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At least 19 recordsLinked to original sources
PubMed2003

Effect of dithiocarbamate pesticide zineb and its commercial formulation, azzurro. IV. DNA damage and repair kinetics assessed by single cell gel electrophoresis (SCGE) assay on Chinese hamster ovary (CHO) cells.

Single cell gel electrophoresis (SCGE) was used to analyse dithiocarbamate zineb- and the zineb-containing technical formulation azzurro-induced DNA damage and repair in CHO cells. Cells were treated with zineb (50.0 microg/ml) or azzurro (100.0 microg/ml) for 80min, washed and reincubated in pesticide-free medium for 0-12h until SCGE. Viability of treated cells (0 h) did not differ from control remaining unchanged up to 6h of incubation. After 12h, viability decreased up to 70 and 54% in zineb- and azzurro-treated cultures, respectively. SCGE revealed at 0 h the absence of undamaged cells and an increase of slightly damaged and damaged cells in zineb-treated cultures or by an increase in damaged cells in azzurro-treated cultures. For both chemicals, a time-dependent repair of pesticide-induced DNA damage within a 0-12h post-treatment incubation period was observed. Overall, damaged cells decreased as a function of the repair time for both pesticides while the slightly damaged cells decreased as a function of the repair time of zineb-induced DNA damage. Concomitantly, a time-dependent increase of undamaged cells was observed within the 0.5-12h repair time for both pesticides. At 12h after treatment, no differences in the frequencies of undamaged, slightly damaged and damaged cells were found between both zineb- or azzurro-treated cultures and control values as well as between zineb- and azzurro-treated cells. Immediately after exposure, nuclear DNA from zineb and azzurro-treated cells were larger and wider than nuclear DNA from untreated cells. When damaged cells were allowed to repair, a time-dependent decrease of the amount of free DNA migrating fragments was observed committed only to damaged cells but not in slightly or undamaged cells. On the other hand, no time-dependent alteration on nuclear DNA width within the 0-12h repair period was observed.

Animals↗
PubMed2003

Vitamin E prevents ethylene bis(dithiocarbamate) pesticide zineb-induced sister chromatid exchange in Chinese hamster ovary cells.

The in vitro effect of the antioxidant alpha-tocopherol, vitamin E, on deleterious effects induced by the dithiocarbamate fungicide zineb and its commercial formulation azzurro on Chinese hamster ovary (CHO) cells was studied by using frequency of sister chromatid exchanges (SCEs), cell cycle progression and mitotic index (MI) as genetic end points. Both zineb and azzurro activities were tested within the range 0.1-100.0 microg/ml on exponentially growing CHO cells preincubated for 24 h in the presence or absence of 50.0 microg/ml vitamin E. SCE frequencies increased significantly over control values in a concentration-dependent manner in zineb- and azzurro-treated cultures at concentrations of 0.1-10.0 and 0.1-25.0 microg/ml, respectively. When target cells were preincubated with vitamin E, the number of SCEs was significantly lower than that observed in cells exposed only to 1.0-10.0 microg/ml zineb or 1.0-25.0 microg/ml azzurro, but higher than control values. Cytotoxicity was observed at concentrations higher than 25.0 and 50.0 microg/ml zineb and azzurro, respectively, regardless of the absence or presence of vitamin E. Regression analysis showed that the proliferative rate index decreased as a function of the concentration of zineb (0.1-10.0 microg/ml concentration range) and azzurro (0.1-25.0 microg/ml concentration range) titrated into cultures. For both chemicals, progressive concentration-related inhibition of the mitotic activity from cultures was observed when 10.0 microg/ml zineb or 1.0-25.0 microg/ml azzurro was employed. However, no significant alteration in cell cycle progression or MI was observed between vitamin E-preincubated cultures and those treated only with zineb and azzurro.

Animals↗
PubMed2003

Effect of the dithiocarbamate pesticide zineb and its commercial formulation, the azzurro. V. Abnormalities induced in the spindle apparatus of transformed and non-transformed mammalian cell lines.

Abnormalities induced in the mitotic spindle by zineb and azzurro (1.0-25.0 micro g/ml, 24h) were evaluated in Chinese hamster ovary (CHO) and HeLa cells, and in non-transformed human fibroblasts (NTHF). Spindles were stained with FITC-conjugated anti-beta tubulin. Treatment with 10.0 micro g/ml of zineb induced complete inhibition of cell viability in NTHF cells while 10.0 micro g/ml of azzurro decreased cell growth down to 62%. Higher doses of both compounds induced cell death. In HeLa and CHO cells, 15.0 micro g/ml of zineb and 10.0-15.0 micro g/ml of azzurro decreased viability, whereas 25.0 micro g/ml of both compounds was cytotoxic. A significantly decreased mitotic index (MI) was observed in NTHF treated with 5.0 micro g/ml zineb or azzurro, whereas 10.0 micro g/ml of both chemicals were necessary to induce the same phenomenon in HeLa and CHO cells. Treatment with 1.0-5.0 micro g/ml of zineb or azzurro induced a dose-dependent increase of degenerated spindles in NTHF and the number of degenerated or multipolar spindles in HeLa and CHO cells increased in a dose-dependent manner with 1.0-10.0 micro g/ml zineb and azzurro. Although zineb and azzurro were able to induce mitotic spindle abnormalities in all cell types, non-transformed cells were less resistant than immortalized cells.

Animals↗
PubMed1991

Radiotracer study on residues and residue distribution of zineb in plant-soil system.

In view of the widespread use of zineb on food plants and the toxicity of one of its metabolites, ETU, a study on the residues and residue distribution of zineb and ETU in plant-soil systems was carried out. The half-life values for total zineb residues on egg-plant leaves and in soil were observed to be over three and two weeks, respectively. Egg-plant skin contained higher amount of zineb residues than the fruit pulp. Washing with water greatly reduced zineb residue levels, especially those in the fruit skin. Compared with zineb, ETU is much easier to be uptaken by plants and to leach into deeper layer of soil due to its high water solubility. Therefore, attention should be paid to the contents of ETU in zineb formulations as impurity and formation of ETU in the environment.

Carbon Radioisotopes↗
PubMed1995

Effects of the subchronic administration of zinc ethylene-bis-dithiocarbamate (zineb) to rabbits.

The effects of subchronic administration (90 d) of zineb were studied in male New Zealand White rabbits. Rabbits were allotted to 3 groups of 8 animals each and offered diets containing 0, 0.3 or 0.6% zineb. A marked decline in weight gain, hemoglobin concentration, hematocrit, and erythrocyte and leucocyte counts occurred at the highest zineb dosage. There was a dose-related depression in circulating thyroid hormones, whereas serum lipid concentration, particularly that of cholesterol and triglycerides, increased. Hepatic lipid concentration was considerably reduced in rabbits exposed to 0.6% zineb. Neither serum testosterone nor the activities of selected testicular enzymes showed changes suggestive of testicular involvement. Pathological changes were in agreement with biochemical findings; there was a marked dose-related enlargement of the thyroid showing histological colloid struma. An increase in relative weight and moderate glycogenosis were detected in liver, whereas no lesions occurred in testes. It was concluded that thyroid and liver are the main targets for zineb toxicity in the rabbit. Unlike the results from previous studies conducted on other food-producing species, repeated exposure of rabbits to zineb failed to cause testicular damage. This might be related to the inability of zineb to significantly accumulate in the testes.

Analysis of Variance↗
PubMed2002

Effect of dithiocarbamate pesticide zineb and its commercial formulation, azzurro. II. micronucleus induction in immunophenotyped human lymphocytes.

The frequency of micronuclei was measured in human peripheral B-lymphocytes and some T-lymphocyte subpopulations exposed in vitro to 1.0-100.0 microg/ml of the dithiocarbamate pesticide zineb and its commercial formulation azzurro. The peripheral mononuclear lymphocytes were stimulated in vitro with phytohemagglutinin after pesticide treatment and B-lymphocytes and the various T-lymphocyte subsets were classified by the MAC (morphology, antibody, chromosomes) method, which allows the immunological identification of different cell lineages. An increased frequency of micronuclei in CD20(+) (P < 0.01), CD3(+) (P < 0.01), and CD8(+) lymphocytes (P < 0.01) was observed only when 25.0 microg/ml of zineb and azzurro were employed. The frequency of micronuclei in treated CD8(+) cells did not differ from treated CD20(+) lymphocytes (P > 0.05). Lower concentrations of pesticides did not increase the frequency of micronuclei from that observed in control cultures. Furthermore, for both zineb and azzurro cytotoxicity was observed at doses higher than 50.0 microg/ml. Significant increases in the proportion of CD20(+) (P < 0.01) and CD8(+) cells (P < 0.01) among mitotic and interphasic lymphocytes from both zineb- and azzurro-treated cultures were observed only when a concentration of 25.0 microg/ml was employed. In contrast, significant decreases in the proportion of CD3(+) (P < 0.01) and CD4(+) cells (P < 0.01) were found for both mitotic and interphasic lymphocytes from zineb- and azzurro-treated cultures. The MAC methodology revealed that among the different lymphocyte subpopulations analyzed (CD20, CD3, CD4, and CD8), the induction of micronuclei by zineb and its commercial formulation azzurro was restricted to CD20(+) B-cells and T-suppressor/cytotoxic CD8(+) lymphocytes.

Adult↗
PubMed1980

Species-dependent effects of dietary lindane and/or zineb on the activation of aflatoxin B1 into mutagenic derivatives.

Sprague-Dawley rats and Swiss mice were given diets containing lindane, 125 ppm, or zineb, 5200 ppm, or a mixture of both at the above-mentioned concentrations for 2 and 4 weeks. The effect of pesticide ingestion on the ability of liver S9 to metabolize aflatoxin B1 (AFB1) into mutagenic derivatives was tested by the Salmonella (TA100)/microsome test according to Ames. Control mouse-liver S9 was less efficient (13%) than the corresponding preparation from control rat liver. The ingestion of lindane produced a similar increase in the activities of both rat- (68%) and mouse-liver S9 (62%). Pretreatment with zineb inhibited (46%) rat-liver S9 but caused a marked increase (400%) in the activity of mouse-liver S9. Concomitant exposure to both pesticides showed that lindane released the inhibitory action of zineb on rat-liver S9 and reduced the stimulatory effect of zineb on mouse-liver S9. The inducing action of zineb in mice was a function of the dietary concentration of the pesticide. No effect was observed at dietary concentrations of zineb up to and including 500 ppm.

Aflatoxin B1↗
PubMed2002

Effect of dithiocarbamate pesticide zineb and its commercial formulation, azzurro. III. Genotoxic evaluation on Chinese hamster ovary (CHO) cells.

The in vitro genotoxicity exerted by the dithiocarbamate fungicide zineb, and its commercial formulation azzurro, were studied in Chinese hamster ovary (CHO) cells by the analysis of the sister chromatid exchange (SCE), cell-cycle progression and single cell gel electrophoresis (SCGE) assays. Both zineb and azzurro activities were tested within the range of 0.1-100.0 microg/ml. Concentrations of 0.1-25.0 microg/ml of zineb or azzurro induced a significant dose-dependent increase in SCE frequency over control values. For both test compounds, while doses ranging from 0.1 to 1.0 microg/ml did not alter the rate of cell proliferation, a significant delay in cell-cycle progression was observed within the 5.0-25.0 microg/ml dose-range. A regression test showed that either the proliferative replication index or the mitotic activity of cultures decreased as a function of the pesticide concentration within the 1.0-25.0 microg/ml dose-range. Doses higher than 50.0 microg/ml were cytotoxic. SCGE assay revealed an increase in zineb-induced DNA damage by enhancing the proportion of slightly damaged cells in the 25.0-100.0 microg/ml dose-range and by increasing in a dose-dependent manner the proportion of damaged cells within the 1.0-100.0 microg/ml dose-range. Overall, image analysis showed statistically significant positive relationships between zineb concentration and DNA damage (expressed by image length and width) and between length and width of the damaged cells. In azzurro-treated cells, only when 100.00 microg/ml was employed a significant increase in the frequency of damaged cells over control values affecting the totality of the cells was observed only when 100.0 microg/ml was employed. When lower doses were employed, no DNA damage was revealed. Based on these results, the evaluation of zineb as a genotoxic/non-genotoxic compound for human health should be reconsidered. Even though we demonstrate that the pesticide induces large DNA alterations in vitro, does no necessarily mean that the chemical should be considered clastogenic.notoxic

Animals↗
PubMed2004

Column preconcentration and spectrophotometric determination of ziram and zineb in commercial samples and foodstuffs using (1,2'-pyridylazo)-2-naphthol (PAN)-naphthalene as adsorbate.

A procedure has been developed for the determination of zinc(II) bis(dimethyldithiocarbamate) (ziram) and zinc(II) ethylenebis(dithiocarbamate) (zineb) after preconcentration on a column using naphthalene-(1,2'-pyridylazo)-2-naphthol (PAN) as adsorbent. Ziram and zineb are quantitatively retained on the column in the pH range of 9.0-12.5 and at a flow rate of 1-2 mL/min. The solid mass consisting of the Zn-PAN complex along with naphthalene is dissolved from the column with 5 mL of dimethylformamide (DMF). Absorbance of the complex was measured at 550 nm; Beer's law is obeyed over the concentration ranges of 2.0-22.0 microg of ziram and 5.0-19.8 microg of zineb in 10 mL of the final DMF solution. Ten replicate determinations on a sample solution containing 20 microg of ziram and 18 microg of zineb gave a mean absorbance of 0.33 with relative standard deviations of 0.80 and 0.70%, respectively. The interference of various ions has been studied. The method has been employed for the determination of ziram and zineb in commercial samples and in various foodstuffs, and the results were compared with the earlier reported methods.

Adsorption↗
PubMed2001

Effect of the dithiocarbamate pesticide zineb and its commercial formulation azzurro. I. Genotoxic evaluation on cultured human lymphocytes exposed in vitro.

The in vitro cytogenetic effects exerted by the dithiocarbamate fungicide zineb and one of its commercial formulations currently used in Argentina, azzurro, were studied in whole blood human lymphocyte cultures. The genotoxicity of the fungicides was measured by analysis of the frequency of chromosomal aberrations and sister chromatid exchanges (SCEs) and cell cycle progression assays. Both zineb and azzurro activities were tested within the range 0.1-100.0 microg/ml immediately after in vitro lymphocyte stimulation. Only concentrations of 50.0 and 100.0 microg/ml zineb and azzurro induced a significant increase in SCE frequency over control values. Furthermore, this genotoxicity appears to be correlated with its cytotoxicity, measured as cell cycle kinetics, since both a significant delay in cell cycle progression and a significant reduction in proliferative rate index were only observed in those cultures treated with these fungicide concentrations. For both chemicals, a progressive dose-related inhibition of the mitotic activity of cultures was observed when increasing the fungicide concentration. Moreover, only the mitotic activity statistically differed from control values when doses of zineb or azzurro <10 microg/ml were employed. For both fungicides the mitotic index reached the minimal value at doses of 100 microg/ml. Both products induced a significant dose-dependent increase in the number of abnormal cells, chromatid-type and chromosome-type aberrations as well as in the total number of aberrations in the 0.1-100.0 microg/ml dose range. Based on these results, the evaluation of zineb as a controversial genotoxic/non-genotoxic compound for human health should be reconsidered. Instead, we demonstrate that the fungicide induces large DNA alterations and should be considered as a clastogenic mutagen.

Adult↗
PubMed2002

Flow injection/atomic absorption spectrometric determination of zineb in commercial formulations of pesticide based on slurry sampling.

This paper reports on a new strategy for the slurry sampling determination of dithiocarbamate pesticide zineb [[ethylenebis(dithiocarbamato)]zinc] employing a FIA system with a flame atomic absorption spectrometry detector. In the flow system, an on-line alkaline hydrolysis of the pesticide is performed, allowing the release of Zn(II) ions to the solution, which are easily detected by a flame AAS technique. Several parameters that could affect the performance of the analytical methodology were studied, such as the concentration of NH3(aq) used in the hydrolysis step, the effect of the presence of Triton X-100 on the sensitivity and precision, and the FIA parameters (carrier flow rate and mixing coil volume). Under optimized conditions, aqueous slurries containing 2.5 to 25 microg ml(-1) zineb provided good linear calibration fits. From the obtained data, a detection limit (3sigma) of 1.0 microg ml(-1) zineb was found and a repeatability of 2.7% was obtained from 12 measurements of a slurry containing 2.5 microg m(-1) zineb. On the other hand, a precision (reproducibility) of 7.8% was achieved from three determinations of a sample containing 128 mg g(-1) of the pesticide. Also, the developed system provides a sampling frequency of 72 h(-1).

Flow Injection Analysis↗
PubMed1991

Pathologic changes, tissue distribution, and extent of conversion to ethylenethiourea after subacute administration of zinc ethylene-bis-dithiocarbamate (zineb) to calves with immature rumen function.

The toxicity of zinc ethylene-bis-dithiocarbamate (zineb), a widely used fungicide, was studied in four 4-week-old Friesian calves with immature rumen function. Calves were first subjected to liver biopsy, and thereafter, 3 of them were orally administered 200 mg of zineb/kg of body weight daily for 80 days, whereas the fourth calf served as control and remained untreated. Clinical, hematologic, and pathologic (including ultrastructural) findings were recorded. The distribution in body fluids and tissues of the parent compound and one of its main metabolites, ethylenethiourea (ETU), also was examined. Treated calves had unthrifty appearance and reduction in weight gain. They also had remarkable impairment of thyroid function, as reflected by reduction in serum concentrations of triiodothyronine and thyroxine and increase in weight of the thyroid gland associated with epithelial vacuolization and foci of hyperplasia. Moderate increase in liver glycogen content and impairment in maturation of germ cells were recorded consistently. Whereas zineb was widely distributed in body tissues, ETU accumulated mainly in the liver and the thyroid gland, although noticeable concentrations also were attained in muscle. Data were consistent with involvement of ETU mainly in the pathogenesis of thyroid gland lesions, and indicate that unweaned calves given zineb develop a clinicopathologic syndrome that does not differ qualitatively from that already described in adult cattle exposed to zineb.

Age Factors↗
PubMedDate not supplied

[Study of the effect of the fungicide zineb on microorganisms].

Changes in yeast cells induced by the fungicide zineb were studied using biochemical, genetic techniques and electron microscopy. The primary changes involved anabolic processes since RNA and protein content increased in the cells. The data were consistent with a larger size of mitochondria. The oxidative-reductive activity of cell extracts did not change under the action of the fungicide. Zineb at a concentration of 0.5 to 50 mg/litre exerted a genetic activity towards indicator microorganisms. The changes in the morphophysiological characteristics of yeast growth under the action of zineb are presumed to be of a protective nature. Zineb traces in soil must be controlled in terms of the microbiological index.

Drug Resistance, Microbial↗
PubMed1978

[Action of a dithiocarbamate (zinebe) on the liver biosynthesis of RNA and proteins in the rat (author's transl)].

Zineb (zinc ethylene bisdithiocarbamate) inhibits the transcriptional activity of an in vitro system functioning with either RNA polymerases of isolated rat liver nuclei or purified E. coli RNA polymerase. Zineb also inhibits the in vitro aminoacid incorporation mediated by a polysomal standard system, by interacting with some pH 5 enzyme components(s). When rats fed a balanced semi-synthetic diet containing zineb (5 200 mg/kg) for ten weeks, one may observe a decrease in the RNA and protein syntheses in liver. The consequences of the ingestion of small but repeated doses of zineb are discussed.

Amino Acids↗
PubMed1985

The effect of maneb, zineb, and ethylenethiourea on the humoral activity of the pituitary-thyroid axis in rat.

Ethylenebisdithiocarbamates (EBDCs) maneb and zineb are widely used fungicides the final metabolite of which is ethylenethiourea (ETU). EBDCs distort the humoral activity of the thyroid gland, and ETU is especially active in this respect. Male Wistar rats were exposed either to exogenous (100 ng i.p.) or endogenous (+4 degrees C) TRH stimulation. ETU (100-500 mg/kg i.p.) caused no changes in serum TSH levels whereas zineb (70-500 mg/kg i.p.) significantly decreased the bursts induced by cold or exogenous TRH. Maneb (20-200 mg/kg i.p.) significantly decreased the cold-induced TSH response while it had no effect on the TRH-stimulated TSH secretion. None of the agents caused significant changes in serum T3 or T4 levels. It seems that maneb, and zineb, but not ETU, inhibit rat TSH secretion through an action on the endogenous TRH at the hypothalamic or pituitary level. The mechanism behind this action may be the inhibition of dopamine-beta-hydroxylase.

Animals↗
PubMed1985

Studies on the mechanism of nabam- and zineb-induced inhibition of the hepatic microsomal monooxygenases of the male rat.

In vitro effects of the ethylene bis-dithiocarbamate fungicides, nabam and zineb, on the hepatic microsomal monooxygenases of male rats were examined. Incubation of nabam and zineb with hepatic microsomes, without NADPH, leads to an inhibition of the metabolism of aminopyrine and aniline and to a denaturation of cytochrome P-450 into cytochrome P-420; in addition nabam causes the destruction of cytochrome P-450. Addition of NADPH into the incubation medium increases the inhibition of the monooxygenases, principally the inhibition of the metabolism of aniline induced by nabam. We studied the in vitro effects of three of the chief breakdown products of these fungicides: ethylene bis-isothiocyanate sulfide (EBIS), ethylene thiourea (ETU), and carbon disulfide (CS2). EBIS appears to be the only metabolite affecting directly (without NADPH) the hepatic monooxygenases activity. EBIS accounted partly for nabam-induced inhibition of the hepatic microsomal monooxygenases. The data suggest that the decrease of monooxygenases activity seen on incubation of nabam with hepatic microsomes may be due to the denaturation and destruction of cytochrome P-450 resulting from covalent binding of the compounds with cysteine sulfhydryl groups in cytochrome P-450. Inhibition of monooxygenase activity induced by zineb seems to be due to the reaction with the sulfhydryl groups of cytochrome P-450 and to another mechanism, probably related to its lipophilic character.

Aminopyrine N-Demethylase↗
PubMed1986

Uptake, distribution and retention of zineb and ziram in rainbow trout (Salmo gairdneri).

In short-term static bioaccumulation experiments with 14C-labelled zinc ethylenebisdithiocarbamate (zineb) and zinc dimethyldithiocarbamate (ziram) both compounds were rapidly disseminated through the tissues. Whole-body accumulation was low, with bioconcentration factors less than 100. Whole-body elimination was rapid with 45% and 25% of the initial radioactivity from ziram and zineb, respectively, being retained by the end of the 16-day depuration period. Pigmented tissues appeared to be major distribution sites as well. This may be related to the affinity of the compounds and/or their degradation products to melanin or to complexation with phenoloxidase, a copper-containing enzyme involved in melanin synthesis. Autoradiography also revealed a high labelling of thyroid follicles. The results show that dithiocarbamates are selectively localized in various tissues, reported to be the target organs for their toxic action. The observed differences in toxicokinetics between zineb and ziram may, in part, explain the differences in toxicity to fish between ethylenebisdithiocarbamates and dialkyldithiocarbamates.

Animals↗
PubMed2002

Evaluation of genotoxicity of captan, maneb and zineb in the wing spot test of Drosophila melanogaster: role of nitrosation.

The wing spot test in Drosophila melanogaster is a suitable system for the analysis of genotoxic activity of compounds that need metabolic transformation to render them active. We have analysed the genotoxicity of three fungicides for which it was reported that the metabolic processes taking place in vivo may determine their activity. The compounds analysed are captan, maneb, zineb and ethylenethiourea (ETU) (a metabolic derivative of ethylenebisdithiocarbamates like maneb and zineb). We have also evaluated the ability of ETU to form genotoxic derivatives in vivo analysing this compound in combined treatments with sodium nitrite. Both standard and high bioactivation NORR strains have been used. Captan, usually considered a mutagen in vitro but a non-mutagen in vivo, gave negative results in the wing spot test with both crosses. Positive results were obtained for maneb in the standard cross and for ETU in both the standard and the high bioactivation cross. The genotoxicities of maneb and ETU were higher when treatments were made on media in which nitrosation is favoured. A low absorption of the fungicide and an inefficient availability of the compound in the target may explain negative results obtained with zineb in both crosses. The results obtained in this study with the wing spot test demonstrate once again the suitability of this in vivo assay, in which absorption, distribution and metabolism processes take place, for the evaluation of genotoxicity of compounds to which humans are exposed.

Animals↗