February 17, 2010

Tim Leighton Office of Pesticide Programs U.S. Environmental Protection Agency One Potomac Yard (South Building) 2777 South Crystal Drive Arlington, VA 22202

Dear Tim:

The AEATF has reviewed the December 16, 2009 HSRB final report of October 20-21, 2009 meeting. A revised protocol in track changes th at incorporates EPA and HSRB comments at the meeting and summary of changes to the protocol are attached. The AEATF also has reviewed the final HSRB report and provides the below re sponses to the comments on the aerosol study protocol.

The Board raised the concerns highlighted in it alics below. Our respons e/clarification follows.

1. Use of the Results : EPA plans to use the data generated from the proposed aerosol study generically to estimate dermal and inhalation exposures and ri sks for other antimicrobial ingredients where the product is packaged in a pressurized aerosol spray can. However, other variables can affect rates of exposure, including different nozzle sizes, spray and ejection rates, the size of th e particles generated, and the ge neration of nonvolatile active ingredients. Inhalation versu s dermal exposure may also vary with these variables.

It is also unclear if occupati onal handler exposure can be used to estimate exposure of nonprofessionals using similar consumer products. However, for risk assessment purposes it was felt that exposure among occupational users is likely to exceed that of consumers; the higher frequency of exposures among occupatio nal users is likely to exceed a plausibly higher individual but less frequent exposure among nonprofessional users.

Response : We agree that dermal an d inhalation exposure risks to antimicrobial ingredients delivered using a pressurized aerosol spray can will be impacted by different nozzle sizes, spray and ejection rates, the size of the part icles generated and the generation of nonvolatile active ingredients. The aerosol products re presented by the AEATF II have been divided into four major use categories:

1. Hard-surface disinfectant fine sprays

2. Foaming aerosol products

3. Soft surface disinfectants

4. Air freshenersMr. Tim Leighton February 17, 2010 Page 2

Prior to selecting a product that represents the four major use categories, keeping in mind that we wanted to select a product that represents an inhalation exposure worst-case situation, a non-human pilot study was conducted. In that study, one representative and commercially available product was selected from each categor y. The study design and results of the pilot study were presented in Appendix A of the Ae rosol Application Scen ario: Rationale for Study Design. The results of the pilot study clea rly show that the hard-surface fine spray and the air freshener used generated the most inha lation and/or dermal exposure potential. The total mass of the active ingredient dispensed per unit time for the hard-surface fine spray is more than double the air freshener; based on that information, inhalation and dermal exposure will likely be higher for the hard surfac e fine spray. Additionally, the hard-surface spray product will be used to a much greater ex tent in a day, especially in commercial use,

than the air freshener. Based on the availa ble data, the hard-surface fine spray would represent a high and conservative choice for exposure monitoring studies. The selected product should also meet objectives of the study and test material selection criteria, i.e.:

• Serve as surrogate for most aerosol use categories

• Use pattern represents high-end expo sure – a conservative scenario

• Use scenario covers most influential variables of exposure

o Highest percentage of active ingredient

o Nozzle size of majority of aerosol products

o Particle size distribution repr esentative of fine spray

o Used for hard surface and confined spaces

• Having stable active ingredient

• Results can be extrapolated to most products on the market

Since the goal of this study is to select one surrogate for most aerosol use categories, the product selected for this study was a hard-surface disinfectant fine spray, the “Clorox Disinfection Spray.”

We agree with the HSRB regarding occupationa l handler exposure a nd non-professional

exposure.

2. Sample Size and Analysis : Raw and descriptive data will be provided, but no statistical analyses have been planned. Sample size adequ acy cannot be judged without a statistical analysis plan. Placing 18 subjects into three clusters of six each re quires consideration of cluster effects and may complicate analysis of the results. Assumed constants related to exposure to the active ingredient may also pr ove to be incorrect, and additional subjects may

need to be enrolled.Mr. Tim Leighton February 17, 2010 Page 3

Response : If the benchmark accuracy goal (i.e., K=3) is not met once the data are collected and analyzed, the AEATF II will, in consultation with regulatory agencies, determine the best course of action to take. This may mean th e development of guidance for the use of these data that takes the increased imprecision of the estimates into account. It is possible that collection of additional clusters might be considered.

3. Application of Spray : The target number of cans sprayed in each location by each worker on each day could be specified better within th e protocol. For example, does a worker need to continue spraying a room if the target applica tion is met before completion of that room? Additional protocol clar ifications needed include: addre ssing the issue of the interval between sampling at different sites (currently , it appears that no two monitoring events can occur within the same building within one week); clarifying the issue of using empty apartments rather than motel rooms; and clarify ing the effect of ex haust vent effects on exposure, which could be differen t than indicated in the protocol.

Response : We will clarify in the protocol the target numbers of cans sprayed in each location by each worker on each day. Workers will be given full cans as well as half full cans, as specified in the protocol. A worker does NOT need to continue spraying a room if the target application is met. Two monitoring events can occur within the same building, but not the same room within ONE DAY. The next day the same room could be used. Regarding the use of apartments rather than motel rooms, we have surveyed the Fresno area

and have found a number of motels with full kitchens. We will be using hotels/motels exclusively for the study and will not be using apartments.

4. Quality Assurance and Control (QA/QC) : QA/QC can be improved by:

a. Determining likely differences in the air sampling results depending on the method used (e.g., depending on the air sampling equipment us ed, differences in the orifice diameters and air flow sampling rates could affect ae rosol collection efficie ncies and effects).

b. Setting the minimal spike to two to four tim es that of the limit of quantitation (LOQ; cf. AEATF II 2009b: 42, 46).

c. Considering other variables that may influe nce the measurement of exposure, including whether the surface being treated is dry or wet at the time of the next spray application, and whether the applicant accidentally wi ped the surface after spraying. Data accumulated during gross deviations from the protocol should also be excluded. Finally, the protocol should indicate that there will be a maximum of two workers on any given day in the same location.Mr. Tim Leighton February 17, 2010 Page 4

Response :

a. The determination of differences in air sa mpling results based on the difference in the orifice diameter, etc., would im ply comparing different products . This is not in the scope of this study since we will be using one product. In this study, we will be using the same sampling equipment for all subjects. The equi pment will be calibrated daily for air flow sampling rate.

b. The LOQ for field fortification will be correct ed. The minimum spike of four times the LOQ will be incorporated in the protocol.

c. At the time of application, all treated surfaces will be dry. The same room will be treated three times on three separate days. The goal is to have two ME/day/l ocations, and complete the application of the product to different rooms. Back-up workers will also be available in case the primary worker does not show up.

If you have any questions, please contact me at (703) 741-5637 or via email at has_shah@americanchemistry.com

.

Sincerely,

Hasmukh Shah Manager, AEATF

Cc: John Carley Kelly Sherman