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

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 0.2-0.6 after 24 h in plasma and from 0.2-0.7 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.

NATURVETENSKAP Geovetenskap och miljövetenskap Miljövetenskap hsv//swe
NATURAL SCIENCES Earth and Related Environmental Sciences Environmental Sciences hsv//eng
Chiral analysis
enantioselective toxicokinetics
adrenocortical carcinoma
enantiomer fraction
absolute configuration
Environmental chemistry
Miljökemi
miljökemi
Environmental Chemistry

Lindström, V.Department of Environmental Toxicology, Uppsala University (författare)
Eriksson, L.Stockholms universitet,Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi,Division of Structural Chemistry (författare)
Brandt, I.Department of Environmental Toxicology, Uppsala University (författare)
Bergman, Å.Stockholms universitet,Institutionen för miljökemi (författare)
Stockholms universitetInstitutionen för miljökemi (creator_code:org_t)

Av författaren/redakt...: cantillana, T.; Lindström, V.; Eriksson, L.; Brandt, I.; Bergman, Å.

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