10/03/03 FRI 0 7 : 3 2 FAX IHOOl Facsimile Cover Sheet To: R. Solana/J. Bugg Company: Philip Morris USA Inc. Phone: 804-2744617 Fax: 804-274-7182 From: Richard Izac, Ph.D. Company: Philip Morris USA Inc. Phone: 804-274-3220 Fax: 804-274-4167 Date: 3 October 2003 Pages including this 3 cover page: Comments: RickAJoy, Kevin Osborne has not responded to our request for review as yet. Everyone else has reviewed the abstract and a few minor changes were made. Please note that the submission deadline is today. Richard CONFIDENTIALITY NOTICE: This facsimile transmission (and/or the documents accompanying it) may contain confidential information belonging to the sender. T h e information is intended only for the use of t h e addressee or entity named above. If you are not the intended recipient, you a r e hereby notified t h a t any disclosure, copying, distribution or the taking of any action in reliance of the contents of this information is strictly prohibited by law. If you have received this transmission in error, please immediately notify us by telephone to arrange for the return of these documents. http://legacy.library.ucsf.edu/tid/icc95g00/pdf '3009172024 10/03/03 FRI 07:33 FAX 11 September2003 % 002 MIZ WSAMRB Manuscript Review Form WSA/MRB MANUSCRIPT REVIEW FORM WSA Project Number: 01222 Title: ACUTE RESPIRATORY RESPONSES IN MICE EXPOSED TO POLYMEP, AND TOBACCO COMBUSTION PRODUCTS USING A DIN FURNACE Author(s): R Lemus1. KM Lee2, MS Werleyi. "Philip Morris USA, Richmond, VA, USA; iBattelle Tox NW, Richland, WA, USA. Indicate non PM affiliation and underline coordinating author | | Manuscript Journal/book title Presentation Society of Toxicology, Baltimore, MD, March 2004 Meeting name, location and date IE] Abstract • • Poster Full manuscript planned Submission Deadline: 10/03/2003 • Presentation • No full manuscript planned Anticipated WSA/MRB review date: Research Results Discussion held Date: 07/14/2003 Peer reviewers identified Names: Chuck Gaworski and Willie McKinney Required approvals identified Names: Ken Podraza, Rick Solana, Roger Walk • Persons for additional input Names: Ed Carmines • Persons to keep informed Names: Reviewing MRB: M PM USA MRB Patent Status: PMI MRB To be filled by Manager/Director [in consultation with author(s), and/or the Law Department, if necessary] 0 No interest • ryC L —' Reviewed by Manager/Director D Reviewedb Law Need to file before release v r~[Y He viewed oy ui rector Wy ckJ*±.&ttN A&L, /, management, Q Patent application filed k i<\ "T^so^rcj^ ^ r^/ Reviewed by Scientific '—' Communication i—I *—J • J Approved by Vice President Date: Date: Date: ?A«/o Date: r/u/>j Date: DRAFT - for discussion purpose only http://legacy.library.ucsf.edu/tid/icc95g00/pdf '3009172025 10/03/03 @003 FRI 0 7 : 3 3 FAX DRAFT as 10/01/03 ACUTE RESPONSES IN MICE EXPOSED TO POLYMER AND TOBACCO COMBUSTION PRODUCTS USING A DIN FURNACE. R Lemus\ KM Lee2, MS Werley1. Philip Morris USA, Richmond, VA, USA; 2Battelle Tox NW, Richland, WA, USA. The acute toxicity of combustion products (CP) from polymers possibly found in manufacturing parts was evaluated using a previously validated system consisting of a Deutsches Institut fur Normung (DIN) 53-436 furnace connected to an animal exposure unit. Polymers [wool, Nylon 6, 6/6, and 12, acrylonitrile-butadiene (AB), or AB-styrene] were individually mixed with tobacco blend (TB) at 0, 3, 10, &. 30% (w/w). Male Swiss Webster mice were exposed to 150 /xg of total particulate matter (TPM)/L for 30-min by nose-only inhalation to CP generated at ~750°C. CO/C0 2 , NCVNOx, TPM, hydrogen cyanide (HCN), formaldehyde, acetaldehyde, acrolein, and nicotine were measured in the test atmosphere. Respiratory function (Buxco Biosystems) during exposure, postexposure blood cyanide (CN~) and carboxyhemoglobin (COHb) levels, respiratory tract histopathology (1 & 7 days postexposure), alveolar macrophages (AM), LDH and protein changes in BAL fluid (Day 1) were evaluated. Experimental replacement of tobacco mass with polymer generally increased TPM, HCN, some aldehydes and CO, while nicotine was decreased. Body weights were overall comparable among polymer, TB and sham groups. Postexposure COHb levels were not different among all exposed groups. Blood CN~ levels were below ELOQ (0.2 /xg/g) for all groups. More respiratory irritation was observed in the groups with 30% Nylon 6/6 or AB based on delayed postexposure recovery of depressed respiratory function. Day-1 postexposure lesions in nasoturbinates, lateral wall, and maxilloturbinates in exposed groups were minimal to moderate and limited to the anterior nose area. Necrosis was observed with some of the 30% groups compared to TB or lower polymer ratio groups, but all lesions were resolved by day 7. The only change in BAL parameters was a slight decrease in the ratio of resting/activated AM in the exposed groups compared to control. These results show that nose lesions were the most distinct acute toxicity related to CP from polymer-TB mixtures and from the polymers tested Nylon 6/6 and AB were potentially more toxic. http://legacy.library.ucsf.edu/tid/icc95g00/pdf '3009172026