Source: https://www.federalregister.gov/documents/2008/02/06/E8-1784/clothianidin-pesticide-tolerance
Timestamp: 2017-08-18 11:49:33
Document Index: 700708972

Matched Legal Cases: ['art 178', 'art 178', 'art 178', 'art 178', 'art 2', '§ 180']

A Rule by the Environmental Protection Agency on 02/06/2008
This regulation is effective February 6, 2008. Objections and requests for hearings must be received on or before April 7, 2008, and must be filed in accordance with the instructions provided in 40 CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
73 FR 6851
6851-6856 (6 pages)
EPA-HQ-OPP-2007-0280
FRL-8346-9
E8-1784
https://www.federalregister.gov/d/E8-1784 https://www.federalregister.gov/d/E8-1784
This regulation establishes a tolerance for residues of clothianidin in or on sugar beet roots, tops and molasses. Bayer CropScience requested this tolerance under the Federal Food, Drug, and Cosmetic Act (FFDCA).
EPA has established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2007-0280. To access the electronic docket, go to http://www.regulations.gov, select “Advanced Search,” then “Docket Search.” Insert the docket ID number where indicated and select the “Submit” button. Follow the instructions on the regulations.gov website to view the docket index or access available documents. All documents in the docket are listed in the docket index available in regulations.gov. Although listed in the index, some information is not publicly available, e.g., Confidential Business Information (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 in the electronic docket at http://www.regulations.gov, or, if only available in hard copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The Docket Facility telephone number is (703) 305-5805.
Kable Bo Davis, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: Start Printed Page 6852(703) 306-0415; e-mail address: davis.kable@epa.gov.
Under section 408(g) of FFDCA, any person may file an objection to any aspect of this regulation and may also request a hearing on those objections. You must file your objection or request a hearing on this regulation in accordance with the instructions provided in 40 CFR part 178. To ensure proper receipt by EPA, you must identify docket ID number EPA-HQ-OPP-2007-0280 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 as required by 40 CFR part 178 on or before April 7, 2008.
In addition to filing an objection or hearing request with the Hearing Clerk as described in 40 CFR part 178, please submit a copy of the filing that does not contain any CBI for inclusion in the public docket that is described in ADDRESSES. Information not marked confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice. Submit this copy, identified by docket ID number EPA-HQ-OPP-2007-0280, by one of the following methods:
In the Federal Register of April 30, 2007 (72 FR 21263) (FRL-8124-5), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 6F7159) by Bayer CropScience, 2 T.W. Alexander Drive, Research Triangle Park, NC 27709. The petition requested that 40 CFR 180.586 be amended by establishing a tolerance for residues of the insecticide clothianidin, (E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine, in or on beet, sugar, root at 0.02 parts per million (ppm); beet, sugar, tops at 0.04 ppm; and beet, sugar, molasses at 0.06 ppm. That notice referenced a summary of the petition prepared by Bayer CropScience, the registrant, which is available to the public in the docket, http://www.regulations.gov. There were no comments received in response to the notice of filing.
Upon completing review of the current clothianidin database, the Agency concluded that the appropriate tolerance levels for clothianidin residues in or on pending crops should be established as follows: Beet, sugar, roots at 0.02 ppm, beet, sugar, molasses at 0.05 ppm and beet, sugar, dried pulp at 0.03 ppm. The Agency no longer considers sugar beet tops to be a significant livestock feedstuff; therefore, a separate tolerance for tops is not required.
Consistent with FFDCA section 408(b)(2)(D), and the factors specified in FFDCA section 408(b)(2)(D), 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 for the petitioned-for tolerance for residues of clothianidin on beet, sugar, roots at 0.02 ppm, beet, sugar, molasses at 0.05 ppm and beet, sugar, dried pulp at 0.03. EPA's assessment of exposures and risks associated with establishing the tolerance follows.
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 Start Printed Page 6853concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. Specific information on the studies received and the nature of the adverse effects caused by clothianidin as well as the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov. The risk assessment is available in the docket established by this action, which is described under ADDRESSES, and is identified as EPA-HQ-OPP-2007-0280 in that docket.
Clothianidin does not appear to exhibit toxicity towards a consistent specific target organ. Decreases in body weight and body weight gain were observed in rats, dogs, and mice. In single-dose studies, mice (acute toxicity category II) appear more sensitive than rats (category IV). Clinical signs of neurotoxicity were exhibited in both mice (decreased motor activity, tremors, and deep respirations at 50 milligram/kilogram (mg/kg)) and rats (transient signs of decreased arousal, motor activity, and locomotor activity at 100 mg/kg) in acute neurotoxicity studies following exposure by gavage; however, no indications of neurotoxicity were observed following dietary exposure in the subchronic neurotoxicity study in rats. In a developmental neurotoxicity study in rats, decreased body weights, body weight gains, motor activity, and acoustic startle response amplitude (females) were seen in offspring at doses lower than those resulting in maternal toxicity. Although the NOAELs were similar for the subchronic and chronic feeding studies in the rat, a greater spectrum of effects was observed in the chronic study (decreased body weight, body weight gain, and food consumption plus additional observations in the liver, ovary, and kidney) versus the subchronic study (effects only on body weight and food consumption). In the rat, administration via the oral route appears to be more toxic than via the dermal route. In longer term studies, dogs exhibited clinical signs of anemia. The only observed effects in mice following chronic dietary administration were increases in vocalization and decreases in body weight and body weight gain. Clothianidin has been classified as not likely to be carcinogenic to humans.
There was no evidence of increased quantitative or qualitative susceptibility of rat or rabbit offspring in developmental studies; however, increased quantitative susceptibility of rat pups was seen in both the reproduction and developmental neurotoxicity studies. The degree of concern for both of these studies is low because the observed effects are well characterized, and there are clear NOAELs and LOAELs. The NOAEL for the effects of concern identified in the reproduction study (decreased mean body weight gain and absolute thymus weights in pups, delayed sexual maturation, and an increase in still births) is the basis for the endpoint selected for the chronic dietary and short-term, intermediate-term and long-term non-dietary risk assessments.
In adult rats, a guideline immunotoxicity study shows no clothianidin-mediated immunotoxicity at doses lower than those resulting in generalized signs of toxicity (e.g., decreases in body weight); however, it cannot be concluded that a similar lack of effects will occur in offspring. Based on evidence of decreased absolute and adjusted organ weights of the thymus and spleen in multiple studies in the clothianidin data base and on evidence of increased quantitative susceptibility of juvenile rats, compared to adults, in the 2-generation reproduction study to these effects, a developmental immunotoxicity (DIT) study has been required.
For hazards that have a threshold below which there is no appreciable risk, the toxicological level of concern (LOC) is derived from the highest dose at which the NOAEL in the toxicology study identified as appropriate for use in risk assessment. However, if a NOAEL cannot be determined, the LOAEL is sometimes used for risk assessment. Uncertainty/safety factors (UFs) are used in conjunction with the LOC to take into account 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. Safety is assessed for acute and chronic risks by comparing aggregate exposure to the pesticide to the acute population adjusted dose (aPAD) and chronic population adjusted dose (cPAD). The aPAD and cPAD are calculated by dividing the LOC by all applicable UFs. Short-term, intermediate-term, and long-term risks are evaluated by comparing aggregate exposure to the LOC to ensure that the margin of exposure (MOE) called for by the product of all applicable UFs is not exceeded.
A summary of the toxicological endpoints for clothianidin used for human risk assessment can be found at http://www.regulations.gov in document “Clothianidin: Human Health Risk Assessment for Proposed Use on Sugar Beet” at pages 18-20 in docket ID number EPA-HQ-OPP-2007-0280.
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to clothianidin, EPA considered exposure under the petitioned-for tolerances as well as all existing clothianidin tolerances in (40 CFR 180.586). EPA assessed dietary exposures from clothianidin in food as follows:
In estimating acute dietary exposure, EPA used food consumption information from the U.S. Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide Continuing Surveys of Food Intake by Individuals (CSFII). The acute assessment is based on maximum residues of clothianidin observed in clothianidin and thiamethoxam field trials and assumes 100 percent crop treated (%CT).
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA 1994-1996 and 1998 CSFII. The chronic assessment is based on average residues from clothianidin and thiamethoxam field trials and assumes 100% CT.
iii. Cancer. Because clothianidin is not expected to pose a cancer risk, a quantitative dietary exposure assessment for the purposes of assessing cancer risk was not conducted.
iv. Anticipated residue and percent crop treated (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 residues that have been measured in food. If EPA relies on such information, EPA must pursuant to FFDCA section 408(f)(1) require that Start Printed Page 6854data 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. For the present action, EPA will issue such data call-ins as are required by FFDCA section 408(b)(2)(E) and authorized under FFDCA section 408(f)(1). Data will be required to be submitted no later than 5 years from the date of issuance of this tolerance.
The acute assessment is based on maximum residues of clothianidin observed in clothianidin field trials and assumes 100% crop treated. The chronic assessment is based on average residues from clothianidin field trials and also assumes 100% CT.
The Agency believes that the three conditions listed in Unit III. have been met. With respect to Condition 1, PCT estimates are derived from Federal and private market survey data, which are reliable and have a valid basis. 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 clothianidin may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency lacks sufficient monitoring data to complete a comprehensive dietary exposure analysis and risk assessment for clothianidin 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 environmental fate characteristics of clothianidin. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found at http://www.epa.gov/​oppefed1/​models/​water/​index.htm.
Based on the First Index Reservoir Screening Tool (FIRST) and Screening Concentration in Ground Water (SCI-GROW) models, the estimated environmental concentrations (EECs) of clothianidin for acute exposures are estimated to be 7.29 parts per billion (ppb) for surface water and 5.84 ppb for ground water. The EECs for chronic exposures are estimated to be 1.35 ppb for surface water and 5.84 ppb for ground water.
Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For acute dietary risk assessment, the water concentration value of 7.29 ppb was used to access the contribution to drinking water. For chronic dietary risk assessment, the water concentration of value 5.84 ppb was used to access the contribution to drinking water.
Clothianidin is currently registered for the following residential non-dietary sites: Turfgrass. EPA assessed residential exposure using the following assumptions: The following exposure scenarios were assessed for residential post-application risks: Toddlers playing on treated turf, adults performing yard work on treated turf, and adults and youths playing golf on treated turf.
Additional information on residential exposure assumptions can be found at www.regulations.gov (Docket ID EPA-HQ-OPP-2007-0280, pages 26 through 27).
Clothianidin is a member of the neonicotinoid class of pesticides and is a metabolite of another neonicotinoid, thiamethoxam. Structural similarities or common effects do not constitute a common mechanism of toxicity. Evidence is needed to establish that the chemicals operate by the same, or essentially the same sequence of major biochemical events (EPA, 2002). Although clothianidin and thiamethoxam bind selectively to insect nicotinic acetylcholine receptors (nAChR), the specific binding site(s)/receptor(s) for clothianidin, thiamethoxam, and the other neonicotinoids are unknown at this time. Additionally, the commonality of the binding activity itself is uncertain, as preliminary evidence suggests that clothianidin operates by direct competitive inhibition, while thiamethoxam is a non-competitive inhibitor. Furthermore, even if future research shows that neonicotinoids share a common binding activity to a specific site on insect nicotinic acetylcholine receptors, there is not necessarily a relationship between this pesticidal action and a mechanism of toxicity in mammals. Structural variations between the insect and mammalian nAChRs produce quantitative differences in the binding affinity of the neonicotinoids towards these receptors, which, in turn, confers the notably greater selective toxicity of this class towards insects, including aphids and leafhoppers, compared to mammals. While the insecticidal action of the neonicotinoids is neurotoxic, the most sensitive regulatory endpoint for clothianidin is based on unrelated effects in mammals, including changes in body and thymus weights, delays in sexual maturation, and still births. Additionally, the most sensitive toxicological effect in mammals differs across the neonicotinoids (e.g., testicular tubular atrophy with thiamethoxam; mineralized particles in thyroid colloid with imidaclopid). Thus, there is currently no evidence to indicate that neonicotinoids share common mechanisms of toxicity, and EPA is not following a cumulative risk approach based on a common mechanism of toxicity for the neonicotinoids. 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 concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism released by EPA's Office of Pesticide Programs on EPA's website at http://www.epa.gov/​pesticides/​cumulative/​.
Note that because clothianidin is a major metabolite of thiamethoxam, EPA has combined exposure to clothianidin resulting both from thiamethoxam use and from use of clothianidin as an active ingredient and has compared this aggregate exposure estimate to relevant endpoints for clothianidin. EPA has taken the further conservative step of assuming that, in instances where both thiamethoxam and clothianidin are Start Printed Page 6855registered for use on a crop, both pesticides will, in fact, be used on that crop.
2. Prenatal and postnatal sensitivity. In the developmental neurotoxicity study, toxicity in the offspring was observed at a lower dose level than the dose that caused toxicity in the maternal animals. Maternal effects included decreased body weights, body weight gains, and food consumption. Effects seen in the offspring included decreased body weights, body weight gains, motor activity, and acoustic startle response in the females. However, EPA determined that the degree of concern for the developmental neurotoxicity study is low and there are no residual uncertainties for prenatal and/or postnatal toxicity due to the results of the developmental neurotoxicity study because the observed effects are well characterized and there are clear NOAELs/LOAELs.
In the 2-generation reproduction study, offspring toxicity (decreased body weight gains, delayed sexual maturation in males, decreased absolute thymus weights in F1 pups of both sexes, and an increase in stillbirths in both generations) was seen at a lower dose than the dose that caused parental toxicity. Based on evidence of decreased absolute and adjusted organ weights of the thymus and spleen in multiple studies in the clothianidin data base and on evidence of increased quantitative susceptibility of juvenile rats, compared to adults, in the 2-generation reproduction study to these effects. EPA has required that testing be conducted to assess immune system function in adults and in young animals following exposure during the period of organogenesis. No quantitative or qualitative susceptibility was observed in either of the developmental rat or rabbit studies. In the rat, no developmental toxicity was observed at the highest dose tested, although this dose level induced decreases in body weight gain and food consumption in the dams. In the rabbit, premature deliveries, decreased gravid uterine weights, an increase in litter incidence of a missing lobe of the lung, and a decrease in the litter average for ossified sternal centra per fetus were noted at a dose level in which maternal death, a decrease in food consumption, and clinical signs (scant feces and orange urine) were observed. Since the developmental effects observed in the rabbit study were seen in the presence of maternal toxicity, they are not considered to be qualitatively more severe than the maternal effects.
3. Conclusion. The exposure data for clothianidin are complete or are estimated based on data that reasonably accounts for potential exposures. The acute dietary exposure assessment is based on maximum residues of clothianidin observed in clothianidin and thiamethoxam field trials and assumes 100% CT. The chronic assessment is based on average residues from clothianidin and thiamethoxam field trials and also assumes 100% CT. For water, the highest acute estimate from conservative models was used for both the acute and the chronic dietary exposure analyses. By using these conservative assessments, acute and chronic exposures/risks will not be underestimated. The residential exposure assessment utilizes residential standard operation procedures (SOPs) to assess post-application exposure to children as well as incidental oral ingestion by toddlers. The residential SOPs are based on reasonable worst-case assumptions and will not likely underestimate exposure/risk. These assessments are unlikely to underestimate the potential exposure to 74,800 infants and children resulting from the use of clothianidin.
The toxicology data base for clothianidin, however, is not complete for FQPA purposes. A complete complement of acceptable developmental, reproduction, developmental neurotoxicity, mammalian neurotoxicity and special neurotoxicity studies are available; however, due to evidence of decreased absolute and adjusted organ weights of the thymus and spleen in multiple studies in the clothianidin database, and because juvenile rats in the two-generation reproduction study appear to be more susceptible to these effects, EPA has determined that testing should be conducted to assess immune system function in adults and in young animals following developmental exposures. Given the levels at which this testing should be conducted it could result in selection of a more protective (i.e., lower) regulatory endpoint.
Due to the uncertainty with regard to potential effects on immune system function in young animals, EPA cannot conclude that there are reliable data supporting selection of a children's safety factor different from the presumptive 10X factor. Therefore, the 10X FQPA children's safety factor will be retained. This safety factor will be in the form of a database uncertainty factor to account for the lack of the testing with regard to immune system function with clothianidin.
1. Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food and water to clothianidin will occupy 45% of the aPAD for the population group (children 1-2 years old) receiving the greatest exposure.
2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that exposure to clothianidin from food and water will utilize 16% of the cPAD for the population group (children 1-2 years old). Based on the use pattern, chronic residential exposure to residues of clothianidin is not expected.
3. Short-term / Intermediate-term risk. Short-term aggregate and intermediate-term aggregate exposures take into account residential exposure plus chronic exposure to food and water (considered to be a background exposure level).
Clothianidin is currently registered for use(s) that could result in short-term residential exposure and the Agency has determined that it is appropriate to aggregate chronic food and water and short-term exposures for clothianidin.
EPA has determined that, for clothianidin, the toxicological effects Start Printed Page 6856are the same across oral, dermal, and inhalation routes of exposure and has selected the same endpoint and dose for short-term and intermediate-term exposure scenarios. Therefore, the exposures are simply summed (combined/aggregated) for use in risk calculations. Short- and intermediate aggregate risk estimates range from an MOE of 1,100 for toddlers (food + water + treated turf + treated soil + dermal) to 22,000 for youth golfers (food + water + post-application treated turf). The short-term and intermediate-term aggregate risks associated with the registered and proposed uses of clothianidin do not exceed the Agency's LOC for the general U.S. population or any population subgroup.
4. Aggregate cancer risk for U.S. population. Clothianidin has been classified as a “not likely human carcinogen.” It is not expected to pose a cancer risk.
Adequate liquid chromotography/mass spectrometry/mass spectrometry (LC/MS/MS) methods are available for both collecting data and enforcing tolerances for clothianidin residues in plant (Bayer Methods 00552 and 109240-1) and animal (Bayer Method 00624) commodities. The validated limit of quantitation (LOQ) for clothianidin in plant commodities is 0.010 ppm, except for wheat straw (0.020 ppm), and the validated LOQs are 0.010 ppm in milk and 0.020 ppm in animal tissues. All three of these methods have been reviewed by EPA's Analytical Chemistry Laboratory (ACL), approved for tolerance enforcement, and forwarded to FDA for inclusion in PAM Volume II.
There are no established or proposed Canadian, Mexican, or Codex maximum residue limits (MRLs) for clothianidin residues on sugar beet commodities.
Therefore, the tolerance is established for residues of (E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine, in or on beet, sugar, roots at 0.02 ppm, beet, sugar, molasses at 0.05 ppm and beet, sugar, dried pulp at 0.03.
2. Section 180.586 is amended by alphabetically adding the following commodities to the table in paragraph (a) to read as follows:
§ 180.586
[FR Doc. E8-1784 Filed 2-5-08; 8:45 am]