cyazofamid on food and feed crops 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.
In conducting the acute dietary risk assessment EPA used the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCIDTM) and LifelineTM, 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. The following assumptions were made for the acute exposure assessments: As an acute dietary endpoint was not identified for the general population including infants and children, the acute dietary analysis was performed for the population subgroup females 13 to 49 years old only. The assumptions of this dietary exposure assessment are tolerance level residues and 100% crop-treated.
At the 95th percentile of exposure, the Tier 1 acute DEEM- FCIDTMand LifelineTManalysis gave the results listed in Table 3. For the acute analysis, the exposure at the 95th percentile for Females 13 to 49 years old is 0.003769 mg/kg/day for DEEM-FCIDTMor
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0.004013 mg/kg/day for LifelineT, which utilizes TMand LifelineTM. The results of the LifelineTMand DEEM-FCIDTManalyses are fully consistent.
A summary of the acute dietary exposure estimates for cyazofamid and its metabolote CCIM used for human risk assessment are shown in Table 3 of this unit:
Table 3.--Acute Dietary Exposure Estimates for Cyazofamid
DEEM-FCIDTM
LifeLineTM aPAD (mg/kg/--------------------------------------------------- Population Subgroup
day) Exposure
Exposure (mg/kg/day) %aPAD\1\ (mg/kg/day) %aPAD\1\
Females 13-49 years old
1.0 0.003769
TMand LifelineTM, 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. The following assumptions were made for the chronic exposure assessments: The assumptions of this dietary exposure assessment are tolerance level residues and 100% crop-treated.
The Tier 1 chronic DEEM-FCIDTMand LifelineTM analysis gave the results listed in Table 4. For the chronic analysis, the most highly exposed population subgroup and the highest risk estimate was for Children 1 to 2 years old. The chronic exposures for Children 1 to 2 years old are 0.004778 mg/kg/day for DEEM- FCIDTM) or 0.004529 mg/kg/day for LifelineTM), which utilize TMand Lifeline TM) of the chronic PAD for cyazofamid. The results of the LifelineTMand DEEM-FCIDTManalyses are fully consistent.
A summary of the chronic dietary exposure estimates for cyazofamid used for human risk assessment is shown in Table 4 of this unit:
Table 4.--Chronic Dietary Exposure Estimates for Cyazofamid
DEEM-FCIDTM
LifeLineTM cPAD (mg/kg/--------------------------------------------------- Population Subgroup
day) Exposure
Exposure (mg/kg/day) %cPAD\1\ (mg/kg/day) %cPAD\1\
General U.S. Population
0.95 0.001016
1,000 mg/kg/day) did not cause maternal systemic toxicity nor did it elicit reproductive or offspring toxicity.
iv. The Agency concluded that the concern is low for the quantitative susceptibility seen in the rat developmental toxicity study and there are no residual uncertainties because:
a. The developmental effect is well identified with clear NOAEL/ LOAEL.
b. The developmental effect (increased bent ribs) is a variation rather than a malformation.
c. The developmental effect is seen only at the limit dose of 1,000 mg/kg/day.
d. This endpoint is used to establish the acute RfD for Females 13- 49 years old.
e. The overall toxicity profile indicates that cyazofamid is not a very toxic compound.
v. There were no indications of pre- or postnatal toxicity and no residual uncertainties from the rabbit developmental study or the rat two generation reproduction study.
vi. The exposure assessments are Tier 1, conservative, high-end assessments and will not underestimate the potential dietary (food and water) exposures.
vii. There are no proposed residential uses.
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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 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
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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.
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Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food to cyazofamid will occupy TMor 0.004529 mg/kg/day for LifelineTM, which utilize TMand LifelineTM) of the chronic PAD for cyazofamid. EPA does not expect the aggregate exposure to exceed 100% of the cPAD, as shown in Table 6 of this unit:
Table 6.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Cyazofamid
Maximum Ground Surface Chronic Chronic Water
Water Chronic Population Subgroup
cPAD (mg/kg/ Food
Water EDWC\3\ EDWC\3\ DWLOC\4\ day) Exposure\1\ Exposure\2\ (ppb or (ppb or (ppb or (mg/kg/day) (mg/kg/day) [mu]g/L) [mu]g/L) [mu]g/L)
General U.S. Population
0.95 0.001016
0.95
NA
NA 3.3 x 104
All Infants (
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