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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Recent study, well reported in open literature.

Data source

Reference
Reference Type:
publication
Title:
Percutaneous absorption of 5 glycol ethers through human skin in vitro.
Author:
Venier M, Adami G, Larese F, Maina FG, Renzi N.
Year:
2004
Bibliographic source:
Toxicology in Vitro 18, 665–671.

Materials and methods

Principles of method if other than guideline:
Absorption across full thickness human skin was evaluated in vitro. Skin membranes were placed in static diffusion cells and both neat and in water diluted substance was included in the donor chamber for 8 h. Concentrations in the receptor chamber were measured by GC/FID.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Source: Merck Schuchard
Purity: >98%.
Radiolabelling:
no

Administration / exposure

Vehicle:
other: 6.65% in 0.9% NaCl in water.
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: Surgical waste. Male and females, 47–62 years old.
- Ethical approval if human skin: no information.
- Type of skin: Human abdomen full thickness.
- Preparative technique: Subcutaneous fat removed and hair shaved.
- Thickness of skin (in mm): 1mm average.
- Membrane integrity check: Method of storage shown not to change permeability in separate studies (Franz, 1975; Lawrence, 1997).
- Storage conditions: -25 C for a period up to 4 months.

PRINCIPLES OF ASSAY
- Diffusion cell: static diffusion cells following the Franz Method. 3.29cm2 exposed skin area.
- Receptor fluid: 14ml 0.9% NaCl solution in water, stirred continuously.
- Solubility of test substance in receptor fluid: fully miscible.
- Static system: yes
- Test temperature: 32C (comparable to hand temperature.)
- Occlusion: yes
- Other: Substance was applied as neat liquids (0.2ml) or as a saturated aqueous solutions (6.65% v/v) under infinite dose. Aliquots of 1.5 ml drawn from receiving solution of each cell by syringe at 0.5, 1, 2, 4 and 8 hr. This volume was immediately replaced by adding fresh saline solution. The samples were frozen until analysis by GC/FID analysis.

Results and discussion

Percutaneous absorptionopen allclose all
Remarks on result:
other: Average flux
Remarks:
Neat compound: 59±36µg/cm2/hr
Remarks on result:
other: Average flux
Remarks:
6.65% solution: 162±43µg/cm2/hr

Any other information on results incl. tables

Other reported data:

 Parameter  Neat solution  6.65% aqueous solution
 Lag time (h)  1.03±0.63 2.01±0.18
 Kp (µm/h)  6±4 32±8 
 Total recovered dose inreceptor fluid (% of dose)  3.35 41.8

Applicant's summary and conclusion

Executive summary:

In an in vitro skin permeation study, the rate of 2 -(2 -butoxyethoxy)ethyl acetate penetration in vitro through human skin was determined. The rate of flux of neat substance was measured at 59 ± 36ug/cm2/hr. The rate of flux of substance was approximately 2.5x faster when present as a saturated aqueous solution (6.65% v/v) but the lag time increased by a factor of 2.