Reaction mass of 2-methoxy-2-methylbutane and 4-methoxypent-2-ene

Dermal absorption

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

Test material information

Constituent 1

Reference substance name:

2-methoxy-2-methylbutane

EC Number:

213-611-4

EC Name:

2-methoxy-2-methylbutane

Cas Number:

994-05-8

Molecular formula:

C6H14O

IUPAC Name:

1,1-dimethylpropyl methyl ether

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:

 K_p= K_m * D/h                                                                         [1]                             

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

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

 

To derive the initial absorption of neat TAME, the K_p 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) = rho_liquid* (D/h)                                       [2]

(rho_liquid 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 = K_p/K_m                                                                                          [3]

(K_p is the permeability coefficient; K_m is the stratum corneum/water partition coefficient)

 

Substitution of equation 3 in 2 gives:

Initial absorption (mg/cm²/hr) = rho_liquid* K_p/K_m                                                                  [4]

 

The density of TAME is 770 mg/cm³; the K_p and K_m 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.