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 Mop Scenario Design and Protocol 

for Exposure Monitoring 

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 Bucket and Mop Equipment 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 Unpublished protocol dated January 16, 2008, prepared by 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 AEA03 and GPL Study No. 070265. 134 

p., plus 335 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. 33-166)1 Volume 1 

of the 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. 8-31) 

• IIRB Approval Letter (pp. 168-169) 

• IIRB-approved English consent materials (pp. 170, 172-181) 

• IIRB-approved Spanish consent materials (pp. 171, 182-193) 

• Product Label for test material (p. 88) 

• MSDS for test material (pp. 103-104) 

• Recruiting materials (pp. 106-111) 

Volume 2 of the submitted package includes the following additional supporting 

documents—also considered in this review: 

• Correspondence between the investigator and IIRB (pp. 6, 143, 167-190) 

• Protocol and appendices as initially submitted to IIRB (pp. 7-141) 

• Mop scenario design as initially submitted to IIRB (pp. 144-166) 

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

from initial submission (pp. 191-325) 

• IIRB approval letter of January 22, 2008 (pp. 327-328) 

• Minutes of 1/22/08 IIRB Meeting and IIRB Membership List (pp. 331-336) 

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 mopping. Mopping can be 

accomplished with different equipment and techniques. AEATF II defines the 

mopping application scenario as the mop-based application of a label-specified enduse formulation containing an antimicrobial chemical, including the tasks of mopping 

 

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

to Volume 1 are to “page N of 193”, and all page references to Volume 2 are to “page N of 336.” 

Page 2 of 41 
and emptying dirty mop-bucket solution. The scope of mop choices includes bucketdipped sponge mops, bucket-dipped string mops, ready-to-use mop systems, and 

automated “Zamboni-type” floor cleaners. From this array of choices, the regulatory 

consensus was to monitor bucket-dipped string mops. 

EPA intends to use the data developed by the AEATF II for the mopping scenario to 

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

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

of mops (i.e., sponge, string, RTU), different floor surfaces, 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 mop study 

generically to estimate dermal and inhalation exposures and risks for other 

antimicrobial ingredients where mopping is consistent with product labeling use 

directions. Antimicrobial products are have been grouped by EPA into the 12 Use 

Categories listed below. Although mopping of indoor floors may occur in many Use 

Categories, most mop 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 

EPA believes that the AEATF mop scenario is 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 mopping scenario as defined in 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 

mop scenario and has incorporated random elements were feasible. The AEATF 

proposes to monitor dermal and inhalation exposures using passive dosimetry 

techniques to measure exposure of human subjects mopping indoor floor surfaces. 

The proposed sample size is the default scheme defined in the AEATF-II Governing 

Document, involving 3 clusters (sites) with 6 subjects at each. This is believed 

adequate to provide data to meet EPA’s needs. 

Page 3 of 41 
The mop scenario will consists of professional applicators mopping indoor floor 

surfaces with a string mop and emptying dirty mop solution from the bucket into a 

sink or drain. The mopping task will occur over a range of durations (i.e., 30 – 90 

minutes) that represent professional applicators’ daily exposures. The focus on 

professional applicators is a practical necessity, given that consumer mopping tasks 

are of shorter duration and are likely to result in very low exposures, at or below the 

limit of detection of the analytical methods used. Because of longer task duration and 

consequent exposure to greater quantities of antimicrobial, professional mop 

applicator exposure is expected to be greater than that of consumers. 

The AEATF-II mopping study is further limited to application using string mops and 

buckets which is typically used by professionals. String mops are believed to entail 

higher exposure potential than other kinds of mops based on the observation that 

string mops have greater surface area than sponge or RTU mop heads, increasing the 

opportunity for dermal contact. In addition, application using string mops typically 

involves a “figure 8” motion that creates greater potential for inadvertent dermal 

contact compared to the “back and forth” motion used with other types of mops. The 

scenario does not include the pouring of concentrate into the bucket. Mixer/loader 

exposure will be monitored in a separate mixing/loading study, which will allow the 

regulatory agencies to assess either professional products intended for use with 

automatic dispensers or RTU mops, or products which require open pouring of the 

treatment solution into a bucket. 

The amount of DDAC to be handled by each subject will be randomly selected. The 

subjects will be randomly ordered as they are enrolled. At each site tasks are defined 

with durations from 30 to 90 minutes at 10 minute intervals. The first subject 

selected will be assigned to the task with the longest mop duration, although if the 

subject is unable to complete the assigned duration, the monitoring event may fit the 

specification for a shorter mopping task. As additional subjects are assigned to tasks, 

all defined mopping durations will be reflected in one monitoring event. The amount 

of DDAC applied will vary among the subjects on the basis of task duration. 

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. 

The mop scenario design calls for three clusters of MEs, each at a different site. It 

specifies 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 mopping. 

Page 4 of 41 
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 

• 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 mop scenario calls for monitoring 6 subjects at each of three sites as they mop 

floors and dispose of spent mop solution. Therefore, a total of 18 test subjects will be 

monitored. Two additional test subjects will be enrolled for each site, making a total 

of 24 subjects in all, in case some subjects withdraw or fail to meet all eligibility 

criteria. 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 mopping tasks of differing durations at one of the three 

test sites. 

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 the mop scenario 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. 

Page 5 of 41 
2. Proposed pattern of human exposure: The AEATF proposes to select professional 

applicators (i.e., janitors) as subjects for the mopping scenario. The test subjects will 

use SANI-CARE LEMON QUAT to conduct mopping activities using a string mop 

and bucket over a range of time durations extending from 30 to 90 minutes in 10 

minute increments. The mopping activities include actual mopping (without remopping any surface during a given monitoring event) and emptying the mop bucket 

at the end of the task. Mopping and disposal of the remaining solution will be 

conducted by each subject as they would normally work. The test subjects will not 

pour the concentrate or mix the mop solution – these tasks will be monitored in a 

separate AEATF study. 

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. 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 

mopping duration (e.g., 30 – 90 minutes). 

The EPA believes that the AEATF mopping study will represent typical worker 

methods of applying the test substance to indoor floors. The selection of janitorial 

subjects, test material, and mopping activities is justified as described in the protocol. 

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

exposures resulting from mopping activities of indoor floors. Dermal and inhalation 

exposure will be measured using whole-body dosimeters (inner and outer), socks for 

foot exposure, 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. Foot exposure is generally not measured in pesticide 

studies unless there is the potential for foot exposure. However, for mopping there is 

the potential for foot exposure and therefore it has been included. The hand/face 

wash is an appropriate method to determine hand exposure. 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. 

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 mopping study is described in 

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

Page 6 of 41 
reliable. The QA/QC plan includes field recovery analyses, travel recovery analyses, 

storage stability studies, and break-through analyses. Method validation results 

should be included in the final study report. 

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 and transported and 

stored in the same was as the actual study samples, and will be 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 mop 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. 

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 

Page 7 of 41 
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: 

• AEATF did not provide information on how or where the remaining treatment solution in 

the mop bucket will be disposed of. More specificity is needed to ensure that the disposal 

activity is well documented and representative of typical disposal events. 

• 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 to 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 mopping 

application monitoring study is to develop more accurate information on worker 

exposures to antimicrobials while they mop indoor floors. Because many millions of 

Americans apply antimicrobial products with a mop, 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: Twenty-four adult subjects will be recruited from the 

janitorial/cleaning service population of Fresno County. Participants will selfidentify 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 

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. 

Page 8 of 41 
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 

approve 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 mopping floors with antimicrobials, usable by EPA and other 

regulatory agencies to support exposure assessments for a wide variety of 

antimicrobial products. 

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. 

Page 9 of 41 
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 

preferred language 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. 

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. 

The following specific deficiencies should be corrected before the research is initiated: 

• Better provision is need for ensuring that Spanish-speaking candidates are fully informed 

and fully comprehend what they have been told. It would be better for candidate 

interviews to be conducted by a member of the research team fluent in Spanish than to 

rely on a translator. 

• 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: 

Page 10 of 41 
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 AEA03 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 I) 

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 mop field study protocol have been reviewed by EPA, 

PMRA, and CDPR to determine the appropriate mopping scenario to assess exposure as 

accurately as possible, but while ensuring that any error does not underestimate exposure. 

Many varied antimicrobial products can be applied by mops, from typical consumer 

applications to kitchen floors to commercial applications in hotels, hospitals, schools, or 

restaurants, to applications in agricultural premises. Mop choices include string mops, 

sponge mops, and ready-to-use mops. From this array of choices, the regulatory 

consensus was to select the string mop. The string mop is believed to represent the high 

end of exposure potential because “...string mops have greater surface area than readyto-use mop heads, increasing the opportunity for dermal contact. In addition, application 

using string mops involves a ‘figure 8’ motion that creates greater potential for 

inadvertent dermal contact compared to the ‘back and forth’ motion used with ready to 

use mop systems.” (V1:12)2 The AEATF mop protocol appropriately proposes to use a 

string mop and Brite 6185 Mop Bucket with 6127-01 Wringer.

Activities included in the mopping scenario are mopping floors and emptying the mop 

bucket. The scenario does not include pouring concentrate into the mop bucket. 

Mixer/loader exposure will be monitored in a separate study. This separation of tasks 

will allow regulatory agencies to assess accurately the exposure associated with either 

professional products that use automatic dispensers or other products requiring open 

pouring. 

 

2 This pagination convention is used throughout this review. “V1” refers Volume I of the AEATF submission—the 

“primary documents” volume for the mop scenario design and protocol. “V2” refers to Volume II of the AEATF 

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

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

the expression “p. N of 193”. Volume 2 page references are always from the expression “p. N of 336.” 

Page 12 of 41 
 Attachment 1 

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

selected to provide longer mopping periods then are typical for consumers, to reduce the 

likelihood of undetectable residues on sampling materials. Although shorter durations 

typical of consumer mopping 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 mopping 

durations indicated in the Antimicrobial Exposure Joint Venture (AEJV) survey—60 

minutes—is within the range of professional mopping durations proposed. Thus the 

scenario design will generate exposure monitoring 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 the mopping scenario. The CMA 

data for mopping includes 6 monitoring events and is characterized by low field 

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 string mop 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 mop technology typically used by professionals, i.e., 

string mop and bucket systems (source: Johnson Diversey), are expected to have 

higher exposure potential than those often used by consumers, e.g., sponge mops, 

ready-to-use mops. This higher exposure assumption has been discussed with the 

regulatory agencies (e.g., US EPA, California EPA) and is considered likely given the 

nature of applicator handling with string and bucket mop systems, i.e., sting mops 

have greater surface area than ready-to-use mop heads, increasing the opportunity for 

dermal contact. In addition, application using string mops involves a ‘figure 8’ 

motion that creates greater potential for inadvertent dermal contact compared to the 

‘back and forth’ motion used with ready-to-use mop systems.” (V1:12) 

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 mopping 

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

assumption is supported by the previous CMA study. 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 

Page 13 of 41 
Attachment 1 

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

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

in...” (V1:18). 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 mopping durations. The AEATF cites existing 

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

ISSA indicates professional applicators mop an average of 83 minutes per day. The 

AEJV indicates that consumer’s average ~10 minutes per event. The mop protocol 

will monitor mopping for 30 to 90 minutes; task durations will be predefined to vary 

by approximately ten minutes. (V1:53) Each subject will mop from 2000 to 6000 ft2

of floor space. 

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 mopping 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.” (V1:23) The use of 

professional applicators is believed to be a reasonable surrogate for the range of 

potential users that may mop 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 

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 mop application study uses the reasonable default option of a random sample 

from the volunteer pool.” (V1:23) 

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

(V1:19) 

Page 14 of 41 
Attachment 1 

“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.” (V1:21) 

“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.” (V1:23) 

”24 subjects are recruited randomly from the pool of qualifying volunteers. These 24 

subjects are randomly divided into three groups of eight subjects each.” (V1:53) 

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

the ME in the longest mopping duration stratum (i.e., stratum F, 80-90 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, 70-80 minutes). As long as each subject achieves the target mopping 

duration, the process is continued down to the shortest duration stratum (A, 30-40 

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.” (V1:54) 

(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 mopping application scenario is defined as the mop-based application of a labelspecified end-use formulation containing an antimicrobial chemical. This includes the 

tasks of mopping and dirty mop bucket solution emptying. It is common in institutional 

settings today that automated dispensing systems provide the applicator with ready to use 

mop solutions, and the applicator does not mix and load the end-use mop solution in a 

bucket. Therefore, the applicator’s exposure during a single workday in these conditions 

would arise only from the tasks of application and intermittent disposing or emptying the 

dirty mop bucket solution.” (V1:11) 

“Mopping will be conducted by each participant as they would normally work. Past 

observation indicates a wide variety of application methods (Figure 8, side to side, back 

and forth motion), wringing preference (thorough agitation vs. dipping prior to wringing) 

and degree of wringing (single pull vs. multiple). Each subject will not re-mop any 

surface during a given monitoring event (ME). Disposal of the mopping solution 

remaining in the buckets will be conducted by each participant as they would normally 

do.” (V1:50-51) 

Page 15 of 41 
Attachment 1 

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

The study will monitor professional janitors, so any differences in behavior that a 

consumer may exhibit while mopping will not be monitored. However, given that 

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

not considered to be a limiting factor. 

The mop scenario excludes the task of diluting a concentrated product prior to mopping. 

The exposures to pouring a liquid concentrate will be monitored in a separate 

mixing/loading study as outlined in the AEATF Governing Document. “...a mop 

applicator could also be manually mixing and loading the mop solution, i.e., preparing 

the end-use dilution by adding a concentrate to the water in a bucket. In these cases, the 

daily exposure for an antimicrobial handler would arise from two discrete tasks, i.e., 

mopping (including dirty mop solution disposal) and mixing/loading of mop solution. 

These mixing and loading tasks are not included as part of the AEATF II mopping 

application scenario.” (V1:11) 

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 mopping, 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.” (V1:40) 

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

PPE requirements as protective eyewear.” (V1:41) 

“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 

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

subjects.” (V1:44) 

Page 16 of 41 
Attachment 1 

 “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).” (V1:48)

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

AEATF-II proposes for the mop scenario 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. 

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

small number of expensive experimentally-obtained monitoring events (MEs) are 

possible.” (V1:15)

“... a practical goal for this study is that the small sample of mopping 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.” (V1:16) 

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

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

used.” (V1:24) 

“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 mop 

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.” (V1:5) 

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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 Bucket 

and Mop Equipment 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 mopping application monitoring study is to develop more 

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

assessments for mopping application.” (V1:15) 

 

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

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

(V1:38) 

Page 18 of 41 
Attachment 2 

“A practical goal for this study is that the small sample of mopping 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.” (V1:16) 

(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 mopping indoor surfaces with an antimicrobial pesticide product.” 

(V1:38) 

“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 mopping 

application methods.” (V1: 12) 

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

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

but was lacking in other areas.” (V1:13) 

“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 a bucket and string mop. 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.” (V1:p41) 

(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 mop to apply an antimicrobial pesticide to indoor floors. 

 

(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. 

Page 19 of 41 
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.” (V1:42) 

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 mopping 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 mopping application.” 

(V1:15) 

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

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

(V1:38)” 

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.” (V1:78) 

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).... 1. There is assumed random 

Page 20 of 41 
Attachment 2 

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

population.” (V1:24) 

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

reference model for the combination of purposive and random diversity selection.” 

(V1:24) 

“...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.” 

(V1:25). 

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. (V1:28-29) 

(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. (V1:23) 

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

mopping 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. 

(V1:54) 

(e) Can the data be statistically analyzed? 

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

(V1:81). 

(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 

Page 21 of 41 
Attachment 2 

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.” (V1:77-78)

(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 mopping for extended durations can inform assessments of the 

likely exposure of others mopping for shorter durations with other classes of 

equipment. EPA is confident that this design will provide data on mopping 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). 

(V1:47). 

Test subjects will be exposed during mopping activities using a String Mop and Brite 

6185 Mop Bucket with 6127-01 Wringer. Mopping activities include actual mopping 

and emptying the mop bucket at the end of the task. Test subjects will not pour the 

concentrate. (V1:11, 49-50 and 63). 

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

substance to indoor floors”. (V1:51) 

(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.” (V1:47) 

“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). 

“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. 

Page 23 of 41 
Attachment 2 

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.” (V1:48) 

(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 mopping floors per 

day by professional cleaners, taking into account the limit of quantitation associated 

with the analytical method. (V1:20-21) 

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

and the sensitivity of the analytical method. (V1:48) 

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

label directions. (V1:49) 

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

handled will vary with the duration of mopping. 

(c) What duration of exposure is proposed? 

Each predefined ME will last from 30 to 90 minutes, with rest breaks at 30-minute 

intervals in longer-duration MEs. (V1:20-21) 

Mopping duration will range between 30 and 90 minutes. This interval is partitioned 

into six mopping duration strata as follows: 

A. 30 minutes to less than 40 minutes 

B. 40 minutes to less than 50 minutes 

C. 50 minutes to less than 60 minutes 

D. 60 minutes to less than 70 minutes 

E. 70 minutes to less than 80 minutes 

F. 80 minutes to 90 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 mopping duration will be recorded to the nearest 

minute. (V1:53) 

Any test subjects not able to mop 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. (V1:54) 

Page 24 of 41 
Attachment 2 

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

Times for Healthcare – Mop/Wipe Operations (V1:22) includes 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. (V1:69-71) 

“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.” (V1:69) 

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. (V1:65-66). SOP 

citations for monitoring methods provided V1:70-71. 

“....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...” (V1:67) 

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

include two laboratory fortified samples, a solvent blank and a control” (V1:76) 

Storage stability of DDAC fortified matrices were measured (V1:77). 

(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...” (V1:67) “per SOP AEATF II – 10F and – 10G” 

(V1:68). 

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

(V1:69) 

Page 25 of 41 
Attachment 2 

(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 (V1:68) 

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 (V1:72). Triplicate samples at each of the two 

fortification levels (V1:73) 

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

(V1:80) 

(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.” (V1:78) 

 

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 mopping scenario. 

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

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

(V1:46) 

(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.” (V1:55) 

(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.” (V1:55). 

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

sample? 

No discussion is 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 V1:58-

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. (V1:59) 

(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 V1:55-58 

(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.” (V1:55-56) 

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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.” (V1:59) 

(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.” (V1:59) 

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. (V1:44-45) 

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. (V1:177-178) 

(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. (V1: 44-45, 48-49, 60) 

(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 (i.e., 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. Inhalation exposure from mopping with 

a low vapor pressure chemical such as DDAC is expected to be minimal. 

Page 30 of 41 
Attachment 2 

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

Heat stress index above 95 (V1:61) 

Other medical reasons (V1:61) 

“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.” (V1:61) 

(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.

“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 

Page 31 of 41 
Attachment 2 

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.” (V1:60-61) 

(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.” (V1:60) 

“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.” (V1:61)

(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.” (V1:179) 

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.” (V1:45-46) 

(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 

Page 32 of 41 
Attachment 2 

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.” (V1:45-46) 

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

research? 

“Results from the study may benefit EPA and janitorial workers by reducing uncertainty 

about the range of exposure experienced by consumers and workers handling 

antimicrobials. Registrants of antimicrobials will benefit because they will provide EPA 

with data on exposure that has been made a condition of re-registration for a number of 

antimicrobials, and they may be aided in registering new antimicrobials using the data 

generated from this study.” (V1:45-46)

(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.” (V1:46) 

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 

Page 33 of 41 
Attachment 2 

(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 (V2:6, 43, 167-190), the 

IIRB’s approval letter (V1:168-169 and V2:327-328), minutes of the IIRB meeting at 

which the proposed research was discussed and approved (V2:331-333), and an 

appropriate membership list (V2:334-336) 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.” 

(V1:38-39) 

8. Informed Consent 

(a) Will informed consent be obtained from each prospective subject? 

Yes. 

(b) Will informed consent be appropriately documented, consistent with the 

requirements of 40 CFR §26.1117? 

Yes. See Attachment 5. 

Page 34 of 41 
Attachment 2 

(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 (V1:58) 

(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.” (V1:55)

“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.” (V1:55-56) 

“Flyers will direct interested workers to contact the study Field Coordinator or Spanishspeaking coordinator directly.” (V1:56) 

“A Spanish translator will be available at recruitment meetings to ensure communication 

with anyone preferring Spanish over English.” (V1:57) 

(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 

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 

Page 35 of 41 
Attachment 2 

(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.” (V1:57) 

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.” (V1:55-56) 

9. Respect for Subjects 

(a) How will information about prospective and enrolled subjects be managed to ensure 

their privacy? 

Page 36 of 41 
Page 37 of 41 

Attachment 2 

“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.” (V1:180) 

“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.” (V1:178) 

(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.” (V1:179) 

“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.” (V1:180) 

(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. (V1:180-181) 
Page 38 of 41 

Attachment 3 

§ 26.1111 Criteria for IRB approval of research 

AEATF-II Mop Scenario/Protocol AEA02/070265: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 Mop Scenario/Protocol AEA02/070265: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 Mop Scenario/Protocol AEA02/070265:Feb xx, 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 Mop Scenario/Protocol AEA02/070265: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 

reviewed by the IRB, 

• approved sample consent documents, 

• progress reports submitted by investigators, and reports of injuries 

to subjects. 

Y 

n/a 

Y 

n/a 

V1:8-166; 

V2:13-172; 194-328 

V1:172-192 

(2) Minutes of IRB meetings . . . in sufficient detail to show 

• attendance at the meetings; 

• actions taken by the IRB; 

• the vote on these actions including the number of members voting 

for, against, and abstaining; 

• the basis for requiring changes in or disapproving research; 

• a written summary of the discussion of controverted issues and 

their resolution. 

Y V2:340-345 

(3) Records of continuing review activities. n/a 

(4) Copies of all correspondence between the IRB and the investigators. Y V2:4-12; 172-193; 330-335 

(5) ● A list of IRB members identified by name; earned degrees; 

representative capacity; indications of experience such as board 

certifications, licenses, etc., sufficient to describe each member’s 

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 

governing panel or board, stockholder, paid or unpaid consultant. 

Y 

Y 

V2:333-335 

V2:333 

(6) Written procedures for the IRB in the same detail as described in 

§26.1108(a) and §26.1108(b). 

Y Separately submitted to EPA 

under confidentiality claim 

All information relevant to the proposed research specified by § 26.1115(a) 

(7) Statements of significant new findings provided to subjects, as required 

by §26.1116(b)(5). 

n/a 

(1) The potential risks to human subjects Y V1:43-44 

(2) The measures proposed to minimize risks to the human 

subjects; 

Y V1:45 

(3) The nature and magnitude of all expected benefits of such 

research, and to whom they would accrue 

Y Nature V1:45-46. No 

discussion of magnitude of 

benefits 

(4) Alternative means of obtaining information comparable to what 

would be collected through the proposed research; and 

Y V1:42 

§1125(a) 

a discussion of: 

(5) The balance of risks and benefits of the proposed research. Y V1:46 

§1125(b): All information for subjects and written informed consent 

agreements as originally provided to the IRB, and as approved by the IRB. 

Y Orig V2:71-80; 252-261 

Approved V1:172-192 

§1125(c): Information about how subjects will be recruited, including any 

advertisements proposed to be used. 

Y V1:55-59; 106; 109-110 

§1125(d): A description of the circumstances and methods proposed for 

presenting information to potential human subjects for the purpose of 

obtaining their informed consent. 

Y V1:56-57 

§1125(e): All correspondence between the IRB and the investigators or 

sponsors. 

The following Information, to the 

Y V2:4-12; 172-193; 330-335 

extent not already included: 

§1125(f): Official notification to the sponsor or investigator . . . that 

research involving human subjects has been reviewed and approved by 

an IRB. 

Y V1:168-169