US EPA

2130072 

Technical Report 

Synthesis And Identification Of Dihydrodiol Metabolites Of Benzo(b)fluoranthene And Benzo(j)fluoranthene 

Amin, S; Hussain, N; Huie, K; Balanikas, G; Rice, JE; Lavoie, EJ; Hecht, SS 

1985 

NIOSH/00154564 

Mechanisms 

Mechanisms 

The dihydrodiol metabolities of benzo(b)fluoranthene (205992) and benzo(j)fluoranthene (205823) were synthesized and identified. Metabolism experiments were conducted via the incubation of either benzo(b)fluoranthene or benzo(j)fluoranthene with cofactors and a supernatant obtained from the livers of F344-rats treated with 500 milligrams per kilogram of Aroclor-1254 (11097691) 5 days prior to sacrifice. The synthesis of 1,2-dihydro-1,2-dihydroxybenzo(b)fluoranthene began with methyl-11H-benzo(b)fluorene-11-carboxylate which was converted in high yield to a carboxyethyl derivative. The synthesis of 11,12-dihydro-11,12-dihydroxybenzo(b)fluoranthene began with 2-methylfluoranthene. In order to synthesize 2,3-dihydro-2,3-dihydroxybenzo(j)fluoranthene, methyl-11H-benzo(a)fluorene-11-carboxylate was converted to the corresponding diester with hydrolysis and decarboxylation yielding 11H-benzo(a)fluorene-11-propionic-acid, which was converted to its acid chloride and cyclized to the critical ketone intermediate. Other metabolites detected included 9,10-dihydro-9,10-dihydroxybenzo(j)fluoranthene and 4,5-dihydro-4,5-dihydroxybenzo(j)fluoranthene. The authors conclude that the key intermediate for the synthesis of the latter substance is 4-oxo-4,5,6,6a-tetrahydrobenzo(j)fluoranthene.