Page 1 of 24 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM DATE: 03 NOV 2005 SUBJECT: PP#: 4E6834. Novaluron in/ on Brassica, head and stem, subgroup 5A. Health Effects Division ( HED) Risk Assessment. DP#: 313322. PC Code: 124002. Decision#: 353816.

FROM: Sarah J. Levy, M. S., Chemist Mary Clock Rust, Biologist Pramod Terse, Ph. D., Toxicologist Registration Action Branch 1 ( RAB1)/ HED ( 7509C)

THROUGH: P. V. Shah, Ph. D., Branch Senior Scientist RAB1/ HED ( 7509C)

TO: Dan Kenny ( PM Team 01) Registration Division ( RD; 7505C)

The HED of the Office of Pesticide Programs ( OPP) is charged with estimating the risk to human health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and exposure data and conduct dietary, occupational, residential, and aggregate exposure assessments, as needed, to estimate the risk to human health that will result from all registered and proposed uses of novaluron ( N [[[ 3 chloro 4[ 1,1,2 trifluoro 2( trifluoromethoxy) ethoxy] phenyl] amino] carbonyl] 2,6 difluorobenzamide). A summary of the findings and an assessment of human risk resulting from the registered and proposed tolerances for novaluron is provided in this document. The risk assessment, residue chemistry data review, and dietary risk assessment were provided by Sarah Levy ( RAB1), the hazard characterization by Pramod Terse ( RAB1), the occupational/ residential exposure assessment by Mary Clock Rust ( RAB1), and the drinking water assessment by James Hetrick of the Environmental Fate and Effects Division ( EFED).

NOTE: HED completed a Section 3 risk assessment for the use of novaluron in/ on cotton, pome fruit and potato ( Memo, M. Clock Rust, et al., 25 MAR 2004; DP# 295824). This document contains only those aspects of the risk assessment which are affected by the addition of the proposed novaluron use. Page 2 of 24 Recommendation for Tolerances and Registration The HED Hazard Identification Assessment Review Committee ( HIARC) requested a 28 day inhalation toxicity study as a condition of registration. However, based on the low volatility and low inhalation toxicity ( Category IV) of novaluron and inhalation margins of exposure ( MOEs) > 1000 for the proposed uses in this risk assessment, novaluron qualifies for a waiver of the 28 day inhalation toxicity study for the proposed uses [ HED Standard Operating Procedure ( SOP) 2002.01: Guidance: Waiver Criteria for Multiple Exposure Inhalation Toxicity Studies, 15 AUG 2002]. The requirement for the 28 day inhalation toxicity study is waived for this action only. If in the future, requests for new uses or formulations are submitted that may result in a significant change in either the toxicity profile or exposure scenarios, HED will reconsider this data requirement.

Provided Sections B and F are submitted, HED concludes that the toxicological and residue chemistry databases, as well as the aggregate risk assessments, support conditional registration of the requested new uses and establishment of the following permanent tolerance for residues of novaluron per se as follows:

Brassica, head and stem, subgroup 5A . . . . . . . . . . . . . . . . . . . . . . . . . 0.50 ppm HED recommends that conversion of conditional registration to unconditional registration may be considered upon submission of the following residue chemistry data:

° Radiovalidation of the gas chromatography ( GC)/ electron capture detection ( ECD) plant analytical method, using radiolabeled samples from the metabolism studies, in order to determine whether the method adequately extract aged ( weathered) residues of novaluron.

° An interference study is also required to determine whether other pesticides registered on the same commodities interfere with the determination of novaluron; an interference study may be waived if a specific single analyte confirmatory method is submitted. Page 3 of 24 Table of Contents 1.0 EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 4 of 23 2.0 PHYSICAL/ CHEMICAL PROPERTIES CHARACTERIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 9 of 23 3.0 HAZARD CHARACTERIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 10 of 23 3.1 Endocrine Disruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 12 of 23 4.0 EXPOSURE ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 12 of 23 4.1 Summary of Proposed Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 12 of 23 4.2 Dietary Exposure/ Risk Pathway . . . . . . . . . . . . . . . . . . . . . . . . Page 13 of 23 4.3 Water Exposure and Risk Pathway . . . . . . . . . . . . . . . . . . . . . . Page 16 of 23 4.4 Dietary Exposure Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 17 of 23 4.5 Residential Exposure and Risk Pathway . . . . . . . . . . . . . . . . . . Page 18 of 23 5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 18 of 23 6.0 CUMULATIVE RISK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 19 of 23 7.0 OCCUPATIONAL EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 19 of 23 7.1 Occupational Handler . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 19 of 23 7.2 Occupational Postapplication . . . . . . . . . . . . . . . . . . . . . . . . . . Page 21 of 23 7.3 Incident Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 22 of 23 8.0 DATA NEEDS/ LABEL REQUIREMENTS . . . . . . . . . . . . . . . . . . . . . Page 23 of 23 8.1 Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 23 of 23 8.2 Residue Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 23 of 23 8.3 Occupational/ Residential Exposure . . . . . . . . . . . . . . . . . . . . . . Page 23 of 23 Page 4 of 24 1.0 EXECUTIVE SUMMARY Under Section 3 of the Federal Insecticide, Fungicide and Rodenticide Act ( FIFRA), as amended, Makhteshim Agan of North America ( MANA), Inc. has applied for registration of the active insecticidal ingredient novaluron for use on Brassica, head and stem, subgroup 5A. Novaluron is currently registered for use on cotton; pome fruit; Vegetables, tuberous and corm, group 1C; and greenhouse/ shadehouse grown ornamental plants. Novaluron tolerances have been established in 40 CFR § 180.598 for plant and livestock commodities and are expressed in terms of novaluron per se. All uses for novaluron, either proposed or existing, are agricultural or commercial in nature. No residential uses are proposed, nor are any of the uses expected to result in recreational exposure.

Novaluron, a benzoylphenyl urea compound, is a pesticide chemical belonging to the class of insecticides called insect growth regulators. Novaluron slowly kills the insects over a period of a few days by disrupting cuticle formation and deposition causing insect mortality during molting. This memorandum serves as HED's estimate of exposure and risk resulting from the proposed uses.

Hazard Characterization The toxicological database for novaluron is adequate to support Section 3 registration and permanent tolerances.

Novaluron has low acute toxicity via the oral ( Toxicity Category IV), dermal ( Toxicity Category III) and inhalation routes ( Toxicity Category IV). No ocular ( Toxicity Category IV) or dermal irritation ( Toxicity Category IV) was noted. Novaluron is not a dermal sensitizer.

In subchronic and chronic toxicity studies, novaluron primarily produced hematotoxic effects such as methemoglobinemia, decreased hemoglobin, decreased hematocrit, decreased red blood corpuscles ( RBCs or erythrocytes) associated with increased erythropoiesis.

The rat and rabbit developmental toxicity studies were tested up to the limit doses that produced no maternal and/ or developmental toxicity. In the two generation reproductive toxicity study, both maternal and offspring toxicity were evidenced by spleenomegaly, whereas reproductive toxicity was observed only in males as evidenced by decreases in epididymal sperm counts and increased age at preputial separation in the F 1 generation.

Acute/ subchronic neurotoxicity screening batteries were performed using novaluron in rats. Neurotoxic effects of novaluron were evidenced by clinical signs ( piloerection, fast/ irregular breathing), functional observation battery ( FOB) parameters ( head swaying, abnormal gait) and neuropathology ( sciatic and tibial nerve degeneration only at limit dose ( 2000 mg/ kg/ day). No signs of neurotoxicity or neuropathology were observed in the subchronic neurotoxicity study in rats at doses up to 1752 mg/ kg/ day in males and 2000 mg/ kg/ day in females. Therefore, HED's Page 5 of 24 HIARC concluded that there is not a concern for neurotoxicity resulting from exposure to novaluron.

There was no concern for mutagenic activity as indicated by several mutagenicity studies such as a bacterial ( Salmonella, E. coli) reverse mutation assay, an in vitro mammalian chromosomal aberration assay, an in vivo mouse bone marrow micronucleus assay and bacterial DNA damage or repair assay. There was no evidence of carcinogenic potential in either the rat or mouse carcinogenicity studies. Therefore, novaluron was classified as " not likely to be carcinogenic to humans."

Dose Response and Endpoint Selection The oral acute reference dose ( aRfD) for the general population, including infants and children, was not established since an endpoint of concern attributable to a single dose was not identified. The chronic reference dose ( cRfD) of 0.011 mg/ kg/ day was determined on the basis of the chronic carcinogenicity study in rat. An uncertainty factor ( UF) of 100 ( 10 fold for interspecies extrapolation and 10 fold for intraspecies variability) was applied to the no observed adverseeffect level ( NOAEL) of 1.1 mg/ kg/ day to derive the cRfD. The lowest observed adverse effectlevel ( LOAEL) of 30.6 mg/ kg/ day was based on evidence of RBC damage and turnover resulting in a regenerative anemia. The Food Quality Protection Act ( FQPA) Safety Factor ( SF) of 1X is applicable for chronic dietary risk assessment. Therefore, the cPAD is 0.011 mg/ kg/ day.

In accordance with the EPA Draft Guidelines for Carcinogen Risk Assessment ( JUL 1999), novaluron is classified as " not likely to be carcinogenic to humans" based on the lack of evidence for carcinogenicity in mice and rats.

The HIARC concluded that no special FQPA SF is needed ( i. e., 1X) since there are no residual uncertainties for pre and/ or post natal toxicity. The decision was based on a lack of increased susceptibility in the rat and/ or rabbit developmental toxicity studies at levels up to the limit dose. Also, no increased qualitative and/ or quantitative evidence of increased susceptibility was found following pre/ post natal exposure in a 2 generation reproduction study in rats.

HIARC met on 16 DEC 2003 to select endpoints for risk assessment and to evaluate the potential for increased susceptibility of infants and children from exposure to novaluron according to the FEB 2002 OPP 10X guidance document. This was a re evaluation of the toxicology database subsequent to the initial evaluation by the HIARC on 07 JUN 2001 ( TXR# 014682). The special FQPA SF was reduced to 1X based on toxicological considerations by the HIARC ( 16 DEC 2003; TXR # 0052361), the conservative residue assumptions used in the dietary and residential exposure risk assessments, and the completeness of the residue chemistry and conservative drinking water assessment evaluated by the risk assessment team. Page 6 of 24 A 10% dermal absorption factor was based on an acceptable dermal absorption study in rats in which the maximum total absorbed dose ( expressed as percent of administered dose) ranged from approximately 0.5% to 10% of the applied dose. The level of concern ( LOC) for residential dermal exposures and occupational dermal and inhalation exposures are for MOEs < 100. Endpoints applicable to risk assessments performed for novaluron in this document are summarized in the table below.

Exposure Scenario Dose Endpoint Study/ Effect Chronic dietary NOAEL = 1.1 mg/ kg/ day cRfD and cPAD = 0.011 mg/ kg/ day Combined chronic toxicity/ carcinogenicity feeding study rat Erythrocyte damage and turnover resulting in a regenerative anemia at the LOAEL of 30.6 mg/ kg/ day.

Intermediate term dermal ( 10% absorption rate) NOAEL = 4.38 mg/ kg/ day Target MOE = 100 ( residential and occupational) 90 day feeding study rat clinical chemistry and histopathology at the LOAEL of 8.64 mg/ kg/ day Short term inhalation Intermediate term inhalation Residues of Concern The HED Metabolism Assessment and Review Committee ( MARC) concluded that for tolerance and risk assessment purposes, novaluron per se is the only residue of concern in plant and livestock matrices, and rotational crops. In drinking water, the MARC concluded that parent and degradates chlorophenyl urea ( 1[ 3 chloro 4( 1,1,2 trifluoro 2 trifluoromethoxyethoxy) phenyl] urea) and chloroaniline ( 3 chloro 4( 1,1,2 trifluoro 2 trifluoromethoxyethoxy) aniline) are the residues of concern for risk assessment purposes.

Chronic Dietary Exposure Estimates A chronic dietary risk assessment was conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database ( DEEM FCID   , Version 2.03). The chronic dietary assessment conducted, was an update of the previous dietary assessment conducted in 2004; i. e., the current commodities associated with this petition were added at the HED recommended tolerance level to the last dietary assessment. Estimated drinking water concentrations ( EDWCs), provided by EFED, were included in this assessment as well. In the last dietary assessment, the chronic analysis assumed 100% crop treated for all commodities; incorporated average field trial residues; empirical processing factors for apple juice ( translated to pear juice); and DEEM   ( ver 7.76) default processing factors for the remaining processed commodities. Furthermore, anticipated residues ( ARs) were calculated for meat and milk commodities and HED recommended tolerances were used for poultry commodities ( partially refined, Tier 2 analysis). For this action, the resulting food exposure estimates were less than HED's level of concern (# 71% cPAD); children 1 2 years old were the most highly exposed population subgroup. The chronic analysis could be further refined through the following: use of anticipated market share data for the proposed commodities, % crop treated data for registered Page 7 of 24 commodities; preparation/ cooking factors; and/ or ARs for poultry commodities and commodities associated with Brassica, head and stem, subgroup 5A.

Drinking Water Estimates Concentrations of novaluron and its chlorophenyl urea and chloroaniline degradates in surface water and ground water were estimated by EFED using modeling. Tier 2 Pesticide Root Zone Model/ Exposure Analysis Modeling System ( PRZM/ EXAMS) modeling was performed to estimate drinking water concentrations for novaluron ( parent) in surface water. Tier 1 modeling ( FQPA Index Reservoir Screening Tool ( FIRST)) was used to estimate concentrations of the chlorophenyl urea and chloroaniline degradates in surface water. For groundwater, the Screening Concentration in Ground Water ( SCI GROW) model was used to predict groundwater concentrations for novaluron and the chlorophenyl urea and chloroaniline degradates.

Drinking water estimates from EFED are meant to represent upper bound estimates of the concentrations that might be found in surface water and groundwater based upon existing and proposed uses. Chronic estimates for the terminal degradate, chloroaniline, are the highest ( 2.61 ppb). This is consistent with the expected degradation pattern for novaluron. Therefore, the EDWC value for chloroaniline was used to assess chronic aggregate risk.

Aggregate Exposure Scenarios and Risk Conclusions Including all existing and proposed uses, human health risk assessments have been conducted for the following exposure scenario only: chronic dietary exposures ( food + water). The chronic aggregate exposure and risk estimate is below HED's level of concern. Because there are no uses of novaluron that could result in residential exposures, this aggregate risk assessment takes into consideration dietary food + water exposure only.

Occupational Exposure Estimates Handler: Based on the proposed use patterns, HED expects the most highly exposed occupational pesticide handlers are likely to be mixer/ loaders using open pour of liquids for aerial and groundboom application and applicators using open cab groundboom or aerial spray equipment. HED performed an assessment of these exposure scenarios. All occupational handler risk estimates are below HED's level of concern ( MOE> 100) provided workers wear protective gloves when handling novaluron.

Post Application: There is a potential for post application exposure to workers from pesticides during the course of typical agricultural activities. For the current action, intermediate term postapplication dermal exposure was assessed using conservative assumptions for the proposed uses. Post application inhalation exposure is considered to be negligible. Page 8 of 24 To make a conservative estimate of post application exposure based on the proposed crop uses, HED chose hand harvesting Brassica with a transfer coefficient ( TC) of 5,000 cm2/ hr. The resulting intermediate term dermal MOE of 440 does not exceed HED's level of concern.

Restricted Entry Interval ( REI): The proposed Diamond 0.83 ( head and stem Brassica) label carries a 12 hour REI. Novaluron falls into Category IV for acute dermal toxicity, primary eye irritation and primary skin irritation. Therefore, an interim worker protection standard ( WPS) REI of 12 hours is adequate to protect agricultural workers from post application exposures to novaluron.

Recommendation for Tolerances and Registration The HED HIARC requested a 28 day inhalation toxicity study as a condition of registration. However, based on the low volatility and low inhalation toxicity ( Category IV) of novaluron and inhalation MOEs > 1000 for the proposed uses in this risk assessment, novaluron qualifies for a waiver of the 28 day inhalation toxicity study for the proposed uses [ HED SOP 2002.01: Guidance: Waiver Criteria for Multiple Exposure Inhalation Toxicity Studies, 15 AUG 2002]. The requirement for the 28 day inhalation toxicity study is waived for this action only. If in the future, requests for new uses or formulations are submitted that may result in a significant change in either the toxicity profile or exposure scenarios, HED will reconsider this data requirement.

Provided Sections B and F are submitted, HED concludes that the toxicological and residue chemistry databases, as well as the aggregate risk assessments, support conditional registration of the requested new uses and establishment of the following permanent tolerance for residues of novaluron per se as follows:

Brassica, head and stem, subgroup 5A . . . . . . . . . . . . . . . . . . . . . . . . . 0.50 ppm HED recommends that conversion of conditional registration to unconditional registration may be considered upon submission of the following residue chemistry data:

° Radiovalidation of the GC/ ECD plant analytical method, using radiolabeled samples from the metabolism studies, in order to determine whether the method adequately extract aged ( weathered) residues of novaluron.

° An interference study is also required to determine whether other pesticides registered on the same commodities interfere with the determination of novaluron; an interference study may be waived if a specific single analyte confirmatory method is submitted. Page 9 of 24 O N H N H O F F Cl O O CF 3 F F F 2.0 PHYSICAL/ CHEMICAL PROPERTIES CHARACTERIZATION The review of product chemistry data associated with this petition is under the purview of RD. All applicable product chemistry data requirements must be met for a Section 3 registration of the proposed use of novaluron on Brassica, head and stem, subgroup 5A.

Table 1. Novaluron Nomenclature.

Compound Chemical Structure Common name Novaluron Trade name RimOn Technical IUPAC name 1[ 3 chloro 4( 1,1,2 trifluoro 2 trifluoromethoxyethoxy) phenyl] 3[ 2,6 difluorobenzoyl] urea CAS name N[[[ 3 chloro 4[ 1,1,2 trifluoro 2( trifluoromethoxy) ethoxy] phenyl] amino] carbonyl] 2,6 difluorobenzamide CAS # 116714 46 6 End use product/ EP1 RimOn 7.5 WG Insecticide ( EPA Reg. No. 66222 57) RimOn 0.83 EC Insecticide ( EPA Reg. No. 66222 35) Diamond 0.83 EC Insecticide ( EPA Reg. No. 66222 35)

1 Note to RD: The novaluron labels RimOn 0.83 EC and Diamond 0.83 EC have different trade names, but the same registration numbers.

Table 2. Physicochemical Properties of the Technical Grade of Novaluron.

Parameter Value Reference ( MRID)

Melting point/ range 176.5  178.0 ° C 44961006 pH 6.5 44961005 Density 1.56 g/ cm3 at 22 ° C 44961006 Water solubility 3 : g/ L at 20 ° C 44961005 44961006 Solvent solubility ( at 25 ° C) 8.39 mg/ L in n heptane 1.88 g/ L in xylene 14.5 g/ L in methanol 198 g/ L in acetone 113 g/ L in ethyl acetate 0.98 g/ L in n octanol Vapor pressure ( mm Hg) 1.2 x 10 7 44961006 Dissociation constant, pKa Not determined due to low water solubility 44961006 Octanol/ water partition coefficient, Log( KOW) 4.3 at 25 ° C 44961006 Table 2. Physicochemical Properties of the Technical Grade of Novaluron.

Parameter Value Reference ( MRID)

Page 10 of 24 UV/ visible absorption spectrum Molar absorption coefficients of at 3 maximum absorbances: 15,400 L/ mol C cm at 253 µ m ( neutral) 9,780 L/ mol C cm at 253 µ m ( acidic) 20,500 L/ mol C cm at 263 µ m ( basic) 44961006 3.0 HAZARD CHARACTERIZATION A detailed hazard characterization for novaluron is presented in HED's previous risk assessment ( Memo, M. Clock Rust, et al., 25 MAR 2004 ; DP # 295824). The doses and toxicological endpoints selected for various exposure scenarios applicable to this risk assessment are summarized in Table 3.

Table 3. Summary of Toxicological Dose and Endpoints for Novaluron.

Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern ( LOC) for Risk Assessment Study and Toxicological Effects Acute Dietary Not applicable None An endpoint of concern attributable to a single dose was not identified. An acute RfD was not established.

Chronic Dietary ( all populations) NOAEL= 1.1 mg/ kg/ day UF = 100 Chronic RfD = 0.011 mg/ kg/ day FQPA SF = 1X cPAD = chronic RfD FQPA SF = 0.011 mg/ kg/ day Combined chronic toxicity/ carcinogenicity feeding in rat LOAEL = 30.6 mg/ kg/ day based on erythrocyte damage and turnover resulting in a regenerative anemia.

Short Term Incidental Oral ( 1 30 days) NOAEL= 4.38 mg/ kg/ day Residential LOC for MOE = 100 Occupational LOC for MOE = 100 90 day feeding study in rat LOAEL = 8.64 mg/ kg/ day based on clinical chemistry ( decreased hemoglobin, hematocrit and RBC counts) and histopathology ( increased hematopoiesis and hemosiderosis in spleen and liver).

Intermediate Term Incidental Oral ( 1 6 months) NOAEL= 4.38 mg/ kg/ day Residential LOC for MOE = 100 Occupational LOC for MOE = 100 90 day feeding study in rat LOAEL = 8.64 mg/ kg/ day based on clinical chemistry ( decreased hemoglobin, hematocrit and RBC counts) and histopathology ( increased hematopoiesis and hemosiderosis in spleen and liver). Table 3. Summary of Toxicological Dose and Endpoints for Novaluron.

Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern ( LOC) for Risk Assessment Study and Toxicological Effects Page 11 of 24 Short Term Dermal ( 1 30 days) Not applicable None No toxicity observed at the limit dose in dermal study and there were no developmental toxicity concerns at the limit dose; therefore, quantification of short term dermal risk is not necessary.

Intermediate Term Dermal ( 1 6 months) Oral NOAEL = 4.38 mg/ kg/ day ( dermal absorption rate = 10%) Residential LOC for MOE = 100 Occupational LOC for MOE = 100 90 day feeding study in rat LOAEL = 8.64 mg/ kg/ day based on clinical chemistry ( decreased hemoglobin, hematocrit and RBC counts) and histopathology ( increased hematopoiesis and hemosiderosis in spleen and liver).

Long Term Dermal (> 6 months) Oral NOAEL= 1.1 mg/ kg/ day ( dermal absorption rate = 10 %) Residential LOC for MOE = 100 Occupational LOC for MOE = 100 Combined chronic toxicity/ carcinogenicity feeding in rat LOAEL = 30.6 mg/ kg/ day based on erythrocyte damage and turnover resulting in a regenerative anemia.

Short Term Inhalation ( 1 30 days) Oral NOAEL = 4.38 mg/ kg/ day ( inhalation absorption rate = 100%) Residential LOC for MOE = 100 Occupational LOC for MOE = 100 90 day feeding study in rat LOAEL = 8.64 mg/ kg/ day based on clinical chemistry ( decreased hemoglobin, hematocrit and RBC counts) and histopathology ( increased hematopoiesis and hemosiderosis in spleen and liver).

Intermediate Term Inhalation ( 1 6 months) Oral NOAEL = 4.38 mg/ kg/ day ( inhalation absorption rate = 100%) Residential LOC for MOE = 100 Occupational LOC for MOE = 100 90 day feeding study in rat LOAEL = 8.64 mg/ kg/ day based on clinical chemistry ( decreased hemoglobin, hematocrit and RBC counts) and histopathology ( increased hematopoiesis and hemosiderosis in spleen and liver).

Long Term Inhalation (> 6 months) Oral NOAEL= 1.1 mg/ kg/ day ( inhalation absorption rate = 100%) Residential LOC for MOE = 100 Occupational LOC for MOE = 100 Combined chronic toxicity/ carcinogenicity feeding in rat LOAEL = 30.6 mg/ kg/ day based on erythrocyte damage and turnover resulting in a regenerative anemia.

Cancer Not likely to be carcinogenic to humans Page 12 of 24 UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose ( a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable Page 13 of 24 3.1 Endocrine Disruption EPA is required under the Federal Food Drug and Cosmetic Act ( FFDCA), 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 was 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 has 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, novaluron may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption.

4.0 EXPOSURE ASSESSMENT References: residue chemistry summary  Memo, S. Levy, 03 NOV 2005; DP# 322978 dietary exposure analysis  Memo, S. Levy, 03 NOV 2005; DP# 322553 drinking water summary  Memo, I. Maher, 11 FEB 2004; no DP Barcode and electronic correspondence, J. Hetrick to M. Rust, 03 OCT 2005 4.1 Summary of Proposed Uses The petitioner provided a copy of the product label Diamond EC Insecticide formulation( 0.83 lb ai/ gal, EPA Reg. No. 66222 35); see Table 4 below. ( Note to RD: The novaluron labels RimOn 0.83 EC ( 0.83 lb ai/ gal, EPA File Symbol 66222 35) and Diamond 0.83 EC have different trade names, but the same registration numbers.) A summary of the proposed uses of novaluron on head and stem Brassica vegetables is presented in Table 4. Page 14 of 24 Table 4. Summary of Novaluron End Use Products Associated with the Subject Petitions.

Trade Name Reg. No. ai (% of formulation) Formulation Type Target Crops Target Pests Label Version Diamond 0.83 EC1 ( Novaluron 10 EC2) 66222 35 10% ( 0.83 lb/ gal) EC Head and Stem Brassica Vegetables Foliar feeding insects such as alfalfa and cabbage loopers, armyworm, cabbage webworm, corn earworm, cucumber beetles, cutworm species, diamondback moth, imported cabbageworm, lepidopterian and dipteran leafminer, leafhopper species, lygus bugs, flea beetles, onion thrips, southern cabbageworm, stink bugs, thrips, vegetable weevil, whitefly Label copyright date of 2004 1 Crompton Corporation ( alternate brand name) 2 MANA Table 5. Summary of Directions for Proposed Uses of Novaluron.

Trade Name Applic. Timing, Type, and Equip. Applic. Rate ( lb ai/ A) Max. No. Applic. per Season Max. Seasonal Applic. Rate ( lb ai/ A) PHI1 ( days) Use Directions and Limitations Head and Stem Brassica Vegetables Diamond 0.83 EC ( Novaluron 10 EC) Application should be made when majority of population is at egg hatch to second instar.

Ground and air application 0.06 0.078 3 0.15 7 Applications may be made using ground equipment ( minimum of 10 gal/ A) or aerial ( minimum of 2 gal/ A) with a 7 to 14 day retreatment interval ( RTI).

1 PHI= pre harvest interval 4.2 Dietary Exposure/ Risk Pathway Nature of the Residue  Plants: Adequate metabolism studies for novaluron are available on apples, cabbage, cotton, and potatoes. These studies indicate that novaluron is not extensively metabolized in these crops. The parent compound, novaluron, was either the only residue component identified or was the predominant residue component in all analyzed plant matrices. The reviewed studies also indicate novaluron, when foliarly applied during the vegetative growth stage, is not readily translocated to mature apple fruit, potato tubers or cottonseed ( Memo, G. Kramer, 22 MAR 2004; DP# 285474). Based on these studies, the MARC determined that the residue of concern in crops for purposes of tolerance enforcement and risk assessment is novaluron per se ( Memo, G. Kramer et al., 03 FEB 2004; DP# 297646). Page 15 of 24 Nature of the Residue  Livestock: HED also previously concluded that the nature of the residue in livestock is adequately understood based on the submitted goat and poultry metabolism studies ( Memo, G. Kramer, 22 MAR 2004; DP# 285474). The HED MARC determined that the residue of concern in livestock for purposes of tolerance enforcement and risk assessment is novaluron per se ( Memo, G. Kramer et al., 03 FEB 2004; DP# 297646).

Residue Analytical Enforcement Method  Plant: MANA previously submitted a GC/ ECD residue analytical method for the analysis of novaluron residues in/ on pome fruit, cabbage, and potato commodities; HED concluded that the method was adequate for gathering data on novaluron. The method was adequately validated by the petitioner and by an independent laboratory. HED also concluded that the method may be used for tolerance enforcement pending completion of a successful petition method validation ( PMV) by the Analytical Chemistry Branch ( ACB)/ Biological and Economics Analysis Division ( BEAD) and provided radiovalidation and interference studies are submitted by the petitioner ( Memo, G. Kramer, 22 MAR 2004; DP# 285474).

ACB concluded that based upon review of the submitted method validation data, without laboratory validation, the GC/ ECD residue analytical method appears to be suitable for food tolerance enforcement in plants ( apples, cabbage, potatoes). ACB recommended that the analytical method met the general requirements of the Residue Chemistry Test Guidelines, 860.1340 for residue analytical methods to enforce tolerances. Furthermore, based on ACB's review of the data, without EPA laboratory validation, the petitioner has provided evidence of successful ILVs for the method. Since the petitioner has provided adequate method validation data and the independent laboratories found no significant method deficiencies during the ILVs, ACB recommended that the analytical methods do not need to be laboratory validated by EPA ( Memo, S. Levy, 15 SEP 2004; DP# 306998). This method was sent to the Food and Drug Administration ( FDA) to be published in the Pesticide Analytical Manual, volume II ( PAM II) as a Letter Method ( Memo, S. Levy, 15 SEP 2004; DP# 307595). Radiovalidation of the GC/ ECD method is still required, using radiolabeled samples from the metabolism studies, in order to determine whether the method adequately extract aged ( weathered) residues of novaluron. An interference study is still required to determine whether other pesticides registered on the same commodities interfere with the determination of novaluron; an interference study may be waived if a specific single analyte confirmatory method is submitted.

Magnitude of the Residue  Plants: The following paragraphs are summaries of the residue data submitted in support of this request.

Head and Stem Brassica: MANA and Crompton Corporation have submitted field trial data depicting the magnitude of the residue of novaluron in/ on head/ stem Brassica vegetables ( cabbage and broccoli). Twelve field trials were conducted, six each for cabbage and broccoli, in the United States during the 2002 growing season. Cabbage trials were located in EPA Regions 1 ( PA), 2 ( GA), 3 ( FL), 5 ( IL), 6 ( TX), and 10 ( CA). Broccoli trials were located in EPA Regions Page 16 of 24 6 ( TX), 10 ( CA, 4 trials), and 12 ( OR). The number and locations of field trials are in accordance with OPPTS Guideline 860.1500. At each trial location, Novaluron 10 EC ( 0.834 lb ai/ gallon) formulation was applied three times to cabbage and broccoli plants using ground spray application equipment. The RTI was 5 8 days, beginning at 19 to 22 days prior to normal harvest and ending 7 to 8 days prior to normal harvest. The application rates were 0.048 0.052 lb ai/ A ( for cabbage) and 0.049 to 0.052 lb a. i./ A ( for broccoli) applied in 30 37 GPA. An adjuvant ( crop oil concentrate ( COC)) was added to the spray mixture for all applications at a nominal rate of 1% v/ v.

The results from these trials show that the maximum novaluron residues in/ on cabbage with wrapper leaves and without wrapper leaves were 0.481 and < 0.051 ppm, from samples treated at 0.149 to 0.154 lb a. i./ A/ season ( 1x application rate), and with 6 8 day RTIs and 7 8 day PHIs. The results from the broccoli trials show that the maximum residues of novaluron in/ on broccoli were 0.379 ppm from samples treated at 0.149 to 0.153 lb a. i./ A/ season ( 1x application rate), and with 5 7 days RTIs and 7 8 day PHIs. Residue decline data from cabbage and broccoli show that novaluron residues decline slightly with increasing PHIs. HED concludes that the cabbage and broccoli data support the proposed use on Brassica, head and stem, subgroup 5A and a tolerance level of 0.50 ppm.

Processed Food and Feed: There are no processed food/ feed items associated with head and stem Brassica vegetables; therefore, a discussion of processed food/ feed is not germane to this petition.

Confined/ Field Accumulation in Rotational Crops: HED previously concluded that the appropriate plant back interval ( PBI) for all non labeled crops is 30 days. Furthermore, the petitioner was requested to submit a revised Section B indicating that only registered crops may be rotated to a treated field within 30 days of the final application ( Memo, G. Kramer, 22 MAR 2004; DP# 285474). This requirement was not included on the Diamond EC label; this is a deficiency. A field accumulation study in rotational crops has not been submitted. Provided the petitioner submits a revised Section B for the Diamond EC label indicating that only registered crops may be rotated to a treated field within 30 days of the final application, a field accumulation study was not be required for this petition.

Tolerance Summary: Permanent tolerances for novaluron have been established for a variety of commodities under 40 CFR § 180.598. There are currently no established Codex, Canadian, or Mexican maximum residue limits ( MRLs) for novaluron. The appropriate tolerance level was calculated using the methodology formulated by the NAFTA MRL/ Tolerance Harmonization Workgroup for calculating statistically based pesticide tolerances for plant commodities based on field trial residue data. Below in Table 6 is the proposed and HED recommended tolerance summary for novaluron. Page 17 of 24 Table 6. Tolerance Summary for Novaluron.

Commodity Proposed Tolerance ( ppm) HED Recommended Tolerance ( ppm) Comments ( correct commodity definition)

Brassica, head and stem, subgroup 5A 0.5 0.5 Brassica, head and stem, subgroup 5A 4.3 Water Exposure and Risk Pathway The following information concerning the environmental fate and drinking water assessment of novaluron was provided by EFED ( Memo, M. Janson, et al., 06 MAY 2005; DP# 307166 and electronic correspondence, J. Hetrick to M. Rust, 03 OCT 2005). At the present time, surface and ground water monitoring data are not available for novaluron.

The HED MARC concluded that parent and the chlorophenyl urea and chloroaniline degradates are residues of potential concern to be included in the drinking water assessment.

Modeling and Drinking Water Estimates Monitoring data for novaluron, chlorophenyl urea and chloroaniline in surface water and ground water were not found. Novaluron is not included in the USGS National Water Quality Assessment ( NAWQA) Program, the Pesticides in Ground Water Database ( USEPA, 1992), and it was not an analyte in the National Pesticide Survey ( USEPA, 1990). Monitoring data are not available for novaluron or its chlorophenyl urea and chloroaniline degradates, in surface water or ground water. Concentrations in surface water and ground water were estimated using modeling.

Tier 2 PRZM/ EXAMS modeling was performed to estimate drinking water concentrations for surface water for novaluron per se. The scenarios were selected to provide high end drinking water concentrations for each crop and represent the geographic locations where the specific crops are grown in large quantities.

The most conservative estimates were obtained for airblast applications to Pennsylvania apples at the maximum annual application rate of 0.96 lb a. i./ acre, applied three times at 0.32 lb a. i./ acre with an interval between applications of ten days.

For surface water, the 1 in 10 year annual mean EDWC for the parent novaluron is 1.8 : g/ L ( ppb).

A Tier I drinking water analysis was performed for the chlorophenyl urea and chloroaniline degradates. The FIRST model was used to obtain surface water estimates. As a conservative assumption, the model assumed chlorophenyl urea was directly applied, i. e., as granular, to the field, assuming no spray drift and no foliar interception. The FIRST model estimates a peak and an annual average value based on the Index Reservoir scenario. Page 18 of 24 For surface water, the annual average EDWC for chlorophenyl urea is 0.86 : g/ L ( ppb) and the annual average EDWC for chloroaniline is 2.6 : g/ L ( ppb). Both of these estimates are based upon the maximum application rate in apples.

For groundwater, the SCI GROW model was used to predict a groundwater concentration for novaluron at the annual application rate of 0.96 lb a. i./ acre ( i. e., three applications of 0.32 lb a. i./ acre). The estimate for the parent novaluron is 5.5 x 10 3 : g/ L in drinking water from shallow ground water sources. For the chlorophenyl urea degradate, the predicted ground water concentration is 4.5 x 10 3 : g/ L, and for the chloroaniline degradate the concentration is 9.0 x 10 3 : g/ L. These concentrations were estimated with the same assumptions used for surface water modeling, and may be considered as both the peak and annual average upper bound exposures.

These EDWC values are meant to represent upper bound estimates of the concentrations that might be found in surface water and groundwater based upon existing and proposed uses. Of the three EDWC values, chronic estimates for the terminal metabolite, chloroaniline are the highest ( 100% conversion from parent to aniline was assumed). This is consistent with the expected degradation pattern for novaluron. Therefore, the EDWC value for the chloroaniline degradate ( 2.6 ppb) was used to assess chronic aggregate risk.

4.4 Dietary Exposure Analysis A chronic dietary risk assessment was conducted using the DEEM FCID   ( ver. 2.03) model which uses food consumption data from the USDA's CSFII from 1994 1996 and 1998. An acute dietary assessment was not conducted for novaluron because an endpoint of concern attributable to a single dose was not identified. A cancer dietary assessment was not conducted because novaluron was classified as " not likely to be carcinogenic to humans."

The current chronic dietary assessment is an update of the previous dietary assessment conducted in 2004 ( i. e., the current commodities associated with this petition were added at the HEDrecommended tolerance level to the last dietary assessment.) Furthermore, drinking water was incorporated directly in the dietary assessment using the average annual concentration. In the last dietary assessment, the chronic analysis assumed 100% crop treated for all commodities; incorporated average field trial residues; empirical processing factors for apple juice ( translated to pear juice); and DEEM   ( ver 7.76) default processing factors for the remaining processed commodities. Furthermore, ARs were calculated for meat and milk commodities and recommended tolerances were used for poultry commodities ( partially refined, Tier 2 analysis). The resulting chronic dietary risk estimate ( food + water) was less than HED's levels of concern (< 100% cPAD; see Table 7). Page 19 of 24 Table 7. Summary of Dietary Exposure and Risk for Novaluron.

Population Subgroup Chronic Dietary Dietary Exposure ( mg/ kg/ day) % cPAD General U. S. Population 0.002158 20 All Infants (< 1 year old) 0.003662 33 Children 1 2 years old 0.007778 71 Children 3 5 years old 0.005948 54 Children 6 12 years old 0.003577 33 Youth 13 19 years old 0.001866 17 Females 13 49 years old 0.001418 13 Adults 20 49 years old 0.001516 14 Adults 50+ years old 0.001348 12 4.5 Residential Exposure and Risk Pathway All uses for novaluron, either proposed or existing, are agricultural or commercial in nature. No residential uses are proposed, nor are any of the uses expected to result in recreational exposure. Therefore, a residential exposure assessment was not performed for this action.

5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION Including all existing and proposed uses, human health risk assessments have been conducted for the following exposure scenario: chronic dietary exposures ( food + water only). The chronic dietary exposure and risk estimate is below HED's level of concern. An acute dietary assessment was not conducted for novaluron because an endpoint of concern attributable to a single dose was not identified. A cancer dietary assessment was not conducted because novaluron was classified as " not likely to be carcinogenic to humans."

Because there are no uses of novaluron that could result in residential exposures, this aggregate risk assessment takes into consideration dietary food + water exposure only; therefore, the chronic aggregate estimates would be the same as the chronic dietary exposure results shown in Table 7. Page 20 of 24 6.0 CUMULATIVE RISK Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to novaluron and any other substances and novaluron does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that novaluron has a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http:// www. epa. gov/ pesticides/ cumulative/.

7.0 OCCUPATIONAL EXPOSURE Reference: occupational and residential exposure/ risk assessment  Memo, M. Clock Rust. DP# 315780.

Occupational exposure and risks were assessed based on the proposed uses on Brassica. Aerial and ground application of liquids are the proposed methods of application.

An appropriate endpoint for quantification of short term dermal risk assessment was not identified by HIARC since no adverse effects were observed at the limit dose in a 21 day dermal toxicity study in rats, and there were no developmental toxicity concerns at the limit dose. Therefore, a corresponding short term dermal risk assessment for this duration is not required. For handlers, short and intermediate term inhalation risk was assessed, as was intermediate term dermal risk. For post application workers, intermediate term dermal risk was assessed ( post application inhalation exposure is considered to be negligible).

7.1 Occupational Handler Based on the proposed use patterns, HED expects the most highly exposed occupational pesticide handlers are likely to be:

1) mixer loaders using open pour loading of an EC ( liquid); 2) applicators using open cab groundboom equipment; 3) applicators using open cab air blast equipment.

Aerial applicators were not assessed since exposure data indicate they are exposed to far less pesticide residue than applicators using open cab ground equipment ( airblast or groundboom).

For some of the application methods, the same individual might perform multiple activities. The HED Science Advisory Council for Exposure ( ExpoSAC) draft SOP ( 29 MAR 2000) directs that although the same individual may perform all tasks in some cases, they shall be assessed separately. Page 21 of 24 The available exposure data for combined mixer/ loader/ applicator scenarios are limited in comparison to the data available for monitoring of these two activities separately. These exposure scenarios are outlined in the Pesticide Handler Exposure Database ( PHED) Surrogate Exposure Guide ( AUG 1998). HED has adopted a methodology to present the exposure and risk estimates separately for the job functions in some scenarios and to present them as combined in other cases. Most exposure scenarios for hand held equipment ( such as hand wands, backpack sprayers, and push type granular spreaders) are assessed as a combined job function. With these types of hand held operations, all handling activities are assumed to be conducted by the same individual. The available monitoring data support this and HED presents them in this way. Conversely, for equipment types such as fixed wing aircraft, groundboom tractors, or air blast sprayers, the applicator exposures are assessed and presented separately from those of the mixers and loaders. By separating the two job functions, HED determines the most appropriate levels of personal protective equipment ( PPE) for each aspect of the job without requiring an applicator to wear unnecessary PPE that might be required for a mixer/ loader ( i. e., chemical resistant gloves may only be necessary during the pouring of a liquid formulation).

No chemical specific data were available with which to assess potential exposure to pesticide handlers. There are three basic risk mitigation approaches considered appropriate for controlling occupational exposures. These include administrative controls, the use of PPE, and the use of engineering controls. Occupational handler exposure assessments were completed by HED using baseline, PPE, and engineering controls. ( Note: Administrative controls available generally involve altering application rates for handler exposure scenarios. These are typically not utilized for completing handler exposure assessments.) The baseline clothing/ PPE level scenario for occupational exposure scenarios is generally an individual wearing long pants, a long sleeved shirt, no chemical resistant gloves, and no respirator. The first level of mitigation generally applied is PPE. As reflected in the calculations included herein, PPE may involve the use of an additional layer of clothing, chemical resistant gloves, and a respirator. The next level of mitigation considered in the risk assessment process is the use of appropriate engineering controls which, by design, attempt to eliminate the possibility of human exposure. Examples of commonly used engineering controls include closed tractor cabs, closed mixing/ loading/ transfer systems, and water soluble packets.

Aerial application results in the highest occupational exposure estimates for mixer/ loaders due to the assumption of a larger area treated ( 1200 acres).

For a summary of estimated exposures and risks, see Table 8 below. Page 22 of 24 Table 8. Estimated Handler Exposure and Risk from the Use of Novaluron on Head and Stem Brassica.

Unit Exposure1 mg a. i./ lb handled Application Rate2 Units Treated3 Per Day Average Daily Dose4 mg a. i./ kg bw/ day MOE5 ST Inhal. IT Combined Mixer/ Loader  Liquid  Open Pour  Supporting Aerial Operations for Head and Stem Brassica Dermal: SLNG 2.9 HC SLWG 0.023 HC Inhal 0.0012 HC 0.078 lb a. i./ A 1200 A Dermal: SLNG 0.39 SLWG 0.0031 Inhal 0.0016 2,700 NG 11 WG 930 Applicator  Groundboom  Open Cab for Head and Stem Brassica Dermal: SLNG 0.014 HC SLWG 0.014 MC Inhal 0.00074 HC 0.078 lb a. i./ A 200 A Dermal: SLNG/ WG 0.00031 Inhal 0.00016 2,700 NG/ WG 9,300 1. Unit Exposures are taken from " PHED SURROGATE EXPOSURE GUIDE", Estimates of Worker Exposure from PHED Version 1.1, August 1998. Inhalation. Unit Exposures = mg a. i./ pound of active ingredient handled. Data Confidence: HC = High Confidence. 2. Applic. Rate. = Taken from proposed RimOn ® labels for 10 % EC and 7.5% WG. 3. Units Treated are taken from " Standard Values for Daily Acres Treated in Agriculture"; SOP No. 9.1. ExpoSAC; Revised 5 July 2000; 4. Average Daily Dose ( ADD) = Unit Exposure * Applic. Rate * Units Treated * absorption factor ÷ Body Weight ( 70 kg). ( Assumes 10 % dermal absorption and 100 % inhalation absorption.) 5. MOE = NOAEL ÷ ADD. No short term dermal endpoint was identified therefore only short term inhalation risk is presented ( NOAEL = 4.38 mg a. i./ kg bw/ day). The intermediate term dermal and inhalation endpoints are the same ( NOAELs = 4.38 mg a. i./ kg bw/ day respectively) and are identified from the same study. Therefore, dermal exposure is summed with inhalation exposure and risk is presented for " baseline" work clothing and NO gloves ( NG) as well as " baseline" work clothing WITH the use of protective gloves ( WG).

All occupational risk estimates are below HED's level of concern ( MOE> 100) provided workers wear protective gloves when handling novaluron.

7.2 Occupational Postapplication There is a potential for post application exposure to workers from pesticides during the course of typical agricultural activities.

The HIARC determined that there were no signs of systemic toxicity at the limit dose of 1,000 mg/ kg/ day in a 4 week dermal toxicity study in rats. As a result, HIARC did not identify an endpoint for the quantification of short term dermal risk assessment, and a corresponding risk assessment for this duration is not required. Dermal postapplication exposure over the intermediate term duration ( more than 30 consecutive days) is not typically expected to occur based on the use pattern ( 7 14 day application interval).

However, for the last risk assessment ( Memo, M. Clock Rust, et al., 25 MAR 2004; DP# 295824), HED's Risk Assessment Review Committee ( RARC) recommended that postapplication exposure be assessed for the intermediate term duration as a conservative measure. Likewise, for the current action, intermediate term post application was assessed using Page 23 of 24 conservative assumptions for the proposed uses.

HED in conjunction with the Agricultural Re entry Task Force ( ARTF) has identified a number of post application agricultural activities that may occur. HED has also identified TCs ( expressed as cm ² / hr) relative to the various activities. To make a conservative estimate of post application exposure based on the proposed crop uses, HED chose hand harvesting Brassica with a TC of 5,000 cm2/ hr ( central value from ARF012 TCs ranging from 2862 to 7584 cm2/ hr). Lacking compound specific data, HED assumed 20% of the application rate is available as foliar dislodgeable residue on day zero after application. This and the TC estimate for irrigation are adapted from the ExpoSAC SOP No. 003 ( 07 MAY 1998  Revised 07 AUG 2000). The following convention may be used to estimate post application exposure.

Surrogate Dislodgeable Foliar Residue ( DFR): DFR = application rate * 20% available as dislodgeable residue * ( 1 D) t * 4.54 x 108 µ g/ lb * 2.47 x 10 8 A/ cm2 and,

Average Daily Dose ( ADD) = DFR µ g/ cm2 * TC cm2/ hr * hr/ day * 0.001 mg/ µ g * 1/ 70 kg bw therefore, 0.078 lb a. i./ A * 0.20 * ( 1 0) 0 * 4.54 x 108 µ g/ lb * 2.47 x10 8 A/ cm ² = 0.18 µ g/ cm2   0.18 µ g/ cm2 * 5,000 cm2/ hr * 8 hr/ day * 0.001 mg/ µ g * 0.10 dermal absorption * 1/ 70 kg bw = 0.010 mg/ kg bw/ day Since MOE = NOAEL ÷ ADD then 4.38 mg/ kg bw/ day ÷ 0.010 mg/ kg bw/ day = 440 A MOE of 100 is adequate to protect agricultural workers from post application exposures to novaluron. The estimated MOE is based upon conservative assumptions and is > 100; therefore, estimated risks from post application exposures do not exceed HED's level of concern.

7.3 Incident Data OPP's Incident Data System ( IDS) ( 29 DEC 2003) indicates " no incident data" are recorded for novaluron. Page 24 of 24 8.0 DATA NEEDS/ LABEL REQUIREMENTS 8.1 Toxicology ° The HED HIARC requested a 28 day inhalation toxicity study as a condition of registration. However, based on the low volatility and low inhalation toxicity ( Category IV) of novaluron and inhalation MOEs > 1000 for the proposed uses in this risk assessment, novaluron qualifies for a waiver of the 28 day inhalation toxicity study for the proposed uses [ HED SOP 2002.01: Guidance: Waiver Criteria for Multiple Exposure Inhalation Toxicity Studies, 15 AUG 2002]. The requirement for the 28 day inhalation toxicity study is waived for this action only. If in the future, requests for new uses or formulations are submitted that may result in a significant change in either the toxicity profile or exposure scenarios, HED will reconsider this data requirement.

8.2 Residue Chemistry ° Revised Section B. ° Revised Section F. ° Radiovalidation of the GC/ ECD plant analytical method, using radiolabeled samples from the metabolism studies, in order to determine whether the method adequately extract aged ( weathered) residues of novaluron. ° An interference study to determine whether other pesticides registered on the same commodities interfere with the determination of novaluron; an interference study may be waived if a specific single analyte confirmatory method is submitted.

8.3 Occupational/ Residential Exposure ° None.

cc: S. Levy ( RAB1), P. Terse ( RAB1), M. Clock Rust ( RAB1) RDI: RAB1 Branch ( 02 NOV 2005), P. V. Shah ( 03 NOV 2005) S. Levy: 806T: CM# 2: ( 703) 305 0783: 7509C: RAB1


[Federal Register: January 11, 2010 (Volume 75, Number 6)]
[Notices]
[Page 1421-1425]
[DOCID:fr11ja10-88]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. IA-2971/803-200]

BlackRock, Inc.; Notice of Application

January 4, 2010.
AGENCY: Securities and Exchange Commission (``SEC'' or ``Commission'').

ACTION: Notice of application for an exemptive order under Section 206A
of the Investment Advisers Act of 1940 (the ``Advisers Act'').

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Applicant: BlackRock, Inc. (``Applicant'' or ``BlackRock'').

Relevant Advisers Act Sections: Exemption requested under section 206A
of the Advisers Act from subsections (a)(2)(iii)(A)(3) and
(a)(2)(iii)(B) of Advisers Act rule 206(4)-3.

Summary of Application: Applicant requests that the Commission issue an
order under section 206A of the Advisers Act exempting it and its
investment advisory subsidiaries from Advisers Act rule 206(4)-
3(a)(2)(iii)(A)(3), which requires any cash solicitor for an investment
adviser to provide a prospective client with a separate solicitor's
disclosure document at the time of the solicitation, and from Advisers
Act rule 206(4)-3(a)(2)(iii)(B), which requires an investment adviser
to receive a prospective client's written acknowledgement of receipt of
the separate solicitor's document prior to entering into any advisory
contract with that client.

Filing Dates: The application was filed on April 27, 2009, and an
amended and restated application was filed on October 30, 2009.

Hearing or Notification of Hearing: An order granting the application
will be issued unless the Commission orders a hearing. Interested
persons may request a hearing by writing to the Commission's Secretary
and serving Applicant with a copy of the request, personally or by
mail. Hearing requests should be received by the SEC by 5:30 p.m. on
February 10, 2010 and should be accompanied by proof of service on
Applicant, in the form of an affidavit or, for lawyers, a certificate
of service. Hearing requests should state the nature of the writer's
interest, the reason for the request, and the issues contested. Persons
may request notification of a hearing by writing to the Commission's
Secretary.

ADDRESSES: Secretary, Securities and Exchange Commission, 100 F Street,
NE., Washington, DC 20549-1090. Applicant, BlackRock, Inc., c/o Howard
B. Surloff, 40 East 52nd Street, New York, New York 10022.

FOR FURTHER INFORMATION CONTACT: Sarah G. ten Siethoff, Senior Counsel,
or Daniel S. Kahl, Branch Chief, at<PHONE_NUMBER> (Office of
Investment Adviser Regulation, Division of Investment Management).

SUPPLEMENTARY INFORMATION: The following is a summary of the
application. The complete application may be obtained for a fee at the
SEC's Public Reference Branch, 100 F Street, NE., Washington, DC 20549-
0102 (telephone<PHONE_NUMBER>)).

Applicant's Representations

    1. Applicant is a publicly traded holding company conducting
investment management and ancillary businesses primarily through a
variety of directly or indirectly wholly owned registered investment
advisory

subsidiaries (the ``BlackRock Advisory Subsidiaries''). A substantial
portion of the BlackRock Advisory Subsidiaries' business involves
advising high net worth clients through a ``wrap fee'' program
(``Private Investors'') and advising institutional clients generally
through traditional separate account arrangements (``Institutional
Separate Accounts'' or ``ISA''). Broker-dealer subsidiaries controlled
by Merrill Lynch & Co., Inc. (``Merrill Lynch'') solicit clients for
the Private Investors and ISA businesses.
    2. On September 29, 2006, BlackRock acquired substantially all of
Merrill Lynch's global investment management business (the ``MLIM
Business'') from Merrill Lynch in exchange for issuing a substantial
equity interest in itself to Merrill Lynch (the ``Transaction''). That
equity interest, as of January 1, 2009, represented a 48.2% economic
interest in BlackRock and a 44.2% voting interest in BlackRock. A
substantial portion of BlackRock's current Private Investors and ISA
businesses, including the investment advisory clients serviced by these
businesses, were acquired in the Transaction and formerly were
important parts of the MLIM Business.
    3. On December 26, 2008, BlackRock and Merrill Lynch entered into
an Exchange Agreement pursuant to which Merrill Lynch and BlackRock
agreed to exchange (i) 49,865,000 shares of BlackRock common stock held
by Merrill Lynch for a like number of shares of BlackRock's Series B
non-voting convertible participating preferred stock, and (ii)
12,604,918 shares of BlackRock's Series A non-voting convertible
participating preferred stock held by Merrill Lynch for a like number
of shares of Series B Preferred Stock (the ``Exchange''), in effect
reducing Merrill Lynch's voting interest in BlackRock to 4.6%, while
its economic interest remains largely unchanged at 46.3% on a fully
diluted basis.
    4. Prior to the Transaction, broker-dealer subsidiaries controlled
by Merrill Lynch (``ML Broker-Dealers''), through their registered
representatives, solicited clients for the investment adviser
subsidiaries controlled by Merrill Lynch that conducted the Private
Investors and ISA portions of the MLIM Business, in exchange for a cash
fee and in reliance on subsection (a)(2)(ii) of rule 206(4)-3 under the
Advisers Act (the ``Control-Affiliate Solicitor Provision''). The
Control-Affiliate Solicitor Provision allows ``partner[s], officer[s],
director[s] or employee[s] of a person which controls, is controlled
by, or is under common control with [an] investment adviser'' to
solicit clients for the investment adviser in exchange for a cash fee
so long as the solicitor discloses the identity of his employer and the
nature of the affiliation between his employer and the recommended
adviser at the time of the solicitation or referral. The Control-
Affiliate Solicitor Provision does not require solicitors and advisers
to follow any other particularized requirements in making these
required disclosures. The ML Broker-Dealers never used the independent
solicitor disclosure procedures contained in subsection (a)(2)(iii) of
rule 206(4)-3 under the Advisers Act (the ``Independent Solicitor
Provision''), which contains several specific requirements that an
independent solicitor must follow, when referring clients to the MLIM
Business because Merrill Lynch controlled both the MLIM Business and
the ML Broker-Dealers.
    5. Notwithstanding Merrill Lynch's significant economic stake in
BlackRock, due to the particular and unique facts and circumstances of
the BlackRock-Merrill Lynch relationship, BlackRock has concluded that
Merrill Lynch does not ``control'' it for purposes of the Advisers Act.
In addition to the absence of voting power indicative of control,
BlackRock and Merrill Lynch have entered into a stockholder agreement
in connection with the Transaction (the ``Stockholder Agreement'') that
contractually denies Merrill Lynch the right to decide how to vote its
BlackRock shares on any matter other than a very limited number of
extraordinary proposals (primarily related to issues impacting Merrill
Lynch's ownership interest in BlackRock), prohibits Merrill Lynch from
otherwise attempting to influence or control BlackRock, and imposes a
number of other limitations governing the BlackRock voting securities
Merrill Lynch beneficially owns. The Stockholder Agreement's
limitations on Merrill Lynch's rights as a holder of BlackRock voting
securities, and as an investor in BlackRock generally, deny Merrill
Lynch the power and ability to control BlackRock ordinarily associated
with the ownership of such a large economic stake in a company.\1\
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    \1\ BlackRock has not asked the Commission to confirm, and the
Commission is not confirming, BlackRock's conclusion that Merrill
Lynch does not control it within the meaning of the Advisers Act.
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    6. BlackRock represents that the Stockholder Agreement, as well as
several other agreements entered into in connection with the
Transaction, serve to create a long-standing close affiliation between
BlackRock and Merrill Lynch for the purpose of achieving their mutual
business and economic objectives, even though they do not result in
Merrill Lynch ``controlling'' BlackRock within the meaning of the
Advisers Act. The Stockholder Agreement, as well as these other
agreements, are publicly available in BlackRock's filings with the
Commission.
    7. The nature of the close, ongoing relationship between BlackRock
and Merrill Lynch is publicly disclosed, discussed and summarized on
BlackRock's internet website, BlackRock's Form ADV Part II, in
BlackRock's client documentation, in BlackRock's periodic filings under
the Securities Exchange Act of 1934, as amended (the ``Exchange Act''),
and in other generally available public information. BlackRock
represents that this comprehensive disclosure serves to ensure that the
exact nature and extent of the close affiliation between BlackRock and
Merrill Lynch is readily apparent to the public and the market at
large.
    8. BlackRock represents that BlackRock and the BlackRock Advisory
Subsidiaries will abide by the following solicitation procedures:
    a. The referral agreement between BlackRock and Merrill Lynch (the
``BLK-MER Referral Agreement'') requires that ML Broker-Dealers
disclose to potential clients the relationship between Merrill Lynch
and BlackRock at the time of a referral to a BlackRock Advisory
Subsidiary. ML Broker-Dealers will provide prominent written disclosure
to potential clients regarding the relationship between Merrill Lynch
and BlackRock at or prior to the time of a referral to a BlackRock
Advisory Subsidiary. This prominent written disclosure will also
address Merrill Lynch's resulting conflict of interest in recommending
BlackRock.
    b. When a ML Broker-Dealer solicits any prospective client for a
BlackRock Advisory Subsidiary, the prospective client will receive the
BlackRock Advisory Subsidiary's written disclosure statement required
by Rule 204-3 promulgated under the Advisers Act (the ``ADV Part II
Disclosure Document''). The BlackRock Advisory Subsidiary's ADV Part II
Disclosure Document will be delivered by the BlackRock Advisory
Subsidiary (and not by the solicitor) not later than the time that a
fully executed investment advisory contract is provided to the client,
although not necessarily at the time of the solicitation itself. The
BlackRock Advisory Subsidiary's ADV Part II Disclosure Document will
contain detailed disclosures about the nature of the affiliation
between Merrill Lynch and BlackRock and specifically

draw potential clients' attention to the inherent bias a ML Broker-
Dealer has to recommend a BlackRock Advisory Subsidiary. BlackRock will
ensure that these additional disclosures conform, in all material
respects, to the disclosures required by the Independent Solicitor
Provision.
    c. If a BlackRock Advisory Subsidiary accepts a client referred by
a ML Broker-Dealer, the prospective client will enter into a written
investment management agreement with the BlackRock Advisory Subsidiary.
Clients referred through the Private Investors channel will be provided
with and will generally execute a form investment management agreement
that will contain further disclosures about the nature of the
relationship between Merrill Lynch and BlackRock in addition to those
that will be provided in the BlackRock Advisory Subsidiary's ADV Part
II Disclosure Document and at the time of the referral. Clients
referred through the ISA channel will often be provided with a form
investment management agreement with similar disclosures, but many
prefer to use their own form investment management agreement and
consequently these disclosures may not appear in the investment
management agreement. BlackRock Advisory Subsidiaries will not
separately charge any client any explicit amount, in addition to the
advisory fee, for the cost of obtaining that client's account, and no
differential with respect to the amount or level of advisory fees
charged by a BlackRock Advisory Subsidiary will be attributable to the
solicitation arrangements with ML Broker-Dealers described in the
Application.
    d. BlackRock Advisory Subsidiaries and ML Broker-Dealers will
engage in this solicitation arrangement pursuant to the BLK-MER
Referral Agreement. BlackRock represents that the BLK-MER Referral
Agreement complies with subsections (A)(1) and (A)(2) of the
Independent Solicitor Provision.

Applicant's Legal Analysis

    1. Section 206A of the Advisers Act grants the Commission the
authority to ``conditionally or unconditionally exempt any person or
transaction * * * from any provision or provisions of [the Advisers
Act] or of any rule or regulation thereunder, if and to the extent that
such exemption is necessary or appropriate in the public interest and
consistent with the protection of investors and the purposes fairly
intended by the policy and provisions of [the Advisers Act].''
    2. Section 206 of the Advisers Act is a general anti-fraud
provision applicable to investment advisers. Rule 206(4)-3 (``the Cash
Solicitation Rule'') was adopted under section 206(4) of the Advisers
Act because the Commission determined that the nature of the conflict
of interest mandated disclosure to clients of cash compensation
arrangements between solicitors and recommended investment advisers,
which alerts clients to the personal incentive the solicitor has to
recommend one particular adviser over another.
    3. The Control-Affiliate Solicitor Provision (subsection (a)(2)(ii)
of the Cash Solicitation Rule) applies to anyone who is ``(A) a
partner, officer, director or employee of [the] investment adviser, or
(B) a partner, officer, director or employee of a person which
controls, is controlled by, or is under common control with [the]
investment adviser.'' All investment advisers and solicitors must meet
certain threshold requirements to rely on the Cash Solicitation Rule
regardless of any affiliation between the investment adviser and the
solicitor. However, where the Control-Affiliate Solicitor Provision
applies, the Cash Solicitation Rule requires only that either (1) the
solicitor's status as a partner, officer, director or employee of the
adviser be disclosed to the prospective client; or (2) the solicitor's
status as a partner, officer, director or employee of a company
affiliated with the adviser, along with the nature of the affiliation
between the solicitor's employer and the investment adviser, be
disclosed to the prospective client at the time of the solicitation or
referral.
    4. The Independent Solicitor Provision (subsection (a)(2)(iii) of
the Cash Solicitation Rule) contains several specific requirements: (A)
The written solicitation agreement between the adviser and solicitor
must contain specific terms; (B) the solicitor must deliver to the
prospective client, at the time of solicitation, the adviser's ADV Part
II Disclosure Document and a separate written disclosure document
described in subsection (b) of the Cash Solicitation Rule (the
``Independent Solicitor Disclosure Document'' and the required delivery
of both the adviser's ADV Part II Disclosure Document and the
Independent Solicitor Disclosure Document being the ``Part II and
Independent Solicitor Disclosure Document Delivery Requirement''); (C)
the adviser must receive a signed and dated acknowledgement of the
client's receipt of the ADV Part II Disclosure Document and the
Independent Solicitor Disclosure Document prior to, or at the time of,
entering into any written or oral investment advisory contract (the
``Signed Acknowledgement Requirement''); and (D) the adviser must make
a bona fide effort to ascertain whether the solicitor has complied with
the terms of the written solicitation agreement and must have a
reasonable basis for believing that the solicitor has so complied.
    5. The Independent Solicitor Disclosure Document must contain the
following information: (i) The names of the solicitor and investment
adviser; (ii) the nature of the relationship, including any
affiliation, between the solicitor and the investment adviser; (iii) a
statement that the solicitor will be compensated for his solicitation
services by the investment adviser; (iv) the terms of such compensation
arrangement, including a description of the compensation paid or to be
paid to the solicitor; and (v) the amount, if any, for the cost of
obtaining his account the client will be charged in addition to the
advisory fee, and the differential, if any, among clients with respect
to the amount or level of advisory fees charged by the investment
adviser if such differential is attributable to the existence of any
arrangement pursuant to which the investment adviser has agreed to
compensate the solicitor for soliciting clients for, or referring
clients to, the investment adviser.
    6. BlackRock asserts that, as articulated in the adopting release
for the Cash Solicitation Rule, the key policy rationale underlying the
limited disclosure regime of the Control-Affiliate Solicitor Provision
is that ``[a]s long as a client is aware that the recommended adviser
is the solicitor's employer or a close affiliate of the solicitor's
employer, there appears to be little need to require the imposition of
additional disclosure and recordkeeping requirements.'' BlackRock
further asserts that the Control-Affiliate Solicitor Provision reflects
the argument advanced by commenters considering the Cash Solicitation
Rule that ``there is little basis for assuming that potential clients
will be any less aware of the inherent bias when an employee recommends
an adviser who is a person associated with his employer than when he
recommends the advisory services of his own employer.'' Thus, BlackRock
submits, one rationale for expanding the scope of the Control-Affiliate
Solicitor Provision to include persons part of an organization that is
closely affiliated with the recommended adviser is that it should be
readily apparent to the public that the close affiliation between the
solicitor and adviser creates an inherent bias to recommend the
affiliated adviser.
    7. Pursuant to the Exchange, Merrill Lynch beneficially owns
approximately

a 46.3% economic interest in BlackRock on a fully diluted basis;
however, its ownership of BlackRock's outstanding voting securities is
reduced to approximately 4.9%. Although BlackRock asserts that this
relationship is not a ``control'' relationship as defined under the
Advisers Act, the disclosure of Merrill Lynch's ownership of such a
large block of BlackRock's capital stock, combined with the economic
stake represented thereby, is sufficient to provide the same alert to
the investing public and potential clients as to a ML Broker-Dealer's
``inherent bias'' in recommending a BlackRock Advisory Subsidiary and
is, in effect, a ``close affiliation'' for the purposes of satisfying
the concerns underlying the Cash Solicitation Rule and the rationale
for the less onerous disclosure elements of the Control-Affiliate
Solicitor Provision.
    8. The unique affiliation relationship between BlackRock and
Merrill Lynch is consistently discussed, summarized and disclosed on
BlackRock's Internet Web site, BlackRock's Form ADV Part II, in
BlackRock's client documentation, in BlackRock's filings under the
Exchange Act, in registration statements for BlackRock's funds
registered under the Investment Company Act of 1940 and in other
generally available public information. BlackRock submits that these
multiple avenues of disclosure serve to ensure that the exact nature
and extent of the close affiliation between BlackRock and Merrill Lynch
is readily apparent to the public and market at large. In addition, ML
Broker-Dealers would provide prominent written disclosure to potential
clients regarding the relationship between Merrill Lynch and BlackRock
at or prior to the time of a referral to a BlackRock Advisory
Subsidiary. This prominent written disclosure would also address
Merrill Lynch's resulting conflict of interest in recommending
BlackRock.
    9. BlackRock seeks only exemptions from subsections
(a)(2)(iii)(A)(3) and (a)(2)(iii)(B) of the Cash Solicitation Rule--the
Part II and Independent Solicitor Disclosure Document Delivery
Requirement and the Signed Acknowledgement Requirement. BlackRock
submits that the BLK-MER Referral Agreement contains terms that satisfy
subsections (a)(2)(iii)(A)(1)-(2) of the Cash Solicitation Rule.
BlackRock proposes to adhere to subsection (a)(2)(iii)(C) of the Cash
Solicitation Rule, which requires that the recommended investment
adviser make a bona fide effort to ascertain whether the solicitor has
complied with the referral agreement, and have a reasonable basis for
so believing. BlackRock has represented that BlackRock Advisory
Subsidiaries' ADV Part II Disclosure Documents would contain, in all
material respects, the disclosures required by the Independent
Solicitor Disclosure Document. Subsection (b)(5) of the Cash
Solicitation Rule requires that the Independent Solicitor Disclosure
Document disclose the terms of the compensation arrangement between the
solicitor and the recommended adviser. BlackRock Advisory Subsidiaries'
ADV Part II Disclosure Documents would disclose in general terms the
fact that ML Broker-Dealers are compensated by the BlackRock Advisory
Subsidiaries for their solicitation activities, but the details
regarding the amount of compensation and the methods by which such
amounts are determined would not be disclosed. BlackRock argues that
this information would not be informative in this context because
particularized disclosure as to the solicitation fee paid to ML Broker-
Dealers would not help draw a potential client's focus to the
significant economic benefit that ML Broker-Dealers derive due to
Merrill Lynch's approximately 46.3% economic interest in BlackRock.
    10. BlackRock submits that the purpose of the detailed requirements
of the Independent Solicitor Provision is to ensure that the fact of a
solicitor's bias in favor of a recommended adviser is presented in a
clear and unmistakable manner that ensures that potential clients
become aware of this bias. BlackRock argues that the inherent bias on a
ML Broker-Dealer's part to recommend a BlackRock Advisory Subsidiary is
clearly disclosed and unmistakable as a result of the close affiliation
between Merrill Lynch (the solicitor's parent entity) and BlackRock
(the recommended adviser's parent entity) such that, within the policy
framework of the Cash Solicitation Rule, these additional disclosures
need not be expressly made in a separate Independent Solicitor
Disclosure Document.
    11. BlackRock asserts that the Commission granting the order
requested by its application would be appropriate in the public
interest because (i) it would preserve for current and future Merrill
Lynch brokerage clients the significant investment experience and
resources of BlackRock currently available to such clients, while at
the same time ensuring that such clients will continue to receive the
protections intended by the Cash Solicitation Rule, (ii) requiring
strict compliance with the Independent Solicitor Provision would create
risks that client investment options might be reduced as a result of ML
Broker-Dealers being discouraged from recommending BlackRock Advisory
Subsidiaries, (iii) clients might find a change in procedure and
documentation confusing and burdensome, and (iv) additional costs
associated with such strict compliance might ultimately result in
greater expenses for clients.

Applicant's Conditions

    1. The Applicant will rely on the Order only for so long as the
Cash Solicitation Rule in effect as of the date of the Order is
operative. If the Commission, subsequent to the date of the Order,
adopts a new rule governing the payment of cash fees by registered
investment advisers to persons soliciting clients on their behalf (a
``New Cash Solicitation Rule''), the Applicant agrees to rely on the
Order only until the compliance date for such New Cash Solicitation
Rule.
    2. The Applicant will rely on the Order only for so long as Merrill
Lynch beneficially owns 25% or more of the Applicant's outstanding
capital stock. If Merrill Lynch ever ceases to beneficially own at
least 25% of the Applicant's outstanding capital stock, the Applicant
represents that it will not rely on the relief granted by the Order.
    3. The Applicant will require that the BlackRock Advisory
Subsidiaries and the ML Broker-Dealers provide clear disclosure of the
Applicant's relationship with Merrill Lynch to potential clients
referred to BlackRock Advisory Subsidiaries by ML Broker-Dealers in
exchange for a cash fee. This disclosure will be provided by ML Broker-
Dealers' disclosure to potential clients of the relationship between
Merrill Lynch and BlackRock at the time of a referral to a BlackRock
Advisory Subsidiary pursuant to the BLK-MER Referral Agreement, and via
delivery of (i) a BlackRock Advisory Subsidiary's ADV Part II
Disclosure Document; and (ii) a form investment management agreement
provided to each client referred to a BlackRock Advisory Subsidiary
through the Private Investors channel and often provided to clients
referred through the ISA channel. The Applicant will require that all
such disclosures be substantially similar to the disclosures described
in the Application and be provided pursuant to procedures substantially
similar to those described in the Application. Additionally, the ML
Broker-Dealers will provide prominent written disclosure to potential
clients regarding the relationship between Merrill Lynch and BlackRock
at or prior to the time of a referral to a BlackRock Advisory
Subsidiary. This prominent written

disclosure will also address Merrill Lynch's resulting conflict of
interest in recommending BlackRock.
    4. The Applicant will require the BlackRock Advisory Subsidiaries
to comply with subsection (a)(2)(iii)(C) of the Cash Solicitation Rule.
Further, the Applicant represents that it will require the BlackRock
Advisory Subsidiaries to continue to comply with subsection (A)(2) of
the Independent Solicitor Provision. To comply with subsection
(a)(2)(iii)(C) of the Cash Solicitation Rule, the Applicant agrees to
require the BlackRock Advisory Subsidiaries to make a bona fide effort
to ascertain whether ML Broker-Dealers have complied with the terms of
the BLK-MER Referral Agreement, any amendment thereof, or any
subsequently executed referral agreement with ML Broker-Dealers, and
have a reasonable basis for believing that ML Broker-Dealers have so
complied.

    For the Commission, by the Division of Investment Management,
under delegated authority.
Florence E. Harmon,
Deputy Secretary.
[FR Doc. 2010-196 Filed 1-8-10; 8:45 am]
BILLING CODE 8011-11-P


Prevalidation Study Plan for Sliced Testes Assay Gary Timm Presented to EDMVS August 20, 2003 Sliced Testes Assay Prevalidation/ Validation Study Plan ° June EDMVS Meeting Discussed:

  Objectives of validation study   Data interpretation procedure   Basic sliced testes protocol   Prevalidation study design   Reference chemicals   Laboratory selection   Validation study design   Measurements of reliability   Data analysis and reporting June Proposal for Prevalidation Studies ° Conduct prevalidation studies in two laboratories   Baseline study   Pilot study   Multichemical study June Proposal for Prevalidation Studies ( 2)

° Baseline study   Run optimized protocol   3 runs without hCG   3 runs with hCG challenge   Measure testosterone formation and LDH   No test chemical   Three replicate studies June Proposal for Prevalidation Studies ( 3)

° Pilot studies of positive controls   Aminoglutethimide ( positive control)

  Ethane dimethanesulfonate ( Leydig cell toxicant)

  Two labs   Three replicates June Proposal for Prevalidation Studies ( 4)

° Multichemical studies   9 chemicals   2 laboratories   2 replicate studies ° Validation in 6 laboratories would begin after the successful conclusion of these studies EDMVS Responses to Questions 1. Does the EDMVS agree with the stated objectives and data interpretation in the proposed Validation Study Plan? Yes, but:

° Concerns expressed about the assay   Accuracy and sensitivity of sliced testes assay   Potentially better assays on the horizon; don't invest too heavily in sliced testes assay   Need a reliable means to detect Leydig cell toxicity EDMVS Responses to Questions 2. Does the EDMVS agree with the structure of the prevalidation and validation Program?

° Yes, agreed that two laboratories was a reasonable choice for prevalidation.

° Concern that program should be more efficient   Do we need to look at data from multiple time points or is end of assay OK?

  Use data from prevalidation to pick number of labs for validation, do not rely on literature values EDMVS Responses to Questions ° Concerns about positive control chemicals   Aminoglutethimide may not be a good positive control chemical   EDS may not be a good cytotoxicant reference chemical ° Concerns about reference chemicals   Should not attempt to cover every known mode of action, use phamacologic agents of known mode of action   Ideally should choose only chemicals with a single mode of action, however selectivity seems to be dose dependent.

  Should include several cytotoxicants during prevalidation EDMVS Responses to Questions 3. Have we selected appropriate measures of reliability?

  Yes, but the endpoints being used for the power calculations need to be clearly stated   Need to verify linearity in baseline Testosterone production curve   Should estimate potency of test chemicals by calculating an EC10 or EC50. EDMVS Responses to Questions 4. Are the number of replicates taken over both prevalidation and validation sufficient to generate robust statistics?

  Yes, three replicates seems sufficient in prevalidation. If the variability is small,

consider reducing to 2 in validation   Need to add more negative chemicals   Negatives should include evaluation of influence of pH and osmolality EDMVS Responses to Questions 5. Should dosing solutions be prepared centrally or on site?

  The stock solution should be prepared centrally   Dilutions should be made on site with instructions provided by the lead lab or chemical repository EDMVS Responses to Questions 6. Do doses need to be confirmed by analytical chemistry?

  The identity and purity of the neat test substance should be checked by the chemical repository   The suitability and solubility of the test substance should be checked and the concentration of stock solution should be confirmed by the repository   Labs should save aliquots of dosing solutions should for analysis; analysis should be performed only " for cause" EDMVS Responses to Questions 6. Naïve labs/ trained labs issue   No naïve labs! Training is necessary to minimize interlaboratory difference in techniques   Competency of labs should be demonstrated by conducting a positive control prior to full validation effort   Incompetent laboratories should be excluded Issue: Leydig cell toxicity ° Concerns:

  Don't want false positive by artificially high in vitro dosing that kills cells   Don't want general cytotoxicants to trigger positive, 2 gen is wrong follow up for general cytotoxicants   May be " red herring." If cytotoxic to Leydig cells at biologically relevant concentration levels, isn't this a legitimate positive? Leydig cell toxicity ( cont)

° EPA Options:

1. Use LDH assay for cell viability 2. Use 3  HSD staining specific for Leydig cell viability instead of the more general LDH assay Issue: Choice of reference chemicals ° EPA confirmed by search of literature that selectivity is not unique but is dose dependent.

° EPA will select reference chemicals that work at key stages of steroidogenesis ° EPA will run 4 known cytotoxicants to select the best positive control for cytotoxicity EPA Listened and Redesigned Prevalidation Program ° Focus only on prevalidation; validation will be a separate work assignment.

° Redesigned the prevalidation program: lead lab and 3 participating labs ° Lead lab:

  Baseline, testes variability study   Test of positive control   Cytotoxicity studies   Multichemical studies   Training of participating laboratories' personnel Redesigned Prevalidation Program ° Participating Laboratories ( 3) and lead lab   Baseline studies in triplicate ° measure testosterone with and without hCG ° no test chemical   Positive control studies ° Positive control ( aminoglutethimide)

° Reference cytotoxicant Baseline and Testes Variability Study ( Lead Lab)

° Purpose:

  To demonstrate competence of lead lab using optimized assay   To obtain testosterone production data as a function of time in the absence of inhibitors   To estimate Leydig cell density after 4 hr incubation   To evaluate the variability in contralateral testes fragments to decide on future experimental design:

° Randomized fragments ° Block design using single testes Baseline and Testes Variability Study ( Lead Lab)

° Study Design:

  5 animals   24 runs ( a run corresponds to an incubation vial containing 1 testes fragment)

  Incubate for 4 hours with and without hCG   3 replicate studies with measurements ( samples) at 5 time points for runs 1 6. ( A replicate study is an independent study.)

  2 replicate studies with measurements at 2 and 4 hrs ( incubation times) for fragments 7 24 Baseline and Testes Variability Study 23,24 1,2 B 5 Y 2,4 21,22 1,2 A 5 Y 2,4 19,20 1,2 B 4 Y 2,4 17,18 1,2 A 4 Y 2,4 15,16 1,2 B 3 Y 2,4 13,14 3,4 A 3 Y 2,4 11,12 1,2 B 2 Y 2,4 9,10 3,4 A 2 Y 2,4 7,8 1,2 B 1 Y 2,4 4 6 2 A 1 3 Y 0 5 1 3 1 A 1 3 N 0 5 Run Fragment number Testis Animal hCG Sample time Baseline Study Design 4 6 3 Y Media 1 3 3 N Media Testes fragment Number runs hCG Sample Type 13 15 3 Y Media + AG ( high) 10 12 3 Y Media + AG ( med) 7 9 3 Y Media + AG ( low) 4 6 3 Y Media vehicle control 1 3 3 N Media vehicle control Testes fragment Number runs hCG Sample type Positive Control Study Design Cytotoxicity Study Design 25 27 3 Y Toxicant B high 22 24 3 Y Toxicant B med 19 21 3 Y Toxicant B low 16 18 3 Y Toxicant A high 13 15 3 Y Toxicant A med 10 12 3 Y Toxicant A low 7 9 3 Y Positive control 4 6 3 Y Media control 1 3 3 N Media control Testes fragment Number runs hCG Sample type Multichemical Study Design 34 36 3 N Chem B high 31 33 3 Y Chem B high 28 30 3 Y Chem B med 25 27 3 Y Chemical B low 22 24 3 N Chem A high 19 21 3 Y Chem A high 16 18 3 Y Chem A med 13 15 3 Y Chemical A low 10 12 3 Y Cytotox control 7 9 3 Y Positive control 4 6 3 Y Media control 1 3 3 N Media control Testes fragment Number runs hCG Sample type Reference Chemicals by Mode of Action Dimethoate StAR Lindane cAMP inhibitor ER binder Bisphenol A cAMP inhibitor P450c17, arom Ketoconazole P450SCC Aromatase Aminoglutethimide P450SCC Mode 2 Chemical Mode of Action Reference Chemicals by Mode of Action Aromatase Econazole P450c17 AR antagonist Flutamide P450c17 Epostane 3  HSD ER binder Genestein 3  HSD Mode 2 Chemical Mode of Action Reference Chemicals by Mode of Action Ethane dimethanesulfonate Leydig cell toxicant Mode 2 Chemical Mode of Action AR binder Vinclozolin Negative chemical Finasteride 5  reductase Prochloraz Aromatase Summary ° Lead lab:

  Baseline, testes variability study   Test of positive control   Cytotoxicity studies   Multichemical studies   Training of participating laboratories' personnel ° Participating Laboratories ( 3) and lead lab   Baseline studies in triplicate   Positive control studies in triplicate ° Estimated completion 4 30 2004


[Federal Register Volume 85, Number 97 (Tuesday, May 19, 2020)]
[Proposed Rules]
[Page 29906]
[FR Doc No: 2020-10833]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 79, 80, 86, 1037, and 1090

[EPA-HQ-OAR-2018-0227; FRL-10009-56-OAR]
RIN 2060-AT31

Public Hearing for Fuels Regulatory Streamlining

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notification of public hearing.

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

SUMMARY: The Environmental Protection Agency (EPA) is announcing a
virtual public hearing to be held May 28, 2020, on its proposal for the
``Fuels Regulatory Streamlining Rule,'' which was signed on April 13,
2020. EPA is proposing to update its existing gasoline, diesel, and
other fuels programs to improve overall compliance assurance and
maintain environmental performance, while reducing compliance costs for
industry and EPA.

DATES: EPA will hold a virtual public hearing on May 28, 2020. Please
refer to the SUPPLEMENTARY INFORMATION section for additional
information on the public hearing.

ADDRESSES: The virtual public hearing will be held on May 28, 2020. The
hearing will begin at 10:00 a.m. Eastern Time (ET) and end when all
parties who wish to speak have had an opportunity to do so. All hearing
attendees (including even those who do not intend to provide testimony)
should notify the contact person listed under FOR FURTHER INFORMATION
CONTACT by May 21, 2020. Additional information regarding the hearing
appears below under SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: Nick Parsons, Office of Transportation
and Air Quality, Assessment and Standards Division, Environmental
Protection Agency, 2000 Traverwood Drive, Ann Arbor, MI 48105;
telephone number:<PHONE_NUMBER>; email address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: EPA is proposing to streamline its existing
fuel quality regulations in 40 CFR part 80 by removing expired
provisions, eliminating redundant compliance provisions (e.g.,
duplicative registration requirements that are required by every EPA
fuels program), removing unnecessary and out-of-date requirements, and
replacing them with a single set of provisions and definitions in 40
CFR part 1090 that will apply across all gasoline, diesel, and other
fuels programs that EPA currently regulates. This action does not
propose to change the stringency of the existing fuel quality
standards. The Fuels Regulatory Streamlining proposal was signed on
April 13, 2020, and will be published separately in the Federal
Register. The pre-publication version is available at https://www.epa.gov/diesel-fuel-standards/fuels-regulatory-streamlining.
    Participation in virtual public hearing. Please note that EPA is
deviating from its typical approach because the President has declared
a national emergency. Because of current CDC recommendations, as well
as state and local orders for social distancing to limit the spread of
COVID-19, EPA cannot hold in-person public meetings at this time.
    The virtual public hearing will provide interested parties the
opportunity to present data, views, or arguments concerning the
proposal (which is available at https://www.epa.gov/diesel-fuel-standards/fuels-regulatory-streamlining). EPA may ask clarifying
questions during the oral presentations but will not respond to the
presentations at that time. Written statements and supporting
information submitted during the comment period will be considered with
the same weight as any oral comments and supporting information
presented at the public hearing. EPA recommends submitting the text of
your oral comments as written comments to the rulemaking docket.
Written comments must be received by the last day of the comment
period, as specified in the notice of proposed rulemaking.
    EPA is also asking all hearing attendees to pre-register for the
hearing, even those who do not intend to provide testimony. This will
help EPA ensure that sufficient phone lines will be available.
    Please note that any updates made to any aspect of the hearing
logistics, including potential additional sessions, will be posted
online at the EPA's Fuels Regulatory Streamlining website (https://www.epa.gov/diesel-fuel-standards/fuels-regulatory-streamlining). While
EPA expects the hearing to go forward as set forth above, please
monitor our website or contact the person listed in the FOR FURTHER
INFORMATION CONTACT section to determine if there are any updates.
    If you require the services of a translator or special
accommodations such as audio description, please pre-register for the
hearing and describe your needs by May 21, 2020. EPA may not be able to
arrange accommodations without advanced notice.
    How can I get copies of the proposed action and other related
information? EPA has established a docket for this action under Docket
ID No. EPA-HQ-OAR-2018-0227. EPA has also developed a website for the
Fuels Regulatory Streamlining rule, including the proposal, which is
available at https://www.epa.gov/diesel-fuel-standards/fuels-regulatory-streamlining. Please refer to the notice of proposed
rulemaking for detailed information on accessing information related to
the proposal.

    Dated: May 14, 2020.
Karl Moor,
Deputy Assistant Administrator, Office of Air and Radiation.
[FR Doc. 2020-10833 Filed 5-18-20; 8:45 am]
 BILLING CODE 6560-50-P