Bromethalin   中文名称: 溴杀灵

Absorption, Distribution and Excretion
A metabolism study was conducted in Fischer 344 rats following oral admin of (14)C-bromethalin at 1 mg/kg. Blood samples were taken from the orbital sinus at 0.25, 0.5, 1, 2, 4, and 24 hours, and at 2, 3, 4, 6, 8, 11, 14, 17, and 21 days after dosing. Based on radiolabeled material, the plasma half-life was 134 hours (5.6 days). The half-life of the distributive phase suggested distribution in total body water.

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Metabolism / Metabolites
The major metabolite formed in the rat is desmethyl bromethalin.
The major route of metabolism in the rat is N-demethylation.

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Biological Half-Life
5.6 days (plasma);
The half life of bromethalin is 5.6 days /in Fischer 344 rats following oral admin of 1 mg/kg (14)C-bromethalin/.

Toxicity Summary
IDENTIFICATION AND USE: Brometalin is a solid. It is a rodenticide, effective against rodents resistant to anticoagulant rodenticides. HUMAN STUDIES: Mild gastrointestinal upset is possible. CNS target symptoms: include hyperexcitability, altered mental status, ataxia, tremor, seizures, coma, cerebral edema, increased intracranial pressure and paralysis. A delusional 21-year-old male presented to a hospital with altered mental status the day after ingesting a bromethalin-based rodenticide. He died 7 days after his self-reported exposure. His clinicopathologic course was characterized by altered mental status, obtundation, increased cerebrospinal fluid pressure, cerebral edema, death, and diffuse histologic vacuolization of the white matter in the central nervous system seen on microscopic examination at autopsy. The presence of a demethylated form of bromethalin in the patient's liver and brain was confirmed by gas chromatography with mass spectrometry. There were 129 calls related to human bromethalin exposures. The age range of cases was 7 months-90 years old, with the majority of exposures (89 cases; 70.6%), occurring in children younger than 5 years of age (median age of 2 years). Most exposures occurred in the pediatric population as a result of exploratory oral exposure. One hundred and thirteen patients (89.7%) had no effects post exposure, while 10 patients (7.9%) had a minor outcome. Adverse effects were minor, self-limited, and mostly gastrointestinal upset. ANIMAL STUDIES: Rats received daily gavage doses of 0, 5, 25, or 125 ug/kg/day of bromethalin technical for 13 weeks. The NOEL in rats was 25 ug/kg/day. The LOEL in rats was 125 ug/kg/day, based on spongy degeneration (leukoencephalomyelopathy) observed in most of the central white fiber tracts of the brain, cerebellum, pons, brain stem, and thoracic spinal cord of both sexes and optic nerves of males. Dogs given a single oral dose of bromethalin at 6.25 mg/kg developed a toxic syndrome characterized by hyperexcitability, tremors, seizures, depression, and death within 15-63 hours after bromethalin administration. Gross lesions included mild cerebral edema (2/5) and mild pulmonary congestion (2/5). Histologic lesions included diffuse white matter spongiosis (5/5), mild microgliosis (3/5), optic nerve vacuolization (3/5), mild thickening of Bowman's capsule (2/5), and occasional splenic megakaryocytes (2/5). Electroencephalogram (EEG) recordings were obtained before and during the clinical syndrome induced by a bromethalin rodenticide given to dogs. Nine dogs given 6.25 mg bromethalin/kg po developed clinical signs and EEG abnormalities 15-58 hr postdosing. Predominant abnormal EEG changes included spike and spike-and-wave EEG patterns (66%), high voltage slow wave (HVSA, 50-150 microV, 1-6 Hz) activity (44%) photoconvulsive or photoparoxysmal irritative responses (44%), and marked voltage depression (dominant activity <10 microV) in all leads (33%). Male and female dogs were orally dosed by gavage for 90 days at levels of 0, 5, 25, 125, or 200 ug/kg/day with bromethalin technical. The NOEL in dogs was 25 ug/kg/day. The LOEL in dogs was 125 ug/kg/day based on spongy degeneration observed in nervous tissue components in both sexes of dogs. At the high dose, 3 male dogs displayed the following neurotoxic signs before death or being sacrificed moribund: salivation and hypoactivity, followed by trembling, myoclonia, hyperesthesia, groaning, and decubitus. Bromethalin did not produce acute delayed neurotoxicity in the hen. Cats typically develop paralytic syndrome irrespective of dose of bromethalin. In rats, there were no compound-related external, visceral or skeletal effects in bromethalin-treated fetuses in comparison to controls on either a litter or fetal basis. Definitive post mortem confirmation of intoxication by the neurotoxic rodenticide bromethalin can be challenging. Brain lesions are not specific and detection of bromethalin and its metabolites are unpredictable due to rapid photodegradation and inconsistent behavior in tissues. ECOTOXICITY STUDIES: In cases of wildlife species with unknown deaths or inconsistent clinical signs with normal or minimal histological findings, bromethalin toxicosis should be considered as a differential. Adipose tissue is the tissue of choice and can be easily harvested from a live or deceased animal to help confirm or rule out bromethalin exposure or intoxication.

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Toxicity Data
LC50 (rat) = 24 mg/m3/1h

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Interactions
The following drugs ... may increase ... response to coumarin or indandione derivatives: alcohol (acute intoxication), allopurinol, aminosalicylic acid, amiodarone, anabolic steroids, chloral hydrate, chloramphenicol, cimetidine, clofibrate, co-trimoxazole, danazol, dextrothyroxine sodium, diazoxide, diflunisal, disulfiram, erythromycin, ethacrynic acid, fenoprofen calcium, glucagon, ibuprofen, indomethacin, influenza virus vaccine, isoniazid, meclofenamate, mefenamic acid, methylthiouracil, metronidazole, miconazole, nalidixic acid, neomycin (oral), pentoxifylline, phenylbutazone, propoxyphene, propylthiouracil, quinidine, quinine, salicylates, streptokinase, sulfinpyrazone, sulfonamides, sulindac, tetracyclines, thiazides, thyroid drugs, tricyclic antidepressants, urokinase, vitamin E. /Coumarin & indandione derivatives/
The following drugs ... may ... decrease ... response to coumarin or indandione derivatives: alcohol (chronic alcoholism), barbiturates, carbamazepine, corticosteroids, corticotropin, ethchlorvynol, glutethimide, griseofulvin, mercaptopurine, methaqualone, oral contraceptives containing estrogen, rifampin, spironolactone, vitamin K. /Coumarin & indandione derivatives/
...Treatment of bromethalin-dosed rats (10/group) with EGB /(Gingko biloba extract)/ was associated with a statistically significant (P<0.05) decr in clinical sign severity, compared with bromethalin-dosed saline soln-treated rats. All rats given bromethalin and saline soln developed clinical signs of toxicosis including CNS depression, hind limb weakness, ataxia, paralysis, and coma. Some rats given bromethalin and EGB developed clinical signs, however, none developed hind limb paralysis. ...

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Non-Human Toxicity Values
LD50 Dog oral 4700 ug/kg
LD50 Cat oral 1800 ug/kg
LD50 Mouse oral 2200 ug/kg
LD50 Rabbit oral 13 mg/kg
For more Non-Human Toxicity Values (Complete) data for Bromethalin (8 total), please visit the HSDB record page.

Bromethalin is a C-nitro compound.

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Mechanism of Action
Acute rodenticide, acting as an uncoupler of oxidative phosphorylation.

C14H7BR3F3N3O4

577.9342

574.794

63333-35-7

44465

Pale yellow crystals
White crystals; powder at 25 °C
Free flowing meal with a slight yellow color
Pale yellow crystals from ethanol

2.065g/cm3

533.2ºC at 760 mmHg

150-151ºC

276.2ºC

1.645

7.623

94.88

0

8

2

27

563

0

CN(C1=C(C=C(C=C1C(F)(F)F)[N+]([O-])=O)[N+]([O-])=O)C2=C(C=C(C=C2Br)Br)Br

USMZPYXTVKAYST-UHFFFAOYSA-N

InChI=1S/C14H7Br3F3N3O4/c1-21(13-9(16)2-6(15)3-10(13)17)12-8(14(18,19)20)4-7(22(24)25)5-11(12)23(26)27/h2-5H,1H3

N-methyl-2,4-dinitro-N-(2,4,6-tribromophenyl)-6-(trifluoromethyl)aniline

EL-614; EL 614; Bromethalin

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。