Review of Histopathological Changes in the Respiratory Tract of Rat Induced by Inhalation of the Mainstream Smoke of Standard Reference Cigarette 1R4F
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1 Review of Histopathological Changes in the Respiratory Tract of Rat Induced by Inhalation of the Mainstream Smoke of Standard Reference Cigarette 1R4F A. Teredesai LSRO Meeting, Dec., 13, 2001 Slide 1 INBIFO/CRC
2 Outline Goal Anatomy and Histology Histotechnical Work Results INBIFO Literature LSRO Meeting Dec., 13, 2001 Slide 2 INBIFO/CRC
3 Goal Overview of the methods and procedures regarding the histotechnical work and histopathological evaluation as well as an overview of the histopathological changes following subchronic exposure to cigarette smoke LSRO Meeting Dec., 13, 2001 Slide 3 INBIFO/CRC
4 Rationales Inhalation studies, special emphasis on the histopathology of the target organs, i.e., respiratory tract organs Regulatory guidelines (OECD, EPA) Human relevance - association of tobacco smoke inhalation with laryngeal and bronchial cancers in humans LSRO Meeting Dec., 13, 2001 Slide 4 INBIFO/CRC
5 Rat Respiratory Tract LSRO Meeting Dec., 13, 2001 Slide 5 INBIFO/CRC
6 Nose Anatomy vestibule cartilagenous septum that divides the nasal cavity into 2 halves dorsal, middle, and ventral meatuses turbinates or conchae Histology 3 basic epithelial types squamous epithelium respiratory epithelium olfactory epithelium LSRO Meeting Dec., 13, 2001 Slide 6 INBIFO/CRC
7 Anatomy Larynx consists of 5 cartilages epiglottis thyroid cricoid arytenoid u-shaped LSRO Meeting Dec., 13, 2001 Slide 7 INBIFO/CRC
8 Histology 4 types of epithelium squamous respiratory pseudostratified cuboidal squamoid LSRO Meeting Dec., 13, 2001 Slide 8 INBIFO/CRC
9 Trachea Anatomy connects the larynx with the lungs 15 incomplete cartilaginous rings dorsally interconnected by ligaments tracheal bifurcation at the level of 6th rib into a smaller left and larger right extrapulmonary main bronchus Histology pseudostratified respiratory epithelium ciliated cells serous cells mucous (goblet) cells basal cells LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC
10 Lung Man Rat Left lung 2 lobes 10 segmental bronchi 1 lobe 12 to 13 segmental bronchi Right lung 3 lobes 10 segmental bronchi 4 lobes 14 to 15 segmental bronchi few subsegmental bronchi LSRO Meeting Dec., 13, 2001 Slide 10 INBIFO/CRC
11 Cells of the Pulmonary Parenchyma Alveolar type I epithelial cells Alveolar type II epithelial cells Pulmonary endothelial cells Interstitial cells Macrophages LSRO Meeting Dec., 13, 2001 Slide 11 INBIFO/CRC
12 Tissue Sectioning Method Sections at pre-established levels nose: Young (1981) larynx: Lewis (1980) trachea: INBIFO lung: Lamb and Reid (1969) Purpose adequate morphological evaluation uniform histological examination ensure correct comparison within and among studies LSRO Meeting Dec., 13, 2001 Slide 12 INBIFO/CRC
13 Histopathological Evaluation Recording of findings in a consistent manner Use of standardized dictionary of criteria Consistent scoring system Evaluation in a blinded fashion, i.e., without the knowledge of treatment groups LSRO Meeting Dec., 13, 2001 Slide 13 INBIFO/CRC
14 Results INBIFO Study reference subchronic cigarette smoke inhalation studies Experimental condition nose only mode TPM concentration range 40 to 200 µg TPM/l exposure duration: 6 h/d, 7 d/week for 21 or 90 days LSRO Meeting Dec., 13, 2001 Slide 14 INBIFO/CRC
15 Histopathology Nose respiratory epithelium (levels 1 and 2) reserve cell hyperplasia squamous metaplasia goblet cell hypertrophy/hyperplasia olfactory epithelium (levels 2, 3, and 4) ulceration atrophy squamous metaplasia LSRO Meeting Dec., 13, 2001 Slide 15 INBIFO/CRC
16 Nasal Septum, Level 1, Normal LSRO Meeting Dec., 13, 2001 Slide 16 INBIFO/CRC
17 Nasal Septum, Level 1, Goblet Cell Hypertrophy/Hyperplasia LSRO Meeting Dec., 13, 2001 Slide 17 INBIFO/CRC
18 Nasal Septum, Level 1, Goblet Cell Hypertrophy/Hyperplasia, AB-PAS Stain LSRO Meeting Dec., 13, 2001 Slide 18 INBIFO/CRC
19 Dorsolateral Wall, Nose Level 1, Normal LSRO Meeting Dec., 13, 2001 Slide 19 INBIFO/CRC
20 Dorsolateral Wall, Nose Level 1, Squamous Metaplasia LSRO Meeting Dec., 13, 2001 Slide 20 INBIFO/CRC
21 Maxilloturbinate Tip, Nose Level 1, Normal LSRO Meeting Dec., 13, 2001 Slide 21 INBIFO/CRC
22 Maxilloturbinate Tip, Nose Level 1, Hyperplasia INBIFO/CRC CONFIDENTIAL LSRO Meeting Dec., 13, 2001 Slide 22 INBIFO/CRC
23 Dorsomedial Region, Nose Level 2, Normal Olfactory Epithelium (low power) LSRO Meeting Dec., 13, 2001 Slide 23 INBIFO/CRC
24 Dorsomedial Region, Nose Level 2, Normal Olfactory Epithelium (high power) INBIFO/CRC CONFIDENTIAL LSRO Meeting Dec., 13, 2001 Slide 24 INBIFO/CRC
25 Dorsomedial Region, Nose Level 2, Olfactory Epithelium, Atrophy LSRO Meeting Dec., 13, 2001 Slide 25 INBIFO/CRC
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