IFIN BULLETIN #219: Another piece of the osteosarcoma puzzle.

Jan 5, 2001.

Dear All,

Today, my wife, Ellen, who is a veritable sleuth when it comes to combing
the PubMed line and other databases for fluoride articles, forwarded me an
article  by Mihashi and Tsutsui from 1996, which I had overlooked. It
provides an important piece in the fluoride and osteosarcoma puzzle. They
have demonstrated a highly plausible mechanism for how fluoride could
induce bone cancer. I am surprised we haven't heard more about this study.
We print the abstract below.

In paragraphs 25--29 of my "Statement of Concern" which can be found on our
web page at http://www.fluoridealert.org/fluoride-statement.htm), I have
written about some of the interesting history and politics surrounding the
possible connection between water fluoridation  and the incidence of
osteosarcoma in young males. The scientific evidence is not clear cut and
the situation has been obfuscated rather than clarified by US agencies and
the NRC.

When animal and epidemiological studies give mixed results, as in the case
of fluoride and osteosarcoma, toxicologists working in the public interest
will often adopt a "weight of evidence approach", whereas toxicologists
working for corporate interests will usually insist on "absolute proof"
before conceding that a problem is serious enough to demand action. We have
seen this played out again and again with chemicals, or products, for which
there are huge financial interests at stake, such as asbestos, tobacco,
tetraethyl lead, DDT, PCBs, dioxins and, of course, fluoride.

The study by Mihashi and Tsutsui, by giving a plausible biological
mechanism for fluoride's carcinogenic action in bones, adds to the "weight
of evidence" that we may have a serious problem here.

We have:

 1) a plausible biological mechanism.
 2) we have an increase in cortical bone defects in the first fluoridation
    experiment in which medical evidence was collected.
 3) we have predictions raised based upon these observations.
 4) we have animal experiments which show an increase in osteosarcoma in male
    rats which is dose dependent.
 5) we have two human epidemiological studies which found an increase in
    osteosarcoma in young men in fluoridated communities.

but

  6) we also have other animal studies (financed by Procter and Gamble) which
     did not find any osteosarcomas, and
  7) we have several other epidemiological studies which have not found an
     association between osteosarcoma in young males living in fluoridated
     communities.

Do these studies neatly cancel one another out? How large does the red flag
have to be, before our government acts?  Or as the late John Colquhoun
asked in a videotaped interview, "How many cavities would have to be saved
to justify the death of one young man from osteosarcoma."

In Europe, more and more attention is being given to the Precautionary
Principle, which is an effort to resolve questions like this. Simply stated
this principle states "if in doubt, leave it out!" A more sophisticated
definition was provided by scientists attending the 1998 Wingspread
Conference, in Raccine, Wisconsin:

 "When an activity raises threats of harm to human health or the
environment, precautionary measures should be taken even if some cause and
effect relationships are not fully established scientifically".

If the Precautionary Principle doesn't apply to fluoridation, what does it
apply to? Even more importantly, after all the science has been gathered
and all the risks computed, and all the alternatives examined, the really
key question is: who decides? Who decides which chemicals flow from our
taps? Who decides what risks are acceptable?

Paul Connett.

P.S.

 Turning to the politics of the matter. This report lends further weight to
the  request by Dr. Bill Hirzy (Vice-President of the union representing
professionals at the US EPA headquarters) for a an independent review of
the tumor slides in the NTP bioassay. He made this request in a submission
he made before a Senate Committee. Below we have given an extended quote
from his sunbmission. The full text is available at
http://www.fluoridealert.org/testimony.htm

"In 1990, the results of the National Toxicology Program cancer bioassay
on sodium fluoride were published (10), the initial findings of which
would have ended fluoridation. But a special commission was hastily
convened to review the findings, resulting in the salvation of
fluoridation through systematic down-grading of the evidence of
carcinogenicity. The final, published version of the NTP report says
that there is, "equivocal evidence of carcinogenicity in male rats,"
changed from "clear evidence of carcinogenicity in male rats."
The change prompted Dr. William Marcus, who was then Senior Science
Adviser and Toxicologist in the Office of Drinking Water, to blow the
whistle about the issue (22), which led to his firing by EPA. Dr. Marcus
sued EPA, won his case and was reinstated with back pay, benefits and
compensatory damages. I am submitting material from Dr. Marcus to the
Subcommittee dealing with the cancer and neurotoxicity risks posed by
fluoridation.

We believe the Subcommittee should call for an independent review of the
tumor slides from the bioassay, as was called for by Dr. Marcus (22),
with the results to be presented in a hearing before a Select Committee
of the Congress. The scientists who conducted the original study, the
original reviewers of the study, and the "review commission" members
should be called, and an explanation given for the changed findings."

Paul Connett.



Two definitions (from:  http://medical-dictionary.com/)

* Clastogenic:  This adjective describes any substance or process which
causes breaks in chromosomes.

* Genotoxic:    Describes a poisonous substance which harms an organism by
damaging its DNA.

---------------------------------------------------------

Mutat Res 1996 May;368(1):7-13

Clastogenic activity of sodium fluoride to rat vertebral body-derived cells
in culture.

Mihashi M, Tsutsui T

Department of Pharmacology, School of Dentistry at Tokyo, Nippon Dental
University, Japan.

The US National Toxicology Program has shown equivocal evidence of
carcinogenic activity of sodium fluoride (NaF) in male F344/N rats based on
the occurrence of five osteosarcomas in treated animals. In the study the
osteosarcomas developed mainly in the rat vertebrae. To provide a possible
mechanistic basis for the observed tumors, the genotoxic effects of NaF on
the possible target organ of NaF carcinogenesis were examined. Rat
vertebral body-derived (RVBd) cells were established from trabecular bone
of vertebral bodies of a male F344/N rat 6 weeks of age and treated with
NaF. RVBd cells in secondary culture exhibited a high level of alkaline
phosphatase (ALP) activity when the cells at confluence were assayed by ALP
staining. When the histochemical examination was performed on RVBd cell
colonies, most of the colonies were stained positively for ALP. Confluent
RVBd cells were responsive to 10(-8) M 1 alpha.25-dihydroxyvitamin D3 with
a 7.7-fold increase in osteocalcin production over base line values. The
von Kossa staining demonstrated that in the presence of 2 mM
beta-glycerophosphate, RVBd cells that were allowed to grow past confluence
for approximately 2 months formed mineralized nodules. When RVBd cells in
tertiary culture were treated with NaF at 0.5-2.0 mM for 24-72 h, the
growth and/or survival of the treated cells was reduced in a dose-dependent
manner. Significant increases in the frequencies of chromosome aberrations
were induced in a dose- and treatment time-dependent fashion when NaF was
administered to RVBd cells at 0.5 and 1.0 mM for 24 and 48 h. The results
indicate that NaF is genotoxic to rat vertebrae, providing a possible
mechanism for the vertebrae, as a target organ of NaF carcinogenesis.

PMID: 8637511, UI: 96236424