Spectroscopic Investigation of the Effect of Microstructure and Energetic Offset on the Nature of Interfacial Charge Transfer States in Polymer: Fullerene Blends.

Despite performance improvements of organic photovoltaics, the mechanism of photoinduced electron-hole separation at organic donor-acceptor interfaces remains poorly understood. Inconclusive experimental and theoretical results have produced contradictory models for electron-hole separation in which the role of interfacial charge-transfer (CT) states is unclear, with one model identifying them as limiting separation and another as readily dissociating. Here, polymer-fullerene blends with contrasting photocurrent properties and enthalpic offsets driving separation were studied. By modifying composition, film structures were varied from consisting of molecularly mixed polymer-fullerene domains to consisting of both molecularly mixed and fullerene domains. Transient absorption spectroscopy revealed that CT state dissociation generating separated electron-hole pairs is only efficient in the high energy offset blend with fullerene domains. In all other blends (with low offset or predominantly molecularly mixed domains), nanosecond geminate electron-hole recombination is observed revealing the importance of spatially localized electron-hole pairs (bound CT states) in the electron-hole dynamics. A two-dimensional lattice exciton model was used to simulate the excited state spectrum of a model system as a function of microstructure and energy offset. The results could reproduce the main features of experimental electroluminescence spectra indicating that electron-hole pairs become less bound and more spatially separated upon increasing energy offset and fullerene domain density. Differences between electroluminescence and photoluminescence spectra could be explained by CT photoluminescence being dominated by more-bound states, reflecting geminate recombination processes, while CT electroluminescence preferentially probes less-bound CT states that escape geminate recombination. These results suggest that apparently contradictory studies on electron-hole separation can be explained by the presence of both bound and unbound CT states in the same film, as a result of a range of interface structures.

CATALOGIC 301C model - validation and improvement.

In Europe, REACH legislation encourages the use of alternative in silico methods such as (Q)SAR models. According to the recent progress of Chemical Substances Control Law (CSCL) in Japan, (Q)SAR predictions are also utilized as supporting evidence for the assessment of bioaccumulation potential of chemicals along with read across. Currently, the effective use of read across and QSARs is examined for other hazards, including biodegradability. This paper describes the results of external validation and improvement of CATALOGIC 301C model based on more than 1000 tested new chemical substances of the publication schedule under CSCL. CATALOGIC 301C model meets all REACH requirements to be used for biodegradability assessment. The model formalism built on scientific understanding for the microbial degradation of chemicals has a well-defined and transparent applicability domain. The model predictions are adequate for the evaluation of the ready degradability of chemicals.

Accounting for data variability, a key factor in in vivo/in vitro relationships: application to the skin sensitization potency (in vivo LLNA versus in vitro DPRA) example.

When searching for alternative methods to animal testing, confidently rescaling an in vitro result to the corresponding in vivo classification is still a challenging problem. Although one of the most important factors affecting good correlation is sample characteristics, they are very rarely integrated into correlation studies. Usually, in these studies, it is implicitly assumed that both compared values are error-free numbers, which they are not. In this work, we propose a general methodology to analyze and integrate data variability and thus confidence estimation when rescaling from one test to another. The methodology is demonstrated through the case study of rescaling the in vitro Direct Peptide Reactivity Assay (DPRA) reactivity to the in vivo Local Lymph Node Assay (LLNA) skin sensitization potency classifications. In a first step, a comprehensive statistical analysis evaluating the reliability and variability of LLNA and DPRA as such was done. These results allowed us to link the concept of gray zones and confidence probability, which in turn represents a new perspective for a more precise knowledge of the classification of chemicals within their in vivo OR in vitro test. Next, the novelty and practical value of our methodology introducing variability into the threshold optimization between the in vitro AND in vivo test resides in the fact that it attributes a confidence probability to the predicted classification. The methodology, classification and screening approach presented in this study are not restricted to skin sensitization only. They could be helpful also for fate, toxicity and health hazard assessment where plenty of in vitro and in chemico assays and/or QSARs models are available. Copyright © 2016 John Wiley & Sons, Ltd.

QSAR Toolbox - workflow and major functionalities.

The OECD QSAR Toolbox is a software application intended to be used by governments, the chemical industry and other stakeholders in filling gaps in (eco)toxicity data needed for assessing the hazards of chemicals. The development and release of the Toolbox is a cornerstone in the computerization of hazard assessment, providing an 'all inclusive' tool for the application of category approaches, such as read-across and trend analysis, in a single software application, free of charge. The Toolbox incorporates theoretical knowledge, experimental data and computational tools from various sources into a logical workflow. The main steps of this workflow are substance identification, identification of relevant structural characteristics and potential toxic mechanisms of interaction (i.e. profiling), identification of other chemicals that have the same structural characteristics and/or mechanism (i.e. building a category), data collection for the chemicals in the category and use of the existing experimental data to fill the data gap(s). The description of the Toolbox workflow and its main functionalities is the scope of the present article.

Reduced voltage losses yield 10% efficient fullerene free organic solar cells with >1 V open circuit voltages.

Optimization of the energy levels at the donor-acceptor interface of organic solar cells has driven their efficiencies to above 10%. However, further improvements towards efficiencies comparable with inorganic solar cells remain challenging because of high recombination losses, which empirically limit the open-circuit voltage (Voc) to typically less than 1 V. Here we show that this empirical limit can be overcome using non-fullerene acceptors blended with the low band gap polymer PffBT4T-2DT leading to efficiencies approaching 10% (9.95%). We achieve Voc up to 1.12 V, which corresponds to a loss of only Eg/q - Voc = 0.5 ± 0.01 V between the optical bandgap Eg of the polymer and Voc. This high Voc is shown to be associated with the achievement of remarkably low non-geminate and non-radiative recombination losses in these devices. Suppression of non-radiative recombination implies high external electroluminescence quantum efficiencies which are orders of magnitude higher than those of equivalent devices employing fullerene acceptors. Using the balance between reduced recombination losses and good photocurrent generation efficiencies achieved experimentally as a baseline for simulations of the efficiency potential of organic solar cells, we estimate that efficiencies of up to 20% are achievable if band gaps and fill factors are further optimized.

[HISTORY OF GYNECOLOGICAL DISORDERS, OBSTERIC PATHOLOGY AND ANDROGEN LEVELS AS PROGNOSTIC FACTORS AND INDICES OF MYOCARDIAL INJURY AMONG POSTMENOPAUSAL WOMEN WITH ACUTE CORONARY SYNDROME.]

The study ob]ective was assessment of pathogenetic and prognostic significance of gynecologic and obstetrical pathology and the concentrations of sex steroids in adult women with acute coronaty syndrome (ACS). The study group included 120 postmenopausal women with ACS treated in the Clinic of Cardiology, University Hospital "Alexandrovska" between 2011 and 2013. Sex hormones were measured in 57 patients. Enzyme, electrochemiluminescent, enzyme-linked immunologic and immunoturbodimeric methods were used for the examined indices assessment. The history for gynecologic disorders and pregnancy complications was associated with coronaiy atherosclerotic burden (SYNTAX score - 4,6+/-8,8 vs 8,5+/-9,3, p=0,003), gynecologic history only - with lower 17Beta-estradiol levels (139,01+/-167,66 vs 113,51+/-304,1, p=0,004) and coronaly atherosclerosis severity (5,5+/-9,3 vs 8,0+/-10,3, p=0,058). Abnormally high endogenous concentrations of androgens were found among the patients with ACS with ST elevation, STEMI (27,5% vs 77,8%, p=0,004), with significantly more intense acute infiammatoty response (8,7+/-3,21 vs 11,07+/-2,85, p=0,044 3a WBC) and more extensive acute myocardial damage (57,8+/-12,6 vs 45,3 ml, p=O,OO8 for e]ection fraction 33,7+/-37,4 vs 117+/-144,22 U/L, p=0,031 for CPK-MB; 0,89+/-8 18 vs 1,87+/-0,4 ng/ml, p=0,009 for hsTnT). The gynecologic and obstetrical history and hyperandrogenism are related to the extent and severity of coronary atherosclerosis, occurrence of STEMI, more intense acute inflammatory response and myocardial injury among postmenopausal women with ACS.

SURGICAL STRATEGY FOR PATIENTS UNDERGOING CAROTID ENDARTERECTOMY.

UNLABELLED: Carotid endarterectomy (CEA) is a surgical intervention that aims to reduce neurological symptoms in carotid atherosclerosis and prevent brain damage and subsequent neurological deficit. AIM: To study the major risk factors, surgical techniques, applied diagnostic methods and perioperative complications occurring in patients undergoing CEA. MATERIALS AND METHODS: 496 surgical interventions on the occasion of stenoses and/or occlusions of the carotid arteries were performed for the period 1987-2009 at the department of Vascular Surgery and Angiology of "St. Ekaterina" - University Hospital - Sofia. All patients were operated using standard access under general or local anaesthesia. During surgeries, evaluation of cerebral hemodynamics and function was performed by transcranial Doppler Ultrasound (TCD) and cerebral oximetry (CO). Carotid shunting was selectively applied in cases of deterioration of the values of CO and TCD during cross clamping of the carotid arteries. RESULTS: The highest relative share among cerebrovascular complications took stroke with 2.7% share in the group of asymptomatic patients and 1.7% - in the symptomatic group. Considering the other types of complications with the largest relative share were cardiac complications in both groups of patients - hemodynamic disorders and myocardial infarction. CONCLUSION: Low values of postoperative mortality and stroke after CEA in our study are comparable with other leading centers, proving that CEA is safe and effective surgical procedure for stroke prevention in both symptomatic and asymptomatic patients. Accurate perioperative diagnostic allows a good approach for choosing the correct surgical strategy.

Ankyrin is the major oxidised protein in erythrocyte membranes from end-stage renal disease patients on chronic haemodialysis and oxidation is decreased by dialysis and vitamin C supplementation.

Chronically haemodialysed end-stage renal disease patients are at high risk of morbidity arising from complications of dialysis, the underlying pathology that has led to renal disease and the complex pathology of chronic kidney disease. Anaemia is commonplace and its origins are multifactorial, involving reduced renal erythropoietin production, accumulation of uremic toxins and an increase in erythrocyte fragility. Oxidative damage is a common risk factor in renal disease and its co-morbidities and is known to cause erythrocyte fragility. Therefore, we have investigated the hypothesis that specific erythrocyte membrane proteins are more oxidised in end-stage renal disease patients and that vitamin C supplementation can ameliorate membrane protein oxidation. Eleven patients and 15 control subjects were recruited to the study. Patients were supplemented with 2 × 500 mg vitamin C per day for 4 weeks. Erythrocyte membrane proteins were prepared pre- and post-vitamin C supplementation for determination of protein oxidation. Total protein carbonyls were reduced by vitamin C supplementation but not by dialysis when investigated by enzyme linked immunosorbent assay. Using a western blot to detect oxidised proteins, one protein band, later identified as containing ankyrin, was found to be oxidised in patients but not controls and was reduced significantly by 60% in all patients after dialysis and by 20% after vitamin C treatment pre-dialysis. Ankyrin oxidation analysis may be useful in a stratified medicines approach as a possible marker to identify requirements for intervention in dialysis patients.

Surgical treatment of symptomatic and ruptured abdominal aortic aneurysms.

Despite the increased volume of patients undergoing selective reconstruction on the occasion of abdominal aortic aneurysms (AAA) in the last decades, the number of patients with rupture of abdominal aortic aneurysms (RAAA) is not significantly decreased. RAAA is catastrophic and life-threatening condition. It remains a challenge to every practitioner. To optimize the surgical practice we studied the literature for the treatment of symptomatic and rupture aneurysm of the abdominal aorta.

Surgical strategy for patients undergoing carotid endarterectomy.

UNLABELLED: Carotid endarterectomy (CEA) is a surgical intervention that aims to reduce neurological symptoms in carotid atherosclerosis and prevent brain damage and subsequent permanent neurological deficit. AIM: To study the major risk factors, surgical techniques, applied diagnostic methods and perioperative complications occurred in patients undergoing CEA. MATERIALS AND METHODS: 496 surgical interventions on the occasion of stenosis and/or occlusions of the carotid arteries were performed for the period 1987-2009 at the department of Vascular Surgery and Angiology of "St. Ekaterina"- University Hospital - Sofia. All patients were operated using standard access under general or local anaesthesia. During surgeries, the evaluation of cerebral hemodynamics and function was performed by transcranial Doppler Ultrasound (TCD) and cerebral oximetry (CO). Carotid shunting was selectively applied in cases of deterioration of the values of CO and TCD during cross clamping of the carotid arteries. RESULTS: With the highest relative share among cerebrovascular complications was stroke with 2.7% share in the group of asymptomatic patients and 1.7%--in the symptomatic group. When considering the other types of complications with the largest relative share were cardiac complications in both groups of patients--hemodynamic disorders and myocardial infarction. CONCLUSION: Low values of postoperative mortality and stroke after CEA in our study are comparable with other leading centers, proving that CEA is safe and effective surgical procedure for stroke prevention in both symptomatic and asymptomatic patients. Accurate perioperative diagnostic allows a good approach for choosing the correct surgical strategy.

Direct cooperation between androgen receptor and E2F1 reveals a common regulation mechanism for androgen-responsive genes in prostate cells.

We have studied the regulation of ATAD2 gene expression by androgens in prostate cells. ATAD2 is a coactivator of the androgen receptor (AR) and the MYC protein. We showed that ATAD2 expression is directly regulated by AR via an AR binding sequence (ARBS) located in the distal enhancer of its regulatory region. The gene is also regulated by the E2F1 transcription factor. Using knockdown and chromatin immunoprecipitation technique approaches, we could demonstrate that AR and E2F1 functionally collaborate and physically interact between each other. From the analysis of chromatin conformation, we conclude that this cooperation results from a chromatin looping over the ATAD2 promoter region between the ARBS and E2F1 binding site in an androgen-dependent manner. Furthermore, we could show that several genes overexpressed in prostate cancer and potentially involved in several aspects of tumor development have an ARBS and an E2F1 binding site in their regulatory regions and exhibit the same mechanism of regulation by both transcription factors as ATAD2.

Simulation of chemical metabolism for fate and hazard assessment. V. Mammalian hazard assessment.

Animals and humans are exposed to a wide array of xenobiotics and have developed complex enzymatic mechanisms to detoxify these chemicals. Detoxification pathways involve a number of biotransformations, such as oxidation, reduction, hydrolysis and conjugation reactions. The intermediate substances created during the detoxification process can be extremely toxic compared with the original toxins, hence metabolism should be accounted for when hazard effects of chemicals are assessed. Alternatively, metabolic transformations could detoxify chemicals that are toxic as parents. The aim of the present paper is to describe specificity of eukaryotic metabolism and its simulation and incorporation in models for predicting skin sensitization, mutagenicity, chromosomal aberration, micronuclei formation and estrogen receptor binding affinity implemented in the TIMES software platform. The current progress in model refinement, data used to parameterize models, logic of simulating metabolism, applicability domain and interpretation of predictions are discussed. Examples illustrating the model predictions are also provided.

Simulation of chemical metabolism for fate and hazard assessment. IV. Computer-based derivation of metabolic simulators from documented metabolism maps.

Computer simulation of xenobiotic metabolism and degradation is usually performed proceeding from a set of expert-developed rules modelling the actual enzyme-driven chemical reactions. With the accumulation of extensive metabolic pathway data, the analysis required to derive such chemical reaction patterns has become more objective, but also more convoluted and demanding. Herein we report on our computer-based approach for the analysis of metabolic maps, leading to the construction of reaction rules statistically suitable for simulation purposes. It is based on the set of so-called bare transformations which encompass all unique reaction patterns as obtained by a heuristically enhanced maximum common subgraph algorithm. The bare transformations guarantee that no existing metabolite is missed in simulation at the expense of an enormous amount of false positive predictions. They are rendered more selective by correlating the generated true and false positives to the locations of typical chemical functional groups in the potential reactants. The approach and its results are illustrated for a metabolic map collection of 15 cycloalkanes.

Simulation of chemical metabolism for fate and hazard assessment. III. New developments of the bioconcentration factor base-line model.

The new development of the bioconcentration factor (BCF) base-line model of Dimitrov et al. [SAR QSAR Environ. Res. 6 (2005), pp. 531-554] is presented. The model applicability domain was expanded by enlarging the training set of the model up to 705 chemicals. The list of chemical-dependent mitigating factors was expanded by including water solubility of chemicals. The original empirical term for estimating ionization of chemicals was mechanistically analysed using two different approaches. In the first one, the ionization potential of chemicals was estimated based on the acid dissociation constant (pK(a) ). This term was found to be less adequate for inclusion in the ultimate BCF model, due to overestimating ionization of chemicals. The second approach, estimating the ionization as a ratio between distribution and partition coefficients (log P and log D), was found to be more successful. The new ionization term allows modelling of chemicals with both acidic and basic functionalities and chemicals undergoing different degrees of ionization. The significance of the different mitigating factors which can reduce the maximum bioconcentration potential of the chemicals was re-formulated and model parameters re-evaluated.

Simulation of chemical metabolism for fate and hazard assessment. I: approach for simulating metabolism.

Information regarding the metabolism of xenobiotic chemicals plays a central role in regulatory risk assessments. In regulatory programmes where metabolism studies are required, the studies of metabolic pathways are often incomplete and the identification of activated metabolites and important degradation products are limited by analytical methods. Because so many more new chemicals are being produced than can be assessed for potential hazards, setting assessment priorities among the thousands of untested chemicals requires methods for predictive hazard identification which can be derived directly from chemical structure and their likely metabolites. In a series of papers we are sharing our experience in the computerized management of metabolic data and the development of simulators of metabolism for predicting the environmental fate and (eco)toxicity of chemicals. The first paper of the series presents a knowledge-based formalism for the computer simulation of non-intermediary metabolism for untested chemicals, with an emphasis on qualitative and quantitative aspects of modelling metabolism.

Simulation of chemical metabolism for fate and hazard assessment. II CATALOGIC simulation of abiotic and microbial degradation.

The unprecedented pollution of the environment by xenobiotic compounds has provoked the need to understand the biodegradation potential of chemicals. Mechanistic understanding of microbial degradation is a premise for adequate modelling of the environmental fate of chemicals. The aim of the present paper is to describe abiotic and biotic models implemented in CATALOGIC software. A brief overview of the specificities of abiotic and microbial degradation is provided followed by detailed descriptions of models built in our laboratory during the last decade. These are principally new models based on unique mathematical formalism already described in the first paper of this series, which accounts more adequately than currently available approaches the multipathway metabolic logic in prokaryotes. Based on simulated pathways of degradation, the models are able to predict quantities of transformation products, biological oxygen demand (BOD), carbon dioxide (CO(2)) production, and primary and ultimate half-lives. Interpretation of the applicability domain of models is also discussed.

Cell cycle regulated expression of NCoR might control cyclic expression of androgen responsive genes in an immortalized prostate cell line.

In this work we have studied the mechanisms of regulation of expression of androgen receptor (AR) target genes. We have used an immortalized non-tumorigenic prostate cell line RWPE-1-AR(tag) constitutively expressing an exogenous AR as a model. We observed that all studied AR target genes exhibited a specific expression during the G1 phase of the cell cycle despite the constitutive expression of AR. Importantly, we found that the expression of NCoR, an AR co-repressor, was downregulated during the G1 phase and expressed as mRNA and protein specifically during the S phase. The role of NCoR in repressing androgen-induced expression of AR target genes in S phase was further demonstrated by altering expression of NCoR during the cell cycle through knockdown or induced overexpression. Using two alternative techniques we show that AR binds directly to target DNA in the chromatin only during the G1 phase. These data support the hypothesis that NCoR might control a cell cycle dependent regulation of expression AR target genes in prostate cells.

Ghrelin signaling in human mesenteric arteries.

The hypothesis is that the ghrelin signal pathway consists of new participants including a local second mediator in human mesenteric arteries. The contractile force of isometric artery preparations was measured using a wire-myograph. Whole-cell patch clamp experiments were performed on freshly isolated single smooth muscle cells from the same tissue. After the addition of ghrelin (100 nmol) the outward potassium currents conducted through iberiotoxin-sensitive calcium-activated potassium channels with a large conductance were almost entirely abolished. The effect of ghrelin on potassium currents was insensitive to selective inhibitors of cAMP-dependent protein kinase and soluble guanylate cyclase, but was eliminated in the presence of des-octanoyl ghrelin and O-(octahydro-4,7-methano-1H-inden-5-yl) carbonopotassium dithioate (D-609). Ghrelin dose-dependently increased the force of contraction of native, endothelium-denuded and mostly of endothelium-denuded and treated with tetrodotoxin human mesenteric arteries preconstricted with 1 nmol endothelin-1. This effect of ghrelin was blocked when the bath solution contained 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), 4-amino-5-(4-methylphenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2), D-609, 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203x), pertussis toxin, 2-aminoethyl diphenylborinate (2-APB), indomethacin, (5Z,13E)-(9S,11S,15R)-9,15,Dihydroxy-11-fluoro-15-(2-indanyl)-16,17,18,19,20,pentanor-5,13-prostadienoic acid (AL-8810) - a non-selective prostanoid receptor antagonist, 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazolo (SC-560) - a selective cyclooxygenase 1 inhibitor, ozagrel - a selective thromboxane A(2) synthase inhibitor or T prostanoid receptor antagonist GR32191B. It is concluded that ghrelin increases the force of contraction of human mesenteric arteries by a novel mechanism that involves Src kinase, mitogen-activated protein kinase kinase (MEK), cyclooxygenase 1 and T prostanoid receptor agonist, most probably thromboxane A(2).

Diabetics on dialysis in the Republic of Macedonia: A nationwide epidemiological study.

BACKGROUND: Incidence increase of diabetes mellitus (DM) has taken epidemic proportions in the world. Diabetic nephropathy (DN) is a most serious complication, taking a leading place as a factor in the progression of chronic kidney disease (CKD). Dialysis treatment of these patients is complex, expensive, and exerts an excessive burden on the health budgets of the affected countries. METHODS: We performed a nationwide precise observational study with the aim of analysing diabetics on dialysis in dialysis centres throughout the Republic of Macedonia (RM) in 2002 and in 2006; to compare the results from patients records; and to gather data on the epidemiology, clinical characteristics and complications of diabetes type 1 (DM1) and diabetes type 2 (DM2). RESULTS: The prevalence of HD patients in RM was 1114 vs 1074 in 2002 and 2006, respectively. Of these, 109 (9.78%) vs. 115 (10.71%) had DM in 2002 and 2006, respectively. The percentage of diabetics on dialysis between different centers varied between 3% to 21% vs. 2.4% to 22.07% in 2002 and 2006, respectively. The mean age of the patients was 58+/-10.29 vs. 56.5+/-10.71 in 2002 and 2006, respectively. Patients with DM1 were 19 (17.43%) vs. 15 (13.04%) and with DM2 were 90 (82.57%) vs. 100 (86.96%) in 2002 and 2006, respectively. 28 (25.68%) vs. 31 (26.96%) patients were on oral anti-diabetic drugs and 62 (57.21%) vs. 69 (60%) patients were on insulin in 2002 and 2006, respectively. Mean age of DM1 patients was 47+/-11.6 y. vs. 45+/-7.32 y. respectively and of DM2 was 60.37+/-8.33 y. vs. 61.14+/-10.23 y., in 2002 and 2006, respectively. Mean time of insulin treatment was 9.5+/-6.63 y. vs. 10.85+/-9.29 y. in 2002 and 2006. Mean Body Mass Index (BMI) was 26.4 vs. 23.49+/-4.74 kg/m2 in DM1 and 25.5 vs. 24.77+/-3.70 kg/m2 in DM2 patients in 2002 and 2006, respectively. Thrombosis of first arteriovenous fistulae (AVF) occurred in 41% vs. 25.22% in 2002 and 2006, respecttitvely. Hepatitis C virus (HCV) infection was confirmed in 57% vs. 44% of DM patients in 2002 and 2006, respectively. Most common co-morbidity in patients was hypertension, 91% vs. 80.87% in 2002 and 2006, respectively. CONCLUSION: The number of diabetics on dialysis in the Republic of Macedonia did not increase in the period from 2002 to 2006. In DM2 diabetics on dialysis the frequency of complications is higher and time on dialysis is shorter than in DM1 patients. Early detection of diabetic nephropathy by primary care physicians as well as collaborative treatment by diabetologists, nephrologists, cardiologists and ophthalmologists before and during dialysis are important for improvement of treatment and survival of diabetic patients on dialysis.

Development of a biodegradation model for the prediction of metabolites in soil.

The awareness of air, soil and water pollution has driven the search for better methods for the assessment of the environmental fate of industrial chemicals. This paper is focused on the simulation of formation and transformation of metabolites in soil. The key challenges in the development of a simulator for predicting metabolic fate of chemicals in soil are the complexity of the soil compartment and incompleteness of metabolic information. Based on the collected data for metabolic fate of 183 chemicals a set of soil specific transformations were defined and used to develop a simulator for metabolism in soil. The analysis of outliers showed that the low predictability for some chemicals is due to: 1) incomplete documented metabolic pathways with missing intermediates and/or 2) reactions of condensation that are not simulated in the current version of the model. Hence, further improvement of the model requires expanding the metabolism database and further refinement of the logic of metabolic transformations used in the simulator.