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Links Between Multiple Chemical Sensitivity
and Asthma in a Rat Model
of Cholinergic Hypersensitivity: a Brief Review

Toxicology and Industrial Health
August 1999, Volume 15, Issue 5, Pages 517 - 521



Individuals with multiple chemical sensitivity (MCS) also commonly report
symptoms of asthma, but, as far as we have been able to determine, no one
has yet suggested that an abnormal cholinergic system may provide the
link between asthma and MCS.

The present brief review provides evidence for such a link by summarizing
recent findings in a genetic
animal model of cholinergic hyperresponsiveness.

The Flinders Sensitive Line (FSL) rats were developed by selective breeding
for increased responses to
an anticholinesterase agent similar to commonly
organophosphate pesticides.

Relative to their control line, the Flinders Resistant Line (FRL) rats, the FSL
rats are more sensitive to
drugs that stimulate acetylcholine receptors, alcohol,
diazepam, and drugs that have a selective effect on dopamine or serotonin

These findings raise the possibility that the FSL rats may resemble individuals
with MCS.

Hyperresponsiveness of the airways is a hallmark of asthma.

The procedure known as whole-body plethysmography, where breathing
can be monitored in freely moving animals, was employed to study the FSL
and FRL rats. The FSL rats exhibited a greater index of bronchoconstriction
than the FRL rats in response to
both a cholinergic agonist and an allergen

Thus, the FSL rats are more sensitive both to a variety of drugs unrelated
to the cholinergic system and to
cholinergic- and allergen-induced

An abnormal cholinergic system may therefore contribute to both MCS
and asthma.

[NOTE:  Marie did not have any respiratory or asthmatic symptoms before
the exposures to the unethically and illegally applied pesticides and solvents
at Southwest Baptist University

Severe exposure to these toxins caused permanent changes and damage
to Marie's cholinergic system due to the
refusal of SBU officials to provide
her with
the timely and required medical care and information on these
cholinesterase inhibiting pesticides.

As stated in emedicine: EMERGENCY MEDICINE:  An on-line Medical
Toxicity, Organophosphate and Carbamate:
     Exposure to organophosphates and carbamates produces a characteristic,
     treatable syndrome in humans. Its recognition and timely intervention is
     of great importance to emergency physicians and their patients.

irreversibly bind to cholinesterase causing the
     phosphorylation and deactivation of acetylcholinesterase
. The subsequent
     accumulation of acetylcholine at the neural synapse causes an initial
     overstimulation followed by eventual exhaustion and disruption of neural
     transmission in the central and peripheral nervous systems (CNS and PNS).

     If the organophosphate/cholinesterse bond is not broken by pharmacologic
[that is, the administration of the antidote (atropine sulfate)
     and other drug therapies] within 24 hours, large amounts of cholinesterase
     are destroyed causing long-term morbidity or death
. ...

Had the antidote been administered promptly, the damage due to the permanent
irreversibly binding of the organophosphates to the cholinesterase receptors
would have been minimized.

Medical authorities now recognize the link between the
disruption of the
cholinergic system by organophosphate pesticides
and other chemicals
as one of three
primary causes of Occupational Asthma.

As the American Academy of Allergy, Asthma, and Immunology (AAAAI)
describes in its literature on Occupational Asthma:

  Occupational Asthma:  Causes

  Occupational asthma may be caused by one of three mechanisms.
  These include:

  *Direct irritant effects ...
  *Allergy (long-term exposure) ...
*Pharmacologic mechanisms     

     Inhalation of some substances in aerosol form
can directly lead
     to the accumulation of naturally occurring chemicals in the body,
     such as histamine or acetylcholine within the lung, which in turn
     lead to asthma.

     For example, insecticides, used in agricultural work {or in illegal,
     indoor applications at Southwest Baptist University}, can cause a
     buildup of acetylcholine, which causes airway muscles to contract,
constricting airways. ]

For more information on cholinergic responses to toxins, please see:

Congressional Testimony on Chemical Intolerance
and Toxicant Induced Low Tolerance
(TILT) October 26, 1999

Dr. Claudia Miller

Correspondence to:
H. OVERSTREET , David H. Overstreet, Ph.D.,
Bowles Center for Alcohol Studies, CB 7178, 3011 Thurston-Bowles Building,
University of  North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178.
Tel.: (919)966-5678. Fax: (919)966-5679.   

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