Number Of Congeners Research Articles

Pentachlorophenol and hydroxylated polychlorinated biphenyl metabolites in umbilical cord plasma of neonates from coastal populations in Québec.

Concentrations of polychlorinated biphenyls (PCBs), hydroxylated metabolites of PCBs (HO-PCBs) and octachlorostyrene (4-HO-HpCS), and pentachlorophenol (PCP) were determined in umbilical cord plasma samples from three different regions of Québec. The regions studied included two coastal areas where exposure to PCBs is high because of marine-food-based diets--Nunavik (Inuit people) and the Lower North Shore of the Gulf of St. Lawrence (subsistence fishermen)--and a southern Québec urban center where PCB exposure is at background levels (Québec City). The main chlorinated phenolic compound in all regions was PCP. Concentrations of PCP were not significantly different among regions (geometric mean concentration 1,670 pg/g, range 628-7,680 pg/g wet weight in plasma). The ratio of PCP to polychlorinated biphenyl congener number 153 (CB153) concentration ranged from 0.72 to 42.3. Sum HO-PCB (sigma HO-PCBs) concentrations were different among regions, with geometric mean concentrations of 553 (range 238-1,750), 286 (103-788), and 234 (147-464) pg/g wet weight plasma for the Lower North Shore, Nunavik, and the southern Québec groups, respectively. Lower North Shore samples also had the highest geometric mean concentration of sum PCBs (sum of 49 congeners; sigma PCBs), 2,710 (525-7,720) pg/g wet weight plasma. sigma PCB concentrations for Nunavik samples and southern samples were 1,510 (309-6,230) and 843 (290-1,650) pg/g wet weight plasma. Concentrations (log transformed) of sigma HO-PCBs and sigma PCBs were significantly correlated (r = 0.62, p < 0.001), as were concentrations of all major individual HO-PCB congeners and individual PCB congeners. In Nunavik and Lower North Shore samples, free thyroxine (T4) concentrations (log transformed) were negatively correlated with the sum of quantitated chlorinated phenolic compounds (sum PCP and sigma HO-PCBs; r = -0.47, p = 0.01, n = 20) and were not correlated with any PCB congeners or sigma PCBs. This suggests that PCP and HO-PCBs are possibly altering thyroid hormone status in newborns, which could lead to neurodevelopmental effects in infants. Further studies are needed to examine the effects of chlorinated phenolic compounds on thyroid hormone status in newborns.

Synthesis of polybrominated diphenyl ethers and their capacity to induce CYP1A by the Ah receptor mediated pathway.

Polybrominated diphenyl ethers (PBDEs) have become widely distributed as environmental contaminants due to their use as flame retardants. Their structural similarity to other halogenated aromatic pollutants has led to speculation that they might share toxicological properties such as hepatic enzyme induction. In this work we synthesized a number of PBDE congeners, studied their affinity for rat hepatic Ah receptor through competitive binding assays, and determined their ability to induce hepatic cytochrome P-450 enzymes by means of EROD (ethoxyresorufin-O-deethylase) assays in human, rat, chick, and rainbow trout cells. Both pure PBDE congeners and commercial PBDE mixtures had Ah receptor binding affinities 10(-2)-10(-5) times that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. In contrast with polychlorinated biphenyls, Ah receptor binding affinities of PBDEs could not be related to the planarity of the molecule, possibly because the large size of the bromine atoms expands the Ah receptor's binding site. EROD activities of the PBDE congeners followed a similar rank order in all cells. Some congeners, notably PBDE 85, did not follow the usual trend in which strength of Ah receptor binding affinity paralleled P-450 induction potency. Use of the gel retardation assay with a synthetic oligonucleotide indicated that in these cases the liganded Ah receptor failed to bind to the DNA recognition sequence.

Methylene retention indexes for isolated toxaphene congeners.

Toxaphene was a heavily used, broad-spectrum insecticide, which was banned in most countries in the 1980s. Early data suggested that a limited number of congeners in the technical mixture were responsible for its toxicity to insects. However, toxaphene research has historically focused on analyzing total toxaphene, largely due to insufficient analytical methodology to measure the individual congeners. In recent years, congener-specific toxaphene research has flourished due to analytical advances leading to the identification of several congeners, about 25 of which are commercially available. However, the high price of these standards may inhibit toxaphene research in some laboratories. We report here the methylene retention indexes for 28 isolated toxaphene congeners. When used in conjunction with mass spectrometry, methylene retention indexes provide an alternative method for identifying these compounds when direct comparison with standard compounds is not practical.

CHIRAL METAL COMPLEXES. PART 52. THE STRUCTURES OF CO-CRYSTALLISED DIASTEREOISOMERIC DNA PROBES SHOWING INTRAMOLECULAR π-π INTERACTIONS

The structure of Δ-α1,2-[Co(R-picpnMe2)(S-phe)](ClO4)2-H2O where R-picpnMe2 is N',N'-dimethyl-3R-methyl-l,6-di(2-pyridyl)-2,5-diazahexane and 5-phe is the S-phenylalaninate anion has been determined to be orthorhombic, space group P212121 , with a = 9.959(4), b = 15.919(7), c= 19.59(3) Å, Dc = 1.515Mgm−3 and Z = 4. The structure was refined by least-squares methods to R = 0.050 for 2328 independent reflections with l > 2[sgrave](I) for diffractometer data collected at 293 K. The cobalt atom has the expected octahedral coordination with the N4 tetradentate adopting Δ-α topology and with the phenylalaninate ligand completing the coordi—nation sphere. Two geometric isomers possible for the asymmetric complex, α1 and α2 (depend—ing upon the relative mode of coordination of the aminoacidate relative to the trans orientation of the methyl group of the tetradentate), are observed to co-crystallise in a 1:1 ratio. In these species, the phenyl ring is weakly bonded to one of the pyridyl rings of the tetradentate, as has been found in a number of congeners. The R-phe analogue has also been synthesised. The per-chlorate salt contains both possible isomers. NMR studies indicate that the π-π interaction observed in the solid state for Δ-α1,2-[Co(R-picpnMe2)(S-phe)]2+ is preserved in solution.

Synthesis and structure?Activity studies of some antitumor congeners ofL-canaline

A number of congeners of the antitumor compound L-canaline, [l-2-amino-4-(aminooxy)butyric acid], a structural analog of L-ornithine, have been synthesized and their growth-inhibitory effects evaluated in cultured MIA-PaCa-2 cells, a human pancreatic adenosarcoma, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results indicate that L-canaline congeners in which the carbon chain length has been increased by one methylene unit exhibit a significant loss in cytotoxicity relative to the parent compound. Congeners in which the carbon chain length is decreased by one methylene unit retain the cytotoxicity of the parent compound against cultured MIA-PaCa-2 cells. Loss of the aminooxy or α-amino group of L-canaline severely curtails cell growth-inhibitory activity. With the exception of the n-octyl ester, esterification of L-canaline with simple alcohols has little effect on overall growth-inhibiting activity. It is noteworthy that the unnatural D-enantiomer of canaline is as deleterious to MIA-PaCa-2 cell growth as the naturally occurring L-enantiomer. Drug Dev. Res. 47:170–177, 1999. © 1999 Wiley-Liss, Inc.

Cytochrome P450-mediated enzyme activities and polychlorinated biphenyl accumulation in harp seal ( Phoca groenlandica)

The presence and activities of hepatic cytochrome P450 (CYP) isoforms in Barents Sea harp seals ( n=13) were studied using catalytic activities, selective inhibitors, and western blots. In addition the polychlorinated biphenyl (PCB) burden was measured in both the blubber and the food of the seals. The CYP activities and CYP isoforms present were related to the blubber PCB load and the relative presence of each PCB congener in seals relative to their food (metabolic index). The CYP activities measured were 2–7 times higher than in ringed and harp seals from other studies, suggesting induction due to contaminant exposure. However, PCB burdens were surprisingly low and were not related to the CYP activities. Probably these high activities were due to exposure to other contaminants or due to the diet consisting mainly of crustaceans, which are rich in carotenes. Carotenes have been shown to be potent CYP inducers in several laboratory animals. The CYP studies indicated the presence of CYP1A, -2B and -3A isoforms. A decrease in the relative presence of a number of PCB congeners in seal blubber relative to their food, supposed to be due to CYP-mediated metabolism, corresponded with the metabolic capabilities of the CYP isoforms found.

An evaluation of proposed frameworks for grouping polychlorinated biphenyl (PCB) congener data into meaningful analytic units.

Polychlorinated biphenyls (PCBs) have been associated with a variety of health outcomes. Enhanced laboratory techniques can provide a relatively large number of individual PCB congeners for investigation. However, to date there are no established frameworks for grouping a large number of PCB congeners into meaningful analytic units. In a case-control study of serum PCB levels on breast cancer risk, measured levels of 56 PCB congener peaks were available for analysis. We considered several approaches for grouping these compounds based on 1) chlorination, 2) factor analysis, 3) enzyme induction, 4) enzyme induction and occurrence, and 5) enzyme induction, occurrence, and other toxicological aspects. The utility of a framework was based on the mechanism of biologic actions within each framework, lack of collinearity among congener groups, and frequency of detection of PCB congener groups in measured serum levels of 192 healthy postmenopausal women. Most participants had detectable levels for the proposed PCB congeners groups, using degree of chlorination as a grouping framework. In addition, the previously proposed grouping approach based on enzyme induction, occurrence, and other toxicological aspects was an applicable alternative to the crude approach of grouping by degree of chlorination. Grouping these congeners with respect to P450 enzyme induction activity, and the previously proposed framework based on enzyme induction and occurrence, did not fit these data as well, because only a small proportion of participants had detectable levels for the congener groups with the greatest toxicological potential. Statistical grouping did not result in an interpretable and meaningful clustering of these exposures. In these data, grouping with respect to degree of chlorination and the previously proposed framework based on enzyme induction, occurrence, and other toxicological aspects were the most useful approaches to reducing a large number of PCB congeners into meaningful analytic units. Factors affecting the utility of the proposed grouping frameworks are discussed.

On the design and selection of polychlorinated biphenyls for use in biological test systems

The polychlorinated biphenyls (PCBs) consist of a large number of individual congeners with varying degree of chlorination and possible substitution patterns. No single congener can be used as a representative congener for the whole class of compounds. Multivariate chemical characterisation (principal component analysis) in combination with factorial design provide tools by which small sets of structurally representative congeners can be determined. These tools are suggested to be used in the design of biological experiments in order to introduce systematic structural variation in the congeners to be tested and to make it possible to construct quantitative structure-activity relationships (QSARs). A QSAR based on bioaccumulation factors (BAFs) in fish for 20 systematically selected PCBs made it possible to predict BAFs for all 134 non-tested tetra-through hepta-chlorinated congeners. The use of these systematic and balanced sets of congeners in the experimental protocol will provide increased knowledge of the environmental behaviour of the PCBs.

Morphometry of Liver Lesions in an Ultrastructural Pathology Study

Some pathologic alterations in animal tissue sections, because of low resolution, are not identified using light microscopy. Availability of higher resolution in electron microscopy (EM) confers a decisive role on EM for diagnostic pathology that is well accepted. Much has already been contributed by EM in understanding of liver diseases. However, EM has been further refined by adding a quantitative facet to the results. Morphometric technique allows transfer of facts acquired from 2-dimensional samples, e.g., electron micrographs, to a 3-dimensional perspective. In addition, the technique is valuable in determining the significance of the alterations especially in instances where the changes numerically are either scanty or indistinguishable from a normal appearance of the cells or tissues (Fig. 1).In our work on the effects of several different PCB congeners, one of the compounds, namely, congener number 153 was studied to obtain morphometric data on the lesions in the liver of rats given the congener in the diets for 13 weeks.

Polycyclic compounds beyond the propellanes and fenestranes: [m.n.o.p.q]centropenta- and [m.n.o.p.q.r]centrohexacyclanes

Several new homo- and heterocyclic topologically nonplanar organic compounds ( 11, 14, 17–20) with centrohexacyclic ( K 5 type) molecular frameworks are described. Besides some centrohexaquinanes comprising five-membered rings exclusively (‘[5.5.5.5.5.5]centrohexacyclanes’), a number of congeners containing two six or two seven-membered rings have been synthesized for the first time (‘[6.5.6.5.5.5]- and [7.5.7.5.5.5]centrohexacyclanes’). Based on [m.n.o.p]fenestranes, a notation is proposed to define unequivocally the mutual orientation of the various rings.

Mapping Drug Interactions at the Covalent Topoisomerase II-DNA Complex by Bisantrene/Amsacrine Congeners

To identify structural determinants for the sequence-specific recognition of covalent topoisomerase II-DNA complexes by anti-cancer drugs, we investigated a number of bisantrene congeners, including a 10-azabioisoster, bearing one or two 4, 5-dihydro-1H-imidazol-2-yl hydrazone side chains at positions 1, 4, or 9 of the anthracene ring system. The studied bisantrene/amsacrine (m-AMSA) hybrid and bisantrene isomers were able to poison DNA topoisomerase II with an intermediate activity between those of bisantrene and m-AMSA. Moving the side chain from the central to a lateral ring (from C-9 to C-1/C-4) only slightly modified the drug DNA affinity, whereas it dramatically affected local base preferences of poison-stimulated DNA cleavage. In contrast, switching the planar aromatic systems of bisantrene and m-AMSA did not substantially alter the sequence specificity of drug action. A computer-assisted steric and electrostatic alignment analysis of the test compounds was in agreement with the experimental data, since a common pharmacophore was shared by bisantrene, m-AMSA, and 9-substituted analogs, whereas the 1-substituted isomer showed a radically changed pharmacophoric structure. Thus, the relative space occupancy and electron distribution of putative DNA binding (aromatic rings) and enzyme binding (side chains) moieties are fundamental in directing the specific action of topoisomerase II poisons and in determining the poison pharmacophore.

Toxaphene congeners differ from toxaphene mixtures in their dysmorphogenic effects on cultured rat embryos

The presence of persistent organic pollutants, including the pesticide toxaphene has been reported even in remote regions such as the Arctic and is becoming a health concern. The technical mixture of toxaphene contains over 800 different congeners. The numbers of prevalent congeners, however, decrease along the food chain. About 20 major congeners are found in fish, eight in marine mammals and only two major ones in human, 2- exo,3- endo,5- exo,6- endo,8,8,10,10-octachlorobornane (T 2) and 2- exo,3- endo,5- exo,6- endo,8,8,9,10,10-nonachlorobornane (T 12). Embryotoxicity of these individual congeners is not known, as previous studies focused on the toxaphene technical mixture. We studied the relative dysmorphogenic activity of toxaphene technical mixture and individual congeners (T 2 and T 12) using rat embryo culture. Explanted embryos (0–2 somites) were treated for 48 h with concentrations of 0 (DMSO 0.01%), 100, 1000 and 5000 ng/ml of either (a) toxaphene technical mixture; (b) T 2; (c) T 12; or (d) a 50:50 mixture of T 2 and T 12. The treatment period corresponds to gestational days (GD) 10–12, a period within the critical time of morphogenesis and organogenesis. Both the technical mixture and the two individual congeners had a significant adverse effects on the total morphological score, somite number, head and crown rump length and the central nervous system scores of embryos. All treatments caused a high incidence of central nervous system defects. The T 2 and T 12 congeners differed in their spectrum of abnormalities as exposure to T 2 caused limb and flexion defects which were not observed with the T 12 congener. Differences were also observed in the type of toxicity and the target sites between the technical mixture and the congeners. T 2 showed a more potent adverse effect on the morphological score as compared to the technical mixture. Both T 2 and T 12 were less inhibitory on growth than the technical mixture as indicated by crown-rump length but they showed a stronger inhibitory effect on otic system development. The mixture of T 2+T 12 showed a synergistic effect on decreasing crown-rump and head length. Conversely, the combination of T 2 and T 12 inhibited the strong adverse effect of the individual congeners on otic development. The results suggest environmentally predominant toxaphene congeners can have organ specific embryotoxic effects not predicted by the toxaphene technical mixture.

GC/MS procedures for the determination of PCBs in environmental matrices

This paper describes GC/MS methods for the determination of PCBs in air, fish, sediment, soil, vegetation and water, all validated by analysis of appropriate standard reference materials. An important feature is the fact that up to 92 PCB congeners containing between three and seven chlorines are determined. The use of such a large number of individual congeners results in ΣPCB values that exceed those obtained using the smaller number of individual congeners routinely reported in some laboratories. Such underestimation of ΣPCB has important implications for the studies of the environmental fate of these compounds and may have led to an underestimation of their environmental persistence as an overall class.

Organochlorine contaminants in the Northern shrimp, Pandalus borealis, collected from the Northwest Atlantic

Northern shrimp, Pandalus borealis, were sampled at two commercially important locations in the Northwest Atlantic and soft tissues analysed for a variety of organo-chlorine pollutants. Sampling facilitated examination of the environmental and experimental variability to determine if and how location, season, sex or size affects results. Organochlorine compounds including polychlorinated biphenyls, polychlorinated dibenzo- p-dioxins and dibenbenzofurans were non-detectable in muscle tissue (DLs = 0.01 − 0.5 ng/g and 0.1 − 0.5 pg/g, for the two groups, wet weight). Concentrations were highest in hepatopancreas, the tissue with a higher lipid content (mean = 28% vs 0.27% in muscle. The larger variation in the tissue distribution of contaminants was observed in April versus November females. Higher concentrations were observed in November eggs and in hepatopancreas of females sampled in April. The present study indicates the presence of a larger number of PCB and PCDF congeners in the hepatopancreas of shrimp, a lower link in the Northwest Atlantic food chain, as compared to livers of previously studied finfish species.

Polychlorinated biphenyls in Barents and Greenland Seas fish.

PCBs are widespread, persistent organochlorines which have the potential for harmful biological effects. The number of possible congeners is 209, but few only are both prevalent and toxic. Commercially-produced PCBs (e.g. Aroclors) consist of mixtures containing between 50 and 90 congeners. According to the classification of PCBs based on potential toxicity, environmental prevalence and relative abundance in animal tissues, the number of environmental ly threatening PCB congeners reduces to about 36, of which 25 account for 50 to 75% of the total PCBs in biological compartments (McFarland and Clarke 1989). Their dispersion and accumulation through the ecosystem is reflected by their presence in air, snow, ice, fish, birds and mammals in the polar regions, in the surface and sub-surface water of oceans, in the atmosphere, and in a wide range of plankton, fish, and marine and terrestrial mammals including humans (Safe 1984; Waid 1987). It has been estimated that about 3 1% of the 1.2 million tons of PCBs that have been produced are still present in the environment (Borlakoglu and Haegele 1991). Seven major fish species collected in the Barents and Greenland seas have been studied in an attempt to answer the question raised by Ottar (1981): “is the Arctic marine environment, as a result of its cold climate, a sink for semi-volatile organics, such as PCBs, PCDD/PCDFs, organochlorine pesticides, polyaromatic hydrocarbons (PAHs) and metals, such as mercury, emitted in the mid-latitudes?“. This work is part of a broader ecotoxicological study on stable residues in European Arctic seas (Joiris et al. 1995a, b; 1997).

Synthesis and structure-activity studies of some antitumor congeners of L-canavanine

A number of congeners of the antitumor compound L-canaline, [l-2-amino-4-(aminooxy)butyric acid], a structural analog of L-ornithine, have been synthesized and their growth-inhibitory effects evaluated in cultured MIA-PaCa-2 cells, a human pancreatic adenosarcoma, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results indicate that L-canaline congeners in which the carbon chain length has been increased by one methylene unit exhibit a significant loss in cytotoxicity relative to the parent compound. Congeners in which the carbon chain length is decreased by one methylene unit retain the cytotoxicity of the parent compound against cultured MIA-PaCa-2 cells. Loss of the aminooxy or α-amino group of L-canaline severely curtails cell growth-inhibitory activity. With the exception of the n-octyl ester, esterification of L-canaline with simple alcohols has little effect on overall growth-inhibiting activity. It is noteworthy that the unnatural D-enantiomer of canaline is as deleterious to MIA-PaCa-2 cell growth as the naturally occurring L-enantiomer. Drug Dev. Res. 47:170–177, 1999. © 1999 Wiley-Liss, Inc.

Characterization of three Aroclor mixtures using a new cyanobiphenyl stationary phase

The retention characteristics of all 209 polychlorinated biphenyl (PCB) congeners were determined on a new p,p-cyanobiphenyl stationary phase using gas chromatography with electron capture detection (GC-ECD). Response factors were determined relative to decachlorobiphenyl, PCB 209. Several congeners that coelute on the phases routinely used for PCB analysis are separated on this phase, including the hexachlorobiphenyls 138, 163, and 164. The p,p-cyanobiphenyl stationary phase exhibits altered retention for planar congeners, such that the toxic coplanar PCBs 77, 126, and 169 are eluted free from interference. Of the 209 congeners, 61 were separated using the p,p-cyanobiphenyl phase in conjunction with GC-ECD. When analyzed by gas chromatography with mass selective detection (GC-MSD), the number of congeners determined increased to 133. Therefore GC-MSD was used with the p,p-cyanobiphenyl phase to characterize three PCB mixtures: Aroclor 1242, Aroclor 1254, and Aroclor 1260.

Patterns of species diversity on an oceanic versus a continental island mountain: a hypothesis on species diversification1

Abstract. The vegetation on a wet mountain slope on Haleakala (an oceanic island) is compared with that on Kinabalu (a continental island) to examine relationships between regional floristic richness and α‐ and β‐diversities. The two mountains are similar in their constant tropical climate, generic and family‐level floristic elements and geological age of the summit regions, but different in regional floristic richness (rich on Kinabalu vs. poor on Haleakala). α‐diversity of canopy and subcanopy tree species was much higher on Kinabalu than in comparable zones on Haleakala. Average turnover rate of species (as logarithmic community similarity) on the slope was one order of magnitude greater on Kinabalu than on Haleakala (0.127 vs. 0.017 per 100 m alt.). While there were genera with wide altitudinal ranges on both mountains, a large proportion of the genera was differentiated into parapatric altitudinal congeners on Kinabalu. By contrast, most genera are altitudinally monotypic on Haleakala. The number of sympatric congeners per genus, and the frequency of multi‐specific genera per plot were high on lower slopes but decreased with increasing altitude on Kinabalu, whereas the values were low across all altitudes on Haleakala. These patterns suggest that sympatric and parapatric species radiation was less on Haleakala than on Kinabalu. This may be related to Haleakala's initially poor and disharmonic flora.

The phase distribution of polychlorobiphenyl congeners in surfactant-amended sediment slurries

The surfactant-aided recoveries of polychlorobiphenyls (PCBs) from a sample of Ashtabula River (Ohio) sediment were compared to calculated recoveries based on an equilibrium phase distribution model. The equilibrium model contains as parameters: (i) the surfactant concentration in the micelles, [ S] mic, (ii) the mass of organic carbon in the sediment (or soil) per aqueous volume, oc, (iii) a constant characterizing solute affinity for the micelle ( β = K m K ow ), and (iv) a constant characterizing solute affinity for the sediment carbon ( α = K oc K ow ). The recovery of specific PCB congeners from the sediment by surfactant micelles at equilibrium were invariant with congener number as predicted by the model. This invariant behavior results from the fact that the PCBs are partitioned between two lipophilic phases (soil organic carbon and micelles) through hydrophobic interactions. Surfactants chosen as solubilizing agent were Brij 30, polyoxyethylene-10-lauryl ether, Brij 35, Triton X-705, Tween 20, Tween 80, Tween 85, Exxal F5715, Pluronic P-65, and sodium dodecylsulfate.

A systematic nomenclature system for toxaphene congeners part 1: Chlorinated bornanes

A systematic code for a comprehensive numbering of toxaphene congeners on the basis of IUPAC rules has been developed. All chlorinated bornanes were characterized with a descriptor consisting of up to six letters and numbers. Each descriptor presents both enantiomers in the case of chiral compounds. Furthermore, chlorinated bornane congeners with a known structure are presented with both IUPAC nomenclature and the new systematic code. A computer program listing all the congener numbers is available from the authors.