Page 1 of 26 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM DATE: 11/ 22/ 02 SUBJECT: PP# 7F04850  FQPA Human Health Risk Assessment for Safener HOE 107892 ( Mefenpyr diethyl)  Proposal for Tolerances of Residues in/ on Barley and Wheat.

DP Barcode: D262816 PRAT Case: 288950 Submission No.: S529372 Caswell No.: 811800 Chemical#: 811800 Class: Safener 40 CFR: § 180.509 TO: K Boyle/ R. Forrest/ PM Team 5 MUIERB/ RD ( 7505C)

FROM: Yan Donovan, Chemist Pamela Hurley, Toxicologist Margarita Collantes, Biologist RAB2/ HED ( 7509C)

THRU: Douglas Dotson, Chemist Ed Budd, Toxicologist Shih Chi Wang, Biologist RAB2/ HED ( 7509C)

THRU: Richard A. Loranger, Branch Senior Scientist RAB2/ HED ( 7509C) Page 2 of 26 Cl N N Cl COOCH 2 CH 3 C H 3 COOCH 2 CH 3 1.0 EXECUTIVE SUMMARY General Background:

AgrEvo USA Company ( now Bayer CropScience) has submitted a petition for the establishment of permanent tolerances for residues of a herbicide safener, HOE 107892 {[ 1( 2,4 dichlorophenyl) 4,5 dihydro 5 methyl 1H pyrazole 3,5 dicarboxylic acid, diethyl ester]}, ( proposed common name: mefenpyr diethyl), in/ on wheat and barley commodities.

Safeners are added to herbicidal active ingredients in formulations to protect crops from potential adverse effects of the herbicides. Although safeners are not considered to be pesticidal by the Agency, they are often similar in molecular structure to active pesticides. Thus, the Agency has established tolerances for safeners ( e. g., see 40 CFR § 180.460, § 180.469, and § 180.471).

The formulation is proposed for a single seasonal broadcast application to wheat in the 2 to 6 leaf stage before jointing. Ground application may be made in a minimum of 10 gallons of spray solution/ A. Under dense weed populations or adverse growing conditions, high spray volumes ( 15 20 gallon/ acre) may be required. Aerial application may be made in a minimum of 5 gallons of water per broadcast acre.

The petitioner is proposing the establishment of tolerances for residues of HOE 107892 and its 2,4 dichlorophenyl pyrazoline containing metabolites in/ on the following commodities:

Barley, grain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.05 ppm Barley, hay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.5 ppm Barley, straw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.0 ppm Barley, pearled . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.06 ppm Barley, flour . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.07 ppm Barley, bran . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.385 ppm Wheat, grain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.05 ppm Wheat, forage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.75 ppm Wheat, hay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.5 ppm Wheat, straw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.75 ppm Wheat, germ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.415 ppm Wheat, bran . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.385 ppm Wheat, flour . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.07 ppm Wheat, shorts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.415 ppm HOE 107892 HOE 107892 is a member of a new chemical class. Page 3 of 26 Section 18 Emergency Exemptions were approved for uses on durum wheat and barley in 1996 and 1998, respectively, and as a result, HOE 107892 has temporary tolerances for wheat and barley raw agricultural commodities ( 40 CFR 180.509, due to expire 12/ 31/ 03). For the purposes of those Section 18s only, it was assumed that there would be no quantifiable residues of HOE 107892 in wheat grain or straw and that there would be no quantifiable residues in meat, milk, poultry, or eggs resulting from the use. HOE 107892 has no other registered uses; PP# 7F04850 will be the first permanent food use.

HED has evaluated the toxicological, residue chemistry and exposure databases for HOE 107892.

Hazard Assessment The toxicology data base is complete, and the quality of the data is sufficient to characterize the toxicity of this chemical. There is a fairly high confidence in the hazard and dose response assessments conducted.

The HED Hazard Identification Assessment Review Committee ( HIARC) met on 10/ 13/ 98 to evaluate the toxicology data base, establish Reference Doses ( RfDs) and select toxicological endpoints for dietary and occupational exposure risk assessments. The HIARC also addressed the potential enhanced sensitivity of infants and children from exposure to HOE 107892, as required by the Food Quality Protection Act ( FQPA) of 1996. The toxicology database supports the requested regulatory action and there is a fairly high degree of confidence in the scientific quality of the data. The available toxicology data are considered adequate to define the toxicity of the chemical. The HIARC classified HOE 107892 as " not likely to be a human carcinogen" based on negative rat and mouse carcinogenicity studies as well as negative mutagenicity studies. Although HOE 107892 was not tested at sufficiently high dose levels for an adequate rat carcinogenicity study, based on the overall toxicology database and weight of the evidence from the negative mouse carcinogenicity and mutagenicity studies, it is unlikely that repeating the study at higher dose levels would significantly change the target organs or the effects observed. There are no data gaps for this particular use; however, a new rat carcinogenicity study will be requested if new uses result in significantly higher residues in human foods and/ or there is significantly higher occupational ( or future residential) exposure due to changes in parameters such as the method of application.

In general, HOE 107892 has low acute toxicity. In subchronic and chronic studies in animals, it was shown to affect 2 major target organs: the liver and the hematopoietic system. None of the observed effects in the toxicological studies on HOE 107892 are of major toxicological significance. They are all mild. The most significant effects appear to be decreased mean body weight and mean body weight gain, increased mean spleen weights and an increase in the severity ( but not in the incidence) of splenic extramedullary hematopoiesis in rats in a 2 generation reproduction study. Minimal intrahepatic cholestasis in the liver was observed in dogs, accompanied by increases in liver weights and alkaline phosphatase. Hepatocellular hypertrophy and increases in liver weights were observed in other studies and are usually considered to be related to induction of drug metabolizing enzymes. There is no evidence of carcinogenicity in either rats or mice and no evidence of a mutagenic, clastogenic or genotoxic response. There does not appear to be any increased susceptibility in rats or rabbits to in utero and/ or postnatal Page 4 of 26 exposure to HOE 107892. Developmental effects were only observed at levels which were parentally toxic. In addition, there is no evidence of neurotoxicity in any of the available studies. Finally, HOE 107892 does not appear to be an endocrine disrupter.

FQPA Decision The HED FQPA Safety Factor Committee ( SFC) met on December 7, 1998 to evaluate the hazard and exposure data for HOE 107892 and recommended that the FQPA Safety Factor ( as required by the Food Quality Protection Act of August 3, 1996) be removed because there is no indication of increased susceptibility to infants and children, dietary exposure estimates are likely to result in an overestimate of the actual exposure, estimates for ground and surface source drinking water exposure are upper bound concentrations and there are currently no registered residential uses and thus, this type of exposure to infants and children is not expected.

Dose Response Assessment The HIARC selected a chronic RfD of 0.57 mg/ kg/ day ( NOAEL = 57.3; Uncertainty Factor = 100) for use in assessing chronic dietary risk. This RfD is based on the 2 generation reproduction study in the rat, in which decreases in mean body weight and body weight gain, increases in mean spleen weight and increases in the severity of splenic extramedullary hematopoiesis were observed.

Acute dietary and short, intermediate and long term dermal and inhalation toxicological endpoints were not selected because no appropriate endpoint could be identified in the available studies, including the developmental studies in rats and rabbits; a 28 day dermal study in rats ( 21 exposure periods over 29 days) showed no dermal or systemic toxicity at dose levels up to 1000 mg/ kg/ day; HOE 107892 has low acute inhalation toxicity and/ or because the use pattern indicates that there is minimal concern for either long term dermal exposure or any significant inhalation exposure. Therefore, no risk assessments were conducted for these exposure scenarios.

As stated previously, on 10/ 13/ 98, HOE 107892 was classified by the HIARC as " not likely to be a human carcinogen". This was based on weight of the evidence from negative rat and mouse carcinogenicity studies as well as negative mutagenicity studies. In light of the negative mouse and mutagenicity studies, although the dose levels in the rat study are not adequate, the Committee determined that a new rat study would not provide any additional information on the effects of concern for this particular use.

Exposure Scenarios and Risk Conclusions Residential Exposure Estimates Page 5 of 26 HOE 107892 currently has no registered or proposed residential uses. Therefore, a residential exposure assessment is not required at this time.

Dietary Exposure Estimates On 2/ 8/ 00, the HED's Metabolism Assessment Review Committee ( MARC) determined that the regulable residues in animal commodities should be the parent compound and the three 2,4 dichlorophenyl pyrazoline containing metabolites HOE 113225, HOE 109453, and HOE 094270 ( Memo of Y. Donovan, 3/ 27/ 00, D263039).

Based on data from a barley metabolism study, the MARC has recommended that regulation of HOE on plants be based on the parent compound and the three metabolites ( HOE 113225, HOE 109453, and HOE 094270) which are also detected by the proposed polar extraction GC/ MS method ( 7/ 16/ 96 memo of D. Davis). The above metabolites are formed by hydrolysis of one or both ethyl ester groups followed by decarboxylation in the case of HOE 094270.

A GC/ MSD method for the enforcement of tolerances for barley and wheat commodities has been forwarded to the Agency analytical lab for petition method validation. The Agency analytical lab concluded that this method is suitable for food tolerance enforcement of HOE107892 and the three metabolites HOE 094270, HOE 113225 and/ or HOE 109453 in/ on plants.

An adequate enforcement method capable of determining residues in/ on animal commodities is required since the Agency is recommending tolerances be established on meat byproducts ( liver and kidney). The petitioner has proposed a study protocol for development of an animal method. RAB2 concluded that this requirement can be made a condition of registration.

HOE 107892 chronic dietary exposure assessment was conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database ( DEEM FCID   , Version 1.3), which incorporates consumption data from USDA's Continuing Survey of Food Intakes by Individuals ( CSFII), 1994 1996 and 1998. The 1994 96, 98 data are based on the reported consumption of more than 20,000 individuals over two non consecutive survey days. Foods " as consumed" ( e. g., apple pie) are linked to EPA defined food commodities ( e. g. apples, peeled fruit  cooked; fresh or N/ S; baked; or wheat flour  cooked; fresh or N/ S, baked) using publicly available recipe translation files developed jointly by USDA/ ARS and EPA. Consumption data are averaged for the entire U. S. population and within population subgroups for chronic exposure assessment, but are retained as individual consumption events for acute exposure assessment.

The analysis assumed tolerance level residues and 100% crop treated for all proposed uses ( i. e., a Tier 1 analysis). Estimated exposures are less than 1% of the chronic Population Adjusted Dose ( cPAD) for the general U. S. population and all population subgroups, including those of infants and children. The proposed use of HOE 107892 on barley and wheat is expected to result in dietary ( food only) risks that are less than the Agency's level of concern for the general U. S. population and all population subgroups, including those of infants and children.

Drinking Water Exposure Estimates Page 6 of 26 EFED provided the environmental fate analysis and the results of maximum estimated environmental concentrations ( EECs) of HOE 107892 in surface and ground water for chronic exposure. For surface water, the FIRST ( Tier 1) index reservoir simulation model for a single application of HOE 107892 at an exaggerated rate of 0.090 kg/ ha ( 0.080 lb/ acre) results in the peak and chronic concentrations of combined parent and metabolites of 5 ppb and 3 ppb, respectively. The groundwater result from SCI GROW2 is approximately 4 µ g/ L ( ppb).

Aggregate Risk Assessment Conclusions:

Acute Aggregate Risk ( Food + Water)

Not required since no endpoint was selected.

Chronic Aggregate Risk ( Food + Water + Residential)

Chronic aggregate risk includes exposures from food, water, and residential uses. Using the most conservative Tier I analysis, it is estimated that the chronic exposures to HOE 107892 from food for the general US population and all population subgroups will utilize < 1% of the cPAD. EFED's EEC of HOE 107892 in surface and ground water for chronic exposure is very small compared to the DWLOC, which ranged from 5700 to 20000 ppb. Currently there are no registered or proposed residential uses that could result in residential exposures. Therefore, HED concludes that there is a reasonable certainty that no harm will result to adults, infants and children from chronic aggregate exposure to HOE 107892 residues.

Short and Intermediate Term Aggregate risk ( Residential + Chronic Food + Chronic Water)

There are no registered residential uses of HOE 107892. Therefore, a short and intermediateterm aggregate risk assessment for HOE 107892 is not required.

Cancer HOE 107892 has been classified by HED HIARC as a " not likely human carcinogen." A cancer risk assessment is not required.

Occupational Exposure Workers may be exposed to HOE 107892 during mixing, loading, application and postapplication activities. Based on the proposed application rates and use scenarios, short and intermediateterm exposures may occur. Chronic exposure ( 6 or more months of continuous exposure) is not expected. Since the HIARC did not select dermal or inhalation toxicological endpoints, neither dermal nor inhalation risk assessments were performed.

The acute toxicity effects for HOE 107892 are all in categories III and IV and therefore only require a 12 hour REI.

Recommendations: Page 7 of 26 Cl N N Cl COOCH 2 CH 3 C H 3 COOCH 2 CH 3 HED concludes that there is a reasonable certainty that no harm will result to the U. S. Population including infants and children from chronic aggregate exposure to HOE 107892 residues. HED recommends that permanent tolerances be established for residues of HOE 107892 and its 2,4 dichlorophenyl pyrazoline containing metabolites in/ on the following commodities:

Barley, grain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.05 ppm Barley, hay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.2 ppm Barley, straw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.5 ppm Wheat, grain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.05 ppm Wheat, forage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.2 ppm Wheat, hay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.2 ppm Wheat, straw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.5ppm Meat byproducts ( of cattle, goats, hogs, horses and sheep). . . . . . . . . . . . . . 0.1ppm Residue Chemistry deficiencies

Multiresidue method testing for parent and metabolites;

Animal analytical method ( condition of registration);

A revised Section F to change the proposed tolerances to match the above recommended tolerances.

Agency memoranda supporting this risk assessment include the following:

1. HIARC report on HOE 107892 ( 11/ 24/ 98); 2. FQPA report on HOE 107892 ( 12/ 17/ 98); 3. HED Residue Chemistry memo of 11/ 22/ 02, Y. Donovan, D238730 ; 4 HED DEEM memo of 11/ 22/ 02, Y. Donovan, D286489; 5. EFED memos of 03/ 18/ 97, Alex Clem, D226076, and 11/ 26/ 01, Alex Clem, D262735; 6. HED ORE memo of 04/ 12/ 00, M. Collantes, D263518.

2.0 PHYSICAL/ CHEMICAL PROPERTIES CHARACTERIZATION The chemical structure of HOE 107892 is as follows:

HOE 107892 Page 8 of 26 Product chemistry for HOE 107892 has been previously reviewed by HED ( memo of 6/ 24/ 99, J. Stokes, D231514, PP# 6E4722). Some of the physical properties of HOE 107892 are summarized below:

Color: white to light beige Physical State: normally solid, but can also occur as a supercooled molten mass Odor: weak, non characteristic odor M. P.: 43 0 to 47 0C ( 109  116 F) Density: 1.31 g/ cm3 at 20 0C Vapor pressure: N/ A pH: Neat Water insolubility/ non dispersibility prevented measurement of pH Octanol/ Water Partition Coefficient: log P = 3.83 Solubility: 20 mg/ L, pH 6.2 ( distilled water, 20 0C) 17 mg/ L, pH 0.9 ( sulfuric acid, pH 1, 20 0C) organic solvents: n hexane, 35 g/ L acetone, > 500 g/ L Hydrolysis: in Citrate: > 365 days, in Borate/ KCl: 0.35 days. Half life: 17 days( photolysis) 3 days ( aerobic soil metabolism)

3.0 HAZARD CHARACTERIZATION ( Attachment 1, HIARC report on11/ 24/ 98)

3.1 Hazard Profile Table 1. Acute Toxicity of HOE 107892 Technical.

Guideline Number Study Type MRID #( S). Results Toxicity Category 81 1 Acute Oral 43972211 Oral LD50: Males > 5,000 mg/ kg Females > 5,000 mg/ kg IV 81 2 Acute Dermal 43972213 Dermal LD50: M > 4,000 mg/ kg F > 4,000 mg/ kg III 81 3 Acute Inhalation 43972214 Inhalation LC50: Males: > 1.32 mg/ L Females > 1.32 mg/ L III 81 4 Primary Eye Irritation 43972215 Slight ocular irritant. PIS: 12.8. III 81 5 Primary Dermal Irritation 43972216 PII: 0.17. Not a dermal irritant. IV 81 6 Dermal Sensitization 43972217, 44280001 A slight dermal sensitizer. N/ A Page 9 of 26 Table 2. Toxicity Profile of HOE 107892 Technical.

Study Type MRID No. Results 28 Day Dermal Toxicity Rat 44089201 NOAEL = 1000 mg/ kg/ day ( HDT); LOAEL not determined. No effects were observed in the study.

Subchronic Feeding Mouse 43972218 NOAEL 89.3/ 105.4 mg/ kg/ day ( M/ F) LOAEL= 449.0/ 523.5 mg/ kg/ day ( M/ F; decreased body and kidney weight, increased liver weight and hepatocyte hypertrophy in males; decreased bilirubin and increased lactic acid dehydrogenase values in females)

Subchronic Feeding Rat 43972219 NOAEL = 206.7/ 223.0 ( M/ F) mg/ kg/ day LOAEL = 660.6/ 708.9 ( M/ F) mg/ kg/ day ( decreased body weight gains; decreased erythrocyte counts, hemoglobin and hematocrit values; and increased reticulocyte counts and mean corpuscular volume).

Subchronic Feeding Dog 43972220 NOAEL = 80.5/ 81.2 mg/ kg/ day ( M/ F) LOAEL = 341.0/ 336.1 mg/ kg/ day ( M/ F; increased absolute and relative liver weights and alkaline phosphatase activities in both sexes; focal liver lesions in females; slight anemia in both sexes; decrease in mean body weight and body weight gain in females and decreased food consumption in both sexes).

Chronic Feeding Dog 44316402 NOAEL = 51.4/ 57.6 mg/ kg/ day ( M/ F) LOAEL= 260.2/ 282.2 mg/ kg/ day ( M/ F; high ALP levels and increased absolute and relative liver weights in both sexes and grade 1 ( minimal) intrahepatic cholestasis in the liver: 2/ sex).

Chronic toxicity/ Carcinogenicit y Rat 43972222 43972223 NOAEL= 48.5/ 60.0 mg/ kg/ day ( M/ F) LOAEL= 251.6/ 318.0 mg/ kg/ day ( M/ F: significant increases in reticulocyte counts).

Carcinogenicity Mouse 43972224 43972225 NOAEL ( males) = 350.8 mg/ kg/ day NOAEL ( females) = 463.4 mg/ kg/ day LOAEL ( males & females) = Not determined, however study considered adequate for carcinogenicity based on results of subchronic study.

Developmental Toxicity Rat 43972221 Maternal NOAEL < 1000 mg/ kg/ day ( only dose tested) Maternal LOAEL = 1000 mg/ kg/ day ( decreases in body weight gain and food efficiency during the first week of treatment and on increases in absolute and relative spleen weights). Developmental NOAEL = 1000 mg/ kg/ day Developmental LOAEL = Not achieved Postnatal Developmental Toxicity Rat 44654201 Maternal NOAEL < 1000 mg/ kg/ day ( only dose tested) Maternal LOAEL = 1000 mg/ kg/ day ( decreases in body weight gain and food efficiency during the first week of treatment). Developmental NOAEL < 1000 mg/ kg/ day Developmental LOAEL = 1000 mg/ kg/ day ( marginal decreases in fetal body weight and body weight gain during lactation). Study Type MRID No. Results Page 10 of 26 Developmental Toxicity Rabbit 44089202 Maternal NOAEL = 100 mg/ kg/ day Maternal LOAEL = 250 mg/ kg/ day ( higher rate of abortions and marginal decreases in body weight gain, food efficiency index and food consumption). Developmental NOAEL = 100 mg/ kg/ day Developmental LOAEL = 250 mg/ kg/ day ( higher rate of abortions).

Reproductive Toxicity 44661601 Parental Offspring/ Systemic NOAEL = 57.3 mg/ kg/ day for males; 76.0 mg/ kg/ day for females. Parental Offspring/ Systemic LOAEL = 306.0 mg/ kg/ day for males; 392.0 mg/ kg/ day for females ( decreased mean body weight and mean body weight gain in parents and offspring and an increase in mean spleen weight and an increase in the severity ( but not in the incidence) of splenic extramedullary hematopoiesis in females). Reproductive NOAEL = 306.0 mg/ kg/ day ( males), 392.0 mg/ kg/ day ( females): HDT Reproductive LOAEL = Not determined Gene Mutation  Salmonella & E. Coli 43972226 Non mutagenic ( ± ) activation.

Gene Mutation  HGPRT with V79 cells 43972230 Non mutagenic ( ± ) activation.

Micronucleus Assay 43972228 No clastogenic response at any dose or sacrifice time.

DNA Repair Assay 43972229 No clear evidence of genotoxicity. However, study not acceptable.

Chinese Hamster Lung Fibroblast Assay 43972227 No clastogenic response ( ± ) activation. Study Type MRID No. Results Page 11 of 26 Metabolism Rat 44654204 44654203 44661602 3 Single dose of 1 or 100 mg/ kg bw: urinary excretion  76 88% of administered radioactivity with 59 72% excreted within first 24 hours. Fecal excretion ranged from 13 32%. 83 91% of administered dose excreted ( urine and feces) by 24 hours and 91 to > 99% excreted by 48 hours. At least 68 88% of administered dose absorbed. Recovery in tissues/ animal: 0.24% of administered radioactivity ( range: 0.07  0.51%). General order of concentration plasma > whole blood > lungs > subcutaneous fat > heart > kidneys> retroperitoneal fat > liver> gonads > pancreas > skeletal muscle. No volatile radioactivity detected 0 24 hours after dosing. Between 100 106% of administered radioactivity recovered.

Single dose of 1 or 100 mg/ kg bw: Radioactivity rapidly excreted: total of 78 92% excreted by 48 hours. Renal excretion predominant route of elimination ( 65 72% by 48 hours), indicating that at least 65 72% of the administered dose was absorbed. None of test material found in its original form in urine. Three metabolites identified in urine: Hoe 109453 ( 63 62% and 42 48%), Hoe 113225 ( 0.2 2% and 14 28%), and Hoe 094270 ( 2 3% and 2%) each for males and females, respectively. 13 26% of the radioactivity was recovered in the feces by 48 hours. In addition to the three metabolites identified in urine, the parent was also present in the feces: Hoe 107892 ( 8% and 1 3%), Hoe 109453 ( 2 8% and 4 7%), Hoe 113225 ( 5 6% and 1 3%), and Hoe 094270 ( 0.30 0.50 and 0.53 1.16%) each for males and females, respectively. Proposed metabolic steps: consecutive hydrolysis ( saponification) of the two carboxylic acid ester groups and a decarboxylation of one of the carboxylic groups, resulting in an aromatization of the pyrazoline ring ( Hoe 107892

Hoe 113225

Hoe 109453

Hoe 094270). Enterohepatic circulation is unlikely to play a major role. In males, there appears to be either lower intestinal absorption or a higher biliary excretion of Hoe 107892 compared to females.

General Toxicity Profile HOE 107892 has low acute toxicity. It is classified in Toxicity Categories III or IV in the acute oral, dermal, inhalation and irritation studies. It is a slight dermal sensitizer.

The database on HOE 107892 indicates that there appears to be 2 major target organs: the liver and the hematopoietic system. Both the liver and hematological effects are observed in NMRI mice ( both sexes), Wistar rats ( both sexes), and Beagle dogs ( both sexes). There does not appear to be sex sensitivity. There appears to be a dose response relationship between the doses tested and the effects observed; however, in the case of the effects on the hematopoietic system, often the effects are very mild and are only observed at the highest dose level tested.

Liver Page 12 of 26 Following administration of the test chemical, increases in liver weight and hepatocellular hypertrophy were observed in short, intermediate and long term studies in mice; effects were observed at lower dose levels in the longer term studies. In dogs, increases in liver weights and alkaline phosphatase levels were observed in short, intermediate and long term studies. Liver pathology ( focal lesion: hemorrhage, necrosis and inflammation) appeared by 13 weeks at 336 mg/ kg/ day ( a 4 week study at a similar dose level showed no microscopic effects). After 1 year exposure, increased liver weights, intrahepatic cholestasis and high alkaline phosphatase levels were observed at a dose level in the same range ( 282 mg/ kg/ day). In general, longer exposure periods did not produce liver effects at lower dose levels; however, intrahepatic cholestasis is likely to be a more serious effect than the focal lesion observed in the 13 week study and the former was observed in 2 male and 2 female dogs, whereas the latter was only observed in 1 female. In rats, one special 4 week study showed that HOE 107892 induces hepatic drug metabolizing enzymes. Induction of hepatic drug metabolizing enzymes are not considered to be adverse, i. e. they are considered to be biologically but not toxicologically significant.

Hematopoietic System The effects on the hematopoietic system are very mild ( in some cases they are not even considered to be adverse effects); however, they indicate that the chemical is causing hemolysis of the red blood cells. As a result, cells are being produced in the bone marrow so fast that they are immature and low in hemoglobin. This is indicated by decreases in erythrocytes, hemoglobin and hematocrit levels, decreased mean corpuscular hemoglobin concentration, increases in reticulocyte and mean corpuscular volume, enlarged spleens, more severe hematopoiesis and hemosiderin deposits. The hematological effects are observed after short and intermediate exposure in mice, intermediate exposure in dogs and after short, intermediate and long term exposure in rats. Although the effects on the hematopoietic system are similar in both the short and longer term studies, they do not necessarily occur at lower doses in the longer term studies. For example, the effects are not observed in the 1 year dog study ( highest dose tested: 282 mg/ kg/ day); whereas, they are observed at 336 mg/ kg/ day in the 13 week dog study.

Carcinogenic Effects:

In accordance with the EPA Proposed Guidelines for Carcinogen Risk Assessment ( April 10, 1996), the Hazard Identification Assessment Review Committee ( HIARC, 10/ 13/ 98) classified HOE 107892 as a " not likely to be a human carcinogen". This classification is based on the lack of evidence of carcinogenicity in male and female mice as well as in male and female rats. In addition, none of the mutagenicity studies tested positively. Although the dose levels in the rat study were not adequate, the Committee determined that a new rat study would not provide any additional information on the effects of concern for this particular use. Therefore, a new rat carcinogenicity study will not be requested unless new uses result in significantly higher residues in human foods and/ or there is significantly higher occupational ( or future residential) exposure due to changes in parameters such as the method of application.

Developmental/ Reproductive Effects: Page 13 of 26 Two developmental rat studies were conducted, one using the standard guideline and the other allowing the dams to give birth and following the pups until weaning. In the prenatal developmental toxicity study in rats, no evidence of developmental toxicity was seen, even in the presence of maternal toxicity. In the developmental toxicity study in rabbits, developmental toxicity was seen in the presence of maternal toxicity. A higher rate of abortions occurred at the highest dose level tested ( 250 mg/ kg/ day). An examination of the individual litter data provided no evidence as to whether or not the higher rate was due to maternal toxicity or developmental toxicity. Therefore, both the maternal and developmental NOAELs and LOAELs were based on this effect. In the two generation reproduction study and in the postnatal developmental toxicity study in rats, effects in the offspring were observed only at or above treatment levels which caused parental toxicity. Developmental effects in these two studies consisted of decreases in body weight and body weight gain of the pups in the presence of either decreased body weight and body weight gain or hematopoietic effects in the parents.

Mutagenic Effects:

HOE 107892 was tested in gene mutation assays in Salmonella typhimurium, E. coli and Chinese hamster lung fibroblasts V79 cells, in in vitro and in vivo cytogenetics assay ( Chinese hamster lung fibroblasts and mouse micronucleus) and in an unscheduled DNA synthesis assay in human A 549 cells. There was no evidence of a mutagenic, clastogenic or genotoxic response under the conditions of the assays, either with or without metabolite activation. In the unscheduled DNA synthesis assay, a cytotoxic and/ or insoluble level was not evaluated in the S9 activated phase of the study and overall assay sensitivity was compromised because of the high levels of radioactive label ( indicating that replicative DNA synthesis was not successfully blocked) in all experimental groups. Therefore, this particular study was classified as Unacceptable and does not satisfy the guideline requirement for a UDS assay ( § 84 2).

Neurotoxic Effects:

No neurotoxicity studies are available. There is no evidence of neurotoxicity in any of the available studies.

Metabolites:

The HED Metabolism Committee met on 6/ 20/ 96 and on 02/ 08/ 00 and determined that the residues of concern for HOE 107892 are the parent compound and free metabolites, HOE 113225, HOE 109453 and HOE 094270. No additional potential HOE 107892 degradates of significant toxicological concern were either identified or expected which should be included in the tolerance expression or risk assessment.

Endocrine Disruption:

There is no evidence of endocrine disruption with HOE 107892.

Toxicological Significance of Effects: Page 14 of 26 None of the observed effects in the toxicological studies on HOE 107892 are of major toxicological significance. They are all mild. Of the observed effects previously discussed, the HIARC believed that the endpoints from the 2 generation reproduction study ( decreased mean body weight and mean body weight gain in parents and offspring, increased mean spleen weights and an increase in the severity ( but not in the incidence) of splenic extramedullary hematopoiesis) were considered to be the most significant. The observed intrahepatic cholestasis in the liver in the chronic dog study was minimal, although it was seen in 4/ 12 dogs. In that study, it was considered to be a toxicological effect ( although minor) along with the increases in liver weights and alkaline phosphatase. Hepatocellular hypertrophy and increases in liver weights are often related to induction of drug metabolizing enzymes ( actually measured in the rat) and are not considered to be significant toxicological effects, except in the case of the chronic dog study due to the presence of other microscopic effects in the liver.

3.2 FQPA Considerations ( Attachment 2, FQPA report on 12/ 17/ 98)

Rationale and Findings Regarding Recommendation on Special FQPA Safety Factor Although no neurotoxicity studies are available, there is no evidence of neurotoxicity in any of the subchronic, developmental, reproductive or chronic toxicity studies. The postnatal developmental toxicity study provided no evidence of developmental neurotoxicity with any of the parameters examined ( sex, external abnormalities, viability, general behavior, times of pinna separation, coat growth start, incisor eruption and eyelid opening, hearing, vision, righting reflex, trainability, memory and retrainability).

The data provided no indication of increased susceptibility in rats or rabbits to in utero and/ or postnatal exposure to HOE 107892 and there are no exposure or toxicity data gaps that are critical to the assessment of potential hazard to infants and children.

The FQPA Committee recommended that the FQPA safety factor be removed because: 1) the toxicology data base is complete; 2) there is no indication of increased susceptibility of rats or rabbit fetuses to in utero and/ or postnatal exposure in the developmental and reproductive toxicity studies; 3) a developmental neurotoxicity study is not required; 4) dietary ( food) exposure estimates are expected to be unrefined ( assuming tolerance level residues and 100% CT) and will likely result in an overestimate of the actual dietary exposure; 5) EFED models are used for ground and surface source drinking water exposure assessments resulting in estimates that are upper bound concentrations; and 6) there are currently no registered residential uses of HOE 107892, therefore, this type of exposure to infants and children is not expected.

Application of the FQPA Safety Factors ( Population Subgroups / Risk Assessment Scenarios) This recommendation is applicable to all population subgroups for all exposure routes and durations.

3.3 Dose Response Assessment Discussion of Toxicological Database for Risk Assessment Purposes: Page 15 of 26 The toxicology database for HOE 107892 is complete for the purpose of this risk assessment and it defines the toxicity of the chemical to a certain extent. In some cases the test chemical was not tested at sufficiently high dose levels for an adequate study. However, based on the overall data, it is unlikely that repeating any studies with higher dose levels would significantly change the target organs or the effects observed. Most likely, the effects already noted would be more severe. There is a fairly high degree of confidence in the scientific quality of the toxicology database. There are no problems with the reproduction study, the study on which the chronic dietary endpoint is based. There are no other studies upon which toxicological endpoints are based.

With the exception of the chronic feeding/ carcinogenicity study in the rat and the unscheduled DNA synthesis study, all of the studies are considered to be acceptable guideline studies ( the rabbit developmental toxicity study is only marginally acceptable because only 8 litters were ultimately available for examination in the high dose group). Although the dose levels in the chronic feeding/ carcinogenicity study in the rat are not adequate for a negative carcinogenicity study, the HIARC Committee determined that a new rat study would not provide any additional information on the effects of concern for this particular use. The main target organs for this chemical have been adequately defined by other studies in the rat and in other species. Therefore, a new study will not be requested unless new uses result in significantly higher residues in human foods and/ or there is significantly higher occupational ( or future residential) exposure due to changes in parameters such as the method of application. The unscheduled DNA synthesis study is also classified as unacceptable; however, there are sufficient acceptable mutagenicity studies available to satisfy the testing requirements for mutagenicity.

In the developmental rat studies, although a maternal NOAEL cannot be defined, the observed effects are not of sufficient severity to rate the study unacceptable ( decreases in body weight gain and food consumption in the first week only at the limit dose, 1000 mg/ kg/ day). Also, in the standard rat developmental study, no developmental toxicity is observed at the limit dose. Therefore, sensitivity to infants and children as defined by FQPA can be addressed. In the postnatal developmental toxicity study, marginal decreases in fetal body weight and body weight gain during lactation are observed at 1000 mg/ kg/ day. Since this effect is only marginal and since the maternal effects are similar and are also marginal, sensitivity to infants and children can still be addressed, particularly because some parameters for postnatal behavioral/ developmental effects were examined in this study ( sex, external abnormalities, viability, general behavior, times of pinna separation, coat growth start, incisor eruption and eyelid opening, hearing, vision, righting reflex, trainability, memory and retrainability).

Only one endpoint was selected for risk assessment  the chronic dietary endpoint. The adverse effects associated with this endpoint are decreases in mean body weight and body weight gain, increases in mean spleen weight and an increase in the severity ( but not the incidence) of splenic extramedullary hematopoiesis. This endpoint is considered to be conservative because the level of concern is not high for these effects. The hematological effects observed in the selected study are very mild and consist of only an increase in severity, not incidence. The decreases in body weight and body weight gain are borderline toxicologically significant. Decreases in mean body weight and body weight gain are indicators of the overall well being of the animal. If the decreases are significant, usually other effects are observed as well. In this Page 16 of 26 case, the decreases in body weight gain are observed predominantly in parental males from the reproduction study. Body weights were generally 8 11% lower than controls and body weight gains were generally 12 13% lower than controls. These decreases are not huge and are only slight in females.

For the chronic dietary endpoint, the chronic dog study, the chronic rat study and the rat reproduction study have the most sensitive endpoints. The chronic rat study has a slightly lower endpoint; however, the NOAEL is based on increases in reticulocyte counts with no supporting histopathology or statistically significant changes in other hematological effects. The chronic dog study also has a slightly lower endpoint; however, the NOAEL is based on minimal intrahepatic cholestasis in the liver and increased alkaline phosphatase values and liver weights. The HIARC decided that the endpoints from the 2 generation reproduction study ( decreased mean body weight and mean body weight gain in parents and offspring, increased mean spleen weights and an increase in the severity ( but not in the incidence) of splenic extramedullary hematopoiesis) were considered to be the most significant and thus appropriate for risk assessment.

An acute dietary endpoint was not selected because no appropriate endpoint could be identified in any of the oral toxicity studies including the developmental studies in rats and rabbits.

Endpoints for dermal risk assessment were not selected because a 28 day dermal study in rats showed no dermal or systemic toxicity at dose levels up to 1000 mg/ kg/ day. In addition, no developmental effects were observed in the developmental rat study at 1000 mg/ kg/ day, the limit dose.

No endpoints for inhalation risk assessment were selected because HOE 107892 has low acute inhalation toxicity ( Category III) and because the use pattern ( 1 application/ growing season with either aerial application or spray boom equipment that is as low to the ground as possible) indicates that there is minimal concern for potential inhalation exposure.

The doses and toxicological endpoints selected for various exposure scenarios are summarized below.

Table 3. Summary of Toxicological Endpoints for Use in Human Risk Assessment EXPOSURE SCENARIO DOSE ( mg/ kg/ day) ENDPOINT STUDY Acute Dietary No appropriate endpoint for risk assessment was identified in oral toxicity studies including the developmental studies in rats and rabbits.

Chronic Dietary NOAEL = 57.3 Decrease in mean body weight and body weight gain in parents and offspring and an increase in mean spleen weight and in severity of splenic extramedullary hematopoiesis in females. 2 generation reproduction study Table 3. Summary of Toxicological Endpoints for Use in Human Risk Assessment EXPOSURE SCENARIO DOSE ( mg/ kg/ day) ENDPOINT STUDY Page 17 of 26 UF = 100 Chronic RfD = 0.57 mg/ kgday Chronic PADa = 0.57 mg/ kg/ day Short Term ( Dermal) No dermal or systemic toxicity observed in 28 day dermal study up to 1000 mg/ kg/ day and no developmental effects observed in developmental rat study at 1000 mg/ kg/ day. Therefore, no endpoint was identified for risk assessment.

Intermediate Term ( Dermal) See short term dermal.

Long Term ( Dermal) Based on the current use pattern ( i. e. 1 application/ season), long term exposure via dermal route is not expected. Therefore, an endpoint was not identified.

Inhalation ( Any Time Period) Based on the low acute toxicity ( Category III) and the use pattern ( 1 application/ growing season with either aerial application or spray boom equipment that is as low to the ground as possible), there is minimal concern for potential inhalation exposure. Therefore, no endpoint was identified.

Carcinogenicity ( Any route of exposure) HOE 107892 is classified as not likely to be a human carcinogen.

a Chronic PAD = Chronic Population Adjusted Dose = Chronic RfD ÷ FQPA Factor ( 1 in this case)

3.4 Endocrine Disruption EPA is required under the Federal Food Drug and Cosmetic Act, as amended by FQPA, to develop a screening program to determine whether certain substances ( including all pesticide active and other ingredients) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC), EPA determined that there were scientific bases for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP).

When the appropriate screening and/ or testing protocols being considered under the Agency's EDSP have been developed, HOE 107892 may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption.

4.0 EXPOSURE ASSESSMENT Page 18 of 26 4.1 Summary of Registered Uses HOE 107892 is a member of a new chemical class. Section 18 Emergency Exemptions were approved for uses on durum wheat and barley in 1996 and 1998, respectively, and as a result, HOE 107892 has temporary tolerances for wheat and barley raw agricultural commodities ( 40 CFR 180.509, due to expire 12/ 31/ 03). For the purposes of those Section 18s only, it was assumed that there would be no quantifiable residues of HOE 107892 in wheat grain or straw and that there would be no quantifiable residues in meat, milk, poultry, or eggs resulting from the use. HOE 107892 has no other registered uses; PP# 7F04850 will be the first permanent food use.

4.2 Dietary Exposure/ Risk Pathway Residue chemistry data for the proposed use of HOE 107892 on wheat and barley have been reviewed by HED. Below are summaries from that review ( Memo of 11/ 22/ 02, Y. Donovan, D238730).

4.2.1 Residue Profile ( Attachment 3, HED memo of 11/ 22/ 02, Y. Donovan, D238730).

Nature of the Residue Based on summary data from the barley metabolism study, the Metabolism Assessment Review Committee has recommended that regulation of HOE be based on the parent compound and those free metabolites ( HOE 113225, HOE 109453, and HOE 094270) which are also detected by the proposed polar extraction GC/ MS method. The Committee did not at that time identify any additional potential degradation compounds of toxicological significance which might be included in the tolerance expression and/ or risk assessment ( 7/ 16/ 96 memo of D. Davis). The above metabolites are formed by hydrolysis of one or both ethyl ester groups followed by decarboxylation in the case of HOE 094270.

Additional data from a wheat metabolism study conducted primarily to generate weathered material for radiovalidation of the proposed enforcement method, show the same metabolic pathways as that of the barley metabolism study. HOE 094270 was the major metabolite in wheat grain and straw, accounting for 19.67% of total radioactive residues ( TRR; 0.0079 ppm) in grain and 7.1 9.2% TRR ( 0.60 0.75 ppm) in straw; metabolites HOE 113225 and HOE 109453 were also detected at low levels. The parent, HOE 107892 was detected in wheat straw only at 1.1% TRR. In wheat straw, 23% of the TRR was shown to be composed of minor unknown components ( each < 3 4% TRR), which released HOE 109453 and HOE 094270 on hydrolysis.

The qualitative nature of the residue in animals is adequately understood based on acceptable studies conducted on goats and laying hens. The metabolic pathways are the same as those in plants. These data have been presented to HED's Metabolism Assessment Review Committee ( MARC), and the MARC concluded that the regulable residues in animal commodities should be the parent compound and the free metabolites HOE 113225, HOE 109453, and HOE 094270. The Committee also concluded that the parent compound and three metabolites ( HOE 113225, HOE 109453, and HOE 094270) are also residues of concern in water and soil ( Memo of Y. Donovan, 3/ 27/ 00, D263039). Page 19 of 26 Based on the poultry metabolism study, RAB2 tentatively concludes that there is no reasonable expectation of finite residues [ § 180.6( a)( 3)] in eggs and poultry tissues; however, should the dietary burden for poultry increase due to the addition of HOE 107892 treated poultry feed commodities through new uses, a poultry feeding study may be needed.

Residue Analytical Methods The petitioner proposes a new GC/ MSD method for the enforcement of tolerances for barley and wheat commodities. Radiovalidation and independent method validation ( ILV) data have been submitted for this method. This method has been forwarded to the Agency analytical lab for petition method validation, and the Agency analytical lab concluded that this method is suitable for food tolerance enforcement of HOE107892 and the three metabolites HOE 094270, HOE 113225 and/ or HOE 109453.

The abilities of the plant methods to extract aged residues were demonstrated by the plant metabolism studies wherein 50 72% of the total radioactive residues were extracted by acetonewater mixtures similar to those used in these methods.

An adequate enforcement method capable of determining residues in/ on animal commodities is required since the Agency is recommending tolerances be established on meat byproducts ( liver and kidney). The petitioner has proposed a study protocol for development of an animal method. RAB2 concluded that this requirement can be made a condition of registration.

Multiresidue Method ( MRM) No data have been submitted concerning recovery of residues of HOE 107892 using FDA multiresidue method protocols ( PAM Vol. I). All petitioners are expected to provide recovery data for parent compounds and all metabolites of concern through these methods. Because tolerances are being proposed for HOE 107892 and metabolites, this requirement applies to the safener and its metabolites as well. The petitioner should refer to the directions for the protocols found in PAM I, Appendix II for further information. RAB2 does not object to this requirement being made a condition of registration.

Crop Field Trials The petitioner has provided adequate residue data reflecting higher than maximum proposed use pattern for HOE 107892 specified for barley and wheat. Field studies on wheat and barley were conducted such that the application of the safener was at 100g/ ha, which equals to 0.089 lb safener/ A. Following a single broadcast foliar application of HOE 107892 at 100g/ ha ( 0.089 lb safener/ A), grain and straw samples were collected at 55 days PHI, hay and forage were harvested just prior to jointing. Maximum residues of HOE 107892 and its metabolite HOE 094270 on barley and wheat grain were less than 0.05 ppm. On barley and wheat hay total residues of HOE 107892 and the three metabolites were less than 0.5 ppm, and on barley and wheat straw were less than 1.0 ppm. Although the other metabolites were not measured in grain, the barley metabolism study showed HOE 094270 to be the only identified residue in grain ( 61% TRR). Therefore, the proposed tolerance of 0.05 ppm on wheat and barley grain is adequate. Residue decline data were inconclusive for both barley and wheat commodities because of the low Page 20 of 26 levels of residues detected. Taking into account the exaggerated application rate, RAB2 recommends that the wheat and barley forage and hay tolerances be decreased to 0.2 ppm, and wheat and barley straw tolerances be decreased to 0.5 ppm. A revised Section F is needed.

Meat, Milk, Poultry, Eggs ( MMPE) According to the goat metabolism study conducted at 11.23 ppm (

25x and

20x the maximum theoretical dietary burden for beef and dairy cattle, respectively), the TRR were  0.001 ppm in milk, 0.061 ppm in liver, 0.170 ppm in kidney, 0.003 0.004 ppm in muscle ( hindquarter, flank, and loin), and 0.010 0.016 ppm in fat ( subcutaneous, perirenal, and omental). Residues in milk plateaued at 0.001 ppm by Day 3 of dosing. These residues ( especially those in kidneys) are at such significant levels that, normally a ruminant feeding study would be required to determine the levels at which tolerances for milk and ruminant tissues. However in this case where the chemical poses very low dietary risk ( HED DEEM memo of 11/ 22/ 02, Y. Donovan, D286489), RAB 2 is willing to waive the feeding study based on the fact that the petitioner is going to develop an animal analytical method for enforcement purpose, and RAB2 will recommend a conservative tolerance of 0.1 ppm be set on meat byproduct based on the goat metabolism study. For risk assessment, RAB2 recommends using the following levels: meat at 0.002 ppm, meat byproduct at 0.1 ppm, fat at 0.01 ppm, and milk at 0.002 ppm. The tissue residues apply to cattle, goats, hogs, horses and sheep.

Rotational Crops Rotational crop data were submitted with this petition. [ Phenyl 14C] HOE 107892 was applied to soil at a rate significantly higher than the proposed use rate. Spinach, carrot, and wheat were planted back at 29 days and 1 year. Based on the results of the residue uptakes, RAB2 recommends a 30 day plantback for leafy, fruiting, and root vegetables, and 12 month plantback for all other crops other than wheat and barley, which can be replanted at any time. If the petitioner desires to have 30 day plantback for all other crops, limited field trials are needed, or the petitioner can choose to analyze the TRR in the 29 day wheat grain and straw samples in the rotational crop studies to determine if there are any residues of concern in the rotational crops.

International Harmonization of Tolerances No Codex, Canada, or Mexican tolerances are established for residues of HOE 107892 and metabolites. Therefore, international harmonization is not an issue for this petition.

4.2.2 Acute And Chronic Dietary ( Attachment 4 HED memo of 11/ 22/ 02, Y. Donovan, D286489)

Acute dietary exposure analysis is not needed because no endpoint was selected.

Chronic Dietary Exposure and Risk. cPAD = chronic RfD = 0.57 mg/ kg bwt/ day.

HOE 107892 chronic dietary exposure assessment was conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database ( DEEM FCID   , Version 1.3), which incorporates consumption data from USDA's Continuing Surveys of Food Intakes by Page 21 of 26 Individuals ( CSFII), 1994 1996 and 1998. The 1994 96, 98 data are based on the reported consumption of more than 20,000 individuals over two non consecutive survey days. Foods " as consumed" ( e. g., apple pie) are linked to EPA defined food commodities ( e. g. apples, peeled fruit  cooked; fresh or N/ S; baked; or wheat flour  cooked; fresh or N/ S, baked) using publicly available recipe translation files developed jointly by USDA/ ARS and EPA. Consumption data are averaged for the entire U. S. population and within population subgroups for chronic exposure assessment, but are retained as individual consumption events for acute exposure assessment.

For chronic exposure and risk assessment, an estimate of the residue level in each food or foodform ( e. g., orange or orange juice) on the food commodity residue list is multiplied by the average daily consumption estimate for that food/ food form. The resulting residue consumption estimate for each food/ food form is summed with the residue consumption estimates for all other food/ food forms on the commodity residue list to arrive at the total average estimated exposure. Exposure is expressed in mg/ kg body weight/ day and as a percent of the cPAD. This procedure is performed for each population subgroup.

The analysis assumed tolerance level residues and was also assumed that 100% of the crop would be treated. No processing studies was required due to the fact that field trials conducted at exaggerated rate (> 5X) showed no detectable residues in wheat and barley grains, and therefore no tolerance is needed for processed commodities. A default processing factor of 1.92 was used for dried beef in this dietary exposure analysis. No other commodities in this analysis used DEEM default processing factors.

The DEEM FCID   analyses estimate the dietary exposure of the U. S. population and various population subgroups. The results reported in Table 2 are for the general U. S. Population, all infants (< 1 year old), children 1 2, children 3 5, children 6 12, youth 13 19, Adults 20 49 years, females 13 49, and adults 50+ years.

Risk estimates for dietary ( food only) exposure to HOE 107892 are less than 1% of the cPAD for all population subgroups. Exposure estimates for the major population subgroups are shown in Table 4. The complete list of results from the chronic exposure analysis are included as Attachment 2.

Table 4. Results of the Tier 1 chronic dietary ( food only) exposure analysis for HOE 107892 proposed uses on barley and wheat.

Population Subgroup Estimated Dietary Exposure, mg/ kg bwt/ day % cPAD*

U. S. Population 0.000113 < 1%

All Infants (< 1 year) 0.000068 < 1%

Children, 1 2 years 0.000295 < 1%

Children, 3 5 years 0.000273 < 1%

Children, 6 12 years 0.000186 < 1%

Youth 13 19 years 0.000107 < 1% Table 4. Results of the Tier 1 chronic dietary ( food only) exposure analysis for HOE 107892 proposed uses on barley and wheat.

Page 22 of 26 Adults 20 49 years 0.000091 < 1%

Females, 13 49 years 0.000082 < 1%

Adults 50+ years 0.000074 < 1%

* Actual values range from 0.0 to 0.1%.

This analysis represents a conservative estimate of dietary ( food only) exposure and risk from the proposed use of HOE 107892 on barley and wheat. Further refinement, through the use of anticipated residues, percent of crop treated estimates and/ or monitoring data, would result in a reduction in the exposure estimates and the associated risk. In this analysis, even without further refinement, the risk estimate is below the Agency's level of concern ( 100% of the PAD) for the general U. S. population and all population subgroups.

4.3 Water Exposure/ Risk Pathway ( Attachment 5, EFED memos of 03/ 18/ 97, Alex Clem, D226076, and of 11/ 26/ 01, Alex Clem, D262735)

Laboratory studies indicate the principal mode of dissipation of HOE 107892 to be aerobic metabolism in soil ( microbially mediated hydrolysis), with secondary contribution by soil sensitized photolysis. Concentrations of HOE 107892 would decrease relatively rapidly in soil with a DT50 of approximately a few days to one week. However, in the process, by products which are structurally very similar to parent and longer lived are formed ( HOE 094270, HOE 113225, and HOE 109453).

Surface Water: Results from the EFED FIRST ( Tier 1) index reservoir simulation model for a single application of HOE 107892 at an exaggerated rate of 0.090 kg/ ha ( 0.080 lb/ acre) are calculated. As discussed in the attached 1997 assessment, the tabulated concentrations are the summations ( in parent equivalent concentrations) of relatively short lived parent and several longer lived transformation products that are structurally similar to parent. Although parent has soil half lives of approximately a few days to a week, the similar by products are much longer lived. For example, the metabolite HOE 094270 reached a maximum concentration that was equivalent to about 72% of parent after around 30 60 days of aerobic soil incubation, and had an estimated DT50 of 100 200 days. The peak and chronic concentrations of combined parent and metabolites computed from FIRST in parent equivalents are about 5 ppb and 3 ppb, respectively Groundwater Results from SCI GROW2: The database of pesticide chemicals used to develop and update the SCI GROW2 regression model shows that the highest pesticide concentration measured on a one pound per acre application basis for a certain mobile and persistent pesticide of similar molecular weight is roughly 55 µ g/ L ( ppb). The current minimum value for Koc in the database used to develop SCI GROW2 is 11 mL/ g, while maximum values for aerobic soil metabolism half life are roughly 1000 days. Since HOE 107892 has Koc and aerobic soil metabolism half lives well within the bounds covered by the model, as do its structurally similar transformation products ( from collateral laboratory evidence and reasonable Page 23 of 26 inference), groundwater concentrations of HOE 107892 applied at exaggerated rate of 0.080 lb/ acre/ year and any associated transformation products ( in equivalent molar concentrations) are not likely to exceed individually or in combination 55 µ g/ L/( lb/ acre) x 0.080 lb/ acre or approximately 4 µ g/ L ( ppb).

4.4 Residential Exposure/ Risk Pathway ( Attachment 6, HED memo of 4/ 12/ 00, M. Collantes, D263518)

At present, there are no registered or proposed residential uses of HOE 107892. Therefore a residential exposure risk assessment is not required at this time.

5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION Aggregate exposure risk assessments were performed for chronic aggregate exposure ( food + drinking water). Since HED does not have ground and surface water monitoring data to calculate a quantitative aggregate exposure, drinking water levels of comparison ( DWLOCs) were calculated. A DWLOC is a theoretical upper limit on a pesticide's concentration in drinking water in light of total aggregate exposure to a pesticide in food, drinking water, and through residential uses. A DWLOC will vary depending on the toxic endpoint, drinking water consumption, body weights, and pesticide uses. Different populations will have different DWLOCs. HED uses DWLOCs in the risk assessment process to assess potential concern for exposure associated with pesticides in drinking water. DWLOC values are not regulatory standards for drinking water.

To calculate chronic DWLOCs, the dietary food estimates ( from DEEM   ) were subtracted from the chronic PAD value to obtain the maximum water exposure level. DWLOCs were then calculated using the standard body weights and drinking water consumption figures: 70kg/ 2L ( adult male and US Population), 60 kg/ 2L ( adult female), and 10kg/ 1L ( infant & children).

5.1 Acute Risk ( Food + Water) Not required.

5.2 Short and Intermediate term Risk ( Food + Residential + Water)

Not required.

5.3 Chronic Risk Assessment ( Food + Residential + Water)

Table 5 summarizes the chronic aggregate exposure to HOE 107892 residues. The EECs generated by EFED are less than HED's DWLOCs. There are no residential uses. Thus, chronic aggregate risk estimates are below HED's level of concern.

Table 5. Chronic Aggregate Exposures to HOE 107892 Residues. Page 24 of 26 Scenario/ Population Subgroup cPAD, ( mg/ kg/ day ) Chronic Food Exposure, ( mg/ kg/ day) Maximum Chronic Water Exposure1, ( mg/ kg/ day) Ground Water EEC2, ( ppb) Surface Water EEC2, ( ppb) Chronic DWLOC 3, ( ppb)

U. S. Population 0.57 0.000113 0.57 4 3 20000 All infants (< 1 year old) 0.57 0.000068 0.57 4 3 5700 Children, 1 2 years 0.57 0.000295 0.57 4 3 5700 Females ( 13 49 years old) 0.57 0.000082 0.57 4 3 17000 1 Maximum chronic water exposure ( mg/ kg/ day) = cPAD ( mg/ kg/ day)  chronic food exposure from DEEM ( mg/ kg/ day). 2 EECs from EFED studies. 3 Chronic DWLOCs were calculated as follows:

DWLOC ( µ g/ L)

maximum water exposure ( mg/ kg/ day) x body weight ( kg) consumption ( L/ day) x 0.001 mg/ µ g 5.4 Cancer Risk HOE 107892 has been classified by HED HIARC as a " not likely human carcinogen." A cancer risk assessment is not required.

6.0 CUMULATIVE RISK FQPA ( 1996) stipulates that when determining the safety of a pesticide chemical, EPA shall base its assessment of the risk posed by the chemical on, among other things, available information concerning the cumulative effects to human health that may result from dietary, residential, or other non occupational exposure to other substances that have a common mechanism of toxicity. The reason for consideration of other substances is due to the possibility that low level 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. A person exposed to a pesticide at a level that is considered safe may in fact experience harm if that person is also exposed to other substances that cause a common toxic effect by a mechanism common with that of the subject pesticide, even if the individual exposure levels to the other substances are also considered safe.

HED did not perform a cumulative risk assessment as part of this tolerance action for HOE 107892 because HED has not yet initiated a review to determine if there are any other chemical substances that have a mechanism of toxicity common with that of HOE 107892. For purposes of this tolerance action, EPA has assumed that HOE 107892 does not have a common mechanism of toxicity with other substances.

On this basis, the Registrant must submit, upon EPA's request and according to a schedule determined by the Agency, such information as the Agency directs to be submitted in order to evaluate issues related to whether HOE 107892 shares a common mechanism of toxicity with any Page 25 of 26 other substance and, if so, whether any tolerances for HOE 107892. need to be modified or revoked. If HED identifies other substances that share a common mechanism of toxicity with HOE 107892. HED will perform aggregate exposure assessments on each chemical, and will begin to conduct a cumulative risk assessment.

HED has recently developed a framework that it proposes to use for conducting cumulative risk assessments on substances that have a common mechanism of toxicity. This guidance was issued for public comment on January 16, 2002 ( 67 FR 2210 2214) and is available from the OPP Website at: http:// www. epa. gov/ pesticides/ trac/ science/ cumulative_ guidance. pdf. In the guidance, it is stated that a cumulative risk assessment of substances that cause a common toxic effect by a common mechanism will not be conducted until an aggregate exposure assessment of each substance has been completed.

Before undertaking a cumulative risk assessment, HED will follow procedures for identifying chemicals that have a common mechanism of toxicity as set forth in the " Guidance for Identifying Pesticide Chemicals and Other Substances that Have a Common Mechanism of Toxicity" ( 64 FR 5795 5796, February 5, 1999).

7.0 Occupational Exposure ( HED memo of 04/ 12/ 00, M. Collantes, D263518)

7.1 Occupational Handler HOE 107892 ( mefenpyr diethyl) is a safener to be used in a postemergent herbicide.

Workers may be exposed to HOE 107892 during mixing, loading, application and postapplication activities. Based on the proposed application rates and use scenarios, short and intermediateterm exposures may occur. Chronic exposure ( 6 or more months of continuous exposure) is not expected.

On November 24, 1998, the HIARC met and concluded that no dermal or systemic toxicity was observed following 21 repeated dermal applications of HOE 107892 on Wistar rats over 29 days. Therefore, the potential for risk from dermal exposure is negligible and no short or intermediateterm dermal endpoints were selected. Furthermore, HIARC concluded that based on the current use pattern ( i. e., 1 application/ season), long term exposure via the dermal route is not expected and no endpoint was selected for long term dermal exposure.

HIARC also concluded that based on the low acute inhalation toxicity ( Toxicity Category III) and the use pattern ( 1 application/ growing season with either aerial application or spray boom equipment that is as low to the ground as possible), there is minimal concern for potential inhalation exposure and risk. Therefore, the Committee did not select an inhalation endpoint. Since the HIARC did not select dermal or inhalation toxicological endpoints, dermal and inhalation risk assessments were not required.

7.2 Post Application Page 26 of 26 In accordance with the Worker Protection Standards ( WPS), the REI is based on the acute toxicity of the " technical active ingredient material".

However, the acute toxicity effects for HOE 107892 are all in categories III and IV and therefore would require a 12 hour REI if considered as an active ingredient.

8.0 DATA NEEDS There are no data gaps pertaining to toxicity studies.

RAB2 has previously concluded that data gaps pertaining to residue chemistry are as follow:

Multiresidue method testing for parent and metabolites

Animal analytical method ( condition of registration)

A revised Section F to change the proposed tolerances to match the above recommended tolerances.

Attachments: 1. HIARC report on HOE 107892 ( 11/ 24/ 98); 2. FQPA report on HOE 107892 ( 12/ 17/ 98); 3. HED Residue Chemistry memo of 11/ 22/ 02, Y. Donovan, D238730 ; 4 HED DEEM memo of 11/ 22/ 02, Y. Donovan, D286489; 5. EFED memos 03/ 18/ 97, Alex Clem, D226076, and 11/ 26/ 01, Alex Clem, D262735; 6. HED ORE memo of 04/ 12/ 00, M. Collantes, D263518.

cc with Attachments: Y. W. Donovan. cc without Attachments: Pamela Hurley, Margarita Collantes, RAB2 reading file, PP# 7F04850.


[Federal Register Volume 79, Number 152 (Thursday, August 7, 2014)]
[Rules and Regulations]
[Pages 46173-46175]
[FR Doc No: 2014-18659]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 25

[Docket No. FAA-2014-0303; Special Conditions No. 25-561-SC]

Special Conditions: Airbus Model A350-900 Airplane; Operation
Without Normal Electrical Power

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Final special condition; request for comments.

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SUMMARY: These special conditions are issued for the Airbus Model A350-
900 airplane. This airplane will have a novel or unusual design feature
associated with operation without normal electrical power. The
applicable airworthiness regulations do not contain adequate or
appropriate safety standards for this design feature. These special
conditions contain the additional safety standards that the
Administrator considers necessary to establish a level of safety
equivalent to that established by the existing airworthiness standards.

DATES: The effective date of these special conditions is August 7,
2014. We must receive your comments by September 22, 2014.

ADDRESSES: Send comments identified by docket number FAA-2014-0303
using any of the following methods:
     Federal eRegulations Portal: Go to http://www.regulations.gov/ and follow the online instructions for sending
your comments electronically.
    Mail: Send comments to Docket Operations, M-30, U.S. Department of
Transportation (DOT), 1200 New Jersey Avenue SE., Room W12-140, West
Building Ground Floor, Washington, DC, 20590-0001.
    Hand Delivery or Courier: Take comments to Docket Operations in
Room W12-140 of the West Building Ground Floor at 1200 New Jersey
Avenue SE., Washington, DC, between 9 a.m. and 5 p.m., Monday through
Friday, except federal holidays.
    Fax: Fax comments to Docket Operations at<PHONE_NUMBER>.
    Privacy: The FAA will post all comments it receives, without
change, to http://www.regulations.gov/, including any personal
information the commenter provides. Using the search function of the
docket Web site, anyone can find and read the electronic form of all
comments received into any FAA docket, including the name of the
individual sending the comment (or signing the comment for an
association, business, labor union, etc.). DOT's complete Privacy Act
Statement can be found in the Federal Register published on April 11,
2000 (65 FR 19477-19478), as well as at http://DocketsInfo.dot.gov/.
    Docket: Background documents or comments received may be read at
http://www.regulations.gov/ at any time. Follow the online instructions
for accessing the docket or go to the Docket Operations in Room W12-140
of the West Building Ground Floor at 1200 New Jersey Avenue SE.,
Washington, DC, between 9 a.m. and 5 p.m., Monday through Friday,
except federal holidays.

FOR FURTHER INFORMATION CONTACT: Nazih Khaouly, FAA, Airframe and
Flightcrew Interface Branch, ANM-111, Transport Airplane Directorate,
Aircraft Certification Service, 1601 Lind Avenue SW., Renton,
Washington 98057-3356; telephone<PHONE_NUMBER>; facsimile (425) 227-
1320.

SUPPLEMENTARY INFORMATION: The FAA has determined that notice of, and
opportunity for prior public comment on, these special conditions is
impracticable because these procedures would significantly delay
issuance of the design approval and thus delivery of the affected
aircraft. In addition, the substance of these special conditions has
been subject to the public-comment process in several prior instances
with no substantive comments received. The FAA therefore finds that
good cause exists for making these special conditions effective upon
publication in the Federal Register.

Comments Invited

    We invite interested people to take part in this rulemaking by
sending written comments, data, or views. The most helpful comments
reference a specific portion of the special conditions, explain the
reason for any recommended change, and include supporting data.
    We will consider all comments we receive by the closing date for
comments. We may change these special conditions based on the comments
we receive.

Background

    On August 25, 2008, Airbus applied for a type certificate for their
new Model A350-900 airplane. Later, Airbus requested, and the FAA
approved, an extension to the application for FAA type certification to
November 15, 2009. The Model A350-900 airplane has a conventional
layout with twin wing-mounted Rolls-Royce Trent XWB engines. It
features a twin-aisle, 9-abreast, economy-class layout, and
accommodates side-by-side placement of LD-3 containers in the cargo
compartment. The basic Airbus Model A350-900 airplane configuration
will accommodate 315 passengers in a standard two-class arrangement.
The design cruise speed is Mach 0.85 with a maximum take-off weight of
602,000 lbs.
    The Airbus Model A350-900 airplane fly-by-wire control system
requires a continuous source of electrical power to maintain an
operable flight-control system. The current rule, Title 14, Code of
Federal Regulations (14 CFR) 25.1351(d), Amendment 25-72, requires safe
operation under visual flight rules (VFR) conditions for at least five
minutes after loss of all normal electrical power. This rule was
structured around a traditional design utilizing mechanical control
cables for flight control while the crew took time to sort out the
electrical failure, start engine(s) if necessary, and re-establish some
of the electrical-power-generation capability.
    To maintain the same level of safety associated with traditional
designs, Airbus Model A350-900 airplanes must be designed for operation
with the normal sources of engine- or Auxiliary Power Unit (APU)-
generated electrical power inoperative. Service experience has shown
that loss of all electrical power from the airplane's engine and APU-
driven generators is not extremely improbable. Therefore, it must be
shown that the airplane is capable of recovering adequate primary
electrical-power generation for safe flight and landing with the use of
its emergency electrical-power systems. These emergency electrical-
power systems must be able to

power loads that are essential for continued safe flight and landing.

Type Certification Basis

    Under 14 CFR 21.17, Airbus must show that the Airbus Model A350-900
airplane meets the applicable provisions of 14 CFR part 25, as amended
by Amendments 25-1 through 25-129.
    If the Administrator finds that the applicable airworthiness
regulations (i.e., 14 CFR part 25) do not contain adequate or
appropriate safety standards for the Airbus Model A350-900 airplane
because of a novel or unusual design feature, special conditions are
prescribed under Sec.  21.16. These special conditions are an extension
of part 25 due to the inadequacies of the existing part 25 requirements
to address loss of all normal electrical power.
    Special conditions are initially applicable to the model for which
they are issued. Should the type certificate for that model be amended
later to include any other model that incorporates the same novel or
unusual design feature, the special conditions would also apply to the
other model under Sec.  21.101.
    In addition to the applicable airworthiness regulations and special
conditions, the Airbus Model A350-900 airplane must be shown to comply
with the fuel-vent and exhaust-emission requirements of 14 CFR part 34,
and the noise-certification requirements of 14 CFR part 36. The FAA
must issue a finding of regulatory adequacy under section 611 of Public
Law 92-574, the ``Noise Control Act of 1972.''
    The FAA issues special conditions, as defined in 14 CFR 11.19,
under Sec.  11.38, and they become part of the type-certification basis
under Sec.  21.17(a)(2).

Novel or Unusual Design Features

    The Airbus Model A350-900 airplane incorporates the following novel
or unusual design features: The capability of continued safe flight and
landing that are dependent on one or more continuous sources of
electrical power.
    Due to rapid improvements in airplane technology, the applicable
airworthiness regulations do not contain adequate or appropriate safety
standards for these design features. These special conditions for the
Airbus Model A350-900 airplane contain the additional safety standards
that the Administrator considers necessary to establish a level of
safety equivalent to that established by the existing airworthiness
standards.
    In addition to an electronic flight-control system, a number of
systems that have traditionally been mechanically operated have been
implemented as electrically powered systems on the Model A350-900
airplane. The criticality of some of these systems is such that their
failure will either reduce the capability of the airplane or the
ability of the crew to cope with adverse operating conditions, or
prevent continued safe flight and landing of the airplane.

Discussion

    The current rule, 14 CFR 25.1351(d), Amendment 25-72, requires safe
operation under VFR conditions for at least five minutes after loss of
all normal electrical power. This rule was structured around
traditional airplane designs that use mechanical control cables and
linkages for flight control. These manual controls allow the flightcrew
to maintain aerodynamic control of the airplane for an indefinite time
after loss of all electrical power. Under these conditions, the
mechanical flight-control system provides the flightcrew with the
ability to fly the airplane while attempting to identify the cause of
the electrical failure, start the engine(s) if necessary, and
reestablish some of the electrical-power-generation capability, if
possible.
    To maintain the same level of safety associated with traditional
designs, the Airbus Model A350-900 airplane must be designed for
operation with the normal sources of engine- and APU-generated
electrical power inoperative. The FAA has identified electrically
powered functions required to safely complete a maximum ETOPS diversion
as another potential catastrophic effect from the loss of all normal
electrical power. Service history has shown that analytical means have
not been accurate at anticipating common-cause failures, nor have such
means been accurate at predicting that loss of all normal sources of
electrical power is extremely improbable.
    Airbus must demonstrate that the airplane is capable of recovering
adequate primary electrical-power generation during ETOPS, and for
continued safe flight and landing. An alternative source of electrical
power would have to be provided for the time necessary to restore the
minimum power-generation capability necessary during ETOPS, and for
continued safe flight and landing.
    These special conditions contain the additional safety standards
that the Administrator considers necessary to establish a level of
safety equivalent to that established by the existing airworthiness
standards.

Applicability

    As discussed above, these special conditions are applicable to the
Airbus Model A350-900. Should Airbus apply at a later date for a change
to the type certificate to include another model incorporating the same
novel or unusual design feature, the special conditions would apply to
that model as well.

Conclusion

    This action affects only certain novel or unusual design features
on the Airbus Model A350-900 airplane. It is not a rule of general
applicability.

List of Subjects in 14 CFR Part 25

    Aircraft, Aviation safety, Reporting and recordkeeping
requirements.

    The authority citation for these special conditions is as follows:

    Authority: 49 U.S.C. 106(g), 40113, 44701, 44702, 44704.

The Special Conditions

    Accordingly, pursuant to the authority delegated to me by the
Administrator, the following special conditions are issued as part of
the type certification basis for Airbus Model A350-900 airplanes.
    In lieu of the requirements of 14 CFR 25.1351(d) the following
special conditions apply:
    1. The applicant must show by test, or a combination of test and
analysis, that the airplane is capable of continued safe flight and
landing with all normal sources of engine- and APU-generated electrical
power inoperative as prescribed by paragraphs 1.a. and 1.b. below. For
purposes of these special conditions, normal sources of electrical
power generation do not include any alternate power sources such as
batteries, ram-air turbine (RAT), or independent power systems such as
the flight-control permanent magnet generating system. In showing
capability for continued safe flight and landing, consideration must be
given to systems capability, effects on flightcrew workload and
operating conditions, and the physiological needs of the flightcrew and
passengers for the longest diversion time for which approval is sought.
    a. Common mode failures, cascading failures, and zonal physical
threats must be considered in showing compliance with this requirement.
    b. In showing compliance with this requirement, the ability to
restore operation of portions of the electrical-power generation and
distribution system may be considered if it can be shown that
unrecoverable loss of those portions of the system is extremely
improbable. An alternative source of electrical power must be provided
for the time required to restore the minimum electrical-power
generation capability required for continued safe

flight and landing. Unrecoverable loss of all engines may be excluded
when showing that unrecoverable loss of critical portions of the
electrical system is extremely improbable.
    2. Regardless of any electrical generation-and-distribution system-
recovery capability shown under paragraph 1, above, sufficient
electrical-system capability must be provided to--
    a. allow time to descend, with all engines inoperative, at the
speed that provides the best glide distance, from the maximum operating
altitude to the top of the engine-restart envelope, and
    b. subsequently allow multiple start attempts of the engines and
APU. This capability must be provided in addition to the electrical
capability required by existing part 25 requirements related to
operation with all engines inoperative.
    3. The electrical energy the airplane uses in descending with
engines inoperative, from the maximum operating altitude at the best
glide speed, and in making multiple attempts to start the engines and
APU, must be considered when showing compliance with paragraphs 1 and 2
of these special conditions, and with existing 14 CFR part 25
requirements related to continued safe flight and landing.

    Issued in Renton, Washington, on July 23, 2014.
John P. Piccola, Jr.,
Acting Manager, Transport Airplane Directorate, Aircraft Certification
Service.
[FR Doc. 2014-18659 Filed 8-6-14; 8:45 am]
BILLING CODE 4910-13-P


[Federal Register Volume 86, Number 98 (Monday, May 24, 2021)]
[Notices]
[Pages 27905-27907]
[FR Doc No: 2021-10842]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-91921; File No. SR-CboeBZX-2021-023]

Self-Regulatory Organizations; Cboe BZX Exchange, Inc.; Order
Approving a Proposed Rule Change To Extend the Cutoff Time for
Accepting on Close Orders Entered for Participation in the Exchange's
Closing Auction and To Clarify Changes to the Definitions of Late-
Limit-On-Close and Late-Limit-On-Open Orders

May 18, 2021.

I. Introduction

    On March 26, 2021, Cboe BZX Exchange, Inc. (``Cboe BZX'' or
``Exchange'') filed with the Securities and Exchange Commission
(``Commission''), pursuant to Section 19(b)(1) of the Securities
Exchange Act of 1934 (``Act''),\1\ and Rule 19b-4 thereunder,\2\ a
proposed rule change to modify Exchange Rule 11.23 to amend the cutoff
time for accepting on close orders entered for participation in the
Exchange's Closing Auction and to make clarifying changes to the
definitions of Late-Limit-On-Close and Late-Limit-On-Open orders. The
proposed rule change was published for comment in the Federal Register
on April 9, 2021.\3\ The Commission received no comments on the
proposed rule change. This order approves the proposed rule change.
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    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
    \3\ See Securities Exchange Act Release No. 91479 (April 5,
2021), 86 FR 18580 (``Notice'').
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II. Description of the Proposal

    Exchange Rule 11.23(c) currently provides that Users may submit
Limit-on-Close (``LOC'') \4\ and Market-on-Close (``MOC'') \5\ orders
to the Exchange until 3:55 p.m. ET (``Closing Auction Cutoff''), at
which point any additional LOC and MOC orders will be rejected.\6\
Users may submit Late-Limit-on-Close (``LLOC'') \7\ orders between 3:55
p.m.

and 4:00 p.m. and any LLOC orders submitted before 3:55 p.m. or after
4:00 p.m. will be rejected.\8\ Exchange Rule 11.23(c) also provides
that Eligible Auction Orders \9\ designated for the Exchange's Closing
Auction \10\ may not be cancelled between 3:55 p.m. and 4:00 p.m.\11\
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    \4\ Exchange Rule 11.23(a)(13) defines Limit-on-Close as ``. . .
a BZX limit order that is designated for execution only in the
Closing Auction.''
    \5\ Exchange Rule 11.23(a)(15) defines Market-on-Close as ``. .
. a BZX market order that is designated for execution only in the
Closing Auction or Cboe Market Close.''
    \6\ See Exchange Rule 11.23(c)(1)(A).
    \7\ Exchange Rule 11.23(a)(11) defines ``Late-Limit-On-Close''
as ``. . . a BZX limit order that is designated for execution only
in the Closing Auction. To the extent a LLOC bid or offer received
by the Exchange has a limit price that is more aggressive than the
NBB or NBO, the price of such bid or offer is adjusted to be equal
to the NBB or NBO, respectively, at the time of receipt by the
Exchange. Where the NBB or NBO becomes more aggressive, the limit
price of the LLOC bid or offer will be adjusted to the more
aggressive price, only to the extent that the more aggressive price
is not more aggressive than the original User entered limit price.
The limit price will never be adjusted to a less aggressive price.
If there is no NBB or NBO, the LLOC bid or offer, respectively, will
assume its entered limit price.''
    \8\ See Exchange Rule 11.23(c)(1)(A).
    \9\ See Exchange Rule 11.23(a)(8).
    \10\ See Exchange Rule 11.23(c).
    \11\ See Exchange Rule 11.23(c)(1)(B).
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    As described in more detail in the Notice,\12\ the Exchange now
proposes to amend Exchange Rule 11.23(c) to extend the cutoff time for
accepting on close orders to permit the submission of LOC and MOC
orders until 3:59 p.m. ET, to allow the submission of LLOC orders
between 3:59 p.m. and 4:00 p.m. ET, and to prevent the cancellation of
Eligible Auction Orders designated for the Closing Auction between 3:59
p.m. and 4:00 p.m. ET. As proposed, Exchange Rule 11.23(c)(1)(A) would
provide that Users may submit LOC and MOC orders until 3:59 p.m., at
which point any additional LOC and MOC orders submitted would be
rejected. Proposed Exchange Rule 11.23(c)(1)(A) would also provide that
users may submit LLOC orders between 3:59 p.m. and 4:00 p.m., and any
LLOC orders submitted before 3:59 p.m. or after 4:00 p.m. would be
rejected. As proposed, Exchange Rule 11.23(c)(1)(B) would provide that
Eligible Auction Orders designated for the Closing Auction may not be
cancelled between 3:59 p.m. and 4:00 p.m.
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    \12\ See Notice, supra note 3.
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    The Exchange also proposes to amend the definitions of LLOC and
Late-Limit-on-Open (``LLOO'') \13\ in Exchange Rule 11.23(a).
Currently, Exchange Rules 11.23(a)(11) and (a)(12) provide that, to the
extent a LLOC or LLOO bid or offer received by the Exchange has a limit
price that is more aggressive than the National Best Bid (``NBB'') or
National Best Offer (``NBO''), the price of such bid or offer is
adjusted to be equal to the NBB or NBO, respectively, at the time of
receipt by the Exchange. Where the NBB or NBO becomes more aggressive,
the limit price of the LLOC or LLOO bid or offer will be adjusted to
the more aggressive price, only to the extent that the more aggressive
price is not more aggressive than the original User entered limit
price. The limit price will never be adjusted to a less aggressive
price. If there is no NBB or NBO, the LLOC or LLOO bid or offer,
respectively, will assume its entered limit price. The Exchange
proposes to amend these definitions to clarify that, rather than never
be adjusted to a less aggressive price, the limit price of a LLOC order
or a LLOO order would not be adjusted to a less aggressive price,
unless otherwise provided by Exchange rules. The Exchange stated that,
for example, a short sale LLOO or LLOC order entered at a price less
than the NBB while a short sale circuit breaker pursuant to Regulation
SHO was in effect would be re-priced by the Exchange's System \14\ at
one minimum price variation above the NBB pursuant to Exchange Rules
11.9(g)(5) and (6).\15\
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    \13\ Exchange Rule 11.23(a)(12) defines the term Late-Limit-On-
Open as ``. . . a BZX limit order that is designated for execution
only in the Opening Auction. To the extent a LLOO bid or offer
received by the Exchange has a limit price that is more aggressive
than the NBB or NBO, the price of such bid or offer is adjusted to
be equal to the NBB or NBO, respectively, at the time of receipt by
the Exchange. Where the NBB or NBO becomes more aggressive, the
limit price of the LLOO bid or offer will be adjusted to the more
aggressive price, only to the extent that the more aggressive price
is not more aggressive than the original User entered limit price.
The limit price will never be adjusted to a less aggressive price.
If there is no NBB or NBO, the LLOO bid or offer, respectively, will
assume its entered limit price. Notwithstanding the foregoing, a
LLOO order entered during the Quote-Only Period of an IPO will be
converted to a limit order with a limit price equal to the original
User entered limit 137 price and any LLOO orders not executed in
their entirety during the IPO Auction will be cancelled upon
completion of the IPO Auction.''
    \14\ Exchange Rule 1.5(aa) provides that the term ``System''
means ``the electronic communications and trading facility
designated by the Board through which securities orders of Users are
consolidated for ranking, execution and, when applicable, routing
away.''
    \15\ See Notice, supra note 3, at 18581.
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III. Discussion and Commission's Findings

    The Commission has carefully reviewed the proposed rule change and
finds that it is consistent with the requirements of the Act and the
rules and regulations thereunder applicable to a national securities
exchange and, in particular, the requirements of Section 6(b) of the
Act.\16\ Specifically, the Commission finds that the proposal is
consistent with Section 6(b)(5) of the Act,\17\ which requires, among
other things, that a national securities exchange have rules designed
to prevent fraudulent and manipulative acts and practices, to promote
just and equitable principles of trade, to foster cooperation and
coordination with persons engaged in facilitating transactions in
securities, to remove impediments to and perfect the mechanism of a
free and open market and a national market system, and, in general, to
protect investors and the public interest.
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    \16\ 15 U.S.C. 78f. In approving this proposed rule change, the
Commission has considered the proposed rule change's impact on
efficiency, competition, and capital formation. See 15 U.S.C.
78c(f).
    \17\ 15 U.S.C. 78f(b)(5).
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    As discussed above, the Exchange proposes to amend Exchange Rule
11.23(c) to extend the cutoff time for accepting on close orders to
permit the submission of LOC and MOC orders until 3:59 p.m.,\18\ to
allow the submission of LLOC orders between 3:59 p.m. and 4:00
p.m.,\19\ and to prevent the cancellation of Eligible Auction Orders
designated for the Closing Auction between 3:59 p.m. and 4:00 p.m.\20\
The Exchange asserts that extending the Closing Auction Cutoff for
submitting on close orders will assist market participants in managing
their trading at the close by allowing them to retain control over
their orders for a longer period of time.\21\ The Exchange expects that
this would reduce risk for those market participants participating in
the Closing Auction and improve price discovery by facilitating the
additional participation of market participants.\22\ The Commission
believes that extending the cutoff time to submit LOC, MOC and LLOC
orders and to cancel Eligible Auction Orders to 3:59 p.m. ET would
allow market participants to retain flexibility with respect to
submitting and cancelling their orders, while still providing time for
market participants to react to and offset imbalances. As a result, the
Commission believes that the proposal could encourage participation in
the Closing Auction by market participants that are unwilling to give
up flexibility and control over these orders. The Commission notes that
the Exchange has represented that another exchange uses a 3:59 p.m. ET
cutoff time for the entry of MOC and LOC orders in its closing
auction.\23\
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    \18\ See proposed Exchange Rule 11.23(c)(1)(A).
    \19\ Id.
    \20\ See proposed Exchange Rule 11.23(c)(1)(B).
    \21\ See Notice, supra note 3, at 18581.
    \22\ Id. at 18582.
    \23\ Id. at 18581, 18582.
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    In addition, as discussed above, the Exchange proposes to amend the
definitions of LLOC and LLOO in Exchange Rule 11.23(a), which currently
state that the limit price of these orders will never be adjusted to a
less aggressive price, in order to clarify that the limit price of LLOC
and LLOO orders, respectively, would not be adjusted to a less
aggressive price unless otherwise provided by Exchange

rules.\24\ The Exchange has explained that its System, in certain
instances, may adjust the limit price of LLOC and LLOO orders to a less
aggressive price pursuant to other Exchange Rules.\25\ The Commission
believes that the proposed amendments to the definitions of LLOC and
LLOO would provide greater transparency regarding the operation of the
Exchange.
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    \24\ See proposed Exchange Rules 11.23(a)(11) and (a)(12).
    \25\ See supra note 15 and accompanying text.
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IV. Conclusion

    It is therefore ordered, pursuant to Section 19(b)(2) of the
Act,\26\ that the proposed rule change (SR-CboeBZX-2021-023) be, and
hereby is, approved.
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    \26\ 15 U.S.C. 78s(b)(2).

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\27\
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    \27\ 17 CFR 200.300-3(a)(12).
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J. Matthew DeLesDernier,
Assistant Secretary.
[FR Doc. 2021-10842 Filed 5-21-21; 8:45 am]
BILLING CODE 8011-01-P