3,3',4',5-四氯水杨酰苯胺 | 1154-59-2

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3,3',4',5-四氯水杨酰苯胺
• 中文别名: 3,3,4,5-四氯水杨酰苯胺
• 英文名称: 3,3',4',5-tetrachlorosalicylanilide
• 英文别名: BS-200；3,3′,4′,5-tetrachlorosalicylanilide；Tetrachlorosalicylanilide；TCSA；3,5-dichloro-N-(3,4-dichloro-phenyl)-2-hydroxy-benzamide；3,5,3',4'-tetrachlorosalicylanilide；3,5-dichloro-N-(3,4-dichlorophenyl)-2-hydroxybenzamide
• CAS: 1154-59-2
• 化学式: C₁₃H₇Cl₄NO₂
• mdl: MFCD00041745
• 分子量: 351.016
• InChiKey: SJQBHPJLLIJASD-UHFFFAOYSA-N

物化性质

• 熔点：
  162 °C
• 沸点：
  408.1±45.0 °C(Predicted)
• 密度：
  1.6676 (rough estimate)
• 颜色/状态：
  Crystalline solid
• 溶解度：
  In water, 0.16 mg/L at 25 °C (est)
• 蒸汽压力：
  3.0X10-10 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits very toxic fumes of /chlorides and nitrogen oxides/.
• 解离常数：
  pKa = 6.8 (phenol) (est)
• 稳定性/保质期：
  避免与不相容材料接触，与强氧化剂反应。

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

毒理性

• 相互作用

为了研究氧中间体（OIs）可能参与接触光敏化过程，实验小鼠在光敏化前接受了长效脂质体超氧化物歧化酶（L-SOD）的治疗。对3,3',4',5'-四氯水杨酰替苯胺（TCSA）的光敏化作用被L-SOD预处理的小鼠显著抑制。这种抑制并不是由抑制细胞介导，也不是因为使用L-SOD产生的无响应状态。相反，这种抑制似乎是由于未能产生光敏原。L-SOD治疗诱导了对TCSA接触光敏性的抑制，但对TCSA或二硝基氟苯的普通接触敏感性没有影响，这表明光敏原的产生比普通接触变应原的产生更关键地依赖于OIs的存在。结果提供了证据，证明OIs是在氧存在下通过光吸收产生的，并与生物底物反应形成光敏原。

To investigate the possible participation of oxygen intermediates (OIs) in the contact photosensitization process, mice were treated with long-acting liposomal-superoxide dismutase (L-SOD) before photosensitization. Photosensitization to 3,3',4',5-tetrachlorosalicylanilide (TCSA) was significantly suppressed by the pretreatment of mice with L-SOD. This suppression was not mediated by suppressor cells or due to an unresponsive state produced by the use of L-SOD. Rather, the suppression appeared to be due to the failure of production of photoallergen. L-SOD treatment induced the suppression of contact photosensitivity to TCSA but not ordinary contact sensitivity to TCSA or dinitrofluorobenzene, suggesting that the production of photoallergen is more critically dependent on the presence of OIs than that of ordinary contact allergen. The results provide evidence that OIs are produced by light absorption in the presence of oxygen and react with the biologic substrate to form photoallergens.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

3,3',4',5-四氯水杨酰替苯胺（TCSA）联合UVA在老鼠身上诱导出明显的接触性光敏反应（CPS）。在致敏前给予环磷酰胺（Cy）会导致耳肿胀进一步增加。当UVB辐射在远离致敏部位的地方给予时，会引起与剂量相关的CPS抑制。Cy并没有消除UVB诱导的抑制作用。

A marked contact photosensitivity (CPS) response to 3,3',4',5 tetrachlorosalicylanilide (TCSA) plus UVA was induced in mice. Cyclophosphamide (Cy), given prior to sensitization, caused a further increase in ear swelling. When UVB radiation was given at a site distant from that used for sensitization it caused a dose-related suppression of CPS. Cy did not eliminate the UVB-induced suppression.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

为了评估局部防晒霜对长波紫外线A（UVA）的保护效果，研究人员开发了一种动物模型，使用BALB/cJ小鼠，这些小鼠已经诱导了对3,3',4',5-四氯水杨酰基苯胺的接触光敏性。小鼠在被剪短的背部皮肤上被致敏，然后在耳朵上进行挑战。通过挑战后耳朵厚度的变化来测量光敏性的程度。评估了两种剂量的每种局部防晒霜的效果，通过在挑战时抑制接触光敏性反应的程度来判断。对照实验使用每种防晒霜的基质进行。在这个测试系统中，含有UVA吸收化学物质的某些但不是所有防晒霜显示出积极抑制接触光敏性。几种防晒霜在5微升/平方厘米时的抑制效果比在2微升/平方厘米时更好，这表明存在剂量相关效应。然而，一种防晒霜在2微升/平方厘米时给出了更大的抑制效果。测试的几种基质也抑制了接触光敏性反应。一个意外的发现是，测试的两种基质增强了接触光敏性反应。

An animal model /was developed/ to assess the ultraviolet A (UVA) protective effect of topical sunscreens with the use of BALB/cJ mice in which contact photosensitivity to 3, 3', 4', 5 tetrachlorosalicylanilide had been induced. The mice were sensitized on the clipped dorsal skin and challenged on the ears. Changes in ear thickness after challenge were used to measure the degree of photosensitivity. The efficacy of two doses of each topical sunscreen was assessed by the degree of suppression of the contact photosensitivity response at challenge. Control studies were performed with the base of each sunscreen. Some but not all sunscreens that contained UVA-absorbing chemicals showed active suppression of contact photosensitivity in this test system. Several sunscreens gave greater suppression at 5 uL/sq cm than at 2 uL/sq cm, which suggests a dose-related effect. One sunscreen, however, gave greater suppression at 2 uL/sq cm. Several of the bases tested also suppressed the contact photosensitivity response. An unexpected finding was an enhancement of the contact photosensitivity reaction by two of the bases tested.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

这项研究旨在使用接触光敏性小鼠模型（CPS）对3,3',4',5-四氯水杨酰替苯胺（TCSA）进行UVA范围内防晒霜防护效果的体内评估。小鼠通过在腹部涂抹TCSA并接受UVA照射（TCSA/UVA）进行致敏，5天后，在耳垂进行TCSA/UVA挑战。四种防晒剂，分别为苯酮-3、 Parsol 1789、对氨基苯甲酸和2-乙基己基对甲氧基肉桂酸酯，在照射前涂抹于耳垂上。通过抑制耳肿胀反应和TCSA-表皮细胞光加合物的形成程度来评估它们的防护效果。两种UVA吸收型防晒剂，苯酮-3和Parsol 1789，显著抑制了耳肿胀反应，而两种UVB吸收型防晒剂的抑制效果要小得多。UVA吸收型防晒剂通过抑制TCSA-表皮细胞光加合物的形成发挥作用。

This study was conducted to investigate in vivo evaluation of protectiveness by sunscreens in the UVA range using a mouse model of contact photoallergy (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA). Mice were sensitized with TCSA painting plus UVA irradiation (TCSA/UVA) on the abdomen and, 5 days later, challenged with TCSA/UVA on the earlobe. Each of four sunscreen agents, benzophenone-3, Parsol 1789, p-aminobenzoic acid, and 2-ethyl-hexyl-p-methoxycinnamate, was applied to the earlobes before irradiation. Their protective efficacy was evaluated in the degree of inhibition of both ear swelling responses and TCSA-epidermal cell photoadduct formation. Two UVA-absorbing sunscreens, benzophenone-3 and Parsol 1789, dramatically inhibited the ear swelling response, while the two UVB-absorbers exhibited a much less suppressive effect. The UVA-absorbing agents functioned via inhibiting the formation of TCSA-epidermal cell photoadducts.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22
• 海关编码：
  2924299090

SDS

Name:	3 3 4 5-Tetrachlorosalicylanilide 99% (UV-Vis) Material Safety Data Sheet
Synonym:	Benzamide,3,5-Dichloro-N-(3,4-Dichlorophenyl)-2-Hydroxy
CAS:	1154-59-2

Section 1 - Chemical Product MSDS Name:3 3 4 5-Tetrachlorosalicylanilide 99% (UV-Vis) Material Safety Data Sheet
Synonym:Benzamide,3,5-Dichloro-N-(3,4-Dichlorophenyl)-2-Hydroxy

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
1154-59-2	Benzamide,3,5-dichloro-n-(3,4-dichloro	99	214-576-8

Hazard Symbols: XN
Risk Phrases: 22

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful if swallowed.The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
Harmful if swallowed. May cause irritation of the digestive tract.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 1154-59-2: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white to off-white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 162 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C13H7Cl4NO2
Molecular Weight: 351.01

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, irritating and toxic fumes and gases, carbon dioxide, oxides of chlorine.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 1154-59-2: VN8900000 LD50/LC50:
CAS# 1154-59-2: Oral, rat: LD50 = 243 mg/kg.
Carcinogenicity:
Benzamide,3,5-dichloro-n-(3,4-dichlorophenyl)-2-hydroxy- - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XN
Risk Phrases:
R 22 Harmful if swallowed.
Safety Phrases:
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 1154-59-2: No information available.
Canada
CAS# 1154-59-2 is listed on Canada's DSL List.
CAS# 1154-59-2 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 1154-59-2 is listed on the TSCA inventory.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  3,3',4',5-四氯水杨酰苯胺 、 氯甲酸乙酯 以 吡啶 为溶剂， 反应 1.0h， 以62%的产率得到6,8-dichloro-3-(3,4-dichloro-phenyl)-benzo[e][1,3]oxazine-2,4-dione
  参考文献：
  名称：

  抗分枝杆菌物质的化学结构与其对非典型菌株的活性之间的关系。第 14 部分：3-Aryl-6,8-dihalo-2H-1,3-benzoxazine-2,4 (3H) -diones

  摘要：

  6,8-二氯-3-苯基-2H-苯并恶嗪-2,4(3H)-二酮的八种衍生物和6,8-二溴-3-苯基-2H-1,3-苯并恶嗪-的九种衍生物苯环上取代的 2,4 (3H)-二酮是通过相应的水杨酰苯胺与氯甲酸乙酯反应制备的。在体外评估了这些化合物对结核分枝杆菌、堪萨斯分枝杆菌和鸟分枝杆菌的抗分枝杆菌活性。它们的活性随着苯环上取代基的疏水性和吸电子能力的增加而增加。

  DOI：

  10.1002/(sici)1521-4184(199801)331:1<3::aid-ardp3>3.0.co;2-2
• 作为产物：
  描述：

  3,5-二氯水杨酸 、 3,4-二氯苯胺 在 三氯化磷 作用下， 以 氯苯 为溶剂， 反应 3.0h， 以92%的产率得到3,3',4',5-四氯水杨酰苯胺
  参考文献：
  名称：

  抗分枝杆菌物质的化学结构与其对非典型菌株的活性之间的关系。第 14 部分：3-Aryl-6,8-dihalo-2H-1,3-benzoxazine-2,4 (3H) -diones

  摘要：

  6,8-二氯-3-苯基-2H-苯并恶嗪-2,4(3H)-二酮的八种衍生物和6,8-二溴-3-苯基-2H-1,3-苯并恶嗪-的九种衍生物苯环上取代的 2,4 (3H)-二酮是通过相应的水杨酰苯胺与氯甲酸乙酯反应制备的。在体外评估了这些化合物对结核分枝杆菌、堪萨斯分枝杆菌和鸟分枝杆菌的抗分枝杆菌活性。它们的活性随着苯环上取代基的疏水性和吸电子能力的增加而增加。

  DOI：

  10.1002/(sici)1521-4184(199801)331:1<3::aid-ardp3>3.0.co;2-2

文献信息

• Identification of halosalicylamide derivatives as a novel class of allosteric inhibitors of HCV NS5B polymerase
  作者：Yaya Liu、Pamela L. Donner、John K. Pratt、Wen W. Jiang、Teresa Ng、Vijaya Gracias、Steve Baumeister、Paul E. Wiedeman、Linda Traphagen、Usha Warrior、Clarence Maring、Warren M. Kati、Stevan W. Djuric、Akhteruzzaman Molla

  DOI：10.1016/j.bmcl.2008.04.068

  日期：2008.6

  elongation pocket that is occupied by diketoacids, but a mutually exclusive binding mode with respect to the allosteric thumb pocket that is occupied by the benzimidazole class of inhibitors. Therefore, halosalicylamides represent a novel class of allosteric inhibitors of HCV NS5B polymerase.

  卤水杨酰胺衍生物通过高通量筛选被鉴定为 HCV NS5B 聚合酶的有效抑制剂。随后的结构和活性关系揭示了水杨酰胺部分对最佳活性的绝对要求。水杨酰胺部分的羟基或酰胺基团的甲基化消除了活性，而两个苯环上的取代是可接受的。卤代水杨酰胺衍生物在延伸核苷酸方面显示出非竞争性，并显示出针对基因型 1-3 HCV NS5B 聚合酶的广泛基因型活性。抑制剂竞争研究表明与噻二嗪类化合物占据的起始口袋的加性结合模式和由二酮酸占据的延伸口袋的加性结合模式，但是对于被苯并咪唑类抑制剂占据的变构拇指口袋而言，这是一种相互排斥的结合模式。因此，卤代水杨酰胺代表了一类新型的 HCV NS5B 聚合酶变构抑制剂。
• [EN] BIARYL COMPOUNDS AS ANTIMICROBIAL AND CHEMOTHERAPEUTIC AGENTS<br/>[FR] COMPOSÉS BIARYLE UTILISÉS EN TANT QU'AGENTS ANTIMICROBIENS ET CHIMIOTHÉRAPEUTIQUES
  申请人：UNIV RICE WILLIAM M

  公开号：WO2017083702A1

  公开（公告）日：2017-05-18

  In one aspect, the present disclosure provides diaryl compounds of the formula presented herein. The application also provides compositions and methods of treatment thereof. In some embodiments, these compounds are used in the treatment of bacterial infections or in the treatment of cancer.

  在某个方面，本发明提供了所述公式的二苯基化合物。该申请还提供了其组合物和治疗方法。在某些实施例中，这些化合物用于治疗细菌感染或癌症的治疗。
• Phosphate transport inhibitors
  申请人：Jozefiak H. Thomas

  公开号：US20070021509A1

  公开（公告）日：2007-01-25

  Disclosed are compounds which have been identified as inhibitors of phosphate transport. Many of the compounds are represented by Structural Formula (I): Ar 1 —W—X—Y—Ar 2 ; or a pharmaceutically acceptable salt thereof. Ar 1 and Ar 2 are independently a substituted or unsubstituted aryl group or an optionally substituted five membered or six membered non-aromatic heterocylic group fused to an optionally substituted monocylic aryl group. W and Y are independently a covalent bond or a C1-C3 substituted or unsubstituted alkylene group. X is a heteroatom-containing functional group, an aromatic heterocyclic group, substituted aromatic heterocyclic group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, an olefin group or a substituted olefin group. Also disclosed are methods of treating a subject with a disease associated with hyperphosphatemia, as well as a disease mediated by phosphate-transport function. The methods comprise the step of administering an effective amount of the one of the compounds described above.

  本发明涉及已被鉴定为磷酸盐转运抑制剂的化合物。其中许多化合物由结构式（I）表示：Ar1-W-X-Y-Ar2；或其药学上可接受的盐。其中，Ar1和Ar2独立地为取代或未取代的芳基团或可选取代的五元或六元非芳基杂环团与可选取代的单环芳基团融合。W和Y独立地为共价键或C1-C3取代或未取代的烷基链。X为含杂原子的官能团、芳基杂环团、取代的芳基杂环团、非芳基杂环团、取代的非芳基杂环团、烯烃基或取代的烯烃基。本发明还涉及治疗与高磷血症相关的疾病以及由磷酸盐转运功能介导的疾病的方法。该方法包括给予上述化合物之一的有效量。
• Animal litter composition
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP0109275A2

  公开（公告）日：1984-05-23

  Solid absorbent materials, having adsorbed thereto from about 25 ppm to about 500 ppm of a halogenated aromatic hydrocarbon bacteriostat, when used as animal litter products, effectively prevent the development of urine odours. Absorbent pads having adsorbed thereto from about 5000 ppm to about 30,000 ppm of the bacteriostat when used as liners in litter boxes likewise effectively control odour development.

  固体吸收材料吸附了约 25ppm 至约 500ppm 的卤代芳香烃抑菌剂，用作动物粪便产品时，可有效防止尿味的产生。 吸收垫吸附了约 5000ppm 至约 30000ppm 的抑菌剂，用作猫砂箱的衬垫时，同样可有效控制气味的产生。
• Antimicrobial non-woven fabric
  申请人：MICROBAN PRODUCTS COMPANY

  公开号：EP0113254A1

  公开（公告）日：1984-07-11

  An antimicrobial agent is incorporated into the binder of a non-woven fabric where it resides in colloidal suspension within the amorphous zones of the polymer. Thus incorporated it migrates to the surface of the binder and onto the fibers of the non-woven fabric to inhibit the growth of bacteria and fungi.

  将抗菌剂加入无纺布的粘合剂中，使其在聚合物的无定形区内处于胶体悬浮状态。 这样，抗菌剂就会迁移到粘合剂的表面和无纺布的纤维上，从而抑制细菌和真菌的生长。

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