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Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Organic ultraviolet filters (OUVFs) are new hydrophobic organic pollutants in the aquatic environment. When ingested by aquatic organisms, OUVFs can induce a variety of toxic effects in organisms and be transferred to offspring. However, as the main active ingredient in sunscreens, OUVFs have rarely been investigated for their melanin interference toxicity or transgenerational toxic effects on aquatic organisms and their interactive toxic effects with nanoplastics (NPs). Here, we show the mechanism by which OUVFs interfere with melanogenesis in parental or offspring zebrafish and the effect of polystyrene (PS) NPs on the melanin-interference effect of OUVFs. We found that EHS induced significant enrichment of the melanogenesis pathway, inhibited the expression of the key melanin gene microphthalmia-associated transcription factor a (mitfa) and induced the mitf tyrosinase (tyr)-dopachrome tautomerase (dct)-tyrosinase related protein 1 (tyrp1) signaling cascade in parents, which ultimately induced a decrease in melanin content. After reproduction, transgenerational melanin interference effects of EHS may occur through the maternal inheritance of mitfa. Coexisting PS-NPs may inhibit the melanin interference toxicity or transgenerational toxicity of EHS by reducing ultraviolet irritation to the skin through adsorption of EHS. Our results demonstrate the ecotoxic potential of OUVFs in terms of melanin interference and the interference of PS-NP carrier effects on the toxicity of OUVFs. We anticipate that our assay will contribute to the assessment of the toxic effects of OUVFs and provide a basis for the interactive ecotoxicity assessment of PS-NPs and hydrophobic organic pollutants., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023. Published by Elsevier B.V.)

Amyl salicylate (AS) is a fragrance massively used as a personal care product and following the discharged in wastewaters may end up in the aquatic environment representing a potential threat for the ecosystem and living organisms. AS was recently detected in water of the Venice Lagoon, a vulnerable area continuously subjected to the income of anthropogenic chemicals. The lagoon is a relevant area for mollusc farming, including the Mediterranean mussels (Mytilus galloprovincialis) having an important economic and ecological role. Despite high levels of AS occurred in water of the Lagoon of Venice, no studies investigated the possible consequences of AS exposures on species inhabiting this ecosystem to date. For the first time, we applied a multidisciplinary approach to investigate the potential effects of the fragrance AS on Mediterranean mussels. To reach such a goal, bioaccumulation, cellular, biochemical, and molecular analyses (RNA-seq and microbiota characterization) were measured in mussels treated for 7 and 14 days with different AS Venice lagoon environmental levels (0.1 and 0.5 μg L -1 ). Despite chemical investigations suggested low AS bioaccumulation capability, cellular and molecular analyses highlighted the disruption of several key cellular processes after the prolonged exposures to the high AS concentration. Among them, potential immunotoxicity and changes in transcriptional regulation of pathways involved in energy metabolism, stress response, apoptosis and cell death regulations have been observed. Conversely, exposure to the low AS concentration demonstrated weak transcriptional changes and transient increased representation of opportunistic pathogens, as Arcobacter genus and Vibrio aestuarianus. Summarizing, this study provides the first overview on the effects of AS on one of the most widely farmed mollusk species., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, a 120-day whole-life cycle exposure and oviposition experiment on zebrafish with maternal and paternal mixed mating strategy was conducted to investigate the epigenetic mechanism of DNA methylation in ethylhexyl salicylate (EHS, 1, 10, 100 μg/L)-induced transgenerational effects. Results showed that EHS could induce the decrease of DNA methyltransferase 1 (DNMT1) activity and average global DNA methylation level in maternal parents and the increase of the above indexes in paternal parents, while the change of glycine N-methyltransferase activity was opposite to DNMT1. The average global DNA methylation levels were significantly increased in the offsprings of both parents exposed and father-only exposed to EHS, suggesting that EHS-induced epigenetic modifications may be stable and heritable. Hierarchical clustering analysis of promoter at different methylation sites showed that the DNA methylation pattern of offsprings were similar to that of the paternal parents, meaning that the offsprings may have inherited paternal DNA methylation pattern with eya2, pcdh2g5 and pcdh2g1 as key genes and lead to high locomotor activity in offsprings. KEGG pathway analysis showed that parental exposure to EHS may interfere with the central nervous system, insulin function system, melanogenesis system and the normal development of somatic axis of offsprings., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: This study aimed to assess the risk factors and impact of rhabdomyolysis on treatments, outcomes, and resource utilization in hospitalized patients for salicylate intoxication in the United States., Materials and Methods: The National Inpatient Sample was utilized to identify hospitalized patients with a primary diagnosis of salicylate intoxication from 2003-2014. Rhabdomyolysis was identified using hospital diagnosis code. We compared the clinical characteristics, in-hospital treatment, outcomes, and resource utilization between patients with and without rhabdomyolysis., Results: A total of 13,805 hospital admissions for salicylate intoxication were studied. Of these, rhabdomyolysis developed in 258 (1.9%) admissions. The risk factors for rhabdomyolysis were age>20 years, male sex, volume depletion, hypokalemia, sepsis, and seizure. After adjustment for baseline clinical characteristics, salicylate intoxication patients with rhabdomyolysis required more invasive mechanical ventilation, and renal replacement therapy. Rhabdomyolysis was significantly associated with higher risk of failure of any organ systems, and in-hospital mortality. Length of hospital stay and hospitalization cost were higher when rhabdomyolysis occurred during hospital stay., Conclusions: Rhabdomyolysis was not common in hospitalized patients for salicylate intoxication but it was associated with increased morbidity, mortality, and resource utilization., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

BACKGROUND Over-the-counter medications that contain aspirin are widely used, and patients generally regard them as safe. However, the side effects of salicylate toxicity can be severe, and delay in the diagnosis may increase the risk of mortality. Neurologic symptoms are a common presenting feature of salicylate toxicity in the elderly, and their recognition may allow earlier diagnosis. This report is of a case of a 61-year-old woman who presented with acute focal neurologic deficit associated with salicylate toxicity and who had a previous history of stroke. CASE REPORT A 61-year-old woman presented to the Emergency Department after awakening with left-sided weakness. She had a history of ischemic stroke with an associated seizure disorder. The patient denied recent seizure, and brain magnetic resonance imaging (MRI) showed no evidence of an acute stroke. Following her arrival, she became acutely confused and complained of tinnitus, shortness of breath, and blurred vision. On direct questioning, she gave a history of excessive use of salicylate for the previous two to three weeks. Her initial serum salicylate level was significantly increased at 78.1 mg/dl (upper therapeutic limit, 19.9 mg/dl). She recovered completely following treatment with oral activated charcoal, intravenous sodium bicarbonate, and potassium replacement. CONCLUSIONS This case demonstrates that physicians should consider salicylate toxicity as a possible cause of exacerbation of neurological deficit in elderly patients.

Homosalate is an organic ultraviolet filter used in most sunscreens but has been reported to be toxic to marine organisms. The estrogenic activity of homosalate has also been reported, but its endocrine-disrupting effect remains unclear. Although homosalate has been detected in human placental tissues, its effect on the survival of human trophoblast cells needs to be investigated. Therefore, in this study, we evaluated if HTR8/SVneo, a human trophoblast cell line, treated with homosalate showed decreasing proliferative activity in a dose-dependent manner. Homosalate promoted the death of HTR8/SVneo cells with elevated lipid peroxidation and intracellular Ca 2+ concentration. It also induced endoplasmic reticulum stress and mitochondrial morphological disturbances associated with the differentiation of human trophoblast cells. However, when the intracellular Ca 2+ or reactive oxygen species were removed using BAPTA-AM or N-acetyl-L-cysteine (NAC), the cell proliferation suppressed by homosalate was restored. Homosalate also significantly inhibited the invasion of HTR8/SVneo cells. Furthermore, it modulated phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways, which were involved in the cross-talk between both signaling pathways in HTR8/SVneo cells. Thus, homosalate adversely affects the survival, proliferation, and invasiveness of human trophoblast cells and therefore pregnant women should practice caution while using personal care products containing homosalate., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to evaluate the subcutaneous response induced by Roeko Guttaflow2 (RG), Sealapex Xpress (SX), AH Plus (AHP) sealers., Methods: 100 BALB/c mice received implants in the subcutaneous tissue with the tested materials (10 animals per period for each evaluated sealer) and were evaluated after different experimental periods (7, 21 and 63 days), in each animal was placed a tube, the control group was an empty tube. Histological analysis evaluated semi-quantitatively the inflammatory infiltration, collagen fiber formation and tissue thickness. In addition, immunohistochemistry was performed for interleukin-6 (IL-6). Data were statistically analyzed (α = 0.05)., Results: RG promoted a greater collagen fiber formation at 7 days and 63 days compared to the CG (p = 0.004) and AHP (p = 0.005) respectively, while at 21 days, the SX promoted a greater reaction (p = 0.021). For the tissue thickness, there was a greater reaction at 7 days with CG (p = 0.0156) and with RG at 63 days (p = 0.03). Regarding the inflammatory infiltrate, there was no difference at 7 days and 63 days (p = 0.5; p = 0.27), while at 21 days, a statistically difference was found between SX, CG (p = 0.04) and RG (p = 0.027). In addition, the presence of IL-6 was observed in almost all groups, with a more intense marking at 7days., Significance: All cements evaluated presented a satisfactory tissue response, however, RG was the one that presented a more satisfactory tissue response., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: Chronic salicylate toxicity is an uncommon, potentially life-threatening poisoning that requires high clinical suspicion in order to make the diagnosis. We created a simulation case that challenges learners to analyze case information, construct a differential diagnosis of an elevated anion gap metabolic acidosis with respiratory alkalosis, and initiate treatment for this toxicity., Methods: The simulation case was designed for emergency medicine residents and pediatric emergency medicine fellows. The activity began with a brief overview of the monitors, equipment, and simulation experience. For interns, a team of two learners comanaged the case; for senior learners, the case was managed solo. The learners had 15 minutes to complete a focused history and physical exam, request and interpret labs and studies, and initiate specific treatments. The simulation was followed by a 15-minute facilitated debrief session that included an overview of key learning points and learner performance based on an evaluation checklist., Results: Residents completed a postparticipation questionnaire consisting of six questions rated on a 5-point Likert scale. Overall, residents reported a high degree of satisfaction with the simulation experience. The case and debrief were effective in meeting the educational objectives and proved to be an effective modality to fill this educational gap., Discussion: This simulation exercise was effective in showing residents the uncommon presentation of chronic salicylate toxicity. Learners reported increased confidence in recognizing and managing this ingestion. The simulation experience closed an identified education gap and provided an experiential learning opportunity that accomplished the targeted learning objectives., Competing Interests: None to report.

Introduction: Salicylate poisoning is a serious toxicologic problem with a complex pathophysiology that requires prompt diagnosis and action for a favorable outcome. A simulated experience in the evaluation and management of an aspirin-overdose patient allows learners to construct a differential diagnosis from an array of symptoms and signs, analyze a mixed acid-base disturbance, and explore the multistep management of this disorder., Methods: This simulation exercise was designed for second-year medical students. At the start of the session, teams received a 10-minute introduction to the activity. Upon entering a room in a simulated Emergency Department, teams had 15 minutes to complete a focused history and physical exam of the patient, interpret arterial blood gas and basic metabolic panel data, and administer treatment based on key findings and a presumptive diagnosis. The scenario was followed by a 90-minute facilitated debriefing session. An alternative 45-minute debriefing guideline is also included., Results: Students voluntarily completed a 13-question, 5-point Likert-scale survey about the educational exercise immediately following the session. They evaluated the preparatory materials and briefing, the simulation scenario, the usefulness of the debriefing, and their confidence in their understanding of salicylate poisoning following the session. Students reported a favorable response to the overall experience and the debriefing, as well as an increase in confidence following the session., Discussion: This simulation exercise was successful in exposing students to the clinical presentation of salicylate toxicity and giving them the opportunity to apply and synthesize basic science knowledge during the scenario., Competing Interests: None to report.

The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.

Ginkgolic acids (GAs) are thought to be the potentially hazardous constituents corresponding to the toxic side effects of Ginkgo products. In this study, toxicological and metabolomics studies of GAs were carried out by ultra-performance liquid chromatography-high-definition mass spectrometry (UPLC-HDMS). Significant changes in serum clinical chemistry were observed in the both low (100 mg/kg) and high (900 mg/kg) doses. Especially the serum enzyme of ALT, AST, LDH, and CK decreased in treated groups. The histopathological observation demonstrated hepatic steatosis in liver and tubular vacuolar degeneration in kidney. These results demonstrated the hepatotoxicity and nephrotoxicity of GAs. Functional disorders are more likely to be toxic induced by GAs. Metabolic profiling within seven days revealed the change of the body status after oral administration. The results indicated the body function was significantly influenced at the 3rd day and could recover in seven days. Metabolomic analysis showed alterations in 14 metabolites from plasma such as LysoPC(18:0), LysoPC(18:2) and other lipids. The results suggested that exposure to GAs could cause disturbances in liver and kidney function associated with the metabolisms of lipids, glucose and the enzyme activity., (Copyright © 2017. Published by Elsevier B.V.)

Chemical warfare agents are an actual threat and victims' decontamination is a main concern when mass exposure occurs. Skin decontamination with current protocols has been widely documented, as well as surface decontamination. However, considering hair ability to trap chemicals in vapour phase, we investigated hair decontamination after exposure to sulphur mustard simulants methyl salicylate and 2-chloroethyl ethyl sulphide. Four decontamination protocols were tested on hair, combining showering and emergency decontamination (use of Fuller's earth or Reactive Skin Decontamination Lotion RSDL ® ). Both simulants were recovered from hair after treatment, but contents were significantly reduced (42-85% content allowance). Showering alone was the least efficient protocol. Concerning 2-chloroethyl ethyl sulphide, protocols did not display significant differences in decontamination efficacy. For MeS, use of emergency decontaminants significantly increased showering efficacy (10-20% rise), underlining their usefulness before thorough decontamination. Our results highlighted the need to extensively decontaminate hair after chemical exposure. Residual amounts after decontamination are challenging, as their release from hair could lead to health issues., (Copyright © 2016. Published by Elsevier B.V.)

The UK's Initial Operational Response (IOR) is a revised process for the medical management of mass casualties potentially contaminated with hazardous materials. A critical element of the IOR is the introduction of immediate, on-scene disrobing and decontamination of casualties to limit the adverse health effects of exposure. Ad hoc cleansing of the skin with dry absorbent materials has previously been identified as a potential means of facilitating emergency decontamination. The purpose of this study was to evaluate the in vitro oil and water absorbency of a range of materials commonly found in the domestic and clinical environments and to determine the effectiveness of a small, but representative selection of such materials in skin decontamination, using an established ex vivo model. Five contaminants were used in the study: methyl salicylate, parathion, diethyl malonate, phorate and potassium cyanide. In vitro measurements of water and oil absorbency did not correlate with ex vivo measurements of skin decontamination. When measured ex vivo, dry decontamination was consistently more effective than a standard wet decontamination method ("rinse-wipe-rinse") for removing liquid contaminants. However, dry decontamination was ineffective against particulate contamination. Collectively, these data confirm that absorbent materials such as wound dressings and tissue paper provide an effective, generic capability for emergency removal of liquid contaminants from the skin surface, but that wet decontamination should be used for non-liquid contaminants., Competing Interests: The authors have declared that no competing interests exist.

By integrating positive and negative feedback loops, biological systems establish intricate gene expression patterns linked to multistability, pulsing, and oscillations. This depends on the specific characteristics of each interlinked feedback, and thus one would expect additional expression programs to be found. Here, we investigate one such program associated with an antagonistic positive and negative transcriptional autoregulatory motif derived from the multiple antibiotic resistance (mar) system of Escherichia coli. We studied the dynamics of the system by combining a predictive mathematical model with high-resolution experimental measures of the response both at the population and single-cell level. We show that in this motif the weak positive autoregulation does not slow down but rather enhances response speedup in combination with a strong negative feedback loop. This balance of feedback strengths anticipates a homogeneous population phenotype, which we corroborate experimentally. Theoretical analysis also emphasized the specific molecular properties that determine the dynamics of the mar phenotype. More broadly, response acceleration could provide a rationale for the presence of weak positive feedbacks in other biological scenarios exhibiting these interlinked regulatory architectures.

Background: Although the activity of tinnitus-related ion co-transporter are known, their mRNA expressions has seldom been reported. We aimed to investigate the mRNA expressions of tinnitus-related ion co-transporter genes, and treatment effects of Spirulina., Methods: The mRNA expressions of K(+)-Cl(-) co-transporter (KCC2) and Na-K-2Cl co-transporter 1 (NKCC1) genes in the cochlea and brain of mice were evaluated after tinnitus was induced by intraperitoneal injection of salicylate. The effects of spirulina water extract on these gene expressions were investigated., Results: Compared to the control group, the tinnitus scores increased significantly, however, the salicylate-induced tinnitus could be reduced significantly by spirulina water extract. The tinnitus group had higher of borderline significance mRNA expression of KCC2 gene in the cochlear, significantly higher in the temporal lobes and in the frontal lobes. Meanwhile, compared to the tinnitus group, the spirulina group had significantly lower mRNA expression of KCC2 gene in the cochlear, temporal lobes, frontal lobes and parahippocampus/hippocampus. However, the NKCC1 mRNA expression was not significantly different between three groups in the cochlea and these brain areas., Conclusion: Salicylate-induced tinnitus might be associated with increased mRNA expression of KCC2 gene, but not with mRNA expressions of NKCC1 gene in the cochlear and some tinnitus-related brain areas. Spirulina reduced the expression of KCC2 genes in salicylate-induced tinnitus.

Context Since methods utilised in the treatment of glioblastoma multiforme (GBM) are inadequate and have too many side effects, usage of herbal products in the treatment process comes into prominence. Lichens are symbiotic organisms used for medicinal purposes for many years. There are various anticancer treatments about components of two lichen species used in the present study. Objective Antitumor potential of three lichen secondary metabolites including olivetoric acid (OLA) and physodic acid (PHA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) and psoromic acid (PSA) isolated from Rhizoplaca melanophthalma (DC.) Leuckert (Lecanoraceae) were investigated on human U87MG-GBM cell lines and primary rat cerebral cortex (PRCC) cells for the first time. Materials and methods PRCC cells used as healthy brain cells were obtained from Sprague-Dawley rats. The treatments were carried out on the cells cultured for 48 h. Cytotoxic effects of different concentrations (2.5, 5, 10, 20 and 40 mg/L) of metabolites on the cells were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. Total antioxidant capacity (TAC) and total oxidant status (TOS) parameters were used for assessing oxidative alterations. Oxidative DNA damage potentials of metabolites were investigated via evaluating 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels. Results Median inhibitory concentration (IC50) values of OLA, PHA and PSA were 125.71, 698.19 and 79.40 mg/L for PRCC cells and 17.55, 410.72 and 56.22 mg/L for U87MG cells, respectively. It was revealed that cytotoxic effects of these metabolites showed positive correlation with concentration, LDH activity and oxidative DNA damage. Discussion and conclusion The present findings obtained in this study revealed that primarily OLA and then PSA had high potential for use in the treatment of GBM.

The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, as well as, environmental safety. Repeated dose toxicity was determined using to have the most conservative systemic exposure derived NOAEL of 47 mg/kg/day. A dietary 13-week subchronic toxicity study conducted in rats on a suitable read across analog resulted in a MOE of 2350 while considering 10.3% absorption from skin contact and 100% from inhalation. A MOE of >100 is deemed acceptable., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Salicylate's ototoxic properties have been well established, inducing tinnitus and a sensory hearing loss when administered in high doses. Peripherally, acute dosing of salicylate causes frequency dependent reductions in DPOAEs and CAP amplitudes in low (<10 kHz) and high (>20 kHz) frequencies more than mid frequencies (10-20 kHz), which interestingly corresponds to the pitch of behaviourally-matched salicylate-induced tinnitus. Chronic salicylate dosing affects the peripheral system by causing a compensatory temporary enhancement in DPOAE amplitudes and up-regulation of prestin mRNA and protein expression. Despite salicylate's antioxidant properties, cultured cochlea studies indicate it also impairs spiral ganglion neurons (SGNs) by paradoxically causing an upsurge of superoxide radicals leading to apoptosis. Centrally, salicylate alters γ-aminobutyric acid (GABA) and serotonin mediated neurotransmission in the central nervous system (CNS), which results in classical and non-classical auditory regions showing hyperactivity after salicylate administration. In the auditory cortex (AC) and lateral amygdala (LA), neuron characteristic frequencies (CF) shift upward and downward to mid frequencies (10-20 kHz) altering tonotopy following salicylate administration. Additionally, current source density (CSD) analysis showed enhanced current flow into the supergranular layer of the auditory cortex after a high systemic dose of salicylate. In humans, auditory perception changes following salicylate or aspirin, including decreased word discrimination and temporal integration ability. The results of previous studies have partially identified the mechanisms that are involved in salicylate-induced tinnitus and hearing loss, however to date some interactions remain convoluted. This review discusses current knowledge of salicylate ototoxicity and interactions.

Objectives: The aim of the present study was to investigate the effects of root canal sealers on the cytotoxicity of 3T3 fibroblasts during a period of 5 weeks., Material and Methods: Fibroblasts (3T3, 1×105 cells per well) were incubated with elutes of fresh specimens from eight root canal sealers (AH Plus, Epiphany, Endomethasone N, EndoREZ, MTA Fillapex, Pulp Canal Sealer EWT, RoekoSeal and Sealapex) and with elutes of the same specimens for 5 succeeding weeks after immersing in simulated body fluid. The cytotoxicity of all root canal sealers was determined using the MTT assay. Data were analyzed using ANOVA and Tukey's test., Results: RoekoSeal was the only sealer that did not show any cytotoxic effects (p<0.05). All the other tested sealers exhibited severe toxicity initially (week 0). MTA Fillapex remained moderately cytotoxic after the end of experimental period. Toxicity of the other tested sealers decreased gradually over time. The evaluated root canal sealers presented varying degrees of cytotoxicity, mainly in fresh mode., Conclusions: RoekoSeal had no cytotoxic effect both freshly mixed and in the other tested time points. MTA Fillapex was associated with significantly less cell viability when compared to the other tested root canal sealers.

The aim of this work was to evaluate the effects of different times of extraction on the cytotoxicity of six representatives of different root canal sealer groups-Real Seal SE, AH Plus, GuttaFlow, Sealapex, Roth 801, and ThermaSeal Plus-with human gingival fibroblasts. The materials were prepared according to manufacturers' specifications, and were incubated in culture medium (DMEM) at 37ºC for 1, 7, 14, 21, and 28 days, with daily washing, to simulate periodontal ligament clearance. Human fibroblasts were exposed to the final extracts at 24 hours, and cell viability was determined by MTT assay, with exposure to unconditioned DMEM as a negative control. Statistical analysis comparing cytotoxicities at each exposure time was performed by ANOVA with Scheffé adjustment for multiple comparisons at a 95% confidence level. Results indicated that GuttaFlow was significantly less cytotoxic than all other sealers (p < 0.05) at 1 day of extraction. After 7 days of extraction, cell viability for GuttaFlow was significantly increased as compared with that of all groups except sealer AH Plus. At day 14, cytotoxicity of Sealapex was significantly higher than that of all other sealers (p < 0.05). At days 21 and 28, there were no significant differences in cytotoxicity among sealer groups. All materials presented some level of cytotoxicity to fibroblasts, while GuttaFlow was the least cytotoxic sealer tested. However, the cytotoxicity of all materials seemed to decrease similarly in a time-dependent manner.

Background: Changes in the gene expressions for tumor necrosis factor-α (TNF-α) and/or interleukin-1β (IL-1β) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-α, IL-1β, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (IC) of mice after intraperitoneal injections of salicylate., Methods: Forty-eight 3-month-old male SAMP8 mice were randomly and equally divided into two groups: salicylate-treated and saline-treated. All mice were trained to perform an active avoidance task for 5 days. Once conditioned, an active avoidance task was performed 2 hours after daily intraperitoneal injections of saline, either alone or containing 300 mg/kg sodium salicylate. Total numbers of times (tinnitus score) the mice climbed during the inter-trial silent period for 10 trials were recorded daily for 4 days (days 7 to 10), and then mice were euthanized for determination of mRNA expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC at day 10., Results: Tinnitus scores increased in response to daily salicylate treatments. The mRNA expression levels of TNF-α increased significantly for the salicylate-treated group compared to the control group in both cochlea (1.89 ± 0.22 vs. 0.87 ± 0.07, P < 0.0001) and IC (2.12 ± 0.23 vs. 1.73 ± 0.22, p = 0.0040). mRNA expression levels for the IL-1β gene also increased significantly in the salicylate group compared to the control group in both cochlea (3.50 ± 1.05 vs. 2.80 ± 0.28, p < 0.0001) and IC (2.94 ± 0.51 versus 1.24 ± 0.52, p = 0.0013). Linear regression analysis revealed a significant positive association between tinnitus scores and expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC. In addition, expression levels of the TNF-α gene were positively correlated with those of the NR2B gene in both cochlea and IC; whereas, the expression levels of the IL-1β gene was positively correlated with that of the NR2B gene in IC, but not in cochlea., Conclusion: We conclude that salicylate treatment resulting in tinnitus augments expression of the TNF-α and IL-1β genes in cochlea and IC of mice, and we suggest that these proinflammatory cytokines might lead to tinnitus directly or via modulating the NMDA receptor.

The toxicity of perfluorinated surfactants perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorobutane sulfonate (PFBS) and PF-656 as well as the sulfosuccinate surfactant docusate sodium has been examined using two bioluminescence inhibition assays based on the marine bacterium Vibrio fischeri and the self-luminescent cyanobacterial recombinant strain Anabaena CPB4337. We also determined multigenerational toxicity towards the growth of the algae Pseudokirchneriella subcapitata. With EC(50) values in the 43-75 mg/L range, docusate sodium exhibited a higher toxicity towards the three organisms than PFOS, PFOA, PF-656 and PFBS. We investigated the toxicological interactions of the most toxic surfactant, docusate sodium, with two chlorinated compounds, triclosan and 2,4,6-trichlorophenol (TCP), in their binary and ternary mixtures using the method of the combination index based on the median-effect equation. In general, the binary mixture of the chlorinated compounds triclosan and TCP exhibited antagonism, which was stronger for the growth test using P. subcapitata. Except for the green alga, the binary mixtures of docusate sodium with TCP or triclosan showed synergism at medium to high effect levels; the synergistic behaviour predominating in the ternary mixture and in the three tested species. This result highlights the potential toxicological risk associated with the co-occurrence of this surfactant with other pollutants., ((c) 2010 Elsevier Ltd. All rights reserved.)

In order to evaluate the cesium-induced toxic functional changes in organisms, transmembrane activities of cesium 5-sulfosalicylate (Cs(H(2)Ssal)) into human erythrocyte in vitro is presented in this paper, including kinetic characteristic of transport process and pathways involved in it. The uptake amount of Cs(H(2)Ssal) by erythrocyte was determined both by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) and spectrofluorimetry. The pathways of Cs(H(2)Ssal) transporting into erythrocyte are proposed according to inhibition investigation. The influence of Cs(H(2)Ssal) on morphological properties of erythrocytes was examined using Scanning Electron Microscopy (SEM) to determined the endurable concentration extent of erythrocytes to Cs(H(2)Ssal). Results show that transmembrane of Cs(H(2)Ssal) has characteristic of first-order kinetic process during the first 2h, and four pathways were involved in its transporting activities: Ca(2+) channel, Na(+)-K(+) pump, Na(+)-Cs(+) countertransport, and anion Cl(-)/CsCO(3)(-) exchange. The transmembrane process of Cs(H(2)Ssal) can both prevent the uptake of K(+) and induces abnormal accumulation of extracellular K(+) as well as occupy some K(+)-binding sites in protein, causing some tissues losing their activities and functions. Only high concentrations of Cs(H(2)Ssal) could change morphological properties of erythrocytes greatly and cause hemolysis eventually.

Aim: To examine the effect of three commercial mouth rinses (Hexidine 0.2%, Listerine Cool Mint, Betadine 1%) upon cultured human gingival fibroblast proliferation., Materials and Methods: Human gingival fibroblasts were cultured and incubated in Dulbecco's Minimum Eagle's Medium containing Chlorhexidine, Listerine, Povidone-Iodine at varying concentrations (1%, 2%, 5%, 10%, 20% and 100% of the given solution) at 37 degrees C for 1, 5 and 15 min. Control cells received an equal volume of Dulbecco's Minimum Eagle's Medium without adding mouth rinses, for similar duration of exposure at 37 degrees C. Following incubation the media were removed, cells were washed twice with medium, supplemented with 10% Fetal Bovine Serum, and fibroblasts in the test and control group were allowed to recover in the same media for 24 h., Results: In all the three groups, the proliferation inhibition was dependent on the concentration of solublized mouth rinses in the cell culture but independent of the duration of exposure to all three mouth rinses. The results showed that all three solutions were toxic to cultured human gingival fibroblasts, Chlorhexidine being the most cytotoxic. It was seen that at dilute concentrations (1% and 2% of given solutions) Listerine was more cytotoxic than Chlorhexidine and Povidone-Iodine., Conclusion: These results suggest that Chlorhexidine, Listerine and Povidone-Iodine are capable of inducing a dose-dependent reduction in cellular proliferation of fibroblasts. The results presented are interesting, but to know the clinical significance, further studies are needed.

While salicylates (non-steroidal anti-inflammatory drugs) have been detected in the aquatic environment, few studies have focused on the mechanism of action of these pharmaceuticals on aquatic organisms. We reported previously that salicylate disrupted the acute trophic hormone-stimulated corticosteroidogenesis in rainbow trout (Oncorhynchus mykiss) interrenal tissue in vitro. Here, we tested the hypothesis that this drug will inhibit the adaptive plasma cortisol response and the associated metabolic response to an acute stressor in trout. Fish were fed salicylate-laced feed (100 mg/kg body weight) for 3 days, subjected to an acute (5 min) handling disturbance and sampled 1, 4 and 24 h after the stressor exposure. Salicylate treatment attenuated the stressor-induced plasma cortisol but not glucose or lactate elevations. The disruption of cortisol response corresponded with a significant reduction in transcript levels of the steroidogenic acute regulatory protein (StAR), but not peripheral-type benzodiazepine receptor, cytochrome P450 side-chain cleavage or 11beta-hydroxylase. Salicylate did not modify the stressor-induced elevation of brain glucocorticoid receptor (GR) protein expression, while liver GR protein content was reduced. Salicylate impact on liver metabolic capacity involved depressed liver glycogen content, whereas no significant changes in liver hexokinase, glucokinase, lactate dehydrogenase, pyruvate kinase, phosphoenolpyruvate carboxykinase, aspartate aminotransferase and alanine aminotransferase activities were observed. Taken together, salicylate impairs the stressor-mediated plasma cortisol response and the associated liver metabolic capacity in trout. The mode of action of salicylate involves disruption of StAR and liver GR, two key proteins critical for cortisol production and target tissue responsiveness to this steroid, respectively.

Non-steroidal anti-inflammatory drugs (NSAIDS) have been detected in the aquatic environment, but little is known about either their impact or mode of action in aquatic organisms. We tested the hypothesis that NSAIDs disrupt the evolutionarily conserved heat shock response, critical for defense against stressor-mediated proteotoxicity, in rainbow trout (Oncorhynchus mykiss). Trout fry were exposed by immersion to a range of salicylate or ibuprofen concentrations (1, 10, 100 or 1000 microg/L) for 4d. Ibuprofen, but not salicylate, at all concentrations induced heat shock protein 70 (hsp70) in trout liver. We used the highest concentration of the drugs to investigate their mode of action on the heat shock response. Fry were subjected to a standardized heat shock, 10 degrees C above ambient (13 degrees C) for 1h, and the temporal changes in liver hsp70 mRNA and protein content as well as glucose dynamics during recovery from the heat stressor assessed. Ibuprofen exposure did not modify hsp70 mRNA abundance, but significantly depressed the heat shock-induced hsp70 protein expression in the liver and gill of trout. Salicylate exposure elevated hsp70 mRNA abundance and delayed the hsp70 expression after a heat shock. Liver glucose levels and the activities of hexokinase, pyruvate kinase and lactate dehydrogenase, were elevated by NSAIDs suggesting enhanced tissue glycolytic capacity. Effects on whole body glucose dynamics, induced by the heat shock, were either absent with ibuprofen or completely modified by salicylate. Overall, NSAIDs disrupt the heat shock response in rainbow trout, while the mode of action of salicylate and ibuprofen in impacting the cellular stress response appears distinct.

A toxicologic and dermatologic review of ethyl hexyl salicylate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of cis-3-hexenyl salicylate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of hexyl salicylate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 1,3-dimethyl-3-butenyl salicylate when used as a fragrance ingredient is presented.

Large doses of aspirin produce reversible hearing loss and tinnitus. These effects have been attributed to the salicylate ion, the active component of aspirin. Salicylate acts as a competitive antagonist at the anion-binding site of prestin, the motor protein of sensory outer hair cells. This provides an explanation for the hearing loss induced by aspirin. However, the molecular mechanism of salicylate-induced tinnitus remains obscure. One physiological explanation is that salicylate ototoxicity is likely to originate in an alteration to arachidonic acid metabolism. Arachidonic acid potentiates NMDA receptor currents. We therefore tested the involvement of cochlear NMDA receptors in the occurrence of tinnitus. Tinnitus was assessed with a behavioural test based on an active avoidance paradigm. Results showed that the tinnitus induced by salicylate may be suppressed by the introduction of NMDA antagonists into the cochlear fluids. To determine if the activation of NMDA receptors was linked to cyclooxygenase inhibition, we investigated the effect of mefenamate (a potent cyclooxygenase inhibitor). Since NMDA antagonists also blocked mefenamate-induced tinnitus, we suggest that salicylate-induced tinnitus is mediated by cochlear NMDA receptors through the inhibition of cyclooxygenase activity. Target cochlear NMDA receptors may therefore present a therapeutic strategy for the treatment of tinnitus.

A toxicologic and dermatologic review of trans-2-hexenyl salicylate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of methyl 4-methylsalicylate when used as a fragrance ingredient is presented.

A toxicological and dermatological review of ethyl salicylate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of methyl salicylate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of butyl salicylate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of isobutyl salicylate when used as a fragrance ingredient is presented.

An evaluation and review of a structurally related group of fragrance materials.

A toxicologic and dermatologic review of isoamyl salicylate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of benzyl salicylate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic review of 3-methyl-2-butenyl salicylate when used as a fragrance ingredient is presented.