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Interindividual differences in o,p'-DDD enantiomer kinetics examined in Göttingen minipigs
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
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2009 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 76, no 2, 167-172 p.Article in journal (Refereed) Published
Abstract [en]

Five minipigs were given a single oral dose of a racemic mixture of o,p'-DDD (30 mg kg(-1)b.w., EF=0.49). Blood plasma and subcutaneous adipose tissue were collected for analysis, at different time-points over 180 d. At the end of the experiment also liver, kidney and brain tissue were collected. Low concentrations of o,p'-DDD still remained after 180 d in plasma (mean 0.5+/-0.3 ng g(-1)f.w.) and in adipose tissue (mean 40+/-40 ng g(-1)f.w.). The mean concentrations in liver and kidney were 500+/-300 pg g(-1)f.w. and 90+/-50 pg g(-1)f.w., respectively. The enantiomers of o,p'-DDD were isolated by HPLC and the absolute configuration of the enantiomers were determined by X-ray crystallography and polarimetry as R-(+)-o,p'-DDD and S-(-)-o,p'-DDD. The enantiomer fractions (EFs) of o,p'-DDD were determined in plasma, adipose tissue and kidney using GC/ECD equipped with a chiral column. The EFs of o,p'-DDD in the individual minipigs showed large variability, ranging from 0.2 to 0.6 after 24h in plasma and from 0.2 to 0.7 after 90 d in adipose tissue. Hence in two of the minipigs, the S-(-)-o,p'-DDD enantiomer was dominating while the other enantiomer, R-(+)-o,p'-DDD was dominating in three minipigs. We propose that a yet not identified factor related to polymorphism, regulating the metabolism and/or elimination of the enantiomeric o,p'-DDD, is responsible for the differences in enantiomeric retention of the compound in the minipigs.

Place, publisher, year, edition, pages
2009. Vol. 76, no 2, 167-172 p.
Keyword [en]
Chiral analysis, Enantioselective toxicokinetics, Adrenocortical carcinoma, Enantiomer fraction, Absolute configuration
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-108056DOI: 10.1016/j.chemosphere.2009.03.050ISI: 000267155600003PubMedID: 19394667OAI: oai:DiVA.org:uu-108056DiVA: diva2:234068
Available from: 2009-09-04 Created: 2009-09-04 Last updated: 2017-12-13Bibliographically approved

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