The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA).

Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to . BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists.

European Medicines Agency Conflicts With the European Food Safety Authority (EFSA) on Bisphenol A Regulation.

The European Food Safety Authority (EFSA) has revised their estimate of the toxicity of bisphenol A (BPA) and, as a result, have recommended reducing the tolerable daily intake (TDI) by 20 000-fold. This would essentially ban the use of BPA in food packaging such as can liners, plastic food containers, and in consumer products. To come to this conclusion, EFSA used a systematic approach according to a pre-established protocol and included all guideline and nonguideline studies in their analysis.

An Iron Macrocyclic Complex Containing Four "Hybrid" Pyridinium Amidate/Amidate N-Donors as a Catalyst for Oxidations with Hydrogen Peroxide.

The macrocyclic proligand [H L][OTf] , which contains four carboxamide functions and two conjugated pyridinium groups, is easily deprotonated by the weak base sodium acetate to give the corresponding neutral proligand [H L]. Metallation of [H L] with iron(II) chloride proceeds rapidly to form the macrocyclic complex, [Fe Cl(L)]. This is an effective catalyst for the oxidation of the organic dye orange II by hydrogen peroxide in aqueous solution, and the kinetic parameters for this reaction have been determined.

The Mechanism of Formation of Active Fe-TAMLs Using HClO Enlightens Design for Maximizing Catalytic Activity at Environmentally Optimal, Circumneutral pH.

Fe-TAML/peroxide catalysis provides simple, powerful, ultradilute approaches for removing micropollutants from water. The typically rate-determining interactions of HO with Fe-TAMLs (rate constant ) are sharply pH-sensitive with rate maxima in the pH 9-10 window. Fe-TAML design or process design that shifts the maximum rates to the pH 6-8 window of most wastewaters would make micropollutant eliminations even more powerful.

On TAML Catalyst Resting State Lifetimes: Kinetic, Mechanistic, and Theoretical Insight into Phosphate-Induced Demetalation of an Iron(III) Bis(sulfonamido)bis(amido)-TAML Catalyst.

At ambient temperatures, neutral pH and ultralow concentrations (low nM), the bis(sulfonamido)bis(amido) oxidation catalyst [Fe{4-NOCH-1,2-(COCMeSO)CHMe}(OH)] () has been shown to catalyze the addition of an oxygen atom to microcystin-LR. This persistent bacterial toxin can contaminate surface waters and render drinking water sources unusable when nutrient concentrations favor cyanobacterial blooms. In mechanistic studies of this oxidation, while the pH was controlled with phosphate buffers, it became apparent that iron ejection from becomes increasingly problematic with increasing [phosphate] (0.

Detoxification of oil refining effluents by oxidation of naphthenic acids using TAML catalysts.

The environmental problem stemming from toxic and recalcitrant naphthenic acids (NAs) present in effluents from the oil industry is well characterized. However, despite the numerous technologies evaluated for their destruction, their up-scaling potential remains low due to high implementation and running costs. Catalysts can help cutting costs by achieving more efficient reactions with shorter operating times and lower reagent requirements.

Quantifying evolving toxicity in the TAML/peroxide mineralization of propranolol.

Oxidative water purification of micropollutants (MPs) can proceed via toxic intermediates calling for procedures for connecting degrading chemical mixtures to evolving toxicity. Herein, we introduce a method for projecting evolving toxicity onto composite changing pollutant and intermediate concentrations illustrated through the TAML/HO mineralization of the common drug and MP, propranolol. The approach consists of identifying the key intermediates along the decomposition pathway (UPLC/GCMS/NMR/UV-Vis), determining for each by simulation and experiment the rate constants for both catalytic and noncatalytic oxidations and converting the resulting predicted concentration versus time profiles to evolving composite toxicity exemplified using zebrafish lethality data.

Designing Materials for Aqueous Catalysis: Ionic Liquid Gel and Silica Sphere Entrapped Iron-TAML Catalysts for Oxidative Degradation of Dyes.

Materials have been developed that encapsulate a homogeneous catalyst and enable it to operate as a heterogeneous catalyst in water. A hydrophobic ionic liquid within the material was used to dissolve Fe-TAML and keep it from leaching into the aqueous phase. One-pot processes were used to entrap Fe-TAML in basic ionic liquid gels, and ionic liquid gel spheres structured via a modified Stöber synthesis forming SiO particles of uniform size.

Predicting Properties of Iron(III) TAML Activators of Peroxides from Their III/IV and IV/V Reduction Potentials or a Lost Battle to Peroxidase.

A cyclic voltammetry study of a series of iron(III) TAML activators of peroxides of several generations in acetonitrile as solvent reveals reversible or quasireversible Fe and Fe anodic transitions, the formal reduction potentials (E°') for which are observed in the ranges 0.4-1.2 and 1.

TAML- and Buffer-Catalyzed Oxidation of Picric Acid by HO: Products, Kinetics, DFT, and the Mechanism of Dual Catalysis.

Studies of the oxidative degradation of picric acid (2,4,6-trinitrophenol) by HO catalyzed by a fluorine-tailed tetraamido macrocyclic ligand (TAML) activator of peroxides [Fe{4,5-ClCH-1,2-(COCMeCO)CF}(OH)] () in neutral and mildly basic solutions revealed that oxidative degradation of this explosive demands components of phosphate or carbonate buffers and is not oxidized in their absence. The TAML- and buffer-catalyzed oxidation is subject to severe substrate inhibition, which results in at least 1000-fold retardation of the interaction between the iron(III) resting state of and HO. The inhibition accounts for a unique pH profile for the TAML catalysis with the highest activity at pH 7.

Oxidative Catalysis by TAMLs: Obtaining Rate Constants for Non-Absorbing Targets by UV-Vis Spectroscopy.

Understanding the catalysis of oxidative reactions by TAML activators of peroxides, i. e. iron(III) complexes of tetraamide macrocyclic ligands, advocated a spectrophotometric procedure for quantifying the catalytic activity of TAMLs for colorless targets (k ', M  s ), which is incomparably more advantageous in terms of time, cost, energy, and ecology than NMR, HPLC, UPLC, GC-MS and other similar techniques.

Zero-Order Catalysis in TAML-Catalyzed Oxidation of Imidacloprid, a Neonicotinoid Pesticide.

Bis-sulfonamide bis-amide TAML activator [Fe{4-NO C H -1,2-(NCOCMe NSO ) CHMe}] (2) catalyzes oxidative degradation of the oxidation-resistant neonicotinoid insecticide, imidacloprid (IMI), by H O at pH 7 and 25 °C, whereas the tetrakis-amide TAML [Fe{4-NO C H -1,2-(NCOCMe NCO) CF }] (1), previously regarded as the most catalytically active TAML, is inactive under the same conditions. At ultra-low concentrations of both imidacloprid and 2, 62 % of the insecticide was oxidized in 2 h, at which time the catalyst is inactivated; oxidation resumes on addition of a succeeding aliquot of 2. Acetate and oxamate were detected by ion chromatography, suggesting deep oxidation of imidacloprid.

A Synthetically Generated LFeOH Complex.

High-valent Fe-OH species are important intermediates in hydroxylation chemistry. Such complexes have been implicated in mechanisms of oxygen-activating enzymes and have thus far been observed in Compound II of sulfur-ligated heme enzymes like cytochrome P450. Attempts to synthetically model such species have thus far seen relatively little success.

Structural, Mechanistic, and Ultradilute Catalysis Portrayal of Substrate Inhibition in the TAML-Hydrogen Peroxide Catalytic Oxidation of the Persistent Drug and Micropollutant, Propranolol.

TAML activators enable unprecedented, rapid, ultradilute oxidation catalysis where substrate inhibitions might seem improbable. Nevertheless, while TAML/HO rapidly degrades the drug propranolol, a micropollutant (MP) of broad concern, propranolol is shown to inhibit its own destruction under concentration conditions amenable to kinetics studies ([propranolol] = 50 μM). Substrate inhibition manifests as a decrease in the second-order rate constant k for HO oxidation of the resting Fe-TAML (RC) to the activated catalyst (AC), while the second-order rate constant k for attack of AC on propranolol is unaffected.

Bis phenylene flattened 13-membered tetraamide macrocyclic ligand (TAML) for square planar cobalt(III).

The preparation, characterization, and evaluation of a cobalt(III) complex with 13-membered tetraamide macrocyclic ligand (TAML) is described. This is a square-planar (X-ray) = 1 paramagnetic (H NMR) compound, which becomes an = 0 diamagnetic octahedral species in excess d-pyridine. Its one-electron oxidation at an electrode is fully reversible with the lowest value (0.

Iron(III) Ejection from a "Beheaded" TAML Activator: Catalytically Relevant Mechanistic Insight into the Deceleration of Electrophilic Processes by Electron Donors.

Kinetic studies of the acid-induced ejection of iron(III) show that the more electron-rich tetra-amido-N macrocyclic ligand (TAML) activator [Fe{(MeCNCOCMeNCO)CMe}OH] (4), which does not have a benzene ring in its head component ("beheaded" TAML), is up to 1 × 10 times more resistant than much less electron-rich [Fe{1,2-CH(NCOCMeNCO)CMe}OH] (1a) to the electrophilic attack. This counterintuitive increased resistance is seen in both the specific acid (k = k[H]/(K + [H])) and phosphate general acid (k = (kK + k[H])/(K+[H])) demetalation pathways. Insight into this reactivity puzzle was obtained from coupling kinetic data with theoretical density functional theory modeling.

Targeting of High-Valent Iron-TAML Activators at Hydrocarbons and Beyond.

TAML activators of peroxides are iron(III) complexes. The ligation by four deprotonated amide nitrogens in macrocyclic motifs is the signature of TAMLs where the macrocyclic structures vary considerably. TAML activators are exceptional functional replicas of the peroxidases and cytochrome P450 oxidizing enzymes.

Analysis of Hydrogen Atom Abstraction from Ethylbenzene by an FeO(TAML) Complex.

It was shown previously (Chem. Eur. J.

Homogeneous Catalysis Under Ultradilute Conditions: TAML/NaClO Oxidation of Persistent Metaldehyde.

TAML activators enable homogeneous oxidation catalysis where the catalyst and substrate (S) are ultradilute (pM-low μM) and the oxidant is very dilute (high nM-low mM). Water contamination by exceptionally persistent micropollutants (MPs), including metaldehyde (Met), provides an ideal space for determining the characteristics and utilitarian limits of this ultradilute catalysis. The low MP concentrations decrease throughout catalysis with S oxidation (k) and catalyst inactivation (k) competing for the active catalyst.

A "Beheaded" TAML Activator: A Compromised Catalyst that Emphasizes the Linearity between Catalytic Activity and pK.

Studies of the new tetra-amido macrocyclic ligand (TAML) activator [Fe{(MeCNCOCMeNCO)CMe}OH] (4) in water in the pH range of 2-13 suggest its pseudo-octahedral geometry with two nonequivalent axial HO ligands and revealed (i) the anticipated basic drift of the first pK of water to 11.38 due to four electron-donating methyl groups alongside (ii) its counterintuitive enhanced resistance to acid-induced iron(III) ejection from the macrocycle. The catalytic activity of 4 in the oxidation of Orange II (S) by HO in the pH range of 7-12 is significantly lower than that of previously reported TAML activators, though it follows the common rate law (v/[Fe] = kk[HO][S]/(k[HO] + k[S]) and typical pH profiles for k and k.

NaClO-Generated Iron(IV)oxo and Iron(V)oxo TAMLs in Pure Water.

The unique properties of entirely aliphatic TAML activator [Fe{(MeCNCOCMeNCO)CMe}OH] (3), namely the increased steric bulk of the ligand and the unmatched resistance to the acid-induced demetalation, enables the generation of high-valent iron derivatives in pure water at any pH. An iron(V)oxo species is readily produced with NaClO at pH values from 2 to 10.6 without any observable intermediate.

Use of a Battery of Chemical and Ecotoxicological Methods for the Assessment of the Efficacy of Wastewater Treatment Processes to Remove Estrogenic Potency.

Endocrine Disrupting Compounds pose a substantial risk to the aquatic environment. Ethinylestradiol (EE2) and estrone (E1) have recently been included in a watch list of environmental pollutants under the European Water Framework Directive. Municipal wastewater treatment plants are major contributors to the estrogenic potency of surface waters.

TAML/H2O2 Oxidative Degradation of Metaldehyde: Pursuing Better Water Treatment for the Most Persistent Pollutants.

The extremely persistent molluscicide, metaldehyde, widely used on farms and gardens, is often detected in drinking water sources of various countries at concentrations of regulatory concern. Metaldehyde contamination restricts treatment options. Conventional technologies for remediating dilute organics in drinking water, activated carbon, and ozone, are insufficiently effective against metaldehyde.