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Hydroxylated and methylsulfone-containing metabolites of polychlorinated biphenyls in the plasma and blubber of bowhead whales (Balaena mysticetus).

Bowhead whale (Balaena mysticetus) blubber (n = 20) and plasma (n = 19) samples were collected during the 1997 to 2000 Inuit subsistence harvests in Barrow, Alaska, USA, to quantify the concentrations of methylsulfone (MeSO2)-containing and hydroxylated (OH) polychlorinated biphenyl (PCB) metabolites in this cetacean. The distribution of MeSO2-PCBs in blubber was dominated by 4-MeSO2-substituted congeners, the most abundant being 4-MeSO2-CB-70, 3'-MeSO2-CB-132, and 4-MeSO2-CB-64. Mean (+/- 1 standard error) sum (sigma) MeSO2-PCBs concentrations in blubber were low (6.23 +/- 0.81 ng g(-1) lipid normalized) compared to concentrations previously reported in other marine mammals. However, similar ratios of MeSO2-PCB metabolites to parent PCB congeners among marine mammals suggest that cytochrome P450 2B-like biotransformation and other necessary enzyme-mediated processes and mechanisms that influence the formation and clearance of MeSO2-PCBs exist in the bowhead whale. Pentachlorophenol was the most abundant halogenated phenolic compound quantified in bowhead plasma (1.55 +/- 0.19 ng g(-1) wet wt). Despite indirect evidence for arene epoxidation of the biphenyl moiety inferred from MeSO2-PCB formation, sumOH-PCB concentrations in bowhead plasma were low (1.52 +/- 0.31 ng g(-1) wet wt) compared to humans and marine mammals and were comprised of only two detectable OH-PCB congeners (4'-OH-CB-130 and 4-OH-CB-187). Further research is required to elucidate the toxicokinetics and distribution of OH-PCBs in this cetacean.

Adipose Tissue↗

Effects of exposure duration and recovery time during pulsed exposures.

In pulsed toxicant exposures, the concentration, duration, and frequency of pulses can change through time. However, the conventional median lethal concentration (LC50) method cannot adequately predict the effects of pulsed exposure, because it is associated with fixed exposure duration and constant concentration and does not include postexposure (latent) mortality. Many studies that tried to address the effects of pulsed exposure only provided qualitative or semiquantitative predictions. Survival time experiments conducted here quantified the effect of exposure duration on latent mortality, and the effect of recovery time between two pulses on mortality during a second pulse also was examined. This was done by exposing amphipods (Hyalella azteca) to two contrasting toxicants, copper sulfate (CuSO4) and sodium pentachlorophenol (NaPCP). In the exposure duration experiments, the amphipods were exposed to two toxicant concentrations for three durations. No significant effect of duration on latent mortality was detected within the experimental range; however, duration still may need to be considered under other conditions. In the recovery time experiments, the amphipods were provided four recovery times, and their survivals during the second exposure were modeled. Recovery time had a significant effect on the second-exposure mortality. Given enough time, the amphipods could recover to a state similar to their original toxicant resistance state. The complete recovery time for CuSO4 was fivefold longer than that for NaPCP. It is important to quantify the effects of latent mortality, pulse duration and concentration, and recovery time for pulsed exposures. Survival analysis provides a better way to address these issues than does the conventional LC50 method.

Amphipoda↗

Effects of pesticides on soil invertebrates in laboratory studies: a review and analysis using species sensitivity distributions.

Species sensitivity distributions (SSD) and 5% hazardous concentrations (HC5) are distribution-based approaches for assessing environmental risks of pollutants. These methods have potential for application in pesticide risk assessments, but their applicability for assessing pesticide risks to soil invertebrate communities has not been evaluated. Using data obtained in a systematic review, the present study investigates the relevance of SSD and HC5 for predicting pesticide risks to soil invertebrates. Altogether, 1950 laboratory toxicity data were obtained, representing 250 pesticides and 67 invertebrate taxa. The majority (96%) of pesticides have toxicity data for fewer than five species. Based on a minimum of five species, the best available endpoint data (acute mortality median lethal concentration) enabled SSD and HC5 to be calculated for 11 pesticides (atrazine, carbendazim, chlorpyrifos, copper compounds, diazinon, dimethoate, gamma-hexachlorocyclohexane, lambda-cyhalothrin, parathion, pentachlorophenol, and propoxur). Arthropods and oligochaetes exhibit pronounced differences in their sensitivity to most of these pesticides. The standard test earthworm species, Eisenia fetida sensu lato, is the species that is least sensitive to insecticides based on acute mortality, whereas the standard Collembola test species, Folsomia candida, is among the most sensitive species for a broad range of toxic modes of action (biocide, fungicide, herbicide, and insecticide). These findings suggest that soil arthropods should be tested routinely in regulatory risk assessments. In addition, the data indicate that the uncertainty factor for earthworm acute mortality tests (i.e., 10) does not fully cover the range of earthworm species sensitivities and that acute mortality tests would not provide the most sensitive risk estimate for earthworms in the majority (95%) of cases.

Animals↗

Effects of pesticides on soil invertebrates in model ecosystem and field studies: a review and comparison with laboratory toxicity data.

A systematic review was carried out to investigate the extent to which higher-tier (terrestrial model ecosystem [TME] and field) data regarding pesticide effects can be compared with laboratory toxicity data for soil invertebrates. Data in the public domain yielded 970 toxicity endpoint data sets, representing 71 pesticides and 42 soil invertebrate species or groups. For most pesticides, the most frequent effect class was for no observed effects, although relatively high numbers of pronounced and persistent effects occurred when Lumbricidae and Enchytraeidae were exposed to fungicides and when Lumbricidae, Collembola, and Arachnida were exposed to insecticides. No effects of fungicides on Arachnida, Formicidae, or Nematoda or of herbicides on Lumbricidae, Formicidae, or Nematoda were observed in any studies. For most pesticides, higher-tier no-observed-effect concentration or lowest-observed-effect concentration values cannot be determined because of a lack of information at low pesticide concentrations. Ten pesticides had sufficient laboratory data to enable the observed higher-tier effects to be compared with 5% hazardous concentrations (HC5) estimated from acute toxicity laboratory data (atrazine, carbendazim, chlorpyrifos, diazinon, dimethoate, gamma-hexachlorocy-clohexane, lambda-cyhalothrin, parathion, pentachlorophenol, and propoxur). In eight cases, higher-tier effects concentrations were within or below the 90% confidence interval of the HC5. Good agreement exists between the results of TME and field tests for carbendazim, but insufficient information is available for a comparison between TME and field studies for other pesticides. Availability and characteristics (e.g., taxonomic composition and heterogeneity) of the higher-tier effects data are discussed in terms of possible developments in risk assessment procedures.

Animals↗

Contaminant sensitivity of threatened and endangered fishes compared to standard surrogate species.

Standard environmental assessment procedures are designed to protect terrestrial and aquatic species. However, it is not known if endangered species are adequately protected by these procedures. At present, toxicological data obtained from studies with surrogate test fishes are assumed to be applicable to endangered fish species, but this assumption has not been validated. Static acute toxicity tests were used to compare the sensitivity of rainbow trout, fathead minnows, and sheepshead minnows to several federally listed fishes (Apache trout, Lahontan cutthroat trout, greenback cutthroat trout, bonytail chub, Colorado pikeminnow, razorback sucker, Leon Springs pupfish, and desert pupfish). Chemicals tested included carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin. Results indicated that the surrogates and listed species were of similar sensitivity. In two cases, a listed species had a 96-h LC50 (lethal concentration to 50% of the population) that was less than one half of its corresponding surrogate. In all other cases, differences between listed and surrogate species were less than twofold. A safety factor of two would provide a conservative estimate for listed cold-water, warm-water, and euryhaline fish species.

Animals↗

A field validation of two sediment-amphipod toxicity tests.

A field validation study of two sediment-amphipod toxicity tests was conducted using sediment samples collected subtidally in the vicinity of a polycyclic aromatic hydrocarbon (PAH)-contaminated Superfund site in Elliott Bay (WA, USA). Sediment samples were collected at 30 stations with a 0.1 m2 grab from which subsamples were taken for sediment toxicity testing and geochemical and macrofaunal analyses. Standard 10-d sediment-amphipod toxicity tests were conducted with Rhepoxynius abronius and Leptocheiros plumulosus. Sediments were analyzed for 33 PAHs, pentachlorophenol, polychlorinated biphenyls, acid-volatile sulfide, simultaneously extracted metals (Cd, Cu, Zn, Pb, Ni), total organic carbon, and grain size. Sediment temperature, oxygen-reduction potential, water depth, and interstitial water salinity were also measured. Polycyclic aromatic hydrocarbons, quantified as total PAH toxic units (TU(PAH)), were confirmed to be an important common causal agent of the changes in the two toxicity test (% survival R. abronius, % survival L. plumulosus) and five macrofaunal community (number of species, S; numerical abundance, A: total biomass, B: Swartz's dominance index, SDI; Brillouin's index, H) endpoints. Two other macrofaunal community metrics (the complement of Simpson's index, 1 - SI, and McIntosh's index, MI) were less sensitive to TU(PAH) than the two toxicity test endpoints. The sensitivities of R. abronius and L. plumulosus to TU(PAH) were statistically indistinguishable. Field validations were conducted by testing the association between or among each toxicity test endpoint, each of seven macrofaunal community metrics (S, A, B, SDI, H, 1 - SI, MI), and TU(PAH) by (1) Spearman's coefficient of rank correlation, (2) Kendall's coefficient of concordance, (3) G tests of independence, and (4) regression analysis. Some field validations based on multivariable tests of association (e.g., points 2 and 3) among toxicity test, field, and stressor endpoints produced false positive results. Both toxicity test endpoints were validated as indicators of changes in S, A, SDI, and H by all the methods tested. The resolution power of the relationships between the laboratory toxicity test and macrofaunal field endpoints was low (< or = three classes) but sufficient to discriminate ecologically important effects. We conclude that standard sediment-amphipod toxicity tests are ecologically relevant and that, under the proper conditions, their results can be used for lab-to-field extrapolation.

Amphipoda↗

Use of disposable GRC electrodes for the detection of phenol and chlorophenols in liquid chromatography.

In this study, a wall-jet flow cell with a GRC (graphite reinforced by carbon) electrode was designed for the amperometric detection of phenol and chlorophenols in liquid chromatography. The voltammetric responses of these analytes at the GRC electrodes are very similar to those at conventional glassy carbon electrodes. As the GRC electrodes were made of the same materials as commercially available mechanical pencil leads, they exhibit the advantages of low cost, simple surface renewability, lower residual current, and good electrode-to-electrode reproducibility, and thus can be used as disposable-type electrodes. Chromatographic separations of phenol, o-chlorophenol (o-CP), 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) were achieved with an ODS column using a mobile phase containing a mixture of CH3CN and H20 (40:60) containing 25 mM L-(+)tartaric acid (pH = 4.5). Amperometric detections were based on the electrochemical oxidation of these compounds around +0.9 V vs. Ag/AgCl. Under the optimized conditions, linear calibrations were obtained in a range up to 100 microM for phenol, o-CP, 2,4-DCP, 2,4,6-TCP, and 200 microM for PCP, with the correlation coefficients r2 of 0.9992, 0.9997, 0.9986, 0.9992, and 0.9968, respectively. The chromatographic detection limits for the tested analytes were obtained at pmol levels.

Journal Article↗

An organic solvent-free microwave-assisted extraction of some priority pollutants of phenols in lake sediments.

Alkaline water was used for the microwave-assisted extraction of some priority pollutants of phenols in sediments, i.e. phenol (Ph), 2-chlorophenol (2CP), 2,4-dichlorophenol (2,4DCP), 4-chlorophenol (4CP), 4-dinitrophenol (4NP) and pentachlorophenol (PCP). This organic solvent-free extraction procedure was optimized by studying the parameters such as pH, volume of the alkaline water, extraction pressure and time. Under the optimized conditions, the recoveries of phenols were in the range of 80% to 110%. The extracts were then cleaned-up and concentrated by microcolumn solid phase extraction (SPE) and determined by gas chromatography-flame ionization detection system. The relative standard deviation of the overall-method for most phenol determinations was about 5.0% (n = 6). The proposed method, which needs little volume (1 mL) of ethanol for SPE, has been applied to determine these phenols in sediment samples, and the analytical results are in good agreement with those achieved by Soxhlet extraction.

Journal Article↗

Sulfation in dog.

Sulfation has been thoroughly studied in several species including e.g. man and rat. However, one important species often used for pharmacological drug studies is the dog. Here we describe recent advances as well as older data in the field of dog sulfation. Species differences in sulfation have been reported. Stereoselectivity, inhibition by pentachlorophenol, bioactivation of DNA binding species, and gender differences have also been observed for canine sulfotransferases (SULTs). Several drugs are being sulfated in vivo in dog, e.g. xamoterol, 4'-hydroxypropanolol, paracetamol and salicylamide. However, studies have shown that also e.g. canine hepatocytes and liverslices will sulfate substrates e.g. paracetamol and 7-hydroxycoumarin in in vitro experiments. Recently, three different enzymes have been cloned and characterized from canine liver, cSULT1A1, cSULT1B1 and cSULT1D1. cSULT1A1 being very similar to the human ortholog in terms of substrate specificity and is also ubiquitously expressed in canine tissues. The cSULT1B1 enzyme is also very similar in both distribution pattern as well as substrate preference compared to the human ortholog. The third enzyme, cSULT1D1, sulfates dopamine with high efficiency and it has no counterpart in man since it is found as a pseudogene. The importance of amino acid residue 247 in cSULT1D1 will be discussed since it can alter the ratio of sulfation of dopamine versus para-nitrophenol. In addition, the phenomenon of the high expression of the canine enzymes in colon is discussed.

Animals↗

Inhibition of sulfotransferases by xenobiotics.

The sulfotransferase (SULT) family comprises important phase II conjugation enzymes for the detoxification of xenobiotics and modulation of the activity of physiologically important endobiotics such as thyroid hormones, steroids, and neurotransmitters. SULT enzymes catalyze the transfer of a sulfuryl group, donated by 3'-phosphoadenosine-5'-phosphosulfate (PAPS), to an acceptor substrate that may be a hydroxy group or an amine group in a process originally called sulfation, but more correctly referred to as sulfonation or sulfurylation. SULT activity may be inhibited when humans are exposed to certain xenobiotics including drugs (mefenamic acid, salicylic acid, clomiphene, danazol etc.), dietary chemicals (catechins, food colorants, flavonoids and phytoestrogens etc.), and environmental chemicals (hydroxylated polychlorinated biphenyls, hydroxylated polyhalogenated aromatic hydrocarbons, pentachlorophenol, triclosan and bisphenol A, etc.). Inhibition of individual SULT isoforms may cause adverse effects on human health. For example, hydroxylated polychlorinated biphenyls have been shown to interfere with the transport of thyroid hormones, inhibit estradiol sulfonation, and inhibit thyroid hormone sulfonation, thereby potentially disrupting the thyroid hormone system. Formation of sulfate conjugates of toxic xenobiotics usually decreases their toxicity, so inhibition of this pathway may lead to prolonged exposure to the compounds. Conversely, some sulfate conjugates are chemically reactive, inhibition of their formation may protect from toxicity. This manuscript will review the literature concerning the inhibition of SULTs by xenobiotics including isoform-selective effects, inhibition kinetics and health effects resulting from the inhibition.

Animals↗

Metabolic studies on pentachloronitrobenzene (PCNB) in rats.

The metabolism of PCNB in rats was studied. Metabolites isolated from rat excreta and identified were: N-acetyl-S-(pentachlorophenyl)cysteine, pentachlorothiophenol, pentachlorothioanisole, 2,3,4,5-tetrachlorothiophenol, 2,3,4,5-tetrachlorothioanisole, 2,3,4,6- and/or 2,3,5,6-tetrachloro-thiophenol and -thioanisole, 1,4-bis(methylthio)tetrachlorobenzene, 1,4-dimercapto-tetrachlorobenzene and/or 4-methylthio-tetrachlorothiophenol, pentachlorophenol, pentachloroanisole, 2,3,4,5-tetrachlorophenol, 2,3,4,5-tetrachloroanisole, 2,3,4,6- and/or 2,3,5,6-tetrachloro-phenol and -anisole, pentachlorobenzene, 2,3,4,5-tetrachloronitrobenzene, pentachloroaniline and 2,3,4,5-tetrachloroaniline.

Absorption↗

Studies on the biliary excretion and metabolites of hexachlorobenzene in the rat.

1. The biliary excretion of metabolites of hexachlorobenzene (HCB) was studied in rats dosed intragastrically with 14C-HCB. Approx. 80% dose was absorbed from the gastrointestinal tract. An average of 3.6% dose was recovered in the bile of bile-duct-cannulated rats in 48 h. 2. By g.l.c.-mass spectrometry, 2.0 and 1.8% of the 14C excreted in the 24 h bile was shown to be due to unchanged HCB and pentachlorobenzene (PCB), respectively. The major metabolite pentachlorophenol (PCP) accounted for 24.2%. 3. Sulphur-containing metabolites were not identified. However, the hepatic GSH concn. decreased by 50% within 24 h following oral administration of HCB (200 mg/kg).

Animals↗

Effects of toxic chemicals on the respiratory activity of cultured mouse neuroblastoma cells.

Twenty common toxic chemicals were tested for their ability to inhibit respiratory activity in cultured mouse neuroblastoma C1300 cells, clone 41A3. Pentachlorophenol and hexachlorophene exhibited the properties of uncouplers of oxidative phosphorylation, whereas for KCN, pyridine, 2,5-hexandione, NaAsO2, K2Cr2O7, HgCl2, methylmercury and triethyltin more simple time-courses of inhibition were obtained. Ethanol, methanol, dimethyl sulphoxide, benzidine, nickel acetate, MnCl2, phenol, CoCl2, Na2SeO3 and CdCl2 did not cause any significant changes in respiratory activity. Among the effective compounds, those with well-known neurotoxic properties were the most potent in inhibiting respiration in 41A3 cells.

Animals↗

Sulphation of the flavonoids quercetin and catechin by rat liver.

1. The isolated perfused rat liver forms three sulphated metabolites from each of the flavonoids, quercetin and catechin: these are secreted into the bile and the perfusate. 2. Quercetin gives two double conjugates, containing sulphate and glucuronic acid, and one sulphate: catechin gives one such double conjugate and two sulphates. 3. This sulphation is not inhibited by 60 microM 2,6-dichloro-4-nitrophenol which almost completely inhibits the sulphation of harmol in this perfused liver system. 4. The sulphation of harmol by the perfused liver is not inhibited by the flavonoids. 5. Unfractionated sulphotransferases from rat liver catalyse sulphate conjugation of quercetin and catechin in vitro by a reaction inhibited by pentachlorophenol or dichloronitrophenol: the flavonoids inhibit the sulphation of 4-nitrophenol by this system. 6. The results with the two systems are discussed and shown to be compatible.

Animals↗

Chlorinated phenols: occurrence, toxicity, metabolism, and environmental impact.

Pentachlorophenol and the lower chlorinated phenols, tetra- and trichlorophenols, have gained an increasing use as fungicides, herbicides, insecticides, and precursors in the synthesis of other pesticides since the early 1930s. World-wide production totals about 200,000 tons. Production and use of chlorinated phenols have caused industrial hygiene problems but, otherwise, have not been recognized to create more than limited environmental problems. The introduction of modern analytical techniques, however, has revealed the ubiquitous occurrence of chlorophenols in the environment, and the discovery of chlorinated dimers, such as dibenzo-p-dioxins and dibenzofurans, as impurities in commercial chlorophenol formulations, has made a reevaluation of the chlorinated phenols necessary. The present article reviews recent studies on the toxicity and metabolism in mammals and aquatic organisms and the degradation of the chlorophenols under various conditions in the environment. Finally, the hazards of burning of chlorophenol wastes are discussed, as well as health considerations with regard to humans and the environment.

Animals↗

Toxicological and neuropsychological findings in patients presenting to an environmental toxicology service.

Patients presenting to an environmental toxicology service are frequently convinced that their multiple symptoms are caused by exposure to environmental toxicants. In order to evaluate the patients' hypotheses, 120 consecutive patients referred by health care providers to the environmental toxicology service for various symptoms were included in an open prospective study. The basic diagnostic procedure included an environmental toxicology questionnaire, psychological tests, a 45 minute interview, a physical examination and standard biomonitoring for cadmium, mercury, lead, lindane, hexachlorobenzene, DDT, DDE, DDD, and pentachlorophenol and a salivary test for mercury released from amalgam. Allergic disease was found in 42 patients. Nineteen of the 42 patients also had psychosomatic disorders. An unusually high release of mercury from amalgam fillings in the saliva test was found in six patients. An environmental toxic exposure was demonstrated in 19 patients (4 lead, 8 DDE, 6 mercury--most likely from broken thermometers, 1 neurotoxic alkyl naphtol derivatives). Ten of the 19 patients had psychosomatic disorders and six had medical/neurological disorders. Only two patients had symptoms attributable to environmental exposure alone. Rather classical psychosomatic disorders were diagnosed in 83 patients. Of the 37 patients without identifiable neuropsychological dysfunction, 18 had allergic disorders and 12 had other medical diagnoses. The diagnosis of a toxic environmental exposure should be performed in an integrated diagnostic approach covering environmental toxicology and medicine as well as psychosomatic medicine.

Adolescent↗

Effects of restricted feeding on the absorption, metabolism, and accumulation of pentachlorobenzene in rats.

To investigate the effect of restricted feeding (RF) on the absorption, metabolism, and accumulation of pentachlorobenzene (PECB), rats were fed either ad libitum (AD) or a restricted diet (at 25 or 50% of AD) for 15 days. On the 7th day (day 0), PECB (15 mg/rat) was orally administered. Daily fecal weight and the total amount of PECB excreted into feces were decreased by RF, indicating an increase in PECB absorption due to its prolonged retention in the gastrointestinal tract. However, the amount of PECB excreted was only 4.8% of the dose given to the AD group, and 2.1 and 2.4% of that given to the 50 and 25% restricted diet groups, respectively. The concentrations of PECB and pentachlorophenol, and major metabolite, in blood of the restricted diet groups were higher on day 2 and day 4, while lower on day 6 and day 8 than those of the AD group. On day 8, PECB in liver, kidney, brain, and fat tissue were also lower in the restricted diet groups; the PECB levels in such tissue in the 25 and 50% restricted diet groups were 10-40 and 5-11% of that in the AD group, respectively. These results indicate that PECB metabolism was increased by RF. As PECB is lipophilic, it is most likely that the fat tissue mass, which was markedly decreased by RF, contributed to the enhancement of PECB metabolism. The mechanism seemed to be as follows: as fat tissue mass accumulating PECB decreased, the concentration of PECB in the liver increased, thus the amount of PECB metabolites formed was increased.

Absorption↗

Increase in number and size of kidney concretions as a result of PCP exposure in the freshwater snail Planorbarius corneus (Gastropoda, Pulmonata).

Molluscan kidneys are able to excrete solids in the urine in the form of concretions. It is thought that increased formation of these concretions occur under pollutant, environmentally or reproductive induced stress. This study examined the formation of concretions in the kidney of the freshwater snail Planorbarius corneus L. experimentally exposed to pentachlorophenol (PCP). Light microscopic histopathological analysis of the PCP-exposed P. corneus revealed significantly enhanced production of the kidney concretions when compared to the kidneys of control individuals. Measurements of the number of kidney concretions, the apparent area of the concretions, and the epithelial area filled with concretions indicated an increase in the number and size of concretions in all treated snails. Lipofuscin content of excretory cell concretions was detected.

Animals↗