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I DIDN'T KNOW THAT ...
While most mushroomers know that gyromitrin in the false morel (Gyromitra
escuelnete) converts to monomethylhydrazine, the information available to the
public about Agaricus bisporus by mushroom cultivators, wholesale/retail
distributors, and from the Mushroom Council fails to warn consumers against
the dangers of eating raw mushrooms.
And the warning is this: Agaritine in button mushrooms (Agaricus bisporus)
converts to toxic derivatives - N2-carboxyphenyl hydrazine and
phydroxymethylphenyl hydrazines - through metabolic activation, depending
on the type of enzyme - and a sauté or rinse does not eliminate the agaritine.
In a report, however, issued in 2014 in conjunction with the Mushroom and
Health Summit[1]
, the Mushroom Council and a cadre of public and private
sector nutritionists and health research specialists, touted all of the benefits of
mushroom consumption, and summarily dismissed any connection between
Agaricus and toxicity:
Currently available evidence indicates that the consumption of A. bisporus
mushrooms poses no toxicologic risk to humans (55). Fresh mushrooms contain
200–500 mg agaritine/kg fresh weight (56), an aromatic hydrazine-derivative
mycotoxin. High amounts of chemically synthesized and chemically modified
hydrazine compounds, including agaritine, were reported to have carcinogenic
effects in mice (57–60). However, these effects could not be replicated in a later
study (61). Review of these studies by others concluded that the studies were not
performed in accordance with approved protocols for carcinogenicity studies, such as
those outlined by the International Conference on Harmonization (62).
The Mushroom Council clearly ignored the research done by Toth and various
collaborators[2]
, and many subsequent research studies have confirmed the same
results implicating the agaritine in Agaricus with tumor growth in mice and rats.
[1]
The Journal of Nutrition Supplement: Mushrooms and Health Summit Proceedings, Mary Jo Feeney, Johanna
Dwyer, Clare M. Hasler-Lewis, John A. Milner, Manny Noakes, Sylvia Rowe, Mark Wach, Robert B.
Beelman, Joe Caldwell, Margherita T. Cantorna, Lisa A. Castlebury, Shu-Ting Chang, Lawrence J. Cheskin
Roger Clemens, Greg Drescher, Victor L. Fulgoni III, David B. Haytowitz, Van S. Hubbard, David Law, Amy
Myrdal Miller, Bart Minor, Susan S. Percival, Gabriela Riscuta, Barbara Schneeman, Suzanne Thornsbury,
Cheryl D. Toner, Catherine E. Woteki, and Dayong Wu.
[2]
Toth B. Carcinogenesis by N2-[gamma-L(+)-glutamyl]-4-carboxyphenylhydrazine of Agaricus bisporus in
mice. Anticancer Res 1986;6:917–20. 58. Toth B, Gannett P. Carcinogenesis study in mice by 3-methylbutanal
methylformylhydrazone of Gyromitra esculenta. In Vivo 1990;4:283–8. 59. Toth B, Nagel D. Studies of the

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In their 2014 publication, Sinha and Mason[3]
of the National Institutes of
Health also cite the toxicity of agaritine:
Substituted hydrazines are present in the edible mushroom Araricus bisporus.
Degradation of Agaritine, N2-[L-(+)-glutamyl]-4-(hydroxymethyl) phenyl hydrazine,
the parent hydrazine found in this mushroom, results in the formation of various
other substituted hydrazines, e.g., N2-carboxyphenyl hydrazine and
phydroxymethylphenyl hydrazine derivatives, which are carcinogenic and lead to the
formation of tumors in mice [47-50].
Moreover, Sinha and Mason[4]
also reported on possible multiple pathways for
hydrazine toxicity[5]
:
A number of studies have clearly shown that these mono-substituted hydrazines
undergo extensive metabolism, catalyzed by cytochrome P450, peroxidases and
oxyhemoglobin, to free radical species, resulting in covalent binding with proteins
and DNA [51-53]. However, there remains some debate in the literature, as
substituted hydrazines also form alkyldiazonium ions (Figure 3), which are known to
directly alkylate cellular macromolecules and thus have been implicated in the
mutagenic and carcinogenic activity of these hydrazines [47-50]. Studies carried out
in vitro have also shown that both free radical intermediates and diazonium ions
induce DNA strand breaks and covalently alkylate adenine and guanine bases
[49,50]. One of the most interesting conclusions from such studies has been the
implication of the formation of both hydroxyl and aryl radicals from the diazonium
ions [50]. While the role of the diazonium ions in cytotoxicity of hydrazine
derivatives in not known, it is of interest to note that the formation of aryl radicals
from substituted hydrazines has been shown to correlate with their cytotoxicity [54].
This would suggest that, irrespective of the metabolic pathway (cytochrome P450 or
tumorigenic potential of 4-substituted phenylhydrazines by the subcutaneous route. J Toxicol Environ
Health1981;8:1–9. 60. Toth B, Patil K. Carcinogenesis by a single dose of Nmethyl- Nformylhydrazine. J
Toxicol Environ Health 1980;6:577–84. 61. Toth B, Erickson J, Gannett P. Lack of carcinogenesis by the baked
mushroom Agaricus bisporus in mice: different feeding regimen. In Vivo 1997;11:227–31.
[3]
Biotransformation of Hydrazine Derivatives in the Mechanism of Toxicity, 2014, Birandra K Sinha and
Ronald P Mason, http://omicsonline.org/open-access/biotransformation-of-hydrazine-dervatives-in-the-
mechanism-of-toxicity-2157-7609-5-168.pdf. Laboratory of Pharmacology and Toxicology, National Institutes
of Environmental Health Sciences, NIH, USA.
[4]
Biotransformation of Hydrazine Derivatives in the Mechanism of Toxicity, 2014, Birandra K Sinha and
Ronald P Mason, http://omicsonline.org/open-access/biotransformation-of-hydrazine-dervatives-in-the-
mechanism-of-toxicity-2157-7609-5-168.pdf. Laboratory of Pharmacology and Toxicology, National Institutes
of Environmental Health Sciences, NIH, USA.

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peroxidases), free radicals would be generated from the activation of hydrazines, as
both pathways would produce free radical intermediates, resulting in hydrazine-
induced toxicity.
With regard to the Mushroom Council it is important to know that the Council
is composed of fresh market producers/importers who average more than
500,000 pounds of mushrooms produced/imported annually; Council programs
are authorized by the Mushroom Promotion, Research and Consumer
Information Act of 1990 and administered by the Mushroom Council under the
supervision of the Agricultural Marketing Service. There is a BIG cultivated
mushroom lobby in this country.
It is obvious that posing limits on the type of consumption of any food
decreases its marketability. This is certainly the case with Agaricus bisporus. In
fact on the Council's website there are no safety guidelines about mushroom
consumption and mushroom preparation. The following Table[6]
provides the
information lacking from the Mushroom Council's website
(www.MushroomCouncil.org) and from the cited Report[7]
prepared with its
collaboration:
[6]
Schulzova, V., Peroutka, R., Gry, J. and Anderson, H.C. Influence of storage and
household processing on the agaritine content of cultivated Agaricus mushroom. Food
Additives and Contaminants, 19(9), 853-863.
[7]
The Journal of Nutrition Supplement: Mushrooms and Health Summit Proceedings, Mary Jo Feeney, Johanna
Dwyer, Clare M. Hasler-Lewis, John A. Milner, Manny Noakes, Sylvia Rowe, Mark Wach, Robert B.
Beelman, Joe Caldwell, Margherita T. Cantorna, Lisa A. Castlebury, Shu-Ting Chang, Lawrence J. Cheskin
Roger Clemens, Greg Drescher, Victor L. Fulgoni III, David B. Haytowitz, Van S. Hubbard, David Law, Amy
Myrdal Miller, Bart Minor, Susan S. Percival, Gabriela Riscuta, Barbara Schneeman, Suzanne Thornsbury,
Cheryl D. Toner, Catherine E. Woteki, and Dayong Wu.

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Table 5.2 The influence of storage and household processing on the agaritine
content of Agaricus mushrooms.
(a) 100% agaritine in fresh mushrooms before processing
(b) 20 grams sliced mushroom
Unlike the Mushroom Council, mushroom experts have long advised against
raw mushroom consumption, and David Campbell’s article "On Eating Raw
Mushrooms" is just one example.
(www.mykoweb.com/articles/EatingRawMushrooms.html) The same article was also
published in The Mushroom Log, Ohio Mushroom Society, Jan/Feb 2009.
(www.ohiomushroom.org_ oms...ter_JanFeb)
Process Conditions Time Amount of
agaritine
remaining in the
mushroom (a)
Drying 25◦C 24 h 82%
Drying 50◦C 7.5 h 76%
Drying 40-60◦C 7 h 81%
Freezing without
Thawing
-18◦C 7 days 75%
Freezing with
Thawing
-18◦C 7 days 52%
Freezing without
Thawing
-18◦C 30 days 41%
Freezing with
Thawing
-18◦C 30 days 23%
Household
processing
Cooking Boiling water 5 min 44%
Cooking Boiling water 60 min 12%
Dry baking 200◦C 10 min 77%
Deep-frying 150◦C 10 min 50%
Deep-frying 170◦C 5 min 52%
Frying 150◦C 10 min 43%
Microwave
heating
1000 W, 2450
MHz (b)
1 min 35%

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* * *
I have consumed pounds of raw Agaricus and improperly prepared Agaricus in
my lifetime, and of course the responsibility is all mine. However, at a time
when health care and health issues are ostensibly finally a national priority,
even in Washington, I am concerned about the quality of the publications, in
terms of research, especially those available to the general public and prepared
in collaboration with public entities. I have also written to the USDA about my
concern, and you can do the same.