T01034: Risk assessment of dietary dioxins

Wednesday 24 March 2004

This research project aims to refine the risk assessment of the human health effects of dioxins and dioxin-like PCBs ingested through the diet.

Study Duration : September 2003 to December 2007

Contractor : University of Nottingham

Background

In 2001 the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) reviewed the tolerable daily intake (TDI) for dioxins and dioxin-like polychlorinated biphenyls (PCB&#39s) and identified gaps in knowledge related to the risk assessment of dioxins during pregnancy.

Research Approach

This study will address gaps in knowledge related to the risk assessment of dioxins; specifically, we will be looking at factors underlying the toxicokinetic and toxicodynamic factors used in the dioxin assessment.

2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) toxicokinetics.
The objective is to relate dose of TCDD to maternal burden, foetal burden and biological endpoints in the same experiment. In view of the complexity of TCDD toxicokinetics, it is essential to have both an acute dose study as a positive control, and a chronic study where TCDD administration is more representative of human exposure. TCDD concentration will be determined in tissues of pregnant rats (liver, fat and blood), and total foetus at gestation day 16 and 21, using the sensitive and specific gas chromatography-mass spectrometry (GC-MS) method. Biological endpoints will be:

the effects of TCDD on induction of marker genes, such as CYP1A1 and androgen receptor. These are markers of biological effect, and potentially surrogate markers for toxicity;
the effects of TCDD on epididymal sperm count, sperm motility and sex organ histopathology in adult males born to dams exposed during pregnancy.

Outcomes.
This proposed study aims to provide data which will reduce uncertainty in the dioxin risk assessment. Specifically, this study will address:

TCDD toxicokinetics. The direct measurement of TCDD maternal and foetal burdens in rat, at doses that are demonstrated to produce biological and toxicological endpoints, will provide a more reliable basis for extrapolation to humans.
TCDD toxicodynamics. This work will characterise the relative affinity of rat and human aryl hydrocarbon receptor (AhR) to a range of dioxins, and provide a rational basis for setting a factor for inter-species differences in toxicodynamics.

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T01034: Risk assessment of dietary dioxins

Background

Research Approach

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