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Dermal absorption

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Administrative data

Endpoint:
dermal absorption
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: QSAR, published in peer reviewed literature, adequate for assessment.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Reference
Reference Type:
publication
Title:
A simple dermal absorption model: Derivation and application
Author:
ten Berge, W.
Year:
2009
Bibliographic source:
Chemosphere 75, 1440-1445

Materials and methods

Principles of method if other than guideline:
Dermal absorption was predicted using a QSAR.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethoxy-2-methylpropane
EC Number:
211-309-7
EC Name:
2-ethoxy-2-methylpropane
Cas Number:
637-92-3
Molecular formula:
C6H14O
IUPAC Name:
2-ethoxy-2-methylpropane

Results and discussion

Percutaneous absorption
Parameter:
percentage
Absorption:
ca. 0.3 %
Remarks on result:
other: Permeability coefficient (Kp) = 0.0063 cm/hour

Any other information on results incl. tables

The model predicted a permeability coefficient of 0.0063 cm/hour.

Derivation of the initial dermal absorption

 

As is deduced in EHC 235 (2006), the following equation is true:

 Kp= Km * D/h                                                                 [1]                             

(Kpis the permeability coefficient; Kmis the pseudo-homogeneous partition, or distribution coefficient between the stratum corneum and the vehicle; D is the effective diffusion coefficient; h is the membrane thickness)

 

To derive the Kpfor the neat substance, the aqueous Kphas to be divided by the stratum corneum/water partition coefficient (Km). The Km(stratum corneum/water) for ETBE was calculated to be 3.12 by using the QSAR described by ten Berge (2009).

Since the aqueous Kpwas 0.0063 cm/hour, the Kpfor neat liquid is: 0.0063 / 3.12 = 0.0020 cm/hour.

 

To derive the initial absorption of neat ETBE, the Kpfor neat liquid has to be multiplied by the density. The density of ETBE is 750 mg/cm3.

Therefore the initial absorption of neat ETBE is 0.0020 cm/hour x 750 mg/cm3= 1.5 mg/cm2/hour

 

The above mentioned explanation can alternatively be expressed as follows:

Initial absorption (mg/cm2/hr) = rholiquid* (D/h)                                       [2]

(rholiquidis the density of the liquid (mg/m3); D is the diffusion coefficient of the liquid in the stratum corneum (cm2/hr); h is the thickness of the stratum corneum)

 

D/h = Kp/Km                                                                                          [3]

(Kpis the permeability coefficient; Kmis the stratum corneum/water partition coefficient)

 

Substitution of equation 3 in 2 gives:

Initial absorption (mg/cm2/hr) = rholiquid* Kp/Km                                                                  [4]

 

The density of ETBE is750 mg/cm3; the Kpand Kmwere determined to be 0.0063 cm/hour and 3.12, respectively.

As such, the initial absorption (mg/cm2/hr) = 750 * 0.0063/3.12 = 1.5 mg/cm2/hour

 

In conclusion, the initial absorption of neat ETBE is 1.5 mg/cm2/hour.

Correction for evaporation

Since ETBE is very volatile, a strong competition between evaporation and skin absorption will occur in case the skin is exposed to neat ETBE.

Based on the REACH Guidance appendix R14.1, it was calculated that the evaporation rate of ETBE is 602 mg/cm2/hour.

Therefore, of each dose of ETBE exposed to the skin 0.25% (1.5/602) is available for skin absorption because of the majority of the ETBE evaporates before absorption can occur.

As such, the percentage of dermal absorption of ETBE is assumed considered to be 0.25%. For the calculation of the dermal DNEL, a percentage of dermal absorption of 0.3% is used (which is worst case).

 

In conclusion, the percentage of dermal absorption of ETBE is 0.3%. This value is used for the calculation of the DNEL for dermal exposure.

References

 

EHC 235 Environmental Health Criteria 235: Dermal Absorption, World Health Organization 2006.

 

ten Berge W, 2009. A simple dermal absorption model: derivation and application. Chemosphere 75(11), 1440-5.

Applicant's summary and conclusion