Interindividual differences in o, p′-DDD enantiomer kinetics examined in Göttingen minipigs

• Published in: Chemosphere (Oxford) 2009-06, Vol.76 (2), p.167-172
• Main Authors: Cantillana, T., Lindström, V., Eriksson, L., Brandt, I., Bergman, Å.
• Format: Article
• Language: English
• Subjects: Absolute configuration; adipose tissue; Administration, Oral; Adrenocortical carcinoma; Animals; Applied sciences; Biologi; Biology; blood plasma; Chiral analysis; Chromatography, Gas; Crystallography, X-Ray; DDD (pesticide); Enantiomer fraction; enantiomers; Enantioselective toxicokinetics; Exact sciences and technology; kidneys; Kinetics; minipigs; Mitotane - administration & dosage; Mitotane - analysis; Mitotane - pharmacokinetics; NATURAL SCIENCES; NATURVETENSKAP; pharmacokinetics; Pollution; Stereoisomerism; Swine; Swine, Miniature; Time Factors; Tissue Distribution
• ISSN: 0045-6535; 1879-1298; 1879-1298
• DOI: 10.1016/j.chemosphere.2009.03.050

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 24 h 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.