Cancer effects of formaldehyde: a proposal for an indoor air guideline value

Formaldehyde is a ubiquitous indoor air pollutant that is classified as “Carcinogenic to humans (Group 1)” (IARC, Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropanol-2-ol. IARC monographs on the evaluation of carcinogenic risks to humans, vol 88. World Health Organization, Lyon, pp 39–325, 2006). For nasal cancer in rats, the exposure–response relationship is highly non-linear, supporting a no-observed-adverse-effect level (NOAEL) that allows setting a guideline value. Epidemiological studies reported no increased incidence of nasopharyngeal cancer in humans below a mean level of 1 ppm and peak levels below 4 ppm, consistent with results from rat studies. Rat studies indicate that cytotoxicity-induced cell proliferation (NOAEL at 1 ppm) is a key mechanism in development of nasal cancer. However, the linear unit risk approach that is based on conservative (“worst-case”) considerations is also used for risk characterization of formaldehyde exposures. Lymphohematopoietic malignancies are not observed consistently in animal studies and if caused by formaldehyde in humans, they are high-dose phenomenons with non-linear exposure–response relationships. Apparently, these diseases are not reported in epidemiological studies at peak exposures below 2 ppm and average exposures below 0.5 ppm. At the similar airborne exposure levels in rodents, the nasal cancer effect is much more prominent than lymphohematopoietic malignancies. Thus, prevention of nasal cancer is considered to prevent lymphohematopoietic malignancies. Departing from the rat studies, the guideline value of the WHO (Air quality guidelines for Europe, 2nd edn. World Health Organization, Regional Office for Europe, Copenhagen, pp 87–91, 2000), 0.08 ppm (0.1 mg m−3) formaldehyde, is considered preventive of carcinogenic effects in compliance with epidemiological findings

Identifying an indoor air exposure limit for formaldehyde considering both irritation and cancer hazards

Formaldehyde is a well-studied chemical and effects from inhalation exposures have been extensively characterized in numerous controlled studies with human volunteers, including asthmatics and other sensitive individuals, which provide a rich database on exposure concentrations that can reliably produce the symptoms of sensory irritation. Although individuals can differ in their sensitivity to odor and eye irritation, the majority of authoritative reviews of the formaldehyde literature have concluded that an air concentration of 0.3 ppm will provide protection from eye irritation for virtually everyone. A weight of evidence-based formaldehyde exposure limit of 0.1 ppm (100 ppb) is recommended as an indoor air level for all individuals for odor detection and sensory irritation. It has recently been suggested by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), and the US Environmental Protection Agency (US EPA) that formaldehyde is causally associated with nasopharyngeal cancer (NPC) and leukemia. This has led US EPA to conclude that irritation is not the most sensitive toxic endpoint and that carcinogenicity should dictate how to establish exposure limits for formaldehyde. In this review, a number of lines of reasoning and substantial scientific evidence are described and discussed, which leads to a conclusion that neither point of contact nor systemic effects of any type, including NPC or leukemia, are causally associated with exposure to formaldehyde. This conclusion supports the view that the equivocal epidemiology studies that suggest otherwise are almost certainly flawed by identified or yet to be unidentified confounding variables. Thus, this assessment concludes that a formaldehyde indoor air limit of 0.1 ppm should protect even particularly susceptible individuals from both irritation effects and any potential cancer hazard

Diagnostic fonctionnel du complexe tourbeux de la Réserve naturelle régional de la tourbière de Vred (Nord)

International audienc

Diagnostic fonctionnel du complexe tourbeux de la Réserve naturelle régionale de la Tourbière de Vred (Nord).

International audienc

Rassembler et innover pour mieux conserver les tourbières en Pays de Loire. Les points clés du Programme régional d’actions en faveur des tourbières (PRAT).

International audienc

Ethionamide biomimetic activation and an unprecedented mechanism for its conversion into active and non-active metabolites

International audienceEthionamide (ETH), a second-line anti-tubercular drug that is regaining a lot of interest due to the increasing cases of drug-resistant tuberculosis, is a pro-drug that requires an enzymatic activation step to become active and to exert its therapeutic effect. The enzyme responsible for ETH bioactivation in Mycobacterium tuberculosis is a monooxygenase (EthA) that uses flavin adenine dinucleotide (FAD) as a cofactor and is NADPH- and O2-dependant to exert its catalytic activity. In this work, we investigated the activation of ETH by various oxygen-donor oxidants and the first biomimetic ETH activation methods were developed (KHSO5, H2O2, and m-CPBA). These simple oxidative systems, in the presence of ETH and NAD+, allowed the production of short-lived radical species and the first non-enzymatic formation of active and non-active ETH metabolites. The intermediates and the final compounds of the activation pathway were well characterized. Based on these results, we postulated a consistent mechanism for ETH activation, not involving sulfinic acid as a precursor of the iminoyl radical, as proposed so far, but putting forward a novel reactivity for the S-oxide ethionamide intermediate. We proposed that ETH is first oxidized into S-oxide ethionamide, which then behaves as a "ketene-like" compound via a formal [2 + 2] cycloaddition reaction with peroxide to give a dioxetane intermediate. This unstable 4-membered intermediate in equilibrium with its open tautomeric form decomposes through different pathways, which would explain the formation of the iminoyl radical and also that of different metabolites observed for ETH oxidation, including the ETH-NAD active adduct. The elucidation of this unprecedented ETH activation mechanism was supported by the application of isotopic labelling experiments

A robust nanoporous supramolecular metal–organic framework based on ionic hydrogen bonds

International audienceHydrogen-bond assembly of tripod-like organic cations [H3-MeTrip]3+ (1,2,3-tri(4′-pyridinium-oxyl)-2-methylpropane) and the hexa-anionic complex [Zr2(oxalate)7]6− leads to a structurally, thermally, and chemically robust porous 3D supramolecular framework showing channels of 1 nm in width. Permanent porosity has been ascertained by analyzing the material at the single-crystal level during a sorption cycle. The framework crystal structure was found to remain the same for the native compound, its activated phase, and after guest resorption. The channels exhibit affinities for polar organic molecules ranging from simple alcohols to aniline. Halogenated molecules and I2 are also taken up from hexane solutions by this unique supramolecular framework

Effect of Ligand Substitution around the Dy-III on the SMM Properties of Dual-Luminescent Zn-Dy and Zn-Dy-Zn Complexes with Large Anisotropy Energy Barriers: A Combined Theoretical and Experimental Magnetostructural Study

The new dinuclear (ZnDyIII)-Dy-II and trinuclear (ZnDyIII)-Dy-II-Zn-II complexes of formula [(LZnBrDy(ovan) (NO3)(H2O)](H2O)center dot 0.5(MeOH) (1) and [((LZnBr)-Zn-1)(2)Dy(MeOH)(2)](ClO4) (3) (L and L-1 are the dideprotonated forms of the N,N'-2,2-dimethylpropylenedi(3-methoxysalicylideneiminato and 2-{(E)-[(3-{[(2E,3E)-3-(hydroxyimino)butan-2-ylidene ]amino}-2,2-dimethylpropyl)imino]methyl}-6-methoxyphenol Schiff base compartmental ligands, respectively) have been prepared and magnetostructurally characterized. The X-ray structure of 1 indicates that the Dy-III ion exhibits a DyO9 coordination sphere, which is made from four O atoms coming from the compartmental ligand (two methoxy terminal groups and two phenoxido bridging groups connecting Zn-II and Dy-III ions), other four atoms belonging to the chelating nitrato and ovanillin ligands, and the last one coming to the coordinated water molecule. The structure of 3 shows the central Dy-III ion surrounded by two L1Zn units, so that the Dy-III and Zn-II ions are linked by phenoxido/oximato bridging groups. The Dy ion is eight-coordinated by the six O atoms afforded by two L1 ligands and two O atoms coming from two methanol molecules. Alternating current (AC) dynamic magnetic measurements of 1, 3, and the previously reported dinuclear [LZnClDy(thd)(2)] (2) complex (where thd = 2,2,6,6-tetramethyl-3,5-heptanedionato ligand) indicate single molecule magnet (SMM) behavior for all these complexes with large thermal energy barriers for the reversal of the magnetization and butterfly-shaped hysteresis loops at 2 K. Ab initio calculations on 1-3 show a pure Ising ground state for all of them, which induces almost completely suppressed quantum tunnelling magnetization (QTM), and thermally assisted quantum tunnelling magnetization (TA-QTM) relaxations via the first excited Kramers doublet, leading to large energy barriers, thus supporting the observation of SMM behavior. The comparison between the experimental and theoretical magnetostructural data for 13 has allowed us to draw some conclusions about the influence of ligand substitution around the Dy-III on the SMM properties. Finally, these SMMs exhibit metal- and ligand-centered dual emissions in the visible region, and, therefore, they can be considered as magnetoluminescent bifunctional molecular materials

Analysis of the Role of Peripheral Ligands Coordinated to Zn-II in Enhancing the Energy Barrier in Luminescent Linear Trinuclear Zn-Dy-Zn Single-Molecule Magnets

Three new Dy complexes have been prepared according to a complex-as-ligand strategy. Structural determinations indicate that the central Dy ion is surrounded by two LZn units (L2- is the di-deprotonated form of the N2O2 compartmental N,N-2,2-dimethylpropylenedi(3-methoxysalicylideneiminato) Schiff base. The Dy ions are nonacoordinate to eight oxygen atoms from the two L ligands and to a water molecule. The Zn ions are pentacoordinate in all cases, linked to the N2O2 atoms from L, and the apical position of the Zn coordination sphere is occupied by a water molecule or bromide or chloride ions. These resulting complexes, formulated (LZnX)-Dy-(LZnX), are tricationic with X=H2O and monocationic with X=Br or Cl. They behave as field-free single-molecule magnets (SMMs) with effective energy barriers (U-eff) for the reversal of the magnetization of 96.9(6)K with (0)=2.4x10(-7)s, 146.8(5)K with (0)=9.2x10(-8)s, and 146.1(10)K with (0)=9.9x10(-8)s for compounds with ZnOH2, ZnBr, and ZnCl motifs, respectively. The Cole-Cole plots exhibit semicircular shapes with parameters in the range of 0.19 to 0.29, which suggests multiple relaxation processes. Under a dc applied magnetic field of 1000Oe, the quantum tunneling of magnetization (QTM) is partly or fully suppressed and the energy barriers increase to U-eff=128.6(5)K and (0)=1.8x10(-8)s for 1, U-eff=214.7K and (0)=9.8x10(-9)s for 2, and U-eff=202.4K and (0)=1.5x10(-8)s for 3. The two pairs of largely negatively charged phenoxido oxygen atoms with short DyO bonds are positioned at opposite sides of the Dy3+ ion, which thus creates a strong crystal field that stabilizes the axial M-J=+/- 15/2 doublet as the ground Kramers doublet. Although the compound with the ZnOH2 motifs possesses the larger negative charges on the phenolate oxygen atoms, as confirmed by using DFT calculations, it exhibits the larger distortions of the DyO9 coordination polyhedron from ideal geometries and a smaller U-eff value. Ab initio calculations support the easy-axis anisotropy of the ground Kramers doublet and predict zero-field SMM behavior through Orbach and TA-QTM relaxations via the first excited Kramers doublet, which leads to large energy barriers. In accordance with the experimental results, ab initio calculations have also shown that, compared with water, the peripheral halide ligands coordinated to the Zn2+ ions increase the barrier height when the distortions of the DyO9 have a negative effect. All the complexes exhibit metal-centered luminescence after excitation into the UV -* absorption band of ligand L2- at =335nm, which results in the appearance of the characteristic Dy-III ((F9/2HJ/2)-F-4-H-6; J=15/2, 13/2) emission bands in the visible region

Multistep Photochemical Reactions of Polypyridine-Based Ruthenium Nitrosyl Complexes in Dimethylsulfoxide

International audienceThe photorelease of nitric oxide (NO·) has been investigated in dimethylsulfoxide (DMSO) on two compounds of formula [Ru(R-tpy)(bpy)(NO)](PF6)3, in which bpy stands for 2,2′-bipyridine and R-tpy for the 4′-R-2,2′:6′,2″-terpyridine with R = H and MeOPh. It is observed that both complexes are extremely sensitive to traces of water, leading to an equilibrium between [Ru(NO)] and [Ru(NO2)]. The photoproducts of formula [Ru(R-tpy)(bpy)(DMSO)](PF6)2 are further subjected to a photoreaction leading to a reversible linkage isomerization between the stable Ru-DMSO(S) (sulfur linked) and the metastable Ru-DMSO(O) (oxygen linked) species. A set of 4 [Ru(R-tpy)(bpy)(DMSO)]2+ complexes (R = H, MeOPh, BrPh, NO2Ph) is investigated to characterize the ratio and mechanism of the isomerization which is tentatively related to the difference in absorbance between the Ru-DMSO(S) and Ru-DMSO(O) forms. In addition, the X-ray crystal structures of [Ru(tpy)(bpy)(NO)](PF6)3 and [Ru(MeOPh-tpy)(bpy)(DMSO(S))](PF6)2 are presented