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EC number: 273-103-3 | CAS number: 68937-96-2
Numeric (log mol/L)
Numeric (log Papp in 10-6cm/s)
Intestinal absorption (human)
Numeric (% Absorbed)
Numeric (log Kp)
P-glycoprotein I inhibitor
P-glycoprotein II inhibitor
Numeric (log L/kg)
Fraction unbound (human)
Numeric (log BB)
Numeric (log PS)
Numeric (log ml/min/kg)
Renal OCT2 substrate
Max. tolerated dose (human)
Numeric (log mg/kg/day)
hERG I inhibitor
hERG II inhibitor
Oral Rat Acute Toxicity (LD50)
Oral Rat Chronic Toxicity (LOAEL)
Numeric (log mg/kg_bw/day)
Numeric (log ug/L)
Numeric (log mM)
The metabolism of S3, S4 and S5 components of di-tert-butyl polysulphide by cytP450 was evaluated by the Xenosite P450 Metabolism 1.0 software. XenoSite is able to predict the site of metabolism (SOM) of a molecule for cytP4501A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 CYP isoforms. Xenosite computes a probability score varying between 0 and 1 (a high probability to be a SOM is characterized by a high score), which reflects both the confidence of the model that a particular atom is metabolised and the statistical likelihood that its prediction for that atom is correct, but they do not explicit model selectivity (which molecules are substrates of a given CYP enzyme). According to the cyt P450 isoforms and the S3, S4 and S5 components of di-tert-butyl polysulphide are preferentially metabolized on the disulphide bridges.
The dermal absorption of di-tert-butyl polysulphide leads to the following results, obtained using the SkinPerm v2.04 model according to the input data:
Deposition over time
End time observation 8 hr
Total deposition (mg) or deposition rate (mg/cm²/hr)
Fraction absorbed (%)
Amount absorbed (mg)
Lag time stratum corneum (min)
Max. derm. abs. (mg/cm²/h)
No data on toxicokinetics, metabolism and distribution are available for di-tert-butyl polysulphide.
The assessment of the toxicokinetics of di-tert-butyl polysulphide is based on the available toxicological data and the physicochemical properties as suggested by the REACH Guidance Chapter R.7c:
Molecular weight : 206 g/mol
Vapeur pressure: 15.6 Pa @ 20°C
Water solubility: 4 mg/L at 20°C
Partition coefficient log Kow = 5.6
Based on its physicochemical properties, di-tert-butyl polysulphide is expected to be well absorbed by the respiratory and gastro-intestinal tracts. Limited absorption is expected through the skin.
Di-tert-butyl polysulphide is a highly lipophilic substance (log Kow 5.6) with a very low water solubility, therefore its absorption may be limited by its inability to dissolve into GI fluids and hence make contact with the mucosal surface. However, as any highly lipophilic and poorly soluble in water compounds, it may be taken up by micellular solubilisation.
According to the hydrolysis study (Mollandin, 2011), di-tert-butyl polysulphide is not expected to hydrolyse at pH relevant to the GI tract.
Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, the rates of absorption of di-tert-butyl polysulphide were 100 and 90% for a dose of 1 and 1000 mg, respectively (Danish QSAR). Similarly, oral human absorption rates of 85-88% were predicted by the pkCSM method (Pires et al., 2015) for the main components (S3, S4 and S5 fractions) of di-tert-butyl polysulphide.
In addition, the toxicological effects observed during the repeated dose toxicity studies in rats (OECD 407 and 421) indicate a significant absorption by the oral route.
Therefore, according to the REACH Guidance, a default value of 100% oral absorption will be used for risk assessment of di-tert-butyl polysulphide.
Di-tert-butyl polysulphide is a substance with a low volatility, its vapour pressure is 15.6 Pa at 25°C. As any highly lipophilic and poorly soluble in water compounds, di-tert-butyl polysulphide may be taken up by micellular solubilisation.
Therefore, according to the REACH Guidance, a default value of 100% inhalation absorption will be used for risk assessment of di-tert-butyl polysulphide.
The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore if the water solubility is between 1-100 mg/l absorption is anticipated to be low to moderate. Above a logP of 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high.
The rate of absorption was estimated using the IH SkinPerm model using a Kp derived from the EPI Dermwin model. For an instantaneous deposition of 1000 mg over 1000 cm² of skin or a deposition over time of 1 mg/cm²/h, the absorption rates were 8% and 1%, respectively.
Therefore, according to the REACH Guidance, a default value of 10% skin absorption will be used for risk assessment of di-tert-butyl polysulphide.
Once absorbed via the gastrointestinal tract it is likely that di-tert-butyl polysulphide will be distributed systemically into cells due to its lipophilic properties and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues. No high first pass effect in the liver is expected due to lack of functional groups, which are only introduced by enzymatic reactions. According to the pkCSM method (Pires et al., 2015) for predicting small-molecule pharmacokinetic properties, the main components (S3, S4 and S5) of di-tert-butyl polysulphide substance are expected to have a low fraction unbound to serum proteins, and to readily cross the blood-brain barrier.
Steady state volume of distribution (VDss human) (log L/kg)
VDss is considered low if below 0.71 L/kg (log VDss < -0.15) and high if above 2.81 L/kg (log VDss > 0.45)
Fraction unbound to serum proteins (human) (Fu)
the predicted fraction that would be unbound in plasma is calculated
Blood Brain Barrier (BBB) permeability (log BB)
a logBB > 0.3 is considered to readily cross the blood-brain barrier
CNS permeability (blood-brain permeability- surface area product, log PS)
Compounds with a logPS > -2 are considered to penetrate the CNS, while those with logPS < -3 are considered as unable to penetrate the CNS
In silico cytochrome P450 metabolism
The metabolism of the main components (S3, S4 and S5) of di-tert-butyl polysulphide by cytP450 was evaluated by the Xenosite P450 Metabolism 1.0 software. XenoSite is able to predict the site of metabolism (SOM) of a molecule for cytP4501A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 CYP isoforms. Xenosite computes a probability score varying between 0 and 1 (a high probability to be a SOM is characterized by a high score), which reflects both the confidence of the model that a particular atom is metabolised and the statistical likelihood that its prediction for that atom is correct, but they do not explicit model selectivity (which molecules are substrates of a given CYP enzyme). The disulphide bounds are the preferential sites of cytP450 metabolism of the main components (S3, S4 and S5) of di-tert-butyl polysulphide.
The clearance rates by the pkCSM platform (Pires et al., 2015) of the main components (S3, S4 and S5) of di-tert-butyl polysulphide were predicted to be high but decreased as the molecular weight increase (1.76, 1.35 and 1.03 ml/min/kg).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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