Relevance of mouse lung tumors to human risk assessment.
J Toxicol Environ Health B Crit Rev
; 23(5): 214-241, 2020 07 03.
Article
em En
| MEDLINE
| ID: mdl-32452303
ABSTRACT
Mouse lung is a common site for chemical tumorigenicity, but the relevance to human risk remains debated. Long-term bioassays need to be assessed for appropriateness of the dose, neither exceeding Maximum Tolerated Dose (MTD) nor Kinetically based Maximum Dose (KMD). An example of the KMD issue is 1,3-dichloropropene (1,3-D), which only produced an increased incidence of lung tumors at a dose exceeding the KMD. In addition, since mouse lung tumors are common (>1% incidence), the appropriate statistical significance is p < .01. Numerous differences exist for mouse lung and tumors compared to humans, including anatomy, respiratory rate, metabolism, tumor histogenesis, and metastatic frequency. The recent demonstration of the critical role of mouse lung specific Cyp2 F2 metabolism in mouse lung carcinogenicity including styrene or fluensulfone indicates that this tumor response is not qualitatively or quantitatively relevant to humans. For non-DNA reactive and non-mutagenic carcinogens, the mode of action involves direct mitogenicity such as for isoniazid, styrene, fluensulfone, permethrin or cytotoxicity with regeneration such as for naphthalene. However, the possibility of mixed mitogenic and cytotoxic modes of action cannot always be excluded. The numerous differences between mouse and human, combined with epidemiologic evidence of no increased cancer risk for several of these chemicals make the relevance of mouse lung tumors for human cancer risk dubious.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Modelos Animais de Doenças
/
Neoplasias Pulmonares
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Toxicol Environ Health B Crit Rev
Assunto da revista:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos