Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys

Abstract

A defined mixture of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) was subcutaneously administered to marmoset monkeys (Callithrix jacchus). Tissue concentrations in hepatic and adipose tissue were measured at different times after treatment (1-28 weeks). One week after application high concentrations could be detected for the 2,3,7,8-substituted congeners only. The percent of the administered dose in whole liver differed for the various 2,3,7,8-substituted congeners, ranging from 24.5 +/- 4.5% for 2,3,7,8-TCDD to 74.1 +/- 4.9% for 2,3,4,6,7,8-H6CDF. Therefore, the concentration ratio (liver/adipose tissue) was also very different, ranging from about 1 (2,3,7,8-T4CDD or 2,3,7,8-T4CDF) to greater than 10 in the case of some higher chlorinated PCDDs and PCDFs. Half-lives of PCDDs and PCDFs were very different for the various 2,3,7,8-substituted congeners. For the most toxic compound (2,3,7,8-T4CDD) a t/2 of about 8 weeks in hepatic tissue and about 11 weeks in adipose tissue was found when calculated from data obtained later than 6 weeks after injection. For 2,3,7,8-T4CDD and 1,2,3,7,8-P5CDD the decreases in hepatic concentrations were much faster during the first 6 weeks after administration (t/2 of 4 weeks). This was apparently due to redistribution phenomena. Half-life increased with increasing degrees of chlorination. In some cases (e.g. OCDD, OCDF) no significant decrease in tissue concentrations could be observed after 28 weeks. The shortest t/2 was determined for 2,3,7,8-T4CDF: shorter than 6 days in hepatic tissue and about 10 days in adipose tissue. Calculation of the body burden of the non-2,3,7,8-substituted PCDDs/PCDFs 1 week after injection revealed that all groups of isomers were present at less than 5%. Consequences of these findings for the use of TCDD-toxic-equivalency factors are discussed and a change in strategy is suggested.

Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 1. Effects on peripheral lymphocyte subpopulations of a non-human primate (Callithrix jacchus) after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

“…Following the dose of 10 ng TCDD/kg body wt the decrease in the percentage of the CD4+CDw29 § cells was not observed at the time of maximum absorption of the substance, i. e. about 1 week after the injection (Abraham et al 1989;Neubert et al 1990a), but clearly later (Fig. 2).…”

“…1990;Neubert et at. 1990a) that following a single subcutaneous dose of 120 ng TCDD/kg body wt (similar to one of the higher doses used in our study), the following tissue levels were found at the time of maximum absorption (1 week after the injection) (Table 10).…”

Low doses of 2,3,7,8-tetrachlorodibenzo- p -dioxin increase transforming growth factor β and cause myocardial fibrosis in marmosets ( Callithrix jacchus )

“…Animals of this non-human primate species had been studied before in our laboratory when we focused on TCDD-induced changes in the immune system (Neubert et al 1990(Neubert et al , 1992(Neubert et al , 1993Stahlmann and Neubert 1995).…”

Polychlorinated dibenzo-p-dioxins and the human immune system: 4. Studies on two Spanish families with increased body burdens of highly chlorinated PCDDs

“…The persistence of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in the environment, food and people (Geyer et al, 2002;Kahn et al, 1988;Needham et al, 1994;Needham et al, 1999;Neuberger et al, 1999;Neubert et al, 1990;Tohyama, 2002) continues to be of concern, but it has proven difficult to ascertain the true risks for human health with respect to the various congeners and mixtures of these contaminants (called here collectively, dioxins), especially at a low dose range (Neubert, 1997/98). Originally, most of the concern was based on experimental evidence showing an excessive toxicity, including some carcinogenicity, of the most potent chemical, 2,3,7,, in the liver of rodents, and in humans on the induction of chloracne (Baccarelli et al, 2005), skin lesions for which a special mouse strain may be a model (Panteleyev et al, 1997).…”

“…Alterations in the expression of some surface receptors on lymphocytes are the most sensitive endpoints after exposure of Callithrix to various PCDDs or to polybrominated congeners (Neubert et al, 1990;Neubert et al, 1991;Neubert et al, 1992b;Neubert et al, 1992c;Neubert et al, 1993b;Neubert et al, 1994b;Neubert et al, 1995). Single doses as low as 10 ng TCDD/kg body weight will reduce the number of CD4 -.…”