DCOIT is a representative isothiazolinone that stimulates gonadotropin-releasing hormone receptor (GnRHR)-mediated follicle-stimulating hormone and luteinizing hormone synthesis in the brain. DCOIT interferes with G protein-coupled receptor, MAPK, and Ca2+ signaling cascades.

Physicochemical Properties

Molecular Formula	C11H17CL2NOS
Molecular Weight	282.23
Exact Mass	281.04
CAS #	64359-81-5
PubChem CID	91688
Appearance	Crystals from hexane
Density	1.3±0.1 g/cm3
Boiling Point	322.6±52.0 °C at 760 mmHg
Melting Point	36-40ºC
Flash Point	148.9±30.7 °C
Vapour Pressure	0.0±0.7 mmHg at 25°C
Index of Refraction	1.552
LogP	4.34
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	7
Heavy Atom Count	16
Complexity	281
Defined Atom Stereocenter Count	0
SMILES	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
InChi Key	PORQOHRXAJJKGK-UHFFFAOYSA-N
InChi Code	InChI=1S/C11H17Cl2NOS/c1-2-3-4-5-6-7-8-14-11(15)9(12)10(13)16-14/h2-8H2,1H3
Chemical Name	4,5-dichloro-2-octyl-1,2-thiazol-3-one
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ADME/Pharmacokinetics	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/Toxicokinetics	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. 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.
References	[1].Isothiazolinone Disrupts Reproductive Endocrinology by Targeting the G-Protein-Coupled Receptor Signaling. Environ Sci Technol. 2024 Jan 3.
Additional Infomation	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.

Solubility Data

Solubility (In Vitro)

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

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.5432 mL	17.7160 mL	35.4321 mL
	5 mM	0.7086 mL	3.5432 mL	7.0864 mL
	10 mM	0.3543 mL	1.7716 mL	3.5432 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.