Ethyl acrylate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Principles of method if other than guideline:

Experimental Design::
14C-Acrylic acid or 14C-ethyl acrylate was applied to freshly excised skin from male adult mice mounted in Franz Diffusion Cells. These pilot studies were designed to determine the optimum sampling times and extent of recovery of the volatile materials. In addition Tyrode's bathing solution were compared with a bathing solution consisting of a 6% aqueous solution of Volpo 20, a non-ionic surfactant.. The test compounds were applied either neat or as a 10 or 1% solution in acetone to determine the effects of concentration and vehicle on the rate and extent of dermal penetration.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl acrylate

EC Number:

205-438-8

EC Name:

Ethyl acrylate

Cas Number:

140-88-5

Molecular formula:

C5H8O2

IUPAC Name:

ethyl acrylate

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male

Details on test animals or test system and environmental conditions:

Species/Strain: male mouse skin (CD-1; Charles River Kingston; Stone Ridge, N.Y.).

B. Animals/Husbandry:
1. Animals:
Experiment 1: Eighteen (18) male CD-i mice born 09/20/84, were selected from a group of mice specifically ordered for this study. They were received from Charles River Kingston (Stone Ridge, N.Y.) on 10/09/84, uniquely identified using ear tags, and quarantined/ acclimated for at least one week prior to randomization.
Experiment 2: Eighteen (18) male CD-1 mice born 09/20/84, were selected from a group of mice specifically ordered for this study. They were received from Charles River Kingston (Stone Ridge, N.Y.) on 10/09/84, uniquely identified using ear tags, and quarantined/ acclimated for at least one week prior to randomization.
Experiment 3: Six (6) male CD-1 mice were selected from a group of mice specifically ordered for this study. They were received from Charles River Kingston (Stone Ridge, N.Y.), uniquely identified using ear tags, and quarantined/ acclimated for at least one week prior to randomization.
Experiment 4: Six (6) male CD-1 mice were selected from a group of mice specifically ordered for this study. They were received from Charles River Kingston (Stone Ridge, N.Y.) uniquely identified using ear tags, and quarantined/ acclimated for at least one week prior to randomization.
Consecutive animal identification numbers were assigned by the Rohm and Haas Company Laboratory Animal Science Unit (LASU) in the form "84-#####."

Administration / exposure

Details on in vitro test system (if applicable):

Skin Sections:
All mice were killed by cervical dislocation. The hair on the back was removed using electric clippers equipped with a "fine" blade (Oster USA, model 42, Milwaukee, WI.). A 4x4 cm section of whole skin was removed with a scalpel, and placed on "Whatman No. 1" filter paper moistened with 0.9% saline.

Franz Diffusion Cells:
The skin sections were mounted in 15 mm (internal diameter) Franz Diffusion Cells (Crown Glass Co., Somerville N.J.). The skin was bathed from beneath with Tyrode's solution (Tyrode, M.V., Arch. Int. Pharmacodyn. Ther. 20:205, 1910) or 6% Volpo 20 (Croda Inc., N.Y. Lot. No. 8058) at 37°C. The bathing solutions were stirred under gentle vacuum for 30 min before use. Each cell was closed with a ground glass stopper immediately after dose application and remained closed throughout the exposure period. Temperature was maintained by the circulation of thermostatically controlled water (37°C) into the jacket surrounding the chamber with the bathing solution in it. The temperature of the bathing solutions was maintained by stirring with a Teflon covered magnetic stirring bar.

Results and discussion

Total recovery:

Results presented below are for the EA only as this dataset is for Ethyl Acrylate.
1. Experiment 1:
A total of 31-64% of the dose of ethyl acrylate was recovered at the end of the 24 hr study. Between 8 and 19% of the dose could not be wiped off and remained in/on the skin. A total of 19-37% of the dose had penetrated the skin and was recovered in the bathing solution by 24 hr. The percent of dose recovered from the bathing solution at 24 hr was greater at the low concentrations (1 and 10%) compared to the high concentration (100%).

2. Experiment 2:
Experiment 2 was a repeat of Experiment 1 with Volpo substituted for Tyrode's as the bathing solution.
A total of 57-83% of the dose of ethyl acrylate was recovered at the end of the 24 hr study. Between 9 and 21% of the dose could not be wiped off and remained in/on the skin. A total of 40-55% of the dose had penetrated the skin and was recovered in the bathing solution by 24 hr. The percent of dose recovered from the bathing solution at 24 hr was comparable among the applied concentrations of EA. Penetration of EA with Volpo as the bathing solution was greater than with Tyrode's at all concentrations.

3. Experiment 3:
Charcoal traps contained 26-41% of the dose of ethyl acrylate at 5 hr. Total recovery at the 100% dose was only 59% as compared to 105% for the 1% dose. This may have been due to a loss of 14C-material from the traps or to saturation of the binding capacity of the charcoal.

4. Experiment 4:
Charcoal traps contained 23-26% of the dose of ethyl acrylate at 5 hr. Total recovery was 96 and 88% for the 1 and 100% dose, respectively.

Percutaneous absorption

Percutaneous absorption 1

Time point:

24 h

Dose:

Experiment 1

Parameter:

amount

Absorption:

>= 19 - <= 37 %

Remarks on result:

other: A total of 19-37% of the dose had penetrated the skin and was recovered in the bathing solution by 24 hr.

Percutaneous absorption 2

Time point:

24 h

Dose:

Experiment 2

Parameter:

amount

Absorption:

>= 40 - <= 55 %

Remarks on result:

other: A total of 40-55% of the dose had penetrated the skin and was recovered in the bathing solution by 24 hr.

Percutaneous absorption 3

Time point:

5 h

Dose:

Experiment 3

Parameter:

amount

Remarks on result:

other: Charcoal traps contained 26-41% of the dose of ethyl acrylate at 5 hr.

Percutaneous absorption 4

Time point:

5 h

Dose:

Experiment 4

Parameter:

amount

Remarks on result:

other: Charcoal traps contained 23-26% of the dose of ethyl acrylate at 5 hr.

Applicant's summary and conclusion

Conclusions:

A technique was been developed for measuring the rate and extent of EA dermal absorption, and the rate of EA evaporation from mouse skin in vitro.
At each dose, EA penetrated the skin generally more rapidly and to a greater extent with Volpo as the bathing solution (40 to 55% at 24 hr) compared to Tyrode's (19 to 37%). EA, dissolved in acetone, penetrated more rapidly and to a greater degree than neat (100%) EA. Approximately 23 to 41% of the dose evaporated off the skin and was retained by the charcoal trap in the cap.

Executive summary:

The in vitro dermal absorption of 14C-acrylic acid (AA;TD 84-998; 0.61 mCi/ml) and 14C-ethyl acrylate (EA; TD 84-998;

0.41 mCi/m1) was evaluated in excised male mouse skin (CD-1; Charles River Kingston; Stone Ridge, N.Y.). Four experiments were performed:

Exp #1: 14C-AA and 14C-EA (1, 10, and 100%; acetone vehicle); 25 ul aliquots; Tyrode's bathing solution; 24 hr exposure.

Exp #2: 14C-AA and 14C-EA (1, 10, and 100%; acetone vehicle); 25 ul aliquots; Volpo bathing solution; 24 hr exposure.

Exp #3: 14C-EA (1 and 100%); 25 ul aliquots; Tyrode's bathing solution; 5 hr exposure; charcoal traps utilized

Exp #4: same as Exp #3, except charcoal traps were extracted immediately after collection.

For the purposes of this dataset, only the EA results are discussed below.

A technique has been developed for measuring the rate and extent of EA dermal absorption, and the rate of EA evaporation

from mouse skin in vitro.

At each dose, EA penetrated the skin generally more rapidly and to a greater extent with Volpo as the bathing solution (40 to 55% at 24 hr) compared to Tyrode's (19 to 37%). EA, dissolved in acetone, penetrated more rapidly and to a greater degree than neat

(100%) EA. Approximately 23 to 41% of the dose evaporated off the skin and was retained by the charcoal trap in the cap.