Bond Resonance Energy Verification of σ-Aromaticity in Cycloalkanes.

The Klein-Larson bonding model is best suited for describing σ-conjugation and σ-aromaticity of cycloalkanes. Methylene groups (-CH2-) in cycloalkanes are isoconjugates with ethylene groups (-CH═CH-) in annulenes, both contributing two electrons to cyclic conjugation and aromaticity. As in the case of π-aromatic stabilization, σ-aromatic stabilization must be associated with ring-current diamagnetism. Both nucleus-independent chemical shift (NICS) and bond resonance energy (BRE) values support this interpretation. Bond resonance energy has been used to determine local ring aromaticity in nonalternant hydrocarbons, alternant hydrocarbons, heterocyclic conjugated molecules, fullerenes, pure boron clusters, and porphyrins. This contribution represents the first application of bond resonance energy toward the evaluation of σ-aromaticity/σ-antiaromaticity of polycyclic alkanes.

Mitigation of the inhibitory effects of co-existing substances on the Fenton process by UV light irradiation.

Co-existing substances (substances not targeted for degradation) can negatively affect wastewater treatment process performance. Here, we quantitatively evaluated the effects of propanal, a common co-existing substance, on the degradation of the azo-dye Orange II, a common pollutant, by the Fenton process to provide data for the development of measures to reduce the effects of co-existing substances on this wastewater treatment process. Inhibition rate (IR; ratio of the reaction rate constants obtained in the absence and presence of propanal) was calculated to examine the effects of propanal on the degradation of Orange II. The IRs for the Fenton process in the first phase and the second phase were 1.6 and 4.2, respectively. However, addition of ultraviolet irradiation to the Fenton process (i.e., the photo-Fenton process) resulted in a comparable IR for the first phase but a markedly lower IR for the second phase. We attributed this to the improvement of the photo-reduction reaction rate due to complexation of propanal with ferric ions, which compensated for the scavenger effects (the trapping of OH radicals) of propanal. Thus, ultraviolet irradiation reduced the inhibitory effects of propanal on the degradation of Orange II by the Fenton process.

Comparison of rates of direct and indirect migration of phosphorus flame retardants from flame-retardant-treated polyester curtains to indoor dust.

In this study, the pathways for migration of phosphorus flame retardants (PFRs), tris(1,3-dichloroisopropyl) phosphate (TDCPP) and tricresyl phosphate (TCsP) which were detected from curtains often, from flame-retardant-treated polyester curtains to indoor dust were investigated. Two possible migration pathways were compared quantitatively: (1) an indirect pathway in which the PFRs in the curtains first evaporate from the curtains and are then adsorbed onto indoor dust and (2) a direct pathway in which the PFRs are directly transferred to dust placed on the curtains. The contribution of the indirect pathway was evaluated by means of emission cell tests, which showed that the area-specific emission rates from curtains treated with PFRs were 0.044 (TDCPP, Curtain 5), 0.17 (TDCPP, Curtain 8), and 0.060 (TCsP, Curtain 12) µg m-2 h-1 at 20 °C (averaged during 24 h). The contribution of the direct pathway was evaluated by measurement of the time dependence of PFR concentrations on the indoor dust placed on the curtains. These measurements indicated that PFR concentrations on the dust increased with time and that the direct migration rates of PFRs from curtains treated with PFRs were 4.4 (TDCPP, Curtain 5), 12 (TDCPP, Curtain 8), and 7.0 (TCsP, Curtain 12) µg m-2 h-1 at 20 °C (averaged during 24 h), or 71-120 times the indirect migration rate. This result suggests that the direct pathway can be expected to predominate.

Aromatic Character of Irregular-Shaped Nanographenes.

We found that the Clar sextet formula with the maximum number of sextet rings cannot always be defined meaningfully for large irregular-shaped PAHs. It is true that edge structure is always a primary determinant of the PAH aromaticity pattern. In large PAH molecules, every edge structure modifies the aromaticity pattern near the edge, but its influence fades on going away from the edge. It follows that different textures of the aromaticity pattern appear near different edges. As a result, the entire aromaticity pattern does not always match with a single Clar formula or a single weighted superposed Clar formula. Such an unusual feature of aromaticity patterns could not have been observed distinctly if we had not explored the aromaticity patterns of large irregular-shaped PAH molecules systematically. We used the superaromatic stabilization energy (SSE) as a local aromaticity index, which is the only index of this kind not disturbed by the aromaticity of adjacent benzene rings.

In Vitro Transformation of Chlorinated Parabens by the Liver S9 Fraction: Kinetics, Metabolite Identification, and Aryl Hydrocarbon Receptor Agonist Activity.

We investigated the kinetics of in vitro transformation of a dichlorinated propyl paraben (2-propyl 3,5-dichloro-4-hydroxybenzoate; Cl2PP) by the rat liver S9 fraction and assessed the aryl hydrocarbon receptor (AhR) agonist activity of the metabolite products identified in HPLC and GC/MS analysis and by metabolite syntheses. The results indicated that the chlorination of Cl2PP reduced its degradation rate by approximately 40-fold. Two hydroxylated metabolite products showed AhR agonist activity of up to 39% of that of the parent Cl2PP when assessed in a yeast (YCM3) reporter gene assay. The determination of the metabolic properties of paraben bioaccumulation presented here provides further information on the value of risk assessments of chlorinated parabens as a means to ensure human health and environmental safety.

Chronic toxicity of parabens and their chlorinated by-products in Ceriodaphnia dubia.

The chronic toxicity of 12 compounds of parabens and their chlorinated by-products was investigated using 7-day Ceriodaphnia dubia test under static renewal condition in order to generate information on how to disinfect by-products of preservatives that are discharged in aquatic systems. The mortality and inhibition of reproduction tended to increase with increasing hydrophobicity and decreased with the degree of chlorination of parabens. The EC50 values for mortality, offspring number, and first brood production ranged between 0.30-3.1, 0.047-12, and 1.3-6.3 mg L(-1) , respectively. For the number of neonates, the most sensitive endpoint, the no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) values ranged from 0.63 to 10 mg L(-1) and from 1.2 to 19 mg L(-1) , respectively. Methylparaben (MP), benzylparaben (BnP), and dichlorinated BnP (Cl2 BnP) elicited a significant decrease in offspring numbers even at their lowest concentration tested; the NOEC for these compounds was determined to be less than the lowest test concentration (1.3, 0.04, and 0.63 mg L(-1) for MP, BnP, and Cl2 BnP, respectively). Propylparaben (PP), chlorinated PP, isopropylparaben (iPP), and chlorinated iPP exhibited nonmonotonic concentration-dependent response; their NOEC and LOEC values could not be determined. The multivariate approach involving principal component analysis and hierarchical cluster analysis revealed four groups that corresponded to the toxicological profiles of parabens. Our results suggested that disinfection of parabens by chlorination could reduce aquatic toxicity of original compounds. The findings obtained in our study together with the data available on paraben concentrations in aquatic systems can be used to perform preliminary risk assessment by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentration (PNEC) for the marine aquatic environment. The calculated PEC/PNEC ratios ranged from 0.0012 to 0.2, with the highest value observed in MP. This suggested that there are negligible environmental risks for aquatic organisms at current use levels.

Constrained Clar formulas of coronoid hydrocarbons.

Aromatic character of coronoid hydrocarbons is greatly influenced by the shapes of outer and inner peripheries. The most aromatic rings in coronoids are jutting benzene rings on the armchair edges, if any. Clar formulas of many coronoids conform to the aromaticity patterns. However, placement of all aromatic sextets on highly aromatic rings is sometimes forbidden by the presence of the central cavity. The magnitude of aromatic stabilization energy due to macrocyclic conjugation [SSE(mc)] and the NICS(1) value at the center of the cavity strongly depend on the structure of the superposed Clar formula. Localization of π-electrons in fixed aromatic sextets effectively suppresses macrocyclic conjugation. The sign of SSE(mc) is determined by the number of carbon atoms that form the hub cycle.

Determination of potential dermal exposure rates of phosphorus flame retardants via the direct contact with a car seat using artificial skin.

Dermal exposure to phosphorus flame retardants (PFRs) has received much attention as a major alternative exposure route in recent years. However, the information regarding dermal exposure via direct contact with a product is limited. In addition, in the commonly used dermal permeability test, the target substance is dissolved in a solvent, which is unrealistic. In this study, a dermal permeability test of PFRs in three car seats was performed using artificial skin. The PFR concentrations in the car seats are 0.12 wt% tris(2-chloroethyl) phosphate (TCEP), 0.030-0.25 wt% tris(2-chloroisopropyl) phosphate (TCPP), 0.15 wt% triphenyl phosphate (TPhP), 0.89 wt% cresyl diphenyl phosphate (CsDPhP), 0.074 wt% tricresyl phosphate (TCsP), and 0.46-4.7 wt% diethylene glycol bis [di (2-chloroisopropyl) phosphate (DEG-BDCIPP). The mean skin permeation rates for a contact time of 24 h are 14 (TCEP), 5.4-160 (TCPP), 0.67 (CsDPhP), 0.38 (TPhP), and 3.3-58 ng cm-2 h-1 (DEG-BDCIPP). The concentrations of TCsP in receptor liquid were lower than the limit of quantification at the contact time of 24 h. The skin permeation rates were significantly affected by the type of car seat (e.g., fabric or non-fabric). The potential dermal TCPP exposure rate for an adult via direct contact with the car seat during the average daily contact time (1.3 h), which was the highest value assessed in this study, was estimated to be 16,000 ng kg-1 day-1, which is higher than that related to inhalation and dust ingestion reported as significant exposure route of PFRs in previous studies. These facts reveal that dermal exposure associated with direct contact with the product might be an important exposure pathway for PFRs.

Evaluation of the potentials of rice varieties and water management practices for reducing human health risks associated with polluted river water irrigated rice in Bangladesh.

The consumption of arsenic and trace-metal-contaminated rice is a human health concern worldwide, particularly in Bangladesh. In this study, the effects of rice varieties and water management practices on the concentrations of arsenic and trace metals in rice grains were investigated to reduce human health risks related to rice consumption. In addition, the performance of risk reduction using the optimum combination of rice variety and water management practices was quantitatively assessed using Monte Carlo simulation, in which non-carcinogenic and carcinogenic risk distributions under the status quo and the optimum combination were compared. The experimental results revealed that Dular and BRRI dhan45 (rice varieties) cultivated under alternate wetting and drying (AWD) and continuous flooding (CF) conditions showed the lowest hazard quotient (HQ) values for copper, cadmium, and arsenic and the lowest target cancer risk (TR) for arsenic. In Dular and BRRI dhan45 (AWD and CF) varieties, the proportion of the population for which HQs exceeded 1.0 (the reference value) tended to decrease (except for arsenic), compared with populations for which the rice varieties and water management practices were not specified. These results suggest that the use of optimum combinations of rice varieties and water management practices could reduce non-carcinogenic and carcinogenic risks associated with arsenic and trace metals uptake via rice grain consumption by the Bangladeshi people.

Superaromatic stabilization energy as a novel local aromaticity index for polycyclic aromatic hydrocarbons.

Superaromatic stabilization energy (SSE), previously proposed by us, can be used as a novel local aromaticity index for benzene rings in polycyclic aromatic hydrocarbons (PAHs). SSE can be interpreted as the first local aromaticity index explicitly related to all relevant circuits in a polycyclic π-system, an origin of local aromaticity, being free of local aromaticity arising from adjacent six-site circuits. Therefore, this quantity is best suited for characterizing the electronic structure of large pericondensed PAHs and graphene nanoflakes.

Analytical study of superaromaticity in cycloarenes and related coronoid hydrocarbons.

Recently synthesized septulene is a unique cycloarene molecule in that no macrocyclic conjugation circuits can be chosen from the π-system. This molecule has essentially no superaromatic stabilization energy (SSE) and can be viewed as an ideal nonsuperaromatic macrocycle. SSEs for kekulene and other cycloarenes are also very small. In these hydrocarbons, a macrocycle formed by fused benzene rings effectively suppresses not only the aromaticity inherent in macrocyclic (4n+2)-site conjugation circuits but also the antiaromaticity inherent in macrocyclic (4n±1)-site circuits. Comparative study of superaromaticity in multilayered coronoid hydrocarbons revealed that not only SSE but also the HOMO contribution to SSE is minimized in odd-layered coronoids.

Macrocyclic aromaticity of porphyrin units in fully conjugated oligoporphyrins.

Individual porphyrin macrocycles in fully conjugated oligoporphyrins exhibit different degrees of macrocyclic aromaticity. We proposed a theoretical method for estimating the degrees of macrocyclic aromaticity of these porphyrin units. This method, based on the concept of bond resonance energy, is applicable to all types of porphyrin oligomers. We then found that the degree of macrocyclic aromaticity is very sensitive to the way of oligomerization. In general, it is markedly suppressed by linkage or substitution at meso positions but is fairly insensitive to direct edge-to-edge fusion. These predictions are consistent with observed chemical shifts of protons attached to the porphyrin macrocycles. Antiaromatic circuits are created in doubly- and triply-linked porphyrin oligomers. These circuits must be the origin of paramagnetic currents induced around the naphthalene-like junction zones in triply-linked oligomers. The same approach may be applied to other fully conjugated systems consisting of two or more maclocyclic units.

Validity and limitations of the bridged annulene model for porphyrins.

According to the bridged annulene model, macrocyclic aromaticity of a porphyrinoid species can be attributed to the annulene-like main macrocyclic conjugation pathway (MMCP). Macrocyclic aromaticity, however, is given theoretically as a sum of contributions from all macrocyclic circuits. We found that the aromaticity due to each macrocyclic circuit is determined formally but broadly by Hückel's [4n + 2] rule of aromaticity. Nitrogen atoms in the pyrrolic rings effectively suppress the variation in the number of π electrons staying along each macrocyclic circuit. As a result, all or most macrocyclic circuits in oligopyrrolic macrocycles are made aromatic (or antiaromaitc) in phase with the MMCP. Thus, the MMCP is not a determinant of macrocyclic aromaticity but can be regarded as a good indicator of this quantity. This is why the bridged annulene model appears to hold for many porphyrins.

Mechanoanions produced by mechanical fracture of bacterial cellulose: ionic nature of glycosidic linkage and electrostatic charging.

Mechanoanions were produced by heterogeneous scission of the glycosidic linkages of the main chain of bacterial cellulose (BC); scission was induced by mechanical fracture of the BC in a vacuum in the dark at 77 K. The mechanoanions were detected using electron-spin-trapping methods with tetracyanoethylene. The yield of mechanoanions was positively correlated with the absolute value of the change in the Mulliken atomic charge, which was used as a descriptor of the ionic nature of the glycosidic linkage. Homogeneous scission of the glycosidic linkages induced by mechanical fracture generated mechanoradicals, the electron affinity of which was estimated on the basis of the energy of the lowest unoccupied molecular orbital for the model structure of the mechanoradical. It was concluded that the electrostatic charging of BC is caused by electron transfer from mechanoanions to mechanoradicals, which have high electron affinities. The electrostatic charge density of BC in a vacuum in the dark at 77 K was estimated to be 6.00 × 10(-1) C/g.

Prediction of the main macrocyclic conjugation pathway for porphyrinoids from the ring current distribution.

For some porphyrinoids, such as orangarin and amethyrin, the main route of macrocyclic pi-circulation is different from the main macrocyclic conjugation pathway predicted by porphyrin chemists. Our analytical theory of ring-current diamagnetism allows us to predict the main macrocyclic conjugation pathway from the ring current distribution. We can now interpret macrocyclic aromaticity and macrocyclic circulation consistently within the same theoretical framework.

Probabilistic exposure assessment of aggregate rates of dermal exposure of Japanese women and children to parabens in personal care products.

Parabens (p-hydroxybenzoic acids) are commonly used as preservatives in personal care products. Although the rate of exposure to a single product may be small, it is possible for an individual to have marked exposure to parabens through the use of multiple personal care products (aggregate exposure). To assess the risks associated with aggregate exposure to parabens, we estimated the dermal exposure rate distributions of four major parabens (methylparaben, MP; ethylparaben, EP; propylparaben, PP; butylparaben, BP) in various products for women (>20 years old) and children (1-3 years old) by using the probabilistic exposure assessment tool ConsExpo. Integrated exposure rates were then calculated as the sum of exposure rates for individual products. Aggregate exposure rates for women were 1.2 (median) (0.13 [5%ile], 6.9 [95%ile]), 0.43 (0.029, 3.0), 0.35 (0.032, 1.9), and 0.25 (0.027, 1.2) mg kg-bw-1 day-1 for MP, EP, PP, and BP, respectively. Those for children were 0.47 (0.054, 2.2), 0.11 (0.012, 0.60), 0.13 (0.012, 0.78), and 0.13 (0.0065, 0.85) mg kg-bw-1 day-1 for MP, EP, PP, and BP, respectively. Integrated exposure rates for women were several times those for children. In both cases, personal care products that were applied to larger areas of skin and were used more frequently were more likely to be associated with higher exposure rates. According to the results of a risk assessment using a margin of exposure approach, aggregate rates of exposure to PP and BP, but not MP or EP, were high enough to warrant concern about disruption of the reproductive system.

Acute toxicity of parabens and their chlorinated by-products with Daphnia magna and Vibrio fischeri bioassays.

The acute toxicity of 21 parabens and their chlorinated derivatives was investigated by means of two toxicity bioassays: Daphnia magna immobilization test and the inhibition of bioluminescence of Vibrio fischeri. The median effective concentration (EC(50)) values of the tested parabens ranged from 2.2 to 62 mg l(-1) in the D. magna test and from 0.0038 to 5.9 mg l(-1) in the V. fischeri test at 15 min after exposure. The toxicity of dichlorinated methyl- and n-propylparaben, the most commonly used preservatives in cosmetics, toward D. magna was 3.9- and 2.8-fold that of their corresponding parent compounds. Toxicity toward D. magna showed a linear relationship with log P, indicating that toxicity increases with increasing hydrophobicity. On the other hand, the correlations of toxicity toward V. fischeri with hydrophobicity and with the degree of chlorination were poor. In addition, the results of the present study indicated that the V. fischeri test was more sensitive than the D. magna test for the determination of the acute toxicity of parabens. A complete assessment of the ecological and toxicological risks of parabens may require the examination of chlorinated parabens as well as the parent pollutants, as described in the present study.

Evaluation of estrogenic activity of parabens and their chlorinated derivatives by using the yeast two-hybrid assay and the enzyme-linked immunosorbent assay.

We assessed the estrogen agonist activities of 21 parabens and their chlorinated derivatives by using yeast two-hybrid assays incorporating either the human or medaka (Oryzias latipes) estrogen receptor alpha (hERalpha and medERalpha, respectively), and by using hERalpha competitive enzyme-linked immunosorbent assay (ER-ELISA). In the two-hybrid assay with hERalpha, five parabens and three chlorinated derivatives exhibited estrogenic activity, and their relative activity (17beta-estradiol [E2] = 1) ranged from 2.0 x 10(-5) to 2.0 x 10(-4), with the highest activity observed in i-butylparaben. In the medERalpha assay, six parabens and six chlorinated derivatives exhibited estrogenic activity and their relative activity ranged from 2.7 x 10(-5) to 3.5 x 10(-3), with the highest activity observed in benzylparaben, its monochlorinated derivative, i-butylparaben, and n-butylparaben. Although medERalpha demonstrated an activity to E2 that was three times lower than that demonstrated by hERalpha, medERalpha has a higher sensitivity to parabens than hERa (1.3-8.9 times). Five parabens and two chlorinated derivatives exhibited a binding affinity to ERa in the ER-ELISA; of the parabens, i-butylparaben exhibited the strongest binding affinity. The yeast two-hybrid assay and the ER-ELISA also revealed that many of the assayed chlorinated parabens were much weaker than the parent compound. In addition, the results mainly showed that parabens with a bulk substituent (e.g., i-butyl and benzyl groups) had a higher activity than those with a sterically small substituent. It is considered that derivatization masks the apparent estrogenic activity of parabens, but the resulting chlorinated compounds may represent a potential hazard and therefore other toxicity tests should be performed to determine the toxicity of the chlorinated derivatives.

Dermal exposure to plasticizers in nail polishes: An alternative major exposure pathway of phosphorus-based compounds.

Phosphorus-based compounds are used as plasticizers in the manufacture of many products found in the indoor environment. Here we quantitatively investigated dermal exposure to phosphorus-based compounds contained in 45 nail polishes purchased in Japan. The alternative plasticizer triphenyl phosphate (TPhP) was detected in some samples of the nail polishes made in the USA (concentration, 1.1-1.8 wt%). The potential dermal exposure rates for TPhP, estimated using ConsExpo (version 5.0; Dutch National Institute for Public Health and the Environment), were in the range 200 (5%ile)-1700 (50%ile)-5000 (95%ile) ng kg-bw-1 day-1, which is more than 1400 times the reported values for exposure via dust ingestion and inhalation. Thus, dermal exposure via nail polish may be a major route of exposure to TPhP. The margin of exposure range for TPhP was 3.6 × 105-4.1 × 104-1.4 × 104. For comparison, the potential dermal exposure rate range for the conventional plasticizer dibutyl phthalate and the alternative plasticizer acetyl tributyl citrate was 360-3500-14,000 and 430-4100-17,000 ng kg-bw-1 day-1, respectively, and the margin of exposure range was 4.1 × 103-4.2 × 102-1.1 × 102 and 2.3 × 105-2.4 × 104-5.9 × 103, respectively.

Organic pollutants in paper-recycling process water discharge areas: first detection and emission in aquatic environment.

In this study, eight compounds have been identified and quantified from the samples collected from paper-recycling process water discharge areas. In particular, five aryl hydrocarbons, including a novel chlorinated aryl ether, were identified for the first time as environmental pollutants. In the effluent stream, concentration levels of up to 1600 microg L(-1) and 190 microg g(-1) were detected in the surface water and surface sediment, respectively. The results of this study have raised concerns regarding the organic chemicals used in thermal paper and the environmental consequences of their release.