Re: HYB: Colchicine (use, toxicity, handling) (more than most of you want to know)

From: rdhager@dmv.com

In medicine, colchicine is used mainly to treat acute pain associated
with gout. It works by stopping the formation of white blood cells which
try to "gobble" crystals of uric acid that form in the joints when it is
not eliminated from the body properly. These WBC's are "mediators" of
the inflammatory response, which actually causes the pain. Colchicine
affects DIVIDING cells, so it first affects those parts of the body
where cells replicate rapidly. Colchicine has been used with relatively
safety for over a century. Before lab tests were readily available, it
was used as a diagnosis and treatment for gout. If it worked, you had
gout! The beauty of the drug is that the dose is easily titrated for
each patient. The usual dose is 0.6 mg, repeated every one to two hours,
until pain is relieved or diarrhea develops. Diarrhea is the first sign
of toxicity when taken orally. It is caused by the cells lining the
intestines not being able to reproduce. Most patients need fewer than 10
tablets (6 mg) to treat the acute attack. Lethal dose is estimated to be
20 to 60 mg (taken at once), so it has a relatively narrow therapeutic
index. Obviously, toxicity is avoided by incremental dosing.

In horticulture, colchicine has been used extensively to induce
polypoidy. Dr. Currier McEwen's books on Siberian and Japanese irises
discuss its use. With his success rates, it would be great to find a
method with a higher success/survival rate. More plantsmen are familiar
with its use on daylilies, but it has been tried with varying degrees of
success with many species. One researcher has reported extremely high
conversion rates with magnolias.

Colchicine toxicity is dose related (both concentration and length of
exposure) and using common sense can reduce the chance of exposure. The
greatest hazards are from acute poisoning, including skin or eye
contact, ingestion or inhalation. It is a corrosive irritant and can
sensitize the area to other irritants. It can also permeate the skin.
Eye contact can cause corneal damage and blindness. Inhalation can cause
diarrhea, sneezing, coughing and burning of the throat. Severe
over-exposure can result in lung damage, choking and death.

Even though colchicine affects cell division and has been used for a
long time, data is not available to document carcinogenic, mutagenic or
teratogenic effects, even with long term exposure. It can, however,
cause damage to blood, kidneys, lungs and nerves, which may be
irreversible.

Practically speaking, accidental poisoning is the biggest problem with
colchicine in horticultural applications. Buy the smallest quantity you
need to make a concentrated stock solution. It can be mixed by adding a
little water to the vial and pouring the contents into the stock bottle.
Add sufficient water to make the desired concentration. (I recommend a
250 mg in 50ml to make a 0.5% solution. 50 ml less than 2 fl.oz.)
Concentrated stock solutions are lethal. One teaspoonful of a 0.5%
solution taken orally would deliver a 20 mg dose, which could kill a
child. Stock solutions should be carefully labeled as poison and kept in
child resistant containers out of the reach of children. They should be
stored in the refrigerator. I recommend keeping the bottle wrapped in
foil and placed inside a larger container which is sealed with tape.
Ideally, it should be stored in a refrigerator which is not used for
food. Once the stock solution is diluted to application concentration
(0.025% to 0.05%) the chance of accidental ingestion, is greatly
reduced, but contact with skin, eyes, mucous membranes or inhalation can
still cause considerable pain and suffering. The Material Safety Data
Sheet (MSDS) that accompanies the powder indicates that gloves, mask and
goggles are required for handling the product. I think this should apply
to the dilute solution also.

It is not illegal to buy or sell colchicine powder, but there are
perceived and real liability risks in selling a hazardous product to
someone who may not use it properly. Most companies and universities
have policies in place to protect against such liabilities. It is
illegal to buy or sell it for human use without proper authorization. I
doubt that you will find colchicine powder at your local independent
drugstore, but they are able to get it, though not through their normal
distributors. It is available through several chemical supply companies,
but to my knowledge, they will sell only to trade customers, including
industry, schools, pharmaceutical manufacturers, hospitals, etc. If you
know someone with purchasing authority in one of those fields, they may
be unwilling to order it for you, even if it is available through one of
their established vendors. Just remember that their job is on the line. 

If you really want to experiment with colchicine, do your homework. Read
up on it and write your own plan for its use, including proper handling,
application, disposal, calculations of concentrations, estimated human
exposure in worst and best case scenarios and plan for remediation in
case of spill or exposure. Sign and date it. BTW, this is no more than
would be expected for use in a university laboratory. Present a copy of
this document to the supplier you choose. It will make it easier to
obtain.

Using colchicine is expensive. Before you use it the first time, plan on
spending in excess of $75 for the chemical, shipping and handling
charges, gloves, masks, goggles applicators, etc. Obviously, I still
think it's worth the expense and risk.
  
R. Dennis Hager
on Delmarva
where colchicine is going to be applied to Japanese and Siberian
seedlings very soon--gloves, mask, goggles and all.

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