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Hydrazine Derivatives
- Naturally occurring hydrazines, such as agaritine, are
found in edible mushrooms, and the Committee were informed
that human consumption of the commercially grown edible
mushroom Agaricus bisporus is increasing. The
Committee was advised by the COC and COM that the
chemical structure of agaritine and its putative metabolites
(N acetyl 4 (hydroxymethyl) phenylhydrazine and 4
(hydroxymethyl) benzene diazonium ion) give rise to
concern about mutagenic and carcinogenic potential, a
concern strengthened by the activity of agaritine in
bacterial mutation assays. The data concerning the mutagenic
potential of agaritine in mammalian cells in vivo and
in vitro are limited and insufficient to allow any
firm conclusions to be reached. The stabilised forms of the
putative metabolites of agaritine showed evidence of
carcinogenicity in long term testing in Swiss mice, although
the studies were of unusual design.
N-acetyl-4-(hydroxymethyl)phenylhydrazine induced an
increased incidence of tumours of the lung and blood
vessels; 4-(hydroxymethyl)benzene diazonium ion
tetrafluoroborate induced an increase in glandular stomach
adenocarcinomas. There was evidence that agaritine itself
was carcinogenic in laboratory animals, but further testing
would be necessary to confirm this.
- The Committee agreed with the concerns of the COC
and COM that the structure and mutagenic potential of
agaritine suggested that future research was needed. In
order to proceed with this assessment, information on
absorption, distribution, metabolism and possible
detoxification of this compound by mammals was needed. The
data available indicate that there are other toxins present
in A. bisporus and that toxic effects in laboratory
animals fed mushrooms cannot be directly attributed to
agaritine. The Committee recommended that more knowledge was
required on the nature, bioavailability, and toxicology,
including mutagenic potential, of the other toxins present
in A. bisporus, before a definitive conclusion could
be reached and welcome the research that MAFF was
funding to address these questions. The Committee
agreed with the COC and COM that the data currently
available were not of sufficient concern to require the need
for measures to reduce agaritine intake by the population.
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