Source: https://www.federalregister.gov/documents/2010/08/18/2010-20300/n-alkyl-c8-c18-primary-amines-and-acetate-salts-exemption-from-the-requirement-of-a-tolerance
Timestamp: 2017-09-22 07:14:11
Document Index: 571565431

Matched Legal Cases: ['art 180', 'art 178', 'art 178', 'art 178', 'art 2', '§180', '§180', '§\u2009180']

Federal Register :: N-alkyl (C8-C18) Primary Amines and Acetate Salts; Exemption from the Requirement of a Tolerance
N-alkyl (C8-C18) Primary Amines and Acetate Salts; Exemption from the Requirement of a Tolerance
75 FR 50891
50891-50896 (6 pages)
EPA-HQ-OPP-2009-0046
FRL-8836-4
2010-20300
https://www.federalregister.gov/d/2010-20300 https://www.federalregister.gov/d/2010-20300
This regulation establishes an exemption from the requirement of a tolerance for residues of N-alkyl (C8-C18) primary amines and acetate salts where the alkyl group is linear and may be saturated and/or unsaturated, herein referred to in this document as NAPAAS, when used as a surfactant and related adjuvants of surfactants for pre-harvest and post-harvest uses under 40 CFR 180.910 and application to animals under 40 CFR 180.930 at a maximum concentration in formulated end-use products of 10% by weight in herbicide products, 4% by weight in insecticide products, and 4% by weight in fungicide products. The Joint Inerts Task Force (JITF), Cluster Support Team Number 25 submitted a petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting an establishment of an exemption from the requirement of a tolerance. This regulation eliminates the need to establish a maximum permissible level for residues of NAPAAS.
EPA has established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2009-0046. All documents in the docket are listed in the docket index available at http://www.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.
You may access a frequently updated electronic version of 40 CFR part 180 through the Government Printing Office's e-CFR cite at http://www.gpoaccess.gov/​ecfr. To access the Harmonized Test Guidelines referenced in this document electronically, please go to http://www.epa.gov/​oppts and select “Test Methods and Guidelines.”
Under section 408(g) of FFDCA, 21 U.S.C. 346a, 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 submission of objections and requests for hearings appear in 40 CFR part 178. 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-2009-0046 in the subject line on the first page of your submission. All objections and requests for a hearing must be in writing, and must be received by the Hearing Clerk on or before October 18, 2010. Addresses for mail and hand delivery of objections and hearing requests are provided in 40 CFR 178.25(b).
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 your copies, identified by docket ID number EPA-HQ-OPP-2009-0046, by one of the following methods:
In the Federal Register of February 4, 2010, (75 FR 5793) (FRL-8807-5), EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 346a, announcing the filing of a pesticide petition (PP 9E7627) by The JITF, Cluster Support Team 25 (CST 25), c/o CropLife Start Printed Page 50892America, 1156 15th Street, NW., Suite 400, Washington, DC 20005. The petition requested that 40 CFR 180.910 and 40 CFR 180.930 be amended by establishing an exemption from the requirement of a tolerance for residues of NAPAAS when used as at surfactant and related adjuvants of surfactants in pesticide formulations applied to pre-harvest and post-harvest crops and animals. These uses are considered inert ingredients in pesticide products. The concentration in formulated end-use products not to exceed 10% by weight in herbicide products, 4% by weight in other pesticidal products. That notice referenced a summary of the petition prepared by the JITF, Cluster Support Team Number 25 (CST 25), the petitioner, which is available in the docket, http://www.regulations.gov. There were no comments received in response to the notice of filing.
Consistent with section 408(c)(2)(A) of FFDCA, and the factors specified in FFDCA section 408(c)(2)(B), 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 NAPAAS including exposure resulting from the exemption established by this action. EPA's assessment of exposures and risks associated with NAPAAS follows.
EPA has evaluated the available toxicity data and considered their 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. Specific information on the studies received and the nature of the adverse effects caused by NAPAAS as well as the NOAEL and the LOAEL from the toxicity studies are discussed in this unit.
The available mammalian toxicology database for NAPAAS consists of one Harmonized Test Guideline 870.3650 (combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats); acute oral, dermal, and eye toxicity data; and in vitro mutagenicity data.
The NAPAAS are not acutely toxic by the oral route of exposure but are corrosive to the skin and are severe eye irritants. There is no clear target organ identified for the NAPAAS. In the Harmonized Test Guideline 870.3650 study on the representative surfactant, treatment-related microscopic lesions were observed in both sexes, which included histomorphologic changes in the stomach (hyperplasia and hyperkeratosis of the squamous mucosa of the forestomach), and erosions, ulcers, inflammatory cell infiltrations, and/or edema in the submucosa of the forestomach and glandular areas of the mucosa. The accumulation of macrophages was most prevalent in the mesenteric lymph nodes and small intestine where they were large with an abundant amount of pale foamy cytoplasm. In the mesenteric lymph node and liver, coalescence of the large macrophages occurred forming microgranulomas. Thymic atrophy was observed in both sexes. Histologically, the thymus was smaller due to a decrease in the amount of cortical lymphocytes, which may be an indirect or secondary phenomenon, as thymic atrophy often occurs in animals under stress. No evidence of potential neurotoxicity was observed in females, and the reduced motor activity observed in the high-dose males was considered to be secondary to the gastrointestinal irritation and general malaise and not a neurotoxic effect.
There was no evidence of increased susceptibility to the offspring following prenatal and postnatal (four days) exposure and reproductive toxicity was not observed. There is no evidence of mutagenicity or carcinogenicity.
Primary amines and primary amine acetates are biologically equivalent and follow the same metabolic pathways of oxidation by monoamine oxidases to generate the C8-C10 fatty acid and ammonia. The fatty acid would be degraded by well-known pathways (β-oxidation) to successive releases of acetic acid, which enters into intermediary metabolism or is metabolized ultimately to carbon dioxide and water. The CST 25 NAPAAS primary amines and primary amine acetate salt may also be conjugated, whether by glucuronidation or sulfonation, and excreted directly.
There are no chronic toxicity studies available for this series of surfactants. The Agency used a qualitative structure activity relationship (SAR) database, DEREK 11, to determine if there were structural alerts suggestive of Start Printed Page 50893carcinogenicity. No structural alerts were identified.
Specific information on the studies received and the nature of the adverse effects caused by the NAPAAS, as well as, the NOAEL and the LOAEL from the toxicity studies can be found at http://www.regulations.gov in the document “N-Alkyl (C8-C18) Primary Amines and Acetate Salts (NAPAAS - JITF CST 25 Inert Ingredients). Health Risk Assessment to Support Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations,” pp. 8-12 and 19-22 in docket ID number EPA-HQ-OPP-2009-0046.
Once a pesticide’s toxicological profile is determined, EPA identifies toxicological points of departure (POD) and levels of concern to use in evaluating the risk posed by human exposure to the pesticide. For hazards that have a threshold below which there is no appreciable risk, the toxicological POD is used as the basis for derivation of reference values for risk assessment. PODs are developed based on a careful analysis of the doses in each toxicological study to determine the dose at which no adverse effects are observed (the NOAEL) and the lowest dose at which adverse effects of concern are identified (the LOAEL). Uncertainty/safety factors are used in conjunction with the POD to calculate a safe exposure level - generally referred to as a population-adjusted dose (PAD) or a reference dose (RfD); and a safe margin of exposure (MOE). For non-threshold risks, the Agency assumes that any amount of exposure will lead to some degree of risk. Thus, the Agency estimates risk in terms of the probability of an occurrence of the adverse effect expected in a lifetime. For more information on the general principles EPA uses in risk characterization and a complete description of the risk assessment process, see http://www.epa.gov/​pesticides/​factsheets/​riskassess.htm.
A summary of the toxicological endpoints for NAPAAS used for human risk assessment is discussed in Unit IV.A of the final rule published in the Federal Register of July 29, 2009, (74 FR 37578) (FRL-8428-9).
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to NAPAAS, EPA considered exposure under the proposed exemption from the requirement of a tolerance. EPA assessed dietary exposures from NAPAAS in food as follows:
i. Acute exposure. No adverse effects attributable to a single exposure of the NAPAAS inerts were seen in the toxicity databases; therefore, an acute exposure assessment for the NAPAAS is not necessary.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment, EPA used food consumption information from the United States Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide Continuing Surveys of Food Intake by Individuals (CSFII). As to residue levels in food, no residue data were submitted for the NAPAAS. In the absence of specific residue data, EPA has developed an approach which uses surrogate information to derive upper bound exposure estimates for the subject inert ingredient. Upper bound exposure estimates are based on the highest tolerance for a given commodity from a list of high-use insecticides, herbicides, and fungicides. A complete description of the general approach taken to assess inert ingredient risks in the absence of residue data is contained in the memorandum entitled “Alkyl Amines Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water) Dietary Exposure and Risk Assessments for the Inerts.” (D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID number EPA-HQ-OPP-2008-0738.
In the dietary exposure assessment, the Agency assumed that the residue level of the inert ingredient would be no higher than the highest tolerance for a given commodity. Implicit in this assumption is that there would be similar rates of degradation (if any) between the active and inert ingredient and that the concentration of inert ingredient in the scenarios leading to these highest of tolerances would be no higher than the concentration of the active ingredient.
The Agency believes the assumptions used to estimate dietary exposures lead to an extremely conservative assessment of dietary risk due to a series of compounded conservatisms. First, assuming that the level of residue for an inert ingredient is equal to the level of residue for the active ingredient will overstate exposure. The concentration of active ingredient in agricultural products is generally at least 50% of the product and often can be much higher. Further, pesticide products rarely have a single inert ingredient; rather there is generally a combination of different inert ingredients used which additionally reduces the concentration of any single inert ingredient in the pesticide product in relation to that of the active ingredient. In the case of NAPAAS, EPA made a specific adjustment to the dietary exposure assessment to account for the use limitations of the amount of NAPAAS that may be in formulations (to no more than 10% by weight in herbicide products, 4% by weight in insecticide products, and 4% by weight in fungicide products) and assumed that the NAPAAS are present at the maximum limitation rather than at equal quantities with the active ingredient. This remains a very conservative assumption because surfactants are generally used at levels far below this percentage. For example, EPA examined several of the pesticide products associated with the tolerance/commodity combination which are the driver of the risk assessment and found that these products did not contain surfactants at levels greater than 2.25% and that none of the surfactants were NAPAAS.
Second, the conservatism of this methodology is compounded by EPA’s decision to assume that, for each commodity, the active ingredient which will serve as a guide to the potential level of inert ingredient residues is the active ingredient with the highest tolerance level. This assumption overstates residue values because it would be highly unlikely, given the high number of inert ingredients, that a single inert ingredient or class of ingredients would be present at the level of the active ingredient in the highest tolerance for every commodity. Finally, a third compounding conservatism is EPA’s assumption that all foods contain the inert ingredient at the highest tolerance level. In other words, EPA assumed 100% of all foods are treated with the inert ingredient at the rate and manner necessary to produce the highest residue legally possible for an active ingredient. In summary, EPA chose a very conservative method for estimating what level of inert residue could be on food, then used this methodology to choose the highest possible residue that could be found on food and assumed that all food contained this residue. No consideration was given to potential degradation between harvest and consumption even though monitoring data shows that tolerance level residues are typically one to two orders of magnitude higher than actual residues in food when distributed in commerce.
Accordingly, although sufficient information to quantify actual residue levels in food is not available, the compounding of these conservative Start Printed Page 50894assumptions will lead to a significant exaggeration of actual exposures. EPA does not believe that this approach underestimates exposure in the absence of residue data.
iii. Cancer. The Agency used a qualitative structure activity relationship (SAR) database, DEREK 11, to determine if there were structural alerts suggestive of carcinogenicity. No structural alerts for carcinogenicity were identified. The Agency has not identified any concerns for carcinogenicity relating to the inerts NAPAAS. Therefore a cancer dietary exposure assessment is not necessary to assess cancer risk.
iv. Anticipated residue and percent crop treated (PCT) information. EPA did not use anticipated residue and/or PCT information in the dietary assessment for NAPAAS. Tolerance level residues and/or 100 PCT were assumed for all food commodities.
2. Dietary exposure from drinking water. For the purpose of the screening level dietary risk assessment to support this request for an exemption from the requirement of a tolerance for NAPAAS, a conservative drinking water concentration value of 100 ppb based on screening level modeling was used to assess the contribution to drinking water for the chronic dietary risk assessments for parent compound. These values were directly entered into the dietary exposure model.
The Agency has reviewed the submitted petition as well as all available data on the use of these inert ingredients in pesticide formulations, and concludes that the NAPAAS inerts are not used in formulations that would be applied in and around the home or in a way that would result in residential exposures; therefore, a residential exposure risk assessment is not required for the NAPAAS inerts.
EPA has not found NAPAAS to share a common mechanism of toxicity with any other substances, and NAPAAS does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that NAPAAS does not have 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 EPA's website at http://www.epa.gov/​pesticides/​cumulative.
2. Prenatal and postnatal sensitivity. In the case of the NAPAAS, there was no increased susceptibility to the offspring of rats following prenatal and postnatal exposure in the Harmonized Test Guideline 870.3650 reproductive/developmental screening study. Decreased pup body weight was observed at 40 and 80 milligrams/kilogram/day (mg/kg/day) where maternal/paternal toxicity was manifested as microscopic lesions in the stomach, jejunum, thymus, and lymph nodes at 20, 40, and 80 mg/kg/day. Since the rat reproduction/developmental study identified a clear NOAEL of 20 mg/kg/day for offspring effects, and the selected point of departure of 5 mg/kg/day (parental NOAEL for stomach/jejunum/thymus/lymph node lesions) for the dietary risk assessment is protective of the offspring effects, there are no residual concerns.
i. The toxicity database for the NAPAAS inerts is considered adequate for assessing the risks to infants and children. The toxicity data available on the NAPAAS consists of one Harmonized Test Guideline 870.3650 combined repeated dose toxicity study with the reproduction/development toxicity screening test (rat); acute oral, dermal, and eye toxicity data; and in vitro mutagenicity data. The Agency noted changes in thymus weight and thymus atrophy. However, these were determined to be non-specific changes not indicative of immunotoxicity. In addition, no blood parameters were affected. Furthermore, these compounds do not belong to a class of chemicals that would be expected to be immunotoxic. Therefore, these identified effects do not raise a concern necessitating an additional uncertainty.
ii. There is no indication that NAPAAS is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity.
iii. There is no evidence that NAPAAS results in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction study.
iv. There are no residual uncertainties identified in the exposure databases. The food exposure assessments are considered to be highly conservative as they are based on the use of the highest tolerance level from the surrogate pesticides for every food and 100 PCT is assumed for all crops. EPA made conservative (protective) assumptions in the ground water and surface water modeling used to assess exposure to NAPAAS in drinking water. EPA used similarly conservative assumptions to assess postapplication exposure of children as well as incidental oral exposure of toddlers. These assessments will not underestimate the exposure and risks posed by NAPAAS.
Determination of safety section. EPA determines whether acute and chronic dietary pesticide exposures are safe by comparing aggregate exposure estimates to the acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA calculates the lifetime probability of acquiring cancer given the estimated aggregate exposure. Short-term, intermediate-term, and chronic-term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the appropriate PODs to ensure that an adequate MOE exists.
1. Acute risk. An acute aggregate risk assessment takes into account acute exposure estimates from dietary consumption of food and drinking water. No adverse effect resulting from Start Printed Page 50895a single oral exposure was identified and no acute dietary endpoint was selected. Therefore, NAPAAS is not expected to pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to NAPAAS from food and water will utilize 106% of the cPAD for children 1-2 years old, the population group receiving the greatest exposure. There are no residential uses for NAPAAS.
3. Aggregate cancer risk for U.S. population. The Agency has not identified any concerns for carcinogenicity relating to NAPAAS.
4. Determination of safety. EPA notes that the risk for children is slightly above a cPAD of 100%. The dietary exposure estimates overstate dietary risk because it assumes that the NAPAAS are present at the maximum limitation (10% by weight in herbicide products, 4% by weight in insecticide products, and 4% by weight in fungicide products) because surfactants are generally used at levels far below these percentages. EPA examined several of the pesticide products associated with the tolerance/commodity combinations which are the drivers of the risk assessment and found that these products did not contain surfactants at levels greater than 2.25% and that none of the surfactants were NAPAAS. Therefore, given the exceptionally conservative nature of the exposure assessment, EPA believes that actual risks are significantly lower and are not of concern. Based on this risk assessment, EPA concludes that there is a reasonable certainty that no harm will result to the general population, or to infants and children from aggregate exposure to NAPAAS residues.
EPA is establishing a limitation on the amount of NAPAAS that may be used in end-use pesticide formulations. That limitation will be enforced through the pesticide registration process under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. 136 et seq. EPA will not register any pesticide for sale or distribution that contains a maximum concentration in formulated end-use products of NAPAAS greater than 10% by weight in herbicide products, 4% by weight in insecticide products, and 4% by weight in fungicide products.
The Agency is not aware of any country requiring a tolerance for NAPAAS nor have any CODEX Maximum Residue Levels (MRLs) been established for any food crops at this time.
Therefore, an exemption from the requirement of a tolerance is established under 40 CFR 180.910 and 40 CFR 180.930 for N-alkyl (C8-C18) primary amines and acetate salts where the alkyl group is linear and may be saturated and/or unsaturated when used as an inert ingredient (surfactant and related adjuvants of surfactants) in pesticide formulations applied to pre-harvest and post-harvest crops and animals at a maximum concentration in formulated end-use products of 10% by weight in herbicide products, 4% by weight in insecticide products, and 4% by weight in fungicide products.
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 final rule has been exempted from review under Executive Order 12866, this final 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) or Executive Order 13045, entitled Protection of Children from Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 1997). 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., 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).
Start Printed Page 50896 Authority: 21 U.S.C. 321(q), 346a and 371.
2. In §180.910, the table is amended by adding alphabetically the following inert ingredients to read as follows:
N-alkyl (C8-C18) primary amines and accetate salts; Exemption from the requirement of a tolerance.
N-alkyl (C8-C18) primary amines and their acetate salts where the alkyl group is linear and may be saturated and/or unsaturated (CAS Reg. Nos. 61790-57-6, 61790-58-7, 61790-59-8, 61790-60-1, 61788-46-3, 61790-33-8, 68155-38-4) Concentration in formulated end-use products not to exceed 10% by weight in herbicide products, 4% by weight in insecticide products, and 4% by weight in fungicide products. Surfactants, related adjuvants of surfactants
3. In §180.930, the table is amended by adding alphabetically the following inert ingredients to read as follows:
§ 180.930
[FR Doc. 2010-20300 Filed 8-17-10; 8:45 am]