浓度为 100、300 和 1000 µM 的二甲嗪会强烈抑制 HepG2 细胞活力 [1]。二甲嗪（3、10、30 µM；24 h）促进 HepG2 细胞的能量代谢从有氧三羧酸循环（TCA）和氧化磷酸化转变为无氧糖酵解[1]。在 HepG2 细胞中，异丙嗪（3、10、30 µM；24 小时）可抑制复合物 IV 活性 [1]。

三氯芬酸（46.3、139、417 mg/kg；口服；单次）在肾脏（18.64%）、脑（23.58%）、胃（21.94%）和肝脏（35.84%）中蓄积[1]。异丙嗪（46.3、139、417 mg/kg；口服；单剂量）比任何其他器官都更能提高小鼠肝脏和大脑中的 MDA 水平[1]。

RT-PCR[1]
细胞类型： HepG2 细胞
测试浓度： 3、10、30 µM
孵育时间： 24 小时
实验结果： 30 µM 时，乳酸脱氢酶 B (LDHB) 水平显着增加，6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶略有增加3（PFKFB3）。在 3、10 和 30 µM 噻嗪酮处理下，ATP 水平以浓度依赖性方式分别降低至载体对照水平的 91.3%、87.9 和 67.2%。乳酸水平显着增加。

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免疫荧光[1]
细胞类型： HepG2 细胞
测试浓度： 3、10、30 µM
孵育时间： 24 小时
实验结果： 在 3、10 和 30 ℃ 进行噻嗪酮处理后，复合物 IV 的活性显着抑制至载体对照水平的 82.2、69.2 和 63.4%分别为μM。

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细胞活力测定[1]
细胞类型： HepG2 细胞
测试浓度： 3、10、30 µM
<孵育时间： 24 小时
实验结果： 以不依赖浓缩物的方式显着提高细胞内 ROS 水平，并降低 mtDNA 含量。

Animal/Disease Models: Male C57BL/6 mice (6 to 8weeks old)[1].
Doses: 46.3, 139, 417 mg/kg
Route of Administration: Oral administration; single
Experimental Results: Tended to elevate the MDA level in all organs, and the most significant concentration-dependent increases were observed in the liver and brain. demonstrated the highest concentrations in the liver (35.84%) followed by the brain (23.58%), stomach (21.94%) and kidney (18.64%), while the levels in the mouse spleen and heart were below the limit of detection.

Absorption, Distribution and Excretion
(14)C-buprofezin (radiochemical purity >97%) administered by gavage to 5 rats/sex/dose at 10 and 100 mg/kg; in males, 90-91% of dose eliminated by 48 hr (20-21% in urine, 69-71% in feces); in females, 87-89% of dose eliminated by 48 hr (13-14% in urine, 73-76% in feces); elimination faster in males during 1st 24 hr, but equalized by 48 hr; <1% of dose remained in body by 7 days; > or =30% of male dose and > or =38% of female dose recovered in bile at 24 hr; chromatography of urine, bile, and feces indicated extensive conjugation; bile cannulation of 3M/3F revealed that fecal metabolites were likely of bile origin.
[(14)C-phenyl]-buprofezin (2 or 22.5 mCi/mmol; >97% radiochemical purity) suspended in 1 mL of olive oil was administered by gavage to fasted /rats/ at 10 and 100 mg/kg (number of animals varied with the experiment); over 90% of administered dose was excreted by 48 hr at both concentrations; by 96 hr at both concentrations, 70-74% of dose excreted in feces (though a delay at the high dose relative to the low dose was noted through 24 hr), 21-25% in urine, very low amounts excreted as expired (14)C-CO2; at 10 mg/kg, 12% of the parent compound was excreted into the feces; Cmax in blood occurred at 9 hr for both doses after which concentrations declined biphasically (t1/2 =13 and 60 hr); peak levels of radiolabel occurred in tissues at 5-9 hr post dose, after which tissue levels decreased biphasically with a t1/2 of 3.5-15 hr and 15-72 hr for the 2 phases; by 96 hr tissue residue levels were low.
Male rats /were/ fed diet containing buprofezin at 200 or 1000 ppm for up to 24 weeks; 3/dose were sacrificed on days 2 and 4 and on weeks 1, 2, 4, 8, 12, 16, and 24; buprofezin levels measured by gas-liquid chromatography after extraction from blood, brain, liver, kidney, adipose tissue, and muscle; detection limit: 0.1 ppm; 200 ppm: only adipose tissue attained levels high enough to consistently detect, remaining stable between 4 days and 24 weeks at a mean concentration of 0.43-1.10 ppm; an occasional animal showed detectable levels in liver, while kidney, muscle, and brain never showed detectable levels; 1000 ppm: adipose tissue peaked at 10.53 ppm on day 4, declining to 3.40 ppm at 24 weeks; liver retained a stable concentration of 0.21-0.96 over the entire period; kidneys were near or below the detection limit for 8 weeks and undetectable thereafter; brain was near or below the detection limit for 1 week and undetectable thereafter; muscle was near or below the detection limit for 2 weeks and undetectable thereafter (no measurement at 4 weeks); test article thus did not accumulate in any tissue at either concentration.

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Metabolism / Metabolites
[(14)C-phenyl]-buprofezin (2 or 22.5 mCi/mmol; >97% radiochemical purity) suspended in 1 mL of olive oil was administered by gavage to fasted /rats/ at 10 and 100 mg/kg (number of animals varied with the experiment); ... metabolite studies revealed hydroxylation of the phenyl ring, oxidation of sulfur, and cleavage of the thiadiazin ring, with evidence of glucuronic and sulfuric conjugation.
/In/ ruminants: 2-tert-butylimino-5-(4-hydroxyphenyl)-3-isopropyl-1,3,5- thiadiazinan-4-one (BF2) was the major residue identified in liver and kidney (residue in fat and muscle were < or =0.020 ppm) and N-(4-hydroxyphenyl)acetamide (BF23) was the major residue identified in milk from the ruminant metabolism study (all other residue were <10% total radioactive residue (TRR); 3.5x maximum theoretical dietary burden (MTDB)). ...The residues of concern in milk are buprofezin and BF23; ... the residues of concern in ruminant tissues are buprofezin and BF2.

Toxicity Summary
IDENTIFICATION AND USE: Buprofezin is a solid. It is used as insecticide (chitin synthesis inhibitor). HUMAN EXPOSURE AND TOXICITY: There was no buprofezin-related increase in abnormal cells or in aberrations in human lymphocyte cultures with or without metabolic activation. ANIMAL STUDIES: The skin of rats was treated for 6 hours/day for 24 days with 0, 100, 300 or 1000 mg/kg/day. There was an increased incidence of focal hepatocellular necrosis for the 1000 mg/kg females. In long-term rat studies, increases in thyroid weight at 6, 12, and 24 month and in liver weight at 12 and 24 months were noted. Also hepatocyte necrosis and hyperplastic nodules in both sexes, interstitial pneumonia in males, interstitial heart edema and other heart effects in females were all noted at the high dose. Reduced maternal body weight and total litter resorption were noted in developmental studies. Buprofezin was not mutagenic in five Salmonella typhimurium tester strains (TA98, TA100, TA1535, TA1537, and TA1538) with or without metabolic activation. ECOTOXICITY STUDIES: A 48-hr acute exposure of buprofezin resulted in daphnid immobility at an EC(50) of 0.44 mg/L. In a 14-day chronic exposure study of buprofezin (0, 0.025, 0.05, 0.10 and 0.15 mg/L), the development and reproduction of daphnids were all significantly affected and the body length was more sensitive than other observed parameters. However, the adverse effects of buprofezin on parental daphnids can be passed on to their offspring and cannot be recovered in a short time. Malformations were observed when the embryos and larvae of African catfish (Clarias gariepinus) were exposed to more than 5 mg/L.

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Interactions
... In the present study, the combined effects of the heavy metal nickel (NiSO4) and insect growth regulator buprofezin on the induction of embryo toxicity in zebrafish were assessed. By applying nonlinear regression to the concentration-response data with each of the chemicals using the Hill and Langmuir functions and computing the predictions using the model of concentration addition (CA), we confirmed that NiSO4 and buprofezin acted together to produce synergistic embryotoxicity in zebrafish. Subsequently, we further found that the combination of NiSO4 and buprofezin formed a complex that facilitated the uptake of nickel (Ni) and buprofezin by the embryos. Following this, we clarified that an oxidative mechanism of the complex might underlie the synergistic embryotoxicity of NiSO4 and buprofezin.

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Non-Human Toxicity Values
LD50 Mouse oral >5 g/kg
LD50 Rat dermal >5 g/kg
LD50 Rat (male) oral 2198 mg/kg
LD50 Rat (female) oral 2355 mg/kg
LC50 Rat inhalation >2.2 mg/L (4 hr) /Applaud 70 DF/

[1]. Potential hepatic toxicity of buprofezin at sublethal concentrations: ROS-mediated conversion of energy metabolism. J Hazard Mater. 2016 Dec 15;320:176-186.

[2]. Inhibition of chitin biosynthesis by buprofezin analogs in relation to their activity controlling Nilaparvata lugens Stål. Pestic Biochem Physiol, 1985, 24(3): 343-347.

Buprofezin is a 2-(tert-butylimino)-5-phenyl-3-(propan-2-yl)-1,3,5-thiadiazinan-4-one in which the C=N double bond has Z configuration. It has a role as an insecticide and a member of homopteran inhibitor of chitin biosynthesis.

C16H23N3OS

305.44

305.156

69327-76-0

Buprofezin-d6;2140803-94-5

50367

White to off-white solid powder

1.18

273°C (12 torr)

104-106°C

176-178°C

1.52-1.522

4.185

61.21

0

3

3

21

408

0

PRLVTUNWOQKEAI-UHFFFAOYSA-N

InChI=1S/C16H23N3OS/c1-12(2)19-14(17-16(3,4)5)21-11-18(15(19)20)13-9-7-6-8-10-13/h6-10,12H,11H2,1-5H3

2-tert-butylimino-5-phenyl-3-propan-2-yl-1,3,5-thiadiazinan-4-one

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)

DMSO: 100 mg/mL (327.40 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (8.18 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (8.18 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (8.18 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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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。