Day 039 - 20 Oct 94 - Page 71
1 Q. On page 9: "This work was confirmed by a study in which
2 male ... rats were exposed to 1 or 2% BHA in a powdered
3 diet for 104 weeks with animals sacrificed in groups of 10
4 every 8 weeks during the course of the study. ...
5 Hyperplasia of the forestomach was observed in a few
6 animals of both treatment groups at the first observation
7 time, 8 weeks after the start of the exposure."
8
9 Please drop your eye down to the next paragraph: "A 104
10 week exposure of male and female .. rats to 0.5 or 2% BHA
11 in pellets was also reported." Again this is Ito -- mostly
12 Ito up to 1987: "There were approximately 50 rats per
13 exposure group. The mean body weights of both sexes were
14 reduced in those animals given 2%", and so on and so
15 forth. Are you still saying that this is an insufficient
16 number of animals exposed to a variety of dosages?
17 A. Yes, I am, because what matters, I think, amongst other
18 things, is the numbers of animals at each dose group.
19 I mean -----
20
21 MR. JUSTICE BELL: Why do you say more than 50? It appears that
22 50 is a pretty typical group and there is often less, but
23 Ito, upon whom you rely quite strongly for some of his
24 initial findings, seems to think that 50 was sufficient to
25 try and get some useful indicator. Without any disrespect
26 to you, these are people who are spending a lot of their
27 time carrying out animal experiments, are they not?
28 A. Indeed they are.
29
30 Q. And have nothing to gain from doing their work less than
31 thoroughly?
32 A. That, of course, is true. I cannot put words into
33 Professor Ito's -----
34
35 Q. What does Professor Ito have to gain from it?
36 A. It would be inappropriate for me to put words into
37 Professor Ito's mouth, but I would be very surprised if he
38 would not say that he would be delighted to work with
39 larger groups if he could obtain the funding enabling him
40 to do so. 50 animals per dose group is the standard. The
41 current orthodox protocol for long-term feeding study
42 involves using 50 animals per gender per dose group.
43
44 My response to that is to say, if that is to be the
45 orthodox experimental approach, and that is supposed to be
46 the model of the effects on humans and adverse effects
47 occur, then they should be taken at face value and not
48 simply disregarded. If you want to disregard them as
49 disproportionately high doses but you want a test that is
50 sufficiently sensitive, not merely to ensure that if the
51 compound causes cancer it causes cancer at a rate lower
52 than 5 or 10 per cent in the population, but causes cancer,
53 if at all, at a very much lower rate, it is only possible
54 to gain confidence that the rate would be significantly
55 lower if you have a large enough population of animals that
56 will give you that sensitivity. With 50 animals per gender
57 per dose group you cannot be confident that the real --
58 I mean, let us suppose you have -----
59
60 MR. JUSTICE BELL: Just pause for a moment because what you are
