Promotion of Altered Hepatic Foci by 2,3′,4,4′,5-Pentachlorobiphenyl in Sprague-Dawley Female Rats

Abstract

The tumor promotion potential of 2,3',4,4',5-pentachlorobiphenyl (PCB-118) was studied in a two-stage initiation/promotion bioassay in female Sprague-Dawley rats. The animals were initiated by intraperitoneal administration of iV-nitrosodiethylamine after partial hepatectomy. After 5 weeks of recovery, the promotion period commenced by once-weekly subcutaneous administrations of PCB-118 at six dose levels (10, 40, 160, 640, 2500, and 10,000 /ig/kg body weight/week) for 20 weeks. In addition, three of these dose levels (40, 640, and 10,000 ^g/kg body weight/week) were administered for 52 weeks. Evaluation of hepatic foci positive for glutathione S-transferase P demonstrated that the mono-ortho chlorine substituted congener PCB-118 significantly increased the number of foci/cm 3 of liver in the two highest dose groups after 20 weeks, but did not significantly increase the percentage of the liver occupied by foci. After 52 weeks of treatment, both the percentage and the number of foci/cm 3 were significantly increased in the highest dose group. A toxic equivalency factor based on foci development during 20 weeks of treatment would be less than 0.00002. Altered relative liver and thymus weights were observed after treatment with both substances as well as an induction of methyl cholanthrene-and phenobarbital-inducibie isoenzymes of cytochrome P450 monooxygenase. These results show that PCB-118 has a potency to enhance foci growth in rat liver, although the potency is low compared to that of structurally related compounds. © 1997 Society of Toxicology.As a result of an extended, worldwide, and regular use of commercial mixtures of polychlorinated biphenyls (PCBs), these persistent compounds are widely spread in the environment. In many countries this use is nowadays restricted and

Toxic Equivalency Factors (TEFs) for PCBs, PCDDs, PCDFs for Humans and Wildlife

“…Based on studies with chicken embryos, it has been concluded that birds can be highly responsive toward non-ortho PCBs, although much of the information available concerns induction of CYPlAI and not distinct toxic (118) New data support the original value (91,96,108); no revision is recommended. 0.0001 0.0001 2',3,4,4',5-PentaCB (123) No new data are available; no revision is recommended.…”

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“…Tumour promotion experiments have shown that after initiation with a genotoxic carcinogen, technical PCB mixtures and individual dioxin-like and non dioxin-like congeners as well as TCDD act as liver tumour promoters in rats (Anderson et al, 1986;Buchmann et al, 1986;1990;Hemming et al, 1993;Haag-Grönlund et al, 1997;Dean et al, 2002). The promoting activity of di-ortho PCB such as PCB 47, 52, 49, and 153 has been demonstrated in short-term assays in which orally administered congeners promoted development of preneoplastic lesions in rat liver following induction by various initiators (Hemming et al, 1993;Preston et al, 1985).…”