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Understanding enantioselective processes: a laboratory rat model for alpha-hexachlorocyclohexane accumulation
E M Ulrich1, K L Willett, A Caperell-Grant
1School of Public and Environmental Affairs and Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
Environmental Science & Technology
|May 2, 2001
Summary
High enantiomeric ratios of alpha-hexachlorocyclohexane (alpha-HCH) in wildlife brains were investigated in rats. Results suggest brain metabolism is not responsible for these elevated enantiomeric ratios.
Area of Science:
- Environmental Science
- Toxicology
- Pharmacology
Background:
- Cyclodextrin gas chromatography columns are widely used for chiral separations.
- Researchers have observed high enantiomeric ratios (ER) of alpha-hexachlorocyclohexane (alpha-HCH) in wildlife brains.
Purpose of the Study:
- To investigate the high enantiomeric ratios of alpha-HCH in the brain using a laboratory rat model.
- To determine if enantioselective metabolism or transport across the blood-brain barrier contributes to high brain ERs.
Main Methods:
- Rats were pretreated with phenobarbital (PB) or left untreated before dosing with alpha-HCH.
- Animals were sacrificed at 1 or 24 hours post-dosing.
- Tissue slices (brain and liver) were used to compare alpha-HCH concentrations and ERs.
Main Results:
- In vivo, brain ERs ranged from 2.8 to 13.5, while blood, fat, and liver showed ERs closer to 1.
- PB pretreatment reduced alpha-HCH concentrations in liver slices but not in brain slices.
- In vitro, brain slices showed an average ER of 1.11, while liver slices showed 0.76 in PB-pretreated rats.
Conclusions:
- The high enantiomeric ratios of alpha-HCH observed in rat brains are consistent with wildlife data.
- Enantioselective metabolism within the brain is not the primary mechanism driving these high brain ERs.
- Transport mechanisms across the blood-brain barrier may play a role in the observed enantiomeric enrichment.