Day 039 - 20 Oct 94 - Page 69


     
     1   Q.   I am going to pause there because it may be there is
     2        something I have missed in all of this.  Do those not seem
     3        to you to be experiments which used graded dosages in order
     4        to determine the no-effect level or, rather, the adverse
     5        effect level?
     6        A.  They do not, for one very simple reason; you prefaced
     7        your remarks, when you drew my attention to this document,
     8        by quoting some things that I had said about responses to
     9        affect relatively high doses.  What you quoted me as saying
    10        correctly was that I think an appropriate response is to
    11        conduct studies at lower doses in larger groups.
    12
    13        What we have here are studies of lower doses, but in some
    14        cases very considerably smaller groups.  If you look back
    15        on to what is page 6 of the original JECFA document and the
    16        work by David Clayson and others, I mean, groups of five
    17        rats are very, very small rats by the standards of
    18        contemporary work.  But the largest single group, the
    19        largest group size in any of the studies to which you have
    20        drawn my attention here were 50 rats.
    21
    22   Q.   No.
    23        A.  But that is a standard sample size.  What I was
    24        suggesting, on the contrary, was lower doses in groups
    25        significantly larger than 50 per gender per dose group.
    26
    27   Q.   I thought you might say that, you see, Dr. Millstone, which
    28        is why I read you what you said.  I did not try and
    29        interpret it.  You said this:  "Now, given that human
    30        beings do not consume BHA at those levels", that is to say
    31        five per cent?
    32        A.  Two per cent.
    33
    34   Q.   Or two per cent in this case.  You are quite right: "...
    35        and given that it might possibly be the case that the
    36        symptoms that were exhibited by those laboratory animals
    37        arose by some gross overloading of their biochemistry"?
    38        A.  Yes.
    39
    40   Q.   "It seems to me the sensible thing to do would be to
    41        require further studies at lower doses, perhaps closer to
    42        those consumed by humans, but in correspondingly larger
    43        groups of rodents which might more effectively model the
    44        effects ... humans", and so on and so forth.
    45
    46        Please explain to me (because plainly I have not understood
    47        it) what in all of that is the significance of your
    48        reference to an apparent failure by the studies to use
    49        lower doses?
    50        A.  OK.  It is not a failure to use lower doses.  It is a 
    51        failure to test lower doses in larger groups.  As I tried 
    52        to explain yesterday, if we just concentrate on the UK, we 
    53        have a population in the order of 55 million people.  If we
    54        do a three-dose study plus a control with 50 animals per
    55        dose group per both genders, at each dose group, you have a
    56        maximum rodent population there of 400 rodents.
    57
    58        Now, for reasons that I also refer to in some of my written
    59        evidence, given there is random variation within the
    60        control groups and within the animals, these experiments

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