Abstract: Within EU marketing authorization procedures of human and veterinary medicinal products (HMP and VMP), an environmental risk assessment (ERA) has to be performed. In the event that an unacceptable environmental risk is identified, risk mitigation measures (RMM) shall be applied in order to reduce environmental exposure to the pharmaceutical. Within the authorization procedures of HMP, no RMM have been applied so far, except for specific precautions for the disposal of the unused medicinal product or waste materials. For VMP, a limited number of RMM do exist. The aim of this study was to develop consistent and efficient RMM. Therefore, existing RMM were compiled from a summary of product characteristics of authorized pharmaceuticals, and new RMM were developed and evaluated. Based on the results, appropriate RMM were applied within the authorization procedures of medicinal products. For HMP, except for the existing precautions for disposal, no further reasonable measures could be developed. For VMP, two specific precautions for disposal and 17 specific precautions for use in animals were proposed as RMM.
Abstract: Chemical atherogenesis is an emerging field that describes how environmental pollutants and endogenous toxins perturb critical pathways that regulate lipid metabolism and inflammation, thus injuring cells found within the vessel wall. Despite growing awareness of the role of environmental pollutants in the development of cardiovascular disease, the field of chemical atherogenesis can broadly include both exogenous and endogenous poisons and the study of molecular, biochemical, and cellular pathways that become dysregulated during atherosclerosis. This integrated approach is logical because exogenous and endogenous toxins often share the same mechanism of toxicity. Chemical atherogenesis is a truly integrative discipline because it incorporates concepts from several different fields, including biochemistry, chemical biology, pharmacology, and toxicology. This review will provide an overview of this emerging research area, focusing on cellular and animal models of disease.
Abstract: For more than 100 years, an electrochemical plant has been operating in Flix (Catalonia, Spain) by the Ebro River. Its activities have originated a severe accumulation of environmental contaminants (metals, organochlorinated pesticides and radionuclides) in sediments of the Flix reservoir, while mercury (Hg) has been also frequently released to the air. Environmental exposure to industrial pollutants has been associated with decreased intelligence and behavioral problems. In the present study, we assessed, in 53 children living in the village of Flix and the surroundings, the relationships between the concentrations of a number of trace elements (As, Be, Cd, Cs, Hg, Mn, Ni, Pb, Sn, Tl, U and V) in hair and the levels of testosterone in blood, with respect to potential neuropsychological alterations. Lead (Pb) and Hg showed the highest mean concentrations in hair samples. However, the current Hg levels were lower than those previously found in children living in the same zone, while the concentration of the remaining elements was similar to those reported in the scientific literature. The outcomes of certain neuropsychological indicators showed a significant correlation with metals, such as Pb and uranium (U). More specifically, these elements were negatively correlated with working memory and hit reaction time, suggesting impulsivity. In summary, although Pb and U concentrations in hair were within standard levels, both metals could be correlated with certain, but minor, neuropsychological alterations in the childhood population of Flix. These findings should be confirmed by future birth cohort studies, with bigger study populations and using more complex statistical analyses, focused on human exposure to these specific elements.
Abstract: An experimental assessment of personal exposure to PM10 in 59 office workers was carried out in Dublin; Ireland. Two hundred and fifty five samples of 24 hour personal exposure were collected in real time over a 28 month period. The investigation included an assessment of the uptake of pollutants in the lungs during various daily activities using a Human Respiratory Tract Model. The results of the investigation showed that indoor air quality was the overriding determinant of average daily personal exposure as participants in the study spent over 92% of their time indoors. Exposure in the workplace and exposure at home were the most important microenvironments in total uptake of particulate matter. Exposure while commuting or shopping were found to play a minor role in comparison. The investigation highlighted the importance of considering pollutant uptake as well as personal exposure among receptors where variations in levels of physical activity and duration of exposure are present.
Toxics2013, 1(1), 46-59; doi:10.3390/toxics1010046 - published online 25 November 2013 Show/Hide Abstract
Abstract: Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D). Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.
Toxics2013, 1(1), 36-45; doi:10.3390/toxics1010036 - published online 19 November 2013 Show/Hide Abstract
Abstract: Due to the widespread use of silver nanoparticles in consumer products, the toxicity of silver nanoparticles has also been studied in relation to their application. However, most genotoxicity studies of silver nanoparticles have been performed in vitro. Therefore, this study evaluated the DNA damage to lung cells caused by repeated inhalation of silver nanoparticles. Male Sprague Dawley rats were exposed to silver nanoparticles for 12 weeks in a whole-body inhalation chamber. The animals were divided into one control group and three dose groups that were exposed to silver nanoparticles (14–15 nm diameter) at concentrations of 0.66 × 106 particles/cm3 (49 μg/m3, low dose), 1.41 × 106 particles/cm3 (117 μg/m3, middle dose), and 3.24 × 106 particles /cm3 (381 μg/m3, high dose), respectively, for six hours/day over 12 weeks. The rats were sacrificed after the 12-week exposure period and the DNA damage assessed using a Comet assay of cells obtained from the right lungs. The olive tail moment values were 2.93 ± 0.19, 3.81 ± 0.23, 3.40 ± 0.22, and 5.16 ± 0.32 for the control, low-, middle-, and high-dose groups, respectively. Although no dose-dependent results were observed, a significant increase in the level of DNA damage was noted for the high-dose group.