Docket #: EPA-HQ-OPP-2009-0813

COMPANY NOTICE OF FILING

EPA Registration Division contact: Sidney Jackson  SEQ CHAPTER \h \r 1  (703)305-7610

 Interregional Research Project No. 4

PP9E7604

	EPA has received a pesticide petition PP9E7604 from   SEQ CHAPTER \h \r 1 Interregional Research Project No. 4, 500 College Road East, Suite 201W, Princeton, NJ, 08540-6635, in cooperation with Bayer CropScience, Research Triangle Park, North Carolina  27709 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 180.473 by establishing a tolerance for residues of glufosinate-ammonium (butanoic acid, 2-amino-4-(hydroxymethylphosphinyl)-monoammonium salt) and its metabolites, 2-acetamido-4-methylphosphinico-butanoic acid and 3-methylphosphinico-propionic acid, expressed as 2-amino-4-(hydroxymethylphosphinyl)butanoic acid equivalents in or on the raw agricultural commodities corn, sweet, kernel plus cob with husks removed at 0.2 parts per million (ppm), corn, sweet, forage at 4.0 ppm, and corn, sweet, stover at 6.0 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of the FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data support granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

	1. Plant metabolism.   SEQ CHAPTER \h \r 1 A confined rotational crop study has been submitted and reviewed by the Agency.  Based on the previously submitted and reviewed confined and field rotational crop studies, the EPA has determined that the residues of concern in rotational crops, for the purpose of risk assessments and tolerance expression are glufosinate ammonium (HOE 061517) and 2 methylphosphinicoacetic acid (HOE 064619).  The results of these studies are consistent with other metabolism studies conducted with glufosinate-ammonium on other crops and support the contention that the nature of residues found in plants as a result of a treatment of glufosinate-ammonium is well understood.

	2. Analytical method.   SEQ CHAPTER \h \r 1 The enforcement analytical method utilizes gas chromatography for detecting and measuring levels of glufosinate-ammonium and metabolites with a general limit of quantification of 0.05 ppm.  This method allows detection of residues at or above the proposed tolerances.

	3. Magnitude of residues. Tolerances are currently listed in 40 CFR §180.473(a) for field corn grain, forage and stover.

B. Toxicological Profile

	1. Acute toxicity.   SEQ CHAPTER \h \r 1 Glufosinate-ammonium has been classified as toxicity category III for acute oral, dermal, and inhalation toxicity; and for eye irritation.  Glufosinate-ammonium is not a dermal irritant (toxicity category IV) nor is it a dermal sensitizer.  The oral lethal dose (LD)50 is 4010 milligrams per kilogram (mg/kg) in male rats and 3030 mg/kg in female rats.

	2. Genotoxicty.   SEQ CHAPTER \h \r 1 Based on results of a complete genotoxicity database, there is no evidence of mutagenic activity in a battery of studies, including:  Salmonella spp., E. coli, in vitro mammalian cell gene mutation assays, mammalian cell chromosome aberration assays, in vivo mouse bone marrow micronucleus assays, and unscheduled DNA synthesis assays.

	3. Reproductive and developmental toxicity.   SEQ CHAPTER \h \r 1 In a developmental toxicity study, groups of 20 pregnant female Wistar rats were administered glufosinate-ammonium by gavage at doses of 0, 0.5, 2.24 10, 50 and 250 mg/kg/day from days 7 to 16 of pregnancy.  The no-observed adverse effect level (NOAEL) for maternal toxicity is 10 mg/kg/day; the lowest-observed adverse effect level (LOAEL) is 50 mg/kg/day based on vaginal bleeding and hyperactivity in dams.  In the fetus, the NOAEL is 50 mg/kg/day, based on dilated renal pelvis observations at the LOAEL of 250 mg/kg/day.  In a developmental toxicity study, groups of 15 pregnant female Himalayan rabbits were administered glufosinate-ammonium by gavage at doses of 0, 2.0, 6.3, or 20.0 mg/kg/day from days 7 to 19 of pregnancy.  In maternal animals, decreases in food consumption and body weight gain were observed at the 20 mg/kg/day dose level.  The NOAEL for maternal toxicity was 6.3 mg/kg/day and that for developmental toxicity was 20 mg/kg/day.

In a multi-generation reproduction study, glufosinate-ammonium was administered to groups of 30 male and 30 female Wistar/Han rats in the diet at concentrations of 0, 40, 120, or 360 ppm.  The LOAEL for systemic toxicity is 120 ppm based on increased kidney weights in both sexes and generations. The systemic toxicity NOAEL is 40 ppm. The LOAEL for reproductive/developmental toxicity is 360 ppm based on decreased numbers of viable pups in all generations.  The NOAEL is 120 ppm.

  SEQ CHAPTER \h \r 1 In a developmental neurotoxicity study, groups of 25 bred female rats were fed glufosinate ammonium at doses of 0, 200, 1000 or 4500 ppm in the diet. Body weights and food consumption were decreased at 1000 and 4500 ppm. No effects were seen in treated animals for the functional observation battery, developmental landmarks, grip strength, startle response or learning and memory. Motor activity was increased at the mid and high dose. The NOAEL for developmental neurotoxicity was determined to be 200 ppm.

	4. Subchronic toxicity.   SEQ CHAPTER \h \r 1 In a sub-chronic oral toxicity study, glufosinate-ammonium was administered to 10 NMRI mice/sex/ dose in the diet at levels of 0, 80, 320 or 1,280 ppm (equivalent to 0, 12, 48 or 192 millgrams/kilogram/day (mg/kg/day)) for 13 weeks.  Significant (p< 0.05) increases were observed in serum aspartate aminotransferase and in alkaline phosphatase in high-dose (192 mg/kg/ day) males.  Also observed were increases in absolute and relative liver weights in mid-(48 mg/kg/day) and high-dose males.  The NOAEL is 12 mg/kg/day, the LOAEL is 48 mg/kg/day based on the changes in clinical biochemistry and liver weights.

	5. Chronic toxicity.   SEQ CHAPTER \h \r 1 In a combined chronic toxicity/oncogenicity study, glufosinate-ammonium was administered to 50 Wistar rats/sex/dose in the diet for 130 weeks at dose levels of 0, 40, 140, or 500 ppm (mean compound intake in males was 0, 1.9, 6.8, and 24.4 mg/kg/day and for females was 0, 2.4, 8.2 and 28.7 mg/kg/day, respectively).  A dose-related increase in mortality was noted in females at 140 and 500 ppm, whereas in males increased absolute and relative kidney weights were noted at 140 ppm and 500 ppm.  The NOAEL was considered to be 40 ppm.  No treatment-related oncogenic response was noted.

In an oncogenicity study, glufosinate-ammonium was administered to 50 NMRI mice/sex/dose in the diet at dose levels of 0, 80, 160 (males only) or 320 (females only) ppm for 104 weeks.  The NOAEL for systemic toxicity is 80 ppm (10.82/16.19 mg/kg/day in males/females (M/F)), and the LOAEL is 160/320 ppm (22.60/ 63.96 mg/kg/day in M/F), based on increased mortality in males, increased glucose levels in males and females, and changes in glutathione levels in males.  No increase in tumor incidence was found in any treatment group.

In a chronic feeding study, technical glufosinate-ammonium was fed to male and female beagle dogs for 12 months in the diet at levels of 2.0, 5.0, or 8.5 mg/kg/day.  The NOAEL is 5.0 mg/kg/day based on clinical signs of toxicity, reduced weight gain and mortality 8.5 mg/kg/day.

In a rat oncogenicity study, glufosinate-ammonium was administered to Wistar rats (60/sex/group) for up to 24 months at 0, 1,000, 5,000, or 10,000 ppm (equivalent to 0, 45.4, 228.9, or 466.3 mg/kg/day in males and 0, 57.1, 281.5, or 579.3 mg/kg/day in females).  The LOAEL for chronic toxicity is 5,000 ppm (equivalent to 228.9 mg/kg/day for male rats and 281.5 mg/kg/day for females), based on increased incidences of retinal atrophy.  The chronic NOAEL is 1,000 ppm.  Under the conditions of this study, there was no evidence of carcinogenic potential.  Dosing was considered adequate based on the increased incidence of   SEQ CHAPTER \h \r 1 retinal atrophy.

	6. Animal metabolism.   SEQ CHAPTER \h \r 1 Studies conducted in rats using 14C- glufosinate-ammonium have shown that the compound is poorly absorbed (5-10%) after oral administration and is rapidly eliminated primarily as the parent compound.  The highest residue levels were found in liver and kidney tissues.

The metabolic profile and the quantitative distribution of metabolites were very similar in both goat and hen.  The vast majority of the dose was excreted, primarily as parent compound.  The very limited residues found in edible tissues, milk and eggs were comprised principally of glufosinate and 3-methylphosphinico-propionic acid (Hoe 061517), with lesser amounts of N-acetyl-L-glufosinate (Hoe 099730) and 2-methylohosphinico-acetic acid (Hoe 064619).

	7. Metabolite toxicology.    SEQ CHAPTER \h \r 1 Additional testing has been conducted with the major metabolites, 3-methylphosphinico-propionic acid, and N-acetyl-L-glufosinate.  Based on sub-chronic and developmental toxicity study results, a profile of similar or less toxicity was observed for the metabolites as compared to the parent compound, glufosinate-ammonium.

8. Endocrine disruption.   SEQ CHAPTER \h \r 1 No special studies have been conducted to investigate the potential of glufosinate-ammonium to induce estrogenic or other endocrine effects.  However, no evidence of estrogenic or other endocrine effects have been noted in any of the toxicology studies that have been conducted with this product and there is no reason to suspect that any such effects would be likely.

C. Aggregate Exposure

	1. Dietary exposure.   SEQ CHAPTER \h \r 1 Tolerances have been established (40CFR part 180.473) for the combined residues of glufosinate-ammonium and metabolites in or on a variety of raw agricultural commodities. No appropriate toxicological endpoint attributable to a single exposure was identified in the available toxicity studies. EPA did not, therefore, establish an acute reference dose (RfD) for the general population. An acute RfD of 0.0063 mg/kg/day was established, however, for the females 13+ subgroup, based on a developmental NOAEL of 6.3 mg/kg/day in the rabbit and a 100x uncertainty factor (10x inter- 10x intra-species extrapolation) and a 10x FQPA data uncertainty factor. EPA determined that the Special FQPA uncertainty factor would be 1X for the acute dietary risk assessment based on conclusions of the HIARC and the complete residue and environmental fate data bases. The developmental LOAEL (20 mg/kg/day) was based on increased fetal death in the presence of maternal toxicity. There was no qualitative or quantitative indication of increased susceptibility in the prenatal developmental toxicities in rats and rabbits or in the 2-generation reproductive study in rats with parent compound or metabolites of concern. Toxicological studies showed clinical signs in short term studies described as aggressive behavior, piloerection and a high startle response at dosages of 300 mg/kg/day. Based on these effects, EPA determined that a 10x FQPA data uncertainty factor was appropriate for the risk assessment for the food and feed use of glufosinate-ammonium. Using the 10x FQPA data uncertainty factor, the acute population adjusted dose (aPAD) for glufosinate-ammonium is 0.0063 mg/kg/day.

 The analyses were conducted using Exponent, Inc.’s DEEM™ software. Consumption data used in this program were taken from USDA’s CSFII, 1994-1996 and 1998. An updated water estimate was added to EPA Assessment (D289227. 2 August 2003. Author: D. Young). A retreat interval of 28 days was used for apples as opposed to a 14 day retreat interval. Under this scenario, the acute estimated environmental concentration (EEC) from use in apples for sucker control drops to 67 ppb, and the next highest exposure level becomes that associated with weed control in tree nut crops at 74 ppb.

Acute dietary risk was expressed as a percentage of the acute Population Adjusted Dose (aPAD) of 0.0063 mg/kg bw/day based on a NOAEL of 6.3 mg/kg bw/day with an uncertainty factor of 1000. The EPA identified an acute endpoint of concern for females of childbearing age. No endpoint attributed to a single exposure was identified for the general population, including infants and children. The estimated risk from acute dietary exposure (95th percentile) for women 13-50 years of age was 85.6% of the aPAD. Beef liver (31%), water (40%) and potato (22%) were the major contributors to the acute exposure for this subgroup.

Chronic dietary risk was expressed as a percentage of the chronic Population Adjusted Dose (cPAD) of 0.006 mg/kg bw/day based on a NOAEL of 6.0 mg/kg bw/day with an uncertainty factor of 1000. The most highly exposed subpopulation was infants (<1 year) at 57.0% of the cPAD. The chronic value for the the U.S Population was 20.9% of the cPAD. A major contributor to the overall dietary exposure for the <1 year old subgroup was water at 86% and water at 72% for the U.S. Population.

	2. Non-dietary exposure.  Glufosinate-ammonium is currently registered for use on the following non-food sites: areas around ornamentals, shade trees, Christmas trees, shrubs, walks, driveways, flower beds, farmstead buildings, in shelter belts, and along fences.  It is also registered for use as a post-emergent herbicide on farmsteads, areas associated with airports, commercial plants, storage and lumber yards, highways, educational facilities, fence lines, ditch banks, dry ditches, schools, parking lots, tank farms, pumping stations, parks, utility rights-of -way, roadsides, railroads, and other public areas and similar industrial and non-food crop areas.

The EPA has determined that there are no acute or chronic non-dietary exposure scenarios.  Further, the Agency has determined that it is not appropriate to aggregate short- and intermediate-term non-dietary exposure with dietary exposures in risk assessments because the end-points are different.

D. Cumulative Effects.  EPA has indicated that, at this time, the Agency does not have available data to determine whether glufosinate-ammonium has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment.  Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, glufosinate-ammonium does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance petition, therefore, it has not been assumed that glufosinate-ammonium has a common mechanism of toxicity with other substances.

E. Safety Determination

	1. U.S. population. Using the conservative assumptions described above, based on the completeness and reliability of the toxicity data, it is concluded that chronic dietary exposure to the registered and proposed uses of glufosinate-ammonium will utilize at most 20.9% of the chronic reference dose for the US Population. The actual exposure is likely to be much less as more realistic data and models are developed. Exposures below 100% of the reference dose are generally assumed to be of no concern because the reference dose represents the level at or below which daily aggregate exposure over a lifetime will not pose appreciable risk to human health.

The acute population of concern, female 13-50 yrs. utilizes ~85.6% of the aPAD and the actual exposure is likely to be far less.

It is not appropriate to aggregate non-dietary exposures with dietary exposures uses because the toxicity end-points are different. Therefore, there is a reasonable certainty that no harm will occur to the US Population from aggregate exposure (food, drinking water and nonresidential) to residues of glufosinate-ammonium and metabolites.

	2. Infants and children. The toxicological data base is sufficient for evaluating prenatal and postnatal toxicity for glufosinate-ammonium.  There are no prenatal or postnatal susceptibility concerns for infants and children, based on the results of the rat and rabbit developmental toxicity studies and the 2-generation reproduction study. Based on clinical signs of neurological toxicity in short and intermediate dermal toxicity studies with rats, and due to the lack of a DNT (study submitted January 2005 – MRID 48455701) EPA determined that an added FQPA data uncertainty factor of 10x is appropriate for assessing the risk of glufosinate-ammonium derived residues in crop commodities.

Using the conservative assumptions described in the exposure section above, the percent of the cPAD that will be used for exposure to residues of glufosinate-ammonium in food and water is 57.0 percent for infants less than on year of age. Of this, water composes 86% of the total. As in the adult situation, drinking water levels of comparison are higher than the worst case drinking water estimated concentrations, if they occur at all.

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฀The Codex Alimentarius Commission has established Maximum Residue Limits (Codex MRLs) for residues of glufosinate-ammonium and metabolites in or on field corn kernels (i.e., maize) at 0.1 ppm.


[Federal Register Volume 76, Number 220 (Tuesday, November 15, 2011)]
[Notices]
[Pages 70811-70812]
[FR Doc No: 2011-28983]

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DEPARTMENT OF TRANSPORTATION

Pipeline and Hazardous Materials Safety Administration

Notice of Applications for Modification of Special Permit

AGENCY: Office of Hazardous Materials Safety, Pipeline and Hazardous
Materials Safety Administration (PHMSA), DOT.

ACTION: List of Applications for Modification of Special Permits.

-----------------------------------------------------------------------

SUMMARY: In accordance with the procedures governing the application
for, and the processing of, special permits from the Department of
Transportation's Hazardous Material Regulations (49 CFR part 107,
subpart B), notice is hereby given that the Office of Hazardous
Materials Safety has received the applications described herein. This
notice is abbreviated to expedite docketing and public notice. Because
the sections affected, modes of transportation, and the nature of
application have been shown in earlier Federal Register publications,
they are not repeated here. Requests for modification of special
permits (e.g. to provide for additional hazardous materials, packaging
design changes, additional mode of transportation, etc.) are described
in footnotes to the application number. Application numbers with the
suffix ``M'' denote a modification request. These applications have
been separated from the new application for special permits to
facilitate processing.

DATES: Comments must be received on or before November 30, 2011.
    Address Comments To: Record Center, Pipeline and Hazardous
Materials Safety Administration, U.S. Department of Transportation,
Washington, DC 20590.
    Comments should refer to the application number and be submitted in
triplicate. If confirmation of receipt of comments is desired, include
a self-addressed stamped postcard showing the special permit number.

FOR FURTHER INFORMATION CONTACTS: Copies of the applications are
available for inspection in the Records Center, East Building, PHH-30,
1200 New Jersey Avenue Southeast, Washington DC or at http://regulations.gov.
    This notice of receipt of applications for modification of special
permit is published in accordance with part 107 of the Federal
hazardous materials transportation law (49 U.S.C. 5117(b); 49 CFR
1.53(b)).

    Issued in Washington, DC, on November 3, 2011.
Donald Burger,
Chief, General Approvals and Permits.

                                          Modification Special Permits
----------------------------------------------------------------------------------------------------------------
                                                                   Regulation(s)       Nature of special permit
    Application No.       Docket No.          Applicant               affected                  thereof
----------------------------------------------------------------------------------------------------------------
11526-M...............  ..............  Linde Gas North        49 CFR 180.209.......  To modify the special
                                         America LLC Bear, DE.                         permit to authorize
                                                                                ultrasonic examination of
                                                                                certain steel cylinders.
12399-M...............  ..............  Linde Gas North        49 CFR 180.209.......  To modify the special
                                         America LLC Murray                            permit to authorize
                                         Hill, NJ.                                     ultrasonic examination of
                                                                                certain aluminum
                                                                                cylinders.
12706-M...............  ..............  RAGASCO AS Raufoss,    49 CFR 173.34;         To modify the special
                                         NO.                    173.201; 173.301;      permit to authorize an
                                                                173.304.               alternative test and
                                                                                inspection procedure.
13350-M...............  ..............  National Aeronautics   49 CFR 173.201.......  To modify the special
                                         & Space                                       permit to authorize
                                         Administration                                additional transportation
                                         (NASA) Washington,                            locations.
                                         DC.
14509-M...............  ..............  Pacific Consolidated   49 CFR 173.302         To modify the special
                                         Industries, LLC        (a)(1), 173.304a       permit to authorize the
                                         Riverside, CA.         (a)(1), 175.3.         transportation of
                                                                                cylinders containing
                                                                                oxidizing gases without a
                                                                                rigid outer packaging
                                                                                capable of passing the
                                                                                Flame Penetration and
                                                                                Resistance Test and the
                                                                                Thermal Resistance Test
14574-M...............  ..............  KMG Electronic         49 CFR 180.407(c),     To modify the special
                                         Chemicals Houston,     (e) and (f).           permit to authorize
                                         TX.                                           additional Class 8
                                                                                hazardous materials and
                                                                                to add 19 new cargo
                                                                                tanks.
14728-M...............  ..............  International          49 CFR 173.416(c)....  To modify the special
                                         Isotopes Inc. Idaho                           permit to authorize an
                                         Falls, ID.                                    increase in the number of
                                                                                times the packaging can
                                                                                be used.
14977-M...............  ..............  REC Advanced Silicon   49 CFR 173.301(f)....  To modify the special
                                         Materials LLC Silver                          permit to authorize the
                                         Bow, MT.                                      transportation in
                                                                                commerce of certain DOT
                                                                                Specification cylinders
                                                                                and ton containers
                                                                                containing Silane without
                                                                                pressure relief devices.
15036-M...............  ..............  UTLX Manufacturing,    49 CFR 173.31(e)       To modify the special
                                         Incorporated           (2)(ii), 173.244       permit to authorize the
                                         Alexandria, LA.        (a)(2), 173.314,       manufacture, marking,
                                                                179.100, 179.101,      sale and use of three
                                                                179.102-3, 179.15(b)   additional non-DOT
                                                                and 179.16.            specification tank cars
                                                                                for transportation of
                                                                                chlorine and certain
                                                                                other materials toxic by
                                                                                inhalation.
----------------------------------------------------------------------------------------------------------------

[FR Doc. 2011-28983 Filed 11-14-11; 8:45 am]
BILLING CODE 4909-60-M