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Biomedical subjects

D G Dixon

Publications and source records attributed to D G Dixon.

At least 19 recordsLinked to original sources

Disease and gill lesions in yellow perch (Perca flavescens) exposed to oil sands mining-associated waters.

Adult yellow perch were stocked into experimental ponds designed to test the biological effects of aquatic reclamation alternatives currently being pursued by the oil sands mining industry. Water-quality characteristics of oil sands-influenced water in the experimental ponds included increased salinity and elevated trace organics associated with raw oil sands (bitumen). After 3 and 10 months of exposure to affected waters, perch gross pathologies including severe fin erosion and virally induced tumors were observed in exposed individuals. Gill histopathology revealed large aneurysms accompanied by a proliferation of chloride and epithelial cells in the interlamellar spaces. Gill pathologies were not paralleled by a decrease in plasma sodium, calcium, or chloride. The frequencies of gross pathologies and gill changes were correlated to the concentrations of the oil sands-related compounds. As inorganic and organic compounds associated with oil sands activities are highly intercorrelated, and the observed lesions and changes are not diagnostic of particular toxicants, it was not possible to isolate the causative chemical factor(s) responsible. The incidence of observed lesions and gill pathologies could not be conclusively linked to increased mortality rates observed in the exposed populations. Evidence of recovery in the pathologies was observed between 3 and 10 months of exposure, coincident with a stabilization in population numbers.

Animals↗

Effect of maintaining rainbow trout in creosote microcosms on lens optical properties and liver 7-ethoxyresorufin-O-deethylase (EROD) activity.

Previously, exposure of fish to polycyclic aromatic hydrocarbons (PAHs) in both field and laboratory settings has been associated with eye damage, but this has only been expressed qualitatively. In this study, an automated scanning laser system has been employed to quantitatively evaluate changes in lens optical quality in rainbow trout (Oncorhynchus mykiss) following their in vivo exposure to creosote, which is a complex mixture with many PAHs. Rainbow trout were placed in 12,000-L outdoor microcosms dosed with 0, 3, or 10 microl/L liquid creosote for a 28-day period. Collected fish were examined for changes in focal length variability (FLV), lens size, and weight. These measurements were compared with induction of hepatic ethoxyresorufin-O-deethylase (EROD) activity and hepatic and water concentrations of priority pollutant PAHs. The optical quality of rainbow trout lenses was significantly reduced following creosote exposure, as indicated by increased FLV. Lens damage was significantly related to hepatic EROD activity, and both effects rose with creosote dose. Analytical measurements of microcosm water indicated elevated concentrations of PAHs in creosote-dosed ponds, including compounds capable of inducing rainbow trout EROD activity in vitro. Hepatic concentrations of PAHs were low and not related to creosote dose, likely due to rapid metabolism and elimination. This study demonstrates for the first time employment of a highly sensitive and quantitative technique to measure lens damage in fish exposed to contaminants in situ. The relationship between this effect and hepatic CYP1A activity may suggest a mechanistic linkage, which could lead to the use of EROD activity as an indicator of toxic effect rather than just chemical exposure.

Animals↗

Pathway of anthracene modification under simulated solar radiation.

Exposure of polycyclic aromatic hydrocarbons (PAHs) to sunlight results in rapid structural photomodification generally via oxidation reactions. These PAH modification products are in many cases more toxic than their parent compounds. In this study, anthracene (ANT), a rapidly photooxidized PAH, was irradiated with simulated solar radiation (SSR, 100 micromol m(-2) s(-1)) in aqueous solution to examine the photomodification pathway. The photoproducts formed were identified by HPLC. The ANT product profile after 9 h in SSR was very complex, with more than 20 compounds detected. The photoproducts formed were anthraquinones, benzoic acids, benzaldehydes and phenols showing the process to be oxidative in nature. Some of the anthraquinones were themselves subject to photooxidation, and were thus intermediates in the product pathway. The kinetics of ANT photooxidation revealed a pseudo first-order reaction with a half-life of 2 h under the SSR source used. The kinetics of product formation allowed deduction of a probable photomodification pathway. This study indicates that PAH photooxidation products are likely to exist as complex, dynamically changing mixtures in PAH contaminated aquatic environments.

Anthracenes↗

Fractional simplex designs for interaction screening in complex mixtures.

In mixture experiments, one may be interested in estimating not only main effects but also some interactions. Main effects and significant interactions in a mixture may be estimated through appropriate mixture experiments, such as simplex-centroid designs. However, for mixtures with a large number of factors, the run size for these designs becomes impractically large. A subset of a full simplex-centroid design may be used, but the problem remains regarding which factor-level settings should be selected. In this paper, we propose a solution that considers design points with either one or p individual nonzero factor-level settings. These fractional simplex designs provide a means of screening for interactions and of investigating the behavior of many-component mixtures as a whole while greatly reducing the run size compared with full simplex-centroid designs. The means of construction of the design arrays is described, and designs for < or = 31 factors are presented. Some of the proposed methodology is illustrated using generated data.

Algorithms↗

Plant growth-promoting bacteria that decrease heavy metal toxicity in plants.

Kluyvera ascorbata SUD165 and a siderophore-overproducing mutant of this bacterium, K. ascorbata SUD165/26, were used to inoculate tomato, canola, and Indian mustard seeds which were then grown in soil for 25-42 days in the presence of either nickel, lead, or zinc. The parameters that were monitored included plant wet and dry weight, protein and chlorophyll content in the plant leaves, and concentration of heavy metal in the plant roots and shoots. As indicated by a decrease in the measured values of these parameters, in all instances, plant growth was inhibited by the presence of the added metal. Both bacterial strains were effective, although not always to a statistically significant extent, at relieving a portion of the growth inhibition caused by the metals. In most cases, the siderophore overproducing mutant K. ascorbata 165/26 exerted a more pronounced effect on plant growth than did the wild-type bacterium K. ascorbata SUD165. The data suggest that the ability of these bacteria to protect plants against the inhibitory effects of high concentrations of nickel, lead, and zinc is related to the bacteria providing the plants with sufficient iron.

Biodegradation, Environmental↗

Impacts of structural photomodification on the toxicity of environmental contaminants: anthracene photooxidation products.

The toxicity of polycyclic aromatic hydrocarbons (PHAs) is known to be enhanced by light via photosensitization reactions (production of active oxygen) and photomodification of the chemicals (e.g., oxidation) to more toxic compounds. Anthracene (ANT) toxicity in particular has been found to increase dramatically following photomodification. The objective of this study was to identify the photooxidation products of ANT and assess the toxicity of selected photoproducts. High performance liquid chromatography (HPLC) analysis of anthracene photooxidation revealed a complex array of oxidation products; prevalent among these were anthraquinone (ATQ) and hydroxy-anthraquinones (hATQs). Eleven of these compounds were tested for toxicity using growth inhibition of the duckweed Lemna gibba L. G-3. All but one of the compounds tested were found to be toxic, and when UV radiation was present in the light source toxicity was generally enhanced. The chemicals were also irradiated under SSR prior to toxicity testing. In about half the cases, the ATQ compounds were rapidly photooxidized and the resultant photoproducts were more toxic than the parent compounds. Interestingly, 2-hydroxyanthraquinone, which was not subject to photooxidation, was the most toxic of the compounds tested. As a light stable compound it presents the risk of a persistent environmental hazard.

Anthracenes↗

Ability of polycyclic aromatic hydrocarbons to induce 7-ethoxyresorufin-o-deethylase activity in a trout liver cell line.

Along with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 24 unsubstituted polycyclic aromatic hydrocarbons (PAHs) were evaluated for their ability to induce 7-ethoxyresorufin-o-deethylase (EROD) activity in the rainbow trout liver cell line RTL-W1. When the duration and cell density of exposure were increased, the EC(50) for EROD induction was relatively constant for TCDD, but increased for PAHs. Regardless of exposure conditions, EROD activity was not induced by 9 PAHs: naphthalene, phenanthrene, anthracene, pyrene, perylene, acenaphthylene, acenaphthene, fluorene, and fluoranthene. Two PAHs, benzo[g,h,i]perylene and coronene, induced EROD activity inconsistently. The remaining 13 PAHs consistently induced EROD activity. The EC(50)s for induction exhibited approximately a 110-fold range. The order of potency, from most to least potent, was benzo[k]fluoranthene, dibenzo[a,i]pyrene, dibenzo [a,h]anthracene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, benzo [b]fluoranthene, pentacene, benzo[b]anthracene, benzo[b] fluorene, chrysene, benzo[a]anthracene, benzo[e]pyrene, and triphenylene. When the induction potency was expressed relative to TCDD, the toxic equivalency factors (TEFs) ranged from 0.001 to 0.000 01. When expressed relative to benzo[a]pyrene, the TEFs ranged from 3.44 to 0. 03.

Animals↗

Ability of 16 priority PAHs to be directly cytotoxic to a cell line from the rainbow trout gill.

Sixteen polycyclic aromatic hydrocarbons (PAHs) were screened for their ability to be directly cytotoxic to a cell line from the rainbow trout gill, RTgill-W1. Exposure times of 2 h or less were sufficient for direct cytotoxicity to be detected, which appeared to be caused by a common mechanism, the general perturbation of membranes. This was judged by the similarity of results obtained for three fluorescent indicator dyes, alamar Blue, 5-carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM) and neutral red. Among the 16 PAHs tested, just two- and three-ring PAHs were found to be directly cytotoxic. These were naphthalene approximately = acenaphthylene approximately = acenaphthene > fluorene approximately = phenanthrene. The results suggest that water solubility and lipophilicity are the critical properties determining the direct cytotoxicity of PAHs and that they do so by influencing PAH accumulation in membranes. Only naphthalene was effective at concentrations well below its water solubility limit. Therefore, direct cytotoxicity is likely to be most environmentally relevant only with naphthalene.

Acenaphthenes↗

Ability of 16 priority PAHs to be photocytotoxic to a cell line from the rainbow trout gill.

Sixteen polycyclic aromatic hydrocarbons (PAHs) were screened for their ability to be photocytotoxic to a cell line from the rainbow trout gill, RTgill-W1. PAHs could be divided into one of three groups: incapable of being photocytotoxic, able to be both photocytotoxic and directly cytotoxic, or capable of being only photocytotoxic. Photocytotoxicity was distinct from direct cytotoxicity in that EC50 values were lower with the neutral red assay immediately after the PAH/UV treatment than with alamar Blue or CFDA-AM, indicating a more specific action on lysosomes. As well, in photocytotoxicity but not in direct cytotoxicity, the three assays showed increased impairment 24 h after treatment. Most PAHs were found to be strictly photocytotoxic; however, only six compounds were photocytotoxic at concentrations theoretically achievable in water. When photocytotoxic PAHs were ranked relative to fluoranthene to establish fluoranthene equivalent factors (FEFs), benzo[a]pyrene and benzo[g,h,i]perylene were found to be most potent. However, when the water solubility of each compound was taken into account in order to calculate the potential environmental photocytotoxic potency (PEPP), fluoranthene and pyrene appeared to have the most potential to impact fish through photocytotoxicity.

Animals↗

Amelioration of the photo-induced toxicity of polycyclic aromatic hydrocarbons by a commercial humic acid.

The ability of a commercial (Aldrich Chemical Co.) humic acid (AHA) to ameliorate the photo-induced toxicity of polycyclic aromatic hydrocarbons (PAHs) was examined using Lemna gibba L. (G3). Plants were exposed to anthracene and benzo(a)pyrene both with and without AHA and grown under visible light as well as lighting that simulates relative abundances of UV-A and UV-B in natural sunlight (SSR). Modest additions of 1.6 mg.L-1 AHA were sufficient to ameliorate the photo-induced toxicity of 2 mg.L-1 anthracene by improving growth rates to nearly 50% of controls and inducing minor recovery from complete chlorosis in the most highly affected plants. Benzo(a)pyrene induced minor, but significant, chlorosis under SSR, and AHA additions always increased growth rate and chlorophyll content, although to less of a degree than anthracene toxicity under SSR. The protective effects of AHA on anthracene toxicity increased linearly with increases in AHA concentrations up to 6.2 mg.L-1. Slopes of these relationships changed in the presence of UV light relative to visible light treatments; thus UV changed the extent to which AHA mediates PAH toxicity. However, the net effect was still for AHA to ameliorate PAH photo-induced toxicity even though UV has the potential to photooxidize AHA and enhance the production of potentially toxic reactive oxygen species from AHA photosensitization.

Anthracenes↗

Environmental health assessment of the benthic habitat adjacent to a pulp mill discharge. I. Acute and chronic toxicity of sediments to benthic macroinvertebrates.

In this study, we assessed the acute and chronic toxicity of sediments contaminated by bleached kraft pulp mill effluent (BKME). Sediments were collected in August 1991 and 1992, and May 1993 from eight stations exposed directly to the effluent and from four reference sites.Acute toxicity was determined for five macroinvertebrates (Hyalella azteca, Daphnia magna, Chironomus riparius, Hexagenia spp., and Tubifex tubifex) using pore water, elutriate, and bulk sediment exposures. Chronic toxicity was assessed using C. tentans and H. azteca (growth and survival) and D. magna and T. tubifex (reproduction) in bulk sediment exposures. Mortality declined with decreasing proximity to the outfall; acute toxicity (>20% mortality after 48 h)was observed at the two stations closest to the outfall (300 and 400 m). At 300 m, pore water was consistently more toxic than elutriate or bulk sediment phases, resulting in 100% mortality for all invertebrates except T. tubifex (23%). Elutriate exposures were toxic to C. riparius (88%), D. magna (54%), and Hexagenia (47%), but not H. azteca. Bulk sediments were toxic to Hexagenia (100%) and D. magna(88%), but not to C. riparius or H. azteca. In chronic tests, mortality in H. azteca and T. tubifex was highest at 300 and 400 m, indicating that toxicity observed in the short-term aqueous exposures adequately predicted long-term toxicity in bulk sediments. In both acute and chronic tests, mortality was significantly correlated with the concentration of extractable organic chlorines (EOCl) in the sediment, with LC50 values ranging from 4500 to 5500 mg EOCl/kg organic carbon. Growth of C. tentans larvae was depressed at 300 and 400 m in August 91 but enhanced in May 93 relative to the reference sites. Growth of H.azteca also declined near the outfall in August 91 sediments and was approximately one half that observed in 92/93 sediments; however, growth did not differ among stations in 92 or 93. Reproductive output in D. magna (neonates) and T. tubifex (cocoons) was highest at 300 and 400 m. In T. tubifex, the number of hatched young was lowest at these stations. This study provides evidence that toxicity may occur in sediments exposed to BKME, and emphasizes the need to incorporate sediment toxicity bioassessment as part of efforts directed toward remedial action in the pulp and paper industry.

Animals↗

Evaluation of critical body residue QSARs for predicting organic chemical toxicity to aquatic organisms.

The critical body residue (CBR) is the concentration of chemical bioaccumulated in an aquatic organism that corresponds to a defined measure of toxicity (e.g., mortality). The CBR can provide an alternative measure of toxicity to traditional waterborne concentration measurements (e.g., concentration in water causing 50% mortality). The CBR has been suggested as a better estimator of dose than the external water concentration and has been postulated to be constant for chemicals with the same mode of action. CBR QSARs have both theoretical and experimental support, developed primarily from studies on the acute toxicity of narcotic chemicals to small fish. CBR QSARs are less well developed for the aquatic toxicity of non-narcotic chemicals. CBRs vary substantially with the mode of action and toxicity endpoint, and may be affected by genetic, hormonal or environmental variation. CBR QSARs may not be applicable to very hydrophobic chemicals, chemicals with specific modes of action, or those with toxicity controlled by kinetic processes such as biotransformation. CBRs models have not been developed or evaluated for sediment and dietary exposure routes. Application of CBR QSARs to contaminated site assessments will require further research and development.

Animals↗

Photoinduced effects of polycyclic aromatic hydrocarbons on Brassica napus (Canola) during germination and early seedling development.

It has recently been demonstrated that light dramatically enhances the toxicity of polycyclic aromatic hydrocarbons (PAHs) to the duckweed Lemna gibba L. G-3 (L. Ren, X.-D. Huang, B.J. McConkey, D.G. Dixon, and B.M. Greenberg, 1994, Ecotoxicol. Environ. Saf. 28, 160-171). To extend this research to terrestrial plants, Brassica napus L. (oil seed rape) seeds were germinated in the presence of three PAHs; anthracene (ANT), benzo[a]pyrene (BAP), and fluoranthene. The chemicals were applied both in intact form and following photomodification in UV-B radiation; toxicity was assessed in simulated solar radiation (SSR), a light source with a visible light:UV-A:UV-B ratio similar to that of sunlight. Germination efficiency, root and shoot growth, and chlorophyll content, measured after 6 days of exposure, were used as toxicity endpoints. Intact and photomodified PAHs had little impact on shoot fresh weight or chlorophyll content, but markedly inhibited root fresh weight, with the photomodified PAHs having greater impacts than the intact PAHs. The decline in root fresh weight was not attributable to a decline in germination frequency or delayed germination. However, the seedlings produced shorter roots in the presence of either intact or photomodified PAHs. To explore the role of actinic radiation on PAH toxicity, seedlings were incubated in SSR, visible light and darkness with either intact or photomodified PAHs. Inhibition of root growth was only achieved by the intact chemicals if actinic radiation was present. However, with photomodified ANT or photomodified BAP, root fresh weight accumulation was inhibited in SSR, visible light and darkness. Thus, intact PAHs are hazardous to terrestrial plants in the presence of light, but once the compounds are photomodified, actinic radiation is no longer an absolute requirement for phytotoxic activity.

Brassica↗

Photoinduced toxicity of PAHs to the foliar regions of Brassica napus (canola) and Cucumbis sativus (cucumber) in simulated solar radiation.

Simulated solar radiation and natural sunlight can enhance polycyclic aromatic hydrocarbon (PAH) toxicity, previously reported in terms of inhibited production of Lemna gibba leaves and diminished growth of Brassica napus seedling roots. This work has been extended to examine the photoinduced impact of PAHs on the foliar regions of terrestrial plants. To carry out these experiments two crop species, B. napus (canola) and Cucumbis sativus (cucumber), were chosen to test the photoinduced toxicity of six PAHs (anthracene, phenanthrene, benzo(a)anthracene, benzo(a)pyrene, flouranthene, and pyrene). Aqueous solutions containing PAHs were sprayed on the foliage of the plants. It was found that all the PAHs tested had negative impacts on the foliage of the plants and the concentrations that induced toxicity were consistent with those observed for inhibition of growth of L. gibba. The impacts were observed as diminished biomass accumulation, induction of chlorosis, and inhibition of photosynthesis. It may be concluded from this work that PAHs in rain and surface waters could be harmful to photosynthetic tissues of terrestrial plants.

Brassica↗

Effects of age and coion (K+ and Na+) on the toxicity of thiocyanate to rainbow trout (Oncorhynchus mykiss) during pulse or continuous exposure.

Thiocyanate (SCN-) is released to the aquatic environment as a result of the treatment of cyanide-bearing wastes from precious-metal mining activity. During continuous exposure alevin rainbow trout (1- and 10-day-old) were approximately 90% more tolerant of SCN- than juveniles (2-month-old). Pulse exposure of alevins for periods > or = 48 hr were required before postexposure stress reduced tolerance (by approximately 30%) in the 24-hr period following exposure. In contrast, stressing of juveniles after exposures of > or= 9 hr consistently reduced tolerance by approximately 60%. While coion (K+ or Na+ for SCN- derived from either KSCN or NaSCN) had no influence on SCN- toxicity for alevins, juveniles exhibited reduced tolerance in the presence on Na+. Although sudden death syndrome was apparent in juveniles, none occurred with alevins. Overall, juveniles were less tolerant of SCN- than alevins, possibly because of the enhanced efficiency of SCN- uptake by gill respiration versus the predominantly vitelline membrane respiration of alevins.

Aging↗

HPLC determination of plasma thiocyanate concentrations in fish blood: application to laboratory pharmacokinetic and field-monitoring studies.

The pharmacokinetics of thiocyanate (SCN-) in the blood plasma of 35-g rainbow trout (Oncorhynchus mykiss) were followed during a 20-day exposure to 39.8 mg SCN- liter-1 and the subsequent 16-day depuration period. SCN- concentrations were determined by reverse-phase HPLC. Kinetic constants were estimated using a one-compartment first-order kinetic model fitted to the data by the computer programs BIOFAC and SYSTAT. The respective BIOFAC and SYSTAT estimates for the uptake rate constant (k1, 0.55 and 0.49 day-1), the depuration rate constant (k2, 0.34 and 0.29 day-1), and the bioconcentration factor (BCF, 1.61 and 1.66) were similar for both methods of calculation. Field studies were conducted to determine the impact of SCN- on white sucker (Catostomus commersoni) populations in waters receiving SCN(-)-bearing effluents. The assessment was based on SCN- concentrations in water and fish plasma, and the thyroid histology of the fish. Although SCN- was detected in the water at one site, no SCN- was detected in fish plasma and none of the thyroid pathology characteristic of chronic SCN- exposure was present. The results suggest that SCN- was not a hazard to the white sucker populations studied.

Animals↗

Increased polycyclic aromatic hydrocarbon toxicity following their photomodification in natural sunlight: impacts on the duckweed Lemna gibba L. G-3.

The authors previously demonstrated that simulated solar radiation (SSR), with a fluence rate of only 40 mumol m-2 sec-1, increased polycyclic aromatic hydrocarbon (PAH) toxicity to the duckweed Lemna gibba and that PAHs photomodified in SSR (generally oxygenation of the ring system) are more toxic than the parent compounds (Huang et al., Environ. Toxicol. Chem., 1993, 12, 1067-1077). It is not known, however, to what extent toxicity of PAHs can increase due to photomodification. Thus, natural sunlight, which has a high fluence rate (approximately 2000 mumol m-2 sec-1), was used to photomodify anthracene, benzo[a]pyrene, fluoranthene, phenanthrene, and pyrene. Toxicity was based on growth inhibition of L. gibba, measured as the rate of production of new leaves over an 8-day period. Initially, the toxicity of the PAHs applied in intact form was probed, with the compounds demonstrating greater toxicity in sunlight than in SSR. Next the PAHs were photomodified in sunlight prior to incubation with the plants. The half-lives of the PAHs in sunlight ranged from 12 min to 30 hr. Although most of the products of PAH photomodification are not yet identified, the degree that PAH toxicity increased following photomodification in sunlight could still be probed. The mixtures of photomodified chemicals that were derived from each PAH in sunlight were applied of L. gibba and growth inhibition under 100 mumol m-2 sec-1 of SSR was determined. The LC50s for the PAH photoproducts generated in sunlight were an order of magnitude lower than the LC50s for the PAHs applied in intact form.

Anthracenes↗