Toxicoloal PATKOLCOY. 307_314 9o8 Pallulogists cunyugul Dy Inc SoCicry HToxicoiogc Review of Chronic Inhalation Studies with Mainstream Cigarette Smoke in Rats and Mice * CHRISTOPHER R. CoGGivs Lorillard Tobucco Co Greensboro, North Carolina 27408-7018 ABSRACT (Evic thc rcsults of a rcprcsentativ cxposcd tis pARS sclection of chrcnic inhalaticn studics with rals ard nastrcAt cizereite smorc desctibt innzaticn cxposucr ind 11t0pilha 021c? ciinaet tcConcc Fanou 4hon: Man' Lotze Smokc-induccd cpithelial IYper- Micics nosc-only eiDosuM systemis Mhener" ctners simoiy u5ed TGoc body chinther Aorg hyperplasla. and squamcus mctaplasia Kcnc icpcncd conducling Jicwavs IoS[ fudics; Incrcascd rophye macrophages associatcd with alvcolar Lung numoct? inui-_lyvcclz #ere Ccrisiontly claplasie adcrama aocnccaci statistically significant malignant lung tumots rcportcd the studics the incidetce nomas Wert lCrcRSE cpldemiological studics rofulu Ia GoCics FSu Tmola Adosune noine aprc Possiblc rcisons fo; tnis lack corclzion Arc Famnans ZIYEn toxicolagy: Cigarette Keuw'ard smcko; inhilalion rodent TcsDirlory INTRODUCTION [eria for inclusion of studies wcrc (a) such ovcrall duration consistent with the induction of cuncer; includ- Rats uscd routinely sludics of experi- nd mcc ing those studies where details pathology, sub carcinogenesis (12, 30, 33) , leading others (11) to Eros: menta sequent histopathology; both wcre lacking; and (6) &- consider   that these laboratory resuits the main tailed histopathological descrptions, no matter what the source of information that is used regulatory stan- duration of the cxperiment. for  potential   human dards The (unstated) exposures. presumption is that the rodent carcinogenic responses ac curately predict human carcinogenic responses (27). The present review was perforted to verify whether the mea- cigarette smoke in rodents reflects thc sured response t0 smokers (19, strong cpidemiological findings in human 31). This paper is critical review of the scientific literature relating t0 the pulmonary pathology of rats and mice ex- There posed by inhalation to cigarette large smo# published  literature this subject; amount selection of the major papers is pre - space rcasons only findings sented: the reviewed similar thosc in pa- thcte pcrs not so selected. Although ae numerous repons smoke inhalation  studies with  ther small animals hamsters (2-8 (e & and rabbits) and larget animals dogs these species will be considered in future Jnd pnmales) Rigorous criteria by which to evaluate Lhe results reviewS selected in accord with accepted standards of [Oxi- Wuceng cology: pathology, carcinogcnesis. and Reviews of the carlier literalure are available (32, 36) . the present review includes only the more recent work animal inhalation studies with cigarette smoke Cri- ]
Toxicoloal PATKOLCOY. cunyugul Dy Inc SoCicry 307_314 9o8 HToxicoiogc Pallulogists Review of Chronic Inhalation Studies with Mainstream Cigarette Smoke in Rats and Mice * CHRISTOPHER R. CoGGivs Lorillard Tobucco Co Greensboro, North Carolina 27408-7018 ABSRACT tis pARS (Evic thc rcsults of a rcprcsentativ sclection of chrcnic inhalaticn studics with rals ard cxposcd nastrcAt cizereite smorc desctibt innzaticn cxposucr ind 11t0pilha 021c? ciinaet tcConcc Fanou 4hon: Man' Micics nosc-only eiDosuM systemis Mhener" ctners simoiy u5ed Lotze TGoc body chinther Smokc-induccd cpithelial IYper- rophye hyperplasla. and squamcus mctaplasia Kcnc icpcncd conducling Jicwavs IoS[ fudics; Aorg Incrcascd numoct? inui-_lyvcclz macrophages #ere Ccrisiontly associatcd with alvcolar claplasie Lung adcrama aocnccaci nomas Wert rcportcd the studics statistically significant lCrcRSE the incidetce malignant lung tumots Ia GoCics FSu Tmola Adosune noine aprc rofulu cpldemiological studics Famnans Possiblc rcisons fo; tnis lack corclzion Arc ZIYEn Keuw'ard Cigarette smcko; inhilalion toxicolagy: rodent TcsDirlory INTRODUCTION uscd routinely [eria for inclusion of such studies wcrc (a) ovcrall duration consistent with the induction of cuncer; includ- ing those studies where details Eros: pathology, sub sequent histopathology; both wcre lacking; and (6) &- tailed histopathological descrptions, no matter what the duration of the cxperiment. Rats nd mcc sludics of experi- menta carcinogenesis (12, 30, 33) , leading others (11) to consider   that these laboratory resuits the main source of information that is used regulatory stan- dards for  potential   human exposures. The (unstated) presumption is that the rodent carcinogenic responses ac curately predict human carcinogenic responses (27). The present review was perforted to verify whether the mea- sured response t0 cigarette smoke in rodents reflects thc strong cpidemiological findings in human smokers (19, 31). This paper is critical review of the scientific literature relating t0 the pulmonary pathology of rats and mice ex- posed by inhalation to cigarette smo# There large amount published  literature this subject; space rcasons only selection of the major papers is pre - sented: the reviewed findings similar thosc in pa- pcrs not so selected. Although thcte ae numerous repons smoke inhalation  studies with  ther small animals (e & hamsters and rabbits) and larget animals (2-8 dogs Jnd pnmales) these species will be considered in future reviewS Rigorous criteria by which to evaluate Lhe results Wuceng selected in accord with accepted standards of [Oxi- cology: pathology, and carcinogcnesis. Reviews of the carlier literalure are available (32, 36) . the present review includes only the more recent work animal inhalation studies with cigarette smoke Cri- ]