Congeneric Groups Research Articles

Self-association of C3 and C6 epimers of hyodeoxycholate anions in aqueous medium: Hydrophobicity, critical micelle concentration and aggregation number

Hyodeoxycholic acids anion (HD) and it's 3- and 6-epimers (3e-HD and 6e-HD) are suitable for biopharmaceutical application since they possess α equatorial i.e. β axial OH groups so their membranotoxicity is reduced. Self-association of stereoisomers 3e-HD and 6e-HD has not been studied so far. According to the capacity factor (k, RPHPLC), hydrophobicity decreases in the following series: HD>3e-HD>6e-HD. However, critical micelle concentration (CMC) is the lowest for the 6e-HD (10mM, 25°C) and the highest for 3e-HD (38mM, 25°C), which is contrary to expectations according to their hydrophobicity. Aggregation number (n) has the highest value for 6e-HD (8, 25°C) and the lowest value for the stereoisomer 3e-HD (4, 25°C). The change in demicellisation capacity factor (∆Cp) decreases in the following series: 6e-HD (316Jmol−1K−1)>HD (260Jmol−1K−1)>3e-HD (181Jmol−1K−1). In the plane of ln k – ln CMC epimer 6e-HD is outliner related to the hydrophobic congeneric group. This suggests that, in formation of micelles of HD and 3e-HD, besides hydrophobic effect other interactions are neglected. However, in formation of 6e-HD micelle, beside hydrophobic effect significant interaction exists different from hydrophobic interaction (formation of hydrogen bonds between building units of the micelle).

Risk of POP mixtures on the Arctic food chain.

The exposure of the Arctic ecosystem to persistent organic pollutants (POPs) was assessed through a review of literature data. Concentrations of 19 chemicals or congeneric groups were estimated for the highest levels of the Arctic food chain (Arctic cod, ringed seals, and polar bears). The ecotoxicological risk for seals, bears, and bear cubs was estimated by applying the concentration addition (CA) concept. The risk of POP mixtures was very low in seals. By contrast, the risk was 2 orders of magnitude higher than the risk threshold for adult polar bears and even more (3 orders of magnitude above the threshold) for bear cubs fed with contaminated milk. Based on the temporal trends available for many of the chemicals, the temporal trend of the mixture risk for bear cubs was calculated. Relative to the 1980s, a decrease in risk from the POP mixture is evident, mainly because of international control measures. However, the composition of the mixture substantially changes, and the contribution of new POPs (particularly perfluorooctane sulfonate) increases. These results support the effectiveness of control measures, such as those promulgated in the Stockholm Convention, as well as the urgent need for their implementation for new and emerging POPs. Environ Toxicol Chem 2017;36:1181-1192. © 2017 SETAC.

Highly conserved Z and molecularly diverged W chromosomes in the fish genus Triportheus (Characiformes, Triportheidae).

The main objectives of this study were to test: (1) whether the W-chromosome differentiation matches to species' evolutionary divergence (phylogenetic concordance) and (2) whether sex chromosomes share a common ancestor within a congeneric group. The monophyletic genus Triportheus (Characiformes, Triportheidae) was the model group for this study. All species in this genus so far analyzed have ZW sex chromosome system, where the Z is always the largest chromosome of the karyotype, whereas the W chromosome is highly variable ranging from almost homomorphic to highly heteromorphic. We applied conventional and molecular cytogenetic approaches including C-banding, ribosomal DNA mapping, comparative genomic hybridization (CGH) and cross-species whole chromosome painting (WCP) to test our questions. We developed Z- and W-chromosome paints from T. auritus for cross-species WCP and performed CGH in a representative species (T. signatus) to decipher level of homologies and rates of differentiation of W chromosomes. Our study revealed that the ZW sex chromosome system had a common origin, showing highly conserved Z chromosomes and remarkably divergent W chromosomes. Notably, the W chromosomes have evolved to different shapes and sequence contents within ~15-25 Myr of divergence time. Such differentiation highlights a dynamic process of W-chromosome evolution within congeneric species of Triportheus.

Parameters of micellization and hydrophobicity of sodium salts of 7-buthyl (butylidene) and 7-octyl (octylidene) derivatives of the cholic and the deoxycholic acid in a water solution: Pattern recognition — Linear hydrophobic congeneric groups

In this paper the influence of hydrophobicity is analysed (expressed with the reversed phase HPLC capacity factor, k) of the steroid skeleton anion derivatives with next groups placed in a position C7 of the steroid skeleton: octyl, octylidene, butyl, and butylidene group; the influence on their micellization parameters: aggregation number (n) and critical micelle concentration (CMC). If the examined derivative is more hydrophobic (higher values of k), CMC values are lower. Examined molecules have the same length of C7 hydrocarbon chain but different position of a double bond in the ring B (endocyclic between C6 and C7, and exocyclic on the C7) and have a different hydrophobicity as well as different CMC values. This can be explained using conformation analysis according to which conformation of the B ring of the steroid skeleton determines conformation of the C7 hydrocarbon chain, i.e. the degree of their departuring from steroid skeleton mean plane and approaching to convex surface of the molecule. In the plane lnk–n new derivatives with octyl/octylidene i.e. buthyl/butylidene group form two linear congeneric group: GE-LCC and H-LCC. Bile acid anions that form the H-LCC group, due the steric reasons, have a low possibility for formation of hydrogen bonds between different building units of a micelle. In the plane lnk–lnCMC only one linear hydrophobic congeneric group is formed which suggests that in micelles, on CMC, hydrogen bonds between building units are not present. Values of partition coefficients of nitrazepan for analysed derivatives micelles suggest that, in formation of mixed micelles of nitrazepan C7 alkyl chain from twisted conformation switches to elongated conformation and takes part in ecraning of the guest molecule.

Chemometric and conformational approach to the analysis of the aggregation capabilities in a set of bile salts of the allo and normal series

Bile salts are steroid biosurfactants that have a significant role in fat digestion, cholesterol micellar solubilization, and regulation of metabolism. They are important in pharmaceutical studies as modulators of the transport-permeability of drugs or as ligands for certain receptors. For the rational application of bile salts in medicine, it is necessary to have detailed knowledge of their aggregation capabilities (which determine their membranotoxicity and solubilization capacity). From the examination of bile salt derivatives, the in plane of lnk (RPHPLC) and micelle aggregation number n, as well as the anion of 7-oxodeoxycholic acid (7-OxD) and anion of cholic acid (C), are considered to be outliers, related to linear hydrophobic congeneric groups, which means that their micelles, in addition to being determined by hydrophobic interactions, are determined by hydrogen bonds, i.e., they form micelles with higher aggregation numbers than would be expected from the hydrophobicity of their steroid skeleton. For bile salts of the normal series in the formation of hydrogen bonds in secondary micelles, the crucial structural elements of the steroid skeleton are: α-equatorial-C3OH group and α-axial-C12OH group. Bile salts of the allo series, including allocholic (aC), allodeoxycholic (aDC) and allochenodeoxycholic acid (aCD), belong to the linear hydrophobic congeneric group. Their micelles are determined by hydrophobic interactions. It is assumed that for the analyzed allo derivatives, the A ring of the steroid skeleton is in the twisted boat conformation, which explains the spatial sheltering of their C3OH group in micelles.

How does gut passage impact endozoochorous seed dispersal success? Evidence from a gut environment simulation experiment

Endozoochory of temperate grassland species is a widespread phenomenon and may accelerate and/or increase germination in some plant species. However, the mechanisms causing this altered germination success are only partly understood. In this study, germination of common grassland species was evaluated after simulated herbivore digestion in a standardized lab environment. Ruminants (cattle) and hindgut fermenters (horses) were used as model organisms in this simulation experiment. Three major digestive processes were studied through mechanical, thermal and chemical treatments of the seeds simulating mastication, body temperature and digestive fluids, respectively. Congeneric groups of annuals and perennials were tested with 15 species belonging to the plant families Cistaceae, Cyperaceae, Fabaceae, Poaceae and Urticaceae. No differences between the impact of the simulated herbivore gut environments of cattle and horses could be found, but major differences in germination behaviour were found among plant species. For most of the tested plant species, treatments had a decelerating and inhibiting effect on germination compared to the untreated seeds. However, species of the Cistaceae and Fabaceae benefitted from mechanical treatments. Species of the Cyperaceae and Poaceae were hardly impaired by any of the treatments and even germinated better after chemical treatments. Thermal treatments, simulating the body temperature, prohibited germination in most cases. The germination success of Urtica urens was significantly higher after all treatments, which suggests seeds are specifically well adapted to gut passage, and hence to endozoochorous dispersal.

Prediction of Mutagenicity of Chemicals from Their Calculated Molecular Descriptors: A Case Study with Structurally Homogeneous versus Diverse Datasets.

Variation in high-dimensional data is often caused by a few latent factors, and hence dimension reduction or variable selection techniques are often useful in gathering useful information from the data. In this paper we consider two such recent methods: Interrelated two-way clustering and envelope models. We couple these methods with traditional statistical procedures like ridge regression and linear discriminant analysis, and apply them on two data sets which have more predictors than samples (i.e. n << p scenario) and several types of molecular descriptors. One of these datasets consists of a congeneric group of Amines while the other has a much diverse collection compounds. The difference of prediction results between these two datasets for both the methods supports the hypothesis that for a congeneric set of compounds, descriptors of a certain type are enough to provide good QSAR models, but as the data set grows diverse including a variety of descriptors can improve model quality considerably.

Micellization parameters (number average, aggregation number and critical micellar concentration) of bile salt 3 and 7 ethylidene derivatives: Role of the steroidal skeleton II

BackgroundBile salts are steroidal biosurfactants. Micellar systems of bile salts are not only important for solubilization of cholesterol, but they also interact with certain drugs thus changing their bioavailability. MethodsThe number-average aggregation numbers (n¯) are determined using the Moroi–Matsuoka–Sugioka thermodynamic method. Critical micellar concentrations were determined by spectrofluorometric method using pyren and by surface tension measurements. ResultsMicelles of ethylidene derivatives possess the following values for n¯: 7-Eth-D (n¯=11 (50mM)–n¯=14.8 (100mM)); 12-Ox-7-Eth-L (n¯≈8.8, without concentration dependence) and 7,12-diOx-3-Eth-Ch (n¯≈2.9, without concentration dependence). In the planes n¯–ln k and ln CMC–ln k derivative 7-Eth-D is outlier in respect to hydrophobic linear congeneric groups. ConclusionGibbs energy of formation for 7-Eth-D anion micelles in addition to the Gibbs energy of hydrophobic interactions consists excess Gibbs energy (GE) from hydrogen bond formation between building blocks of micelles. Gibbs energy of formation for 7,12-diOx-3-Eth-Ch and 12-Ox-7-Eth-L anion micelle is determined by the Gibbs energy of hydrophobic interactions. Relative increase in hydrophobicity and aggregation number for ethylidene derivatives is larger when ethylidene group is introduced from the C7 lateral side of steroidal skeleton then it is when ethylidene group is on C3 carbon. General significancePosition of outlier towards hydrophobic congeneric groups from n¯–ln k and ln CMC–ln k planes indicates the existence of excess Gibbs energy (GE) which is not of hydrophobic nature (formation of hydrogen bonds). For the bile salt micelles to have GE (formation of secondary micelles) it is necessary that steroidal skeleton possesses C3-α-(e)-OH and C12-α-(a)-OH groups.

Stomatal sensitivity to vapour pressure deficit relates to climate of origin in Eucalyptus species.

Selecting plantation species to balance water use and production requires accurate models for predicting how species will tolerate and respond to environmental conditions. Although interspecific variation in water use occurs, species-specific parameters are rarely incorporated into physiologically based models because often the appropriate species parameters are lacking. To determine the physiological control over water use in Eucalyptus, five stands of Eucalyptus species growing in a common garden were measured for sap flux rates and their stomatal response to vapour pressure deficit (D) was assessed. Maximal canopy conductance and whole-canopy stomatal sensitivity to D and reduced water availability were lower in species originating from more arid climates of origin than those from humid climates. Species from humid climates showed a larger decline in maximal sap flux density (JSmax) with reduced water availability, and a lower D at which stomatal closure occurred than species from more arid climates, implying larger sensitivity to water availability and D in these species. We observed significant (P < 0.05) correlations of species climate of origin with mean vessel diameter (R(2) = 0.90), stomatal sensitivity to D (R(2) = 0.83) and the size of the decline in JSmax to restricted water availability (R(2) = 0.94). Thus aridity of climate of origin appears to have a selective role in constraining water-use response among the five Eucalyptus plantation species. These relationships emphasize that within this congeneric group of species, climate aridity constrains water use. These relationships have implications for species choices for tree plantation success against drought-induced losses and the ability to manage Eucalyptus plantations against projected changes in water availability and evaporation in the future.

Jejunogastroplasty as an alternative method of gastrointestinal tract reconstruction after gastrectomy

To prove the surgical safety and functional efficiency of jejunogastroplasty with duodenal passage preservation as an alternative method of gastrointestinal tract reconstruction after gastrectomy. It was analyzed the results of treatment of 60 patients who underwent gastrectomy for stomach cancer for the period from September 2009 to May 2013. Two congeneric groups by 30 patients who underwent Roux-en-Y reconstruction (control group) and jejunogastroplasty (comparison group) were prospectively compared. Immediate results did not significantly differ in the both groups. Blood loss was 528±61.0 and 507±71.2 ml, incidence of complications--20.0 and 6.7%, frequency of esophagostomy failure--3.3% and 0, postoperative mortality rate--3.3% and 0, duration of postoperative hospital-stay--12.4±1.3 and 10.9±1.2 days respectively (p<0.05). In remote postoperative period the number of patients with stable body mass index or its positive changes was 52.9 and 81.8% in control and main groups, with dumping syndrome--47.1 and 9.1%, with diarrhea--35.3 and 4.5% respectively (p<0.05). Index of good state of health in main group was 68.2%, in control group--17.6% (p<0.05). In authors' opinion safety and physiological efficiency of jejunogastroplasty allow you considering its priority for primary reconstruction after gastrectomy and alternativeness to Roux-en-Y technique.

Wittig reaction (with ethylidene triphenylphosphorane) of oxo-hydroxy derivatives of 5β-cholanic acid: Hydrophobicity, haemolytic potential and capacity of derived ethylidene derivatives for solubilisation of cholesterol

Bile acid salts are biosurfactants which form mixed micelles with phospholipids in vertebrates. These mixed micelles are suitable for solubilisation of cholesterol. For therapeutic purposes some bile acid salts as sodium ursocholate are used. However, bile acid anions possess low capacity for solubilisation of cholesterol. Thus, synthesis of more hydrophobic and less membranotoxic bile acid derivatives is of the great interest. In this paper Wittig reaction between ethylidene triphenylphosphorane and different bile acids oxo derivatives is examined. Wittig reaction of bile acids has not been studied much. C12 oxo group is inert in this reaction. If Wittig reaction happens on C7 oxo group stereospecifically E ethylidene stereoisomer is obtained, while the same reaction on C3 oxo group leads to more reactive not sterospecific product. In this paper stereochemical course of investigated Wittig reactions is thoroughly analysed. Hydrophobicity of derived products is determined over the temperature (T) dependence on retention coefficients (k) in reversed phase high resolution chromatography. Using method of principle components on k=f(T) matrix it is found that values of first principle components best describe hydrophobicity of analysed bile acids, while the second principal component is responsible for their hydrophilicity. By in silico molecular descriptors: valence connectivity index of order 3 (X3v) and packing density index (PDI), linear regression equations are obtained that can be used to predict hydrophobicity (over retention coefficient) of bile acids that belong to set of more congeneric groups. Membranotoxicity is determined by haemolytic potential. Monoethylidene derivatives of bile acids (in the form of anions) have lower membranotoxicity than deoxycholic acids anion. Sodium salt of deoxycholic acid 7-ethylidene derivative has 11% greater capacity for solubilisation of cholesterol monohydrate than sodium salt of deoxycholic acid.

Contrasting xylem vessel constraints on hydraulic conductivity between native and non-native woody understory species.

We examined the hydraulic properties of 82 native and non-native woody species common to forests of Eastern North America, including several congeneric groups, representing a range of anatomical wood types. We observed smaller conduit diameters with greater frequency in non-native species, corresponding to lower calculated potential vulnerability to cavitation index. Non-native species exhibited higher vessel-grouping in metaxylem compared with native species, however, solitary vessels were more prevalent in secondary xylem. Higher frequency of solitary vessels in secondary xylem was related to a lower potential vulnerability index. We found no relationship between anatomical characteristics of xylem, origin of species and hydraulic conductivity, indicating that non-native species did not exhibit advantageous hydraulic efficiency over native species. Our results confer anatomical advantages for non-native species under the potential for cavitation due to freezing, perhaps permitting extended growing seasons.

Determination and importance of temperature dependence of retention coefficient (RPHPLC) in QSAR model of nitrazepams’ partition coefficient in bile acid micelles

Linear dependence between temperature (t) and retention coefficient (k, reversed phase HPLC) of bile acids is obtained. Parameters (a, intercept and b, slope) of the linear function k=f(t) highly correlate with bile acids’ structures. Investigated bile acids form linear congeneric groups on a principal component (calculated from k=f(t)) score plot that are in accordance with conformations of the hydroxyl and oxo groups in a bile acid steroid skeleton.Partition coefficient (Kp) of nitrazepam in bile acids’ micelles is investigated. Nitrazepam molecules incorporated in micelles show modified bioavailability (depo effect, higher permeability, etc.). Using multiple linear regression method QSAR models of nitrazepams’ partition coefficient, Kp are derived on the temperatures of 25°C and 37°C. For deriving linear regression models on both temperatures experimentally obtained lipophilicity parameters are included (PC1 from data k=f(t)) and in silico descriptors of the shape of a molecule while on the higher temperature molecular polarisation is introduced. This indicates the fact that the incorporation mechanism of nitrazepam in BA micelles changes on the higher temperatures. QSAR models are derived using partial least squares method as well. Experimental parameters k=f(t) are shown to be significant predictive variables. Both QSAR models are validated using cross validation and internal validation method. PLS models have slightly higher predictive capability than MLR models.

Syntheses, structures and luminescence behaviors of mono- and dinuclear complexes of type [M(L)(NCS)2]n [M = Zn/Hg, n = 1; M = Cd, n = 2; L = (N,N-diethyl,N′-(pyridin-2-yl)benzylidene)ethane-1,2-diamine]: Variation of coordination matrices and nuclearities with the change of congeneric metal ions

One-pot reaction of zinc(II)/cadmium(II)/mercury(II) acetate, a tridentate Schiff base (L) and ammonium thiocyanate in a 1:1:2 molar ratio in MeOH solution at room temperature results in neutral mono-/dinuclear compound of the type [Zn(L)(NCS)2] (1)/[Cd(L)(NCS)(SCN)]2 (2)/[Hg(L)(SCN)2] (3) [L=(N,N-diethyl,N′-(pyridin-2-yl)benzylidene)ethane-1,2-diamine]. X-ray crystallographic study reveals an interesting variation in ligational motifs of thiocyanate from terminal N-coordination (in 1) to both terminal N-coordination and symmetrical double end-to-end bridging (in 2) and terminal S-coordination (in 3). In mononuclear 1/3, each metal(II) center adopts a distorted square pyramidal geometry with ZnN5 (for 1)/HgN3S2 (for 3) chromophore, whereas each cadmium(II) center in centrosymmetric dinuclear 2 has distorted octahedral environment with a CdN5S chromophore. Interesting variations in coordination matrices, nuclearities, and molecular and crystalline architectures are observed in these congeneric Group 12 metal ion complexes. Compounds 1–3 display high energy intraligand 1(π–π*) fluorescence in the solid state and in DMF solutions at room temperature.

QSPR study of the effect of steroidal hydroxy and oxo substituents on the critical micellar concentration of bile acids

Measurements of the fluorescence intensity of 1,6-diphenylhexatriene (DPH) as a probe molecule allowed the determination of critical micellar concentrations (CMCs) for 30 bile acid (BA) molecules belonging to three linear congeneric groups, with three (Group I) and two (Group II) oxygen atoms from OH or oxo groups bound to the steroid skeleton, and glyco conjugated cholic acid and glyco conjugated cholic acid derivatives (Group III). The CMC values are related to the structure of the steroid nucleus by constructing novel molecular descriptors with 2D and 3D characteristics of topological descriptors. Namely, with conventional topological descriptors (first-order connectivity index, third-order connectivity index, Wiener-index, Balaban-index, molecular topological index, cluster count, etc.) BA molecules from the same congeneric group have identical values, so that these descriptors cannot be used to form a new model for the given congeneric group. The linear regressions (models) obtained in this work for each congeneric group relate the CMCs to this new descriptor. Statistical parameters of these models, as well as their predictivity, indicate the significance of the obtained equations, that is that the micelle formation is influenced not only by the number of OH and oxo groups in the steroid nucleus but also by their steric environment.

Retention Mechanism of Selected Ionic Liquids On a Pentafluorophenylpropyl Polar Phase: Investigation using RP-HPLC

This study investigated the retention mechanism of a congeneric group of imidazolium ionic liquid cations with alkyl functional groups of different lengths, an aryl substituent, and one pyridinium cation on a pentafluorophenylpropyl silica-based stationary phase. The influence of organic modifier type and content in the mobile phase on the retention mode of alkylimidazolium ionic liquid cations shows a 'U-shaped' relationship. The use of this stationary phase gives excellent linearity and detection limits in the ppt range. The method is also readily applicable to the highly selective analysis of plant extracts previously spiked with ionic liquids.

Molecular and morphological supertree of stony corals (Anthozoa: Scleractinia) using matrix representation parsimony

The supertree algorithm matrix representation with parsimony was used to combine existing hypotheses of coral relationships and provide the most comprehensive species-level estimate of scleractinian phylogeny, comprised of 353 species (27% of extant species), 141 genera (63%) and 23 families (92%) from all seven suborders. The resulting supertree offers a guide for future studies in coral systematics by highlighting regions of concordance and conflict in existing source phylogenies. It should also prove useful in formal comparative studies of character evolution. Phylogenetic effort within Scleractinia has been taxonomically uneven, with a third of studies focussing on the Acroporidae or its most diverse genera. Sampling has also been geographically non-uniform, as tropical, reef-forming taxa have been considered twice as often as non-reef species. The supertree indicated that source trees concur on numerous aspects of coral relationships, such as the division between robust versus complex corals and the distant relationship between families in Archaeocoeniina. The supertree also supported the existence of a large, taxonomically diverse and monophyletic group of corals with many Atlantic representatives having exsert corallites. Another large, unanticipated clade consisted entirely of solitary deep-water species from three families. Important areas of ambiguity include the relationship of Astrocoeniidae to Pocilloporidae and the relative positions of several, mostly deep-water genera of Caryophylliidae. Conservative grafting of species at the base of congeneric groups with uncontroversial monophyletic status resulted in a more comprehensive, though less resolved tree of 1016 taxa.

Predictability of the mixture toxicity of 12 similarly acting congeneric inhibitors of photosystem II in marine periphyton and epipsammon communities

Testing of single chemicals with single species is common ecotoxicological practice in contrast to contaminated environments where highly diverse biological communities are exposed to highly diverse mixtures of chemical compounds. We, therefore, investigated whether mixture toxicity approaches that have been used successfully for single species, might also be applied on a community level of biological complexity. Twelve inhibitors of photosystem II, selected by QSAR and chemometrical approaches as the structurally most similar from a congeneric group of phenylurea herbicides, were tested singly and as mixtures on two types of marine microalgal communities, periphyton and epipsammon. Inhibition of photosynthesis was measured in short-term tests using incorporation of radiolabelled carbon ( 14 C ) to estimate photosynthetic rates. Two basic concepts, concentration addition (CA) and independent action (IA), were used to predict the toxicities of the mixtures. Congeneric and similar-acting substances such as the phenylureas are expected to comply with CA rather than IA. The aim of the present study was to evaluate whether these concepts can be used to predict mixture toxicity also to periphyton and epipsammon photosynthesis, i.e. at the level of natural communities. We found that deviations between observed and predicted mixture toxicity were relatively small but that CA predictions were the more accurate ones. The predictions proved to be robust, when based on single substance information even from different seasons, years, and sites. We conclude that the concept of CA for predicting mixture toxicity applies also at the community level of algal testing; at least when a physiological short-term effect indicator is used that matches the mechanism of action of the substances.

Predictability of the mixture toxicity of 12 similarly acting congeneric inhibitors of photosystem II in marine periphyton and epipsammon communities

Testing of single chemicals with single species is common ecotoxicological practice in contrast to contaminated environments where highly diverse biological communities are exposed to highly diverse mixtures of chemical compounds. We, therefore, investigated whether mixture toxicity approaches that have been used successfully for single species, might also be applied on a community level of biological complexity. Twelve inhibitors of photosystem II, selected by QSAR and chemometrical approaches as the structurally most similar from a congeneric group of phenylurea herbicides, were tested singly and as mixtures on two types of marine microalgal communities, periphyton and epipsammon. Inhibition of photosynthesis was measured in short-term tests using incorporation of radiolabelled carbon ( 14 C ) to estimate photosynthetic rates. Two basic concepts, concentration addition (CA) and independent action (IA), were used to predict the toxicities of the mixtures. Congeneric and similar-acting substances such as the phenylureas are expected to comply with CA rather than IA. The aim of the present study was to evaluate whether these concepts can be used to predict mixture toxicity also to periphyton and epipsammon photosynthesis, i.e. at the level of natural communities. We found that deviations between observed and predicted mixture toxicity were relatively small but that CA predictions were the more accurate ones. The predictions proved to be robust, when based on single substance information even from different seasons, years, and sites. We conclude that the concept of CA for predicting mixture toxicity applies also at the community level of algal testing; at least when a physiological short-term effect indicator is used that matches the mechanism of action of the substances.

Safety evaluation of natural flavour complexes

Natural flavour complexes (NFCs) are chemical mixtures obtained by applying physical separation methods to botanical sources. Many NFCs are derived from foods. In the present paper, a 12-step procedure for the safety evaluation of NFCs, ‘the naturals paradigm’, is discussed. This procedure, which is not intended to be viewed as a rigid check list, begins with a description of the chemical composition of the commercial product, followed by a review of the data on the history of dietary use. Next, each constituent of an NFC is assigned to one of 33 congeneric groups of structurally related substances and to one of three classes of toxic potential, each with its own exposure threshold of toxicological concern. The group of substances of unknown structure is placed in the class of greatest toxic potential. In subsequent steps, for each congeneric group the procedure determines the per capita intake, considers metabolic pathways and explores the need and availability of toxicological data. Additional toxicological and analytical data may be required for a comprehensive safety evaluation. The procedure concludes with an evaluation of the NFC in its entirety, also considering combined exposure to congeneric groups. The first experiences with the use of this procedure are very promising. Future safety evaluations of larger numbers of NFCs will indicate the usefulness of the system, either in its present form or in a form modified on the basis of experience.