### 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 4test rule. Please add each reviewas a separate document to the docket forthat 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



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### OCCUPATIONAL SAFETY AND HEALTHADMINISTRATION 200 CONSTITUTIONAVENUE, 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: Reviewof Percutaneous Absorption and Cutaneous Disposition of [14C]- Dicyclopentadiene In Vitro in Human Skin (77-73-6) Areviewofthe 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 TSCASection 4Test Rule requiring in vitro dermal absorption rate determinations for several chemicals used in theworkplace (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 TSCASection 4Test Rule (section 799.5115(h)) . Skin discs that had been obtained by cutting human cadaver abdominal skin with a dermatome to a thickness of 200to 500 gm were mounted in a static diffusion cell using 0 .9 % saline as receptor fluid

. The temperature ofthe skin could not be maintained at 32°Cfor all skin disks. Most ofthe skin temperatures ranged from32 7L 1°C . It was reported that these small differences did not appear to change thekinetics of absorption significantly. Radiolabeled [14C] dicyclopentadiene in isopropyl myristate at a target concentration of25 mg/mL was applied over the epidermal surface under infinite dose and occluded conditions. There was no explanation provided as to why the dicyclopentadienewas 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 fromthe 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 

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### 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 ofdicyclopentadiene using six skin experiments representing three human subjects. Themean Kp was reported to be 0 .0000215 cm/h (SD=0 .00000480) . There was no loss in skin integrityover the course of the testing. Short-termdermal 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 approximatebriefskin contact rather than the more prolonged exposures often necessary to achieve steady state. Six skin experiments were carried out for durations of 10 and 60minutes, respectively. The short-termpenetration 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 theTSCA Section 4 Test Rule. The data presented in the studyreport appear to be reliable and areuseful for estimating the amount of chemical absorbed across the skin fromdermal contact with dicyclopentadiene. A completed Study Report ReviewFormis attached.

### Review of TSCASection 4 Fin al Study Report CITBProject 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: InVitro Technologies, Inc Test Standard: 799.5115(h) Date Study Received by EPA : Date Study Dueto EPA : NA Special Instructions (e.g., regarding approved protocol modifications, etc .) : 

### Part I . Test Report and Study Conduct Enter one ofthe following codes into each ofthe checkboxes 1 through 13: Agree [A] . Disag ee [D] . Not Applicable [NA], or Cannot Determine fCl andaddcomment below, as needed [ D] 1 . The study report indicates evidence of gross, unauthorized or undocumented deviation from the EPAtest 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 oftest standard or testing protocol (CITB PM describe or attach) were notfollowed or are inadequately documented. [ D] 4 . There is evidence that laboratory Standard Operating Procedures (SOPs) were inadequately followed. [ D] 5. The Statement of QualityAssurance (QA) inspections, their dates, and findings were missing or not signed. There is evidence that QAprocedures may be inadequate. [ D] 6 . There is evidence that Good Laboratory Practice Standards (GLPS) were inadequately followed. [D] 7. Thetest, control, or reference substances aredifferent from that specified in the section 4test rule or EnforceableConsent Agreement (ECA) . [NA ] 8

. Animal identification is inadequate or unclear; use ofunhealthy animals or otherfactors (e.g., deviations from

temperature, lighting, dosing) are apparent . [D] 9 . The study report inadequately describes the study method. REVIEW

OF TSCA SECTION4FINAL STUDY REPORT March 2006Version[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 ofstudyconducted), 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 applyto this reviewand add comments below as Wropriate Part A . To be fi lled out by Reviewer Study Conduct 1 . The studywas well-conducted. [ ] 2 . The study was generallywell-conducted,with some minor [ ] deficiencies (list in notes below) . 3. The studyconductwas 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 . Ifrepeated, 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 ofthe skin could not be maintained at 32°Cfor all skin disks. Most of the skin temperatures ranged from32 ± 1°C . It was reported that these small differences did not appear to change the kinetics of absorption significantly. 

### Themajor problem

withthis study was that there was no explanation ofwhythe 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 fromthis study are notuseful . 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 SECTION4 FINAL STUDY REPORT 2 March 2006VersionStudyAcceptability 3. The studyis acceptable . 4 . The study may not be acceptable (provide rationale in memo to CITB chief) .

REVIEW

OF TSCA SECTION4FINAL 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)