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EPA Science Assessment of 

AEATF II Hand Wipe/Wash 

Removal Efficiency (Paint) 

Protocol 

Tim Leighton

Kelly Sherman

USEPA

Office of Pesticide Programs

Jonathan Cohen, PhD

ICF International

April 8, 2014
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Organization of Presentations

Background and Science Assessment

• Tim Leighton (USEPA)

• Jonathan Cohen, PhD (ICF International)

Ethics Assessment

• Kelly Sherman (USEPA)
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Overview

Hand Wipe/Wash Removal Efficiency Protocol

 Regulatory Context

 Study Objective

 Need for Study

 Test Material

 Hand Wash Procedure

 Summary of Hand Wash Experiment

 Risk Estimates

 Compliance with Scientific Standards

 Discussion/Conclusions
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Regulatory Context

 This is a proposal for research involving 

intentional exposure of human subjects with the 

intent to submit the resulting data to EPA under 

FIFRA

 The following regulatory requirements apply:

 40 CFR §26.1125 requires prior submission of the 

protocol and supporting documentation

 40 CFR §26.1601 requires review of the protocol by 

EPA and the HSRB 
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Study Objective

 The primary objective of this study is to determine the 

removal efficiency of BIT in latex paint, and in isopropyl 

alcohol (IPA) from human hands

 Paint portion of the study to be used to correct hand 

wipe/wash samples in BIT-treated painting studies

 IPA portion of the study to be used to correct hand 

wipe/wash samples in non-paint liquid studies in the 

future and to compare the efficiency results from 

paint versus IPA solutions
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The Need For A Hand Wipe/Wash Removal 

Efficiency Study to Support the Painting Study

 Removal of dried paint from hands will require 

a robust hand wash method/procedure

 As noted in Brouwer et al. (2000)’s review of 

the literature:

“It is recommended to conduct sampling 

efficiency studies prior to field sampling, under 

conditions that are quite similar to conditions of 

exposure regarding exposure process, levels of 

skin loading, and time of residence of the 

compound on the skin.”
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Selected Test Material

 1,2-benzisothiazoline-3-one (BIT) 

 Material preservative

 EPA Registration Number 5385-121

 CAS Number 2634-33-5
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Hand Wipe/Wash Procedure

 Hand wipe/wash procedure will mimic the 

procedure used in brush/roller study, including: 

 Hand scrubbed with gauze sponge

• Sponge soaked with 50/50 IPA & distilled water

• Scrub until dried paint is loosened or removed

 Hand then rinsed with same solution

• While rinsing subject will rub fingers to palm

• 250 mL of 50/50 IPA & distilled water rinse

 Collect sponge & rinse water in steel bowl
Summary of Hand Wipe/Wash Experiment

 20 test subjects

 4 Groups, 5 test subjects per Group, 2 

hands per subject (n = 10 per Group)

 Volume of treatment solutions:

 Paint 500 μL per palm

 IPA 100 μL per palm

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Summary of Hand Wipe/Wash Experiment (ctd)

 Concentration of treatment solutions:

 Paint = 120 and 600 ppm BIT

 IPA = 0.786 and 3.9 mg BIT/mL IPA

 Palm surface area treated ~50 cm2

 Two loading rates (~1.6 and 7.8 μg/cm2)

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Summary Table 

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Fortification of Hands with Treatment Solution

 Hand will be pre-washed with Ivory soap and 

water and then dried

 Two treatment solution experiments:

 BIT-treated latex paint (500 μL/palm)

 BIT-treated IPA solution (100 μL/palm)

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Fortification of Hands (continued)

 Micropipettes used to fortify palm with 

treatment solution

 Glass capillary tube will be used to 

spread treatment solution on palm 

(2 cm from palm’s edges)

 Treatment solution allowed to dry for 45 

minutes prior to wipe/wash procedure

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Toxicity of Test Material (Dermal)

 The 90-day dermal rat study (MRID 45184601) is 

used to assess BIT

 LOAEL is 100 mg/kg/day based on macroscopic 

and microscopic changes to the stomach mucosa

 Uncertainties in study based on irritation in the 

stomach from dermally applied dose

• Measures were taken to avoid ingestion of test material

• Selection of LOAEL protective approach

 BIT classified as acute dermal Tox CAT IV (slight 

irritant) and as a moderate dermal sensitizer
Subject’s Potential Dose Estimates to Paint 

Maximum Dose (mg/kg/day) =

0.39 mg/hand x 2 hands x (1/80 kg)=

0.0098 mg/kg/day

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Potential Risk Estimates 

Margin of Exposure (MOE) = LOAEL/Dose = 

100 mg/kg / 0.0098 mg/kg = 10,000

Target MOE 1,000

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Analytical Phase

 Matrices – hand wipe/washes

 Method validation

 QA/QC plan 

 Field recovery analysis

 Storage stability studies
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Compliance with Scientific Standards

 This protocol has addressed the following:

Test Guidelines – none applicable

Good Laboratory Practices (GLPs) 

(40 CFR Part 160)

 Recommendations in Brouwer et al (2000) 

used as a guide to review the hand 

wipe/wash efficiency protocol
Discussion based on Brouwer et al (2000)

 The sample size of 10 palms/group approximates that found 

in the literature (sample sizes in literature from 3 to 12)

 The proposed hand loading (1.6 and 7.8 μg/cm2) 

approximates the anticipated hand exposures in the 

brush/roller exposure study

 The average hand loading in the PHED paint brush study 

was 10.5 μg/cm2(range of 4.8 to 19.7 μg/cm2)

 PHED paint study hand sampling based on cotton gloves

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Discussion (continued)

 Residence time is proposed to be 45 min

 BIT dermal absorption (rats) is 1.7% over 4 hours 

 Paint study exposure anticipated up to 3 to 4 hours; 

but not all exposure occurs at time 0

 Method of contamination: palm versus whole hand

 Hand wipe/wash procedure will mimic that used in 

actual exposure study. Suggest video tape procedure.

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Summary Conclusion

• This protocol is likely to yield scientifically reliable 

information, satisfying the following criteria:

 It would produce important information to fill an 

identified scientific/regulatory need;

 This need cannot be addressed except by research 

with human subjects;

 It has a clear scientific objective; and

 The study, as designed, should produce data 

adequate to achieve the objective.
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EPA Ethics Assessment 

of AEATF II Hand Wash 

Removal Efficiency 

Protocol

Kelly Sherman

Human Research Ethics Reviewer

Office of Pesticide Programs
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Value to Society

 This study will allow for accurate interpretation of 

the results of the AEATF’s Brush and Roller study 

and possibly other studies

 Many consumers and workers apply paint that 

contains antimicrobial products, so reliable data on 

potential dermal and inhalation exposure are 

needed to support EPA exposure assessments

 Existing data have limitations
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Subject Selection

 Subjects will be recruited through newspaper 

advertisements

 Callers will be informed about the study using an 

IRB-approved script

 Callers will be screened for eligibility, and then 

scheduled for informed consent meetings

 Inclusion/Exclusion Criteria are complete and 

appropriate except that “allergies or sensitivities 

to BIT” should be added
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Subject Selection 2

 No potential subjects are from a vulnerable 

population

 Subjects will be recruited through newspaper 

advertisements, not through employers

 Recruitment materials and interactions with 

potential subjects will be conducted in English 

or Spanish, depending on subject preference
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Consent Process

 Principal investigator (or bilingual researcher) meets 

individually with interested candidate

 Provides information about study design in candidate’s 

preferred language

 Applies eligibility criteria

 Reviews Informed Consent Document

 Provides label and MSDS

 Answers questions

 Principal Investigator confirms understanding and 

solicits consent to participate
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Risks and Risk Minimization

Two categories of risk; protocol provides 

appropriate measures to minimize each

1. Skin reaction to test material or rubbing alcohol 

used to wash the hands

2. Unwanted disclosure of pregnancy test results
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Benefits

• No direct benefits to subjects

• Sponsors will benefit from improved 

exposure and risk assessments

• Likely societal benefit is higher quality 

exposure and risk assessments for 

antimicrobial products
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Risk-Benefit Balance

 Risks have been effectively minimized

 Residual risks to subjects will be low

 Risks to subjects are reasonable in 

light of potential societal benefits
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Respect for Participants

 Participant privacy will be maintained

 Proposed payments to subjects are 

reasonable

 Participants will be free to withdraw at any 

time, for any reason
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Independent Ethics Review

 Schulman Associates IRB was the 

reviewing institutional review board

 Schulman Associates reviewed and 

conditionally approved the protocol and 

supporting documents

• Full approval will be issued after reviews by 

CDPR, EPA, and HSRB

• Spanish translations will be created after 

approval of English versions
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Applicable Ethical Standards

 This is a proposal 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

 The primary ethical standards applicable to 

this research are 40 CFR 26, subparts K and L
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Revisions Requested by EPA

Before Research Proceeds

 Add “sensitivities” and “BIT or other chemicalbased products” to the exclusion criteria

 In the consent form, describe the test product 

as a pesticide

 Obtain final IRB approval
Revisions Requested by EPA

in Future Protocols

 Incorporate the HSRB’s forthcoming 

guidance about how to provide personal 

exposure results to subjects

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Compliance with Ethical Standards

 All requirements of §26.1111, §26.1116, and 

§26.1117 are met

 All requirements of §26.1125 are met

 Requirements of §26.1203 are met

 If EPA’s and HSRB’s requested corrections are 

made, research conducted according to this 

scenario and protocol will likely meet the 

applicable requirements of 40 CFR part 26, 

subparts K and L
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Charge Questions

If the proposed AEATF II hand wash removal efficiency 

study proposal is revised as suggested in EPA’s review 

and if the research is performed as described:

1) Is this research likely to generate scientifically reliable 

data, useful for determining the removal efficiency of 

BIT from the hands due to dermal exposure associated 

with the use of latex paint and non-paint liquid 

solutions containing BIT? 

2) Is the research likely to meet the applicable 

requirements of 40 CFR part 26, subparts K and L?