 Page 1 of 16 United States Prevention, Pesticides EPA 738 R 06 012 Environmental Protection and Toxic Substances June 2006 Agency ( 7508P)

Report of the Food Quality Protection Act ( FQPA) Tolerance Reassessment Progress and Risk Management Decision ( TRED) for Streptomycin Page 2 of 16 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES June 30, 2006 CERTIFIED MAIL Dear Registrant:

This is the Environmental Protection Agency's ( hereafter referred to as EPA or the Agency) " Report of the Food Quality Protection Act ( FQPA) Tolerance Reassessment Progress and Risk Management Decision for Streptomycin," which was approved on June 30, 2006. This document is also known as a Tolerance Reassessment Decision, or TRED. A Notice of Availability of this tolerance reassessment decision will be published in the Federal Register. Because of the extensive collaboration with registrants and other federal agencies prior to and during the 60 day public comment period and because relatively few comments were received during the 60 day public comment period, the TRED document and final risk assessments are being issued without an additional public comment period. The TRED, supporting risk assessments, and response to comments for streptomycin are available to the public in EPA's Pesticide Docket EPA HQ OPP 2005 0493 at: http:// www. regulations. gov. EPA issued a reregistration eligibility decision for streptomycin in September 1992.

The streptomycin TRED was developed through EPA's public participation process, published in the Federal Register on May 14, 2004, which provides opportunities for public involvement in EPA's pesticide tolerance reassessment and reregistration programs. Developed in partnership with USDA and with input from EPA's advisory committees and others, the public participation process encourages public involvement starting early and continuing throughout the pesticide risk assessment and risk mitigation decision making process. The public participation process encompasses full, modified, and streamlined versions that enable EPA to tailor the level of review to the level of refinement of the risk assessments, as well as to the amount of use, risk, public concern, and complexity associated with each pesticide. Through the public participation process, EPA is making a commitment to both involve the public and meet statutory deadlines.

Background The Federal Food, Drug and Cosmetic Act ( FFDCA), as amended by FQPA, requires EPA to reassess all the tolerances in effect on or before the enactment of FQPA on August 3, 1996. In reassessing these tolerances, EPA must consider, among other things, aggregate risks from non occupational sources of pesticide exposure, whether there is increased susceptibility to infants and children, and the cumulative effects of pesticides with a common mechanism of toxicity. Once a safety finding has been made, Page 3 of 16 the tolerances are considered reassessed. Existing tolerances associated with streptomycin have been reassessed in accordance with FFDCA, as amended by FQPA.

In addition to the assessment of direct risks posed by dietary exposure, EPA also assessed the potential for pesticidal uses of streptomycin to contribute to antibiotic resistance. In late 2004, EPA held an internal " problem formulation" meeting for the streptomycin and oxytetracycline TREDs. During this meeting EPA noted that these chemicals' potential contributions to antibiotic resistance were not fully understood. Recognizing that pesticidal uses of streptomycin and/ or oxytetracycline may possibly contribute to antibiotic resistance of bacterial pathogens with potential adverse public health consequences, and that other entities may have more expertise in evaluating antibiotic resistance, EPA requested input from three other agencies.

In May 2005, EPA hosted two conference calls with U. S. Centers for Disease Control and Prevention ( CDC), U. S. Food and Drug Administration ( FDA) Center for Drug Evaluation and Research and Center ( CDER) and Center for Veterinary Medicine ( CVM), and U. S. Department of Agriculture ( USDA) to discuss antibiotic resistance. EPA then met internally to discuss the options for addressing potential concerns resulting from the continued use of antibiotics as pesticides and evaluate the appropriateness and feasibility of conducting a qualitative antibiotic resistance risk assessment based on FDA CVM's Guidance for Industry # 152 ( Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern). Based on the discussion and evaluation, EPA included in its risk assessments a qualitative assessment of antibiotic resistance modeled on FDA CVM's Guidance for Industry # 152 ( see the Streptomycin HED Chapter dated February 7, 2006 and the Oxytetracycline HED Chapter dated June 19, 2006).

In February 2006, EPA opened a 60 day public comment period for the preliminary risk assessments. During the public comment period, EPA received 9 comments relating to the use of streptomycin. Comments were received from U. S. Apple Association, Michigan State University, Virginia Polytechnic and State University, Northwest Horticultural Council, Keep Antibiotics Working, and 4 plant pathologists from around the U. S. The majority of the respondents were supportive of the use of streptomycin on fruit trees and ornamentals and indicated that it is an integral and critical component in disease control programs. Another respondent urged EPA to implement steps to minimize the potential contribution to antibiotic resistance from the use of streptomycin. All of these comments were considered and incorporated into EPA's risk management decisions and this document represents EPA's response to public comments.

EPA has completed its review of the dietary and residential risks and is issuing its risk management decision for streptomycin. Page 4 of 16 Regulatory Decision EPA has evaluated the aggregate risks from the supported registered uses and has determined that there is a reasonable certainty that no harm to any population subgroup will result from exposure to streptomycin.

Acute dietary exposure was not estimated because no acute toxicity was identified in any of the relevant studies in the streptomycin database. The chronic dietary exposure estimate ( food + water) for the U. S. population is 4% of the chronic Population Adjusted Dose ( cPAD). The chronic dietary exposure estimate for the most highly exposed population subgroup, all infants ( children < 1 year of age), is 9% of the cPAD. Dietary risk estimates for food and water are below EPA's level of concern. This assessment is considered conservative since tolerance level residues and screening level water estimates were included in the dietary assessment; however percent crop treated information was incorporated.

The inhaled chronic exposure estimate from homeowner application to fruit trees and shrubs using a low pressure handwand ( 0.000067 mg/ kg/ day) is below EPA's level of concern ( margin of exposure = 75,000).

The chronic aggregate ( dietary + residential) risk estimate is below EPA's level of concern. The highest exposure from food and water was for all infants ( 9% of the cPAD). When EPA aggregated inhalation exposure ( 0.000067 mg/ kg/ day) and dietary exposure for the General U. S. Population ( 0.001980 mg/ kg/ day), the increment in exposure was minimal; therefore, aggregate risk is below EPA's level of concern. Exposure from dermal absorption is also expected to be minimal.

The 5 tolerances currently established at 40 CFR 180.245 for residues of streptomycin in/ on raw agricultural commodities are now considered reassessed under section 408( q) of the FFDCA ( see Table 6). In addition, EPA will propose two new tolerances for dry and succulent bean under 40 CFR § 180.245( a)( 1).

Use Profile Streptomycin ( Case Number 0169) includes the active ingredients streptomycin ( PC Code 006306) and streptomycin sulfate ( PC Code 006310). Most end use products express both streptomycin sulfate and pure streptomycin content. In this document, " streptomycin" refers to both streptomycin and streptomycin sulfate.

Table 1. Chemicals in Case Number 0169 PC Code Chemical Name 006306 streptomycin, a. k. a. D Streptamine, O 2 deoxy 2( methylamino) alpha Lglucopyranosyl 1> 2) O 5 deoxy 3 C formyl alpha L lyxofuranosyl( 1> 4) N, N' bis( aminomethyl)

006310 streptomycin sulfate Page 5 of 16 Streptomycin is an antibiotic pesticide used to control bacterial diseases in certain fruits, vegetables, seeds, and ornamental crops. The majority of streptomycin is used on apples and pears. Other crops treated include celery, philodendron, tomato, peppers, dieffenbachia cuttings, chrysanthemums, roses, pyracantha, potatoes, and tobacco. The estimated total domestic pesticidal use ( annual average) is approximately 20,000 lbs. active ingredient ( ai) per year. Approximately 10,000 lbs. ai are used annually on apples and 7,000 lbs. ai are used annually on pears. All other uses are less than 500 lbs. ai annually. Streptomycin is also registered with FDA to treat infectious diseases in animals and humans. Although firm estimates are not available, literature studies report that the estimated percentage of antibiotics applied to plants compared to all other antibiotic use is < 0.5% ( McManus, 2002).

Streptomycin is typically applied by ground or aerial spray and is also used as a liquid soak, dust treatment, and seed treatment. Spray applications are generally made in the spring according to weather and crop development. If conditions are favorable for fire blight, streptomycin may be used every 3 to 4 days, 5 to 7 days, or 10 to 14 days depending on crop type and application method.

Alternative Control Measures:

Streptomycin is one of few tools available to combat fire blight, a potentially devastating disease in fruit trees. Non antibiotic alternatives include copper, prohexadione, biological controls, Fosetyl Al, pruning, and planting resistant cultivars. Antibiotic alternatives include oxytetracycline.

Copper: Copper provides reasonable protection against fire blight disease if applied as preventive sprays in combination with use of disease forecasting models. Copper is effective in reducing the percent of infected blossom cluster infections on apples. The efficacy of copper is dependent upon many factors such as disease pressure, application timing, and its persistence on plant surfaces. The persistence is dependent upon weather conditions. In current disease management, copper plays an important part in a fire blight management program, but can only be safely applied in the early spring or autumn when the trees are dormant.

Prohexadione: Prohexadione ® has no pesticidal properties. It reduces linear growth of branches resulting in reduced tree canopy volume. Prohexadione treatment of trees reduces their susceptibility to fire blight. It may be an additional tool in the management of fire blight.

Biological Control Agent: BlightBan ® ( a. i. Pseudomonas fluorescens strain A506) is used to complement streptomycin ( see below); it is not a replacement for streptomycin and other antibiotics. Commercial use of Blightban is limited due to poor efficacy and high cost. Page 6 of 16 Fosetyl Al: Aliette ® , a fungicide, is also registered for fire blight control, but data supporting this use are not convincing of its efficacy against fire blight. No practical control activity was observed in experimental trials in Michigan. Fosetyl Al is not used commercially for the control of fire blight because it does not appear to be efficacious.

Pruning: The branches and tree limbs that show fire blight disease symptoms in the late season are removed from the trees and destroyed to prevent the spread of disease and source of inoculums for the next year. This practice is effective in reducing the primary inoculums and tree death.

Resistant Cultivars: Red Delicious variety of apple has some resistance against the fire blight disease but it is not grown widely because most consumers prefer other varieties. All other commercially grown varieties are susceptible.

Oxytetracycline: Oxytetracycline is a registered antibiotic for the control of fire blight. Oxytetracycline has been used under emergency exemption in controlling fire blight disease on apples.

Human Health Effects ( For a complete discussion, see the Streptomycin HED Chapter dated February 7, 2006.)

No acute dietary endpoint was selected because no acute toxicity was identified in any of the relevant studies in the streptomycin database.

The chronic dietary endpoint for all populations is based on decreased body weight gain observed in a 2 year rat feeding study at the LOAEL of 10 mg/ kg/ day. The NOAEL in this study was 5 mg/ kg/ day. An uncertainty factor of 100 ( 10X for interspecies extrapolation and 10X for intra species variation) was applied to the NOAEL resulting in a chronic reference dose ( cRfD) of 0.05 mg/ kg/ day. The 2 year rat feeding study endpoint was used by FDA to set tolerances for animal drug residues of streptomycin in meat, by the World Health Organization to evaluate safety of streptomycin drug residues in meat, and by EPA in the 1992 streptomycin RED.

A summary of the toxicological dose and endpoints for streptomycin that were used in the dietary risk assessment is shown below in Table 2.

Table 2. Toxicological Dose and Endpoints used in the Dietary Risk Assessment Exposure Scenario Dose Used in Risk Assessment, UF FQPA SF and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary N/ A  toxicity attributable to acute exposure was not identified Page 7 of 16 Exposure Scenario Dose Used in Risk Assessment, UF FQPA SF and Level of Concern for Risk Assessment Study and Toxicological Effects Chronic Dietary ( All populations) NOAEL= 5 mg/ kg/ day UF = 100 cRfD1 = 0.05 mg/ kg/ day FQPA SF = 1X cPAD2 = 0.05 mg/ kg/ day 2 year feeding study in rats LOAEL = 10 mg/ kg/ day based on reduced body weight gain Cancer Inadequate Information to Assess Carcinogenic Potential3 UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, chronic RfD = chronic reference dose, N/ A = not applicable 1 cRfD = NOAEL UF 2 cPAD = cRfD FQPA SF 3 No evidence of carcinogenicity was found in a literature search of toxicity in animals. The report of the FDA 2 year feeding study in rats did not report evidence of tumors; however, not enough information was available in the summary to determine whether all required tissues were examined microscopically. A carcinogenicity study in mice was not available.

For the first 30 years of its use, the drug streptomycin was frequently used to treat pregnant women. It is now known that children may be born with hearing loss or inner ear problems from treatment of the mother with streptomycin during pregnancy. It is possible that the developing fetus is more sensitive than the mother to streptomycininduced inner ear toxicity. Some children of mothers treated during pregnancy with streptomycin were born with hearing deficits, while the mothers presumably did not show evidence of hearing loss during treatment. However, these effects occurred after treatment at pharmacological doses of approximately 15 mg/ kg/ day by intramuscular injection. This corresponds to approximately 1500 mg/ kg/ day by the oral route, with 1% oral absorption, which is much higher than the oral NOAEL of 5 mg/ kg/ day selected for chronic dietary exposure. Other teratogenic effects were not attributed to prenatal streptomycin exposure and no teratogenic effects were noted in a rabbit developmental study at the high dose of 10 mg/ kg/ day. Therefore, there is no residual uncertainty for pre and/ or post natal toxicity. Because the dose selected for risk assessment ( 5 mg/ kg/ day) is much lower than the injected dose at which potential susceptibility occurs ( 1500 mg/ kg/ day) in humans, and because of the adequacy of the exposure database, there are no residual concerns and the FQPA safety factor can be reduced to 1X.

No evidence of carcinogenicity was found in a literature search of toxicity in animals. However, in accordance with EPA's Guidelines for Carcinogen Risk Assessment, streptomycin is classified as " Inadequate Information to Assess Carcinogenic Potential" due to the lack of guideline carcinogenicity studies. The report of the FDA 2 year feeding study in rats did not report evidence of tumors; however, not enough information was available in the summary to determine whether all required tissues were examined microscopically. Page 8 of 16 EPA's use of information derived from the pharmaceutical uses of streptomycin is in accordance with EPA's Final Rule promulgated on January 26, 2006 related to Protection for Subjects in Human Research, which is codified in 40 CFR Part 26.

Drinking Water Exposure and Risk Assessment ( For a complete discussion, see the Streptomycin Chronic Dietary Assessment dated January 9, 2006.)

Drinking water exposure to pesticides can occur through ground and surface water contamination. EPA considers both acute ( one day) and chronic ( lifetime) drinking water risks and uses either modeling or actual monitoring data, if available, to estimate those risks. Since available water monitoring data are considered inadequate to determine surface and ground water drinking water exposure estimates, estimated drinking water concentrations ( EDWCs) are calculated from surface and ground water models FIRST V 1.0 and SCI GROW V 2.3, respectively. The EDWCs are based on application methods, rates, and use sites that would likely yield the highest drinking water concentrations.

Tier I ( screening level) EDWCs were calculated for streptomycin even though the active ingredient of most products is streptomycin sulfate. Streptomycin sulfate generally exists in the form of a salt powder, which has an ionic bond that disappears when dissolved in water producing streptomycin and sulfate ions; thus, the drinking water modeling conducted for streptomycin provides a valid prediction for the pesticide streptomycin sulfate.

Table 3 presents estimates for surface water ( acute " peak" and chronic/ cancer values) and groundwater based on aerial applications of streptomycin to apples.

Table 3. Highest surface/ ground water EDWCs for streptomycin1 Crop Spray Type Chronic Surface Water EDWC Chronic Ground Water EDWC Apples Aerial 51.4 ppb 1.2 ppb 1 Streptomycin is the dissociation product of the pesticide a. i. streptomycin sulfate Concentrations in surface water ( 51.4 ppb) and ground water ( 1.2 ppb) represent upper bound estimates of the concentrations that might be found in surface water and ground water due to the use of streptomycin on apples. These drinking water exposure estimates were incorporated into an aggregate chronic dietary assessment using both food and water concentrations. Page 9 of 16 Acute and Chronic Dietary ( Food + Water) Exposure and Risk Assessment ( For a complete discussion, see the Streptomycin Chronic Dietary Assessment dated January 9, 2006.)

Acute dietary risk assessments were not conducted because no toxicity attributable to acute exposure could be identified based on the data currently available for streptomycin.

Chronic dietary risk assessments were conducted using the Dietary Exposure Evaluation Model ( DEEM FCID   ) , Version 2.03, which used food consumption data from the United States Department of Agriculture's ( USDA's) Continuing Surveys of Food Intakes by Individuals ( CSFII) from 1994 1996 and 1998. In addition, FDA has established tolerances for residues of streptomycin in uncooked, edible tissues of chickens, swine, and calves of 2.0 ppm in kidney and 0.5 ppm in other tissues as listed in 21CFR Part 556.610. Accordingly, streptomycin residues in animals were also considered for inclusion in this assessment. However, 2002 USDA Food Safety and Inspection Service ( USDA FSIS) National Residue Data reported no streptomycin residues in/ on all livestock animals tested ( 2 to 634 animals in each production class). Therefore, EPA considered livestock commodities to have zero residues of streptomycin.

The chronic dietary assessments assumed tolerance level residues on treated crops and incorporated percent crop treated information. EDWCs from modeled values for either surface or ground water sources were also included. The chronic dietary exposure estimates for food and water are below EPA's level of concern. The highest exposure and risk estimates were for all infants (< 1 year old) using surface water as the drinking water source and children 1 to 2 years old using ground water as the drinking water source. The exposure for all infants utilized 9.0% of the cPAD and the exposure for children 1 to 2 years old utilized 4.9% of the cPAD. The chronic dietary exposure estimates for food and water are below EPA's level of concern ( see Table 4).

Table 4. Summary of Dietary ( Food + Water) Exposure and Risk for Streptomycin Surface Water Ground Water Population Subgroup EDWC ( ppb) Total ( Food + Water) Exposure ( mg/ kg/ day) % cPAD EDWC ( ppb) Total ( Food + Water) Exposure ( mg/ kg/ day) % cPAD General U. S. Population 51.4 0.001980 4.0 1.2 0.000922 1.8 All Infants (< 1 year old) 51.4 0.004479 9.0 1.2 0.001010 2.0 Children 1 2 years old 51.4 0.004021 8.0 1.2 0.002449 4.9 EDWC = estimated drinking water concentration, cPAD = chronic population adjusted dose Page 10 of 16 Residential Risk ( For a complete discussion, see the Streptomycin HED Chapter dated February 7, 2006.)

At this time, products containing streptomycin are registered for residential use on home garden orchards ( apples and pears), and ornamentals ( pyracantha, chrysanthemums, dieffenbachia, philodendron, and roses). Dermal and inhalation exposure to residential handlers can occur when they mix, load, or apply streptomycin for use in a sprayer.

Oral absorption of chemicals related to streptomycin is less than 1% because of the charged nature of the molecules. Because the skin has a protective barrier role in comparison to the lining of the gastrointestinal tract, dermal absorption is expected be much less than that by the oral route. Although a dermal exposure study is not available for streptomycin, dermal absorption at environmental concentrations is expected to be so minimal that toxicity by the dermal route is not of concern. Therefore, quantification of risk following dermal exposure is not required at this time.

A chronic inhalation exposure assessment was conducted for homeowner application to fruit trees and shrubs using a low pressure handwand. The resulting margin of exposure ( MOE) is 75,000. MOEs ( calculated as NOAEL ÷ dose) greater than 100 do not exceed EPA's level of concern; because the MOE for this use is greater than 100, risk from residential inhalation exposure does not exceed EPA's level of concern. The inhalation exposure assessment is considered a reasonable worst case scenario for homeowners because streptomycin is poorly absorbed by the oral and dermal routes; therefore, a postapplication dermal and oral exposure assessment was not conducted.

Aggregate Risk ( For a complete discussion, see section the Streptomycin HED Chapter dated February 7, 2006.)

In accordance with the FQPA, EPA must consider and aggregate pesticide exposures and risks from all potential sources including food, drinking water, and residential exposures. In an aggregate assessment, exposures are combined and compared to quantitative estimates of hazard ( e. g., a NOAEL). When aggregating exposures and risks from various sources, EPA considers both the route and duration of exposure. In general, exposures from various sources are aggregated only when the toxic effect determined by the endpoint selected for each route is the same. In the case of streptomycin, an aggregate assessment was performed using high end exposures and conservative endpoints. No exposures of concern were identified. Since the screening level aggregate assessment did not show risks of concern, EPA concludes with reasonable certainty that combined residues of streptomycin from food, drinking water and residential exposures will not result in an aggregate risk of concern to any population subgroup. Page 11 of 16 An acute aggregate assessment was not conducted because acute toxicological effects attributable to streptomycin could not be identified.

A chronic aggregate assessment for food, water, and residential exposure was conducted because a chronic toxicological endpoint was identified for streptomycin. Streptomycin residues in livestock animals resulting from FDA approved uses were also considered for inclusion in this assessment. Livestock residues did not impact the aggregate assessment since the USDA FSIS National Residue Data reported no streptomycin residues in/ on all livestock animals tested. The highest exposure and risk estimates for food and water were for all infants using surface water as a drinking water source, and children 1 to 2 years old using ground water as the drinking water source. The food and water exposure for all infants was 0.004479 mg/ kg/ day, which utilized 9.0% of the cPAD; and the food and water exposure for children 1 to 2 years old was 0.002449 mg/ kg/ day, which utilizes 4.9% of the cPAD. Even though chronic exposure from uses of streptomycin in residential settings is unlikely, as a worst case scenario EPA aggregated the residential inhalation exposure of 0.000067 mg/ kg/ day with the food and water exposure for the General U. S. Population of 0.001980 mg/ kg/ day. The combined inhalation and dietary exposure is below EPA's level of concern. Results of the dietary ( food + drinking water) exposure and risk assessment are presented in Table 4.

Intermediate term aggregate risk estimates were not calculated because no intermediate term residential exposures are expected.

Pharmaceutical Aggregate Risk Section 408 of the FFDCA requires EPA to consider potential sources of exposure to a pesticide and related substances in addition to the dietary sources expected to result from a pesticide use subject to the tolerance. In order to determine whether to maintain a pesticide tolerance, EPA must " determine that there is a reasonable certainty of no harm." Under FFDCA section 505, the Food and Drug Administration reviews human drugs for safety and effectiveness and may approve a drug notwithstanding the possibility that some users may experience adverse side effects. EPA does not believe that, for purposes of the section 408 dietary risk assessment, it is compelled to treat a pharmaceutical user the same as a non user, or to assume that combined exposures to pesticide and pharmaceutical residues that lead to a physiological effect in the user constitutes " harm" under the meaning of section 408 of the FFDCA.

Rather, EPA believes the appropriate way to consider the pharmaceutical use of streptomycin in its risk assessment is to examine the impact that the additional nonoccupational pesticide exposures would have to a pharmaceutical user exposed to a related ( or, in some cases, the same) compound. Where the additional pesticide exposure has no more than a minimal impact on the pharmaceutical user, EPA could make a reasonable certainty of no harm finding for the pesticide tolerances of that compound under section 408 of the FFDCA. If the potential impact on the pharmaceutical user as a result of co exposure from pesticide use is more than minimal, then EPA would not be able to conclude that dietary residues were safe, and would need to discuss with FDA Page 12 of 16 appropriate measures to reduce exposure from one or both sources. EPA provided its findings with respect to streptomycin to FDA in a letter dated May 24, 2006, which is available in the public docket ( EPA HQ OPP 2005 0493).

The pesticidal exposure estimates described in the May 24, 2006 letter reflect the dietary dose from pesticidal uses of streptomycin that a user treated with a pharmaceutical streptomycin product would receive in a reasonable worst case scenario. EPA's pesticide exposure assessment has taken into consideration the appropriate population, exposure route, and exposure duration for comparison with exposure to the pharmaceutical use of streptomycin.

EPA estimates that the pharmaceutical streptomycin exposure a user is expected to receive from a typical therapeutic dose ( 15 mg/ kg/ day) is 3,000 to 21,000 times greater than the estimated dietary exposure from the pesticidal sources of streptomycin ( 0.000704 mg/ kg/ day to 0.004479 mg/ kg/ day). Therefore, because the pesticide exposure has no more than a minimal impact on the total dose to a pharmaceutical user, EPA believes that there is a reasonable certainty that the potential dietary pesticide exposure will result in no harm to a user being treated therapeutically with streptomycin. FDA is aware of EPA's conclusions regarding pesticide exposure in users receiving treatment with a pharmaceutical streptomycin drug product and FDA's June 7, 2006 response to EPA is available the public docket ( EPA HQ OPP 2005 0492).

Cumulative Risk Assessment FQPA requires that EPA consider " available information" concerning the cumulative effects of a particular pesticide's residues and " other substances that have a common mechanism of toxicity." The Agency considers other substances because lowlevel exposures to multiple chemical substances that cause a common toxic effect by a common mechanism could lead to the same adverse health effect, as would a higher level of exposure to any of the other substances individually.

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to streptomycin and any other substances, and streptomycin does not appear to produce a toxic metabolite that is also produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that streptomycin has a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http:// www. epa. gov/ pesticides/ cumulative/. Page 13 of 16 Tolerance Reassessment Summary Tolerances for the pesticidal residues of streptomycin are established under 40 CFR 180.245. A summary of the streptomycin tolerance reassessment is presented in Table 5. FDA tolerances established in 21 CFR Part 556.610 are Table 5. Tolerance Reassessment Summary for Streptomycin Commodity Current Tolerance ( ppm) Reassessed Tolerance ( ppm) Comments Tolerances Under 40 CFR § 180.245( a)( 1) Pome, fruit 0.25 0.25 Tolerances To Be Proposed Under 40 CFR § 180.245( a)( 1)

Bean, dry None 0.5 EPA has adequate data to support dry beans.

Bean, succulent None 0.5 EPA has adequate data to support succulent beans. Tolerances Under 40 CFR § 180.245( a)( 2) Celery 0.25 0.25 Pepper 0.25 0.25 Tomato 0.25 0.25 Tolerances Under 40 CFR § 180.245( a)( 3) Potato 0.25 0.25 FDA has established tolerances for residues of streptomycin in uncooked, edible tissues of chickens, swine, and calves of 2.0 ppm in kidney and 0.5 ppm in other tissues as listed in 21CFR Part 556.610. These tolerances are regulated by FDA and are not included in this tolerance reassessment decision; however, the residues from these uses were included in EPA's dietary risk assessment.

Antibiotic Resistance ( For a complete discussion, see the Streptomycin HED Chapter dated February 7, 2006.)

Bacterial resistance to streptomycin as a result of drug use has long been recognized. EPA recognizes that pesticidal uses of streptomycin may contribute to antibiotic resistance of bacterial pathogens with potential adverse public health consequences. After evaluating available data and consulting with CDC, FDA CDER, FDA CVM, and USDA, EPA determined that insufficient data were available to conduct a quantitative antibiotic resistance assessment and instead conducted a qualitative antibiotic resistance assessment based on FDA CVM's Guidance for Industry # 152.

Because anticipated dietary residues are extremely low ( conservatively estimated at 0.001980 mg/ kg/ day for the General U. S. Population), it is unlikely that antibiotic resistance from pesticidal use of streptomycin would result from food exposure. Bacterial resistance to streptomycin from pesticidal use of streptomycin with adverse public health consequences could theoretically occur from ( 1) development of resistance in bacterial pathogens present in orchards or ( 2) from development of resistance from Page 14 of 16 non pathogenic bacteria in orchards which later transferred their resistance to human bacterial pathogens.

The possibility of antibiotic resistance resulting in adverse human health consequences is determined principally by the likelihood of non pathogenic organisms in orchards transferring their resistance to pathogens in the human environment. Antibiotic resistance from pesticidal use of streptomycin is unlikely to result directly from dietary residues of streptomycin because dietary residues are very low. The maximum aggregate dietary exposure is 0.004479 mg/ kg/ day which is very small when compared to a 15 mg/ kg/ day drug dose. The drug dose is 3,000 times greater than the estimated pesticidal dietary exposure. The small dose from pesticidal exposure would not be expected to select for resistant bacteria because very few bacteria would be killed by this small dose. If bacterial resistance to streptomycin from pesticidal use occurs, it is most likely that it would be caused by development of resistance from non pathogenic bacteria in orchards which later transferred their resistance to human bacterial pathogens.

In setting or revising tolerances under section 408 of the FFDCA, EPA must determine that " there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue." Because the risk of antibiotic resistance does not arise from the ingestion of pesticide residues, the risk has not been aggregated for the purposes of this action. EPA may consider the risk of antibiotic resistance in future actions such as registration review or approval of new uses for streptomycin. EPA is requiring use and usage information as well as additional environmental fate data to address the uncertainties regarding potential antibiotic resistance from the pesticidal uses ( see Table 6). Based on these new data, EPA may also require an antibiotic resistance monitoring study to be conducted in orchards or other high use areas. This study is held in reserve and, if deemed appropriate, will be required through a separate data call in. Additional label statements will also be required that will ensure judicious use of streptomycin.

Additional Generic Data Requirements Toxicity for streptomycin was assessed using the extensive database for streptomycin from its use as a human drug and using animal toxicity studies submitted to FDA. Toxicological and environmental fate data requirements were waived for streptomycin in the 1992 RED. Since the RED, EPA has become aware of the increasing importance of antibiotic resistance. Therefore, the following environmental fate and use data requirements presented in Table 6 are necessary to better understand the fate of pesticidal streptomycin in the environment and to support the continued registration of streptomycin.

Table 6. Streptomycin Generic Data Requirements Guideline Study Title 810.1000 Use and Usage Information 810.1000 Antibiotic Resistance in Orchards1 835.1230 Sediment and soil adsorption/ desorption for parent and Degradates 835.2130 Hydrolysis as a Function of pH and Temperature Page 15 of 16 Guideline Study Title 835.2210 Direct Photolysis Rate in Water by Sunlight 835.4100 Aerobic Soil Metabolism 1 Based on the results of the required environmental fate data, EPA may require a special study to be conducted on antibiotic resistance in orchards. This study is being held in reserve and, if deemed appropriate, will be required through a separate data call in.

Required Label Changes Table 7 presents the label amendments required for all products containing streptomycin.

Table 7. Streptomycin Label Changes Summary Table Description Amended Labeling Language Placement on Label General Application Restrictions " This product contains the antibiotic streptomycin. To reduce the development of drug resistant bacteria and maintain the effectiveness of this and other antibacterial products, this product should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria." Directions for Use General Application Restrictions " This material is not to be used for medical or veterinary purposes." Directions for Use Conclusions EPA has evaluated the dietary and residential risks from the supported registered uses and has determined that there is a reasonable certainty that no harm to any population subgroup will result from chronic exposure to streptomycin and considers the existing tolerances reassessed. Although not related to the FQPA safety finding, there are uncertainties about the pesticidal contributions to antibiotic resistance. To better understand the fate of pesticidal streptomycin in the environment and its potential contribution to antibiotic resistance, EPA is requiring additional use and environmental fate data. EPA is also requiring label amendments that will ensure judicious use of streptomycin.

Please contact Lance Wormell of my staff with any questions regarding this decision. He may be reached by phone at ( 703) 603 0523 or by e mail at wormell. lance@ epa. gov.

Sincerely,

Debra Edwards, Ph. D., Director Special Review and Reregistration Division Page 16 of 16 Technical Support Documents for the Streptomycin TRED 1. Kit Farwell ( USEPA/ OPPTS/ OPP/ HED). STREPTOMYCIN SULFATE ( 006310) and STREPTOMYCIN ( 006306), HED Chapter of the Tolerance Reassessment Eligibility Document ( TRED), Revised After Phase 1 Error Only Corrections. DP Barcode D310386. February 7, 2006.

2. Subijoy Dutta ( USEPA/ OPPTS/ OPP/ EFED). Tier I Estimated Drinking Water Concentrations of Streptomycin and Streptomycin Sulfate for use in the Human Health Risk Assessment as part of the Tolerance Reregistration Eligibility Decision ( TRED). DP Bar Code D310392. November 30, 2005.

3. Toiya Goodlow ( USEPA/ OPPTS/ OPP/ HED). Streptomycin/ Streptomycin Sulfate: Chronic Dietary Exposure Assessment for the Tolerance Reassessment Eligibility Decision ( TRED). DP Barcode D310391. January 9, 2006.

4. Monica S. Hawkins ( USEPA/ OPPTS/ OPP/ HED). Review of Streptomycin Incident Reports. DP Barcode D310389. August 24, 2005.


[Federal Register: September 9, 2009 (Volume 74, Number 173)]
[Rules and Regulations]
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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2009-0381; Directorate Identifier 2009-NM-008-AD;
Amendment 39-16016; AD 2009-18-19]
RIN 2120-AA64

Airworthiness Directives; Airbus Model A330-200 and -300 Series
Airplanes and Model A340-200 and -300 Series Airplanes

AGENCY: Federal Aviation Administration (FAA), Department of
Transportation (DOT).

ACTION: Final rule.

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SUMMARY: We are adopting a new airworthiness directive (AD) for the
products listed above. This AD results from mandatory continuing
airworthiness information (MCAI) originated by an aviation authority of
another country to identify and correct an unsafe condition on an
aviation product. The MCAI describes the unsafe condition as:

    An A340 operator has reported an uncommanded engine N[deg]4 shut
down during taxi after landing.
    The root cause of this event has been identified as failure of
the fuel pump Non Return Valve (NRV) preventing the collector cell
jet pump from working. This led to engine N[deg]4 collector cell
fuel level to drop below the pump inlet and consequently causing
engine N[deg]4 flame out.
* * * * *
    Multiple NRV failures in combination with failure modes trapping
fuel could potentially increase the quantity of unusable fuel on
aircraft possibly leading to fuel starvation which could result in
engine in-flight shut down and would constitute an unsafe condition.
* * * * *

We are issuing this AD to require actions to correct the unsafe
condition on these products.

DATES: This AD becomes effective October 14, 2009.
    The Director of the Federal Register approved the incorporation by
reference of certain publications listed in this AD as of October 14,
2009.

ADDRESSES: You may examine the AD docket on the Internet at http://
www.regulations.gov or in person at the U.S. Department of
Transportation, Docket Operations, M-30, West Building Ground Floor,
Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC.

FOR FURTHER INFORMATION CONTACT: Vladimir Ulyanov, Aerospace Engineer,
International Branch, ANM-116, Transport Airplane Directorate, FAA,
1601 Lind Avenue, SW., Renton, Washington 98057-3356; telephone (425)
227-1138; fax<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Discussion

    We issued a notice of proposed rulemaking (NPRM) to amend 14 CFR
part 39 to include an AD that would apply to the specified products.
That NPRM was published in the Federal Register on April 29, 2009 (74
FR 19464). That NPRM proposed to correct

an unsafe condition for the specified products. The MCAI states:

    An A340 operator has reported an uncommanded engine N[deg]4 shut
down during taxi after landing.
    The root cause of this event has been identified as failure of
the fuel pump Non Return Valve (NRV) preventing the collector cell
jet pump from working. This led to engine N[deg]4 collector cell
fuel level to drop below the pump inlet and consequently causing
engine N[deg]4 flame out.
    A330 aircraft which have a similar design are also impacted by
this issue.
    Multiple NRV failures in combination with failure modes trapping
fuel could potentially increase the quantity of unusable fuel on
aircraft possibly leading to fuel starvation which could result in
engine in-flight shut down and would constitute an unsafe condition.
    To prevent such an event, this Airworthiness Directive (AD)
requires a periodic operational test to check the correct operation
of NRV and to apply the associated corrective actions.

The corrective action includes replacing any failed NRV with a new NRV.
You may obtain further information by examining the MCAI in the AD
docket.

Comments

    We gave the public the opportunity to participate in developing
this AD. We considered the comment received.

Request To Clarify Applicability Statement and Paragraphs (f)(1) and
(f)(2) of the NPRM

    Airbus suggests that we revise the NPRM to specify all models in
the Applicability statement and in paragraphs (f)(1) and (f)(2) of the
proposed AD.
    We agree. For clarity, we have revised the applicability statement
and paragraphs (f)(1), (f)(2), (f)(3)(i), and (f)(3)(ii) of this AD to
identify all affected models as specified in the applicable type
certificate data sheet.

Conclusion

    We reviewed the available data, including the comment received, and
determined that air safety and the public interest require adopting the
AD with the changes described previously. We determined that these
changes will not increase the economic burden on any operator or
increase the scope of the AD.

Differences Between This AD and the MCAI or Service Information

    We have reviewed the MCAI and related service information and, in
general, agree with their substance. But we might have found it
necessary to use different words from those in the MCAI to ensure the
AD is clear for U.S. operators and is enforceable. In making these
changes, we do not intend to differ substantively from the information
provided in the MCAI and related service information.
    We might also have required different actions in this AD from those
in the MCAI in order to follow our FAA policies. Any such differences
are highlighted in a NOTE within the AD.

Costs of Compliance

    We estimate that this AD affects 50 products of U.S. registry. We
also estimate that it takes about 5 work-hours per product to comply
with the basic requirements of this AD. The average labor rate is $80
per work-hour. Based on these figures, we estimate the cost of this AD
to the U.S. operators to be $20,000, or $400 per product.

Authority for This Rulemaking

    Title 49 of the United States Code specifies the FAA's authority to
issue rules on aviation safety. Subtitle I, section 106, describes the
authority of the FAA Administrator. ``Subtitle VII: Aviation
Programs,'' describes in more detail the scope of the Agency's
authority.
    We are issuing this rulemaking under the authority described in
``Subtitle VII, Part A, Subpart III, Section 44701: General
Requirements.'' Under that section, Congress charges the FAA with
promoting safe flight of civil aircraft in air commerce by prescribing
regulations for practices, methods, and procedures the Administrator
finds necessary for safety in air commerce. This regulation is within
the scope of that authority because it addresses an unsafe condition
that is likely to exist or develop on products identified in this
rulemaking action.

Regulatory Findings

    We determined that this AD will not have federalism implications
under Executive Order 13132. This AD will not have a substantial direct
effect on the States, on the relationship between the national
government and the States, or on the distribution of power and
responsibilities among the various levels of government.
    For the reasons discussed above, I certify this AD:
    1. Is not a ``significant regulatory action'' under Executive Order
12866;
    2. Is not a ``significant rule'' under the DOT Regulatory Policies
and Procedures (44 FR 11034, February 26, 1979); and
    3. Will not have a significant economic impact, positive or
negative, on a substantial number of small entities under the criteria
of the Regulatory Flexibility Act.
    We prepared a regulatory evaluation of the estimated costs to
comply with this AD and placed it in the AD docket.

Examining the AD Docket

    You may examine the AD docket on the Internet at http://
www.regulations.gov; or in person at the Docket Operations office
between 9 a.m. and 5 p.m., Monday through Friday, except Federal
holidays. The AD docket contains the NPRM, the regulatory evaluation,
any comments received, and other information. The street address for
the Docket Operations office (telephone<PHONE_NUMBER>) is in the
ADDRESSES section. Comments will be available in the AD docket shortly
after receipt.

List of Subjects in 14 CFR Part 39

    Air transportation, Aircraft, Aviation safety, Incorporation by
reference, Safety.

Adoption of the Amendment

0
Accordingly, under the authority delegated to me by the Administrator,
the FAA amends 14 CFR part 39 as follows:

PART 39--AIRWORTHINESS DIRECTIVES

0
1. The authority citation for part 39 continues to read as follows:

    Authority:  49 U.S.C. 106(g), 40113, 44701.

Sec.  39.13  [Amended]

0
2. The FAA amends Sec.  39.13 by adding the following new AD:

2009-18-19 Airbus: Amendment 39-16016. Docket No. FAA-2009-0381;
Directorate Identifier 2009-NM-008-AD.

Effective Date

    (a) This airworthiness directive (AD) becomes effective October
14, 2009.

Affected ADs

    (b) None.

 Applicability

    (c) This AD applies to the airplanes identified in paragraphs
(c)(1) and (c)(2) of the AD, certificated in any category.
    (1) Airbus Model A330-201, -202, -203, -223, -243, -301, -302, -
303, -321, -322, -323, -341, -342, and -343 series airplanes, all
serial numbers.
    (2) Airbus Model A340-211, -212, -213, -311, -312, and -313
series airplanes, all serial numbers.

Subject

    (d) Air Transport Association (ATA) of America Code 28: Fuel.

Reason

    (e) The mandatory continuing airworthiness information (MCAI)
states:
    An A340 operator has reported an uncommanded engine N[deg]4 shut
down during taxi after landing.

    The root cause of this event has been identified as failure of
the fuel pump Non Return Valve (NRV) preventing the collector cell
jet pump from working. This led to engine N[deg]4 collector cell
fuel level to drop below the pump inlet and consequently causing
engine N[deg]4 flame out.
    A330 aircraft which have a similar design are also impacted by
this issue.
    Multiple NRV failures in combination with failure modes trapping
fuel could potentially increase the quantity of unusable fuel on
aircraft possibly leading to fuel starvation which could result in
engine in-flight shut down and would constitute an unsafe condition.
    To prevent such an event, this Airworthiness Directive (AD)
requires a periodic operational test to check the correct operation
of NRV and to apply the associated corrective actions.
    The corrective action includes replacing any failed NRV with a
new NRV.

Actions and Compliance

    (f) Unless already done, do the following actions.
    (1) For Airbus Model A330-201, -202, -203, -223, -243, -301, -
302, -303, -321, -322, -323, -341, -342, and -343 series airplanes:
At the later of the times in paragraphs (f)(1)(i) and (f)(1)(ii) of
this AD, perform an operational test for correct functioning of the
NRV and apply all applicable corrective actions, in accordance with
instructions defined in Airbus Mandatory Service Bulletin A330-28-
3108, including Appendix 1, dated October 13, 2008. Do all
applicable corrective actions before further flight.
    (i) Within 24 months or 8,000 flight hours after the effective
date of this AD, whichever occurs first.
    (ii) Before the accumulation of 10,000 total flight hours after
the first flight of the airplane.
    (2) For Airbus Model A340-211, -212, -213, -311, -312, and -313
series airplanes: At the later of the times in paragraphs (f)(2)(i)
and (f)(2)(ii) of this AD, perform an operational test for correct
functioning of the NRV and apply all applicable corrective actions,
in accordance with instructions defined in Airbus Mandatory Service
Bulletin A340-28-4123, including Appendix 1, dated October 13, 2008.
Do all applicable corrective actions before further flight.
    (i) Within 24 months or 9,000 flight hours after the effective
date of this AD, whichever occurs first.
    (ii) Before the accumulation of 25,000 total flight hours after
the first flight of the airplane.
    (3) Repeat the operational test specified in paragraph (f)(1) or
(f)(2) of this AD as applicable, at the applicable interval in
paragraph (f)(3)(i) or (f)(3)(ii) of this AD.
    (i) For Airbus Model A330-201, -202, -203, -223, -243, -301, -
302, -303, -321, -322, -323, -341, -342, and -343 series airplanes:
At intervals not to exceed 10,000 flight hours.
    (ii) For Airbus Model A340-211, -212, -213, -311, -312, and -313
series airplanes: At intervals not to exceed 25,000 flight hours.
    (4) Submit a report of the findings (both positive and negative)
of the inspection required by paragraph (f)(1) or (f)(2) of this AD
to Airbus, at the time specified in paragraph (f)(4)(i) or
(f)(4)(ii) of this AD, as applicable. The report must include the
information specified in Appendix 1 of Airbus Mandatory Service
Bulletin A330-28-3108 or A340-28-4123, both dated October 13, 2008,
as applicable. Send the report to Airbus Department SEEE6, Airbus
Customer Services Directorate, 1 Rond Point Maurice Bellonte, 31707
Blagnac Cedex France, Attn: SDC32 Technical Data and Documentation
Services; fax: +33 5 61 93 28 06; e-mail<EMAIL_ADDRESS>    (i) If the inspection was done after the effective date of this
AD: Submit the report within 30 days after the inspection.
    (ii) If the inspection was done on or prior to the effective
date of this AD: Submit the report within 30 days after the
effective date of this AD.

FAA AD Differences

    Note 1: This AD differs from the MCAI and/or service information
as follows: No differences.

Other FAA AD Provisions

    (g) The following provisions also apply to this AD:
    (1) Alternative Methods of Compliance (AMOCs): The Manager,
International Branch, ANM-116, FAA, has the authority to approve
AMOCs for this AD, if requested using the procedures found in 14 CFR
39.19. Send information to ATTN: Vladimir Ulyanov, Aerospace
Engineer, International Branch, ANM-116, Transport Airplane
Directorate, FAA, 1601 Lind Avenue, SW., Renton, Washington 98057-
3356; telephone<PHONE_NUMBER>; fax<PHONE_NUMBER>. Before using any
approved AMOC on any airplane to which the AMOC applies, notify your
appropriate principal maintenance inspector (PMI) or the principal
avionics inspector (PAI), as appropriate, or lacking a principal
inspector, your local Flight Standards District Office.
    (2) Airworthy Product: For any requirement in this AD to obtain
corrective actions from a manufacturer or other source, use these
actions if they are FAA-approved. Corrective actions are considered
FAA-approved if they are approved by the State of Design Authority
(or their delegated agent). You are required to assure the product
is airworthy before it is returned to service.
    (3) Reporting Requirements: For any reporting requirement in
this AD, under the provisions of the Paperwork Reduction Act, the
Office of Management and Budget (OMB) has approved the information
collection requirements and has assigned OMB Control Number 2120-
0056.

Related Information

    (h) Refer to MCAI European Aviation Safety Agency Airworthiness
Directive 2008-0209, dated November 27, 2008; Airbus Mandatory
Service Bulletins A330-28-3108 and A340-28-4123, both including
Appendix 1, both dated October 13, 2008; for related information.

Material Incorporated by Reference

    (i) You must use Airbus Mandatory Service Bulletin A330-28-3108,
including Appendix 1, dated October 13, 2008; or Airbus Mandatory
Service Bulletin A340-28-4123, including Appendix 1, dated October
13, 2008; as applicable; to do the actions required by this AD,
unless the AD specifies otherwise.
    (1) The Director of the Federal Register approved the
incorporation by reference of this service information under 5
U.S.C. 552(a) and 1 CFR part 51.
    (2) For service information identified in this AD, contact
Airbus SAS--Airworthiness Office--EAL, 1 Rond Point Maurice
Bellonte, 31707 Blagnac Cedex, France; fax +33 5 61 93 45 80, e-mail
<EMAIL_ADDRESS>Internet http://www.airbus.com.
    (3) You may review copies of the service information at the FAA,
Transport Airplane Directorate, 1601 Lind Avenue, SW., Renton,
Washington. For information on the availability of this material at
the FAA, call<PHONE_NUMBER> or<PHONE_NUMBER>.
    (4) You may also review copies of the service information that
is incorporated by reference at the National Archives and Records
Administration (NARA). For information on the availability of this
material at NARA, call<PHONE_NUMBER>, or go to: http://
www.archives.gov/federal_register/code_of_federal_regulations/
ibr_locations.html.

    Issued in Renton, Washington, on August 26, 2009.
Ali Bahrami,
Manager, Transport Airplane Directorate, Aircraft Certification
Service.
[FR Doc. E9-21409 Filed 9-8-09; 8:45 am]

BILLING CODE 4910-13-P


[Federal Register Volume 83, Number 245 (Friday, December 21, 2018)]
[Notices]
[Pages 65656-65657]
[FR Doc No: 2018-27727]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

Combined Notice of Filings #1

    Take notice that the Commission received the following electric
corporate filings:

    Docket Numbers: EC19-34-000.
    Applicants: Peony Solar LLC.
    Description: Application for Authorization Under Section 203 of the
Federal Power Act, et al. of Peony Solar LLC.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5176.
    Comments Due: 5 p.m. ET 1/3/19.

    Take notice that the Commission received the following exempt
wholesale generator filings:

    Docket Numbers: EG19-33-000.
    Applicants: Valentine Solar, LLC.
    Description: Notice of Self-Certification of Exempt Wholesale
Generator Status of Valentine Solar, LLC.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5102.
    Comments Due: 5 p.m. ET 1/3/19.

    Take notice that the Commission received the following electric
rate filings:

    Docket Numbers: ER10-1276-009; ER10-1287-008; ER10-1292-008; ER10-
1303-008; ER10-1319-010; ER10-1353-010; ER18-1183-001; ER18-1184-001.
    Applicants: Consumers Energy Company, CMS Energy Resource
Management Company, Grayling Generation Station Limited Partnership,
Genesee Power Station Limited Partnership, CMS Generation Michigan
Power, LLC, Dearborn Industrial Generation, L.L.C., Delta Solar Power
I, LLC, Delta Solar Power II, LLC.
    Description: Supplement to September 11, 2108 Notice of Non-
Material Change-In-Status of Consumer Energy Company, et al.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5136.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER10-2877-002.
    Applicants: Cobb Electric Membership Corporation.
    Description: Supplement to December 29, 2017 Triennial Market Power
Update for the Central Region of Cobb Electric Membership Corporation.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5180.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER12-348-006; ER15-1378-002.
    Applicants: Mercuria Energy America, Inc., Mercuria Commodities
Canada Corporation.
    Description: Supplement to December 20, 2017 Updated Triennial
Market Analysis for the Southeast Region of the Mercuria Sellers.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5179.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER12-543-004.
    Applicants: CleanChoice Energy, Inc.
    Description: Notice of change in status of CleanChoice Energy, Inc.
    Filed Date: 12/12/18.
    Accession Number: 20181212-5361.
    Comments Due: 5 p.m. ET 1/2/19.

    Docket Numbers: ER17-2415-002.
    Applicants: Pilesgrove Solar, LLC.
    Description: Report Filing: Refund Report of Pilesgrove to be
effective N/A.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5159.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER17-2515-003.
    Applicants: Chambers Cogeneration, Limited Partnership.
    Description: Report Filing: Refund Report to be effective N/A.
    Filed Date: 12/12/18.
    Accession Number: 20181212-5265.
    Comments Due: 5 p.m. ET 1/2/19.

    Docket Numbers: ER18-89-002.
    Applicants: Frenchtown I Solar, LLC.
    Description: Report Filing: Refund Report of Frenchtown I and II to
be effective N/A.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5142.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER18-90-002.
    Applicants: Frenchtown II Solar, LLC.
    Description: Report Filing: Refund Report of Frenchtown I and II to
be effective N/A.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5148.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER18-2401-001.
    Applicants: PJM Interconnection, L.L.C.
    Description: Compliance filing: Response to Deficiency Notice re:
Order No. 844 Compliance Filing to be effective 1/1/2019.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5107.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER19-130-001.
    Applicants: Midcontinent Independent System Operator, Inc., ALLETE,
Inc.
    Description: Tariff Amendment: 2018-12-13_SA 3182 MP-GRE T-L IA
Substitute (Straight River) to be effective 10/18/2018.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5114.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER19-302-001.
    Applicants: NTE Southeast Electric Company, LLC.
    Description: Supplement to December 12, 2018 NTE Southeast Electric
Company, LLC tariff filing.
    Filed Date: 12/12/18.
    Accession Number: 20181212-5353.
    Comments Due: 5 p.m. ET 1/2/19.

    Docket Numbers: ER19-537-001; ER14-608 002; ER16-1644 002; ER17-
1214 001.
    Applicants: MRP San Joaquin Energy, LLC, High Desert Power Project,
LLC,MRP Generation Holdings, LLC, Coso Geothermal Power Holdings, LLC.
    Description: Notice of Change in Status of MRP San Joaquin Energy,
LLC, et al.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5222.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER19-545-000.
    Applicants: Buena Vista Energy, LLC.
    Description: Sec.  205(d) Rate Filing: Request for Cat. 1 Seller
Status in the SW Region to be effective 12/13/2018.
    Filed Date: 12/12/18.
    Accession Number: 20181212-5249.
    Comments Due: 5 p.m. ET 1/2/19.

    Docket Numbers: ER19-546-000.
    Applicants: Kumeyaay Wind LLC.
    Description: Sec.  205(d) Rate Filing: Request for Cat. 1 Seller
Status in the SW Region to be effective 12/13/2018.
    Filed Date: 12/12/18..
    Accession Number: 20181212-5252

    Comments Due: 5 p.m. ET 1/2/19.

    Docket Numbers: ER19-547-000.
    Applicants: PJM Interconnection, L.L.C.
    Description: Sec.  205(d) Rate Filing: Amendment to ISA, SA No.
4311 and CSA, SA No. 4218; Queue No. AA1-065 to be effective 11/9/2015.
    Filed Date: 12/12/18.
    Accession Number: 20181212-5254.
    Comments Due: 5 p.m. ET 1/2/19.

    Docket Numbers: ER19-548-000.
    Applicants: PJM Interconnection, L.L.C.
    Description: Sec.  205(d) Rate Filing: Amended ISA, SA No. 5238;
Queue No. AD1-084 to be effective 11/12/2018.
    Filed Date: 12/12/18.
    Accession Number: 20181212-5314.
    Comments Due: 5 p.m. ET 1/2/19.

    Docket Numbers: ER19-549-000.
    Applicants: American Transmission Systems, Incorporated, PJM
Interconnection, L.L.C.
    Description: Sec.  205(d) Rate Filing: ATSI submits OIA SA No. 2852
& IA SA No. 5196 to be effective 12/14/2018.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5000.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER19-550-000.
    Applicants: Tucson Electric Power Company.
    Description: Compliance filing: Compliance Filing Related to Tax
Cuts and Jobs Act to be effective 3/21/2018.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5083.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER19-551-000.
    Applicants: Northern States Power Company, a Minnesota corporation.
    Description: Sec.  205(d) Rate Filing: NSP-CHAK-L-Bluff Ck-LV Bush
Repl Ltr Agmt NOC-556 to be effective 12/14/2018.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5092.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER19-552-000.
    Applicants: PJM Interconnection, L.L.C.
    Description: Sec.  205(d) Rate Filing: Original ISA, Service
Agreement No. 5241, Non-queue NQ157 to be effective 11/13/2018.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5124.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER19-553-000.
    Applicants: PJM Interconnection, L.L.C.
    Description: Sec.  205(d) Rate Filing: Original ISA, SA No. 5242
Non-Queue NQ158 to be effective 11/13/2018.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5138.
    Comments Due: 5 p.m. ET 1/3/19.

    Docket Numbers: ER19-554-000.
    Applicants: GenOn Energy Management, LLC, NRG California South LP.
    Description: Application to Recover Fuel Costs, et al. of GenOn
Energy Management, LLC, et al.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5184.

    Comments Due: 5 p.m. ET 1/3/19.
    Take notice that the Commission received the following qualifying
facility filings:

    Docket Numbers: QF19-575-000.
    Applicants: UE-00211NJ.
    Description: Form 556 of UE-00211NJ.
    Filed Date: 12/13/18.
    Accession Number: 20181213-5175.
    Comments Due: None-Applicable.

    The filings are accessible in the Commission's eLibrary system by
clicking on the links or querying the docket number.
    Any person desiring to intervene or protest in any of the above
proceedings must file in accordance with Rules 211 and 214 of the
Commission's Regulations (18 CFR 385.211 and 385.214) on or before 5:00
p.m. Eastern time on the specified comment date. Protests may be
considered, but intervention is necessary to become a party to the
proceeding.
    eFiling is encouraged. More detailed information relating to filing
requirements, interventions, protests, service, and qualifying
facilities filings can be found at: http://www.ferc.gov/docs-filing/efiling/filing-req.pdf. For other information, call<PHONE_NUMBER>
(toll free). For TTY, call<PHONE_NUMBER>.

    Dated: December 14, 2018.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2018-27727 Filed 12-20-18; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register Volume 87, Number 84 (Monday, May 2, 2022)]
[Notices]
[Pages 25644-25645]
[FR Doc No: 2022-09235]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-N-0354]

Acrotech Biopharma LLC; Withdrawal of Approval of New Drug
Application for MARQIBO (VinCRIStine Sulfate LIPOSOME Injection), 5
milligrams/5 milliliters

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is
withdrawing approval of new drug application (NDA) for MARQIBO
(vinCRIStine sulfate LIPOSOME injection), 5 milligrams (mg)/5
milliliters (mL), held by Acrotech Biopharma LLC (Acrotech), 29
Princeton Hightstown Rd., East Windsor, NJ 08520. Acrotech has
voluntarily requested that FDA withdraw approval of this application

and has waived its opportunity for a hearing.

DATES: Approval is withdrawn as of May 2, 2022.

FOR FURTHER INFORMATION CONTACT: Kimberly Lehrfeld, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6226, Silver Spring, MD 20993-0002, 301-
796-3137, [email protected].

SUPPLEMENTARY INFORMATION: On August 9, 2012, FDA approved NDA 202497
for MARQIBO (vinCRIStine sulfate LIPOSOME injection), 5 mg/5 mL, for
the treatment of adult patients with Philadelphia chromosome-negative
(Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse
or whose disease has progressed following two or more anti-leukemia
therapies, under the Agency's accelerated approval regulations, 21 CFR
part 314, subpart H. The accelerated approval of MARQIBO (vinCRIStine
sulfate LIPOSOME injection) for Ph-ALL included a required
postmarketing clinical trial intended to verify the clinical benefit of
MARQIBO (vinCRIStine sulfate LIPOSOME injection).
    On September 24, 2021, FDA published the Federal Register notice
``Oncologic Drugs Advisory Committee; Notice of Meeting; Establishment
of a Public Docket; Request for Comments,'' announcing that MARQIBO
(vinCRIStine sulfate LIPOSOME injection) would be discussed at an
Oncologic Drug Advisory Committee Meeting (ODAC) scheduled for December
2, 2021 (86 FR 53067). On October 27, 2021, FDA met with Acrotech to
discuss the planned ODAC meeting. At that meeting, the Agency
recommended the applicant voluntarily request withdrawal of approval
for MARQIBO (vinCRIStine sulfate LIPOSOME injection), 5 mg/5mL, due to
the lack of verification of clinical benefit. The postmarketing trial
required to verify clinical benefit had not been completed, and patient
recruitment to fulfill the PMR appeared to be significantly challenging
due to the treatment options that are currently available.
    On November 19, 2021, Acrotech submitted a letter asking FDA to
withdraw approval of NDA 202497 for MARQIBO (vinCRIStine sulfate
LIPOSOME injection), 5 mg/5mL, pursuant to Sec.  314.150(d) (21 CFR
314.150(d)) and waiving its opportunity for a hearing. On November 23,
2021, FDA acknowledged Acrotech's request for withdrawal of approval of
the NDA and waiver of its opportunity for hearing. FDA also cancelled
the ODAC meeting scheduled for December 2, 2021, since Acrotech's
withdrawal request made discussion at an advisory committee meeting
moot.
    For the reasons discussed above, and in accordance with the
applicant's request, approval of NDA 202497 for MARQIBO (vinCRIStine
sulfate LIPOSOME injection), 5 mg/5mL, and all amendments and
supplements thereto, is withdrawn under Sec.  314.150(d). Distribution
of MARQIBO (vinCRIStine sulfate LIPOSOME injection) 5 mg/5mL, into
interstate commerce without an approved application is illegal and
subject to regulatory action (see sections 505(a) and 301(d) of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(a) and 331(d)).

    Dated: April 26, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-09235 Filed 4-29-22; 8:45 am]
BILLING CODE 4164-01-P


[Federal Register Volume 88, Number 108 (Tuesday, June 6, 2023)]
[Notices]
[Pages 37063-37064]
[FR Doc No: 2023-11932]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. CD23-8-000]

Moulton Niguel Water District; Notice of Preliminary
Determination of a Qualifying Conduit Hydropower Facility and
Soliciting Comments and Motions To Intervene

    On May 23, 2023, Moulton Niguel Water District filed a notice of
intent to

construct a qualifying conduit hydropower facility, pursuant to section
30 of the Federal Power Act (FPA). The proposed Bridlewood Flow Control
Facility Hydroelectric Energy Recovery Project would have an installed
capacity of 224 kilowatts (kW), and would be located along the
applicant's existing water supply system in Laguna Hills, Orange
County, California.
    Applicant Contact: Gregg Semler, InPipe Energy, 920 SW 6th Ave.,
12th Floor, Portland, OR 97204,<PHONE_NUMBER>, [email protected].
    FERC Contact: Christopher Chaney,<PHONE_NUMBER>,
[email protected].
    Qualifying Conduit Hydropower Facility Description: The project
would consist of: (1) two 112-kW Centrifugal pump as turbine generating
units and (2) appurtenant facilities. The proposed project would have
an estimated annual generation of approximately 820 megawatt-hours.
    A qualifying conduit hydropower facility is one that is determined
or deemed to meet all the criteria shown in the table below.

      Table 1--Criteria for Qualifying Conduit Hydropower Facility
------------------------------------------------------------------------
      Statutory provision              Description       Satisfies (Y/N)
------------------------------------------------------------------------
FPA 30(a)(3)(A)................  The conduit the                      Y
                                  facility uses is a
                                  tunnel, canal,
                                  pipeline, aqueduct,
                                  flume, ditch, or
                                  similar manmade water
                                  conveyance that is
                                  operated for the
                                  distribution of water
                                  for agricultural,
                                  municipal, or
                                  industrial
                                  consumption and not
                                  primarily for the
                                  generation of
                                  electricity.
FPA 30(a)(3)(C)(i).............  The facility is                      Y
                                  constructed,
                                  operated, or
                                  maintained for the
                                  generation of
                                  electric power and
                                  uses for such
                                  generation only the
                                  hydroelectric
                                  potential of a non-
                                  federally owned
                                  conduit.
FPA 30(a)(3)(C)(ii)............  The facility has an                  Y
                                  installed capacity
                                  that does not exceed
                                  40 megawatts.
FPA 30(a)(3)(C)(iii)...........  On or before August 9,               Y
                                  2013, the facility is
                                  not licensed, or
                                  exempted from the
                                  licensing
                                  requirements of Part
                                  I of the FPA.
------------------------------------------------------------------------

    Preliminary Determination: The proposed Bridlewood Flow Control
Facility Hydroelectric Energy Recovery Project will not alter the
primary purpose of the conduit, which is for municipal water supply.
Therefore, based upon the above criteria, Commission staff
preliminarily determines that the operation of the project described
above satisfies the requirements for a qualifying conduit hydropower
facility, which is not required to be licensed or exempted from
licensing.
    Comments and Motions to Intervene: Deadline for filing comments
contesting whether the facility meets the qualifying criteria is 30
days from the issuance date of this notice. Deadline for filing motions
to intervene is 30 days from the issuance date of this notice.
    Anyone may submit comments or a motion to intervene in accordance
with the requirements of Rules of Practice and Procedure, 18 CFR
385.210 and 385.214. Any motions to intervene must be received on or
before the specified deadline date for the particular proceeding.
    Filing and Service of Responsive Documents: All filings must (1)
bear in all capital letters the ``COMMENTS CONTESTING QUALIFICATION FOR
A CONDUIT HYDROPOWER FACILITY'' or ``MOTION TO INTERVENE,'' as
applicable; (2) state in the heading the name of the applicant and the
project number of the application to which the filing responds; (3)
state the name, address, and telephone number of the person filing; and
(4) otherwise comply with the requirements of sections 385.2001 through
385.2005 of the Commission's regulations.\1\ All comments contesting
Commission staff's preliminary determination that the facility meets
the qualifying criteria must set forth their evidentiary basis.
---------------------------------------------------------------------------

    \1\ 18 CFR 385.2001-2005 (2022).
---------------------------------------------------------------------------

    The Commission strongly encourages electronic filing. Please file
motions to intervene and comments using the Commission's eFiling system
at http://www.ferc.gov/docs-filing/efiling.asp. Commenters can submit
brief comments up to 6,000 characters, without prior registration,
using the eComment system at http://www.ferc.gov/docs-filing/ecomment.asp. You must include your name and contact information at the
end of your comments. For assistance, please contact FERC Online
Support at [email protected],<PHONE_NUMBER> (toll free), or
(202) 502-8659 (TTY). In lieu of electronic filing, you may send a
paper copy. Submissions sent via the U.S. Postal Service must be
addressed to: Kimberly D. Bose, Secretary, Federal Energy Regulatory
Commission, 888 First Street NE, Room 1A, Washington, DC 20426.
Submissions sent via any other carrier must be addressed to: Kimberly
D. Bose, Secretary, Federal Energy Regulatory Commission, 12225 Wilkins
Avenue, Rockville, MD 20852. A copy of all other filings in reference
to this application must be accompanied by proof of service on all
persons listed in the service list prepared by the Commission in this
proceeding, in accordance with 18 CFR 385.2010.
    Locations of Notice of Intent: The Commission provides all
interested persons an opportunity to view and/or print the contents of
this document via the internet through the Commission's website at
http://www.ferc.gov/docs-filing/elibrary.asp. Enter the docket number
(i.e., CD23-8) in the docket number field to access the document. You
may also register online at http://www.ferc.gov/docs-filing/esubscription.asp to be notified via email of new filings and issuances
related to this or other pending projects. Copies of the notice of
intent can be obtained directly from the applicant. For assistance,
call toll-free 1-866-208-3676 or email [email protected]. For
TTY, call<PHONE_NUMBER>.

    Dated: May 30, 2023.
Kimberly D. Bose,
Secretary.
[FR Doc. 2023-11932 Filed 6-5-23; 8:45 am]
BILLING CODE 6717-01-P