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.
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.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
癌症分类：B2组可能的人类致癌物
Cancer Classification: Group B2 Probable Human Carcinogen
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
该物质可以通过吸入其气溶胶和通过摄入被身体吸收。
The substance can be absorbed into the body by inhalation of its aerosol and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
吸入症状
咳嗽。喉咙痛。
Cough. Sore throat.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
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/
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%.
代森锰锌被杀菌剂抗性行动委员会 (FRAC)2 分类为作用方式 M 组、多位点杀菌剂。它主要用于防治真菌引起的病害。它干扰含有巯基的酶，破坏真菌细胞质和线粒体内的多种生化过程。它的作用机理包括破坏病原体的细胞膜、干扰生物合成、阻止病原体侵入植物细胞等，对高等真菌和低等真菌都有防治效果。然而，代森锰锌对细菌病害的效果较弱，因为它主要通过破坏病原体细胞膜进行防治，而细菌的细胞膜相对简单，且能自行修复，因此对细菌病害的防治效果有限。在使用代森锰锌时，需要注意剂量控制，以免对植物造成伤害，并且在细菌性病害多发的地块，可能需要添加其他杀菌剂来配合使用。
Novel pyrazolylcarboxanilides of the formula (I)
in which
R, R
1
, R
2
and R
3
are as defined in the description, a plurality of processes for preparing these substances and their use for controlling unwanted microorganisms, and also novel intermediates and their preparation.
The invention relates to novel thiazolylbiphenylamides of the formula (I)
in which
R
1
, R
2
, R
3
, R
4
, R
5
and R
6
are as defined in the disclosure, to a process for preparing these compounds and to their use for controlling unwanted micro-organisms.
This invention relates to novel pyrazolylcarboxanilides of formula (I)
in which R, R1, R2 and R3 are as defined in the disclosure, to a plurality of processes for preparing these substances and their use for controlling unwanted microorganisms, and to novel intermediates and their preparation.
The invention relates to novel thiazolylbiphenylamides of the formula (I)
in which R1, R2, R3, R4, R5 and R6 are as defined in the disclosure, to a process for preparing these compounds and to their use for controlling unwanted micro-organisms.
