FILE NAME: company. wpt ( 1/ 1/ 2005) ( xml) Template Number P25 COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE ( 1/ 1/ 2005)

EPA Registration Division contact: [ Tony Kish, Product Manager 22 ( 703) 308 9443.]

TEMPLATE:

[ BASF Corporation]

[ PP 0F6139 and PP 4F6850] EPA has received revised pesticide petitions [ PP 0F6139 and PP 4F6850]) from [ BASF Corporation], [ P. O. Box 13528, Research Triangle Park, NC, 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.

1. by establishing a tolerance for the combined residues of [ the fungicide pyraclostrobin, carbamic acid, [ 2[[[ 1( 4 chlorophenyl) 1H pyrazol 3 yl] oxy] methyl] phenyl] methoxy, methyl ester and its metabolite methyl N[[[ 1( 4 chlorophenyl) pyrazol 3 yl] oxy] o tolyl] carbamate ( BF 500 3); expressed as parent compound in or on the raw agricultural commodities [ pea and bean, dried shelled, except soybean, subgroup 6C of crop group 6] at [ 0.5 ppm], and [ strawberry] at [ 1.2 ppm], parts per million ( ppm). The petitioner has submitted a revised Section F for PP 0F6139 and for PP 4F6850 proposing an increase in the current 0.3 ppm tolerance for pea and bean, dried shelled, except soybean, subgroup 6C, and 0.4 ppm established strawberry tolerance, respectively. EPA established a tolerance in pea and bean, dried shelled, except soybean, subgroup 6C, at 0.3 ppm, in a Final Rule dated October 29, 2004, conditional on submission of additional field residue data from Region 11. Upon EPA evaluation of the submitted conditional data, the petitioner has requested EPA to establish the permanent tolerance at 0.5 ppm. Similarly, EPA established a temporary tolerance in strawberry at 1.5 ppm in a Final Rule dated October 29, 2004, conditional on submission of additional field residue data. This temporary tolerance expired December 31, 2005 and is currently at 0.4 ppm. Upon EPA evaluation of the submitted conditional data, the petitioner has requested EPA to establish the permanent tolerance at 1.2 ppm.

A. Residue Chemistry 1. Plant metabolism. Plant and animal metabolism. Nature of the residue studies ( OPPTS 860.1300) were conducted in grape, potato and wheat as representative crops in order to characterize the fate of pyraclostrobin in all crop matrices. Pyraclostrobin demonstrated a similar pathway and fate in all three crops. In all three crops the pyraclostrobin Residues of Concern ( ROC) of were characterized as parent ( pyraclostrobin) and BAS 500 3), methyl N[[[ 1 ( 4 chlorophenyl) pyrazol 3yl] oxy] o tolyl] carbamate. In hens the residues of concern were determined to be parent compound and a hydroxlated metabolite, BAS 500 16. In goats the residues of concern were determined to be parent and a hydroxylated metabolite BAS 500 10.]

2. Analytical method. [ In plants the method of analysis is aqueous organic solvent extraction, column clean up and quantitation by LC/ MS/ MS. In animals the method of analysis involves base hydrolysis, organic extraction, column clean up and quantitation by LC/ MS/ MS or derivatization ( methylation) followed by quantitation by GC/ MS.]

3. Magnitude of residues. [ Field trials were conducted in the United States in Region 11 required as a condition of registration to establish the magnitude of the residues in pea and bean, dried shelled, except soybean, subgroup 6C. Field trials were also conducted required as a condition of the temporary tolerance in strawberry during the 2005 growing season in California. All field trials were carried out using the maximum labeled rates, maximum number of applications, and the proposed pre harvest interval.]

B. Toxicological Profile 1. Acute toxicity. Pyraclostrobin and its formulated products have favorable acute toxicity. The acute toxicity studies place technical pyraclostrobin in toxicity category IV for acute oral and acute inhalation and category III for acute dermal. Pyraclostrobin is category III for both eye and skin irritation, and it is not a dermal sensitizer. Two formulated end use products are proposed, an Emulsifiable Concentrate ( EC) and an Extruded Granule ( EG). The EC has an acute oral toxicity category of II, acute dermal of III, acute inhalation of IV, eye and skin irritation categories of III, and is not a dermal sensitizer. The EG has acute oral and dermal toxicity categories of III, acute inhalation of IV, eye irritation of III, skin irritation of IV and is not a dermal sensitizer.

2. Genotoxicty. Pyraclostrobin was negative for inducing mutations in both an in vitro Ames test and an in vitro CHO/ HGPRT Locus Mammalian Cell Mutation Assay. Pyraclostrobin also demonstrated no chromosomal effects in an in vitro V79 Cells CHO Cytogenetic Assay and an in vivo Mouse Micronucleus test. An additional in vitro study investigating DNA damage and repair also showed no effects. Pyraclostrobin has been tested in a total of 5 genetic toxicology assays consisting of in vitro and in vivo studies. It can be stated that pyraclostrobin did not show any mutagenic, clastogenic or other genotoxic activity when tested under the conditions of the studies mentioned above. Therefore, pyraclostrobin does not pose a genotoxic hazard to humans.

3. Reproductive and developmental toxicity. The reproductive and developmental toxicity of pyraclostrobin was investigated in a 2 generation rat reproduction study as well as in rat and rabbit teratology studies. There were no adverse effects on reproduction, systemic toxicity to adults or developmental toxicity in the two generation study so the NOAEL is the highest dose tested of 300 ppm ( approximately 32.6 mg/ kg bw/ day).

No teratogenic effects were noted in either the rat or rabbit developmental studies. In the rat study, maternal toxicity observed at the mid and high dose consisted of decreased food consumption and body weight gain. Developmental changes noted at the high dose were increased incidences of dilated renal pelvis and cervical ribs with no cartilage. The maternal NOAEL was 10 mg/ kg bw and the developmental NOAEL was 25 mg/ kg bw.

In the rabbit teratology study, maternal toxicity observed at the mid and high doses consisted of decreased food consumption and body weight gain ( severe at the high dose). An increased postimplantation loss was also observed at the mid and high doses due to an increase in early resorptions. In rabbits, these types of effects are often observed with significant stress on the mothers ( as seen by the body weight gain decrease in this study) and not indicative of frank developmental toxicity. The NOAEL for both maternal and developmental toxicity was 5 mg/ kg bw.

4. Subchronic toxicity. The subchronic toxicity of pyraclostrobin was investigated in 90 day feeding studies with rats, mice and dogs, and in a 28 day dermal administration study in rats. A 90 day neurotoxicity study in rats was also performed. Generally, mild toxicity was observed. At high dose levels in feeding studies, general findings in all three species were decreased food consumption and body weight gain and a thickening of the duodenum. Anemia occurred at high dose levels in both rats and mice with accompanying extramedullary hematopoiesis of the spleen in rats. In rats only, a finding of liver cell hypertrophy was indicative of a physiological response to the handling of the chemical. The lowest NOAEL in the 90 day feeding studies was from the dog study and determined to be 5.8 mg/ kg bw/ day.

In the 28 day repeat dose dermal study, no systemic effects were noted up to the highest dose tested of 250 mg/ kg bw/ day.

In a 90 day rat neurotoxicity study, a direct neurotoxic effect was not observed.

5. Chronic toxicity. Pyraclostrobin was administered to groups of 5 male and 5 female purebred Beagle dogs in the diet at concentrations of 0, 100, 200 and 400 ppm over a period of 12 months. Signs of toxicity were observed at the high dose. Diarrhea was observed throughout the study period for both sexes. High dose males and females initially lost weight and body weight gain was decreased for the entire study period for females. Hematological changes observed were an increase in white blood cells in males, and an increase in platelets in both sexes at the high dose. Clinical chemistry demonstrated a decrease in serum total protein, albumin, globulins and cholesterol in high dose animals of both sexes possibly due to the diarrhea and reduced nutritional status of the animals. The NOAEL was 200 ppm ( ca. 5.5 mg/ kg bw/ day males; 5.4 mg/ kg bw/ day females). In an oncogenicity study, pyraclostrobin was administered to groups of 50 male and 50 female Wistar rats at dietary concentrations of 0; 25; 75, and 200 ppm for 24 months. In a companion chronic toxicity study, 20 rats/ sex were used at the same dose levels as in the oncogenicity study. A body weight gain depression of 10 11% in males and 14 22% in females with an accompanying decrease in food efficiency was observed at the high dose. There was no evidence that pyraclostrobin produced a carcinogenic effect in rats. The NOAEL for the chronic rat and the cancer rat study is 75 ppm ( ca. 3.4 mg/ kg bw/ day males; 4.7 mg/ kg bw/ day females).

Pyraclostrobin was administered to groups of 50 male and 50 female B6C3F1 mice at dietary concentrations of 0, 10, 30, 120 and 180 ppm ( females only) for 18 months. Body weights were reduced at the highest doses tested in both males and females. At the high dose, body weight gain decreases of 27% in females and 29% in males with an accompanying decrease in food efficiency were observed. No other signs of toxicity were noted at any dose level. The NOAEL was found to be 30 ppm ( ca. 4.1 mg/ kg bw/ day) for males. The Agency determined that the body weight effect at the high dose in females was not sufficient to determine an MTD. Therefore the NOAEL for females is considered greater than the highest dose tested of 32.8 mg/ kg bw/ day. There was no evidence that pyraclostrobin produced a carcinogenic effect in mice. .]

6. Animal metabolism. In a rat metabolism study with pyraclostrobin, 10 13% of the administered dose was excreted in the urine and 74 91% in the feces within 48 hours. Excretion via bile was significant accounting for 35 38% of the administered dose. By 120 hours after dosing, very little radioactivity remained in tissues. Pyraclostrobin was rapidly and almost completely metabolized. Very little unchanged parent was detected. The phase one biotransformation is characterized by N demethoxylation, various hydroxylations, cleavage of the ether bond and further oxidation of the two resulting molecule parts. Conjugation of the formed hydroxyl groups by glucuronic acid or sulfate also occurred. In summary, pyraclostrobin is extensively metabolized and rapidly eliminated primarily via the bile, with no evidence of accumulation in tissues.

7. Metabolite toxicology. A comparison of the rat metabolism results with the plant metabolism/ residue results indicates that toxicology studies performed with the parent pyraclostrobin are sufficient to cover dietary exposure. Plant residues are primarily the parent compound with a fraction ( up to 10 20% at most) being the demethoxylated parent. This metabolite is referred to as BF 500 3 in the plant studies and as 500M07 in the rat study. This metabolite in the rat is the first step in the major biotransformation process leading to the majority of the metabolites determined in the major excretion pathway.

8. Endocrine disruption. Endocrine effects. No specific tests have been conducted with pyraclostrobin to determine whether the chemical may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen or other endocrine effects. However, there were no significant findings in other relevant toxicity studies ( i. e., subchronic and chronic toxicity, teratology and multi generation reproductive studies) which would suggest that pyraclostrobin produces endocrine related effects. C. Aggregate Exposure 1. Dietary exposure. Exposure assessments were conducted to evaluate the potential risk due to acute and chronic dietary exposure of the U. S. population to residues of pyraclostrobin. This fungicide and its desmethoxy metabolite, in or on raw agricultural commodities, and metabolites in or on animal fat, liver, meat and meat byproducts were expressed as the parent compound. The tolerance values previously established for various cereals, vegetables, fruits, and animal products are listed in the U. S. EPA final rule published in the Federal Register October 29, 2004 ( Vol 69, No. 209, p 63083   63100) and U. S. 40 CFR § 180.582. This analysis included all current and proposed tolerance values for pea and bean, dried shelled, except soybean, subgroup 6C ( 0.5 ppm), and strawberry ( 1.2 ppm).

The pyraclostrobin chronic reference dose ( cRfD) is 0.034 mg/ kg bw/ day based on the NOAEL of 3.4 mg/ kg bw/ day in the rat chronic toxicity study and a 100X safety factor. The acute reference dose ( aRfD) is 3 mg/ kg b. w./ day for the general population based on a NOAEL from the acute neurotoxicity study of 300 mg/ kg bw/ day and a 100X safety factor. For females of child bearing years ( 13 49 years), the aRfD is 0.05 mg/ kg b. w./ day based on the NOAEL of 5 mg/ kg bw/ day from the rabbit teratology study and a 100X safety factor. The EPA determined that the FQPA safety factor should be 1X for all exposure scenarios. Therefore, the acute Population Adjusted Dose ( aPAD) and the chronic Population Adjusted Dose ( cPAD) are the same as the aRfD and cRfD, respectively.

i. Food Acute Dietary Exposure Assessment The acute dietary exposure estimates were based on tolerance values, default process factors, 100% crop treated values for all commodities except for leafy vegetables, pome fruit and stone fruit crop groups where the percent crop treated (% CT) values listed in the Federal Register October 29, 2004 ( Vol 69, No. 209, p 63083   63100) were utilized. The consumption data was from the USDA Continuing Survey of Food Intake by Individuals ( CSFII 1994  1996, 1998) and the EPA Food Commodity Ingredient Database ( FCID) using Exponent's Dietary Exposure Evaluation Module ( DEEM FCID) software.

The acute population adjusted dose ( aPAD) used for females 13 49 years of age was 0.05 mg/ kg bw/ day and 3.0 mg/ kg bw/ day for all other sub populations. Considering the exposure assumptions discussed above, pyraclostobin acute dietary exposure from food is less than 3.5 % aPAD for the U. S. population and all sub populations except females 13 49 years of age that occupies 49.8 % of the aPAD. The results of the acute dietary assessment are presented in Table 1.

Table 1. Results for Pyraclostrobin Acute Dietary Exposure Analysis Considering all Current Tolerances and the Tolerances Proposed in Pea and Bean, Dried Shelled, Except Soybean, Subgroup 6C, and Strawberry, using DEEM FCID at the 95th Percentile Population Exposure Estimate % aPAD Subgroups ( mg/ kg b. w./ day)*

U. S. Population 0.034714 1.16 All Infants (< 1 year old) 0.057006 1.90 Children ( 1 2 years old) 0.09389 3.13 Children ( 3 5 years old) 0.069549 2.32 Children ( 6 12 years old) 0.043189 1.44 Youth ( 13 19 years old) 0.028389 0.95 Females ( 13 49 years old) 0.024881 49.8 Adults ( 20 49 years old) 0.024374 0.81 Adults ( 50+ years old) 0.025418 0.85 aPAD = acute population adjusted dose * Exposure Estimate ( 95th percentile) was based on tolerance values, default processing factors, and considering 100% crop treated for all commodities except for leafy vegetables, pome and stone fruit which included the percent crop treated values listed in the Federal Register Vol 69, No. 209, October 29, 2004 ( 95% percentile)

The results of the analysis show that for all sub populations, the exposures are below the Agency's level of concern (< 100% aPAD). Additional refinements in the dietary risk assessment ( i. e. utilizing anticipated residue values, process factors, percent crop treated values for all crops) would further reduce the estimated exposure values.

Chronic Dietary Exposure Assessment The chronic dietary exposure estimates were based on tolerance values, default process factors, % crop treated values for all commodities listed in the Federal Register October 29, 2004 ( Vol 69, No. 209, p 63083   63100). The consumption data was from the USDA Continuing Survey of Food Intake by Individuals ( CSFII 1994  1996, 1998) and the EPA Food Commodity Ingredient Database ( FCID) using Exponent's Dietary Exposure Evaluation Module ( DEEMFCID software. The tolerance values included the proposed pea and bean, dried shelled, except soybean, subgroup 6C ( 0.5 ppm), and strawberry ( 1.2 ppm).

The chronic population adjusted dose ( cPAD) used for U. S. population and all sub populations is 0.034 mg/ kg bw/ day. Considering the exposure assumptions discussed above, pyraclostobin chronic dietary exposure from food for the U. S. population was 10.4% of the cPAD. The most highly exposure population sub group was children 1 2 years of age at 40.4% cPAD. The results of the chronic dietary assessment are presented in Table 2. Table 2. Results for Pyraclostrobin Chronic Dietary Exposure Analysis Considering all Current Tolerances and the Tolerances Proposed in Pea and Bean, Dried Shelled, Except Soybean, Subgroup 6C, and Strawberry, using DEEM FCID Population Exposure Estimate % cPAD Subgroups ( mg/ kg b. w./ day)

U. S. Population 0.003521 10.4 All Infants (< 1 year old) 0.010015 29.5 Children ( 1 2 years old) 0.013736 40.4 Children ( 3 5 years old) 0.009366 27.5 Children ( 6 12 years old) 0.005123 15.1 Youth ( 13 19 years old) 0.002591 7.6 Females ( 13 49 years old) 0.002443 7.2 Adults ( 20 49 years old) 0.002309 6.8 Adults ( 50+ years old) 0.002658 7.8 cPAD = chronic population adjusted dose * Exposure estimates based on tolerance values, default processing factor, and considering % crop treated listed in the Federal Register Vol 69, No. 209, October 29, 2004.

The results of the analysis show that for all sub populations, the exposures are below a level of concern (< 100% cPAD). Additional refinements in the chronic dietary risk assessment ( i. e. utilizing anticipated residue values, process factors) would further reduce the estimated exposure values.

ii. Drinking water. Based on the PRZM/ EXAMS and SCIGROW models, the peak EDWCs of pyraclostrobin for acute exposure are estimated to be 22.6 ug/ L ( ppb) in surface water and 0.02 ug/ L in shallow ground water. The peak EDWCs for chronic exposure are estimated to be 1.9 ug/ L in surface water and 0.02 ug/ L in shallow ground water. These concentrations are based on maximum applications to turf, which have the highest labeled application rate of any pyraclostrobin use.

Drinking water contributions were assessed based on the maximum estimated pyraclostrobin water concentrations ( acute  22.6 ug/ L, chronic 1.9 ug/ L), and water consumption and body weights reported in CSFII, using DEEM FCID software. The acute and chronic estimated water exposure values are summarized in Tables 3 and 4, respectively. Minimal exposure of pyraclostrobin occurs through drinking water with < 0.5% the aPAD and cPAD for all subpopulations with the exception of females 13 49 years of age with a 2.2% aPAD. Table 3. Results for Pyraclostrobin Acute Water Exposure Analysis Considering the Maximum Estimated Acute Drinking Water Concentration using DEEM FCID Population Water Exposure Estimate % aPAD Subgroups ( mg/ kg b. w./ day)

U. S. Population 0.001181 0.04 All Infants (< 1 year old) 0.004451 0.15 Children ( 1 2 years old) 0.001852 0.06 Children ( 3 5 years old) 0.001692 0.06 Children ( 6 12 years old) 0.001178 0.04 Youth ( 13 19 years old) 0.000958 0.03 Females ( 13 49 years old) 0.001100 2.20 Adults ( 20 49 years old) 0.001094 0.04 Adults ( 50+ years old) 0.000988 0.03 aPAD = acute population adjusted dose Based on estimated acute surface water value of 22.6 ug/ L Table 4. Results for Pyraclostrobin Chronic Water Exposure Analysis Considering the Maximum Estimated Chronic Drinking Water Concentration using DEEM FCID Population Water Exposure Estimate % cPAD Subgroups ( mg/ kg b. w./ day)

U. S. Population 0.00004 0.1 All Infants (< 1 year old) 0.000131 0.4 Children ( 1 2 years old) 0.000059 0.2 Children ( 3 5 years old) 0.000056 0.2 Children ( 6 12 years old) 0.000038 0.1 Youth ( 13 19 years old) 0.000029 0.1 Females ( 13 49 years old) 0.000037 0.1 Adults ( 20 49 years old) 0.000037 0.1 Adults ( 50+ years old) 0.000039 0.1 cPAD = chronic population adjusted dose Based on estimated chronic surface water value of 1.9 ug/ L Acute Aggregate Exposure and Risk ( Food and water) The aggregate acute risk includes residues of pyraclostrobin from food and water ( Table 5). Exposures from residential uses are not included in the acute aggregate assessment. The results demonstrate that there are no safety concerns for any subpopulation based on established and new uses, and that the results clearly meet the FQPA standard of reasonable certainty of no harm.

Table 5. Estimated Acute Aggregate Exposure and Risk of Pyraclostrobin Population Subgroup aPAD ( mg/ kg/ day) Food Exposure ( mg/ kg/ day) Water Exposure ( mg/ kg/ day) Total Exposure ( mg/ kg/ day) % aPAD U. S. Population 3 0.034714 0.001181 0.035895 1.20 All Infants (< 1 yr old) 3 0.057006 0.004451 0.061457 2.05 Children 1 2 years 3 0.09389 0.001852 0.095742 3.19 Children 3 5 years 3 0.069549 0.001692 0.071241 2.37 Children 6   12 years 3 0.043189 0.001178 0.044367 1.48 Youth 13 19 years 3 0.028389 0.000958 0.029347 0.98 Females 13 49 years 0.05 0.024881 0.001100 0.025981 51.96 Adults 20 49 years 3 0.024374 0.001094 0.025468 0.85 Adults + 50 3 0.025418 0.000988 0.026406 0.88 Short and Intermediate Term Aggregate Exposure and Risk ( food, water, and residential) Short term aggregate risk from pyraclostrobin takes into account exposures from dietary consumption ( food and water) and residential exposure from turf use. Post application exposure from the turf use is considered short term. The aggregate MOE from food, water, and residential exposure are 115 and 257 for the children 1 2 years old and the US population, respectively. These MOE are greater than the target MOE of 100 which indicates there is no safety concern. The results of the analysis are shown in Table 6.

Table 6. Estimated Short/ Intermediate Term Aggregate Exposure and Risk of Pyraclostrobin Population NOAEL ( mg/ kg/ day) Target MOE1 Food Exposure ( mg/ kg/ day) Water Exposure ( mg/ kg/ day) Residential Exposure2 ( mg/ kg/ day) Total Exposure ( mg/ kg/ day) MOE3 US 5.8 100 0.003521 0.00004 0.019 0.022561 257 Child 1 2 yr old 5.8 100 0.013736 0.000059 0.036425 0.05022 115 1 Target MOE is 100. 2 Residential Exposure = Exposure to adult while playing golf. 3 Aggregate MOE = ( NOAEL / ( Food + Water + Residential Exposure)

Chronic Aggregate Exposure and Risk ( food and water) The aggregate chronic risk includes residues of pyraclostrobin from food and water ( Table 7). Exposures from residential uses are not included in the chronic aggregate assessment. The results demonstrate there are no safety concerns for any subpopulation based on established and new uses, and that the results clearly meet the FQPA standard of reasonable certainty of no harm.

Table 7. Estimated Chronic Aggregate Exposure and Risk of Pyraclostrobin Population Subgroup cPAD ( mg/ kg/ day) Food Exposure ( mg/ kg/ day) Water Exposure ( mg/ kg/ day) Total Exposure ( mg/ kg/ day) % cPAD U. S. Population 0.034 0.003521 0.00004 0.003561 10.47 All Infants (< 1 yr old) 0.034 0.010015 0.000131 0.010146 29.84 Children 1 2 years 0.034 0.013736 0.000059 0.013795 40.57 Children 3 5 years 0.034 0.009366 0.000056 0.009422 27.71 Children 6   12 years 0.034 0.005123 0.000038 0.005161 15.18 Youth 13 19 years 0.034 0.002591 0.000029 0.00262 7.71 Females 13 49 years 0.034 0.002443 0.000037 0.00248 7.29 Adults 20 49 years 0.034 0.002309 0.000037 0.002346 6.90 Adults + 50 0.034 0.002658 0.000039 0.002697 7.93 Aggregate Cancer Risk for U. S. Population The aggregate MOE value ( considering food and drinking water) was calculated for pyraclostrobin and is shown in Table 8. The 36 year average of pyraclostrobin in surface water that was estimated by PRZM/ EXAMS for use in the chronic/ cancer risk assessment is 1.2 ug/ L. The results demonstrate there are no safety concerns for US population based on established and new uses, and that the results clearly meet the FQPA standard of reasonable certainty of no harm. Table 8. Aggregate Cancer Risk of Pyraclostrobin to the U. S. Population Population NOAEL ( mg/ kg/ day) Food Exposure ( mg/ kg/ day) Water Exposure ( mg/ kg/ day) Total Exposure ( mg/ kg/ day) Total MOE U. S. Population 32.80 0.003521 0.000025 0.003546 9250 2. Non dietary exposure. Pyraclostrobin is registered for use on residential and recreational turf. The applications to turf will be made only by professional pest control operators. Therefore, residential handler exposure was not evaluated. The exposure assessment cited in this notice of filing was transcribed from the most recent Federal Register Notice on pyraclostrobin ( U. S. EPA final rule published in the Federal Register October 29, 2004 [ Vol 69, No. 209, p 63083   63100). The EPA evaluated the following post application exposure scenarios 1) adults and toddler post application dermal exposure 2) toddlers' incidental ingestion of pesticide residues on lawns form hand to mouth transfer, 3) toddlers' object to mouth transfer from mouthing pesticide treated turfgrass, and 4) toddlers' incidental ingestion of soil from pesticide treated residential areas. The post application exposure assessment was based on generic assumptions specified in the Recommended Revisions to the Residential Standard Operating Procedures and recommended approaches by an EPA science advisory council. A dermal absorption value of 14% was used in the assessment of pyraclostrobin. The exposure and risk estimates for the residential exposure scenarios are assessed for the day of application because adults and toddlers could contact treated turf immediately after application. All short / intermediate term MOE were greater than 100 which indicates that exposure from all residential scenarios result in exposures below a level of concern.

D. Cumulative Effects Section 408( b)( 2)( D)( v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider    available information'' concerning the cumulative effects of a particular pesticide's residues and    other substances that have a common mechanism of toxicity.' Pyraclostrobin is a foliar fungicide which belongs to the new class of strobilurin chemistry. It is a synthetic analog of strobilurin A, a naturally occurring antifungal metabolite of the mushroom Strobillurus tenacellus ( Anke et. al., 1977). The active ingredient acts in the fungal cell through inhibition of electron transport in the mitochondrial respiratory chain at the position of the cytochrome bc1 complex. The protective effect is due to the resultant death of the fungal cells by disorganization of the fungal membrane system. Pyraclostrobin also acts curatively to prevent the increase and spread of fungal infections by inhibiting mycelial growth and sporulation on the leaf surface. BAS 500F inhibits spore germination, germ tube growth and penetration into the host tissues The EPA is currently developing methodology to perform cumulative risk assessments. At this time, there is no available data to determine whether BAS 500 F 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, pyraclostrobin does not appear to produce a toxic metabolite common to other substances.

E. Safety Determination 1. U. S. population. Based on this risk assessment, BASF concludes that there is a reasonable certainty that no harm will result to the general population from the aggregate exposure to pyraclostrobin residues. 2. Infants and children. Based on this risk assessment, BASF concludes that there is a reasonable certainty that no harm will result to infants or children from the aggregate exposure to pyraclostrobin residues.

F. International Tolerances No Codex or Mexican maximum residue levels ( MRLs) have been proposed or are established for residues of pyraclostrobin. Therefore, no tolerance discrepancies exist between countries for this chemical. Since the application for registration of pyraclostrobin was reviewed jointly with the Pest Management Regulatory Agency ( PMRA) of Canada, several Canadian MRLs for pyraclostrobin are proposed and are expected to be published soon. However, the joint review is expected to have eliminated the potential for discrepancies between U. S. tolerances and Canadian MRLs.


UNITED STATES OF AMERICA

DEPARTMENT OF TRANSPORTATION

OFFICE OF THE SECRETARY

WASHINGTON, DC

Issued by the Department of Transportation on April 21, 2006

NOTICE OF ACTION TAKEN -- DOCKET OST-2004-17490

________________________________________________________________________
_________________________________

This serves as notice to the public of the action described below, taken
by the Department official indicated (no additional confirming order
will be issued in this matter).

Application of UNITED AIR LINES, INC. (UNITED) filed 2/13/06, for:

XX	Renewal of exemption for two years under 49 U.S.C. 40109 to provide
the following service:

Scheduled foreign air transportation of persons, property, and mail
between Chicago, Illinois, and Cozumel, Mexico.  United states that it
will continue to provide seasonal nonstop service in this market.

Applicant rep:	Jeffrey Manley<PHONE_NUMBER>		DOT Analyst: Tretha
Chromey<PHONE_NUMBER>

D I S P O S I T I O N

XX	Granted (subject to conditions, see below)

The above action was effective when taken: April 21, 2006 through April
21, 2008, or until 90 days after final Department action on United’s
corresponding certificate application in Docket OST-99-5846, whichever
occurs earlier.

Action taken by:	Paul L. Gretch, Director

			Office of International Aviation

XX The authority granted is consistent with the aviation agreement
between the United States and Mexico.

Except to the extent exempted or waived, this authority is subject to
the terms, conditions, and limitations indicated:	XX Holder’s
certificates of public convenience and necessity

XX Standard exemption conditions (attached)

Conditions:  The U.S.-Mexico exemption authority granted is subject to
the dormancy notice requirements set forth in condition 7 of Appendix A
of Order 88-10-2.

On the basis of data officially noticeable under Rule 24(g) of the
Department's regulations, we found the applicant qualified to provide
the exemption services authorized.

Under authority assigned by the Department in its regulations, 14 CFR
Part 385, we found that (1) our action was consistent with Department
policy; (2) grant of the authority was consistent with the public
interest; and (3) grant of the authority would not constitute a major
regulatory action under the Energy Policy and Conservation Act of 1975.
To the extent not granted, we denied all requests in the referenced
Docket.  We may amend, modify, or revoke the authority granted in this
Notice at any time without hearing at our discretion.

Persons entitled to petition the Department for review of the action set
forth in this Notice under the Department’s regulations, 14 CFR
§385.30, may file their petitions within seven (7) days after the date
of issuance of this Notice.  This action was effective when taken, and
the filing of a petition for review will not alter such effectiveness.

An electronic version of this document is available on the World Wide
Web at:

  HYPERLINK "http://dms.dot.gov//reports/reports_aviation.asp"
http://dms.dot.gov//reports/reports_aviation.asp

U.S. Carrier Exemption Conditions

In the conduct of the operations authorized, the U.S. carrier
applicant(s) shall:

(1)  Hold at all times effective operating authority from the government
of each country served;

(2)  Comply with applicable requirements concerning oversales contained
in 14 CFR 250 (for scheduled operations, if authorized);

(3)  Comply with the requirements for reporting data contained in 14 CFR
241;

(4)  Comply with requirements for minimum insurance coverage, and for
certifying that coverage to the Department, contained in 14 CFR 205;

(5)  Except as specifically exempted or otherwise provided for in a
Department Order, comply with the requirements of 14 CFR 203, concerning
waiver of Warsaw Convention liability limits and defenses;

(6)  Comply with all applicable requirements of the Federal Aviation
Administration and with all applicable U.S. Government requirements
concerning security, including, but not limited to, 49 CFR Part 1544.
To assure compliance with all applicable U.S. Government requirements
concerning security, the holder shall, before commencing any new service
(including charter flights) to or from a foreign airport, contact its
International Principal Security Inspector (IPSI) to advise the IPSI of
its plans and to find out whether the Transportation Security
Administration has determined that security is adequate to allow such
airport(s) to be served; and

(7)  Comply with such other reasonable terms, conditions, and
limitations required by the public interest as may be prescribed by the
Department of Transportation, with all applicable orders and regulations
of other U.S. agencies and courts, and with all applicable laws of the
United States.

The authority granted shall be effective only during the period when the
holder is in compliance with the conditions imposed above.

05/2004

 In the present application, United references its pending application
to amend its certificate for Route 566 to include Chicago-Cozumel.  See
Docket OST-99-5846.  We will handle the certificate request separately.

 United states that due to Hurricane Wilma it did not operate service
during the Winter 2005-2006 season, but that it intends to resume its
seasonal service on or before December 16, 2006.  (See the
Department’s action dated February 21, 2006, in the present docket,
granting United’s motion for a dormancy waiver in this matter.)


COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE

EPA Registration Division contact: Hope Johnson;<PHONE_NUMBER>

>

<Bayer CropScience >

< 4F8291 >

<	EPA has received a pesticide petition (4F8291) from Bayer CropScience,
2 T.W. Alexander Drive, Research Triangle Park, NC 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 by establishing a
tolerance for residues of pyrimethanil
(4,6-dimethyl-N-phenyl-2-pyrimidinamine)  in or on the raw agricultural
commodities berries and small fruit: caneberry (crop subgroup 13-07A) at
15.0 parts per million (ppm) and berries and small fruit: bushberry
(crop subgroup 13-07B) at 8.0 parts per million (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 supports granting of the petition. Additional data
may be needed before EPA rules on the petition.

A. Residue Chemistry

	1. Plant metabolism. The metabolic profile of pyrimethanil has been
investigated following application to five different crops (apple,
carrots, grapes, lettuce and tomatoes) and is well understood.  In
plants, pyrimethanil is the only significant residue ranging from
essentially all of the Total Radioactive Residues (TRR) in carrots and
tomatoes to 44% in lettuce.  Limited metabolism of pyrimethanil occurs
with minor amounts (less than 10%) of the phenyl and pyrimidyl
hydroxylated metabolites (AE C614276, AE C614277, AE C614278, and AE
C621312) being released after acid hydrolysis.  Analysis of the foliage
from apples and carrots confirmed that the metabolism of pyrimethanil in
plants proceeded primarily via hydroxylation of the aromatic ring
structures as well as the methyl groups.

	2. Analytical method. The plant metabolism studies demonstrated that
analysis for the parent compound, pyrimethanil is sufficient to enable
the assessment of the relevant residues in crop commodities.
Pyrimethanil was extracted from crops by homogenization with acetone.
An aliquot of the extract was diluted with a mixture of acetonitrile and
water with subsequent residue determination by HPLC-MS/MS.  The method
allows the detection and measurement of residues in or on agricultural
commodities at or above the proposed tolerance level.

	3. Magnitude of residues. Magnitude of residue trials were conducted
for pyrimethanil on blackberry/raspberry as representative of the
caneberry (Crop Subgroup 13-07 A) and blueberry as a representative of
bushberry (Crop Subgroup 13-07B). Trials were conducted in the various
required regions across the United States in accordance with EPA
guidance for crop field trials under OPPTS 860.1500.

B. Toxicological Profile

	1. Acute toxicity.  Pyrimethanil shows low toxicity by the oral
(toxicity category III), inhalation (toxicity category III), and dermal
(toxicity category IV) routes. It is slightly irritating to the eyes and
non-irritating to the skin in rabbit studies. Pyrimethanil is not a
dermal sensitizer.  Acute neurotoxicity of pyrimethanil in the rat was
assessed, the NOAEL was 100 mg/kg due to reduced body temperature in
males, and transient behavioral effects observed at the high dose tested
(HDT).

	2. Genotoxicty. Pyrimethanil is not mutagenic or genotoxic in any assay
in either the presence or absence of metabolic activation.

	3. Reproductive and developmental toxicity. Pyrimethanil is not a
developmental or reproductive toxicant.  An oral developmental toxicity
study in the Sprague Dawley rat did not reveal any evidence of
teratogenic potential. The maternal and developmental NOAEL was 85
mg/kg/day.  An oral developmental toxicity study in New Zealand rabbits
did not reveal any evidence of teratogenic potential and the NOAEL was
45 mg/kg/day. The maternal and developmental LOAEL was 300 mg/kg/day due
to reduced body weights, reduced fecal production, and food consumption
in the dams and decreased mean body weight, body weight gain, food
consumption, and an increased incidence of fetuses with 13 thoracic
vertebrae and ribs. A two-generation reproduction study in the
Sprague-Dawley rats did not indicate any disruption of reproductive
function.  The NOAEL for maternal and developmental toxicity was 20.9
mg/kg/day due to reduced body weights at higher dose levels, and the
reproductive NOAEL was 266.7 mg/kg/day, the HDT.

	4. Subchronic toxicity. A 28–day dietary toxicity study was conducted
in CD- 1 mice established a NOAEL of 202 mg/kg/day.  A 90-day dietary
toxicity study in Sprague-Dawley rats showed a NOAEL of 54.5 and 66.7,
in males and females, respectively. A 90-day dietary toxicity study was
conducted in CD-1 mice and demonstrated a NOAEL of 139 and 203 mg/kg/day
in males and females, respectively, based on changes found in the
kidney, liver, thyroid, and urinary bladder at higher dose levels.  A
90-day oral toxicity study in dogs showed a NOAEL of 80 mg/kg/day due to
decreased body weight and food consumption and changes in clinical
chemistry endpoints at 800 mg/kg/day.  A subchronic neurotoxicity study
in Sprague-Dawley rats indicated no treatment-related findings in
behavioral assessments, neuropathology or brain morphometrics. The NOAEL
was 44.3 mg/kg/day in females based upon decreased mean body weight,
body weight gain and food consumption at 429.9 mg/kg/day. There were no
treatment related effects in males at any dose level up to 391.9
mg/kg/day.  A 28-day immunotoxicity study conducted in female
Sprague-Dawley rats revealed no evidence of immune suppression at dose
levels up to and including 652 mg/kg/day, the HDT.

	5. Chronic toxicity. A 12-month chronic toxicity study in the dog
demonstrated a NOAEL of 30 mg/kg/day due to a decrease in mean body
weight gain and mean consumption of food and water at higher dose
levels. Two oncogenicity studies were conducted using CD-1 mice
continually exposed to pyrimethanil by administration in the diet. These
lifetime feeding studies demonstrated no evidence of oncogenic potential
at dose levels up to, and including 984 mg/kg/day (males) and 1217
mg/kg/day (females), the HDT. A 2-year combined chronic
toxicity/oncogenicity study conducted in the Sprague-Dawley rat showed a
NOAEL of 17 mg/kg/day (males) and 22 mg/kg/day (females) due to
decreased body weight gain and food consumption, and effects on the
liver and thyroid at 221 mg/kg/day (males) and 291 mg/kg/day (females).
The results of mechanistic studies, demonstrate that the thyroid effects
are likely secondary due to induction of enzymes in the liver involved
in metabolism of thyroid hormones, a well characterized,
threshold-mediated mechanism.

	6. Animal metabolism. Metabolism and pharmacokinetic studies in the rat
show rapid absorption and elimination within 24-hours of pyrimethanil
administration. The major routes of elimination were the urine
(approximately 72% of the administered dose), and the feces (17-18% of
the administered dose). The main pathways of metabolism involved
oxidation to phenols in either or both aromatic rings. The minor pathway
of metabolism involved oxidation of the methyl group to the
corresponding alcohol.

	7. Metabolite toxicology. Not applicable. The primary residue of
concern in both crop and animal commodities is pyrimethanil.

	8. Endocrine disruption. There is no evidence to suggest that
pyrimethanil has any potential primary endocrine disruption.  Chronic,
life span, and multi-generational bioassays in mammals and acute and
subchronic studies on aquatic organisms and wildlife did not reveal any
potential endocrine effects. Changes in the thyroid are secondary to
induction of metabolic enzymes in the liver, and not due to a direct
effect on endocrine mediated functions.

C. Aggregate Exposure

	1. Dietary exposure. For dietary analysis, an acute reference dose
(aRfD) of 0.45 mg/kg/day was derived for females 13 – 49 yrs. from an
NOAEL of 45 mg/kg/day in the rabbit developmental study, based on an
increased incidence of fetuses with 13 thoracic vertebrae and ribs, and
an uncertainty factor of 100.  For the general population including
infants and children, the acute reference dose is 1 mg/kg/day from on an
NOAEL of 100 mg/kg/day in the acute rat neurotoxicity study, based on
transient behavioral effects, and an uncertainty factor of 100.  A
chronic reference dose (cRfD) of 0.17 mg/kg/day for all populations was
derived from the chronic toxicity study in the rat,  based on decreased
body weight gain and food consumption, increased liver weights and
histopathological changes, and an uncertainty factor of 100.  EPA has
evaluated the potential for increased susceptibility of infants and
children from exposure to pyrimethanil and has determined there was no
quantitative or qualitative evidence of increased susceptibility
following prenatal exposure (in rats and rabbits), or postnatal exposure
(in rats). There were no effects on fertility or reproduction in the
two-generation reproduction study in rats. The special FQPA safety
factor has been reduced to 1X based on toxicological considerations, the
nature of the assumptions used in the dietary exposure risk assessments,
the completeness of the residue chemistry and environmental fate
databases, and the lack of the potential for residential exposures.
Acute and chronic Population Adjusted Doses (aPAD and cPAD) are,
therefore, the same as the reference doses for the populations and
subpopulations of interest.

	i. Food. Dietary exposure to pyrimethanil was estimated from potential
residues on food using DEEM-FCID Ver. 3.16 software for dietary
analyses.  Consumption data used in this program were taken from NHANES
WWEIA 2003-2008.  The acute Tier 1 assessments used 100% crop treated
and tolerance level residue values.  The chronic Tier 2 assessment is
based on tolerances, average residue values for key crops and percent
crop treated values for key crops from the 2004 EPA assessment.  All
registered uses plus proposed uses on the caneberries and bushberries
crop subgroups were included in the assessment.  Acute exposure (95th
percentile) for food only utilizes 12.5% of the aPAD for Females 13-49
yrs. old and 9.6% and 34% of the aPAD for the US Population and Children
1-2 yrs. old respectively.  Chronic exposure utilizes 13.5% for the US
Population and 75% for Children 1-2 yrs. old, the most highly exposed
subpopulation.  These are conservative estimates and actual exposures
are likely to be much less.

	ii. Drinking Water. EPA drinking water values (2011) were used in the
assessment.  EDWCs were calculated for use on strawberries (the scenario
resulting in the highest drinking water exposure), and included
pyrimethanil and its major metabolite (2-amino-4,6-dimethylpyrimidine).
The surface water estimated drinking water concentrations (EDWCs) were
determined using PRZM/EXAMS (Pesticide Root Zone Model/Exposure Analysis
Modeling System).  Ground water EDWCs, calculated using SCI-GROW
(Screening Concentration in Ground Water), model were lower than the
surface water EDWCs.  For surface water, the maximum estimated peak
acute concentration of the combined residues is 86.5 (g/L. The maximum
estimated annual mean non-cancer chronic exposure concentration for the
combined residues (adjusted for regional percent cropped area) is 29.4
(g/L.  The addition of the acute estimated drinking water concentration
(EDWC) of 86.5 ppb resulted in 9.8% of the aPAD utilized for the US
Population, 13% of the aPAD utilized for females 13-49 yrs. old, and 38%
utilized for Children 1-2 yrs. old, the most highly exposed
subpopulation.  The addition of the chronic EDWC of 29.4 ppb utilized
13.8% of the cPAD for the US Population and 76% of the cPAD for Children
1-2 yrs. old, the most highly exposed subpopulation.  In conclusion, the
results of these conservative acute and chronic estimates (including
drinking water) are acceptable for all population subgroups examined.
Therefore, there is a reasonable certainty that no harm will result from
exposure to potential residues of pyrimethanil in food and drinking
water.

	2. Non-dietary exposure. Pyrimethanil is not registered for use on any
sites that would result in residential exposure.  Therefore, the
aggregate risk is the sum of the risk from food and water.

D. Cumulative Effects

	Section 408(b)(2)(D)(v) requires that, when considering whether to
establish, modify, or revoke a tolerance, the Agency consider
“available information” concerning the cumulative effects of a
particular pesticide’s residues and “other substances that have a
common mechanism of toxicity.”   EPA has not made a common mechanism
of toxicity finding as to pyrimethanil and any other substances and
pyrimethanil does not appear to produce a toxic metabolite produced by
other substances.

E. Safety Determination

	1. U.S. population. Risk assessments for pyrimethanil are based on a
complete and reliable toxicity data package and highly conservative
assumptions. Chronic aggregate dietary (food and water) exposure will
utilize about 14% of the cPAD for the US Population.  Acute aggregate
dietary exposure (food and water) for the U.S. population, utilizes 10%
of the aPAD.  Therefore, there is a reasonable certainty that no harm
will occur to the US Population from aggregate exposure (food and
drinking water) to residues of pyrimethanil.

	2. Infants and children. EPA has determined that the toxicology
database for pyrimethanil regarding potential pre- and post-natal
effects in children is complete and does not indicate any particular
developmental or reproductive concerns.  The special FQPA SF has been
reduced to 1X.  Using the conservative assumptions described in the
exposure section above, chronic dietary exposure to residues of
pyrimethanil in food and water for Children 1-2 yrs. old (the most
highly exposed sub group) is about 76% of the cPAD.  Acute aggregate
dietary exposure to residues of pyrimethanil in food and water for
Children 1-2 yrs. old (the most highly exposed sub group) is 38% of the
aPAD.  There are no non-dietary concerns for infants and children.
Therefore, there is a reasonable certainty that no harm will occur to
infants and children from aggregate exposure to residues of
pyrimethanil.

F. International Tolerances

	Codex tolerances are currently not available for pyrimethanil on
caneberries or bushberries. Tolerances have been established for
caneberries and bushberries in the EU at 10 ppm and 5 ppm, respectively.

 PAGE

 PAGE   6


[Federal Register Volume 84, Number 232 (Tuesday, December 3, 2019)]
[Proposed Rules]
[Pages 66082-66084]
[FR Doc No: 2019-25987]

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

DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2019-0766; Product Identifier 2019-NE-23-AD]
RIN 2120-AA64

Airworthiness Directives; General Electric Company Turbofan
Engines

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Notice of proposed rulemaking (NPRM).

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

SUMMARY: The FAA proposes to adopt a new airworthiness directive (AD)
for all General Electric Company (GE) CF34-8C1, CF34-8C5, CF34-8C5A1,
CF34-8C5B1, CF34-8C5A2, CF34-8C5A3, CF34-8E2, CF34-8E2A1, CF34-8E5,
CF34-8E5A1, CF34-8E5A2, CF34-8E6, and CF34-8E6A1 turbofan engine
models. This proposed AD was prompted by a predicted reduction in the
cyclic life of the combustion chamber assembly aft flange, which could
result in certain combustion chamber assemblies failing before reaching
their published life limit. This proposed AD would require revisions to
the Airworthiness Limitations Section (ALS) of the manufacturer's
Instructions for Continued Airworthiness (ICA) and to the air carrier's
approved Continued Airworthiness Maintenance Programs (CAMP) to
incorporate initial and repetitive fluorescent penetrant inspections
(FPIs) of the combustion chamber assembly. The FAA is proposing this AD
to address the unsafe condition on these products.

DATES: The FAA must receive comments on this proposed AD by January 17,
2020.

ADDRESSES: You may send comments, using the procedures found in 14 CFR
11.43 and 11.45, by any of the following methods:
     Federal eRulemaking Portal: Go to https://www.regulations.gov. Follow the instructions for submitting comments.
     Fax:<PHONE_NUMBER>.
     Mail: U.S. Department of Transportation, Docket
Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New
Jersey Avenue SE, Washington, DC 20590.
     Hand Delivery: Deliver to Mail address above between 9
a.m. and 5 p.m., Monday through Friday, except Federal holidays.
    For service information identified in this NPRM, contact General
Electric Company, GE Aviation, Room 285, 1 Neumann Way, Cincinnati, OH
45215; phone:<PHONE_NUMBER>; email<EMAIL_ADDRESS>You
may view this service information at the FAA, Engine and Propeller
Standards Branch, 1200 District Avenue, Burlington, MA. For information
on the availability of this material at the FAA, call<PHONE_NUMBER>.

Examining the AD Docket

    You may examine the AD docket on the internet at https://www.regulations.gov by searching for and locating Docket No. FAA-2019-
0766; or in person at Docket Operations between 9 a.m. and 5 p.m.,
Monday through Friday, except Federal holidays. The AD docket contains
this NPRM, the regulatory evaluation, any comments received, and other
information. The street address for Docket Operations is listed above.
Comments will be available in the AD docket shortly after receipt.

FOR FURTHER INFORMATION CONTACT: David Bethka, Aerospace Engineer, ECO
Branch, FAA, 1200 District Avenue, Burlington, MA 01803; phone: 781-
238-7129; fax:<PHONE_NUMBER>; email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Comments Invited

    The FAA invites you to send any written relevant data, views, or
arguments about this proposal. Send your comments to an address listed
under the ADDRESSES section. Include ``Docket No. FAA-2019-0766;
Product Identifier 2019-NE-23-AD'' at the beginning of your comments.
The FAA specifically invites comments on the overall regulatory,
economic, environmental, and energy aspects of this NPRM. The FAA will
consider all comments received by the closing date and may amend this
NPRM because of those comments.
    The FAA will post all comments received, without change, to https://www.regulations.gov, including any personal information you provide.
The FAA will also post a report summarizing each substantive verbal
contact it receives about this NPRM.

Discussion

    The FAA was notified by the manufacturer that they found a
reduction in the cyclic life of the combustion chamber assembly when
updating their life analysis. As a result, the manufacturer added a
scheduled maintenance check. This condition, if not addressed, could
result in combustion chamber assemblies failing before reaching their
published life limit.

Related Service Information Under 1 CFR Part 51

    The FAA reviewed GE CF34-8E Engine Manual Temporary Revision (TR)
05-0085, dated February 21, 2019; GE CF34-8C TR 05-0141, dated February
21, 2019; and GE CF34-8C TR 05-143, dated February 13, 2019. These TRs,
differentiated by GE CF34-8 turbofan engine model, identify the
combustion chamber assembly part number, life limit cycles, and new
inspections.
    The FAA also reviewed GE CF34-8E TR 05-0086, dated February 13,
2019, and GE CF34-8C TR 05-0142, dated February 13, 2019. These TRs,
differentiated by GE CF34-8 turbofan engine model, describe new
inspection threshold limits and re-inspection interval limits for the
combustion chamber assembly.
    This service information is reasonably available because the
interested parties have access to it through their normal course of
business or by the means identified in the ADDRESSES section.

FAA's Determination

    The FAA is proposing this AD because it evaluated all the relevant
information and determined the unsafe condition described previously is
likely to exist or develop in other products of the same type design.

Proposed AD Requirements

    This proposed AD would require revisions to the ALS of the
manufacturer's ICA and the air carrier's approved CAMP to incorporate
initial

and repetitive FPIs of the combustion chamber assembly.

Costs of Compliance

    The FAA estimates that this proposed AD affects 1,216 GE CF34-8C
turbofan engine models and 638 GE CF34-8E turbofan engine models
installed on airplanes of U.S. registry.
    The FAA estimates the following costs to comply with this proposed
AD:

                                                 Estimated Costs
----------------------------------------------------------------------------------------------------------------
                                                                                Cost per      Cost on U.S.
                Action                         Labor cost           Parts cost        product        operators
----------------------------------------------------------------------------------------------------------------
Revise the ALS and CAMP (GE CF34-8C     1 work-hour x $85 per                 $0             $85        $157,590
 and CF34-8E).                           hour = $85.
FPI combustion chamber assembly (GE     6 work-hours x $85 per                 0             510         620,160
 CF34-8C).                               hour = $510.
FPI combustion chamber assembly (GE     5 work-hours x $85 per                 0             425         271,150
 CF34-8E).                               hour = $425.
----------------------------------------------------------------------------------------------------------------

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.
    The FAA is 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.
    This AD is issued in accordance with authority delegated by the
Executive Director, Aircraft Certification Service, as authorized by
FAA Order 8000.51C. In accordance with that order, issuance of ADs is
normally a function of the Compliance and Airworthiness Division, but
during this transition period, the Executive Director has delegated the
authority to issue ADs applicable to engines, propellers, and
associated appliances to the Manager, Engine and Propeller Standards
Branch, Policy and Innovation Division.

Regulatory Findings

    The FAA determined that this proposed AD would not have federalism
implications under Executive Order 13132. This proposed AD would 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 proposed
regulation:
    (1) Is not a ``significant regulatory action'' under Executive
Order 12866,
    (2) Will not affect intrastate aviation in Alaska, 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.

List of Subjects in 14 CFR Part 39

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

The Proposed Amendment

    Accordingly, under the authority delegated to me by the
Administrator, the FAA proposes to amend 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 airworthiness
directive (AD):

General Electric Company: Docket No. FAA-2019-0766; Product
Identifier 2019-NE-23-AD.

(a) Comments Due Date

    The FAA must receive comments by January 17, 2020.

(b) Affected ADs

    None.

(c) Applicability

    This AD applies to all General Electric Company (GE) CF34-8C1,
CF34-8C5, CF34-8C5A1, CF34-8C5B1, CF34-8C5A2, CF34-8C5A3, CF34-8E2,
CF34-8E2A1, CF34-8E5, CF34-8E5A1, CF34-8E5A2, CF34-8E6, and CF34-
8E6A1 turbofan engine models, including engine models marked on
engine data plate as CF34-8C5/B, CF34-8C5/M, CF34-8C5A1/B, CF34-
8C5A1/M, CF34-8C5B1/B, CF34-8C5A2/B, and CF34-8C5A2/M.

(d) Subject

    Joint Aircraft System Component (JASC) Code 7240, Turbine Engine
Combustion Section.

(e) Unsafe Condition

    This AD was prompted by a predicted reduction in the cyclic life
of the combustion chamber assembly aft flange. The FAA is issuing
this AD to prevent failure of the combustion chamber assembly. The
unsafe condition, if not addressed, could result in combustion
chamber assemblies failing before reaching their published life
limit, uncontained release of the combustion chamber assembly,
damage to the engine, and damage to the airplane.

(f) Compliance

    Comply with this AD within the compliance times specified,
unless already done.

(g) Required Actions

    (1) Within 90 days after the effective date of this AD, revise
the Airworthiness Limitations Section of the GE Instructions for
Continued Airworthiness. For air carrier operations, within 90 days
after the effective date of this AD, also revise the approved
continuous airworthiness maintenance program. These revisions must
incorporate the following requirements for fluorescent penetrant
inspections (FPI) of the combustion chamber assembly aft flange.
    (i) For a combustion chamber assembly with part number (P/N)
4145T11G08, P/N 4145T11G09, P/N 4180T27G01, or P/N 4180T27G03
installed on GE CF34-8E turbofan engine models, revise CF34-8E
Engine Manual GEK112031 by:
    (A) Replacing Table 801, Static Structures--Life Limits (``Table
801''), with the revised Table 801 in Task 05-11-05-200-801 of GE
CF34-8E Engine Manual Temporary Revision (TR) 05-0085, dated
February 21, 2019, and
    (B) Adding Task 05-21-03-200-801 of GE CF34-8E TR 05-0086, dated
February 13, 2019 (``GE CF34-8E TR 05-0086'').
    (ii) For a combustion chamber assembly with P/N 4126T87G04, P/N
4126T87G05, P/N 4126T87G07, P/N 4126T87G08, P/N

4180T27G04, P/N 4923T82G01, or P/N 4923T82G02 installed on GE CF34-
8C1 turbofan engine models, or with P/N 4145T11G08, P/N 4145T11G10,
P/N 4180T27G02, P/N 4180T27G04, or P/N 4923T82G02 installed on GE
CF34-8C5, CF34-8C5/M, CF34-8C5A1, CF34-8C5A1/M, CF34-8C5A2, CF34-
8C5A2/M, CF34-8C5A3, or CF34-8C5B1 turbofan engine models, revise
CF34-8C Engine Manual GEK105091 by:
    (A) Replacing Table 801, (For -8C1) and Table 802 (For -8C5)
Static Structures--Life Limits (``Table 801'' and ``Table 802''),
with the revised Tables 801 and 802 in Task 05-11-05-200-801 of GE
CF34-8C Engine Manual TR 05-0141, dated February 21, 2019, and
    (B) Adding Task 05-21-03-200-801 of GE CF34-8C TR 05-0142, dated
February 13, 2019 (``GE CF34-8C TR 05-0142'').
    (iii) For a combustion chamber assembly with P/N 4145T11G08, P/N
4145T11G10, P/N 4180T27G02, P/N 4180T27G04, or P/N 4923T82G02
installed on GE CF34-8C5B1/B CF34-8C5/B, CF34-8C5A1/B, or CF34-
8C5A2/B turbofan engine models (Business Jet), revise CF34-8C Engine
Manual GEK105091 by:
    (A) Replacing Table 801 (For/B -8C5 Models) Static Structures--
Life Limits with the revised Table 801 in Task 05-11-25-200-801 of
GE CF34-8C TR 05-143, dated February 13, 2019, and
    (B) Adding Task 05-21-03-200-801 of GE CF34-8C TR 05-0142.
    (2) For any combustion chamber assembly that has exceeded the
initial inspection threshold (in cycles) specified in GE CF34-8E TR
05-0086 or GE CF34-8C TR 05-0142:
    (i) Perform the initial FPI of the combustion chamber assembly
aft flange within 2,200 cycles after the effective date of this AD
in accordance with GE CF34-8E TR 05-0086 or GE CF34-8C TR 05-0142.
Thereafter, perform repetitive FPIs in accordance with the intervals
in GE CF34-8E TR 05-0086 or GE CF34-8C TR 05-0142.
    (ii) If, during the FPI required by paragraph (g)(2)(i) of this
AD, a crack is found in the combustion chamber assembly aft flange,
disposition the assembly in accordance with paragraph 2.A. of GE
CF34-8E TR 05-0086, or paragraph 2.A. of GE CF34-8C TR 05-0142.

(h) Alternative Methods of Compliance (AMOCs)

    (1) The Manager, ECO Branch, FAA, has the authority to approve
AMOCs for this AD, if requested using the procedures found in 14 CFR
39.19. In accordance with 14 CFR 39.19, send your request to your
principal inspector or local Flight Standards District Office, as
appropriate. If sending information directly to the manager of the
certification office, send it to the attention of the person
identified in paragraph (i)(1) of this AD. You may email your
request to<EMAIL_ADDRESS>    (2) Before using any approved AMOC, notify your appropriate
principal inspector, or lacking a principal inspector, the manager
of the local flight standards district office/certificate holding
district office.

(i) Related Information

    (1) For more information about this AD, contact David Bethka,
Aerospace Engineer, ECO Branch, FAA, 1200 District Avenue,
Burlington, MA 01803; phone:<PHONE_NUMBER>; fax:<PHONE_NUMBER>; email:
<EMAIL_ADDRESS>    (2) For service information identified in this AD, contact
General Electric Company, GE Aviation, Room 285, 1 Neumann Way,
Cincinnati, OH 45215; phone:<PHONE_NUMBER>; email:
<EMAIL_ADDRESS>You may view this referenced service
information at the FAA, Engine and Propeller Standards Branch, 1200
District Avenue, Burlington, MA. For information on the availability
of this material at the FAA, call<PHONE_NUMBER>.

    Issued in Burlington, Massachusetts, on November 25, 2019.
Robert J. Ganley,
Manager, Engine and Propeller Standards Branch, Aircraft Certification
Service.
[FR Doc. 2019-25987 Filed 12-2-19; 8:45 am]
 BILLING CODE 4910-13-P


From:
"Cornelius, Jay"<EMAIL_ADDRESS>Sent:
Tue, 06 Dec 2022 13:11:18
To:
"Jones; DonnaLee"<EMAIL_ADDRESS><EMAIL_ADDRESS><EMAIL_ADDRESS>"McGinn; Kevin"<EMAIL_ADDRESS>"Shappley; Ned"<EMAIL_ADDRESS><EMAIL_ADDRESS><EMAIL_ADDRESS>Cc:
Dolby, Abigail<EMAIL_ADDRESS>Subject:
RE: ABC Coke - Coke Oven RTR, ICR Enclosure 2 (Part) - Cooling Tower Testing Plan (REVISED)
Dr. Jones,

Earlier this week, our cooling tower testing contractor requested additional information for their report, which we provided.  I expect their final report to be available shortly, but have reached out to them for an update.

As for the flare testing, ABC proposed that we submit Method 21 data from past actual emergency flare events (2019 to present) in lieu of testing our emergency flares during non-emergency conditions.  This data is attached.

Regards,

Jay Cornelius
Manager  -  Environmental Control
Office:<PHONE_NUMBER>
<EMAIL_ADDRESS>
<<Method 21.pdf>>

From: Jones, DonnaLee<EMAIL_ADDRESS>Sent: Tuesday, December 6, 2022 11:44 AM
To: Cornelius, Jay<EMAIL_ADDRESS><EMAIL_ADDRESS>McGinn, Kevin<EMAIL_ADDRESS>Shappley, Ned<EMAIL_ADDRESS><EMAIL_ADDRESS>Cc: Dolby, Abigail<EMAIL_ADDRESS>Subject: RE: ABC Coke - Coke Oven RTR, ICR Enclosure 2 (Part) - Cooling Tower Testing Plan (REVISED)

Hi Jay - We were wondering if you had your cooling tower test report ready? Also any flare testing.

Thanks in advance for your attention to this.

Regards,
Donna Lee Jones, Ph.D.
Senior Technical Advisor, Metals Sector
U. S. Environmental Protection Agency
Office of Air Quality Planning and Standards
Sector Policies and Programs Division / Metals & Inorganic Chemicals Group (D243-02)
Research Triangle Park, NC  27711
Tele:<PHONE_NUMBER>
--------------------------------------------------------------------------------
Fax<PHONE_NUMBER>
"Reasonableness never fails to be appreciated."  - anon.

Pronouns - She/Her/Hers
Salutation - Dr./Ms.

-----Original Message-----
From: Cornelius, Jay<EMAIL_ADDRESS>Sent: Tuesday, September 27, 2022 1:27 PM
To: Jones, DonnaLee<EMAIL_ADDRESS><EMAIL_ADDRESS>Mcginn, Kevin<EMAIL_ADDRESS>Shappley, Ned<EMAIL_ADDRESS><EMAIL_ADDRESS>Subject: ABC Coke - Coke Oven RTR, ICR Enclosure 2 (Part) - Cooling Tower Testing Plan (REVISED)

Good afternoon,

Please find revised Cooling Tower Testing Plan attached.

Jay Cornelius
ABC Coke

 -----Original Message-----

Sorry. A correction. See below from Kevin.

"..there should be 7 runs for THC, so if they amended table 2-1, it should be to indicate THC on all testing runs, i.e. THC and VOHAP for the second line of testing and THC, H2S, COS, and CS2 for the 3rd. The first line would still be 1 for THC, and the subsequent lines would still be 3. They are doing 7 total runs, we just want to be sure that THC is included as a parameter in all 7 runs."

Regards,
Donna Lee Jones, Ph.D.
Senior Technical Advisor, Metals Sector
U. S. Environmental Protection Agency
Office of Air Quality Planning and Standards
Sector Policies and Programs Division / Metals & Inorganic Chemicals Group (D243-02)
Research Triangle Park, NC  27711
Tele:<PHONE_NUMBER>
--------------------------------------------------------------------------------
Fax<PHONE_NUMBER>
"Reasonableness never fails to be appreciated."  - anon.

Pronouns - She/Her/Hers
Salutation - Dr./Ms.

-----Original Message-----
From: Jones, DonnaLee<EMAIL_ADDRESS>Sent: Friday, September 23, 2022 2:43 PM
To: Cornelius, Jay<EMAIL_ADDRESS><EMAIL_ADDRESS><EMAIL_ADDRESS>Shappley, Ned<EMAIL_ADDRESS>Mcginn, Kevin<EMAIL_ADDRESS>Subject: RE: ABC Coke - Coke Oven RTR, ICR Enclosure 2 (Part) - Cooling Tower Testing Plan

Hi. We need some clarification and correction for your test plan. The 114 requires, in Table 1B "Perform at least seven (7) test runs of standard Appendix P, AND three (3) test runs of Appendix P with the TO-15A finish" (emphasis added with the "AND"). Then under TRS, the 114 requires facilities to "perform at least three (3) test runs on the cooling tower inlets." In Table 2-1 of the ABC plan, the schedule indicates THC testing only during Run 1 (i.e., # runs are equal to "1"). We want to confirm whether during subsequent runs (i.e., not just Run 1) the ABC plan also includes "performing the THC analysis that is standard with Appendix P to acquire the 7 test runs for THC required by the ICR" during ALL THREE runs? The bulleted list in the ABC plan's Section 2.1 seems to imply this, but to be sure that there is no confusion, we would like a clarification and correction.

Please submit a revised plan with this correction. In Table 2-1, in the row for THC, the number of runs should equal "3".

Regards,
Donna Lee Jones, Ph.D.
Senior Technical Advisor, Metals Sector
U. S. Environmental Protection Agency
Office of Air Quality Planning and Standards
Sector Policies and Programs Division / Metals & Inorganic Chemicals Group (D243-02)
Research Triangle Park, NC  27711
Tele:<PHONE_NUMBER>
--------------------------------------------------------------------------------
Fax<PHONE_NUMBER>
"Reasonableness never fails to be appreciated."  - anon.

Pronouns - She/Her/Hers
Salutation - Dr./Ms.


[Federal Register Volume 84, Number 107 (Tuesday, June 4, 2019)]
[Notices]
[Pages 25800-25801]
[FR Doc No: 2019-11591]

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

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. EL19-77-000]

Oklahoma Gas and Electric Company v. Southwest Power Pool, Inc.;
Notice of Complaint

    Take notice that on May 24, 2019, pursuant to sections 206, 306 and
309 of the Federal Power Act, 16 U.S.C. 824e, 825e and 825h and Rule
206 of the Rules of Practice and Procedure of the Federal Energy
Regulatory Commission (Commission), 18 CFR 385.206 (2019), Oklahoma Gas
and Electric Company (OG&E or Complainant) filed a formal complaint
against Southwest Power Pool, Inc. (SPP or Respondent) requesting that
the Commission rules, that if SPP requires OG&E to refund revenue
credits for use of transmission facilities that OG&E sponsored during a
historical period of approximately five and one half years from April,
2010 to September, 2015, it would violate its contractual commitments
and tariff obligations to OG&E, and orders that SPP not seek refunds or
unwind those payments, all as more fully explained in the complaint.
    OG&E certifies that copies of the complaint were served on the
contacts for SPP, as listed on the Commission's list of Corporate
Officials.
    Any person desiring to intervene or to protest this filing must
file in accordance with Rules 211 and 214 of the Commission's Rules of
Practice and Procedure (18 CFR 385.211 and 385.214). Protests will be
considered by the Commission in determining the

appropriate action to be taken, but will not serve to make protestants
parties to the proceeding. Any person wishing to become a party must
file a notice of intervention or motion to intervene, as appropriate.
The Respondent's answer and all interventions, or protests must be
filed on or before the comment date. The Respondent's answer, motions
to intervene, and protests must be served on the Complainants.
    The Commission encourages electronic submission of protests and
interventions in lieu of paper using the ``eFiling'' link at http://www.ferc.gov. Persons unable to file electronically should submit an
original and 5 copies of the protest or intervention to the Federal
Energy Regulatory Commission, 888 First Street NE, Washington, DC
20426.
    This filing is accessible on-line at http://www.ferc.gov, using the
``eLibrary'' link and is available for electronic review in the
Commission's Public Reference Room in Washington, DC. There is an
``eSubscription'' link on the website that enables subscribers to
receive email notification when a document is added to a subscribed
docket(s). For assistance with any FERC Online service, please email
<EMAIL_ADDRESS>or call<PHONE_NUMBER> (toll free). For
TTY, call<PHONE_NUMBER>.
    Comment Date: 5 p.m. Eastern Time on June 13, 2019.

    Dated: May 28, 2019.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2019-11591 Filed 6-3-19; 8:45 am]
 BILLING CODE 6717-01-P


[Federal Register Volume 88, Number 154 (Friday, August 11, 2023)]
[Notices]
[Pages 54624-54625]
[FR Doc No: 2023-17267]

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-2629]

Postmarketing Approaches To Obtain Data on Under-Represented
Populations in Clinical Trials; Draft Guidance for Industry;
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a draft guidance for industry entitled
``Postmarketing Approaches to Obtain Data on Under-Represented
Populations in Clinical Trials.'' The purpose of this draft guidance is
to describe FDA requirements and provide recommendations for obtaining
safety and effectiveness information on drug and biological products,
when appropriate, in the postmarketing setting in historically under-
represented patient populations in clinical trials.

DATES: Submit either electronic or written comments on the draft
guidance by October 10, 2023 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final
version of the guidance.

ADDRESSES: You may submit comments on any guidance at any time as
follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2022-D-2629 for ``Postmarketing Approaches to Obtain Data on Under-
Represented Populations in Clinical Trials.'' Received comments will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through
Friday,<PHONE_NUMBER>.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information

redacted/blacked out, will be available for public viewing and posted
on https://www.regulations.gov. Submit both copies to the Dockets
Management Staff. If you do not wish your name and contact information
to be made publicly available, you can provide this information on the
cover sheet and not in the body of your comments and you must identify
this information as ``confidential.'' Any information marked as
``confidential'' will not be disclosed except in accordance with 21 CFR
10.20 and other applicable disclosure law. For more information about
FDA's posting of comments to public dockets, see 80 FR 56469, September
18, 2015, or access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852,<PHONE_NUMBER>.
    You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
    Submit written requests for single copies of the draft guidance to
the Division of Drug Information, Center for Drug Evaluation and
Research, Food and Drug Administration, 10001 New Hampshire Ave.,
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002; or Office
of Communication, Outreach and Development, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or
Office of the Center Director, Guidance and Policy Development, Center
for Devices and Radiological Health, 10903 New Hampshire Ave., Bldg.
66, Rm. 5431, Silver Spring, MD 20993-0002. Send one self-addressed
adhesive label to assist that office in processing your requests. See
the SUPPLEMENTARY INFORMATION section for electronic access to the
draft guidance document.

FOR FURTHER INFORMATION CONTACT: Nicole Gormley, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave, Bldg. 22, Silver Spring, MD 20993-0002,<PHONE_NUMBER>; or
Anne Taylor, Center for Biologics Evaluation and Research, Food and
Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301,
Silver Spring, MD 20993-0002,<PHONE_NUMBER>, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry
entitled ``Postmarketing Approaches to Obtain Data on Under-Represented
Populations in Clinical Trials.'' The purpose of this draft guidance is
to describe FDA requirements and provide recommendations for obtaining
safety and effectiveness information on drug and biological products,
when appropriate, in the postmarketing setting in historically
underrepresented patient populations in clinical trials. FDA
regulations require sponsors to present information from premarket
clinical trials on the safety and effectiveness of drugs in terms of
gender, age, and racial subgroups. These clinical trials should include
patient populations that are historically underrepresented in clinical
research, including but not limited to, populations based on race,
ethnicity, sex, age, geographic location, gender identity,
socioeconomic status, disability, pregnancy status, lactation status,
and co-morbidity. Obtaining information early in development can be
advantageous in that information may help inform subsequent clinical
trials and ultimately result in more efficient, informative, and
successful drug development. However, if despite the sponsor's best
efforts, these populations are not adequately represented in premarket
clinical trials or if the data suggests there may be serious safety
concerns in these populations, it may be appropriate to collect such
data in the postmarketing setting. Reviews of clinical trial data
indicate that there is often underrepresentation of patient
populations, based on race, ethnicity, sex, or age. The draft guidance
discusses mechanisms by which FDA can require or request information on
safety and effectiveness be collected in the postmarketing setting;
design and statistical considerations for subpopulation analyses; and
postmarketing approaches to obtain information on the benefit-risk
profile in underrepresented clinical trial populations.
    Underrepresentation in clinical trials remains a significant issue
despite the Agency's efforts to encourage sponsors and investigators to
improve representation of historically under-represented patient
populations. We welcome further dialogue in other settings or
collaborative efforts to explore methods to enhance representation in
clinical trials.
    This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the current thinking of FDA on
``Postmarketing Approaches to Obtain Data on Under-Represented
Populations in Clinical Trials.'' It does not establish any rights for
any person and is not binding on FDA or the public. You can use an
alternative approach if it satisfies the requirements of the applicable
statutes and regulations.

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. The
previously approved collections of information are subject to review by
the Office of Management and Budget (OMB) under the Paperwork Reduction
Act of 1995 (44 U.S.C. 3501-3521). The collections of information in 21
CFR parts 50 and 56 have been approved under OMB control number 0910-
0130; the collections of information in 21 CFR part 314 have been
approved under OMB control number 0910-0001; the collections of
information in 21 CFR part 312 have been approved under OMB control
number 0910-0014; the collections of information in 21 CFR part 601
have been approved under OMB control number 0910-0338; and the
collections of information pertaining to submission of a biologics
license application (BLA) under section 351(k) of the Public Health
Service Act have been approved under OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance
at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: August 8, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-17267 Filed 8-10-23; 8:45 am]
BILLING CODE 4164-01-P