|Title||Statistical modelling of variability and uncertainty in risk assessment of nanoparticles|
|Source||Wageningen University. Promotor(en): Cajo ter Braak, co-promotor(en): Hilko van der Voet. - Wageningen : Wageningen University - ISBN 9789462578197 - 205|
Mathematical and Statistical Methods - Biometris
|Publication type||Dissertation, internally prepared|
|Keyword(s)||modeling - statistics - particles - risk assessment - uncertainty - uncertainty analysis - nanotechnology - probabilistic models - modelleren - statistiek - deeltjes - risicoschatting - onzekerheid - onzekerheidsanalyse - nanotechnologie - waarschijnlijkheidsmodellen|
|Categories||Mathematical Models, Simulation Models|
Engineered nanoparticles (ENPs) are used everywhere and have large technological and economic potential. Like all novel materials, however, ENPs have no history of safe use. Insight into risks of nanotechnology and the use of nanoparticles is an essential condition for the societal acceptance and safe use of nanotechnology.
Risk assessment of ENPs has been hampered by lack of knowledge about ENPs, their environmental fate, toxicity, testing considerations, characterisation of nanoparticles and human and environmental exposures and routes. This lack of knowledge results in uncertainty in the risk assessment. Moreover, due to the novelty of nanotechnology, risk assessors are often confronted with small samples of data on which to perform a risk assessment. Dealing with this uncertainty and the small sample sizes are main challenges when it comes to risk assessment of ENPs. The objectives of this thesis are (i) to perform a transparent risk assessment of nanoparticles in the face of large uncertainty in such a way that it can guide future research to reduce the uncertainty and (ii) to evaluate empirical and parametric methods to estimate the risk probability in the case of small sample sizes.
To address the first objective, I adapted an existing Integrated Probabilistic Risk Assessment (IPRA) method for use in nanoparticle risk assessment. In IPRA, statistical distributions and bootstrap methods are used to quantify uncertainty and variability in the risk assessment in a two-dimensional Monte Carlo algorithm. This method was applied in a human health (nanosilica in food) and an environmental (nanoTiO2 in water) risk context. I showed that IPRA leads to a more transparent risk assessment and can direct further environmental and toxicological research to the areas in which it is most needed.
For the second objective, I addressed the problem of small sample size of the critical effect concentration (CEC) in the estimation of R = P(ExpC > CEC), where ExpC is the exposure concentration. First I assumed normality and investigated various parametric and non-parametric estimators. I found that, compared to the non-parametric estimators, the parametric estimators enable us to better estimate and bound the risk when sample sizes and/or small risks are small. Moreover, the Bayesian estimator outperformed the maximum likelihood estimators in terms of coverage and interval lengths. Second, I relaxed the normality assumption for the tails of the exposure and effect distributions. I developed a mixture model to estimate the risk, R = P(ExpC > CEC), with the assumption of a normal distribution for the bulk data and generalised Pareto distributions for the tails. A sensitivity analysis showed significant influence of the tail heaviness on the risk probability, R, especially for low risks.
In conclusion, to really be able to focus the research into the risks of ENPs to the most needed areas, probabilistic methods as used and developed in this thesis need to be implemented on a larger scale. With these methods, it is possible to identify the greatest sources of uncertainty. Based on such identification, research can be focused on those areas that need it most, thereby making large leaps in reducing the uncertainty that is currently hampering risk assessment of ENPs.