Let adequate sensitivity be defined as the ability to
detect a uniformly distributed whole-body dermal dose at or above 1% of a
nominal chronic No-Effect Level [NOEL] of 100 mg/kg; that is a desirable dermal
dose measurable threshold of 1 mg/kg. For a "standard" 70 kg person, 1
mg/kg equates to a 70 mg deposited dose.
The comparison below is generous toward biological monitoring because a 10%
absorption fraction is actually a large fraction. Because blood in particular is
a transient compartment, the real LOQ is likely to be 10 or 100 times that shown
4. Thus, the proportionate sensitivity of the patch dosimeter is likely to
be better than the other options by factors of at least 3 to more than 30 fold.
70 mg evenly distributed on the 1.92 m2 of a
"standard" person's skin, is 3.65 µg/cm2 (line D in Table
4). A pair of 3" dosimeters (of approximately 50 cm2
collecting area) at a given location would receive approximately 182 µg
(line F). If the laboratory sample were extracted into a volume of 50 mL (a
practical cost option), the resulting limit of quantification (LOQ) is 3.6
µg/mL. If the laboratory sample were concentrated into a volume of 10 mL
(at some additional cost), the resulting limit of quantification (LOQ) is 18
µg/mL (ppm on line H). Of course when a dermal distribution is non-uniform,
one (or more) dosimeter(s) may have easily measurable levels while those on
other body locations could be undetectable, leading to issues of how to
interpret non-detectable samples.
Assuming 10% of a 70 mg dose is instantaneously absorbed (line A in Table
4) into the 5 L of blood in a typical human body, the blood
concentration would be 1.4 µg/mL (line D). If a large 10 mL blood sample
were collected, the initial sample would contain 14 µg (line F). The LOQ
would be proportional to the above sample mass divided by the extraction
volume which will be assumed herein to be the same for blood or urine as for
a dosimeter extraction solvent. One of the problems with blood is its
complex nature, making it difficult to get high extraction efficiencies; a
higher initial solvent extraction volume would have to be reduced to 10 mL.
Another problem is that blood is a transient metabolic compartment within
the body; an absorbed molecule would only stay in the blood long enough to
be transported to a target or metabolic organ such as the liver. Thus, only
a fraction (perhaps 1% to 10%) of the absorbed dose will be in the blood at
any sampling time.
Assuming the same 10% of a 70 mg dose is absorbed and all of it is
excreted (it is possible although not likely for more than 100% of a molar
equivalent metabolite to be excreted) into 1.5 L of urine in 24-hours, the
urine concentration would be 4.67 µg/mL (line D in Table
4). If the entire specimen were processed, the sample would contain 7000 µg;
if only a more normal 100 mL aliquot were processed, the sample would
contain 467 µg (line F). And again assuming the solvent extraction volume
is reduced to 10 mL (line G), leaves a 47 ppm LOQ.
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