Posted by Larry Hoover on September 1, 2004, at 8:25:14
In reply to Re: Ecstasy safely converted and prescribed? » Larry Hoover, posted by Dave001 on August 31, 2004, at 21:12:57
> > Indeed. Inter-species safety factors that I have worked with have been ten-fold, or hundred-fold, in different circumstances. We don't know that those safety factors are necessary. They arise from prudence. Overdosing a rat to produce neuronal damage is not generalizable, even with an a priori conversion factor. We're simpling being prudent.
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> True, though that's an issue not directly related to normalization for metabolic rate.I am truly grateful for your expertise, here. One thing that I seldom see, despite it's obvious value, is closer examination of the a priori assumptions. So very many factors are assumed, that those assumptions all become qualifiers on the validity of the conclusion. Seldom do we see conclusions which overtly express the underlying assumptions.
> > I was speaking to the EPA formulae for HED. The body area formula is the BW ^2/3 formula. I'd welcome another reference, for pharmacokinetic conversions, if you have one handy.
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> I'm assuming by BW you mean a ratio of animal to human weight; e.g., HED = animal dose * (animal weight/human weight)^2/3. Yeah, that is what I would go by in the absence of specific data for a given species, or if there is an extreme inner-species variation in weight.
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> Ah, here we go. I knew this had to be somewhere on their site. See <URL:http://www.fda.gov/cber/gdlns/dose.htm#v>; for dose conversion guidelines.Thank you. My work in toxicology makes different assumptions, though they have a similar effect.
> > > Quite possibly. I would imagine the body naturally kicks the production of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase, etc., into full gear in the presence of such toxins.
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> > Perhaps, if nutrient stores are up to it. Antioxidants are sacrificial. They are consumed, so the physiological stress passes into distinct realms depending on antioxidant capacity at baseline. That was the conclusion of the authors of the rat study, that different outcomes are predicated by those thresholds of depletion.
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> True, though 'nutrient storage' is somewhat ambiguous in the context of enzymes which are endogenously produced "as needed" as opposed to dietary antioxidants.Yes, but....Up-regulation of anitoxidant enzyme formation would not serve well in acute exposures, e.g. overdose of MDMA. It could not possibly happen fast enough. Liver toxicity in acetominophen exposure only begins upon depletion of glutathione. It is the idiosyncratic glutathione concentration which accounts for differences in outcomes from similar expsosures to the toxicant.
It is also one of my own a priori assumptions that the typical person is nutrient deficient. That could become a thread in itself, as I have done extensive research into the subject.
> However, deficiencies of important enzyme cofactors could of course occur.
The minerals in particular. Zinc and selenium, especially so.
> The importance of age in regulating antioxidant defenses has been particularly impressive in many studies I've seen -- I mean to a much greater extant than one might expect.
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> DaveOh, absolutely. It remains to be seen if that observation is the effect of chronic malnutrition. In other words, if simple supplement routines can act in a prophylactic manner.
Lar
poster:Larry Hoover
thread:383476
URL: http://www.dr-bob.org/babble/20040830/msgs/385168.html