[Dioxin-l] References about threshold

[david bell]

Hi Tony
>now that the discussion is coming around to the unanswered questions I
>asked ~5 days ago (specific q's responding to some good info posted by
>Louise), I really wish they'd be answered
><snip> even if linear D/R curve down to one
>molecule isn't as plausible a pardaigm as a threshold concentration needed
>for a biological response, aren't the concentrations in the case of TCDD
>and other ED's so low (espec. compared to current exposures), that it's
>academic?

No ! (I think everyone will agree with this)
If you look at Chapter 8 of the EPA dioxin assessment, they state that they 
can follow a dose response for dioxin down to 10s/ single figures of 
picogrammes of dioxin/kilo, ie they say they can see a linear relationship 
down to this level. (this is the most sensitive part of their data, so 
whether it is truly linear down there is difficult).

But EPA also states that they assume linearity from that level down to the 
proposed level of the TDI, which is 0.01 pg/kg.

So it is critically important to determine where the threshold for toxicity 
actually is (or if there is a threshold), and this question occurs bang in 
the middle of where the regulatory limit for dioxin is. If the threshold is 
1 pg/kg, then you can safely set the TDI at 1 pg/kg. If it is a thousand 
times lower than that, you must go to 1 femtogramme /kg.

><snip>
>David Bell--can you elaborate on your too brief comments about receptor
>binding at 6 pM ('pm' would be abbreviation for molal? anyway).
>ppq(uintillion, in rough terms?   Also, what constant is
>'Kd'--dissasociation? ...in explanatory mode  --thanks!

Under ideal conditions, the dioxin receptor becomes half-occupied at 6 
picoMolar dioxin. It is a measure of the affinity of the receptor for 
dioxin. You will see some binding of dioxin to the receptor below these 
levels, but it falls off quite drastically; there is some mathematical 
description of this type of binding. So for example, at 0.6 picoMolar 
dioxin, you would expect less than 10% of the AhR to have bound dioxin, etc- 
but you should check with someone who knows receptor theory better than I.

if my arithmetic is right, 6 picoMolar TCDD is approx 2 nanogrammes of 
dioxin per kilo of water.

cheers
david



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