Applying toxicokinetics modelling to wildlife risk assessment for pesticide (Vertebrates)
Agnieszka Bednarska, Postdoc, Syngenta Ltd., UK
Contact: Enable-Javascript@To-Read-E-mail-Address
Aim of the Project: The main aim of this postdoctoral project is to explore the mechanisms that drive pesticide risk to birds and mammals by taking into account temporal aspect of absorption, distribution, metabolism and excretion (ADME) processes. It is necessary to develop a toxicokinetic (TK) model that is simple enough to be manageable and applicable across a range of species and exposure patterns but at the same time sufficiently complex for representing all crucial processes. Special attempt will be taken to find methods for model parameterisation that can reduce the need for animal testing.
Questions to be addressed: The current risk assessment can be refined by taking into account physiological processes such as ADME and ecological factors such as feeding rate and avoidance. Therefore the main purpose of the project is to answer the question how can ADME processes and TK modelling help assessing risk more realistically. To answer this, the following questions need to be addressed:
Question 1: How many compartments should be included in the model? Is it necessary to represent target organ(s) as separate compartment(s) or the toxicant concentration in systemic circulation (blood) is sufficient?
Question 2: Can ADME be described as a first order process?
Question 3: Is the avoidance threshold stable (constant) or affected by previous exposure?
Question 4: What is the contribution of different routes of exposure in systemic exposure?
Question 5: How to estimate whether animals recover once the toxicant leaves the system and if yes, how fast?
Question 6: Are in vitro and QSAR approaches useful for model development?
Question 7: Does model provide a basis for extrapolations across duration, dose, route, and exposure patterns as well as species?
The conceptual model for oral exposure was already described and the most possible variables and processes which determine internal concentration and distribution of a toxicant in target organ(s) i.e., ADME processes, physicochemical properties of toxicant, concentration of toxicant in food and its bioavailability, as well as processes which determine feeding rate (e.g., avoidance of contaminated food, availability of alternative food, physiological state of organism) were taken into account.
A review of literature, data collection and extrapolation of existing data (data mining) will be done to check if model can be parameterised based on existing knowledge. Then, variability within and between species in all parameters will be calculated since this can affect ‘safety factors’. The model will be compared with empirical data from acute oral toxicity study (blood concentration measurements) not used for parameterisation or calibration.
Relation to other CREAM Projects: The project is based in Syngenta under supervision of Pernille Thorbek and associated partners are CRD and Bayer. The co-supervisor of the project is Prof Richard Sibly from Reading University. Such cooperation with both companies and academia is a great opportunity to develop a model which will be follow general standards for regulators and provide additional input in pesticide risk assessment as well as will be interesting from the scientific point of views.
Direct collaboration within work package 3 (Vertebrates) is planned.
Supervisor: Pernille Thorbek (Syngenta)
Co-supervisor: Richard Sibly (University of Reading)
Associated partners: CRD; Bayer
