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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

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Percutaneous absorption
Parameter:
percentage
Absorption:
ca. 0.4 %
Remarks on result:
other: permeability coefficient (Kp) = 0.0071 cm/hour

Any other information on results incl. tables

The model predicted a permeability coefficient of 0.0071 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]                             

(Kp is the permeability coefficient; Km is 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 Kp for the neat substance, the aqueous Kp has to be divided by the stratum corneum/water partition coefficient (Km). The Km(stratum corneum/water) for TAME was calculated to be 3.34 by using the QSAR described by ten Berge (2009).

Since the aqueous Kp was 0.0071 cm/hour, the Kp for neat liquid is: 0.0071 / 3.34 = 0.0021 cm/hour.

 

To derive the initial absorption of neat TAME, the Kp for neat liquid has to be multiplied by the density. The density of TAME is 770 mg/cm3.

Therefore the initial absorption of neat TAME is 0.0021 cm/hour x 770 mg/cm3= 1.6 mg/cm2/hour

 

The above mentioned explanation can alternatively be expressed as follows:

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

(rholiquid is 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]

(Kp is the permeability coefficient; Km is 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 TAME is 770 mg/cm3; the Kp and Km were determined to be 0.0071 cm/hour and 3.34, respectively.

As such, the initial absorption (mg/cm2/hr) = 770 * 0.0071/3.34 = 1.6 mg/cm2/hour

 

In conclusion, the initial absorption of neat TAME is 1.6 mg/cm2/hour.

Correction for evaporation

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

Based on the REACH Guidance appendix R14.1, it was calculated that the evaporation rate of TAME is 470 mg/cm2/hour.

Therefore, of each dose of TAME exposed to the skin, 0.34% (1.6/470) is available for skin absorption because of the majority of the TAME evaporates before absorption can occur.

As such, the percentage of dermal absorption of TAME is assumed considered to be 0.34%. For the calculation of the dermal DNEL, a percentage of dermal absorption of 0.4% is used (which is worse-case).

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