Interindividual differences in o,p'-DDD enantiomer kinetics examined in Göttingen minipigs
2009 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 76, no 2, 167-172 p.Article in journal (Refereed) Published
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.
Chiral analysis, Enantioselective toxicokinetics, Adrenocortical carcinoma, Enantiomer fraction, Absolute configuration
IdentifiersURN: urn:nbn:se:uu:diva-108056DOI: 10.1016/j.chemosphere.2009.03.050ISI: 000267155600003PubMedID: 19394667OAI: oai:DiVA.org:uu-108056DiVA: diva2:234068