| Differential Effects of Two Lots of Aroclor 1254: Congener-Specific Analysis and Neurochemical End Points Prasada Rao S. Kodavanti,1 Narayanan Kannan,2 Nobuyoshi Yamashita,3 Ethel C. Derr-Yellin,1 Thomas R. Ward,1 Deborah E. Burgin,4,5 Hugh A. Tilson,1 and Linda S. Birnbaum4 1Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 2Department of Marine Chemistry, University of Kiel, D24105, Kiel, Germany; 3National Institute for Resources and Environment, Hydrospheric Environmental Protection Department, Tsukuba, Japan; 4Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 5Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA
Abstract Aroclor 1254 is a widely studied commercial polychlorinated biphenyl (PCB) mixture which, by definition, contains 54% chlorine by weight. Recent reports indicate substantial differences in the congener composition among Aroclor lots and hence their biologic effects. We designed the current study to compare the effects of two lots of Aroclor 1254 (lots 6024 and 124-191) . We analyzed these two lots for PCB congeners, polychlorinated dibenzofurans (PCDFs) , polychlorinated naphthalenes (PCNs) , and polychlorinated dibenzodioxins (PCDDs) . We used previously established techniques for analyzing intracellular Ca2+ buffering and protein kinase C (PKC) translocation to test their biologic activity in neuronal preparations. PCB congener-specific analysis indicated that ortho and non-ortho congeners in these two lots varied in their percent contribution. Among all congeners, the percentages of non-ortho congeners (PCBs 77, 81, 126, and 169) were higher in lot 6024 (2.9% of total) than in lot 124-191 (0.02% of total) . We detected no dioxins in these two lots (< 2 ppb) . Although there are some differences in the congener composition, total PCNs were similar in both lots: 171 ppm in lot 6024 and 155 ppm in lot 124-191. However, total PCDFs were higher in lot 6024 (38.7 ppm) than in lot 124-191 (11.3 ppm) . When we tested these two Aroclors on Ca2+ buffering and PKC translocation in brain preparations, the effects were significantly different. Although lot 124-191 was more potent on PKC translocation than lot 6024, lot 6024 was slightly more active on Ca2+ buffering than lot 124-191. These effects could not be attributed to the differences in the percentage of non-ortho congeners or PCDFs because they were inactive on these two parameters. The effects could not be attributed to PCNs because the levels were almost similar. The effects seen with two lots of Aroclor 1254 in neuronal cells were also not predicted based on the TCDD toxic equivalents (TEQs) , although TEQs predicted the effects on ethoxyresorufin-O-deethylase (EROD) or methoxyresorufin-O-deethylase (MROD) activities. It is possible that the differential effects seen in neuronal cells could be caused by differences in the composition of ortho-congeners in these two mixtures, because PCBs with ortho-lateral substitutions can exhibit different activities on the selected neurochemical end points. Because of these differential effects with different lot numbers, the composition of Aroclor mixtures used in investigations should be disclosed. Key words: Aroclor 1254, dioxins, polychlorinated biphenyls, protein kinase C, toxic equivalents. Environ Health Perspect 109:1153-1161 (2001) . [Online 5 November 2001] http://ehpnet1.niehs.nih.gov/docs/2001/109p1153-1161kodavanti/ abstract.html Address correspondence to P.R.S. Kodavanti, Neurotoxicology Division, MD 74B, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Telephone: (919) 541-7584. Fax: (919) 541-4849. E-mail: kodavanti.prasada@epa.gov We thank J. Cogliano of NCEA and N. Walker of NIEHS for their comments on the earlier version of this manuscript. D.E.B. was supported in part by the National Institute of Environmental Health Sciences under T32-ES07126 and by the U.S. EPA under cooperative agreement CT902908. Preliminary findings presented in this article were presented at the 38th Annual Meeting of the Society of Toxicology, New Orleans, Louisiana, 14-18 March 1999. The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. EPA, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency nor does mention of tradenames or commercial products constitute endorsement or recommendation for use. Received 18 December 2000 ; accepted 2 May 2001. The full version of this article is available for free in HTML or PDF formats. |