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Comparative placental transfer and fetal uptake of environmental chemicals

The objective of WP3 was to determine the extent of uptake and transfer of selected xenobiotics across the human placenta in order to be able to correlate likely fetal uptake with known maternal exposure. This will provide information on the potential of selected xenobiotics for in utero sensitisation of the fetus and will assist exposure-dose determination. It will also enable comparison with animal data to assist in the extrapolation from animal data to human.

A human ex vivo perfused placenta model was utilised and the transfer of radiolabelled xenobiotics was measured using an open circuit system by analysis of samples taken from both the maternal and fetal circulation over time. Accumulation in the placental tissue was also measured. Each of the xenobiotics investigated crossed the placenta by passive diffusion and there was no evidence of active transport. The extent of transfer was similar irrespective of whether the direction was maternal to fetal or fetal to maternal. Significant accumulation within the perfused area was observed for DDE, DDT and PCB-77 but not DCB. DCB transferred to the fetal circulation most rapidly suggesting that accumulation in the placental tissue might result in delayed transit of the other 3 compounds.

The results confirm passive transfer of organochlorine pollutants from mother to fetus. The results will be disseminated through publication in peer-reviewed journals and will be used to aid further evaluation of fetal exposure.

The objective of WP4 was to determine the biodistribution of the environmental chemicals in vivo. Placental transfer of each of the selected pesticides occurs in vivo with peak uptake reached within 24 hours of maternal administration. Uptake in vivo is generally greater in maternal organs compared with corresponding fetal organs, most notably for the gastro-intestinal tract. Given that the route of administration was oral, this is not surprising. However, despite this there are certain organs where fetal pesticide tissue concentrations matched or exceeded those found in the corresponding maternal organs. Fetal and maternal blood concentrations reached similar levels within 12 hours for DCB and DDT whereas for DDE and PCB-52 fetal concentrations were consistently lower than maternal concentrations. For DCB, fetal concentrations in spleen and muscle to maternal were similar after about 8 hours and concentrations in fetal bone-marrow exceeded those in the maternal organ after about 24 hours. Elevated concentrations, compared with maternal concentrations, were seen in key fetal organs such as blood, spleen, bone-marrow, brain and liver. Such accumulation may impact on development of nervous, immune and hepatic systems with potential for adverse postnatal health effects.

The results will be submitted for publication in a peer-reviewed journal. Further development work should include modelling of the biodistribution in order to extrapolate from animal to human data. This will require access to further human data (e.g. cord blood values) and collaboration with experts in mathematical and pharmacokinetic modelling.

Exchange of information with other groups involved in placental transfer across Europe will provide valuable opportunities for collaboration as there are few groups who have the expertise or necessary facilities. Such collaboration has already been inititiated during the life of the current project and it is planned that this should continue.

Related information

Reported by

University of Bristol
University Hospitals Bristol NHS Foundation Trust Biophysics Research Unit, Bristol Haematology & Oncology Centre, Horfield Road
BS2 8ED Bristol
United Kingdom
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