Butane, 2-ethoxy-2-methyl-

Dermal absorption

Administrative data

Endpoint:

dermal absorption

Type of information:

(Q)SAR

Adequacy of study:

supporting 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-ethoxy-2-methylbutane

EC Number:

618-804-0

Cas Number:

919-94-8

Molecular formula:

C7H16O

IUPAC Name:

2-ethoxy-2-methylbutane

Results and discussion

Any other information on results incl. tables

The model predicted a permeability coefficient of 0.0835 cm/hour. For the calculation of the percentage absorption, an aqueous Kp of 0.0835 cm/hour was used.

Derivation of the initial absorption

 

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

 K_p= K_m* D/h                                                                         [1]                             

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

 

To derive the K_pfor the neat substance, the aqueous K_phas to be divided by the stratum corneum/water partition coefficient (K_m). The K_m(stratum corneum/water) for TAEE was calculated to be 16.3 by using the QSAR described by ten Berge (2009).

Since the aqueous K_pwas 0.0835 cm/hour, the K_pfor neat liquid is: 0.0835 / 16.3 = 0.00513 cm/hour.

 

To derive the initial absorption of neat TAEE, the K_pfor neat liquid has to be multiplied by the density. The density of TAEE is 764 mg/cm³.

Therefore the initial absorption of neat TAEE is 0.0835 cm/hour x 764 mg/cm³= 3.91 mg/cm²/hour

 

The above mentioned explanation can alternatively be expressed as follows:

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

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

 

D/h = K_p/K_m                                                                                          [3]

(K_pis the permeability coefficient; K_mi s 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 TAEE is764 mg/cm³; the K_pand K_mwere determined to be 0.0835 cm/hour and 16.3, respectively.

As such, the initial absorption (mg/cm²/hr) = 764 * 0.0835/16.3 = 3.91 mg/cm²/hour

 

In conclusion, the initial absorption of neat TAEE is 3.91 mg/cm²/hour.

Correction for evaporation

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

Based on the REACH Guidance appendix R14.1, it was calculated that the evaporation rate of TAEE is 219 mg/cm²/hour.

Therefore, of each dose of TAEE exposed to the skin 1.8% (3.91/219) is available for skin absorption because of the majority of the TAEE evaporates before absorption can occur.

As such, the percentage of dermal absorption of TAEE is assumed considered to be 1.8%. For the calculation of the dermal DNEL, a percentage of dermal absorption of 2% is used (as a worst case figure).

 

In conclusion, the percentage of dermal absorption of TAEE is 2%.

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.