디탄

Fungicides

Active substance -> EU Pesticides database: Not approved

Pesticides -> Dithiocarbamates (Pesticide)

log Kow = 1.33

1.33

Slight odor of hydrogen sulfide

Practically odorless

1.99 g/mL at 20 °C

Relative density (water = 1): 1.92

Greyish-yellow free-flowing powder

Yellowish powder

In water, 6.2 ppm, pH 7.5, 25 °C

Insoluble in water

Insoluble in most organic solvents; dissolves in solutions of powerful chelating agents but cannot be recovered from them

Solubility in water: none

138 °C (280 °F)

137.8 °C (tag open cup)

138 °C o.c.

When heated to decomposition it emits very toxic fumes of sulfur oxides, zinc oxide, and nitrogen oxides.

The substance decomposes slowly on heating or on contact with acids and moisture producing toxic and irritating fumes including sulfur oxides, nitrogen oxides, zinc oxide, manganese oxide, hydrogen sulfide, carbon sulfide, ethylene thiuram sulfide, ethylene bisisothiocyanate, ethylene urea and 2-mercaptoimidazoline.

9.8X10-8 mm Hg at 25 °C

Vapor pressure at 20 °C: negligible

Danger

H317: May cause an allergic skin reaction [Warning Sensitization, Skin]

P203, P260, P261, P272, P273, P280, P302+P352, P318, P319, P321, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

Warning

H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P203, P261, P272, P273, P280, P302+P352, P318, P321, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

Hazard Traits - Carcinogenicity; Reproductive Toxicity

Commission Regulation No 844/2012

Mancozeb is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

05/72/EC, Reg. (EU) 2018/1796, Reg. (EU) 2019/2094, Reg. (EU) 2020/2087, Reg. (EU) 84/2018, Reg. (EU) No 540/2011, Reg. (EU) No 762/2013

REACH registered substance: mancozeb (ISO); manganese ethylenebis(dithiocarbamate) (polymeric) complex with zinc salt   (EC: 616-995-5)

Mancozeb (stabilised): HSNO Approval: HSR002904 Approved with controls

Classified as practically nontoxic, mancozeb can cause occupational allergic contact dermatitis. [EXTOXNET] The EBCDCs (ethylenebisdithiocarbamates) can cause irritant and allergic contact dermatitis. EBDCs include ferbam, vapam, maneb, mancozeb, zineb, thiram, and ziram. They are also used as rubber accelerators. Ethylene thiourea (ETU), which may contaminate EBCDCs, is carcinogenic and teratogenic in animal experiments. [LaDou, p. 610] ETU is the major metabolite of EBDCs. [Krieger, p. 1690] In high-dose reproductive studies of animals, mancozeb causes testicular damage, fetal losses, and birth defects (hydrocephalus). [Frazier, p. 230-1] Potential for dermal sensitization; [AIHA: WEELs] Decomposes on heating and on contact with acids and moisture--chemicals produced include manganese oxide. [ICSC] See Ethylene thiourea. See Manganese and linked occupational diseases. The TLV for manganese is for elemental and inorganic compounds. Mancozeb is an organic compound containing manganese.

USEPA/Office of Prevention, Pesticides and Toxic Substances; Reregistration Eligibility Decision Document - Mancozeb EPA 738-R-04-012 (September 2005). The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the USA.[Available from, as of January 31, 2017: http://www.epa.gov/pesticides/reregistration/status.htm]

WHO; Environmental Health Criteria 78: Dithiocarbamate Pesticides, Ethylenethiourea and Propylenethiourea (1988). EHC documents are designed for scientists and administrators responsible for the establishment of safety standards and regulations and provide basic scientific risk evaluations of a wide range of chemicals and groups of chemicals.[Available from, as of March 2, 2017: http://www.inchem.org/pages/ehc.html]

California Environmental Protection Agency/Department of Pesticide Regulation; Summary of Toxicology Data for Mancozeb. Chemical Code No.000211 (December 1, 1986, Revised February 10, 2000)[Available from, as of April 3, 2017: http://www.cdpr.ca.gov/docs/risk/toxsums/toxsumlist.htm]

U114; As stipulated in 40 CFR 261.33, when ethylenebisdithiocarbamic acid, salts and esters, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5). /Ethylenebisdithiocarbamic acid, salts and esters/

Tolerances are established for residues of mancozeb (a coordination product of zinc ion and maneb (manganese ethylenebisdithiocarbamate)), including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in this paragraph is to be determined by measuring only those mancozeb residues convertible to and expressed in terms of the degradate carbon disulfide.[Table#6293]

A tolerance with regional registrations, as defined in section 180.1(l), is established for residues of the fungicide mancozeb, (a coordination product of zinc ion and maneb (manganese ethylenebisdithiocarbamate)), including its metabolites and degradates, in or on the commodity in the following table in this paragraph. Compliance with the tolerance levels specified in this paragraph is to be determined by measuring only those mancozeb residues convertible to and expressed in terms of the degradate carbon disulfide.[Table#6294]

The Agency has completed its assessment of the dietary, occupational, residential, and ecological risk associated with the use of pesticide products containing the active ingredient mancozeb. Based on a review of these data and on public comments on the Agency's assessments for the active ingredient mancozeb, the Agency has sufficient information on the human health and ecological effects of mancozeb to make decisions as part of the tolerance reassessment process under FFDCA and reregistration process under FIFRA, as amended by FQPA. The Agency has determined that mancozeb containing products are eligible for reregistration provided that the risk mitigation measures outlined in this document are adopted, and label amendments are made to reflect these measures. ... Based on its evaluation of mancozeb, the Agency has determined that mancozeb products, unless labeled and used as specified in this document, would present risks inconsistent with FIFRA. Accordingly, should a registrant fail to implement any of the risk mitigation measures identified in this document, the Agency may take regulatory action to address the risk concerns from the use of mancozeb. If all changes outlined in this document are incorporated into the product labels, then all current risks for mancozeb will be adequately mitigated for the purposes of this determination under FIFRA.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer safety standards, such as those described in the Food Quality Protection Act of 1996. Mancozeb is found on List A, which contains most pesticides that are used on foods and, hence, have a high potential for human exposure. List A consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA '88. Case No: 0463; Pesticide type: fungicide; Registration Standard Date: 4/01/87; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision document.; Active ingredient (AI): mancozeb; Data Call-in (DCI) Date(s): 3/3/95; 10/13/95; AI Status: The producers of the pesticide have made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

Decomposes on heating and on contact with acids and moisture. This produces toxic and irritating fumes including sulfur oxides, nitrogen oxides, zinc oxide, manganese oxide, hydrogen sulfide, carbon sulfide, ethylene thiuram sulfide, ethylene bisisothiocyanate, ethylene urea and 2-mercaptoimidazoline.

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Induce vomiting (ONLY IN CONSCIOUS PERSONS!).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Powder, water spray, foam, carbon dioxide.

Keep container tightly closed in a dry and well-ventilated place.

Provision to contain effluent from fire extinguishing. Separated from acids, food and feedstuffs. Dry. Keep in a well-ventilated room.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Do NOT wash away into sewer. Sweep spilled substance into sealable containers. Carefully collect remainder, then remove to safe place.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U114, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or other waters unless in accordance with the requirements of a National Pollutant Discharge Eliminations System (NPDES) permit and the permitting authority has been notified in writing prior to discharge. ... For guidance, contact your State Water Board or Regional Office of the Environmental Protection Agency.

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into sealable containers. Carefully collect remainder. Then store and dispose of according to local regulations. Do NOT wash away into sewer.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

For more Preventive Measures (Complete) data for Mancozeb (17 total), please visit the HSDB record page.

Mancozeb, as a dithiocarbamate fungicide, has been found to exhibit toxicological manifestations in different cells, mainly by generation of free radicals which may alter antioxidant defense systems in cells ... In the present study, the effects of mancozeb (0.2, 2 and 5 ug/mL) or mancozeb+ascorbic acid (100 ug/mL), or ascorbic acid alone or control medium alone on the levels of cell viability, apoptosis, intracellular reactive oxygen species production (ROS), mitochondrial membrane potential (MMP) and ATP levels in rat thymocytes were examined in vitro. Cells treated with mancozeb displayed a concentration-dependent increase of hypodiploid cells and ROS production followed by markedly decreased viability of the cells, MMP and ATP levels. Application of ascorbic acid significantly reduced cytotoxicity in cell cultures treated with 0.2 and 2 ug/mL of mancozeb, together with significantly decreased ROS levels and increased MMP and ATP levels. In cells treated with 5 ug/mL of mancozeb, ascorbic acid failed to reduce toxicity while simultaneously increasing the apoptosis rate of thymocytes. These results suggest that ROS plays a significant role in mancozeb-induced toxicity, through alteration of mitochondrial function. Ascorbic acid administration reduced the toxicity rate in cells treated with lower mancozeb concentrations, while it may have the ability to shift cells from necrosis to apoptosis in the presence of highest mancozeb concentrations.

... This study demonstrates that non-toxic doses of pesticides can induce cellular changes that increase cell sensitivity to other toxins or stress. Pesticide exposure is an environmental risk factor for Parkinson's disease. Manganese (Mn) is essential but high dose exposure may results in neurological dysfunction. Mn-containing dithiocarbamates, maneb (MB) and mancozeb (MZ), are primarily used as pesticides. Studies have shown that MB can augment dopaminergic damage triggered by sub-toxic doses of Parkinsonian mimetic MPTP. However, the mechanism underlying this effect is not clear. Activation of nuclear factor kappa B (NF-kB) has been implicated in MPTP toxicity. Mn stimulates the activation of NF-kB and subsequently induces neuronal injury via an NF-kB dependent mechanism. We speculate that MB and MZ enhance MPTP active metabolite (methyl-4-phenylpyridine ion, MPP(+)) toxicity by activating NF-kB. The activation of NF-kB was observed using Western blot analysis and NF-kB response element driven Luciferase reporter assay. Western blot data demonstrated the nuclear translocation of NF-kB p65 and the degradation of IkB-alpha after MB and MZ 4-hr treatments. Results of NF-kB response element luciferase reporter assay confirmed that MB and MZ activated NF-kB. The NF-kB inhibitor (SN50) was also shown to alleviate cytotoxicity induced by co-treatment of MB or MZ and MPP(+). This study demonstrates that activation of NF-kB is responsible for the potentiated toxic effect of MB and MZ on MPP(+) induced cytotoxicity.

Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development, even though the doses of the single compounds are below their individual NOAELs for anti-androgenic effects. Consequently, we have initiated a large project where the purpose is to study mixture effects of endocrine disrupting pesticides at low doses. In the initial range-finding mixture studies, rats were gavaged during gestation and lactation with five doses of a mixture of the fungicides procymidone, mancozeb, epoxyconazole, tebuconazole and prochloraz. The mixture ratio was chosen according to the doses of each individual pesticide that produced no observable effects on pregnancy length and pup survival in our laboratory and the dose levels used ranged from 25 to 100% of this mixture. All dose levels caused increased gestation length and dose levels above 25% caused impaired parturition leading to markedly decreased number of live born offspring and high pup perinatal mortality. The sexual differentiation of the pups was affected at 25% and higher as anogenital distance was affected in both male and female offspring at birth and the male offspring exhibited malformations of the genital tubercle, increased nipple retention, and decreased prostate and epididymis weights at pup day 13. The results show that doses of endocrine disrupting pesticides, which appear to induce no effects on gestation length, parturition and pup mortality when judged on their own, induced marked adverse effects on these endpoints in concert with other pesticides. In addition, the sexual differentiation of the offspring was affected ...

... In this study the permanent reproductive and neurobehavioral effects of combined exposure to five endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, were examined. Pregnant and lactating rat dams were dosed with a mixture of the five pesticides at three different doses, or with the individual pesticides at one of two doses. Adverse effects were observed in young and adult male offspring from the group exposed to the highest dose of the mixture. These included reduced prostate and epididymis weights, increased testes weights, altered prostate histopathology, increased density of mammary glands, reduced sperm counts, and decreased spatial learning. As no significant effects were seen following single compound exposure at the doses included in the highest mixture dose, these results indicate cumulative adverse effects of the pesticide mixture.

For more Interactions (Complete) data for Mancozeb (6 total), please visit the HSDB record page.

LD50; Species: /Passer domesticus/ (English sparrow) oral ~1500 mg/kg/day /86% a.i./ /from table/

LD50; Species: Phasianus colchicus (Ring-Necked Pheasant); oral via capsule <1500 mg/kg

LC50; Species: Coturnix japonica (Japanese Quail) juvenile age 14 days posthatch; food (corn oil carrier) >5000 ppm for 5 days

LD50; Species: Coturnix japonica (Japanese Quail); oral via capsule >6400 mg/kg

For more Ecotoxicity Values (Complete) data for Mancozeb (59 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an average Koc value of 1000(2), indicates that mancozeb is expected to have low mobility in soil(SRC). Volatilization of mancozeb from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.4X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 9.8X10-8 mm Hg(3), and water solubility, 6.2 mg/L(4). Mancozeb is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure. Utilizing aerobic soil metabolism studies, mancozeb soil biodegradation half-lives of less than 2 days(3) suggest that biodegradation may be an important environmental fate process in soil(SRC).

TERRESTRIAL FATE: In field tests, approximately 90% mancozeb was degraded after less than 6 to 18 weeks under aerobic conditions in moist plough layer with 2-4% humus, with a pH of 5.5-6.5 under a medium air temperature of 11-16 °C(1).

AQUATIC FATE: Based on a classification scheme(1), an average Koc value of 1000(2), indicates that mancozeb may adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.4X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 9.8X10-8 mm Hg(2), and water solubility, 6.2 mg/L(5). According to a classification scheme(6), an estimated BCF of 4(SRC), from an estimated log Kow of 1.33(2) and a regression-derived equation(4), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Utilizing aerobic soil metabolism studies, mancozeb soil biodegradation half-lives of less than 2 days(2) suggest that biodegradation may be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), mancozeb, which has a vapor pressure of 9.8X10-8 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase mancozeb is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 0.6 hours(SRC), calculated from its rate constant of 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase mancozeb may be removed from the air by wet and dry deposition(SRC). Mancozeb contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Mancozeb has a photolysis rate constant of >5.5/day in air which is a half-life of <3 hrs(2).

Mancozeb residues were not found in FDA's Los Angeles surveillance samples, collected in 1982 to 1986 (18,435 total samples)(1). In California's Priority Pesticide program for 1989 in which samples of crops that have been treated with targeted pesticides are analyzed, mancozeb was not detected in all 4 samples of apples, the one sample of dried onion, and in 5 of 8 samples of grapes(2). The other three samples of grapes in which mancozeb was detected were within tolerance(2). While mancozeb residues were not mentioned as present in food in the FDA pesticide residue monitoring program for 1983-1986, the combined occurrence of six ethylene bis-dithiocarbamate fungicides (including mancozeb) was under 2%(3). When present, ethylene bis-dithiocarbamate fungicides were associated with various vegetables(3). Mancozeb was undetected in sesame products marketed in Korea(4). In studies of Ontario-grown fruits from 1980 to 1984, ethylene bis-dithiocarbamate residues were detected in 5 of 179 samples(5). In studies of Ontario-grown vegetables from 1980 to 1985, ethylene bis-dithiocarbamate residues were detected in 7 of 275 composite samples(6). In both Ontario studies, the detection limit was 0.1 ppm, positive samples were well below the maximum residue level, and the particular ethylene bis-dithiocarbamate fungicide detected was not revealed(5-6). In results from three US programs for monitoring chemical residues in foods and feeds from 1970-1976, mancozeb was only found in one sample of large fruit (in 1972)(7). Food processing and cooking result in the degradation of mancozeb and the formation of mancozeb breakdown products, notably ethylenethiourea(8-10). Cooking reduced the level of mancozeb on brinjal fruit by 87%(10). Washing reduced the mancozeb level by 18-23%(10).

Mancozeb was applied at 6 lbs/acre to tomatoes; after nine days the tomatoes were harvested and measured for residues(1). Tomatoes contained mancozeb residues at 0.54, 0.19, and 0.10 ppm that had either not been washed, were washed for 10 mins, or were treated with hot acid for two minutes, respectively(1). While the 10 min wash produced a decrease of 65% in mancozeb residue, the 2 minute hot acid wash produced a decrease of 82% in mancozeb residue(1). Ethylene bis-dithiocarbamate fungicides (including Mancozeb) were found to be the most prevalent residue found on fruits and vegetables analyzed in Switzerland in 1989-90(2). Out of 461 salads analyzed in Geneva, 23 samples had levels of ethylene bis-dithiocarbamate fungicides exceeding tolerance values(2). In 1989, 18,798 food samples were analyzed by the FDA for pesticide residues(3). Of these, only 1278 samples were analyzed for ethylene bis-dithiocarbamates in which Mancozeb was detected (percent positive and concentrations not specified)(3). Vegetables that were analyzed included peppers, leafy vegetables, cantaloupe, squash and peas(3). In 1990, the same study was conducted by the FDA but with 1472 samples being analyzed for ethylene bis-dithiocarbamates(4). Once again, mancozeb was detected; however, percent positive and concentrations were not specified(4).

IDENTIFICATION AND USE: Mancozeb is a greyish-yellow free-flowing powder. It is used for control of many fungal diseases in a wide range of field crops, fruits, nuts, vegetables, and ornamentals. It is also used as seed treatment/protectant. HUMAN EXPOSURE AND TOXICITY: Exposure could lead to toxic epidermal necrolysis (TEN), which is a life-threatening mucocutaneous disease with high mortality. There has been a case of dyshidrotic eczema and sensitization to mancozeb in a florist. A widespread dermatitis was reported by a woman following storage of mancozeb powder in a garage. An epidemiological study suggests that pregnant women living near banana plantations aerially sprayed with mancozeb may be environmentally exposed to Mn, which is a neurotoxicant at high concentrations. Another study demonstrated an augmented risk of cutaneous melanoma among subjects with exposure to mancozeb, in particular among those with occupational sun exposure. There appeared to be an association between mancozeb exposure and a significant increase in the frequencies of cells with structural chromosome aberrations and the number of sister chromatid exchanges per cell in peripheral blood lymphocytes. Slight immunomodulator effect of mancozeb in conditions of low-level, prolonged occupational exposure was observed. ANIMAL STUDIES: Compounds of this class usually have low acute toxicity. Studies in animals suggest that contact dermatitis and thyroid hyperplasia may occur after exposure. Mancozeb was a potent dermal sensitizer in the guinea pig. Cross-sensitization was observed between mancozeb, zineb and maneb. In rats, thyroid follicular cell hyperplasia was seen at 100 ppm and higher doses. Mancozeb exerts dose-dependent damaging effects on the gonads of rats of both sexes. The dose level was 140-1400 mg mancozeb/kg body weight, given twice a week for 4.5 months. Both reproductive and endocrine structures were affected at all dose levels, leading to decreased fertility. In developmental studies in rats, increase in resorbed litters, external hemorrhage and wavy ribs have been observed; no embryotoxicity in absence of maternal toxicity. Rats treated with mancozeb showed dose-dependent signs of depression, adynamia, decreased tonus, disturbances in coordination, paresis, and paralysis of extremities combined with general weakness, lack of appetite, and prostration. Mutagenicity: Bacterial and in vitro mammalian cell systems, chromosome damage in vivo and in mammalian cell transformation tests were negative. Sister chromatid exchanges in Chinese hamster ovary cells in vitro was positive. Mancozeb induces a number of different types of chromosomal aberrations in the bone marrow cells of male mice at various test doses. Mancozeb was examined for its possible mutagenic activity using Salmonella typhimurium tester strains TA97a, TA98, TA100, and TA102 with negative results. In rats treated with mancozeb in vivo, it induced DNA damage as detected by the comet assay and increased the frequency of micronuclei. Acute treatments with mancozeb inhibit cytochrome P450 mediated metabolism. Mancozeb is metabolized to ethylene thiourea (ETU). ETU is a carcinogen, based on thyroid and other cancers in rodents, ETU is also known to cause decreases of thyroxine (T4) and increases in thyroid-stimulating hormone (TSH) in rodents. ECOTOXICITY STUDIES: In a seasonally breeding wildlife bird, Red Munia (Amandava amandava) plasma T4, T3 and TSH were significantly decreased in response to mancozeb. Mancozeb toxicity effects noted in both birds and mammals could be a result of possible hormonal disruptions. The avian reproductive studies noted reproductive effects such as reductions in: egg production; early and late embryo viability; hatchability; offspring weight at hatch and 14-days of age; and the number of 14-day old survivors. Reduced growth rates were noted in tadpoles exposed to mancozeb. Chronic testing in freshwater organisms showed immobility, length and time until first brood in Daphnia and reduced survival and lack of growth effects in fathead minnow. These effects noted in freshwater species could be a result of possible hormonal disruptions. Lettuce exposure to mancozeb was shown to have a significant impact on plant metabolism, with mature leaves tending to be more extensively affected than younger leaves.

/BIRDS and MAMMALS/ Thyroid is an important homeostatic regulator of metabolic activities as well as endocrine mechanisms including those of reproduction. Present investigation elucidated the thyroid disrupting potential of a neonicotinoid imidacloprid and a dithiocarbamate mancozeb in a seasonally breeding wildlife bird, Red Munia (Amandava amandava) who is vulnerable to these two pesticides through diet (seed grains and small insects). Adult male birds were exposed to 0.5% LD50 mg/kg/bwd of both the pesticides through food for 30 days during the preparatory and breeding phases. Weight, volume and histopathology of thyroid gland were distinctly altered. Disruption of thyroid follicles reflected in nucleus-to-cytoplasm ratio (N/C) in epithelial and stromal cells, epithelial cell hypertrophy and altered colloid volume. Impairment of thyroid axis was pesticide and phase specific as evident from the plasma levels of thyroid (T4 and T3) and pituitary (TSH) hormones. In preparatory phase, plasma TSH was increased in response to decrease of T4 on mancozeb exposure showing responsiveness of the hypothalamic-pituitary-thyroid (HPT) axis to feedback regulation. On imidacloprid exposure, however, plasma levels of both T4 and TSH were decreased indicating non-functioning of negative feedback mechanism. Increased plasma T3 in response to both the pesticides exposure might be due to synthesis from non-thyroidal source(s) in a compensatory response to decrease level of T4. In breeding phase, impairment of HPT axis was more pronounced as plasma T4, T3 and TSH were significantly decreased in response to both mancozeb and imidacloprid. Thus, low dose pesticide exposure could affect the thyroid homeostasis and reproduction.

/BIRDS and MAMMALS/ ... Thyroid disruption could potentially interfere with energy metabolism and thermoregulation such that over-winter survival might be compromised ... Thyroid function and ... resting metabolic rates of cotton rats chronically exposed to ... mancozeb /were measured/. In addition, ... norepinephrine-induced nonshivering thermogenesis and cold-induced thermogenesis /were measured/ and then the mancozeb animals /were cold-acclimated/ ... There was no difference between the treated and control animals in any of the metabolic parameters measured. It is concluded that wild rodents exposed to /mancozeb/ are not energetically compromised.

/BIRDS and MAMMALS/ Mancozeb toxicity effects noted in both birds and mammals could be a result of possible hormonal disruptions. The avian reproductive studies reviewed by /USEPA/ noted reproductive effects such as reductions in: egg production; early and late embryo viability; hatchability; offspring weight at hatch and 14-days of age; and the number of 14-day old survivors. For mammals, /USEPA/ noted chronic effects in a 3-month feeding study using rats. Effects noted in females rats included decreased serum thyroxine levels. Male rat effects included: body weight decrements; changes in thyroid hormones; changes in liver enzymes; microscopic changes in the liver and thyroids; increased absolute and relative thyroid weights; and increased relative liver weights. Some developmental effects noted in mammals (that is, rats) were gross developmental defects, central nervous system defects, skeletal defects, cryptorchidism (failure of one or more testes to descend into the scrotum), and abortions.

/BIRDS and MAMMALS/ ... An 80% mancozeb containing fungicide formulation (Dithane M-45) was studied in pheasants after administration as single compounds or in combination. The test materials were injected directly into the air-chamber of eggs on day 12 of the hatching period and evaulation was carried out on day 23 of incubation. ... After the administration of copper-sulfate on day 12 of incubation, the average body weight of pheasant embryos did not decrease significantly compared to the controls. The embryonic mortality was 68%. After the administration of Dithane M-45 on day 12 of incubation, the average body weight of embryos did not decrease compared to the control. The embryonic mortality was 50%. After the individual administration of pesticide, the incidence of developmental anomalies was very high. After the combined administration of copper-sulfate and Dithane M-45 on day 12 of incubation the embryonic mortality markedly increased. The rate of embryo mortality was 93%. /No/ degenerative change in the liver tissue in either the control group or the treated groups /was found/ by light microscopic examination.

For more Ecotoxicity Excerpts (Complete) data for Mancozeb (27 total), please visit the HSDB record page.

Thirty days after being accidentally aerially sprayed with mancozeb when an adjacent potato field was treated, samples of barley, oats, and wheat (including 5-10 cm of straw) one meter from the potato field contained 21, 5.5, and 15 ppm of mancozeb, expressed as maneb(1). Corresponding samples that were 25 meters from the potato field contained 1.0, <0.1, and 0.6 ppm(1). Dislodgable foliar residues of pesticides were studied on leaves that were sampled for 28 days from a sector of a greenhouse where pesticides were applied(2). Mancozeb had an estimated dissipation half-life of 3 days on the plant leaves after application(2).

Cough. Sore throat.

Redness.

Redness. Pain.

Diarrhoea. Nausea. Vomiting.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of December 8, 2016: http://actor.epa.gov/dashboard/]

U114; As stipulated in 40 CFR 261.33, when ethylenebisdithiocarbamic acid, salts and esters, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5). /Ethylenebisdithiocarbamic acid, salts and esters/

Tolerances are established for residues of mancozeb (a coordination product of zinc ion and maneb (manganese ethylenebisdithiocarbamate)), including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in this paragraph is to be determined by measuring only those mancozeb residues convertible to and expressed in terms of the degradate carbon disulfide.[Table#6293]

A tolerance with regional registrations, as defined in section 180.1(l), is established for residues of the fungicide mancozeb, (a coordination product of zinc ion and maneb (manganese ethylenebisdithiocarbamate)), including its metabolites and degradates, in or on the commodity in the following table in this paragraph. Compliance with the tolerance levels specified in this paragraph is to be determined by measuring only those mancozeb residues convertible to and expressed in terms of the degradate carbon disulfide.[Table#6294]

The Agency has completed its assessment of the dietary, occupational, residential, and ecological risk associated with the use of pesticide products containing the active ingredient mancozeb. Based on a review of these data and on public comments on the Agency's assessments for the active ingredient mancozeb, the Agency has sufficient information on the human health and ecological effects of mancozeb to make decisions as part of the tolerance reassessment process under FFDCA and reregistration process under FIFRA, as amended by FQPA. The Agency has determined that mancozeb containing products are eligible for reregistration provided that the risk mitigation measures outlined in this document are adopted, and label amendments are made to reflect these measures. ... Based on its evaluation of mancozeb, the Agency has determined that mancozeb products, unless labeled and used as specified in this document, would present risks inconsistent with FIFRA. Accordingly, should a registrant fail to implement any of the risk mitigation measures identified in this document, the Agency may take regulatory action to address the risk concerns from the use of mancozeb. If all changes outlined in this document are incorporated into the product labels, then all current risks for mancozeb will be adequately mitigated for the purposes of this determination under FIFRA.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer safety standards, such as those described in the Food Quality Protection Act of 1996. Mancozeb is found on List A, which contains most pesticides that are used on foods and, hence, have a high potential for human exposure. List A consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA '88. Case No: 0463; Pesticide type: fungicide; Registration Standard Date: 4/01/87; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision document.; Active ingredient (AI): mancozeb; Data Call-in (DCI) Date(s): 3/3/95; 10/13/95; AI Status: The producers of the pesticide have made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 5000 lb or 2270 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b). /Ethylenebisdithiocarbamic acid, salts and esters/

(AZ) ARIZONA 21 ug/L

(ME) MAINE 6 ug/L

... This study demonstrates that non-toxic doses of pesticides can induce cellular changes that increase cell sensitivity to other toxins or stress. Pesticide exposure is an environmental risk factor for Parkinson's disease. Manganese (Mn) is essential but high dose exposure may result in neurological dysfunction. Mn-containing dithiocarbamates, maneb (MB) and mancozeb (MZ), are primarily used as pesticides. Studies have shown that MB can augment dopaminergic damage triggered by sub-toxic doses of Parkinsonian mimetic MPTP. However, the mechanism underlying this effect is not clear. Activation of nuclear factor kappa B (NF-kB) has been implicated in MPTP toxicity. Mn stimulates the activation of NF-kB and subsequently induces neuronal injury via an NF-kB dependent mechanism. We speculate that MB and MZ enhance MPTP active metabolite (methyl-4-phenylpyridine ion, MPP(+)) toxicity by activating NF-kB. The activation of NF-kB was observed using Western blot analysis and NF-kB response element driven Luciferase reporter assay. Western blot data demonstrated the nuclear translocation of NF-kB p65 and the degradation of IkB-alpha after MB and MZ 4-hr treatments. Results of NF-kB response element luciferase reporter assay confirmed that MB and MZ activated NF-kB. The NF-kB inhibitor (SN50) was also shown to alleviate cytotoxicity induced by co-treatment of MB or MZ and MPP(+). This study demonstrates that activation of NF-kB is responsible for the potentiated toxic effect of MB and MZ on MPP(+) induced cytotoxicity.

Mancozeb (manganese/zinc ethylene bis-dithiocarbamate) is an organometallic fungicide that has been associated with human neurotoxicity and neurodegeneration. In a high-throughput screen for modulators of KCNQ2 channel, a fundamental player modulating neuronal excitability, Mancozeb, was found to significantly potentiate KCNQ2 activity. Mancozeb was validated electrophysiologically as a KCNQ2 activator with an EC50 value of 0.92 +/- 0.23 uM. Further examination showed that manganese but not zinc ethylene bis-dithiocarbamate is the active component for the positive modulation effects. In addition, the compounds are effective when the metal ions are substituted by iron but lack potentiation activity when the metal ions are substituted by sodium, signifying the importance of the metal ion. However, the iron (Fe(3+)) alone, organic ligands alone or the mixture of iron with the organic ligand did not show any potentiation effect, suggesting as the active ingredient is a specific complex rather than two separate additive or synergistic components. Our study suggests that potentiation on KCNQ2 potassium channels might be the possible mechanism of Mancozeb toxicity in the nervous system.

Toxicogenomics has the potential to elucidate gene-environment interactions to identify genes that are affected by a particular chemical at the early stages of the toxicological response and to establish parallelisms between different organisms. The fungicide mancozeb, widely used in agriculture, is an ethylene-bis-dithiocarbamate complex with manganese and zinc. Exposure to this pesticide has been linked to the development of idiopathic Parkinson's disease and cancer. Given that many signaling pathways and their molecular components are substantially conserved among eukaryotic organisms, we used Saccharomyces cerevisiae to get insights into the molecular mechanisms of mancozeb toxicity and adaptation based on expression proteomics. The early global response to mancozeb was analyzed by quantitative proteomics using 2-DE. The target genes (e.g. TSA1, TSA2, SOD1, SOD2, AHP1, GRE2, GRX1, CYS3, PRE3, PRE6, PRE8, PRE9, EFT1, RPS5, TIF11, HSP31, HSP26, HSP104, HSP60, HSP70-family) and the putative main transcription activators (e.g. Yap1, Msn2/Msn4, Met4, Hsf1, Aft1, Pdr1, Skn7, Rpn4p, Gcn4) of the complex mancozeb-induced expression changes are related with yeast response to stress, in particular to oxidative stress, protein translation initiation and protein folding, disassembling of protein aggregates and degradation of damaged proteins. ...

Animal studies offer evidence for the basis of a mechanistic association with some pesticides and the development of PD or Parkinsonian features. Two fungicides, mancozeb and maneb, have dose-dependent toxicity on dopaminergic cells in rats. Both the organic component of the fungicide as well as the manganese ion contributed to the toxicity ...

For more Mechanism of Action (Complete) data for Mancozeb (6 total), please visit the HSDB record page.

... Mancozeb /is/ metabolized to the degradation product ethylene thiourea, which may have toxic properties of its own.

In oral rat metabolism studies conducted with radiolabeled mancozeb and other /ethylenebisdithiocarbamate compounds (EBDC)/, the in vivo metabolic conversion of EBDC to ETU (ethylenethiourea) was 7.5% on a weight-to-weight basis.

In plants, the principal metabolite is ethylenethiourea, which undergoes further metabolism. Ethylenethiuram monosulfide, ethylenethiuroum disulfide, and sulfur are also metabolites.

The major metabolite is ethylene thiourea comprising almost 24% of the bio-available dose in urine and bile. Ethylene thiourea residues in the thyroid and the liver were less than 1 ppm and were nondetectable after 24 hr.

Absorption of /mancozeb/ across skin and mucous membranes is probably very limited.

Ethylenethiourea is a decomposition product and metabolite of the ethylenebis(dithiocarbamate) group of fungicides. Following administration of single oral doses of (14)C ethylenethiourea to pregnant rats, maternal blood maintained peak radioactivity for 2 hr, and the radioactivity was dispersed uniformly between the RBC and plasma. The level of radioactivity was distributed equally among several maternal tissues but was present in lower amounts in embryos. 24 hr after treatment all tissues examined, except blood, were relatively clear of radioactivity, and 72.8% of the total radioactivity given had been excreted in the urine. Elution patterns of metabolites for Sephadex separation suggested that ethylenethiourea was degraded very little. /Ethylenebis(dithiocarbamate) group of fungicides/

Mancozeb appears to be rapidly absorbed from the gastrointestinal tract, distributed to target organs and excreted almost totally by 96 hr.

Rats dosed via a stomach tube with 20 mg (14)C-mancozeb per day for 7 days (equivalent to approx 100 mg/kg body weight) were killed one day after the last dose and the radioactivity in excreta and organs was measured. In the feces, urine, organs and tissues, and carcass, 71%, 16%, 0.31%, and 0.96% of the total radioactivity was detected, respectively. Specifically, the liver contained 0.19%, the kidneys, 0.076%, the thyroid gland, 0.003%, and all other organs, < 0.01%. Most of the labeled material in the feces was mancozeb, indicating that mancozeb was poorly absorbed from the gastrointestinal tract ...

The pharmacokinetics of (14)C-mancozeb (11.54 mCi/g = 25,619 dpm/ug; suspended in 0.5% methylcellulose in distilled water) were studied in Sprague-Dawley CD rats (both sexes) treated with a single oral dose of 1.5 (Group A) or 100 mg/kg (Group B) or a pulse (oral) dose of 1.5 mg/kg (14)C-mancozeb (Group C) which followed 2 weeks of dietary administration of nonradiolabelled mancozeb (84% pure; 15 ppm a.i.). Rats were terminated 96 hours after (14)C-mancozeb treatment. Bile cannulation occurred in both sexes of rat treated at 1.5 (Group D) and 100 mg/kg (Group E) for assessment of excretion in bile at 24 hours. Approximately half of the oral dose of mancozeb was absorbed in rats. Results showed non-linear kinetics occurred between 100 and 1.5 mg/kg. Absorption was moderately rapid (peak levels in 3 and 6 hours at 1.5 and 100 mg/kg, respectively). Elimination was biphasic. Most of the oral dose was eliminated in excreta within 24 hours-evenly divided between feces and urine. Small amounts were excreted in the bile (2-9%). Thyroid contained the greatest concentrations and peak concentrations in thyroid were not proportional to dose. Thyroid (14)C-concentrations were disproportionately less than the respective peak blood levels after 100 mg/kg than after 1.5 mg/kg (14)C-mancozeb indicating saturation at the high dose. Pretreatment with dietary nonradiolabelled mancozeb did not significantly affect the disposition or excretion of (14)C-mancozeb. The in vivo conversion of mancozeb to ETU was determined to be 6.8%.

A wide-spectrum fungicide used on seeds, fruits, vegetables, nuts, and field crops; [EXTOXNET] A protective eradicant and nonsystemic fungicide; [AIHA]

Farming (Pesticides) [Category: Industry]

For mancozeb (USEPA/OPP Pesticide Code: 014504) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Fungicide

Fungicide, seed treatment/protectant.

Used on golf courses, sod farms and in horticulture. In the past, it was also available for use on residential lawns and athletic fields. These uses are no longer allowed.

3465 tons are used annually

In the United Kingdom, mancozeb is used on wheat, winter barley, spring barley, and oats at 253, 12, 1, and 1 tons per year, respectively.

Mancozeb use on various fruits and vegetables, including apples, potatoes, tomatoes, and wheat, in 1987 was 8,660,507 lbs active ingredient per year.

Mancozeb is a polymeric mixture of a zinc salt and the chemical maneb.

Mancozeb is produced by reaction of a concentrated solution of zinc sulfate with a suspension of maneb in water.

Preparation: New Zealand patent 131543; C.B. Lyon et al., United States of America patent 3379610 (1965, 1968 both to Rohm & Haas).

The National Pesticide Information Retrieval System (NPIRS) identifies 24 companies with active labels for products containing the chemical mancozeb. To view the complete list of companies, product names and percent mancozeb in formulated products click the following url and enter the CAS Registry number in the Active Ingredient field.

Maxim MZ (Syngenta Crop Protection, LLC): Active ingredient: Mancozeb 5.7%; Fludioxonil 0.5%.

Ridomil Gold MZ WG (Syngenta Crop Protection, LLC): Active ingredient: Mancozeb 64.0%; Metalaxyl-M 4.0%.

Acrobat MZ Fungicide (BASF Corporation): Active ingredient: Mancozeb 60.0%; Dimethomorph 9.0%.

For more Formulations/Preparations (Complete) data for Mancozeb (29 total), please visit the HSDB record page.

The WHO Recommended Classification of Pesticides by Hazard identifies Mancozeb as unlikely to present an acute hazard in normal use; Main Use: fungicide, other than for seed treatment.

Displays activity against a wide range of foliage fungal diseases.

Spraying may be performed with aerial or ground equipment