Porphyria Educational Services
Porphyria Educational Services Weekly Bulletin
Vol. 2 No. 49 December 10, 2000
FOCUS: TOXICOLOGY
Toxicology is an area of study in porphyria which is often
overlooked. However such study is most useful in understanding
those "triggers" which most often affect porphyria
patients.
The world is full of toxins and for the acute porphyria patients,
the toxins are often lethal.
Toxicology is the study of the way that toxicants work.
Toxicology studies compounds that are harmful to living tissue.
One leading toxiocologuist has stated that the usefulness of
toxicology is I as true today as it was when Paracelsus said it
that "The difference between poison and medicine is a matter
of dose."
The potency of various toxicants can be compared by comparing LD50
values obtained for the various toxicants in similar animals
similarly exposed to the toxicants. The lower the LD50 value, the
more potent the toxin.
Before human are often studied, plant life is studied. Many
plants grow poorly, if at all in the absence of copper (Cu). A
few parts per billion (ppb) Cu usually allows normal growth. A
few parts per million (ppm) may have the toxic effect of
inhibiting growth. It is all in the dosage.
Toxicology studies dealing with pharmaceuticals often explain why
one person reacts and the next person does not react to the same
medication. It is a matter of dosage, and secondarily it is also
based upon the individual's body to metabolize such a
pharmaceutical.
The same goes for inhalation of various substances, be it
department store perfume counters, paints, varnishes and waxes;
roofing tars and asphalting, petroleum fumes,
metal dusts, and pesticides, fungicides, herbicides and such.It
all goes back to the biological effect of an exogenous substance
in an organism showing optimum level, deficiency, and excess of
the contact with a given substance.
Also as porphyria patients know well, they each differ in their
reactions to given substances.
There will be great variation of dose-response for the same
chemical in two different species. This is why some people can
take "no-no" drugs, wash their clothes with chlorine
bleach, use insect repellent, and the next person will need to be
hospitalized due to an acute attack of porphyria.
Very large differences can be observed in potency of toxicants to
various species of related small animals.
The toxicities [or potencies as they are sometimes called,] of
various compounds can be compared to an given scale given below.
TOXICITY RATING
LD50
Virtually non-toxic
> 15,000 mg/kg
Slightly toxic
5000 - 15,000 mg/kg
Moderately toxic
500 - 5000 mg/kg
Very toxic
50 - 500 mg/kg
Extremely toxic
5 - 50 mg/kg
Supertoxic
< 5 mg/kg
The LD50 is used to determine toxicity of a compound and the
ranges listed are those
defined by Klaasen in his toxicologies studies.
Looking at the toxicology of various compounds, Malathion,
ethanol, arsenic, parathion,
cyanide, tetraethylpyrophosphate, and TCDD are among the worse of
the toxins.
For those who are looking at the toxicology of household products
most medical or
hospital libraries have books listing the severity of a given
substance. Each person could
make a detailed list of the items in their home or environment
and check against the
toxic levels cited in the book. Substances that are rated highly
toxic should be avoided
or removed from common use and inhalation in the homs of
porphyria patients.
In a study by Manahan which was completed in 1989, the
specificity of enzyme to substrate is based on close matching of
physical shapes. Anything that changes the shape of the active
site may reduce or eliminate enzyme function. In porphyria
changes in enzymes
are the key essential element in triggering the onset of
porphyria symptoms.
Receptor sites exist in tissues. Many forms of chemical
communication happen, each has a receptor site. Each may be
interfered with by compounds that either copy the chemical
messenger or which change the receptor site so that the chemical
messenger is not
recognized when it arrives. Receptor sites are very specific as
to the size and shape of the molecule that is recognized. This is
how mistakes in chemical communication are eliminated.
Various compounds can interfere with the action of hormones
either by combining with the hormone so that it is no longer 'recognized'
at its receptor site or by modifying the receptor site.
Often porphyria patients do not realize the potential toxin
problems that exist with metals.
Metals can also bind to active sites and interfere with enzyme
function
In porphyria the pathways between cell exposure and expression of
toxicity are often noted in the PN that accompanies an acute
attack.
Dr. Leslie Jones, Toxicology & Cell Biology