Contribution of planar (0-1 Ortho) and nonplanar (2-4 Ortho) fractions of aroclor 1260 to the induction of altered hepatic foci in female Sprague-Dawley rats

The hepatic tumor promoting activity of the planar 0-1 ortho (similar to9.7 % w/w) and the nonplanar 2-4 ortho (similar to 90.3% wlw) fraction of the c ommercial PCB mixture Aroclor 1260 was studied using a medium-term two-stag e initiation/promotion bioassay in female Sprague-Dawley rats. Fractionatio n was carried out on an activated charcoal column. The composition of the e ffluent from the column was tested by GC-ECD. The absence of planar compoun ds in the 2-4 ortho fraction was confirmed by CC-MS analysis. The dioxin-li ke toxic potency of the fractions was determined with the DR-CALUX assay. T he animal experiment was started with the initiation procedure (diethylnitr osamine injection, 30 mg/kg body wt ip, 24 h after 2/3 hepatectomy), follow ed 6 weeks later by the promotion treatment, which consisted of a weekly su bcutaneous injection during 20 weeks. Exposure groups (n = 10) received the following treatments (dose/kg body wt/week): Aroclor 1260 (10 mg), 0-1 ort ho fraction (0.97 mg), 2-4 ortho fraction (1, 3, or 9 mg), a reconstituted 0-4 ortho fraction (9.97 mg), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153; 1 or 9 mg), 2,3,7,8-TCDD (1 mug; positive control) or corn oil (1 mi; vehicl e control). One group did not receive a promotion treatment. All exposure g roups exhibited a significantly increased volume fraction of the liver occu pied by hepatic foci positive for the placental form of glutathione-S-trans ferase-p compared to the corn oil control, except for the groups treated wi th 0-1 ortho fraction and 1 mg PCB 153/kg body wt/week. Approximately 80% o f the total tumor promoting capacity of the reconstituted 0-4 ortho fractio n could be explained by the 24 ortho PCB fraction while the 0-1 ortho fract ion had only a negligible contribution. These results suggest that the majo rity of the tumor promotion potential of PCB mixtures resides in the non-di oxin-like fraction, which is not taken into account in the toxic equivalenc y factor (TEF) approach for risk assessment of PCBs. This may result in an underestimation of the tumor promotion potential of environmental PCB mixtu res, (C) 2000 Academic Press.