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Selected AbstractsGene and protein expressions in human cord blood cells after exposure to acrylonitrileJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2005Cristina Diodovich Abstract Acrylonitrile is a very high volume industrial chemical used primarily in the manufacture of plastics and rubber, which displays a pronounced acute toxicity and may be carcinogenic. The damage to the hematopoietic function by acrylonitrile may result from interference with cytokine production and cytokine receptor binding. Our present data show that acrylonitrile modulates the expression of some genes implicated in cell differentiation, cell-cycle progression, and clonogenic potential of human cord blood cells. A macroarray hybridization analysis showed that expression of the CXCR4, MCP-1, and MRP8 genes was modified by acrylonitrile exposure. Moreover, the acrylonitrile cell target seems to be the myeloid compartment, as assessed by a CFU-GM assay. In particular, the downregulation of CXCR4, MCP1, and MRP8 can be responsible for the observed reduction of cell proliferation and clonogenic capability of CFU-GM precursors. A Western blot assay showed an acrylonitrile-dependent induction of Bax, while Bcl-2 expression changed only after 48 h of chemical exposure. Bax was overexpressed in respect to Bcl-2, and this fact can be responsible for the induction in cell death after 24 h of treatment. C-fos and c-jun were also downregulated after 24 h and 6 h of treatment, respectively. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:204,212, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20090 [source] Resistance of Nutrient-Deprived Listeria monocytogenes 10403S and a ,sigB Mutant to Chemical Stresses in the Presence or Absence of OxygenJOURNAL OF FOOD SCIENCE, Issue 7 2008B. Lungu ABSTRACT:, Nutrient-deprived Listeria monocytogenes have increased resistance to processing control measures. Heat-stressed L. monocytogenes cells produce higher counts under anaerobic conditions and SigB reportedly contributes to the survival of environmentally stressed Gram-positive bacteria. In this study, a wild type (wt) strain, L. monocytogenes 10403S, and a ,sigB mutant, FSLA1-254, were stressed by starvation in phosphate buffered saline coupled with exposure to chemicals with/without oxygen. In the absence of chemicals, the mutant survived starvation almost as well as the wt, suggesting that the starvation survival response (SSR) in L. monocytogenes was SigB-independent. Conversely, in the presence of chemical stresses the SSR results differed depending on the chemical used. In the presence of sodium chloride (SC), both strains were able to express an SSR under aerobic conditions but not under anaerobic conditions. However, in the presence of sodium propionate (SP), the mutant yielded counts that were 2 log CFU/mL lower than the controls and their aerobic counterparts. In the presence of sodium lactate (SL), the mutant yielded counts that were approximately 3 log CFU/mL lower than the wt under anaerobic conditions. Thus, for the chemical stress produced by SC, the SSR appeared to be SigB-independent. The SSR of L. monocytogenes appeared to be SigB-dependent following exposure to SP or SL under anaerobic conditions. Following exposure to sodium diacetate or lauric acid, both strains were unable to express an SSR. No detectable CFUs were observed after 14 to 21 d under either aerobic or anaerobic incubation. Therefore, these 2 chemicals could be used in biocidal formulations against L. monocytogenes cells under aerobic or anaerobic conditions. [source] Benzidine transformation processes in natural sedimentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2006Joel Harden Abstract Aromatic amines, such as benzidine and 3,3,-dichlorobenzidine, are chemicals used in the pigment and dye processes. Release of these compounds into the environment is important because of their carcinogenic and toxic nature. In the present study, the sediment and water samples were collected from Lake Macatawa (Holland, MI, USA) and subsequently spiked with benzidine. The grain size distribution of the sediment samples investigated here ranged in composition from sandy to silty-clay sediment types. The sediment,water systems spiked with benzidine were incubated under anaerobic conditions at 4, 15, and 23°C for 211 d. Degradation of benzidine was observed over the time-course analysis of the sediment,water mixtures. Three possible metabolites (aniline, 2-ethyl-1-hexanol, and 1-amino-2-hexene) were observed during this investigation as a result of gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. No metabolites were observed in autoclaved bottles, suggesting that the transformation of benzidine in the sediment,water mixtures was the result of microbial activity. From sediment,water distribution experiments, benzidine demonstrated higher sorption affinity for the different sediment phases than its degradation product, aniline. Therefore, microbially mediated transformation of benzidine to aniline is expected to yield a greater total concentration of the more mobile compound, aniline, in the water phase and a greater possibility for transport of aniline in the water phase. [source] Impacts of federal precursor chemical regulations on methamphetamine arrestsADDICTION, Issue 4 2005James K. Cunningham ABSTRACT Aims The US government regulated precursor chemicals, ephedrine and pseudoephedrine, multiple times to limit methamphetamine production/availability and thus methamphetamine problems. Research has found that the regulations reduced methamphetamine hospital admissions, but authors have argued that other problems were unaffected. This study examines whether the regulations impacted methamphetamine arrests. Design ARIMA-intervention time-series analysis with control series. Setting California (1982,2001). Measurements Dependent variable series: monthly methamphetamine arrests. Control series: monthly marijuana arrests and cocaine/heroin arrests. Interventions Bulk powder ephedrine and pseudoephedrine: regulated November 1989. Products containing ephedrine as the single active medicinal ingredient: regulated August 1995. Pseudoephedrine products: regulated October 1997. Large-scale producers used ephedrine and pseudoephedrine in these forms. Ephedrine combined with other active medicinal ingredients (e.g. various cold medicines),used mainly by small-scale producers: regulated October 1996. Findings The regulation targeting small-scale producers (1996) had no significant impact. In contrast, methamphetamine arrests stopped rising and dropped 31% to 45% each of the three times precursor chemicals used by large-scale producers were regulated. Within 3 years of the bulk powder regulation (1989) and again within 2 years of the ephedrine single ingredient regulation (1995), arrests fully rebounded. During the 4 years following the last regulation (pseudoephedrine products, 1997) arrests only partially rebounded. These effects parallel those reported on hospital admissions. The control series were generally unaffected. Conclusions Precursor regulations targeting large-scale producers impacted methamphetamine arrests, a criminal justice problem, much as they impacted the public health problem of methamphetamine hospital admissions. Ongoing research is needed to determine whether these problems eventually fully rebound from the last regulation. [source] REACH-driven developments in analysis and physicochemistry,FLAVOUR AND FRAGRANCE JOURNAL, Issue 3 2010A. Chaintreau Abstract The enforcement of the REACH regulation in the fragrance domain has created new challenges for the analytical and physical chemist. Many chemicals used as perfumery ingredients are hydrophobic, because low-polar compounds exhibit a higher substantivity (i.e. persistence after application) than do polar compounds. As a result, the usual protocols are often unsuitable and new methods must be developed. Biodegradation studies sometimes call for the quantification of traces of such hydrophobic analytes in complex media (e.g. waste water, aqueous surfactant solutions). Existing sample preparation techniques are either inefficient or time consuming. A new approach is proposed, based on single-use absorbants, which allows accurate quantification down to the 100 ppb range. This extremely simple technique allows good throughput analyses. Determining the environmental profile of a compound requires the determination of some physical constants. Among these, solubility in water can be obtained from theoretical models or experimentally, but the resulting values may greatly differ as a function of the model or the protocol. Several experimental approaches are critically discussed and compared with a reference technique. The air-to-water partition coefficients are determined by using an improved version of the previously developed static-and-trapped headspace technique. Copyright © 2009 John Wiley & Sons, Ltd. [source] Cross-adaptation of a model human stress-related odour with fragrance chemicals and ethyl esters of axillary odorants: gender-specific effectsFLAVOUR AND FRAGRANCE JOURNAL, Issue 5 2009Charles J. Wysocki Abstract The human axillae have a characteristic odour that is comprised of or generated from a mixture of C6,C11 normal, branched, hydroxy- and unsaturated acids (and other compounds). We used ethyl esters of one of these acids and a palette of fragrance compounds (tested individually) to evaluate the effectiveness of these chemicals to reduce the overall olfactory impact of a model of human stress-related odour (SRO) by cross-adaptation (adaptation to one odorant can reduce sensitivity to other odorants). Sensory volunteers provided hedonic and intensity ratings of the SRO and of each of the potential cross-adapting agents prior to 2.5 min of induced olfactory adaptation to each agent. Across adaptation, possible cross-adaptation was evaluated by intermittent evaluations of the perceived intensity of the SRO. We determined that some potential cross-adapting agents did reduce the impact of the SRO; however, the same chemicals were not necessarily effective for male and female SRO. Indeed, the list of effective chemicals depended upon the gender of the donor of the SRO and the gender of the sensory volunteer, suggesting a gender-specific response to both the SRO-stimuli used and the fragrance chemicals used to cross-adapt it. Copyright © 2009 John Wiley & Sons, Ltd. [source] Combined exposures to anti-androgenic chemicals: steps towards cumulative risk assessmentINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010A. Kortenkamp Summary There is widespread exposure to anti-androgens, a group of chemicals able to disrupt androgen action in foetal life, with irreversible de-masculinizing consequences. Substances of concern include certain phthalates, pesticides and chemicals used in cosmetics and personal care products. Although people come into contact with several anti-androgens, chemicals risk assessment normally does not take account of the effects of combined exposures. However, a disregard for combination effects may lead to underestimations of risks and for this reason, we have assessed the feasibility of conducting cumulative risk assessment, where the focus is on considering the effects of exposure to multiple chemicals, via multiple routes and pathways. Following recent recommendations by the US National Research Council, we have, for the first time, included phthalates and other anti-androgenic chemicals, a total of 15 substances. On the basis of exposure estimates for the individual chemicals and reference doses for anti-androgenicity, we have used the hazard index approach. We show that the cumulative risks from anti-androgen exposures exceed acceptable levels for people on the upper end of exposure levels. The value obtained for median exposures to the 15 substances can be judged tolerable. However, significant knowledge gaps exist that prevent us from arriving at definitive conclusions. Of greatest concern is an absence of appropriate in vivo toxicity data about large numbers of in vitro androgen receptor antagonists. Knowledge about the effect profiles of these chemicals will lead to higher risk estimates. Our analysis suggests that risk reductions can be achieved by limiting exposures to the plasticizer diethyl hexyl phthalate, the cosmetic ingredients butyl- and propyl paraben, the pesticides vinclozolin, prochloraz and procymidone and bisphenol A. [source] Determinants of skin sensitisation potentialJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2008David W. Roberts Abstract Skin sensitisation is an important toxicological endpoint. The possibility that chemicals used in the workplace and in consumer products might cause skin sensitisation is a major concern for individuals, for employers and for marketing. In European REACH (Registration, Evaluation, and Authorisation of Chemicals) legislation, the sensitising potential should therefore be assessed for chemicals below the 10 ton threshold. Development of methods for prediction of skin sensitisation potential without animal testing has been an active research area for some time, but has received further impetus with the advent of REACH and the EU Cosmetics Directive (EU 2003). This paper addresses the issue of non-animal based prediction of sensitisation by a mechanistic approach. It is known that the sequence of molecular, biomolecular and cellular events between exposure to a skin sensitiser and development of the sensitised state involves several stages, in particular penetration through the stratum corneum, covalent binding to carrier protein, migration of Langerhans cells, presentation of the antigen to naïve T-cells. In this paper each of these stages is considered with respect to the extent to which it is dependent on the chemical properties of the sensitiser. The evidence suggests that, although penetration of the stratum corneum, stimulation of migration and maturation of Langerhans cells, and antigen recognition are important events in the induction of sensitisation, except in certain specific circumstances they can be taken for granted. They are not important factors in determining whether a compound will be a sensitiser or not, nor are they important factors in determining how potent one sensitiser will be relative to another. The ability to bind covalently to carrier protein is the major structure-dependent determinant of skin sensitisation potential. A chemistry-based prediction strategy is proposed involving reaction mechanistic domain assignment, reactivity and hydrophobicity determination, and application of quantitative mechanistic modelling (QMM) or read-across. Copyright © 2007 John Wiley & Sons, Ltd. [source] Parabens, oestrogenicity, underarm cosmetics and breast cancer: a perspective on a hypothesisJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2003Philip W. Harvey Abstract A recent review by Darbre (2003) published in this journal (J. Appi. Toxicol. 23: 89,95) has attracted public and scienti,c interest that requires perspective, particularly on the use of esters of p -hydroxybenzoic acid (parabens) as preservatives in underarm cosmetics. Although parabens are generally regarded as safe, recent reports suggest that they are oestrogenic in a variety of in vitro (including MCF7 and ZR-75-1 human breast cancer cell lines) and in vivo tests for oestrogenicity (uterotrophic assays in both rat and mouse). There are also recent reports of adverse reproductive and developmental outcomes in rodent toxicity studies. Of interest is the lack of activity by the oral route but clear activity by the subcutaneous and topical routes, which is of some relevance to the use of underarm cosmetics. There would seem to be a case now to supplement these emerging toxicity data with longer term regulatory standard tests examining other oestrogenic endpoints and at least to consider these ,ndings in more up-to-date risk assessments speci,c for cosmetic use. Further, there are few data on the use of underarm cosmetics and the risk of breast cancer, and although one recent retrospective interview-based study found no association there is a need for more thorough investigation taking into account the type of chemicals used. Darbre has forwarded a hypothesis and called for further work to establish whether or not the use of underarm cosmetics (particularly containing oestrogenic formulants) contributes to the rising incidence of breast cancer. It would seem prudent to conduct this work because the current database is sparse and the effects of long-term low-level exposures to weakly oestrogenic chemicals on human health, particularly their application to the underarm and the risks of breast cancer, are unknown. The role of oestrogens in breast cancer, however, is undisputed. Copyright © 2003 John Wiley & Sons, Ltd. [source] Application of resazurin for estimating abundance of contaminant-degrading micro-organismsLETTERS IN APPLIED MICROBIOLOGY, Issue 5 2001Guerin Aims: The aim of the current study was to test whether resazurin changed colour when incubated with a range of organic chemicals used as growth substrates in bioremediation studies and to determine whether resazurin was more effective in estimating microbial growth than turbidity alone (i.e. no resazurin) or use of the dye, methylene blue. Methods and Results: Resazurin was incubated with a range of organic chemicals that were used as substrates in an MPN assay. Only 1,2-dichlorobenzene, 2,4- D, glycol sulphite and sulphinol reacted to generate false positives. Resazurin was also used to estimate micro-organisms in a series of bioremediation studies. Conclusions: The results showed that resazurin was more sensitive than methylene blue or turbidity alone as an indicator of microbial growth. Significance and Impact of the Study: The significance of the current study is that resazurin should be used in MPN assays for estimating contaminant-degrading micro-organisms instead of turbidity alone or other dyes such as methylene blue. [source] Synthesis, characterization and application of poly[(1-vinyl-2-pyrrolidone)- co -(2-hydroxyethyl methacrylate)] as controlled-release polymeric system for 2,4-dichlorophenoxyacetic chloride using an ultrafiltration techniquePOLYMER INTERNATIONAL, Issue 7 2008Guadalupe del C Pizarro Abstract BACKGROUND: Polymers supporting chemicals used in agriculture have recently been developed to overcome the serious environmental problems of conventional agrochemicals. The success of these formulations is based on a suitable choice of polymer support. Degradable polymeric hydrogels are of particular interest. The gradual release of the bioactive agent can be achieved by hydrolytic or enzymatic cleavage of the linking bond. RESULTS: In this context, poly[(1-vinyl-2-pyrrolidone)- co -(2-hydroxyethyl methacrylate)] [poly(NVP- co -HEMA)] has been used as a bioactive carrier reagent. Herein, we report a controlled-release system with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) using an ultrafiltration system. Hydrolysis was studied by testing the release at various pH values. A high release with poly(NVP- co -HEMA),2,4-D was observed at pH = 7 and 10 after two days (Z = 2). The release percentage of copolymer,herbicide increased at pH = 10. It showed release values between 79.0 and 94.5%. Poly(NVP- co -HEMA),herbicide can release a bioactive compound in aqueous solution at pH = 3, 7 and 10. CONCLUSION: Based on the results of homogeneous hydrolysis, it is argued that the herbicide release rate depends on the pH of the reaction environment. This functional polymer could be employed as a biodegradable material for applications in agrichemical release. Copyright © 2008 Society of Chemical Industry [source] ,13C, ,15N and ,2H isotope ratio mass spectrometry of ephedrine and pseudoephedrine: application to methylamphetamine profilingRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 13 2009Michael Collins Conventional chemical profiling of methylamphetamine has been used for many years to determine the synthetic route employed and where possible to identify the precursor chemicals used. In this study stable isotope ratio analysis was investigated as a means of determining the origin of the methylamphetamine precursors, ephedrine and pseudoephedrine. Ephedrine and pseudoephedrine may be prepared industrially by several routes. Results are presented for the stable isotope ratios of carbon (,13C), nitrogen (,15N) and hydrogen (,2H) measured in methylamphetamine samples synthesized from ephedrine and pseudoephedrine of known provenance. It is clear from the results that measurement of the ,13C, ,15N and ,2H stable isotope ratios by elemental analyzer/thermal conversion isotope ratio mass spectrometry (EA/TC-IRMS) in high-purity methylamphetamine samples will allow determination of the synthetic source of the ephedrine or pseudoephedrine precursor as being either of a natural, semi-synthetic, or fully synthetic origin. Copyright © 2009 Commonwealth of Australia. Published by John Wiley & Sons, Ltd. [source] Simultaneous determination of mercapturic acids derived from ethylene oxide (HEMA), propylene oxide (2-HPMA), acrolein (3-HPMA), acrylamide (AAMA) and N,N -dimethylformamide (AMCC) in human urine using liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2008Thomas Schettgen Mercapturic acids are highly important and specific biomarkers of exposure to carcinogenic substances in occupational and environmental medicine. We have developed and validated a reliable, specific and very sensitive method for the simultaneous determination of five mercapturic acids derived from several high-production chemicals used in industry, namely ethylene oxide, propylene oxide, acrylamide, acrolein and N,N -dimethylformamide. Analytes are enriched and cleaned up from urinary matrix by offline solid-phase extraction. The mercapturic acids are subsequently separated by means of high-performance liquid chromatography on a Luna C8 (2) column and specifically quantified by tandem mass spectrometric detection using isotopically labelled analytes as internal standards. The limits of detection (LODs) for N -acetyl- S -2-carbamoylethylcysteine (AAMA) and N -acetyl- S -2-hydroxyethylcysteine (HEMA) were 2.5,µg/L and 0.5,µg/L urine, while for N -acetyl- S -3-hydroxypropylcysteine (3-HPMA), N -acetyl- S -2-hydroxypropylcysteine (2-HPMA) and N -acetyl- S -(N -methylcarbamoyl)cysteine (AMCC) it was 5,µg/L. These LODs were sufficient to detect the background exposure of the general population. We applied the method on spot urine samples of 28 subjects of the general population with no known occupational exposure to these substances. Median levels for AAMA, HEMA, 3-HPMA, 2-HPMA and AMCC in non-smokers (n,=,14) were 52.6, 2.0, 155, 7.1 and 113.6,µg/L, respectively. In smokers (n,=,14), median levels for AAMA, HEMA, 3-HPMA, 2-HPMA and AMCC were 243, 5.3, 1681, 41.7 and 822,µg/L, respectively. Due to the simultaneous quantification of these mercapturic acids, our method is well suited for the screening of workers with multiple chemical exposures as well as the determination of the background excretion of the general population. Copyright © 2008 John Wiley & Sons, Ltd. [source] Urate oxidase from Aspergillus flavus: new crystal-packing contacts in relation to the content of the active siteACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2005Pascal Retailleau Urate oxidase from Aspergillus flavus (uricase or Uox; EC 1.7.3.3) is a 135,kDa homotetramer with a subunit consisting of 301 amino acids. It catalyses the first step of the degradation of uric acid into allantoin. The structure of the extracted enzyme complexed with a purine-type inhibitor (8-azaxanthin) had been solved from high-resolution X-ray diffraction of I222 crystals. Expression of the recombinant enzyme in Saccharomyces cerevisiae followed by a new purification procedure allowed the crystallization of both unliganded and liganded enzymes utilizing the same conditions but in various crystal forms. Here, four different crystal forms of Uox are analyzed. The diversity of the Uox crystal forms appears to depend strongly on the chemicals used as inhibitors. In the presence of uracil and 5,6-diaminouracil crystals usually belong to the trigonal space group P3121, the asymmetric unit (AU) of which contains one tetramer of Uox (four subunits). Chemical oxidation of 5,6-diaminouracil within the protein may occur, leading to the canonical (I222) packing with one subunit per AU. Coexistence of two crystal forms, P21 with two tetramers per AU and I222, was found in the same crystallization drop containing another inhibitor, guanine. Finally, a fourth form, P21212 with one tetramer per AU, resulted fortuitously in the presence of cymelarsan, an additive. Of all the reported forms, the I222 crystal forms present by far the best X-ray diffraction resolution (,1.6,Å resolution compared with 2.3,3.2,Å for the other forms). The various structures and contacts in all crystalline lattices are compared. The backbones are essentially conserved except for the region near the active site. Its location at the dimer interface is thus likely to be at the origin of the crystal contact changes as a response to the various bound inhibitors. [source] Aqueous Foams: A Field of Investigation at the Frontier Between Chemistry and PhysicsCHEMPHYSCHEM, Issue 4 2008Dominique Langevin Dr. Abstract This paper reviews the properties of aqueous foams. The current state of knowledge is summarized briefly and the interdisciplinary aspects of this field of investigation are emphasized. Many phenomena are controlled by physical laws, but they are highly dependent upon the chemicals used as foam stabilizers: surfactants, polymers, particles. Most of the existing work is related to surfactants and polymer foams, and little is known yet for particle foams although research in this field is becoming popular. This article presents the general concepts used to describe the monolayers and the films and also some of the recent advances being made in this area. [source] Adaptive drug resistance mediated by root,nodulation,cell division efflux pumpsCLINICAL MICROBIOLOGY AND INFECTION, Issue 2009C. Daniels Abstract Bacterial resistance to antibiotics is a major therapeutic problem. Bacteria use the same mechanisms for developing resistance to antibiotics as they do for developing resistance to biocide compounds present in some cleaning and personal care products. Root,nodulation,cell division (RND) family efflux pumps are a common means of multidrug resistance, and induction of their expression can explain the observed cross-resistance found between antibiotics and biocides in laboratory strains. Hence, there is a relationship between the active chemicals used in household products, organic solvents and antibiotics. The widespread use of biocide-containing modern-day household products may promote the development of microbial resistance and, in particular, cross-resistance to antibiotics. [source] |