Metam-sodium   中文名称: 威百亩

Absorption, Distribution and Excretion
Pharmacokinetic and metabolism studies in rats for ... metam sodium ... /were/ tested at two /oral/ dose levels. It was ... excreted mainly in urine with urinary recoveries over 168 hr of ... 37 to 58% ... Excretion via the feces was low --usually ranging from 1.5% to 3.3%. Three different cmpd (MITC, CO2, COS/CS2 ) were found to be excreted via the lungs. Total excretion of the 3 products of the lungs over a 73 hr collection period were about 35% and 50% ... at low and high doses, respectively. There were no differences between males and females in amt excreted via the three excretion routes. Tissue retention at 168 hr was about 2% ... at both dose levels. Total recoveries, incl the % of the doses excreted and that remaining in the tissues combined after 168 hr, ranged from 92.6% to 106%, indicating virtually complete absorption from the GI tract. By the first 24 hr, 85% or more ... at both dose levels had been excreted. /Metam sodium was/ rapidly absorbed from the GI tract with plasma t-max between 0.25 and 1.0 hr. However, plasma half-lives after 24 hr were long, ranging from around 60 to 74 hr ... Tissue and plasma levels at all time periods, and plasma AUCs were consistently higher in females than in males by a substantial amt. The tissue with the highest uptake ... was the thyroid gland. High uptake were also seen by the liver, kidneys, and lung, with the lowest level in testes, brain and eyes.
(14)-Metam sodium was applied to male rats in aq formulations at the nominal dose levels of 0.1, 1 and 10 mg/rat to an area of 11.6 sq cm on the back ... The application site was protected by a glass saddle which contained an activated charcoal filter to adsorb any volatile radioactivity which evaporated from the skin surface. Within each group, 4 animals were killed following a 1, 2, 10, and 24 hr exposure and excreta collected over the study period. For 4 additional animals in each treatment group, the treatment area was washed 10 hr after admin and excretion monitored over a total of 72 hr. Mean % absorbed dose at 10 hr was 2.5% (2.355%, 3.683%, 1.514%, respectively).
Metam sodium technical (purity not stated, conc. = 512.8 g/L ... ) and (14)C-metam sodium ( ... radiochemical purity > 99%; specific activity = 64.52 uCi/mg), buffered at pH 8 (potassium phosphate), were dermally admin to female Crl:CD(SD)BR rats (5 for pretests/2 for the definitive study) at 10 mg/rat (20 uCi/rat). A "saddle" apparatus (consisting of glass) was attached to the backs of an area clipped free of hair ... Males were excluded, as their coarse body hair might have prevented adhesion of the saddle to the skin ... Activated charcoal was suspended between 2 sinters in the saddle and covered with gauze ... At 10 hr post application, the gauzes and the top sinters were removed, the charcoal was collected and the lower sinters removed /and/ ... the treated area of skin and the inside of the saddle were /cleaned/ ... Urine (0 to 4, 4 to 10, 10 to 24, 24 to 48 and 48 to 72 hr), feces (same as urine) and expired air were collected over 72 hr. Volatiles were collected in 4 expired air traps in series: 1) trap for methyl isothiocyanate, 2) carbon dioxide, 3) carbon disulphide, 4) any volatiles which may pass through the first 3 traps (air trap collection times for traps 1, 2 & 3 = same as urine; trap 4 = 0 to 72 hr). At termination, urine, feces, cage washings, cage debris, expired air traps, charcoal adsorbant, back and gauze washings (including elastic bands and sinters) were assessed for radioactivity. Rat blood was also sampled, as was residual carcass. RESULTS: Stability of metam sodium was virtually 100% of radioactivity at 24 hr. The saddle provided a non-occluded, enclosed application site with an adsorbant suspended above it. Saddles remained firmly attached for 12 to 72 hr. No pharmacological or toxicological signs were observed in test animals that were metam sodium induced. After a single dermal application of (14)C-metam sodium to 2 animals, a mean of 85% of radioactivity was recovered within 72 hr, primarily in charcoal adsorbant wash (38%), application site washings (38%) and urine (4.1%) ... MITC (0.7%) and carbon dioxide (1.9%) were the only radioactive components detected in the expired air traps. MITC was detected at a maximum between 10 to 24 hr (after removal of saddle packing). Radioactivity in feces, carcasses, cage washings, air trap 4 washings and the trap for carbon disulphide were low or below the limit of detection throughout the study. The report concluded that metam sodium was not readily absorbed during 10 hr of exposure, since < 8.2% of the applied radioactivity was recovered in urine, feces, expired air traps, cage wash and carcass ...
The biokinetics and metabolism of metam sodium was studied in rats following oral admin of nominal doses of 10 and 100 mg/kg. After a single oral dose of (14)C-metam sodium at 10 mg/kg, means of 52 and 58% dose were excreted in the urine of male and female rats during 0 to 168 hr. A total of 38% was found in the expired air of male rats during 0 to 72 hr of which 0.45% was in trap 1 (containing 2-ethoxyethanol), 19.5% dose was in trap 2 (containing sodium hydroxide soln) and 18.3% dose in trap 3 (containing Viles reagent). In female rats a total of 33.2% was found in the expired air during 0 to 72 hr of which 1.3, 18.1 and 13.8% were found in traps 1, 2, 3. Fecal excretion accounted for 4.5 and 2.9% dose in male and female rats during 0 to 168 hr. After a single oral dose of (14)C-metam sodium at 100 mg/kg, means of 37 and 42% dose were excreted in the urine of male and female rats, respectively, during 0 to 168 hr. A mean of 50% dose was excreted in the expired air of all rats of which 24.3, 6.4 and 19.5% dose were found in traps 1, 2, 3, respectively. Fecal excretion accounted for 1.9 and 1.6% dose in male and female rats. The concn of radioactivity in the tissues of rats sacrificed 168 hr after a single oral dose of (14)C-metam sodium at both doses showed that the highest levels were in the thyroids, adrenals and tissues responsible for excretion and metabolism (liver, kidneys, lungs). After a single oral dose of 10 mg/kg (14)C-metam sodium, peak mean plasma concn of radioactivity occurred at 1 hr for males and females. Within the first 48 hr mean plasma radioactivity declined with a half-live of approx 24 hr. From 72 hr to 240 hr mean concn of plasma radioactivity declined with a half-life of 60.8 hr for males and 74.1 hr for females. After a single oral dose of 100 mg/kg (14)C-metam sodium the peak mean plasma concn of radioactivity occurred at 1 to 2 hr for males and 0.25 to 1 hr for females. Mean concn of plasma radioactivity declined with a half-life of approx 24 hr (males and females) within the first 48 hr after treatment and 62 hr for males and 64 hr for females within 72 to 240 hr after treatment. Using thin-layer chromatography 2 metabolites were detected in the urine. The major metabolite, identified as N-acetyl-S-(N-methylthiocarbamoyl)-L-cycteine, represented 16 to 25% of the dose. The second metabolite, accounting for ca 5 to 10% of the admin dose, could not be exactly characterized but there is evidence that it is a similar type of conjugate as the major metabolite.
For more Absorption, Distribution and Excretion (Complete) data for SODIUM METHYLDITHIOCARBAMATE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Diethyldithiocarbamic acid, the main metabolite of disulfiram, forms methyldithiocarbamate when incubated with 14(C)-nitrosoacetoxymethylmethylamine or 14(C)-methylnitrosourea in different media (bacteria, esterases, rat liver 9000 x g supernatant fraction and microsomes). ...
Pharmacokinetic and metabolism studies in rats for ... metam sodium ... /were/ tested at two dose levels ... Three different cmpd (MITC, CO2, COS/CS2 ) were found to be excreted via the lungs. Total excretion of the 3 products of the lungs over a 73 hr collection period were about 35% and 50% ... at low and high doses, respectively.
At higher doses levels of metam sodium, the neurotoxic effects from the in vivo production of CS2 begin to manifest. Specifically, incidence of meningocele has been noted following oral administration ... Following soil application of metam sodium, both CS2 and H2S can be formed; the relative amt depend on the pH of the soil. Following oral exposure to metam sodium, rats metabolize approximately 20 to 25% of the dose (on a molar basis) to CS2. CS2 is a neurotoxic agent known to cause a variety of effects such as neuropathology and changes in sensory conduction velocity and peroneal motor conduction velocity. Exposure to H2S at low levels in humans can result in eye injury, headaches, nausea, and insomnia.
... Neither metam sodium, MITC, nor any related thioureas or methylated ureas were detected in the extractable radioactivity or the post-extraction solids. The observed radioactivity was shown to be distributed over a variety of natural products indicating complete incorporation of metam sodium into the carbon pool ... Based upon the results of the metabolism studies, residues of metam sodium and MITC are not expected to occur in plants. MITC's volatility in the environment, phytotoxity to crops, and metabolism in plants assure that there is no reasonable expectation of finite residues to be incurred in/on any raw agricultural commodity when these products are applied according to label directions.
Metam sodium technical (purity not stated, conc. = 512.8 g/L ... ) and (14)C-metam sodium ( ... radiochemical purity > 99%; specific activity = 64.52 uCi/mg), buffered at pH 8 (potassium phosphate), were dermally admin to female Crl:CD(SD)BR rats (5 for pretests/2 for the definitive study) at 10 mg/rat (20 uCi/rat) ... MITC (0.7%) and carbon dioxide (1.9%) were the only radioactive components detected in the expired air traps. MITC was detected at a maximum between 10 to 24 hr (after removal of /residual metam sodium/ ... )

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Biological Half-Life
Pharmacokinetic and metabolism studies in rats for ... metam sodium ... /were/ tested at two /oral/ dose levels. ... Plasma half-lives after 24 hr were long, ranging from around 60 to 74 hr ...
The biokinetics and metabolism of metam sodium was studied in rats following oral admin of nominal doses of 10 and 100 mg/kg. ... After a single oral dose of 10 mg/kg (14)C-metam sodium, peak mean plasma concn of radioactivity occurred at 1 hr for males and females. Within the first 48 hr mean plasma radioactivity declined with a half-live of approx 24 hr. From 72 hr to 240 hr mean concn of plasma radioactivity declined with a half-life of 60.8 hr for males and 74.1 hr for females. After a single oral dose of 100 mg/kg (14)C-metam sodium the peak mean plasma concn of radioactivity occurred at 1 to 2 hr for males and 0.25 to 1 hr for females. Mean concn of plasma radioactivity declined with a half-life of approx 24 hr (males and females) within the first 48 hr after treatment and 62 hr for males and 64 hr for females within 72 to 240 hr after treatment. ...

Toxicity Data
LC50 (rat) = 2,270 mg/m3

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Interactions
The drug acts by interfering with alcohol metabolism so that the ingestion of alcohol is followed by distressing & occasionally dangerous symptoms. ... The disulfiram-alcohol reaction ... is not a simple intensification of alcoholic intoxication, although this may play a role. ... The acute drug-alcohol reaction ... is usually considered unpleasant, at times alarmingly so. It consists of flushing, headache, vasodilation, tachycardia, hypotension (after a transient rise in systolic pressure), nausea, restlessness, confusion & many other signs & symptoms. ... The disulfiram-alcohol reaction appears at the same time as excessive concentrations of acetaldehyde in the blood. The enzyme alcohol dehydrogenase generates acetaldehyde from ethanol. Acetaldehyde accumulates presumably because disulfiram inhibits aldehyde dehydrogenase, the enzyme which normally oxidizes this intermediary product of alcohol metabolism to "active" acetate. ... Disulfiram is a potent inhibitor of dopamine beta-oxidase. This enzyme requires copper, which disulfiram apparently removes by chelation. Dopamine beta-oxidase is an essential enzyme in the norepinephrine biosynthetic pathway. ... Disulfiram /exposure/ leads to the depletion of norepinephrine at adrenergic nerve terminals. ... With the sympathomimetic effects of acetaldehyde blocked by disulfiram depletion of the adrenergic transmitter, the direct vasodilator effect of acetaldehyde is unmasked. The latter is presumably responsible for the fall in blood pressure in the disulfiram-alcohol reaction. /Disulfiram/
The effects of dithiocarbamates on the tissue distribution and excretion of lead were examined in rats, with special emphasis on the central nervous system. /One of the compounds tested was/ sodium monomethyldithiocarbamate (metham). Male Sprague-Dawley rats received radioactively labeled lead acetate injected into a tail vein. The dithiocarbamates or thiurams were administered by gastric intubation. One dose was given 2 hr before lead, and another immediately after. The uptake of lead by the brain was increased by ... metham. /It was concluded that/ combined exposure to lead and dithiocarbamates should be avoided.

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Non-Human Toxicity Values
LD50 Rat (male) oral 780 mg/kg /From table/
LD50 Rat oral 1700 mg/kg
LD50 Rat (female) oral 845 mg/kg /From table/
LD50 Rat oral 820 mg/kg /Sodium methyldithiocarbamate, dihydrate/
For more Non-Human Toxicity Values (Complete) data for SODIUM METHYLDITHIOCARBAMATE (19 total), please visit the HSDB record page.

[1]. Resporulation of Calcium Alginate Encapsulated Metarhizium anisopliae on Metham®-Fumigated Soil and Infectivity on Larvae of Tenebrio molitor. J Fungi (Basel). 2022 Oct 21;8(10):1114.

[2]. Chemical fumigants control apple replant disease: Microbial community structure-mediated inhibition of Fusarium and degradation of phenolic acids. J Hazard Mater. 2022 Oct 15;440:129786.

Metham Sodium can cause cancer and developmental toxicity according to The Environmental Protection Agency (EPA).
Metam sodium (compounds, weed, killing, liquid) appears as a yellow to light yellow-green solution with an odor of amine and sulfur that varies in intensity.
Metam-sodium is an organic sodium salt and an organosulfur insecticide. It has a role as a proherbicide, a proinsecticide, a profungicide and a pronematicide. It contains a metam(1-).

C2H4NNAS2

129.17

128.968

137-42-8

137-42-8 Carbation

5366415

White crystals
White crystalline solid

120.3ºC at 760mmHg

Decomposes without melting

26.6ºC

1.079

69.42

1

2

0

6

46.8

0

CNC([S-])=S.[Na+]

AFCCDDWKHLHPDF-UHFFFAOYSA-M

InChI=1S/C2H5NS2.Na/c1-3-2(4)5;/h1H3,(H2,3,4,5);/q;+1/p-1

sodium;N-methylcarbamodithioate

Metham sodium Carbathione Sodium methyldithiocarbamate Carbothion

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。