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Toxicol In Vitro ; 59: 281-291, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31051210

RESUMO

Nitrogen-containing polycyclic aromatic hydrocarbons (PANHs or azaarenes) are compounds structurally similar to PAHs (carbon substituted by a nitrogen) reported to occur at low levels in food. Although limited, literature may suggest possible higher toxicity than for PAHs. Using a battery of in vitro assays, the toxicological properties of uncharacterized PANHs of increasing ring number were compared to those of characterized structural PAH analogues. The parameters measured covered key events relevant to the AOP developed for Benzo(a)pyrene: AhR activation, mutagenicity and DNA-damage with and without metabolic activation and endocrine receptors activation/inhibition. There was a strong correlation between the chemical structure and the biological activities of the compounds. AhR activation was the most sensitive parameter with a direct correlation between potency and ring number. The most potent genotoxic chemicals were found amongst the ones with the highest number of ring, and under metabolic activation. Such an approach allowed designing sub-groups based on biological properties in addition to structural similarities. Within a sub-group, toxicological data of tested chemicals may be used to characterize hazard of biologically similar but toxicologically uncharacterized substances. This indicates that in addition to structural properties, in vitro biological data may be useful to conduct read-across.


Assuntos
Mutagênicos/toxicidade , Nitrogênio/química , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Bioensaio , Linhagem Celular Tumoral , Dano ao DNA , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Humanos , Testes de Mutagenicidade , Mutagênicos/química , Hidrocarbonetos Policíclicos Aromáticos/química , Receptores Androgênicos/metabolismo , Salmonella/efeitos dos fármacos , Salmonella/genética
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