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EC number: 215-572-9
CAS number: 1332-65-6
Copper content in receptor fluid samples following a single topical
application of test material to dermatomed human skin.
Results are expressed both as percent applied dose and as ng copper.
Cuprous oxide composite
Dose level (mg/cm2)
Termination time (h)
Swabbed at 6 h (y/n)
Amount absorbed (%)
Amount absorbed (ng)
Rate of absorption (ng/cm2/hr)
* Absorption ratio given with respect to cupric sulphate, using the
amount absorbed at 24 hours following a swab at 6 hours post-dosing.
Materials and Methods
The comparative in vitro dermal penetration of copper
through human skin was examined following the application of four
different copper containing formulations. Cuprous oxide composite
(approximately 1.05 mg/cm2), cuprous thiocyanate
(approximately 0.73 mg/cm2), copper powder (approximately
0.97 mg/cm2) and cupric sulphate (approximately 0.94 mg/cm2),
were applied at similar dose levels with respect to copper content.
Five static diffusion cells were prepared for each test
formulation at each sampling regime. Dermatomed membranes
(approximately 300 µm thickness) were maintained in the cells at
approximately 32°C. The integrity of the membranes was first tested
using tritiated water (3H20), and any cells
showing a permeability coefficient for water of greater than 3.5 x 10-3
cm/hr were considered damaged and therefore not reported. After removal
of the residual 3H20, the test formulation was
applied to the unoccluded skin samples at a rate of l0µl/cm2.
For each of the test substances there were three sampling
regimes. The first terminated at 6 hours after application of the test
substance, and the second was terminated at 24 hours after application
of test material. In each case the skin surface was swabbed at 6 hours
after application of the test substance to remove unabsorbed material
(representing a wash procedure at the end of a working day). The third
sampling regime terminated at 24 hours post-application but no swab was
performed. For each regime, the receptor fluid was sampled at
Results and Discussion
Comparison of the amount of copper absorbed through human skin
following the application of each test material formulation is best
assessed using the most occupationally relevant sampling regime (swab at
6 hours, receptor fluid collected at 24 hours post application).
The results may be summarised as follows:
% applied dose
The absorption rate (ng/cm2/h)
would normally be calculated from the steepest part of the absorption
profile, which is indicative of steady-state absorption. Since
the cells that were sampled at 6 hours gave the highest rate of
absorption (and are therefore the closest to steady-state absorption),
the absorption rate has been measured using these values.
The results may be summarised as
The level and rate of penetration of copper resulting from the
exposure of human skin to each of the test materials were compared
against those for cupric sulphate (see the ratios for % dose applied in
the table above). There was very little penetration of copper through
the skin from any of the test formulations. The absorption of copper
from the cuprous oxide composite, cuprous thiocyanate and cupric
sulphate formulations was similar with between 0.126 and 0.157% of the
dose being absorbed over the 24 hour period. The level of absorption
was lower from the copper powder formulation (0.038%). If all the
dermal penetration values for copper (6 hour exposure, 24 hour sampling)
are pooled, then the mean value is 0.1106% with a standard deviation of
0.067 (CV 60.94%). It should however be noted that there was some
variation in the data between cells. This was in part due to the fact
that the level of absorption was extremely low for all of the
formulations and the values obtained were very close to the LOQ level,
and in part due to the natural variation in absorption between
individual skin donors.
It is clear from the results that none of the copper compounds
tested readily penetrate human skin when applied as aqueous formulations.
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