Tissue concentrations and induction of a hepatic m

Authors: Wolfgang Körner Georg Golor Thomas Schulz Thomas Wiesmüller Hanspaul Hagenmaier Diether Neubert

Publish Date: 2001/12/01

Volume: 75, Issue: 11-12, Pages: 653-664

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Abstract

Two groups of male Wistar rats were treated 16 times every 3rd day subcutaneously with a defined mixture of polychlorinated dibenzopdioxins PCDDs or of polychlorinated dibenzofurans PCDFs These mixtures contained no measurable amount of 2378TCDD Each single dose was calculated to contain either 57 ng ITEq international 2378T4CDD toxicity equivalencies/kg body weight of the PCDD mixture or 39 ng ITEq/kg body weight of the PCDF mixture Both mixtures contained a large excess of non2378substituted congeners The activities of ethoxyresorufin Odeethylase EROD in liver microsomes were correlated with the corresponding concentrations of PCDDs or PCDFs in hepatic tissue Data were compared with results obtained after single injections of 2378tetrachlorodibenzopdioxin 2378T4CDD As expected a complex kinetic situation resulted because of the different tissue distributions and elimination halflives of the various congeners 1 2378substituted PCDDs the time course of the concentrations in liver and adipose tissue was similar for all congeners the levels increased during the treatment period and decreased after treatment Tissue concentrations of all 2378substituted PCDDs were considerably higher in liver than in adipose tissue The liver/adipose tissue concentration ratios increased with the degree of chlorination The ratio of 12378P5CDD was much lower than those of all other 2378substituted congeners 2 2378substituted PCDFs 12378P5CDF was rapidly eliminated from liver and adipose tissue while 23478P5CDF largely persisted after the treatment period in both tissues 2378T4CDF was eliminated even more rapidly than 12378P5CDF and could not be detected after treatment in both tissues Time courses of the concentrations of 23478P5CDF H6CDFs H7CDFs and OCDF in liver and adipose tissue were similar the levels of all congeners increased during the treatment period but no clearcut decrease was observed within 34 days after the last treatment Tissue concentrations of all 2378substituted PCDFs were higher in liver than in adipose tissue The liver/adipose tissue concentration ratios increased with the degree of chlorination The ratios of 2378T4CDF and 12378P5CDF were much lower than those of all other 2378substituted congeners 3 non2378substituted PCDDs and PCDFs a number of non2378substituted PCDD and PCDF congeners were found in both tissues in concentrations below 1 ng/g In adipose tissue nearly all congeners were found during the treatment period showing a decrease after the treatment In liver samples many higher chlorinated PCDF congeners with 4 chlorine atoms could be detected Most of those substituted in three of the four 2 3 7 and 8positions persisted after treatment In contrast only one 1469substituted isomer of each PCDD homologue group was found during treatment with high recoveries after the third injection but a rapid decline occurred already during the treatment period 4 EROD activity a good linear relationship when using a doublelog plot between the EROD activities and the hepatic concentrations ng ITEq/g tissue was found both in the PCDDtreated r 2 =858 and in the PCDFtreated group r 2=873 A similar correlation r 2 =956 was observed in rats treated with 2378TCDD alone concentration range in liver tissue 02 to 97 ng/g wet weight The concentrationresponse curves for both the PCDD and PCDF mixtures run parallel to the curve for 2378T4CDD However the inductive potency of the PCDD or PCDF mixture was approximately 3fold or 4fold lower respectively compared with the inductive potency of 2378T4CDD Thus the ITE factors overestimated the potency of the mixtures in the concentration range tested and taking EROD induction as an end point

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