Glycol Monophenyl Ether Research Articles

Pharmacokinetics of 2-phenoxyethanol and its major metabolite, phenoxyacetic acid, after dermal and inhaled routes of exposure: application to development PBPK model in rats

2-Phenoxyethanol (PE), ethylene glycol monophenyl ether, is widely used as a preservative in cosmetic products as well as in non-cosmetics. Since PE has been used in many types of products, it can be absorbed via dermal or inhaled route for systemic exposures. In this study, the pharmacokinetic (PK) studies of PE and its major metabolite, phenoxyacetic acid (PAA), after dermal (30mg and 100mg) and inhaled administration (77mg) of PE in rats were performed. PE was administered daily for 4days and blood samples were collected at day 1 and day 4 for PK analysis. PE was rapidly absorbed and extensively metabolized to form PAA. After multiple dosing, the exposures of PE and PAA were decreased presumably due to the induction of metabolizing enzymes of PE and PAA. In dermal mass balance study using [14C]-phenoxyethanol ([14C]PE) as a microtracer, most of the PE and its derivatives were excreted in urine (73.03%) and rarely found in feces (0.66%). Based on these PK results, a whole-body physiologically-based pharmacokinetic (PBPK) model of PE and PAA after dermal application and inhalation in rats was successfully developed. Most of parameters were obtained from the literatures and experiments, and intrinsic clearance at steady-state (CLint,ss) were optimized based on the observed multiple PK data. With the developed model, systemic exposures of PE and PAA after dermal application and inhalation were simulated following no-observed-adverse-effect level (NOAEL) of 500mg/kg/day for dermal application and that of 12.7mg/kg/day for inhalation provided by the Environmental Protection Agency. The area under the concentration-time curve at steady state (AUCss) in kidney and liver (and lung for inhalations), which are known target organs of exhibiting toxicity of PE, as well as AUCss in plasma of PE and PAA were obtained from the model.

Prenatal exposure to glycol ethers and visual contrast sensitivity in 6-year-old children in the PELAGIE mother-child cohort.

Maternal occupational exposure to organic solvents during pregnancy has been associated with decreased visual function in offspring. Glycol ethers (GEs) belong to oxygenated solvents and are widely used both in occupational and domestic contexts. We aimed to assess associations between prenatal GEs exposure and contrast sensitivity in children. Six GE alkoxy carboxylic acidic metabolites (methoxyacetic acid [MAA], ethoxyacetic acid [EAA], ethoxyethoxyacetic acid [EEAA], butoxyacetic acid [BAA], phenoxyacetic acid [PhAA], and 2-methoxypropionic acid [2-MPA]) were measured in first morning void urine samples collected from 220 early-pregnancy women, in the mother-child PELAGIE cohort (France). Trained investigators administered the Functional Acuity Contrast Test (FACT) to the 6-year-old children, providing scores for 5 spatial frequencies (1.5-18 cycles per degree (cpd)). We standardized biomarker urinary concentrations on urine sampling conditions. Values below the LOD were imputed based on log-normal distribution, generating five datasets for multiple imputation. Linear regression models were adjusted for potential confounders. GE metabolites were detected in 70-98% of maternal urine samples. Phenoxyacetic acid (PhAA) had the highest median concentration (0.33mg/L), and 2-methoxypropionic acid (2-MPA) the lowest (0.01mg/L). Children with higher prenatal PhAA concentrations had poorer FACT scores at various spatial frequencies (fourth vs. first quartile: β18cpd=-0.90 (95% confidence interval CI=-1.64, -0.16), β12cpd=-0.92 (95%CI=-1.55, -0.29) and β1.5cpd=-0.69 (95%CI=-1.19, -0.20)). The 2-MPA log-scale concentration was negatively associated with the FACT score at the 3-cpd stimulus. PhAA is the metabolite of ethylene glycol monophenyl ether present in many cosmetics. 2-MPA is the metabolite of an isomer of propylene glycol methyl ether commonly present in household and industrial cleaning products. Although evidence of biological plausibility is lacking, the study suggests adverse impact of ubiquitous prenatal exposure to some GE on visual functioning among children.

Inhibition of germinal vesicle breakdown in Xenopus oocytes in vitro by a series of substituted glycol ethers.

A 24 hour in vitro Xenopus oocyte maturation (germinal vesicle breakdown [GVBD]) assay developed by Pickford and Morris (Environmental Health Perspectives, 1999, 107, 285-292) was used to screen a series of substituted glycol ethers (GEs). Substituted GEs included: ethylene glycol monomethyl ether (EGME); EG monoethyl ether (EGEE); EG monopropyl ether (EGPE); EG monobutyl ether (EGBE); EG monohexyl ether (EGHE); diethylene glycol monomethyl ether (DGME); triethylene glycol monomethyl ether (TGME); ethylene glycol monophenyl ether (EGPhE); EG monobenzyl ether (EGBeE); EG diphenyl ether (EGDPhE); and propylene glycol monophenyl ether (PGPhE). The GEs inhibited progesterone- or androstenedione-induced GVBD with the following relative potency: EGPhE > PGPhE > EGME >> EGEE ≥ EGBeE > EGPE >> EGBE >EGHE > EGDPhE >> DGME ≥ TGME, or EGPhE >> PGPhE >> EGBeE > EGDPhE > EGEE > EGME > EGPE > EGBE, EGHE, DGME and TGME, respectively. Further, [3 H]progesterone or [3 H]androstenedione binding affinities to the oocyte plasma membrane progesterone receptor (OMPR) or classical androgen receptor (AR) were: EGME > EGPhE ≥ PGPhE ≥ EGEE > EGBeE >> EGPE >> EGBE ≥ EGHE > EGDPhE, TGME, and DGME, or EGPhE > PGPhE >> EGBeE > EGDPhE >> EGEE ≥ EGME >> EGPE, EGBE, and EGHE > DGME and TGME, respectively. Binary joint mixture studies with the GVBD model using flutamide (AR antagonist) and EGPhE indicated that flutamide/EGPhE mixture acted in a concentration additive manner. The effects of substituted GE series, however, may be mediated through the OMPR; the potency of EGPhE may be the result of bimodal inhibition of both the OMPR and AR pathways.

Dielectric studies of binary mixtures of ethylene glycol mono phenyl ether with 1-butanol at different temperatures

Static permittivity ([Formula: see text]), refractive index ([Formula: see text]) and density ([Formula: see text]) of binary mixtures of ethylene glycol mono phenyl ether (EGMPE) with 1-butanol (1-BuOH) over the entire range of mole fraction and at temperatures ([Formula: see text], 313.15 and 323.15[Formula: see text]K) have been measured. From the experimental data, parameters such as excess static permittivity ([Formula: see text]), excess permittivity at optical frequency ([Formula: see text]), effective Kirkwood correlation factor ([Formula: see text]), corrective Kirkwood correlation factor ([Formula: see text]) and Bruggeman factor ([Formula: see text]) have been calculated to obtain qualitative and quantitative information about the complex formation through H-bond in binary system. In order to predict the static permittivity of polar–polar binary mixtures six mixing rules were applied and for refractive index five mixing rule were applied. Experimental results of permittivity ([Formula: see text]) and refractive index (n) are compared with those obtained from theoretical calculations. Excess parameters were fitted to the Redlich–Kister type polynomial equation.

Poly(ether-b-amide)/ethylene glycol monophenyl ether gel membrane with superior CO2/N2 separation performance fabricated by thermally induced phase separation method

Polymeric gel membranes contain poly(ether-b-amide) (Pebax) and ethylene glycol monophenyl ether (EPH) was prepared via thermally induced phase separation (TIPS) method for the first time. In the membranes, EPH was used as not only diluent to form the gel structure, but also functional liquid to enhance the CO2 permeability and CO2/N2 selectivity. Comprehensive investigation was carried out to study the phase separation behaviors and membrane performances. Phase diagrams and optical microscope results indicate that the crystallizition of Pebax from a one-phase solution is responsible for the physical network structure of the gel membranes. Meantime, the gel temperature shifted to the lower region with increasing EPH content. Both the pure CO2 permeability and CO2/N2 ideal selectivity of the membranes were simultaneously increased with the increase of EPH content, which can be ascribed to the multiple synergistic effect of (a) the increased solubility of CO2 by Lewis acid-base interactions between CO2 and ethylene oxide groups in EPH, (b) the barrier effect of EPH on the transport of N2 and (c) more permeable amorphous phase was formed in polymer matrix. The overall performance of gel membranes with 60 and 80wt% EPH fall within the attractive region beyond the “Robeson Upper Bound” for CO2/N2 gas pairs. The successful application of TIPS provides a new route to the structure modulation and performance enhancement of polymer gel membranes in the removal of CO2 from gas streams.

Dielectric relaxation studies of binary mixture of diethylene glycol mono phenyl ether and methanol by Time Domain Reflectometry

The complex permittivity spectra of binary liquid mixtures of diethylene glycol mono phenyl ether (DEGMPE) with methanol (MeOH) were determined in a frequency range of 10MHz to 25GHz using Time Domain Reflectometry (TDR) at four different temperatures 283.15, 288.15 293.15 and 298.15K, through entire concentration range. The dielectric parameters viz. static permittivity (ε), high frequency limit dielectric permittivity (ε∞1) and relaxation time (τ) have been obtained by CNLS fit method. From the experimental data, parameters such as excess static permittivity (εE), excess permittivity at optical frequency (ε∞E), excess inverse relaxation time (1/τ)E, effective Kirkwood correlation factor (geff), corrective Kirkwood correlation factor (gf) and some thermo-dynamical parameters have been calculated. Excess parameters were fitted to the Redlich–Kister type polynomial equation.

Dielectric relaxation studies of binary mixture of ethylene glycol mono phenyl ether and methanol by Time Domain Reflectometry

The complex permittivity spectra of binary liquid mixtures of ethylene glycol mono phenyl ether (EGMPE) with methanol (MeOH) were determined in frequency range of 10MHz to 25GHz using Time Domain Reflectometry (TDR) at four different temperatures 283.15, 288.15, 293.15 and 298.15K through entire concentration range. The dielectric parameters viz static permittivity (ε), high frequency limit dielectric permittivity (ε∞) and relaxation time (τ) have been obtained by CNLS fit method. From the experimental data, parameters such as excess static permittivity (εE), excess inverse relaxation time (1/τ)E, Kirkwood correlation factor (gf), effective Kirkwood correlation factor (geff) and Bruggeman's factor (fb) and some thermo-dynamical parameters have been calculated. Excess parameters were fitted to the Redlich–Kister type polynomial equation.

Relative permittivity, density, viscosity, refractive index and ultrasonic velocity of binary mixture of ethylene glycol monophenyl ether and 1-hexanol at different temperatures

Relative permittivity (ε), refractive index (nD), density (ρ), viscosity (η), and ultrasonic velocity (u) of liquid mixtures of ethylene glycol monophenyl ether and 1-hexanol as a function of mole fraction of 1-hexanol have been measured at three different temperatures (303.15, 313.15 and 323.15K). Various acoustical parameters viz., adiabatic compressibility (β), acoustic impedance (Z), free length (Lf), internal pressure (πi), and free volume (Vf) were evaluated from the experimental data. Excess dielectric, excess physico-chemical and excess acoustic parameters were calculated and fitted to the Redlich–Kister relation. The excess viscosity (ηE), excess relative permittivity (εE) and excess adiabatic compressibility (βE) showed negative deviation from ideality over the entire range of concentration of 1-hexanol. Various excess parameters were qualitatively analyzed to gain some insight to the intermolecular interactions in the liquid mixture.

Transdermal Evaporation Delivery System of Praziquantelfor Schistosomiasis Japonicum Chemotherapy

A transdermal evaporation delivery system (TEDS) of praziquantel (PZQ) was developed by selecting ethylene glycol monophenyl ether as a nonvolatile component solvent and ethanol as a volatile component solvent to control efficiently the transmission and morbidity of the global schistosomiasis, providing a convenient administration system of PZQ for both humans and domestic animals. The solubility of PZQ in TEDS was more than 400 mg/mL when the ethanol concentration was 50% (w/w) in the solvent mixture at 32 °C, enabling to adapt requirements for the treatment of schistosomiasis. The highest serum drug concentration reached 35.93 µg/mL after transdermal administration of TEDS of PZQ in rabbits, being 6.3-fold higher than that after oral administration at the same dose. The TEDS of PZQ achieved treatment efficacy with the worm reduction of 100% when it was applied in the experimental treatment of Schistosoma japonicum in rabbits. The TEDS of PZQ that provides passive and nonocclusive delivery, having the inexpensive cost, low skin irritation rates, and precise dose of administration, should find application in the transmission control and chemotherapy of global schistosomiasis.

Dielectric characterization study of liquid‐based materials for mimicking breast tissues

AbstractThe possibility of mimicking different types of breast tissues to realize experimental phantoms has been investigated by measuring the complex permittivity of polyethylene glycol mono phenyl ether (Triton X‐100) and distilled water solutions. In this respect, broad band electromagnetic characterization of several mixtures, at different concentrations, has been carried out in the 0.5–12 GHz frequency range. The good fitting between the dielectric properties of mammary tissues and that of the proposed mixtures, and the stability against temperature in the range 18–30 °C, suggest the possibility of mimicking the dielectric characteristics of breast tissues using easily available and low cost materials. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:1276–1280, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26001

Development of an SPME–GC–MS/MS procedure for the monitoring of 2-phenoxyethanol in anaesthetised fish

2-Phenoxyethanol (ethylene glycol monophenyl ether, C 8H 10O 2) is a promising anaesthetic agent used in fisheries and aquaculture. The aim of this study was to develop a fast and easy method to determine 2-phenoxyethanol residue levels in fish tissue and blood plasma, and, subsequently, to use the method to monitor the dynamics of 2-phenoxyethanol residues in fish treated with anaesthetic. We developed a new procedure that employs solid phase microextraction (SPME) of the target analyte from the sample headspace followed by gas chromatography–mass spectrometry (GC–MS). Both sample handling, aimed at maximum transfer of 2-phenoxyethanol into the headspace, and SPME–GC–MS conditions were carefully optimised. Using a divinylbenzene/Carboxen/polydimethylsiloxane (PDMS/CAR/DVB) fiber for 60 min sampling at 30 °C and an ion trap detector operated in MS/MS mode, we obtained detection (LOD) and quantification (LOQ) limits of 0.03 and 0.1 mg kg −1 of sample, respectively. The method was linear in a range of 0.1–250 mg kg −1 and, depending on the sample matrix and spiking level, a repeatability (expressed as relative standard deviation, R.S.D.) of between 3% and 11% was obtained.

Transdermal Delivery of Praziquantel: Effects of Solvents on Permeation Across Rabbit Skin

To explore a new method for the transdermal delivery of praziquantel (PZQ), the effects of solvents on permeation across rabbit skin were investigated. The solubility of PZQ in five different solvents, ethylene glycol monophenyl ether (EGPE), 1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, and oleic acid, were measured with a UV-Vis spectrophotometer. The determination of the n-octanol/water partition coefficient of PZQ in the five different solutions and assay of serum concentration following PZQ transdermal administration in rabbits were performed using HPLC. The results indicated that the transdermal absorption of the drug was related to the partition coefficient and lipophilic characteristics of the solvent. The optimal solvent for PZQ transdermal delivery was EGPE in our protocol. The solubility of PZQ in EGPE is >400 mg/ml, and the apparent partition coefficient of PZQ in the solution is 0.895 (log P value). After transdermal administration of PZQ in EGPE solution, the bioavailability is 2.85-fold that after oral administration. The serum drug concentration was maintained at 4.0 mug/ml over 4 h, which is sufficient for the treatment of schistosomiasis. At the same time, no apparent side effects were found on the skin. EGPE may thus be a promising vehicle for the transdermal delivery of PZQ in the future.

Method Development and Validation of Preservatives Determination (Benzyl Alcohol, Ethylene Glycol Monophenyl Ether, Methyl Hydroxybenzoate, Ethyl Hydroxybenzoate, Propyl Hydroxybenzoate, and Butyl Hydroxybenzoate) using HPLC

The purpose of the research described herein was to develop a new high performance liquid chromatography (HPLC) method for the assay of benzyl alcohol, ethylene glycol monophenyl ether, methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate, and butyl hydroxybenzoate preservatives. The use of a reversed‐phase C18 column (250 mm×4.0 mm and 5 µm) using a gradient elution system enabled six compounds to be separated simultaneously in a single chromatographic run in less than 12 minutes. The method was successfully validated following ICH guidelines, and it has been demonstrated to be reliable for the assay of benzyl alcohol, ethylene glycol monophenyl ether, methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate, and butyl hydroxybenzoate preservatives used in the manufacturing of drug products.

Effects of Organic Solvents in Luminescent umu Test using S. typhimurium TL210

We evaluated the effects of 15 different organic solvents in the luminescentumutest, a simplified version of the conventionalumutest, by determining the amount of luminescence induced by each solvent and considering its toxicity and stability of the solvents with regard to the following 15 types of solvents: methanol, dimethyl sulfoxide, acetonitrile, 1, 4-dioxane, tetrahydrofuran, acetone, cyclohexane, ethyl alcohol, N, N-dimethylformamide, ethylene glycol monophenyl ether, ethylene glycol dimethyl ether, glycerol formal, 1-methyl-2-pyrolidone, tetrahydrofurfuryl alcohol, and formamide. We found that cyclohexane, methanol, acetonitrile, ethanol, and acetone could be used in the test. Methanol, in particular, was effective for determining the mutagenicity of environmental samples.

In vitro induction of apoptosis vs. necrosis by widely used preservatives: 2-phenoxyethanol, a mixture of isothiazolinones, imidazolidinyl urea and 1,2-pentanediol

Preservatives are added to many final products, such as detergents, cosmetics, pharmaceuticals and vaccines. We conducted an in vitro investigation of the apoptosis- and necrosis-inducing potential of brief applications (10 min) of four common preservatives: ethylene glycol monophenyl ether, 2-phenoxyethanol (EGPE), imidazolidinyl urea (IMU), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMI/MI), and 1,2-pentanediol, a “preservative-non-preservative” best known as pentylene glycol. Using HL60 cells, we monitored the kinetics of cell toxicity with the MTT test and analysed extranuclear end points of apoptosis, i.e. phosphatidylserine exposure and nuclear fragmentation. Preservative treatment resulted in a dose-dependent decrease of cell viability. The mode of cell death was dose-dependent: necrosis occurred at high concentrations while apoptosis, shown by DNA laddering, DNA sub-diploid peak and caspase-3 activation, occurred at lower concentrations 0–24 hr after exposure to a single dose: CMI/MI induced apoptosis at low concentrations (0.001–0.01%) and necrosis at high concentrations (0.5–0.1%); IMU and EGPE required higher concentrations to induce apoptosis (IMU 0.01–0.1% and EGPE 0.01–0.5%) or necrosis (IMU 0.5–1% and EGPE only at 1%). PG induced apoptosis only at 5%. Externalization of PS, a hallmark of apoptosis, occurred early in HL60 treated with low concentrations of CMI/MI and EGPE and was concomitant with the subdiploid peak in HL60 treated with PG. However, it did not occur in HL60 treated with IMU. In conclusion, at appropriate concentrations, each of the four preservatives modulates the apoptotic machinery by a caspase-dependent mechanism. Thus, apoptosis could be a good parameter to evaluate the cytoxicity of these chemical compounds.

Effects of 2-phenoxyethanol on N-methyl-D-aspartate (NMDA) receptor-mediated ion currents.

The actions were examined of 17 frequently used glycol ether compounds on the glutamate receptor-mediated ion currents. The receptors were expressed in Xenopus oocytes by injection of rat brain mRNA. Most of the 17 glycol ethers exerted no effects on the glutamate subreceptors activated by kainate and N-methyl-D-aspartate (NMDA), whereas 2-phenoxyethanol (ethylene glycol monophenyl ether) caused a considerable reduction of NMDA-induced membrane currents in a reversible and concentration-dependent manner. The threshold concentration of the ethylene glycol monophenyl ether effect was < 10 mumol/l. The concentration for a 50% inhibition (IC50) was approximately 360 mumol/l. The results indicate a neurotoxic potential for 2-phenoxyethanol.

High-Barrier Poly(hydroxy amide ethers): Effect of Polymer Structure on Oxygen Transmission Rates. 3

The synthesis of a series of new high-barrier poly(hydroxy amide ethers) is described. The polymers are formed by the reactions of aromatic diglycidyl ethers, with N,N‘-bis(3-hydroxyphenyl)adipamide, HOC6H4NHCO(CH2)4CONHC6H4OH, at 140−160 °C in propylene glycol monophenyl ether solvent using ethyltriphenylphosphonium acetate as initiator. Poly(hydroxy amide ethers) of general structure [−CH2CH(OH)CH2OArOCH2CH(OH)CH2OC6H4NHCO(CH2)4CONHC6H4O−]n are readily prepared in high molecular weight. The mainly amorphous thermoplastics have glass transition temperatures (Tg) of 78−146 °C and oxygen transmission rates (O2TR) that range from 0.2 to 1.8 cc·mil/(100 in.2·atm·day) (barrier units or BU) at 23 °C and 45−90% relative humidity. It was determined that barrier properties improve (i.e., O2TR decreases) as the aromatic core unit, Ar, becomes less bulky or more polar. For example, the poly(hydroxy amide ether) in which Ar is the aromatic unit based on 2,2-bis(4-hydroxyphenyl)-1,1,1,3,3,3-hexafluoropropane has an O2TR of 1.8 BU, while the poly(hydroxy amide ethers) in which Ar is based on the more compact 2,6-dihydroxynaphthylene or more polar 1,1-bis(4-hydroxyphenyl)acetamide units have lower O2TR of 0.2 BU. In one instance, an amorphous poly(hydroxy amide ether) was induced to crystallize, yielding a semicrystalline polymer with significantly lower O2TR. The derivative in which Ar is the 4,4‘-biphenylene unit (O2TR = 0.3 BU, Tg = 110 °C) was annealed at 160 °C to yield a crystalline material with significant improvement in oxygen barrier (O2TR = 0.06 BU, Tg = 117 °C, Tm = 195 °C). Other effects that polymer structure has on O2TR and Tg are discussed.

Ethylene Glycol Monophenyl Ether

The disinfectant ethylene glycol monophenyl ether(EPH) features high-efficiency, safety, low toxicity, non-irritation and non-pollution. EPH can be widely used in detergent and cosmetics as disinfectant and preservative due to its special properties in sterilization, anti-microorganism functions to pseudomonas aeruginosa, Gram-positive and Gram-negative bacteria. The effectiveness of adding EPH in detergent and cosmetics used as disinfectant, preservative and deodorant is described in some examples. So far the EPH is still used as an important disinfectant in the cosmetics market in America and in Japan. Recent years, EPH has been used in domestic daily chemicals enterprises.

Reproductive toxicology. Ethylene glycol monophenyl ether.

Reproductive toxicology. Ethylene glycol monophenyl ether.

Poly(hydroxy amide ethers): New High-Barrier Thermoplastics

The synthesis of a new class of high-barrier polymers, poly(hydroxy amide ethers), is described. The polymers are formed by the reactions of bisphenol-A diglycidyl ether, OCH2CHCH2OC6H4C(CH3)2C6H4OCH2CHCH2O, and amide-containing bisphenols of the general formula HOC6H4NHC(O)RC(O)NHC6H4OH [R = −(CH2)n−, −CH2C6H4CH2−, or −C6H4−] or HOC6H4NHC(O)C6H4OH at 140−160 °C in propylene glycol monophenyl ether solvent using ethyltriphenylphosphonium acetate as initiator. High-molecular-weight poly(hydroxy amide ethers) of the general structure [−CH2CH(OH)CH2OC6H4C(CH3)2C6H4OCH2CH(OH)CH2OC6H4NHC(O)RC(O)NHC6H4O−]n or [−CH2CH(OH)CH2OC6H4C(CH3)2C6H4OCH2CH(OH)CH2OC6H4NHC(O)C6H4O−]n are readily prepared. The amorphous thermoplastics have glass transition temperatures (Tg) of 90−133 °C and oxygen transmission rates (O2TR) which range from 0.7 to 4.6 cc·mil/100 in.2·atm·day (barrier units or BU) at 23 °C and 47−85% relative humidity. The effect that polymer structure has on oxygen barrier properties and Tg is described. The characterization, structure determination, and properties of the poly(hydroxy amide ethers), as well as the amide-containing bisphenol precursors, are also presented.