Day 040 - 21 Oct 94 - Page 18

     
     1        possible to establish a no-untoward-effect level in this
     2        study; yet, nonetheless, they do represent a level of 50
     3        milligrams Amaranth per kilogram body weight as an
     4        effective no-effect-level.  So, there seems to me to be
     5        something rather curious happening here.  They state
     6        explicitly they could not find a no-effect-level, then they
     7        treat a level as if it were a no-effect-level.
     8
     9   MR. JUSTICE BELL:  No, they do not, do they?  You explain it to
    10        me.  It was not possible to establish a no-effect-level
    11        because there was some effect.
    12        A.  Indeed, OK; no-effect-level in respect of the renal
    13        calcification.  So they treat -- given that they did not
    14        find renal calcification below that level, they took that
    15        effect as the one by reference to which a no-effect-level
    16        would be determined and from which an ADI would be
    17        derived.  But that is, as I read it, effectively to
    18        discount the epithelial hyperplasia as if it were an effect
    19        of no significance.
    20
         Now, certainly renal calcification (which is a condition in
    22        which, to put it crudely, the kidney, particularly the
    23        entrance to the kidney, becomes enlarged with chalky
    24        material) is something which does happen in rats of this
    25        kind when they receive relatively high doses and is often
    26        an indication of relatively gross disturbance of their
    27        metabolic systems.
    28
    29        It is not an effect which is found in human beings very
    30        frequently, though it does occur from time to time, but
    31        I would have thought that if they were genuinely following
    32        the nominal rules by which ADI's were supposed to be set,
    33        they ought to be determining their no-effect-level by
    34        reference to any adverse effect and not merely the renal
    35        calcification.
    36
    37        Given that they could not establish a no-effect-level for
    38        epithelial hyperplasia, it seems to me questionable that
    39        they are acting properly in setting the ADI as they did.
    40
    MR. RAMPTON:  Do you accept, Dr. Millstone, that this further
    42        work (which is ignored in your report and your
    43        evidence-in-chief) did establish that the renal
    44        calcification was not an effect of the Amaranth?
    45        A.  Not necessarily.  Oh no, I certainly would not accept
    46        that it showed that the renal calcification was not an
    47        effect of the Amaranth -- on the contrary.
    48
    49   Q.   I do not think you could have read the whole thing.  You
    50        see, they redid some of the work, did they not?  Two 
    51        members of the team, Butler and Conning, were asked to redo 
    52        it or decided to redo it because they were uncertain about 
    53        the renal calcification.  That is the second part of page
    54        171 and the top of the next column.
    55
    56   MR. JUSTICE BELL:  Read it again because it may be important.
    57        Read from below the 82 reference, the second paragraph you
    58        have just been on. I will read it again as well.
    59        A.  May I ask, Mr. Rampton?  It seems to me the key
    60        sentence in this lower paragraph on page 6 of the JECFA