Notice of Filing a Pesticide Petition to Establish a Tolerance for Certain Pesticide Chemicals in or on Food

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice.

SUMMARY:

This notice announces the initial filing of pesticide petitions proposing the establishment of regulations for residues of certain pesticide chemicals in or on various food commodities.

DATES:

Comments, identified by docket control number PF-913, must be received on or before February 17, 2000.

ADDRESSES:

Comments may be submitted by mail, electronically, or in person. Please follow the detailed instructions for each method as provided in Unit I.C. of the “SUPPLEMENTARY INFORMATION.” To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-913 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:

By mail: Shaja R. Brothers, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460; telephone number: (703) 308-3194; e-mail address: brothers.shaja@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

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

B. How Can I Get Additional Information, Including Copies of this Document and Other Related Documents?

1. Electronically. You may obtain electronic copies of this document, and certain other related documents that might be available electronically, from the EPA Internet Home Page at http://www.epa.gov/​. To access this document, on the Home Page select “Laws and Regulations” and then look up the entry for this document under the “Federal Register--Environmental Documents.” You can also go directly to the Federal Register listings at http://www.epa.gov/​fedrgstr/​.

2. In person. The Agency has established an official record for this action under docket control number PF-913. The official record consists of the documents specifically referenced in this action, any public comments received during an applicable comment period, and other information related to this action, including any information claimed as confidential business information (CBI). This official record includes the documents that are physically located in the docket, as well as the documents that are referenced in those documents. The public version of the official record does not include any information claimed as CBI. The public version of the official record, which includes printed, paper versions of any electronic comments submitted during an applicable comment period, is available for inspection in the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2 (CM 2), 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

You may submit comments through the mail, in person, or electronically. To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-913 in the subject line on the first page of your response.

1 . By mail. Submit your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.

2 . In person or by courier. Deliver your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, Rm. 119, CM 2, 1921 Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

3. Electronically. You may submit your comments electronically by e-mail to: “opp-docket@epa.gov,” or you can submit a computer disk as described above. Do not submit any information electronically that you consider to be CBI. Avoid the use of special characters and any form of encryption. Electronic submissions will be accepted in Wordperfect 6.1/8.0 or ASCII file format. All comments in electronic form must be identified by docket control number PF-913. Electronic comments may also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

Do not submit any information electronically that you consider to be CBI. You may claim information that you submit to EPA in response to this document as CBI 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. In addition to one complete version of the comment that includes any information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public version of the official record. Information not marked confidential will be included in the public version of the official record without prior notice. If you have any questions about CBI or the procedures for claiming CBI, please consult the person identified under “FOR FURTHER INFORMATION CONTACT.”

E. What Should I Consider as I Prepare My Comments for EPA?

You may find the following suggestions helpful for preparing your comments:

1. Explain your views as clearly as possible.

2. Describe any assumptions that you used.

3. Provide copies of any technical information and/or data you used that support your views.

4. If you estimate potential burden or costs, explain how you arrived at the estimate that you provide.

5. Provide specific examples to illustrate your concerns.

6. Make sure to submit your comments by the deadline in this notice.

7. To ensure proper receipt by EPA, be sure to identify the docket control number assigned to this action in the subject line on the first page of your response. You may also provide the name, date, and Federal Register citation.

II. What Action is the Agency Taking?

EPA has received pesticide petitions as follows proposing the establishment and/or amendment of regulations for residues of certain pesticide chemicals in or on various food commodities under section 408 of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions contain data or information regarding the elements set forth in section 408(d)(2); however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petitions. Additional data may be needed before EPA rules on the petition.

List of Subjects

• Environmental protection
• Agricultural commodities
• Feed additives
• Food additives
• Pesticides and pests
• Reporting and recordkeeping requirements

Summaries of Petitions

The petitioner summaries of the pesticide petitions are printed below as required by section 408(d)(3) of the FFDCA. The summaries of the petitions were prepared by the petitioner and represents the view of the petitioners. EPA is publishing the petition summaries verbatim without editing them in any way. The petition summaries announce the availability of a description of the analytical methods available to EPA for the detection and measurement of the pesticide chemical residues or an explanation of why no such method is needed.

1. Interregional Project Number 4

9E6012 and 9E6021

EPA has received pesticide petitions (9E6012 and 9E6021) from the Interregional Project Number 4 (IR-4), New Jersey Agricultural Experiment Station, Rutgers University, New Brunswick, New Jersey 08903 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of sethoxydim in or on the raw agricultural commodities (RAC) pistachio and safflower at 0.2 and 15 parts per million (ppm). EPA has determined that the petitions contain data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data support granting of the petitions. Additional data may be needed before EPA rules on the petitions. This notice includes a summary of petitions prepared by BASF Corporation Agricultural Products, P.O. Box 13528, Research Triangle Park, NC 27709.

A. Residue Chemistry

1. Plant metabolism. The qualitative nature of the residues in plants is adequately understood for the purposes of registration.

2. Analytical method. Analytical methods for detecting levels of sethoxydim and its metabolites in or on food with a limit of detection that allows monitoring of food with residues at or above the levels set in these tolerances were submitted to EPA. The proposed analytical method involves extraction, partition, and clean-up. Samples are then analyzed by gas chromatography with sulfur-specific flame photometric detection. The limit of quantitation is 0.05 ppm.

B. Toxicological Profile

1. Acute toxicity. Based on the available acute toxicity data, sethoxydim does not pose any acute dietary risks. A summary of the acute toxicity studies are as follows:

i. Acute oral toxicity— Rat. Toxicity Category III; lethal dose (LD⁵⁰) = 3,125 milligrams/kilograms (mg/kg) male, 2,676 mg/kg female respectively.

ii. Acute dermal toxicity— Rat. Toxicity Category III; LD⁵⁰ > 5,000 mg/kg (male and female).

iii. Acute inhalation toxicity— Rat. Toxicity Category III; lethal concentration (LC⁵⁰) (4-hour) = 6.03 milligram/liter (mg/L) (male), 6.28 mg/L (female) respectively.

iv. Primary eye irritation— Rabbit. Toxicity Category IV; no irritation.

v. Primary dermal irritation— Rabbit. Toxicity Category IV; no irritation.

vi. Dermal sensitization— Guinea pig. Waived because no sensitization was seen in guinea pigs dosed with the end-use product poast 18% active ingredient (a.i.).

2. Genotoxicity. Ames assays were negative for gene mutation in Salmonella typhimurium strains TA98, TA100, TA1535, and TA 1537, with and without metabolic activity. A Chinese hamster bone marrow cytogenetic assay was negative for structural chromosomal aberrations at doses up to 5,000 mg/kg in Chinese hamster bone marrow cells in vivo. Recombinant assays and forward mutations tests in Bacillus subtilis, Escherichia coli, and S. typhimurium were all negative for genotoxic effects at concentrations of greater than or equal to 100%.

3. Reproductive and developmental toxicity. A developmental toxicity study in rats fed dosages of 0, 50, 180, 650, or 1,000 mg/kg/day with a maternal no observed adverse effect level (NOAEL) of 180 mg/kg/day and a maternal lowest observed adverse effect level (LOAEL) of 650 mg/kg/day (irregular gait, decreased activity, excessive salivation, and anogenital staining); and a developmental NOAEL of 180 mg/kg/day, and a developmental LOAEL of 650 mg/kg/day (21 to 22% decrease in fetal weights, filamentous tail, and lack of tail due to the absence of sacral and/or caudal vertebrae, and delayed ossification in the hyoids, vertebral centrum and/or transverse processes, sternebrae and/or metatarsals, and pubes).

A developmental toxicity study in rabbits fed doses of 0, 80, 160, 320, or 400 mg/kg/day with a maternal NOAEL of 320 mg/kg/day and a maternal LOAEL of 400 mg/kg/day (37% reduction in body weight gain without significant differences in group mean body weights and decreased food consumption during dosing) and a developmental NOAEL greater than 400 mg/kg/day highest dose tested (HDT).

A 2-generation reproduction study with rats fed diets containing 0, 150, 600, or 3,000 ppm (approximately 0, 7.5, 30, and 150 mg/kg/day) with no reproductive effects observed under the conditions of the study.

4. Subchronic toxicity. A 21-day dermal study in rabbits with a NOAEL of > 1,000 mg/kg/day limit dose. The only dose-related finding was slight epidermal hyperplasia at the dosing site in nearly all males and females dosed at 1,000 mg/kg/day. This was probably an adaptive response.

5. Chronic toxicity. A summary of the chronic toxicity studies are as follows:

i. A 1-year feeding study with dogs fed diets containing 0, 8.86/9.41, 17.5/19.9, and 110/129 mg/kg/day (males/females) with a NOAEL of 8.86/9.41 mg/kg/day (males/females) based on equivocal anemia in male dogs at the 17.5-mg/kg/day dose level.

ii. A 2-year chronic feeding/carcinogenicity study with mice fed diets containing 0, 40, 120, 360, or 1,080 ppm (equivalent to 0, 6, 18, 54, and 162 mg/kg/day) with a systemic NOAEL of 120 ppm (18 mg/kg/day) based on non-neoplastic liver lesions in male mice at the 360-ppm (54 mg/kg/day) dose level. There were no carcinogenic effects observed under the conditions of the study. The maximum tolerated dose (MTD) was not achieved in female mice.

iii. A 2-year chronic feeding/carcinogenic study with rats fed diets containing 0, 2, 6, or 18 mg/kg/day with a systemic NOAEL greater than or equal to 18 mg/kg/day HDT. There were no carcinogenic effects observed under the conditions of the study. This study was reviewed under current guidelines and was found to be unacceptable because the doses used were insufficient to induce a toxic response and an MTD was not achieved.

A second chronic feeding/carcinogenic study with rats fed diets containing 0, 360, or 1,080 ppm (equivalent to 18.2/23.0, and 55.9/71.8 mg/kg/day (males/females)). The dose levels were too low to elicit a toxic response in the test animals and failed to achieve an MTD or define a LOAEL. Slight decreases in body weights in rats at the 1,080-ppm dose level, although not biologically significant, support a free-standing NOAEL of 1,080 ppm (55.9/71.8 mg/kg/day (males/females)). There were no carcinogenic effects observed under the conditions of the study.

6. Animal metabolism. In a rat metabolism study, excretion was extremely rapid and tissue accumulation was negligible.

7. Metabolite toxicology. As a condition to registration, BASF had been asked to submit additional toxicology studies for the hydroxy-metabolites of sethoxydim. EPA agreed with BASF's recommendation to use the most abundant metabolite, 5-OH-MSO2, as surrogate for all metabolites. Based on these data, it was concluded that the toxicological potency of the plant hydroxy-metabolites is likely to be equal or less than that of the parent compound. The tolerance expression for sethoxydim and its metabolites containing the 2-cyclohexen-1-one moiety, measured as parent. Hence, the hyrdroxy-metabolites are figured into all tolerance calculations.

8. Endocrine disruption. No specific tests have been performed with sethoxydim to determine whether the chemical may have an effect in humans that is similar to an effect produced by naturally-occurring estrogen or other endocrine effects.

C. Aggregate Exposure

1. Dietary exposure—i. Food. For purposes of assessing the potential dietary exposure, BASF has estimated aggregate exposure based on the theoretical maximum residue contribution (TMRC) from existing and pending tolerances for sethoxydim. (The TMRC is a “worst case” estimate of dietary exposure since it is assumed that 100% of all crops for which tolerances are established are treated and that pesticide residues are at the tolerance levels). The TMRC from existing tolerances for the overall U.S. population is estimated at approximately 44% of the chronic population adjusted dose (cPAD). BASF estimates indicate that dietary exposure will not exceed the cPAD for any population subgroup for which EPA has data. This exposure assessment relies on very conservative assumptions 100% of crops will contain sethoxydim residues and those residues would be at the level of the tolerance which results in an overestimate of human exposure.

ii. Drinking water. Other potential sources of exposure of the general population to residues of pesticides are residues in drinking water and exposure from non-occupational sources. Based on the available studies submitted to EPA for assessment of environmental risk, BASF does not anticipate exposure to residues of sethoxydim in drinking water. There is no established maximum concentration level for residues of sethoxydim in drinking water under the Safe Drinking Water Act.

2. Non-dietary exposure. BASF has not estimated non-occupational exposure for sethoxydim. Sethoxydim is labeled for use by homeowners on and around the following use sites: flowers, evergreens, shrubs, trees, fruits, vegetables, ornamental groundcovers, and bedding plants. Hence, the potential for non-occupational exposure to the general population exists. However, these use sites do not appreciably increase exposure. Protective clothing requirements, including the use of gloves, adequately protect homeowners when applying the product. The product may only be applied through hose-end sprayers or tank sprayers as a 0.14% solution. Sethoxydim is not a volatile compound so inhalation exposure during and after application would be negligible. Dermal exposure would be minimal in light of the protective clothing and the low application rate. According to BASF, post-treatment (re-entry) exposure would be negligible for these use sites as contact with treated surfaces would be low. BASF concludes that the potential for non-occupational exposure to the general population is insignificant.

D. Cumulative Effects

BASF also considered the potential for cumulative effects of sethoxydim and other substances that have a common mechanism of toxicity. BASF is aware of one other a.i. which is structurally similar, clethodim. However BASF believes that consideration of a common mechanism of toxicity is not appropriate at this time. BASF does not have any reliable information to indicate that toxic effects produced by sethoxydim would be cumulative with clethodim or any other chemical; thus, BASF is considering only the potential risks of sethoxydim in its exposure assessment.

E. Safety Determination

1. U.S. population. Using the conservative exposure assumptions described above, BASF has estimated that aggregate exposure to sethoxydim will utilize 44% of the cPAD for the U.S. population. EPA generally has no concern for exposures below 100% of the cPAD. Therefore, based on the completeness and reliability of the toxicity data, and the conservative exposure assessment, BASF concludes that there is a reasonable certainty that no harm will result from aggregate exposure to residues of sethoxydim, including all anticipated dietary exposure and all other non-occupational exposures.

2. Infants and children—i. Developmental toxicity. Developmental toxicity was observed in a developmental toxicity study using rats but was not seen in a developmental toxicity study using rabbits. In the developmental toxicity study in rats a maternal NOAEL of 180 mg/kg/day and a maternal LOAEL of 650 mg/kg/day (irregular gait, decreased activity, excessive salivation, and anogenital staining) was determined. A developmental NOAEL of 180 mg/kg/day and a developmental LOAEL of 650 mg/kg/day (21 to 22% decrease in fetal weights, filamentous tail and lack of tail due to the absence of sacral and/or caudal vertebrae, and delayed ossification in the hyoids, vertebral centrum and/or transverse processes, sternebrae and/or metatarsals, and pubes). Since developmental effects were observed only at doses where maternal toxicity was noted, the developmental effects observed are believed to be secondary effects resulting from maternal stress.

ii. Reproductive toxicity. A 2-generation reproduction study with rats fed diets containing 0, 150, 600, or 3,000 ppm (approximately 0, 7.5, 30, and 150 mg/kg/day) produced no reproductive effects during the course of the study. Although the dose levels were insufficient to elicit a toxic response, the registrant has considered this study usable for regulatory purposes and has established a free-standing NOAEL of 3,000 ppm (approximately 150 mg/kg/day).

iii. Chronic population adjusted dose. Based on the demonstrated lack of significant developmental or reproductive toxicity, BASF believes that the cPAD used to assess safety to children should be the same as that for the general population, 0.09 mg/kg/day. Using the conservative exposure assumptions described above, BASF has concluded that the most sensitive child population is that of children ages 1 to 6 years old. BASF calculates the exposure to this group to be approximately 95% of the cPAD for all uses (including those proposed in this document). Based on the completeness and reliability of the toxicity data and the conservative exposure assessment, BASF concludes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the residues of sethoxydim, including all anticipated dietary exposure and all other non-occupational exposures.

F. International Tolerances

A maximum residue level has not been established for sethoxydim on pistachio and safflower by the Codex Alimentarius Commission.

2. Interregional Research Project Number 4

9E6059

A. Residue Chemistry

1. Plant metabolism. The metabolism of prometryn in plants is adequately understood for purposes of this tolerance.

2. Analytical method. Method, gas chromatography is available in PAM Vol. II for plants to enforce the tolerance expression.

3. Magnitude of residues. The nature of the residue in plants is adequately understood for the purposes of this tolerance. Secondary residues in animal commodities are not expected to exceed existing tolerances as result of this use.

B. Toxicological Profile

1. Acute toxicity. A rat acute oral study with a LD⁵⁰ of 1,802 mg/kg for males and a LD⁵⁰ of 2,076 mg/kg for females.

2. Genotoxicity. An Ames salmonella test, prometryn was negative for gene mutation up to cytotoxic solubility limits (1,000-2,000 μg/plate). A chromosomal aberration in vivo Chinese hamster bone marrow test, prometryn was negative for nuclear anomalies (micronuclei) when animals were dosed orally up to 5,000 mg/kg. Prometryn was negative for bacterial DNA repair and gene mutation up to precipitating levels (1,000 μg/plate). In an unscheduled DNA synthesis test, prometryn was negative (measured as UDS) in rat hepatocytes cultured in vitro up to cytotoxic levels (156.25 μg/mL).

3. Reproductive and developmental toxicity. A developmental toxicity study in rats with a maternal and developmental NOAEL of 50 mg/kg and a maternal LOAEL of 250 mg/kg based on salivation and decreases in body weight and food consumption. The developmental LOAEL is 250 mg/kg/day based on significantly decreased and incomplete ossification in the sternebrae and metacarpals. A developmental toxicity study in rabbits with a maternal and developmental NOAEL of 12 mg/kg/day and a maternal LOAEL of 72 mg/kg based on decreased food consumption, and the developmental LOAEL of 72 mg/kg/day, based on increased fetal resorption.

A 2-generation reproduction study in rats with a parental systemic NOAEL of 0.6 mg/kg/day in males and 0.7 mg/kg/day in females and a parental systemic LOAEL of 47.8 mg/kg/day in males and 53.6 mg/kg/day in females based on decreased food consumption, body weight and body weight gain. The reproductive systemic NOAEL is 0.65 mg/kg/day and the reproductive systemic LOAEL is approximately 50 mg/kg/day, based on decreased pup weight.

4. Subchronic toxicity. A 28-day mice pilot feeding study with a NOAEL of 450 mg/kg/day and a LOAEL of 1,500 mg/kg/day based on decreased body weights.

5. Chronic toxicity. A 102-week chronic feeding/carcinogenicity study in mice with a systemic NOAEL of 100 mg/kg/day for females and a systemic LOAEL of 300 mg/kg/day for females based on decreased body weight gain. No effects were observed in males.

A 2-year rat chronic feeding/carcinogenicity study with a systemic NOAEL of 29.45 mg/kg/day for males and 37.25 mg/kg/day for females and a systemic LOAEL of 60.88 mg/kg/day for males and 80.62 mg/kg/day for females based on decreased body weight and body weight gain and an increase in the incidence of renal lesions (mineralized concretions) in males. Prometryn was not carcinogenic under the conditions of the study.

6. Animal metabolism. The metabolism of prometryn in animals is adequately understood for purposes of this tolerance.

7. Metabolite toxicology. Rat metabolism studies showed that radio labeled prometryn is distributed in blood greater than spleen greater than lungs (the three highest tissues measured). Distribution is not dosage-dependant. It is extensively metabolized with less than 2% of recovered¹⁴ C radioactivity representing the parent compound. Twenty-eight metabolites were identified in the urine, and 28 in the feces. Ten metabolites were identified in both urine and feces. Prometryn is excreted predominantly in the urine and feces, with slightly higher concentrations in the urine. The 7-day recovery of¹⁴ C radioactivity averaged 95% for all dosing groups.

C. Aggregate Exposure

1. Dietary exposure—Acute exposure and risk. Acute dietary risk assessments are performed for a 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 margin of exposure (MOE) value for females (13 years and older) was 1,200,000. This value is significantly higher than the Agency's level of concern.

2. Chronic exposure and risk. Assuming 100% of the crop are treated and residues are at tolerance levels, the theoretical maximum residue contribution (TMRC) from the established and proposed tolerances is 0.000056 mg/kg/day and utilizes less than 1% of the chronic population adjusted dose (cPAD) for the U.S. population. For exposure of the most highly exposed subgroup in the population, non-nursing infants, the TMRC is 0.0016 mg/kg/day which utilizes less than 1% of the cPAD.

i. Food. Tolerances have been established 40 CFR 180.222(a) for the residues of prometryn, 2,4-bis(isopropylamino)-6-methylthio-s-triazine, in celery at 0.5 ppm; corn forage, fresh corn, and corn grain at 0.25 ppm; cotton at 1 ppm; cottonseed at 0.25 ppm; and pigeon peas at 0.25 ppm. Tolerances with regional registration have been established 40 CFR 180.222(b) for the residues of prometryn in dill at 0.3 ppm and parsley at 0.1 ppm.

ii. Drinking water. Despite the potential for exposure through drinking water, the percentage of the cPAD that will be utilized by dietary exposure (including drinking water exposure) to residues of prometryn does not exceed 100% for any of the population subgroups. Considering food only, the population subgroup with the largest percentage of the cPAD occupied is 0.0000056 mg/kg/day at < 1% of the cPAD. Therefore taking into account the completeness and reliability of the toxicity data and the conservative exposure assessment, there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to prometryn residues.

2. Non-dietary exposure. Prometryn is currently not registered for residential use such as turf and ornamentals. Therefore, there is no expectation of non-occupational residential exposures.

D. Cumulative Effects

Cumulative exposure to substances with a common mechanism of toxicity. Prometryn is a member of the triazine class of pesticides. Other members of this class include atrazine, simazine, cyanazine, prometon, propazine, metribuzin, hexazinone, ametryn, terbutryne, dipropetryn, and ethiozin.

Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency considers “available information” concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity.” The Agency believes that “available information” in this context might include not only toxicity, chemistry, and exposure data, but also scientific policies and methodologies for understanding common mechanisms of toxicity and conducting cumulative risk assessments. IR-4 does not have, at this time, available data to determine whether prometryn has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. Since there are not metabolites of toxicological concern associated with prometryn, IR-4 has not assumed that prometryn has a common mechanism of toxicity with other substances.

E. Safety Determination

1. U.S. population— Acute risk. The acute aggregate dietary MOE was estimated to be greater than 1,000,000 for females age 13 and older (accounts for both maternal and fetal exposure), the population subgroup of concern. The MOE calculations were based on the developmental NOAEL in rabbits of 12 mg/kg. This risk assessment assumed 100% of the crop was treated with tolerance level residues on all treated crops consumed, resulting in a significant over estimate of dietary exposure. The large acute dietary MOE calculated for females age 13 and older provides assurance that there is a reasonable certainty of no harm for infants and children to prometryn.

2. Chronic risk. Using the conservative exposure assumptions described above, the aggregate exposure to prometryn from food will utilize less than 1% of the cPAD for infants and children. EPA generally has no concern for exposures below 100% of the cPAD because the cPAD represents the level at or below which daily aggregate dietary exposure over a lifetime will not pose appreciable risks to human health. There are no chronic exposure scenarios for non-dietary uses of prometryn which would contribute to the aggregate risk. Taking into account, the completeness and reliability of the toxicity data and the conservative exposure assessment, IR-4 concludes that there is a reasonable certainty that no harm will result from aggregate exposure to prometryn residue's.

3. Infants and children-safety factor— i. In general. In assessing the potential for additional sensitivity of infants and children to residues of prometryn, data were considered from the developmental toxicity studies in the rat and rabbit and a 2-generation reproduction study in the rat. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposure during prenatal development to one or both parents. Reproduction studies provide information relating to effects from exposure to the pesticide on the reproductive capability of mating animals and data on systemic toxicity.

FFDCA section 408 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 unless EPA determines 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. EPA believes that reliable data support using the standard MOE and uncertainty factor (usually 100 for interspecies and intraspecies variability) and not the additional tenfold MOE/uncertainty factor when EPA has a complete data base under existing guidelines and when the severity of the effect in infants or children or the potency or unusual toxic properties of a compound do not raise concerns regarding the adequacy of the standard MOE/safety factor.

ii. Developmental and reproductive toxicity studies. The prenatal and postnatal toxicology data base for prometryn is complete with respect to current toxicological data requirements. The results of these studies indicate that infants and children are not more sensitive to exposure, based on the results of the oral rat and rabbit developmental toxicity studies and the 2-generation reproductive toxicity study in rats. The developmental studies in rats and rabbits demonstrate that no prenatal extra sensitivity is present. However, based on the developmental effects observed in rabbits, an acute dietary risk assessment was performed for women age 13 and older. The MOE was estimated greater than 1,000,000. Therefore, IR-4 concludes that reliable data support use of the standard 100-fold MOE/uncertainty factor and that an additional tenfold safety factor is not needed to protect infants and children.

F. International Tolerances

There are no Codex or Mexican limits for prometryn on cilantro. This proposal will harmonize tolerances with 0.1 ppm Canadian maximum limit for residues in cilantro.