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
