生理药代动力学模型及其在健康风险评价中的应用研究进展

生理药代动力学(Physiologically Based Pharmacokinetic,PBPK)模型在健康风险评估中的应用逐渐成为研究的焦点.简要阐述了PBPK模型的定义及发展历程,在此基础上详细介绍了PBPK模型建立的过程及其在致癌风险评估、混合物健康风险评估中的应用.最后,总结了该模型在健康风险评估应用中的受限因素,提出跨学科合作有利于解决这些受限因素,从而进一步推进该模型在混合物健康风险评价中的应用.     

Toxicity assessment of the maize herbicides S-metolachlor,benoxacor, mesotrione and nicosulfuron,and their corresponding commercial formulations,alone and in mixtures,using the Microtox® test

The Microtox® test, using the prokaryote Vibrio fischeri, was employed to assess the toxicity of the maize herbicides S-metolachlor, benoxacor, mesotrione and nicosulfuron, and their formulated compounds: Dual Gold Safeneur®, Callisto® and Milagro®; alone and in mixtures. For each compound we obtained original IC₅₀ values, with consistent higher toxicities for formulated compounds compared to active ingredients alone. Mixtures of the four herbicides, prepared according to application doses encountered in agriculture, were found to be toxic at a lower concentration than single molecules. Mesotrione and nicosulfuron mixture appeared to be highly toxic to V. fischeri, however, this recommended post-emergence combination for maize crops got its toxicity decreased in formulated compound mixtures, suggesting that chemical interactions could potentially reduce the toxicity. Data comparisons to theoretical models showed a good prediction of mixture toxicity by Concentration Addition concept. Results seemed to exclude any synergistic effects on V. fischeri for the tested herbicide mixtures. Additional work coupling these bioassay data to ecosystemic level studies (aquatic and soil compartments) and data on additives and degradation products toxicity, will help to fill the gap in our knowledge of the environmental impact of these xenobiotics and in the choice of a more sustainable use of pesticides.     

Effect of adjuvants on rainfastness and herbicidal activity of glyphosate deposits on trembling aspen foliage

Abstract

Radiolabelled end‐use mixtures of glyphosate with and without a cationic surfactant (Ethomeen® T/25) and an organosilicone surfactant (Silwet® L‐77) were applied onto trembling aspen (Populus tremuloids Michx.) leaves at the rate of 1.0 kg of AE (acid equivalent) in 35 L/ha area of foliage. A 5‐mm rainfall with an intensity of 10 mm/h was applied at intervals of 0.5, 8, 24, 36, 48, 72, and 96 h after treatment. Glyphosate washoff was determined by liquid scintillation counting of radioactivity in the rain‐washing. At 36 h post‐treatment, both the adjuvants significantly reduced glyphosate washoff (Ethomeen by 69.6% and Silwet by 59.7%) from foliage, compared to the washoff (82.6%) when Vision alone was applied without the adjuvants. Results on the rate of plant growth indicated that with a rain‐free period of 8 h or more, the growth of most seedlings was stunted within 1 or 2 d. Percentage of foliar browning 20 d after treatment with rain‐free period of 8 to 48 h ranged from 8 to 80% for Vision alone, 75 to 100% for Vision with Ethomeen, and 85 to 100% for Vision with Silwet, respectively. Physical properties of the end‐use mixtures were measured with and without the two adjuvants to examine droplet spreading and drying rates in relation glyphosate rainfastness. The Silwet adjuvant lowered the surface tension of the end‐use mixture, but Ethomeen did not. Droplets containing Silwet were spread more than those containing Ethomeen. However, the greater area of contact caused by Silwet did not contribute to a significant increase in the translocation rate of glyphosate into untreated parts of the seedlings, and showed no relationship with rainfastness of glyphosate deposits on trembling aspen.     

Oil-dispersant mixtures: understanding chemical composition and its relation to human toxicity

The ability for the water accommodated fraction (WAF) of oil-dispersant mixtures to become aerosolized following natural sea surface activity markedly increases the probability of inhalation exposure to this aerosolized mixture and subsequent adverse respiratory health effects. Thus, the purpose of this study was to elucidate the chemical composition of WAF of these mixtures as well as determine how this relates to lung epithelial cell cytotoxicity. WAF was prepared by mixing each dispersant (Corexit 9500/9527/9580) with crude oil. For “chemical constituent fingerprinting,” these prepared WAF were extracted prior with dichloromethane, analyzed by Gas chromatography/mass spectrometry, and qualitatively evaluated using the NIST08 database. Results from chemical analysis revealed an increase in structure complexity of the WAF oil-dispersant mixtures when compared to WAF of crude oil only. This complexity was characterized by high molecular weight compounds such as alkyl derivatives, esters, and polycyclic aromatic hydrocarbons. Previously a concentration-dependent reduction in cultured A549 cells was noted at 2 or 24?h time points following exposure to either the WAF-oil/9500 or WAF-oil/9527. Thus, a possible correlation exists between the chemical complexity of these mixtures and the ability to induce lung epithelial cell death in potentially exposed individuals.     

Mechanistic aspects of the thermal formation of halogenated organic compounds including polychlorinated dibenzo‐p‐dioxins. Part IV†: Incorporation of inorganic chlorine into organic matter and thermochemical aromatizations

The pyrolysis and chlorination of petroleum coke in a NaCl‐KCl melt results in the production of CCl₄ and C₆Cl₆. Polychlorinated dibenzo‐p‐dioxins (PCDDs) are produced from the air oxidation and chlorination of coal using HCl or Cl₂. Smoking of tobacco containing ³⁶Cl^e provides CH₃ ³⁶Cl.

At 350°C, the rateof aromatization of 1,3‐cyclohexadiene is negligible as compared to that of 1,4‐cyclohexadiene. The aromatization of the latter diene proceeds through the molecular elimination of hydrogen; while that of 1,3‐cyclohexadiene expecially at higher pressure (10–90 Torr) and at 362–421 °C involves free radical chain mechanism.     

Explosibility of hydrogen–graphite dust hybrid mixtures

To evaluate the hazard of combined hydrogen/dust explosions under severe accident conditions in International Thermonuclear Experimental Reactor (ITER), standard method of 20-L-sphere was used to measure the explosion indices of 4-μm fine graphite dust in lean hydrogen/air mixtures. The mixtures were ignited by a weak electric spark. The tested fuel concentrations were 8–18 vol% H₂ and 25–250 g/m³ dust. If the hydrogen content is higher than 10 vol%, the dust constituent can be induced to explode by the hydrogen explosion initiated by a weak electric spark. Depending on the fuel component concentrations, the explosions proceed in either one or two stages. In two-stage explosions occurring at low hydrogen and dust concentrations, the mixture ignition initiates first a fast hydrogen explosion followed by a slower phase of the dust explosion. With increasing dust concentration, the dust explodes faster and can overlap the hydrogen-explosion stage. At higher hydrogen concentrations, the hybrid mixtures explode in one stage, with hydrogen and dust reacting at the same time scale. Maximum overpressures of hybrid explosions are higher than those observed with hydrogen alone; maximum rates of pressure rise are lower in two-phase explosions and, generally, higher in one-stage explosions, than those characteristic of the corresponding H₂/air mixtures.     

Individual and simultaneous degradation of brominated high impact polystyrene and brominated acrylonitrile-butadiene-styrene and removal of heteroelements (Br,N, and O) from degradation oil by multiphase catalytic systems

Brominated high-impact polystyrene (HIPS-Br), which contained decabromodiphenyl ether flame retardant, and brominated acrylonitrile butadiene styrene (ABS-Br), which contained bromine-containing epoxy-type flame retardant, were degraded at 450°C individually and in a 1/1 mixture by a thermal and catalytic procedure using folded sheet mesoporous (FSM) and ZSM-5 zeolite in liquid phase contact mode. The two polymers produced similar degradation oils but at a higher yield for HIPS-Br. However, the composition and distribution of Br-, N-, and O-containing compounds depended on the type of flame retardant in HIPS-Br and ABS-Br. Multiphase catalytic systems consisting of FSM in liquid phase contact mode and various CaH-, FeO-, CoMo-, and NiMo-based catalysts, or combinations of these catalysts, in vapor phase contact mode were used to decrease the amount of heteroatoms (Br, N, and O) in the degradation oils. Each system gave particular results in terms of mass balance and concentrations of heteroatoms. A FSM (liquid phase contact)/CaHC (vapor phase contact) combination was the best catalytic system to remove Br-, N-, and O-containing compounds from degradation oils.     

Use of two-surfactants mixtures to attain specific HLB values for assisted TPH-diesel biodegradation

In a surfactant assisted biodegradation process, the choice of surfactant(s) is of crucial importance. The question is: does the type of surfactant(i, e. chemical family) affect the biodegradation process at fixed hidrophillic-lypofillic balance(H/B) values? Microcosm assessments were developed using contaminated soil, with around of 5000 mg/kg of hydrocarbons as TPH-diesel. Mixtures of three nonionic surfactants were employed to get a wide range of specific HLB values. Tween20 and Span20 were mixed in the appropriate proportions to get HLB values between 8.6 and 16.7. Tween/Span60 mixtures reached HLB values between 4.7 and 14.9. Finally,Tween/Span80 combinations yielded HLB values between 4.3 and 1.5. TPH-diesel biodegradation was measured at the beginning, and after 8 weeks, as well as the FCU/grsod, as a measure of microorganisms‘ development during the biodegradation period. A second aim of this work was to assess the use of guar gum as a biodegradation enhancer instead of synthetic products. The conclusions of this work are that surfactant chemical family, and not only the HLB value clearly affects the assisted biodegradation rate. Surfactant‘s synergism was clearly observed. Regarding the use of guar gum, no biodegradation enhancement was observed for the three assessed concentrations,i.e., 2, 20, and 200 mg/kg, respectively. On the contrary, TPH-diesel removal was lower as the gum concentration increased. It is quite possible that guar gum was used as a microbial substrate.     

Investigation on working fluids selection for organic rankine cycles with low-temperature heat sources

The Influence of mixed and pure working fluids on the performance of organic Rankine cycles (ORCs) is discussed. Specifically, the performance of mixed and pure working fluids is analyzed based on certain characteristics of low-temperature heat source and heat sink. A method of selecting binary zeotropic mixed working fluids that match with different heat sinks is introduced. Thermodynamic processes of ORCs for various heat sources are simulated in Matlab. The performance characteristics of pure and mixed working fluids are compared under different inlet temperatures and temperature gradients of sensible heat sources. The results demonstrate that when the initial temperature of a heat source is lower and its temperature gradient is higher, and the temperature gradient of the heat sink is higher, mixed working fluids have better performance than pure working fluids. However, for the opposite heat source and heat sink situations, pure working fluids perform better. Mixtures with low critical temperature components exhibit the best performance among all working fluids when the temperature gradient of the heat source is large. The analysis also shows that introduction of a recuperator may reduce the cycle efficiency when the heat source temperature is low and the temperature gradient of the heat source is large.     

Experimental study on vented deflagration of hydrocarbon fuel-air mixtures in a 20-L semi-confined cylindrical vessel with a slight static activation pressure

The overpressure peaks and flame propagation characteristics of hydrocarbon fuel-air mixtures vented deflagration in a 20-L cylindrical vessel with a slight static activation overpressure (P_ST = 2.5 kPa) and five vent opening ratio were studied by a series of experiments. The experiments focused on the effect of vent opening ratio on the overpressure peaks and flame propagation characteristics of hydrocarbon fuel-air mixture vented deflagration. The internal overpressure-time profiles and high-speed photographs of flame propagation processes were obtained. The results showed that three overpressure peaks were distinguished in the internal overpressure-time profiles, caused by the burst vent cover (p_burst), the acceleration of burnt gas (p_fv), and the fierce external deflagration of vented unburned fuel (p_ext), respectively. The changing of the vent opening ratio had almost no effect on the value of p_burst and (dp_burst/dt). With increasing vent opening ratio, the values of p_fv, p_ext, (dp_fv/dt) and (dp_ext/dt) showed a decreasing trend while the values of p_burst and (dp_burst/dt) were nearly constant. The flame presented a hemispherical shape before the vent cover ruptured then developed as a mushroom shape after accelerated to external field. There were three flame speed peaks during flame propagation process, resulted from venting flow acceleration, external deflagration, and axial heat flux formed by internal combustion. With the increase of vent opening ratio, all of the maximum flame speed, external average flame speed, maximum flame distance and external flame duration showed a downward trend, excepting for the internal average flame speed almost remained constant.