A clue about ethidium toxicity

As you know ethidium (aka homidium) is also used as trypanocide in cattle,
sheep, goat ect... No ADI (admitted daily intake) are available for ethidium
however there is one for isometamidium which is a closely related to
homidium and also intercalate in DNA. Also it was found that isometamidium
is transform in homidium in the body (less thant
1%)([Only registered users see links. ]).


The ADI of isometamidium is 0-100 microgramme/kg
([Only registered users see links. ]
ionsourcejecfa_JECFAEVAL57.html+isometamidium+who+ adi&hl=en&ct=clnk&cd=1&gl=uk).


"
An ADI of 0-100 µg per kg of body-weight was established for
isometamidium based on the non-toxic dose level of 50 mg/kg bw/day
in the 13-week rat study and a safety factor of 500. The Committee
chose this safety factor because of the marginal pharmacological
effects seen at the lowest dose in the rat study and the limited
extent of the data available, although it recognized that neither
the drug nor its metabolites were bioavailable when given by the
oral route."


So if isomethidium give rise to 0.1% of homidium, the proportionnal ADI of
homidium could be : 0.1 microgramme par kg so 6 microgramme for a 60 kg
person.

In this study, it is shown that isometamidium have a strongest toxic effect
than homidium: [Only registered users see links. ]


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Sent from the Bio.net - Methods mailing list archive at Nabble.com.

Undergrad wrote:

If you search through the archives of this newsgroup (which I think are
still accessible?) you will find previous discussions of this topic,
including at least one rant of mine.

Isometamidium chloride is a derivative of ethidium/homidium but larger
and I suspect that the presence of the azo (-N=N-) moiety (which is
actually triazo because it is Ar-N-N=N-Ar may make the comparison to
homidium incorrect because isometamidium is probably chemically reactive
(which ethidium is not). Although both molecules contain conjugated
aromatic rings (which makes them interculating agents) they are also
ions (by virtue of having a quaternary nitrogen) and consequently will
not pass readily through undamaged cell membranes. To actually suffer
mutagenic/carcinogenic effects from ethidium bromide it would have to
get access to exposed replicating DNA and in complex multicellular
animals the chances of that would be extremely remote.

Dave Spencer