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At least 19 recordsLinked to original sources
PubMed1983

NTP Carcinogenesis Bioassay of Ziram (CAS No. 137-30-4) in F344/N Rats and B6C3F1 Mice (Feed Study).

A NTP Carcinogenesis bioassay of ziram (89% pure, with 6.5% thiram), a fungicide and a rubber vulcanization accelerator, was conducted in F344/N rats and in B6C3F1 mice. Groups of 50 rats of each sex received diets containing 300 or 600 ppm of commercial grade ziram for 103 weeks; groups of 49 or 50 mice of each sex received diets containing 600 or 1,200 ppm ziram; and groups of 50 rats and 50 mice of each sex served as untreated controls. The average daily consumption of ziram by low-and high-dose rats, through the majority of the study, was about 11 and 22 mg/kg for males and 13 and 26 for females. The average daily consumption of ziram by low-and high-dose mice, through the majority of the study, was 122 and 196 mg/kg for males and about 131 and 248 mg/kg for females. Survival and feed consumption and mean body weights of rats of each sex were not adversely affected by ziram; rats of each sex could have tolerated higher doses. C-Cell carcinomas of the thyroid in male rats occurred with a statistically significant positive trend (P<0.01) and the incidence in the high-dose group was significantly higher (P<0.05) than that in the controls (control, 0/50, 0%; low-dose, 2/49, 4%; high-dose, 7/49, 14%) and higher than that previously observed in control male rats at the same laboratory (18/584, 3%; range 0% to 8%). The combined incidence of males with either C-cell adenoma or carcinoma also showed a statistically significant (P<0.05) positive trend (control, 4/50, 8%; low-dose, 9/49, 18%; high-dose, 12/49, 24%). There were no significant histopathologic changes noted in the follicular cells. Survival of male and female mice was not adversely affected by ziram in feed; mean body weight gain by dosed male mice throughout the study and by high-dose female mice after week 80 was depressed by 15% to 20% relative to the controls. Average daily feed consumption by high-dose males and high-dose females was, respectively, 78% and 85% that of the controls. Mice probably could not have tolerated higher doses. The incidence of alveolar/bronchiolar adenomas was significantly (P<0.05) increased in female mice (control, 2/50, 4%; low-dose, 5/49, 10%; high-dose, 10/50, 20%). The combined incidence of alveolar/bronchiolar adenomas or carcinomas in female mice showed a statistically significant (P<0.05) positive trend. The incidence in the high-dose group was significantly (P<0.05) higher than that in the controls (control, 4/50, 8%; low-dose, 6/49, 12%; high-dose, 11/50, 22%). Pulmonary adenomatous hyperplasia consistent with chronic Sendai virus infection (confirmed by serologic analysis performed on untreated animals from the same animal shipment and present in the same room) was observed in control and dosed male mice (control, 15/49, 31%; low-dose, 19/50, 38%; high-dose, 16/49, 33%) as well as in control and dosed female mice (control, 18/50, 36%; low-dose, 27/49, 55%; high-dose, 26/50, 52%). Six of the 26 high-dose females without pulmonary adenomatous hyperplasia had pulmonary tumors, whereas 4 of the 24 high-dose females without pulmonary adenomatous hyperplasia also had pulmonary tumors. Only 1 of 27 low-dose females with adenomatous hyperplasia had a pulmonary tumor. There was a significant decrease in the incidence of mammary fibroadenomas in high-dose female rats (control, 16/50, 32%; low-dose, 17/50, 34%; high-dose, 8/50, 16%). Significant dose-related decreased incidences of liver carcinomas in male mice (control, 13/49, 27%; low-dose, 8/50, 16%; high-dose, 1/49, 2%) and of liver adenomas in female mice (control, 7/50, 14%; low-dose, 2/50, 4%; high-dose, 0/50, 0%) were observed. Under the conditions of these studies, ziram was carcinogenic for male F344/N rats, causing increased incidences of C-cell carcinomas of the thyroid gland. Ziram was not carcinogenic for either female F344/N rats or for male B6C3F1 mice. Increased incidences of alveolar/bronchiolar adenomas and of combined alveolar/bronchiolar adenomas or carcinomas occurred in female B6C3F1 mice. However, the interpretation of this increase in lung tumors is complicat either female F344/N rats or for male B6C3F1 mice. Increased incidences of alveolar/bronchiolar adenomas and of combined alveolar/bronchiolar adenomas or carcinomas occurred in female B6C3F1 mice. However, the interpretation of this increase in lung tumors is complicated by an intercurrent Sendai virus infection. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Negative Male Mice: Negative Female Mice: Equivocal Synonym: zinc dimethyldithiocarbamate

Journal Article↗
PubMed2003

Thiram and ziram stimulate non-selective cation channel and induce apoptosis in PC12 cells.

The neurotoxicity of dithiocarbamates has been previously reported, however, the detailed mechanism underlying the neurotoxicity is still not fully understood. Among the dithiocarbamates, we investigated thiram and ziram in a neuronal-like pheochromocytoma (PC12) cells. Thiram and ziram strongly induced cell death in both dose- and time-dependent manners with the LC(50) of 0.3 and 2 microM, respectively. The cell death showed typical apoptotic features, such as DNA fragmentation and an increase of subdiploidy nuclei. Interestingly, both thiram and ziram induced rapid and sustained increases of intracellular Ca(2+) in PC12 cells, which were almost completely blocked by flufenamic acid (FFA), an inhibitor of non-selective cation channel. BAPTA-AM, an intracellular Ca(2+) chelator, inhibited the thiram- and ziram-induced apoptotic cell death. These results suggest that thiram and ziram induce apoptotic neuronal cell death by Ca(2+) influx through non-selective cation channels. The present study may provide a clue for understanding the mechanism of neurotoxicity of thiram and ziram.

Animals↗
PubMed2005

Persistent inhibition of human natural killer cell function by ziram and pentachlorophenol.

Ziram is a currently used agricultural fungicide. It is also used as an additive in the production of latex gloves. Because of these uses, there is a potential for human exposure to this compound. Pentachlorophenol (PCP) has been used as an insecticide, fungicide, disinfectant, and ingredient in antifouling paints. Currently, it is used as a wood preservative for power-line poles and fence posts. Measurable levels of PCP have been detected in human blood and urine. In previous studies we demonstrated that both these compounds could cause very significant inhibition of the tumor-killing function of human natural killer (NK) cells. NK lymphocytes play a central role in immune defense against viral infection and the formation of primary tumors. So interference with their function could increase the risk of tumor development. In the present study we examined the effects of exposure to ziram or PCP of brief duration (1 h) on the ability of NK cells to destroy tumor cells. NK cells were exposed to either ziram (5-0.5 microM) or PCP (10-5 microM) for 1 h followed by 0 h, 24 h, 48 h, or 6 days in compound-free media and then were tested for the ability to lyse as well as to bind tumor cells. A 1-h exposure to as little as 2.5 microM ziram decreased the ability of NK cells to lyse target tumor cells, which persisted up to 6 days following exposure. The loss of lytic function for from 24 h to 6 days following exposure was accompanied by a comparable loss of NK capacity to bind tumor cells. Exposure to 10 microM PCP for 1 h caused a progressive loss (greater than 80%) of lytic function within 6 days of exposure. In contrast to ziram, PCP exposure caused no accompanying loss of binding function.

Cells, Cultured↗
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↗
PubMed1992

Further in vitro and in vivo mutagenicity assays with thiram and ziram fungicides: bacterial reversion assays and mouse micronucleus test.

The fungicides thiram and ziram have been assayed in a battery of nine bacterial strains of different genetic specificity. The results obtained suggest the induction of excisable DNA lesion(s), and indicate similar mutability of strains with AT or GC base pairs at target sites. This mutagenic profile is clearly distinct from that of oxidative mutagens, and it does not support the proposed role of oxidative stress in the mechanism of dithiocarbamates mutagenicity in bacteria. Furthermore, the bone marrow micronucleus test has been carried out in B6C3F1 mice with intraperitoneal administration of high grade thiram (12.5-50 mg/kg) and ziram samples (2.5-10 mg/kg in males, and 5-20 mg/kg in females). Thiram produced a significant increase of micronucleated PCEs in male mice sampled 48 h after treatment with 25, 37.5, and 50 mg/kg. No significant increase was detected in treated females. Ziram, tested in a lower range of doses because of its higher toxicity, resulted negative in both sexes. Both the acute toxicity and the ratio polychromatic/normochromatic erythrocytes indicated some sex specificity in the toxic effects induced by these dithiocarbamates in the B6C3F1 mouse.

Animals↗
PubMed1994

Clastogenic effects of the dithiocarbamate fungicides thiram and ziram in Chinese hamster cell lines cultured in vitro.

We report here the results obtained using the dithiocarbamate fungicides thiram and ziram to investigate the induction of chromosomal aberrations (CAs) in Chinese hamster ovary (CHO) cells both in the absence and presence of S9 metabolism, and in a Chinese hamster epithelial liver (CHEL) cells which retain metabolic competence to activate different classes of promutagens/procarcinogens. Both thiram and ziram proved to be strong chromosome breaking agents in the CHEL cells and CHO cells in the presence of S9 metabolism. These findings suggest that thiram and ziram require metabolic conversion to become genetically active, and corroborate the evidence that CHEL cells are suitable to activate and detect a broad spectrum of chemical procarcinogens including these two pesticides.

Animals↗
PubMed1989

Genotoxicity of ziram established through wing, eye and female germ-line mosaic assays and the sex-linked recessive lethal test in Drosophila melanogaster.

The genotoxicity of ziram (zinc-dimethyl dithiocarbamate, CAS No. 137-30-4), a carbamate fungicide, is studied in the wing, eye and female germ-line mosaic assays and the sex-linked recessive lethal test in Drosophila melanogaster. First-, second- and third-instar larvae, carrying suitable recessive genetic markers on their first and third chromosomes, were exposed to ziram. Wings and eyes of adults were screened for the induction of mosaic spots and the eggs laid by adult females for germ-line mosaicism. The Basc method was used to detect sex-linked recessive lethals. Ziram is genotoxic to the somatic and germ cells of Drosophila melanogaster.

Animals↗
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↗
PubMed2000

Simple and sensitive spectrophotometric determination of ziram, zineb and ferbam in commercial samples and foodstuffs using phenylfluorone.

A procedure has been developed for the determination of ziram, zineb and ferbam dithiocarbamate pesticides by converting ziram and zineb into a zinc-phenylfluorone complex and ferbam into an iron phenylfluorone complex, which are then dissolved in water in the presence of cetylpyridinium bromide and pyridine as a surfactant. The method is sensitive, highly selective and can be used for the determination of ziram, zineb and ferbam in commercial samples and in foodstuffs.

Dimethyldithiocarbamate↗
PubMed1990

90-day oral toxicity of ziram: a thyrostatic and hepatotoxic study.

Ziram, a dithiocarbamate fungicide, is extensively used in crop protection. Daily oral doses of ziram (5 and 25 mg kg(-1) day(-1)) for 30, 60 and 90 days produced significant mortality in male rats. The fungicide also caused a significant increase in the thyroid:body weight ratio, histological changes, and a reduced activity of thyroid (125)I uptake and protein bound (125)I. However, the animals did not show any change in the clinical enzyme profile of the liver, serum and brain. It is believed that ETU, the degradation product of ziram and a known antithyroid compound, is the causative agent for the high mortality, as well as for the pronounced thyrostatic and hepatotoxic effects found in the experimental animals.

Journal Article↗
PubMed1983

Pre- and postimplantation embryotoxic effects of zinc dimethyldithiocarbamate (Ziram) in the rat.

Zinc dimethyldithiocarbamate (Ziram) was administered to pregnant CD rats by tube during the first 5 days of pregnancy (preimplantation study, 0, 25, 50, and 100 mg/kg) or during the organogenetic period (teratogenic study, 0, 12.5, 25, 50, and 100 mg/kg). All females were sacrificed on Day 21 of gestation. Their reproductive status was recorded and live fetuses were examined for external, visceral, and skeletal malformations. In the preimplantation study the only observed embryotoxic effect was a reduced fetal weight at 50 and 100 mg/kg dose level. The teratogenic study revealed a slight dismorphogenic effect of Ziram at 100 mg/kg; embryofetotoxic effects appeared at 25 mg/kg dose level and higher. Maternal toxicity was evident at all tested doses.

Abnormalities, Drug-Induced↗
PubMed1989

Epiphyseal lesions of the femur and tibia in rats following oral chronic administration of zinc dimethyldithiocarbamate (ziram).

A 24-month chronic feeding toxicity study with zinc dimethyldithiocarbamate (ziram) was performed on Fischer 344 rats of both sexes (80 animals/sex per group) at dietary levels of 0, 20, 200, or 2000 ppm. Eight animals of either sex from each group were sacrificed after 26, 52 and 78 weeks, and all surviving animals were killed after 104 weeks. Epiphyseal abnormalities in the long bones of the hind legs were observed in both sexes at 2000 ppm. Clinically, 3 male rats showed partial paralysis of the hind legs. At necropsy, marked curvature of the proximal end of the crus which could cause a restricted extension of the tibio-femoral joint was seen in 11 of 34 males killed at terminal sacrifice. While females had neither clinical signs nor gross abnormalities during the study, histopathological examination revealed retarded epiphyseal closure of the proximal end of the tibia in both sexes. Females also showed the epiphyseal lesion at the distal end of the femur. In severely affected rats marked proliferation of epiphyseal cartilaginous tissue was also noted together with the irregular arrangement of chondrocytes. These changes were evident only in aged animals. The incidence of the lesions in all males and females examined in this group was 22/77 (29%) and 13/73 (18%), respectively. The occurrence of the lesions appeared to be caused by impaired regulation of epiphyseal closure which might be related to the treatment with ziram.

Administration, Oral↗
PubMedDate not supplied

Decreased fertility, increased dominant lethals, skeletal malformations induced in the mouse by Ziram fungicide.

The toxic effect of the Ziram fungicide (Zn-dimethyldithiocarbamate) on fertility, its lethal and teratogenic potential were tested on two mouse strains, C3H and AK. The fungicide was administered by gavage to male mice in daily doses of 0.2 mg% and 0.1 mg% along three weeks, then the mice were mated with normal females. Ziram induced changes in the testes and meiotic chromosomes. From among the mated females, 80 per cent of the C3H mice and 20 per cent of the AK remained unfertilized. The dominant lethals have a higher incidence in the AK strain. The skeletal malformation induced were kyphosis, scoliosis, sternum ossification failure; retardation in skeletal development is more obvious in the AK strain.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Increased frequencies of sister chromatid exchanges and micronuclei in "in vitro" lymphocyte cultures treated with the fungicides thiram and ziram.

The two fungicides analysed in this paper, Thiram (TH) and Ziram (ZI) are among the most common residues found in fruit and vegetables sold in Italy. These compounds were tested in "in vitro" lymphocyte cultures, from 16 individuals, at different concentrations (Thiram 5 x 10(-8) M; 5 x 10(-7) M; 5 x 10(-6) M and Ziram 1 x 10(-7) M; 1 x 10(-6) M; 1 x 10(-5) M) in order to ascertain if they are able to modify sister chromatid exchange and/or micronuclei frequencies. Both fungicides produced a significant increase in SCE and Micronuclei frequencies. The two highest doses of TH and ZI were found to be cytotoxic for most of the individuals and were not included in the statistical analysis. With regard to the Proliferation Rate Index (i.e. the number of first, second, third or more mitoses), no difference was found between controls and treated cultures.

Adult↗
PubMed1993

Toxicological effects of ziram, thiram, and dithane M-45 assessed by sperm shape abnormalities in mice.

The three commonly used dithiocarbamate fungicides ziram, thiram, and dithane M-45 were investigated for their mutagenic and carcinogenic potency using sperm shape abnormalities in mice. The fungicides were administered intraperitoneally in single and cumulative doses. All three of the fungicides tested were found to induce significant increase in the frequency of abnormal sperm at all the doses, and a linear dose effect was observed.

Animals↗
PubMedDate not supplied

Spectrophotometric determination of ziram in a commercial sample and wheat by extraction of its copper dimethyldithiocarbamate complex into molten naphthalene.

A method was developed for the determination of zinc(II) dimethyldithiocarbamate by converting it into the copper(II) dithiocarbamate complex, which is then extracted into molten naphthalene. The absorbance is measured at 430 nm versus a reagent blank. Beer's law is obeyed for concentrations of 0.63 x 10(-3) to 17.2 x 10(-3) g/L in the final solution. The method is sensitive and was applied to the determination of ziram in a commercial sample and in wheat grain.

Calibration↗