The Challenge Test for Mercury?
1Challenge Tests for Mercury
Does the “Challenge Test” really show you the “bodyburden” of mercury??
Christopher W. Shade, Ph.D.
For over two decades now, many clinical metals toxicologists have been relying on “challengetests,” also called provocation tests, to diagnose mercury and other metal toxicities. The
diagnostic premise of the testing is that it shows the “body burden” of the individual – that poolof deeply held metals that represents our lifetime accumulation of unexcreted metals.
The literature examining the challenge tests ranges from the years 1991 through 2001 and has
thus far failed to find any evidence of the challenge tests revealing any more than recent
exposures, and in some instances (Frumkin et al, 2001) failing to see exposures made clear byambient testing. Recently, challenge tests have come under fire from federal authorities as adiagnostic tool. The problem is not really that the challenge tests have no use (especially inthe case of lead, where EDTA challenge testing is documented to have slightly better
correlations with bone lead than a do blood lead measurements, or the case of gadolinium
where levels in blood and urine are undetectable without EDTA provocation); the problem isinstead the way they are generally used and interpreted. There are many practitioners who
use the data from challenge tests in scientifically and clinically valid ways, but in general use
the challenge test has three main flaws:
1. The propagation of the myth of a special relevance of the pool identified by thechallenge (i.e. “body burden”) and the yes/no interpretation (i.e. “I found mercury in thepatient”)
2. The use of a non-challenged reference range to compare the challenged test to; this isprobably the biggest problem from a regulatory standpoint since there is such obvious
potential for over-treatment
3. The lack of standardization of the challenge conditions
a. DMPS has very different strength and specificity than DMSA
b. IV vs. oral administration has vastly different pharmacokinetics
c. Use of adjuncts such as EDTA, glutathione, and glycine vastly changes thedynamics of the test and its output
The measurement of mercury in the body and extrapolation to body burden and toxic
conditions is a very complicated field, requiring acute clinical discernment, including integrationof patient history, current exposures, symptomology, and effect of co-morbidities. The
simplification and deification of the challenge test is no longer serving the evolution of the fieldof clinical metals toxicology, and it is now time for the adoption of better tools.
At Quicksilver Scientific, we have develop advanced mercury testing that 1) identifies different
sources of mercury by measuring the relative amounts of the two main forms of mercury in thebody, methylmercury and inorganic mercury, and 2) quantifies excretion capabilities for those
two forms. Unfortunately, instead of being welcomed by the community, there has been quite
a bit of angry backlash and accusation, born mostly of a stubborn refusal to move forward. So
to the question, “Does the challenge test really show you ‘body burden’ of mercury?”;
let’s see what the scientific literature says…

The Challenge Test for Mercury?
2Article #1 – DMSA Challenge of Post-Industrial Exposure versus General Population

Studies of DMPS show that thereis a difference in urinary excretion
between exposed and unexposedgroups.
In the Frumkin study, there was adifference between in excretion
PRIOR to DMSA treatment (pvalues); however following
treatment, there was none.
Ambient levels were actually a
BETTER predictor of past
exposure than challenged levels.
Also, in this study, there was no
signal from amalgam surfaces
during DMSA treatment.
However, such a signal is clearly
evident in studies with DMPS
treatment.

Discussion: Tow main points come out of this study. One is the inability of thechallenge test to show historical exposure, and this is with a group that wasindustrially exposed to extreme levels of mercury. The second point is the inequalityof DMSA and DMPS. Though many people know that DMPS is stronger than DMSA, wehave seen with mercury speciation analysis that DMSA biases toward methylmercuryandDMPSArticle#2 biases toward inorganic mercury.

The Challenge Test for Mercury?
3This DMPS study aimed to show longterm body burden in older dentists versus
acute exposure in short-term factoryworkers. The test aimed to show longterm accumulation in dentists versus
short-term acute exposure in industrial
workers. The challenge test failed toshow a different pattern than the prechallenged testing of plasma and urine
showed – i.e. the DMPS challenge justamplified previously-existing signals.

Above: Linear correlation between pre-challenged urine and pre-challenged plasma

The Challenge Test for Mercury?
4

Above: Linear Correlation between 300mg-PO DMPS-challenged urine and prechallenged urine.

Discussion: Clearly DMPS is very effective in mobilizing inorganic mercury, but themobilization merely amplified a signal that existed in the ambient data. No “bodyburden” was revealed.

The Challenge Test for Mercury?
5
Article #4 –Both blood and non-provoked urine
show the differences in the populations,even three years after removal from thesource. Pre- and Post-challenged urines
were very well correlated.

Article #4 –

The Challenge Test for Mercury?
6Discussion: DMPS challenge certainly shows recent loading, but fails to show difference
between people who never had amalgam and people who formerly had amalgam and people
who never had amalgam, thus failing to show historical exposure. A closer analysis of rate of
excretion during chelation shows the difference between amalgam-free and amalgam
removed, but this would not be obvious upon clinical observation.