Overview of approaches to prepare for September 26-27 meeting
Each of the core groups (Allergen, Chemical, Microbial and Nutrient Groups) has generated initial outlines addressing the five topics of the white paper “template”.
Two groups (Chemical and Microbial) have generated multiple outlines, corresponding to multiple subcategories of chemicals and pathogens. More recently, each of the groups has taken a slightly different approach to building on their earlier work – focusing now on template topic #2: Characterization of the essential features of the fundamental biology and mechanisms (modes of action, or MoA) as related to thresholds/dose-response relationships. Here’s a brief outline of approaches.
Allergens Group
This group is working to put more text around their outline topic #2. In addition, they are attempting to address the generic “focused questions” circulated in May, although information is likely not available to answer several of the questions.
FYI, here is a downloadable PDF to their initial outline for topic #2.
Chemicals Group
This group decided to take an approach that asks “What would it take for a threshold response”, whereby they consider plausible dose-response characteristics for each of the key events for a particular adverse outcome in order to ascertain whether one or more of the steps is rate-limiting. FYI, here is a downloadable PDF to an initial draft showing this approach.
Microbial Group
This group has generated tables outlining key aspects of the biology, pathways and events for sample pathogens (covering the four main categories of pathogen mechanisms). The group is also considering the issue from a disease standpoint (i.e., key steps leading to a given endpoint) for a couple of example pathogens. Here is downloadable PDF to a Topic #2 table.
Nutrients Group
This group is looking at what is known about chemical and biological events occurring on the path from nutrient intake to adverse effect in order to identify characteristics of those events that: 1) support or refute the concept of individual thresholds; 2) assist in identifying thresholds; and 3) cast light on the problem of threshold variability. Recognizing there are many different paths from intake to adverse outcome, the group is focused on reviewing types of key events that should be studied to address the three issues noted. Here is a downloadable PDF to the questions they intend to focus on.
DEFINITIONS
Here is a downloadable PDF to recent discussion regarding definitions, including what is meant by “rate-limiting”.