Foetal uptake of coplanar polychlorinated biphenyl (PCB) congeners in mice.
Earlier studies (Darnerud et al. 1986) have shown that the Ah-receptor binding polychlorinated biphenyl (PCB) congener 3,3',4,4'-tetrachlorobiphenyl (IUPAC number CB-77) accumulated as hydroxy and methylsulphone metabolites in late gestational mice foetuses. In the present paper the foetal accumulation potential in mice of other dioxin-like PCB congeners was studied: 3,3',4,4',5-pentachlorobiphenyl, 3,3',4,4',5,5'-hexachlorobiphenyl and 2,3,3',4,4'-pentachlorobiphenyl (IUPAC numbers CB-126, CB-169, CB-105, to some extent dioxin-like) were compared to results of CB-77 (all congeners 14C-labelled and in equimolar doses (2.0 mumol/kg body wt.)). CB-77 resulted in the comparatively strongest foetal 14C-accumulation, when measured in plasma or whole body homogenate four days after administration (day 17 of pregnancy); the plasma 14C-values (calculated as pmol/g wet wt.) were 760, 130, 60 and 40 for CB-77, -126, 105 and -169, respectively, and the CB-77 derived radioactivity in the foetal compartment was 3.6% of administered dose (i.e. a considerable portion of the remaining maternal body radioactivity). Thin-layer chromatography (TLC) results, suggesting extensive CB-77 metabolism and foetal metabolite uptake, support earlier findings. The effects of CB-77 and CB-169 on foetal 7-ethoxyresorufin-O-deethylase (EROD) activities (day 17 of gestation; two days after 5 mg/kg body wt. dose (14.0-17.0 mumol/kg body wt.)) was about 20 times lower than of CB-126. In the dam, high radioactivity levels were observed in the liver and fat (highest concentrations found in CB-126 and CB-105, respectively). Strain comparison-foetal 14C-uptake (four days after administration of CB-77) in C57BL mice was almost five times higher than in NMRI-may be correlated to earlier observed differences in EROD activities between these strains. The present results indicate that congener and strain differences exist regarding both foetal and maternal distribution patterns of coplanar PCB congeners and point out the difference in foetal disposition between CB-77 and the other studied congeners.
Darnerud
P O
PO
Toxicology Division, National Food Administration, Uppsala, Sweden.
Sinjari
T
T
Jönsson
C J
CJ
D000818:Animals; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D011078:Polychlorinated Biphenyls / Q000737:chemistry* / Q000633:toxicity*; D011247:Pregnancy
D011078:Polychlorinated Biphenyls