Development and application of the physiologically-based toxicokinetic (PBTK) model for ochratoxin A (OTA) in rats and humans.

Ochratoxin A (OTA) is a common fungal toxin frequently detected in food and human plasma samples. Currently, the physiologically based toxicokinetic (PBTK) model plays an active role in dose translation and can improve and enhance the risk assessment of toxins. In this study, the PBTK model of OTA in rats and humans was established based on knowledge of OTA-specific absorption, distribution, metabolism, and excretion (ADME) in order to better explain the disposition of OTA in humans and the discrepancies with other species. The models were calibrated and optimized using the available kinetic and toxicokinetic (TK) data, and independent test datasets were used for model evaluation. Subsequently, sensitivity analyses and population simulations were performed to characterize the extent to which variations in physiological and specific chemical parameters affected the model output. Finally, the constructed models were used for dose extrapolation of OTA, including the rat-to-human dose adjustment factor (DAF) and the human exposure conversion factor (ECF). The results showed that the unbound fraction (Fup) of OTA in plasma of rat and human was 0.02-0.04% and 0.13-4.21%, respectively. In vitro experiments, the maximum enzyme velocity (Vmax) and Michaelis-Menten constant (Km) of OTA in rat and human liver microsomes were 3.86 and 78.17 µg/g min-1, 0.46 and 4.108 µg/mL, respectively. The predicted results of the model were in good agreement with the observed data, and the models in rats and humans were verified. The PBTK model derived a DAF of 0.1081 between rats and humans, whereas the ECF was 2.03. The established PBTK model can be used to estimate short- or long-term OTA exposure levels in rats and humans, with the capacity for dose translation of OTA to provide the underlying data for risk assessment of OTA.

[Comparative Analysis on the Improvement of Air Quality in Beijing During APEC].

In order to evaluate the effects of the implementation of emission reduction measures and the revolution of air quality of Beijing during APEC, the evolution characteristics of air quality was analyzed based on the hourly monitored readings of Olympic Sports Center from 1 to 15 November 2014 released by Environmental Monitoring Station of China, and compared with that in 2013. The results showed that: (1) PM2.5 was the main pollutant in Beijing. The air quality was good during the period of APEC with three obvious pollution events, and it was better than that in the same period in 2013, indicating that the implementation of emission reduction measures had made significant contribution to the improvement of air quality. (2) During the period of APEC, the concentrations of PM2.5 of 5 days were below the World Health Organization (WHO) standard (25 µg · m⁻³), and the concentration of SO2 met the WHO standard during this time. (3) During the period of APEC, the ratio of PM2.5, and PM10 was less than 0.5 when the air quality was good, and gradually increased with the increasing pollution level. The ratio reached 0.9 when the air was seriously polluted. (4) Compared with the same time in 2013, although the implementation of emission reduction measures made contribution to the reduction of the concentration of PM2.5, its contributions to the reduction of SO2 and CO concentration were much more obvious than that of PM2.5, and it had little impact on the reduction of NO2 concentration, and the reduction order of pollutants emission was SO2 > CO > PM > NO2, indicating that the sources, effects and emission reduction of PM2.5 were complex, and further studies are required.

[Analysis on Regional Characteristics of Air Quality Index and Weather Situation in Beijing and Its Surrounding Cities During the APEC].

Analysis on the revolution and regional characteristics of air quality by hourly monitored readings from 1 to 15 November 2014 released by Environmental Monitoring Station of China and research of the impacts of weather situation and meteorological elements released by China Meteorological Administration towards air quality of Beijing and its surrounding cities during the Asia-Pacific Economic Cooperation (APEC) indicated that: (1) The air quality was good because of the implementation of mitigation measures, while the Air Quality Index (AQI) increased along with the termination of mitigation measures. Thus it can be seen that mitigation measures made a great contribution to the improvement of air quality of Beijing and its surrounding cities. (2) Affected by thermal inversion layer, AQI of Beijing and its surrounding cities increased quickly during the initial of the implemental of reducing measures which proved that pollutants would accumulate in the context of unfavourable weather, hence the influence of weather situation towards air quality could not be ignored. (3) Although affected by thermal inversion layer, the concentration of pollutants of Beijing was not accumulated to a high degree at the end period of reducing measures, while Tianjin, Tangshan, Baoding and Xingtai suffered from moderate and severe pollution at the same time which further illustrated that the implementation of mitigation measures have made a great contribution to the improvement of air quality in Beijing during APEC.