Review of the toxicity of chemical mixtures: Theory, policy, and regulatory practice.
ABSTRACT An analysis of current mixture theory, policy, and practice was conducted by examining standard reference texts, regulatory guidance documents, and journal articles. Although this literature contains useful theoretical concepts, clear definitions of most terminology, and well developed protocols for study design and statistical analysis, no general theoretical basis for the mechanisms and interactions of mixture toxicity could be discerned. There is also a poor understanding of the relationship between exposure-based and internal received dose metrics. This confounds data interpretation and limits reliable determinations of the nature and extent of additivity. The absence of any generally accepted classification scheme for either modes/mechanisms of toxic action or of mechanisms of toxicity interactions is problematic as it produces a cycle in which research and policy are interdependent and mutually limiting. Current regulatory guidance depends heavily on determination of toxicological similarity concluded from the presence of a few prominent constituents, assumed from a common toxicological effect, or presumed from an alleged similar toxic mode/mechanism. Additivity, or the lack of it, is largely based on extrapolation of existing knowledge for single chemicals in this context. Thus, regulatory risk assessment protocols lack authoritative theoretical underpinnings, creating substantial uncertainty. Development of comprehensive classification schemes for modes/mechanisms of toxic action and mechanisms of interaction is needed to ensure a sound theoretical foundation for mixture-related regulatory activity and provide a firm basis for iterative hypothesis development and experimental testing.
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ABSTRACT: In saturation diving, divers stay under pressure until most of their tissues are saturated with breathing gas. Divers spend a long time in isolation exposed to increased partial pressure of oxygen, potentially toxic gases, bacteria, and bubble formation during decompression combined with shift work and long periods of relative inactivity. Hyperoxia may lead to the production of reactive oxygen species (ROS) that interact with cell structures, causing damage to proteins, lipids, and nucleic acid. Vascular gas-bubble formation and hyperoxia may lead to dysfunction of the endothelium. The antioxidant status of the diver is an important mechanism in the protection against injury and is influenced both by diet and genetic factors. The factors mentioned above may lead to production of heat shock proteins (HSP) that also may have a negative effect on endothelial function. On the other hand, there is a great deal of evidence that HSPs may also have a "conditioning" effect, thus protecting against injury. As people age, their ability to produce antioxidants decreases. We do not currently know the capacity for antioxidant defense, but it is reasonable to assume that it has a limit. Many studies have linked ROS to disease states such as cancer, insulin resistance, diabetes mellitus, cardiovascular diseases, and atherosclerosis as well as to old age. However, ROS are also involved in a number of protective mechanisms, for instance immune defense, antibacterial action, vascular tone, and signal transduction. Low-grade oxidative stress can increase antioxidant production. While under pressure, divers change depth frequently. After such changes and at the end of the dive, divers must follow procedures to decompress safely. Decompression sickness (DCS) used to be one of the major causes of injury in saturation diving. Improved decompression procedures have significantly reduced the number of reported incidents; however, data indicate considerable underreporting of injuries. Furthermore, divers who are required to return to the surface quickly are under higher risk of serious injury as no adequate decompression procedures for such situations are available. Decompression also leads to the production of endothelial microparticles that may reduce endothelial function. As good endothelial function is a documented indicator of health that can be influenced by regular exercise, regular physical exercise is recommended for saturation divers. Nowadays, saturation diving is a reasonably safe and well controlled method for working under water. Until now, no long-term impact on health due to diving has been documented. However, we still have limited knowledge about the pathophysiologic mechanisms involved. In particular we know little about the effect of long exposure to hyperoxia and microparticles on the endothelium. © 2014 American Physiological Society. Compr Physiol 4:1229-1272, 2014.Comprehensive Physiology. 07/2014; 4(3):1229-72.
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ABSTRACT: During the last years, reference process modeling becomes an efficient approach for reuse in business process modeling (BPM). Many BPM tools provide mechanisms to adapt reference process models in order to meet new needs. However, this adaptation results in a set of variants which have to be managed. One of the most proposed solutions is the configurable process model. Therefore, evolving this configurable process model in terms of activities, a data flows and resources changes becomes a crucial issue. In this paper, we propose a process pattern which guides designers for managing evolution of configurable reference process models.Information Science and Technology (CIST), 2012 Colloquium in; 01/2012
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ABSTRACT: Abstract This study describes the use of pesticides mixtures and their potential association with comet assay results in 223 rice field workers in Colombia. Thirty-one pesticides were quantified in blood, serum and urine (15 organochlorines, 10 organophosphorus, 5 carbamates, and ethylenethiourea) and the comet assay was performed. Twenty-four (77,42%) pesticides were present in the workers. The use of the maximum-likelihood factor analysis identified eight different mixtures. Afterwards, robust regressions were used to explore associations between the factors identified and the comet assay. Two groups of mixtures- α-BHC, HCB and β-BHC (β: 1,21, 95% CI: 0,33-2,10), and pirimiphos-methyl, malathion, bromophos-methyl, and bromophos-ethyl (β: 11,97, 95% CI: 2,34-21,60)- were associated with a higher percentage of DNA damage and comet tail length, respectively. The findings suggest that exposure to pesticides varies greatly among rice field workers.Archives of Environmental and Occupational Health 06/2014; · 0.47 Impact Factor