Comparative Metabolism of Polychlorinated Biphenyls and Tissue Distribution of Persistent Metabolites in Rats, Hamsters, and Guinea Pigs

Abstract

ABSTRACT:The present study was performed to compare the metabolite profiles of polychlorinated biphenyls (PCBs) in the liver and serum of rats, hamsters, and guinea pigs after exposure to a PCB mixture, Kanechlor 500 (100 mg/kg, i.p.). The percentage of contribution of major PCB residues in the liver 5 days after exposure indicated that nonplanar PCBs with 2,4-or 2,3,4-chlorine substitution were more abundant in the liver in the order rats (43% of total PCBs) > hamsters (20%) > guinea pigs (11%), whereas coplanar PCBs with 4-, 3,4-, or 3,4,5-chlorine substitution were predominant in guinea pigs (61%), followed by hamsters and rats (both 26%). The hepatic concentrations of methylsulfonyl metabolites (MeSO 2 -CBs) were higher in the order guinea pigs > rats > hamsters. Whereas hamsters formed minute amounts of MeSO 2 -CBs from 2,5-dichlorosubstituted PCBs, guinea pigs formed higher levels of metaMeSO 2 -CBs derived from 2,3,6-trichloro-substituted PCBs. In contrast, the serum concentrations of phenolic PCBs were higher in the order hamsters > rats > guinea pigs. Metabolites were predominated by 4-OH-2,3,5,3,4-pentaCB (89% contribution) for rats, 3-OH-2,4,5,2,4-pentaCB (56%) for guinea pigs, and dihydroxylated metabolites (39%) for hamsters. The reduced elimination of coplanar PCBs and the specific distribution of MeSO 2 -and phenolic PCBs may have implications for the differences in sensitivity to PCB toxicity among rats, guinea pigs, and hamsters.

Methylsulfonyl polychlorinated biphenyls in fish from an electronic waste‐recycling site in South China: Levels, congener profiles, and chiral signatures

“…These results indicate the meta-position of the 2,5-chlorine-substituted phenyl ring, whereas the para-position of the 2,3,6-chlorinesubstituted phenyl ring in the molecule is the preferred site for methylsulfonylation, and fish may have substrate-specific phase II isozymes that catalyze the nucleophilic reaction of arene oxide intermediates with sulfhydryl groups. Feeding studies with rats exposed to PCBs also showed that 2,5-chlorine-substituted PCBs produced more meta-MeSO 2 -PCBs than paraMeSO 2 -PCBs, whereas 2,3,6-chlorine-substituted PCBs had the opposite metabolic deviation [18,31,32]. However, a different pattern for MeSO 2 -PCB 132, a congener with 2,3,6-chlorine substitution, was observed between the mud carp and northern snakehead.…”

A Novel Mechanism for Polychlorinated Biphenyl-Induced Decrease in Serum Thyroxine Level in Rats

“…The [ 125 I]T 4 , radiolabeled at the 5Ј-position of the outer ring, was obtained from PerkinElmer Life and Analytical Sciences (Waltham, MA). The KC500 used in the present experiments contains 2,2Ј,5,5Ј-tetrachlorobiphenyl (5.6% of total PCBs), 2,2Ј,3,5Ј,6-pentachlorobiphenyl (6.5%), 2,2Ј,4,5,5Ј-pentachlorobiphenyl (10%), 2,3,3Ј,4Ј,6-pentachlorobiphenyl (7.4%), 2,3Ј,4,4Ј,5-pentachlorobiphenyl (7.7%), 2,2Ј,3,4,4Ј,5Ј-hexachlorobiphenyl (5.6%), and 2,2Ј,4,4Ј,5,5Ј-hexachlorobiphenyl (5.4%) as major PCB congeners (Haraguchi et al, 2005). All the other chemicals used herein were obtained commercially in appropriate grades of purity.…”

Electrochemistry-Mass Spectrometry Unveils the Formation of Reactive Triclocarban Metabolites

“…These electrophilic species are known to interact with electrons of chlorinated aromatic compounds (Vrtacnik and Voda, 2003), yielding different hydroxylated and dechlorinated oxidation products (Liu et al, 2009). In vivo, dechlorination reactions have been described for several polychlorinated hydrocarbons, such as the polychlorinated biphenyls (Schnellmann et al, 1984;Ariyoshi et al, 1997;Haraguchi et al, 2005). The mechanism presumably proceeds via an epoxidation of TCC by P450 TCC or 3Ј,4Ј-epoxy TCC, followed by a dechlorination to 3,4-dichloro 4Ј-hydroxycarbanilide, as discussed by Ariyoshi et al (1997) for the metabolism of polychlorinated biphenyl 153.…”