Octanol-water Distribution Coefficient Research Articles

Laboratory Measurements of Pyrene and Acenaphthene Partition into Microplastics

Microplastics are a major environmental issue. In marine systems, these break down into small fragments that may lodge within organisms, but they behave as vectors for chemicals when pollutants such as metals, polycyclic aromatic hydrocarbons (PAHs), pesticides, and pharmaceuticals are absorbed by the particles. The rate and extent of uptake of organic compounds onto microplastics is dependent on a range of factors such as the sites available on the surface, the type of plastic, and the compound being sorbed, with hydrophobicity an important property. Laboratory experiments determined the uptake of pyrene and acenaphthene (and sometimes phenanthrene) onto pellets of polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyoxymethylene (POM), polypropylene (PP) and polystyrene (PS). The kinetics of uptake in the experiments reveals half-lives ~10 h. The extent of partition onto the plastic pellets was similar for pyrene and phenanthrene, though lower for acenaphthene. This was not surprising because the octanol-water distribution coefficient of acenaphthene is about an order of magnitude smaller than that of pyrene, suggesting it is less hydrophobic. The PAHs are distributed most strongly into PP but only weakly into PVC. The fragmentation and oxidation of microplastics means that they sorb increasing amounts of organic material as they age.

The importance of tyrosines in multimers of cyclic RGD nonapeptides: towards αvβ6-integrin targeted radiotherapeutics.

In a recent paper in this journal (RSC Med. Chem., 2023, 14, 2429), we described an unusually strong impact of regiospecific exchange of phenylalanines by tyrosines in 10 gallium-68-labeled trimers of certain cyclic RGD peptides, c[XRGDLAXp(NMe)K] (X = F or Y), on non-specific organ uptakes. We found that there was, in part, no correlation of liver uptake with established polarity proxies, such as the octanol-water distribution coefficient (log D). Since this observation could not be explained straightforwardly, we suggested that the symmetry of the compounds had resulted in a synergistic interaction of certain components of the macromolecules. In the present work, we investigated whether a comparable effect also occurred for a series of 5 tetramers labeled with lutetium-177. We found that in contrast to the trimers, liver uptake of the tetramers was well correlated to their polarity, indicating that the unusual observations along the trimer series indeed was a unique feature, probably related to their particular symmetry. Since the Lu-177 labeled tetramers are also potential agents for treatment of a variety of αvβ6-integrin expressing cancers, these were evaluated in mice bearing human lung adenocarcinoma xenografts. Due to their tumor-specific uptake and retention in biodistribution and SPECT imaging experiments, these compounds are considered a step forward on the way to αvβ6-integrin-targeted anticancer agents. Furthermore, we noticed that the presence of tyrosines in general had a positive impact on the in vivo performance of our peptide multimers. In view of the fact that a corresponding rule was already proposed in the context of protein engineering, we argue in favor of considering peptide multimers as a special class of small or medium-sized proteins. In summary, we contend that the performance of peptide multimers is less determined by the in vitro characteristics (particularly, affinity and selectivity) of monomers, but rather by the peptides' suitability for the overall macromolecular design concept, and peptides containing tyrosines are preferred.

Adsorption of per- and polyfluoroalkyl substances (PFAS) by ionic liquid-modified clays: Effect of clay composition and PFAS structure

Organically modified clays have been reported as a promising class of adsorbents for the treatment of per- and polyfluoroalkyl substances (PFAS), a group of emerging contaminants of widespread concerns. Here, we reported the development and evaluation of ionic liquid (IL)-modified clays prepared with various natural clays to explore the role of clay substrate in the adsorption of eight persistent perfluoroalkyl acids (PFAAs). Based on detailed adsorption isotherm study, we found that the adsorption capacities of PFAAs were closely related to the cation exchange capacities of the raw clays and correspondingly the IL loadings of the modified clays. Additionally, a positive correlation was observed between the adsorption affinity of PFAAs onto IL-modified clays and the octanol–water distribution coefficient (Dow) of PFAAs. Adsorption free energy analysis suggested that both electrostatic and hydrophobic interactions played important roles in the adsorption of PFAAs onto IL-modified clays. Although electrostatic interactions were more predominant, the contribution of hydrophobic interactions increased with the increasing carbon number of perfluoroalkyl moiety of PFAAs, resulting in more favorable adsorption of long-chain PFAAs than their short-chain homologs. The performance of IL-modified clays was further demonstrated for the removal of PFAA mixtures under environmentally relevant conditions. Overall, results of this work can provide important insights into guiding the design of organically modified clay adsorbents for PFAS treatment.

Permeability of Fresh and Frozen Porcine and Human Gingiva and the Effect of Storage Duration.

The gingiva is the target site for some topical drugs, but the permeability of human gingiva has not been systematically evaluated. Pigs are a common animal model for in vitro membrane transport studies. The objectives of this study were to: (a) determine the permeability coefficients of freshly excised human gingiva using model permeants, (b) compare the permeability coefficients of fresh human gingiva with those of fresh porcine gingiva, (c) evaluate the effect of freezing duration on the permeability of porcine gingiva, and (d) compare the permeability coefficients of fresh and cadaver (frozen) human gingiva. A goal was to examine the feasibility of using porcine gingiva as a surrogate for human gingiva. The potential of using frozen tissues in permeability studies of gingiva was also examined. Fresh and frozen porcine gingiva, fresh human gingiva, and frozen cadaver human gingiva were compared in the transport study with model polar and lipophilic permeants. The fresh porcine and human tissues showed similarities in the "permeability coefficient vs. octanol-water distribution coefficient" relationship. The porcine gingiva had a lower permeability than that of the human, with a moderate correlation between the permeability of the fresh porcine and fresh human tissues. The permeability of the porcine tissues for the model polar permeants increased significantly after the tissues were frozen in storage. Moreover, the frozen human cadaver tissue could not be utilized due to the high and indiscriminating permeability of the tissue for the permeants and large tissue sample-to-sample variabilities.

Uptake and depuration of three common antibiotics in benthic organisms: Sea cucumber (Holothuria tubulosa), snakelocks anemone (Anemonia sulcata) and beadlet anemone (Actinia equina)

Antibiotics are widely used drugs in human and veterinary medicine, which has attracted great attention in relation to the development of bacterial resistance, currently a problem of great concern for governments and states, as it is related to the resurgence of infectious diseases already eradicated. Understanding the bioaccumulation of antibiotics in aquatic organisms is an important key to understanding their risk assessment. The present study was designed to study the bioaccumulation of target antibiotics in relevant organisms inhabiting benthic marine environments. The uptake and elimination of ciprofloxacin (CIP), sulfamethoxazole (SMX) and trimethoprim (TMP) were investigated in sea cucumbers (Holothuria tubulosa), snakelock anemone (Anemonia sulcata) and beadlet anemone (Actinia equina) under controlled laboratory conditions. The results show that antibiotics have a particular trend over time during all periods of absorption and depuration. The tissue distribution of antibiotics in sea cucumber is strongly influenced by the structure of the compounds, while CIP is concentrated in the body wall; TMP is concentrated in the digestive tract. Two different approaches were used to estimate bioconcentration factors (BCFs) in different animal models, based on toxicokinetic data and measured steady-state concentrations. The BCF ranges were 456–2731 L/kg, 6–511 L/kg and 9–100 L/kg for TMP, CIP and SMX, respectively. The estimated BCF values obtained classify TMP as cumulative in A. equina and H. tubulosa, underlining the potential bioconcentration in these marine organisms. A correlation was observed between the BCFs of the target antibiotics and the octanol-water distribution coefficient (Dow) (r2 > 0.7). The animal-specific BCF followed the order of beadlet anemone > sea cucumber > snakelock anemone.

Characterization of Porcine Gingiva for Drug Absorption

Gingiva or gum is a part of the periodontium that surrounds the tooth. Its main function is to provide an effective barrier to both mechanical trauma and bacterial invasion. Gingiva is the target site for some topical drugs. The most common disease in gingiva is periodontal diseases (gum infections). Understanding the gingiva barrier properties could provide insights into approaches to effective drug delivery for the gingiva. Porcine gingiva was chosen as the model in the present membrane transport study. The permeability coefficients of gingiva were determined using a modified Franz diffusion cell with small diffusional area (0.03 cm2) and 12 model permeants with different physicochemical properties. The influences of edge effect and aqueous boundary layers were not observed in the modified diffusion cell setup for the small pieces of gingiva tissue samples. Lipophilic permeants exhibit higher permeability coefficients than hydrophilic permeants. A correlation was observed between the Log permeability coefficient (Log P) and Log octanol-water distribution coefficient (Log Dow) in the analysis. The permeant molecular weight (MW) was also a factor in the Log P vs. Log Dow relationship. The coefficient of Log Dow in this three-factor relationship (0.42) suggested that the gingiva barrier was less lipophilic than octanol.

Removal of micropollutants using a membrane bioreactor coupled with powdered activated carbon — A statistical analysis approach

The occurrence of micropollutants in wastewater is largely documented as well as the environmental risk posed by their residues in the aquatic environment. Many investigations have been carried out and plan to study and improve their removal efficiency in existing wastewater treatment plants. At the same time, efforts are being made to develop new technologies or upgrade existing ones to increase the removal of a selection of micropollutants. Due to the great variability in their chemical and physical properties, it would be advisable to find representative compounds or identify the factors which most influence the removal mechanisms under specific conditions. This study analyses the removal efficiencies of a great number of micropollutants in wastewater treated in a membrane bioreactor coupled with powdered activated carbon (PAC), which was the subject of a review article we have recently published. The main operational parameters (i.e. PAC dosage, PAC retention time and sludge retention time) and compound physico-chemical properties (i.e. octanol-water distribution coefficient, charge and molecular weight) were first selected on the basis of a dedicated screening step and then an attempt was carried out to clarify their influence on the removal of micropollutants from wastewater during its treatment. To this end, a statistical analysis, mainly based on exploratory methods (cluster analysis and principal component analysis) and regression analysis, was carried out to compare and discuss the different results published in the scientific literature included in the cited review article. It emerged, that, based on the collected dataset, micropollutant charge and LogDow seem to play the most important role in the removal mechanisms occurring in MBR coupled with PAC.

Adsorption of benzalkonium chlorides onto polyethylene microplastics: Mechanism and toxicity evaluation

Usage of disposable plastic products and disinfectants has been skyrocketing due to the COVID-19 pandemic. The random disposal of plastic products may result in greater microplastic pollution. Benzalkonium chloride is known as one of the most common ingredients of disinfectants. In this study, the adsorption behavior of benzalkonium chlorides (BAC12, BAC14, BAC16) on polyethylene microplastics (PE-MPs) and the combined toxic effects were investigated using batch adsorption experiment and Daphnia magna. The results showed that PE-MPs had strong adsorption capacity for BACs and the adsorption capacity increased (11.03–22.77 mg g−1) with their octanol-water distribution coefficients. The effect of pH was negligible while dissolved organic matter inhibited the adsorption. A slightly inverse relationship between particle size of PE-MPs and adsorption was observed. Additionally, the MP aging with UV/H2O2 increased the adsorption of BAC12 but decreased that of relatively hydrophobic BAC14 and BAC16. The survival rate of Daphnia magna increased up to 100% in the presence of PE-MPs depending upon their adsorption capacities, suggesting that PE-MPs do not act as a carrier but rather as a scavenger for BACs. This study provides important information necessary for environmental risk assessment with regard to the combined pollution of MPs and toxic chemicals.

Adsorption of a diverse range of pharmaceuticals to polyethylene microplastics in wastewater and their desorption in environmental matrices

It is proposed that microplastics discharged from wastewater treatment plants act as a vector of pharmaceuticals. In this study, adsorption of pharmaceuticals to polyethylene microplastics was investigated in municipal wastewater. Pharmaceuticals for study were selected to represent different speciation (anionic, cationic, and neutral) and a range of pH dependant octanol-water distribution coefficients (log DOW). Findings revealed adsorption favoured those in cationic form with the greatest hydrophobicity (e.g., fluoxetine log DOW 2.0 at pH 7.8). Adsorption of anionic pharmaceuticals was restricted due to repulsion with the microplastic's negatively charged surface. Only atorvastatin had any appreciable adsorption due to its comparatively high log DOW value (2.9). Those pharmaceuticals predominantly in neutral form (carbamazepine and ketamine) with log DOW values ≥2.4 had similar adsorption. Freundlich KF values were 3400, 386, 284, 259 and 218 (mg kg−1)(mg L−1)1/n for fluoxetine, propranolol, atorvastatin, ketamine, and carbamazepine, respectively. All pharmaceuticals with log DOW values <1.0 (atenolol, gliclazide, bezafibrate, and ifosfamide) did not adsorb to microplastics, irrespective of their speciation. Changing composition of wastewater (pH, dilution with stormwater and NaCl addition) within the range expected for municipal wastewater had limited influence on adsorption. Pharmaceutical desorption from microplastics was assessed in river water and simulated gastric and intestinal fluids. Solution pH was considered the most important factor for pharmaceutical desorption, influencing both pharmaceutical speciation and microplastic surface charge. Greatest desorption was observed for the cationic pharmaceuticals in gastric fluids due to a reduced surface charge of the microplastics under low pH conditions. Up to 50% desorption of fluoxetine occurred in gastric fluid at 37 °C. These findings show that pharmaceuticals adsorbed to microplastics are ‘bioavailable’. However, this is often overlooked as an exposure route to aquatic organisms because water samples are normally pre-filtered prior to chemical analysis.

Polyamide microplastics in wastewater as vectors of cationic pharmaceutical drugs

Reported here is the first study to investigate the adsorption of pharmaceutical drugs to microplastics in wastewater. Wastewater is an environmental source of microplastics and pharmaceuticals, which is discharged as treated effluent or combined sewer overflows. In this study, adsorption of cationic pharmaceuticals, with a range of octanol-water distribution coefficients, to polyamide (Nylon 12) microplastics was investigated in real wastewater samples. Significant adsorption was observed for the more hydrophobic pharmaceuticals studied, propranolol, amitriptyline, and fluoxetine, with equilibrium reached within 24 h. Microplastic-wastewater distribution coefficients for these three pharmaceuticals were 191, 749 and 1020 L kg−1, respectively. Favourable wastewater conditions for adsorption of pharmaceuticals to polyamide were at pH > 7, summer temperatures (20 °C), and no stormwater dilution. Adsorption of the more hydrophilic pharmaceuticals atenolol, pseudoephedrine, metoprolol, and tramadol was ≤7% under all conditions and considered insignificant. Limited desorption (7–17%) of propranolol, amitriptyline, and fluoxetine was observed in river water over 24 h. This suggests that microplastics may be able to transport adsorbed pharmaceuticals for considerable distances after discharge. In simulated gastric fluids their desorption increased to 24–27% and 40–58% in cold- and warm-blooded temperatures respectively. The findings demonstrate that wastewater microplastics could act as a vector of pharmaceutical drugs, from wastewater treatment plants to aquatic organisms. However, further research is needed to better appreciate the risks posed by pharmaceuticals adsorbed to microplastics in comparison to other organic particulates found in wastewater.

Prediction of permeability across intestinal cell monolayers for 219 disparate chemicals using in vitro experimental coefficients in a pH gradient system and in silico analyses by trivariate linear regressions and machine learning

For medicines, the apparent membrane permeability coefficients (Papp) across human colorectal carcinoma cell line (Caco-2) monolayers under a pH gradient generally correlate with the fraction absorbed after oral intake. Furthermore, the in vitro Papp values of 29 industrial chemicals were found to have an inverse association with their reported no-observed effect levels for hepatotoxicity in rats. In the current study, we expanded our influx permeability predictions for the 90 previously investigated chemicals to both influx and efflux permeability predictions for 207 diverse primary compounds, along with those for 23 secondary compounds. Trivariate linear regression analysis found that the observed influx and efflux logPapp values determined by in vitro experiments significantly correlated with molecular weights and the octanol–water distribution coefficients at apical and basal pH levels (pH 6.0 and 7.4, respectively) (apical to basal, r = 0.76, n = 198; and basal to apical, r = 0.77, n = 202); the distribution coefficients were estimated in silico. Further, prediction accuracy was enhanced by applying a light gradient boosting machine learning system (LightGBM) to estimate influx and efflux logPapp values that incorporated 17 and 19 in silico chemical descriptors (r = 0.83–0.84, p < 0.001). The determination in vitro and/or prediction in silico of permeability coefficients across intestinal cell monolayers of a diverse range of industrial chemicals/food components/medicines could contribute to the safety evaluations of oral intakes of general chemicals in humans. Such new alternative methods could also reduce the need for animal testing during toxicity assessment.

Molecular structural heterogeneity of bisphenols governs their serum albumin binding

Bisphenol A (BPA) and its analogs (bisphenol F, BPF; bisphenol AF, BPAF; bisphenol S, BPS; and tetrabromobisphenol A, TBBPA) are transported by blood and bind estrogen receptors of target organs or cells. They were confirmed to bind human serum albumin (HSA) in blood, and the binding constants of BPA (5.14 × 10 3 M −1 ), BPF (1.05 × 10 4 M −1 ), and BPS (7.89 × 10 3 M −1 ) determined via equilibrium dialysis shows moderate binding ability with multiple binding sites. The HSA-water partition coefficients (log K HW > 3) are greater than their octanol-water distribution coefficients, and may follow the order: TBBPA > BPAF > BPA (3.75) > BPF (3.61) > BPS (3.27). Functional groups and substitutions of bisphenols (BPs) determine the fluorescence quenching of Trp214 in HSA. The effects follow: TBBPA (4.41 × 10 14 M −1 s −1 ) » BPS (4.08 × 10 12 M −1 s −1 ) > BPAF (1.20 × 10 12 M −1 s −1 ) > BPF (3.06 × 10 11 M −1 s −1 ) ≈ BPA (4.47 × 10 11 M −1 s −1 ), which is in line with the molecular docking results. In this process, the enzymatic characteristics of HSA were changed simultaneously, as evidenced by decreased K m and V max except for BPS (increased K m and V max ) and increased catalytic efficiency, which may improve the hydrolysis of other drugs. However, the native conformation of the protein underwent locally adaptive changes due to the reversible binding. Overall, these data provide a mechanistic explanation for the transport of BPs in human blood, which may affect their retention and toxicity. • BPs in serum can be transported by serum albumin (SA). • BPs affiliate SA more than octanol, ranking as TBBPA > BPAF > BPA > BPF > BPS • SA undergoes locally adaptive structural changes regardless of their binding sites.

Predicting the end point potential break values: A case of potentiometric titration of lipophilic anions with cetylpyridinium chloride

The applicability of cetylpyridinium chloride for potentiometric titration of lipophilic anions has been studied. The specially developed cetylpyridinium-selective plasticized electrode has been used for the investigation of the mechanism of interaction between the cetylpyridinium cation and lipophilic anions, which obviously goes through the association reaction resulting in the formation of water-insoluble precipitates. The investigated 54 anions were placed in the selectivity row that strongly correlates with lipophilicity. Additionally, an attempt has been made to find a simple and reliable descriptor suitable for prediction of the value of the end point potential break and thus indicating the applicability of the described potentiometric method for determination of untested lipophilic anions of interest. It has been established that despite being well known lipophilicity estimators, molar weight, octanol–water distribution coefficient logP, logarithm of solubility logS, and hydrophilicity-lipophilicity index can not be separately used for directly predicting the end point potential break values. However, simultaneous analysis of the above descriptors by using the multiple linear regression technique has resulted in the development of a reasonable QSPR model for the estimation of the potential break values near the end point.

Nonlinear sorption of phenols and anilines by organobentonites: Nonlinear partition and space limitation for partitioning

Organobentonites, i.e., bentonites coated with surfactants such as cetyltrimethylammonium (CTAB), are superior and low-cost sorbents for removal of organic contaminants from wastewater. Nonlinear sorption of polar organic compounds such as phenols and anilines by organobentonites were widely observed and interpreted by adsorption mechanism. However, in this study, it was observed that the nonlinear sorption of phenols and anilines by CTAB coated bentonites (CTAB-bentonites) should be attributed to nonlinear partition mechanism with the additional space limitation in CTAB-bentonites for nonlinear partitioning, rather than adsorption mechanism. This nonlinear partition mechanism is supported by that (i) organobentonites is a partition medium, identified by the linear isotherms of polycyclic aromatic hydrocarbons (PAHs) and nitrobenzenes; (ii) sorption coefficients (logKd), the ratio of adsorbed amount (qe) to equilibrium concentration (Ce), and Dubinin-Ashtakhov (DA) model fitted sorption capacity (logQ0) of organic compounds, by a given CTAB-bentonite, are positively correlated with their octanol-water distribution coefficients (logKOW) and solubility in octanol (logSo) respectively; (iii) logKd and logQ0 of a given organic compound by CTAB-bentonites are positively correlated with organic carbon contents (foc) of CTAB-bentonites, but not specific surface area. Specific interaction (i.e., hydrogen-bonding interaction), in addition to van der Waals force, is responsible for the nonlinear partitioning of phenols and anilines into CTAB-bentonites, because of the positively linear relationship between DA model fitted sorption affinity (E) and hydrogen-bonding donor parameter (αm) of organic compounds. These results could help the recognizing of the nonlinear sorption behaviors of organic compounds by organobentonites and promote their environmental applications in wastewater treatment.

Pharmaceuticals' removal by constructed wetlands: a critical evaluation and meta-analysis on performance, risk reduction, and role of physicochemical properties on removal mechanisms.

This paper presents a comprehensive and critical analysis of the removal of pharmaceuticals (PhCs), the governing physicochemical properties, and removal mechanisms in constructed wetlands (CWs). The average removal efficiency of the most widely studied 34 PhCs ranges from 21% to 93%, with the exception of one PhC that exhibited negative removal. Moreover, CWs are effective in significantly reducing the environmental risk caused by many PhCs. Based on risk assessment, 12 PhCs were classified under high risk category (oxytetracycline > ofloxacin > sulfamethoxazole > erythromycin > sulfadiazine > gemfibrozil > ibuprofen > acetaminophen > salicylic acid > sulfamethazine > naproxen > clarithromycin), which could be considered for regular monitoring, water quality standard formulation and control purposes. Biodegradation (aerobic and anaerobic) is responsible for the removal of the majority of PhCs, often in conjunction with other mechanisms (e.g., adsorption/sorption, plant uptake, and photodegradation). The physicochemical properties of molecules play a pivotal role in the elimination processes, and could serve as important predictors of removal. The correlation and multiple linear regression analysis suggest that organic carbon sorption coefficient (Log Koc), octanol-water distribution coefficient (Log Dow), and molecular weight form a good predictive linear regression model for the removal efficiency of PhCs (R2 = 0.65, P-value <0.05).

Estimation of the octanol-water distribution coefficient of basic compounds by a cationic microemulsion electrokinetic chromatography system.

The octanol-water partition coefficient (Po/w), or the octanol-water distribution coefficient (Do/w) for ionized compounds, is a key parameter in the drug development process. In a previous work, this parameter was estimated through the retention factor measurements in a sodium dodecyl sulfate (SDS) - microemulsion electrokinetic chromatography (MEEKC) system for acidic compounds. Nonetheless, when ionized basic compounds were analyzed, undesirable ion pairs were formed with the anionic surfactant and avoided a good estimation of log Do/w. For this reason, an alternative MEEKC system based on a cationic surfactant has been evaluated to estimate Po/w or Do/w of neutral compounds and ionized bases. To this end, it has been characterized through the solvation parameter model (SPM) and compared to the octanol-water partition system. Results pointed out that both systems show a similar partition behavior. Hence, the log Po/w of a set of neutral compounds has been successfully correlated against the logarithm of the retention factor (log k) determined in this MEEKC system. Then, the log Do/w of 6 model bases have been estimated at different pH values and they have been compared to data from the literature, determined by the reference shake-flask and potentiometric methods. Good agreement has been observed between the literature and the estimated values when the base is neutral or partially ionized (up to 99% of ionization).

Estimation of the octanol–water distribution coefficient of acidic compounds by microemulsion electrokinetic chromatography

The feasibility of extending the determination of the lipophilicity of partially ionized acids (log Do/w) by microemulsion electrokinetic chromatography (MEEKC) is tested. Theoretical considerations predict that a linear log Do/w vs. log k correlation can be obtained only when the neutral and ionic forms of an acid follow the same correlation equation and the slope of the correlation is unity. In practice, since the lipophilicity of the neutral acid is much higher than that of the ionic form and the correlation slope is not very different from 1, the general linear correlation for neutral compounds can be applied across most of the ionization range of the acid.The linear correlation between log Po/w and log k of 20 neutral solutes (calibration curve) has been established and extended to 6 acids used as models, tested across their full ionization range. log Do/w-pH, and log k-pH profiles have been obtained for these 6 acids, and plotted log Do/w against log k for any acid at any degree of ionization. Furthermore, the log Do/w of the acids has been estimated from the calibration curve and log k-pH profile, and compared to values in the literature determined using reference methods such as the shake-flask one. Accurate values have been obtained using the MEEKC method when the acids are in their neutral form or partially ionized (ionization degree, α < 0.995). However, this parameter is overestimated when the acids are highly or fully ionized (α ≈ 1). Finally, in order to test the applicability of this method, we have applied the same procedure to estimate log Do/w at pH = 7.4 (blood physiological pH) of a set of 30 additional compounds (including partially and fully ionized acids). The results at this pH follow the same trend observed in the 6 model acids, and validate the application of the method for Do/w determination, except when α is very close to 1.

Prediction of bioconcentration factors in fish and invertebrates using machine learning

The application of machine learning has recently gained interest from ecotoxicological fields for its ability to model and predict chemical and/or biological processes, such as the prediction of bioconcentration. However, comparison of different models and the prediction of bioconcentration in invertebrates has not been previously evaluated. A comparison of 24 linear and machine learning models is presented herein for the prediction of bioconcentration in fish and important factors that influenced accumulation identified. R2 and root mean square error (RMSE) for the test data (n = 110 cases) ranged from 0.23–0.73 and 0.34–1.20, respectively. Model performance was critically assessed with neural networks and tree-based learners showing the best performance. An optimised 4-layer multi-layer perceptron (14 descriptors) was selected for further testing. The model was applied for cross-species prediction of bioconcentration in a freshwater invertebrate, Gammarus pulex. The model for G. pulex showed good performance with R2 of 0.99 and 0.93 for the verification and test data, respectively. Important molecular descriptors determined to influence bioconcentration were molecular mass (MW), octanol-water distribution coefficient (logD), topological polar surface area (TPSA) and number of nitrogen atoms (nN) among others. Modelling of hazard criteria such as PBT, showed potential to replace the need for animal testing. However, the use of machine learning models in the regulatory context has been minimal to date and is critically discussed herein. The movement away from experimental estimations of accumulation to in silico modelling would enable rapid prioritisation of contaminants that may pose a risk to environmental health and the food chain.

Influence of deep water formation by open-sea convection on the transport of low hydrophobicity organic pollutants in the NW Mediterranean Sea

The significance of the offshore vertical convection currents in the transport and sinking of water-soluble organic pollutants into marine deep basins has been evaluated. For this purpose, sediment cores were collected in the Gulf of Lion (GoL) at sites between 26 and 2330 m water depth. The top core layers were analyzed for aromatic and aliphatic hydrocarbons and organochlorine compounds. Organic compounds with logKAW (air water partition coefficient) between −2 and −4, e.g. lindane, PCB 28, PCB 52, phenanthrene, methylphenanthrenes, dimethylphenanthrenes, C14–C23n-alkanes, are found in higher concentrations or exhibit relative concentration increases in the sediments deposited in the continental rise as consequence of the open-sea convection processes associated with the formation of Western Mediterranean Deep Water (WMDW). In contrast, the organic pollutants with intermediate air-water distribution coefficients, logKAW between −2 and 0, and high octanol water distribution coefficients (logKow > 6), e.g. highly chlorinated PCBs, DDTs, DDEs, DDDs, C25–C35n-alkanes, and polycyclic aromatic hydrocarbons with molecular weight higher than 200, occur in association to sediment particles, which are mainly transported by the Northern current along the continental shelf forming the mud belt. The Rhône prodelta is therefore the area of the GoL showing the highest concentrations of this group of organic compounds, which are preferentially associated with water particles. Overall, the results show that vertical open-sea convection processes related with offshore formation of WMDW may have an important role in the transport and accumulation of water soluble pollutants to deep marine environments of the GoL (>2000 m water depth).

Feasibility of the estimation of octanol-water distribution coefficients of acidic drugs by microemulsion electrokinetic chromatography

Previous studies have shown that a microemulsion electrokinetic chromatography (MEEKC) system can estimate the logarithm of the octanol-water partition coefficient (log P&lt;sub&gt;o/w&lt;/sub&gt;) of neutral solutes. In the present work, the applicability of the method to partially and fully ionized acids has been evaluated. Naproxen, a monoprotic acid, has been used as test solute. The retention factor (k) of this compound has been measured in MEEKC at several values of pH and the retention factor-pH profile has been established. As log P&lt;sub&gt;o/w&lt;/sub&gt; correlates with log k&lt;sub&gt;MEEKC&lt;/sub&gt; for neutral compounds, this correlation has been used to estimate the logarithm of the octanol-water partition coefficient of the neutral (log P&lt;sub&gt;o/w(HA)&lt;/sub&gt;), and the fully ionized (log P &lt;sub&gt;o/w(A-)&lt;/sub&gt;) forms of naproxen. Then, the logarithm of the octanol-water distribution coefficient (log D&lt;sub&gt;o/w&lt;/sub&gt;) of the partially ionized form of the acid has been estimated. The comparison of the estimated values with the ones obtained experimentally using the classical procedures, such as the shake-flask method, shows differences under 0.4 log D&lt;sub&gt;o/w&lt;/sub&gt; units either if the acid is partially ionized or in its neutral form in the most part of the pH range. However, the method overestimates the log D&lt;sub&gt;o/w &lt;/sub&gt;of the highly (&amp;gt;99.5 %) or fully ionized form of naproxen.