Document 6525109

10/03/03
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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
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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
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DRAFT - for discussion purpose only
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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.
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