Issues and Challenges in the Application of the IEUBK Model in the Health Risk Assessment of Lead: A Case Study from Blantyre Malawi.

The risk assessment of lead (Pb) requires the use of biokinetic models to translate measured concentrations of Pb in food and environmental media into blood lead (BPb). The aim of this study was to assess the applicability of the Integrated Exposure Uptake Biokinetic (IEUBK) model in the health risk assessment of Pb among children in Blantyre. Children (152) aged 1-6 years were recruited into this cross-sectional study, and foods, house dust, playground soil, water, and venous blood (1 mL) were collected and analyzed for Pb. A seven-day food frequency questionnaire (FFQ) was used to collect food consumption data. The concentrations of Pb ranged from 0.01 to 3.3 mg/kg in food, 2.3 to 265 mg/kg and 1.5 to 482 mg/kg in house dust and playground soil, respectively, as well as 2.0 µg/dL to 50.4 µg/dL and 6.8 to 39.2 µg/dL for measured and predicted BPb, respectively. Various statistical tests indicated less than satisfactory agreement between measured and predicted BPb values. Despite the lack of reliable food consumption data and other limitations, both the predicted and measured BPb values indicate that children in Blantyre are exposed to high levels of Pb, largely through food and soil as a minor source.

Gut microbiota-mediated pesticide toxicity in humans: Methodological issues and challenges in the risk assessment of pesticides.

Many in vivo and in vitro studies have shown that pesticides can disrupt the functioning of gut microbiota (GM), which can lead to many diseases in humans. While the tests developed by the Organization of Economic Cooperation and Development (OECD) are expected to capture most apical effects resulting from GM disruptions, exclusion of GM in the risk assessment might mischaracterize hazards or overestimate/underestimate risks, especially when extrapolating results from one species to another species or population with a substantially different GM. On the other hand, direct assessment of GM-mediated effects may face challenges in identifying hazards, since not all GM perturbations will lead to human adverse effects. In this regard, reliable and validated biomarkers for common GM-mediated adverse effects may be very useful in the identification of GM-mediated pesticide toxicity. Nevertheless, proving causality of GM-mediated effects will need modifications of Bradford Hill criteria as well as Koch's postulates, which are more suitable for the "one-pathogen" paradigm. Furthermore, risk assessment of GM-mediated effects may require pesticide toxicokinetics along the gut, possibly through modeling, and the establishment of the involvement of GM in the mechanism of action (MOA) of the pesticide. Risk assessment of GM mediated effects also requires the standardization of experimental approaches as well as the establishment of microbial reference communities, since variations exist among GM in human populations.

An assessment of applicability of existing approaches to predicting the bioaccumulation of conventional substances in nanomaterials.

The experimental determination of bioaccumulation is challenging, and a number of approaches have been developed for its prediction. It is important to assess the applicability of these predictive approaches to nanomaterials (NMs), which have been shown to bioaccumulate. The octanol/water partition coefficient (KOW ) may not be applicable to some NMs that are not found in either the octanol or water phases but rather are found at the interface. Thus the KOW values obtained for certain NMs are shown not to correlate well with the experimentally determined bioaccumulation. Implementation of quantitative structure-activity relationships (QSARs) for NMs is also challenging because the bioaccumulation of NMs depends on nano-specific properties such as shape, size, and surface area. Thus there is a need to develop new QSAR models based on these new nanodescriptors; current efforts appear to focus on digital processing of NM images as well as the conversion of surface chemistry parameters into adsorption indices. Water solubility can be used as a screening tool for the exclusion of NMs with short half-lives. Adaptation of fugacity/aquivalence models, which include physicochemical properties, may give some insights into the bioaccumulation potential of NMs, especially with the addition of a biota component. The use of kinetic models, including physiologically based pharmacokinetic models, appears to be the most suitable approach for predicting bioaccumulation of NMs. Furthermore, because bioaccumulation of NMs depends on a number of biotic and abiotic factors, it is important to take these factors into account when one is modeling bioaccumulation and interpreting bioaccumulation results. Environ Toxicol Chem 2018;37:2972-2988. © 2018 SETAC.

Dissolution and biodurability: Important parameters needed for risk assessment of nanomaterials.

Biopersistence and biodurability have the potential to influence the long-term toxicity and hence pathogenicity of particles that deposit in the body. Therefore, biopersistence and biodurability are considered to be important parameters needed for the risk assessment of particles and fibres. Dissolution, as a measure of biodurability, is dependent on the chemical and physical properties (size, surface area, etc.) of particles and fibres and also of the suspension medium including its ionic strength, pH, and temperature. In vitro dissolution tests can provide useful insights as to how particles and fibres may react in biological environments; particles and fibres that release ions at a higher rate when suspended in vitro in a specific simulated biological fluid will be expected to do so when they exist in a similar biological environment in vivo. Dissolution of particles and fibres can follow different reaction kinetics. For example, the majority of micro-sized particles and fibres follow zero-order reaction kinetics. In this case, although it is possible to calculate the half-time of a particle or fibre, such calculation will be dependent on the initial concentration of the investigated particle or fibre. Such dependence was eliminated in the shrinking sphere and fibre models where it was possible to estimate the lifetimes of particles and fibres as a measure of their biodurability. The latter models can be adapted for the dissolution studies of nanomaterials. However, the models may apply only to nanomaterials where their dissolution follows zero-order kinetics. The dissolution of most nanomaterials follows first-order kinetics where dependence on their initial concentration of the investigated nanomaterials is not required and therefore it is possible to estimate their half-times as a measure of their biodurability. In dissolution kinetics for micro-sized and nano-sized particles and fibres, knowledge of dissolution rate constants is necessary to understand biodurability. Unfortunately, many studies on dissolution of nanoparticles and nanofibres do not determine the dissolution rates and dissolution rate constants. The recommendation is that these parameters should be considered as part of the important descriptors of particle and fibre physicochemical properties, which in turn, will enable the determination of their biodurability.

Sharing perspectives and experiences of doctoral fellows in the first cohort of Consortium for Advanced Research Training in Africa: 2011-2014.

BACKGROUND: Resolution of public health problems in Africa remains a challenge because of insufficient skilled human resource capacity. The Consortium for Advanced Research Training in Africa (CARTA) was established to enhance capacity in multi-disciplinary health research that will make a positive impact on population health in Africa. OBJECTIVE: The first cohort of the CARTA program describes their perspectives and experiences during the 4 years of fellowship and puts forward suggestions for future progress and direction of research in Africa. CONCLUSIONS: The model of training as shown by the CARTA program is an effective model of research capacity building in African academic institutions. An expansion of the program is therefore warranted to reach out to more African academics in search of advanced research training.