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Sample records for p450-dependent toxic effects

  1. Cytochrome P-450 dependent ethanol oxidation. Kinetic isotope effects and absence of stereoselectivity

    SciTech Connect

    Ekstroem, G.; Norsten, C.; Cronholm, T.; Ingelman-Sundberg, M.

    1987-11-17

    Deuterium isotope effects (/sup D/(V/K)) and stereoselectivity of ethanol oxidation in cytochrome P-450 containing systems and in the xanthine-xanthine oxidase system were compared with those of yeast alcohol dehydrogenase. The isotope effects were determined by using both a noncompetitive method, including incubation of unlabeled of (1,1-/sup 2/H/sub 2/) ethanol at various concentrations, and a competitive method, where 1:1 mixtures of (1-/sup 13/C)- and (/sup 2/H/sub 6/) ethanol or (2,2,2-/sup 2/H/sub 3/)- and (1,1-/sup 2/H/sub 2/) ethanol were incubated and the acetaldehyde formed was analyzed by gas chromatography/mass spectrometry. The /sup D/(V/K) isotope effects of the cytochrome P-450 dependent ethanol oxidation were about 4 with liver microsomes from imidazole-, phenobarbital- or acetone-treated rabbits or with microsomes from acetone- or ethanol-treated rats. Similar isotope effects were reached with reconstituted membranes containing the rabbit ethanol-inducible cytochrome P-450 (LMeb), whereas control rat microsomes and membranes containing rabbit phenobarbital-inducible P-450 LM/sub 2/ oxidized the alcohol with /sup D/(V/K) of about 2.8 and 1.8, respectively. Addition of Fe/sup III/EDTA either to microsomes from phenobarbital-treated rabbits or to membranes containing P-450 LMeb significantly lowered the isotope effect. Incubations of all cytochrome P-450 containing systems of the xanthine-xanthine oxidase systems with (1R)- and (1S)-(1-/sup 2/H) ethanol, revealed, taking the isotope effects into account, that 44-66% of the ethanol oxidized had lost the 1-pro-R hydrogen. The data indicate that cytochrome P-450 dependent ethanol oxidation is not stereospecific and that cleavage of the C/sub 1/-H bond appears to be a rate-determining step in the catalysis by the ethanol-inducible form of P-450. The contribution of hydroxyl radicals in ethanol oxidation by the various enzymic systems is discussed.

  2. Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism

    SciTech Connect

    Fang Cheng; Behr, Melissa; Xie Fang; Lu Shijun; Doret, Meghan; Luo Hongxiu; Yang Weizhu; Aldous, Kenneth; Ding Xinxin; Gu Jun

    2008-02-15

    Chloroform causes hepatic and renal toxicity in a number of species. In vitro studies have indicated that chloroform can be metabolized by P450 enzymes in the kidney to nephrotoxic intermediate, although direct in vivo evidence for the role of renal P450 in the nephrotoxicity has not been reported. This study was to determine whether chloroform renal toxicity persists in a mouse model with a liver-specific deletion of the P450 reductase (Cpr) gene (liver-Cpr-null). Chloroform-induced renal toxicity and chloroform tissue levels were compared between the liver-Cpr-null and wild-type mice at 24 h following differing doses of chloroform. At a chloroform dose of 150 mg/kg, the levels of blood urea nitrogen (BUN) were five times higher in the exposed group than in the vehicle-treated one for the liver-Cpr-null mice, but they were only slightly higher in the exposed group than in the vehicle-treated group for the wild-type mice. Severe lesions were found in the kidney of the liver-Cpr-null mice, while only mild lesions were found in the wild-type mice. At a chloroform dose of 300 mg/kg, severe kidney lesions were observed in both strains, yet the BUN levels were still higher in the liver-Cpr-null than in the wild-type mice. Higher chloroform levels were found in the tissues of the liver-Cpr-null mice. These findings indicated that loss of hepatic P450-dependent chloroform metabolism does not protect against chloroform-induced renal toxicity, suggesting that renal P450 enzymes play an essential role in chloroform renal toxicity.

  3. Effect of zinc deficiency on NADPH and cytochrome P-450 dependent active oxygen generation in rat lung and liver

    SciTech Connect

    Hammermueller, J.D.; Bray, T.M.; Bettger, W.J.

    1986-03-05

    The cyt. P-450 system and cyt. P-450 reductase are involved in the generation of active oxygen species such as H/sub 2/O/sub 2/. The objective of this study was to investigate the effect of short term, severe, dietary zinc deficiency in rats on the formation of active oxygen in vitro. Weanling male Wistar rats were fed egg white-based diets containing less than 1 ppm Zn (ZnD). Controls were fed ad libitum (ZnAl) or pair-fed (ZnPF) a diet containing 100 ppm Zn. After 3 weeks lung and liver microsomes were assayed for H/sub 2/O/sub 2/ production (pmol H/sub 2/O/sub 2//mg protein/min) and cyt. P-450 reductase activity (nmol cyt. C reduced/mg protein/min). For the measurement of H/sub 2/O/sub 2/ production exogenous substrate (aminopyrine) and NADPH (cofactor) were provided to drive the cyt. P-450 system and NaN/sub 3/ was used to inhibit catalase. The results showed a significant effect of dietary Zn on NADPH and cyt. P-450 dependent active oxygen generation and support the hypothesis that Zn has a role in the function of biomembranes.

  4. Acute and subacute effects of miconazole nitrate on hepatic styrene oxide hydrolase and cytochrome P-450-dependent monooxygenase activities in male and female AKR/J mice.

    PubMed

    James, M O

    1988-08-01

    The imidazole-containing anti-fungal drug, miconazole nitrate, was shown to enhance hepatic microsomal styrene oxide hydrolase and inhibit several cytochrome P-450-dependent monooxygenase activities in the AKR/J mouse. Miconazole was a more potent inhibitor of cytochrome P-450-dependent monooxygenase activities in microsomes from male than female mice, and inhibitory potency also varied with substrate. When administered in vivo miconazole nitrate stimulated epoxide hydrolase activity, but had a substrate-dependent biphasic effect on cytochrome P-450-dependent monooxygenase activities. Monooxygenase activities with benzo[a]pyrene and benzphetamine were inhibited to varying degrees in liver homogenate and hepatic microsomes from mice sacrificed 45 min after miconazole administration. After repeated administration of miconazole, liver weight, microsomal protein yield and cytochrome P-450 were increased, as were specific monooxygenase activities with ethoxycoumarin and ethoxyresorufin, but benzphetamine N-demethylase activity was decreased. These results suggested that a metabolite of miconazole was responsible for the inhibition of benzphetamine N-demethylase. It was of special interest that ethoxyresorufin O-deethylase activity was induced in the AKR/J mouse by miconazole, since the AKR/J mouse is not responsive to induction by aromatic hydrocarbons. PMID:3394155

  5. The effect of propylene glycol on the P450-dependent metabolism of acetaminophen and other chemicals in subcellular fractions of mouse liver

    SciTech Connect

    Snawder, J.E.; Benson, R.W.; Leakey, J.E.A.; Roberts, D.W. )

    1993-01-01

    Propylene glycol (PG) decreases the hepatotoxicity of acetominophen (APAP). To elucidate the mechanism for this response, the authors measured the effect of PG on the in vitro metabolism of APAP by subcellular liver fractions from 6-10 week-old male B6C3F1 mice. The fractions were assayed for their ability to bioactivate APAP to N-acetyl-p-benzoquinone imine, which was trapped as APAP-glutathione conjugates or APAP-protein adducts, and for dimethyl-nitrosamine-N-demethylase (DMN), 4-nitrophenol hydroxylase (4-NPOH), and phenacetin-O-deethylase (PAD) activities. Activity in the crude mitochondrial-rich (10,000 [times] g pellet) fraction was low and PG had no effect. PG inhibited DMN and 4-NPOH, indicators of IIE1-dependent activity, and the formation of APAP-glutathione conjugates and APAP-protein adducts in both heavy (15,000 [times] g pellet) and light (100,000 [times] g pellet) microsomes. PAD, a measure of IA2-dependent activity, was not inhibited. These data demonstrate that PG selectively inhibits IIE1 activity, including the bioactivation of APAP, and implicates this as the mechanism for PG-mediated protection of APAP hepatotoxicity in mice. 27 refs., 1 fig., 1 tab.

  6. Effect of human glutathione S-transferases on glutathione-dependent inactivation of cytochrome P450-dependent reactive intermediates of diclofenac.

    PubMed

    Dragovic, Sanja; Boerma, Jan Simon; Vermeulen, Nico P E; Commandeur, Jan N M

    2013-11-18

    Idiosyncratic adverse drug reactions due to the anti-inflammatory drug diclofenac have been proposed to be caused by the generation of reactive acyl glucuronides and oxidative metabolites. For the oxidative metabolism of diclofenac by cytochromes P450 at least five different reactive intermediates have been proposed previously based on structural identification of their corresponding GSH-conjugates. In the present study, the ability of four human glutathione S-transferases (hGSTs) to catalyze the GSH-conjugation of the different reactive intermediates formed by P450s was investigated. Addition of pooled human liver cytosol and recombinant hGSTA1-1, hGSTM1-1, and hGSTP1-1 to incubations of diclofenac with human liver microsomes or purified CYP102A1M11 L437N as a model system significantly increased total GSH-conjugation. The strongest increase of total GSH-conjugation was observed by adding hGSTP1-1, whereas hGSTM1-1 and hGSTA1-1 showed lower activity. Addition of hGSTT1-1 only showed a minor effect. When considering the effects of hGSTs on GSH-conjugation of the different quinoneimines of diclofenac, it was found that hGSTP1-1 showed the highest activity in GSH-conjugation of the quinoneimine derived from 5-hydroxydiclofenac (5-OH-DF). hGSTM1-1 showed the highest activity in inactivation of the quinoneimine derived from 4'-hydroxydiclofenac (4'-OH-DF). Separate incubations with 5-OH-DF and 4'-OH-DF as substrates confirmed these results. hGSTs also catalyzed GSH-conjugation of the o-iminemethide formed by oxidative decarboxylation of diclofenac as well as the substitution of one of the chlorine atoms of DF by GSH. hGSTP1-1 showed the highest activity for the formation of these minor GSH-conjugates. These results suggest that hGSTs may play an important role in the inactivation of DF quinoneimines and its minor reactive intermediates especially in stress conditions when tissue levels of GSH are decreased. PMID:24083800

  7. P450-dependent enzymes as targets for prostate cancer therapy.

    PubMed

    De Coster, R; Wouters, W; Bruynseels, J

    1996-01-01

    Metastatic prostate adenocarcinoma is a leading cause of cancer-related deaths among men. First line treatment is primarily aimed at blocking the synthesis and action of androgens. As primary endocrine treatment, androgen deprivation is usually achieved by orchidectomy or LHRH analogues, frequently combined with androgen receptor antagonists in order to block the residual adrenal androgens. However, nearly all the patients will eventually relapse. Available or potential second line therapies include, among others, alternative endocrine manipulations and chemotherapy. Cytochrome P450-dependent enzymes are involved in the synthesis and/or degradation of many endogenous compounds, such as steroids and retinoic acid. Some of these enzymes represent suitable targets for the treatment of prostate cancer. In first line therapy, inhibitors of the P450-dependent 17,20-lyase may achieve a maximal androgen ablation with a single drug treatment. Ketoconazole at high dose blocks both testicular and adrenal androgen biosynthesis but its side-effects, mainly gastric discomfort, limit its widespread use. A series of newly synthesized, more selective, steroidal 17,20-lyase inhibitors related to 17-(3-pyridyl)androsta-5,16-dien-3beta-ol, may open new perspectives in this field. In prostate cancer patients who relapse after surgical or medical castration, therapies aiming at suppressing the remaining adrenal androgen biosynthesis (ketoconazole) or producing a medical adrenalectomy (aminoglutethimide+hydrocortisone) have been used, but are becoming obsolete with the generalization of maximal androgen blockade in first line treatment. The role of inhibition of aromatase in prostate cancer therapy, which was postulated for aminoglutethimide, could not be confirmed by the use of more selective aromatase inhibitors, such as formestane. An alternative approach is represented by liarozole fumarate (LIA), a compound that blocks the P450-dependent catabolism of retinoic acid (RA). In vitro

  8. Cytochrome P450-dependent eicosapentaenoic acid metabolites are novel BK channel activators.

    PubMed

    Lauterbach, Birgit; Barbosa-Sicard, Eduardo; Wang, Mong-Heng; Honeck, Horst; Kärgel, Eva; Theuer, Jürgen; Schwartzman, Michal L; Haller, Hermann; Luft, Friedrich C; Gollasch, Maik; Schunck, Wolf-Hagen

    2002-02-01

    P450-dependent arachidonic acid (AA) metabolites regulate arterial tone by modulating calcium-activated (BK) potassium channels in vascular smooth muscle cells (VSMC). Because eicosapentaenoic acid (EPA) has been reported to improve vascular function, we tested the hypothesis that P450-dependent epoxygenation of EPA produces alternative vasoactive compounds. We synthesized the 5 regioisomeric epoxyeicosattrienoic acids (EETeTr) and examined them for effects on K(+) currents in rat cerebral artery VSMCs with the patch-clamp technique. 11(R),12(S)-epoxyeicosatrienoic acid (50 nmol/L) was used for comparison and stimulated K(+) currents 6-fold at +60 mV. However, 17(R),18(S)-EETeTr elicited a more than 14-fold increase. 17(S),18(R)-EET and the remaining four regioisomers were inactive. The effect of 17(R),18(S)-EETeTr was blocked by tetraethylammonium but not by 4-aminopyridine. VSMCs expressed P450s 4A1 and 4A3. Recombinant P450 4A1 hydroxylated EPA at C-19 and C-20 and epoxygenated the 17,18-double bond, yielding the R, S- and S, R-enantiomers in a ratio of 64:36. We conclude that 17(R),18(S)-EETeTr represents a novel, potent activator of BK potassium channels. Furthermore, this metabolite can be directly produced in VSMCs. We suggest that 17(R),18(S)-EETeTr may function as an important hyperpolarizing factor, particularly with EPA-rich diets. PMID:11882617

  9. Involvement of singlet oxygen in cytochrome P450-dependent substrate oxidations.

    PubMed

    Osada, M; Ogura, Y; Yasui, H; Sakurai, H

    1999-09-24

    Cytochrome P450 (P450)-dependent p-hydroxylation of aniline and o-deethylation of 7-ethoxycoumarin were examined in rat liver microsomes in the presence of radical scavengers. The addition of beta-carotene, a quencher of singlet oxygen species ((1)O(2)), suppressed the aniline hydroxylation, while the addition of sodium azide (NaN(3)) ((1)O(2) quencher) enhanced the reaction. No other reactive oxygen scavengers or chelating agents such as superoxide dismutase, catalase, dimethylsulfoxide, or deferoxamine altered the reaction. In contrast, the microsomal o-deethylation of 7-ethoxycoumarin was suppressed by the addition of NaN(3). (1)O(2) was detectable during the reaction of microsomes and NADPH by ESR spin-trapping when 2,2,6,6-tetramethyl-4-piperidone (TMPD) was used as a spin trap, and the (1)O(2) was quenched by the additions of beta-carotene, NaN(3), aniline, and 7-ethoxycoumarin. The enhancement effect of NaN(3) in the hydroxylation of aniline appeared to be due to the conformational change of P450 protein, which in turn enhances the binding of aniline to P450 in terms of the spectral dissociation constant (K(s)). In contrast, (1)O(2) appeared to be active in the o-deethylation of 7-ethoxycoumarin. On the basis of the results, the involvement of (1)O(2) in P450-dependent substrate oxygenations is proposed. PMID:10491304

  10. Cytochrome P450-Dependent Metabolism of Caffeine in Drosophila melanogaster

    PubMed Central

    Coelho, Alexandra; Fraichard, Stephane; Le Goff, Gaëlle; Faure, Philippe; Artur, Yves; Ferveur, Jean-François; Heydel, Jean-Marie

    2015-01-01

    Caffeine (1, 3, 7-trimethylxanthine), an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents). A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs) that were highly overexpressed. Flies treated with metyrapone—an inhibitor of CYP enzymes—showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects. PMID:25671424

  11. 1-Ethynylpyrene, a suicide inhibitor of cytochrome P-450 dependent benzo(a)pyrene hydroxylase activity in liver microsomes

    SciTech Connect

    Gan, L.S.L.; Acebo, A.L.; Alworth, W.L.

    1984-08-14

    The preparation of 1-ethynylpyrene (EP) by incubation of EP with liver microsomes in the presence of NADPH yields fluorescent products briefly. Addition of microsomes restores the original rate. The metabolism of EP is initially more rapid in microsomes from 5,6-benzoflavone- (BF) pretreated rats than in those from phenobarbital (PB) pretreated rats or controls. Ep inhibits the hydroxylation of benzo(a)pyrene (BP) by liver microsomes. Ep more effectively inhibits the oxidation of BP in liver microsomes from BF rats than from PB rats or from controls. The inhibition of BP hydroxylation activity due to EP is dependent upon NADPH and is apparently irreversible. Kinetic analyses show that the inhibition of BP hydroxylation is due to loss of the activity by a process that is first order in EP and that reaches a limiting value at infinite EP concentrations. A self-catalyzed inhibition of the cytochrome P-450 dependent BP hydroxylation may occur in the presence of EP. Incubation with EP under conditions that result in loss of BP hydroxylase activity in microsomes from BF rats and 66% of the activity from PB rats causes the loss of 6 and 12% of the cytochrome P-450, respectively. Thus the loss of P-450 content is an insensitive measure of the effect of this inhibitor upon this cytochrome P-450 dependent enzyme activity. Selectivity of the loss of P-450 due to the incubation of the different microsomal preparations with EP is observed to be different than the selectivity for loss of BP hydroxylase activity. It is proposed that the inhibition of cytochrome P-450 dependent enzymes by alkynes need not involve heme alkylation and a resulting loss of P-450 content. In vivo EP does not cause a significant change in the cytochrome P-450 content in the microsomes isolated, or result in the change in BP hydroxylation.

  12. Challenges and pitfalls of P450-dependent (+)-valencene bioconversion by Saccharomyces cerevisiae.

    PubMed

    Gavira, Carole; Höfer, René; Lesot, Agnès; Lambert, Fanny; Zucca, Joseph; Werck-Reichhart, Danièle

    2013-07-01

    Natural nootkatone is a high value ingredient for the flavor and fragrance industry because of its grapefruit flavor/odor, low sensorial threshold and low availability. Valencene conversion into nootkatol and nootkatone is known to be catalyzed by cytochrome P450 enzymes from both prokaryotic and eukaryotic organisms, but so far development of a viable bioconversion process using either native microorganisms or recombinant enzymes was not successful. Using an in silico gene-mining approach, we selected 4 potential candidate P450 enzymes from higher plants and identified two of them that selectively converted (+)-valencene into β-nootkatol with high efficiency when tested using recombinant yeast microsomes in vitro. Recombinant yeast expressing CYP71D51v2 from tobacco and a P450 reductase from arabidopsis was used for optimization of a bioconversion process. Bioconversion assays led to production of β-nootkatol and nootkatone, but with low yields that decreased upon increase of the substrate concentration. The reasons for this low bioconversion efficiency were further investigated and several factors potentially hampering industry-compatible valencene bioconversion were identified. One is the toxicity of the products for yeast at concentrations exceeding 100 mg L⁻¹. The second is the accumulation of β-nootkatol in yeast endomembranes. The third is the inhibition of the CYP71D51v2 hydroxylation reaction by the products. Furthermore, we observed that the formation of nootkatone from β-nootkatol is not P450-dependent but catalyzed by a yeast component. Based on these data, we propose new strategies for implementation of a viable P450-based bioconversion process. PMID:23518241

  13. Mechanism-based inactivation of cytochrome P-450 dependent benzo(a)pyrene hydroxylase activity by acetylenic and olefinic polycyclic arylhydrocarbons

    SciTech Connect

    Gan, L.S.

    1986-01-01

    A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxygenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene (EP), 3-ethynylperylene (EPL), cis- and trans-1-(2-bromo-vinyl)pyrene (c-BVP and t-BVP), and 1-allylpyrene (AP) serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene (BP) hydroxylase, while 1-vinyl-pyrene (VP) and phenyl 1-pyrenyl acetylene (PPA) do not cause a detectable suicide inhibition of the BP hydroxylase. The mechanism-based loss of BP hydroxylase activity caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes. In the presence of NADPH, /sup 3/H-labeled EP covalently attached to P-450 isozymes with a measured stoichiometry of one mole of EP per mole of the P-450 heme. The results of the effects of these aryl derivatives in the mammalian cell-mediated mutagenesis assay and toxicity assay show that none of the compounds examined nor any of the their metabolites produced in the incubation system are cytotoxic to V79 cells.

  14. P450-dependent arachidonic acid metabolism and angiotensin II-induced renal damage.

    PubMed

    Kaergel, Eva; Muller, Dominik N; Honeck, Horst; Theuer, Juergen; Shagdarsuren, Erdenechimeg; Mullally, Alexander; Luft, Friedrich C; Schunck, Wolf-Hagen

    2002-09-01

    Transgenic rats overexpressing both human renin and angiotensinogen genes (dTGR) develop hypertension, inflammation, and renal failure. We tested the hypothesis that these pathological features are associated with changes in renal P450-dependent arachidonic acid (AA) metabolism. Samples were prepared from 5- and 7-week-old dTGR and from normotensive Sprague-Dawley (SD) rats, ie, before and after the dTGR developed severe hypertension and albuminuria. At both stages, dTGR showed significantly lower renal microsomal AA epoxygenase and hydroxylase activities that reached 63% and 76% of the control values at week 7. Furthermore, the protein levels of several potential AA epoxygenases (CYP2C11, CYP2C23, and CYP2J) were significantly reduced. Immunoinhibition studies identified CYP2C23 as the major AA epoxygenase, both in dTGR and SD rats. Immunohistochemistry showed that CYP2C23 was localized in cortical and outer medullary tubules that progressively lost this enzyme from week 5 to week 7 in dTGR. CYP2C11 expression occurred only in the outer medullary tubules and was markedly reduced in dTGR compared with age-matched SD rats. These findings indicate site-specific decreases in the availability of AA epoxygenase products in the kidney of dTGR. In contrast to renal microsomes, liver microsomes of dTGR and SD rats showed no change in the expression and activity of AA epoxygenases and hydroxylases. We conclude that hypertension and end-organ damage in dTGR is associated with kidney-specific downregulation of P450-dependent AA metabolism. Because the products of AA epoxygenation have anti-inflammatory properties, this alteration may contribute to uncontrolled renal inflammation, which is a major cause of renal damage in dTGR. PMID:12215466

  15. Rat liver microsomal cytochrome P450-dependent oxidation of 3,5-disubstituted analogues of paracetamol.

    PubMed

    Bessems, J G; Te Koppele, J M; Van Dijk, P A; Van Stee, L L; Commandeur, J N; Vermeulen, N P

    1996-06-01

    1. The cytochrome P450-dependent binding of paracetamol and a series of 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -CH3, -C2H5, -iC3H7) have been determined with beta-naphthoflavone (beta NF)-induced rat liver microsomes and produced reverse type I spectral changes. Ks,app varied from 0.14 mM for 3,5-diiC3H7-paracetamol to 2.8 mM for paracetamol. 2. All seven analogues underwent rat liver microsomal cytochrome P450-dependent oxidation, as reflected by the formation of GSSG in the presence of GSH. The GSSG-formation was increased in all cases upon pretreatment of rats by beta-naphthoflavone (beta NF) and was generally decreased upon pretreatment by phenobarbital (PB). 3. Rat liver microsomal cytochrome P450 as well as horseradish peroxidase catalysed the formation of 3,5-disubstituted NAPQI analogues from the corresponding parent compounds, as identified by UV-spectrophotometry of the NAPQI analogues and by GC/MS detection of the following GSH-conjugates: 2-glutathione-S-yl-3,5-dimethyl-1,4-dihydroxybenzene, 2-glutathione-S-yl-3,5-dichloro-paracetamol, and 2-glutathione-S-yl-3,5-dibromo-paracetamol. 4. In liver microsomal (beta NF-induced) incubations, apparent K(m) values, as determined for the cytochrome P450 catalysis-dependent oxidation of GSH, for seven 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -CH3, -C2H5, iC3H7) varied from 0.07 to 0.64 mM. Paracetamol exhibited an apparent K(m) of 0.73 mM. Apparent Vmax values for the cytochrome P450 catalysis dependent oxidation of GSH varied from 0.66 nmol min-1 mg-1 protein for paracetamol to 3.0 nmol min-1 mg-1 protein for 3,5-dimethyl-paracetamol. PMID:8810035

  16. Metabolic engineering of light-driven cytochrome P450 dependent pathways into Synechocystis sp. PCC 6803.

    PubMed

    Wlodarczyk, Artur; Gnanasekaran, Thiyagarajan; Nielsen, Agnieszka Zygadlo; Zulu, Nodumo Nokolunga; Mellor, Silas Busck; Luckner, Manja; Thøfner, Jens Frederik Bang; Olsen, Carl Erik; Mottawie, Mohammed Saddik; Burow, Meike; Pribil, Mathias; Feussner, Ivo; Møller, Birger Lindberg; Jensen, Poul Erik

    2016-01-01

    Solar energy provides the energy input for the biosynthesis of primary and secondary metabolites in plants and other photosynthetic organisms. Some secondary metabolites are high value compounds, and typically their biosynthesis requires the involvement of cytochromes P450s. In this proof of concept work, we demonstrate that the cyanobacterium Synechocystis sp. PCC 6803 is an eminent heterologous host for expression of metabolically engineered cytochrome P450-dependent pathways exemplified by the dhurrin pathway from Sorghum bicolor comprising two membrane bound cytochromes P450s (CYP79A1 and CYP71E1) and a soluble glycosyltransferase (UGT85B1). We show that it is possible to express multiple genes incorporated into a bacterial-like operon by using a self-replicating expression vector in cyanobacteria. We demonstrate that eukaryotic P450s that typically reside in the endoplasmic reticulum membranes can be inserted in the prokaryotic membranes without affecting thylakoid membrane integrity. Photosystem I and ferredoxin replaces the native P450 oxidoreductase enzyme as an efficient electron donor for the P450s both in vitro and in vivo. The engineered strains produced up to 66mg/L of p-hydroxyphenylacetaldoxime and 5mg/L of dhurrin in lab-scale cultures after 3 days of cultivation and 3mg/L of dhurrin in V-shaped photobioreactors under greenhouse conditions after 9 days cultivation. All the metabolites were found to be excreted to the growth media facilitating product isolation. PMID:26548317

  17. Participation of P450-dependent oxidation of isoniazid in isonicotinic acid formation in rat liver.

    PubMed

    Ono, Y; Wu, X; Noda, A; Noda, H; Yoshitani, T

    1998-04-01

    By determining the formation amount of isonicotinic acid (INA) from isonicotinic acid hydrazide (isoniazid:INH) in isolated rat hepatocytes, we were able to identify the involvement of the oxidative cleavage of the acid hydrazide. INA formation from INH increased significantly using the isolated hepatocytes prepared from rats pretreated with phenobarbital (PB), 3-methylcholanthrene (3MC), dexamethazone (DEX) and rifampicin (RIF), respectively, in comparison to the control group. On the other hand, a remarkable decrease in INA formation from INH was observed by the addition of such P450 inhibitor as metyrapone or cimetidine as well as an amidase inhibitor bis(p-nitrophenyl)phosphate (BNPP) to the isolated hepatocytes prepared from PB-pretreated rats. By further experiments using rat hepatic microsomes, the oxidative pathway of INA formation in INH metabolism was determined to be P450-dependent, since NADPH and oxygen were both essential for the oxidative pathway of INH to INA and the amount of INA formation was also significantly increased by P450 inducers. Regarding acetylisoniazid (AcINH) and isonicotinic acid amide (INAA), however, INA formation by P450 was little observed in the microsomal experiments. PMID:9586587

  18. Taxol biosynthesis: taxane 13 alpha-hydroxylase is a cytochrome P450-dependent monooxygenase.

    PubMed

    Jennewein, S; Rithner, C D; Williams, R M; Croteau, R B

    2001-11-20

    A central feature in the biosynthesis of Taxol is oxygenation at multiple positions of the taxane core structure, reactions that are considered to be mediated by cytochrome P450-dependent monooxygenases. A PCR-based differential display-cloning approach, using Taxus (yew) cells induced for Taxol production, yielded a family of related cytochrome P450 genes, one of which was assigned as a taxane 10 beta-hydroxylase by functional expression in yeast. The acquired clones that did not function in yeast were heterologously expressed by using the Spodoptera fugiperda-baculovirus-based system and were screened for catalytic capability by using taxa-4(20),11(12)-dien-5 alpha-ol and its acetate ester as test substrates. This approach allowed identification of one of the cytochrome P450 clones (which bore 63% deduced sequence identity to the aforementioned taxane 10 beta-hydroxylase) as a taxane 13 alpha-hydroxylase by chromatographic and spectrometric characterization of the corresponding recombinant enzyme product. The demonstration of a second relevant hydroxylase from the induced family of cytochrome P450 genes validates this strategy for elucidating the oxygenation steps of taxane diterpenoid (taxoid) metabolism. Additionally, substrate specificity studies with the available cytochrome P450 hydroxylases now indicate that there is likely more than one biosynthetic route to Taxol in yew species. PMID:11707604

  19. Downregulation of Mouse Hepatic CYP3A Protein by 3-Methylcholanthrene Does Not Require Cytochrome P450-Dependent Metabolism

    PubMed Central

    Lee, Chunja; Ding, Xinxin

    2013-01-01

    The aryl hydrocarbon receptor (AHR)–dependent induction of cytochromes P450 (P450) such as CYP1A1 by 3-methylcholanthrene (MC) and related polycyclic aromatic hydrocarbons is well characterized. We reported previously that MC treatment triggers a pronounced downregulation, particularly at the protein level, of mouse hepatic Cyp3a11, a counterpart of the key human drug-metabolizing enzyme CYP3A4. To determine whether this effect of MC requires hepatic microsomal P450 activity, we studied liver Cpr-null (LCN) mice with hepatocyte-specific conditional deletion of the NADPH-cytochrome P450 oxidoreductase gene. In vehicle-treated animals, basal levels of CYP3A11 mRNA and CYP3A protein immunoreactivity were elevated by approximately 9-fold in LCN mice compared with wild-type (WT) mice, whereas CYP3A catalytic activity was profoundly compromised in LCN mice. MC treatment caused suppression of CYP3A11 mRNA, CYP3A protein immunoreactivity, and CYP3A catalytic activity in WT mice, and the MC effects at the mRNA and protein levels were maintained in LCN mice. Flavin-containing monooxygenase-3 (Fmo3) induction by MC was suggested previously to occur via an AHR-dependent mechanism requiring conversion of the parent compound to DNA-damaging reactive metabolites; however, hepatic FMO3 mRNA levels were dramatically increased by MC in both WT and LCN mice. MC did not function as a mechanism-based inactivator of CYP3A enzymes in hepatic microsomes prepared from untreated WT mice, under conditions in which 1-aminobenzotriazole caused marked NADPH-dependent loss of total P450 content and CYP3A catalytic activity. These results indicate that MC downregulates mouse hepatic CYP3A protein via a pretranslational mechanism that does not require hepatic microsomal P450-dependent activity. PMID:23846873

  20. Hepatic calcium efflux during cytochrome P-450-dependent drug oxidations at the endoplasmic reticulum in intact liver.

    PubMed

    Sies, H; Graf, P; Estrela, J M

    1981-06-01

    During metabolism of (type I) drugs by cytochrome P-450-dependent monooxygenase of the endoplasmic reticulum, the NADPH/NADP+ ratio in rat liver selectively decreases to approximately one-half of the control values, whereas the NADH/NAD+ ratio remains practically unaffected [Sies, H. & Brauser, B. (1970) Eur. J. Biochem. 15, 521-540]. In view of the observations with isolated mitochondria [Lehninger, A. L., Vercesi, A. & Bababunmi, E. A. (1978) Proc. Natl. Acad. Sci. USA 75, 1690-1694] of stimulated Ca2+ efflux upon nicotinamide nucleotide oxidation, the selective oxidation of NADPH in cytosol and mitochondria during drug oxidations was considered a useful experimental tool for the determination of whether the oxidation of NADPH or of NADH is responsible for Ca2+ efflux. With perfused livers from phenobarbital-treated rats, Ca2+ efflux was demonstrated, amounting to 8 nmol/min per gram of liver (wet weight), with aminopyrine, ethylmorphine, or hexobarbital as drug substrates. Drug-associated Ca2+ release was diminished when the inhibitor metyrapone was also present, or when drug oxidation was suppressed during N2 anoxia or in the presence of antimycin A in livers from fasted rats. Ca2+ efflux was elicited also by infusion of the thiol oxidant diamide, and by t-butyl hydroperoxide. However whereas Ca2+ efflux elicited by these compounds was restricted upon addition of the thiol dithioerythritol, there was little, if any, sensitivity of the drug-associated Ca2+ efflux to the thiol. Further mitochondrial oxidation of NADPH by addition of ammonium chloride had no effect on drug-associated Ca2+ efflux. Prior addition of the alpha-agonist phenylephrine suppressed the Ca2+ release by drug addition. While the molecular mechanism involved in Ca2+ efflux from liver mitochondria and from hepatocytes as well as the regulatory significance are not yet known, it is concluded from the present experiments that in case of nicotinamide nucleotide-linked Ca2+ efflux the oxidation of

  1. Mammalian Cytochrome P450-Dependent Metabolism of Polychlorinated Dibenzo-p-dioxins and Coplanar Polychlorinated Biphenyls

    PubMed Central

    Inui, Hideyuki; Itoh, Toshimasa; Yamamoto, Keiko; Ikushiro, Shin-Ichi; Sakaki, Toshiyuki

    2014-01-01

    Polychlorinated dibenzo-p-dioxins (PCDDs) and coplanar polychlorinated biphenyls (PCBs) contribute to dioxin toxicity in humans and wildlife after bioaccumulation through the food chain from the environment. The authors examined human and rat cytochrome P450 (CYP)-dependent metabolism of PCDDs and PCBs. A number of human CYP isoforms belonging to the CYP1 and CYP2 families showed remarkable activities toward low-chlorinated PCDDs. In particular, human CYP1A1, CYP1A2, and CYP1B1 showed high activities toward monoCDDs, diCDDs, and triCDDs but no detectable activity toward 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD). Large amino acids located at putative substrate-recognition sites and the F-G loop in rat CYP1A1 contributed to the successful metabolism of 2,3,7,8-tetraCDD. Rat, but not human, CYP1A1 metabolized 3,3',4,4',5-pentachlorobiphenyl (CB126) to two hydroxylated metabolites. These metabolites are probably less toxic than is CB126, due to their higher solubility. Homology models of human and rat CYP1A1s and CB126 docking studies indicated that two amino acid differences in the CB126-binding cavity were important for CB126 metabolism. In this review, the importance of CYPs in the metabolism of dioxins and PCBs in mammals and the species-based differences between humans and rats are described. In addition, the authors reveal the molecular mechanism behind the binding modes of dioxins and PCBs in the heme pocket of CYPs. PMID:25123135

  2. Reconstitution of cytochrome P-450-dependent digitoxin 12 beta-hydroxylase from cell cultures of foxglove (Digitalis lanata EHRH.).

    PubMed Central

    Petersen, M; Seitz, H U

    1988-01-01

    Cytochrome P-450-dependent digitoxin 12 beta-hydroxylase from cell cultures of foxglove (Digitalis lanata) was solubilized from microsomal membranes with CHAPS (3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulphonic acid). Cytochrome P-450 was separated from NADPH: cytochrome c (P-450) reductase by ion-exchange chromatography on DEAE-Sephacel. NADPH:cytochrome c (P-450) reductase was further purified by affinity chromatography on 2',5'-ADP-Sepharose 4B. This procedure resulted in a 248-fold purification of the enzyme; on SDS/polyacrylamide-gel electrophoresis after silver staining, only one band, corresponding to a molecular mass of 80 kDa, was present. The digitoxin 12 beta-hydroxylase activity could be reconstituted by incubating partially purified cytochrome P-450 and NADPH:cytochrome c (P-450) reductase together with naturally occurring microsomal lipids and flavin nucleotides. This procedure yielded about 10% of the original amount of digitoxin 12 beta-hydroxylase. PMID:3137929

  3. Cytokine-mediated bone resorption is cytochrome P-450 dependent. Student Research Award 1998.

    PubMed

    Young, N; Chole, R

    1999-12-01

    Localized bone loss leads to much of the morbidity of chronic otitis media. Although the cellular events of bone remodeling have been well established, their regulation remains poorly understood. Various cytokines, including tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, used alone and in combination, are powerful inducers of bone resorption. One of the modulators of cytokine-induced bone resorption is nitric oxide (NO), a product of the action of NO synthase (NOS) on L -arginine to form NO. Cytochrome P-450, an enzyme that is similar to NOS both structurally and functionally, may also have a role in NO production in various cellular systems. The goal of this study was to elucidate a possible role of cytochrome P-450 in bone. In this study cytokine-induced bone resorption was blocked with cimetidine and clotrimazole, which are selective inhibitors of the cytochrome P-450 IIIA family and 7-ethoxyresorufin, a nonspecific cytochrome P-450 inhibitor. A concomitant reduction of NO was also observed. This effect may be explained by cytochrome P-450 being a preferred alternative pathway or providing an essential cofactor to NOS in bone. PMID:10580224

  4. Induction and Characterization of a Cytochrome P-450-Dependent Camphor Hydroxylase in Tissue Cultures of Common Sage (Salvia officinalis).

    PubMed Central

    Funk, C.; Croteau, R.

    1993-01-01

    (+)-Camphor, a major monoterpene of the essential oil of common sage (Salvia officinalis), is catabolized in senescent tissue, and the pathway for the breakdown of this bicyclic ketone has been previously elucidated in sage cell-suspension cultures. In the initial step of catabolism, camphor is oxidized to 6-exo-hydroxycamphor, and the corresponding NADPH- and O2-dependent hydroxylase activity was demonstrated in microsomal preparations of sage cells. Several well-established inhibitors of cytochrome P-450-dependent reactions, including cytochrome c, clotrimazole, and CO, inhibited the hydroxylation of camphor, and CO-dependent inhibition was partially reversed by blue light. Upon treatment of sage suspension cultures with 30 mM MnCl2, camphor-6-hydroxylase activity was induced up to 7-fold. A polypeptide with estimated molecular mass of 58 kD from sage microsomal membranes exhibited antigenic cross-reactivity in western blot experiments with two heterologous polyclonal antibodies raised against cytochrome P-450 camphor-5-exo-hydroxylase from Pseudomonas putida and cytochrome P-450 limonene-6S-hydroxylase from spearmint (Mentha spicata). Dot blotting indicated that the concentration of this polypeptide increased with camphor hydroxylase activity in microsomes of Mn2+-induced sage cells. These results suggest that camphor-6-exo-hydroxylase from sage is a microsomal cytochrome P-450 monooxygenase that may share common properties and epitopes with bacterial and other plant monoterpene hydroxylases. PMID:12231778

  5. Induction and characterization of a cytochrome P-450-dependent camphor hydroxylase in tissue cultures of common sage (Salvia officinalis)

    SciTech Connect

    Funk, C.; Croteau, R. )

    1993-04-01

    (+)-Camphor, a major monoterpene of the essential oil of common sage (Salvia officinalis), is catabolized in senescent tissue, and the pathway for the breakdown of this bicyclic ketone has been previously elucidated in sage cell-suspension cultures. In the initial step of catabolism, camphor is oxidized to 6-exo-hydroxycamphor, and the corresponding NADPH- and O[sub 2]-dependent hydroxylase activity was demonstrated in microsomal preparations of sage cells. Several well-established inhibitors of cytochrome P-450-dependent reactions, including cytochrome c, clotrimazole, and CO, inhibited the hydroxylation of camphor, and CO-dependent inhibition was partially reversed by blue light. Upon treatment of sage suspension cultures with 30 mM MnCl[sub 2], camphor-6-hydroxylase activity was induced up to 7-fold. A polypeptide with estimated molecular mass of 58 kD from sage microsomal membranes exhibited antigenic cross-reactivity in western blot experiments with two heterologous polyclonal antibodies raised against cytochrome P-450 camphor-5-exo-hydroxylase from Pseudomonas putida and cytochrome P-450 limonene-6S-hydroxylase from spearmint (Mentha spicata). Dot blotting indicated that the concentration of this polypeptide increased with camphor hydroxylase activity in microsomes of Mn[sup 2+]-induced sage cells. These results suggest that camphor-6-exo-hydroxylase from sage is a microsomal cytochrome P-450 monooxygenase that may share common properties and epitopes with bacterial and other plant monoterpene hydroxylases. 44 refs., 6 figs., 2 tabs.

  6. Metabolism of fluperlapine by cytochrome P450-dependent and flavin-dependent monooxygenases in continuous cultures of rat and human cells.

    PubMed

    Fischer, V; Wiebel, F J

    1990-04-15

    The metabolism of fluperlapine, a neuroleptic dibenzazepine derivative with a N-methyl-piperazinyl substituent, was investigated in continuous cultures of rat and human cells which express various cytochrome P450-dependent monooxygenase activities. The differentiated rat hepatoma cells H4IIEC3/G- and their variants 2sFou and FGC-5 metabolized fluperlapine predominantly by N-oxygenation and only to a minor degree by N-demethylation or glucuronidation of primary phenolic products. Total fluperlapine metabolism in dedifferentiated rat hepatoma cells H5 and partially differentiated human hepatoma cells HepG2 was much smaller than in the differentiated rat hepatoma lines. This was primarily attributable to their low capacity for N-oxygenation. Human lung adenocarcinoma lines NCI-H322 and NCI-H358 formed only trace amounts of fluperlapine N-oxide. Pretreatment of 2sFou cells with benz(a)anthracene, phenobarbital or dexamethasone markedly increased the formation of N-demethylated and glucuronidated products but did not affect the rate of N-oxide formation. Guanethidine and cysteamine, inhibitors of flavin-dependent monooxygenase activity, reduced fluperlapine N-oxidation more strongly than aldrin epoxidation, a marker for cytochrome P450 activity. In contrast, n-octylamine inhibited aldrin epoxidation but was without effect on fluperlapine N-oxygenation. The results suggest that certain cells in continuous culture are capable of expressing flavin-dependent monooxygenase(s) in addition to cytochrome P450-containing monooxygenases. Such cells may offer useful systems for studying the oxidative metabolism of a broad spectrum of xenobiotics and analysing the importance of the two oxygenation reactions for the biological effects of their substrates. PMID:2322314

  7. Formaldehyde production promoted by rat nasal cytochrome P-450-dependent monooxygenases with nasal decongestants, essences, solvents, air pollutants, nicotine, and cocaine as substrates

    SciTech Connect

    Dahl, A.R.; Hadley, W.M.

    1983-02-01

    To identify compounds which might be metabolized to formaldehyde in the nasal cavity, 32 potential substrates for cytochrome P-450-dependent monooxygenases were screened with rat nasal and, for comparison, liver microsomes. Tested substrates included 6 nasal decongestants, cocaine, nicotine, 9 essences, 3 potential air pollutants, and 12 solvents. Each test substrate, with the possible exception of the air pollutants, contained one or more N-methyl, O-methyl, or S-methyl groups. Eighteen of the tested materials were metabolized to produce formaldehyde by nasal microsomes. Five substrates, namely, the solvents HMPA and dimethylaniline, cocaine, and the essences dimethyl anthranilate and p-methoxyacetophenone, were metabolized to produce formaldehyde at rates exceeding 1000 pmol/mg microsomal protein/min by nasal microsomes. Eight substrates, including four nasal decongestants, nicotine, and an extract of diesel exhaust particles, were metabolized to produce formaldehyde at rates of 200 to 1000 pmol/mg microsomal protein/min. Five other substrates were metabolized to formaldehyde at detectable rates. The results indicate that a variety of materials which often come in contact with the nasal mucosa can be metabolized to formaldehyde by nasal enzymes. The released formaldehyde may influence the irritancy of inhaled compounds and has been suggested to play a role in the tumorigenicity of some compounds.

  8. IMPROVING STRUCTURE-LINKED ACCESS TO PUBLICLY AVAILABLE CHEMICAL TOXICITY INFORMATION

    EPA Science Inventory

    Hepatotoxicity of the Herbicide Alachlor Associated with Glutathione Depletion, Oxidative Damage and Protein S-Cysteinyl Adduction.

    Toxicity of the herbicide alachlor (2-chloro-2',6'-diethtl-N-[methoxtmethtl]-acetanilide) has been attributed to cytochrome P450-dependent me...

  9. Aluminum toxicity. Hematological effects.

    PubMed

    Mahieu, S; del Carmen Contini, M; Gonzalez, M; Millen, N; Elias, M M

    2000-01-01

    Sequential effects of intoxication with aluminum hydroxide (Al) (80 mg/Kg body weight, i.p., three times a week), were studied on rats from weaning and up to 28 weeks. The study was carried out on hematological and iron metabolism-related parameters on peripheral blood, at the end of the 1st, 2nd, 3rd, 4th, 5th and 6th months of exposure. As it was described that hematotoxic effects of Al are mainly seen together with high levels of uremia, renal function was measured at the same periods. The animals treated developed a microcytosis and was accompanied by a decrease in mean corpuscular hemoglobin (MCH). Significantly lower red blood cell counts (RBC million/microl) were found in rats treated during the 1st month. These values matched those obtained for control rats during the 2nd month. From the 3rd month onwards, a significant increase was observed as compared to control groups, and the following values were obtained by the 6th month: (T) 10.0 +/- 0.3 versus (C) 8.7 +/- 0.2 (million/microl). Both MCH and mean corpuscular volume (MCV) were found to be significantly lower in groups treated from the 2nd month. At the end of the 6th month the following values were found: MCH (T) 13.3 +/- 0.1 versus (C) 16.9 +/- 0.3 (pg); MCV (T) 42.1 +/- 0.7 versus (C) 51.8 +/- 0.9 (fl). Al was found responsible for lower serum iron concentration levels and in the percentage of transferrin saturation. Thus, although microcytic anemia constitutes an evidence of chronic aluminum exposure, prolonged exposure could lead to a recovery of hematocrit and hemoglobin concentration values with an increase in red cell number. Nevertheless, both microcytosis and the decrease of MCH would persist. These modifications took place without changes being observed in the renal function during the observation period. PMID:10643868

  10. Effects of micronutrients on metal toxicity.

    PubMed Central

    Peraza, M A; Ayala-Fierro, F; Barber, D S; Casarez, E; Rael, L T

    1998-01-01

    There is growing evidence that micronutrient intake has a significant effect on the toxicity and carcinogenesis caused by various chemicals. This paper examines the effect of micronutrient status on the toxicity of four nonessential metals: cadmium, lead, mercury, and arsenic. Unfortunately, few studies have directly examined the effect of dietary deficiency or supplementation on metal toxicity. More commonly, the effect of dietary alteration must be deduced from the results of mechanistic studies. We have chosen to separate the effect of micronutrients on toxic metals into three classes: interaction between essential micronutrients and toxic metals during uptake, binding, and excretion; influence of micronutrients on the metabolism of toxic metals; and effect of micronutrients on secondary toxic effects of metals. Based on data from mechanistic studies, the ability of micronutrients to modulate the toxicity of metals is indisputable. Micronutrients interact with toxic metals at several points in the body: absorption and excretion of toxic metals; transport of metals in the body; binding to target proteins; metabolism and sequestration of toxic metals; and finally, in secondary mechanisms of toxicity such as oxidative stress. Therefore, people eating a diet deficient in micronutrients will be predisposed to toxicity from nonessential metals. PMID:9539014

  11. Toxic Stress: Effects, Prevention and Treatment

    PubMed Central

    Franke, Hillary A.

    2014-01-01

    Children who experience early life toxic stress are at risk of long-term adverse health effects that may not manifest until adulthood. This article briefly summarizes the findings in recent studies on toxic stress and childhood adversity following the publication of the American Academy of Pediatrics (AAP) Policy Report on the effects of toxic stress. A review of toxic stress and its effects is described, including factors of vulnerability, resilience, and the relaxation response. An integrative approach to the prevention and treatment of toxic stress necessitates individual, community and national focus. PMID:27417486

  12. Bridging environmental mixtures and toxic effects

    PubMed Central

    Allan, Sarah E.; Smith, Brian W.; Tanguay, Robert L.; Anderson, Kim A.

    2012-01-01

    BRIDGES is a bioanalytical tool that combines passive sampling with the embryonic zebrafish developmental toxicity bioassay to provide a quantitative measure of the toxicity of bioavailable complex mixtures. Passive sampling devices (PSDs), which sequester and concentrate bioavailable organic contaminants from the environment, were deployed in the Willamette and Columbia Rivers within and outside of the Portland Harbor Superfund site in Portland, Oregon. Six sampling events were conducted in the summer and fall of 2009 and 2010. PSD extracts were analyzed for polycyclic aromatic hydrocarbon (PAH) compounds and screened for 1201 chemicals of concern using deconvolution reporting software. The developmental toxicity of the extracts was analyzed using the embryonic zebrafish bioassay. BRIDGES provided site-specific, temporally resolved information about environmental contaminant mixtures and their toxicity. Multivariate modeling approaches were applied to paired chemical and toxic effects data sets to help unravel chemistry-toxicity associations. Modeling demonstrated a significant correlation between PAH concentrations and the toxicity of the samples and identified a subset of PAH analytes that were the most highly correlated with observed toxicity. Although this research highlights the complexity of discerning specific bioactive compounds in complex mixtures, it demonstrates methods for associating toxic effects with chemical characteristics of environmental samples. PMID:23001962

  13. Mercury toxicity and neurodegenerative effects.

    PubMed

    Carocci, Alessia; Rovito, Nicola; Sinicropi, Maria Stefania; Genchi, Giuseppe

    2014-01-01

    Mercury is among the most toxic heavy metals and has no known physiological role in humans. Three forms of mercury exist: elemental, inorganic and organic. Mercury has been used by man since ancient times. Among the earliest were the Chinese and Romans, who employed cinnabar (mercury sulfide) as a red dye in ink (Clarkson et al. 2007). Mercury has also been used to purify gold and silver minerals by forming amalgams. This is a hazardous practice, but is still widespread in Brazil's Amazon basin, in Laos and in Venezuela, where tens of thousands of miners are engaged in local mining activities to find and purify gold or silver. Mercury compounds were long used to treat syphilis and the element is still used as an antiseptic,as a medicinal preservative and as a fungicide. Dental amalgams, which contain about 50% mercury, have been used to repair dental caries in the U.S. since 1856.Mercury still exists in many common household products around the world.Examples are: thermometers, barometers, batteries, and light bulbs (Swain et al.2007). In small amounts, some organo mercury-compounds (e.g., ethylmercury tiosalicylate(thimerosal) and phenylmercury nitrate) are used as preservatives in some medicines and vaccines (Ballet al. 2001).Each mercury form has its own toxicity profile. Exposure to Hg0 vapor and MeHg produce symptoms in CNS, whereas, the kidney is the target organ when exposures to the mono- and di-valent salts of mercury (Hg+ and Hg++, respectively)occur. Chronic exposure to inorganic mercury produces stomatitis, erethism and tremors. Chronic MeHg exposure induced symptoms similar to those observed in ALS, such as the early onset of hind limb weakness (Johnson and Atchison 2009).Among the organic mercury compounds, MeHg is the most biologically available and toxic (Scheuhammer et a!. 2007). MeHg is neurotoxic, reaching high levels of accumulation in the CNS; it can impair physiological function by disrupting endocrine glands (Tan et a!. 2009).The most

  14. Linking Arsenic Metabolism and Toxic Effects

    EPA Science Inventory

    Although arsenic has been long recognized as a toxicant and a carcinogen, the molecular basis for few of its adverse effects are well understood. Like other metalloids, arsenic undergoes extensive metabolism involving oxidation state changes and formation of methyl-arsenic bonds ...

  15. EFFECTS OF BRINE ADDITION ON EFFLUENT TOXICITY AND MARINE TOXICITY IDENTIFICATION EVALUATION (TIE) MANIPULATIONS

    EPA Science Inventory

    Little information is available concerning the effect of salinity adjustment on effluent storage and toxicity identification evaluation (TIE) performance. hese factors are important for accurate assessments of potential toxicity to marine organisms. he objective of this study was...

  16. Amiodarone: review of pulmonary effects and toxicity.

    PubMed

    Papiris, Spyros A; Triantafillidou, Christina; Kolilekas, Likurgos; Markoulaki, Despoina; Manali, Effrosyni D

    2010-07-01

    Amiodarone, a bi-iodinated benzofuran derivative, is, because of its high effectiveness, one of the most widely used antiarrhythmic agents. However, adverse effects, especially potentially fatal and non-reversible acute and chronic pulmonary toxicity, continue to be observed. This review provides an update of the epidemiology, pathophysiology, clinical presentation, treatment and outcome of amiodarone pulmonary effects and toxicity. Lung adverse effects occur in approximately 5% of treated patients. The development of lung complications appears to be associated with older age, duration of treatment and cumulative dosage, high levels of its desethyl metabolite, history of cardiothoracic surgery and/or use of high oxygen mixtures, use of iodinated contrast media, and probably pre-existing lung disease as well as co-existing respiratory infections. Amiodarone-related adverse pulmonary effects may develop as early as from the first few days of treatment to several years later. The onset of pulmonary toxicity may be either insidious or rapidly progressive. Cough, new chest infiltrates in imaging studies and reduced lung diffusing capacity in the appropriate clinical setting of amiodarone use, after the meticulous exclusion of infection, malignancy and pulmonary oedema, are the cardinal clinical and laboratory elements for diagnosis. Pulmonary involvement falls into two categories of different grades of clinical significance: (i) the ubiquitous 'lipoid pneumonia', the so-called 'amiodarone effect', which is usually asymptomatic; and (ii) the more appropriately named 'amiodarone toxicity', which includes several distinct clinical entities related to the differing patterns of lung inflammatory reaction, such as eosinophilic pneumonia, chronic organizing pneumonia, acute fibrinous organizing pneumonia, nodules or mass-like lesions, nonspecific interstitial pneumonia-like and idiopathic pulmonary fibrosis-like interstitial pneumonia, desquamative interstitial pneumonia

  17. Importance of endogenous prostaglandins for the toxicity of cyclosporin A to rat endocrine and exocrine pancreas?

    PubMed Central

    Rünzi, M; Peskar, B M; von Schönfeld, J; Müller, M K

    1992-01-01

    Previous work has shown that cyclosporin A is toxic to the endocrine and exocrine pancreas. The aim of this study was to examine whether endogenous eicosanoids play a role in controlling cyclosporin A induced toxicity. Rats were treated for eight days with indomethacin (2 mg/kg, twice daily) in addition to cyclosporin A (5 or 10 mg/kg daily). Effects of drug treatments on exocrine (as assessed by amylase and protein secretion into the pancreatic juice) and endocrine (as assessed by the glucose dependent insulin release) pancreatic functions, and pancreatic formation of prostaglandins and thromboxane were evaluated. Treatment with cyclosporin A in the doses used did not inhibit eicosanoid formation by the pancreatic tissue ex vivo. Indomethacin caused significant inhibition of pancreatic formation of prostaglandin E2, 6k prostaglandin F1 alpha and thromboxane B2. Combined treatment with indomethacin and cyclosporin A (5 or 10 mg/kg) augmented cyclosporin A induced pancreatic toxicity with further impairment of insulin release, amylase secretion, and pancreatic juice protein content, but did not result in more pronounced inhibition of pancreatic eicosanoid formation. The increased toxicity of the combined treatment was, however, associated with raised cyclosporin A whole blood concentrations. The data suggest that the potentiation of pancreatic toxicity of cyclosporin A observed during coadministration of indomethacin is not the result of suppression of endogenous pancreatic eicosanoid biosynthesis, but more likely results from altered cyclosporin A pharmacokinetic which may be caused by an interference of indomethacin with the hepatic cytochrome P-450 dependent monooxygenase involved in cyclosporin A metabolism. The possibility that coadministration of non-steroidal antiinflammatory drugs aggravates toxic effects in cyclosporin A treated patients should be considered. PMID:1280611

  18. Toxic effects of boron on mallard reproduction

    USGS Publications Warehouse

    Smith, G.J.; Anders, V.P.

    1989-01-01

    Boron, a naturally occurring trace element generally considered environmentally innocuous, was documented to severely impair mallard reproduction. Boron is leached from irrigated agricultural soils and transported in drainage water that contaminates wetlands. Until now, only the selenium accumulated in aquatic food chains has been documented to pose a toxic hazard to wildlife in drainage water wetlands. Management of drainage water-contaminated environments must now also consider the adverse effects of boron, as well as the possible interactions of drainage water contaminants.

  19. Human Health Effects Associated with Exposure to Toxic Cyanobacteria

    EPA Science Inventory

    Reports of toxic cyanobacteria blooms are increasing worldwide. Warming and eutrophic surface water systems support the development of blooms. We examine the evidence for adverse human health effects associated with exposure to toxic blooms in drinking water, recreational water a...

  20. Environmental Mercury and Its Toxic Effects

    PubMed Central

    Rice, Kevin M.; Walker, Ernest M.; Wu, Miaozong; Gillette, Chris

    2014-01-01

    Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects. PMID:24744824

  1. Environmental mercury and its toxic effects.

    PubMed

    Rice, Kevin M; Walker, Ernest M; Wu, Miaozong; Gillette, Chris; Blough, Eric R

    2014-03-01

    Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects. PMID:24744824

  2. Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models

    SciTech Connect

    Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

    2011-07-15

    Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds.

  3. Effect of zeolite on toxicity of ammonia in freshwater sediments: Implications for toxicity identification evaluation procedures

    SciTech Connect

    Besser, J.M.; Ingersoll, C.G.; Leonard, E.N.; Mount, D.R.

    1998-11-01

    Techniques for reducing ammonia toxicity in freshwater sediments were investigated as part of a project to develop toxicity identification and evaluation (TIE) procedures for whole sediments. Although ammonia is a natural constituent of freshwater sediments, pollution can lead to ammonia concentrations that are toxic to benthic invertebrates, and ammonia can also contribute to the toxicity of sediments that contain more persistent contaminants. The authors investigated the use of amendments of a natural zeolite mineral, clinoptilolite, to reduce concentrations of ammonia in sediment pore water. Zeolites have been widely used for removal of ammonia in water treatment and in aqueous TIE procedures. The addition of granulated zeolite to ammonia-spiked sediments reduced pore-water ammonia concentrations and reduced ammonia toxicity to invertebrates. Amendments of 20% zeolite (v/v) reduced ammonia concentrations in pore water by {ge}70% in spiked sediments with ammonia concentrations typical of contaminated freshwater sediments. Zeolite amendments reduced toxicity of ammonia-spiked sediments to three taxa of benthic invertebrates (Hyalella azteca, Lumbriculus variegatus, and Chironomus tentans), despite their widely differing sensitivity to ammonia toxicity. In contrast, zeolite amendments did not reduce acute toxicity of sediments containing high concentrations of cadmium or copper or reduce concentrations of these metals in pore waters. These studies suggest that zeolite amendments, used in conjunction with toxicity tests with sensitive taxa such as H. azteca, may be an effective technique for selective reduction of ammonia toxicity in freshwater sediments.

  4. Effect of zeolite on toxicity of ammonia in freshwater sediments: Implications for toxicity identification evaluation procedures

    USGS Publications Warehouse

    Besser, J.M.; Ingersoll, C.G.; Leonard, E.N.; Mount, D.R.

    1998-01-01

    Techniques for reducing ammonia toxicity in freshwater sediments were investigated as part of a project to develop toxicity identification and evaluation (TIE) procedures for whole sediments. Although ammonia is a natural constituent of freshwater sediments, pollution can lead to ammonia concentrations that are toxic to benthic invertebrates, and ammonia can also contribute to the toxicity of sediments that contain more persistent contaminants. We investigated the use of amendments of a natural zeolite mineral, clinoptilolite, to reduce concentrations of ammonia in sediment pore water. Zeolites have been widely used for removal of ammonia in water treatment and in aqueous TIE procedures. The addition of granulated zeolite to ammonia-spiked sediments reduced pore-water ammonia concentrations and reduced ammonia toxicity to invertebrates. Amendments of 20% zeolite (v/v) reduced ammonia concentrations in pore water by ???70% in spiked sediments with ammonia concentrations typical of contaminated freshwater sediments. Zeolite amendments reduced toxicity of ammonia-spiked sediments to three taxa of benthic invertebrates (Hyalella azteca, Lumbriculus variegatus, and Chironomus tentans), despite their widely differing sensitivity to ammonia toxicity. In contrast, zeolite amendments did not reduce acute toxicity of sediments containing high concentrations of cadmium or copper or reduce concentrations of these metals in pore waters. These studies suggest that zeolite amendments, used in conjunction with toxicity tests with sensitive taxa such as H. azteca, may be an effective technique for selective reduction of ammonia toxicity in freshwater sediments.

  5. Toxicity and Neuropharmacological Effects of Elenine

    PubMed Central

    Navarro, Eduardo; Alonso, S. J.; Navarro, R.

    2011-01-01

    Elenine is the aglycone of elenoside, a cytotoxic arylnaphthalene lignan (NSC 644013-W/1) derived from Justicia hyssopifolia. (Family: Acanthaceae). Elenoside is a β-D-glucoside, with a similar chemical structure to etoposide, exhibiting central depressant activity. In the present study, elenine was given to mice and rats at doses of 10, 20, and 40 mg/kg. Acute toxicity (24 h) and general behaviour in mice was studied as well as its effects on muscular relaxant activity, locomotor activity (Varimex test), and the open-field test and were compared with 10 mg/kg of chlorpromazine. Elenine produced a reduction in the permanence time in muscular relaxant activity (traction test). Spontaneous activity was lower in the Varimex test. The ambulation and rearing were lower compared with the control group, and an increase in boluses was observed in the open-field test. Thus, it can be concluded that elenine has central sedative effects at lower doses than those used with elenoside and has a possible application in conditions of anxiety. PMID:21716687

  6. Toxic effects of pentachlorophenol on Lemna polyrhiza.

    PubMed

    Song, Zhihui; Huang, Guolan

    2007-03-01

    This paper reports the toxic effects of pentachlorophenol (PCP) on duckweed, Lemna polyrhiza. The 8-day IC(50) of PCP to L. polyrhiza was 8.08 mg/L. At 0.2 and 0.5 mg/L, PCP inhibited L. polyrhiza chloroplast activity. At low PCP exposures, chloroplast activity was more sensitive than chlorophyll content of L. polyrhiza. At 0.2 and 0.5mg/L, PCP stimulated L. polyrhiza nitrate reductase activity. At 0.2 and 0.5mg/L PCP, duckweed peroxidase activity was 78.3% and 91.0% of the control test, respectively. The bioaccumulation factors (BCFs) of PCP in L. polyrhiza were 79 and 62 at 0.2 and 0.5mg/L PCP, respectively. This is the first study of the effect of PCP on peroxidase activity, nitrate reductase activity, and chloroplast activity of L. polyrhiza. The BCFs of PCP in L. polyrhiza are also for reported the first time. PMID:16325908

  7. Sublethal toxicant effects with dynamic energy budget theory: model formulation.

    PubMed

    Muller, Erik B; Nisbet, Roger M; Berkley, Heather A

    2010-01-01

    We develop and test a general modeling framework to describe the sublethal effects of pollutants by adding toxicity modules to an established dynamic energy budget (DEB) model. The DEB model describes the rates of energy acquisition and expenditure by individual organisms; the toxicity modules describe how toxicants affect these rates by changing the value of one or more DEB parameters, notably the parameters quantifying the rates of feeding and maintenance. We investigate four toxicity modules that assume: (1) effects on feeding only; (2) effects on maintenance only; (3) effects on feeding and maintenance with similar values for the toxicity parameters; and (4) effects on feeding and maintenance with different values for the toxicity parameters. We test the toxicity modules by fitting each to published data on feeding, respiration, growth and reproduction. Among the pollutants tested are metals (mercury and copper) and various organic compounds (chlorophenols, toluene, polycyclic aromatic hydrocarbons, tetradifon and pyridine); organisms include mussels, oysters, earthworms, water fleas and zebrafish. In most cases, the data sets could be adequately described with any of the toxicity modules, and no single module gave superior fits to all data sets. We therefore propose that for many applications, it is reasonable to use the most general and parameter sparse module, i.e. module 3 that assumes similar effects on feeding and maintenance, as a default. For one example (water fleas), we use parameter estimates to calculate the impact of food availability and toxicant levels on the long term population growth rate. PMID:19633955

  8. Cytochrome P-450-dependent monooxygenases in olfactory epithelium of dogs: possible role in tumorigenicity

    SciTech Connect

    Dahl, A.R.; Hadley, W.M.; Hahn, F.F.; Benson, J.M.; McClellan, R.O.

    1982-04-02

    The respiratory tract epithelium of dogs, from the nose to the lungs, was examined for cytochrome P-450 and associated biotransformation activities. In the ethmoturbinates, where olfactory epithelium is located, the amount of cytochrome P-450 was comparable to that in the liver, when measured on the basis of activity per milligram of microsomal protein. The rest of the nasal region also contained large quantities of cytochrome P-450. The presence of these enzymes in the nose may be important in chemical-induced tumorigenesis. The nasal carcinogen hexamethylphosphoramide was shown to be metabolized by nasal microsomal enzymes to another nasal carcinogen, formaldehyde.

  9. [Cytochrome P-450-dependent reactions during intensified biosynthesis of coenzyme A in hepatocytes].

    PubMed

    Sushko, L I; Sheĭbak, V M; Abakumov, G Z; Moĭseenok, A K

    1986-01-01

    After subcutaneous administration into male rats of 4-phosphopantothenic acid and pantethine during 10 days at a dose equivalent to 30 mg/kg of calcium pantothenate total content of CoA was increased in liver tissue. Both these preparations activated the liver endoplasmic reticulum monooxygenase system mainly at the step of substrate hydroxylation. The phenomenon observed appears to occur due to activation of cytochrome P-450 biosynthesis and/or to alterations in phospholipid composition of microsomal membranes. PMID:3765494

  10. Alterations of cytochrome P450-dependent monooxygenase activities in Eriocheir japonicus in response to water pollution.

    PubMed Central

    Ishizuka, M; Hoshi, H; Minamoto, N; Masuda, M; Kazusaka, A; Fujita, S

    1996-01-01

    Eriocheir japonicus, fresh-water crabs inhabiting rivers and estuaries in Japan, were investigated for cytochrome P450 (CYP)-dependent drug-metabolizing enzyme activities to see if these activities reflect the river pollution gradient. From the laboratory dose-response experiments, we found that the polycyclic aromatic hydrocarbon (PAH) 3-methylcholanthrene induced total CYP contents, ethoxycoumarin O-deethylase activity, and bunitrolol 4-hydroxylase activity in crab hepatopancreas. In the field studies, crabs collected from the river with the highest concentration of PAHs exhibited the highest levels of CYP, the highest activities of benzo[a]pyrene 3-hydroxylase, imipramine 2-hydroxylase, bunitrolol 4-hydroxylase, ethoxycoumarin O-deethylase, and the ability to metabolically activate benzo[a]pyrene, but erythromycin N-demethylase activity was not induced. The correlation between PAH levels and drug-metabolizing enzyme activities in female crabs were not as marked as in male crabs. The levels and activities of CYP did not appear to reflect the concentrations of organochlorines and polychlorinated biphenyl congeners (PCBs) studied in the fat of crab hepatopancreas. Images Figure 1. Figure 2. A Figure 2. B Figure 2. C Figure 3. Figure 4. A Figure 4. B Figure 5. A Figure 5. B Figure 5. C Figure 5. D Figure 5. E Figure 5. F Figure 6. PMID:8841764

  11. The Air Toxics Health Effects Database (ATHED)

    SciTech Connect

    Woodall, George M. Smith, Roy L.

    2008-11-15

    The Air Toxics Health Effects Database (ATHED) is currently used by the EPA's Office of Air Quality Planning and Standards (OAQPS) to support risk assessments for the Residual Risk Program. An assessment of the residual risk is required to be performed at a specified time (typically 8years) following the promulgation of a technology-based Maximum Achievable Control Technologies (MACT) standard. The goal of the Residual Risk Program is to assure that the risk that remains after MACT standards are implemented (i.e., the 'residual risk') is acceptable, and if not, to propose additional regulations to mitigate those risks. ATHED maintains all available reference values for each chemical as separate data records, and includes values for all exposure durations (acute, short-term, subchronic and chronic). These values are used as benchmarks to determine acceptable exposure levels to the hazardous air pollutants (HAPs) listed in Section 112 of the Clean Air Act. ATHED also provides useful background information on the uncertainty and/or modifying factors that were applied in the derivation of each reference value, as well as the point of departure and the critical study/studies. To facilitate comparisons across durations for a specific chemical, ATHED data can be graphically presented.

  12. Effects of brine addition on effluent toxicity and marine toxicity identification evaluation (TIE) manipulations

    SciTech Connect

    Ho, K.T.; Burgess, R.M. ); Mitchell, K. . Biology Dept.); Zappala, M. )

    1995-02-01

    Little information is available concerning the effect of salinity adjustment on effluent storage and toxicity identification evaluation (TIE) performance. These factors are important for accurate assessments of potential toxicity to marine organisms. The objective of this study was to determine (a) the effect of salinity adjustment using hypersaline brine on the toxicity of effluents stored up to 40 d, and (b) to determine the effect of salinity adjustment on TIE manipulations. Changes in effluent toxicity over time were examined by using a municipal and an industrial effluent. A toxicity time series was performed for 16 d for the industrial effluent and 40 d for the municipal effluent. Toxicity was measured with modified 48-h acute Mysidopsis bahia and Menidia beryllina tests. Results indicate that, compared to day 0 test results, effluent stored with brine had fewer significant changes in toxicity than did effluent stored without brine. To determine the effects of brine addition on TIE manipulations, the authors conducted a series of manipulations in which one aliquot of an effluent had brine added prior to the TIE manipulations and the other aliquot had brine added after the TIE manipulation. The manipulations conducted were EDTA addition, sodium thiosulfate addition, C[sub 18] extraction, aeration, filtration, and graduated pH manipulations. Toxicity was measured with the modified 48-h acute mysid test. Addition of brine had no effect on the outcome of TIE manipulations. They have concluded that it is operationally easier to add brine as soon as possible after sampling and that effluent tests should be conducted as soon as practical.

  13. Pb Neurotoxicity: Neuropsychological Effects of Lead Toxicity

    PubMed Central

    Mason, Lisa H.; Harp, Jordan P.; Han, Dong Y.

    2014-01-01

    Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored. PMID:24516855

  14. Power equation for all-or-none effects of oxygen toxicity and cumulative oxygen toxicity.

    PubMed

    Arieli, R

    1994-01-01

    Quantification of the level of O2 toxicity may provide a means of setting limits on various hyperoxic exposures. A previously suggested expression for quantitative oxygen toxicity, DMG = a x t2 x PO2c (t-time, DMG-measured level of O2 toxicity), has been adapted for the all-or-none phenomenon: K = t2 x PO2c. A symptom may appear when K reaches a threshold value Kc. Non-linear regression was successfully applied to all-or-none symptoms from the literature: survival, convulsions, substernal distress, reduction in short circuit current and nerve conduction blockade. The generality of these expressions enabled calculation of cumulative oxygen toxicity and a search for the mechanism of oxygen toxicity. Cumulative oxygen toxicity is calculated in three-step calculation loops in three suggested exposure profiles. For a possible recovery period between exposures the expressions took the form: DMGt = DMGc x e-rt, and Kt = Kc x e-rt, where r is the recovery constant. A possibly bimodal distribution of c close to the values of 1 and 4 could be attributed to systemic effects. PMID:8736032

  15. In vitro exploration of potential mechanisms of toxicity of the human hepatotoxic drug fenclozic acid.

    PubMed

    Rodrigues, Alison V M; Rollison, Helen E; Martin, Scott; Sarda, Sunil; Schulz-Utermoehl, Timothy; Stahl, Simone; Gustafsson, Frida; Eakins, Julie; Kenna, J Gerry; Wilson, Ian D

    2013-08-01

    The carboxylic acid NSAID fenclozic acid exhibited an excellent preclinical safety profile and promising clinical efficacy, yet was withdrawn from clinical development in 1971 due to hepatotoxicity observed in clinical trials. A variety of modern in vitro approaches have been used to explore potential underlying mechanisms. Covalent binding studies were undertaken with [(14)C]-fenclozic acid to investigate the possible role of reactive metabolites. Time-dependent covalent binding to protein was observed in NADPH-supplemented liver microsomes, although no metabolites were detected in these incubations or in reactive metabolite trapping experiments. In human hepatocytes, covalent binding was observed at lower levels than in microsomes and a minor uncharacterizable metabolite was also observed. In addition, covalent binding was observed in incubations undertaken with dog and rat hepatocytes, where a taurine conjugate of the drug was detected. Although an acyl glucuronide metabolite was detected when liver microsomes from human, rat and dog were supplemented with UDPGA, there was no detectable UDPGA-dependent covalent binding. No effects were observed when fenclozic acid was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary efflux transporters BSEP and MRP2 or mitochondrial toxicity to THLE or HepG2 cells. These data suggest that Phase 1 bioactivation plays a role in the hepatotoxicity of fenclozic acid and highlight the unique insight into mechanisms of human drug toxicity that can be provided by investigations of biotransformation and covalent binding to proteins. PMID:23609606

  16. Isolation of bacteria from toxic dinoflagellate Alexandrium minutum and their effects on algae toxicity.

    PubMed

    Lu, Y H; Chai, T J; Hwang, D F

    2000-11-01

    Attempts were made to isolate the bacteria from toxic dinoflagellate Alexandrium minutum T1 and to study the effect of these bacteria on the growth and toxicity of A. minutum T1. It was found that intracellular bacterial species including Pasteurella haemolytica, Pseudomonas vesicularis, and Sphingomonas sp., and extracellular bacterial species including Pasteurolla pneumotropica, Morganella wisconsensis, Flavobacterium oryzihabitans, Pseudomonas pseudomallei, and Sphingomonas sp. All of them were cultured and determined to have non-PSP-producing ability. The maximum cell number of A. minutum cultured without isolated bacteria was higher than that cultured with isolated bacteria. The total toxicity of A. minutum cultured with bacteria was similar to that of A. minutum T1 cultured without bacteria from lag phase to stationary phase, but it was lower after stationary phase. The growth of A. minutum T1 cultured without antibiotics was also better than that cultured with antibiotics. The total toxicity of A. minutum cultured without antibiotics was higher than that of A. minutum cultured with antibiotics. However, the cell toxicity of A. minutum did not decrease even if the culture medium was added with antibiotics. PMID:11126517

  17. Modulation of Hepatic and Renal Metabolism and Toxicity of Trichloroethylene and Perchloroethylene by Alterations in Status of Cytochrome P450 and Glutathione

    PubMed Central

    Lash, Lawrence H.; Putt, David A.; Huang, Paul; Hueni, Sarah E.; Parker, Jean C.

    2007-01-01

    The relative importance of metabolism of trichloroethylene (Tri) and perchloroethylene (Perc) by the cytochrome P450 (P450) and glutathione (GSH) conjugation pathways in their acute renal and hepatic toxicity was studied in isolated cells and microsomes from rat kidney and liver after various treatments to modulate P450 activity/expression or GSH status. Inhibitors of P450 stimulated GSH conjugation of Tri and, to a lesser extent, Perc, in both kidney cells and hepatocytes. Perc was a more potent, acute cytotoxic agent in isolated kidney cells than Tri but Perc-induced toxicity was less responsive than Tri-induced toxicity to modulation of P450 status. These observations are consistent with P450-dependent bioactivation being more important for Tri than for Perc. Incubation of isolated rat hepatocytes with Tri produced no acute cytotoxicity in isolated hepatocytes while Perc produced comparable cytotoxicity as in kidney cells. Modulation of P450 status in hepatocytes produced larger changes in Tri- and Perc-induced cytotoxicity than in kidney cells, with non-selective P450 inhibitors increasing toxicity. Induction of CYP2E1 with pyridine also markedly increased sensitivity of hepatocytes to Tri but had little effect on Perc-induced cytotoxicity. Increases in cellular GSH concentrations increased Tri- and Perc-induced cytotoxicity in kidney cells but not in hepatocytes, consistent with the role of GSH conjugation in Tri- and Perc-induced nephrotoxicity. In contrast, depletion of cellular GSH concentrations moderately decreased Tri- and Perc-induced cytotoxicity in kidney cells but increased cytotoxicity in hepatocytes, again pointing to the importance of different bioactivation pathways and modes of action in kidney and liver. PMID:17433522

  18. Toxic effects on survival and reproduction, a process oriented approach

    SciTech Connect

    Bedaux, J.J.M.; Kooijman, S.A.L.M.

    1995-12-31

    The authors present a new analysis of survival and reproduction data from toxicity tests. The analysis is based on the Dynamic Energy Budget theory for feeding, growth and reproduction, and a one-compartment kinetics for the toxic compound. The toxic effect size depends on the internal concentration. Effects on survival occur via the hazard rate, which is set equal to the killing rate times the internal concentration that exceeds a threshold value. Effects on reproduction depend on the mode of action of the toxicant: direct effects (mortality during oogenesis or energy costs per egg), or indirect effects (via growth, maintenance or assimilation). The effects on energetic parameters are quantified by the ratio between the internal concentration that exceeds a threshold value, and the tolerance concentration. The process-based models quantify effects as functions of exposure time and (external) concentration on a mechanistic basis. The parameters (no effect concentration, killing rate, tolerance concentration and elimination rate) are independent from the chosen exposure time of the toxicity test. The standard log-logistic models are purely descriptive, have more parameters and are sensitive to the chosen exposure time. The estimation of no-effect concentrations (NOEC`s as well as parametric NEC`S) in standard statistical analyses is problematic. Application to ring test data for chronic tests on Daphnia magna and other toxicity data reveals that these problems do not occur with the analysis, due to the absence of free gradient parameters. It is possible to obtain estimates for the standard model parameters from the new parameters, but not vice versa. The authors believe that the analysis provides a better basis for risk assessment and QSAR studies than the standard one.

  19. Arsenic Toxicity: The Effects on Plant Metabolism

    PubMed Central

    Finnegan, Patrick M.; Chen, Weihua

    2012-01-01

    The two forms of inorganic arsenic, arsenate (AsV) and arsenite (AsIII), are easily taken up by the cells of the plant root. Once in the cell, AsV can be readily converted to AsIII, the more toxic of the two forms. AsV and AsIII both disrupt plant metabolism, but through distinct mechanisms. AsV is a chemical analog of phosphate that can disrupt at least some phosphate-dependent aspects of metabolism. AsV can be translocated across cellular membranes by phosphate transport proteins, leading to imbalances in phosphate supply. It can compete with phosphate during phosphorylation reactions, leading to the formation of AsV adducts that are often unstable and short-lived. As an example, the formation and rapid autohydrolysis of AsV-ADP sets in place a futile cycle that uncouples photophosphorylation and oxidative phosphorylation, decreasing the ability of cells to produce ATP and carry out normal metabolism. AsIII is a dithiol reactive compound that binds to and potentially inactivates enzymes containing closely spaced cysteine residues or dithiol co-factors. Arsenic exposure generally induces the production of reactive oxygen species that can lead to the production of antioxidant metabolites and numerous enzymes involved in antioxidant defense. Oxidative carbon metabolism, amino acid and protein relationships, and nitrogen and sulfur assimilation pathways are also impacted by As exposure. Readjustment of several metabolic pathways, such as glutathione production, has been shown to lead to increased arsenic tolerance in plants. Species- and cultivar-dependent variation in arsenic sensitivity and the remodeling of metabolite pools that occurs in response to As exposure gives hope that additional metabolic pathways associated with As tolerance will be identified. PMID:22685440

  20. Beneficial effect of sesame oil on heavy metal toxicity.

    PubMed

    Chandrasekaran, Victor Raj Mohan; Hsu, Dur-Zong; Liu, Ming-Yie

    2014-02-01

    Heavy metals become toxic when they are not metabolized by the body and accumulate in the soft tissue. Chelation therapy is mainly for the management of heavy metal-induced toxicity; however, it usually causes adverse effects or completely blocks the vital function of the particular metal chelated. Much attention has been paid to the development of chelating agents from natural sources to counteract lead- and iron-induced hepatic and renal damage. Sesame oil (a natural edible oil) and sesamol (an active antioxidant) are potently beneficial for treating lead- and iron-induced hepatic and renal toxicity and have no adverse effects. Sesame oil and sesamol significantly inhibit iron-induced lipid peroxidation by inhibiting the xanthine oxidase, nitric oxide, superoxide anion, and hydroxyl radical generation. In addition, sesame oil is a potent inhibitor of proinflammatory mediators, and it attenuates lead-induced hepatic damage by inhibiting nitric oxide, tumor necrosis factor-α, and interleukin-1β levels. Because metal chelating therapy is associated with adverse effects, treating heavy metal toxicity in addition with sesame oil and sesamol may be better alternatives. This review deals with the possible use and beneficial effects of sesame oil and sesamol during heavy metal toxicity treatment. PMID:23744838

  1. Joint toxic effects of the type-2 alkene electrophiles.

    PubMed

    Zhang, Lihai; Geohagen, Brian C; Gavin, Terrence; LoPachin, Richard M

    2016-07-25

    Human populations are exposed to complex environmental mixtures of acrolein, methylvinyl ketone (MVK) and other type-2 alkenes. Many members of this chemical class are electrophiles that possess a common molecular mechanism of toxicity; i.e., protein inactivation via formation of stable cysteine adducts. Therefore, acute or chronic exposure to type-2 alkene mixtures could represent a health risk due to additive or synergistic interactions among component chemicals. Despite this risk, there is little experimental information regarding the joint effects of type-2 alkenes. In the present study we used sum of toxic units (TUsum = ∑TUi) to assess the relative toxicity of different type-2 alkene mixtures. These studies involved well characterized environmental type-2 alkene toxicants and included amide (acrylamide; ACR), ketone (methyl vinyl ketone; MVK), aldehyde (2-ethylacrolein; EA) and ester (methyl acrylate; MA) derivatives. In chemico analyses revealed that both binary and ternary mixtures could deplete thiol groups according to an additive joint effect at equitoxic and non-equitoxic ratios; i.e., TUsum = 1.0 ± 0.20. In contrast, analyses of joint effects in SNB19 cell cultures indicated that different permutations of type-2 alkene mixtures produced mostly synergistic joint effects with respect to cell lethality; i.e., TUsum < 0.80. A mixture of ACR and MA was shown to produce joint toxicity in a rat model. This mixture accelerated the onset and development of neurotoxicity relative to the effects of the individual toxicants. Synergistic effects in biological models might occur when different cellular proteomes are targeted, whereas additive effects develop when the mixtures encompasses a similar proteome. PMID:27288850

  2. Toxic effects produced in insects by organophosphorus compounds*

    PubMed Central

    Dahm, P. A.

    1971-01-01

    This paper reviews the toxicity of organophosphorus compounds in relation to cholinesterase inhibition in insects. It covers anticholinesterase effects on different stages of the life cycle and the relationship between cholinesterase inhibition and lethality. Other effects of organophosphorus compounds, which may account for anomalies in insecticidal action, are also considered. PMID:4398522

  3. Synergetic toxic effect of an explosive material mixture in soil.

    PubMed

    Panz, Katarzyna; Miksch, Korneliusz; Sójka, Tadeusz

    2013-11-01

    Explosives materials are stable in soil and recalcitrant to biodegradation. Different authors report that TNT (2,4,6-trinitrotoluene), RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) and HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) are toxic, but most investigations have been performed in artificial soil with individual substances. The aim of the presented research was to assess the toxicity of forest soil contaminated with these substances both individually as well in combinations of these substances. TNT was the most toxic substance. Although RDX and HMX did not have adverse effects on plants, these compounds did cause earthworm mortality, which has not been reported in earlier research. Synergistic effects of explosives mixture were observed. PMID:24005241

  4. Effectiveness of bioremediation in reducing toxicity in oiled intertidal sediments

    SciTech Connect

    Lee, K.; Tremblay, G.H.; Siron, R.

    1995-12-31

    A 123-day field study was conducted with in situ enclosures to compare the effectiveness of bioremediation strategies based in inorganic and organic fertilizer additions to accelerate the biodegradation rates and reduce the toxicity of Venture{trademark} condensate stranded within sand-beach sediments. Comparison of the two fertilizer formulations with identical nitrogen and phosphorus concentrations showed that the organic fertilizer stimulated bacterial productivity within the oiled sediments to the greatest extent. However, detailed chemical analysis indicated that inorganic fertilizer additions were the most effective in enhancing condensate biodegradation rates. The Microtox{reg_sign} Solid-Phase Test (SPT) bioassay was determined to be sensitive to Venture Condensate in laboratory tests. Subsequent application of this procedure to oiled sediment in the field showed a reduction in sediment toxicity over time. However, the Microtox{reg_sign} bioassay procedure did not identify significant reductions in sediment toxicity following bioremediation treatment. An observed increase in toxicity following periodic additions of the organic fertilizer was attributed to rapid biodegradation rates of the fertilizer, which resulted in the production of toxic metabolic products.

  5. Toxicity, mechanism and health effects of some heavy metals

    PubMed Central

    Jaishankar, Monisha; Tseten, Tenzin; Anbalagan, Naresh; Beeregowda, Krishnamurthy N.

    2014-01-01

    Heavy metal toxicity has proven to be a major threat and there are several health risks associated with it. The toxic effects of these metals, even though they do not have any biological role, remain present in some or the other form harmful for the human body and its proper functioning. They sometimes act as a pseudo element of the body while at certain times they may even interfere with metabolic processes. Few metals, such as aluminium, can be removed through elimination activities, while some metals get accumulated in the body and food chain, exhibiting a chronic nature. Various public health measures have been undertaken to control, prevent and treat metal toxicity occurring at various levels, such as occupational exposure, accidents and environmental factors. Metal toxicity depends upon the absorbed dose, the route of exposure and duration of exposure, i.e. acute or chronic. This can lead to various disorders and can also result in excessive damage due to oxidative stress induced by free radical formation. This review gives details about some heavy metals and their toxicity mechanisms, along with their health effects. PMID:26109881

  6. Effects of sample homogenization on solid phase sediment toxicity

    SciTech Connect

    Anderson, B.S.; Hunt, J.W.; Newman, J.W.; Tjeerdema, R.S.; Fairey, W.R.; Stephenson, M.D.; Puckett, H.M.; Taberski, K.M.

    1995-12-31

    Sediment toxicity is typically assessed using homogenized surficial sediment samples. It has been recognized that homogenization alters sediment integrity and may result in changes in chemical bioavailability through oxidation-reduction or other chemical processes. In this study, intact (unhomogenized) sediment cores were taken from a Van Veen grab sampler and tested concurrently with sediment homogenate from the same sample in order to investigate the effect of homogenization on toxicity. Two different solid-phase toxicity test protocols were used for these comparisons. Results of amphipod exposures to samples from San Francisco Bay indicated minimal difference between intact and homogenized samples. Mean amphipod survival in intact cores relative to homogenates was similar at two contaminated sites. Mean survival was 34 and 33% in intact and homogenized samples, respectively, at Castro Cove. Mean survival was 41% and 57%, respectively, in intact and homogenized samples from Islais Creek. Studies using the sea urchin development protocol, modified for testing at the sediment/water interface, indicated considerably more toxicity in intact samples relative to homogenized samples from San Diego Bay. Measures of metal flux into the overlying water demonstrated greater flux of metals from the intact samples. Zinc flux was five times greater, and copper flux was twice as great in some intact samples relative to homogenates. Future experiments will compare flux of metals and organic compounds in intact and homogenized sediments to further evaluate the efficacy of using intact cores for solid phase toxicity assessment.

  7. Synergistic Effects of Toxic Elements on Heat Shock Proteins

    PubMed Central

    Mahmood, Khalid; Mahmood, Qaisar; Irshad, Muhammad; Hussain, Jamshaid

    2014-01-01

    Heat shock proteins show remarkable variations in their expression levels under a variety of toxic conditions. A research span expanded over five decades has revealed their molecular characterization, gene regulation, expression patterns, vast similarity in diverse groups, and broad range of functional capabilities. Their functions include protection and tolerance against cytotoxic conditions through their molecular chaperoning activity, maintaining cytoskeleton stability, and assisting in cell signaling. However, their role as biomarkers for monitoring the environmental risk assessment is controversial due to a number of conflicting, validating, and nonvalidating reports. The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review. The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors. The adoption of heat shock proteins as “suit of biomarkers in a set of organisms” requires further investigation. PMID:25136596

  8. Health effects of toxicants: Online knowledge support.

    PubMed

    Wexler, Philip; Judson, Richard; de Marcellus, Sally; de Knecht, Joop; Leinala, Eeva

    2016-01-15

    Research in toxicology generates vast quantities of data which reside on the Web and are subsequently appropriated and utilized to support further research. This data includes a broad spectrum of information about chemical, biological and radiological agents which can affect health, the nature of the effects, treatment, regulatory measures, and more. Information is structured in a variety of formats, including traditional databases, portals, prediction models, and decision making support tools. Online resources are created and housed by a variety of institutions, including libraries and government agencies. This paper focuses on three such institutions and the tools they offer to the public: the National Library of Medicine (NLM) and its Toxicology and Environmental Health Information Program, the United States Environmental Protection Agency (EPA), and the Organisation for Economic Co-operation and Development (OECD). Reference is also made to other relevant organizations. PMID:26506572

  9. The toxic effects of formaldehyde on the nervous system.

    PubMed

    Songur, Ahmet; Ozen, Oguz Aslan; Sarsilmaz, Mustafa

    2010-01-01

    Formaldehyde (FA) is found in the polluted atmosphere of cities, domestic air (e.g., paint, insulating materials, chipboard and plywood, fabrics, furniture, paper), and cigarette smoke, etc.; therefore, everyone and particularly susceptible children may be exposed to FA. FA is also widely used in industrial and medical settings and as a sterilizing agent, disinfectant, and preservative. Therefore, employees may be highly exposed to it in there settings. Of particular concern to the authors are anatomists and medical students, who can be highly exposed to formaldehyde vapor during dissection sessions. Formaldehyde is toxic over a range of doses; chances of exposure and subsequent harmful effects are increased as (room) temperature increases, because of FA's volatility. Many studies have been conducted to evaluate the effects of FA during systemic and respiratory exposures in rats. This review compiles that literature and emphasizes the neurotoxic effects of FA on neuronal morphology, behavior, and biochemical parameters. The review includes the results of some of the authors' work related to FA neurotoxicity, and such neurotoxic effects from FA exposure were experimentally demonstrated. Moreover, the effectiveness of some antioxidants such as melatonin, fish omega-3, and CAPE was observed in the treatment of the harmful effects of FA. Despite the harmful effects from FA exposure, it is commonly used in Turkey and elsewhere in dissection laboratories. Consequently, all anatomists must know and understand the effects of this toxic agent on organisms and the environment, and take precautions to avoid unnecessary exposure. The reviewed studies have indicated that FA has neurotoxic characteristics and systemic toxic effects. It is hypothesized that inhalation of FA, during the early postnatal period, is linked to some neurological diseases that occur in adults. Although complete prevention is impossible for laboratory workers and members of industries utilizing FA

  10. Toxic effect of lithium in mouse brain

    SciTech Connect

    Dixit, P.K.; Smithberg, M.

    1988-01-01

    The effect of lithium ion on glucose oxidation in the cerebrum and cerebellum of mice was measured in vitro by the conversion of isotopic glucose into /sup 14/CO/sub 2//mg wet weight. Glucose utilization is unaffected by lowest lithium dosage but is inhibited by high lithium concentrations (197-295 mM). Chronic administration of lithium to adult mice decreased the DNA content of the cerebrum and cerebellum at concentrations of 80 and 108 mM. The DNA content of selected postnatal stages of cerebrum and cerebellum was measured starting on Day 1 or 2. This served as another parameter to evaluate glucose oxidation studies at these ages. On the basis of wet weight, both brain parts of neonates of ages 1 and 10 days were approximately one-half that of the adult counterparts. On the basis of DNA content, the cerebrum enhanced its glucose utilization twofold from Day 1 to Day 10 and tripled its utilization from Day 10 to Day 20. The glucose utilization by cerebrum at Day 20 is similar to adult values. In contrast, glucose oxidation in the cerebellum remained relatively constant throughout the postnatal growth. The relative susceptibility of the two brain parts is discussed.

  11. Arsenic and selenium toxicity and their interactive effects in humans.

    PubMed

    Sun, Hong-Jie; Rathinasabapathi, Bala; Wu, Bing; Luo, Jun; Pu, Li-Ping; Ma, Lena Q

    2014-08-01

    Arsenic (As) and selenium (Se) are unusual metalloids as they both induce and cure cancer. They both cause carcinogenesis, pathology, cytotoxicity, and genotoxicity in humans, with reactive oxygen species playing an important role. While As induces adverse effects by decreasing DNA methylation and affecting protein 53 expression, Se induces adverse effects by modifying thioredoxin reductase. However, they can react with glutathione and S-adenosylmethionine by forming an As-Se complex, which can be secreted extracellularly. We hypothesize that there are two types of interactions between As and Se. At low concentration, Se can decrease As toxicity via excretion of As-Se compound [(GS3)2AsSe](-), but at high concentration, excessive Se can enhance As toxicity by reacting with S-adenosylmethionine and glutathione, and modifying the structure and activity of arsenite methyltransferase. This review is to summarize their toxicity mechanisms and the interaction between As and Se toxicity, and to provide suggestions for future investigations. PMID:24853282

  12. Effect of malachite green toxicity on non target soil organisms.

    PubMed

    Gopinathan, R; Kanhere, J; Banerjee, J

    2015-02-01

    Although malachite green (MG), is banned in Europe and US for its carcinogenic and teratogenic effect, the dye being cheap, is persistently used in various countries for fish farming, silk, dye, leather and textile industries. Current research, however, fails to elucidate adequate knowledge concerning the effects of MG in our ecosystem. In the present investigation, for the first time, an attempt has been made to study the effects of MG on soil biota by testing Bacillus subtilis, Azotobacter chroococcum, Saccharomyces cerevisiae, Penicillium roqueforti, Eisenia fetida and seeds of three crop plants of different families. Various tests were conducted for determining cytotoxicity, genotoxicity, acute toxicity, morphological and germination effect. Our data confirmed MG toxicity on fungi and bacteria (gram positive and gram negative organisms) showing elevated level of ROS. Genotoxicity caused in the microorganisms was detected by DNA polymorphism and fragmentation. Also, scanning electron microscopy data suggests that the inhibitory effect of MG to these beneficial microbes in the ecosystem might be due to pore formation in the cell and its eventual disruption. Filter paper and artificial soil test conducted on earthworms demonstrated a LC 50 of 2.6 mg cm(-2) and 1.45 mg kg(-1) respectively with severe morphological damage. However, seed germination of Mung bean, Wheat and Mustard was found to be unaffected in presence of MG up to 100 mL(-1) concentration. Thus, understanding MG toxicity in non target soil organisms and emphasis on its toxicological effects would potentially explicate its role as an environmental contaminant. PMID:25462308

  13. The fungicide mancozeb induces toxic effects on mammalian granulosa cells

    SciTech Connect

    Paro, Rita; Tiboni, Gian Mario; Buccione, Roberto; Rossi, Gianna; Cellini, Valerio; Canipari, Rita; Cecconi, Sandra

    2012-04-15

    The ethylene-bis-dithiocarbamate mancozeb is a widely used fungicide with low reported toxicity in mammals. In mice, mancozeb induces embryo apoptosis, affects oocyte meiotic spindle morphology and impairs fertilization rate even when used at very low concentrations. We evaluated the toxic effects of mancozeb on the mouse and human ovarian somatic granulosa cells. We examined parameters such as cell morphology, induction of apoptosis, and p53 expression levels. Mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of their morphology, and acquired the ability to migrate but not to proliferate. The expression level of p53, in terms of mRNA and protein content, decreased significantly in comparison with unexposed cells, but no change in apoptosis was recorded. Toxic effects could be attributed, at least in part, to the presence of ethylenthiourea (ETU), the main mancozeb catabolite, which was found in culture medium. Human granulosa cells also showed dose-dependent morphological changes and reduced p53 expression levels after exposure to mancozeb. Altogether, these results indicate that mancozeb affects the somatic cells of the mammalian ovarian follicles by inducing a premalignant-like status, and that such damage occurs to the same extent in both mouse and human GC. These results further substantiate the concept that mancozeb should be regarded as a reproductive toxicant. Highlights: ► The fungicide mancozeb affects oocyte spindle morphology and fertilization rate. ► We investigated the toxic effects of mancozeb on mouse and human granulosa cells. ► Granulosa cells modify their morphology and expression level of p53. ► Mancozeb induces a premalignant-like status in exposed cells.

  14. [Acute Toxic Effects of Bromate on Aquatic Organisms].

    PubMed

    Wang, Zhi-wei; Liu, Dong-mei; Zhang, Wen-juan; Cui, Fu-yi

    2016-02-15

    Acute toxic effects of potassium bromate, sodium bromate and potassium bromide on luminescent bacteria, water flea, green alga and zebrafish were studied using standard toxic testing methods. The results showed that the pollutants had no effect on the luminous intensity of luminescent bacteria. The 96 h EC5. of potassium bromate on Scenedesmus obliquus was 738.18 mg x L(-1), 48 h EC50 on Daphnia magna and Moina was 154.01 mg x L(-1) was 161.80 mg x L(-1), while 48 h LC50 was 198 52 mg x L(-1), 175.68 mg x L(-1), and 96 h LC50 on zebrafish was 931.4 mg x L(-1). The 96 h EC50 of sodium bromate on Scenedesmus obliquus was 540.26 mg x L(-1), 48 h EC50 Daphnia magna and Moina was 127.90 mg x L(-1), 111.07 mg x L(-1), while 48 h LC50 was 161.80 mg x L(-1), 123.47 mg x L(-1), and 96 h LC50 on zebrafish was 1065.6 mg x L(-1). But the effects of potassium bromide on the above several kinds of aquatic organisms were far smaller than those of potassium bromate and sodium bromate. The toxic effects on test organisms were due to the impacts of bromate after the comparison of different pollutants, and the effects were more obvious with the increase of exposure time. The order of sensitivity to the toxic effects of bromate was Daphnia magna, Moina > Scenedesmus obliquus > zebrafish > Chlorella vulgaris, luminescent bacteria. PMID:27363170

  15. Protective effect of selenium on methylmercury toxicity: a possible mechanism

    SciTech Connect

    Chang, L.W.; Suber, R.

    1982-09-01

    Young adult male Charles River rats were injected (i.p.) with 2.0 mg/kg b.w. methylmercury chloride (MeHg), with 2.0 mg/kg b.w. sodium selenite (Se), or with 2.0 mg/kg b.w. MeHg and 2.0 mg/kg b.w. Se. Erythrocytic glutathione peroxidase activity was determined and the rate of oxidation of NADPH with t-butyl-hydroperoxide as a substrate was followed at 340 nm and 25/sup 0/C. Toxic signs (crossing reflex of the hind limbs) were displayed by MeHg-treated animals by the 6th week of intoxication. By 8 weeks of the experiment, overt neurological signs (crossing reflex, ataxic gait, and weight loss) were observed in MeHg-treated animals. No observable toxic signs or symptoms were evident in the control animals (saline or Se-treated) and in the MeHg/Se treated rats. Results have confirmed that exposure to methyl-mercury suppresses the activity of glutathione peroxidase. Furthermore, it was demonstrated that with co-administration of selenium (sodium selenite), the inhibitory effect of MeHg on GSH-Px was totally alleviated. These findings suggest that the level of GSH-Px level is important in influencing the toxic consequences in MeHg-intoxicated animals and may be useful as a predictive indicator for methylmercury toxic conditions of the animals. (JMT)

  16. Toxic effects of decomposing red algae on littoral organisms

    NASA Astrophysics Data System (ADS)

    Eklund, Britta; Svensson, Andreas P.; Jonsson, Conny; Malm, Torleif

    2005-03-01

    Large masses of filamentous red algae of the genera Polysiphonia, Rhodomela, and Ceramium are regularly washed up on beaches of the central Baltic Sea. As the algal masses start to decay, red coloured effluents leak into the water, and this tinge may be traced several hundred meters off shore. In this study, possible toxic effects of these effluents were tested on littoral organisms from different trophic levels. Effects on fertilisation, germination and juvenile survival of the brown seaweed Fucus vesiculosus were investigated, and mortality tests were performed on the crustaceans Artemia salina and Idotea baltica, as well as on larvae and adults of the fish Pomatoschistus microps. Fucus vesiculosus was the most sensitive species of the tested organisms to the red algal extract. The survival of F. vesiculosus recruits was reduced with 50% (LC50) when exposed to a concentration corresponding to 1.7 g l -1 dw red algae. The lethal concentration for I. baltica, A. salina and P. microps were approximately ten times higher. The toxicity to A. salina was reduced if the algal extract was left to decompose during two weeks but the decline in toxicity was not affected by different light or temperature conditions. This study indicates that the filamentous red algae in the central Baltic Sea may produce and release compounds with negative effects on the littoral ecosystem. The effects may be particularly serious for the key species F. vesiculosus, which reproduce in autumn when filamentous red algal blooms are most severe.

  17. Toxic effects of formaldehyde on the urinary system

    PubMed Central

    İnci, Mehmet; Zararsız, İsmail; Davarcı, Mürsel; Görür, Sadık

    2013-01-01

    Formaldehyde is a chemical substance with a pungent odor that is highly soluble in water and occurs naturally in organisms. Formaldehyde, when taken into organisms, is metabolized into formic acid in the liver and erythrocytes and is then excreted, either with the urine and feces or via the respiratory system. Form-aldehyde is widely used in the industrial and medical fields, and employees in these sectors are frequently exposed to it. Anatomists and medical students are affected by formaldehyde gas during dissection lessons. Because full protection from formaldehyde is impossible for employees in industrial plants using this chemical and for workers in laboratory conditions, several measures can be implemented to prevent and/or reduce the toxic effects of formaldehyde. In this review, we aimed to identify the toxic effects of formaldehyde on the urinary system. PMID:26328078

  18. Estimating the effects of toxicants on ecosystem services.

    PubMed

    Cairns, J; Niederlehner, B R

    1994-11-01

    Numerous functions of ecosystems are essential to the quality of human life, including the provision of food, the decomposition of sewage, the provision of portable water, and the replacement of breathable air. Although attributes of ecosystems directly of use to human societies are not the only ones worth protecting, emphasizing their services may be the most effective means of communicating risks of toxicants to the general public. However, although spatial and temporal scales of experiments to assess risk vary relatively little, actual spatial scales vary considerably, from local environments to global ecosystems. Generally, models are used to bridge these gaps in scale. In this paper, we examine ways in which toxicity test endpoints have been developed to describe effects of pollutants on essential ecosystem functions and the ways in which results are then extrapolated to scales that risk managers can use. PMID:9738207

  19. Estimating the effects of toxicants on ecosystem services.

    PubMed Central

    Cairns, J; Niederlehner, B R

    1994-01-01

    Numerous functions of ecosystems are essential to the quality of human life, including the provision of food, the decomposition of sewage, the provision of portable water, and the replacement of breathable air. Although attributes of ecosystems directly of use to human societies are not the only ones worth protecting, emphasizing their services may be the most effective means of communicating risks of toxicants to the general public. However, although spatial and temporal scales of experiments to assess risk vary relatively little, actual spatial scales vary considerably, from local environments to global ecosystems. Generally, models are used to bridge these gaps in scale. In this paper, we examine ways in which toxicity test endpoints have been developed to describe effects of pollutants on essential ecosystem functions and the ways in which results are then extrapolated to scales that risk managers can use. Images p936-a PMID:9738207

  20. Effects of ethanol on methyl mercury toxicity in rats

    SciTech Connect

    Tamashiro, H.; Arakaki, M.; Akagi, H.; Murao, K.; Hirayama, K.; Smolensky, M.H.

    1986-01-01

    This study was designed to investigate the effect of different doses of ethanol on the morbidity, mortality, and distribution of mercury in the tissues of groups of rats treated orally once daily with methyl mercury chloride (MMC: 5 mg/kg d) for 10 consecutive days. Ethanol potentiated the toxicity of methyl mercury in terms of neurological manifestations (hindleg crossings and abnormal gait) and mortality. The magnitude of effect depended on the concentration of ethanol administered. The concentration of mercury in the kidney and brain also increased with the dose of ethanol given. These findings indicate that epidemiologic studies designed to evaluate methyl mercury toxicity must take into account the multiple environmental burdens that can affect the population cumulatively and simultaneously.

  1. Glutathione depletion by valproic acid in sandwich-cultured rat hepatocytes: Role of biotransformation and temporal relationship with onset of toxicity

    SciTech Connect

    Kiang, Tony K.L.; Teng Xiaowei; Surendradoss, Jayakumar; Karagiozov, Stoyan; Abbott, Frank S.; Chang, Thomas K.H.

    2011-05-01

    The present study was conducted in sandwich-cultured rat hepatocytes to investigate the chemical basis of glutathione (GSH) depletion by valproic acid (VPA) and evaluate the role of GSH depletion in VPA toxicity. Among the synthetic metabolites of VPA investigated, 4-ene-VPA and (E)-2,4-diene-VPA decreased cellular levels of total GSH, but only (E)-2,4-diene-VPA was more effective and more potent than the parent drug. The in situ generated, cytochrome P450-dependent 4-ene-VPA did not contribute to GSH depletion by VPA, as suggested by the experiment with a cytochrome P450 inhibitor, 1-aminobenzotriazole, to decrease the formation of this metabolite. In support of a role for metabolites, alpha-F-VPA and octanoic acid, which do not undergo biotransformation to form a 2,4-diene metabolite, CoA ester, or glucuronide, did not deplete GSH. A time course experiment showed that GSH depletion did not occur prior to the increase in 2',7'-dichlorofluorescein (a marker of oxidative stress), the decrease in [2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium] (WST-1) product formation (a marker of cell viability), or the increase in lactate dehydrogenase (LDH) release (a marker of necrosis) in VPA-treated hepatocytes. In conclusion, the cytochrome P450-mediated 4-ene-VPA pathway does not play a role in the in situ depletion of GSH by VPA, and GSH depletion is not an initiating event in VPA toxicity in sandwich-cultured rat hepatocytes.

  2. Toxic effects of imidacloprid on adult loach (Misgurnus anguillicaudatus).

    PubMed

    Xia, Xiaohua; Xia, Xiaopei; Huo, Weiran; Dong, Hui; Zhang, Linxia; Chang, Zhongjie

    2016-07-01

    The present investigation was aimed to assess the effects of imidacloprid on the survival, genetic materials, hepatic transaminase activity and histopathology of loach (Misgurnus anguillicaudatus). The values of LC50 (24, 48, 72 and 96h) of imidacloprid were 167.7, 158.6, 147.9 and 145.8mg/L, respectively, and the safety concentration was 42.55mg/L. The erythrocyte micronuclei assays and the comet assay results showed that imidacloprid had genetic toxic effect on the loach erythrocytes. To assess the physiological and biochemical damage caused by imidacloprid, the activities of hepatic glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) were measured and their values declined in treatment groups. Histological examination of testis revealed that imidacloprid treatment resulted in disorganized lobules and cysts structures. In the present work, we also investigated the joint toxicity of pesticides commonly used in paddy fields (imidacloprid and lambda-cyhalothrin) on M. anguillicaudatus, and confirmed that a synergistic effect existing in the binary mixtures. The results of our study provide relevant and comparable toxicity information that are useful for safety application of pesticides. PMID:27299658

  3. Toxic effects of Karenia mikimotoi extracts on mammalian cells

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Yan, Tian; Yu, Rencheng; Zhou, Mingjiang

    2011-07-01

    Karenia is one of the most harmful and representative red tide genus in a temperate zone. Blooms caused by this genus have resulted in massive fish death in the South China Sea and the East China Sea. However, the potential effects of this dinoflagellate on human health through the transfer of toxins via marine food webs, and the mechanisms of toxicity, are still unknown. Therefore, we examined the toxic effects of a strain of K. mikimotoi (isolated from the South China Sea) on the proliferation and morphology of four mammalian cell lines (two normal cell lines and two cancer cell lines). In addition, we carried out a preliminary investigation on the mechanism of toxicity of the alga. The results show that the polar lipid-soluble component of K. mikimotoi significantly inhibited proliferation of the four cell lines, and resulted in the cells becoming spherical, swollen and damaged. The result of Annexin V and PI double-staining confirmed that cell membranes were disrupted. The malonaldehyde (MDA) contents in the medium of the four cell lines treated with the polar-lipid extracts all increased significantly, which indicates that the polar-lipid toxins produced by K. mikimotoi could adversely affect mammalian cells by inducing lipid peroxidation. We conclude that K. mikimotoi is a potential threat to human health, and the comprehensive effect of this dinoflagellate and its mechanisms should be investigated further.

  4. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Toxic or adverse effect incident... Information § 159.184 Toxic or adverse effect incident reports. (a) General. Information about incidents... organism suffered a toxic or adverse effect, or may suffer a delayed or chronic adverse effect in...

  5. Effects-Directed Analysis (EDA) and Toxicity Identification Evaluation (TIE): Complementary but Different Approaches for Diagnosing Causes of Environmental Toxicity

    EPA Science Inventory

    Currently, two approaches are available for performing environmental diagnostics on samples like municipal and industrial effluents, interstitial waters and whole sediments in order to identify anthropogenic contaminants causing toxicological effects. One approach is Toxicity Id...

  6. Toxic effects of selenium and copper on the planarian, Dugesia dorotocephala

    SciTech Connect

    Rauscher, J.D.

    1988-01-01

    Aquatic toxicologists have become increasingly concerned with the effects of sublethal concentrations of toxicants on aquatic organisms. Sublethal effects of toxicants on freshwater invertebrates were reviewed. Selenium (Se) and copper (Cu) are both essential trace elements and toxicants. Se has been reported to alter the toxicity of heavy metals. Planarians, Dugesia dorotocephala, were used as test animals. The objectives of this study were to determine: (1) acute toxicity of Se on planarians and the effect of the number of planarians per test chamber, (2) interaction of the acute toxicity of Se and Cu on planarians, and (3) sublethal effects of Se and Cu on planarians.

  7. Toxic effect of palladium on embryonic development of zebrafish.

    PubMed

    Chen, Mingliang; Chen, Sangxia; Du, Mi; Tang, Shaoheng; Chen, Mei; Wang, Wei; Yang, Hui; Chen, Qiaoyu; Chen, Jianming

    2015-02-01

    Since palladium (Pd) is now increasingly used in modern industry, it progressively accumulates in the environment, especially in aquatic ecosystem. The potential toxicity of Pd has therefore caused extensive concern worldwidely. In the present study, we investigated the toxic effect of Pd on zebrafish development. Acute Pd exposure significantly decreased both the survival rate (LC50: 292.6 μg/L, viz. 2.75 μM) and hatching rate (IC50: 181.5 μg/L, viz. 1.71 μM) of zebrafish during embryonic development. The most common developmental defect observed in Pd treated embryos is pericardiac edema, which occurs in a dose-dependent manner. Whole mount immunostaining and histological studies revealed that Pd exposure would produce the elongated, string-like heart. The heartbeat rate of zebrafish embryos was also decreased after Pd exposure. Consistently, mRNA expression levels of several cardiac-related genes were affected by Pd, suggesting a potential molecular mechanism of Pd-induced cardiac malformation of zebrafish embryo. Moreover, similar to other metals, Pd exposure resulted in the elevated expression of general metal-inducible genes. It was also found that the expression of several antioxidant enzymes was significantly down-regulated in the presence of Pd. Taken together, our study investigated the effects of Pd on zebrafish embryonic development and its potential molecular mechanisms, paving the way for the full understanding of Pd toxicity. PMID:25550166

  8. In vitro toxic effects of different types of carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Khaliullin, T. O.; Fatkhutdinova, L. M.; Zalyalov, R. R.; Kisin, E. R.; Murray, A. R.; Shvedova, A. A.

    2015-11-01

    We have carried out a comparative assessment of industrial single- and multiwalled carbon nanotubes (SWCNTs / MWCNTs) toxic effects in the cultures of macrophages (RAW 264.7) and bronchial epithelial cells (BEAS-2B). Lactate dehydrogenase (LDH) levels were measured directly in the medium. Intracellular reduced glutathione levels (GSH) were determined in culture lysates. Cell viability was determined by fluorescence method. RAW 264.7 were much more sensitive to the effects of carbon nanotubes (CNTs): MWCNT addition was not accompanied by a significant reduction in the viability of macrophages, but caused damage to cell membranes (release of LDH) with a dose and time-dependent oxidative stress. SWCNTs caused a significant decrease in viability and induction of oxidative stress. Improved darkfield microscopy revealed adsorption and accumulation of MWCNTs on the surface and inside the macrophages. Adding SWCNTs to BEAS-2B culture caused small statistically significant dose-and time-dependent decrease in viability and pronounced reduction in glutathione only at the highest concentration of nanoparticles. Bronchial epithelial cells BEAS- 2B appeared to be much less susceptible to MWCNTs. The findings suggest that there are differences in the toxic action of different CNTs and there is a need for thoughtful approach to the assessment of nanomaterials toxicity.

  9. Effects of physicochemical properties of nanomaterials on their toxicity.

    PubMed

    Li, Xiaoming; Liu, Wei; Sun, Lianwen; Aifantis, Katerina E; Yu, Bo; Fan, Yubo; Feng, Qingling; Cui, Fuzhai; Watari, Fumio

    2015-07-01

    Due to their unique size and properties, nanomaterials have numerous applications, which range from electronics, cosmetics, household appliances, energy storage, and semiconductor devices, to medical products such as biological sensors, drug carriers, bioprobes, and implants. Many of the promising properties of nanomaterials arise from their large surface to volume ratio and, therefore, nanobiomaterials that are implantable have a large contact area with the human body. Before, therefore, we can fully exploit nanomaterials, in medicine and bioengineering; it is necessary to understand how they can affect the human body. As a step in this direction, this review paper provides a comprehensive summary of the effects that the physicochemical properties of commonly used nanobiomaterials have on their toxicity. Furthermore, the possible mechanisms of toxicity are described with the aim to provide guidance concerning the design of the nanobiomaterials with desirable properties. PMID:25530348

  10. Effects-directed analysis (EDA) and toxicity identification evaluation (TIE): Complementary but different approaches for diagnosing causes of environmental toxicity.

    PubMed

    Burgess, Robert M; Ho, Kay T; Brack, Werner; Lamoree, Marja

    2013-09-01

    Currently, 2 approaches are available for performing environmental diagnostics on samples like municipal and industrial effluents, interstitial waters, and whole sediments to identify anthropogenic contaminants causing toxicological effects. One approach is toxicity identification evaluation (TIE), which was developed primarily in North America to determine active toxicants to whole-organism endpoints. The second approach is effects-directed analysis (EDA), which has origins in both Europe and North America. Unlike TIE, EDA uses primarily in vitro endpoints with an emphasis on organic contaminants as the cause of observed toxicity. The 2 approaches have fundamental differences that make them distinct techniques. In EDA, the sophisticated and elegant fractionation and chemical analyses performed to identify the causes of toxicity with a high degree of specificity often compromise contaminant bioavailability. In contrast, in TIE, toxicant bioavailability is maintained and is considered critical to accurately identifying the causes of environmental toxicity. However, maintaining contaminant bioavailability comes with the cost of limiting, at least until recently, the use of the types of sophisticated fractionation and elegant chemical analyses that have resulted in the high specificity of toxicant diagnosis performed in EDA. The present study provides an overview of each approach and highlights areas where the 2 approaches can complement one another and lead to the improvement of both. PMID:23893495

  11. Effect of dietary vitamin C and E supplementation on toxicity of methyl oleate hydroperoxide (MOHP), a proposed toxic ozone intermediate

    SciTech Connect

    Calabrese, E.J.; Victor, J.; Stoddard, M.A.

    1985-01-01

    This study assessed the effects of vitamin E (600 mg/day) and/or vitamin C (one gram/day) supplementation for 4 weeks in adult human male volunteers on the in vitro erythrocyte toxicity of a proposed toxic ozone (O/sub 3/) intermediate (i.e. methyl oleate hydroperoxide (MOHP)). The results indicated that neither antioxidant vitamin provided significant protection against MOHP-induced changes in methemoglobin (METHB) and reduced glutathione (GSH) over a wide range of MOHP concentrations.

  12. Toxic waste: behavioral effects of an environmental stressor.

    PubMed

    Horowitz, J; Stefanko, M

    1989-01-01

    This study examines the stress-related behavioral effects that may be associated with living near an ambient stressor: a toxic-waste landfill. Results are based on a telephone survey of 426 persons living in three distance strata from the landfill (within 1 1/2 miles, 1 1/2 to 5 miles, and 5 to 10 miles). The instrument was adapted from the Hopkins Life Checklist (SCL-90) and from surveys used by researchers studying the effects of the Three Mile Island nuclear accident. No significant differences were found across area or amount of stimuli exposure on the dependent variables of bodily effects, anger-hostility, and demoralization. Scattered effects across age, sex, educational level, and home ownership (v rental) occurred; however, these could not be attributed solely to the landfill. PMID:2923989

  13. Effect of fiber, protein source and time of feeding on methotrexate toxicity in rats.

    PubMed

    Funk, M A; Baker, D H

    1991-10-01

    Several rat experiments were conducted to determine effects of fiber and alternate protein sources on methotrexate (MTX) toxicity associated with a casein-based semipurified diet. Additional experiments were conducted to determine the critical time of feeding in relation to toxicity development. Rats adapted to a casein-based semipurified diet developed severe anorexia and diarrhea on d 3 and 4 post-MTX dosing. Addition of amorphous cellulose to the semipurified casein-based diet slightly reduced toxicity symptoms. Additions of crystalline cellulose, hemicellulose and pectin did not lessen toxicity symptoms. Replacing casein with soybean concentrate totally alleviated the toxicity symptoms. Toxicity was lower when 25% of the protein normally supplied by casein was replaced with soybean concentrate, and no toxicity symptoms were present when 50% or more of the protein was provided by soybean concentrate. Replacing casein with whey isolate or hamburger had no effect on toxicity; replacing casein with egg albumen or corn gluten meal lessened toxicity symptoms but did not totally alleviate them. Feeding the casein-based diet only 1 d before and 1 d after MTX injection resulted in toxicity. However, feeding the same diet only after MTX injection did not cause toxicity. Results indicate that fiber sources have little effect on MTX toxicity, but replacing casein with soybean concentrate completely alleviates toxicity symptoms. Time of feeding affects subsequent development of toxicity. PMID:1662714

  14. Toxicity Effect of Silver Nanoparticles in Brine Shrimp Artemia

    PubMed Central

    Arulvasu, Chinnasamy; Jennifer, Samou Michael; Prabhu, Durai; Chandhirasekar, Devakumar

    2014-01-01

    The present study revealed the toxic effect of silver nanoparticles (AgNPs) in Artemia nauplii and evaluated the mortality rate, hatching percentage, and genotoxic effect in Artemia nauplii/cysts. The AgNPs were commercially purchased and characterized using field emission scanning electron microscope with energy dispersive X-ray spectroscopy. Nanoparticles were spherical in nature and with size range of 30–40 nm. Artemia cysts were collected from salt pan, processed, and hatched in sea water. Artemia nauplii (II instar) were treated using silver nanoparticles of various nanomolar concentrations and LC50 value (10 nM) and mortality rate (24 and 48 hours) was evaluated. Hatching percentage of decapsulated cysts treated with AgNPs was examined. Aggregation of AgNPs in the gut region of nauplii was studied using phase contrast microscope and apoptotic cells in nauplii stained with acridine orange were observed using fluorescence microscope. DNA damage of single cell of nauplii was determined by comet assay. This study showed that as the concentration of AgNPs increased, the mortality rate, aggregation in gut region, apoptotic cells, and DNA damage increased in nauplii, whereas the percentage of hatching in Artemia cysts decreased. Thus this study revealed that the nanomolar concentrations of AgNPs have toxic effect on both Artemia nauplii and cysts. PMID:24516361

  15. Fish embryo toxicity test: identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds.

    PubMed

    Klüver, Nils; König, Maria; Ortmann, Julia; Massei, Riccardo; Paschke, Albrecht; Kühne, Ralph; Scholz, Stefan

    2015-06-01

    The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compounds with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided the first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may not yet be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish

  16. Effect of trifluoperazine on toxicity, HIF-1α induction and hepatocyte regeneration in acetaminophen toxicity in mice

    SciTech Connect

    Chaudhuri, Shubhra; McCullough, Sandra S.; Hennings, Leah; Brown, Aliza T.; Li, Shun-Hwa; Simpson, Pippa M.; Hinson, Jack A.; James, Laura P.

    2012-10-15

    Oxidative stress and mitochondrial permeability transition (MPT) are important mechanisms in acetaminophen (APAP) toxicity. The MPT inhibitor trifluoperazine (TFP) reduced MPT, oxidative stress, and toxicity in freshly isolated hepatocytes treated with APAP. Since hypoxia inducible factor-one alpha (HIF-1α) is induced very early in APAP toxicity, a role for oxidative stress in the induction has been postulated. In the present study, the effect of TFP on toxicity and HIF-1α induction in B6C3F1 male mice treated with APAP was examined. Mice received TFP (10 mg/kg, oral gavage) prior to APAP (200 mg/kg IP) and at 7 and 36 h after APAP. Measures of metabolism (hepatic glutathione and APAP protein adducts) were comparable in the two groups of mice. Toxicity was decreased in the APAP/TFP mice at 2, 4, and 8 h, compared to the APAP mice. At 24 and 48 h, there were no significant differences in toxicity between the two groups. TFP lowered HIF-1α induction but also reduced the expression of proliferating cell nuclear antigen, a marker of hepatocyte regeneration. TFP can also inhibit phospholipase A{sub 2}, and cytosolic and secretory PLA{sub 2} activity levels were reduced in the APAP/TFP mice compared to the APAP mice. TFP also lowered prostaglandin E{sub 2} expression, a known mechanism of cytoprotection. In summary, the MPT inhibitor TFP delayed the onset of toxicity and lowered HIF-1α induction in APAP treated mice. TFP also reduced PGE{sub 2} expression and hepatocyte regeneration, likely through a mechanism involving PLA{sub 2}. -- Highlights: ► Trifluoperazine reduced acetaminophen toxicity and lowered HIF-1α induction. ► Trifluoperazine had no effect on the metabolism of acetaminophen. ► Trifluoperazine reduced hepatocyte regeneration. ► Trifluoperazine reduced phospholipase A{sub 2} activity and prostaglandin E{sub 2} levels.

  17. Thymoquinone therapy abrogates toxic effect of cadmium on rat testes.

    PubMed

    Fouad, A A; Jresat, I

    2015-05-01

    The protective effect of thymoquinone was investigated against cadmium-induced testicular toxicity in rats. Testicular toxicity was induced by a single intraperitoneal (i.p.) injection of cadmium chloride (2 mg kg(-1) ). Thymoquinone treatment (10 mg kg(-1)  day(-1) , i.p.) was applied for five consecutive days, starting 3 days before cadmium administration. Thymoquinone significantly attenuated the cadmium-induced decreases in serum testosterone, and testicular reduced glutathione and superoxide dismutase activity and significantly decreased the elevations of testicular malondialdehyde, nitric oxide and cadmium ion levels resulted from cadmium chloride administration. Also, thymoquinone ameliorated the cadmium-induced testicular tissue injury observed by histopathological examination. In addition, thymoquinone significantly decreased the cadmium-induced expression of inducible nitric oxide synthase, tumour necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in testicular tissue. It was concluded that thymoquinone, through its antioxidant and anti-inflammatory activities, may represent a potential candidate to protect the testes against the detrimental effect of cadmium exposure. PMID:24735446

  18. Contaminated marine sediments: Water column and interstitial toxic effects

    SciTech Connect

    Burgess, R.M.; McKinney, R.A. ); Schweitzer, K.A. ); Phelps, D.K. )

    1993-01-01

    The toxicity that contaminated sediments may introduce into the water column has not been measured extensively. In order to quantify this potential toxicity, the seawater overlying two uncontaminated and three contaminated marine sediments was evaluated in the laboratory with the sea urchin Arbacia punctulata fertilization test. Concentration of polychlorinated biphenyls (PCBs) and copper, as representative contaminants, were also measured. To characterize sources of toxicity, samples were chemically manipulated using reversed-phase chromatography, cation exchange, and chelation. Water column toxicity and contaminant concentrations were higher in the suspended exposures than in bedded exposures. Interstitial water toxicity and contaminant concentrations were generally greater than either bedded or suspended exposures. Chemical manipulation indicated that the observed toxicity in water column exposures was probably caused by metallic and/or nonionic organic contaminants. Conversely, manipulation of interstitial water did not result in significantly reduced toxicity, suggesting that other toxicants such as ammonia and hydrogen sulfide may be active.

  19. Contaminated marine sediments: Water column and interstitial toxic effects

    SciTech Connect

    Burgess, R.M.; Schweitzer, K.A.; McKinney, R.A.; Phelps, D.K.

    1993-01-01

    The toxicity that contaminated sediments may introduce into the water column has not been measured extensively. In order to quantify this potential toxicity, the seawater overlying two uncontaminated and three contaminated marine sediments was evaluated in the laboratory with the sea urchin Arbacia punctulata fertilization test. Concentrations of polychlorinated biphenyls (PCBs) and copper, as representative contaminants, were also measured. To characterize sources of toxicity, samples were chemically manipulated using reversed-phase chromatography, cation exchange, and chelation. Water column toxicity and contaminant concentrations were higher in the suspended exposures than in bedded exposures. Interstitial water toxicity and contaminant concentrations were generally greater than either bedded or suspended exposures. Chemical manipulation indicated that the observed toxicity in water column exposures was probably caused by metallic and/or nonionic organic contaminants. Conversely, manipulation of interstitial waters did not result in significantly reduced toxicity, suggesting that other toxicants such as ammonia and hydrogen sulfide may be active.

  20. Effect of biphenyl ether herbicides on the formation of mutagenic intermediates from procarcinogens by rainbow trout

    SciTech Connect

    Miyauchi, M.; Uematsu, T.

    1987-08-01

    Increasing frequencies of tumors among aquatic animals in polluted waters have been reported. Experiments have also shown that exposure of fish to certain well-known and widely distributed xenobiotics causes them to develop tumors in a relatively short time. Formation of mutagenic intermediates from procarcinogens by fish liver homogenates had been reported. It is well established that fish have the ability to biotransform xenobiotics in a manner similar to that of mammalian species. These biotransformation include cytochrome P-450-dependent monooxygenase systems. In fish as well as mammals, cyt. P-450 systems are known to be induced by environmental pollutants. These inducers of cyt. P-450 systems are thought to influence the appearance of toxicity of chemicals. Biphenyl ether herbicides have been widely used all over the world, and particularly in Japan, they are indicated as environmental pollutants. Judging from their structures like as PCB, they are suspected to induce cyt. P-450 systems in fish. In this study, the effects of biphenyl ether herbicides and related compounds on the formation of mutagenic intermediates from procarcinogens by the S-9 fractions from rainbow trout were examined by using the Salmonella/microsome test.

  1. Effects of cadmium on Drosophila: toxicity, proteins, and transfer RNAs

    SciTech Connect

    Jacobson, K.B.; Opresko, L.; Owenby, R.K.; Christie, N.T.

    1981-01-01

    An animal model with well-defined genetic and biochemical characteristics is needed for a detailed understanding of the mechanism of toxicity by metal ions. Drosophila melanogaster was used in the present study to demonstrate a number of responses to Cd/sup 2 +/, including lethality, age-related changes in resistance, alterations of the normal developmental changes in proteins, and alterations in specific transfer RNAs. Genotype-specific differences in resistance to Cd/sup 2 +/ were found: the v; bw strain was 5-10 times more resistant than su(s)/sup 2/v; bw for developmental exposure; upon treatment of the young adults the differences were in the same direction, but the sensitivities differed by only two- to three-fold. The adult fly became more sensitive to Cd/sup 2 +/ as it aged through 2 weeks, but changed little thereafter.The electrophoretic patterns of proteins of adult flies underwent changes during aging from 1 to 8 days; these changes were markedly altered by 0.55 mM CdCl/sub 2/ but not by 0.74 mM ZnCl/sub 2/ in the medium on which the flies were maintained. The appearance of queuosine-containing tRNA was stimulated by CdCl/sub 2/ (0.05-0.8 mM) in the growth medium, but not by ZnCl/sub 2/ (0.07-1.1 mM).Further studies involving D. melanogaster should be useful in defining specific interactions of toxic metal ions with macromolecules to enhance the understanding of the toxic effects of these and similar pollutants.

  2. Toxicity of nanosilver in intragastric studies: Biodistribution and metabolic effects.

    PubMed

    Hendrickson, Olga D; Klochkov, Sergey G; Novikova, Oksana V; Bravova, Irina M; Shevtsova, Elena F; Safenkova, Irina V; Zherdev, Anatoly V; Bachurin, Sergey O; Dzantiev, Boris B

    2016-01-22

    The unique physicochemical properties of silver nanoparticles explain their extensive application in consumer goods, food, and medicinal products. However, the biological effects of nanosilver after peroral exposure of mammals are still debatable. This study describes the biodistribution and biological action of 12nm non-coated silver nanoparticles intragastrically administered to male rats after acute (single exposure) and sub-acute (multiple exposures over 30 days) toxicity experiments. The daily doses were 2000 and 250mg/kg of body weight for single and multiple administrations, respectively. Silver tissue detection was conducted by elemental analysis with the help of atomic absorption spectroscopy. An estimation of the state of exposed animals was made and the dynamics of hematological and biochemical parameters of rats was studied. It was demonstrated that single and multiple administrations resulted in silver accumulation in the liver, kidneys, spleen, stomach, and small intestine. After both one- and repeated-dose exposures, the highest Ag contents were detected in the liver (0.87±0.37μg/g of organ) and kidneys (0.24±0.02μg/g of organ). The concentrations of silver detected in tissues were far smaller than the administered doses (<99%), indicating its efficient excretion from the organism. Acute and sub-acute exposures caused no animal mortality or signs of toxicity, manifested as changes in outward appearance or notable deviations in behavior or locomotor activity. Postmortem study revealed no visible pathomorphological abnormalities of internal organs. Hematological indices and biochemical parameters of the treated rats did not differ from those of the vehicle control animals. Overall, it can be concluded that nanosilver is able to be absorbed from the gastrointestinal tract into the bloodstream and accumulate in the secondary organs of rats. It showed no distinct toxicity under the experimental conditions of this study. PMID:26617184

  3. EFFECT OF CHEMICAL CARRIERS ON AVIAN LC(50) TOXICITY TESTS

    EPA Science Inventory

    The subacute dietary (LC50) toxicity of a pesticide as prescribed by the Federal Insecticide Fungicide and Rodenticide Act and of toxic substances as defined by the Toxic Substances Control Act is a routine data point for many chemicals. The methods under which the LC50 data are ...

  4. Toxic effects of brominated indoles and phenols on zebrafish embryos.

    PubMed

    Kammann, U; Vobach, M; Wosniok, W

    2006-07-01

    Organobromine compounds in the marine environment have been the focus of growing attention in past years. In contrast to anthropogenic brominated flame retardants, other brominated compounds are produced naturally, e.g., by common polychaete worms and algae. Brominated phenols and indoles assumed to be of biogenic origin have been detected in water and sediment extracts from the German Bight. These substances as well as some of their isomers have been tested with the zebrafish embryo test and were found to cause lethal as well as nonlethal malformations. The zebrafish test was able to detect a log K(OW)-related toxicity for bromophenols, suggesting nonpolar narcosis as a major mode of action. Different effect patterns could be observed for brominated indoles and bromophenols. The comparison of effective concentrations in the zebrafish embryo test with the concentrations determined in water samples suggests the possibility that brominated indoles may affect early life stages of marine fish species in the North Sea. PMID:16418895

  5. Aloe vera: A review of toxicity and adverse clinical effects.

    PubMed

    Guo, Xiaoqing; Mei, Nan

    2016-04-01

    The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex. PMID:26986231

  6. Toxic effects of phenol on grey mullet, Mugil auratus Risso

    SciTech Connect

    Krajnovic-Ozretic, M.; Ozretic, B.

    1988-01-01

    Phenolic compounds are frequently found as contaminants in surface waters, including marine coastal waters. Phenols are generally classified as nonspecific metabolic inhibitors, and the main toxic effects are manifested on the nervous system due to the dissolution of lipids, whereas in the circulatory system phenols act as hemolysing agents of the erythrocytes. Data about sublethal effects of phenol, particularly to marine organisms are rather scarce. In several fresh water fish species exposed to phenol, the number of erythrocytes and the amount of serum proteins were decreased while lesion of gill filaments with edema and blood infiltration with degenerative changes in liver were also observed. These investigations concerned the identification of some physiological and biochemical changes in mullet blood as a consequence of exposure to phenol and some observations about the behavior and gross pathology of poisoned fish were also made.

  7. Toxic effects of hexaflumuron on the development of Coccinella septempunctata.

    PubMed

    Yu, Caihong; Fu, Maoran; Lin, Ronghua; Zhang, Yan; Yongquan, Liu; Jiang, Hui; Brock, Theo C M

    2014-01-01

    Studying the toxic risk of pesticide exposure to ladybird beetles is important from an agronomical and ecological perspective since larval and adult ladybirds are dominant predators of herbivorous pest insects (e.g., aphids) in various crops in China. This article mainly deals with the long-term effects of a single application of the insect growth regulator hexaflumuron on Coccinella septempunctata. A 72-h and a 33-day toxicity test with hexaflumuron (single application) were performed, starting with the second instar larvae of C. septempunctata. Exposure doses in the long-term experiment were based on the estimated 72-h acute LR50 (application rate causing 50% mortality) value of 304 g active ingredient (a.i.) ha(-1) for second instar larvae of C. septempunctata. The long-term test used five hexaflumuron doses as treatment levels (1/50, 1/100, 1/200, 1/400, and 1/800 of the 72-h acute LR50), as well as a solvent control and blank control treatment. The measurement endpoints used to calculate no observed effect application rates (NOERs) included development time, hatching, pupation, adult emergence, survival, and number of eggs produced. Analyzing the experimental data with one-way analysis of variance showed that the single hexaflumuron application had significant effects on C. septempunctata endpoints in the 33-day test, including effects on development duration (NOER 1.52 g a.i. ha(-1)), hatching (NOER 3.04 g a.i. ha(-1)), pupation (NOER 3.04 g a.i. ha(-1)), and survival (NOER 1.52 g a.i. ha(-1)). These NOERs are lower than the reported maximum field application rate of hexaflumuron (135 g a.i. ha(-1)) in cotton cultivation, suggesting potential risks to beneficial arthropods. PMID:23917742

  8. Evaluation of MWNT toxic effects on daphnia and zebrafish embryos

    NASA Astrophysics Data System (ADS)

    Olasagasti, Maider; Alvarez, Noelia; Vera, Carolina; Rainieri, Sandra

    2009-05-01

    Organisms of daphnia (Daphnia magna) and zebrafish (Danio rerio) embryos were exposed to a range of different concentrations of COOH-functionalized MWCNT suspended in an aqueous solution of Tween 20. Immobilization of daphnia and growth retardation, inhibition and malformation of zebrafish embryos were the endpoints tested after 24 and 48 hours. Immobilization of daphnia could be observed from 3 to 16 ppm and an increasing mortality of zebrafish embryo was detected at all the concentration tested. To identify more subtle toxic effects, we took advantage of the extensive information available on the zebrafish genome and monitored by RT-PCR the expression patterns of different zebrafish genes that could act as toxicity bio-markers. At some of the concentrations tested, changes in the expression profiles of the genes examined were detected. Our results suggest that MWCNT could potentially represent a risk to human health and environment, therefore a wider range of concentrations and further testing of this molecules should be carried out to define possible limitations in their use.

  9. Toxic effects of chromium on tannery workers at Sialkot (Pakistan).

    PubMed

    Khan, Dilshad Ahmed; Mushtaq, Shahida; Khan, Farooq Ahmad; Khan, Muhammad Qaiser Alam

    2013-03-01

    Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure. Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan. A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included. Blood complete counts, high-sensitive C-reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures. Chromium levels in blood (BCr) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst-200. Results revealed that all the workers were male with average age of 33 years and 15 (13%) had skin rashes, 14 (12%) had chronic bronchitis, 10 (8%) had gastritis and 4 (3%) conjunctivitis. The tannery workers had significantly raised median (interquartile range) of BCr 569 (377-726) nmol/L as compared to 318 (245-397) nmol/L in the control (p < 0.001). Sixty-five (54%) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry. The urinary chromium excretion was significantly high in workers 131 (46-312) nmol/L as compared to 13 (3-26) nmol/L in controls (p < 0.01). The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems. It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot. They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes. PMID:22258629

  10. Lead toxicity: From overt to subclinical to subtle health effects

    SciTech Connect

    Goyer, R.A. )

    1990-06-01

    Although the toxicity of lead was recognized centuries ago, concern was restricted to overt symptoms: colic, encephalopathy, anemia, or renal disease. Two major reasons for lack of progress in restricting toxicity were that interest was limited to occupational exposures and there was lack of awareness of specific biochemical or metabolic effects. Identification of subclinical effects has been possible the last 15 or 20 years because of the development of sensitive measures to detect cognitive and behavioral changes that are not apparent clinically and because of methods to measure the reduced activity of heme enzymes. This progress was driven by basic and clinical research that resulted in a better understanding of cellular toxicology. The new awareness prompted the lowering of acceptable occupational exposures, as measured by blood lead from 80 to 40 to 60 micrograms/dL range, and the establishment of maximum recommended exposures in children to a blood lead level of 25 micrograms/dL. Lowering the lead content in gasoline has been accomplished by a nearly 50% decrease in average blood levels of persons in the United States (NHANES II data). Current research implicates lead as a contributing etiologic factor in a number of common diseases affecting large portions of the population such as subtle cognitive and neurological deficits, hypertension, congenital malformations, immunotoxicity, and deficits in growth and development. For each of these disorders there may be multiple etiologic factors; the scientific challenge is to develop sensitive methodology to detect the specific role of lead. Other potential subtle health effects include the influence of small amounts of lead on cell proliferation and lead as a cofactor in carcinogenesis. 41 refs.

  11. Toxic effects of oil and dispersant on marine microalgae.

    PubMed

    Garr, Amber L; Laramore, Susan; Krebs, William

    2014-12-01

    To better understand the potential impacts of the deepwater horizon oil spill on lower trophic level food sources, a series of toxicological laboratory experiments were conducted with two microalgae species. The acute toxicity of oil (tar mat and MC252 crude oil), dispersant (Corexit 9500A), and dispersed oil on growth inhibition (IC50) and motility of Isochrysis galbana and Chaetoceros sp. were determined. There was no impact on cell division (growth) for microalgae exposed to both oil types and mean motility of I. galbana never dropped below 79 %. However, the addition of dispersant inhibited cell division and motility within 24 h, with Chaetoceros sp. being more susceptible to sublethal effects than I. galbana. These results highlight microalgae sensitivity to the use of dispersants in bioremediation processes, which may be a concern for long-term impacts on fisheries recruitment. PMID:25283369

  12. Effect of trifluoperazine on toxicity, HIF-1α induction and hepatocyte regeneration in acetaminophen toxicity in mice1

    PubMed Central

    Chaudhuri, Shubhra; McCullough, Sandra S.; Hennings, Leah; Brown, Aliza T.; Li, Shun-Hwa; Simpson, Pippa M.; Hinson, Jack A.; James, Laura P.

    2012-01-01

    Oxidative stress and mitochondrial permeability transition (MPT) are important mechanisms in acetaminophen (APAP) toxicity. The MPT inhibitor trifluoperazine (TFP) reduced MPT, oxidative stress, and toxicity in freshly isolated hepatocytes treated with APAP. Since hypoxia inducible factor-one alpha (HIF-1α is induced very early in APAP toxicity, a role for oxidative stress in the induction has been postulated. In the present study, the effect of TFP on toxicity and HIF-1α induction in B6C3F1 male mice treated with APAP was examined. Mice received TFP (10 mg/kg, oral gavage) prior to APAP (200 mg/kg IP) and at 7 and 36 h after APAP. Measures of metabolism (hepatic glutathione and APAP protein adducts) were comparable in the two groups of mice. Toxicity was decreased in the APAP/TFP mice at 2, 4, and 8 h, compared to the APAP mice. At 24 and 48 h, there were no significant differences in toxicity between the two groups. TFP lowered HIF-1α induction but also reduced the expression of proliferating cell nuclear antigen, a marker of hepatocyte regeneration. TFP can also inhibit phospholipase A2, and cytosolic and secretory PLA2 activity levels were reduced in the APAP/TFP mice compared to the APAP mice. TFP also lowered prostaglandin E2 expression, a known mechanism of cytoprotection. In summary, the MPT inhibitor TFP delayed the onset of toxicity and lowered HIF-1α induction in APAP treated mice. TFP also reduced PGE2 expression and hepatocyte regeneration, likely through a mechanism involving PLA2. PMID:22902588

  13. Antagonistic effects of tetrodotoxin on aconitine-induced cardiac toxicity.

    PubMed

    Ono, Takiyoshi; Hayashida, Makiko; Tezuka, Akito; Hayakawa, Hideyuki; Ohno, Youkichi

    2013-01-01

    Aconitine, well-known for its high cardiotoxicity, causes severe arrhythmias, such as ventricular tachycardia and ventricular fibrillation, by opening membrane sodium channels. Tetrodotoxin, a membrane sodium-channel blocker, is thought to antagonize aconitine activity. Tetrodotoxin is a potent blocker of the skeletal muscle sodium-channel isoform Na(v)1.4 (IC50 10 nM), but micromolar concentrations of tetrodotoxin are required to inhibit the primary cardiac isoform Na(v)1.5. This suggests that substantial concentrations of tetrodotoxin are required to alleviate the cardiac toxicity caused by aconitine. To elucidate the interaction between aconitine and tetrodotoxin in the cardiovascular and respiratory systems, mixtures of aconitine and tetrodotoxin were simultaneously administered to mice, and the effects on electrocardiograms, breathing rates, and arterial oxygen saturation were examined. Compared with mice treated with aconitine alone, some mice treated with aconitine-tetrodotoxin mixtures showed lower mortality rates and delayed appearance of arrhythmia. The decreased breathing rates and arterial oxygen saturation observed in mice receiving aconitine alone were alleviated in mice that survived after receiving the aconitine-tetrodotoxin mixture; this result suggests that tetrodotoxin is antagonistic to aconitine. When the tetrodotoxin dose is greater than the dose that can block tetrodotoxin-sensitive sodium channels, which are excessively activated by aconitine, tetrodotoxin toxicity becomes prominent, and the mortality rate increases because of the respiratory effects of tetrodotoxin. In terms of cardiotoxicity, mice receiving the aconitine-tetrodotoxin mixture showed minor and shorter periods of change on electrocardiography. This finding can be explained by the recent discovery of tetrodotoxin-sensitive sodium-channel cardiac isoforms (Na(v)1.1, 1.2, 1.3, 1.4 and 1.6). PMID:24189353

  14. Synergistic effect of piperonyl butoxide on acute toxicity of pyrethrins to Hyalella azteca.

    PubMed

    Giddings, Jeffrey; Gagne, James; Sharp, Janice

    2016-08-01

    A series of acute toxicity tests with the amphipod Hyalella azteca was performed to quantify the synergistic effect of piperonyl butoxide (PBO) on pyrethrin toxicity. Concentrations of PBO <4 µg/L caused no toxicity enhancement, whereas toxicity increased with PBO concentrations between 4 µg/L and 15 µg/L. Additive toxicity calculations showed that true synergism accounted for an increase in pyrethrin toxicity (decrease in median lethal concentration) of 1.4-fold to 1.6-fold and varied only slightly between 4 µg/L and 15 µg/L PBO, whereas direct toxicity of PBO accounted for an additional increase in mixture toxicity (up to 3.2-fold) that was proportional to PBO concentration. The results can be used to assess the risk of measured or predicted co-occurring concentrations of PBO and pyrethrins in surface waters. Environ Toxicol Chem 2016;35:2111-2116. © 2016 SETAC. PMID:26762236

  15. Toxic effects of cisplatin cytostatic drug in mussel Mytilus galloprovincialis.

    PubMed

    Trombini, Chiara; Garcia da Fonseca, Taina; Morais, Matilde; Rocha, Thiago Lopes; Blasco, Julián; Bebianno, Maria João

    2016-08-01

    Antineoplastic drugs used in chemotherapy were detected in aquatic environment: despite the very low concentrations (ng L(-1) to ug L(-1)), due to their potent mechanism of action they could have adverse effects on non-target aquatic organisms particularly under chronic exposure. Cisplatin (CDDP) is one of the most effective anticancer drug currently in use but information on its ecotoxicological effects is very limited. In this study, Mytilus galloprovincialis was used to investigate the toxic effects related to CDDP exposure. Mussels were exposed to cisplatin (100 ng L(-1)) for 14 days: antioxidant (superoxide dismutase, catalase, total and selenium-dependent glutathione peroxidase) and phase II (glutathione-S-transferase) enzymes activities, oxidative damage (lipid peroxidation), genotoxicity (DNA damage) and neurotoxicity (acetylcholinesterase) was evaluated. Results indicate that CDDP at tested concentration induce changes in the antioxidant capacity, oxidative stress in target organs (digestive gland and gills) as well as DNA damage in mussel hemocytes and neurotoxicity representing a risk for non-target organisms. PMID:27183200

  16. A brief study of toxic effects of some medicinal herbs on kidney

    PubMed Central

    Asif, Mohammad

    2012-01-01

    Increased use of complementary and alternative herbal medicines in the treatment of various diseases.Some herbal therapies may be causes of potential toxicity that may be renal toxicity caused by the ingestion of herbs. The goal of this study is the toxic and beneficial effects of medicinal herbs on renal health by which evidence for benefit or toxicity has been found. Included are nephrotoxicity from aristolochic acid and other components within herbs, herb-drug interactions, heavy metal toxicity in herbs and adulterants during careless preparation of herbal medicine, resulting in adverse renal effects and renal toxicity from contaminants within the extracts. The review aims to provide knowledge and guide to encourage future toxicity studies on the kidney by medicinal herbs. PMID:23326775

  17. Toxic effects of butyl elastomers on aerobic methane oxidation

    NASA Astrophysics Data System (ADS)

    Niemann, Helge; Steinle, Lea I.; Blees, Jan H.; Krause, Stefan; Bussmann, Ingeborg; Lehmann, Moritz F.; Treude, Tina

    2013-04-01

    Large quantities of the potent greenhouse gas methane are liberated into the water column of marine and lacustrine environments where it may be consumed by aerobic methane oxidising bacteria before reaching the atmosphere.The reliable quantification of aerobic methane oxidation (MOx) rates is consequently of paramount importance for estimating methane budgets and to understand the controls on water column methane cycling. A widely used set of methods for measuring MOx rates is based on the incubation of water samples during which the consumption of methane is monitored, for instance with radio-tracer assays. Typically, incubation vessels are sealed with butyl rubber stoppers because these elastomers are essentially impermeable for gases at the relevant time scales. We tested the effect of different stopper materials (unmodified- and halogenated butyl rubber) on MOx activity in environmental samples and in cultures of methane oxidising bacteria. MOx rates in samples sealed with unmodified butyl rubber were > 75% lower compared to parallel incubations with halogenated butyl rubber seals, suggesting inhibiting/toxic effects associated with the use of unmodified butyl elastomers. To further explore the cause of these effects, we analysed aqueous extracts of the different stoppers. Halogenated butyl rubber stoppers appeared to bleed off comparably little amounts of organics. In stark contrast, extracts of unmodified butyl rubber were contaminated with various organic compounds including potential bactericides such as benzyltoluenes, phenylalkanes and benzuothiazoles. We also found tetramethylthiourea, a scavenger of active oxygen species, which may inhibit the MOx pathway.

  18. Effects of synergists on the metabolism and toxicity of anticholinesterases*

    PubMed Central

    Wilkinson, C. F.

    1971-01-01

    Insecticide synergists enhance insecticidal action through their ability to block the enzymatic detoxification of insecticides with which they are combined. The structure of the synergist is therefore determined by the nature of the insecticide and the critical biochemical pathway responsible for its degradation. Synergists can be broadly classified as either analogue synergists, whose structure closely resembles that of the insecticide they synergize, or inhibitors of microsomal oxidation. Metabolism of the phenyl methylcarbamates is effected largely by the microsomal enzymes. Consequently microsomal enzyme inhibitors, such as the methylenedioxyphenyl compounds, the aryloxyalkylamines, the thiocyanates, the propynyl aryl ethers, and the 1,2,3-benzothiadiazoles, are all effective carbamate synergists. The detoxification pathways of the organophosphates, however, are more complex and include hydrolysis, dealkylation, and carboxylesterase pathways as well as oxidation. Because phosphorothioates are activated by oxidation, their toxicity is often antagonized by oxidase inhibitors. The effectiveness of different synergists towards resistant strains of insects is likely to vary in a manner that reflects the critical metabolic pathway on which resistance depends. PMID:4398521

  19. Protective effect of crocin on liver toxicity induced by morphine

    PubMed Central

    Salahshoor, Mohammad Reza; khashiadeh, Mojtaba; Roshankhah, Shiva; Kakabaraei, Seyran; Jalili, Cyrus

    2016-01-01

    Crocin, a bioactive molecule of saffron can be purely isolated from the saffron extract. It has different pharmacological effects such as antioxidant and anticancer activities. Morphine is an opioid analgesic drug. It is mainly metabolized in liver and causes devastating effects. It can increase the generation of free radicals. This study was designed to evaluate the protective role of crocin against morphine-induced toxicity in the mouse liver. In this study, various doses of crocin (12.5, 25 and 50 mg/kg) and crocin plus morphine were administered interaperitoneally once daily to 48 male mice for 20 consecutive days. These mice were randomly assigned to 8 groups of 6 each. The liver weight and histology, aspartate amino transferase, alanine aminotransferase, alkaline phosphatase (ALP) and serum nitric oxide levels were studied. The results indicated that morphine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein diameters, liver enzyme levels, and blood serum nitric oxide level compared to saline group (P<0.05). However, crocin administration significantly boosted liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes and nitric oxide levels in all groups compared to the group received morphine alone (P<0.05). It seems that crocin administration could protect the liver damage induced by morphine. The antioxidant effect of crocin may be a major reason for its positive impact on liver parameters. PMID:27168751

  20. Cytogenetic toxicity and no-effect limit dose of pesticides.

    PubMed

    Kumar, D; Khan, P K; Sinha, S P

    1995-04-01

    The no-effect limit dose (NELD) of three commonly used pesticides with respect to their cytogenetic toxicity was determined in a number of test systems using a sufficient number of lower doses to characterize the dose-effect relationship. For lindane, malathion and metacid, this dose was 3.2, 7.0 and 3.0 mg/litre, respectively, for mitosis inhibition and 9.0, 55 and 60 mg/litre, respectively, for chromosome clastogeny in onion root-tip cells. For chromosome clastogeny in mice bone marrow cells, the NELDs of the three pesticides were 1.6, 1.5 and 2.0 mg/kg body weight/day, respectively. These values for dominant lethals and X-chromosome-linked recessive lethals in Drosophila were 20 and 5 micrograms lindane/litre, 2 and 3.5 micrograms malathion/litre and 4 and 5.5 micrograms metacid/litre, respectively. Thus, the NELDs are not only pesticide specific but also organism specific, tissue specific and even damage specific. Furthermore, the NELD values determined are so small that the real human exposure to pesticides cannot be reduced below these levels without compromising the effectiveness of pesticides in use. PMID:7537710

  1. Toxic effects of occupational and environmental chemicals on the testes

    SciTech Connect

    Sever, L.E.; Hessol, N.A.

    1983-01-01

    This paper examines evidence for effects of occupational chemicals on male reproduction. We consider primarily human data, and much of that from epidemiologic studies. We use animal studies to illustrate points, but the theme is the human experience. The approach is based on examining reproductive function as an indicator of toxic effects. Testicular structure and function is briefly discussed. We provide a brief review of relevant structure, function and hormonal control. We describe the anatomy of the testis and its histological structure. We then discuss the testis from the point of view of exocrine and endocrine function and the relationship of the testis to other endocrinological organs. This is followed by a review of methods for assessing human testicular function, including reproductive histories, sperm analysis, assessment of hormonal status, and histological studies. Although the primary focus is on human studies, we consider briefly general categories of chemicals shown to have a testicular effect in animal studies and also animal evidence of mechanisms of action associated with testicular toxicology. Specific chemicals shown to affect reproduction in the human male are reviewed and directions for future research in this area discussed.

  2. Protective effect of crocin on liver toxicity induced by morphine.

    PubMed

    Salahshoor, Mohammad Reza; Khashiadeh, Mojtaba; Roshankhah, Shiva; Kakabaraei, Seyran; Jalili, Cyrus

    2016-01-01

    Crocin, a bioactive molecule of saffron can be purely isolated from the saffron extract. It has different pharmacological effects such as antioxidant and anticancer activities. Morphine is an opioid analgesic drug. It is mainly metabolized in liver and causes devastating effects. It can increase the generation of free radicals. This study was designed to evaluate the protective role of crocin against morphine-induced toxicity in the mouse liver. In this study, various doses of crocin (12.5, 25 and 50 mg/kg) and crocin plus morphine were administered interaperitoneally once daily to 48 male mice for 20 consecutive days. These mice were randomly assigned to 8 groups of 6 each. The liver weight and histology, aspartate amino transferase, alanine aminotransferase, alkaline phosphatase (ALP) and serum nitric oxide levels were studied. The results indicated that morphine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein diameters, liver enzyme levels, and blood serum nitric oxide level compared to saline group (P<0.05). However, crocin administration significantly boosted liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes and nitric oxide levels in all groups compared to the group received morphine alone (P<0.05). It seems that crocin administration could protect the liver damage induced by morphine. The antioxidant effect of crocin may be a major reason for its positive impact on liver parameters. PMID:27168751

  3. Evaluation of toxic and interactive toxic effects of three agrochemicals and copper using a battery of microbiotests.

    PubMed

    Kungolos, A; Emmanouil, C; Tsiridis, V; Tsiropoulos, N

    2009-08-01

    Three commonly used test organisms of different trophic levels (Vibrio fischeri, Pseudokirchneriella subcapitata and Daphnia magna) were exposed to selected agrochemicals (fosthiazate, metalaxyl-M, imidacloprid) and copper, in single doses or in binary mixtures. The toxicity of each single compound varied up to two orders of magnitude, depending on the test species examined. V. fischeri was the most sensitive test organism regarding fosthiazate and metalaxyl-M, indicating an IC(50) value of 0.20 mg/L (0.17-0.25 mg/L) and 0.88 mg/L (0.35-1.57 mg/L), respectively. Imidacloprid was the least toxic compound, indicating an EC(50) value on D. magna of 64.6 mg/L (43.3-122.5 mg/L) and an IC(50) value on V. fischeri of 226 mg/L (159-322 mg/L), while for imidacloprid at a concentration of 1000 mg/L the effect on P. subcapitata was lower than 50%. Copper was the most toxic compound towards all test organisms exhibiting the highest toxic effect on P. subcapitata, with an IC(50) value of 0.05 mg/L (0.003-0.008 mg/L). The toxic effects of the binary mixtures have been compared to the theoretically expected effect, resulting from a simple mathematical model based on the theory of probabilities. The independent action model was used in order to predict the theoretically expected effect. The interactive effects were mostly antagonistic or additive, while in few cases (interactive effects of metalaxyl-M and copper on V. fischeri) a synergistic mode of action was observed for some concentration combinations. Experiments showed that interactive effects of chemicals may vary depending on the test species used as well as on the chemicals and their respective concentrations. Although most of the concentrations of chemicals tested in this study are higher than the ones usually found in natural environment, the evaluation of their interactive toxic effects using a battery of bioassays may comprise a useful tool for the estimation of the environmental hazard of chemicals. PMID:19447473

  4. Fate and toxic effects of environmental stressors: environmental control.

    PubMed

    Zhuang, Jie; Yu, Han-Qing; Henry, Theodore B; Sayler, Gary S

    2015-12-01

    The potential for toxicants to harm organisms in the environment is influenced by the physicochemistry of the substances and their environmental behaviors and transformation within ecosystems. This special issue is composed of 20 papers that report on studies which have investigated the fate and toxicity of various toxicants including engineered nanoparticles, pharmaceuticals and personal care products, antibiotics, pathogens, heavy metals, and agricultural nutrients. The environmental transformations of these substances and how these processes affect their toxicity are emphasized. This paper highlights the important findings and perspectives of the selected papers in this special edition, with an aim of providing insights into full-scale evaluation on the toxicity of various contaminants that exist in ecosystems. General suggestions are provided for the future directions of toxicological research. PMID:26497020

  5. Impact of effects of acid precipitation on toxicity of metals.

    PubMed Central

    Nordberg, G F; Goyer, R A; Clarkson, T W

    1985-01-01

    Acid precipitation may increase human exposure to several potentially toxic metals by increasing metal concentrations in major pathways to man, particularly food and water, and in some instances by enhancing the conversion of metal species to more toxic forms. Human exposures to methylmercury are almost entirely by way of consumption of fish and seafood. In some countries, intakes by this route may approach the levels that can give rise to adverse health effects for population groups with a high consumption of these food items. A possible increase in methylmercury concentrations in fish from lakes affected by acid precipitation may thus be of concern to selected population groups. Human exposures to lead reach levels that are near those associated with adverse health effects in certain sensitive segments of the general population in several countries. The possibility exists that increased exposures to lead may be caused by acid precipitation through a mobilization of lead from soils into crops. A route of exposure to lead that may possibly be influenced by acid precipitation is an increased deterioration of surface materials containing lead and a subsequent ingestion by small children. A similar situation with regard to uptake from food exists for cadmium (at least in some countries). Human metal exposures via drinking water may be increased by acid precipitation. Decreasing pH increases corrosiveness of water enhancing the mobilization of metal salts from soil; metallic compounds may be mobilized from minerals, which may eventually reach drinking water. Also, the dissolution of metals (Pb, Cd, Cu) from piping systems for drinking water by soft acidic waters of high corrosivity may increase metal concentrations in drinking water. Exposures have occasionally reached concentrations which are in the range where adverse health effects may be expected in otherwise healthy persons. Dissolution from piping systems can be prevented by neutralizing the water before

  6. The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a "Central Dogma" for Toxic Mechanisms?

    PubMed

    Park, Yeong-Chul; Lee, Sundong; Cho, Myung-Haing

    2014-09-01

    Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems. PMID:25343011

  7. [Toxic effects of high concentrations of ammonia on Euglena gracilis].

    PubMed

    Liu, Yan; Shi, Xiao-Rong; Cui, Yi-Bin; Li, Mei

    2013-11-01

    Ammonia is among the common contaminants in aquatic environments. The present study aimed at evaluation of the toxicity of ammonia at high concentration by detecting its effects on the growth, pigment contents, antioxidant enzyme activities, and DNA damage (comet assay) of a unicellular microalga, Euglena gracilis. Ammonia restrained the growth of E. gracilis, while at higher concentrations, ammonia showed notable inhibition effect, the growth at 2 000 mg x L(-1) was restrained to 55.7% compared with that of the control; The contents of photosynthetic pigments and protein went up with increasing ammonia dosage and decreased when the ammonia concentration was above 1000 mg x L(-1); In addition, there was an obvious increase in SOD and POD activities, at higher concentration (2 000 mg x L(-1)), activities of SOD and POD increased by 30.7% and 49.4% compared with those of the control, indicating that ammonia could promote activities of antioxidant enzymes in E. gracilis; The degree of DNA damage observed in the comet assay increased with increasing ammonia concentration, which suggested that high dose of ammonia may have potential mutagenicity on E. gracilis. PMID:24455949

  8. Effect of trimetazidine on early and delayed doxorubicin myocardial toxicity.

    PubMed

    Perletti, G; Monti, E; Paracchini, L; Piccinini, F

    1989-01-01

    The influence of the administration of trimetazidine on the myocardial toxicity induced by doxorubicin was studied on an in vivo model in the rat. Trimetazidine was chosen due to its ability to act as a scavenger of oxygen-derived free radicals, which have been implicated in both early and delayed cardiotoxic manifestations after doxorubicin treatment. In the present study, doxorubicin was administered as 4 weekly i.v. injections of 3 mg/kg. The cardiotoxic effects were evaluated by measuring predictive ECG parameters (QT and ST intervals) as well as the contractile performance of atria isolated from treated animals. Heart preparations were also examined by light microscopy. Trimetazidine, 2.5 mg/kg/day i.p. for 3 days before doxorubicin administration plus 2.5 mg/kg/day p.o. for 10 weeks, was unable to prevent the development of doxorubicin-induced long-term cardiotoxicity. However, a significant improvement of the early cardiotoxic signs was observed in trimetazidine-treated rats, as reported in previous investigations. The present findings suggest that different target structures may be involved in the early and delayed free radical-mediated effects of doxorubicin. PMID:2636823

  9. Nutraceutical strategies for ameliorating the toxic effects of alcohol.

    PubMed

    McCarty, Mark F

    2013-04-01

    Rodent studies reveal that oxidative stress, much of it generated via induction/activation of NADPH oxidase, is a key mediator of a number of the pathogenic effects of chronic ethanol overconsumption. The highly reactive ethanol metabolite acetaldehyde is a key driver of this oxidative stress, and doubtless works in other ways to promote alcohol-induced pathology. Effective antioxidant measure may therefore be useful for mitigating the adverse health consequences of alcohol consumption; spirulina may have particular utility in this regard, as its chief phycochemical phycocyanobilin has recently been shown to function as an inhibitor of certain NADPH oxidase complexes, mimicking the physiological role of its chemical relatives biliverdin/bilirubin in this respect. Moreover, certain nutraceuticals, including taurine, pantethine, and lipoic acid, may have the potential to boost the activity of the mitochondrial isoform of aldehyde dehydrogenase, ALDH-2, accelerating conversion of acetaldehyde to acetate (which arguably has protective health effects). Little noticed clinical studies conducted nearly three decades ago reported that pre-ingestion of either taurine or pantethine could blunt the rise in blood acetaldehyde following ethanol consumption. Other evidence suggests that lipoic acid may function within mitochondria to maintain aldehyde dehydrogenase in a reduced active conformation; the impact of this agent on ethanol metabolism has however received little or no study. Studies evaluating the impact of nutracetical strategies on prevention of hangovers - which likely are mediated by acetaldehyde - may represent a quick, low-cost way to identify nutraceutical regimens that merit further attention for their potential impact on alcohol-induced pathology. Measures which boost or preserve ALDH-2 activity may also have important antioxidant potential, as this enzyme functions physiologically to protect cells from toxic aldehydes generated by oxidant stress. PMID

  10. Toxic effect of acyclovir on testicular tissue in rats

    PubMed Central

    Movahed, Elham; Nejati, Vahid; Sadrkhanlou, Rajabali; Ahmadi, Abbas

    2013-01-01

    Background: Acyclovir (ACV), a synthetic purine nucleoside analogue, is known to be toxic to gonads. Objective: The current study evaluated cytotoxicity of ACV on histopathological changes in testis tissue and serum testosterone and lipid peroxidation concentrations of male rats. Materials and Methods: Animals were divided into five groups. One group served as control and one group served as control sham. In the drug treated groups ACV administered for 15 days. 18 days after the last injection, animals were sacrificed. Histopathological and histomorphometrical analysis of the testis was carried out. Serum levels of testosterone and Lipid Peroxidation and potential fertility of animals was evaluated. Results: Male rats exposed to ACV had significant reduction in serum testosterone concentrations at 16 and 48mg/kg dose-levels (p<0.01). ACV induced histopathological changes in the testis and also increase the mean number of mast cells in peritubular or interstitial tissue in the testis at at 16 and 48mg/kg dose-levels (p<0.01). In addition ACV caused increase of serum level of Lipid Peroxidation at 48mg/kg dose-level (p<0.05). As well ACV decreased potential fertility in male rats. Conclusion: The present results highly support the idea that ACV has adverse effect on the reproductive system in male rat. PMID:24639735

  11. [Toxic effects of plant extracts on mosquito larvae].

    PubMed

    Rageau, J; Delaveau, P

    1979-01-01

    Vegetable extracts prepared with 530 species belonging to 120 botanical families are biologically screened with fourth stage larvae of Aedes aegypti. About twenty species are selected. Eight species of Convolvulaceae are specially toxic. PMID:527161

  12. Effects of chronic toxicity on threshold food concentrations

    SciTech Connect

    Cecchine, G.A.; Snell, T.W.

    1995-12-31

    Food shortage and toxicant stress have been proposed separately as structuring factors for zooplankton communities. How these factors interact to affect zooplankton remains poorly understood. The amount of food ingested by filter feeders depends upon food concentration, and a threshold concentration exists below which population growth is zero. A standard 2-d population growth test was used to determine whether toxicant stress altered the food threshold of the freshwater rotifer Brachionus calyciflorus. Threshold toxicant concentrations resulting in zero population growth rate and the NOEC were also compared at starving and abundant food conditions. Nutritional requirements were related to toxic exposure. For example, the threshold concentration of sodium pentachlorophenate (PCP) was 1.5 times lower at low food concentrations (0.3 million Nannochloris cells per milliliter) than at high food concentrations (3 million cells/ml). These results indicate that both factors must be considered in the validation of standard toxicity tests and their extrapolation to field conditions for ecologically meaningful predictions of toxicity.

  13. Toxic substances: Effects on fish. (Latest citations from Pollution Abstracts). Published Search

    SciTech Connect

    Not Available

    1993-05-01

    The bibliography contains citations concerning the biochemical and physiological effects of toxic substances on fish populations. Particular emphasis is placed upon using fish as an indicator of pollution in aquatic ecosystems. Toxicity effects of mercury, zinc, calcium chloride, sodium chloride, lead, cadmium, copper, and aluminum in freshwater and seawater fish are included. (Contains 250 citations and includes a subject term index and title list.)

  14. Effects of a Community Toxic Release on the Psychological Status of Children

    ERIC Educational Resources Information Center

    Greve, Kevin W.; Bianchini, Kevin J.; Stickle, Timothy R.; Love, Jeffrey M.; Doane, Bridget M.; Thompson, Matthew D.

    2007-01-01

    This study sought to determine the emotional effects of a major community toxic release on children in the exposed community while controlling for the potential effects of response bias. Controlling for the response bias inherent in litigated contexts is an advance over previous studies of toxic exposure in children. A randomly selected…

  15. Effect of heating rate on toxicity of pyrolysis gases from some synthetic polymers

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Soriano, J. A.; Kosola, K. L.

    1977-01-01

    The effect of heating rate on the toxicity of the pyrolysis gases from some synthetic polymers was investigate, using a screening test method. The synthetic polymers were polyethylene, polystyrene, polymethyl methacrylate, polycarbonate, ABS, polyaryl sulfone, polyether sulfone, and polyphenylene sulfide. The toxicants from the sulfur-containing polymers appeared to act more rapidly than the toxicants from the other polymers. It is not known whether this effect is due primarily to differences in concentration or in the nature of the toxicants. The carbon monoxide concentrations found do not account for the observed results.

  16. An application of the biotic ligand model to predict the toxic effects of metal mixtures.

    PubMed

    Kamo, Masashi; Nagai, Takashi

    2008-07-01

    The rapidly developing biotic ligand model (BLM) allows us to predict the toxicity of heavy metals in water of various chemistries; however, the current BLM predicts the toxicity of a single metal and not the toxic effects of metal mixtures. The toxic mechanisms of heavy metals are not yet completely understood, but hypocalcemia is suggested to be the most likely toxic mechanism for some metals. The BLM, which predicts the toxicity of metals by the amount of metals binding to ligand, is modified to predict the toxicity by the proportion of nonmetal binding ligand that is available for calcium uptake under the assumption that the organisms die because of hypocalcemia when so few ligands are available for calcium uptake. Because the proportion can be computed when multiple metals are present, the toxic effects of metal mixtures can be predicted. Zinc, copper, and cadmium toxicity to rainbow trout (Oncorhynchus mykiss) are considered. All data are collected from the literature, and a meta-analysis using the modified version of the BLM is conducted. The present study found that the proportion of nonmetal binding ligand is a constant value for any test condition. The proportion is not influenced by water chemistry or by metal species. Using the nature of constant proportion, toxicities of metals are well estimated. In addition, the toxic effects of metal mixtures are the simple sum of the toxicities of each metal (additive effect) corresponding to the bioavailable form of the metals. In terms of total concentration of metals in water, however, nonadditive effects, such as antagonism and synergism, are possible. PMID:18260697

  17. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  18. Morphine effects on gentamicin disposition and toxicity in mice.

    PubMed

    Hurwitz, A; Garty, M; Ben-Zvi, Z

    1988-05-01

    Morphine has been shown to reduce renal and hepatic clearance of several xenobiotics in rodents. After iv administration of gentamicin, 10 to 30 mg/kg, its plasma levels were elevated in mice given morphine, 20 mg/kg sc. Plasma clearance of gentamicin was nearly halved by morphine, due primarily to lowering of the elimination constant of gentamicin from 0.03 to 0.02 min-1 (p less than 0.01). Morphine also significantly reduced urine levels of gentamicin and urine volume. In mice given naloxone, 2 mg/kg sc, morphine did not significantly raise plasma levels of gentamicin nor reduce its elimination into urine. Mice were made tolerant by morphine administration for 9 days at ascending doses to 100 mg/kg twice daily. An acute challenge with morphine, 20 mg/kg, was less effective in raising plasma levels of gentamicin or lowering its urinary elimination in tolerant mice than after chronic saline treatment. Partial tolerance to acutely administered morphine and reversal of morphine effects by naloxone suggest opioid receptor-mediated reduction of glomerular filtration by morphine in mice. Despite marked elevation of plasma gentamicin levels in morphine-treated mice, narcotic administration did not significantly increase the acute toxicity of a single dose of gentamicin. LD50 of acutely administered iv gentamicin was 51.6 mg/kg after saline and 45.3 mg/kg after treatment with morphine, 20 mg/kg sc. However, this dose of morphine enhanced the lethality of intravenously infused gentamicin. Morphine administration significantly reduced the dose of infused gentamicin needed to achieve the critical lethal plasma level. PMID:3368920

  19. Effects of sulfur nutritional level on cadmium toxicity in barley

    SciTech Connect

    Chen, Yichang; Huerta, A.J. )

    1993-05-01

    The effects of S levels on Cd toxicity were studied in barley (Hordeum vulgare L.cv.UC 476). Barley was grown hydroponically in half-strength Hoagland's solution containing either 100% or 10% S in a growth chamber at constant 20 C, 290 umole M[sup [minus]2] s[sup [minus]1] light intensity, and a 16/18 hour light/dark period. Five days after the first true leaf appeared, 15 uM Cd was added to the nutrient solutions where appropriate. At 14 days after beginning of Cd treatment, plants were analyzed for photosynthetic characteristics. The photosynthetic characteristics measured were CO[sub 2] response curves (measured with a LICOR 6200 portable photosynthesis system), and fluorescence measurement system. At 21 days they were analyzed for morphological and biomass measurements. The CO[sub 2] response curves for leaves of plants treated with 10% S did not significantly differ from those of plants treated with 100% S. Treatment with Cd significantly reduced the CO[sup 2] saturated rates of photosynthesis and the reduction was more significant in the 10% S than in the 100% S plants. Photochemical efficiency of PSII (FV/FM) and fluorescence quenching capacity (FQ) were not affected by 10% S as compared to 100% S treatment. Interestingly, treatment with Cd significantly increased both FV/FM and FQ as compared to control., However, S level had no effect on the fluorescence parameters of Cd-treated plants. Leaf and root length, leaf area, root and shoot dry weight were only slightly affected (increased or decreased) by 10% S as compared to 100% S but very significantly reduced by treatment with Cd. Our results agree with the previous reports which show that S (an important component of glutathione and phytochelatins which are low molecular weight Cd binding proteins), is important in regulating Cd detoxification in plants. However, we are continuing to conduct experiments as even lower S concentrations and different Cd concentrations.

  20. Reproductive toxic effects of Tityus serrulatus scorpion venom in rats.

    PubMed

    Cruttenden, Karen; Nencioni, Ana Leonor A; Bernardi, Maria Martha; Dorce, Valquiria A C

    2008-08-01

    Tityus serrulatus is the most venomous scorpion in Brazil. Little is known about the effect of maternal exposure to the venom on fetal development. We investigated the effect of low to moderate doses of the venom (0.3 or 1.0 mg/kg s.c. on either day 5 or day 10 of gestation) on pregnant rats and on their offspring. For dams, we observed their body weight gain and reproductive parameters. For the offspring, we observed their body weight and weight of internal organs and the number of live and dead fetuses, and we investigated whether the venom caused external, visceral, skeletal or histopathological alterations in the offspring. The offspring were examined on gestational day 21. Injection of the venom on gestational day 5 did not change the reproductive parameters of the dams, their weight or fetuses' weight. Rats that received the high dose of the venom (1.0 mg/kg) on gestational day 10 had heavier placentas and heavier fetuses with heavier lungs. Injections on day 10 of gestation did not alter the reproductive parameters of the dams nor their weight gain at either dose. The venom did not cause malformations of the fetal skeleton or viscera and did not delay fetal development with either dose. In conclusion, subcutaneous administration of 0.3 or 1.0 mg/kg T. serrulatus venom to pregnant Wistar rats at either day 5 or day 10 of gestation did not cause maternal or clear fetal toxicity. Subtle increases in placental weight and fetal body and lung weights observed following treatment with 1.0 mg/kg on day 10 of gestation were not associated with histopathological findings. Whether these observations represent a reaction to treatment and, if so, the underlying mechanisms and their toxicological impact remain to be examined further in future studies. PMID:18550329

  1. Toxic effects of isoproturon on periphyton communities a microcosm study

    NASA Astrophysics Data System (ADS)

    Schmitt-Jansen, Mechthild; Altenburger, Rolf

    2005-02-01

    Coastal and estuarine ecosystems are increasingly exposed to herbicide contamination. To study the potential risks of these pollutants, the establishment of periphyton communities under exposure of a concentration series of isoproturon in a range of 0.0024-0.312 mg L -1 was investigated in a microcosm study. After two weeks of growth, chronic effects on biomass development, measured as Chl a fluorescence, taxonomic composition and photosynthetic capacity of PS II of attached microalgae were analysed using a pulse-amplitude modulated (PAM) fluorescence-based method. Algal classes were differentiated according to their pigment systems using four excitation wavelengths. Biomass remained constant up to pre-exposure concentrations of 0.02 mg L -1 isoproturon but decreased within one order of magnitude at the highest test concentration. Algal classes shifted from diatoms to chlorophytes at pre-exposure concentrations of 0.02-0.39 mg L -1. Community structure of diatoms representing the dominant group of attached algae at lower test concentrations was studied by microscopic analysis revealing that species numbers were highest at lowest test concentrations as compared to controls. At higher test concentrations Navicula halophila dominated with 89% of the diatom biomass but was abnormally shaped. Pollution-induced community tolerance (PICT) of periphyton to isoproturon was determined by short-term inhibition tests of photosynthesis. Pre-exposed communities increased their effect concentrations (EC 50) up to threefold within the 0.039 mg L -1 pre-treatment. Our results suggest that attached microalgal communities have a high potential of tolerance development to isoproturon at lower levels of contamination due to the replacement of sensitive species by more tolerant algae, although these species seemed to be affected too. We conclude that herbicide concentrations in river basins, estuaries or coastal zones may change community structure and primary production of

  2. Effects of diphenyl diselenide on methylmercury toxicity in rats.

    PubMed

    Dalla Corte, Cristiane L; Wagner, Caroline; Sudati, Jéssie H; Comparsi, Bruna; Leite, Gerlania O; Busanello, Alcindo; Soares, Félix A A; Aschner, Michael; Rocha, João B T

    2013-01-01

    This study investigates the efficacy of diphenyl diselenide [(PhSe)2] in attenuating methylmercury- (MeHg-)induced toxicity in rats. Adult rats were treated with MeHg [5 mg/kg/day, intragastrically (i.g.)] and/ or (PhSe)2 [1 mg/kg/day, intraperitoneally (i.p.)] for 21 days. Body weight gain and motor deficits were evaluated prior to treatment, on treatment days 11 and 21. In addition, hepatic and cerebral mitochondrial function (reactive oxygen species (ROS) formation, total and nonprotein thiol levels, membrane potential (ΔΨm), metabolic function, and swelling), hepatic, cerebral, and muscular mercury levels, and hepatic, cerebral, and renal thioredoxin reductase (TrxR) activity were evaluated. MeHg caused hepatic and cerebral mitochondrial dysfunction and inhibited TrxR activity in liver (38,9%), brain (64,3%), and kidney (73,8%). Cotreatment with (PhSe)2 protected hepatic and cerebral mitochondrial thiols from depletion by MeHg but failed to completely reverse MeHg's effect on hepatic and cerebral mitochondrial dysfunction or hepatic, cerebral, and renal inhibition of TrxR activity. Additionally, the cotreatment with (PhSe)2 increased Hg accumulation in the liver (50,5%) and brain (49,4%) and increased the MeHg-induced motor deficits and body-weight loss. In conclusion, these results indicate that (PhSe)2 can increase Hg body burden as well as the neurotoxic effects induced by MeHg exposure in rats. PMID:24459674

  3. Effect of pyrolysis temperature and air flow on toxicity of gases from a polycarbonate polymer

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Brick, V. E.; Brauer, D. P.

    1978-01-01

    A polycarbonate polymer was evaluated for toxicity of pyrolysis gases generated at various temperatures without forced air flow and with 1 L/min air flow, using the toxicity screening test method developed at the University of San Francisco. Time to various animal responses decreased with increasing pyrolysis temperature over the range from 500 C to 800 C. There appeared to be no significant toxic effects at 400 C and lower temperatures.

  4. Toxic and osmotic effects of glycerol on human granulocytes

    SciTech Connect

    Armitage, W.J.; Mazur, P.

    1984-11-01

    Human granulocytes are damaged by exposure to concentrations of glycerol as low as 0.5 M. We therefore investigated the addition of glycerol to granulocytes and its subsequent dilution under various conditions to try to distinguish between toxic and harmful osmotic effects of glycerol. The lesion caused by glycerol at 0/sup 0/C was expressed as a loss of plasma membrane integrity (as visualized by fluorescein diacetate) only after incubation (greater than or equal to1 h) at 37/sup 0/C. This damage was not ameliorated when osmotic stress was lessened by reducing the rates of addition and dilution of glycerol to keep the computed cell volume within 80-170% of isotonic cell volume. However, when osmotic stress was reduced further by increasing the temperature of addition and dilution of glycerol from 0/sup 0/ to 22/sup 0/C, the tolerance of the cells to 1 M glycerol increased somewhat. Reducing exposure to glycerol to 3 min or less at 0/sup 0/C greatly increased survival, but this time was too short to allow glycerol to equilibrate intracellularly. Finally, the presence of extra impermeant solute (NaCl or sucrose) in the medium to reduce the equilibrium cell volume to 60% of isotonic cell volume enabled granulocytes to survive 30-min exposure to 1 M glycerol at 0/sup 0/C, but cells had to remain shrunken during the 37/sup 0/C incubation to prevent the loss of membrane integrity. Suspensions that contained damaged granulocytes formed aggregates when incubated at 37/sup 0/C, and these aggregates were responsible for a major fraction of the observed loss in viability.

  5. Effect of food toxicants on voluntary wheel running in rats.

    PubMed

    Squibb, R E; Squibb, R L

    1979-05-01

    Voluntary wheel running in rats in reaction to a dietary deficiency of iron or food toxicants of natural (dioscin) and environmental (cadmium) origins was used to develop a behavioral model by which rapid detection of food contaminants was accomplished following induction of spontaneous activity by techniques of feed restriction. High levels of voluntary wheel running in reference controls were followed by significant depressions in running activity in animals fed the dietary toxicants. Analyses of blood and liver tissues and depressions of testes size confirmed the presence of the insults to metabolism. PMID:438894

  6. Toxicity assessment in marine sediment for the Terra Nova environmental effects monitoring program (1997-2010)

    NASA Astrophysics Data System (ADS)

    Whiteway, Sandra A.; Paine, Michael D.; Wells, Trudy A.; DeBlois, Elisabeth M.; Kilgour, Bruce W.; Tracy, Ellen; Crowley, Roger D.; Williams, Urban P.; Janes, G. Gregory

    2014-12-01

    This paper discusses toxicity test results on sediments from the Terra Nova offshore oil development. The Terra Nova Field is located on the Grand Banks approximately 350 km southeast of Newfoundland (Canada). The amphipod (Rhepoxynius abronius) survival and solid phase luminescent bacteria (Vibrio fischeri, or Microtox) assays were conducted on sediment samples collected from approximately 50 stations per program year around Terra Nova during baseline (1997), prior to drilling, and in 2000, 2001, 2002, 2004, 2006, 2008 and 2010 after drilling began. The frequency of toxic responses in the amphipod toxicity test was low. Of the ten stations that were toxic in environmental effects monitoring (EEM) years, only one (station 30(FE)) was toxic in more than one year and could be directly attributed to Terra Nova project activities. In contrast, 65 (18%) of 364 EEM samples were toxic to Microtox. Microtox toxicity in EEM years was not related to distance from Terra Nova drill centres or concentrations of >C10-C21 hydrocarbons or barium, the primary constituents of the synthetic-based drill muds used at Terra Nova. Of the variables tested, fines and strontium levels showed the strongest (positive) correlations with toxicity. Neither fines nor strontium levels were affected by drill cuttings discharge at Terra Nova, except at station 30(FE) (and that station was not toxic to Microtox). Benthic macro-invertebrate abundance, richness and diversity were greater in toxic than in non-toxic sediments. Therefore, Microtox responses indicating toxicity were associated with positive biological responses in the field. This result may have been an indirect function of the increased abundance of most invertebrate taxa in less sandy sediments with higher gravel content, where fines and strontium levels and, consequently, toxicity to Microtox were high; or chemical substances released by biodegradation of organic matter, where invertebrates are abundant, may be toxic to Microtox. Given

  7. MODEL FOR COMPARISON OF ANIMAL AND HUMAN ALVEOLAR DOSE AND TOXIC EFFECT OF INHALED OZONE

    EPA Science Inventory

    Present models for predicting human pulmonary toxicity of ozone from the toxic effects observed in animals rely on dosimetric measurements of ozone mass balance, and species comparisons of tissue protective mechanisms against ozone. The goal of the present study was to identify a...

  8. Considerations for Incorporating Bioavailability in Effect-Directed Analysis and Toxicity Identification Evaluation.

    EPA Science Inventory

    In order to avoid a bias toward highly toxic but poorly bioavailable compounds in the effect-directed analysis (EDA) of soils and sediments, approaches are discussed to consider bioavailability in EDA procedures. In parallel, complimentary approaches for making toxicity identific...

  9. UTILITY OF TOXICITY TESTS TO MEASURE EFFECTS OF SUBSTANCES ON MARINE ORGANISMS

    EPA Science Inventory

    Toxicity tests using single species, microcosms, and communities of test species are described for laboratory evaluations of marine (estuarine and oceanic) pollution effects. The design of acute, early life-stage, life-cycle, and community toxicity tests is discussed. Uses of tes...

  10. HYDROGEN OXIDATION IN SOILS AS A POSSIBLE TOXIC-EFFECTS INDICATOR

    EPA Science Inventory

    Efficient soil bioassays are needed in a screening array to determine the toxicities of industrial products and wastes. Hydrogen consumption is a common soil microbiological process that we evaluated as a possible soil indicator of toxic effects. Elemental tritium was used as a t...

  11. How might selenium moderate the toxic effects of mercury in stream fish of the Western USA?

    EPA Science Inventory

    The ability of selenium (Se) to moderate mercury (Hg) toxicity is well established in the literature. Mercury exposures that might otherwise produce toxic effects are counteracted by Se, particularly when Se:Hg molar ratios approach or exceed 1. We analyzed whole body Se and Hg c...

  12. Toxicity Studies.

    PubMed

    2016-01-01

    Toxicity studies in the animal models are done to determine the dose level recommended for the treatment of disease as drug. This guideline enables the characterization of adverse effects following repeated daily inhalation exposure to a test. This chapter includes oral and dermal toxicity studies which are discussed as per OECD guidelines. Both acute and subacute toxicity studies are given special emphasis. PMID:26939270

  13. POREWATER CHEMISTRY: EFFECTS OF SAMPLING, STORAGE, HANDLING, AND TOXICITY TESTING

    EPA Science Inventory

    As a general principle, it is nearly impossible to remove a porewater sample from sediment, use it in a toxicity testing vessel with test organisms, and prevent changes in the chemistry of the natural and anthropogenic organic and inorganic constituents. The degree of change in t...

  14. Photocatalytic degradation of the antibiotic chloramphenicol and effluent toxicity effects.

    PubMed

    Lofrano, Giusy; Libralato, Giovanni; Adinolfi, Roberta; Siciliano, Antonietta; Iannece, Patrizia; Guida, Marco; Giugni, Maurizio; Volpi Ghirardini, Annamaria; Carotenuto, Maurizio

    2016-01-01

    Chloramphenicol sodium succinate (CAP, C15H15Cl2N2 Na2O8) is a broad-spectrum antibiotic exhibiting activity against both Gram-positive and Gram-negative bacteria as well as other groups of microorganisms only partially removed by conventional activated sludge wastewater treatment plants. Thus, CAP and its metabolites can be found in effluents. The present work deals with the photocatalytic degradation of CAP using TiO2 as photocatalyst. We investigated the optimization of reaction contact time and concentration of TiO2 considering CAP and its by-products removal as well as effluent ecotoxicity elimination. Considering a CAP real concentration of 25mgL(-1), kinetic degradation curves were determined at 0.1, 0.2, 0.4, 0.8, 1.6 and 3.2gL(-1) TiO2 after 5, 10, 30, 60 and 120min reaction time. Treated samples were checked for the presence of by-products and residual toxicity (V. fischeri, P. subcapitata, L. sativum and D. magna). Results evidenced that the best combination for CAP and its by-products removal could be set at 1.6gL(-1) of TiO2 for 120min with an average residual toxicity of approximately 10%, that is the threshold set for negative controls in most toxicity tests for blank and general toxicity test acceptability. PMID:26256248

  15. Hypoxic radiosensitizers: prospects for effective compounds with fewer toxic side-effects.

    PubMed Central

    Rupp, W. D.; Mroczkowski, Z.; Agrawal, K. C.

    1978-01-01

    Several radiosensitizing chemicals, including a family of simple nitroimidazoles, were examined in E. coli and compared with misonidazole for toxic side-effects on endpoints such as mutagenesis, cell killing and inhibition of the synthesis of the inducible enzyme beta-galactosidase. While all the compounds were similar to misonidazole or better in radiosensitization, marked differences in the various side effects were found. There results show that for E. coli it is possible to find compounds that sensitize as well as misonidazole but which have decreased mutagenicity and fewer other side-effects. Of the compounds examined, KA121 (2,5-dinitroimidazole) is the most promising for future study because it combines good radiosensitization with low mutagenicity and toxicity. PMID:98175

  16. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  17. Individual and combined toxic effects of herbicide atrazine and three insecticides on the earthworm, Eisenia fetida.

    PubMed

    Wang, Yanhua; An, Xuehua; Shen, Weifeng; Chen, Liezhong; Jiang, Jinhua; Wang, Qiang; Cai, Leiming

    2016-07-01

    In the present study, we evaluated the individual and combined toxic effects of herbicide atrazine and three insecticides (chlorpyrifos, lambda-cyhalothrin and imidacloprid) on the earthworm, Eisenia fetida. Results from 48-h filter paper test indicated that imidacloprid had the highest toxicity to E. fetida with an LC50 of 0.05 (0.041-0.058) μg a.i. cm(-2), followed by lambda-cyhalothrin and atrazine with LC50 values ranging from 4.89 (3.52-6.38) to 4.93 (3.76-6.35) μg a.i. cm(-2), while chlorpyrifos had the least toxicity to the worms with an LC50 of 31.18 (16.22-52.85) μg a.i. cm(-2). Results from 14-days soil toxicity test showed a different pattern of toxicity except that imidacloprid was the most toxic even under the soil toxicity bioassay system. The acute toxicity of atrazine was significantly higher than that of chlorpyrifos. In contrast, lambda-cyhalothrin was the least toxic to the animals under the soil toxicity bioassay system. The binary mixture of atrazine-lambda-cyhalothrin and ternary mixture of atrazine-chlorpyrifos-lambda-cyhalothrin displayed a significant synergistic effect on the earthworms under the soil toxicity bioassay. Our findings would help regulatory authorities understand the complexity of effects from pesticide mixtures on non-target organisms and provide useful information of the interaction of various pesticide classes detected in natural environment. PMID:27068296

  18. Effect of culture medium on toxic effect of ZnO nanoparticles to freshwater microalgae

    NASA Astrophysics Data System (ADS)

    Aravantinou, Andriana F.; Tsarpali, Vasiliki; Dailianis, Stefanos; Manariotis, Ioannis D.

    2014-05-01

    The widely use of nanoparticles (NPs) in many products, is increasing over time. The release of NPs into the environment may affect ecosystems, and therefore it is essential to study their impact on aquatic organisms. The aim of this work was to investigate the effect of zinc oxide (ZnO) NPs on microalgae, cultured in different mediums. Chlorococcum sp. and Scenedesmus rubescens were used as freshwater microalgae model species in order to investigate the toxic effects of ZnO NPs. Microalgae species exposed to ZnO NPs concentrations varying from 0.081 to 810 mg/L for different periods of time (24 to 96 h) and two different culture mediums. The aggregation level and particle size distribution of NPs were also determined during the experiments. The experimental results revealed significant differences on algae growth rates depending on the selected culture medium. Specifically, the toxic effect of ZnO NPs in Chlorococcum sp. was higher in cultures with 1/3N BG-11 medium than in BBM medium, despite the fact that the dissolved zinc concentration was higher in BBM medium. On the other hand, Scenedesmus rubescens exhibited the exact opposite behavior, with the highest toxic effect in cultures with BBM medium. Both species growth was significantly affected by the exposure time, the NPs concentrations, and mainly the culture medium.

  19. Effects of calcium, magnesium, and sodium on alleviating cadmium toxicity to Hyalella azteca

    USGS Publications Warehouse

    Jackson, B.P.; Lasier, P.J.; Miller, W.P.; Winger, P.V.

    2000-01-01

    Toxicity of trace metal ions to aquatic organisms, arising through either anthropogenic inputs or acidification of surface waters, continues to be both a regulatory and environmental problem. It is generally accepted that the free metal ion is the major toxic species (Florence et a1.,1992) and that inorganic or organic complexation renders the metal ion non-bioavailable (Meador, 1991, Galvez and Wood, 1997). However, water chemistry parameters such as alkalinity, hardness, dissolved organic carbon and pH influence metal ion toxicity either directly by lowering free metal ion concentration or indirectly through synergistic or antagonistic effects. Alkalinity and salinity can affect the speciation of metal ions by increasing ion-pair formation, thus decreasing free metal ion concentration. For example, Cu was found to be less toxic to rainbow trout in waters of high alkalinity (Miller and Mackay, 1980), due to formation of CuCO3 ion pair, and corresponding reduction in free Cu2+ concentration. The influence of salinity on the toxicity of cadmium to various organisms has been demonstrated in a number of studies (Bervoets et al., 1995, Hall et al., 1995, Lin and Dunson, 1993, Blust et al., 1992). In all these studies the apparent toxicity of cadmium was lowered as salinity was increased due to increased formation of CdC1+ and CDCl2 aqueous complexes that are non-toxic or of much lower toxicity than the free Cd2+ ion. Changes in pH exert both a biological and chemical effect on metal ion toxicity (Campbell and Stokes, 1985). Low pH favors greater metal ion solubility, and, in the absence of complexing ions, reduced speciation of the metal ion, which tends to increase toxicity compared to higher pH. However, Iow pH also enhances competition between H+ and metal ion for cell surface binding sites, which tends to decrease metal ion toxicity.

  20. Periphyton photosynthesis as an indicator of effluent toxicity: Relationship to effects on animal test species

    SciTech Connect

    Lewis, M.A.

    1992-01-01

    The use of freshwater and marine plants in effluent toxicity evaluations is uncommon despite the presence of test methods and recommendations for their use. It has been assumed that aquatic plants are less sensitive than animal test species and consequently, results from toxicity tests with invertebrates and fish have been used often as a surrogate data base. The study evaluated the ability of these animal toxicity tests to provide safe concentrations for in-stream periphyton. The toxicity of several samples of a treated municipal effluent were determined during a five-month period by monitoring short-term changes in periphyton photosynthesis (carbon-14 uptake) and by observing the effects on young production and survival of cultured daphnids and the fathead minnow. The effect levels from the various tests were compared. The effluent was seldom acutely toxic to Daphnia magna and the fathead minnow (Pimephales promelas) but it was consistently acutely and chronically toxic to Ceriodaphnia dubia. Chronic effect levels ranged between 17 and 71% effluent. Significant inhibition and stimulation of periphyton photosynthesis occurred at concentrations of 6 to 39% effluent. Periphyton photosynthesis was a more sensitive effect parameter than animal survival and in some cases than Ceriodaphnia reproductive performance. The results indicate that effluent toxicity tests conducted routinely with daphnids and fish may not be sufficient to predict effects on indigenous flora in receiving waters.

  1. Methods for nanoparticle labeling of ricin and effect on toxicity

    NASA Astrophysics Data System (ADS)

    Wark, Alastair W.; Yu, Jun; Lindsay, Christopher D.; Nativo, Paola; Graham, Duncan

    2009-09-01

    The unique optical properties associated with nanostructured materials that support the excitation of surface plasmons offer many new opportunities for the enhanced optical investigation of biological materials that pose a security threat. In particular, ricin is considered a significant bioterrorism risk due to its high toxicity combined with its ready availability as a byproduct in castor oil production. Therefore, the development of optical techniques capable of rapid on-site toxin detection with high molecular specificity and sensitivity continues to be of significant importance. Furthermore, understanding of the ricin cell entry and intracellular pathways remains poor due to a lack of suitable bioanalytical techniques. Initial work aimed at simultaneously tackling both these issues is described where different approaches for the nanoparticle labeling of ricin are investigated along with changes in ricin toxicity associated with the labeling process.

  2. Effects of toxicants on community metabolism in pools

    USGS Publications Warehouse

    Whitworth, Walter R.; Lane, Thomas H.

    1969-01-01

    Estimates of community metabolism of simulated natural environments were dcrivcd by diel oxygen techniques over a period of nine months. During this time, toxicants were added to some of the pools. "Natural" environmental factors and toxicants that did not affect the communities (0.02 mg/liter p,p' DDT; 0.1 mg/liter antimycin A; and 9.2 mg/liter KMnO,I) usually resulted in simultaneous changes, up or down, in both community photosynthesis and respiration. Concentrations (mg/liter) of 0.9 and 2.6 formalin, 10.0 nigrosine black, 10.0 and 2.0 malachite green, 0.1 Diquat, and 0,.5 and 5.0 CUSO.~ usually tlcprcsscd community oxygen production and increased community respiration for periods of 1 to 20 weeks.

  3. Effects of storage on sediment toxicity, bioaccumulation potential, and chemistry. Final report

    SciTech Connect

    Tatem, H.E.; Brandon, D.L.; Lee, C.R.; Jarvis, A.S.; Rhett, R.G.

    1991-01-01

    Current guidance on storage of sediments for bioassay/bioaccumulation tests requires that samples be held at 4 C and used within 2 weeks of collection. The objective of this study was to determine the effects of sediment storage for 40 weeks on sediment toxicity, bioaccumulation potential, and chemical analyses. Toxicity and bioaccumulation tests were conducted five times during 40 weeks of storage. Chemical analyses were performed three times during this period. The data indicate that sediments can be held for longer than 2 to 4 weeks, in many cases, without significant effect on test results. However, results of the study also show that tests performed at different times can produce different results. This study showed that a sediment that was toxic to mysids remained toxic during 16 weeks of sediment storage. Two sediments that were toxic initially continued to show significant toxicity after 8 and 16 weeks of sediment storage. One sediment, not toxic initially or at 4 weeks, changed during storage, becoming significantly toxic compared to the Atlantic Ocean (Ref) sediment. The bioaccumulation results showed that certain sediment contaminants (lead, mercury, polychlorinated biphenyls, and some polycyclic aromatic hydrocarbons, PAHs), generally do not reveal a statistical change in bioaccumulation, relative to Ref animals, during 16 weeks of sediment storage. Other PAHs, including phenanthrene, anthracene, benzo (a) anthracene, and chrysene, did change in bioaccumulation potential during storage.

  4. Toxicity of CeO2 nanoparticles - the effect of nanoparticle properties.

    PubMed

    Leung, Yu Hang; Yung, Mana M N; Ng, Alan M C; Ma, Angel P Y; Wong, Stella W Y; Chan, Charis M N; Ng, Yip Hang; Djurišić, Aleksandra B; Guo, Muyao; Wong, Mabel Ting; Leung, Frederick C C; Chan, Wai Kin; Leung, Kenneth M Y; Lee, Hung Kay

    2015-04-01

    Conflicting reports on the toxicity of CeO2 nanomaterials have been published in recent years, with some studies finding CeO2 nanoparticles to be toxic, while others found it to have protective effects against oxidative stress. To investigate the possible reasons for this, we have performed a comprehensive study on the physical and chemical properties of nanosized CeO2 from three different suppliers as well as CeO2 synthesized by us, and tested their toxicity. For toxicity tests, we have studied the effects of CeO2 nanoparticles on a Gram-negative bacterium Escherichia coli in the dark, under ambient and UV illuminations. We have also performed toxicity tests on the marine diatom Skeletonema costatum under ambient and UV illuminations. We found that the CeO2 nanoparticle samples exhibited significantly different toxicity, which could likely be attributed to the differences in interactions with cells, and possibly to differences in nanoparticle compositions. Our results also suggest that toxicity tests on bacteria may not be suitable for predicting the ecotoxicity of nanomaterials. The relationship between the toxicity and physicochemical properties of the nanoparticles is explicitly discussed in the light of the current results. PMID:25768267

  5. Toxic effects of thifluzamide on zebrafish (Danio rerio).

    PubMed

    Yang, Yang; Qi, Suzhen; Wang, Donghui; Wang, Kai; Zhu, Lizhen; Chai, Tingting; Wang, Chengju

    2016-04-15

    Thifluzamide is a fungicide widely used to control crop diseases, and it therefore constitutes a hazard to the environment. In this study, zebrafish were selected to assess the aquatic toxicity of thifluzamide. The acute and development toxicity of thifluzamide to embryos, larvae, and adult zebrafish were measured and the corresponding 96h-LC50 values were as follows: adult fish (4.19mg/L) toxic events. PMID:26780700

  6. The Effect of Digestive Capacity on the Intake Rate of Toxic and Non-Toxic Prey in an Ecological Context

    PubMed Central

    Oudman, Thomas; Hin, Vincent; Dekinga, Anne; van Gils, Jan A.

    2015-01-01

    Digestive capacity often limits food intake rate in animals. Many species can flexibly adjust digestive organ mass, enabling them to increase intake rate in times of increased energy requirement and/or scarcity of high-quality prey. However, some prey species are defended by secondary compounds, thereby forcing a toxin limitation on the forager’s intake rate, a constraint that potentially cannot be alleviated by enlarging digestive capacity. Hence, physiological flexibility may have a differential effect on intake of different prey types, and consequently on dietary preferences. We tested this effect in red knots (Calidris canutus canutus), medium-sized migratory shorebirds that feed on hard-shelled, usually mollusc, prey. Because they ingest their prey whole and crush the shell in their gizzard, the intake rate of red knots is generally constrained by digestive capacity. However, one of their main prey, the bivalve Loripes lucinalis, imposes a toxin constraint due to its symbiosis with sulphide-oxidizing bacteria. We manipulated gizzard sizes of red knots through prolonged exposure to hard-shelled or soft foods. We then measured maximum intake rates of toxic Loripes versus a non-toxic bivalve, Dosinia isocardia. We found that intake of Dosinia exponentially increased with gizzard mass, confirming earlier results with non-toxic prey, whereas intake of Loripes was independent of gizzard mass. Using linear programming, we show that this leads to markedly different expected diet preferences in red knots that try to maximize energy intake rate with a small versus a large gizzard. Intra- and inter-individual variation in digestive capacity is found in many animal species. Hence, the here proposed functional link with individual differences in foraging decisions may be general. We emphasize the potential relevance of individual variation in physiology when studying trophic interactions. PMID:26287951

  7. Toxicity and health effects of vehicle emissions in Shanghai

    NASA Astrophysics Data System (ADS)

    Ye, Shun-Hua; Zhou, Wei; Song, Jian; Peng, Bao-Cheng; Yuan, Dong; Lu, Yuan-Ming; Qi, Ping-Ping

    In China, the number of vehicles is increasing rapidly with the continuous development of economy, and vehicle emission pollution in major cities is more serious than ever. In this article, we summarized the results of a series of short-term assays, animal experiments and epidemiology investigations on the genotoxicity, immunotoxicity, respiratory toxicity and health effects of vehicle emissions in Shanghai, including gasoline exhausts (gas condensate and particles), diesel exhaust particles (DEP) and scooter exhaust particles (SEP). The results showed that: (1) Both gases and particulate phases of the exhausts of different kinds of vehicles showed strong mutagenicity in Ames test (TA98 and TA100 strains), rat hepatocyte unscheduled DNA synthesis (UDS) assay, and mouse micronucleus assay, and vehicle emissions could induce the transformation of Syrian hamster embryo (SHE) cells. DEP and SEP could induce the transformation of human diploid cell strain (KMB-13) cells, immunohistochemistry assay showed that c-myc and p21 proteins were highly expressed in the transformed cells. DEP and SEP could also inhibit the gap junctional intercellular communication (GJIC) of BALB/C3T3 cells (2) Vehicle emissions could decrease the number of macrophages in the lung (bronchial alveolar lavage fluid) (BALF) of male SD rats. Vehicle emissions could also increase the proportion of polymorphonuclear leukocytes (PMN), the content of cetyneuraminic acid (NA), the activity of lactate dehydrogenase (LDH), alkali phosphate (AKP), acid phosphate (ACP) in the lung BALF of the animals. (3) In epidemiology investigation, the proportion of those who have respiratory symptoms and chronic obstructive pulmonary diseases (COPD) in the workers who were exposed to DEP ( n=806) were much higher than those of the controls ( n=413). The OR (odd ratio) values of angina, nasal obstruction, phlegm, short of breath and COPD were 2.27, 3.08, 3.00, 3.19 and 2.32, respectively, and the proportion of those who

  8. Toxic effects of the administration of Mikania glomerata Sprengel during the gestational period of hypertensive rats

    PubMed Central

    Fulanetti, F.B.; Camargo, G.G.R.; Ferro, M.C.; Randazzo-Moura, P.

    2016-01-01

    Herbal medicine is an ancient practice that has been gaining acceptance of the medical class through scientific studies that prove its effectiveness. However, its use should still be cautious. Medicinal plants have potential toxic effects not yet discovered, and may have unproven interactions with other medications. The use of drugs during pregnancy is still very dangerous and vigorously studied; however, there are few studies of herbal medicines in pregnant women. Existing studies prioritize on teratogenic or abortifacient effects. The aim of this study was to analyze the toxic effects of Mikania glomerata Sprengel administration, popularly known as “guaco” during the gestational period of hypertensive rats. For this experimental groups consisting of pregnant Wistar rats received treatments with guaco extract (1 to 2 mL). In order to analyze the possible toxic effects of guaco during pregnancy, weight gain of rats was assessed during pregnancy; reproductive performance of rats, morphological parameters, and fetal placental histology were compared. Although some parameters presented significant differences, we can conclude that changes prioritized by literature, such as toxicity, vasodilation and hypotension, have not been caused by guaco. The only fetal changes observed were due to the maternal hypertension. Some studies have reported vasodilator and hypotensive effects of guaco. However, only a few studies exist, and its actual effects remain unknown. Specific studies should be developed with higher doses of guaco for a definitive conclusion of its toxic and non-toxic effects. PMID:26894037

  9. Toxic effects of the administration of Mikania glomerata Sprengel during the gestational period of hypertensive rats.

    PubMed

    Fulanetti, F B; Camargo, G G R; Ferro, M C; Randazzo-Moura, P

    2016-01-01

    Herbal medicine is an ancient practice that has been gaining acceptance of the medical class through scientific studies that prove its effectiveness. However, its use should still be cautious. Medicinal plants have potential toxic effects not yet discovered, and may have unproven interactions with other medications. The use of drugs during pregnancy is still very dangerous and vigorously studied; however, there are few studies of herbal medicines in pregnant women. Existing studies prioritize on teratogenic or abortifacient effects. The aim of this study was to analyze the toxic effects of Mikania glomerata Sprengel administration, popularly known as "guaco" during the gestational period of hypertensive rats. For this experimental groups consisting of pregnant Wistar rats received treatments with guaco extract (1 to 2 mL). In order to analyze the possible toxic effects of guaco during pregnancy, weight gain of rats was assessed during pregnancy; reproductive performance of rats, morphological parameters, and fetal placental histology were compared. Although some parameters presented significant differences, we can conclude that changes prioritized by literature, such as toxicity, vasodilation and hypotension, have not been caused by guaco. The only fetal changes observed were due to the maternal hypertension. Some studies have reported vasodilator and hypotensive effects of guaco. However, only a few studies exist, and its actual effects remain unknown. Specific studies should be developed with higher doses of guaco for a definitive conclusion of its toxic and non-toxic effects. PMID:26894037

  10. Effects of water quality parameters on boron toxicity to Ceriodaphnia dubia.

    PubMed

    Dethloff, Gail M; Stubblefield, William A; Schlekat, Christian E

    2009-07-01

    The potential modifying effects of certain water quality parameters (e.g., hardness, alkalinity, pH) on the acute toxicity of boron were tested using a freshwater cladoceran, Ceriodaphnia dubia. By comparison, boron acute toxicity was less affected by water quality characteristics than some metals (e.g., copper and silver). Increases in alkalinity over the range tested did not alter toxicity. Increases in water hardness appeared to have an effect with very hard waters (>500 mg/L as CaCO(3)). Decreased pH had a limited influence on boron acute toxicity in laboratory waters. Increasing chloride concentration did not provide a protective effect. Boron acute toxicity was unaffected by sodium concentrations. Median acute lethal concentrations (LC(50)) in natural water samples collected from three field sites were all greater than in reconstituted laboratory waters that matched natural waters in all respects except for dissolved organic carbon. Water effect ratios in these waters ranged from 1.4 to 1.8. In subsequent studies using a commercially available source of natural organic matter, acute toxicity decreased with increased dissolved organic carbon, suggesting, along with the natural water studies, that dissolved organic carbon should be considered further as a modifier of boron toxicity in natural waters where it exceeds 2 mg/L. PMID:18841408

  11. Cardiovascular and Hepatic Toxicity of Cocaine: Potential Beneficial Effects of Modulators of Oxidative Stress

    PubMed Central

    Graziani, Manuela; Antonilli, Letizia; Togna, Anna Rita; Grassi, Maria Caterina; Badiani, Aldo; Saso, Luciano

    2016-01-01

    Oxidative stress (OS) is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants) for the treatment of cocaine toxicity. We conclude that available OS modulators do not appear to have clinical efficacy. PMID:26823954

  12. Effect of amino acids on the toxicity of heavy metals to phytoplankton

    SciTech Connect

    Kosakowska, A.; Falkowski, L.; Lewandowska, J. )

    1988-05-01

    Heavy metals distribution in the sea water can be indispensable or delitorious for the organisms living in that environment depending on their concentration and speciation. The bioavailability as well as toxicity of the elements are strongly influenced by the organic matter dissolved in water. The effect of a number of organic compounds, including amino acids, on the toxicity of heavy metals was tested, but there were no reports elucidating compounds representing various types of structure. This paper deals with the effect of amino acids representing various structure groups on the toxicity of copper, cadmium and mercury against to Chlorella vulgaris and Anabeana variabilis.

  13. The Effect of Toxic Tall Fescue on Cellobiose-Utilizing Populations in the Bovine Rumen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A fungal endophyte (Neotyphodium coenophialum) infects tall fescue (Schedonorus arundinaceus Schreb. Dumort), and confers pest resistance through the production of alkaloids. Although, these alkaloids can reach concentrations that are toxic to livestock, their effects on the symbiotic rumen bacteri...

  14. EVALUATING THE HUMAN HEALTH EFFECTS OF HAZARDOUS WASTES: REPRODUCTION AND DEVELOPMENT, NEUROTOXICITY, GENETIC TOXICITY AND CANCER

    EPA Science Inventory

    Several approaches are available for characterizing potential toxicity of wastes. his paper describes biological tests which are appropriate for identifying waste as neurotoxic, genotoxic, or likely to produce developmental or reproductive effects. he tests recommended are, for n...

  15. TOXICITY APPROACHES TO ASSESSING MINING IMPACTS AND MINE WASTE TREATMENT EFFECTIVENESS

    EPA Science Inventory

    The USEPA Office of Research and Development's National Exposure Research Laboratory and National Risk Management Research Laboratory have been evaluating the impact of mining sites on receiving streams and the effectiveness of waste treatment technologies in removing toxicity fo...

  16. Effects of Environmental Toxicants on Metabolic Activity of Natural Microbial Communities

    PubMed Central

    Barnhart, Carole L. H.; Vestal, J. Robie

    1983-01-01

    Two methods of measuring microbial activity were used to study the effects of toxicants on natural microbial communities. The methods were compared for suitability for toxicity testing, sensitivity, and adaptability to field applications. This study included measurements of the incorporation of 14C-labeled acetate into microbial lipids and microbial glucosidase activity. Activities were measured per unit biomass, determined as lipid phosphate. The effects of various organic and inorganic toxicants on various natural microbial communities were studied. Both methods were useful in detecting toxicity, and their comparative sensitivities varied with the system studied. In one system, the methods showed approximately the same sensitivities in testing the effects of metals, but the acetate incorporation method was more sensitive in detecting the toxicity of organic compounds. The incorporation method was used to study the effects of a point source of pollution on the microbiota of a receiving stream. Toxic doses were found to be two orders of magnitude higher in sediments than in water taken from the same site, indicating chelation or adsorption of the toxicant by the sediment. The microbiota taken from below a point source outfall was 2 to 100 times more resistant to the toxicants tested than was that taken from above the outfall. Downstream filtrates in most cases had an inhibitory effect on the natural microbiota taken from above the pollution source. The microbial methods were compared with commonly used bioassay methods, using higher organisms, and were found to be similar in ability to detect comparative toxicities of compounds, but were less sensitive than methods which use standard media because of the influences of environmental factors. PMID:16346432

  17. Potential toxic effects of glyphosate and its commercial formulations below regulatory limits.

    PubMed

    Mesnage, R; Defarge, N; Spiroux de Vendômois, J; Séralini, G E

    2015-10-01

    Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure. PMID:26282372

  18. Effects of sediment bioturbation by Chironomus tentans on toxicity of heavy metals to Ceriodaphnia dubia

    SciTech Connect

    Pearson, M.S.; Clements, W.H.

    1994-12-31

    A laboratory study was conducted to examine the toxicological significance of bioturbation by Chironomus tentans (Diptera: Chironomidae) exposed to mixtures of heavy metals (Cd, Cu, Pb and Zn) in sediment. Overlying water was collected from beakers with and without chironomids. Overlying water samples from beakers with chironomids showed significantly higher levels of total zinc (p = 0.0088), copper (p < 0.0001) and lead (p = 0.0485) compared to beakers without chironomids. Ceriodaphnia dubia chronic toxicity tests were used to evaluate toxicity of the overlying water. Overlying water from beakers without chironomids was not toxic to C. dubia. In contrast, overlying water from beakers with chironomids was acutely toxic to C. dubia at dilutions > 50%. Dilutions of 6.25%, 12.5% and 25% had a reproductive effect on C. dubia. Results of this laboratory experiment indicate that benthic invertebrates may be responsible for increased toxicity of overlying waters.

  19. Use of passive samplers for improving oil toxicity and spill effects assessment.

    PubMed

    Letinski, Daniel; Parkerton, Thomas; Redman, Aaron; Manning, Ryan; Bragin, Gail; Febbo, Eric; Palandro, David; Nedwed, Tim

    2014-09-15

    Methods that quantify dissolved hydrocarbons are needed to link oil exposures to toxicity. Solid phase microextraction (SPME) fibers can serve this purpose. If fibers are equilibrated with oiled water, dissolved hydrocarbons partition to and are concentrated on the fiber. The absorbed concentration (Cpolymer) can be quantified by thermal desorption using GC/FID. Further, given that the site of toxic action is hypothesized as biota lipid and partitioning of hydrocarbons to lipid and fibers is well correlated, Cpolymer is hypothesized to be a surrogate for toxicity prediction. To test this method, toxicity data for physically and chemically dispersed oils were generated for shrimp, Americamysis bahia, and compared to test exposures characterized by Cpolymer. Results indicated that Cpolymer reliably predicted toxicity across oils and dispersions. To illustrate field application, SPME results are reported for oil spills at the Ohmsett facility. SPME fibers provide a practical tool to improve characterization of oil exposures and predict effects in future lab and field studies. PMID:25096583

  20. Toxic substances: Effects on fish. (Latest citations from Pollution abstracts). Published Search

    SciTech Connect

    1995-11-01

    The bibliography contains citations concerning the biochemical and physiological effects of toxic substances on fish populations. Particular emphasis is placed upon using fish as an indicator of pollution in aquatic ecosystems. Toxicity effects of mercury, zinc, calcium chloride, sodium chloride, lead, cadmium, copper, and aluminum in freshwater and seawater fish are included. (Contains 50-250 citations and includes a subject term index and title list.) (Copyright NERAC, Inc. 1995)

  1. Acute and chronic toxicity of endosulfan to crab: Effect on lipid metabolism

    SciTech Connect

    Rafi, G.Md.; Srinivas, T.; Reddy, S.J.; Reddy, D.C.; Ramamurthi, R. )

    1991-12-01

    Endosulfan is toxic to fish and its toxic effects have been studied in several freshwater fish. However, information regarding toxicity of endosulfan to many freshwater invertebrates is fragmentary. Few reports are available on the toxic effect of endosulfan on carbohydrate and protein metabolisms of freshwater field crab, Oziotelphusa senex senex, another nontarget organism of aquatic ecosystem. The work on lipid metabolism under organochloride insecticide (OCI) stress is scant. The OCI tend to accumulate in the lipid rich tissues of the biosystem due to their lipophilic nature. The changes in lipid profiles under OCI stress reported to cause profound changes in the metabolism and physiology of animals. Therefore, this paper presents the effects of endosulfan on lipid metabolism in O. senex senex.

  2. Effect of circadian rhythm on CNS oxygen toxicity.

    NASA Technical Reports Server (NTRS)

    Hof, D. G.; Dexter, J. D.; Mengel, C. E.

    1971-01-01

    The circadian rhythm in susceptibility to oxygen toxicity seizures was investigated by using six groups of 20 male Sprague-Dawley rats (101-196 gm.). The animals were given standard chow, exposed to standard diurnal conditions of light (0700-1900 hr) and dark (1900-0700 hr), and fasted for 15-16 hr prior to exposure to hyperbaric oxygen. The animals were placed in a previously oxygen flushed chamber and raised to 60 psi (gauge) oxygen at a rate of 3 psi/min. Time of exposure started with attainment of 60 psi. End point was first convulsion. The animals' weights were equally distributed within the groups, and the groups were defined by hour of exposure. Time of exposure in minutes prior to seizure was significantly longer in those exposed at 0700-0800 hr and 1000-1100 hr than in four other groups. There was no relationship between animals' weights and time of exposure to seizures. All R values were negative, and the highest R value was -035. These data suggest a definite circadian rhythm in susceptibility to oxygen toxicity seizures.

  3. Radiolysis of selected antibiotics and their toxic effects on various aquatic organisms

    NASA Astrophysics Data System (ADS)

    Kim, Hyun Y.; Yu, Seung H.; Lee, Myun J.; Kim, Tae H.; Kim, Sang D.

    2009-04-01

    This study was conducted to investigate the decomposition of three γ-irradiated antibiotics (e.g., tetracycline, sulfamethazine, and lincomycin) and to compare the toxic effects on Daphnia magna, Vibrio fischeri, and Pseudokirchneriella subcapitata. The median cell growth inhibition concentrations (IC 50) of tetracycline, lincomycin, and sulfamethazine for P. subcapitata dramatically increased (e.g., toxicity decreased) after radiolysis. The results demonstrated that γ-radiation treatment was efficient to decompose antibiotics and thereby their toxicity on P. subcaptitata remarkably decreased due to reduced parent compounds.

  4. Mechanistic model for interpreting the toxic effects of sulfonamides on nitrification.

    PubMed

    Huang, Xiangfeng; Feng, Yi; Hu, Cui; Xiao, Xiaoyu; Yu, Daliang; Zou, Xiaoming

    2016-03-15

    Antibiotics are categorized as pseudopersistent compounds because of their widespread use and continuous emission into the environment. Biological systems such as active sludge and biofilms are still the principal tools used to remove antibiotics in wastewater treatment plants (WWTPs). Consequently, it is important to determine the relationship between toxic effects in biological WWTPs and the structural characteristics of antibiotics. In the present study, toxic effects of 10 sulfonamides (SAs) on nitrification in an active sludge system were studied. The toxicity results (half-effective concentrations, EC50) indicated that the toxicity of sulfadimethoxine (SDM) is approximately 4 times as large as that of sulfadiazine (SD). Based on the toxicity mechanism and the partial least squares regression (PLS) method, an optimum quantitative structure-activity relationship (QSAR) model was developed for the test system. The mechanistic model showed that the pKa, the binding energies between SAs with dihydropteroate synthetase ( [Formula: see text] ) and the binding energies between SAs with ammonia monooxygenase ( [Formula: see text] ) are the key factors affecting the toxic effects of SAs on nitration process in active sludge system, following an order of importance of [Formula: see text] > [Formula: see text] >pKa. PMID:26651069

  5. Spatial dynamics of a nutrient-phytoplankton system with toxic effect on phytoplankton.

    PubMed

    Chakraborty, Subhendu; Tiwari, P K; Misra, A K; Chattopadhyay, J

    2015-06-01

    The production of toxins by some species of phytoplankton is known to have several economic, ecological, and human health impacts. However, the role of toxins on the spatial distribution of phytoplankton is not well understood. In the present study, the spatial dynamics of a nutrient-phytoplankton system with toxic effect on phytoplankton is investigated. We analyze the linear stability of the system and obtain the condition for Turing instability. In the presence of toxic effect, we find that the distribution of nutrient and phytoplankton becomes inhomogeneous in space and results in different patterns, like stripes, spots, and the mixture of them depending on the toxicity level. We also observe that the distribution of nutrient and phytoplankton shows spatiotemporal oscillation for certain toxicity level. PMID:25843351

  6. Toxic effect of silver and platinum nanoparticles toward the freshwater microalga Pseudokirchneriella subcapitata.

    PubMed

    Książyk, Małgorzata; Asztemborska, Monika; Stęborowski, Romuald; Bystrzejewska-Piotrowska, Grażyna

    2015-05-01

    The growing use of nanoparticles in a wide range of products has resulted in their release into the aquatic environment; therefore, an understanding of the toxic effects of nanoparticles on aquatic organisms is of permanent importance. The aim of this study was to evaluate the toxicity of silver and platinum nanoparticles toward the freshwater microalga, Pseudokirchneriella subcapitata. Algal growth and photosynthetic pigments were determined to quantitate the effects of varying concentrations of Ag and Pt nanoparticles. The silver nanoparticles were much more toxic than the platinum ones. The concentrations causing total inhibition of algal growth were 5.0 and 22.2 mg L(-1), respectively. Similar results were obtained by analyzing the concentration of photosynthetic pigments in P. subcapitata exposed to nanoparticles. Thus, simple spectrophotometric determination of chlorophyll is a convenient tool for the analysis of nanoparticle toxicity to algae. PMID:25742926

  7. Toxic Effects of Rhamnus alaternus: A Rare Case Report.

    PubMed

    Ben Ghezala, H; Chaouali, N; Gana, I; Snouda, S; Nouioui, A; Belwaer, I; Ouali, J; Kaddour, M; Masri, W; Ben Salah, D; Amira, D; Ghorbal, H; Hedhili, A

    2015-01-01

    In Tunisia, there are about 478 species of plants commonly used in folk medicine. Medicinal plants and herbal remedies used are responsible for 2% of intoxications listed by Tunisian National Poison Center. Most cases are related to confusion between edible plants and toxic plants lookalikes or to an excessive consumption of therapeutic plants. We report the case of a 58-year-old man admitted to the Emergency Department of the Regional Hospital of Zaghouan (Tunisia), with renal failure and rhabdomyolysis. The patient reported having daily consumption of a homemade tea based on Mediterranean Buckthorn roots, during the last 6 months to treat type 2 diabetes. The aim of this work was to establish an association between the consumption of the herbal remedy and the occurrence of both renal failure and rhabdomyolysis. No similar cases have been reported in recent literature. PMID:26229696

  8. The lifelong effects of early childhood adversity and toxic stress.

    PubMed

    Shonkoff, Jack P; Garner, Andrew S

    2012-01-01

    Advances in fields of inquiry as diverse as neuroscience, molecular biology, genomics, developmental psychology, epidemiology, sociology, and economics are catalyzing an important paradigm shift in our understanding of health and disease across the lifespan. This converging, multidisciplinary science of human development has profound implications for our ability to enhance the life prospects of children and to strengthen the social and economic fabric of society. Drawing on these multiple streams of investigation, this report presents an ecobiodevelopmental framework that illustrates how early experiences and environmental influences can leave a lasting signature on the genetic predispositions that affect emerging brain architecture and long-term health. The report also examines extensive evidence of the disruptive impacts of toxic stress, offering intriguing insights into causal mechanisms that link early adversity to later impairments in learning, behavior, and both physical and mental well-being. The implications of this framework for the practice of medicine, in general, and pediatrics, specifically, are potentially transformational. They suggest that many adult diseases should be viewed as developmental disorders that begin early in life and that persistent health disparities associated with poverty, discrimination, or maltreatment could be reduced by the alleviation of toxic stress in childhood. An ecobiodevelopmental framework also underscores the need for new thinking about the focus and boundaries of pediatric practice. It calls for pediatricians to serve as both front-line guardians of healthy child development and strategically positioned, community leaders to inform new science-based strategies that build strong foundations for educational achievement, economic productivity, responsible citizenship, and lifelong health. PMID:22201156

  9. Occupational diseases associated with toxic substances and their effects upon the energy industry

    SciTech Connect

    Hurd, C.W.

    1984-02-01

    In recent years the concept of ''toxic substances'' and the potential effects therefrom have attracted the attention and concern of the nation. Asbestosis put both society and industry on alert of the potential hazards inherent in the continued development of new chemicals and substances being employed in the work environment. Asbestosis is not the only causative element of occupational diseases. Other toxic substances currently raising concern include Agent Orange, DES (diethylstilbesterol), cotton dust, silicon and, of particular concern to the petroleum industry, benzene.

  10. Interactive effects of temperature and drought on cassava growth and toxicity: implications for food security?

    PubMed

    Brown, Alicia L; Cavagnaro, Timothy R; Gleadow, Ros; Miller, Rebecca E

    2016-10-01

    Cassava is an important dietary component for over 1 billion people, and its ability to yield under drought has led to it being promoted as an important crop for food security under climate change. Despite its known photosynthetic plasticity in response to temperature, little is known about how temperature affects plant toxicity or about interactions between temperature and drought, which is important because cassava tissues contain high levels of toxic cyanogenic glucosides, a major health and food safety concern. In a controlled glasshouse experiment, plants were grown at 2 daytime temperatures (23 °C and 34 °C), and either well-watered or subject to a 1 month drought prior to harvest at 6 months. The objective was to determine the separate and interactive effects of temperature and drought on growth and toxicity. Both temperature and drought affected cassava physiology and chemistry. While temperature alone drove differences in plant height and above-ground biomass, drought and temperature × drought interactions most affected tuber yield, as well as foliar and tuber chemistry, including C : N, nitrogen and cyanide potential (CNp; total cyanide released from cyanogenic glucosides). Conditions that most stimulated growth and yield (well-watered × high temperature) effected a reduction in tuber toxicity, whereas drought inhibited growth and yield, and was associated with increased foliar and tuber toxicity. The magnitude of drought effects on tuber yield and toxicity were greater at high temperature; thus, increases in tuber CNp were not merely a consequence of reduced tuber biomass. Findings confirm that cassava is adaptable to forecast temperature increases, particularly in areas of adequate or increasing rainfall; however, in regions forecast for increased incidence of drought, the effects of drought on both food quality (tuber toxicity) and yield are a greater threat to future food security and indicate an increasing necessity for processing of

  11. Modulatory effects of ixora coccinea flower on cyclophosphamide-induced toxicity in mice.

    PubMed

    Latha, P G; Panikkar, K R

    1999-09-01

    The active fraction of Ixora coccinea flowers showed chemoprotective effects on cyclophosphamide - induced toxicity by increasing the life span of treated mice, preventing body weight loss and maintaining near normal leucocyte and haemoglobin levels compared with cyclophosphamide treated controls. Decreased serum glutamate pyruvate transaminase (SGPT) and serum alkaline phosphatase (SAKP) levels in the Ixora coccinea treated groups indicated protection against hepatic toxicity. The active fraction was identified by phytochemical methods as the triterpenoid, ursolic acid. PMID:10479765

  12. Toxic effects of individual and combined effects of BTEX on Euglena gracilis.

    PubMed

    Peng, Cheng; Lee, Jong-Wha; Sichani, Homa Teimouri; Ng, Jack C

    2015-03-01

    BTEX is a group of volatile organic compounds consisting of benzene, toluene, ethylbenzene and xylenes. Environmental contamination of BTEX can occur in the groundwater with their effects on the aquatic organisms and ecosystem being sparsely studied. The aim of this study was to evaluate the toxic effects of individual and mixed BTEX on Euglena gracilis (E. gracilis). We examined the growth rate, morphological changes and chlorophyll contents in E. gracilis Z and its mutant SMZ cells treated with single and mixture of BTEX. BTEX induced morphological change, formation of lipofuscin, and decreased chlorophyll content of E. gracilis Z in a dose response manner. The toxicity of individual BTEX on cell growth and chlorophyll inhibition is in the order of xylenes>ethylbenzene>toluene>benzene. SMZ was found more sensitive to BTEX than Z at much lower concentrations between 0.005 and 5 μM. The combined effect of mixed BTEX on chlorophyll contents was shown to be concentration addition (CA). Results from this study suggested that E. gracilis could be a suitable model for monitoring BTEX in the groundwater and predicting the combined effects on aqueous ecosystem. PMID:25463212

  13. What are the differences between aerobic and anaerobic toxic effects of sulfonamides on Escherichia coli?

    PubMed

    Qin, Mengnan; Lin, Zhifen; Wang, Dali; Long, Xi; Zheng, Min; Qiu, Yanling

    2016-01-01

    Bacteria in the environment face the threat of antibiotics. However, most studies investigating the toxicity and toxicity mechanisms of antibiotics have been conducted on microorganisms in aerobic conditions, while studies examining the anaerobic toxicity and toxicity mechanisms of antibiotics are still limited. In this study, we determined the aerobic and anaerobic toxicities of sulfonamides (SAs) on Escherichia coli. Next, a comparison of the aerobic and anaerobic toxicities indicated that the SAs could be divided into three groups: Group I: log(1/EC50-anaerobic)>log(1/EC50-aerobic) (EC50-anaerobic/EC50-aerobic, the median effective concentration under anaerobic/aerobic conditions), Group II: log(1/EC50-anaerobic)≈log(1/EC50-aerobic), and Group III: log(1/EC50-anaerobic)toxicities will benefit environmental science, and the results of this study will serve as a reference for the risk assessment of chemicals in the environment. PMID:26748048

  14. The combined toxic effects of nonpolar narcotic chemicals to Pseudokirchneriella subcapitata.

    PubMed

    Hsieh, Shih-Hung; Tsai, Kuo-Pei; Chen, Chung-Yuan

    2006-06-01

    This paper presents the toxicity data of 10 nonpolar narcotic chemicals on Pseudokirchneriella subcapitata (green algae) assessed by a new algal toxicity testing technique conducted under air-tight environment. Based on DO production, median effective concentration (EC50) varies from 1.73 mg/L (1-octanol) to 8,040 mg/L (2-propanol). The endpoint of algal growth rate reveals similar sensitivity as that from DO production. Compared to literature data, Pseudokirchneriella subcapitata and Nitrosomonas are apparently more sensitive to nonpolar narcotics than other organisms such as minnow, daphnia, and Tetrahymena pyriformis. Furthermore, good correlations between toxic effects observed from Pseudokirchneriella subcapitata and other aquatic organisms were found. Hence, algal toxicity test can be considered as a surrogate test for estimating the toxicity of nonpolar chemicals to fathead minnow, Microtox, activated sludge, Daphina magna, and Tetrahymena pyriformis. The combined effects of 13 binary mixtures of nonpolar chemicals were investigated using both additive-index method and isobologram analysis. Overall speaking, the joint actions between these chemicals are strictly additive. Model analyses indicate that these compounds act on identical reaction sites or receptors, which verify that these chemicals are of the same toxicity mechanism (narcosis). PMID:16687162

  15. Detrimental effects of highly efficient interference competition: invasive Argentine ants outcompete native ants at toxic baits.

    PubMed

    Buczkowski, Grzegorz; Bennett, Gary W

    2008-06-01

    The Argentine ant (Linepithema humile) is an invasive species that disrupts the balance of natural ecosystems by displacing indigenous ant species throughout its introduced range. Previous studies that examined the mechanisms by which Argentine ants attain ecological dominance showed that superior interference and exploitation competition are key to the successful displacement of native ant species. The objective of this research was to test the hypothesis that effective interference competition by Argentine ants may also be detrimental to the survival of Argentine ant colonies where Argentine ants and native ants compete at toxic baits used to slow the spread of Argentine ants. To study this hypothesis, we examined the competitive interactions between Argentine ants and native odorous house ants, Tapinoma sessile, in the presence and absence of toxic baits. Results showed that Argentine ants aggressively outcompete T. sessile from toxic baits through efficient interference competition and monopolize bait resources. This has severe negative consequences for the survival of Argentine ants as colonies succumb to the toxic effects of the bait. In turn, T. sessile avoid areas occupied by Argentine ants, give up baits, and consequently suffer minimal mortality. Our results provide experimental evidence that highly efficient interference competition may have negative consequences for Argentine ants in areas where toxic baits are used and may provide a basis for designing innovative management programs for Argentine ants. Such programs would have the double benefit of selectively eliminating the invasive species while simultaneously protecting native ants from the toxic effects of baits. PMID:18559180

  16. Effects of protein-calorie malnutrition and refeeding on fluorouracil toxicity

    SciTech Connect

    Gamelli, R.L.; Foster, R.S. Jr.

    1983-10-01

    Mice were used to study the effects of protein-calorie malnutrition and its reversal on granulocyte-macrophage production and fluorouracil's toxic effect on bone marrow. An in vitro quantitative clonal culture technique for bone marrow granulocyte-macrophage progenitor cells (GM-CFC) was used. Animals on a protein-free but otherwise complete diet for ten days had a significant contraction in total marrow cellularity and GM-CFC numbers paralleling the animal's weight loss. The acute toxic effect of fluorouracil on bone marrow was not increased in protein-deprived animals. On refeeding, there was a biphasic response in the degree of toxic effect on marrow. Animals refed for one day had significantly increased fluorouracil-related marrow abnormalities. However, animals refed for four days, when marrows were repleted, were partially protected from the drug's cytotoxic effects. The increased sensitivity in mice refed for one day was related to more GM-CFC in active DNA synthesis.

  17. Toxicity assessment of wastewaters, river waters, and sediments in Austria using cost-effective microbiotests.

    PubMed

    Latif, Muna; Licek, Elisabeth

    2004-08-01

    The toxicity and chemical quality of surface water and sediment in the River Traun in Austria were studied because of recurrent fish mortality in some alpine rivers over the last few years. The analyses were carried out on samples collected during winter and summer upstream and downstream of two municipal wastewater treatment plants (WWTPs) and on effluents taken at the points of discharge of these two plants. Toxicity tests were performed on 20 samples of surface water, effluent, and sediment pore water. The test battery was composed of microbiotests with protozoans (Protoxkit F), microalgae (Algaltoxkit F), crustaceans (Daphtoxkit F magna and Thamnotoxkit F), and a higher plant (seed germination and root elongation assay on cress). Direct contact tests were performed on whole sediment with crustaceans (Ostracodtoxkit F). The physical-chemical characteristics of the surface water, effluent, and sediment pore water samples analyzed were conductivity, total hardness, pH, O(2), BOD(5), TOC, DOC, AOX, NH(4), NH(3), NO(2), PO(4)--P, Cd, Pb, Cu, and Zn. The toxicity data were expressed as percentage mortality or percentage inhibition, depending on the effect criterion of the respective assay. None of the water samples collected upstream and downstream of the WWTPs showed any significant (short-term) toxicity in either winter or in summer, but the effluents of the first municipal wastewater treatment plant were toxic to some of the test biota. All the sediment pore water samples induced serious inhibition of root growth of cress, and several pore waters were toxic to other test biota as well, particularly at the outlets of the WWTPs. The toxic character of some sediments was confirmed by direct contact tests with the ostracod crustacean. The chemical analyses did not reveal particularly high concentrations of any chemical that is very toxic. As a result no direct causal relationship could be established between the detected toxic effects and the chemical composition of

  18. Toxic Effects of Domoic Acid in the Seabream Sparus aurata

    PubMed Central

    Nogueira, Isabel; Lobo-da-Cunha, Alexandre; Afonso, António; Rivera, Socorro; Azevedo, Joana; Monteiro, Rogério; Cervantes, Rosa; Gago-Martinez, Ana; Vasconcelos, Vítor

    2010-01-01

    Neurotoxicity induced in fish by domoic acid (DA) was assessed with respect to occurrence of neurotoxic signs, lethality, and histopathology by light microscopy. Sparus aurata were exposed to a single dose of DA by intraperitoneal (i.p.) injection of 0, 0.45, 0.9, and 9.0 mg DA kg−1 bw. Mortality (66.67 ± 16.67%) was only observed in dose of 9.0 mg kg−1 bw. Signs of neurological toxicity were detected for the doses of 0.9 and 9.0 mg DA kg−1 bw. Furthermore, the mean concentrations (±SD) of DA detected by HPLC-UV in extracts of brain after exposure to 9.0 mg DA kg−1 bw were 0.61 ± 0.01, 0.96 ± 0.00, and 0.36 ± 0.01 mg DA kg−1 tissue at 1, 2, and 4 hours. The lack of major permanent brain damage in S. aurata, and reversibility of neurotoxic signs, suggest that lower susceptibility to DA or neuronal recovery occurs in affected individuals. PMID:21116416

  19. Individual and combined toxic effects of cypermethrin and chlorpyrifos on earthworm.

    PubMed

    Zhou, Shiping; Duan, Changqun; Michelle, Wong Hang Gi; Yang, Fazhong; Wang, Xuehua

    2011-01-01

    Toxicities were assessed for a pyrethroid (cypermethrin) and an organophosphate insecticide (chlorpyrifos) individually and in combination. A series of tests were conducted on different responses (acute, chronic, behavioral) of earthworms of species Eisenia fetida andrei in the ecological risk assessment of these pesticides. The results showed that the toxicity of the mixture of cypermethrin and chlorpyrifos was significantly higher than either of these pesticides individually, especially on the earthworm's chronic responses. At a concentration of 5 mg/kg, the mixture caused significant reductions on the growth and reproduction rates of earthworms, but did not cause any significant effect when the individual was tested. The increase in toxicity of the pesticide mixture means that the use of toxicity data obtained exclusively from single-pesticide experiments may underestimate the ecological risk of pesticides that actually present in the field. PMID:21793412

  20. Effect of steam activation of biochar produced from a giant Miscanthus on copper sorption and toxicity.

    PubMed

    Shim, Taeyong; Yoo, Jisu; Ryu, Changkook; Park, Yong-Kwon; Jung, Jinho

    2015-12-01

    This study aims to evaluate the physiochemical properties, sorption characteristics, and toxicity effects of biochar (BC) produced from Miscanthus sacchariflorus via slow pyrolysis at 500°C and its steam activation product (ABC). Although BC has a much lower surface area than ABC (181 and 322m(2)g(-1), respectively), the Cu sorption capacities of BC and ABC are not significantly different (p>0.05). A two-compartment model successfully explains the sorption of BC and ABC as being dominated by fast and slow sorption processes, respectively. In addition, both BC and ABC efficiently eliminate the toxicity of Cu towards Daphnia magna. However, ABC itself induced acute toxicity to D. magna, which is possibly due to increased aromaticity upon steam activation. These findings suggest that activation of BC produced from M. sacchariflorus at a pyrolytic temperature of 500°C may not be appropriate in terms of Cu sorption and toxicity reduction. PMID:26318926

  1. Toxicity interactions and ways of reducing side effects of anticancer drugs.

    PubMed

    Gola, A; Orzechowska-Juzwenko, K

    1982-01-01

    Side effects of cytostatics commonly used in the Haematology Clinic are analysed. The toxic action on the host's organs is discussed in L-asparaginase, azathioprine, bleomycine, busulfan, cyclophosphamide, cytosin-arabinoside, daunorubicine, fluorouracil, mercaptopurine, methotrexate, dichlorplatinum, procarbazine and the vinca alkaloids. In addition to toxic symptoms arising from single organs the most important 21 anticancer drugs are gathered in a table. Metabolism of activation and inactivation are mentioned to interprete symptoms of toxicity. Furthermore, the interactions between commonly administered drugs and carcinostatics which may enhance or suppress their carcinostatic efficacy are exposed. A final survey of possible pharmacological rescue measures, which may improve the tolerance of anticancer drugs by diminishing their toxicity is presented. PMID:6184274

  2. COMBINED AND INTERACTIVE EFFECTS OF GLOBAL CLIMATE CHANGE AND TOXICANTS ON POPULATIONS AND COMMUNITIES

    PubMed Central

    Moe, S Jannicke; De Schamphelaere, Karel; Clements, William H; Sorensen, Mary T; Van den Brink, Paul J; Liess, Matthias

    2013-01-01

    Increased temperature and other environmental effects of global climate change (GCC) have documented impacts on many species (e.g., polar bears, amphibians, coral reefs) as well as on ecosystem processes and species interactions (e.g., the timing of predator–prey interactions). A challenge for ecotoxicologists is to predict how joint effects of climatic stress and toxicants measured at the individual level (e.g., reduced survival and reproduction) will be manifested at the population level (e.g., population growth rate, extinction risk) and community level (e.g., species richness, food-web structure). The authors discuss how population- and community-level responses to toxicants under GCC are likely to be influenced by various ecological mechanisms. Stress due to GCC may reduce the potential for resistance to and recovery from toxicant exposure. Long-term toxicant exposure can result in acquired tolerance to this stressor at the population or community level, but an associated cost of tolerance may be the reduced potential for tolerance to subsequent climatic stress (or vice versa). Moreover, GCC can induce large-scale shifts in community composition, which may affect the vulnerability of communities to other stressors. Ecological modeling based on species traits (representing life-history traits, population vulnerability, sensitivity to toxicants, and sensitivity to climate change) can be a promising approach for predicting combined impacts of GCC and toxicants on populations and communities. Environ. Toxicol. Chem. 2013;32:49–61. © 2012 SETAC PMID:23147390

  3. The importance of experimental time when assessing the effect of temperature on toxicity in poikilotherms.

    PubMed

    Nørhave, Nils J; Spurgeon, David; Svendsen, Claus; Cedergreen, Nina

    2014-06-01

    Temperature is an important factor affecting toxicity, determining chemical toxicokinetics and toxicodynamics in poikilothermic organisms. Because metabolic rates are also affected by temperature, interactions between the emergence of toxic effects and time are very likely. The aim of the present study was to investigate how temperature affects the toxicity of copper toward the nematode Caenorhabditis elegans when measured during short, fixed time frames compared with full life cycles. Copper toxicity was tested in 2 experiments at 4 or 6 temperatures in the range of 11 °C to 24 °C, with Cu concentrations spanning from 1 mg Cu/L agar to 40 mg Cu/L agar, respectively. Reproduction and mortality were determined across the entire life cycle, and the time to production of first egg and the population growth rate were calculated. The results showed that the 50% effect concentrations (EC50s) of Cu increased 1.5-fold to 2.5-fold with increasing temperature within the tested range, depending on endpoint. When calculating EC50 on reproduction after 24 h or 96 h, the typical setup for temperature-chemical interaction studies, results ranged from no temperature effect to effects much larger than those for the full life cycle. Studies of temperature effects on toxicity must therefore be carefully designed in relation to the research question being investigated. PMID:24648200

  4. Uptake and toxic effects of surface modified nanomaterials in freshwater aquatic organisms

    NASA Astrophysics Data System (ADS)

    Seda, Brandon Casey

    Nanomaterials are a class of materials with unique properties due to their size, and the association of these properties with the toxicity of nanomaterials is poorly understood. The present study assessed the toxic effects of stable aqueous colloidal suspensions of three distinctly different classes of nanomaterials in aquatic organisms. The fullerene, C70, was stabilized through non-covalent surface modification with gallic acid. Toxicity of C70-gallic acid was confirmed to exhibit similar toxic effects as C60-fullerene, including changes in antioxidative processes in Daphnia magna. Daphnia magna fecundity was significantly reduced in 21d bioassays at C70-gallic concentrations below quantifiable limits (0.03 mg/L C70). Antioxidant enzyme activities of glutathione peroxidase and superoxide dismutase as well as lipid peroxidation suggested that exposed organisms experienced oxidative stress. Carbon dots are a class of nanomaterials proposed for use as nontoxic alternatives to semiconductor quantum dots for photoluminescent applications, because of the difference in toxicity of their core components: carbon as opposed to heavy metals. In vivo analysis of treated organisms by confocal fluorescence microscopy revealed carbon dots were absorbed and systemically distributed regardless of particle size. The present study did not find any evidence of acute toxicity at concentrations up to 10mg/L carbon dots. These concentrations also failed to produce negative effects in Ceriodaphnia dubia bioassays to predict chronic toxicity. Carbon dots also failed to elicit developmental toxic effects in zebrafish. The toxic effects of semiconductor quantum dots have been partially attributed to the release of heavy metals with their degradation, particularly cadmium. Laser ablation inductively coupled mass spectrometry was used to compare the uptake of cadmium, selenium and zinc in Daphnia magna treated to CdSe/ZnS quantum dots or CdCl2. These quantum dots were observed to accumulate

  5. Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity.

    PubMed

    Kudryasheva, N S; Rozhko, T V

    2015-04-01

    The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1--absence of effects (stress recognition), 2--activation (adaptive response), and 3--inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. PMID:25644753

  6. Guidance on health effects of toxic chemicals. Safety Analysis Report Update Program

    SciTech Connect

    Foust, C.B.; Griffin, G.D.; Munro, N.B.; Socolof, M.L.

    1994-02-01

    Martin Marietta Energy Systems, Inc. (MMES), and Martin Marietta Utility Services, Inc. (MMUS), are engaged in phased programs to update the safety documentation for the existing US Department of Energy (DOE)-owned facilities. The safety analysis of potential toxic hazards requires a methodology for evaluating human health effects of predicted toxic exposures. This report provides a consistent set of health effects and documents toxicity estimates corresponding to these health effects for some of the more important chemicals found within MMES and MMUS. The estimates are based on published toxicity information and apply to acute exposures for an ``average`` individual. The health effects (toxicological endpoints) used in this report are (1) the detection threshold; (2) the no-observed adverse effect level; (3) the onset of irritation/reversible effects; (4) the onset of irreversible effects; and (5) a lethal exposure, defined to be the 50% lethal level. An irreversible effect is defined as a significant effect on a person`s quality of life, e.g., serious injury. Predicted consequences are evaluated on the basis of concentration and exposure time.

  7. AMMONIA TOXICITY TO FISHES. EFFECT OF PH ON THE TOXICITY OF THE UN-IONIZED AMMONIA SPECIES

    EPA Science Inventory

    United States and European water quality criteria to protect aquatic life assume that the toxicity of aqueous ammonia is attributable to the un-ionized (NH3) chemical species, and that the ionized (NH4+) species is nontoxic or significantly less toxic than NH3. Data are presented...

  8. Protective effect of allicin against glycidamide-induced toxicity in male and female mice.

    PubMed

    Wang, En-Ting; Chen, Dong-Yan; Liu, Huang-You; Yan, Hai-Yang; Yuan, Yuan

    2015-04-01

    Acrylamide is known to be a neurotoxic, genotoxic, and carcinogenic compound. Glycidamide has a close relationship to the toxic mechanism of acrylamide. In order to explore the toxic mechanism of acrylamide, we further discussed the effects of oral administration of allicin on glycidamide-induced toxicity by determining the hematological parameters like AST, ALT, LDH, BUN, creatinine, ROS, and 8-OHdG, and biochemical parameters such as MDA, MPO, SOD, GST and GSH in the kidney, liver, brain and lung of male and female mice for the first time. We found that the same dose of glycidamide had more toxic effects and damage effects to the mice compared to the previous study of acrylamide. It could markedly increase the level of AST, ALT, LDH, BUN, ROS, 8-OHdG, MDA, MPO while decrease the SOD, GST and GSH. However, our data showed the oral administered allicin with a concentration of 5, 10, and 20 mg/kg b.w./day could significantly decrease the damage indexes of AST, ALT, LDH, BUN, ROS, 8-OHdG, MDA, and MPO, while increase the antioxidant indicators of SOD, GST and GSH. Thus allicin could be used as an effective dietary supplement for the chemoprevention of glycidamide genotoxicity internally, and to prevent the tissue damage and toxicity induced by glycidamide. PMID:25730897

  9. No-observed-effect concentrations in batch and continuous algal toxicity tests

    SciTech Connect

    Chao, M.R.; Chen, C.Y.

    2000-06-01

    In this study, the authors compare the no-observed-effect concentrations (NOECs) of Cd, Ni, Zn, Cu, and Pb based on different response parameters, using batch and continuous algal toxicity tests. For both batch and continuous tests, parameters based on total cell volume (TCV) were found to be less sensitive than those related to cell densities. The above observation mainly occurred because, under the stresses from metal toxicants evaluated in this and a previous study, the mean cell volume (MCV) of algae increased considerably. The increase of MCV compensates for the effects brought about by the reduction in cell density and eventually results in less variation in TCVs. This study shows that parameters based on cell density are quite sensitive and ideal for the estimation of NOECs. In addition, comparison of the NOEC values derived from different culture techniques shows that the continuous methods generally yields lower NOEC values than that obtained by the batch tests. The results of this study also indicate that the NOEC provides more protection to the test organism than the effective concentration at 10% growth reduction (EC10). For toxicity test methods that produce small variations among replicates, the NOEC is still a good indicator of low toxic effect. Furthermore, for the continuous algal toxicity test, a relatively simple approach is proposed to determine the NOEC values based on the algal culture's control charts. The proposed method produced identical results as those based on conventional hypothesis-testing methods.

  10. DEVELOPMENT OF A PROTOCOL FOR TESTING EFFECTS OF TOXIC SUBSTANCES ON PLANTS

    EPA Science Inventory

    This study was designed to devise a rapid, simple, reproducible bioassay procedure to determine effects of so-called 'toxic substances in the environment' on vegetation and provide a standardized procedure for evaluation and comparison of effects of diverse compounds. Eight diffe...

  11. Uptake and Accumulation of Polystyrene Microplastics in Zebrafish (Danio rerio) and Toxic Effects in Liver.

    PubMed

    Lu, Yifeng; Zhang, Yan; Deng, Yongfeng; Jiang, Wei; Zhao, Yanping; Geng, Jinju; Ding, Lili; Ren, Hongqiang

    2016-04-01

    Microplastics have become emerging contaminants, causing widespread concern about their potential toxic effects. In this study, the uptake and tissue accumulation of polystyrene microplastics (PS-MPs) in zebrafish were detected, and the toxic effects in liver were investigated. The results showed that after 7 days of exposure, 5 μm diameter MPs accumulated in fish gills, liver, and gut, while 20 μm diameter MPs accumulated only in fish gills and gut. Histopathological analysis showed that both 5 μm and 70 nm PS-MPs caused inflammation and lipid accumulation in fish liver. PS-MPs also induced significantly increased activities of superoxide dismutase and catalase, indicating that oxidative stress was induced after treatment with MPs. In addition, metabolomic analysis suggested that exposure to MPs induced alterations of metabolic profiles in fish liver and disturbed the lipid and energy metabolism. These findings provide new insights into the toxic effects of MPs on fish. PMID:26950772

  12. Effects of soil properties on copper toxicity to earthworm Eisenia fetida in 15 Chinese soils.

    PubMed

    Duan, Xiongwei; Xu, Meng; Zhou, Youya; Yan, Zengguang; Du, Yanli; Zhang, Lu; Zhang, Chaoyan; Bai, Liping; Nie, Jing; Chen, Guikui; Li, Fasheng

    2016-02-01

    The bioavailability and toxicity of metals in soil are influenced by a variety of soil properties, and this principle should be recognized in establishing soil environmental quality criteria. In the present study, the uptake and toxicity of Cu to the earthworm Eisenia fetida in 15 Chinese soils with various soil properties were investigated, and regression models for predicting Cu toxicity across soils were developed. The results showed that earthworm survival and body weight change were less sensitive to Cu than earthworm cocoon production. The soil Cu-based median effective concentrations (EC50s) for earthworm cocoon production varied from 27.7 to 383.7 mg kg(-1) among 15 Chinese soils, representing approximately 14-fold variation. Soil cation exchange capacity and organic carbon content were identified as key factors controlling Cu toxicity to earthworm cocoon production, and simple and multiple regression models were developed for predicting Cu toxicity across soils. Tissue Cu-based EC50s for earthworm cocoon production were also calculated and varied from 15.5 to 62.5 mg kg(-1) (4-fold variation). Compared to the soil Cu-based EC50s for cocoon production, the tissue Cu-based EC50s had less variation among soils, indicating that metals in tissue were more relevant to toxicity than metals in soil and hence represented better measurements of bioavailability. PMID:26688255

  13. Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

    2010-01-01

    The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

  14. Boron Toxicity Causes Multiple Effects on Malus domestica Pollen Tube Growth.

    PubMed

    Fang, Kefeng; Zhang, Weiwei; Xing, Yu; Zhang, Qing; Yang, Liu; Cao, Qingqin; Qin, Ling

    2016-01-01

    Boron is an important micronutrient for plants. However, boron is also toxic to cells at high concentrations, although the mechanism of this toxicity is not known. This study aimed to evaluate the effect of boron toxicity on Malus domestica pollen tube growth and its possible regulatory pathway. Our results showed that a high concentration of boron inhibited pollen germination and tube growth and led to the morphological abnormality of pollen tubes. Fluorescent labeling coupled with a scanning ion-selective electrode technique detected that boron toxicity could decrease [Ca(2+)]c and induce the disappearance of the [Ca(2+)]c gradient, which are critical for pollen tube polar growth. Actin filaments were therefore altered by boron toxicity. Immuno-localization and fluorescence labeling, together with fourier-transform infrared analysis, suggested that boron toxicity influenced the accumulation and distribution of callose, de-esterified pectins, esterified pectins, and arabinogalactan proteins in pollen tubes. All of the above results provide new insights into the regulatory role of boron in pollen tube development. In summary, boron likely plays a structural and regulatory role in relation to [Ca(2+)]c, actin cytoskeleton and cell wall components and thus regulates Malus domestica pollen germination and tube polar growth. PMID:26955377

  15. Boron Toxicity Causes Multiple Effects on Malus domestica Pollen Tube Growth

    PubMed Central

    Fang, Kefeng; Zhang, Weiwei; Xing, Yu; Zhang, Qing; Yang, Liu; Cao, Qingqin; Qin, Ling

    2016-01-01

    Boron is an important micronutrient for plants. However, boron is also toxic to cells at high concentrations, although the mechanism of this toxicity is not known. This study aimed to evaluate the effect of boron toxicity on Malus domestica pollen tube growth and its possible regulatory pathway. Our results showed that a high concentration of boron inhibited pollen germination and tube growth and led to the morphological abnormality of pollen tubes. Fluorescent labeling coupled with a scanning ion-selective electrode technique detected that boron toxicity could decrease [Ca2+]c and induce the disappearance of the [Ca2+]c gradient, which are critical for pollen tube polar growth. Actin filaments were therefore altered by boron toxicity. Immuno-localization and fluorescence labeling, together with fourier-transform infrared analysis, suggested that boron toxicity influenced the accumulation and distribution of callose, de-esterified pectins, esterified pectins, and arabinogalactan proteins in pollen tubes. All of the above results provide new insights into the regulatory role of boron in pollen tube development. In summary, boron likely plays a structural and regulatory role in relation to [Ca2+]c, actin cytoskeleton and cell wall components and thus regulates Malus domestica pollen germination and tube polar growth. PMID:26955377

  16. Effects of glucose concentrations on cadmium, copper, mercury, and zinc toxicity to a Klebsiella sp

    SciTech Connect

    Brynhildsen, L.; Lundgren, B.V.; Allard, B.; Rosswall, T.

    1988-07-01

    The influence of glucose concentration on Cd, CU, Hg, and Zn toxicity to a Klebsiella sp. was studied by following the degradation of /sup 14/C-labeled glucose at pH 6.0. Uptake of /sup 14/C into the cells was also determined. The carbon concentrations ranged from 0.01 to 40 mg liter/sup -1/, which are equivalent to soluble C concentrations in natural environments. The toxicity of Cu, Cd, and Zn to a Klebsiella sp. was affected considerably by the C concentration. Copper at 10/sup -5/ M was toxic when the carbon concentration was 10 or 40 mg liter/sup -1/, while at 0.01 to 1.0 mg liter/sup -1/ no toxicity was observed. Cadmium and zinc were toxic at 10/sup -2/ M in media containing 0.01 to 1.0 mg of C liter/sup -1/. At C concentrations greater than 1.0 mg liter/sup -1/, the inhibition of glucose degradation and carbon assimilation was observed at 10/sup -3/ M Cd and Zn. The toxicity of mercury seemed to be independent of the C concentration. Results of this study showed that the nutritional state of an organism may have a profound effect on its sensitivity to metals. Metals taken up by energy-driven transport system may be less toxic under conditions of C starvation. The C concentration should be taken into account when evaluating results from toxicity studies, especially as most microorganisms in nature live under energy-limited conditions.

  17. Teratological Effects of a Panel of Sixty Water-Soluble Toxicants on Zebrafish Development

    PubMed Central

    Ali, Shaukat; Aalders, Jeffrey

    2014-01-01

    Abstract The zebrafish larva is a promising whole-animal model for safety pharmacology, environmental risk assessment, and developmental toxicity. This model has been used for the high-throughput toxicity screening of various compounds. Our aim here is to identify possible phenotypic markers of teratogenicity in zebrafish embryos that could be used for the assaying compounds for reproductive toxicity. We have screened a panel of 60 water-soluble toxicants to examine their effects on zebrafish development. A total of 22,080 wild-type zebrafish larvae were raised in 250 μL defined buffer in 96-well plates at a plating density of one embryo per well. They were exposed for a 96-h period starting at 24 h post-fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for developmental toxicity assessment. A total of 9017 survivors were analyzed at 5 days post-fertilization for nine phenotypes, namely, (1) normal, (2) pericardial oedema, (3) yolk sac oedema, (4) melanophores dispersed, (5) bent tail tip, (6) bent body axis, (7) abnormal Meckel's cartilage, (8) abnormal branchial arches, and (9) uninflated swim bladder. For each toxicant, the EC50 (concentration required to produce one or more of these abnormalities in 50% of embryos) was also calculated. For the majority of toxicants (55/60) there was, at the population level, a statistically significant, concentration-dependent increase in the incidence of abnormal phenotypes among survivors. The commonest abnormalities were pericardial oedema, yolk sac oedema, dispersed melanophores, and uninflated swim bladder. It is possible therefore that these could prove to be general indicators of reproductive toxicity in the zebrafish embryo assay. PMID:24650241

  18. Lightsticks content toxicity: effects of the water soluble fraction on the oyster embryonic development.

    PubMed

    de Araujo, Milena Maria Sampaio; Menezes Filho, Adalberto; Nascimento, Iracema Andrade; Pereira, Pedro Afonso P

    2015-11-01

    Lightsticks are artifacts used as attractors in a type of commercial fishery, known as surface longline gear. Despite the excessive use, the contamination risks of these devices have not yet been properly investigated. This research aimed to fill up this gap by determining the chemical composition and the toxicity of lightsticks recently activated, compared to those one year after activation and to the ones collected on the beaches. The analyzes were carried out by Gas Chromatography coupled with Mass Spectrometry (GC-MS). Additionally, the variations in composition and the toxicity of their sea Water Soluble Fractions (WSF) were evaluated based on the WSF-effects of Crassostrea rhizophorae embryonic development. The GC-MS analysis made possible the identification of nineteen substances in the water soluble fraction of the lightsticks, such as dibutyl phthalate (DBP) and dimethyl phthalate (DMP). The value of the WSF-effective concentration (EC50) was in an average of 0.35%. After one year of the lightsticks activation, the toxicity was even higher (0.65%). Furthermore, other substances, also present in the lightsticks-WSF caused persistent toxicity even more dangerous to the environment than DBP and DMP. This essay discusses their toxicity effects and possible environment damages. PMID:26070145

  19. Molecular and Genetic Analysis of the Toxic Effect of Rap1 Overexpression in Yeast

    PubMed Central

    Freeman, K.; Gwadz, M.; Shore, D.

    1995-01-01

    Rap1p is a context-dependent regulatory protein in yeast that functions as a transcriptional activator of many essential genes, including those encoding ribosomal proteins and glycolytic enzymes. Rap1p also participates in transcriptional silencing at HM mating-type loci and telomeres. Overexpression of RAP1 strongly inhibits cell growth, perhaps by interfering with essential transcriptional activation functions within the cell. Here we report a molecular and genetic analysis of the toxic effect of RAP1 overexpression. We show that toxicity does not require the previously defined Rap1p activation and silencing domains, but instead is dependent upon the DNA-binding domain and an adjacent region of unknown function. Point mutations were identified in the DNA-binding domain that relieve the toxic effect of overexpression. Two of these mutations can complement a RAP1 deletion yet cause growth defects and altered DNA-binding properties in vitro. However, a small deletion of the adjacent (down-stream) region that abolishes overexpression toxicity has, by itself, no apparent effect on growth or DNA binding. SKO1/ACR1, which encodes a CREB-like repressor protein in yeast, was isolated as a high copy suppressor of the toxicity caused by RAP1 overexpression. Models related to the regulation of Rap1p activity are discussed. PMID:8601471

  20. Combined effects of dissolved organic material and water hardness on toxicity of cadmium to Daphnia magna

    SciTech Connect

    Penttinen, S.; Kostamo, A.; Kukkonen, J.V.K.

    1998-12-01

    The interaction between dissolved organic material (DOM) and water hardness and their effects on the acute toxicity of cadmium (Cd) to Daphnia magna was studied. At an original hardness of humic lake water, Cd was significantly less toxic in the humic than in the reference water. Furthermore, after dilution down to 10%, the humic water still decreased the lethality significantly. The results suggest that the reduced toxicity of Cd in the lake water is due to complexation with DOC. An increase in water hardness decreased the measured binding coefficient of Cd to DOM. In addition, the acute toxicity of Cd decreased, and the difference between the reference and humic water disappeared. As a conclusion, DOM in the soft lake water had a protective effect against Cd toxicity. In hard water, obviously, the added hardness cations, especially Ca{sup 2+}, effectively competed with Cd{sup 2+} for available binding sites in DOM. Simultaneously, CA{sup 2+} ions interfered also with the uptake of Cd{sup 2+} either by competing in transport through cell membranes or by reducing membrane permeability.

  1. Toxic effects of organic solvents on the growth of blue-green algae

    SciTech Connect

    Stratton, G.W.

    1987-06-01

    Relatively few reports have been published on the comparative toxicity of solvents towards test organisms, and these deal primarily with fish and aquatic invertebrates. Information for microbial systems are more limited with some data available for algae and slightly more for fungi. Aside from direct toxic effects of their own, solvents can interact synergistically and antagonistically with the toxicant in solution. This problem has been well documented with pesticides, and a procedure has been developed to identify and eliminate these effects from bioassays. The first step in choosing a solvent for use in microbial bioassays should be a detailed screening to identify solvents with inherently low toxicity to the test organism, followed by an interaction study to choose the best concentration to use. The purpose of the present study was to compare the inhibitory effects of six solvents commonly used in pesticide bioassays towards five species of blue-green algae (cyanobacteria), in order to identify solvents with low toxicity for use in bioassays.

  2. Selecting a sensitive battery of bioassays to detect toxic effects of metals in effluents.

    PubMed

    de Paiva Magalhães, Danielly; da Costa Marques, Mônica Regina; Fernandes Baptista, Darcilio; Forsin Buss, Daniel

    2014-09-01

    The use of bioassay batteries is necessary to evaluate toxic effects at various biological levels. The selection of bioassays without prior testing and determination of the most sensitive/suitable groups for each impact may allow the discharge of effluents that pose a threat to the environment. The present study tested and selected a battery of sensitive ecotoxicological bioassays for detecting toxic effects of metals. The sensitivities of six organisms were evaluated (algae Pseudokirchneriella subcapitata and Chlorella vulgaris, Cladocera Daphnia similis and Ceriodaphnia dubia, and fish Poecilia reticulata and Danio rerio) after exposure to 10 individual metal species deemed toxic to the aquatic environment (Ag(+), Cd(2+), Cu(+), Cu(2+), Cr(3+), Cr(6+), Pb(2+), Ni(2+), Zn(2+), and Hg(2+)) and to real (steel-mill) and laboratory simulated effluents. In the bioassays, fish were the least sensitive; D. rerio showed no sensitivity to any of the effluents tested. P. subcapitata was a good bioindicator of Cr(3+) toxicity, and D. similis was the most sensitive organism to Hg(2+); but the toxic effect of effluents with higher levels of Hg(2+) was better detected by C. dubia. The most sensitive battery of bioassays to detect low concentrations of dissolved metals in effluents was the 72-h chronic test with C. vulgaris and the 48-h acute test with C. dubia. PMID:25199585

  3. TOXIC EFFECT OF WATER SOLUBLE POLLUTANTS ON FRESHWATER FISH

    EPA Science Inventory

    Studies of the effect of inorganic and organic mercury on trout indicated that uptake was primarily via the gills in non-feeding fish. Organic mercury entered fish at a faster rate than inorganic mercury. Exposure of trout to 10 micrograms Hg/l (methyl form) had no effect on the ...

  4. Toxic effects of marijuana on the cardiovascular system.

    PubMed

    Pratap, Balaji; Korniyenko, Aleksandr

    2012-06-01

    We present a case of marijuana-induced ST segment elevation mimicking Brugada syndrome in a young man. Cannabis can have a multitude of effects on the different organ systems of the body; we take a closer look at its effects on the cardiovascular system, including acute coronary syndrome, arrhythmias and congestive heart failure. PMID:22194141

  5. EFFECTS OF ATMOSPHERIC MIX AND TOXIC FUMES ON MILITARY PERFORMANCE

    EPA Science Inventory

    The present chapter covers the individual and combined neuro-behavioral effects of four of the major products of combustion. hey are carbon monoxide, hydrogen cyanide, carbon dioxide and hypoxic hypoxia. he effects of each were reviewed separately and then the literature of the e...

  6. In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

    PubMed

    Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

    2015-01-01

    The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results. PMID:25694074

  7. Toxic and genotoxic effects of hexavalent chromium in environment and its bioremediation strategies.

    PubMed

    Mishra, Sandhya; Bharagava, Ram Naresh

    2016-01-01

    Chromium is one of the major inorganic environmental pollutants, which is added in the environment through various natural and anthropogenic activities and exists mainly in two forms: Cr(III) and Cr(VI). Cr(VI) is considered to be more toxic than Cr(III) due to its high solubility and mobility. It is a well-reported occupational carcinogen associated with lung, nasal, and sinus cancers. Thus, this review article provides the detailed information on the occurrence, sources of chromium contamination in the environment and their toxicological effects in human, animal, plants as well as in microorganisms, and bioremediation strategies to minimize the toxic effects. PMID:26398402

  8. Reproductive toxicity of 2,4-toluenediamine in the rat. 1. Effect on male fertility

    SciTech Connect

    Thysen, B.; Varma, S.K.; Bloch, E.

    1985-01-01

    Effects of 2,4-toluenediamine (TDA) on reproduction in adult male Sprague-Dawley rats were evaluated. Diets containing 0, 0.01 and 0.03% TDA were fed ad libitum to experimental animals for 10 wk. No signs of toxicity were found. Exposure to the high dose resulted in decreased mating frequency and an increase in infertile matings. Light-microscopic examination of the testes revealed reduced numbers of sperm in the seminiferous tubules and cauda epididymides. These results indicate that TDA is capable of reducing fertility and of exerting an inhibitory or toxic effect on spermatogenesis in the rat.

  9. Automated swimming activity monitor for examining temporal patterns of toxicant effects on individual Daphnia magna.

    PubMed

    Bahrndorff, Simon; Michaelsen, Thomas Yssing; Jensen, Anne; Marcussen, Laurits Faarup; Nielsen, Majken Elley; Roslev, Peter

    2016-07-01

    Aquatic pollutants are often biologically active at low concentrations and impact on biota in combination with other abiotic stressors. Traditional toxicity tests may not detect these effects, and there is a need for sensitive high-throughput methods for detecting sublethal effects. We have evaluated an automated infra-red (IR) light-based monitor for recording the swimming activity of Daphnia magna to establish temporal patterns of toxicant effects on an individual level. Activity was recorded for 48 h and the sensitivity of the monitor was evaluated by exposing D. magna to the reference chemicals K2 Cr2 O7 at 15, 20 and 25 °C and 2,4-dichlorophenol at 20 °C. Significant effects (P < 0.001) of toxicant concentrations, exposure time and incubation temperatures were observed. At 15 °C, the swimming activity remained unchanged for 48 h at sublethal concentrations of K2 Cr2 O7 whereas activity at 20 and 25 °C was more biphasic with decreases in activity occurring after 12-18 h. A similar biphasic pattern was observed after 2,4-dichlorophenol exposure at 20 °C. EC50 values for 2,4-dichlorophenol and K2 Cr2 O7 determined from automated recording of swimming activity showed increasing toxicity with time corresponding to decreases in EC50 of 0.03-0.07 mg l(-1) h(-1) . EC50 values determined after 48 h were comparable or lower than EC50 values based on visual inspection according to ISO 6341. The results demonstrated that the swimming activity monitor is capable of detecting sublethal behavioural effects that are toxicant and temperature dependent. The method allows EC values to be established at different time points and can serve as a high-throughput screening tool in toxicity testing. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26198804

  10. The Effect of Toxic Cyanobacteria on Human and Animal Health

    EPA Science Inventory

    The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

  11. Effect-directed analysis of Elizabeth River porewater: developmental toxicity in zebrafish (Danio rerio).

    PubMed

    Fang, Mingliang; Getzinger, Gordon J; Cooper, Ellen M; Clark, Bryan W; Garner, Lindsey V T; Di Giulio, Richard T; Ferguson, P Lee; Stapleton, Heather M

    2014-12-01

    In the present study, effect-directed analysis was used to identify teratogenic compounds in porewater collected from a Superfund site along the Elizabeth River estuary (VA, USA). Zebrafish (Danio rerio) exposed to the porewater displayed acute developmental toxicity and cardiac teratogenesis, presumably because of elevated sediment levels of polycyclic aromatic hydrocarbons (PAHs) from historical creosote use. Pretreatment of porewater with several physical and chemical particle removal methods revealed that colloid-bound chemicals constituted the bulk of the observed toxicity. Size-exclusive chromatography and normal-phase high-performance liquid chromatography were used to fractionate Elizabeth River porewater. Acute toxicity of porewater extracts and extract fractions was assessed as the pericardial area in embryonic zebrafish. The most toxic fraction contained several known aryl hydrocarbon receptor (AhR) agonists (e.g., 1,2-benzofluorene and 1,2-benzanthracene) and cytochrome P450 A1 (CPY1A) inhibitors (e.g., dibenzothiophene and fluoranthene). The second most toxic fraction contained known AhR agonists (e.g., benzo[a]pyrene and indeno[1,2,3-cd]pyrene). Addition of a CYP1A inhibitor, fluoranthene, increased toxicity in all active porewater fractions, suggesting synergism between several contaminants present in porewaters. The results indicate that the observed acute toxicity associated with Elizabeth River porewater results from high concentrations of AhR agonistic PAHs and mixture effects related to interactions between compounds co-occurring at the Elizabeth River site. However, even after extensive fractionation and chemical characterization, it remains plausible that some active compounds in Elizabeth River porewater remain unidentified. PMID:25196082

  12. EFFECT-DIRECTED ANALYSIS OF ELIZABETH RIVER POREWATER: DEVELOPMENTAL TOXICITY IN ZEBRAFISH (DANIO RERIO)

    PubMed Central

    Fang, Mingliang; Getzinger, Gordon J.; Cooper, Ellen M.; Clark, Bryan W.; Garner, Lindsey V.T.; Di Giulio, Richard T.; Ferguson, P. Lee; Stapleton, Heather M.

    2015-01-01

    In the present study, effect-directed analysis was used to identify teratogenic compounds in porewater collected from a Superfund site along the Elizabeth River estuary (VA, USA). Zebrafish (Danio rerio) exposed to the porewater displayed acute developmental toxicity and cardiac teratogenesis, presumably because of elevated sediment levels of polycyclic aromatic hydrocarbons (PAHs) from historical creosote use. Pretreatment of porewater with several physical and chemical particle removal methods revealed that colloid-bound chemicals constituted the bulk of the observed toxicity. Size-exclusive chromatography and normal-phase high-performance liquid chromatography were used to fractionate Elizabeth River porewater. Acute toxicity of porewater extracts and extract fractions was assessed as the pericardial area in embryonic zebrafish. The most toxic fraction contained several known aryl hydrocarbon receptor (AhR) agonists (e.g., 1,2-benzofluorene and 1,2-benzanthracene) and cytochrome P450 A1 (CPY1A) inhibitors (e.g., dibenzothiophene and fluoranthene). The second most toxic fraction contained known AhR agonists (e.g., benzo[a]pyrene and indeno[1,2,3-cd]pyrene). Addition of a CYP1A inhibitor, fluoranthene, increased toxicity in all active porewater fractions, suggesting synergism between several contaminants present in porewaters. The results indicate that the observed acute toxicity associated with Elizabeth River porewater results from high concentrations of AhR agonistic PAHs and mixture effects related to interactions between compounds co-occurring at the Elizabeth River site. However, even after extensive fractionation and chemical characterization, it remains plausible that some active compounds in Elizabeth River porewater remain unidentified. PMID:25196082

  13. The repellent and persistent toxic effects of essential oils against the poultry red mite, Dermanyssus gallinae.

    PubMed

    Nechita, I S; Poirel, M T; Cozma, V; Zenner, L

    2015-12-15

    The economic impact of the poultry red mite, Dermanyssus gallinae, the lack of new acaricides, the occurrence of resistance and tighter legislation have all led to the need to find new ways to control this pest. One promising alternative method of control focuses on employing repellent and/or toxic effects of selected plant essential oils against D. gallinae. Ten essential oils (basil, thyme, coriander, eucalyptus, lavender, lemon, fir tree, oregano, mint, and juniper) were tested for the persistence of toxic and repellent effects. In filter-paper toxicity bioassays against D. gallinae, the best results were observed for lavender (more than 97% mortality after 48 and 72 h) and thyme (84% at 72 h) at a dose of 0.12 mg/cm(2). In addition, two oils showed significant persistent toxic effects 15 and 30 days post application to filter papers. Thyme was the most effective (100% mortality at 72 h), followed by lavender (nearly 80% mortality after 72 h). Out of the ten oils tested for their repellent effect, thyme was the strongest, with nearly 80% of the tested area avoided by mites; oregano caused a 60% avoidance and lavender exhibited an effect close to 40%. All other oils exhibited a repellent effect of less than 30%. None of the experiments showed a repellent effect for HM (commercial alimentary oil) or negative controls. We found that the thyme and lavender essential oils exhibited promising results when tested in vitro for toxic and repellent effects against D. gallinae; thus, we suggest that future experiments focus on in vivo tests using these oils in farm units. PMID:26548812

  14. Toxic and nontoxic effects of ouabain on the transmitter release from frog motor nerve terminals.

    PubMed

    Maeno, T; Enomoto, K; Hara, N; Sawada, M; Ichinose, M

    1995-01-01

    Toxic and nontoxic effects of ouabain were investigated on frog neuromuscular preparation by measuring the mean quantal content of endplate potentials elicited during repetitive nerve stimulation. In the untreated normal muscles, application of 10 microM ouabain gave rise to a slow exponential increase in the transmitter release (toxic ouabain effect) with a certain delay. This delay was increased with either 100 microM amiloride, a Na(+)-Ca2+ exchange blocker, or the intracellular loading of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a specific intracellular Ca2+ chelator. Measurements of frequency augmentation-potentiation (FAP) revealed a specific nontoxic effect of ouabain: 1 microM ouabain pivoted the long-linear FAP relation counter-clockwise without altering the intercept on the ordinate. Contrary to their action in the toxic effect, both 100 microM amiloride and the intracellular loading of BAPTA failed to counteract the nontoxic effect of 1 microM ouabain. The present results suggest that the toxic and nontoxic effects of ouabain are of different entities. The ouabain-sensitive subtype of Na+,K(+)-ATPase, which is abundant in neural tissues, seems to play a specific role in the process of nontoxic potentiation of transmitter release. PMID:7650860

  15. Xenotransplantation Models to Study the Effects of Toxicants on Human Fetal Tissues1

    PubMed Central

    Spade, Daniel J.; McDonnell, Elizabeth V.; Heger, Nicholas E.; Sanders, Jennifer A.; Saffarini, Camelia M.; Gruppuso, Philip A.; De Paepe, Monique E.; Boekelheide, Kim

    2015-01-01

    Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human-relevant mechanistic data on the many tissue-level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development. PMID:25477288

  16. Effect of binary combinations of selected toxic compounds on growth and fermentation of Kluyveromyces marxianus.

    PubMed

    Oliva, Jose M; Ballesteros, Ignacio; Negro, M José; Manzanares, Paloma; Cabañas, Araceli; Ballesteros, Mercedes

    2004-01-01

    The inhibitory effects of various lignocellulose degradation products on glucose fermentation by the thermotolerant yeast Kluyveromyces marxianus were studied in batch cultures. The toxicity of the aromatic alcohol catechol and two aromatic aldehydes (4-hydroxybenzaldehyde and vanillin) was investigated in binary combinations. The aldehyde furfural that usually is present in relatively high concentration in hydrolyzates from pentose degradation was also tested. Experiments were conducted by combining agents at concentrations that individually caused 25% inhibition of growth. Compared to the relative toxicity of the individual compounds, combinations of furfural with catechol and 4-hydroxybenzaldehyde were additive (50% inhibition of growth). The other binary combinations assayed (catechol with 4-hydroxybenzaldehyde, and vanillin with catechol, furfural, or 4-hydroxybenzaldehyde) showed synergistic effect on toxicity and caused a 60-90% decrease in cell mass production. The presence of aldehydes in the fermentation medium strongly inhibited cell growth and ethanol production. Kluyveromyces marxianus reduces aldehydes to their corresponding alcohols to mitigate the toxicity of these compounds. The total reduction of aldehydes was needed to start ethanol production. Vanillin, in binary combination, was dramatically toxic and was the only compound for which inhibition could not be overcome by yeast strain assimilation, causing a 90% reduction in both cell growth and fermentation. PMID:15176873

  17. The effect of natural organic matter on bioaccumulation and toxicity of chlorobenzenes to green algae.

    PubMed

    Zhang, Shuai; Lin, Daohui; Wu, Fengchang

    2016-07-01

    The effect of natural organic matter (NOM) on toxicity and bioavailability of hydrophobic organic contaminants (HOCs) to aquatic organisms has been investigated with conflicting results and undefined mechanisms, and few studies have been conducted on volatile HOCs. In this study, six volatile chlorobenzenes (CBs) with 1-6 chlorine substitutions were investigated for their bioaccumulation in an acute toxicity to a green alga (Chlorella pyrenoidosa) in the presence/absence of Suwannee River NOM (SRNOM). The fluorescence quenching efficiency of SRNOM increased as the number of chlorine substitutions of CBs increased. SRNOM increased the cell-surface hydrophobicity of algae and decreased the release rates of algae-accumulated CBs, thus increasing the concentration factor (CF) and accumulation of the CBs in the algae. SRNOM increased the toxicity of monochlorobenzene and 1,2-dichlorobenzene, decreased the toxicity of pentachlorobenzene and hexachlorobenzene, and had no significant effect on the toxicity of 1,2,3-trichlorobenzene and 1,2,3,4-tetrachlorobenzene. Relationships between the 96h CF/IC50 (i.e., the CB concentration leading to a 50% algal growth reduction compared with the control) and physicochemical properties of CBs with/without SRNOM were established, providing reasonable explanations for the experimental results. These findings will help with the accurate assessment of ecological risks of organic pollutants in the presence of NOM. PMID:26989981

  18. Studies with the USF/NASA toxicity screening test method - Effect of air flow and effect of fabric dye

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Lopez, M. T.

    1976-01-01

    One sample each of commercial polyurethane and polychloroprene flexible foams were evaluated using the USF/NASA toxicity screening test method. Air flow rates of 0, 0.16, 16, and 48 ml/sec were used to determine the effect of air flow on relative toxicity. Time to first sign of incapacitation and time to death were substantially reduced with both polyurethane and polychloroprene flexible foams by the introduction of 16 to 48 ml/sec air flow. The relative toxicity rankings of these materials were not altered by changes in air flow. Under these test conditions, the polyurethane foam consistently appeared more toxic than the polychloroprene foam. Samples of six different colors from the same fabric were evaluated separately, using the USF/NASA toxicity screening test method, to determine the effect of fabric dye, if any. The material was an upholstery fabric, consisting of 46 percent cotton, 33 percent wool, and 21 percent nylon. There appeared to be no significant effect of fabric dye on relative toxicity, for this material under these test conditions.

  19. The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

    PubMed Central

    Ferrucci, Michela; Giorgi, Filippo S; Bartalucci, Alessia; Busceti, Carla L; Fornai, Francesco

    2013-01-01

    The activity of locus coeruleus (LC) neurons has been extensively investigated in a variety of behavioural states. In fact this norepinephrine (NE)-containing nucleus modulates many physiological and pathological conditions including the sleep-waking cycle, movement disorders, mood alterations, convulsive seizures, and the effects of drugs such as psychostimulants and opioids. This review focuses on the modulation exerted by central NE pathways on the behavioural and neurotoxic effects produced by the psychostimulant methamphetamine, essentially the modulation of the activity of mesencephalic dopamine (DA) neurons. In fact, although NE in itself mediates some behavioural effects induced by methamphetamine, NE modulation of DA release is pivotal for methamphetamine-induced behavioural states and neurotoxicity. These interactions are discussed on the basis of the state of the art of the functional neuroanatomy of central NE- and DA systems. Emphasis is given to those brain sites possessing a remarkable overlapping of both neurotransmitters. PMID:23814540

  20. Effect of algal food concentration on toxicity of two agricultural pesticides to Daphnia carinata.

    PubMed

    Barry, M J; Logan, D C; Ahokas, J T; Holdway, D A

    1995-12-01

    The effects of algal concentration (Selanastrum capricornatum) on the toxicity of the organochlorine pesticide endosulfan and the synthetic pyrethroid esfenvalerate to Daphnia carinata was investigated. The study progressed through four stages: (1) A dose-response experiment on the effects of endosulfan and esfenvalerate on the survival, growth, and reproduction of D. carinata at a single nonlimiting food level. (2) An experiment to investigate the effects of five different food concentrations on survival, growth, and reproduction of D. carinata at sublethal concentrations of endosulfan and esfenvalerate compared with nonexposed controls. (3) An experiment to investigate the effects of route of exposure (water, food-borne, or water+food-borne exposure) on the toxicity of endosulfan to D. carinata. (4) An experiment to investigate the effects of algal concentration on persistence of endosulfan in the water column and on the relative toxicity of the alpha and beta isomers and of endosulfan sulfate to D. carinata. In the first experiment all daphnids exposed to 500 ng/liter esfenvalerate died within 3 days. There was a significant effect of esfenvalerate on reproduction at 50 ng/liter by the second brood. Endosulfan did not cause significant mortality to daphnids but brood size was reduced at 320 micrograms/liter. In the second experiment the toxicity of esfenvalerate increased significantly with decreasing food concentration. In contrast, the toxicity of endosulfan to D. carinata was greatest at the higher food concentrations. Direct water-borne exposure to endosulfan was the most toxic route of exposure and the presence of algae decreased toxicity of this pesticide. The total amount of endosulfan (alpha + beta + endosulfan sulfate) persisting in the water column after 24 hr was greater at high food levels, suggesting that this may be one mechanism for increased toxicity at high food concentrations. The 48-hr LC50s of technical endosulfan, endosulfan sulfate, alpha

  1. Toxic Gas Removal by Dielectric Discharge with Corona Effect

    SciTech Connect

    Moreno, H.; Pacheco, M.; Mercado, A.; Cruz, A.; Pacheco, J.; Yousfi, M.; Eichwald, O.; Benhenni, M.

    2006-12-04

    In this work, a theoretical and experimental study on SO2 and NOx removal by non-thermal plasma technology, more specifically a dielectric barrier (DBD) discharge combined with the Corona effect, is presented. Results obtained from a theoretical study describe the chemical kinetic model of SO2 and NOx removal processes; the effect of OH radicals in removal of both gases is noteworthy. Experimental results of de-SO2 process are reported. Also, optical emission spectroscopy study was applied on some atomic helium lines to obtain temperature of electrons in the non-thermal plasma.

  2. TOXIC EFFECTS OF XENOBIOTICS ON THE PITUITARY GLAND

    EPA Science Inventory

    This overview provides a summary of adverse effects of xenobiotics upon the pituitary gland, an endocrine gland that plays an important role in the regulation of reproductive function. he most common histopathological pituitary lesions observed following exposure to drugs and che...

  3. EVALUATION OF TOXIC EFFECTS OF ORGANIC CONTAMINANTS IN RECYCLED WATER

    EPA Science Inventory

    The report represents the results of a comprehensive series of toxicological studies designed to evaluate the health effects of the application of recycled water for drinking purposes. Water was prepared in a highly advanced domestic sewerage pilot plant. Some 400,000 liters of t...

  4. PROBABILITY AND CONTROL COST EFFECTIVENESS FOR ACCIDENTAL TOXIC CHEMICAL RELEASES

    EPA Science Inventory

    The paper shows how fault tree analysis (FTA) of a process system can be used to compare the relative effectiveness of various equipment, design, and operating measures for release prevention and protection applied to process streams. It also shows how the costs of various safety...

  5. Toxic effects of chromium on Schistosoma haematobium miracidia

    SciTech Connect

    Wolmarans, C.T.; Yssel, E.; Hamilton-Attwell, V.L.

    1988-12-01

    Various heavy metals have recently been evaluated as molluscicides for freshwater snails, which act as intermediate hosts of trematode parasites of medical or veterinary importance. Very little information, however, is available on heavy metals that may be suitable to eliminate the parasites as such. Suitable compounds should also inhibit the penetration ability of parasites as well as stunt the development of those who do not penetrate their hosts. In the light of these requirements, the present study evaluated the effect of chromium on the miracidia of Schistosoma haematobium, which causes urinary bilharzia. Attention was mainly focused on (1) the chromium concentration which resulted in 100% mortality (2) the effect of chromium on the external and internal morphology of the miracidia, and (3) the ability of the miracidia to form sporocytes in vitro and in vivo and to penetrate their intermediate host snail, Bulinus africanus.

  6. Chronic toxicity of phosalone to rats: Effect on erythropoiesis

    SciTech Connect

    Reddy, S.J.; Reddy, D.C.; Kalarani, V.; Ramamurthi, R. )

    1989-12-01

    It is well known that organophosphorus insecticides (OPI) act as nerve poisons by blocking synaptic transmission in cholinergic part of the nervous system. Phosalone (0,0-diethyl-S-(6-chloro-1,3-benzoxozol-2(3H)-onylmethyl)phosphorodithioate), an OPI, is being extensively used to kill insect crop pests in this part of India. Studies on the effects of phosalone on physiology of vertebrates are very few. Prolonged exposure to phosalone has been reported to cause marked changes in body weight, liver weight and RBC of rats. Others reported a decrease in brain SDH activity of rat dosed with phosalone, and a decrease in brain acetylcholinesterase (AchE) activity of fish exposed to phosalone. However, the effect of multiple sublethal doses of phosalone on haemopoietic system of rat has not yet been fully evaluated. The present investigation is one such attempt over a 60 day period.

  7. LIFE CYCLE BIOASSAY FOR ASSESSMENT OF THE EFFECTS OF TOXIC CHEMICALS USING RAPID CYCLING OF BRASSICA

    EPA Science Inventory

    Initial evaluation of a new plant life cycle bioassay for the assessment of the effects of toxic chemicals is presented. he bioassay features a rapid cycling Brassica species that can complete its life cycle in as little as 36 days. he herbicide dalapon (2,2 dichloropropionic aci...

  8. The Use of Paramecium to Observe the Toxic Effect of Cigarette Smoke.

    ERIC Educational Resources Information Center

    Bardell, David

    1986-01-01

    Describes a laboratory experiment in which Paramecium caudatum was used to demonstrate the toxic effect of cigarette smoke on the cilia of epithelium cells lining the trachea and bronchi of smokers. Provides background information and explains the procedure, including how to make a simple mechanical smoking device. (TW)

  9. Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?

    PubMed Central

    Munday, Rex

    2013-01-01

    Okadaic acid (OA) and its derivatives, which are produced by dinoflagellates of the genera Prorocentrum and Dinophysis, are responsible for diarrhetic shellfish poisoning in humans. In laboratory animals, these toxins cause epithelial damage and fluid accumulation in the gastrointestinal tract, and at high doses, they cause death. These substances have also been shown to be tumour promoters, and when injected into the brains of rodents, OA induces neuronal damage reminiscent of that seen in Alzheimer’s disease. OA and certain of its derivatives are potent inhibitors of protein phosphatases, which play many roles in cellular metabolism. In 1990, it was suggested that inhibition of these enzymes was responsible for the diarrhetic effect of these toxins. It is now repeatedly stated in the literature that protein phosphatase inhibition is not only responsible for the intestinal effects of OA and derivatives, but also for their acute toxic effects, their tumour promoting activity and their neuronal toxicity. In the present review, the evidence for the involvement of protein phosphatase inhibition in the induction of the toxic effects of OA and its derivatives is examined, with the conclusion that the mechanism of toxicity of these substances requires re-evaluation. PMID:23381142

  10. Dietary Arsenic Toxicity in Subadult Rainbow Trout: Growth Effects, Nutrient Absorption, and Tissue Bioaccumulation

    EPA Science Inventory

    Dietary arsenic toxicity in subadult (~200 g.) rainbow trout was evaluated in a 70 day test using arsenic-spiked pellet diets containing 50, 104 and 162 ppm arsenite. All organisms in all treatments survived the exposure. Dose dependent effects on percent weight gain, with comm...