Page 1 of 26 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES Date: 09/ 27/ 05 MEMORANDUM SUBJECT: Aquashade: Revised Occupational and Residential Exposure Assessment and Recommendations for the Reregistration Eligibility Decision Document FROM: Wade Britton, Industrial Hygienist Reregistration Branch 3 Health Effects Division ( 7509C)

THROUGH: Catherine Eiden, Branch Chief Reregistration Branch 3 Health Effects Division ( 7509C)

TO: Kendra Tyler, CRM Reregistration Branch 1 SRRD ( 7508C)

DP Barcode: 321915 Pesticide Chemical Codes: 110301, 110302, 110303 Page 2 of 26 TABLE OF CONTENTS 1.0 Occupational and Residential Exposure Assessment for Aquashade ..................................... 4 1.1 Purpose ................................................................................................................... 5 1.2 Summary of Hazard Concerns for Aquashade .......................................................... 5 1.4 Incident Reports ...................................................................................................... 8 1.5 Summary of Use Patterns and Formulations ............................................................. 8 1.5.1 End Use Products...................................................................................... 8 1.5.2 Registered Use Categories and Sites.......................................................... 9 1.5.3 Application Methods ............................................................................... 10 2.0 Occupational Exposures and Risks .................................................................................... 10 2.1 Occupational Handler Exposures and Risks............................................................ 10 2.1.1 Data and Assumptions for Handler Exposure Scenarios ........................... 11 <IP_ADDRESS> Assumptions for Handler Exposure Scenarios ........................... 11 <IP_ADDRESS> Exposure Data for Handler Exposure Scenarios ........................ 12 2.1.2 Aquashade Handler Exposure Scenarios .................................................. 14 2.1.3 Non cancer Aquashade Handler Exposure and Assessment...................... 14 <IP_ADDRESS> Non cancer Aquashade Handler Exposure and Risk Calculations ................................................................................ 14 <IP_ADDRESS> Aquashade Non cancer Risk Summary ( using PHED data)........ 16 2.1.4 Cancer Aquashade Handler Exposure and Risk Assessment ..................... 18 2.1.5 Summary of Risk Concerns and Data Gaps for Occupational Handlers.... 18 <IP_ADDRESS> Summary of Risk Concerns ....................................................... 18 <IP_ADDRESS> Summary of Data Gaps ............................................................. 18 2.1.6 Recommendations for Refining Occupational Handler Risk Assessment ... 18 2.2 Occupational Postapplication Exposures and Risks ................................................ 19 3.0 Residential and Other Non Occupational Exposures and Risks .......................................... 19 3.1 Residential Handler Exposures and Risks ............................................................... 20 3.2 Residential Postapplication Exposures and Risks.................................................... 24 3.2.1 Residential Postapplication Exposure Scenarios....................................... 24 3.2.2 Data and Assumptions for Residential Postapplication Exposure Scenarios                               25 3.2.3 Residential Postapplication Exposure and Noncancer Risk Estimates ....... 25 3.2.4 Residential Postapplication Exposure and Risk Estimates for Cancer.................................................................................................... 26 3.2.5 Recommendations for Refining Residential Postapplication Risk Assessments ........................................................................................... 26 Page 3 of 26 Executive Summary A combination of erioglaucine ( Acid Blue 9 or FD& C Blue No. 1) and tartrazine ( Acid Yellow 23 or FD& C Yellow No. 5) is commonly referred to as Aquashade. The two dyes work by controlling the portion of the light spectrum required for photosynthesis, thereby limiting the growth of filamentous algae and submerged aquatic vegetation. Registered use sites for aquashade include aquatic uses only. Aquashade is registered for use in occupational and residential settings.

Hazard Concerns:

Use Patterns: Aquashade is registered for use as an aquatic algaecide/ herbicide. Application is recommended early in the growing season while growth is on the bottom of the water body or later in the season after the killing and/ or removal of any existent growth. Repeated applications are allowed to maintain an effective concentration of product in the water body. Aquashade may be used in natural or manmade ponds, lakes, fountains, fish farms and fish hatcheries; and may be applied by both professional applicators and homeowners ( Admiral Liquid; EPA Reg. No. 67064 2   approved 3/ 24/ 05). HED does not have chemical specific data for Aquashade application methods, therefore estimates were based on surrogate data from the Pesticide Handlers Exposure Database ( PHED) and the Outdoor Residential Exposure Task Force ( ORETF).

Occupational Handler Risks: Pesticide handler exposure to Aquashade is likely to occur during its use in a variety of occupational environments. The anticipated use patterns and current labeling indicate several occupational exposure scenarios based on the types of equipment and techniques that can be potentially used for Aquashade applications. Short term ( 1 to 30 days) and intermediate term exposures ( 1 to 6 months) may occur; however, long term exposures ( greater than 6 months) are not expected.

All short and intermediate term occupational scenarios assessed ( dermal and inhalation) resulted in estimated MOEs greater than 100 and, therefore, are not of concern. Short and intermediateterm dermal MOEs range from 410 ( Liquids for Pouring Applications) to 4,300 ( Liquids for Garden Hose End Sprayer), and short and intermediate term inhalation MOEs range from 120,000 ( Liquids for Garden Hose End Sprayer) to 1,600,000 ( Liquids for Pouring Applications).

Occupational Postapplication Risks: Since Aquashade is an algaecide/ herbicide, HED is not aware of any postapplication activities which may result in exposure. No harvesting is required, and while scouting may include identifying any algae or aquatic weed regrowth, these activities should not require contact with the treated water body. For these reasons, occupational postapplication exposure of workers to previously treated water bodies is expected to be negligible and was not assessed. Furthermore, any postapplication activities that could potentially occur would not be expected to exceed those assessed from residential exposures to Aquashade which are not of concern. Residential Handler/ Postapplication Risks: Aquashade is labeled for consumer use to control Page 4 of 26 aquatic algae and weeds in ponds and lakes. The anticipated use patterns and current labeling indicate several residential handler scenarios based on the types of equipment and techniques that can potentially be used to make Aquashade applications. Residents or consumers applying Aquashade products to ponds or lakes may be exposed for short term ( 1 to 30 days) duration through skin contact or by inhalation.

All residential handler scenarios assessed ( dermal and inhalation) resulted in estimated MOEs greater than 100 and, therefore, are not of concern. Residential short term dermal MOEs range from 1,930 ( Liquids for Pouring Applications) to 16,000 ( Liquids for LCO Handgun), and shortterm inhalation MOEs range from 550,000 ( Liquids for Garden Hose End Sprayer) to 6,600,000 ( Liquids for Pouring Applications).

Postapplication exposures to children and adults that contact Aquashade treated swimming ponds are anticipated. To address the risk of such exposures, a screening tool called the Swimmer Exposure Assessment Model ( SWIMODEL) was applied. The SWIMODEL uses well accepted screening exposure assessment equations to calculate the total worst case exposure for swimmers expressed as a mass based intake value ( mg/ event). Postapplication residential exposure durations are expected to be short and intermediate term ( 1 to 6 months) in duration. All residential postapplication scenarios assessed ( dermal, ingestion, aural, buccal/ sublingual, and nasal/ orbital routes of exposure) resulted in estimated combined MOEs well above 100 and, therefore, are not of concern.

To better quantify residential Aquashade hazard, results from residential handler and residential postapplication ( i. e., swimmer) risk assessments were aggregated. Aggregate calculations of residential exposure were performed using worst case MOEs resulting from each assessment.

The residential aggregated exposure resulted in an estimated MOE of 1700 and, therefore, is not a risk of concern.

1.0 Occupational and Residential Exposure Assessment for Aquashade Page 5 of 26 1.1 Purpose This document is the occupational and residential non dietary exposure and risk assessment for Aquashade from its use as an algaecide/ herbicide. In this document, which is for use in EPA= s development of the HED chapter of the Aquashade RED Document, EPA presents the results of its review of the potential human health effects of occupational exposure to Aquashade.

1.2 Criteria for Conducting Exposure Assessments An occupational and/ or residential exposure assessment is required for an active ingredient if ( 1) certain toxicological criteria are triggered and ( 2) there is a potential for exposure to handlers ( mixers, loaders, applicators) during use or to persons entering treated sites or exposed to vapors after application is complete. Toxicological endpoints were selected for short and intermediateterm dermal and inhalation exposures to Aquashade. There is a significant potential for exposure in a variety of occupational agricultural settings. Therefore, a risk assessment is required for occupational exposures that can occur as a result of Aquashade use.

1.3 Summary of Hazard Concerns for Aquashade Dermal Route ( non cancer): For short and intermediate term dermal exposures to Aquashade, an endpoint was selected based upon co critical studies, a chronic oral toxicity study in dogs with tartrazine and chronic oral toxicity/ carcinogenicity study in rats with erioglaucine. The dermal endpoint was assigned considering the most protective NOAEL resulting from the two studies, 500 mg/ kg/ day; as determined from the chronic oral toxicity dog study with tartrazine. The resulting NOAEL was the highest dose tested ( HDT) in the selected study.

Inhalation Route ( non cancer): For short and intermediate term inhalation exposures to Aquashade, an endpoint was selected based upon co critical studies, a chronic oral toxicity study in dogs with tartrazine and chronic oral toxicity/ carcinogenicity study in rats with erioglaucine. The inhalation endpoint was assigned considering the most protective NOAEL resulting from the two studies, 500 mg/ kg/ day; as determined from the chronic oral toxicity dog study with tartrazine. The resulting NOAEL was the highest dose tested ( HDT) in the selected study.

Incidental Oral ( non cancer): For short and intermediate term incidental oral exposures to Aquashade, an endpoint was selected based upon co critical studies, a chronic oral toxicity study in dogs with tartrazine and a chronic oral toxicity/ carcinogenicity study in rats with erioglaucine. The incidental oral endpoint was assigned considering the most protective NOAEL resulting from the two studies, 500 mg/ kg/ day; as determined from the chronic oral toxicity dog study with tartrazine. The resulting NOAEL was the highest dose tested ( HDT) in the selected study.

Non Cancer Level of Concern ( LOC): HED's level of concern ( LOC) for Aquashade dermal Page 6 of 26 and inhalation exposures is 100 ( i. e., a margin of exposure ( MOE) less than 100 exceeds HED's level of concern) for occupational scenarios. The level of concern is based on 10X to account for interspecies extrapolation ( differences between humans and animals) to humans from the animal test species and 10X to account for intraspecies sensitivity ( differences among humans).

Carcinogenicity of Aquashade: No evidence for carcinogenicity was seen in rats. Therefore, no cancer endpoints of concern for Aquashade were selected and risks to handlers were not assessed.

Acute Toxicity:

Table 1.3a Acute Toxicity Profile  Admiral WSP ( Erioglaucine 68.13%; Tartrazine 4.51%)

Guideline No. Study Type MRIDs Results Toxicity Category 870.1100 Acute oral [ rats] 45281101 LD50 > 5000 mg/ kg IV 870.1200 Acute dermal [ rabbit] 45144401 LD50 > 2000 mg/ kg III 870.1300 Acute inhalation NA data requirement waived 870.2400 Acute eye irritation [ rabbit] 44902902 No eye irritation III 870.2500 Acute dermal irritation [ rabbit] 45086102 negative IV 870.2600 Skin sensitization [ guinea pig] 44902904 positive Table 1.3b Summary of Toxicological Doses and Endpoints for Aquashade Page 7 of 26 Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects Incidental Oral Short ( 1  30 days)

and Intermediate

Term ( 1   6 months) NOAEL = 500 mg/ kg/ day ( HDT) ( Tartrazine)

Co critical: NOAEL = 631 mg/ kg/ day ( Erioglaucine) Residential MOE = 100 Occupational MOE= NA Chronic oral toxicity in dogs LOAEL = not identified ( Tartrazine)

Co critical:

Combined chronic toxicity/ carcinogenicity study in rats ( Erioglaucine)

LOAEL = 1262 mg/ kg/ day based on decreased body weight in females.

Dermal Short ( 1

30 days) and Intermediate Term ( 1   6 months) NOAEL = 500 mg/ kg/ day ( HDT) ( Tartrazine)

Co critical: NOAEL = 1200 mg/ kg/ day ( HDT) ( Erioglaucine)

UF = 100X ( dermal absorption rate = 100%) Residential MOE = 100 Occupational MOE = 100 Chronic oral toxicity/ carcinogenicity study in rats LOAEL = not identified ( Tartrazine)

Co critical Chronic oral toxicity in dogs LOAEL = not identified ( Erioglaucine)

Inhalation Short ( 1  30 days) and Intermediate Term ( 1   6 months) NOAEL = 500 mg/ kg/ day ( HDT) ( Tartrazine)

Co critical: NOAEL = 1200 mg/ kg/ day ( HDT) ( Erioglaucine)

UF = 100X ( inhalation absorption rate = 100%) Residential MOE = 100 Occupational MOE = 100 Chronic oral toxicity/ carcinogenicity study in rats LOAEL = not identified ( Tartrazine)

Co critical Chronic oral toxicity in dogs LOAEL = not identified ( Erioglaucine)

Cancer ( oral, dermal, inhalation) Classification: No evidence or carcinogenicity Body Weight: The adverse effects for the short and intermediate term dermal and inhalation endpoints are based on studies where the effects were not gender specific, therefore, the body weight of an average adult ( i. e. 70 kg) was used to estimate exposure. Page 8 of 26 1.4 Incident Reports Reference: Review of Aquashade Incident Reports, Chemicals # 110303, # 110301, and # 110302, DP Barcode: D302184, Jerome Blondell, 08/ 22/ 05.

There were almost no reports of ill effects from exposure to Aquashade in the available data bases. The lack of incidents further supports HED's characterization of Aquashade as a low toxicity pesticide with little potential for acute effects.

One report was found in the OPP Incident Data System ( IDS) in which blue water was observed in a government office building in Ohio in 1989. An investigation found that Acid Blue 9 ( a component of Aquashade) had backflowed into the building's potable water system apparently causing 12 illnesses. Ultimately, it was determined that this incident is too poorly documented and not a basis for conclusions about the human toxicity of the product in question.

Reports from scientific literature suggest that there was concern that Aquashade could cloud water to the point of reducing visibility and disorient divers into lakes treated with Aquashade and possibly lead to drowning. However, further studies were conducted and it was concluded that " The results of this study suggest that the drownings reported in North Carolina could not have been solely or primarily due to the addition of Aquashade to the lake water. It appears more likely that a high volume of plant material may have remained in the lake and may have been more responsible for the disorientation of swimmers and divers who drowned. Under the conditions of this experiment, Aquashade does not appear to reduce the visibility of water significantly in a manner that would create unsafe swimming hazards."

There are no incidents reported by the Poison Control Center ( PCC), the California Department of Pesticide Regulation ( CDPR), the National Pesticide Information Center ( NPIC), or the National Institute of Occupational Safety and Health's Sentinel Event Notification System for Occupational Risks ( NIOSH SENSOR).

1.5 Summary of Use Patterns and Formulations 1.5.1 End Use Products Aquashade is an aquatic algaecide/ herbicide which controls the growth of algae and aquatic vegetation. Registered use sites for Aquashade include aquatic uses only. Applications are generally made prior to or early in the growing season when growth is on the bottom of the water body. However, applications can be made later in the growing season when growth is closer to the surface after the killing and/ or removal of any existent growth. Aquashade is formulated for use in occupational settings as either a liquid or water soluble packet ( WSP) product, and can be applied by pouring or dropping the WSP in water body from the shoreline, or possibly by boat for larger water bodies. Residential uses of Aquashade are formulated as a liquid product only ( 67064 2). While not specified on product labeling, applications could be made by LCO handgun Page 9 of 26 or garden hose end sprayer.

Aquashade works by shading portions of the light spectrum required by underwater plant and algal growth. If applied early in the growth season, Aquashade inhibits photosynthesis of filamentous algae and submerged aquatic vegetation.

1.5.2 Registered Use Categories and Sites Aquashade is registered for use in a variety of occupational and residential scenarios and thus these populations could be exposed while performing Aquashade applications. A summary of maximum application rates for registered Aquashade uses is presented in Table 1.5.2.

Table 1.5.2 Summary of Registered Aquashade Commercial Uses Liquid Formulation Product Crop Max App Rate ( lb ai/ acre foot) Amount of Product for Area To Be Treated Application Methods Aquashade ( 33068 1) Ornamental and Recreational Lakes and Ponds, Fish Rearing and Fish Farming Ponds, Golf Course Ponds 1.1 0.5 gallon/ acre foot ( 2 ppm) Pouring Admiral Liquid ( 67064 2) Fountains, Fish Farms, Fish Hatcheries, Golf Courses, Lakes, Manmade Ponds, Swimming Ponds 0.73 0.5 gallon/ acre foot ( 2ppm) Pouring Algae Blocker ( 8709 6) Garden Ponds, Goldfish Ponds, Koi Ponds, Ornamental Ponds 0.22 120 ml / 1500 gallons Pouring Aquashade OA ( 33068 2) Aquariums, Fountains, Ornamental Ponds, Recirculated or Artificial Waterscapes 0.22 1 ounce/ 1000 gallons Pouring Water Soluble Packets ( WSP) Page 10 of 26 Admiral WSP ( 67064 1) Fish Farms, Fish Hatcheries, Fountains, Golf Courses, Manmade Ponds, Swimming Ponds 0.73 2 WSPs/ acre foot ( 11 ounces) WSP 1.5.3 Application Methods According to product labeling, Aquashade can be applied by pouring liquid formulations or dropping the WSP in water body from the shoreline, or from a boat for larger water bodies. While not specified on product labeling, applications could be made by LCO handgun or garden hose end sprayer.

2.0 Occupational Exposures and Risks HED determined that the potential for occupational exposure to Aquashade exists in a variety of occupational environments. The anticipated use patterns and current labeling indicate several occupational exposure scenarios based on the types of equipment and techniques that can potentially be used for Aquashade applications. These include the handling of Aquashade during mixing, loading, and applying processes ( i. e. mixer/ loaders, and mixer/ loader/ applicators). As a result, a risk assessment has been completed for the occupational handler scenario. Short term ( 1 to 30 days) and intermediate term exposures ( 1 to 6 months) may occur; however, long term exposures ( greater than 6 months) are not expected.

2.1 Occupational Handler Exposures and Risks HED uses the term Ahandlers@ to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and that exposures can vary depending on the specifics of each task. Job requirements ( e. g., amount of chemical to be used in an application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

HED uses exposure scenarios to describe the various types of handler exposures that may occur for a specific active ingredient. The use of scenarios as a basis for exposure assessment is described in the U. S. EPA Guidelines for Exposure Assessment ( U. S. EPA; Federal Register Volume 57, Number 104; May 29, 1992). Information from the current labels, use and usage information, toxicology data, and exposure data were all key components in the development of the exposure scenarios. HED has developed a series of general descriptions for tasks that are associated with pesticide applications. Tasks associated with occupational pesticide handlers are categorized using one of the following terms: Page 11 of 26 $ Mixers and/ or Loaders: these individuals perform tasks in preparation for an application. For example, prior to application, mixer/ loaders would mix the Aquashade for open pouring of Aquashade.

$ Mixer/ Loader/ Applicators and or Loader/ Applicators: these individuals are involved in the entire pesticide application process ( i. e., they do all job functions related to a pesticide application event). These individuals would transfer Aquashade into the application equipment and then also apply it.

A chemical can produce different effects based on how long a person is exposed, how frequently exposures occur, and the level of exposure. HED classifies exposures up to 30 days as short term and exposures greater than 30 days up to six months as intermediate term. HED completes both short and intermediate term assessments for occupational scenarios in essentially all cases, because these kinds of exposures are likely and acceptable use/ usage data are not available to justify deleting intermediate term scenarios. Based on use data and label instructions, HED believes that occupational Aquashade exposures may occur over a single day or up to weeks at a time for many use patterns and that intermittent exposures over several weeks also may occur. Some applicators may apply Aquashade over a period of weeks, because they are custom or commercial applicators who are completing a number of applications for a number of different clients. Long term handler exposures are not expected to occur for Aquashade.

Other parameters are also defined from use and usage data such as application rates and application frequency. HED always completes non cancer risk assessments using maximum application rates for each in order to ensure there are no concerns for each specific use.

Occupational handler exposure assessments are completed by HED using different levels of risk mitigation. Typically, HED uses a tiered approach. The lowest tier is designated as the baseline exposure scenario ( i. e., long sleeve shirt, long pants, shoes, socks, and no respirator). If risks are of concern at baseline attire, then increasing levels of personal protective equipment or PPE ( e. g., gloves, double layer body protection, and respirators) are evaluated. If risks remain a concern with maximum PPE, then engineering controls ( e. g., enclosed cabs or cockpits, water soluble packaging, and closed mixing/ loading systems) are evaluated. This approach is used to ensure that the lowest level of risk mitigation that provides adequate protection is selected, since the addition of PPE and engineering controls involves an additional expense to the user and B in the case of PPE B also involves an additional burden to the user due to decreased comfort and dexterity and increased heat stress and respiratory stress.

2.1.1 Data and Assumptions for Handler Exposure Scenarios <IP_ADDRESS> Assumptions for Handler Exposure Scenarios A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. The assumptions used in the risk assessment calculations are detailed Page 12 of 26 below:

C Occupational handler exposure estimates were based on surrogate data from the Pesticide Handlers Exposure Database ( PHED) and the Outdoor Residential Exposure Task Force ( ORETF).

C HED has developed standard unit exposure values for many occupational scenarios to ensure consistency in exposure assessments. These standard values were used to calculate handler exposures for the associated scenarios. For those scenarios where standard values have not been developed, surrogate values based on a similar scenario were used.

C The adverse effects for the short and intermediate term dermal and inhalation endpoints are based on studies where the effects were observed in males and females, therefore, the body weight of an average adult ( i. e. 70 kg) was used to estimate exposure.

C For non cancer assessments, HED assumes the maximum application rates allowed by labels in its risk assessments.

C The average occupational workday is assumed to be 8 hours.

C The daily areas treated were defined for each handler scenario ( in appropriate units) by determining the amount that can be reasonably treated in a single day ( e. g., acres, square feet, cubic feet, or gallons per day). When possible, the assumptions for daily areas treated are taken from the Health Effects Division Science Advisory Committee on Exposure SOP # 9: Standard Values for Daily Acres Treated in Agriculture, which was completed on July 5, 2000. Since Aquashade is not used in agriculture the above source is not applicable. Therefore, the daily area treated with Aquashade was investigated and was assumed to be 25 acre feet per day [ Personal Communication per Email from Dr. Kurt Getsinger ( USACE) to J. Carter ( OPP, BEAD), 8/ 22/ 05]. This high end estimate is recognized to be conservative; however, the value is assumed to result in risks that represent reasonable worst case estimates of exposure to occupational handlers of Aquashade.

<IP_ADDRESS> Exposure Data for Handler Exposure Scenarios HED uses unit exposures to assess handler exposures to pesticides. Unit exposures are estimates of the amount of exposure to an active ingredient a handler receives while performing various handler tasks and are expressed in terms of micrograms or milligrams of active ingredient per pounds of active ingredient handled. HED has developed a series of unit exposures that are unique for each scenario typically considered in our assessments ( i. e., there are different unit exposures for different types of application equipment, job functions, and levels of protection). The unit exposure concept has been established in the scientific literature and also through various exposure monitoring guidelines published by the U. S. EPA and international organizations such as Health Canada and OECD ( Organization for Economic Cooperation and Development). Page 13 of 26 Pesticide Handler Exposure Database ( PHED) Version 1.1 ( August 1998): PHED was designed by a task force of representatives from the U. S. EPA, Health Canada, the California Department of Pesticide regulation, and member companies of the American Crop Protection Association. PHED is a software system consisting of two parts B a database of measured exposures for workers involved in the handling of pesticides under actual field conditions and a set of computer algorithms used to subset and statistically summarize the selected data. Currently, the database contains values for over 1,700 monitored individuals ( i. e., replicates).

Users select criteria to subset the PHED database to reflect the exposure scenario being evaluated. The subsetting algorithms in PHED are based on the central assumption that the magnitude of handler exposures to pesticides are primarily a function of activity ( e. g., mixing/ loading, mixing/ loading/ applying), formulation type ( e. g., liquids, water soluble packets), application method ( e. g., pouring, garden hose end sprayer), and clothing scenarios ( e. g., gloves, double layer clothing).

Once the data for a given exposure scenario have been selected, the data are normalized ( i. e., divided by) by the amount of pesticide handled resulting in standard unit exposures ( milligrams of exposure per pound of active ingredient handled). Following normalization, the data are statistically summarized. The distribution of exposure for each body part ( e. g., chest, upper arm) is categorized as normal, lognormal, or Aother@ ( i. e., neither normal nor lognormal). A central tendency value is then selected from the distribution of the exposure for each body part. These values are the arithmetic mean for normal distributions, the geometric mean for lognormal distributions, and the median for all Aother@ distributions. Once selected, the central tendency values for each body part are composited into a Abest fit@ exposure value representing the entire body.

The unit exposures calculated by PHED generally range from the geometric mean to the median of the selected data set. To add consistency and quality control to the values produced from this system, the PHED Task Force has evaluated all data within the system and has developed a set of grading criteria to characterize the quality of the original study data. The assessment of data quality is based on the number of observations and the available quality control data. These evaluation criteria and the caveats specific to each exposure scenario are summarized in Appendix B, Table B1. While data from PHED provide the best available information on handler exposures, it should be noted that some aspects of the included studies ( e. g., duration, acres treated, pounds of active ingredient handled) may not accurately represent labeled uses in all cases. HED has developed a series of tables of standard unit exposure for many occupational scenarios that can be utilized to ensure consistency in exposure assessments. Unit exposures are used which represent different levels of personal protection as described above. Protection factors were used to calculate unit exposures for varying levels of personal protection if data were not available.

ORETF Handler Studies ( MRID 449722 01): A report was submitted by the ORETF Page 14 of 26 ( Outdoor Residential Exposure Task Force) that presented data in which the application of various products used on turf by homeowners and lawn care operators ( LCOs) was monitored. All of the data submitted in this report were completed in a series of studies. These studies are summarized in the HED Memorandum " Summary of HED's Reviews of ORETF Chemical Handler Exposure Studies: MRID 449722 01", DP Barcode D261948 of April 30, 2001. The studies performed used dacthal as a surrogate compound with a target application rate of 2.0 lbs/ ai. All studies were conducted in accordance with current Agency guidelines, have been reviewed by HED and Health Canada, and the data generated were of high quality.

2.1.2 Aquashade Handler Exposure Scenarios Pesticide handler exposure to Aquashade is likely to occur during its use in a variety of occur during its use in a variety of occupational environments. The anticipated use patterns and current labeling indicate several occupational exposure scenarios based on the types of equipment and techniques that can potentially be used for Aquashade applications. The quantitative exposure/ risk assessment developed for occupational handlers of Aquashade is based on the following scenarios.

Mixer/ Loaders: ( 1) Liquids for Pouring Applications Mixer/ Loader/ Applicators: ( 2) Liquids for Garden Hose End Sprayer ( ORETF) ( 3) Liquids for LCO Handgun ( ORETF)

2.1.3 Non cancer Aquashade Handler Exposure and Assessment <IP_ADDRESS> Non cancer Aquashade Handler Exposure and Risk Calculations Daily Exposure: Daily inhalation handler exposures are estimated for each applicable handler task with the application rate, the area treated in a day, and the applicable inhalation unit exposure using the following formula:

Where:

Daily Exposure = Amount ( mg or Fg ai/ day) deposited on the surface of the skin that is available for inhalation absorption;

day area Treated Area Daily x area ai lbs Rate n Applicatio x handled ai lb ai mg Exposure Unit = day ai mg Exposure Daily Page 15 of 26 Unit Exposure = Unit exposure value ( mg or

g ai/ lb ai) derived from August 1998 PHED data, from ORETF data, study data; Application Rate = Normalized application rate based on a logical unit treatment, such as acres, square feet, or gallons. Maximum values are generally used ( lb ai/ A, lb ai/ sq ft, lb ai/ gal) and Daily Area Treated = Normalized application area based on a logical unit treatment such as acres ( A/ day), square feet ( sq ft/ day), OR gallons per day ( gal/ day).

Daily Dose: The daily inhalation dose is calculated by normalizing the daily exposure by body weight and adjusting, if necessary, with an appropriate inhalation absorption factor. HED did not identify dermal toxicity endpoints for Aquashade, therefore, only inhalation exposures were assessed. For all short and intermediate term exposure scenarios for Aquashade, an average male adult body weight of 70 kilograms was used, since the studies are based on effects observed in males and females. An absorption factor of 100% was used for inhalation dose calculations. Daily dose was calculated using the following formula:

Where:

Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario ( mg pesticide active ingredient/ kg body weight/ day); Daily Exposure = Amount ( mg ai/ day) inhaled that is available for inhalation absorption; Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as the skin or lungs (% of the total available absorbed); and Body Weight = Body weight determined to represent the population of interest in a risk assessment ( kg).

Margins of Exposure: Non cancer inhalation risks for each applicable handler scenario are calculated using a Margin of Exposure ( MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. All MOE values were calculated for inhalation exposure levels.

Where:

MOE = Margin of Exposure, value used by HED to represent risk or how close a chemical exposure is to being a concern ( unitless); ADD = Average Daily Dose or the absorbed dose received from exposure to a pesticide in a given scenario ( mg pesticide active ingredient/ kg ( ) ( ) mg/ kg/ day Dose Daily Average mg/ kg/ day LOAEL NOAEL = MOE   ( )

( kg) Weight Body / 100) (% Factor Absorption x day ai mg Exposure Daily = / day / kg mg Dose Daily Average Page 16 of 26 body weight/ day); and NOAEL or LOAEL = Dose level in a toxicity study, where no observed adverse effects ( NOAEL) or where the lowest observed adverse effects ( LOAEL) occurred in the study Risk values are presented for the route of exposure ( i. e., inhalation) in each scenario, because risk mitigation measures are specific to the route of exposure.

<IP_ADDRESS> Aquashade Non cancer Risk Summary ( using PHED data)

Short and Intermediate term Total Risks: All occupational handler scenarios assessed ( dermal and inhalation) resulted in estimated MOEs greater than 100 and, therefore, are not of concern. Short and intermediate term MOEs do not differ because they share the same toxicological endpoint. A summary of the MOEs estimated for handlers are presented in Table <IP_ADDRESS>. Page 17 of 26 Table <IP_ADDRESS>: Short and Intermediate term Baseline Exposures and Risks for Occupational Handlers of Aquashade Exposure Scenario ( Scenario #) Crop1 Dermal Unit Exposure ( mg/ lb ai) 2 Inhalation Unit Exposure ( Ug/ lb ai) 3 Application Rate ( lb ai / acre foot) 4 Area Treated Daily ( acrefeet 5 Baseline Dermal MOE 6 Baseline Inhalation MOE7 Mixer/ Loader Liquids for Pouring Applications ( 1) Ornamental and Recreational Lakes and Ponds 3.1 1.2 1.1 25 410 1100000 Liquids for Pouring Applications ( 1) Fountains, Fish Farms, Fish Hatcheries, Golf Courses, Lakes, Manmade Ponds, Swimming Ponds 3.1 1.2 0.73 25 620 1600000 Mixer/ Loader/ Applicator Liquids for Garden Hose End Sprayer ( 2) Ornamental and Recreational Lakes and Ponds 0.45 11 1.1 25 2800 120000 Liquids for Garden Hose End Sprayer ( 2) Fountains, Fish Farms, Fish Hatcheries, Golf Courses, Lakes, Manmade Ponds, Swimming Ponds 0.45 11 0.73 25 4300 170000 Liquids for LCO Handgun ( ORETF) ( 3) Ornamental and Recreational Lakes and Ponds 0.50 1.9 1.1 25 2500 670000 Liquids for LCO Handgun ( ORETF) ( 3) Fountains, Fish Farms, Fish Hatcheries, Golf Courses, Lakes, Manmade Ponds, Swimming Ponds 0.50 1.9 0.73 25 3800 100000 Page 18 of 26 1 Crops and use patterns are from product labeling. 2Baseline dermal unit exposures represent long pants, long sleeved shirts, shoes, and socks. Values are reported in the PHED Surrogate Exposure Guide dated August 1998 or are from data submitted by the Outdoor Residential Exposure Task Force dated May 2000. 3Baseline inhalation unit exposures represent no respirator. Values are reported in the PHED Surrogate Exposure Guide dated August 1998 or are from data submitted by the Outdoor Residential Exposure Task Force dated May 2000. 4Application rates are based on maximum values found in various sources including LUIS and various labels. In most scenarios, a range of maximum application rates is used to represent the range of rates for different crops/ sites/ uses. 5Amount treated is based on the area or gallons that can be reasonably applied in a single day for each exposure scenario of concern based on the application method and formulation/ packaging type. ( Standard EPA/ OPP/ HED values). 6 Dermal MOE = NOAEL ( 500 mg/ kg/ day) / Daily dermal dose ( mg/ kg/ day). MOEs are reported to 2 significant figures. 7Inhalation MOE = NOAEL ( 500 mg/ kg/ day) / Daily inhalation dose ( mg/ kg/ day). MOEs are reported to 2 significant figures.

HED believes that the risk estimates presented in this occupational assessment represent the best quality results that could be produced given the exposure, use, and toxicology data that are available. HED also believes that the risks represent reasonable worst case estimates of exposure, because maximum application rates are coupled with medium to high end estimates of area treated daily to define risk estimates that likely fall in the upper percentiles of the actual exposure distributions. Using these worst case assumptions, estimated occupational handler MOEs for all exposure scenarios are greater than 100 and are, therefore, not of concern.

2.1.4 Cancer Aquashade Handler Exposure and Risk Assessment No cancer endpoints of concern for Aquashade were identified; therefore cancer risks to handlers were not assessed.

2.1.5 Summary of Risk Concerns and Data Gaps for Occupational Handlers <IP_ADDRESS> Summary of Risk Concerns A summary of the short and intermediate term risks ( dermal and inhalation) for each exposure scenario is presented in Table <IP_ADDRESS>. The calculated occupational handler exposures for all scenarios resulted in estimated MOEs greater than 100 and, therefore, are not of concern. Shortand intermediate term MOEs do not differ because they share the same toxicological endpoint. Short and intermediate term dermal MOEs range from 410 ( Liquids for Pouring Applications) to 4,300 ( Liquids for Garden Hose End Sprayer), and short and intermediate term inhalation MOEs range from 120,000 ( Liquids for Garden Hose End Sprayer) to 1,600,000 ( Liquids for Pouring Applications).

<IP_ADDRESS> Summary of Data Gaps There are no occupational handler scenarios for Aquashade that have data gaps.

2.1.6 Recommendations for Refining Occupational Handler Risk Page 19 of 26 Assessment In order to refine this occupational risk assessment, data on actual use patterns including rates, timing, and areas treated would better characterize Aquashade risks. Exposure studies for equipment types that lack data or that are not well represented in PHED ( e. g., because of low replicate numbers or data quality) should also be considered based on a review of the quality of the data used in this assessment.

2.2 Occupational Postapplication Exposures and Risks HED uses the term A postapplication @

to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide ( also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Postapplication exposure levels vary over time and depend on such things as the type of activity ( scouting, harvesting, etc.), the nature of the crop or target that was treated, the type of pesticide application ( foliar, soil incorporated, banded, etc.) and the chemical =

s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for postapplication exposure.

Aquashade is generally applied prior to or early in the growing season when growth is on the bottom of the water body. Applications can also be made later in the growing season when growth is closer to the surface after the killing and/ or removal of any existent growth. Since Aquashade is an algaecide/ herbicide, HED is not aware of any postapplication activities which may result in exposure. No harvesting is required, and while scouting may include identifying any algae or aquatic weed regrowth, these activities should not require contact with the treated water body. For these reasons, occupational postapplication exposure of workers to previously treated water bodies is expected to be negligible and was not assessed. Furthermore, any postapplication activities that could potentially occur would not be expected to exceed those assessed from residential exposures to Aquashade which are not of concern.

In accordance with the Worker Protection Standard ( WPS), a restricted entry interval ( REI) is established to mitigate contact with a pesticide in treated agricultural areas. However, since Aquashade has no agricultural applications an REI was not required.

3.0 Residential and Other Non Occupational Exposures and Risks Aquashade is labeled for consumer use to control aquatic algae and weeds in ponds and lakes. The anticipated use patterns and current labeling indicate several residential handler scenarios based on the types of equipment and techniques that can potentially be used to make Aquashade applications. Residents or consumers applying Aquashade products to ponds or lakes may be exposed for short term ( 1 to 30 days) duration through skin contact or by inhalation. Page 20 of 26 Postapplication exposures to children and adults that contact Aquashade treated swimming ponds are anticipated. To address the risk of such exposures, a screening tool called the Swimmer Exposure Assessment Model ( SWIMODEL) was applied. The SWIMODEL uses well accepted screening exposure assessment equations to calculate the total worst case exposure for swimmers expressed as a mass based intake value ( mg/ event). Postapplication residential exposure durations are expected to be short and intermediate term ( 1 to 6 months) in duration.

To better quantify residential Aquashade hazard, results from residential handler and residential postapplication risk assessments were aggregated. Aggregate calculations of residential exposure were performed using worst case MOEs resulting from each assessment.

3.1 Residential Handler Exposures and Risks HED uses the term " handlers" to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct tasks related to applications and that exposures can vary depending on the specifics of each task as was described above for occupational handlers.

3.1.1 Handler Exposure Scenarios Scenarios are used to define risks based on the U. S. EPA Guidelines for Exposure Assessment ( U. S. EPA; Federal Register Volume 57, Number 104; May 29, 1992). Assessing exposures and risks resulting from residential uses is very similar to assessing occupational exposures and risks, with the following exceptions:

  Residential handler exposure scenarios are considered to be short term only, due to the infrequent use patterns associated with homeowner products.

  A tiered approach for personal protection using increasing levels of PPE is not used in residential handler risk assessments. Homeowner handler assessments are based on the assumption that individuals are wearing shorts, short sleeved shirts, socks, and shoes.

  Homeowner handlers are expected to complete all tasks associated with the use of a pesticide product including mixing/ loading if needed as well as the application.

  Label use rates and use information specific to residential products serve as the basis for the risk calculations.

  Area/ volumes of spray or chemical used in the risk assessment are based on HED's guidance specific to residential use patterns.

Aquashade is labeled for consumer use to control aquatic algae and weeds in ponds and lakes; Page 21 of 26 therefore, pesticide handler exposure to Aquashade is likely to occur during its use. The anticipated use patterns and current labeling indicate several residential handler exposure scenarios based on the types of equipment and techniques that can be potentially used for consumer Aquashade applications. The quantitative exposure/ risk assessment developed for residential handlers is based on the following scenarios.

Mixer/ Loader/ Applicators: ( 1) Liquids for Pouring Applications ( using PHED mixer/ loader data) ( 2) Liquids for Garden Hose End Sprayer ( ORETF) ( 3) Liquids for LCO Handgun ( ORETF)

3.1.2 Data and Assumptions for Handler Exposure Scenarios A series of assumptions served as the basis for completing the residential handler risk assessments. Each assumption and factor is detailed below. In addition to these factors, unit exposure values were used to calculate risk estimates. Mostly, these unit exposure values were taken from the Pesticide Handlers Exposure Database ( PHED) and the Outdoor Residential Exposure Task Force ( ORETF) studies. Both PHED and the individual studies are presented below. [ Note: Several of the assumptions and factors used for the assessment are similar to those used in the occupational assessment presented above. As such, only factors that are unique to the residential scenarios are presented below.]

Assumptions and Factors: The assumptions and factors used in the risk calculations include:

C HED has developed standard unit exposure values for many occupational scenarios to ensure consistency in exposure assessments. These standard values were used to calculate handler exposures for the associated scenarios. For those scenarios where standard values have not been developed, surrogate values based on a similar scenario were used.

C HED always considers the maximum application rates allowed by labels in its risk assessments. If additional information such as average or typical rates are available, these values also may be used to allow risk managers to make a more informed risk management decision.

3.1.3 Residential Handler Exposure and Non Cancer Risk Estimates Non cancer risks were calculated using the Margin of Exposure ( MOE) as described in Section 2.1.3. Assessing exposures and risks resulting from residential uses is very similar to assessing occupational exposures and risks, except as described in Section 3.1.1. The overall uncertainty factor applied to Aquashade handler risk assessments is an MOE of 100, which is based on 10X for inter species extrapolation, and 10X for intra species variation.

Risk Summary: A summary of the short term risks ( dermal and inhalation) for each exposure Page 22 of 26 scenario is presented below in Table 3.1.3. All residential handler scenarios assessed resulted in estimated MOEs greater than 100 and, therefore, are not of concern. Short and intermediateterm MOEs do not differ because they share the same toxicological endpoint. Residential shortterm dermal MOEs range from 1,930 ( Liquids for Pouring Applications) to 16,000 ( Liquids for LCO Handgun), and short term inhalation MOEs range from 550,000 ( Liquids for Garden Hose End Sprayer) to 6,600,000 ( Liquids for Pouring Applications). Page 23 of 26 Table 3.1.3: Short term Exposures and Risks for Residential Handlers of Aquashade Exposure Scenario ( Scenario #) Crop1 Dermal Unit Exposure ( mg/ lb ai) 2 Inhalation Unit Exposure ( Ug/ lb ai) 3 Application Rate3 ( lb ai / acre foot) 4 Area Treated Daily ( acrefeet 5 Surface Area ( acres) Depth of Water Body ( feet) Baseline Dermal MOE 6 Baseline Inhalation MOE7 Mixer/ Loader/ Applicator Liquids for Pouring Applications ( 1) Fountains, Fish Farms, Fish Hatcheries, Golf Courses,

Lakes, Manmade Ponds,

Swimming Ponds 3.1 1.2 0.73 8 8 1 1930 5000000 Liquids for Pouring Applications ( 1) Ornamental and Recreational Lakes and Ponds 3.1 1.2 1.1 4 1 4 2600 6600000 Liquids for Garden Hose End Sprayer ( ORETF) ( 2) Fountains, Fish Farms, Fish Hatcheries, Golf Courses,

Lakes, Manmade Ponds,

Swimming Ponds 2.6 11 0.73 8 8 1 2300 550000 Liquids for Garden Hose End Sprayer ( ORETF) ( 2) Ornamental and Recreational Lakes and Ponds 2.6 11 1.1 4 1 4 3100 720000 Liquids for LCO Handgun ( ORETF) ( 3) Fountains, Fish Farms, Fish Hatcheries, Golf Courses,

Lakes, Manmade Ponds,

Swimming Ponds 0.50 1.9 0.73 8 8 1 12000 3100000 Liquids for LCO Handgun ( ORETF) ( 3) Ornamental and Recreational Lakes and Ponds 0.50 1.9 1.1 4 1 4 16000 4200000 Page 24 of 26 1 Crops and use patterns are from product labeling. 2Baseline dermal unit exposures represent short pants and short sleeved shirt Values are reported in the PHED Surrogate Exposure Guide dated August 1998 or are from data submitted by the Outdoor Residential Exposure Task Force dated May 2000. 3Baseline inhalation unit exposures represent no respirator. Values are reported in the PHED Surrogate Exposure Guide dated August 1998 or are from data submitted by the Outdoor Residential Exposure Task Force dated May 2000. 4Application rates are based on maximum values found in various sources including LUIS and various labels. In most scenarios, a range of maximum application rates is used to represent the range of rates for different crops/ sites/ uses. Most application rates upon which the analysis is based are presented as lb ai/ A. 5Amount treated is based on the area or gallons that can be reasonably applied in a single day for each exposure scenario of concern based on the application method and formulation/ packaging type. ( Standard EPA/ OPP/ HED values). 6 Dermal MOE = NOAEL ( 500 mg/ kg/ day) / Daily dermal dose ( mg/ kg/ day). MOEs are reported to 2 significant figures. 7Inhalation MOE = NOAEL ( 500 mg/ kg/ day) / Daily inhalation dose ( mg/ kg/ day). MOEs are reported to 2 significant figures.

3.1.4 Residential Handler Exposure and Risk Estimates for Cancer Residential handler cancer risks were not assessed, since no toxicological endpoint of concern for cancer was selected.

3.1.5 Recommendations for Refining Residential Handler Risk Assessment In order to refine this residential risk assessment, more data on actual use patterns including rates, timing, and areas treated would better characterize Aquashade risks. Exposure studies for many equipment types that lack data or that are not well represented in PHED ( i. e., because of low replicate numbers or data quality) should also be considered based on a review of the quality of the data used in this assessment.

3.2 Residential Postapplication Exposures and Risks HED uses the term postapplication to describe exposures to individuals that occur as a result of being in an environment that has been previously treated with a pesticide. Aquashade can be used in areas that can be frequented by the general population including residential areas ( i. e., swimming ponds). There is potential for dermal, ingestion, aural, buccal/ sublingual, and nasal/ orbital routes of exposure to adults and children following its residential application. The potential for incidental exposures of short term duration exist from the day of application to the water body. Intermediate term exposures could also occur and were considered as well.

3.2.1 Residential Postapplication Exposure Scenarios In order to assess short and intermediate term postapplication risks for children and adults exposed to Aquashade treated residential swimming ponds, the SWIMODEL was applied. The SWIMODEL uses well accepted screening exposure assessment equations to calculate the total worst case exposure for swimmers expressed as a mass based intake value ( mg/ event). Page 25 of 26 3.2.2 Data and Assumptions for Residential Postapplication Exposure Scenarios A series of assumptions and exposure factors served as the basis for completing the residential postapplication risk assessments. The assumptions and factors used in the risk calculations are consistent with current Agency policy for completing residential exposure assessments ( i. e., SOPs for Residential Exposure Assessment). The SWIMODEL was applied incorporating the assumptions and factors of the SOPs for Residential Exposure Assessment. The values used in this assessment include:

  The skin surface area of adults is expected to be 21,000 cm ² as cited in the SOPs for Residential Exposure Assessment. This is the 95th percentile value for females ( EPA Exposure Factors Handbook, 1997).   The body weight for children is assumed to be 22 kg as cited in the SOPs for Residential Exposure Assessment. This is a mean value for 6 year old children.   The skin surface area for children is assumed to be 9,000 cm2 as cited in the SOPs for Residential Exposure Assessment. This is the 90th percentile value for male and female children.   The assumed mean ingestion rate is 0.05 liters per hour for both adults and children as cited in the SOPs for Residential Exposure Assessment. This value may be greater for young children playing in water and accidentally ingesting a remarkable quantity of water ( U. S. EPA SAP, 1999).   The exposure time is assumed to be 3 hours per day. This is the 90th percentile value for time spent swimming in a freshwater pool. ( EPA Child Specific Exposure Factors Handbook, 2002).   The body weight for adult short and intermediate term exposures is assumed to be 70 kg because the studies used to select endpoints were not gender specific.   Acute term exposures were not assessed because no studies were performed from which to determine an endpoint for the exposure duration.   Postapplication residential risks are based on maximum application rates or values specified in the SOPs for Residential Exposure Assessment. The maximum label application rate of 2 mg/ liter ( 2000 ppb) was used to assess short and intermediate term Aquashade exposures.

3.2.3 Residential Postapplication Exposure and Noncancer Risk Estimates Risks were calculated for residential handler and postapplication exposures using the Margin of Exposure ( MOE) approach; the MOE is a ratio of the body burden to the toxicological endpoint of concern. All short and intermediate term residential postapplication scenarios assessed ( dermal, ingestion, aural, buccal/ sublingual, and nasal/ orbital routes of exposure) resulted in estimated combined MOEs greater than 100 and, therefore, are not of concern. A summary of these MOEs are presented in Table 3.2.3. Page 26 of 26 Table 3.2.3 Recreational Swimmer Aquashade MOEs Exposed Person Exposure Duration Water Concentration ( µ g/ L) Dose ( mg/ kg/ day) NOAEL ( mg/ kg/ day) MOE Child   22 kg 2000 0.10 500 4900 Adult   70 kg Short/

Intermediateterm 2000 0.032 500 15600 3.2.4 Residential Postapplication Exposure and Risk Estimates for Cancer No cancer endpoints of concern for Aquashade were identified; therefore postapplication cancer risks to handlers were not assessed.

3.2.5 Recommendations for Refining Residential Postapplication Risk Assessments In order to refine the residential postapplication assessment, data on actual use patterns including rates, timing, and the kinds of tasks performed are required to better characterize Aquashade risks.

3.3 Residential Aggregated Exposure and Risk Estimates To better quantify residential Aquashade hazard, results from residential handler and residential postapplication risk assessments were aggregated. Aggregate calculations of residential exposure were performed using worst case MOEs resulting from each assessment.

The residential aggregated exposure resulted in an estimated MOE of 1700 and, therefore, is not a risk of concern.


[Federal Register: June 16, 2008 (Volume 73, Number 116)]
[Notices]
[Page 34024-34025]
[DOCID:fr16jn08-73]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0132]

Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; State Petitions for
Exemption From Preemption

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by July
16, 2008.

ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
FAX:<PHONE_NUMBER>, or e-mailed to<EMAIL_ADDRESS>All comments
should be identified with the OMB control number 0910-0277. Also
include the FDA docket number found in brackets in the heading of this
document.

FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of the Chief
Information Officer (HFA-250), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.

State Petitions for Exemption From Preemption--21 CFR 100.1(d) (OMB
Control No. 0910-0277)--Extension

    Under section 403A(b) of the Federal Food, Drug, and Cosmetic Act
(the act) (21 U.S.C. 343-1(b)), States may petition FDA for exemption
from Federal preemption of State food labeling and standard of identity
requirements.

Section 100.1(d) (21 CFR 100.1(d)) sets forth the information a State
is required to submit in such a petition. The information required
under Sec.  100.1(d) enables FDA to determine whether the State food
labeling or standard of identity requirement satisfies the criteria of
section 403A(b) of the act for granting exemption from Federal
preemption.
    In the Federal Register of March 4, 2008 (73 FR 11648), FDA
published a 60-day notice requesting public comment on the information
collection provisions. No comments were received.

                                 Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
                         No. of        Annual Frequency     Total Annual        Hours per
  21 CFR Section      Respondents        per Response        Responses           Response         Total Hours
----------------------------------------------------------------------------------------------------------------
100.1(d)                           1                  1                  1                 40                 40
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    The reporting burden for Sec.  100.1(d) is minimal because
petitions for exemption from preemption are seldom submitted by States.
In the last 3 years, FDA has not received any new petitions for
exemption from preemption; therefore, the agency estimates that one or
fewer petitions will be submitted annually. Although FDA has not
received any new petitions for exemption from preemption in the last 3
years, it believes these information collection provisions should be
extended to provide for the potential future need of a State or local
government to petition for an exemption from preemption under the
provisions of section 403(A) of the act.

    Dated: June 10, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-13522 Filed 6-13-08; 8:45 am]

BILLING CODE 4160-01-S


[Federal Register: October 30, 2006 (Volume 71, Number 209)]
[Notices]
[Page 63316-63317]
[DOCID:fr30oc06-87]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Project No. 12646-001]

City of Broken Bow; Notice of Application Accepted for Filing and
Soliciting Motions To Intervene and Protests

October 24, 2006.
    Take notice that the following hydroelectric application has been
filed with the Commission and is available for public inspection.
    a. Type of Application: Original Major License.
    b. Project No: 12646-001.
    c. Date Filed: July, 6 2006.
    d. Applicant: City of Broken Bow.
    e. Name of Project: Pine Creek Lake Dam Hydropower Project.
    f. Location: On the Little River, in the Town of McCurtain County,
OK. The project would be located at the United States Army Corps of
Engineers' (Corps) Pine Creek Lake Dam and would occupy several acres
of land administered by the Corps.
    g. Filed Pursuant to: Federal Power Act, 16 U.S.C. 791 (a)-825(r).
    h. Applicant Contact: Olen Hill, City Manager, City of Broken Bow,
Oklahoma; 210 North Broadway; Broken Bow, Oklahoma 74728; (405) 584-
2282.
    i. FERC Contact: Allyson Conner at<PHONE_NUMBER> or
<EMAIL_ADDRESS>
    j. Deadline for filing motions to intervene and protests: 60 days
from the issuance date of this notice.
    All documents (original and eight copies) should be filed with:
Magalie R. Salas, Secretary, Federal Energy Regulatory Commission, 888
First Street, NE., Washington, DC 20426.
    The Commission's Rules of Practice and Procedures require all
intervenors filing documents with the Commission to serve a copy of
that document on each person on the official service list

for the project. Further, if an intervenor files comments or documents
with the Commission relating to the merits of an issue that may affect
the responsibilities of a particular resource agency, they must also
serve a copy of the document on that resource agency.
    Motions to intervene and protests may be filed electronically via
the Internet in lieu of paper. The Commission strongly encourages
electronic filings. See 18 CFR 385.2001(a)(1)(iii) and the instructions
on the Commission's Web site (http://www.ferc.gov) under the ``e-

Filing'' link.
    k. This application has been accepted for filing, but is not ready
for environmental analysis at this time.
    l. Description of Project: The proposed project, using the existing
Corps' Pine Creek Dam and Reservoir, would consist of: (1) A diversion
structure connecting to the existing outlet conduit; (2) a penstock
connecting the diversion structure to the powerhouse; (3) a 112-foot-
wide by 73-foot-long powerhouse containing two turbine-generator units,
having a totaled installed capacity of 6.4 megawatts; (4) a tailrace
returning flows to the Little River; (5) a one-mile-long, 14.4-kilovolt
transmission line or a 6.5-mile-long, 13.8 kilovolt transmission line
connecting to an existing distribution line; and (6) appurtenant
facilities. The project would have an average annual generation of
16,200 megawatt-hours.
    m. A copy of the application is available for review at the
Commission in the Public Reference Room or may be viewed on the
Commission's Web site at http://www.ferc.gov using the ``eLibrary''

link. Enter the docket number excluding the last three digits in the
docket number field to access the document. For assistance, contact
FERC Online Support at<EMAIL_ADDRESS>or toll-free at 1-
866-208-3676, or for TTY,<PHONE_NUMBER>. A copy is also available for
inspection and reproduction at the address in item h above.
    You may also register online at http://www.ferc.gov/docs-filing/esubscription.asp
 to be notified via e-mail of new filings and

issuances related to this or other pending projects. For assistance,
contact FERC Online Support.
    n. Any qualified applicant desiring to file a competing application
must submit to the Commission, on or before the specified deadline date
for the particular application, a competing development application, or
a notice of intent to file such an application. Submission of a timely
notice of intent allows an interested person to file the competing
development application no later than 120 days after the specified
deadline date for the particular application. Applications for
preliminary permits will not be accepted in response to this notice.
    A notice of intent must specify the exact name, business address,
and telephone number of the prospective applicant, and must include an
unequivocal statement of intent to submit, if such an application may
be filed, either a preliminary permit application or a development
application (specify which type of application). A notice of intent
must be served on the applicant(s) named in this public notice.
    Anyone may submit a protest or a motion to intervene in accordance
with the requirements of Rules of Practice and Procedure, 18 CFR
385.210, 385.211, and 385.214. In determining the appropriate action to
take, the Commission will consider all protests filed, but only those
who file a motion to intervene in accordance with the Commission's
Rules may become a party to the proceeding. Any protests or motions to
intervene must be received on or before the specified deadline date for
the particular application.
    When the application is ready for environmental analysis, the
Commission will issue a public notice requesting comments,
recommendations, terms and conditions, or prescriptions.
    All filings must (1) bear in all capital letters the title
``PROTEST'' or ``MOTION TO INTERVENE,'' ``NOTICE OF INTENT TO FILE
COMPETING APPLICATION,'' or ``COMPETING APPLICATION;'' (2) set forth in
the heading the name of the applicant and the project number of the
application to which the filing responds; (3) furnish the name,
address, and telephone number of the person protesting or intervening;
and (4) otherwise comply with the requirements of 18 CFR 385.2001
through 385.2005. Agencies may obtain copies of the application
directly from the applicant. A copy of any protest or motion to
intervene must be served upon each representative of the applicant
specified in the particular application.

Magalie R. Salas,
Secretary.
 [FR Doc. E6-18137 Filed 10-27-06; 8:45 am]

BILLING CODE 6717-01-P


for that unit to be released.  So what you see here is
a fairly small number of estimated transmissions or
donations that are infected and missed due to test
error.
So walking through these, we see fairly
small contributions to risk from all of the sources,
other than the window period and it's really therefore,
the window period estimates that are the critical
sources of the risk and the critical target of nucleic
acid screening.
And we were challenged, back at the
conference Dr. Tabor alluded to, by Dr. Kessler back in

17
S A G  CORP.S A G  CORP.
202/797-2525
Washington, D.C.
Fax: 202/797-2525
1994 to move forward, to bring the new technology of
nucleic acid amplification to really eliminate the
window period and it was this challenge that I think set
the ball in motion, set the government to both fund and
put a fair bit of regulatory direction in front of us to
move into bringing forward nucleic acid testing.
The window period is again the major target
of the screening.  To understand the window period, one
needs to really look at data from a number of different
sources.  As we'll see as I go through the data, we've
done a lot of work on units from seroconverting plasma
donors where these have been compiled into panels of
serial specimens collected usually at two-times-a-week
intervals from plasma donors and these have been
extremely valuable to characterize the time course and
the dynamics of markers during the window period.
There are also important data coming from
cases with known exposure dates, be these transfusion-
related transmissions or needle-stick accidents and I'll
show you a little bit of data from each of those in the
presentations in a few minutes.  These are important
because these are the types of situations where we can
actually ascertain the time from exposure to
seroconversion or to detectable viremia.  This is

18
S A G  CORP.S A G  CORP.
202/797-2525
Washington, D.C.
Fax: 202/797-2525
important in a concept, that I'll get to in a moment, of
the eclipse phase.
We also have people coming in who have
primary syndromes, be it the primary HIV syndrome, the
flu-like syndrome or hepatitis.  Now these situations
actually are not very informative for the window period
because when people present with clinical symptoms,
they're usually well into the viremic window phase,
usually at peak antigen phase or well into the hepatitis
viremia.  So very little information comes from the
primary syndrome-type cases in terms of early window
period characteristics.
Recipients of seroconverting donors, when
one has a seroconverting donor and does look back, one
can derive a relationship between the time interval
between the seropositive and the prior seronegative
donation and whether or not transmission occurred.  And
from that, one can derive an estimate for an infectious,
transmissible window and this was done by Lyle Pederson
about a decade ago now for HIV.  These seroconverting
donors, though, are so rare today and the frequency of
look-back transmission is so rare that actually we've
been unable to update these estimates of infectious
window from sort of a human transmission perspective

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over the last decade.
Cohort studies are quite valuable and
actually I'll show you some data for hepatitis C where
we've done some analysis recently of some cohorts for
hepatitis C viremia from seroconverters in high-risk
cohorts and I think, again, an important source of data,
although usually the samples in the freezer from these
cohort subjects are separated by three to six months,
and so don't give us nearly as refined an understanding
as these plasma panels.
And finally, animal model studies, which
are quite important and I think we're coming back to
these to understand many of the unanswered questions in
terms of when infectivity occurs during the early window
period.
The new concept that's kind of evolved over
the last few years by combining data from exposure to
seroconversion with the data from plasma panels, for
example, is the concept of an early eclipse phase
following exposure before one can detect any evidence of
viremia in the blood by nucleic acid testing or
infectivity studies.
So we talk now about an early window period
that probably is not infectious and it cannot be closed

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with any testing method simply because there is no virus
in the blood, followed by the development of infectious
viremia.  And this is really the target of nucleic acid
testing, to close the infectious viremic window period,
recognizing that we're never going to completely close
the theoretical exposure to viremia window phase.
For HIV, we do have some significant data
in terms of time from exposure to seroconversion and
this is from health care workers who acquired HIV from
a needle-stick or other accident.  And this is data from
CDC, Glen Satten analysis, looking at a series of about
52 health care workers who became infected and had a
reasonable sampling of testing after the exposure.  And
from this analysis, there was an estimate of around 40
days average time from exposure to seroconversion.  And
this was based on a mix of antibody assays in the late
1980s, early 1990s, so we probably estimate today and
most data would support that there's probably about a
20- to 25-day period from exposure to antibody
seroconversion.
But we've really gained an enormous insight
into the dynamics and time course is from these plasma
seroconversion panels.  This is a representative panel
showing the time, somewhat arbitrarily dated here from

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the date of the first available specimen and then the
viral load, in this case, quantitative PCR.  We can see
that these individuals are giving at usually twice a
week intervals, quite regularly, and then these people
are typically detected based on the antibody
seroconversion in the past.  And then fortunately, the
companies have retained in the freezers and are now
required to retain for several months the prior
donations.  So when a donor seroconverts, we can then go
back and retrieve the earlier components and build
panels of serial samples and then go back and
characterize them for the development of antibody and
other markers.  So here you can see that the antibody
comes up on approximately Day 28 or so.  We can detect
antigen for about four or five days prior to antibody
and then RNA can be detected in this particular panel a
couple days prior to the detection of antigen.
By compiling data from a large number of
these panels, we can derive figures such as this, which
is what's called a box and whisker plot, which divides
the time course of viremia up into different stages:
the RNA-only period, the p24 antigen EIA negative phase,
and then on through the development of antibody
reactivity by EIA and Western blots.

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An analysis of these kind of data can yield
two parameters.  One is the duration of each of these
stages.  In this analysis, which is based on the RNA
determinations by the Roche monitor assay which has
about a 200-copy sensitivity, Glen Satten analyzed this
data to yield an estimate of about three and a half days
for the RNA-only phase; five days for the p24 antigen
positive pre-antibody phase; and then progressive
periods when the EIA is reactive, but the blot negative,
the blot indeterminant and then going through an early
incomplete Western blot pattern.  What you can also
determine then is for each of these stages the
distribution of viral load during each stage and we can
see that the RNA-only stage, in this case, had an
average copy number of a couple thousand and low copy
number, down to the limit of sensitivity of the assay,
of approximately 100, whereas the p24 antigen phase, the
viral load is typically much higher.
In a more recent analysis of data, actually
from alpha and NGI, we've looked at the distribution of
viral load in the RNA-only phase, versus the p24 antigen
pre-seroconversion phase for a larger number of
seroconversions.  I think this is based on around 40 or
50 seroconverters and we have a fairly large number,

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both of RNA-only samples and of p24 antigen positive
samples.  This RNA assay was also more sensitive,
sensitivity down to the 100-copy or so range.
This distribution then lets us look at the
-- a more formal analysis of the viral load distribution
and in this analysis for the p24 antigen-positive phase,
the median copy number is 140,000 and the 2.5 percent
confidence limit, so in other words, you detect 97.5
percent of the antigenemic samples had copy numbers
estimated at greater than 7,000 copies.  So this is
important because this is a parameter that's sort of
been floated as a target goal that we, in introducing
minipool NAT, one of the objectives is obviously to
replace the antigen assay and in order to do that with
high confidence the assay should have at least 7,000
copy sensitivity, the minipool NAT assay.
In contrast, if we want to completely close
the RNA window we would basically have to have an assay
that's extraordinarily sensitive because the RNA-only
phase has samples that do have copy numbers down at 100
copies or less.  The median copy number is about 2,000.
So during the RNA-only phase, the viral load is
substantially lower than can be confidentially detected
uniformly with minipool NAT.

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This is some data from Sue Stramer,
directly, empirically kind of addressing the issue of
can we comfortably eliminate the p24 antigen assay once
we introduce minipool NAT and Sue took a large number of
samples, 92 samples, from 25 seroconverting panels and
ran those samples at the 1 to 128 dilution that is the
dilution that Red Cross was operating at.  And she was
able to demonstrate 100-percent detection.  So all of
these samples that were antigen positive had very high
copy number of RNA.  And in addition, there were 21
samples that were detected as RNA-positive that were p24
antigen-negative and they were detected even at the 1 to
128 dilution.  So data like this for HIV is very
reassuring that we can not only replace the p24 antigen
test, but interdict and identify a number of additional
viremic specimens.
We've gone a little bit further in terms of
modeling the antigen-RNA relationship and this slide
summarizes a correlation analysis between the level of
RNA and the S to CO range of the p24 antigen assay.  To
ask the question of what is the cut-off of the -- what's
the RNA concentration at the cut-off of the p24 antigen
assay.  So this is a regression analysis of 146 samples
from seroconversion panels.  And what this tells us is

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that the cut-off of the p24 antigen assay is just almost
exactly at 10,000 genome equivalence per mL.  So that
would tell us that as long as our nucleic acid screening
test in the context, for example, of minipool screening
is as sensitive as 10,000 copies, it should detect every
single seroconverter who is detected by antigen at the
cut off-of the antigen assay.  So again, another
parameter that's useful as we try to set a target
objective for minipool screening.
Now as we try to project back, that's kind
of empiric analysis of hard numbers.  As we've tried to
project back to the RNA load prior to the detection of
RNA, we've used a parameter called the doubling time, so
we've taken these panels and we've looked at
particularly the early ramp-up phase prior to any
antibody during which the RNA levels are increasing and
derive the slope and using that slope we can estimate
the doubling time or the rate at which the virus is
increasing in the concentration in plasma or time.  And
for HIV we've recently updated this analysis and the
doubling time is estimated at approximately 30 hours, so
the concentration of virus in the plasma doubles every
30 hours.  But in addition, using that slope, we can
back-estimate a theoretical concentration of virus at

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earlier time points for each seroconverter.  And using
this projection approach here, you can see that in this
population of seroconverting plasma donors, we would
estimate that there would be a single copy of RNA per
mL, about 20 days before the peak viremia.  And this is
quite consistent with the number I alluded to earlier of
approximately a 20 day period from exposure to
detectable virus.  So this suggests that perhaps there
might be infectivity existing prior to RNA for a period
of five or ten days.
But more recently, in collaboration with
Harvey Alter and J.P. Allain, we've begun to do studies
in chimpanzees that are directly asking the question of
when does infectivity occur during the eclipse phase.
And this paper was published a few months ago in
Transfusion and what was done in this sort of pilot
seminal experiment that is now being expanded was to
take a chimpanzee and infect that animal with HIV and
draw blood from that animal on actually twice weekly
bases through the early seroconversion window period.
And that first animal detected detectable viremia about
five weeks following inoculation and then finally
seroconverted out at Week 8.  Now the blood and plasma
in the cells from each of these sampling time points was

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frozen away and then after the characterization of the
window period virology, we went back and took material
from bleeds extending back several bleeds prior to
detectable viremia and used that material to inoculate
a second chimpanzee to ask the question of when did
infectivity occur relative to the ability to detect
virus by amplification methods or culture.  And what was
discovered was that the sample collected two weeks
before viremia was not infectious, this second chimp did
not become infected.  Likewise, the sample collected a
week before detectable viremia, a full month into the
eclipse phase was, again, not infectious in a secondary
passage attempt.  And finally, the first viremic sample
was shown to transmit.  So again, in a single chimp
experiment this study suggests that this eclipse phase
is not infectious and even though we can theoretically
project back that there may be a very low copy number in
the body that we're not able to detect any infectivity
until the time when we can detect the viral RNA.  I'll
close with -- this is really the kind of experiment that
we're really very interested in expanding, both for HIV
and hepatitis C.
Moving on to hepatitis C, it's a very
different window period.  With HIV we have this very

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rapid ramp-up phase and then quick seroconversion within
a week or so.  With HCV, as illustrated in this plasma
panel, we similarly have a very rapid ramp-up phase, but
then there's a very prolonged viremic pre-seroconversion
period, averaging in different studies in the range of
50 to 60 days of high-titer viremia prior to antibody
seroconversion.  And this slide actually again from Sue
Stramer shows that this viremia is so high-titer that
actually you can't even tell the difference in terms of
an S-to-CO ratio or a quantitative analysis of the
samples, be they tested undiluted or at 128 dilution,
very consistent detection because the viral load is so
high during this prolonged window phase.
This is a summary of Sue's data.  I think
in this case with NGI, looking at the viral load
distributions particularly focusing out here, during the
RNA-only phase prior to antibody and the lower
confidence bound on the viral load distribution during
the 60-day or so viremic pre-seroconversion window is
around 10,000 copies.  So very, very high copy number
and very amenable, as we'll talk later, to minipool
testing.
And Sue again formally looked at the
question of how many of the window phase samples could

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be detected at a high dilution as she addressed the
question of the value of minipool testing.  In this
particular example from 22 panels looking at two
different lots, I think this is Gen-Probe's assay.  She
determined that at 1 to 128 dilution she could pick up
93 to 94 percent of the samples that could be detected
undiluted.  So a very high proportion of the window
phase samples can be detected at a 1 to 128 dilution and
I think the majority of those samples that were missed
could be detected at the current 1 to 16 dilution
factor.
There were a few surprising observations
that are still in need of further study.  For example,
in a couple of these samples that went negative at the
1 to 128 dilution, so they were reactive at the NEAT,
but went negative at the 1 to 128, the viral load in
these samples was really quite high, 100,000; 90,000.
These samples should have been readily detectable at a
1 to 128 dilution given the sensitivity of the assays.
This has led to some concern that there may be some
aggregation phenomenon going on, complexing or for some
reason that these samples are not diluting out as
predicted based on the viral load, suggesting that
perhaps minipool testing may have some surprises in

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terms of matrix effects or failure of seropositives --
I'm sorry, viremic samples to be fully represented when
they're sampled in the context of pipetting to create
the pool.  So just one area of continued concern in need
of further study.
In addition to looking at these plasma
seroconverting panels, we've also done similar analysis
of the cohort, the transfusion transmitted viruses study
from the late 1980s.  In this population, we have a
fairly large number, about 100 HCV seroconverting
recipients.  The advantage of these samples is that the
date of transfusion is known, so you actually know the
date that these recipients were infected by transfusion
of a known seropositive and we actually have the samples
so we can go back and characterize the viral load and
the virus itself in the transmitting unit.  That lets us
then really benchmark the time course to detectable
viremia relative to the day of exposure, i.e., the day
of transfusion.
And this is just a representative panel
from this cohort showing a very similar pattern of a
very rapid detection of high level virus, persistent
high level plateau viremia prior to the development of
ALT and full antibody seroconversion.  When we look at

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a large number of these panels we see that we can
detect, this is the serial case number, over on this
axis and this is time course following the transfusion.
We can detect viral RNA typically with one to two
weeks.   The vast majority of cases, in fact, the very
first specimen collected following transfusion is
already viremic and often at peak viremia.  And then
downstream, about 50 to 60 days later, ALT comes up in
an antibody seroconversion.
In a formal survival analysis of this data
has yielded time estimates for the time from transfusion
or exposure to first detected RNA and that's averaging
around 12 days following exposure,  we can detect virus
RNA.  And then about 50 days after exposure, ALT
elevation occurs on average and seroconversion occurs 70
to 80 days.  So this gives us again a very consistent
finding relative to the plasma seroconversion panels of
around a 50-day viremic
pre-antibody period.
In TTVS like the plasma donor panels, if we
look at the viral load during the window period, it
averages 10
5
to 10
6
copy numbers, so very high viral
load, very amenable to minipool screening.
So for HCV this just summarizes, we believe

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[Federal Register: March 12, 2009 (Volume 74, Number 47)]
[Notices]
[Page 10745-10746]
[DOCID:fr12mr09-67]

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2009-N-0664]

Anti-Infective Drugs Advisory Committee; Notice of Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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    This notice announces a forthcoming meeting of a public advisory
committee of the Food and Drug Administration (FDA). The meeting will
be open to the public.
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recommendations to the agency on FDA's regulatory issues.
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a.m. to 5 p.m.
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    Dated: March 3, 2009.
Randall W. Lutter,
Deputy Commissioner for Policy.
[FR Doc. E9-5285 Filed 3-11-09; 8:45 am]

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