Day 038 - 19 Oct 94 - Page 13
1 the animals at high doses, claiming that the doses are
2 massively greater than human beings could conceivably
3 ingest or would involve drinking heroic quantities of
4 liquid, consuming massive amounts of food in a day, and are
5 unrealistic.
6
7 Of course, they may in that respect be unrealistic, but
8 given that they have, as it were, chosen to use the high
9 doses to compensate for the relatively small groups, I do
10 not think one can do what these committees typically do,
11 which is disregard the effects emerging at higher doses.
12 So, I think doses are important, but the importance which I
13 attach to them is not necessarily the importance which
14 Professor Walker and the members of the Committee on
15 Toxicity, the Scientific Committee for Food, and the Joint
16 Expert Committee on Food Allergies will ascribe to.
17
18 MR. JUSTICE BELL: Is scaling up the dose, as you put it, in the
19 tests to compensate for the relatively small size of the
20 laboratory animals and relatively short life, or is it
21 because you may expect to get a reaction (if there is going
22 to be one) more quickly, and is the first multiplier of ten
23 the one which is supposed to take account of the different
24 physiology between an animal and a man or a woman just
25 because that is a safety factor; for safety reasons we will
26 assume (although we do not know it) that human physiology
27 is ten times more vulnerable than animal physiology?
28 A. I would not quite characterise it in that way. I think
29 you have put your finger on several important points, but
30 -----
31
32 Q. Because it is the latter which I was led to understand by
33 Professor Walker, not that it was related to difference in
34 size or difference in life-span?
35 A. I think there are two different sets of considerations
36 which are overlapping here. One concerns the design of the
37 tests; the second set concerns the interpretation of the
38 results.
39
40 If we start with the former set of considerations relating
41 to the design of the tests, you are correct to suggest that
42 the difference in size between rodents and humans is one
43 consideration that purportedly justifies the scaling up of
44 the dose; there is the size of the animal, the life-span of
45 the animal and the size of the population of animals, the
46 relatively small groups of animals and the relatively large
47 group of humans.
48
49 The size of the animals is, to some extent, presumed to be
50 accounted for in the ways in which the dose is measured,
51 where the doses are normally calculated in terms of
52 physical quantity of test compound per unit mass of the
53 laboratory animal. So, it is in typically milligrams per
54 kilogram body weight of the animal.
55
56 So, the relative size of the animal is sometimes thought
57 not to justify the scaling up of the dose. It is usually
58 the difference in the population sizes and the lifetimes.
59 I think it is worth pointing out, though, that I have
60 searched in vain through the toxicological literature for a
