of 48
Current View
Multiple Chemical Sensitivity:
Toxicological and Sensitivity Mechanisms
Martin L. Pall
Professor Emeritus of Biochemi
stry and Basic Medical Sciences,
Washington State University an
d Research Director, The Tenth
Paradigm Research Group
638 NE 41st Ave.
Portland, OR 97232-3312 USA
Cases of multiple chemical sensit
ivity (MCS) are reported to be
initiated by seven classes of chemical
s. Each of the seven acts along a
specific pathway, indirectly producin
g increases in NMDA activity in the
mammalian body. Members of each
of these seven classes have their
toxicant responses lowered by NMDA
antagonists, showing that the
NMDA response is import
ant for the toxic action
s of these chemicals.
The role of these chemicals acting as
toxicants, in initiating cases of
MCS has been confirmed by genetic
evidence showing that six genes
that influence the metabolism of
these chemicals, all influence
susceptibility to MCS. It is likely
that chemicals act along these same
pathways, leading to increased NM
DA activity when they trigger
sensitivity responses in MCS patients.
The chronic nature of MCS and also related multisystem illnesses is
thought to be produced by a bioche
mical vicious cycle mechanism, the
NO/ONOO- cycle, which is initiated by various stressors that increase
nitric oxide and peroxynitrite levels (with some but not others acting
via NMDA stimulation). The NO
/ONOO- cycle is based on well
documented individual mechanisms.
The interaction of this cycle with
previously documented MCS mechanis
ms, notably neural sensitization
and neurogenic inflammation, expl
ains many of the previously
unexplained properties of MCS. This overall mechanism is also
supported by physiological corre
lates found in MCS and related
multisystem illnesses, objectively me
asurable responses to low level
chemical exposure in MCS patients,
many studies of apparent animal
models of MCS and also evidence
from therapeutic trials of MCS-
related illnesses. Some have argued
that MCS is a psychogenic illness,
but this view is completely inconsis
tent with this diverse data on MCS
and related illnesses and the literatur
e claiming psychogenesis of MCS
is deeply flawed. In addition, two ra
re predictions that can be used to
test psychogenesis both lead to
rejection of the psychogenic
hypothesis. While the NO/ONOO- cycle mechanism for MCS is
supported by many different observa
tions, there are also multiple
areas where further
study is needed.
Key Words: Peroxynitrite; oxidative stress; excitotoxicity;
mitochondrial dysfunction; long term potentiation; chronic fatigue
syndrome/myalgic encephalomyelitis; fibromyalgia
Multiple chemical sensitivity (1) (MCS), also known as chemical
intolerance, multiple chemical sensitivities, chemical sensitivity, or
toxicant induced loss of tolerance (T
ILT) is an illness or disease where
previous chemical exposure appear
s to initiate the wide ranging
sensitivities characteristic of MCS.
The inference that cases of MCS
are initiated by previous chemical exposure is implied by the TILT
name (2). Case initiation by such
previous chemical exposure was also
a requirement for a person to fit the
Cullen case definition (3) for MCS.
The role of previous chemical ex
posures is widely discussed in the
influential Ashford and Miller book
which reviewed MCS (4) and at
least 50 studies have shown that such
previous chemical exposure is
characteristic of and appears to in
itiate most MCS cases (reviewed in
1,4-6). Some have claimed that MCS is a psychogenic illness and
have advocated the name idiopathic
environmental intolerance (IEI).
This name argues, in essence, that
chemical exposure is not involved
in initiating such sensitivity and th
at we have no idea what the cause
may be, that is that it is idiopath
ic. Both of these contentions have
been vigorously challenged (1). Th
is paper is primar
ily a separately
written and much shorter version of
reference 1 and the reader is
referred to that study for a much
more extensive documentation of
many of the observations contained below.
What Types of Chemicals Initiate
Cases of MCS and How Can They Act
as Toxicants?
Perhaps the largest single challenge in understanding MCS is how can
the diverse chemicals implicated
in initiating cases of MCS and
triggering sensitivity symptoms in those already sensitive act to
produce a common response in the
body? The MCS skeptic, Ronald
Gots has challenged MCS researcher
s, arguing that the diverse types
of chemicals reportedly involved cannot possibly produce a common