DCOIT (Kathon 930)   中文名称: 4,5-二氯-N-辛基-4-异噻唑啉-3-酮

Absorption, Distribution and Excretion
Dermal absorption of RH-287 was examined in male Crl:CD:BR rats. There were six experimental groups of 4 rats each. Two concentrations of RH-287 were employed, 3% and 0.045%. Dermal application was made to a shaved 2 x 2 cm area on the interscapular region of the back, which was fitted with a contoured glass ring secured with cyanoacrylate glue and a porous top secured with rubber bands after application of the test substance in a dose aliquot of 60 uL. Two groups (A and B) received either 3% of 0.045% RH287 and urine and feces samples obtained at 10 hours post-dose, at which time the animals were killed and analysis for radioactivity performed in whole blood, plasma, and remaining carcass. Two additional groups (C and D) received either 3% or 0.045% RH-287 and were subjected to the same procedures as groups A and B, except exposure duration was 24 hours. The last two groups (E and F) received either 3% or 0.045 % RH-287, and urine and feces samples taken at 0, 10, 24, 48, and 72 hours post-dose. Animals in this group were sacrificed at 72 hours post-dose and analysis for radioactivity performed as for the other groups. Results of this study showed that at a dose of 0.045% RH-287, 44-50% of the dose was absorbed after a 10 hour exposure, and 70% after a 24 hour exposure. Administration of 3% RH-287 resulted in 31-34% absorption after 10 hours of exposure, and 52% absorption after 24 hours exposure.

Toxicity Summary
IDENTIFICATION AND USE: 4,5-Dichloro-2-octyl-3-isothiazolone (DCOIT) is a solid. It is used as a marine antifoulant. HUMAN STUDIES: An outbreak of occupational contact dermatitis occurred due to the biocide DCOIT. Eight of 19 persons, six females, 20 to 63 years old, employed in a Japanese textile finishing factory developed edematous reddish eruptions on their forearms, upper arms, face, or neck. The subjects have been sensitized to DCOIT without apparent cross sensitization to DCOIT. ANIMAL STUDIES: In dogs decreased body weight and food consumption, hematologic and clinical chemistry parameter changes observed at 1500 ppm. After inhalation in rats at concentrations of 0.02, 0.63, and 6.72 mg/cu m for 6 hours per day, 5 days per week, for thirteen weeks, treatment-related microscopic lesions in the nose, larynx, and lungs were observed in mid- and high-dose treated rats. Minimal or mild subacute inflammation of the nose was observed in increased incidence, as was transitional respiratory epithelial hyperplasia and goblet cell hyperplasia. In the epiglottis, hyperplasia of the squamous and cuboidal epithelium was observed in mid- and high dose rats, as was chronic-active inflammation of the epiglottis. Goblet cell hyperplasia and acute inflammation was observed in increased incidence in the lungs of high dose rats. In the developmental study in rabbits, there were no treatment-related external, visceral, or skeletal malformations or variations. In rats, fetuses at 100 mg/kg/day showed an increase in the number of fetuses with wavy ribs, along with an increase in number of litters with this effect as well as the severity of the effect. It was not mutagenic in Salmonella strains TA1535, TA1537, TA98, TA100 with or without metabolic activation. It induced clastogenic response in Chinese hamster ovary in vitro cytogenetic assays in the presence or absence of metabolic activation. ECOTOXICITY STUDIES: In marine medaka (Oryzias melastigma) gene transcription analysis showed that DCOIT had positive regulatory effects mainly in male of the hypothalamus-pituitary-gonadal-liver axis with lesser extent in females. The stimulated steroidogenic activities resulted in increased concentrations of steroid hormones, including estradiol (E2), testosterone (T), and 11-KT-testosterone (11-KT), in the plasma of both sexes, leading to an imbalance in hormone homeostasis and increased E2/T ratio. The relatively estrogenic intracellular environment in both sexes induced the hepatic synthesis and increased the liver and plasma content of vitellogenin (VTG) or choriogenin. Furthermore, parental exposure to DCOIT transgenerationally impaired the viability of offspring, as supported by a decrease in hatching and swimming activity. DCOIT induced differential expression of 26 proteins in male brains and of 27 proteins in female brains of the marine medaka (Oryzias melastigma) after a 28-day exposure to environmentally-realistic concentration at 2.55 ug/L.

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Interactions
The toxicity of three antifoulants (Sea-Nine, Irgarol, and TBT) was determined individually and in mixtures in two tests with microalgae. Effects on periphyton community photosynthesis and reproduction of the unicellular green algae Scenedesmus vacuolatus were investigated. The tested antifoulants were highly toxic in both tests. Observed mixture toxicities were compared with predictions derived from two concepts: Independent Action (IA), assumed to be more relevant for the tested mixtures that were composed of dissimilarly acting substances, and Concentration Addition (CA), regarded as a reasonable worst-case approach in predictive mixture hazard assessment. Despite the corresponding mechanistic basis, IA failed to provide accurate predictions of the observed mixture toxicities. Results show the same pattern in both assays. Mixture effects at high concentrations were slightly overestimated and effects at low concentrations were slightly underestimated. Maximum observed deviations between observed and IA-predicted concentrations amount to a factor of 4. The suggested worst-case approach using CA was protective only in effect regions above 20%. Nevertheless, the application of any concept that accounts for possible mixture effects is more realistic than the present chemical-by-chemical assessment.

[1].Isothiazolinone Disrupts Reproductive Endocrinology by Targeting the G-Protein-Coupled Receptor Signaling. Environ Sci Technol. 2024 Jan 3.

4,5-dichloro-2-n-octyl-3(2H)-isothiazolone is a 1,2-thiazole that is 1,2-thiazol-3(2H)-one substituted by chloro groups at positions 4 and 5 and an octyl group at position 2. It is used as a fungicide. It has a role as an environmental contaminant, a xenobiotic and a fungicide. It is an organochlorine compound and a member of 1,2-thiazoles.

C11H17CL2NOS

282.23

281.04

64359-81-5

91688

Crystals from hexane

1.3±0.1 g/cm3

322.6±52.0 °C at 760 mmHg

36-40ºC

148.9±30.7 °C

0.0±0.7 mmHg at 25°C

1.552

4.34

50.24

0

2

7

16

281

0

ClC1=C(SN(C1=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])Cl

PORQOHRXAJJKGK-UHFFFAOYSA-N

InChI=1S/C11H17Cl2NOS/c1-2-3-4-5-6-7-8-14-11(15)9(12)10(13)16-14/h2-8H2,1H3

4,5-dichloro-2-octyl-1,2-thiazol-3-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)

Typically soluble in DMSO (e.g. 10 mM)

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。