title: Differential effects of two lots of aroclor 1254: congener-specific analysis and neurochemical end points.
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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. kodavanti.prasada@epa.gov
authors.forename: P R
authors.initials: PR
authors.lastname: Kodavanti
authors.forename: N
authors.initials: N
authors.lastname: Kannan
authors.forename: N
authors.initials: N
authors.lastname: Yamashita
authors.forename: E C
authors.initials: EC
authors.lastname: Derr-Yellin
authors.forename: T R
authors.initials: TR
authors.lastname: Ward
authors.forename: D E
authors.initials: DE
authors.lastname: Burgin
authors.forename: H A
authors.initials: HA
authors.lastname: Tilson
authors.forename: L S
authors.initials: LS
authors.lastname: Birnbaum
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000009:adverse effects* / Q000737:chemistry*; D001572:Benzofurans / Q000032:analysis; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000493:pharmacokinetics; D020111:Chlorodiphenyl (54% Chlorine) / Q000009:adverse effects* / Q000737:chemistry; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007536:Isomerism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D011078:Polychlorinated Biphenyls / Q000032:analysis; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000032:analysis; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D020318:Rats, Long-Evans; D015203:Reproducibility of Results; D018570:Risk Assessment; D012989:Soil Pollutants / Q000032:analysis
chemical_list: D013956:Antithyroid Agents; D001572:Benzofurans; D000072317:Polychlorinated Dibenzodioxins; D012989:Soil Pollutants; D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D011494:Protein Kinases; D002118:Calcium