The complexity of nuclear hormone receptors’ regulation of gene t

The complexity of nuclear hormone receptors’ regulation of gene transcription can not be overstated. There is a multiplicity of controls including for example, heterodimerisation of receptors, coactivator availability, selleck and multiple feedback systems, etc. The final step in the exposure–dose–response

paradigm is the toxic response. There are many possible types of toxicity including acute, subacute and chronic insults. Among acute one would list necrosis, apoptosis and malformation; in subacute organ growth for example and an example of a chronic toxicity is cancer (Elcombe et al., 2002). The presentation concluded that the safety evaluation of all pesticides, whether or not suspected

of endocrine activity, should be based on an understanding of both mechanism of action and exposure levels. Attendees were divided into four groups by the Workshop Organising Committee (OC), with each group containing representatives from for-profit (industry) and non-profits (NGO, government and academia). Questions prepared by the OC were assigned to each group and instructions were to prepare a short VX-770 nmr presentation on the group’s position indicating whether unanimity, consensus, limited agreement, or no agreement was reached. These four terms were defined by the Chairman of the Workshop (Dr. Neil Carmichael of ECETOC) Sulfite dehydrogenase in his introductory presentation as follows: Unanimity No significant disagreement Question 1: Are levels of exposure just as important as potency in discussions on endocrine-active pesticides? and Should both be given equal weight in regulatory decisions? Here, unanimity was reached for ‘yes’ to both questions. The group agreed that both parameters, hazard and exposure, are needed for informed discussion. The group further stated that risk assessment principles must be used and that risk assessment should be transparent

and open-minded so that trust and respect among the various stakeholders could be maintained. A discussion on how to generate trust and the importance of trust and respect between industry and academia followed. It was noted that dialog is impossible in a situation of distrust and accusation. A proposition for defining different classes of endocrine disrupters depending on their level of hazard was put forth. Three categories were suggested: i) substance should be banned It was clearly stated in the group presentation that adequate evidence for the decision scheme for such a classification must be available. A suggestion in the discussion was that scientists actively publishing in the field agree on the appropriate tests and that a ‘ring test’ of case studies be performed i.e., several laboratories perform the proposed tests and compare results.

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