Environmental hazard and risk assessment of thiochemicals. Application of integrated testing and intelligent assessment strategies (ITS) to fulfil the REACH requirements for aquatic toxicity.

REACH requires information on hazardous properties of substances to be generated avoiding animal testing where possible. It is the objective of the present case study with thiochemicals to extract as much information as possible from available experimental data with fish, daphnia and algae and to fill data gaps for analogues to be registered under REACH in 2018. Based on considerations of chemical similarity and common mode of action (MOA) the data gaps regarding the aquatic toxicity of the thiochemicals were largely closed by trend analysis ("category approach") and read-across within the same group, for example, thioglycolates or mercaptopropionates. Among 16 thiochemicals to be registered by 2018 there are only 2 substances with sufficient data. 36 data gaps for 14 thiochemicals were identified. Most of the required data (>60%) could be estimated by in silico methods. Only 14 tests (6 algae, 6 daphnia, 1 limit fish test and 1 acute fish test) were proposed. When the results of these tests are available it has to be discussed whether 2 further fish (limit) tests are required. For two substances (exposure-based) waiving was suggested. The relatively high toxicity of the thiochemicals is manifested in low predicted no-effect concentrations (PNECs). Only preliminary predicted environmental concentrations (PECs) could be derived for the thiochemicals for which a risk assessment has to be performed (production rate >10 t/y). The preliminary PEC/PNEC ratios indicate no risk for the aquatic compartment at the production site. PECs due to down-stream use must not exceed the estimated PNECs.

Validated Stability Indicating High Performance Liquid Chromatographic Determination of Lesinurad.

Lesinurad is a novel selective uric acid reabsorption inhibitor which has been newly approved for the treatment of the chronic gout. The behavior of lesinurad under various stress conditions (hydrolysis, oxidation, thermal and photolysis) has been investigated as per ICH guidelines. The drug has been found to be labile to acidic hydrolysis, basic hydrolysis and oxidation but stable in neutral, thermal and photolytic conditions. A high performance liquid chromatographic method has been developed for selective determination of the studied drug in the presence of its related degradation products. Good chromatographic resolution has been achieved using a reversed phase BDS Hypersil C18 stationary phase with an isocratic elution of a mobile phase consists of acetonitrile:water (65:35, v/v) at a flow rate of 1 mL/min and UV detection at 290 nm. Two degradation products have been identified by IR and mass spectral scans. The method was validated according to ICH guidelines. The linearity range has been found to be acceptable over the concentration range of 1-20 µg/mL. The developed method has been successfully applied for the estimation of lesinurad in its pharmaceutical dosage form and could be used for the routine analysis of the studied drug in the quality control laboratories.

Surface enhanced infrared absorption spectroscopy based on gold nanostars and spherical nanoparticles.

Plasmonic anisotropic nanoparticles possess a number of hot spots on their surface due to the presence of sharp edges, tips or vertices, leading to a high electric field strength surrounding the nanostructures. In this paper, we explore different plasmonic nanostructures, including anisotropic gold nanostars (AuNSts) and spherical gold nanoparticles, in surface-enhanced infrared absorption spectroscopy (SEIRAS) in an attenuated total reflection (ATR) configuration. In our experiments, we observed up to 10-times enhancement of the infrared (IR) absorption of thioglycolic acid (TGA) and up to 2-times enhancement of signals for bovine serum albumin (BSA) protein on plasmonic nanostructure-based films deposited on a silicon (Si) internal reflection element (IRE) compared to bare Si IRE. The dependence of the observed enhancement on the amount of AuNSts present at the surface of the IRE has been demonstrated. Quantitative studies with both, TGA and BSA were performed, observing that the SEIRA signal can be correlated to the concentration of analyte molecules present within the evanescent field. The calibration curves in the presence of the AuNSts showed enhanced sensitivity as compared with the bare Si IRE. We finally compare efficiencies of anisotropic AuNSts and spherical citrate-capped and "bare" laser-synthesized gold nanoparticles as SEIRAS substrates for the detection of TGA and BSA. The signal obtained from AuNSts was at least 2 times higher for TGA molecules in comparison with spherical gold nanoparticles, which was explained by a more efficient generation of hot spots on anisotropic surface due to the presence of sharp edges, tips or vertices, leading to a high electric field strength surrounding the AuNSts.

AG-690/11026014, a novel PARP-1 inhibitor, protects cardiomyocytes from AngII-induced hypertrophy.

Poly(ADP-ribose) polymerase-1 (PARP-1) enzyme, as a sensor of DNA damage, could convert nicotinamide adenine dinucleotide (NAD) into long poly(ADP-ribose) chains and regulate many cellular processes, including DNA repair, gene transcription, cell survival and chromatin remodeling. However, excessive activation of PARP-1 depletes its substrate NAD and leads to cell death. Mounting evidences have shown that PARP-1 overactivation plays a pivotal role in the pathogenesis of cardiac hypertrophy and heart failure. In present study, a novel PARP-1 inhibitor AG-690/11026014 (6014) was identified based on virtual screening and validated by bioassay. Our results further showed that 6014 prevented the cardiomyocytes from AngII-induced hypertrophy, accompanying attenuation of the mRNA and protein expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), and reduce in the cell surface area. Additionally, 6014 reversed the depletion ofcellular NAD and SIRT6 deacetylase activity induced by AngII in cardiomyocytes. These observations suggest that anti-hypertrophic effect of 6014 might be partially attributed to the rescue of NAD depletion and subsequent restoring of SIRT6 activity by inhibition of PARP-1. Moreover, 6014 attenuated the generation of oxidative stress via suppression of NADPH oxidase 2 and 4, which might probably contribute to the inhibition of PARP-1.

Determination of thioglycolic acid in cosmetics by capillary electrophoresis.

A new and simple method for the accurate determination of thioglycolic acid (TGA) in cosmetics was developed using capillary electrophoresis (CE) with diode array detection at 236nm. The CE separation was performed on an uncoated fused silica capillary with a separation buffer solution containing 300mmolL(-1) tri-sodium phosphate and 0.5mmolL(-1) cetyltrimethylammonium bromide at a voltage of -5kV. Both the intra- and inter-day precisions of the method were 1.4%. The calibration curve between the corrected peak areas and the concentrations of the TGA was linear within the concentration range of 0.006-1.0mgmL(-1) with a correlation coefficient (r) of 0.9998. The limit of detection and limit of quantitation were 0.002mgmL(-1) (S/N=3) and 0.006mgmL(-1) (S/N=10), respectively. The average recoveries at the spiked levels of 0.125, 0.250 and 0.500mgmL(-1) were 96.9%, 102.3% and 94.0% with the relative standard derivations of 2.1%, 3.9% and 2.2%, respectively. The method was cross-validated by both high performance liquid chromatographic and ion chromatographic method. Eighty-five commercial depilatory creams and hair-treatment products were analyzed with satisfactory results.

Measurement of concentrations of thioglycolic acid, dithiodiglycolic acid and ammonia in indoor air of a beauty salon.

OBJECTIVES: Among the many chemicals used in a hair salon, exposure to thioglycolic acid (TGA) used for permanent waving solutions (PWS) potentially causes adverse health effects. However, no report has been previously published on the indoor air concentrations of TGA in a beauty salon that contributes to assessment of exposure to TGA of hairdressers and their customers. This study aimed to demonstrate the present concentration levels of TGA in indoor air of a beauty salon where the PWS containing ammonium thioglycolate was actually used for perm treatments. METHODS: A field measurement of TGA, dithiodiglycolic acid (DTDGA, a reaction product of TGA and cysteine residues of hair keratin) and ammonia was carried out in a beauty salon located at Tokyo, Japan, from June 30 to July 2. Both TGA and DTDGA were collected in water using an impinger and determined by high performance liquid chromatography (HPLC). RESULTS: The indoor air concentrations of TGA were below the limit of detection of 0.008 mg m(-3) at every event and much lower than occupational safety guideline levels set by the NIOSH and ACGIH. Meanwhile, the concentrations of ammonia ranged from 0.15 to 0.87 mg m(-3), and relatively higher concentrations were found during perm events and in samples collected near stations used for perm treatments. Concentrations of DTDGA varied from <0.026 mg m(-3) to 0.75 mg m(-3). CONCLUSIONS: There was a different emission process of TGA and ammonia from PWS, and airborne TGA is not important as a possible exposure route for hairdressers and customers in this beauty salon.

Mercury reduction and oxidation by reduced natural organic matter in anoxic environments.

Natural organic matter (NOM)-mediated redox cycling of elemental mercury Hg(0) and mercuric Hg(II) is critically important in affecting inorganic mercury transformation and bioavailability. However, these processes are not well understood, particularly in anoxic water and sediments where NOM can be reduced and toxic methylmercury is formed. We show that under dark anoxic conditions reduced organic matter (NOM(re)) simultaneously reduces and oxidizes Hg via different reaction mechanisms. Reduction of Hg(II) is primarily caused by reduced quinones. However, Hg(0) oxidation is controlled by thiol functional groups via oxidative complexation, which is demonstrated by the oxidation of Hg(0) by low-molecular-weight thiol compounds, glutathione, and mercaptoacetic acid, under reducing conditions. Depending on the NOM source, oxidation state, and NOM:Hg ratio, NOM reduces Hg(II) at initial rates ranging from 0.4 to 5.5 h(-1), which are about 2 to 6 times higher than those observed for photochemical reduction of Hg(II) in open surface waters. However, rapid reduction of Hg(II) by NOM(re) can be offset by oxidation of Hg(0) with an estimated initial rate as high as 5.4 h(-1). This dual role of NOM(re) is expected to strongly influence the availability of reactive Hg and thus to have important implications for microbial uptake and methylation in anoxic environments.

Gas-phase Smiles rearrangement in structural analysis of a pseudo-oxidative impurity generated in the pharmaceutical synthesis of S-(thiobenzoyl)thioglycolic acid.

Several mass spectrometry (MS) techniques including accurate MS and MS/MS, as well as hydrogen/deuterium (H/D) exchange, were utilized to characterize a pseudo-oxidative reaction by-product (impurity I) in the pharmaceutical synthesis of S-(thiobenzoyl)thioglycolic acid. The negative ion MS/MS data provided complementary structural information to the positive ion MS/MS data. An understanding of the gas-phase Smiles rearrangement upon collision-induced dissociation (CID) in the negative ion MS/MS mode played an important role in structural elucidation of impurity I. The theoretical calculations by density functional theory (DFT) at the B3LYP/6-311G(d,p) level provided insights into the thermochemistry of the Smiles rearrangement reaction. This pseudo-oxidative impurity is proposed to be generated via the base-catalyzed hydrolysis in solution.

Determination of thioglycolic acid in hair-waving products by disposable electrochemical sensor coupled with high-performance liquid chromatography.

A disposable electrochemical sensor coupled with high-performance liquid chromatography (HPLC) was developed for the determination of thioglycolic acid (TGA) in commercial hair-waving products. The quantitative determination of TGA was first investigated by using a preanodized (*) screen-printed carbon electrode (SPCE*). Because of the electrocatalytic effect of the SPCE*, the peak potential (Epa) was shifted less positively as the current magnitude increased. HPLC was used in this study to eliminate interference from the matrix of real samples. The effects of various parameters, such as preanodization potential, preanodization time, solution pH, detection potential, and mobile phase, were studied in detail. Under optimized conditions, the linear range for TGA is up to 20 ppm, correlation coefficient (r2) = 0.998, with a detection limit of 0.042 ppm (signal-to-noise ratio = 3). The practical application of the proposed method was demonstrated by the determination of TGA concentration in commercial hair-waving products.

Simultaneous estimation of Cefixime and Erdosteine in capsule dosage form by spectrophotometric method.

Two accurate, precise, rapid and economical methods viz. Absorption correction method and Dual wavelength method were developed for the estimation of Cefixime (CEF) and Erdosteine (ERDO) in capsule dosage form. In both the methods linearity was observed in the concentration range of 2-25 microg/ml for Cefixime and 3-37.5 microg/ml for Erdosteine. The results of the analysis have been validated statistically and by recovery studies. The percentage assay was found to be 100.03 +/- 0.68 for Cefixime and 99.5 +/- 1.0 for Erdosteine (Mean +/- S.D) by method A and 99.54 +/- 0.84 for Cefixime and 100.54 +/- 1.3 for Erdosteine (Mean +/- S.D) by method B respectively.

Synthesis and characterization of thiomers of polyaspartamide type.

Synthesis of poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)]-thioglycolic acid (PHEA-TGA) conjugate as a new polyaspartamide thiomer is described. The parent polymer PHEA is chemically modified by introducing sulphydryl-bearing compound thioglycolic acid. By varying the reaction conditions several batches of PHEA-TGA conjugates were prepared and analyzed. Tensile studies revealed that total work of adhesion of PHEA-TGA increased more than twice compared to the unmodified polymer. Microparticles prepared from the thiolated polymer preserved its bioadhesive properties.

Identification and quantitation of compounds in a series of allelopathic and non-allelopathic rice root exudates.

An investigation of the chemical basis for rice allelopathy to the rice weed arrowhead (Sagittaria montevidensis) was undertaken using GC/MS and GC/MS/MS techniques. Twenty-five compounds were isolated and identified from the root exudates of both allelopathic and non-allelopathic rice varieties. Phenolics, phenylalkanoic acids, and indoles were among the chemical classes identified. Two indoles previously unreported in rice were detected in the exudates, 5-hydroxy-2-indolecarboxylic acid and 5-hydroxyindole-3-acetic acid. Several other compounds identified in this study have not previously been reported in rice root exudates, namely mercaptoacetic acid, 4-hydroxyphenylacetic acid, and 4-vinylphenol. The levels of 15 compounds present in the exudates were quantified using GC/MS/MS. Six of the seven most abundant compounds were phenolic acids. Significant differences exist between the allelopathic and non-allelopathic cultivars in their production of three of these six compounds. Greater amounts of trans-ferulic acid, p-hydroxybenzoic acid, and caffeic acid were detected in the exudates of allelopathic cultivars. The seventh compound, abietic acid, was significantly higher in the non-allelopathic cultivars.

[Study on analysis of thioglycolic acid in cosmetics by ion chromatography].

OBJECTIVE: An analytical method of determinating thioglycolic acid in cosmetics by ion-exchange chromatography suppressed conductivity detection has been developed. METHODS: A high capacity anion exchange column, IonPacAS11-HC column was used. 25mmol/L NaOH + 1% methanol was used as eluent, and the flow rate was set up at 0.85ml/min. Samples were pretreated by extraction with CHCl3 to remove some organic substance, and then upper clean liquid was injected. RESULTS: The influence of samples' pH, coexist anion and the concentration of methanol in eluent on determination was discussed. The method enjoyed a wide linear range and good precision. The detection limit was 2.3mg/kg. The average recoveries were 91.5% - 10.0%, and the relative standard deviation (RSD%) was less 0.941. CONCLUSION: The results showed that the method was simple, accurate and might be good for application.

[Thiodiglycol metabolism in Alcaligenes xylosoxydans subsp. denitrificans]. / Metabolism tioglikolia kul'turoi Alcaligenes xylosoxydans subsp. denitrificans.

The investigation of the degradation of thiodiglycol (the major product of mustard gas hydrolysis) by Alcaligenes xylosoxydans subsp. denitrificans strain TD2 showed that thiodiglycol is metabolized through the oxidation of its primary alcohol groups and the subsequent cleavage of C-S bonds in the intermediate products, thiodiglycolic and thioglycolic acids. The end products of these reactions are SO4(2-) ions and acetate, the latter being involved in the central metabolism of strain TD2. The oxidation of the sulfur atom gives rise to diglycolsulfoxide, which is recalcitrant to further microbial degradation. Based on the data obtained, a metabolic pathway of thiodiglycol transformation by A. xylosoxydans subsp. denitrificans strain TD2 is proposed.

Transformation of thiodiglycol by resting cells of Alcaligenes xylosoxydans PGH10.

A new strain of Alcaligenes xylosoxydans able to aerobically cometabolize thiodiglycol, the primary hydrolysis product of sulfur mustard, was isolated and tested in a laboratory scale stirred tank reactor. The strain, named PGH10, cannot use TDG as sole carbon and energy source for growth, but resting cells previously grown on either rich broth or defined mineral media efficiently metabolize this compound through [(2-hydroxyethyl)thio]acetic acid and thiodiacetic acid as intermediates. Degradation of TDG by PGH10 is shown to take place at late exponential and stationary phase but is not triggered by carbon exhaustion. Cultures pregrown to saturation for 48 h in the absence of TDG can be stored and used for degradation of TDG, reducing significantly the time required to achieve the reduction of the compound concentration to undetectable levels. Degradation can take place in buffered media with no carbon source added, although best results were obtained in mineral media supplemented with citrate or fructose. Oxidation to [(2-hydroxyethyl)thio]acetic acid and thiodiacetic acid was proposed to be catalyzed by a butanol-dehydrogenase activity. Inhibition of TDG transformation in the presence of several alcohols is also shown.

Effect of genetic variation on induced neutrophilia in mice.

Mice from a variety of strains were injected with a sterile irritant (Brewer's thioglycolate) and killed bacteria (Staphylococcus aureus, Staphylococcus epidermidis, or Escherichia coli) to determine their effect on accumulation of neutrophils in the peritoneal cavity. Peak accumulation occurred around 15 h postinjection and showed significant strain-related variation. C57BL/10 mice were identified as having a high-responder phenotype and BALB/c mice a low-responder phenotype. Inheritance of the high-responder phenotype followed simple Mendelian genetics: (BALB/c x C57BL/10)F1 mice were found to be more responsive than either parental phenotype. Major histocompatibility complex H-2d haplotype was found to convey an augmented neutrophil response in conjunction with B10 background high-responder genes (B10.D2/n) but the H-2d haplotype per se was not the only factor in determining high responsiveness. Gram-positive and gram-negative bacteria appeared to activate different immune mechanisms. Both gram-negative bacteria and lipopolysaccharides (LPS) induced a response similar to, but less potent than, that induced by Brewer's thioglycollate. Neutralization of the LPS content of Brewer's thioglycolate abrogated the response.

Mercaptoethanol poisoning: report of a fatal case and analytical determinations.

A suicide due to oral intake of 2-mercaptoethanol is reported. High concentrations of 2-mercaptoethanol and its metabolite 2-mercaptoacetate were found by gas chromatography in the urine and gastric content of the victim. These compounds were also identified by gas chromatography/mass spectrometry. Increased amounts of inorganic sulfate were furthermore found in the urine. Case history and autopsy findings are presented, and the metabolism of 2-mercaptoethanol is discussed.