Studies of κ2- and κ3-tripyridylamine complexes of ruthenium and π-stacking by pyridyls.

The reaction of tris(pyridin-2-yl)amine with [CyRuCl2]2 (Cy = p-isopropyltoluene or cymene) in refluxing diglyme led to the formation of cis-[RuCl2{κ2-(2-py)3N}2]·CHCl3 (1a) after recrystallization from chloroform/pentane, or cis-dichloridobis[tris(pyridin-2-yl)amine-κ2N,N']ruthenium(II) dichloromethane disolvate, [RuCl2(C15H12N4)2]·2CH2Cl2 or cis-[RuCl2{κ2-(2-py)3N}2]·2CH2Cl2 (1b). Treatment of 1a with one equivalent of silver(I) hexafluoridoantimonate in dichloromethane gave [RuCl{κ2-(2-py)3N}{κ3-(2-py)3N}][SbF6]·CH2Cl2 (2a). Crystallization of 2a from chloroform provided chlorido[tris(pyridin-2-yl)amine-κ2N,N'][tris(pyridin-2-yl)amine-κ3N,N',N'']ruthenium(II) hexafluoridoantimonate chloroform monosolvate, [RuCl(C15H12N4)2][SbF6]·CHCl3 or [RuCl{κ2-(2-py)3N}{κ3-(2-py)3N}][SbF6]·CHCl3 (2b). Complex 2a reacted with a further equivalent of silver(I) hexafluoridoantimonate to give [Ru{κ3-(2-py)3N}2][SbF6]2 (3). The reaction of (2-py)3N with [CyRuCl2]2 in dichloromethane followed by treatment with excess sodium hexafluoridoantimonate gave the known complex [CyRuCl{κ2-(2-py)3N}][SbF6] (4). Complex 2 is a rare example of a complex containing both κ2- and κ3-(2-py)3N. Intramolecular π-stacking interactions determine the orientation of the free pyridyl in the κ2 complexes. An interesting encapsulation of methylene chloride hydrogen-bonded tetramers was noted in one case.

Preparation of Cellulose-Based Activated Carbon Fibers with Improved Yield and Their Methylene Chloride Adsorption Evaluation.

The recent rapid growth of the battery industry has led to a rapid increase in methylene chloride emissions. Methylene chloride causes health and social problems in humans. In this study, cellulose-based activated carbon fibers (CACFs) with improved yield were prepared for the removal of methylene chloride. The concentration of ammonium phosphate in the pretreatment controlled the crosslink density of cellulose fibers and improved the yield. From the results, the specific surface area and total pore volume of cellulose-based activated carbon fibers pretreated with ammonium phosphate (AP-CACFs) were determined to be 1920-2060 m2/g and 0.83-1.02 cm3/g, respectively, and the total yield improved by 6.78-11.59% compared to that of CACFs (4.97%). In particular, a correlation between the textural properties of CACFs and methylene chloride adsorption/desorption behavior was obtained. This correlation can be used to develop efficient adsorbents for methylene chloride removal.

Diverse dihydroagarofuran sesquiterpene derivatives from the stem and branch of Tripterygium wilfordii.

Ten new dihydroagarofuran sesquiterpene polyol esters, tripterdines A-J (1-10) were isolated from the stem and branch of Tripterygium wilfordii. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses, including UV, IR, HRESIMS, NMR, and CD exciton chirality method. The structures of compounds 1, 3, and 6 were confirmed by X-ray crystallographic analyses. The anti-inflammatory and cytotoxic activities were assessed for all the compounds (1-10). Compounds 3, 5 and 10 exhibited potent anti-inflammatory activities with the secretion level of TNF-α ranging from 43.86% to 51.27%, and the IL-6 ranging from 32.44% to 50.64%. In addition, compounds 1, 3, 7 and 9 showed weak cytotoxicities against three human tumor cell lines (Huh7, MCF-7 and HCT-116).

Solvent exposed occupations and risk of Parkinson disease in Finland.

INTRODUCTION: Epidemiologic and toxicology studies suggest that exposure to various solvents, especially chlorinated hydrocarbon solvents, might increase Parkinson disease (PD) risk. METHODS: In a population-based case-control study in Finland, we examined whether occupations with potential for solvent exposures were associated with PD. We identified newly diagnosed cases age 45-84 from a nationwide medication reimbursement register in 1995-2014. From the population register, we randomly selected non-PD controls matched on sex, along with birth and diagnosis years (age). We included 11,757 cases and 23,236 controls with an occupation in the 1990 census, corresponding to age 40-60. We focused on 28 occupations with ≥ 5% probability of solvent exposure according to the Finnish Job Exposure Matrix. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression modeling, adjusting for age, sex, socioeconomic status, and smoking probability. RESULTS: Similar proportions of cases (5.5%) and controls (5.6%) had an occupation with potential exposure to any solvents. However, all occupations with a point estimate above one, and all significantly or marginally significantly associated with PD (electronic/telecommunications worker [OR = 1.63, 95% CI 1.05-2.50], laboratory assistant [OR = 1.40, 95% CI 0.98-1.99], and machine/engine mechanic [OR = 1.23, 95% CI 0.99-1.52]) entailed potential for exposure to chlorinated hydrocarbon solvents, specifically. Secondary analyses indicated exposure to polycyclic aromatic hydrocarbons and some metals might contribute to the association for mechanics. CONCLUSION: PD risk might be slightly increased in occupations with potential exposure to chlorinated hydrocarbon solvents. Confirmation is required in additional studies that adjust for other occupational exposures and smoking.

Methylene Chloride Burns: A Case Report and Review of Literature.

Chemical burns account for a small percentage of burns but contribute to significant number of burn-related mortalities. The major challenge posed by chemical burns is difficulty in correct depth estimation, as the damage continues to progress until they are effectively neutralized. Besides the most common etiology of chemical burns by alkalis and acids, there are many other unique causes of chemical burns. The author describes a case of chemical burns by heavy duty paint remover, the main composition of which is methylene chloride. Although several studies about methylene chloride poisoning are available in literature, only one case report of burns due to methylene chloride exists in literature. These burns are unique in their presentation. The author describes the presentation and challenges in management of this burn. Clinical trial registration Not applicable.

Removing Acrylic Conformal Coating with Safer Solvents for Re-Manufacturing Electronics.

Conformal coating is typically composed of polymeric film and is used to protect delicate electronic components such as printed-circuit boards. Without removing conformal coating, it would be difficult to repair these complicated electronics. Methylene chloride, also called dichloromethane (DCM), has a widespread usage in conformal coating stripper products. The high toxicity of DCM increases human health risk when workers are exposed to DCM during the conformal coating removal processes. Therefore, the replacement of DCM would be beneficial to greatly improve the overall safety profile for workers in the electronics and coating industries. This research identified and evaluated alternative chemicals for replacing DCM used in acrylic conformal coating stripping operations. The solubility of an acrylic conformal coating was measured and characterized using Hansen solubility parameters (HSP) theory. Coating dwell time tests using various solvent blends verified the accuracy of the created HSP solubility sphere. A data processing method was also developed to identify and screen potential alternative solvent blends in terms of safety, toxicity, and cost-effectiveness. The identified safer solvent blends were demonstrated to provide equivalent stripping performance as compared to DCM based coating strippers within an acceptable cost range. The results of this research will be of value to other types of conformal coatings, such as silicone and polyurethane, where DCM is commonly used in similar coating stripping operations. By safely removing conformal coating, delicate electronics would be available for re-manufacturing, enabling a circular economy.

A Case Series of Chemical Dermal Injury Requiring Operative Intervention after Prolonged Dermal Methylene Chloride Exposure.

INTRODUCTION: Methylene chloride, also known as dichloromethane, is a volatile hydrocarbon used in paint strippers and removers. Toxicity from methylene chloride may include narcosis and elevated carbon monoxide (CO) levels. Significant injury to the skin can occur after prolonged exposure to methylene chloride and other hydrocarbon-based solvents causing a chemical dermal injury. CASE REPORT: This case series describes three male patients with prolonged exposure to a methylene chloride-containing paint remover to the bilateral hands with two of the three patients requiring transfer to a tertiary burn center and operative intervention. The clinical significance and impressive resolution of dermal injury from prolonged methylene chloride exposure are highlighted with detailed images and a literature review. DISCUSSION: Chemical dermal injury secondary to methylene chloride exposure likely results from destruction of lipids within the epidermis and dermis and direct chemical injury. Prolonged exposure to skin can result in clinically important injury that requires management by a burn specialist and may necessitate operative intervention. The severity of the dermal injury can range from severe to mild and should be considered by a clinician after skin exposure to hydrocarbons.

Evaluation of the carcinogenicity of dichloromethane in rats, mice, hamsters and humans.

Dichloromethane (DCM) is a high production volume chemical (>1000 t/a) mainly used as an industrial solvent. Carcinogenicity studies in rats, mice and hamsters have demonstrated a malignant tumor inducing potential of DCM only in the mouse (lung and liver) at 1000-4000 ppm whereas human data do not support a conclusion of cancer risk. Based on this, DCM has been classified as a cat. 2 carcinogen. Dose-dependent toxicokinetics of DCM suggest that DCM is a threshold carcinogen in mice, initiating carcinogenicity via the low affinity/high capacity GSTT1 pathway; a biotransformation pathway that becomes relevant only at high exposure concentrations. Rats and hamsters have very low activities of this DCM-metabolizing GST and humans have even lower activities of this enzyme. Based on the induction of specific tumors selectively in the mouse, the dose- and species-specific toxicokinetics in this species, and the absence of a malignant tumor response by DCM in rats and hamsters having a closer relationship to DCM toxicokinetics in humans and thus being a more relevant animal model, the current classification of DCM as human carcinogen cat. 2 remains appropriate.

New meliacarpin-type (C-seco) and C-ring intact limonoids from the fruits of Melia toosendan.

Toosendansins E-I (1-5), five new limonoids together with nine known limonids(6-14), were isolated and identified from the fruits of Melia toosendan. Their skeletons were belonged to meliacarpins (1 and 2), nimbin (3), and vilasinins (4 and 5). All the isolates were identified using 1D & 2D NMR spectroscopic experiments, and the absolute configurations of 1 and 2 with 1,3-dicinnamoyl moieties were achieved by CD method. Compounds 1 and 4 showed moderate inhibitory activity against osteosarcoma cell line U-2 OS, and compound 4, ohchinolal (12), meliatoxin B1 (13) and 1,12-diacetyltrichichilin B (14) showed obvious reversal activity of multidrug resistance in MCF-7 cell line at 6.25 µM.

Solvent-based paint and varnish removers: a focused toxicologic review of existing and alternative constituents.

Paint and varnish removers constitute a major potential source of organic solvent exposure to contractors and home improvement enthusiasts. Unfortunately, the leading paint remover formulations have traditionally contained, as major ingredients, chemicals classified as probable human carcinogens (eg, methylene chloride) or reproductive toxicants (eg, N-methylpyrrolidone). In addition, because of its unique toxicology (ie, hepatic conversion to carbon monoxide compounding generic solvent narcosis and arrythmogenesis), high volatility, and rigorous requirements for personal protective equipment, methylene chloride exposures from paint removers have been linked to numerous deaths involving both occupational and consumer usage. The aim of this review is to summarize the known toxicology of solvent-based paint remover constituents (including those found in substitute formulations) in order to provide health risk information to regulators, chemical formulators, and end-users of this class of products, and to highlight any data gaps that may exist.

New triterpenoids, steroids and lignan from the stem barks of Entandrophragma utile.

Eight new compounds (Entanutilins O-V; 1-8), including four limonoids, two steroids, one triterpenoid and one lignan were isolated from the stem barks of Entandrophragma utile. Their structures were determined by detailed spectroscopic analyses (HRESIMS and 1D/2D-NMR). Bioactivity screening indicated that compounds 1, 6 and 7 exhibited effective in reversing resistance in MCF-7/DOX cells at a nontoxic concentration of 30 µM with 18.18-, 7.43- and 7.94-fold enhancing effect, respectively, meanwhile, compounds 5 and 6 showed moderate NO inhibitory activities in LPS-activated RAW 264.7 macrophages.

Biological monitoring of occupational exposure to dichloromethane by means of urinalysis for un-metabolized dichloromethane.

The objective of the study is to establish exposure-excretion relationship between dichlorometane (DCM) in air (DCM-A) and in urine (DCM-U) in workplace to confirm a previous report. Male workers in a screen-printing plant participated in the study. Time-weighted average DCM-A was measured by diffusive sampling followed by gas-chromatography (GC), and DCM in end-of-shift urine samples was by head-space GC. The data were subjected to regression and other statistical analyses. In practice, 30 sets of DCM-A and DCM-U values were available. The geometric mean DCM-A was 8.4 ppm and that of DCM-U (as observed) was 41.1 µg/l. The correlation coefficients (0.70-0.85) were statistically significant across the correction for urine density. Thus, the analysis for un-metabolized DCM in end-of-shift urine samples is applicable for biological monitoring of occupational exposure to DCM, in support of and in agreement with the previous report. In conclusion, biological monitoring of occupational DCM exposure is possible by use of analysis for un-metabolized DCM in end-of-shift urine.

Acute and delayed toxicity from co-ingestion of methylene chloride and methanol.

Methylene chloride is a volatile, chlorinated hydrocarbon and colorless solvent found in multiple industrial products including paint strippers, metal cleaners, automotive products, pesticides and aerosol containers. Occupational exposure to methylene chloride is reported in automotive technicians, painters, and other industrial workers with adverse health effects including gastrointestinal, neurological, as well as hepato-renal injuries. International Agency for Research on Cancer (IARC) classifies methylene chloride as a 2 A carcinogen. Through a series of reactions catalyzed by cytochrome P450 2E1 (CYP2E1), metabolism of methylene chloride leads to the formation of formyl chloride, and ultimately carbon monoxide (CO). Most reports of methylene chloride toxicity are due to dermal and inhalational exposure in occupational settings. Ingestion of methylene chloride is uncommon, yet can lead to significant toxicity and prolonged CO toxicity. Methylene chloride is frequently formulated with methanol; individuals who intentionally ingest methylene chloride can experience concomitant methanol toxicity. We present a case of acute ingestion of paint stripper containing methanol and methylene chloride. We discuss the clinical presentation, key management decisions, relevant pathophysiology and biochemistry, as well as the clinical course and management.

[Occupational acute mixed gas poisoning due to improper disposal of hazardous waste].

Objective: To investigate an occupational hazardous gas poisoning incident caused by gas leakage in the process of hazardous waste treatment. Methods: An investigation was conducted on a case of occupational acute hazardous gas poisoning caused by waste treatment gas leakage in Shandong province in December 2017. Meanwhile, the clinical data of 5 cases of poisoning patients were analyzed, and the accident related poison test report and other relevant data were analyzed. Results: The incident was caused by the toxic waste did not do labeling work, the workers' protection measures were not in place, the illegal operation and the blind rescue, resulting in a total of 5 people died on the spot, 12 people were hospitalized with poisoning. Among them, 5 patients admitted to our hospital showed varying degrees of damage to the nervous system and respiratory system. After active treatment, they all got better and were discharged. Conclusion: The poisoning is mainly caused by hydrogen sulfide dichloromethane hydrogen cyanide gas leakage serious production liability accident, clinical main performance for the nervous system circulatory system respiratory system and other system damage.

Dichloromethane-Induced Chemical Burn of the Hand: A Report of Two Cases

Occupational acute mixed gas poisoning due to improper disposal of hazardous waste / 中华劳动卫生职业病杂志

Objective@#To investigate an occupational hazardous gas poisoning incident caused by gas leakage in the process of hazardous waste treatment.@*Methods@#An investigation was conducted on a case of occupational acute hazardous gas poisoning caused by waste treatment gas leakage in Shandong province in December 2017. Meanwhile, the clinical data of 5 cases of poisoning patients were analyzed, and the accident related poison test report and other relevant data were analyzed.@*Results@#The incident was caused by the toxic waste did not do labeling work, the workers' protection measures were not in place, the illegal operation and the blind rescue, resulting in a total of 5 people died on the spot, 12 people were hospitalized with poisoning. Among them, 5 patients admitted to our hospital showed varying degrees of damage to the nervous system and respiratory system. After active treatment, they all got better and were discharged.@*Conclusion@#The poisoning is mainly caused by hydrogen sulfide dichloromethane hydrogen cyanide gas leakage serious production liability accident, clinical main performance for the nervous system circulatory system respiratory system and other system damage.

New triterpenoids with diverse side-chains from the barks of Melia Toosendan.

Nine new euphane- and apotirucallane-type triterpenoids (Toosendines A-I; 1-9), along with three known tirucallane-type compounds were isolated from the barks of Melia toosendan. Their structures were elucidated based on detailed spectroscopic analyses (HRESIMS, 1D/2D-NMR) and circular dichroism spectra. Results of bioactivities screening exhibited that compounds 1, 4 and 5 showed remarkable NO inhibitory activities in LPS-activated RAW 264.7 macrophages, meanwhile, compounds 1 and 4 showed moderate cytotoxicities against U2OS human cancer cell line.

Isocoumarin derivatives from the endophytic fungus, Pestalotiopsis sp.

Five new isocoumarin derivatives, pestalactone A-C (1-3) and pestapyrone D-E (4-5), together with two known compounds (6-7) were isolated from the solid cultures of the endophytic fungus Pestalotiopsis sp. obtained from Photinia frasery. Their structures were mainly determined by extensive spectroscopic analysis, Mo2(OCOCH3)4-induced electronic circular dichroism (ECD), and ECD calculation. Compounds 1 and 2 were rare isocoumarin derivatives and derived from distinctive polyketide pathways. Compound 3 exhibited potent antifungal activity against Candida glabrata (ATCC 90030) with an MIC50 value of 3.49±0.21µg/mL.

New phenalenone derivatives from Pinellia ternata tubers derived Aspergillus sp.

Nine new phenalenone derivatives (1-9), along with two known analogues (10-11) have been isolated from the solid cultures of an endophytic fungus Aspergillus sp. which was obtained from Pinellia ternate. Their structures were established through interpretations of spectroscopic evidence, and some of their absolute configurations were determined by electronic circular dichroism (ECD) and Mo2(OCOCH3)4 induced ECD. All of the phenalenones are unusual acyclic diterpenoid adducts, which are diversely oxidized and partly epoxidized to form different heterocycles. In addition, compound 10 exhibited significant antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis with MIC50 values of 1.87, 2.77, and 4.80µg/mL, respectively.

Anti-inflammatory action of 2-carbomethoxy-2,3-epoxy-3-prenyl-1,4-naphthoquinone (CMEP-NQ) suppresses both the MyD88-dependent and TRIF-dependent pathways of TLR4 signaling in LPS-stimulated RAW264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Rubia cordifolia L. have been widely used as a traditional herbal medicine in Northeast Asia for treating inflammatory diseases. AIM OF THE STUDY: To elucidate the anti-inflammatory mechanism of 2-carbomethoxy-2,3-epoxy-3- prenyl-1,4-naphthoquinone (CMEP-NQ), purified from the roots of R. cordifolia L. as the major anti-inflammatory component, in LPS-treated RAW264.7 murine macrophage cells. MATERIALS AND METHODS: Anti-inflammatory activity of CMEP-NQ was investigated in LPS-treated RAW264.7 cells by measuring the levels of NO, PGE2, and cytokines (IL1ß, IL-6, TNF-α) in the culture supernatants and the TLR4-mediated intracellular events including association of MyD88 with IRAK1, activation of IRAK1, TAK1, MAPKs, NF-κB/AP-1, and IRF3, and generation of ROS. RESULTS: Pretreatment of RAW264.7 cells with CMEP-NQ reduced LPS-induced production of NO and PGE2 by suppressing iNOS and COX-2 gene expression. CMEP-NQ also reduced the secretion of IL-1ß, IL-6, and TNF-α by down-regulating mRNA levels. Under these conditions, TLR4-mediated MyD88-dependent events were inhibited by CMEP-NQ, including the association of MyD88 with IRAK1, phosphorylation of IRAK1, TAK1, and MAPKs (ERK, JNK and p38 MAPK), and activation of NF-κB and AP-1. As TRIF-dependent events of TLR4 signaling, phosphorylation of IRF3 and induction of iNOS protein expression were also inhibited by CMEP-NQ. However, the binding of FITC-conjugated LPS to cell surface TLR4 was not affected by CMEP-NQ. Following LPS stimulation, intracellular ROS production was first detected by DCFH-DA staining at 1h; then it continuously increased until 16h. Although CMEP-NQ failed to exhibit DPPH radical- or ABTS radical-scavenging activity in vitro, LPS-induced ROS production in RAW264.7 cells was more efficiently blocked by CMEP-NQ than by NAC. CONCLUSIONS: These results demonstrate that the suppressive effect of CMEP-NQ on LPS-induced inflammatory responses in RAW264.7 cells was mainly exerted via its inhibition of TLR4-mediated proximal events, such as MyD88-dependent NF-κB/AP-1 activation and ROS production, and TRIF-dependent IRF3 activation.