title: A Comparison of Rodent and Nonrodent Laryngeal and Tracheal Bifurcation Sensitivities in Inhalation Toxicity Studies and Their Relevance for Human Exposure.
abstract: In inhalation toxicity studies, drug-induced lesions are frequently reported in the larynx and sometimes at the tracheal bifurcation (carina) in the rat, but less so in the dog or monkey, bringing into question the relevance of these rodent findings for humans. The rat larynx is widely considered to be more sensitive than that of the dog and monkey in its response to inhaled xenobiotics, although we could find no published data to support this. In this review, data from 52 inhalation studies involving rodent and nonrodent species were collated and reviewed. These data showed that the rodent larynx, and to a lesser extent the carina, was far more commonly affected by treatment than those of the nonrodent. This review indicates the greater susceptibility of the rodent larynx and carina and emphasizes their lack of relevance for man. Observations and data suggest that the human larynx is much closer to the beagle dog and cynomolgus monkey in its response to inhaled xenobiotics and that greater clinical relevance should be placed on any specific findings in these animal models.
authors.affiliation: 1 Huntingdon Life Sciences, Cambridgeshire, UK.
authors.forename: Vasanthi
authors.initials: V
authors.lastname: Mowat
authors.affiliation: 2 DA Nonclinical Safety Ltd., Godmanchester, Cambridgeshire, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Alexander
authors.affiliation: 3 ToxPath Consultancy Ltd, Stradbroke, Suffolk, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Pilling
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004285:Dogs; D006965:Hyperplasia; D007830:Larynx / Q000187:drug effects / Q000473:pathology*; D008679:Metaplasia; D051379:Mice; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology*; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods*; D014132:Trachea / Q000187:drug effects / Q000473:pathology*; D057170:Translational Research, Biomedical
keywords: comparison; dog; inhalation toxicity; larynx; nonhuman primate; rodent; tracheal bifurcation