reversal of dose-response

Alan Stern ahstern at EOHSI.RUTGERS.EDU
Tue Jan 9 13:47:32 EST 1996

It seems intuitive to me that it should be possible to observe reversal of
the classic systemic dose-response relationship at elevated doses, at least
for some target organs/systems, when cells of the target organ which are
mediating an adverse response in response to the toxicant  are killed by a
larger dose of the toxicant than that which causes the mediation of the
adverse response.  I have seen one  example of this referred to in the
carcinogenesis literature where cells which have received a heritable
mutation can undergo one of three responses: 1.  death; 2.  clonal growth; or
3.  stasis.  The cell death response in this case corresponds to the
phenomenon of interest.  However, while I have seen this concept in several
places, I have seen no empirical data for it.  Another possible example of
this might be effects on the immune system, where immune receptor cells
and/or immune activation cells would be activated to mediate the adverse
immune response at low doses, but would be killed at higher doses and the
adverse response would therefore become inactivated.  Is anyone aware of
published references which could provide support for such a toxicologic

Alan H. Stern, Dr.P.H.,D.A.B.T.
New Jersey Dept. Env. Protection
Univ. Med. and Dentistry of NJ

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