RIFM fragrance ingredient safety assessment, cyclohexanol, CAS Registry Number 108-93-0.

The existing information supports the use of this material as described in this safety assessment. Cyclohexanol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that cyclohexanol is not genotoxic. Data on cyclohexanol provide a calculated margin of exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. Data show that there are no safety concerns for cyclohexanol for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; cyclohexanol is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to cyclohexanol is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; cyclohexanol was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

Assessment of the antibiofilm and antiquorum sensing activities of Eucalyptus globulus essential oil and its main component 1,8-cineole against methicillin-resistant Staphylococcus aureus strains.

Antibacterial resistance is an increasingly serious threat to global public health. The search for new anti-infection agents from natural resources, with different mode of actions and competitive effects became a necessity. In this study, twenty height methicillin-resistant Staphylococcus aureus (MRSA) strains were investigated for their biofilm formation ability. Subsequently, the antibiofilm effects of Eucalyptus globulus essential oil and its main component 1,8-cineole, against MRSA, as well as their antiquorum sensing potential, were evaluated. Our results displayed the potent efficacy of both E. globulus essential oil and 1,8-cineole against the development of biofilms formed by the methicillin-resistant strains. Additionally, E. globulus essential oil showed more potent of anti-QS activity, even at a low concentration, when compared to 1,8-cineole. All these property of tested agents may pave the way to prevent the development of biofilm formation by MRSA and subsequently the spreading of nosocomial infection.

Design, formulation and optimization of valsartan transdermal gel containing iso-eucalyptol as novel permeation enhancer: preclinical assessment of pharmacokinetics in Wistar albino rats.

OBJECTIVE: The aim of this study was to develop and optimize a transdermal gel formulation of valsartan using Box-Behnken design and to evaluate it for pharmacokinetic study. METHODS: The independent variables were Carbopol 940 (X1), PEG 400 (X2) and ethanol (X3) while valsartan flux (Y1), Tlag (Y2) and gel viscosity (Y3) were the dependent variables. Iso-eucalyptol was added in all gel formulations as permeation enhancer except for control gel. RESULTS: It was observed that the permeation rate of valsartan significantly increased in direct proportion to the ethanol concentration, but significantly decreased in direct proportion to polymer concentration. Lag time and viscosity decreased in reverse proportion to ethanol concentration. The optimized valsartan gel formulation (VGF-OPT) yielded flux of 143.27 ± 7.11 µg/cm(2)/h and 27.55 ± 2.51 µg/cm(2)/h across rat and human cadaver skin, respectively. In vivo pharmacokinetic study of VGF-OPT-transdermal therapeutic system containing iso-eucalyptol showed a significant increase in the bioavailability (2.52 times) compared with oral formulation of valsartan by virtue of better permeation through Wistar rat skin. CONCLUSION: It was concluded that the developed transdermal gel accentuates the flux of valsartan and could be used as an antihypertensive dosage form for effective transdermal delivery of valsartan.

Assessment of ion imprinted polymers based on Pd(II) chelate complexes for preconcentration and FAAS determination of palladium.

New ion-imprinted polymeric (IIP) materials were synthesized by copolymerization of 4-vinylpyridine (VP) and styrene as functional monomers and divinylbenzene as a cross-linking agent with chelating complexes of Pd(II) in the presence of 2,2-azobisisobutyronitrile as an initiator. The complexes of Pd(II) with ammonium pyrrolidinedithiocarbamate (APDC), N,N'-diethylthiourea (DET), and dimethylglyoxime (DMG) were used for this purpose. Chloroform, ethanol, and cyclohexanol were applied as porogens. The ion-imprinted polymers were tested in a flow mode as sorbents for solid-phase extraction of palladium from aqueous solutions. The conditions of Pd(II) separation on all polymers were optimized. The efficiencies of retention of Pd on different polymers in the presence of high excess of interfering ions were compared. The effect of the used porogen on the analytical performance of the prepared polymers was also investigated. The calculated sorbent capacities for Pd(II) were in the range from 9.25 mg g(-1) to 13.3 mg g(-1). The sorbent with Pd(II) imprinted as Pd-DMG-VP complex in chloroform was used for preconcentration of trace amounts of Pd. The detection limit for 100mL of the sample was 5 µg L(-1) using flame atomic absorption spectrometry (FAAS). The developed method was applied for the determination of Pd in water samples.

Sensitive spectrofluorimetric method of analysis for venlafaxine in spiked rat plasma and formulations.

A simple, sensitive, accurate and affordable spectrofluorimetric method was developed and validated for the determination of venlafaxine, both in marketed preparations as well as in spiked rat plasma. Venlafaxine depicted strong native fluorescence property in freshly prepared 0.05 M sulphuric acid. The excitation and emission wavelengths were found to be 237.0 nm and 301.0 respectively. Effect of variations in pH, temperature, concentration, change in molarities of different solvents, and effect of excipients were studied. The calibration graph in case of dosage forms and in spiked plasma was found to be rectilinear in the concentrations of 15-600 ng/ml and 20-650 ng/ml respectively. The intra- day and inter-day accuracy measurements of VEN in formulations ranged from 0.29 to 0.44% and 0.27 to 0.49%, respectively. The intra-day and inter-day accuracy in measurement of VEN in plasma ranged from 0.062 to 2.26% and 0.52 to 2.32%, respectively. The limit of detection (LOD) was found to be 6.0 ng/mL and 4.0 ng/mL in plasma and formulations respectively. The mean recovery of VEN from plasma was 97.46.

Experimental and computational morphology of three polymorphs of the free base of Venlafaxine: a comparison of morphology prediction methods.

In this paper the experimental and the computational studies of the morphology of three polymorphs of the free base of Venlafaxine ((N,N-dimethyl)-2-(1-hydroxy cyclohex-1-yl)-2-(4-methoxyphenyl) ethylamine) are reported. The morphology of all polymorphs has been predicted using the Bravais-Friedel-Donnay-Harker method, the attachment energy method and kinetic Monte Carlo growth simulations and these predictions have been compared with experimental observations. The Monte Carlo simulations allow for a detailed simulation of the growth process, including driving force and growth mechanism, which leads to a semi-quantitative prediction of the growth morphologies of all three phases. For phase I two distinct growth habits are found experimentally under the same conditions. This is explained by the occurrence of a spiral growth mechanism in one of the two, which was observed using AFM and which is also supported by the Monte Carlo simulations. The habit of phase II could only be explained from simulations when a spiral growth mechanism is assumed; the shape of phase III could not be modeled accurately from the Monte Carlo simulations. Although the shape of the crystal is reproduced accurately, some of the indices of the faces predicted are not in agreement with the indices measured. The deviations are interpreted to be due to the presence of domains in the crystals as a result of the layered structure.

Hyperfine coupling dependence of the effects of weak magnetic fields on the recombination reactions of radicals generated from polymerisation photoinitiators.

The recombination reactions of free radicals formed from the photolysis of a series of polymerisation photoinitiators were studied using time-resolved infrared spectroscopy. All molecules showed Zeeman magnetic field effects (MFEs) in the field range 0-37 mT and those molecules that produced radical pairs with average hyperfine couplings greater than 5 mT showed substantial inverted field effects at fields of less than 10 mT (so-called low field effects, LFEs). Monte Carlo simulations with full treatment of all the isotropic hyperfine couplings in the spin Hamiltonian reproduced well the observed field effects. The use of the usual analysis based on the calculated B1/2 value for the radical pair was found to be inappropriate in systems with substantial LFEs, but simple correlations between this B1/2 value and the observed field features were established.