Di-tert-dodecyl disulphide

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

dermal absorption, other

Remarks:

Mathematical simulation

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

IH SkinPerm mathematical tool for estimating dermal absorption

Specific details on test material used for the study:

Canonical SMILES
CCCCCCCCCC(C)(C)SSC(C)(C)CCCCCCCCC

Time point:

8 h

Dose:

1000 mg/h (deposition)

Parameter:

percentage

Absorption:

0 %

Reference 2

Endpoint:

dermal absorption, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

The Dermal Permeability Coefficient Program (DERMWIN) v2.00 estimates the dermal permeability coefficient (Kp), the dermally absorbed dose per event (DAevent) and Dermal Absorbed Dose (DAD) of organic compounds via water contact.

Specific details on test material used for the study:

SMILES (used for QSAR prediction): CCCCCCCCCC(C)(C)SSC(C)(C)CCCCCCCCC

Parameter:

rate

Remarks:

Kp (est)

Absorption:

0.18 cm/h

                 Kp (est): 0.18 cm/hr

SMILES : CCCCCCCCCC(C)(C)SSC(C)(C)CCCCCCCCC

CHEM   :

MOL FOR: C24 H50 S2

MOL WT : 402.79

------------------------------ Dermwin v2.01 ----------------------------------

Log Kow  (estimated)  :  12.46

Log Kow (user-entered):  6.50   (used in Kp calculations)

GENERAL Equation:   log Kp = -2.80 + 0.66 log Kow - 0.0056 MW

   Kp (predicted): 1.80e-001  cm/hr

Dermally Absorbed Dose per Event for Organic Compounds - Water Contact:

  Water Conc (mg/cm3): 8.3e-006  (estimated by program)

  Fraction Absorbed  : 1.0000

  DA(event):  1.38e-005 mg/cm2-event (using eqn 3.2 & 3.3)

                  (tau = 19.4 hr,  t* = 76.5 hr)

Dermally Absorbed Dose (70 kg Adult) - Water Contact:

  DAD:  1.46e-003 mg/kg-day (using eqn 3.1)

Description of key information

No data on toxicokinetics, metabolism and distribution are available for di-tert-dodecyl disulphide (DTDDS). Based on its physicochemical properties, DTDDS is expected to be well absorbed by the respiratory and gastro-intestinal tracts; Limited absorption is expected through the skin.

The assessment of the toxicokinetics of DTDDS is based on the available toxicological data and the physicochemical properties of DTDDS as suggested by the REACH Guidance Chapter R.7c:

Molecular weight: 402.7 g/mole 

Vapour pressure: 0.00031 Pa @ 25°C

Water solubility: < 30 µg/L at 20°C 

Partition coefficient log Kow = > 6.5

 

ABSORPTION

Oral route

DTDDS is a highly lipophilic substances (log Kow >6.5 and very low water solubility), 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, DTDDS may be taken up by micellular solubilisation.

 

Inhalation route

DTDDS is a substance with a low volatility, its vapour pressure is 3.1 10e-4 Pa at 25°C and its boiling point is 244.9°C at 101 kPa. As any highly lipophilic and poorly soluble in water compounds, DTDDS may be taken up by micellular solubilisation.

 

Dermal absorption

The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore if the water solubility is below 1 mg/l, dermal uptake is likely to be low. Above a logP of 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow.

The rate of absorption was estimated using the IH SkinPerm model using a Kp derived from the EPI Dermwin model. For a skin deposition of 1000 mg/h four 8 h, DTDDS is virtually not absorbed.

Therefore, according to the REACH Guidance, a default value of 10% skin absorption will be used for DTDDS.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100