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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Referenceopen allclose all

Endpoint:
basic toxicokinetics, other
Remarks:
G.I. human passive absorption
Type of information:
calculation (if not (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
Objective of study:
absorption
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
Model to predict either high or low fraction absorbed for an orally administered, passively transported substance on the basis of a new absorption parameter. The model includes only two inputs: the octanol-water partition coefficient (Kow) and the dimensionless oversaturation number (OLumen). The latter is the ratio of the concentration of drug delivered to the gastro-intestinal (GI) fluid to the solubility of the compound in that environment.
Specific details on test material used for the study:
SMILES (used for QSAR prediction): C(S)COCCOCCS
Species:
other: Human
Route of administration:
oral: unspecified
Type:
absorption
Results:
Absorption from gastrointestinal tract for 1 mg dose: 50%
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 valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
IH SkinPerm (v2.04) is a mathematical tool for estimating dermal absorption. The rate of mass build-up (or loss) on the skin comes from the deposition rate onto the skin minus the absorption rate into the Stratum Corneum (SC) and the amount evaporating from the skin to the air.
Species:
other: human
Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on study design:
DATA INPUT
Molecular weight: 182.30 g/mol
Temperature: 20 °C
Vapour Pressure: 0.39 Pa
Water solubility: 11400 mg/L
Log Kow: 0.66
Density: 1113 mg/cm3
Melting point: -110°C

SCENARIO PARAMETERS
- Instantaneous deposition
Deposition dose*: 1000 mg
Affected skin area**: 1000 cm²
Maximum skin adherence***: 2 mg/cm²
Thickness of stagnant air****: 1 cm
Weight fraction: 1
Timing parameters
. Start deposition: 0 hr
. End time observation: 8 hr
Report parameters
. Calculation (intervals/hr): 10000
. Report (intervals/hr): 100

- Deposition over time
Affected skin area**: 1000 cm²
Maximum skin adherence***: 1 mg/cm²
Dermal deposition rate: 2 mg/cm²/hr
Thickness of stagnant air****: 1 cm
Weight fraction: 1
Timing parameters
. Start deposition: 0 hr
. Duration of deposition: 8hr
. End time observation*: 8 hr
Report parameters
. Calculation (intervals/hr): 10000
. Report (intervals/hr): 100

*Default value defined according to the internal validation study
**Estimated skin surface of two hands of an adult.
***The skin adherence field is greyed out and a default of -1 is indicated if the substance is a liquid at 25°C. Smart logic is built into IH SkinPerm; the program recognizes whether a substance is a solid or liquid at standard temperature (25°C) based on the physicochemical properties. For substances
that are solids at 25°C a maximum adherence value up to 2 mg/cm² is allowed based on studies of soil-on-skin adherence. If the deposition rate results in an increase above the input figure (0.2-2 mg/cm²), it is assumed that the surplus disappears just by removal from the skin.
*** 3 cm if clothing involved, 1 cm if bare skin involved

Time point:
8 h
Dose:
1000 mg
Parameter:
percentage
Absorption:
8.74 %
Remarks on result:
other: Instantaneous deposition
Time point:
8 h
Dose:
1 mg/cm²/h
Parameter:
percentage
Absorption:
1.09 %
Remarks on result:
other: Deposition over time for 8 hr
Conclusions:
The dermal absorption of DMDO is estimated to be low (<= 10%).
Executive summary:

The dermal absorption of DMDO leads to the following results, obtained using the SkinPerm v2.04 model according to the input data:

 

Instantaneous deposition

 

Deposition over time

End time observation 8 hr

Total deposition (mg) or deposition rate (mg/cm²/hr)

1000

1

Fraction absorbed (%)

8.74

 1.09

Amount absorbed (mg)

87.4

Lag time stratum corneum (min)

57.6

Max. derm. abs. (mg/cm²/h)

0.00547

Description of key information

The data available on dimercapto-1,8-dioxa-3,6-octane (DMDO) and the estimations from its physico-chemical properties indicate significant a absorption by oral and inhalation routes of exposure with a low rate of dermal absorption, widespread distribution and no bioaccumulation potential.

The absorption/excretion, toxicokinetics, metabolism and distribution data of DMDO were evaluated from the available toxicological data and the physicochemical properties as suggested by the REACH Guidance Chapter R.7c:

Molecular weight: 182

Water solubility: 11400 mg/L @ 20°C

Partition coefficient log Kow = 1.6

Vapor pressure : 0.39 Pa @ 20°C

 

ABSORPTION

Oral

Generally, oral absorption is favored for molecular weights below 500 g/mol. This characteristic combined with the moderate lipophilic log Pow value and water solubility allow dissolution of DMDO in the gastro-intestinal fluids and contact with the mucosal surface.

In an acute oral toxicity study performed on rats, DMDO lead to a LD50 between 50 and 300 mg/kg bw. Furthermore, repeated administration of DMDO in a subacute toxicity study and a reproduction/developmental toxicity screening study indicate that the compound, and/or its metabolites, were bioavailable.

Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, the rates of absorption of DMDO were 50% for both a dose of 1 and 1000 mg (Danish QSAR database).

 

Inhalation

Based on the vapor pressure of approximately 0.39 Pa, DMDO vapors might not become available for inhalation to a significant extend. Nevertheless, If the substance would reach the lungs, absorption directly across the respiratory tract epithelium by passive diffusion is likely to occur due to its log Pow value and water solubility.

 

Dermal

Based on physico–chemical properties, DMDO is expected to penetrate skin as the logPow value and water solubility favor dermal penetration. It is general accepted that if a compound’s water solubility falls between 100-10000 mg/L, absorption can be anticipated to be moderate to high. Moreover, for substances with a logPow between 1 and 4, both penetration into stratum corneum and partition into the epidermis are likely to occur. However, these are not further supported by the results achieved from an acute dermal toxicity study performed on rats. During this study, no test item related mortality and clinical sign were observed. The LD0 was above 2000 mg/kg bw. Moreover, DMDO did not cause skin irritation and sensitization, which in turn may favor direct absorption into the systemic circulation.

The dermal absorption of DMDO was estimated with IH SkinPerm v2.04 model (AIHA, 2018). Compared to in vitro data from OECD 428 studies, IH skinPerm allowed the estimation of the dermal absorption rate with a good confidence and a low frequency of underestimation for liquids (Arkema’s internal validation study, 2018). According to the data input, IH SkinPerm v2.04 model leads to the following results:

 

 

Instantaneous deposition

End time observation 8 hr

Deposition over time

End time observation 8 hr

Total deposition (mg) or deposition rate (mg/cm²/hr)

1000

1

Fraction absorbed (%)

8.74

1.09

Amount absorbed (mg)

87.4

Lag time stratum corneum (min)

57.6

Max. derm. abs. (mg/cm²/h)

0.00547

 

Therefore, according to the REACH Guidance, default values of 50, 10 and 100% will be assumed of the oral, dermal and inhalation absorption of DMDO.

 

DISTRIBUTION and METABOLISM

According to the REACH Guidance, as a small molecule a wide distribution of DMDO is expected. This assumption is confirmed by the changes in spleen shown in the repeated dose toxicity studies in rats following oral application.

 

ELIMINATION

According to the REACH Guidance, the n-Octanol/water partition coefficient is not suggestive of accumulation of unchanged DMDO in fatty tissues subsequent to absorption. Therefore, no potential for bioaccumulation is to be expected for DMDO.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information