In-vitromethods for testing dermal absorption and penetration of toxic gases

Abstract

This technical note provides details of an experimental technique for in-vitro skin studies with atmospheric chemical challenge. There appear to be major evidence gaps in relation to dermal exposure of gases. We describe a modification of standard OECD protocols for an atmospheric delivery system which can be used to understand interaction of toxic gases and the skin. The system can be used to examine the mechanisms by which skin uptake occurs. Auxiliary components which allow for parameter variation such as temperature and relative humidity are also described. Methodology presented in this technical note uses examples of gas challenges (ammonia, chlorine) to illustrate its application to gases of differing physicochemical properties. This adapted protocol can be applied in the context of HAZMAT scenarios involving atmospheric toxic chemical release and dermal absorption potential under variable exposure conditions.

Is the skin an important exposure route for workers during cyanogen fumigation?

“…The physicochemical properties of cyanogen are shown in Table . The overall experimental approach addressed skin penetration and absorption (defined as the amounts passing through the epidermal layer, and retained in the epidermal layer, respectively), and the moderating effects of clothing and a period of post‐exposure ventilation using fresh air, as described previously …”

“…Franz diffusion cells with a diffusion‐available surface area of 0.64 cm 2 and a receptor volume of 5 mL were combined with a donor compartment modified for flow‐through gas delivery to the surface of the skin . Following donor consent (ethics approval #273.10 SACHRE), freshly excised human abdominal skin was obtained from surgical procedure.…”

“…The overall experimental approach addressed skin penetration and absorption (defined as the amounts passing through the epidermal layer, and retained in the epidermal layer, respectively), and the moderating effects of clothing and a period of post-exposure ventilation using fresh air, as described previously. 11 An OECD guideline for the conduct of skin absorption studies was adopted, 12 using fresh human skin from abdominoplasty surgery. Transdermal permeation experiments were set up with skin being mounted in static Franz diffusion cells and placed in a stirrer unit (PermeGear, Hellertown, PA, USA).…”

“…Transdermal permeation experiments were set up with skin being mounted in static Franz diffusion cells and placed in a stirrer unit (PermeGear, Hellertown, PA, USA). 11 Cyanogen was delivered directly to the skin surface from a gas cylinder (10 000 ppm in nitrogen, MESA, Santa ana, California, USA) via a test atmosphere generator. 13 Lower concentrations were produced by dilution of the certified gas mixture with air, using calibrated rotameters.…”

“…4 Franz diffusion cells with a diffusion-available surface area of 0.64 cm 2 and a receptor volume of 5 mL were combined with a donor compartment modified for flow-through gas delivery to the surface of the skin. 11,14 Following donor consent (ethics approval #273.10 SACHRE), freshly excised human abdominal skin was obtained from surgical procedure. Within one hour of excision from the donor, the epidermis was harvested from full thickness skin, and prepared epidermal sheets were stored at −20 ∘ C until use (up to 2 months).…”