COT agenda and papers: 22 June 2010

Agenda and papers for the meeting of the Committee at 10.00am on Tuesday 22 June 2010 in Conference Rooms 4 and 5, 4th floor, Aviation House, London.

1. Apologies for absence

2. Draft minutes of the meeting held on 4th May 2010 - TOX/MIN/2010/03

3. Matters arising

4. Draft discussion paper on Idiopathic Environmental Intolerance (IEI) and behavioural conditioning - TOX/2010/14

In October 2009, COT considered a discussion paper that presented an overview of the evidence relating to toxicological mechanisms of idiopathic environmental intolerance (IEI). In discussion about the paper, COT considered that they needed information on psychological aspects of IEI to assist them in their provision of advice. This discussion paper provides Members with information on the principles of behavioural conditioning, sensitisation and generalisation and their potential application to the development of IEI.

5. Definition of an endocrine disruptor for regulatory purposes - TOX/2010/15

The Committee has been asked to discuss and agree the introduction into the new European Plant Protection Products (PPP) Regulation (1107/2009) of an exclusion criterion for approval which explicitly indicates that any active substance, safener and synergist with endocrine disrupting properties that may cause adverse effects in humans cannot be approved for marketing and use unless the exposure of humans under realistic proposed conditions of use is negligible.

6. Health Assessment of Endocrine Disrupting Chemicals – the Danish EPA report and exposure time trends to phthalates - TOX/2010/16

At the February 2010 meeting, Members were presented with a paper summarising a recent report by the Danish Environmental Protection Agency (EPA). At that meeting, the Committee welcomed the approach of studying total exposures from a range of different scenarios, and asked to see the full report to review the exposure estimates and endpoints used for each substance in the report’s risk assessment. The Committee also felt that it would be useful to obtain information on time trends in exposure to a selection of the compounds investigated. The focus of this paper is to provide the Committee with the requested information from the Danish EPA report, and information on time trends in exposure to endocrine disrupting chemicals - to provide a preliminary indication of the type of data available, focus was placed on phthalates.

7. T01045 – Assessment of joint endocrine effects of multi-component mixture of food contaminants and additives - TOX/2010/17 Reserved Business

The Committee has been asked to consider the final report of the FSA funded project contract T01045. A considerable body of work exists on mixtures of chemicals with similar modes of action. This has shown that knowledge of the effects of individual chemicals can be used to predict mixture effects accurately using the concept of dose addition. However, there are few data for mixtures of chemicals with diverse modes of action, especially when individual components are present at low levels i.e. levels around the 'no observed effect levels' (NOELs). This project addressed this gap, focusing on endocrine disrupting effects (using in vitro tests for estrogenicity and anti-androgenicity) and aimed to develop methods of predicting the effects of mixtures of chemicals with known properties.

8. Use of toxicogenomics in toxicology – design, analysis and statistical issues - TOX/2010/18

In 2001, the COT/COM/COC held a Joint Symposium to discuss issues relating to the use of genomics and proteomics in toxicology. The Committees agreed to periodically review the literature to consider whether the conclusions made in 2001 needed revising. A series of COT discussion papers followed resulting in a joint statement published in 2004 that updated the previous conclusions reached from the 2001 Joint Symposium. This discussion paper focuses on issues represented by study design/reproducibility, evaluation and statistical analysis of raw data, variation in transcriptomics and high density vs. low density array design as they relate to transcriptomic studies.

9. FSA funded project on expression of uncertainty in risk assessment - TOX/2010/19

The Committee will be presented with a draft report of this project. In 2007 the COT published its report on variability and uncertainty in toxicology. The COT report concluded there was a need to develop a framework for the transparent expression of uncertainty in hazard characterisation which would enable COT, and other committees that perform toxicological evaluations, to improve communications to a wide range of stakeholders including the public with regards to the sources of variability and uncertainty in their risk assessments. This study aimed to address this requirement by developing and testing a framework for the qualitative expression of uncertainties. A review of existing approaches for qualitative evaluation of uncertainties in risk assessment will be undertaken, the potential suitability of these approaches will be evaluated, and the most promising approach (or combination of approaches) identified and incorporated into the framework. Experts were invited to provide a direct and thorough test of the applicability and usability of the identified framework using one of four case studies, based on previous COT statements. This will be achieved as part of a workshop on evaluation and expression of uncertainties in risk assessment, held in conjunction with the COT’s annual out-of-town meeting.

10. Paper for Information:

FSA Scientific Advisory Committees (SACs) update - TOX/2010/20

This information paper provides an update on agenda items being discussed by other FSA scientific advisory committees. Some of the agenda items will be reserved business and so will not be published on the website.

11. Any other business

12. Date of next meeting – 14th September 2010 Conference Rooms 4 & 5, Aviation House, 125 Kingsway, London WC2 6NH