IRRITANCY TO THE RABBIT EYE MUCOSA OF CREAM SHAMPOOS 675 to support this. Beckley (7) compared the rabbit, dog and monkey Buehler and Newmann (8) compared rabbit and monkey and Roudabush and Terhaar (9) com- pared rabbit and guineapig. However, it is still not possible to conclude that any one species is the animal of choice. It may well be that the rabbit, which is a convenient laboratory animal, is as useful a species as any other, provided the data obtained is interpreted on a com- parative basis. I agree that the standard tests could be modified, and indeed many suggestions have been published. We are in agreement with the inclusion of animals in which the eyes are washed shortly after instillation of the test material. This is of definite value. The rabbit eye does respond differently to the human eye as regards the nature of its secretions. In the human eye watery "tears" are produced, but in the rabbit eye the watery secretions seen during the first, say 20 hr, are superseded by a white, viscous secretion. I do not know the exact significance of this, and would be grateful if anybody knows of any relevant publications. Nevertheless, this is obviously a different response to the test material. It is possible that some preparations we put into the eye may become bound to those secretions and thereby increase the period of corneal exposure. MR. F. D. GRA•NCER: Was there any correlation between the degree of irritancy experienced and the viscosity of the shampoos and/or the miscibility of those shampoos with the tear secretion? In other words, is the degree of irritancy in some way proportional to the degree of eradication of the irritant from the eye and was this looked into? MR. R. E. DAvtEs: We have not studied this problem in detail, although I hope we will eventually discover the cause of the irritation to the rabbit eye. This was not the subject of our brief. We simply took the five cream shampoos that were considered to hold the "lion's share" of the market at that time, and assessed their irritancy according to standard test procedures. However, we are now most interested in trying to find a causative relationship between the biological effect and the composi- tion of the shampoos. At this time our results are too provisional to be of any value. There is no obvious relationship with the chemical composition of the shampoos, and it may be that the physical factors are more important. The viscosity of the shampoo, as we have already heard from Mr. Pugh, may well be an important feature, possibly reducing the chance of accidental entry into the eye. MR. D. BAss: The discussions and conclusions claim that cream shampoo formula- tions are to be regarded as eye irritants. This is not true of all cream shampoo formula- tions, as it is possible to produce a cream shampoo using an amphoteric detergent which does not irritate or even sting the eye. Furthermore, it would be possible to reduce the high irritation of shampoos that have been tested in this paper by replacing a proportion of the detergent with an amphoteric. The work described is interesting but of little value unless it is correlated with the detergent used. MR. R. E. DAVIES: I believe I have answered a certain amount of your question already. The purpose of our brief was not to correlate biological activity with the (7) Beckley, J. H. Toxicol. Appl. Pharrnacol. ? Suppl. 2.93 (1965) (8) Buehler, E. V. and Newman, E. V. ibid õ 701 (1964) (9) Roudabush, R. L. and Terhaar, ibid 7 559 (1965)

676 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS composition of the shampoos. I would agree with you that our experience with amphoteric detergents does suggest that they are less irritant. I can add that none of the shampoos tested here contained amphoteric detergent. MR. W. S. B•AcI•: I assume that the shampoos that have been tested are the usual standard anionic type of sulphurated alcohols? MR. R. E. DAw•s: I think you could accept that. The five cream shampoos, as we stated in our paper, were purchased from a local chemist's chop. They were all standard shampoo formulations. DR. K. H. HARPER: I cannot accept Mr. Van Abb•'s arguments that because they receive no complaints that a shampoo has caused damage in the eye, this indicates that it is not irritant. He made the assertion that the shampoo must get into the eye, and that this must indicate freedom from irritancy. I hardly feel that one can adopt any code of practice with this as the basic premise. One has to have a little more information than mere conjecture of this nature. I think there is a close analogy with the paper by Brasch and Amoore (10). They have developed a method for testing detergency and find with this test something like 90% removal of fat. They do not say that because a compound has this effect it has severely detergent properties and therefore is of no value in a shampoo. Instead, they attempt to correlate this result with human experience. In other words, they have a model that they can interpret and, I think, the same is true of the rabbit eye test. One assesses the most severe reaction that a compound is capable of producing, and then needs to interpret this in terms of the possible human response. I think the Procter & Gamble people reported that in their experience materials producing primary irritation indices of the order of more than 2.5 invariably led to an increase in the number of consumer complaints. To me this seems a realistic approach to the problem. You draw a comparison with materials that you know to be irritant in human practice and ones that are not, and there the rabbit eye and the rabbit skin tests can be of predictive value. MR. N.J. VAN ABBr.: I would not like to suggest that the rabbit test has no rele- vance. I was referring to the way in which it is used and the extent to which you can draw conclusions. It does not seem to me that there is any evidence to suggest that the responses of the rabbit eye to neat cream shampoo are likely to correlate in any way with human experience. I do not believe that cream shampoos are not irritants to the human eye because we have not received any complaints.What I believe is that the responses obtained by cream shampoos in the human eye will bear no relation to the responses to neat shampoos in the rabbit eye. It is really a matter of quantity and not quality. DR. J. McL. PHI•.P: I want to support Dr. Harper in what he has just said. It is most important that you do pay attention to complaints and that you go to quite considerable lengths to have these investigated to make quite sure that your particular product has caused a complaint, and to determine exactly the degree of damage, using an ophthalmologist if necessary. If you set even a few of these accidents against your own predictive testing, then the rabbit eye test can be an extremely useful tool to all marketing and research members of industry. (10) Brasch S. V. and Arnoore. Miss J. A. J. Soc. Cosmetic Chemists 18 651 {1967).