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Development of physiologically-based toxicokinetic-toxicodynamic (PBTK-TD) model for 4-nonylphenol (4-NP) reflecting physiological changes according to age in males: Application as a new risk assessment tool with a focus on toxicodynamics
2022
Jeong, Seung-Hyun | Jang, Ji-Hun | Lee, Yong-Bok
Environmental exposure to 4-nonylphenol (4-NP) is extensive, and studies related to human risk assessment must continue. Especially, prediction of toxicodynamics (TDs) related to reproductive toxicity in males is very important in risk-level assessment and management of 4-NP. This study aimed to develop a physiologically-based-toxicokinetic-toxicodynamic (PBTK-TD) model that added a TD prostate model to the previously reported 4-n-nonylphenol (4-n-NP) physiologically-based-pharmacokinetic (PBPK) model. Modeling was performed under the assumption of similar TKs between 4-n-NP and 4-NP because TK experiments on 4-NP, a random-mixture, are practically difficult. This study was very important to quantitatively predict the TKs and TDs of 4-NP by age at exposure using an advanced PBTK-TD model that reflected physiological-changes according to age. TD-modeling was performed based on the reported toxic effects of 4-NP on RWPE-1 cells, a human-prostate-epithelial-cell-line. Through a meta-analysis of reported human physiological data, body weight, tissue volume, and blood flow rate patterns according to age were mathematically modeled. These relationships were reflected in the PBTK-TD model for 4-NP so that the 4-NP TK and TD changes according to age and their differences could be confirmed. Differences in TK and TD parameters of 4-NP at various ages were not large, within 3.61-fold. Point-of-departure (POD) and reference-doses for each age estimated using the model varied as 426.37–795.24 and 42.64–79.52 μg/kg/day, but the differences (in POD or reference doses between ages) were not large, at less than 1.87-times. The PBTK-TD model simulation predicted that even a 100-fold 4-NP PODₘₐₙ dose would not have large toxicity to the prostate. With a focus on TDs, the predicted maximum possible exposure of 4-NP was as high as 6.06–23.60 mg/kg/day. Several toxicity-related values estimated by the dose-response curve were higher than those calculated, depending upon the PK or TK, which would be useful as a new exposure limit for prostate toxicity of 4-NP.
Показать больше [+] Меньше [-]Measurements of odours by sensory analysis or olfactometry
2001
Gouronnec, A.M. (Commissariat a l'Energie Atomique, Gif sur Yvette (France). Institut de Protection et de Surete Nucleaire)
L'olfactometrie ou la mesure des odeurs par analyse sensorielle permet de quantifier les odeurs. Les methodes disponibles donnent acces a la mesure de trois grandeurs: la concentration d'odeur, l'intensite de l'odeur et la gene olfactive. Dans les deux premiers cas, la mesure fait appel a un jury d'experts preselectionnes et dans le troisieme cas, la methode fait appel a un jury de population locale. Il est ainsi possible, non seulement de caracteriser les sources d'odeur et de les comparer entre elles, mais aussi de caracteriser l'environnement d'une source d'odeur
Показать больше [+] Меньше [-]Ni and TiO2 nanoparticles cause adhesion and cytoskeletal changes in human osteoblasts [Erratum: July 2022, Vol.227(6), p.2229]
2021
Štefančík, Michal | Válková, Lucie | Veverková, Jana | Balvan, Jan | Vičar, Tomáš | Babula, Petr | Mašek, Josef | Kulich, Pavel | Pávková Goldbergová, Monika
Titanium-based alloys have established a crucial role in implantology. As material deteriorates overtime, nanoparticles of TiO₂ and Ni are released. This study is focused on the impact of TiO₂ and Ni nanoparticles with size of 100 nm on cytoskeletal and adhesive changes in human physiological and osteoarthritic osteoblasts. The impact of nanoparticles with concentration of 1.5 ng/mL on actin and tubulin expression and gene expression of FAK and ICAM-1 was studied. The cell size and actin expression of physiological osteoblasts decreased in presence of Ni nanoparticles, while TiO₂ nanoparticles caused increase in cell size and actin expression. Both cell lines expressed more FAK as a response to TiO₂ nanoparticles. ICAM-1 gene was overexpressed in both cell lines as a reaction to both types of nanoparticles. The presented study shows a crucial role of Ni and TiO₂ nanoparticles in human osteoblast cytoskeletal and adhesive changes, especially connected with the osteoarthritic cells. Graphical abstract
Показать больше [+] Меньше [-]Lighting for work: a study on the effect of underground low-light environment on miners’ physiology
2022
Li, Jing | Qin, Yaru | Guan, Cheng | Xin, Yanli | Wang, Zhen | Qi, Ruikang
Low-light environment affects human physiology, psychology, and behavior. It causes errors in work and increases accidents. In this study, we built a coal mine lighting simulation experiment system. The system not only includes an experimental environment simulation system and a physiological indicator test system, but also adds a miners’ working simulation system. We aim to study the effect of different illumination levels (0lx, 10lx, 50lx, 100lx, and 200lx) on three indicators: heart rate, electrodermal activity, and respiration. The results show illuminance has a significant negative correlation with all the above three indicators. Heart rate seems to be most significantly affected by illuminance, and it changes significantly from the normal level (200lx) at 50lx. By contrast, the respiratory rate and electrodermal activity change significantly at 10lx. When the illuminance is 50~100lx, all the three indicators return to the normal level. The results suggest that coal mine illumination should be around 50~100lx. When the minimum illumination is less than 10lx, accidents tend to increase.
Показать больше [+] Меньше [-]Haze and health impacts in ASEAN countries: a systematic review
2018
Ramakreshnan, Logaraj | Aghamohammadi, Nasrin | Fong, ChngSaun | Bulgiba, Awang | Zaki, RafdzahAhmad | Wong, LiPing | Sulaiman, NikMeriam
Seasonal haze episodes and the associated inimical health impacts have become a regular crisis among the ASEAN countries. Even though many emerging experimental and epidemiological studies have documented the plausible health effects of the predominating toxic pollutants of haze, the consistency among the reported findings by these studies is poorly understood. By addressing such gap, this review aimed to critically highlight the evidence of physical and psychological health impacts of haze from the available literature in ASEAN countries. Systematic literature survey from six electronic databases across the environmental and medical disciplines was performed, and 20 peer-reviewed studies out of 384 retrieved articles were selected. The evidence pertaining to the health impacts of haze based on field survey, laboratory tests, modelling and time-series analysis were extracted for expert judgement. In specific, no generalization can be made on the reported physical symptoms as no specific symptoms recorded in all the reviewed studies except for throat discomfort. Consistent evidence was found for the increase in respiratory morbidity, especially for asthma, whilst the children and the elderly are deemed to be the vulnerable groups of the haze-induced respiratory ailments. A consensual conclusion on the association between the cardiovascular morbidity and haze is unfeasible as the available studies are scanty and geographically limited albeit of some reported increased cases. A number of modelling and simulation studies demonstrated elevating respiratory mortality rates due to seasonal haze exposures over the years. Besides, evidence on cancer risk is inconsistent where industrial and vehicular emissions are also expected to play more notable roles than mere haze exposure. There are insufficient regional studies to examine the association between the mental health and haze. Limited toxicological studies in ASEAN countries often impede a comprehensive understanding of the biological mechanism of haze-induced toxic pollutants on human physiology. Therefore, the lack of consistent evidence among the reported haze-induced health effects as highlighted in this review calls for more intensive longitudinal and toxicological studies with greater statistical power to disseminate more reliable and congruent findings to empower the institutional health planning among the ASEAN countries.
Показать больше [+] Меньше [-]A systemic approach to identify signaling pathways activated during short-term exposure to traffic-related urban air pollution from human blood
2018
Vargas, José Eduardo | Kubesch, Nadine | Hernandéz-Ferrer, Carles | Carrasco-Turigas, Glória | Bustamante, Mariona | Nieuwenhuijsen, Mark | González Juan R.,
The molecular mechanisms that promote pathologic alterations in human physiology mediated by short-term exposure to traffic pollutants remains not well understood. This work was to develop mechanistic networks to determine which specific pathways are activated by real-world exposures of traffic-related air pollution (TRAP) during rest and moderate physical activity (PA). A controlled crossover study to compare whole blood gene expression pre and post short-term exposure to high and low of TRAP was performed together with systems biology analysis. Twenty-eight healthy volunteers aged between 21 and 53 years were recruited. These subjects were exposed during 2 h to different pollution levels (high and low TRAP levels), while either cycling or resting. Global transcriptome profile of each condition was performed from human whole blood samples. Microarrays analysis was performed to obtain differential expressed genes (DEG) to be used as initial input for GeneMANIA software to obtain protein-protein (PPI) networks. Two networks were found reflecting high or low TRAP levels, which shared only 5.6 and 15.5% of its nodes, suggesting specific cell signaling pathways being activated in each environmental condition. However, gene ontology analysis of each PPI network suggests that each level of TRAP regulate common members of NF-κB signaling pathway. Our work provides the first approach describing mechanistic networks to understand TRAP effects on a system level.
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