April 22, 2009 

Note to Pam Mosley: 

RE : 3 Reviews of dermal absorption studies to add to Docket No. EPA-HQ-OPPT2003-0006 

Attached are 3 reviews of dermal absorption rate studies conducted to comply with a 

TSCA section 4 test rule. Please add each review as a separate document to the docket 

for that rule, EPA-HQ-OPPT-2003-0006. Following is a description of each review: 

1 . Review of In Vitro Dermal Absorption Rate Testing for Dicyclopentadiene (77-73-6). 

2. Review of In Vitro Dermal Absorption Rate Testing for Diphenylamine (122-39-4) . 

3 . Review of In Vitro Dermal Absorption Rate Testing for Diacetone Alcohol (123-42-

2). 

Catherine Roman 

Project Manager, CITB, CCD, OPPT 

202-564-8172 

I Illi' IIIIi II`!i II !~ II'! ~I~I 

a o u ~ o 0 0 A ,. 

CONTAINS NO CB 

:5ryM 
OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION 

200 CONSTITUTION AVENUE, NW 

WASHINGTON D.C. 20210 

October 14, 2008 

TO: Catherine Roman 

. Chemical Information and Testing Branch (7405M) 

Office of Pollution, Prevention and Toxics 

US EPA 

FROM: Loretta Schuman 

" Directorate of Standards and Guidance 

OSHA 

SUBJECT: Review of Percutaneous Absorption and Cutaneous Disposition of [14C]-

Dicyclopentadiene In Vitro in Human Skin (77-73-6) 

A review of the study report entitled "Percutaneous Absorption and Cutaneous Disposition of 

[14C]-Dicyclopentadiene In Vitro in Human Skin" is provided below. The report was submitted 

by the American Chemistry Council, in response to the TSCA Section 4 Test Rule requiring in 

vitro dermal absorption rate determinations for several chemicals used in the workplace (69 FR 

22402,4/26/2004) . 

Study Summary 

In vitro dermal absorption testing of dicyclopentadiene was undertaken at In Vitro 

Technologies, Inc. using a test standard specified in the TSCA Section 4 Test Rule (section 

799 .5115(h)). Skin discs that had been obtained by cutting human cadaver abdominal skin with a 

dermatome to a thickness of 200 to 500 gm were mounted in a static diffusion cell using 0.9 % 

saline as receptor fluid. The temperature of the skin could not be maintained at 32°C for all skin 

disks. Most of the skin temperatures ranged from 32 7L 1°C. It was reported that these small 

differences did not appear to change the kinetics of absorption significantly. Radiolabeled [14C] 

dicyclopentadiene in isopropyl myristate at a target concentration of 25 mg/mL was applied over 

the epidermal surface under infinite dose and occluded conditions . There was no explanation 

provided as to why the dicyclopentadiene was in isopropyl myristate rather than applied neat. It 

was reported that the amount of dicyclopentadiene dosed onto the skin discs appeared to simulate 

an infinite dose under the experimental conditions used. This was inferred from the observation 

that the total amount absorbed was less than 5% even after exposure for 24 hours and that the 

amount of dicyclopentadiene absorbed into the receptor fluid reached a steady state. Receptor 

CONTAINS NO C 

-319669 
fluid was sampled for radioactivity at regular intervals for up to 24 hours . Skin membrane 

integrity was evaluated by measuring the absorption of tritiated water before and after testing. 

The permeability coefficient (Kp) was calculated from the steady state flux of dicyclopentadiene 

using six skin experiments representing three human subjects. The mean Kp was reported to be 

0.0000215 cm/h (SD = 0.00000480). There was no loss in skin integrity over the course of the 

testing. 

Short-term dermal penetration experiments with [14C] dicyclopentadiene in isopropyl 

myristate using the in vitro diffusion cell method were also conducted under finite dosing at the 

target concentration of 25 mg/mL (i .e . 200 ~tL) and occluded conditions. These tests were 

intended to approximate brief skin contact rather than the more prolonged exposures often 

necessary to achieve steady state. Six skin experiments were carried out for durations of 10 and 

60 minutes, respectively . The short-term penetration rates were calculated to be 0.185 and 0.162 

gg/cm2/h for the 10- and 60- minute time periods, respectively under this experimental protocol . 

This study complies with the test standard required by the TSCA Section 4 Test Rule. 

The data presented in the study report appear to be reliable and are useful for estimating the 

amount of chemical absorbed across the skin from dermal contact with dicyclopentadiene. A 

completed Study Report Review Form is attached. 
Review of TSCA Section 4 Final Study Report 

CITB Project Manager: Catherine Roman 

Chemical Name: Dicyclopentadiene 

CAS Registry Number: 77-73-6 

Report Title: Percutaneous Absorption and Cutaneous Disposition of [14C]-

Dicyclopentadiene In Vitro in Human Skin 

Test Sponsor: American Chemistry Council 

Testing Lab: In Vitro Technologies, Inc 

Test Standard : 799.5115(h) 

Date Study Received by EPA: Date Study Due to EPA: NA 

Special Instructions (e .g ., regarding approved protocol modifications, etc.) : 

Part I. Test Report and Study Conduct 

Enter one of the following codes into each of the checkboxes 1 through 13 : Agree [A]. Disag ee [D]. Not 

Applicable [NA], or Cannot Determine fCl and add comment below, as needed 

[ D ] 1 . The study report indicates evidence of gross, unauthorized or undocumented deviation from 

the EPA test standard requirements, including "shall," "must," or "will" violations . List 

significant test standard deviations and "shall," "must," or "will" violations in comments below. 

[A ] 2. The study report indicates evidence of deviations from the "should" statements in the study 

protocol that may have a bearing on the study conclusions. List these in comments below. 

[NA ] 3. Approved modifications of test standard or testing protocol (CITB PM describe or attach) were 

not followed or are inadequately documented . 

[ D ] 4. There is evidence that laboratory Standard Operating Procedures (SOPs) were inadequately 

followed. 

[ D ] 5 . The Statement of Quality Assurance (QA) inspections, their dates, and findings were missing or 

not signed. There is evidence that QA procedures may be inadequate . 

[ D] 6. There is evidence that Good Laboratory Practice Standards (GLPS) were inadequately followed. 

[D] 7. The test, control, or reference substances are different from that specified in the section 4 test 

rule or Enforceable Consent Agreement (ECA). 

[NA ] 8. Animal identification is inadequate or unclear; use of unhealthy animals or other factors (e.g ., 

deviations from temperature, lighting, dosing) are apparent . 

[D] 9. The study report inadequately describes the study method. 

REVIEW OF TSCA SECTION 4 FINAL STUDY REPORT 

March 2006 Version 
[D] 10. The study report inadequately describes the test system. 

[ D] 11 . The study report inadequately describes the dosage information. 

[ D ] 12 . The study report does not accurately reflect the individual animal data (or that of other discrete 

observations pertinent to the type of study conducted), or individual data were not provided. 

[ D] 13 . The study report inadequately describes the calculations, interpolations, data transformations, 

statistical analyses, or modeling parameters used. 

Part II. Conclusions 

Place a check mark beside the suxnmary statement(s) that apply to this review and add comments below as 

Wropriate 

Part A. To be filled out by Reviewer 

Study Conduct 1 . The study was well-conducted. [ ] 

2. The study was generally well-conducted, with some minor [ ] 

deficiencies (list in notes below) . 

3. The study conduct was significantly deficient or questionable, (give [XI 

reasons in notes below) . 

Data Reliability 4. The study results are precise and accurate . [ ] 

5. Appropriate methods were used to determine [XI 

statistical significance . 

6. If repeated, the test results would be expected to be the [ X ] 

same. 

Data Utility 7. The data are useful for risk assessment for the endpoint tested. [ ] 

8. The data are useful for some other purpose (e .g., dose-setting). [ ] 

9. The data are not useful for any purpose (describe in notes below) . [X] 

Reviewer Comments (continue on separate page, if needed) : The temperature of the skin could not 

be maintained at 32°C for all skin disks. Most of the skin temperatures ranged from 32 ± 

1°C. It was reported that these small differences did not appear to change the kinetics of 

absorption significantly. 

The major problem with this study was that there was no explanation of why the 

dicyclopentadiene was diluted in isopropyl myristate rather than applied neat. If there is 

a good explanation, then the data are useful . If there is no explanation, or no reason, and 

the substance should have been applied neat, then the data from this study are not useful. 

Reviewer Name/Title/Branch/Division/Office: Loretta Schuman, Directorate of Standards and 

Guidance, OSHA 

Reviewer Signature: 

Part B. To be filled out by CITB PM 

Tiered Testing Decision 1 . The tiered testing trigger was met, additional testing is indicated. [ ] 

(when applicable) 2. The trigger for additional (tiered) testing was not met. [ ] 

REVIEW OF TSCA SECTION 4 FINAL STUDY REPORT 2 

March 2006 Version 
Study Acceptability 3 . The study is acceptable . 

4. The study may not be acceptable 

(provide rationale in memo to CITB chief) . 

REVIEW OF TSCA SECTION 4 FINAL STUDY REPORT 

March 2006 Version 
"Gulledge, William" 

<William Gulledge@america 

nchemistry .com> 

12/05/2008 11 :24 AM 

Catherine: 

To Catherine Roman/DC/USEPA/US@EPA 

cc 

bcc 

Subject RE: Dermal absorption test of Dicyclopentadiene 

We went back to the 2005 study records to address your question, but 

after receiving the information, I remembered the discussion with the 

lab back in 2005 . We could not test DCPD neat because at room 

temperature, DCPD is a solid . According to the test rule we followed 

during the study, solids are to be dissolved in water or in isopropyl 

myristate if solubility is a concern . Dicyclopentadiene was dissolved 

in isopropyl myristate to form a solution of sufficient concentration so 

as to achieve steady-state absorption . I don't think that complete 

explanation was in the study report, but we believe the procedure was 

correct . Thanks . 

Bill Gulledge 

American Chemistry Council 

1300 Wilson Blvd . 

Arlington, VA 22209 

(703) 741-5613 

-----Original Message----- 

From : Roman .Catherine@epamail .epa .gov 

[mailto :Roman .Catherine@epamail .epa .gov] 

Sent : Thursday, November 13, 2008 2 :28 PM 

To : Gulledge, William 

Cc : Mattheisen .Mike@epamail .epa .gov 

Subject : Dermal absorption test of Dicyclopentadiene 

On June 13, 2006, you submitted a final report for the dermal absorption 

rate testing of dicyclopentadiene (CAS # 77-73-6) on behalf of the 

Dicyclopentadiene Dermal Absorption Task Group in response to a TSCA 

section 4 test rule . The rule was "In Vitro Dermal Absorption Rate 

Testing of Certain Chemicals of Interest to the Occupational Safety and 

Health Administration" (60 FR 22402, April 26, 2004) . 

Recently I received a review of that study and the reviewer had a 

concern that I hope you can address . The reviewer asked "why was the 

test substance, dicyclopentadiene, diluted with isopropyl myristate 

instead of applied neat to the skin samples in the experiment?" 

Although the test standard may allow for what was done per 799 .5115 

(h)(5)(vi), the report does not provide a reason . I have attached 

copies of the reviews and a pdf copy of the rule which contains the test 

standard, with the cited paragraph (799 .5115(h)(5)(vi)) on page 22439 . 

Please respond to me at roman.catherine@epa .gov . 

(See attached file : dicyclopentadiene test review 101408 .doc) (See 

attached file : Review of TSCA Section 4 Final Study Report 

dicyclopentadiene .doc) 

(See attached file : EPA-HQ-OPPT-2003-0006-0001 .pdf) 
Catherine Roman 

USEPA 

1200 Pennsylvania Ave ., NW, 7405M 

Washington, DC 20460 

(202) 564-8172 

(202) 564-4765 (Fax)