Re: fetal exposure - threshold effects

[Chris Alston <alstonc@odrge.odr.georgetown.edu>]

Andrew

Maybe I'm not understanding your questions correctly, but the fetal effects
discussed, teratogenetic ones, are exactly those for which one might
reasonably expect to see sigmoidal dose-response curves and "practical
thresholds," because they appear to be deterministic (i.e., nonstochastic).
The evidence for the latter is, by definition, that one (typically)
observes "sigmoidal dose-response curves" and "practical thresholds."

The LNT model/hypothesis is for stochastic effects, e.g., the induction of
cancer. Whether in adult vs. child is, I think, neither here nor there, in
this context, except that a contrasting example might be the risks of
subsequent leukemias to children who were irradiated in utero.

Cheers
cja
alstonc@odrge.odr.georgetown.edu


At 01:06 PM 10/12/99 -0500, you wrote:
>I am reading NCRP 128 (Radionuclide Exposure of the Embryo/Fetus) and
>noticed (page 41, section 6.1.2) a part that reads "Typically, experiments
>in rodents have yielded sigmoidal dose-response curves for external
>malformations and skeletal defects, and no-effect levels of practical
>thresholds are sometimes detectable.  In general, the threshold for
>teratogenesis during the early or main inductive phase appears to be lower
>(about 0.05 to 0.1 Gy) than during major organogenesis (threshold range 0.15
>to 0.25 Gy)...Although insufficient data exist to construct unequivocal
>dose-response curves for teratogenesis specific to the human embryo, there
>are no reasons to believe that the foregoing threshold ranges are not
>generally applicable."  
>
>A comment to similar effect is made by Brent in "The Biological Basis of
>Radiation Protection Practice (page 26):  "Prior to summarizing the effects
>of irradiation at different stages of gestation it is important to emphasize
>that all the effects described are produced at or above specific doses.
>Since the vast majority of embryopathological effects are threshold
>phenomena, subthreshold doses will not produce these effects."
>
>My questions are (and please bear in mind that I am not an adherent to the
>LNT model):  
>
>Why would there exist a threshold for fetal exposure but not for adult
>exposure?  
>
>Why would a fetal dose-response curve be sigmoidal but an adult curve
>linear?
>
>Does this mean that the mechanism for fetal teratogenic effects differs
>somehow from the mechanism for adult stochastic effects?
>
>
>Please note that I am NOT trying to re-open the perennial
>LNT/threshold/hormesis debate.  I'm just curious about the basis for
>statements that seem, on the surface, to be mutually contradictory.  
>
>Thanks in advance for any light anyone can help to shed.
>
>Andy
>
>(PS - please remember, too, if you respond that my academic background is in
>geology - you don't need to use words of one syllable or less, but there's a
>limit to the amount of jargon I can follow.)
>
>Andrew Karam, CHP              (716) 275-1473 (voice)
>Radiation Safety Officer       (716) 275-3781 (office)
>University of Rochester        (716) 256-0365 (fax)
>601 Elmwood Ave. Box HPH       Rochester, NY  14642
>
>Andrew_Karam@URMC.Rochester.edu
>http://Intranet.urmc.rochester.edu/RadiationSafety
>
>We cannot prove that those are in error who tell us that society has
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>all before us, and with just as much apparent reason.  On what principle
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>expect nothing but deterioration before us?    Lord Thomas B. Macaulay,
>1830
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