Hair Analysis Panel Discussion: Section 5.1
5.1 Pharmacokinetic Issues
The group acknowledged that little is known about the transfer kinetics of substances into hair (i.e., their "normal" percolation or rate of appearance in hair). Factors such as transit times, pools in the body, permeability of basal membranes, and co-factors that may be involved in transit are not known. Without this knowledge, interpretation of hair analysis results is greatly limited. Individual panelist input focused on possible ways to fill data gaps. Specifically:
Hair is a nonvascular tissue (separate from liquid phase transfer
kinetics). Understanding the rate of uptake in the hair, if any,
for substances of interest is of critical importance. Experimental
models are needed (RB, MK).
Implanting human hair on hairless mice, administering a radioactive
isotope, and following its movement to hair may be an effective
method for determining the incorporation of metals into hair (TC).
Studying the uptake of arsenite used in the treatment of leukemia
might be a possible human model to use to increase our understanding
of pharmacokinetics and dose-response relationships, realizing that
administered doses are much higher than they would ever be expected
in an environmental setting (MK).
Identifying the "transportable" form or metabolite(s) of substances
of interest may provide the best biomarker. Methyl mercury may serve
as a model. The key is understanding the transport mechanism. It
may be worthwhile to pursue organo metals and their behavior (e.g,
dimethyl arsenic acid, butyl tin); they may serve as more unique
markers of exposure (TC, MK, SS, LW).
When interpreting data, studying nutritional status should be
considered because it may play a role in the uptake and distribution
of metals. For example, iron and calcium can increase the uptake
of lead into the hair. Zinc levels in hair may be high in "failure
to thrive" cases because hair has stopped growing (LW, SS).
Obtaining data to better correlate exposure, blood/urine, and hair levels would enable a better understanding of the relationship of elements in the various body compartments. It would help correlate external concentration with internal doses. Few such data exist, with the exception of NHANES data, which evaluate lead levels across hair, blood, and urine (which correlated poorly). It was speculated that such substance-specific relationships could be studied further as part of the NHANES program (DP, LW).