Ha 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

OFFICE OF 

PREVENTION, PESTICIDES AND 

TOXIC SUBSTANCES 

March 10, 2008 

MEMORANDUM

SUBJECT: Science and Ethics Review of AEATF Scenario Design and Protocol for 

Exposure Monitoring in Wipe Scenarios 

FROM: John M. Carley 

 Human Research Ethics Review Officer 

 Timothy Leighton 

 Antimicrobials Division 

 Cassi Walls, Ph.D. 

 Antimicrobials Division 

TO: Norm Cook, Chief 

 Risk Assessment and Science Support Branch (RASSB) 

 Antimicrobials Division 

REF: Selim, S. (2008) A Study for Measurement of Potential Dermal and 

Inhalation Exposure During Application of a Liquid Antimicrobial 

Pesticide Product Using Trigger Spray and Wipe or Ready to Use Wipes 

for Cleaning Indoor Surfaces. Unpublished protocol dated January 16, 

2008, prepared by Golden Pacific Laboratories for the Antimicrobial 

Exposure Assessment Task Force II under Sponsor ID AEA02 and GPL 

Study No. 070264. 140 p., plus 346 p. supplement containing IRB 

correspondence. 

We have reviewed the referenced proposal from both scientific and ethics perspectives. 

Scientific aspects of the proposed research are assessed in terms of the recommendations 

of the EPA Guidelines Series 875 and of the EPA Human Studies Review Board. Ethical 

aspects of the proposed research are assessed in terms of the standards defined by 40 

CFR 26 subparts K and L and the recommendations of the EPA Human Studies Review 

Board. 

Page 1 of 41 
A. Completeness of Protocol Submission 

The submitted protocol was reviewed for completeness against the required elements 

listed in 40 CFR §26.1125. EPA’s checklist is appended to this review as Attachment 6. All 

elements of required documentation are provided in the submitted protocol package. 

In addition to the final protocol and its appendices A through L (pp. 33-171)1, Volume 3 

of the AEATF submitted package includes the following supporting documents—all considered 

in this review: 

• Transmittal Letter (pp. 4-5) 

• 40 CFR 26.1125 Checklist (p. 7) 

• Mopping Application Scenario: Rationale for Study Design (pp. 9-31) 

• IIRB Approval Letter (pp. 173-174) 

• IIRB-approved English consent materials (pp. 175, 177-186) 

• IIRB-approved Spanish consent materials (pp. 176, 187-198) 

• Product Label for test material (p. 89) 

• MSDS for test material (pp. 104-105) 

• Recruiting materials (pp. 107-112) 

Volume 4 of the submitted package includes the following additional supporting 

documents—also considered in this review: 

• Correspondence between the investigator and IIRB (pp. 5, 146, 171-195) 

• Protocol and appendices as initially submitted to IIRB (pp. 7-145) 

• Wipe scenario design as initially submitted to IIRB (pp. 14148-170) 

• Protocol as revised 1/16/08 and resubmitted to IIRB, with appendices unchanged 

from initial submission (pp. 197-335) 

• IIRB approval letter of January 22, 2008 (pp. 337-338) 

• Minutes of 1/22/08 IIRB Meeting and IIRB Membership List (pp. 340-346) 

B. Summary Assessment of the Scenario Design 

Supporting details are in attachment 1 

1. Scenario Design: The Antimicrobials Division (AD) assesses potential occupational 

and consumer exposure from various antimicrobial products that are applied by a 

multitude of application techniques including wiping. AEATF-II defines a wiping 

application scenario as the wipe-based application of a label-specified end-use 

formulation containing an antimicrobial chemical. 

 

1 Most page images in the submitted volumes bear more than one page number. All page references in this review 

to Volume 3 are to “page N of 198”, and all page references to Volume 4 are to “page N of 346.” 

Page 2 of 41 
The act of wiping—moving a hand-held rag over a hard surface to clean/disinfect it—

can be accomplished in many ways. Wipe methods include spray-and-wipe, readyto-use wipes (RTU), and bucket-dipped rag or sponge wipes. From this array of 

choices the regulatory consensus was to monitor all three techniques. Two of them 

are proposed in this protocol: (1) spray-and-wipe, and (2) RTU wipe. The third 

method of wiping, using a sponge or rag dipped into a bucket of treatment solution, 

will be monitored by the AEATF under the soak/immersion/dip scenario. 

EPA intends to use the data developed by the AEATF II for the two wipe scenarios to 

describe a typical handler’s daily exposure to the antimicrobial wipe solution. The 

data must be generic enough to be useful for estimating exposures using various types 

of wipes (i.e., spray-and-wipe, RTU wipe), different hard surfaces (i.e., walls, table 

tops, bathrooms, etc.), room configurations, types of buildings (i.e., homes, schools, 

medical facilities, commercial office buildings, etc.), handlers (i.e., professional and 

consumer), and antimicrobial active ingredients. AD plans to use the data generated 

from the proposed wipe study generically to estimate dermal and inhalation exposures 

and risks for other antimicrobial ingredients where wipe application is consistent with 

product labeling use directions. Antimicrobial products have been grouped by EPA 

into the 12 Use Categories presented below. Although wiping of hard surfaces may 

occur in many Use Categories, most wipe applications are expected to occur in Use 

Categories II, III, IV, and V. 

I Agricultural premises and equipment 

II Food handling/storage establishments/premises and equipment 

III Commercial/institutional/industrial premises and equipment 

IV Residential and public access premises 

V Medical premises and equipment 

VI Human drinking water systems 

VII Material preservatives 

VIII Industrial processes 

IX Antifouling coatings 

X Wood preservatives 

XI Swimming pools 

XII Aquatic areas 

The EPA believes that the AEATF wipe scenarios are well defined and we expect that 

resulting data will meet the needs of EPA and other regulatory agencies. The 

diversity of daily exposures under the two wiping scenarios addressed by this 

proposal will thus adequately describe a typical handler’s daily exposure to the 

antimicrobial treatment solution. 

2. Sampling Design: The AEATF has described in detail their sampling design for the 

wipe scenarios and has incorporated random elements where feasible. The AEATF 

proposes to monitor dermal and inhalation exposures using passive dosimetry 

techniques to measure exposure to human subjects wiping horizontal and vertical 

hard surfaces above floor level. Specifically, the wiping to be monitored will occur in 

Page 3 of 41 
individual offices, bathrooms, kitchen areas, hallways, dining areas. The proposed 

sample size is the default scheme outlined in the AEATF-II Governing Document, 

involving of 3 clusters (sites) with 6 subjects at each. This is believed adequate to 

provide data to meet EPA’s needs. 

In the spray-and-wipe scenario workers will use a 32-ounce trigger-pump spray bottle 

with a nozzle adjustable to produce a fine spray, referred to in the protocol as an All 

Purpose Cleaner (APC). The standard APC spray bottle (size/volume, trigger pump 

configuration, and fine mist) has been purposively selected to represent the type and 

size most commonly used by janitors and consumers. 

The spray-and-wipe scenario does not include diluting the concentrate or pouring the 

solution into the trigger pump sprayer. Mixer/loader exposure will be monitored in a 

separate study. This separation of tasks into multiple scenarios will allow regulatory 

agencies to assess exposure associated with either professional products that use 

automatic dispensers or RTU trigger-pump sprayers or products requiring mixing of 

the antimicrobial solution. 

In the RTU wipe scenario workers will use wipes pre-saturated with antimicrobial 

solution, taken one-at-a-time from a roll of wipes in a plastic housing. 

The study location has been purposively selected to be Fresno County, CA. EPA 

believes that the application of an antimicrobial product in an indoor environment 

will not vary substantially from one city to another, and therefore that the selection of 

Fresno County is reasonable. Fresno is close to the laboratory conducting the study, 

it is large enough to have a substantial population of professional janitors, and it 

contains many suitable vacant buildings. Conducting all monitoring in a single 

geographic area will save resources and will not adversely effect the results of the 

research. 

Each of the two wipe scenario designs calls for three clusters of MEs, each at a 

different site. The designs specify further that each site must be a different type of 

building, that monitoring at different sites must be separated by at least one week, and 

that each selected building must include appropriate surfaces for wiping. 

Within Fresno County, three sites will be selected using a stratified random sampling 

approach. A list of all available vacant buildings in Fresno County will be compiled, 

and stratified into three classes of buildings: office building, retail space, or meeting 

facility. Properties in each of the three categories will be “investigated independently 

and in random order until a single acceptable facility is found for each category.” 

The acceptance criteria are that the building: 

• Is available for 1-month rental 

• Has a functional HVAC system 

• Has operating electrical service 

Page 4 of 41 
• Meets minimum surface area requirement with acceptable diversity in 

available surfaces (e.g., hallways, bathrooms, stairs, empty rooms) 

• Does not require cleaning or maintenance before use 

The result is a “random sample of one facility from the population of all acceptable 

facilities of each type in Fresno County.” The two distinct wiping scenarios will be 

monitored independently at the same sites—i.e., a total of three buildings will be 

selected, and both spray-and-wipe and RTU wipe monitoring will be conducted in 

each building. 

Each of the two wipe scenarios calls for monitoring 6 subjects at each of three sites. 

Two additional subjects will be enrolled for each scenario/site in case some subjects 

withdraw or fail to meet all eligibility criteria, making a total of 48 subjects to be 

enrolled in the study. Subjects will be professional janitors, selected randomly from 

among those who respond to flyers posted in randomly selected janitorial service 

companies in the Fresno area, and who meet the eligibility criteria for participation. 

Enrolled subjects will be randomly assigned to one of the two scenarios and to wiping 

tasks of differing durations at one of the three test sites. 

AEATF-II proposes to recruit only professional janitors as subjects. The selection of 

janitors as subjects is justified in the protocol. Enrolled subjects will be listed in 

random sequence, and assigned to purposively predefined task durations ranging from 

30 to 120 minutes. The amount of DDAC applied/handled will vary among the 

subjects depending on the duration of the task to which each is assigned. The first 

subject to be assigned will be assigned to the task of the longest duration, but may not 

be able to fulfill the design duration. Additional subjects will be assigned, each in 

turn to the longest task duration for which monitoring data have not yet been 

collected, until all the task durations are complete. 

In order to make the most effective use of a limited number of monitoring events, the 

overall sampling design is purposive. No feasible opportunities to incorporate 

random elements in the sampling design, however, have been overlooked. 

3. Choice of Surrogate Material: The choice of DDAC as the antimicrobial material 

for this scenario is appropriate. It is widely used, readily available, and there is a 

reliable and sensitive analytical method available for it. 

C. Summary Assessment of the Scientific Aspects of the Study Design 

Supporting details are in attachment 2

1. Statistical design: AEATF-II proposes for each of the wipe scenarios the default 

design of 3 clusters of 6 monitoring events (MEs) each, as discussed in the Governing 

Document. No characteristics of this scenario have been identified which would 

justify a departure from this norm. 

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2. Proposed pattern of human exposure: The AEATF proposes to select professional 

applicators (i.e., janitors) as subjects for the wiping scenarios. The test subjects will 

use SANI-CARE LEMON QUAT to conduct wiping activities using a spray & wipe 

or RTU wipes over a range of time durations extending from 30 to 120 minutes in 15 

minute increments. In the spray & wipe scenario, workers will spray a fine mist of 

dilute material in water with a trigger pump sprayer, followed by a hand wiping using 

a commercially available cotton hand towel. In the RTU wipe scenario, workers will 

wipe down hard surfaces using a pre-moistened wipe pulled from a plastic container. 

In both scenarios workers will be instructed to work as they would normally work. 

Surface wiped will range from 1000 to 4000 ft2, depending on work speed and task 

duration. 

SANI-CARE LEMON QUAT which contains the active ingredients didecyl dimethyl 

ammonium chloride (DDAC) at a concentration of 2.54% and n-alkyl dimethyl 

benzyl ammonium chloride (ADBAC) at a concentration of 1.69% will be used as a 

diluted treatment solution (1:64) per label directions in the spray & wipe scenario. 

The concentration of the test material will be constant for all subjects. Variation in 

exposures will result from differing exposure durations. Thus, the total amount of ai 

handled will vary by the wiping duration (e.g., 30 to 120 minutes). 

EPA believes that the AEATF wiping study will represent typical worker activities 

applying the test substance to hard surfaces under both the spray & wipe and the RTU 

wipe scenarios. The selection of janitorial subjects, test material, and mopping 

activities is adequately described and justified in the protocol. 

3. Endpoints and Measures: The AEATF proposes to measure dermal and inhalation 

exposures resulting from wiping activities of hard surfaces. Dermal and inhalation 

exposure will be measured using whole-body dosimeters (inner and outer), hand/face 

washes, and personal air monitors. The Agencies are most interested in the inner 

dosimeters to assess potential exposure and/or dose. The outer dosimeters will add to 

the existing data base on the development of protection factors for single layer of 

clothing. The personal air samplers will collect residues from the breathing zone with 

the sampling cartridge facing downwards (mimicking nostrils). The sampling train 

will consist of OVS tubes with glass filters backed by XAD sorbent. Because the air 

sampling will not size particles, the Agencies will assume all of the residues are 

inhalable and/or respirable (which tends to overestimate inhalation exposure). The 

sampling pumps will be calibrated prior to use. 

The output of treatment solution for each spray bottle will be measured prior to the 

study using tap water by measuring the volume output from 10 trigger pulls. 

Additionally the amount of treatment solution used by each subject during the 

monitoring event will be recorded by weight before and after each use. The surface 

area wiped will also be recorded. 

The RTU wipe scenario will consist of a roll of wipes in a plastic housing. The roll 

of wipes will be provided to the subjects pre-saturated (i.e., RTU). The researchers 

Page 6 of 41 
will collect 10 wipes from each roll prior to the study and determine the amount of 

DDAC per wipe. During the study, the number of wipes per monitoring event will be 

recorded allowing for an estimate of the amount of DDAC applied. The surface area 

wiped will also be recorded. 

Environmental parameters of the work area such as air temperature, and relative 

humidity will also be documented. The HVAC system will be described and the air 

turnover rates will be measured or estimated. 

4. QA/QC Plan: The AEATF QA/QC plan for the wiping study is described in 

sufficient detail and is adequate to ensure that the measurements are accurate and 

reliable. The QA/QC plan includes field recovery analyses, travel recovery analyses, 

storage stability studies, break-through analyses, and method validation. 

Primary components of the field recovery analyses include: two fortification levels 

per matrix, triplicate samples per fortification level, exposed to ambient conditions 

for the maximum duration of exposure, and WBD not covered during exposure 

duration. Field recovery samples will be fortified in the field, transported and stored 

in the same way as the actual study samples, and analyzed concurrently with the 

actual exposure samples. Correction for loss in field recoveries will correct for all 

phases of potential losses. 

Travel fortifications will also be used as insurance if low recoveries are obtained in 

the field recoveries. However, travel recoveries will not be analyzed if acceptable 

recoveries are observed in the field recovery samples. 

Storage stability samples have been run prior to the development of the protocol and 

indicate stability over the six-month period assessed. 

5. Statistical Analysis Plan: The results of physical sample analysis will be provided in 

the final report. The AEATF II will not statistically analyze the monitoring data. 

However, the wipe monitoring data will be imported into the AEATF database 

(BHED®) where they will be available to regulatory agencies for later statistical 

analyses. The study documentation will report a confidence-interval-based approach 

to determine the relative accuracy for the arithmetic mean and 95th percentile of 

exposure normalized by amount of ai handled. The report will further provide the 

intraclass correlation for clusters (ICC) and its confidence interval, using a variance 

components model. In addition, the effects of ignoring clusters in the estimation of 

means and percentiles will be determined by comparing the estimates of a no-cluster 

model to those of the random effects model. 

Page 7 of 41 
D. Compliance with applicable Scientific standards 

This protocol adequately addresses the following elements according to applicable scientific 

standards: 

• Scientific objective 

• Experimental design for achieving objectives 

• Quantification of the test materials 

• Data collection, compilation and summary of test results 

• Justification for selection of test substance and dilution rate 

• Justification for sample size 

• Fortification levels and number of samples for laboratory, field, and storage stability 

samples 

Additionally, the AEATF has addressed the technical aspects provided in the applicable 

exposure monitoring guidelines (i.e. Series 875 Group A and OECD Applicator Guidelines) as 

well as Good Laboratory Practices (GLPs). 

The following elements in the protocol require revision before the research goes forward: 

• The type of wipe to be used in the spray & wipe scenario is inadequately specified. 

• The efficiency of residue removal through the hand-wash and face/neck wipe methods 

must be addressed, as well as the possibility of an adjustment in resulting data to 

compensate for potential incomplete residue removal. 

E. Summary Assessment of Ethical Aspects of the Proposed Research 

Supporting details are in Attachment 2. 

1. Societal Value of Proposed Research: The purpose of the proposed wiping 

application monitoring study is to develop more accurate information on worker 

exposures to antimicrobials as they clean indoor surfaces using either a spray & wipe 

technique or ready-to-use wipes. Because many millions of Americans apply 

antimicrobial products in these ways, the research question is important; it cannot be 

answered with confidence without new monitoring data meeting contemporary 

standards of quality and reliability. 

2. Subject Selection: Forty-eight adult subjects will be recruited from the janitorial/ 

cleaning service population of Fresno County. Participants will self-identify in 

response to flyers soliciting interest, posted in the workplaces of janitorial services 

companies. Participants will be screened in random sequence from among 

responders, and in that sense will be representative of the population of janitorial 

service workers in the Fresno area. There is no reason to think that janitorial service 

Page 8 of 41 
workers in Fresno are not representative of janitorial service workers in any other 

area of the United States. 

Inclusion/exclusion criteria are complete and appropriate. Pregnant or nursing 

women and employees or relatives of employees of the investigators are excluded 

from participation. 

No potential subjects are from a vulnerable population. Recruitment materials and 

interactions with potential subjects will be conducted in both English and Spanish. 

To minimize the potential for coercion or undue influence from their employers, 

subjects will not be recruited directly through contract janitorial service companies. 

Flyers will encourage interested workers to contact the investigators directly. 

Subjects who participate fully will be paid $100/day. Alternate subjects who are 

enrolled but are not actually monitored will be paid $50 for their trouble. 

3. Risks to Subjects: The proposed test material is EPA-registered for the use 

proposed, is of low toxicity to mammals, and will be used in full compliance with the 

approved label. Risks to subjects include risks of a reaction to the test material or the 

solvents used to obtain residues from hands and face/neck; of discomfort and possibly 

heat-related illness associated with wearing two layers of clothing while doing 

physically demanding work; of a cardiovascular adverse event attributable to physical 

exertion; of discomfort or inconvenience from wearing the air sampling device; of 

embarrassment from disrobing in the presence of a research technician; of an 

unexpected result of pregnancy testing. All identified risks are characterized as of 

low probability. 

Risks are minimized by exclusion of candidates known to be sensitive to quaternary 

ammonium compounds or in poor health or with broken skin on hands, face, or neck; 

testing in a controlled-temperature environment; alerting subjects to signs and 

symptoms of heat stress; monitoring heat index with associated stopping rules; 

limited time of exposure with rest periods at 30-min intervals, or more frequently if 

requested; close observation of subjects; training of experienced technicians to 

minimize embarrassment; incorporation of procedures to keep results of pregnancy 

testing private and to permit discrete withdrawal; provision of appropriate work 

clothing and PPE. 

4. Benefits: This research offers no direct benefits to the subjects, but subjects may 

request their individual results, from which they may learn that their work practices 

produce more or less exposure than average. The principal benefit of this research is 

likely to be reliable data about the dermal and inhalation exposure of workers and the 

general population wiping indoor surfaces with antimicrobials, usable by EPA and 

other regulatory agencies to support exposure assessments for a wide variety of 

antimicrobial products. 

Page 9 of 41 
5. Risk/Benefit Balance: Risks to subjects have been thoughtfully and thoroughly 

minimized in the design of the research. The low residual risk is reasonable in light 

of the likely benefits to society from new data supporting more accurate applicator 

exposure assessments for a wide range of antimicrobial products used for mopping. 

6. Independent Ethics Review: The proposed research has been reviewed and 

approved by the Independent Investigational Review Board, Inc., (IIRB) of Plantation 

FL. The submitted materials include a full record of correspondence between the 

investigators and the IIRB.

7. Informed Consent: Informed consent will be obtained from each prospective 

subject and appropriately documented. Literacy in English or Spanish is a criterion 

for inclusion. 

Both English and Spanish-language recruiting flyers will be available, and will 

encourage interested workers to contact either the study Field Coordinator or 

Spanish-speaking coordinator directly. A Spanish translator will be available at 

recruitment meetings. Consent forms are available in both languages. 

The protocol and consent form indicate that the Principal Investigator, who is not 

fluent in Spanish, will be relied on to inform candidates, who will also be provided 

product labels and MSDSs, both of which are available only in English. These 

procedures may not be adequate to ensure comprehension by candidates whose 

language of choice is Spanish. 

8. Respect for Subjects: Subject identifying information will be recorded only once; 

all subsequent data records and reports will refer to individual subjects only by an 

arbitrary code. Provision is made for discrete handling of pregnancy testing, required 

of female subjects on the day of testing. Candidates and subjects will be repeatedly 

reminded that they are free to decline to participate or to withdraw at any time for any 

reason, without penalty. Medical care for research-related injuries will be provided at 

no cost to the subjects. 

F. Compliance with Applicable Ethical Standards 

This is a protocol for third-party research involving intentional exposure of human 

subjects to a pesticide, with the intention of submitting the resulting data to EPA under the 

pesticide laws. Thus the primary ethical standards applicable to this proposal are 40 CFR 26, 

Subparts K and L. In addition, the requirements of FIFRA §12(a)(2)(P) for fully informed, fully 

voluntary consent of subjects apply, and because the research will be conducted in California, the 

provisions of California Code of Regulations Title 3, Section 6710 apply as well. A detailed 

evaluation of how this proposal addresses applicable standards of ethical conduct is included in 

Attachment 2. 

Page 10 of 41 
The following specific deficiencies should be corrected before the research is initiated: 

• Better provision is needed to ensure that Spanish-speaking candidates are fully informed 

and fully comprehend what they have been told. 

• References in the consent forms to “normal business hours” should be replaced by 

references expressed in California local time, and care must be taken to ensure that a 

Spanish-speaking responder can be reached at any telephone number cited as a source for 

further information. 

40 CFR 26 Subpart L, at §26.1703, as amended effective August 22, 2006, provides in 

pertinent part: 

EPA shall not rely on data from any research involving intentional exposure of 

any human subject who is a pregnant woman (and therefore her fetus), a nursing 

woman, or a child. 

The protocol requires that subjects be at least 18 years old and excludes female subjects who are 

pregnant or lactating. Thus §26.1703 would not forbid EPA to rely on a study executed 

according to this protocol. 

Attachments: 

1. Summary Review of Mopping Scenario Design dated 14 Jan 08 

2. Summary Review of AEATF-II Protocol AEA02 dated 16 Jan 08

3. §26.1111 Criteria for IRB approval of research 

4. §26.1116 General requirements for informed consent 

5. §26.1117 Documentation of informed consent 

6. §26.1125 Criteria for Completeness of Proposals for Human Research 

Page 11 of 41 
Attachment 1 

EPA Scenario Review: AEATF-II Mop Application Scenario/Protocol 

Title: MOPPING APPLICATION SCENARIO: RATIONALE FOR STUDY 

DESIGN (Pages 9-31 in AEATF-II Volume 3) 

Date: 14 January 2008 

Sponsor: American Chemistry Council 

Antimicrobial Exposure Assessment Task Force II 

c/o Has Shah, Ph.D. 

1300 Wilson Blvd 

Arlington VA 22209 

 

1. Scope of Scenario Design 

(a) Is the scenario adequately defined? 

Preliminary versions of the wipe protocol have been reviewed by EPA/PMRA/CDPR to 

determine the appropriate wiping scenarios for regulatory purposes (i.e., to assess 

exposure accurately assess exposure as accurately as possible, but to ensure any error 

does not underestimate exposure). Many varied antimicrobial products can be applied by 

wipes vary greatly from typical consumer applications in home 

furnishings/bathrooms/windows/etc to commercial applications in hotels, hospitals, 

schools, or restaurants, to applications in agricultural premises. Wipe choices include 

spray and wipe, ready-to-use wipes, and bucket-dipped rag and/or sponge wipes. From 

this array of choices, the regulatory consensus was to monitor all three of these choices, 

two of the choices in this wipe protocol. This wipe protocol will include spray & wipes 

as well as the RTU wipes. The actual wipes to be used in the trigger pump scenario are 

imprecisely described; this should be corrected before execution. Paper towels are also 

used in this type of task but differences in exposure are not expected because 

rags/sponges/paper towels are all expected to be saturated. The third choice for wiping, 

use of a sponge or cloth rag dipped into a bucket of treatment solution will be monitored 

by the AEATF at a later date under the soak/immersion/dip scenario as outlined in the 

Governing Document. 

Activities included in the wiping scenario are wiping horizontal and vertical surfaces that 

are above the floor level. “Further, buildings are preferred if they provide diverse indoor 

room sizes and area configurations, e.g., individual offices, bathrooms, kitchen areas, 

hallways, dining areas”. (V3:53)2 The actual activity of the subject while wiping “...will 

 

2 This pagination convention is used throughout this review. “V3” refers Volume 3 of the AEATF submission—the 

“primary documents” volume for the wipe scenario design and protocol. “V4” refers to Volume 4 of the AEATF 

submission—the “secondary documents” for the wipe scenario design and protocol. Entries after the colon are page 

references; many page images bear more than one page number. In volume 3 the cited page number is always from 

the expression “p. N of 198”. Volume 4 page references are always from the expression “p. N of 346.” 

Page 12 of 41 
Attachment 1 

be conducted by each participant as they would normally work. Each subject will not rewipe any surface during a given monitoring event (ME). Past observation indicates a 

wide variety of application methods (oval, side to side, back and forth motion).” (V3:51) 

The scenario does not include the pouring of the concentrate into the trigger pump 

sprayer. The mixer/loader portion of the exposure will be conducted in a separate 

mixing/loading study. This separation of tasks has been selected to allow for the 

regulatory agencies to assess professional products that use automatic dispensers and/or 

RTU trigger pump sprayers as opposed to open pouring. The RTU wipes will be 

provided to the subjects already saturated. 

The AEATF proposes to recruit only professional janitors. Janitors have been selected to 

provide longer wiping periods then are typical for consumers so that there is a greater 

likelihood for detectable residues on sampling matrices. Although shorter durations 

typical of consumer wiping (AEJV survey indicates an average ~5 minutes) are believed 

to result in detectable residues on the hands, other parts of the body are more likely to 

provide measurable residues only when longer exposure durations are sampled. 

Nonetheless, the upper range of consumer wiping durations indicated in the 

Antimicrobial Exposure Joint Venture (AEJV) survey (i.e., 60 minutes) is within the 

range of professional wiping durations (i.e., 30 to 120 minutes) proposed. Thus the 

scenario design will result in exposure data directly usable to estimate consumer as well 

as professional exposures. 

(b) Is there a need for the data? Will it fill an important gap in understanding? 

The CMA study is the only source of exposure data for wiping scenarios. The CMA data 

for wiping includes 6 monitoring events and is characterized by poor recoveries. Based 

on these data limitations, the Antimicrobial Division is requiring dermal and inhalation 

exposure data in many of its assessments to fill this data gap. 

2. Rationale for Scenario Sampling Design 

(a) Are the variables in the mopping scenario design likely to capture diverse exposures 

at the high-end? 

The design choices in the wipe scenario to provide diversity in sampling include (1) 

application equipment; (2) multiple indoor sites in one geographic location; (3) varying 

the amount of active ingredient handled by the subjects; and (4) using different workers 

for each monitoring event. 

Application equipment. “The All Purpose Cleaner (APC) trigger sprayer to be used in 

this study is supplied by Buckeye International. It is used as standard janitorial and 

home consumer equipment in the US. The size of the spray bottle is 32 ounces, 

which is the most common size in use. The adjustable nozzle will be set to a fine 

spray that would normally be used to apply antimicrobials to surfaces prior to wiping. 

APC sprayers are the most-used surface disinfectant method in many commercial 

and home settings.” (V3:49) 

Page 13 of 41 
Attachment 1 

Sites. Three sites (i.e., buildings) in Fresno County, CA, will be selected for this study. 

The choice of one geographical location of Fresno County assumes indoor wiping 

will not differ substantially from one geographic location to another. This 

assumption is supported by the previous CMA study (“...variability in dermal and 

inhalation exposures across workers was most primarily influenced by the application 

method and by implication, each individual worker’s implementation of that 

application method (i.e., their work practices and behavior), rather than the location 

or setting in which the application method is performed.”) (V3:17) Moreover, the 

available training material for janitorial practices is supported by national 

organizations (e.g., International Sanitary Supply Association (ISSA)), not regional 

differences. The choice of sampling vacant buildings allows the researchers “...to be 

free from personal interferences with non-subjects... It also allows the focus to be on 

wiping only as opposed to the broad range of janitorial activities a subject might 

engage in...” (V3:18). Finally, the geographic area selected in close to the 

laboratory conducting the study and will save resources. 

Amount of AI Handled. The amount of active ingredient handled will be varied among 

monitoring events by varying the wiping durations. The AEATF cites existing survey 

data from ISSA and the Antimicrobial Exposure Joint Venture (AEJV). The ISSA 

indicates professional applicators wipe an average of 213 minutes per day. The 

AEJV indicates that consumers average ~5 minutes per event. The wipe protocol will 

monitor wiping for 30 to 120 minutes in increments of approximately 15 minutes. 

(V3:51) This will encompass 1000 to 4000 ft2

 of surface area depending on working 

speed and task duration. 

Varying Subjects. The goal of the study is to monitor professional applicators, so the 

selection of janitors is appropriate to the goal of the study. Each monitoring event 

will use a separate individual to maximize diversity. “Each surrogate worker 

provides his/her unique set of behaviors to the wiping task. Use of the same worker 

for all monitoring events would over-represent a single type of behavior. As a result, 

diversification of worker behavior among MEs is accomplished by simply requiring 

that each ME be based on a different surrogate worker.” (V3:23) The use of 

professional applicators is a reasonable surrogate for the range of potential users that 

may wipe with an antimicrobial product such as consumers, building 

staff/maintenance workers, school janitors, for-hire janitorial firms, etc. 

(b) How have random elements been incorporated into the scenario sampling design? 

“Surrogate worker selection: This process results in a simple random sample of 

qualifying subjects from the volunteer pool. Note, however, that is not the same as a 

random sample from the existing population of professional janitorial workers. By 

definition, volunteers are self-selected and could have different characteristics than nonvolunteers. Such distinctions have no relevance in this case, however. There is no 

particular need to obtain a random sample from the Fresno janitorial population. This 

existing population is not the target population for the study. The MEs are synthetic 

constructs that attempt to predict aspects of a future handler-day population. It is 

Page 14 of 41 
Attachment 1 

purposive by definition. Thus, a random sample of just one ME component (e.g. subject) 

from a subpopulation (e.g. Fresno County) provides no statistical advantage. In fact, a 

random sample of subjects from the volunteer pool is not the only possibility. For 

example, a more diverse sample of surrogate workers from this pool could also be 

acceptable if a clear diversifying characteristic were available for all workers. Lacking 

this, the wiping application study uses the reasonable default option of a random sample 

from the volunteer pool.” (V3:23) 

“A stratified random sampling approach will be used to locate acceptable facilities. 

(V3:19) 

“The properties within each of these three categories (office, retail or meeting) will be 

investigated independently and in random order until a single acceptable facility is found 

for each category.” 

“Each ME will be randomly assigned to a different task duration interval.” (V3:21) 

“Individuals who express a desire to participate in the study within a fixed period of time 

will be contacted and screened in random order. Surrogate workers are randomly 

assigned to MEs. “(V3:23) 

48 subjects are recruited randomly from the pool of qualifying volunteers. These 48 

subjects are randomly divided into six groups of eight subjects each. (V3:54) 

“The eight subjects in each site are ordered randomly. The first subject is then assigned to 

the ME in the longest wiping duration stratum (i.e., stratum F, 105-120 minutes). No 

other assignments of subjects to MEs are made until the subject completes the monitoring 

task in this stratum. When the ME is complete, the next subject in order is assigned to the 

next longest stratum (E, 90-105 minutes). As long as each subject achieves the target 

wiping duration, the process is continued down to the shortest duration stratum (A, 30-45 

minutes) and six MEs have been obtained, one for each of the six strata. If this process 

proceeds as expected, the last two subjects are never used for MEs.” (V3:54) 

(c) What feasible opportunities to incorporate random elements in the design—if any— 

have been overlooked? 

No feasible opportunities to incorporate additional random elements in the sampling 

design are apparent. 

(d) What typical patterns of exposure will likely be included by the sampling design? 

The wipe protocol proposes to monitor two distinct wipe application techniques. The two 

wipe methods include a spray & wipe and a RTU wipe. The spray & wipe scenario will 

consist of a worker spraying a fine mist onto a hard surface with a trigger pump sprayer, 

followed by hand wiping with a commercially available cotton towel. The RTU wipe 

scenario consists of the worker using a pre-moistened wipe pulled from a plastic 

Page 15 of 41 
Attachment 1 

container to wipe hard surfaces. The workers will be instructed to work as they would 

normally work. 

 (e) What typical patterns of exposure will likely be excluded by the sampling design? 

The study is designed to monitor professional janitors, so any different behaviors a 

consumer might exhibit while wiping will be excluded. Given that wiping is not a 

specialized task, exclusion of consumers from the sampling design is not a limiting 

factor. 

The types of wipes available to applicators range from RTU wipes to some type of cloth, 

sponge, or paper towel. RTU wipes on the market all appear to be similar (i.e., clothbased). Other types of wipes such as bucket and sponge/rag will not be included in this 

particular wipe protocol. The bucket and sponge/rag exposure scenario will be monitored 

under the scenario of immersion/dip/soak as outlined in the AEATF Governing 

Document. 

 

The wipe protocol does not monitor the activity of diluting a concentrated product prior 

to use in the spray & wipe scenario. The exposures associated with pouring a liquid 

concentrate will be monitored in a separate mixing/loading scenario as outlined in the 

AEATF Governing Document. 

3. Is the proposed test material an appropriate surrogate? 

The test substance, DDAC, is an appropriate choice for the development of surrogate 

exposure data because it is stable, is characterized by a low vapor pressure (estimated to 

be 2E-11 mmHg), diluted solutions are not dermally irritating, no systemic toxicity was 

seen in a 90-day dermal rat study, the product is registered for the intended use (i.e., 

wiping), and DDAC has been demonstrated to have a low analytical limit of detection. 

“The test material, Sani-Care Lemon Quat, an EPA approved product, containing didecyl 

dimethyl ammonium chloride (DDAC), CAS No. 7173-51-5, and n-alkyl dimethyl benzyl 

ammonium chloride (ADBAC), CAS No. 68424-85-1 will be applied at a target rate not 

to exceed the maximum label-recommended rate. The test material will be used in this 

study in accordance with the product label.” (V3:40) 

“Sani-Care Lemon Quat is a professional use product, and the product label specifies the 

PPE requirements as protective eyewear.” (V3:41) 

“Based on its safety profile, DDAC and ADBAC have been approved for use in many 

formulations, and are extensively used in many janitorial products. The test material, 

Sani-Care Lemon Quat has also been tested for acute effects and has been approved by 

the EPA. The EPA has recently re-registered both DDAC and ADBAC and issued REDs 

for both (EPA, 2006 a,b). Additionally, the safety of the test material has been established 

through long term professional use of the product. The product will be used according to 

its label. The Sani-Care Lemon Quat concentrated formulation will be handled only by 

Page 16 of 41 
Attachment 1 

researchers and the diluted material (1:64) in a ready-to-use form will be provided to the 

subjects.” (V3:44)

 “The freezer storage stability of DDAC on the different matrices to be used in this study 

has been completed showing that DDAC is stable on the different matrices when stored 

in a freezer for 6 months (GPL, 2005).” (V3:48) 

4. What is the rationale for the proposed cluster design and sample size? 

AEATF-II proposes for the wipe scenarios the default design of three clusters of six 

monitoring events (MEs) each, as discussed in the Governing Document. No 

characteristics of these scenarios have been identified which would justify a departure 

from this norm. 

“For the wiping application scenario (as is true for all AEATF II scenarios) only a small 

number of expensive experimentally-obtained monitoring events (MEs) are possible.” 

(V3:15) 

“... a practical goal for this study is that the small sample of wiping application MEs be 

biased towards increased diversity of handling conditions. As a result, the diverse sample 

of MEs is expected to at least cover the middle portion of the future exposure 

distribution, cover the upper portion of the future exposure distribution, and capture the 

range of exposure variation that is expected to exist.” (V3:16) 

“For the wipe application study, random nested (or cluster) sampling is used as the 

reference model for the combination of purposive and random diversity selection actually 

used.” (V3:24) 

“Benchmark objectives specify accuracy goals that must be achieved within the reference 

sampling model when sample size is adequate. In this study, ‘sample size’ means the 

number of clusters (NC) and the number of MEs per cluster (NM). For the wipe 

application study, the benchmark objective is that sample estimates of the arithmetic 

mean and 95th percentile of normalized exposure are accurate to within 3-fold 95% of the 

time.” (V3:5) 

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Attachment 2 

EPA Protocol Review: AEATF-II Mop Application Scenario/Protocol 

Title: A Study for Measurement of Potential Dermal and Inhalation Exposure 

During Application of a Liquid Antimicrobial Pesticide Product Using Trigger 

Spray and Wipe or Ready to Use Wipes for Cleaning Indoor Surfaces

 

Date: 16 January 2008 

Principal Investigator and sub-investigators: 

Sami Selim, Ph.D. 

Megan T. Boatwright 

Tami I. Belcher 

 

Participating Laboratories: 

Golden Pacific Laboratories, LLC 

4720 W. Jennifer Ave. Suite 105 

Fresno, CA 93722 

Grayson Research, LLC 

211 N Main Street 

 Creedmoor NC 27522 

Sponsor: American Chemistry Council 

Antimicrobial Exposure Assessment Task Force II 

c/o Has Shah, Ph.D. 

1300 Wilson Blvd 

Arlington VA 22209 

 

Reviewing IRB: Independent Investigational Review Board 

6738 West Sunrise Blvd Suite 102 

Plantation FL 33313 

 

1. Societal Value of Proposed Research 

(a) What is the stated purpose of the proposed research? 

“The primary purpose of the wiping application monitoring study is to develop more 

accurate information on worker exposures to antimicrobials . . . to support exposure 

assessments for wiping application.” (V3:15) 

 

“This study is being conducted to determine potential dermal and inhalation exposures 

associated with wiping indoor surfaces with an antimicrobial pesticide product.” (V3:38) 

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Attachment 2 

“A practical goal for this study is that the small sample of wiping application MEs be 

biased towards increasing diversity of handling conditions. . . . The diverse sample of 

MEs is expected to at least cover the middle portion of the future exposure distribution, 

cover the upper portion of the future exposure distribution, and capture the range of 

exposure variation that is expected to exist.” (V3:16) 

(b) What research question does it address? Why is this question important? 

Would the research fill an important gap in understanding? 

“This study is being conducted to determine potential dermal and inhalation exposures 

associated with wiping indoor surfaces with an antimicrobial pesticide product.” (V3:38) 

“Since 1992 the EPA has conducted professional and consumer mixer/loader and 

applicator exposure and risk assessments relying primarily on the exposure data in 

PHED. . . . However, PHED does not include any data directly relevant to wiping 

application methods.” (V3:12) 

“The CMA study represents the only existing data in the case of the wiping scenario. . . 

Based on EPA’s review, CMA’s study data met some regulatory agency requirements, 

but was lacking in other areas.” (V3:13) 

“Currently, US EPA relies upon the results of the CMA study conducted more than 

15 years ago to characterize exposure from mopping using an antimicrobial 

(Popendorf et al. 1992). That study has a total of 6 measurements of whole body 

exposure at levels above the Limit of Quantification (LOQ). Analytical methods, 

exposure dosimetry methods and regulatory needs have changed significantly since 

that time. EPA has requested confirmatory exposure monitoring data for a number of 

antimicrobial use scenarios in Registration Eligibility Decision (RED) documents 

issued over the last 2 years. There appears to be no publicly available data with which 

to make a credible estimate of exposure for persons using either a trigger spray and 

wipe or ready-to-use wipes. Thus, the rationale for conducting this study is to 

measure dermal and inhalation exposure in a large enough group of typical users to 

adequately estimate central tendency and variability for this use of antimicrobial 

pesticides.” (V3:41) 

(c) How would the study be used by EPA? 

EPA will consider the data from this study in assessing exposures of occupational or 

residential applicators using a trigger spray and wipe or RTU wipes to apply an 

antimicrobial pesticide to indoor hard surfaces 

 

(d) Could the research question be answered with existing data? If so, how? 

Due to the limitations of existing data, the research question cannot be answered with 

confidence relying on existing data. 

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Attachment 2 

(e) Could the question be answered without newly exposing human subjects? If so 

how? If not, why not? 

“Human subjects are required in this study because they will normally be exposed to the 

test material when performing their daily activities. There are no acceptable methods or 

models that could be used to extrapolate subjects’ exposure.” (V3:42) 

2. Study Design 

(a) What is the scientific objective of the study? If there is an explicit hypothesis, what 

is it? 

“The primary purpose of the wiping application monitoring study is to develop more 

accurate information on worker exposures to antimicrobials. These data will consist of 

dermal and inhalation exposure estimates derived from monitoring subjects under 

conditions constructed to broadly represent those expected for the future application of 

arbitrary antimicrobial pesticides. AEATF II anticipates the resulting database will 

contain sufficient data to support exposure assessments for wiping application.” (V3:15) 

“This study is being conducted to determine potential dermal and inhalation exposures 

associated with wiping indoor surfaces with an antimicrobial pesticide product.” 

(V3:38)” 

“The primary objective of this study is to monitor exposure to subjects who wipe 

horizontal and vertical surfaces with a liquid antimicrobial pesticide product. Each 

monitored applicator will apply product using either a trigger-spray-and-wipe or readyto-use (RTU) wipes and will generally involve work periods of 30 to 120 minutes.” 

(V3:40) 

No hypothesis is stated, nor is the study designed to test an hypothesis. 

(b) Can the study as proposed achieve that objective or test this hypothesis? 

The objective cited above can be achieved by the study as proposed. 

“...large deviations from the benchmark goals may affect the regulatory usefulness of the 

data. If large deviations from the benchmark goals are observed the AEATF II will, in 

consultation with regulatory agencies, determine the best course of action to take. This 

may mean the 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.” (V3:78) 

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Attachment 2 

2.1 Statistical Design 

(a) What is the rationale for the choice of sample size?

“The goal is to use these data to characterize some ‘population’ aspect of the future 

exposure to arbitrary antimicrobial pesticides. Hence, this study is more closely 

aligned with the random sampling situation (1)....” “There is assumed random 

sampling from a population and the goal is to estimate some characteristic of that 

population. . . .” (V3:24) 

“For each scenario in the wiping application study, random nested (or cluster) 

sampling is used as the reference model for the combination of purposive and random 

diversity selection. . . . ” (V3:24) 

“...the benchmark objective is that sample estimates of the arithmetic mean and 95th

percentile of normalized exposure are accurate to within 3-fold 95% of the time.” 

(V3:25). 

Monte Carlo simulations were used to identify the most economical number of 

clusters (3) and subjects per cluster (6) consistent with achieving design levels of 

precision in the results (V3:28-29) 

(b) What negative and positive controls are proposed? Are proposed controls 

appropriate for the study design and statistical analysis plan? 

No positive or negative controls are proposed. This is appropriate for the study 

design and statistical analysis plan. 

(c) How is the study blinded? 

The study is not blinded. 

(d) What is the plan for allocating individuals to treatment or control groups? 

Candidates selected randomly from among respondents to recruiting flyers will be 

assigned randomly to one or another ME, pre-defined in terms of its duration and 

location. (V3:23) 

MEs with longer durations will be executed first; a subject who is unable to continue 

wiping for the designed duration of the ME will be reassigned to a shorter ME, and 

the next subject in random order will be assigned to the uncompleted longer ME. 

(V3:54) 

(e) Can the data be statistically analyzed? 

The results of the analysis from the sampling will be provided in the final report. 

(V3:81). 

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Attachment 2 

(f) What is the plan for statistical analysis of the data? 

“The AEATF II will not statistically analyze the monitoring data in order to 

characterize exposure or investigate the relationship between exposure and other 

factors (e.g., room size, level of residual organic matter, environmental conditions 

including temperature, humidity, air turnover rate, etc.) However, regulators and 

other users of the constructed database (BHED) may choose to conduct such 

analyses. The extent of AEATF II’s data analyses will be limited to the statistical 

characterization of data adequacy for inclusion in BHED scenario monographs. Two 

specific types of analyses will be performed (these analyses are discussed in more

detail in the AEATF II’s Governing Document (AEATF, 2008a): 

“1. Evaluation of benchmark adequacy. A confidence interval based approach 

will be used to determine the realized relative accuracy for the arithmetic 

mean and 95th percentile of exposure normalized by amount of ai handled. 

“2. Cluster effects. The intraclass correlation for clusters (ICC) and its 

confidence interval will be estimated using a variance components model. In 

addition, the effects, if any, of ignoring clusters in the estimation of means and 

percentiles will be determined by comparing the estimates of a no-cluster 

model to those of the random effects model. 

“We note that the analysis in (1) above may suggest that the realized accuracy bounds 

differ from the benchmark targets to some extent. This does not invalidate the study 

since small deviations would be expected and are of little practical concern. However 

large deviations from the benchmark goals may affect the regulatory usefulness of the 

data. If large deviations from benchmark goals are observed the AEATF II will, in 

consultation with regulatory agencies, determine the best course of action to take. 

This may mean the 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.” (V3:77-78)

(g) Are proposed statistical methods appropriate to answer the research question? 

 Yes. 

(h) Does the proposed design have adequate statistical power to definitively answer 

the research question? 

Because of its Purposive Diversity Sampling Design, the study will support only 

limited inferences. EPA believes, nonetheless, that it is likely to characterize reliably 

the exposures of professional janitors in the Fresno area, that those exposures are 

likely to be similar for other professional janitors elsewhere, and that the exposures of 

professional janitors wiping for extended durations can inform assessments of the 

likely exposure of others wiping with similar methods for shorter durations. EPA is 

confident that this design will provide data on wiping exposures more accurate and 

reliable than currently available data. 

Page 22 of 41 
Attachment 2 

2.2 How and to what will human subjects be exposed? 

The test subjects will be exposed to SANI-CARE LEMON QUAT (EPA Reg. No. 

47371-131-559) which contains active ingredients 2.54% didecyl dimethyl ammonium 

chloride (DDAC) and 1.69% n-alkyl dimethyl benzyl ammonium chloride (ADBAC). 

(V3:47). 

Test subjects will be exposed during wiping activities. Two distinct wiping scenarios are 

to be monitored, including a spray and wipe method and a RTU wipe method. The spray 

and wipe method will use a 32 ounce spray bottle with an adjustable nozzle using a fine 

spray. This trigger pump spray bottle is referred to as an “All Purpose Cleaner (APC 

trigger sprayer... supplied by Buckeye International”. After using the trigger pump 

sprayer subjects will wipe surfaces with cotton rags. The RTU wipes are pre-saturated 

with antimicrobial solution, and will be prepared by the researchers. Test subjects will 

not pour the concentrate. Exposure while pouring the concentrate will be monitored in a 

separate study. (V3:11, 49-50 and 64). 

“...represent typical consumer and professional worker methods of applying the test 

substance to indoor horizontal and vertical surfaces above floor level”. (V3:51) 

(a) What is the rationale for the choice of test material and formulation? 

“The test substance for these studies is the formulated product, LEMON QUAT, 

containing didecyl dimethyl ammonium chloride (DDAC) and n-Alkyl dimethyl 

benzyl ammonium chlorides (ADBAC). The quaternary ammonium antimicrobials 

are commonly known as “quats”. DDAC is the active ingredient selected for 

measurement, based on its stability, abundance in the formulation, and sensitivity of 

its analytical method.” (V3:47) 

“LEMON QUAT is an end use product registered with the EPA for use on smooth 

surfaces in indoor environments. LEMON QUAT contains didecyl dimethyl 

ammonium chloride (DDAC) and n-Alkyl dimethyl benzyl ammonium chlorides 

(ADBAC). DDAC was selected as the analyte based primarily upon its abundance 

(3x the largest ADBAC homologue), and on its stability, and the sensitivity of its 

analytical method. The quats ADBAC and DDAC have complete toxicology 

databases with low mammalian toxicity. Virtually all quat antimicrobial products 

contain more than a single quat, i.e., a readily available product containing only 

DDAC was not apparent. 

“The analytical method for DDAC on the proposed monitoring matrices at very low 

concentrations has been validated (GPL, 2004). Additionally, DDAC is a single quat 

(as opposed to ADBAC, the other active ingredient in LEMON QUAT which is an 

homologous series of quats) and has the requisite degree of stability under field, 

storage and transit conditions. The freezer storage stability of DDAC on the different 

matrices to be used in this study has been completed showing that DDAC is stable on 

the different matrices when stored in a freezer for 6 months (GPL, 2005). 

Page 23 of 41 
Attachment 2 

“The very sensitive and selective analytical method developed for the analysis of 

DDAC on different study matrices will allow for the detection and quantification of 

extremely low levels of active ingredient in the collected samples. This will allow for 

shorter exposure time, thus minimizing the risk to research study subjects. 

“Additionally, Sani-Care Lemon Quat has been deemed suitable by the Sponsor and 

EPA as a surrogate compound for generating exposure data for other antimicrobial 

pesticides.” (V3:48) 

(b) What is the rationale for the choice of dose/exposure levels and the staging of 

dose administration? 

Concentration of test materials is constant for all subjects, as is equipment. Variation 

in exposure results from monitoring events (MEs) of differing durations. MEs of 

predefined duration will bracket the range of typical time spent wiping indoor 

surfaces per day by professional cleaners and consumers, taking into account the limit 

of quantitation associated with the analytical method. (V3:20-21) 

DDAC was selected because of its relatively high concentration (2.54%), its stability, 

and the sensitivity of the analytical method. (V3:47) 

The SANI-CARE LEMON QUAT product will be diluted 1:64 with tap water as per 

label directions. (V3:50) 

The same dilute concentration will be used by all MEs. The total amount of ai 

handled will vary by the duration of wiping. 

(c) What duration of exposure is proposed? 

“Wiping duration will range between 30 and 120 minutes. This interval is partitioned 

into six mopping duration strata as follows: 

A. 30 minutes to less than 45 minutes 

B. 45 minutes to less than 60 minutes 

C. 60 minutes to less than 75 minutes 

D. 75 minutes to less than 90 minutes 

E. 90 minutes to less than 105 minutes 

F. 105 minutes to 120 minutes 

At each site, a single ME is targeted for each stratum. . . . As long as the subject is 

within the correct stratum, it is unnecessary to control the duration more precisely. 

However, the subject’s actual wiping duration will be recorded to the nearest minute.” 

(V3:54) 

Any test subjects not able to wipe for the given duration are allowed to stop and as 

long as the duration was a minimum of 30 minutes the dosimeters will be analyzed. 

Durations of less then 30 minutes will not be analyzed. (V3:55) 

Page 24 of 41 
Attachment 2 

Table 1 Justification for Duration of Task and Area Treated Estimated Cleaning 

Times for Healthcare – Mop/Wipe Operations (V3:22) provides estimates of exposure 

durations from the International Sanitary Supply Association (ISSA). 

2.3 Endpoints and Measures 

(a) What endpoints will be measured? Are they appropriate to the question(s) 

being asked? 

Residues of the surrogate chemical on inner and outer passive dosimeters, on hands 

and face/neck, and in personal air samplers. (V3:70-72) 

“Light level, air temperature, and relative humidity of the work area for the duration 

of exposure monitoring will be documented with automated instrumentation logging. 

. . . HVAC will be described in detail and the air turnover rate will be measured or 

estimated.” (V3:69) 

Dermal and inhalation exposures will be measured using inner and outer dosimeters 

consisting of 100% cotton long underwear/long johns, long pants, long-sleeved shirts, 

100% cotton socks, hand wash, face wash, and personal air sampling pumps (OVS 

tube with glass filter and XAD2 sorbent tubes run at 2 L/min. (V3:65-66). SOP 

citations for monitoring methods provided V3:70-72. 

“....each [personal air monitors] pump will be calibrated to a nominal sample flow 

rate of approximately 2 L/min... Flow rates will be measured before and after each 

exposure monitoring period...” (V3:67) 

The validated method (GPL-MTH-052) will be tested. “Each analytical set will 

include two laboratory fortified samples, a solvent blank and a control” (V3:76) 

“The single pull output of each trigger sprayer used in the study will be determined 

by a calibration run (using tap water and 10 pulls) and the results will be documented 

in the raw data.” (V3:50)

Storage stability of DDAC-fortified matrices was measured (V3:77).

(b) What steps are proposed to ensure measurements are accurate and reliable? 

The AEATF SOPs provide specific procedures to ensure accurate measurements such 

as calibration of application solution dispensing (i.e., SOP 10F (V6:70 of 100) and 

inhalation monitoring devices (i.e., SOPs 10A and 10G (V6:58 and 74 of 100)). 

“....each [personal air monitors] pump will be calibrated to a nominal sample flow 

rate of approximately 2 L/min... Flow rates will be measured before and after each 

exposure monitoring period . . . . per SOP AEATF II – 10F and – 10G” (V3:67-68). 

Page 25 of 41 
Attachment 2 

“[air temp, humidity] monitoring equipment will be calibrated or standardized.” 

(V3:69) 

(c) What QA methods are proposed? 

Section 10.2.3 Air Sampling for Ambient Pre-existing DDAC discusses sampling for 

background air concentrations of DDAC (V3:68) 

Field recovery evaluation procedures provided in SOP 8E. Fortification levels (two 

levels provided) for each matrix (i.e., dosimeter) listed in table format with the lower 

fortification levels 4x the LOQ (V3:72). Triplicate samples at each of the two 

fortification levels (V3:73) 

“This study will be conducted according to FIFRA GLP Standards (40 CFR 160).” 

(V3:81) 

(d) How will uncertainty be addressed? Will point estimates be accompanied by 

measures of uncertainty? 

“...large deviations from the benchmark goals may affect the regulatory usefulness of 

the data. If large deviations from the benchmark goals are observed the AEATF II 

will, in consultation with regulatory agencies, determine the best course of action to 

take. This may mean the 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.” (V3:78) 

 

3. Subject Selection 

3.1 Representativeness of Sample 

(a) What is the population of concern? How was it identified? 

The target population is the distribution of future handler/days of applicators applying 

antimicrobial pesticides in the wiping scenario. 

“The community of individuals that use wipes to clean/disinfect surfaces is enormous 

and includes millions of workers and at least 100 million residents in the U.S. alone” 

(V3:46) 

(b) From what populations will subjects be recruited? 

“Adult subjects will be recruited from the janitorial/cleaning service population of 

Fresno County. The most-recent US Census indicates that 40% of the population in 

Fresno, CA metropolitan area is Hispanic. The proportion of Hispanics in service 

industries, e.g., janitorial services, may be even higher than the general population. 

Therefore, to adequately represent the ethnic diversity in the Fresno area, recruitment 

Page 26 of 41 
Attachment 2 

materials and all interactions with potential subjects will be conducted in both English 

and Spanish.” (V3:56) 

(c) Are expected participants representative of the population of concern? If not, 

why not? 

Expected participants will self-identify in response to flyers soliciting interest, posted 

in the workplaces of janitorial services companies. They may differ in unknowable 

ways from other workers who do not step forward. Participants will be screened in 

random sequence from among responders, and in that sense will be representative of 

the population of janitorial service workers in the Fresno area. There is no reason to 

think that janitorial service workers in Fresno are not representative of janitorial 

service workers in any other area of the United States. 

“The most-recent US Census indicates that 40% of the population in Fresno, CA 

metropolitan area is Hispanic. The proportion of Hispanics in service industries, e.g., 

janitorial services, may be even higher than the general population.” (V3:56). 

(d) Can the findings from the proposed study be generalized beyond the study 

sample? 

No discussion was provided on the generalizability of the results. 

3.2 Equitable Selection of Subjects 

(a) What are the inclusion/exclusion criteria? Are they complete and appropriate? 

Inclusion/exclusion criteria are complete and appropriate. They are listed on V3:58-

59 and below: 

“Inclusion Criteria: 

• Males or females, 18 to 65 years of age 

• In good health 

• Willingness to sign the Informed Consent Form and Subject Self Reporting 

Demographic Form 

• Speak and read English or Spanish 

• Reside within Fresno County, California 

• Have experience working in janitorial services 

Exclusion Criteria 

• Skin conditions on the surface of the hands or face/neck (e.g., psoriasis, 

eczema, cuts or abrasions) 

• Pregnancy, as shown by a urine pregnancy test 

• Lactation 

• Allergies to household chemical-based products, soaps or isopropyl alcohol 

Page 27 of 41 
Attachment 2 

• Declines to sign the Informed Consent Form or the Subject Self Reporting 

Demographic Form 

• Does not read and understand English or Spanish 

• Is less than 18 or more than 65 years old 

• Is not in good health 

• Severe respiratory disorders (e.g., moderate or severe asthma, emphysema) 

• Cardiovascular disease (e.g., history of myocardial infarcts, stroke, congestive 

heart failure or uncontrolled high blood pressure) 

• Is an employee of Golden Pacific Laboratories or Grayson Research, or is 

related by blood or marriage to personnel in either company.” 

(b) What, if any, is the relationship between the investigator and the subjects? 

Employees and relatives of employees of the investigators are excluded from 

participation as subjects. (V3:59) 

(c) If any potential subjects are from a vulnerable population, what is the 

justification for including them? 

No potential subjects are from a vulnerable population. 

(d) What process is proposed for recruiting and informing potential subjects? 

The recruiting process is described in V3:56-59 

(e) If any subjects are potentially subject to coercion or undue influence, what 

specific safeguards are proposed to protect their rights and welfare? 

“Janitorial services located in Fresno County and providing professional cleaning 

services for commercial buildings in the Fresno County, CA area will be contacted 

and asked to post flyers soliciting study subjects independently from the janitorial 

service. . . . Those janitorial service managers expressing a willingness to post the 

flyers will be invited to a meeting. . . . At this meeting, the managers will be provided 

with the flyer and the informed consent form. One purpose of these meetings will be 

to . . . impress upon the managers the need to remain neutral (un-coercive) in their 

interactions with employees regarding study participation. Also, the meeting may 

provide an opportunity to hear from organized labor, if any of the shops represented 

are unionized. . . . To avoid the potential for coercion, subjects will not be recruited 

directly through contract janitorial service companies. Flyers will direct interested 

workers to contact the study Field Coordinator or Spanish-speaking coordinator 

directly.” (V3:56-57) 

Page 28 of 41 
Attachment 2 

3.3 Remuneration of Subjects 

(a) What remuneration, if any, is proposed for the subjects? 

“Individuals that are not tested including anyone signing the informed consent form 

but not subsequently being monitored will be compensated for their time and 

inconvenience at the rate of $50 per day. . . . Subjects participating in a monitoring 

event (ME) will be compensated at $100 for the single day that they are monitored. 

The values for compensation are based roughly on a day’s wage of $100 and 

represents potential lost time from secondary sources of employment, travel time and 

incidental expenses incurred in study participation. Compensation will be in the form 

of cash (U.S. currency) at the completion of participation.” (V3:60) 

(b) Is proposed remuneration so high as to be an undue inducement? 

No 

(c) Is proposed remuneration so low that it will only be attractive to economically 

disadvantaged subjects? 

No 

(d) How and when would subjects be paid? 

“Compensation will be in the form of cash (U.S. currency) at the completion of 

participation.” (V3:60) 

4. Risks to Subjects 

4.1 Risk characterization 

(a) Have all appropriate prerequisite studies been performed? What do they show 

about the hazards of the test materials? 

The proposed test material is EPA-registered, with an essentially complete supporting 

database. The test material is of low toxicity to mammals. 

(b) What is the nature of the risks to subjects of the proposed research? 

Risks are of a reaction to the test material or the solvents used to obtain residues from 

hands and face/neck; of discomfort and possibly heat-related illness associated with 

wearing two layers of clothing; of a cardiovascular adverse event attributable to 

physical exertion; of discomfort or inconvenience from wearing the air sampling 

device; of embarrassment from disrobing in the presence of a research technician; of 

an unexpected result of pregnancy testing. (V3:43-45) 

Page 29 of 41 
Attachment 2 

Risks discussed in the consent form include risk of a reaction to the test material, risk 

of over-exertion and stroke or heart attack, risk of discomfort, risk of stinging from 

alcohol wash and wipes, a small possibility of heat stress, risk of embarrassment, 

possible surprise at the results of a pregnancy test, unknown risks to the unborn, and 

unknown or unforeseeable risks including risks of allergic reaction or interaction with 

a medication. (V3:177-186) 

(c) What is the probability of each risk associated with the research? How was this 

probability estimated? 

All identified risks are characterized as of low probability. No quantitative estimates 

are reported. 

4.2 Risk minimization 

(a) What specific steps are proposed to minimize risks to subjects? 

Use of test materials shown to be of low toxicity to mammals; use in strict accord 

with approved labeling; exclusion of candidates known to be sensitive to quaternary 

ammonium compounds; exclusion of candidates in poor health or with broken skin on 

hands, face, or neck; testing in a controlled-temperature environment; alerting 

subjects to signs and symptoms of heat stress; monitoring heat index with associated 

stopping rules; limited time of exposure with rest periods at 30-min intervals, or more 

frequently if requested; close observation of subjects; training of experienced 

technicians to minimize embarrassment; incorporation of procedures to keep results 

of pregnancy testing private and to permit discrete withdrawal; provision of 

appropriate work clothing and PPE. (V3: 43-45, 48-49, 60-62) 

(b) How do proposed dose/exposure levels compare to established NOELs/NOAELs 

for the test materials? 

The DDAC risk assessment developed to support the Reregistration Eligibility 

Decision (RED) document provides for the selection of the toxicological endpoints 

for risk assessment purposes. The dermal toxicological endpoints indicate that low 

concentrations of DDAC (0.13% ai tested in a 21-day dermal toxicity study, MRID 

45656601) display no dermal irritation effects and no systemic effects up to and 

including the limit dose of 1000 mg/kg/day. The proposed use of DDAC in this 

protocol by subjects exposed to a diluted treatment solution of 0.04% ai (1/64 product 

dilution x 2.54% ai in product = 0.04% ai) will not trigger a risk of concern. The 

inhalation toxicological endpoint identified for DDAC for all exposure durations is 

based on two oral toxicity studies (prenatal developmental toxicity in rats, MRID 

41886701, and a chronic toxicity study in dogs, MRID 41970401). The selected 

NOAEL from both studies is 10 mg/kg/day. The inhalation exposure from the spray 

portion of the wipe study has the potential for inhalation exposure to aerosols. 

Page 30 of 41 
Attachment 2 

There are two studies in PHED for inhalation exposure monitored while spraying an 

aerosol product. The PHED data are based on an application of an insecticide around 

baseboards in a kitchen.3 The PHED inhalation unit exposure is 2.4 mg/lb ai sprayed. 

The proposed product dilution directions are to use 2 oz product/gallon of water x 

2.54% ai in product x 8.34 lb per gallon density of water x (1 gallon/128 fluid oz) = 

0.0033 lb ai/gallon. Therefore, assuming 1 gallon of treatment solution sprayed x 

0.0033 lb ai/gallon x 2.4 mg/lb ai unit exposure x (1/60 kg BW) = 0.00013 

mg/kg/day. The margin of exposure (MOE) = 10 mg/kg/day / 0.00013 mg/kg/day 

inhalation dose = 77,000. 

 (c) What stopping rules are proposed in the protocol?

Heat stress index above 95 (V3:62) 

Other medical reasons (V3:61) 

“If two or more subjects withdraw or are withdrawn from the study for the same 

medical reasons, the study will be suspended until the cause of the withdrawal is fully 

investigated and determined.” (V3:61) 

(d) How does the protocol provide for medical management of potential illness or 

injury to subjects? 

SOP 11.B for Management of Heat Stress (V6:78-92) 

SOP 11.C for Emergency Procedures (V6:93-95) 

(e) How does the protocol provide for safety monitoring? 

“If a subject reports an adverse skin reaction during the work period, they will be 

asked to immediately stop working. Research staff will then assist the subject in 

gently washing exposed skin with clean water and mild soap. After drying the area 

with a clean towel, the Principal Investigator will be contacted for further 

instructions.

“The extra layer of clothing worn by subjects may increase the risk of heat-related 

illness. To minimize the possibility of heat stress, the study will be conducted indoors 

in an environment where the heat index (HI) is expected to be less than 85. Research 

personnel shall monitor the heat index, and stop subjects’ work if the heat index

exceeds 95. The SOP AEATF 11.B describes the procedure for identification and 

control of heat stress. The poster “Controlling Heat Stress Made Simple” will be 

posted at the field site. 

 

3 This PHED insecticide use scenario will be replaced by the data generated from this protocol for antimicrobial 

uses. 

Page 31 of 41 
Attachment 2 

“In brief, researchers will observe subjects for possible signs of early heat illness such 

as fatigue, dizziness, irritability, or decreased concentration, especially if the worker 

has been working for a while. If these symptoms are observed, the subjects will be 

asked whether they would like to rest for a moment. If they answer affirmatively,

they will stop working, be given their choice of water or a sports drink, and the 

Principal Investigator will be immediately contacted for further medical management 

instructions. If they answer negatively, they will be permitted to continue working, 

and frequently thereafter asked whether they would like to rest for a moment. Any

affirmative answer will be handled as described above.

“If subjects develop visible signs or report symptoms of distress such as pronounced 

fatigue, headache, cramps, feeling faint, increased pulse, muscle spasms, heavy 

sweating (or dry skin if previously sweating), extreme thirst, or rapid breathing, the 

subjects will be asked to stop working immediately, and given their choice of water

or a sports drink. The Principal Investigator will immediately be contacted for further 

medical management instructions. If the worker’s condition appears to be serious, a 

member of the study team will call 911 and allow emergency medical personnel to

respond and treat the subject.” (V3:61-62) 

(f) How does the protocol provide for post-exposure monitoring or follow-up? Is it 

of long enough duration to discover adverse events which might occur? 

“Subjects will be instructed to inform the Principal Investigator or research staff 

immediately if they feel ill, suffer a skin reaction or experience any other 

unanticipated adverse effects they feel may be related to the study during or following 

conduct of the study.” (V3:61) 

“If two or more subject develop an adverse skin reaction after they leave the study 

site, all subjects will be contacted by the Principal Investigator to determine whether 

further medical management is appropriate.” (V3:62)

(g) How and by whom will medical care for research-related injuries to subjects be 

paid for? 

“If you are injured as a result of being in this study, medical treatment will be 

available from a near-by health care facility that knows about this study. The people 

who are paying for this study will pay any costs of your medical treatment that are not 

covered by your own insurance or by a third party. If necessary, Golden Pacific 

Laboratories will transport you to receive medical attention and pay costs associated 

with reasonable and appropriate treatment of any injuries you get as a result of 

participating in this study.” (V3:183) 

Page 32 of 41 
Attachment 2 

5. Benefits 

(a) What benefits of the proposed research, if any, would accrue to individual subjects? 

“While there are no direct benefits to the subjects participating in this research study, 

there are indirect benefits to both the volunteers and society. . . . If individual workers 

request their results, they may find that their work practice produces more or less 

exposure than average, and this could be a useful learning tool.” (V3:45) 

(b) What benefits to society are anticipated from the information likely to be gained 

through the research? 

“Products containing antimicrobial chemicals are used extensively in hospitals, schools, 

homes, etc. to control pathogenic bacteria and viruses known to produce increased 

morbidity and mortality in humans, domestic animals and pets. Measuring exposure of 

workers in this research study will produce reliable data about the dermal and inhalation 

exposure of workers and the general population performing these tasks. The resulting 

data will improve the completeness and accuracy of the database used by the EPA to 

assess exposure to these chemicals. The ability to accurately predict risk may allow other 

chemical classes of antimicrobials to also be registered based on exposure estimates 

generated from the data to be produced by this study.” (V3:45) 

(c) How would societal benefits be distributed? Who would benefit from the proposed 

research? 

Not addressed.

(d) What is the likelihood that each identified societal benefits would be realized? 

The research is very likely to produce more accurate and reliable information concerning 

exposure in the mop scenario, with resulting societal benefits in the form of more 

accurate and confident assessments of applicator exposure and risk.

6. Risk/Benefit Balance: How do the risks to subjects weigh against the anticipated 

benefits of the research, to subjects or to society? 

“The benefit of maintaining and potentially adding new antimicrobials that protect both 

the subjects involved in this research as well as society (including subjects’ families) in 

general from microbial diseases far outweighs any incremental risks to subjects. 

Mortality and morbidity from microbial pathogens is well-documented. The very slight 

risks from participation in this study are far lower than the risk of not being able to use 

effective antimicrobials for lack of information on the exposure to users.” (V3:45-46) 

Page 33 of 41 
Attachment 2 

7. Independent Ethics Review 

(a) What IRB reviewed the proposed research? 

Independent Investigational Review Board, Inc., Plantation FL (IIRB) 

(b) Is this IRB independent of the investigators and sponsors of the research? 

Yes 

(c) Is this IRB registered with OHRP? 

Yes 

(d) Is this IRB accredited? If so, by whom? 

Not reported. IIRB is not listed as an accredited organization on the AAHRPP website 

(www.aahrpp.org). AAHRPP does not identify organizations for which accreditation is 

pending. 

(e) Does this IRB hold a Federal-Wide Assurance from OHRP? 

Not reported. IIRB is not listed as holding an FWA on the OHRP website. 

(f) Are complete records of the IRB review as required by 40 CFR 26.1125 provided? 

The transmittal of the protocol and related materials to the IIRB (V4:5, 146, 171-196), 

the IIRB’s approval letter (V3:1173-174 and V4:337-338), minutes of the IIRB meeting 

at which the proposed research was discussed and approved (V4:341-343), and an 

appropriate membership list (V4:344-346) are provided. Acceptable documentation of 

IIRB procedures has previously been provided directly to EPA under a claim of 

confidentiality. 

(g) What standard(s) of ethical conduct would govern the work? 

“The primary ethical standards applicable to this proposal are 40CFR 26, Subparts K and 

L. In addition, the requirements of FIFRA §12(a)(2)(P) for fully informed, fully 

voluntary consent of subjects apply, and since the study will be conducted in California, 

the provisions of the California Code of Regulations, Title 3, §6710 would apply.” 

(V3:39) 

8. Informed Consent 

(a) Will informed consent be obtained from each prospective subject? 

Yes. 

Page 34 of 41 
Attachment 2 

(b) Will informed consent be appropriately documented, consistent with the 

requirements of 40 CFR §26.1117? 

Yes. See Attachment 5. 

(c) Do the informed consent materials meet the requirements of 40 CFR §26.1116, 

including adequate characterization of the risks and discomforts to subjects from 

participation in the research, the potential benefits to the subject or others, and the 

right to withdraw from the research? 

Yes. See Attachment 4. 

(d) What is the literacy rate in English or other languages among the intended research 

subjects? 

Literacy in English or Spanish is a criterion for inclusion (V3:59) 

(e) What measures are proposed to overcome language differences, if any, between 

investigators and subjects? 

“Janitorial services located in Fresno County and providing professional cleaning 

services for commercial buildings in the Fresno County, CA area will be contacted and 

asked to post flyers soliciting study subjects independently from the janitorial service. . . . 

The initial contact with service providers will determine language preference (English 

and/or Spanish) for the flyers.” (V3:56)

“Those janitorial service managers expressing a willingness to post the flyers will be 

invited to a meeting . . . . At this meeting, the managers will be provided with the flyer 

and the informed consent form. One purpose of these meetings will be to determine if 

the Spanish translations seems intelligible to the particular dialects that may be 

represented in the County.” (V3:56) 

“Flyers will direct interested workers to contact the study Field Coordinator or Spanishspeaking coordinator directly.” (V3:57) 

“A Spanish translator will be available at recruitment meetings to ensure communication 

with anyone preferring Spanish over English.” (V3:57) 

(f) What measures are proposed to ensure subject comprehension of risks and 

discomforts? 

“A Spanish translator will be available at recruitment meetings to ensure communication 

with anyone preferring Spanish over English. The Principal Investigator will share 

information on the study design with interested participants, and provide them with 

copies of the IRB approved Informed Consent Form (Appendix B) and answer their 

questions. The Principal Investigator will describe the study to the individual in great 

detail and encourage each potential subject to ask questions and request clarification at 

Page 35 of 41 
Attachment 2 

any time during this process as well as in all activities that follow. The Principal 

Investigator will provide each potential subject with a copy of the product label 

(Appendix A) and MSDS (Appendix E) and answer any questions regarding the product 

to be tested. The Principal Investigator will go over the Inclusion and Exclusion Criteria 

(see 9.1.3 below) for the study and answer any questions that the potential subjects have. 

They will be provided with copies of the Informed Consent Form (Appendix B), the 

Subject Self-Reporting Demographic Form (Appendix D) and the State of California 

Department of Pesticide Regulation “Experimental Subject’s Bill of Rights” (Appendix 

C) and encouraged to take them home with them to discuss with family and friends. The 

Principal Investigator will explain to potential subjects wishing to remain in 

consideration that they may withdraw from the research study at any time without penalty 

to their compensation. The Principal Investigator will then read the “Experimental 

Subject’s Bill of Rights” to the potential subjects. The amount and form of 

compensation, the potential risks and discomforts and treatment and compensation for 

injury will be more fully explained and potential subjects encouraged to ask questions. If 

the potential subjects do not have any questions and are interested in participating in this 

research study, they will then be asked to sign the Informed Consent Form and then fill 

out the Subject Self-Reporting Demographic Form.” (V3:57-58) 

Since the label and MSDS are available only in English, and since the Principal 

Investigator is not fluent in Spanish, these procedures may not be adequate to ensure 

subject comprehension of risks and discomforts.

(g) What specific procedure will be followed to inform prospective subjects and to seek 

and obtain their consent? 

See procedure quoted in 8(f) above. 

(h) What measures are proposed to ensure fully voluntary participation and to avoid 

coercion or undue influence? 

“Janitorial services located in Fresno County and providing professional cleaning 

services for commercial buildings in the Fresno County, CA area will be contacted and 

asked to post flyers soliciting study subjects independently from the janitorial service. 

The initial contact with service providers will determine language preference (English 

and/or Spanish) for the flyers. . . . Those janitorial service managers expressing a 

willingness to post the flyers will be invited to a meeting. . . . One purpose of these 

meetings . . . will be to impress upon the managers the need to remain neutral (uncoercive) in their interactions with employees regarding study participation. 

“To avoid the potential for coercion, subjects will not be recruited directly through 

contract janitorial service companies. Flyers will direct interested workers to contact the 

study Field Coordinator or Spanish-speaking coordinator directly.” (V3:57) 

Page 36 of 41 
Page 37 of 41 

Attachment 2 

9. Respect for Subjects 

(a) How will information about prospective and enrolled subjects be managed to ensure 

their privacy?

“Each volunteer will be assigned an identification number, and all research data will be 

recorded under that number. All analysis and reporting will be done using data identified 

only by the identification number. Your name will appear only in the field raw data, and 

there only once. The document linking your name to the identification number will be 

stored separately, in a locked cabinet, away from all other study data. You will not be 

identified by name or any other personal identifier in any reports of this study.” (V3:184) 

“On the day of the test all female volunteers under 50 will be given a pregnancy test kit 

like ones you can buy at the drug store. A female researcher will be able to explain how 

to use it and answer questions. After you give yourself the test, we’ll ask you if you want 

to continue in the study or withdraw; if you decide to withdraw, you won’t be asked why. 

. . . If you want to continue in the study, a female researcher trained to understand the 

results of this pregnancy test will check the results with you privately. No-one but you 

and she will see the results, and they will not be recorded.” (V3:183) 

(b) How will subjects be informed of their freedom to withdraw from the research at 

any time without penalty? 

See passage quoted in 8(f) above, and these passages from the consent document:

“If you decide to participate in this study it will be because you want to. There will be no 

direct benefit to you if you do decide to participate, and no harm to you if you decide not 

to. The choice is up to you. Your alternative is not to participate.” (V3:184) 

“You are free to withdraw from this study at any time, for any reason. Simply tell Dr. 

Selim or another member of the research team if you wish to withdraw. Your decision 

not to participate in this study or to withdraw from this study will not affect your future 

medical care and will involve no penalty or loss of benefits to which you are otherwise 

entitled.” (V3:185) 

(c) How will subjects who decline to participate or who withdraw from the research be 

dealt with? 

Those who decline to participate will simply go their way. The consent form states that 

subjects who withdraw will suffer “no loss of benefits to which you are otherwise 

entitled”, but is unclear whether and how much they would be paid. Subjects who are 

withdrawn by the investigators—and all participating subjects in the case that the entire 

study is stopped—are promised payment in full. (V3:184-185) 
Page 38 of 41 

Attachment 3 

§ 26.1111 Criteria for IRB approval of research 

AEATF-II Wipe Scenario/Protocol AEA02/070264:Jan 16, 2008) 

Criterion Y/N Comment/Page Reference 

(a)(1)(i) Risks to subjects are minimized by using procedures which are consistent with 

sound research design and which do not unnecessarily expose subjects to risk. 

Y 

(a)(1)(ii) Risks to subjects are minimized, whenever appropriate, by using procedures 

already being performed on the subjects for diagnostic or treatment purposes. 

n/a 

(a)(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to 

subjects, and the importance of the knowledge that may reasonably be expected to 

result. In evaluating risks and benefits, the IRB should consider only those risks and 

benefits that may result from the research (as distinguished from risks and benefits 

subjects would receive even if not participating in the research). The IRB should not 

consider possible long-range effects of applying knowledge gained in the research (for 

example, the possible effects of the research on public policy) as among those 

research risks that fall within the purview of its responsibility. 

Y 

(a)(3) Selection of subjects is equitable, taking into account the purposes of the 

research and the setting in which it will be conducted, and being particularly cognizant 

of the special problems of research involving vulnerable populations, such as 

prisoners, mentally disabled persons, or economically or educationally disadvantaged 

persons. 

Y 

(a)(4) Informed consent will be sought from each prospective subject or the subject’s 

legally authorized representative, in accordance with, and to the extent required by 

§26.1116. 

Y 

(a)(5) Informed consent will be appropriately documented, in accordance with, and to 

the extent required by §26.1117. 

Y 

(a)(6) When appropriate, the research plan makes adequate provision for monitoring 

the data collected to ensure the safety of subjects. 

Y 

(a)(7) When appropriate, there are adequate provisions to protect the privacy of 

subjects and to maintain the confidentiality of data. 

Y 

(b) When some or all of the subjects are likely to be vulnerable to coercion or undue 

influence, additional safeguards have been included in the study to protect the rights 

and welfare of these subjects. 

Y 
Page 39 of 41 

Attachment 4 

§26.1116 General requirements for informed consent 

AEATF-II Wipe Scenario/Protocol AEA02/070264:Jan 16, 2008 

Criterion Y/N Comment/Page Reference 

No investigator may involve a human being as a subject in research covered by this 

subpart unless the investigator has obtained the legally effective informed consent of the 

subject or the subject’s legally authorized representative 

OK 

An investigator shall seek such consent only under circumstances that provide the 

prospective subject or the representative sufficient opportunity to consider whether or not 

to participate and that minimize the possibility of coercion or undue influence 

OK 

The information that is given to the subject or the representative shall be in language 

understandable to the subject or the representative 

N More attention is needed to ensure 

bilingual competence among 

investigators who conduct 

recruitment and consent interviews 

No informed consent, whether oral or written, may include any exculpatory language 

through which the subject or the representative is made to waive or appear to waive any of 

the subject’s legal rights, or releases or appears to release the investigator, the sponsor, 

the institution or its agents from liability for negligence 

OK 

(1) A statement that the study involves research, an explanation of the 

purposes of the research and the expected duration of the subject’s 

participation, a description of the procedures to be followed, and identification 

of any procedures which are experimental 

OK 

(2) A description of any reasonably foreseeable risks or discomforts to the 

subject 

OK 

(3) A description of any benefits to the subject or to others which may 

reasonably be expected from the research 

OK 

(4) A disclosure of appropriate alternative procedures or courses of treatment, 

if any, that might be advantageous to the subject 

n/a 

(5) A statement describing the extent, if any, to which confidentiality of records 

identifying the subject will be maintained 

OK 

(6) For research involving more than minimal risk, an explanation as to 

whether any compensation and an explanation as to whether any medical 

treatments are available if injury occurs and, if so, what they consist of, or 

where further information may be obtained 

OK Although research doesn’t involve 

more than minimal risk, compensation and treatment of injuries are 

provided for 

(7) An explanation of whom to contact for answers to pertinent questions 

about the research and research subjects’ rights, and whom to contact in the 

event of a research-related injury to the subject 

OK Must ensure Spanish capability, 

and express all time references in 

California time 

(a) In seeking informed consent the following information 

shall be provided to each subject 

(8) A statement that participation is voluntary, refusal to participate will involve 

no penalty or loss of benefits to which the subject is otherwise entitled, and the 

subject may discontinue participation at any time without penalty or loss of 

benefits to which the subject is otherwise entitled 

OK 

(1) A statement that the particular treatment or procedure may involve risks to 

the subject (or to the embryo or fetus, if the subject may become pregnant) 

which are currently unforeseeable 

OK 

(2) Anticipated circumstances under which the subject’s participation may be 

terminated by the investigator without regard to the subject’s consent 

OK 

(3) Any additional costs to the subject that may result from participation in the 

research 

OK 

(4) The consequences of a subject’s decision to withdraw from the research 

and procedures for orderly termination of participation by the subject 

OK 

(5) A statement that significant new findings developed during the course of 

the research which may relate to the subject’s willingness to continue 

participation will be provided to the subject 

n/a 

(b) When appropriate, one or 

more of the following elements 

of information shall also be 

provided to each subject 

(6) The approximate number of subjects involved in the study OK 

(e) If the research involves intentional exposure of subjects to a pesticide, the subjects of 

the research must be informed of the identity of the pesticide and the nature of its pesticidal 

function. 

OK 
Page 40 of 41 

Attachment 5 

§26.1117 Documentation of informed consent 

AEATF-II Wipe Scenario/Protocol AEA02/070264:Jan 16, 2008

Criterion Y/N Comment/Page Reference 

(a) Informed consent shall be documented by the use of a written consent form 

approved by the IRB and signed by the subject or the subject’s legally authorized 

representative. A copy shall be given to the person signing the form. 

OK 

(b)(1) The consent form may be a written consent document that embodies the 

elements of informed consent required by §26.1116. This form may be read to the 

subject or the subject’s legally authorized representative, but in any event, the 

investigator shall give either the subject or the representative adequate opportunity to 

read it before it is signed; or 

OK 

(b)(2) The consent form may be a short form written consent document stating that the 

elements of informed consent required by §26.1116 have been presented orally to the 

subject or the subject’s legally authorized representative. When this method is used, 

there shall be a witness to the oral presentation. Also, the IRB shall approve a written 

summary of what is to be said to the subject or the representative. Only the short form 

itself is to be signed by the subject or the representative. However, the witness shall 

sign both the short form and a copy of the summary, and the person actually obtaining 

consent shall sign a copy of the summary. A copy of the summary shall be given to the 

subject or the representative, in addition to a copy of the short form. 

n/a 
Page 41 of 41 

Attachment 6 

40 CFR 26.1125 Prior submission of proposed human research for EPA review

AEATF-II Wipe Scenario/Protocol AEA02/070264:Jan 16, 2008

Any person or institution who intends to conduct or sponsor human research covered by §26.1101(a) shall, after receiving 

approval from all appropriate IRBs, submit to EPA prior to initiating such research all information relevant to the proposed 

research specified by §26.1115(a), and the following additional information, to the extent not already included:

Requirement Y/N Comments/Page Refs 

(1) Copies of 

• all research proposals reviewed by the IRB, 

• scientific evaluations, if any, that accompanied the proposals 

• approved sample consent documents, 

ors, and reports of injuries 

Y 

n/a 

97-335 

3:175-198 

reviewed by the IRB, 

• progress reports submitted by investigat

to subjects. 

Y 

n/a 

V3:8-171; 

V4:7-170; 1

V

(2) u

• t the meetings; 

ding the number of members voting 

ges in or disapproving research; 

V4:341-342 

Min tes of IRB meetings . . . in sufficient detail to show 

attendance a

• actions taken by the IRB; 

• the vote on these actions inclu

for, against, and abstaining; 

• the basis for requiring chan

• a written summary of the discussion of controverted issues and 

their resolution. 

Y 

(3) c Re ords of continuing review activities. n/a 

(4) Copies of all correspondence between the IRB and the investigators. Y V4:5, 146, 171-194 

(5) 

representative capacity; indications of experience such as board 

nt to describe each member’s 

governing panel or board, stockholder, paid or unpaid consultant. 

● A list of IRB members identified by name; earned degrees; Y V4:344-346 

certifications, licenses, etc., sufficie

chief anticipated contributions to IRB deliberations; 

• any employment or other relationship between each member and 

the institution, for example, full-time employee, a member of

Y V4:344 

(6) Writ

§26.1108(a) and §26.1108(b). 

Y eparately submitted to EPA 

nder confidentiality claim 

ten procedures for the IRB in the same detail as described in S

u

All information relevant to the proposed research specified by § 26.1115(a) 

(7) t

by § .

Sta ements of significant new findings provided to subjects, as required n/a 

26 1116(b)(5). 

(1) The potential risks to human subjects Y V3:43-45

(2) The measures proposed to minimize risks to the human 

subjects; 

Y V3:45 

(3) The nature and magnitude of all expected benefits of such 

research, and to whom they would accrue 

Y Nature V3:45. No discussion 

of magnitude of benefits 

(4) Alternative means of obtaining information comparable to what 

esearch; and 

Y V3:42 

would be collected through the proposed r

§1125(a) 

ssion of: a discu

(5) The balance of risks and benefits of the proposed research. Y V3:45-46 

§1125(

agreements as originally provided to the IRB, and as approved by the IRB. 

::64-74; 254-264 

Approved V3:177-198 

b): All information for subjects and written informed consent Y Orig V4

§11

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c): Information about how subjects will be recruited, including an

sements proposed to be used. 

Y V3:56-58; 107-112 

§11

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25( ethods proposed for 

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obtaining their informed consent. 

d): A description of the circumstances and m Y 

ting information to potential human subjects for the purpose of 

V3:57-58 

§1125(

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e): All correspondence between the IRB and the investigators or 

rs. 

The following

Y V4: 

extent not alread

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y included: 

research involving human subjects has been reviewed and approved by 

§1125(f): Official notification to the sponsor or investigator . . . that 

an IRB. 

Y V3:173-174