The probabilistic aggregate consumer exposure model (PACEM): Validation and comparison to a lower-tier assessment for the cyclic siloxane D5

a b s t r a c t a r t i c l e i n f o Current practice of chemical risk assessment for consumer product ingredients still rarely exercises the aggregation of multi-source exposure. However, focusing on a single dominant source/pathway combination may lead to a significant underestimation of the risk for substances present in numerous consumer products, which often are used simultaneously. Moreover, in most cases complex multi-route exposure scenarios also need to be accounted for. This paper introduces and evaluates the performance of the Probabilistic Aggregate Consumer Exposure Model (PACEM) applied in the context of a tiered approach to exposure assessment for ingredients in cosmetics and personal care products (C&PCPs) using decamethylcyclopentasiloxane (D5) as a worked example. It is demonstrated that PACEM predicts a more realistic, but still conservative aggregate exposure within the Dutch adult population when compared to a deterministic point estimate obtained in a lower tier screening assessment. An overall validation of PACEM is performed by quantitatively relating and comparing its estimates to currently available human biomonitoring and environmental sampling data. Moderate (by maximum one order of magnitude) overestimation of exposure is observed due to a justified conservatism built into the model structure, resulting in the tool being suitable for risk assessment

On the dynamics of the adenylate energy system: homeorhesis vs homeostasis.

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life

Spathian (Lower Triassic) ammonoids from western USA (Idaho, California, Utah and Nevada)

The Early Triassic marine deposits are distributed over a large area in the Western United State and are very rich in ammonoids. The detailed bed by bed study of their stratigraphic distribution allowed us to present a new very precise biochronological framework of the Spathian stage (Middle to Late Olenekian). Nineteen new ammonoid species belonging to the genera Pseudosvalbardiceras ?, Prohungarites, Silberlingeria, Bajarunia, Hemilecanites, Arctomeekoceras, Xenoceltites, Nordophiceratoides, Sibirites, Columbites, Hellenites and Svalbardiceras and eighteen new spathian ammonoid genera (Courtilloticeras, Yvesgalleticeras, Marcouxia, Jeanbesseiceras, Tapponnierites, Gaudemerites, Deweveria, Ceccaisculitoides, Coscaites, Eschericeratites, Carteria, Goricanites, Tardicolumbites, Cowboyiceras, Nordophiceratoides, Glabercolumbites) have been described in a recent preliminary report by Guex et al. (2005) on the basis of unpublished material collected in the western USA (Idaho, Utah, Nevada and California). In addition, one new genus (Rudolftruempyiceras) and four new species are also described in the present work. The precise stratigraphic description of the collected sections is given in the present Memoir and the stratigraphic distribution of 88 species belonging to 51 genera is established herein. Twenty-three new biochronological horizons are defined thanks to these new data. The Cowboy Pass section (Utah) records a very interesting terrestrial (red beds and very shallow water deposits) transition between the marine Late Smithian and the Earliest Spathian faunas. That worldwide short lived regression followed by a major transgression fits the model proposed by Guex et al. 2001 and Morard et al. 2003 for the Pliensbachian - Toarcian transition: major volcanic SO2 emissions generating a short but major cooling and glaciation associated with an important sea level fall and large scale emersions, followed by a warming inducing a transgressive episode with some anoxic deposits

Quantification and molecular characterization of the feline leukemia virus A receptor

Virus receptors and their expression patterns on the cell surface determine the cell tropism of the virus, host susceptibility and the pathogenesis of the infection. Feline thiamine transport protein 1 (fTHTR1) has been identified as the receptor for feline leukemia virus (FeLV) A. The goal of the present study was to develop a quantitative, TaqMan real-time PCR assay to investigate fTHTR1 mRNA expression in tissues of uninfected and FeLV-infected cats, cats of different ages, in tumor tissues and leukocyte subsets. Moreover, the receptor was molecularly characterized in different feline species. fTHTR1 mRNA expression was detected in all 30 feline tissues investigated, oral mucosa scrapings and blood. Importantly, identification of significant differences in fTHTR1 expression relied on normalization with an appropriate reference gene. The lowest levels were found in the blood, whereas high levels were measured in the oral mucosa, salivary glands and the musculature. In the blood, T lymphocytes showed significantly higher fTHTR1 mRNA expression levels than neutrophil granulocytes. In vitro activation of peripheral blood mononuclear cells with concanavalin A alone or followed by interleukin-2 led to a transient increase of fTHTR1 mRNA expression. In the blood, but not in the examined tissues, FeLV-infected cats tended to have lower fTHTR1 mRNA levels than uninfected cats. The fTHTR1 mRNA levels were not significantly different between tissues with lymphomas and the corresponding non-neoplastic tissues. fTHTR1 was highly conserved among different feline species (Iberian lynx, Asiatic and Indian lion, European wildcat, jaguarundi, domestic cat). In conclusion, while ubiquitous fTHTR1 mRNA expression corresponded to the broad target tissue range of FeLV, particularly high fTHTR1 levels were found at sites of virus entry and shedding. The differential susceptibility of different species to FeLV could not be attributed to variations in the fTHTR1 sequence