Re: Potassium iodide, continued

[carol marcus <csmarcus@ucla.edu>]

At 10:06 PM 9/18/99 -0500, you wrote:
>Two recent postings to RADSAFE dealt in whole or in part with the NRC's
>proposed rule on KI (the "fighter jet" rule).  They came from the NRC's
>Patricia Sullivan (PAMS718) and Dr. Carol Marcus.  I'd like to respond
>briefly to both.
>
>Ms. Sullivan's thoughtful posting raises a number of issues.  She
>suggests that KI cannot have been effective in Poland because
>administration did not begin until 2 to 4 days after the accident, and
>KI, to be effective, must be administered just before, during, or just
>after the release.  I would answer that the usefulness of KI depends not
>on when the radioactive release occurs, but when the radioactive iodine
>is inhaled or ingested.  It took some time for the winds to bring
>radioactivity to other parts of Europe; moreover, it came not in a
>single release, but over a period of days.  Thus the notion that Polish
>children received KI too late to derive any benefit is not, I think,
>correct.
>
>I do not take issue with the proposition that ingestion, especially of
>milk, was the principal source of children's exposure to radioiodines
>after Chernobyl.  (Ms. Sullivan writes that in the former Soviet Union,
>"It is believed that the increases in thyroid cancer can be attributed
>mostly to ingestion.")  "Mostly" is not the same as "exclusively,"
>however.  If it is conceded that inhalation was responsible for some of
>the post-Chernobyl cancers, then it is worth asking whether it is worth
>spending a small amount of money to achieve an additional level of
>protection against inhaled radioiodines.  
>
>As far as the claim that not enough radioiodine reached Poland to have
>caused any thyroid cancer, I can say only that Dr. Janusz Naumann, the
>distinguished Polish physician and teacher who directed his country's
>administration of KI, takes issue with it.  She might wish to contact
>either Dr. Nauman or Dr. Jan Wolff, of NIH, who with Dr. Naumann
>co-authored a paper in an American medical journal on the Polish
>experience with KI.  She and other RADSAFERS might usefully consult
>"Radiation and Thyroid Cancer," a book published earlier this year.  It
>consists of papers delivered at the 1998 Cambridge University conference
>of that name.  The conference was co-sponsored by the European
>Commission, the U.S. Department of Energy, the National Cancer
>Institute, and Cambridge University.
>
>Ms. Sullivan is correct in saying that U.S. policy emphasizes evacuation
>and interdiction of food supplies.  But evacuation is not always
>feasible, and even when it is, people can be irradiated while
>evacuating, as EPA stressed in a 1992 report.  It's worth noting that
>back in the years when nuclear power plants were being licensed,
>opponents of plants would often argue that a particular site could not
>be evacuated in the event of an accident that tied up roads or in bad
>weather conditions, or the like.  In response, the NRC at that time took
>the position that evacuation was not necessarily the be-all and end-all,
>and that in some situations, sheltering would be preferable.  (The 1992
>EPA report also said that there would be situations in which sheltering
>is preferable.)  The current guidance, stating that evacuation is
>invariably the best approach, was not issued until 1996, the year after
>I filed my petition for rulemaking on KI.  I continue to believe that
>there may be situations in which sheltering is the option of choice --
>if only because other options don't exist -- and that in those
>situations, the availability of KI could improve protection and could
>not impair it.
>
>It did not occur to me, until I read Ms. Sullivan's posting, that anyone
>would take my reference to my own experience with thyroid cancer as
>suggesting that KI could have prevented my illness.  That wasn't my
>intention at all, and I apologize if what I wrote was unclear.  I was
>trying to make the point that my own experience of thyroid cancer leads
>me to believe that (1) it is an illness well worth preventing, and (2)
>to the extent that current U.S. policy is grounded on the notion that
>the illnesses that KI can prevent are inconsequential, that policy is
>seriously flawed.  Anyone who reads the transcript of the public meeting
>on KI that the NRC held on November 22, 1983, will find that the NRC
>staff represented the effects of radiation-caused thyroid disease in the
>mildest terms:  never using the word "cancer," never mentioning a
>lifetime on medication, never referring to possible fatalities, but
>instead referring to a "relatively minor operation" involving "a few
>days loss."  
>
>To Ms. Sullivan's point that some states have already implemented KI
>stockpiling, without being required to do so by the federal government,
>that's true.  (They are Tennessee, Alabama, Arizona, and Maine).  But in
>the case of Maine (and also Ohio, which is in the process of moving to
>stockpile KI), the state decision to stockpile has come not because of
>the information provided by the NRC, but in spite of it.  I was at the
>meeting in Maine in 1996 in which the state's advisory committee
>recommended unanimously in favor of stockpiling KI, and it is fair to
>say that they were not happy at the contrast between what the NRC had
>been telling them and what their own research turned up.  At this point,
>after so many years of inaccurate and inadequate information provided to
>the states and the public by NRC, a rule change seems to me the only
>reasonably sure way of rectifying the problem.  
>
>Dr. Marcus's posting can be dealt with briefly.  I wish she had been at
>the Cambridge conference to offer her novel suggestion that the
>post-Chernobyl thyroid cancers were caused by KI, rather than by
>radioactive iodines.  I wonder what "we" she had in mind when she wrote,
>"We don't know why young children near Chernobyl developed thyroid
>cancer...."  The doctors and scientists who are the world's foremost
>experts on radiation and thyroid cancer were at Cambridge, and they did
>not seem to be in the dark on that point.  I suggest that she consult
>their published articles.
>
>Dr. Marcus seems to be suggesting that I-131 does not cause thyroid
>cancer, based upon the releases from Hanford and persons receiving
>radioiodine for medical reasons.  The director of the Hanford study, Dr.
>Tom Hamilton, recently told a meeting of the NRC's KI Core Group that he
>himself would "gobble KI" in the event of a nuclear accident.  Clearly
>he does not put the interpretation on the Hanford data that Dr. Marcus
>does.  Regarding medical uses of radioiodine, the argument has been made
>by my old friend and colleague, Dr. Myron Pollycove of the NRC, that a
>long-term study by Dr. L.-E. Holm of the Swedish Radiation Protection
>Institute (finding no increase in thyroid cancer among patients treated
>with I-131 for Graves' disease) proves that I-131 is not carcinogenic,
>and that KI is therefore unnecessary.  Dr. Holm spoke at Cambridge, and
>afterwards took questions from the floor.  I mentioned the argument just
>described, and asked him to comment.  He replied that he was aware that
>this argument was being made, that it was a misinterpretation of the
>results of his study, and that he himself favored stockpiling of KI.
>
>I hope that European experts, with direct experience of Chernobyl and
>its consequences, will contribute their thoughts to this discussion.
>
>Peter Crane
>pgcrane@erols.com
>************************************************************************
>The RADSAFE Frequently Asked Questions list, archives and subscription
>information can be accessed at http://www.ehs.uiuc.edu/~rad/radsafe.html
>

Dear Radsafers:

As a scientist as well as a physician, I am not terribly impressed with the
opinions of so-called "experts" so much as I am interested in the high
quality data upon which theories and decisions are made.  As far as
Chernobyl is concerned, we know that the rate of papillary thyroid carcinoma
in very young children in regions nearby appears to be much higher than
previously noted.  However, there are no really useful data beyond that.
Something associated with the Chernobyl accident appears to have caused the
thyroid cancer.  Was it one or more radioiodines? In the air?  In the food?
Was it external radiation?  Was it a stable element or compound associated
with the accident, either directly or indirectly?  Was it an indirect
effect, such as induction of thyroiditis that itself can be a prelude to
cancer?  We may never know.  We have no measurements of radiation absorbed
dose from different radioiodines in the children who developed thyroid
cancer and those who did not, and we have no dose-response data, the sine
qua non for establishing a causal relationship.

Notice how Mr. Crane, a lawyer, not a scientist or a physician, fails to
admit his error concerning the use of the Physician's Desk Reference (PDR)
rather than the United States Pharmacopeia-Drug Information (USP-DI) for
information on the adverse effects and adverse drug interactions of
supersaturated potassium iodide (SSKI).  His statement that a comment letter
confused side effects of iodinated contrast material with those of SSKI
gives the illusion that no side effects of SSKI occur, especially as he
states that the PDR does not list any.  My comment letter, submitted some
years ago, described in detail the adverse effects and adverse drug
interactions of SSKI; if someone else confused SSKI with iodinated contrast
material, I have no knowledge of it.  However, I doubt that this happened,
and would like to see that comment letter.

The PDR has some usefulness, but generally not for radioactive drugs.  The
PDR is a document in which manufacturers pay to have all or part of their
FDA-approved package inserts reprinted in a book.  They may reprint the
whole insert, part of the insert, or just the name of the drug and none of
the insert.  Obviously the more you print, the more it costs.  Hundreds of
drugs, perhaps even thousands, are in the PDR by name only, with no
information published at all.  The PDR is distributed free of charge to
practicing physicians.  It is basically a form of advertising.  The quality
of the information that is published is tied to the quality of the
FDA-approved package insert.  In the case of radiopharmaceuticals, the
FDA-approved package insert is often the last place to go for valid drug
information.  This is because the people at FDA reviewing
radiopharmaceuticals, and especially their managers, are generally poorly
qualified to do so.  Some good work done by a few competent underlings is
usually killed before it gets out, so it is not surprising to find an
incorrect physical constant, ridiculous or incomplete indications, or no
valid understanding of relevant radiochemistry in describing kit
reconstitution. There are even situations in which instructions are mutually
exclusive, or recommended administered activity is incorrect or misleading.
You don't use the PDR as a valid scientific document.  It has some useful
information for the physician, but it is basically an advertising document.

The USP-DI, on the other hand, is crafted by a non-profit, NON-GOVERNMENT
group  whose drug standards (published in the USP) are, by law, the national
standards.  FDA hates it, but the Food, Drug, and Cosmetic Act gives
responsibility for creating drug standards to the USP, not the FDA.  FDA
enforces the standards; USP does not.  Those who write standards and drug
information for the USP are highly qualified and experienced professionals,
and their work is voluntary.  Draft standards and draft drug information are
published for comment, and all comments are answered.  Standards and drug
information are continually updated, and comments may be submitted by anyone
at any time for any drug.  The experts of the USP panels do not always agree
with the FDA-approved package insert, and are free to add, subtract, and
ignore whatever they judge appropriate.  They also write monographs on drugs
that are not FDA-approved, although this in recent years has generally been
done only for radiopharmaceuticals.  In the past, the USP and the USP-DI
have been sent to the NRC, but I'm not sure who has it and I'm not sure if
NRC even knows enough to buy the updates.  In any case, that is where the
good drug information is to be found.  Peter, go look up SSKI.  Most of the
problems with this drug will not be seen with a single dose, but may occur
with multiple doses.


Ciao, Carol

Carol S. Marcus, Ph.D., M.D.
<csmarcus@ucla.edu>

************************************************************************
The RADSAFE Frequently Asked Questions list, archives and subscription
information can be accessed at http://www.ehs.uiuc.edu/~rad/radsafe.html