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Three-Dimensional Mapping of the Lesions Induced by β-β'-Iminodiproprionitrile, Methyl Iodide and Methyl Methacrylate in the Rat Nasal Cavity

School of Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, United Kingdom

John R. Foster

AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom

John A. Nash

Syngenta CTL, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, United Kingdom

Celia J. Reed

School of Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, United Kingdom, c.j.reed{at}livjm.ac.uk

The nasal cavity is an important target organ for toxicity, and many chemicals induce site-specific lesions in this region. The factors responsible for this site-selectivity have not been unequivocally identified, but probably include regional dosimetry and bioactivation. The purpose of this study was to map, in 3 dimensions, the lesions induced by β-β'-iminodipropionitrile (IDPN), methyl iodide (MeI) and methyl methacrylate (MMA) in the rat nasal cavity. Animals were administered IDPN (150 mg/kg, IP) or exposed via inhalation to MeI (100 ppm, 2 hours) or MMA (400 ppm, 4 hours) and sacrificed after 24 hours. Heads were decalcified, step-sections (1 every 400 µm) cut and stained, and the severity of the epithelial lesion graded as mild (vacuolation and pyknosis), moderate (undulation and mild stripping), or marked (complete stripping). These grades were mapped onto a 3D-model of a rat nasal cavity using the KS400 imaging system (Imaging Associates, Thame, UK). Despite the different routes of exposure the lesions induced by the 3 compounds had very similar distributions, predominantly affecting the dorsal-medial aspects of the ethmoturbinates and, in the case of MMA, the organ of Rodolfo Masera. These results suggest that, with these chemicals, local bioactivation plays a more important role than dosimetry in determining lesion distribution.

Key Words: 3D mapping • methyl iodide • methyl methacrylate • β-β'-iminodipropionitrile • rat • nasal cavity.

Toxicologic Pathology, Vol. 31, No. 3, 340-347 (2003)
DOI: 10.1080/01926230390204388


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