186 research outputs found
Assessing binary mixture effects from genotoxic and endocrine disrupting environmental contaminants using infrared spectroscopy
Benzo[a]pyrene (B[a]P), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent contaminants and concern has arisen over co-exposure of organisms when the chemicals exist in mixtures. Herein, attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy was used to identify biochemical alterations induced in cells by single and binary mixtures of these environmental chemicals. It was also investigated as a method to identify if interactions are occurring in mixtures and as a possible tool to predict mixture effects. Mallard fibroblasts were treated with single and binary mixtures of B[a]P, PCB126, PCB153, BDE47 and BDE209. Comparison of observed spectra from cells treated with binary mixtures with expected additive spectra, which were created from individual exposure spectra, indicated that in many areas of the spectrum, less-than-additive binary mixture effects may occur. However, possible greater-than-additive alterations were identified in the 1650-1750 cm-1 lipid region and may demonstrate a common mechanism of B[a]P and PCBs or PBDEs, which can enhance toxicity in mixtures
Genotoxic mixtures and dissimilar action: Concepts for prediction and assessment
This article has been made available through the Brunel Open Access Publishing Fund. This article is distributed under the terms of the
creative commons Attribution license which permits any use, distribution, and reproduction in any medium, provided the original author(s)and the source are credited.Combinations of genotoxic agents have frequently been assessed without clear assumptions regarding their expected (additive) mixture effects, often leading to claims of synergisms that might in fact be compatible with additivity. We have shown earlier that the combined effects of chemicals, which induce micronuclei (MN) in the cytokinesis-block micronucleus assay in Chinese hamster ovary-K1 cells by a similar mechanism, were additive according to the concept of concentration addition (CA). Here, we extended these studies and investigated for the first time whether valid additivity expectations can be formulated for MN-inducing chemicals that operate through a variety of mechanisms, including aneugens and clastogens (DNA cross-linkers, topoisomerase II inhibitors, minor groove binders). We expected that their effects should follow the additivity principles of independent action (IA). With two mixtures, one composed of various aneugens (colchicine, flubendazole, vinblastine sulphate, griseofulvin, paclitaxel), and another composed of aneugens and clastogens (flubendazole, doxorubicin, etoposide, melphalan and mitomycin C), we observed mixture effects that fell between the additivity predictions derived from CA and IA. We achieved better agreement between observation and prediction by grouping the chemicals into common assessment groups and using hybrid CA/IA prediction models. The combined effects of four dissimilarly acting compounds (flubendazole, paclitaxel, doxorubicin and melphalan) also fell within CA and IA. Two binary mixtures (flubendazole/paclitaxel and flubendazole/doxorubicin) showed effects in reasonable agreement with IA additivity. Our studies provide a systematic basis for the investigation of mixtures that affect endpoints of relevance to genotoxicity and show that their effects are largely additive.UK Food Standards Agenc
Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?
© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio
Where are the Uranus Trojans?
The area of stable motion for fictitious Trojan asteroids around Uranus'
equilateral equilibrium points is investigated with respect to the inclination
of the asteroid's orbit to determine the size of the regions and their shape.
For this task we used the results of extensive numerical integrations of orbits
for a grid of initial conditions around the points L4 and L5, and analyzed the
stability of the individual orbits. Our basic dynamical model was the Outer
Solar System (Jupiter, Saturn, Uranus and Neptune). We integrated the equations
of motion of fictitious Trojans in the vicinity of the stable equilibrium
points for selected orbits up to the age of the Solar system of 5 billion
years. One experiment has been undertaken for cuts through the Lagrange points
for fixed values of the inclinations, while the semimajor axes were varied. The
extension of the stable region with respect to the initial semimajor axis lies
between 19.05 < a < 19.3 AU but depends on the initial inclination. In another
run the inclination of the asteroids' orbit was varied in the range 0 < i < 60
and the semimajor axes were fixed. It turned out that only four 'windows' of
stable orbits survive: these are the orbits for the initial inclinations 0 < i
< 7, 9 < i < 13, 31 < i < 36 and 38 < i < 50. We postulate the existence of at
least some Trojans around the Uranus Lagrange points for the stability window
at small and also high inclinations.Comment: 15 pages, 12 figures, submitted to CMD
Oriented Matroids -- Combinatorial Structures Underlying Loop Quantum Gravity
We analyze combinatorial structures which play a central role in determining
spectral properties of the volume operator in loop quantum gravity (LQG). These
structures encode geometrical information of the embedding of arbitrary valence
vertices of a graph in 3-dimensional Riemannian space, and can be represented
by sign strings containing relative orientations of embedded edges. We
demonstrate that these signature factors are a special representation of the
general mathematical concept of an oriented matroid. Moreover, we show that
oriented matroids can also be used to describe the topology (connectedness) of
directed graphs. Hence the mathematical methods developed for oriented matroids
can be applied to the difficult combinatorics of embedded graphs underlying the
construction of LQG. As a first application we revisit the analysis of [4-5],
and find that enumeration of all possible sign configurations used there is
equivalent to enumerating all realizable oriented matroids of rank 3, and thus
can be greatly simplified. We find that for 7-valent vertices having no
coplanar triples of edge tangents, the smallest non-zero eigenvalue of the
volume spectrum does not grow as one increases the maximum spin \jmax at the
vertex, for any orientation of the edge tangents. This indicates that, in
contrast to the area operator, considering large \jmax does not necessarily
imply large volume eigenvalues. In addition we give an outlook to possible
starting points for rewriting the combinatorics of LQG in terms of oriented
matroids.Comment: 43 pages, 26 figures, LaTeX. Version published in CQG. Typos
corrected, presentation slightly extende
Debris disk size distributions: steady state collisional evolution with P-R drag and other loss processes
We present a new scheme for determining the shape of the size distribution,
and its evolution, for collisional cascades of planetesimals undergoing
destructive collisions and loss processes like Poynting-Robertson drag. The
scheme treats the steady state portion of the cascade by equating mass loss and
gain in each size bin; the smallest particles are expected to reach steady
state on their collision timescale, while larger particles retain their
primordial distribution. For collision-dominated disks, steady state means that
mass loss rates in logarithmic size bins are independent of size. This
prescription reproduces the expected two phase size distribution, with ripples
above the blow-out size, and above the transition to gravity-dominated
planetesimal strength. The scheme also reproduces the expected evolution of
disk mass, and of dust mass, but is computationally much faster than evolving
distributions forward in time. For low-mass disks, P-R drag causes a turnover
at small sizes to a size distribution that is set by the redistribution
function (the mass distribution of fragments produced in collisions). Thus
information about the redistribution function may be recovered by measuring the
size distribution of particles undergoing loss by P-R drag, such as that traced
by particles accreted onto Earth. Although cross-sectional area drops with
1/age^2 in the PR-dominated regime, dust mass falls as 1/age^2.8, underlining
the importance of understanding which particle sizes contribute to an
observation when considering how disk detectability evolves. Other loss
processes are readily incorporated; we also discuss generalised power law loss
rates, dynamical depletion, realistic radiation forces and stellar wind drag.Comment: Accepted for publication by Celestial Mechanics and Dynamical
Astronomy (special issue on EXOPLANETS
Planetary Dynamics and Habitable Planet Formation In Binary Star Systems
Whether binaries can harbor potentially habitable planets depends on several
factors including the physical properties and the orbital characteristics of
the binary system. While the former determines the location of the habitable
zone (HZ), the latter affects the dynamics of the material from which
terrestrial planets are formed (i.e., planetesimals and planetary embryos), and
drives the final architecture of the planets assembly. In order for a habitable
planet to form in a binary star system, these two factors have to work in
harmony. That is, the orbital dynamics of the two stars and their interactions
with the planet-forming material have to allow terrestrial planet formation in
the habitable zone, and ensure that the orbit of a potentially habitable planet
will be stable for long times. We have organized this chapter with the same
order in mind. We begin by presenting a general discussion on the motion of
planets in binary stars and their stability. We then discuss the stability of
terrestrial planets, and the formation of potentially habitable planets in a
binary-planetary system.Comment: 56 pages, 29 figures, chapter to appear in the book: Planets in
Binary Star Systems (Ed. N. Haghighipour, Springer publishing company
Ablation and Chemical Alteration of Cosmic Dust Particles During Entry into the Earth's Atmosphere
Mixture Risk Assessment of Complex Real-Life MixturesâThe PANORAMIX Project
Humans are involuntarily exposed to hundreds of chemicals that either contaminate our environment and food or are added intentionally to our daily products. These complex mixtures of chemicals may pose a risk to human health. One of the goals of the European Unionâs Green Deal and zero-pollution ambition for a toxic-free environment is to tackle the existent gaps in chemical mixture risk assessment by providing scientific grounds that support the implementation of adequate regulatory measures within the EU. We suggest dealing with this challenge by: (1) characterising âreal-lifeâ chemical mixtures and determining to what extent they are transferred from the environment to humans via food and water, and from the mother to the foetus; (2) establishing a high-throughput whole-mixture-based in vitro strategy for screening of real-life complex mixtures of organic chemicals extracted from humans using integrated chemical profiling (suspect screening) together with effect-directed analysis; (3) evaluating which human blood levels of chemical mixtures might be of concern for childrenâs development; and (4) developing a web-based, ready-to-use interface that integrates hazard and exposure data to enable component-based mixture risk estimation. These concepts form the basis of the Green Deal project PANORAMIX, whose ultimate goal is to progress mixture risk assessment of chemicals.Horizon 2020 research and innovation programme, the Green Deal project PANORAMIX Grant Agreement No. 10103663
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