dermatology - DermaAmin

Basics of Metal Skin Penetration: Scope and Limitations 27
thus a permeability coefficient characterizing the compound can only be
calculated through prior conversion as given below, yielding an ‘‘apparent’’
Kp. When diffusion experiments are reported as the percent of the applied
dose, disappearance over a time interval t is given either as [% lost/(time)],
or as a first-order disappearance constant, k (min 1 ), for that time interval.
Assuming steady-state conditions, either of these parameters can then be
converted to the disappearance over a time interval t and is given either
as [% lost/(time)], or as a first-order disappearance constant, k (min 1 ),
for that time interval. Assuming steady-state conditions, either of these
parameters can then be converted to the permeability coefficient, Kp. That is
Kp ¼ J ð% lossÞ
¼
DC ½timeðhrÞŠ
CA VA
¼
100 A CA
ð% lossÞ
½timeŠ
VA
100 A
where J (mol/cm 2 /hr) is the chemical flux, C (mol/L) is the chemical concentration
gradient across the skin (which is reasonably assumed to be equal
to the applied concentration C A), V A (mL) is the volume of chemical solution
applied, and A (cm 2 ) is the area of application.
It follows, therefore, that, for a five-hour application of 1 mL of solution
to a 3.14 cm 2 area of skin
Kp;5 ¼ ð% lossÞ 5
1570
Kp ¼ J ðfraction lostÞ
¼
DC ½timeðhrÞŠ
CA VA
A CA
where, assuming first-order disappearance kinetics (characterized by rate
constant, k, min 1 ),
ðfraction lostÞ ¼1 expf 60 k ½timeðhrÞŠg
Thus, for a one-hour application of 1 mL of solution to 3.14 cm 2 of
skin, Kp is calculated as
Kp ¼ð1 expð 60 kÞÞ=3:14
Together with the toxicity of a chemical the percent of a substance
absorbed is the second most critical factor for risk assessment; it gives a measure
for human exposure and an indication of the amount potentially
absorbed in (the worst) case of total body immersion. For a chemical applied
at 100 mg/cm 2 , at 1% absorption, for instance, the extent of systemic exposure
to the compound applied on the entire body area of an average human
adult (18,000 cm 2 ) would be in the milligram range in the course of 24 hours.
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