Environmental Protection Agency (EPA).
This regulation establishes tolerances for residues of lactofen in or on cotton undelinted seed, cotton gin byproducts, and peanut. Valent U.S.A. Corporation requested this tolerance under the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of 1996 (FQPA).
This regulation is effective September 24, 2004. Objections and requests for hearings must be received on or before November 23, 2004.
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-2004-0293. 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, Start Printed Page 57208is 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.Start Further Info
FOR FURTHER INFORMATION CONTACT:
Joanne I. Miller, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: (703) 305-6224; e-mail address: email@example.com.End Further Info End Preamble Start Supplemental Information
I. General Information
A. 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.
B. 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 at http://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/.
II. Background and Statutory Findings
In the Federal Register of January 29, 2003 (68 FR 4475) (FRL-7287-6), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of pesticide petitions (PP 8F3591 and 9F3798) by Valent U.S.A. Corporation, 1333 North California Blvd., Suite 600, Walnut Creek, CA 94596-8025. The petitions requested that 40 CFR 180.432 be amended by establishing tolerances for residues of the herbicide lactofen, 1-(carboethoxy)ethyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate, in or on cottonseed at 0.01 part per million (ppm), cotton gin byproducts at 0.02 ppm (PP 9F3798), and peanut nutmeats at 0.01 ppm (PP 8F3591). That notice included a summary of the petitions prepared by Valent U.S.A. Corporation, the registrant. There were no comments received in response to the notice of filing.
The proposed and established tolerances are corrected to conform to the Food and Feed Commodity Vocabulary Database (http://www.epa.gov/pesticides/foodfeed/) and to lower the established tolerances for snap bean and soybean to 0.01 ppm as required by the Lactofen Tolerance Reassessment (http://www.epa.gov/pesticides/reregistration/lactofen/) to read as follows: Tolerances for residues of the herbicide lactofen, 1-(carboethoxy)ethyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate, in or on beans, snap, succulent (excluding limas) at 0.01 ppm; cotton, undelinted seed at 0.01 ppm; cotton, gin byproducts at 0.02 ppm; peanut at 0.01 ppm; and soybean, seed at 0.01 ppm.
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).
III. 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 tolerances for residues of lactofen on cotton, undelinted seed at 0.01 ppm; cotton, gin byproducts at 0.02 ppm; and peanut at 0.01 ppm ppm. EPA's assessment of exposures and risks associated with establishing the tolerances follows.
A. 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 lactofen 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.Start Printed Page 57209
|Guideline No.||Study Type||Results|
|870.3100||13-Week oral toxicity—rodents (rat)||NOAEL = 14.1 milligrams/kilogram/day (mg/kg/day). LOAEL = 73.7 mg/kg/day based on decreased body weight, increased incidence of anemia, increased levels of serum enzymes and bilirubin, decreased levels of glucose, increased liver weights, and increased incidence of microscopic liver lesions.|
|870.3100||90-Day oral toxicity—rodents (mouse)||NOAEL = not established. LOAEL = 28.6 mg/kg/day based on changes clinical chemistry parameters, increases in organ weight, and histopathological findings.|
|870.3700||Prenatal developmental—rodents (rat)||Maternal NOAEL = 50 mg/kg/day. Maternal LOAEL = 150 mg/kg/day based on signs of toxicity (excessive salivation, lethargy, dried red material around the nares and inguinal regions) and statistically significant decreases in body weight gain. Developmental NOAEL = 50 mg/kg/day. Developmental LOAEL = 150 mg/kg/day based on decreased fetal weight and skeletal abnormalities (increased incidence of bent ribs and/or limb bones) and reduced ossification of vertebral arches.|
|870.3700||Prenatal developmental—nonrodents (rabbit)||Maternal NOAEL ≥ 20 mg/kg/day. Maternal LOAEL > 20 mg/kg/day Highest Dose Tested (HDT). Developmental NOAEL ≥ 20 mg/kg/day. Developmental LOAEL > 20 mg/kg/day HDT.|
|870.3800||Reproduction and fertility effects||Parental/Systemic NOAEL = 2.6 mg/kg/day. Parental/Systemic LOAEL = 26.2 mg/kg/day based on mortality and decreased male fertility. Reproductive NOAEL = 2.6 mg/kg/day. Reproductive LOAEL = 26.2 mg/kg/day based on decreased male fertility. Offspring NOAEL = 2.6 mg/kg/day. Offspring LOAEL = 26.2 mg/kg/day based on reduced pup body weigh and decreases in the absolute and relative spleen weight.|
|870.4100||Chronic toxicity—dogs||NOAEL = 0.79 mg/kg/day. LOAEL = 3.96 mg/kg/day based on increased incidence of proteinaceous casts in the kidneys, and statistically significant increases in the absolute weights of the thyroid and adrenal glands in males.|
|870.4300||Combined Chronic toxicity Carcinogenicity—rats||NOAEL = 2 mg/kg/day. LOAEL = 19 mg/kg/day based on statistically significant increases in the incidence of mottled or discolored livers and changes in clinical chemistry. No evidence of carcinogenicity.|
|870.4300||Carcinogenicity—mice||NOAEL = not established. LOAEL = 1.4 mg/kg/day Lowest Dose Tested (LDT) based on hepatocytomegaly, increased liver weight, and increased sinusoidal cell pigmentation. Likely to be carcinogenic to humans at high enough doses to cause these biochemical and histopathological effects (peroxisome proliferation) in the livers of rodents but unlikely to be carcinogenic at doses below those causing these changes.|
|870.5100||Gene mutation in S. typhimurium/mammalian microsome mutagenicity assay.||No cytotoxicity evident at 50 μg (gram)/plate in the absence or presence of metabolic activation. PPG-844 induced a dose-related increase in revertant colonies of strain TA1538 in the absence of S9 activation; however, no effect seen in strain TA98 (derived from TA1538).|
|870.5100||Gene mutation in S. typhimurium/mammalian microsome mutagenicity assay||Cytotoxicity was not evident for any strain up to the limit dose (5,000Fg/plate). No evidence of PPG-844 induced mutagenic effect.|
|870.5375||In vitro cytogenetic assay with Chinese Hamster Ovary (CHO) cells||No evidence of clastogenic effect in the presence or absence of S9 activation.|
|870.5375||Mammalian cells in culture gene mutation in CHO cells||No evidence of cytotoxicity at any dose tested. No clear indication of mutagenic effect in the presence or absence of S9 activation.|
|870.5550||Unscheduled DNA Synthesis||No unscheduled DNA synthesis.|
|Start Printed Page 57210|
|In vivo DNA covalent binding in mouse liver||A covalent binding index of 1.4 ± 0.6 was determined for lactofen. This suggests a low binding to mouse hepatic DNA may occur. This finding could not be attributed solely to DNA binding since some protein-binding of the parent compound and/or metabolite could be occurring.|
|Analysis of biochemical and microscopic parameters in Chimpanzee liver||Aryl CoA oxidase, catalase, and carnitine acetlytransferase activities not affected by treatment. No nuclear enlargement, cytoplasmic eosinophilia, or hepertrophy observed in liver biopsies after 0, 1, and 3 months of treatment. Slight + response for peroxisomal staining (brown stippling).|
|Results of the analysis of biochemical parameters in mouse and rat liver Following Exposure to PPG-844||Catalase and CN-insensitive palmiloyl CoA oxidase increased. Rats (2,000 ppm) and mice (50 ppm) showed increased nuclear enlargement, cytoplasmic eosinophilia, hypertrophy, and peroxisomes in number of peroxisomes. The NOAEL for this study was established at 0.3 mg/kg/day, based on increased activities of liver enzymes and increased incidence of liver histopathological findings at the LOAEL of 1.5 mg/kg/day.|
|Measurement of peroxisome proliferation in primary rat hepatocytes induced by PPG-844 and five of its metabolites||Concentration-dependent increase in CN-insensitive palmitoyl CoA oxidase activities with each of the metabolites. EM: Lactofen (0.01 millimole (mM)) increased number of peroxisomes and glycogen aggregates. Other metabolites showed occasional peroxisomes.|
B. 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 lactofen used for human risk assessment is shown in Table 2 of this unit:Start Printed Page 57211
|Exposure Scenario||Dose Used in Risk Assessment, Interspecies and Intraspecies and any Traditional UF||Special FQPA SF and Level of Concern for Risk Assessment||Study and Toxicological Effects|
|Acute Dietary (Females 13-50 years of age)||NOAEL = 50 mg/kg/day UF = 100 Acute RfD = 0.5 mg/kg/day||Special FQPA SF = 3 aPAD = acute RfD/Special FQPA SF = 0.17 mg/kg/day||Rat Developmental Toxicity Study LOAEL = 150 mg/kg/day based on decreased fetal weight and skeletal abnormalities.|
|Acute Dietary (General population including infants and children)||An endpoint attributable to a single dose (exposure) was not identified from the available studies, including the developmental toxicity studies in rats and rabbits.|
|Chronic Dietary (All populations)||NOAEL = 0.79 mg/kg/day UF = 100 Chronic RfD = 0.008 mg/kg/day||Special FQPA SF = 1 cPAD = chronic RfD/Special FQPA SF = 0.008 mg/kg/day||Dog chronic toxicity LOAEL = 3.96 mg/kg/day based on increased incidence of proteinaceous casts in the kidneys, and statistically significant increases in the absolute weights of the thyroid and adrenal glands in males.|
|Cancer (Oral, dermal, inhalation)||Lactofen acts via a peroxisome proliferation mechanism of action. Likely to be carcinogenic to humans at high enough doses to cause these biochemical and histopathological effects (peroxisome proliferation) in the livers of rodents but unlikely to be carcinogenic at doses below those causing these changes. Lactofen is considered to be a threshold carcinogen. NOAEL = 0.3 mg/kg/day based on increased activities of liver enzymes and increased incidence of liver histopathological findings at the LOAEL of 1.5 mg/kg/day.|
C. Exposure Assessment
1. Dietary exposure from food and feed uses. Tolerances have been established (40 CFR 180.432) for the residues of lactofen in or on succulent snap bean and soybeans. Risk assessments were conducted by EPA to assess dietary exposures from lactofen 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.
The Dietary Exposure Evaluation Model (DEEMTM) analysis evaluated the individual food consumption as reported by respondents in the USDA 1989-1992 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: The acute dietary analysis uses average food residue values from field trial studies and percent crop treated (PCT) information.
ii. Chronic exposure. In conducting this chronic dietary risk assessment, the DEEMTM analysis evaluated the individual food consumption as reported by respondents in the USDA 1989-1992 CSFII and accumulated exposure to the chemical for each commodity. The following assumptions were made for the chronic exposure assessments: The chronic dietary analysis utilized average residue values based on field trial studies, concentration factors from processing studies, and PCT information.
iii. Cancer. In conducting this cancer dietary risk assessment, the DEEMTM analysis evaluated the individual food consumption as reported by respondents in the USDA 1989-1992 CSFII and accumulated exposure to the chemical for each commodity. The following assumptions were made for the chronic exposure assessments: The chronic dietary analysis utilized the average consumption values for food and average residue values for those foods over a 70-year lifetime.
iv. Anticipated residue and PCT information. Section 408(b)(2)(E) of FFDCA authorizes EPA to use available data and information on the anticipated residue levels of pesticide residues in food and the actual levels of pesticide chemicals that have been measured in food. If EPA relies on such information, EPA must require that data be provided 5 years after the tolerance is established, modified, or left in effect, demonstrating that the levels in food are not above the levels anticipated. Following the initial data submission, EPA is authorized to require similar data on a time frame it deems appropriate. As required by section 408(b)(2)(E) of FFDCA, EPA will issue a data call-in for information relating to anticipated residues to be submitted no later than 5 years from the date of issuance of this tolerance.
Section 408(b)(2)(F) of FFDCA states that the Agency may use data on the actual percent of food treated for assessing chronic dietary risk only if the Agency can make the following findings:
Condition 1, that the data used are reliable and provide a valid basis to show what percentage of the food derived from such crop is likely to contain such pesticide residue.
Condition 2, that the exposure estimate does not underestimate exposure for any significant subpopulation group
Condition 3, if data are available on pesticide use and food consumption in a particular area, the exposure estimate does not understate exposure for the population in such area.
In addition, the Agency must provide for periodic evaluation of any estimates used. To provide for the periodic evaluation of the estimate of PCT as required by section 408(b)(2)(F) of FFDCA, EPA may require registrants to submit data on PCT.
The Agency used PCT information as follows:
|Succulent snap beans||5|
The Agency believes that the three conditions listed in this unit have been met. With respect to Condition 1, PCT estimates are derived from Federal and private market survey data, which are Start Printed Page 57212reliable and have a valid basis. EPA uses a weighted average PCT for chronic dietary exposure estimates. This weighted average PCT figure is derived by averaging State-level data for a period of up to 10 years, and weighting for the more robust and recent data. A weighted average of the PCT reasonably represents a person's dietary exposure over a lifetime, and is unlikely to underestimate exposure to an individual because of the fact that pesticide use patterns (both regionally and nationally) tend to change continuously over time, such that an individual is unlikely to be exposed to more than the average PCT over a lifetime. For acute dietary exposure estimates, EPA uses an estimated maximum PCT. The exposure estimates resulting from this approach reasonably represent the highest levels to which an individual could be exposed, and are unlikely to underestimate an individual's acute dietary exposure. The Agency is reasonably certain that the percentage of the food treated is not likely to be an underestimation. As to Conditions 2 and 3, regional consumption information and consumption information for significant subpopulations is taken into account through EPA's computer-based model for evaluating the exposure of significant subpopulations including several regional groups. Use of this consumption information in EPA's risk assessment process ensures that EPA's exposure estimate does not understate exposure for any significant subpopulation group and allows the Agency to be reasonably certain that no regional population is exposed to residue levels higher than those estimated by the Agency. Other than the data available through national food consumption surveys, EPA does not have available information on the regional consumption of food to which lactofen may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency lacks sufficient monitoring exposure data to complete a comprehensive dietary exposure analysis and risk assessment for lactofen in drinking water. Because the Agency does not have comprehensive monitoring data, drinking water concentration estimates are made by reliance on simulation or modeling taking into account data on the physical characteristics of lactofen.
The Agency uses the Generic Estimated Environmental Concentration (GENEEC) or the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) to estimate pesticide concentrations in surface water and Screening Concentration in Ground Water (SCI-GROW), which predicts pesticide concentrations in ground water. In general, EPA will use GENEEC (a tier 1 model) before using PRZM/EXAMS (a tier 2 model) for a screening-level assessment for surface water. The GENEEC model is a subset of the PRZM/EXAMS model that uses a specific high-end runoff scenario for pesticides. GENEEC incorporates a farm pond scenario, while PRZM/EXAMS incorporate an index reservoir environment in place of the previous pond scenario. The PRZM/EXAMS model includes a percent crop area factor as an adjustment to account for the maximum percent crop coverage within a watershed or drainage basin.
None of these models include consideration of the impact processing (mixing, dilution, or treatment) of raw water for distribution as drinking water would likely have on the removal of pesticides from the source water. The primary use of these models by the Agency at this stage is to provide a screen for sorting out pesticides for which it is unlikely that drinking water concentrations would exceed human health levels of concern.
Since the models used are considered to be screening tools in the risk assessment process, the Agency does not use estimated environmental concentrations (EECs), which are the model estimates of a pesticide's concentration in water. EECs derived from these models are used to quantify drinking water exposure and risk as a %RfD or %PAD. Instead drinking water levels of comparison (DWLOCs) are calculated and used as a point of comparison against the model estimates of a pesticide's concentration in 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 from residential uses. Since DWLOCs address total aggregate exposure to lactofen they are further discussed in the aggregate risk sections in Unit III.E.
Based on the PRZM/EXAMS and SCI-GROW models, the EECs of lactofen for acute exposures are estimated to be 0.39 parts per billion (ppb) for surface water and 0.006 ppb for ground water. The EECs for chronic exposures are estimated to be 0.008 ppb for surface water and 0.006 ppb for ground water.
3. From non-dietary exposure. The term “residential exposure” is used in this document to refer to non-occupational, non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets).
Lactofen is not registered for use on any sites that would result in residential exposure.
4. Cumulative effects from substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information” concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity.”
Lactofen is a member of the diphenyl ether group of herbicides, which includes acifluorfen (lactofen's major metabolite), nitrofen, oxyfluorfen, and fomefasen. In addition, lactofen degrades to acifluorfen in the environment. The Agency has evidence that these compounds induce similar toxic effects but has not yet determined whether these compounds exhibit a common mechanism of toxicity. The Agency defers the cumulative risk assessment of lactofen and the other diphenyl ethers to a later date. For the purposes of this tolerance action, therefore, EPA has not assumed that lactofen has a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA's OPP concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's web site at http://www.epa.gov/pesticides/cumulative/.
D. Safety Factor for Infants and Children
1. In general. Section 408 of FFDCA provides that EPA shall apply an additional tenfold margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the data base on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. Margins of safety are incorporated into EPA risk assessments either directly through use of a MOE analysis or through using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk to humans. In applying this provision, EPA either retains the default value of 10X when reliable data do not support the choice of a different factor, or, if reliable data are available, EPA uses a different additional safety Start Printed Page 57213factor value based on the use of traditional uncertainty factors and/or special FQPA safety factors, as appropriate.
2. Prenatal and postnatal sensitivity. The toxicology database for lactofen is complete for FQPA purposes except for a developmental toxicity study in rabbits. Based on the quality of the exposure data, EPA determined that the 10X SF to protect infants and children should be reduced to 3X and still be protective for any possible toxicity to infants and children which might be observed in the missing rabbit developmental study. The FQPA factor was reduced based on the following:
i. The available data provide no indication of quantitative or qualitative increased susceptibility from in utero and/or postnatal exposure to lactofen in rats.
ii. The available rabbit developmental toxicity study was considered unacceptable because dosing was not done at a high enough level to observe significant toxicity. However, the study provides sufficient information to indicate that the NOAEL for both maternal and developmental effects will be 20 mg/kg/day (the HDT that elicited no significant toxicity) or higher. The acute dietary risk assessment for which the missing rabbit developmental study could potentially be used currently uses a NOAEL = 50 mg/kg/day from the rat developmental study. Risk estimates using a new developmental rabbit study could increase at most by a factor of 2.5X (50/20 mg/kg/day); therefore, a 3X UF is protective for any toxicity which might be observed in the outstanding rabbit developmental study.
iii. Endpoints for other risk assessments (chronic and cancer) utilize NOAELs significantly lower than 20mg/kg/day; therefore the developmental rabbit study will not affect these assessments. Based on mechanistic studies with transgenic mice, lactofen has been classified as a non-genotoxic hepatocarcinogen in rodents with peroxisome proliferation being a plausible mode of action. Lactofen is currently classified as likely to be carcinogenic to humans at high enough doses to cause the biochemical and histopathological changes in the liver of rodents, but unlikely to be carcinogenic to humans below those doses causing these changes. A non-linear methodology (MOE) was applied for the estimation of human cancer risk using a NOAEL of 0.3 mg/kg/day. Generally, for threshold cancer effects where the mode of action is well understood, the general margin of exposure that indicates a reasonable certainty of no harm would be 100 (10X for intraspecies extrapolation and 10X for interspecies variation). Given that the % cPAD (Food) is < 0.1 % and the cancer MOE is 300,000 for the U.S. population, a 100 fold safety factor would be protective for chronic and cancer toxicity.
iv. Adequate actual data, surrogate data, and/or modeling outputs are available to satisfactorily assess food exposure and to provide a screening level drinking water exposure assessment (there are currently no residential uses). Since there is uncertainty associated with the data gap for a developmental toxicity study in rabbits with lactofen the safety factor is reduced to 3X.
3. Conclusion. There is a complete toxicity data base for lactofen except for a developmental toxicity study in rabbits and exposure data are complete or are estimated based on data that reasonably accounts for potential exposures.
E. 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 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. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food to lactofen will occupy <0.1% of the aPAD for females 13 years and older. In addition, there is potential for acute dietary exposure to lactofen in drinking water. After calculating DWLOCs and comparing them to the EECs for surface and ground water, EPA does not expect the aggregate exposure to exceed 100% of the aPAD, as shown in Table 4 of this unit:
|Population Subgroup||aPAD (mg/kg)||% aPAD (Food)||Surface Water EEC (ppb)||Ground Water EEC (ppb)||Acute DWLOC (ppb)|
|Females 13 years and older||0.17||<0.1%||0.39||0.006||5,100|
2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that exposure to lactofen from food will utilize <0.1% of the cPAD for the U.S. population, <0.1 % of the cPAD for children 1-6, and <0.1% of the cPAD for Females 13 years and older. There are no residential uses for lactofen that Start Printed Page 57214result in chronic residential exposure to lactofen. In addition, there is potential for chronic dietary exposure to lactofen in drinking water. After calculating DWLOCs and comparing them to the EECs for surface and ground water, EPA does not expect the aggregate exposure to exceed 100% of the cPAD, as shown in Table 5 of this unit:
|Population Subgroup||cPAD mg/kg/day||% cPAD (Food)||Surface Water EEC (ppb)||Ground Water EEC (ppb)||Chronic DWLOC (ppb)|
3. Short-term risk. Short-term aggregate exposure takes into account residential exposure plus chronic exposure to food and water (considered to be a background exposure level).
Lactofen is not registered for use on any sites that would result in residential exposure. Therefore, the aggregate risk is the sum of the risk from food and water, which do not exceed the Agency's level of concern.
4. Aggregate cancer risk for U.S. population. Lactofen is considered to be a threshold carcinogen. Because lactofen is considered to be unlikely to be carcinogenic at low doses, the chronic exposure value is compared with a NOAEL to determine the cancer risk estimate. DWLOCs were calculated based on NOAEL of 0.3 mg/kg/day from a special 7-week rodent study which evaluated peroxisome proliferation in the liver of rats and mice. The aggregate cancer risk is presented in Table 6 of this unit.
|Population Subgroup||Cancer MOE from food alone||Surface Water EEC (ppb)||Ground Water EEC (ppb)||Cancer DWLOC (ppb)|
5. The Agency also conducted an aggregate chronic and cancer risk assessment for acifluorfen, derived from the use of the herbicides lactofen and sodium acifluorfen, by comparing the total acifluorfen surface water and groundwater EECs with the corresponding DWLOCs. As indicated in Table 7 of this unit, the EECs for all exposures were less than the corresponding DWLOCs; therefore, the Agency has no concern for the aggregate risk of the acifluorfen degradate from both lactofen and sodium acifluorfen.
|Population Subgroup||Surface Water EEC (ppb) (Chronic)||Surface Water EEC (ppb) (Cancer)||Ground Water EEC (ppb)||Chronic DWLOC (ppb)||Cancer DWLOC (ppb)|
6. Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to the general population, and to infants and children from aggregate exposure to lactofen residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (example—gas chromotography) is available to enforce the tolerance expression. The method may be requested from: Chief, Analytical Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; e-mail address: firstname.lastname@example.org.
B. International Residue Limits
No maximum residue limits (MRLs) for lactofen have been established or proposed by Codex, Canada, or Mexico for any agricultural commodity; therefore, no compatibility questions exist with respect to U.S. tolerances.
The following data must be submitted: Developmental toxicity study in rabbits.
Therefore, the tolerance is established for residues of lactofen, 1-(carboethoxy)ethyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate, in or on cotton, undelinted seed at 0.01 ppm; cotton, gin byproducts at 0.02 ppm, and peanut at 0.01 ppm.
In addition, this regulatory action is part of the tolerance reassessment requirements of section 408(q) of FFDCA, 21 U.S.C. 346a(q), as amended by FQPA. By law, EPA is required to reassess all tolerances in existence on August 2, 1996 by August 2006. This regulatory action will count for two reassessments toward the August 2006 deadline.
VI. Objections and Hearing Requests
Under section 408(g) of FFDCA, as amended by FQPA, any person may file an objection to any aspect of this regulation and may also request a hearing on those objections. The EPA procedural regulations which govern the Start Printed Page 57215submission of objections and requests for hearings appear in 40 CFR part 178. Although the procedures in those regulations require some modification to reflect the amendments made to FFDCA by FQPA, EPA will continue to use those procedures, with appropriate adjustments, until the necessary modifications can be made. The new section 408(g) of FFDCA provides essentially the same process for persons to “object” to a regulation for an exemption from the requirement of a tolerance issued by EPA under new section 408(d) of FFDCA, as was provided in the old sections 408 and 409 of FFDCA. However, the period for filing objections is now 60 days, rather than 30 days.
A. What Do I Need to Do to File an Objection or Request a Hearing?
You must file your objection or request a hearing on this regulation in accordance with the instructions provided in this unit and in 40 CFR part 178. To ensure proper receipt by EPA, you must identify docket ID number OPP-2004-0293 in the subject line on the first page of your submission. All requests must be in writing, and must be mailed or delivered to the Hearing Clerk on or before November 23, 2004.
1. Filing the request. Your objection must specify the specific provisions in the regulation that you object to, and the grounds for the objections (40 CFR 178.25). If a hearing is requested, the objections must include a statement of the factual issues(s) on which a hearing is requested, the requestor's contentions on such issues, and a summary of any evidence relied upon by the objector (40 CFR 178.27). Information submitted in connection with an objection or hearing request may be claimed confidential by marking any part or all of that information as CBI. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. A copy of the information that does not contain CBI must be submitted for inclusion in the public record. Information not marked confidential may be disclosed publicly by EPA without prior notice.
Mail your written request to: Office of the Hearing Clerk (1900L), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460--0001. You may also deliver your request to the Office of the Hearing Clerk in Suite 350, 1099 14th St., NW., Washington, DC 20005. The Office of the Hearing Clerk is open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Office of the Hearing Clerk is (202) 564-6255.
2. Copies for the Docket. In addition to filing an objection or hearing request with the Hearing Clerk as described in Unit VI.A., you should also send a copy of your request to the PIRIB for its inclusion in the official record that is described in ADDRESSES. Mail your copies, identified by docket ID number OPP-2004-0293, to: Public Information and Records Integrity Branch, Information Resources and Services Division (7502C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001. In person or by courier, bring a copy to the location of the PIRIB described in ADDRESSES. You may also send an electronic copy of your request via e-mail to: email@example.com. Please use an ASCII file format and avoid the use of special characters and any form of encryption. Copies of electronic objections and hearing requests will also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format. Do not include any CBI in your electronic copy. You may also submit an electronic copy of your request at many Federal Depository Libraries.
B. When Will the Agency Grant a Request for a Hearing?
A request for a hearing will be granted if the Administrator determines that the material submitted shows the following: There is a genuine and substantial issue of fact; there is a reasonable possibility that available evidence identified by the requestor would, if established resolve one or more of such issues in favor of the requestor, taking into account uncontested claims or facts to the contrary; and resolution of the factual issues(s) in the manner sought by the requestor would be adequate to justify the action requested (40 CFR 178.32).
VII. Statutory and Executive Order Reviews
This final rule establishes a tolerance under section 408(d) of FFDCA in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993). Because this rule has been exempted from review under Executive Order 12866 due to its lack of significance, this rule is not subject to Executive Order 13211, entitled Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355, May 22, 2001). This final rule does not contain any information collections subject to OMB approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or contain any unfunded mandate as described under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor does it require any special considerations under Executive Order 12898, entitled Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations (59 FR 7629, February 16, 1994); or OMB review or any Agency action under Executive Order 13045, entitled Protection of Children from Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 1997). This action does not involve any technical standards that would require Agency consideration of voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since tolerances and exemptions that are established on the basis of a petition under section 408(d) of FFDCA, such as the tolerance in this final rule, do not require the issuance of a proposed rule, the requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.) do not apply. In addition, the Agency has determined that this action will not have a substantial direct effect on States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government, as specified in Executive Order 13132, entitled Federalism (64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to develop an accountable process to ensure “meaningful and timely input by State and local officials in the development of regulatory policies that have federalism implications.” “Policies that have federalism implications” is defined in the Executive order to include regulations that have “substantial direct effects on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government.” This final rule directly regulates growers, food processors, food handlers and food retailers, not States. This action does not alter the relationships or distribution of power and responsibilities established by Congress in the preemption provisions of section 408(n)(4) of FFDCA. For these same reasons, the Agency has determined that this rule does not have any “tribal implications” as described in Executive Order 13175, Start Printed Page 57216entitled Consultation and Coordination with Indian Tribal Governments (65 FR 67249, November 6, 2000). Executive Order 13175, requires EPA to develop an accountable process to ensure “meaningful and timely input by tribal officials in the development of regulatory policies that have tribal implications.” “Policies that have tribal implications” is defined in the Executive order to include regulations that have “substantial direct effects on one or more Indian tribes, on the relationship between the Federal Government and the Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes.” This rule will not have substantial direct effects on tribal governments, on the relationship between the Federal Government and Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes, as specified in Executive Order 13175. Thus, Executive Order 13175 does not apply to this rule.
VIII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the Small Business Regulatory Enforcement Fairness Act of 1996, generally provides that before a rule may take effect, the agency promulgating the rule must submit a rule report, which includes a copy of the rule, to each House of the Congress and to the Comptroller General of the United States. EPA will submit a report containing this rule and other required information to the U.S. Senate, the U.S. House of Representatives, and the Comptroller General of the United States prior to publication of this final rule in the Federal Register. This final rule is not a “major rule” as defined by 5 U.S.C. 804(2).Start List of Subjects
List of Subjects in 40 CFR Part 180
- Environmental protection
- Administrative practice and procedure
- Agricultural commodities
- Pesticides and pests
- Reporting and recordkeeping requirements
Dated: September 16, 2004.
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:End Amendment Part Start Part
PART 180—[AMENDED]End Part Start Amendment Part
1. The authority citation for part 180 continues to read as follows:End Amendment Part Start Amendment Part
2. Section 180.432 is revised to read as follows:End Amendment Part
(a) Tolerances are established for residues of the herbicide lactofen, 1-(carboethoxy)ethyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2- nitrobenzoate, in or on the following raw agricultural commodities:
|Commodity||Parts per million|
|Beans, snap, succulent (excluding limas)||0.01|
|Cotton, gin byproducts||0.02|
|Cotton, undelinted seed||0.01|
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]End Supplemental Information
[FR Doc. 04-21500 Filed 9-23-04; 8:45 am]
BILLING CODE 6560-50-S