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Deborah E. Burgin,¹ Janet J. Diliberto,² Ethel C. Derr-Yellin,³ Narayanan Kannan,⁴ Prasada R.S. Kodavanti,³ and
Linda S. Birnbaum²

¹Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA; ²Experimental Toxicology Division, and ³Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ⁴Department of Marine Chemistry, University of Kiel, Kiel, Germany

Abstract

Aroclor 1254 is a commercial mixture of polychlorinated biphenyls (PCBs) , which is defined as being 54% chlorine by weight. However, the congener composition varies from lot to lot. Two lots which have been used in toxicity studies, 124-191 and 6024 (AccuStandard) , were analyzed for their congener composition. Lot 6024 has approximately 10 times the dioxin toxic equivalents (TEQ) of lot 124-191. The purpose of this study was to determine if the difference in the TEQ of the two lots explains the different in vivo responses seen on a weight basis. Male Long-Evans rats (70 days old) were treated orally with a single dose of 0-1,000 mg/kg of each lot. Hepatic ethoxy-, methoxy-, and pentoxyresorufin O-deethylase (EROD, MROD, and PROD, respectively) activities as well as serum thyroxine (T₄) concentrations and measures of oxidative stress were determined 4 days after treatment. Results, on a weight basis, indicate that lot 6024 led to a greater induction of EROD, MROD, and PROD but not total T₄ reduction. The differences in TEQ between the lots explained the differential induction of EROD and MROD but did not account for the induction of PROD nor decreases in T₄. PROD induction is not due to dioxin-like congeners, whereas the decrease in serum T₄ levels may involve multiple mechanisms. Effects on the antioxidants ascorbic acid and uric acid were seen only at the highest mass dose for both lots and were not explained by the difference in TEQ. These results illustrate that the differences in the TEQ explain the differences in the strict dioxin-like effects (EROD, MROD induction) , but the non-dioxin-like congeners cause other effects that are not associated with the aryl hydrocarbon receptor (e.g., PROD) . In addition, supra-additive effects also occur in the mixture (T₄, oxidative stress) . Thus, current results demonstrate that overall toxicity cannot be predicted on the basis of the TEQ values. It is also critical that the lot number is reported in studies conducted with Aroclor 1254 because the congener composition and therefore the effects observed can be very different. Key words: Aroclor 1254, dioxin, hepatic enzymes, oxidative stress, polychlorinated biphenyls, thryroid hormones, toxic equivalents. Environ Health Perspect 109:1163-1168 (2001) . [Online 5 November 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p1163-1168burgin/ abstract.html

Address correspondence to D.E. Burgin, Experimental Toxicology Division, MD 74, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 USA. Telephone: (919) 541-0465. Fax: (919) 541-5394. E-mail: burgin.deborah@epa.gov

We thank B. Slezak, M. DeVito, J. Hamm, G. Hatch, D. Ross, V. Richardson, and F. McQuaid for their excellent technical assistance ; J. Richards and K. Crissman for measures of oxidative stress ; D. House for statistical analysis ; and J. McKinney and N. Walker for their comments on the manuscript.

D.E. Burgin was supported in part by the National Institute of Environmental Health Sciences under T32-ES07126 and by the U.S. Environmental Protection Agency under cooperative agreement CT902908.

This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Approval does not signify that the contents necessarily reflect the view and policies of the agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Received 5 February 2001 ; accepted 16 April 2001.