26, 509-522 (1975) 1975 Society of Cosmetic Chenists of Great Britain
Cough irritation by deodorant sprays E. M. STAAL, W. BREE and P. L. C. A. RIJNBEEK* Synopsis--The causes of RESPIRATORY IRRITATION provoked by DEODORANT SPRAYS have been investigated. For this purpose, the irritant potential of several deodorant spray formulations was determined. The quantitative evaluation of cough stimulation was carried out on a large number of subjects. The various features of the method are discussed in detail. This investigation has shown that the main causes of cough stimulation by deodorant sprays are the antimicrobial agents included in the formulae. INTRODUCTION Cough, triggered by inhalation of an aerosol, is a common mani- festation, very tiresome for the user; it should be considered as a technical defect of the aerosol, particularly with aerosols for cosmetic use sprayed towards the body. Cougl is caused by irritation of the mucous membranes of the nose, throat and respiratory tract. With aerosols, in some circumstances, the sprayed contents may trigger such an irritation. The chemical and pharma- cological bases of this irritation are hardly known. Previous investigation (1, 2, 3, 4, 5, 6) refer mainly to inhalation toxicity in general terms. For this reason, the investigation described here on the causes of cough stimu- lation has been focused on formulation characteristics of aerosols and * Research Laboratory Drogerijen Maatschappij Brabantsestraat 17, Amersfoort, The Nether- lands. 5O9 510 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS particularly to deodorant sprays which are known to induce coughing on some occasions. A method was developed in our laboratories to quantify this effect; this so-called Consumer Test Method derived the average value for a numerical rating given by a number of test subjects, with respect to the feature being investigated. The different facets of this test method will be discussed in more detail. The investigation was carried out on 'wet' deodorant sprays without antiperspirant ingredients. Such products are designed to reduce the bac- terial skin flora, thereby preventing the products of bacterial metabolism from giving rise to malodour. Deodorant sprays containing anti-oxidants and odour-absorbers were excluded. Experience had shown that, in spite of similarities in composition, there were wide differences between the irritant properties of commercial sprays. It therefore seemed likely that one or more factors responsible for cough stimulation might be identified. The spray formulae investigated for cough-stimulating activity ranged in composition within the following limits: Fatty substances 0-0.30o Perfume 0-0.20o Bactericides 0-0.25o Solvent 0-50o Propellant up to 100o By changing the proportions of the five main components, a number of different deodorant sprays could be prepared, each of which was tested for cough-stimulating potential. No formula without both fatty substances and solvents was studied, as this would have meant that the bactericide would have been sprayed as a dry powder. Fatty substances Perfumes MATERIALS Isopropyl myristate Propylene glycol Isopropyl isostearate Isopropyl palmitate Various COUGH IRRITATION BY DEODORANT SPRAYS 511 Bactericides 2,3,5,2',3',5' hexachloro-6,6' dihydroxydiphenylmethane 2,4,4' trichloro-2' hydroxydiphenylether 3,4,4' trichlorocarbanilide 4,4' dichloro-3-trifluoromethylcarbanilide, 3,5-dibromo-3' trifluoromethyl-salicylanilide, 2,5,4' tribromosalicylanilide. Solvent Absolute ethanol, not denatured Propellant Monofluorotrichloromethane (F 11) Difluorodichloromethane (F12) To test the influence of the spray pattern and of the spray rate on cough stimulation, several valve combinations (Deutsche Pr//zisions-Ventil) with different actuator, stem and housing orifices were used. TEST METHOD The cough-stimulating potential of each deodorant spray was determined under conditions as near to normal use as possible. Randomly chosen volunteers were asked to give absolute appraisals of the irritant properties of the spray being tested. In this respect the test method deviates from the several standard methods which are used in sensory testing (7). The value obtained by averaging the numerical ratings given by the tested subjects is probably influenced by a combination of chemical, physical and psychological factors, as occurs in practice. From this angle, the method offers advantages compared with instrumental analytical methods, which yield data influenced only by physical and/or chemical, but not psycho- logical, factors. For optimum results in consumer testing, the following criteria are applicable: Ten people or more should be interrogated. All interrogated subjects should collaborate on a voluntary basis. Each test should be completed as quickly as possible, preferably within lh. 512 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The assessment procedure for an individual subject should be as brief as possible, avoiding complicated or long and tedious procedures; Not more than two tests should be carried out daily with a given subject in the panel and the interval between two successive tests should not be less than 4 h. Each subject should be clearly told what characteristics of the test pro- duct should be considered. The way in which the testing procedure is carried out should be chosen individually by the subject. The investigator should ensure that subjects cannot influence each other's opinion. During each test, each subject should give an absolute appraisal about a given feature; no comparison material whatever should be available at any time during the test. The subject's appraisal about the feature being tested should be ex- pressed by a rating: 0, 1, 2, 3 or 4 (4 = greatest effect, whether good or bad). To find out if there is any significant difference between two test series, the Wilcoxon's Q-test may be used, with a one-side overrun probability of 5%. For each consumer test, the ratings obtained were averaged and multi- plied by 2.5. The figure so obtained was called the factor for the aspect being investigated. (Minimum value 0, maximum value 10.) The factor on a 0-10 scale gave a figure suitable for ready interpretation of cough stimulation. After statistical analysis by the Q-test it became evident that a difference of 1 point between two factors was significant. All factors, therefore, were rounded to 0.5. Observations concerning the application of the test method to deodorant spray cough stimulation were: The cough stimulation test panel included 11 women and 21 men, aged between 18 and 45. No difference appeared betveen appraisal by men and by women, or between age groups. Two sprays were investigated each day, one in the morning and one in the afternoon. Hardly any difference appeared between morning and after- noon tests. COUGH IRRITATION BY DEODORANT SPRAYS 513 Each subject was free to choose how to make the test. Two different methods were used: some subjects (19o) tended to direct the aerosol spray towards the face from arm's length. The remaining sub- jects sprayed horizontally in front of the body and then remained immersed within the spray cloud. No overall difference in findings appeared between the two groups although, with the second method, the sprayed amounts of fluid were generally greater. Respiratory tract irritation was expressed as an integer, according to the following table: 0 no cough, 1 slight cough, 2 moderate cough, 3 strong cough, 4 very strong cough. After averaging, multiplication by 2.5 and rounding to 0.5, a value was obtained for each spray, giving a measure of the cough-stimulating poten- tial: the cough factor (CF). Cough-stimulating activity was assessed twice for each deodorant spray investigated. Reproducibility appeared to be good. The whole investigation lasted about 2 yr, with a total of 212 irritation tests. EXPERIMENTAL Preliminary studies Since at the beginning of this investigation nothing was known about the possible cough-stimulating potential of the various ingredients, first the cough-stimulating activity of a deodorant spray with a composition in common use was determined 514 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Composition 7o Isopropyl myristate 0.3 Perfume 0.2 Bactericide 0.2 Ethanol 24.3 F11 25.0 F12 50.0 100.0 The fragrance used was a green flowery type. The bactericide was chosen arbitrarily from the six types listed above and was used as the standard bactericide throughout the investigation. The aerosol was equipped with a valve having a stem orifice of 0.45 mm and an actuator orifice of 0.50 mm; the spray angle was about 16 . All preliminary tests were carried out with this deorodant spray; initially the investigation was designed to show whether the consumer test did actually ensure good quantitative reproducibility of the cough-stimulating irritation. This preliminary study indicated that the test method was suitable for the purpose and the spray mentioned above gave a cough factor (CF) of 6.0. This standard spray was used for reference throughout the main investi- gation, a run with it being included in each large test series. The standard spray was tested, overall on 22 occasions by the panel, leading to cough factors as follows: 4 times: CF = 5.5 12 times: CF = 6.0 6 times: CF = 6.5 Between the two extreme values, 5.5 and 6.5, Wilcoxon's Q-test only once showed a significant difference. A number of screening tests were performed, in order to identify a possible main cause for cough stimulation. Several formulae were tested, one ingredient being omitted each time. Table I gives a summary of the formulae used, with corresponding CF values. Clearly the formulation without bactericide was less cough-stimulating than the others. Formulae C, E and G (respectively without perfume, with- out ethanol and without F12) also gave significantly lower CF values than the standard, but not as low as the bactericide-free formula. COUGH IRRITATION BY DEODORANT SPRAYS Table I. Elimination series of deodorant ingredients 515 Composition: A B C D E F G* Isopropyl myristate 0.3 -- 0.3 0.3 0.3 0.3 0.3 Perfume 0.2 0.2 -- 0.2 0.2 0.2 0.2 Bactericide 0.2 0.2 0.2 -- 0.2 0.2 0.2 Ethanol 24.3 24.6 24.5 24.5 -- 24.3 24.3 F11 25.0 25.0 25.0 25.0 49.3 -- 75.0 F12 50.0 50.0 50.0 50.0 50.0 75.0 -- CF 6.0 6.0 4.5 1.5 4.5 6.5 4.5 Difference from the standard value -- not sign. sign. sign. sign. not sign. sign. * Aerosol brought to an internal pressure of 0.009 Nm - (= 8 atmospheres) with nitrogen. To exclude a possible cumulative effect of the irritant influences of perfume, ethanol and F12 on the respiratory tract, the following formula was also tested. Table 1I. Cumulative effect of perfume, ethanol and propellant Composition: H* Isopropyl myristate 0.3 Bactericide 0.2 Fll 99.5 CF 4.5 Difference from standard sign. * Aerosol brought to an internal pres- sure of 0.009 Nm - with nitrogen. Further evidence is that formulae E, F, G and H are associated with spray patterns which are totally different from that of the standard spray. Attempts at reproducing spray patterns as close as possible to that of the standard formula by means of other valves and variations of the pressure by means of nitrogen, had only partial success. To determine whether differences in the spray pattern and spray rate influence respiratory tract irritation, several aerosols were tested, each time with the standard formula but completely different valves. Here attempts were made to obtain spray patterns that were as different as possible from each other. 516 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table III. Effect of varying spray pattern Valve specification: Housing orifice 2.0 mm 2.0-0.50 mm 2.0 mm Stem orifice 0.45 mm 2 x 0.50 mm 0.45 mm Actuator orifice 0.50 mm 0.50 mm 0.33 mm Spray rate 1 g s 4 0.6 g s -x 0.4 g s 4 Spray angle 16 10 12 CF 6.0 5.5 6.0 Difference from standard -- not sign. not sign. The results show that a different spray pattern of the aerosol hardly influenced cough stimulation (see also Table VII(a) and (b)). Further studies of the influence of the ethanol and propellant concentra- tions, which influence the spray pattern, were thus simplified. Having completed the above screening tests, a systematic investigation into the influence of the ingredients of the deodorant spray on the respira- tory tract could then be performed. Influence of fatty substances During the preliminary tests, the presence or absence of isopropyl myristate in the standard formula apparently had no influence on cough stimulation. The influence of other fatty substances was determined by replacing iso- propyl myristate in the formula successively by: propylene glycol, isopropyl isostearate and isopropyl palmitate, each time at a concentration of 0.3. With all these sprays cough stimulation corresponded to that induced by the standard formula (CF = 6.0). Since the irritant influence of fatty substances might interact with that of bactericides, the above formulae were re-tested in bactericide-free sprays; no difference was found from formula D, the bactericide-free modified formula (CF = 1.5). Influence of perfumes It was decided not to test single ingredients of perfumes for cough stimu- lation, partly because the preliminary tests had shown that perfumes only had a limited influence on respiratory tract irritation and also because the great number of ingredients used in perfumes would have made a global investigation impossible. COUGH IRRITATION BY DEODORANT SPRAYS 517 It was therefore considered sufficient to test a number of perfumes with distinctive characteristics' woody, green, spicy, fruity, flowery and cologne. These perfumes were used in the standard formula at a concentration of 0.2%' none of these sprays showed any significant shift from the standard CF value (CF = 6.0). The above-mentioned perfume types were also tested in the bactericide- fi'ee formula' here also the type of perfume was shown not to influence the CF give by formula D, the bactericide-free low-irritation formula (CF -- 1.5). The influence of perfume concentration was also investigated. Various concentrations of a standard fragrance were added to the standard formula and each of these sprays was tested for cough stimulation. The same set of concentrations was also tested in the bactericide-free formula. The resulting CF values are given in Table IV. Table IV. Effect of perfume concentration Perfume Standard formula Standard formula concentration with bactericide without bactericide O.2O% 6.O 1.5 0.13% 6.5 1.5 O.O6% 6.O 1.5 O% 4.5 O.5 Compared with the standard formulae, the perfume-free sprays gave significantly lower CF values; thus, among those perfumes used in these tests cough-stimulating irritation is apparently influenced not by the kind of perfume, but by the presence or absence of perfume. Influence of bactericides During the preliminary tests, the standard bactericide apparently had a strong influence on the irritant activity. For a better knowledge of this dependence, the cough-stimulating activity of a standard formula with increasing concentrations of bactericide was investigated. These measurements were repeated with five other bactericides con- sidered for inclusion in deodorant sprays. The CF values found are reported in Table V. JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table V. Effect of type and concentration of bactericide Concentration % Bactericide 0 0.05 0.10 0.15 0.20 0.25 Standard 3.0 4.5 6.0 6.5 7.0 A I 2.0 2.5 4.0 6.5 7.5 B 1.5 1.0 1.5 2.0 2.0 1.5 C 1.5 1.5 1.5 2.5 2.5 D I 1.5 4.0 5.0 7.0 7.0 E 3.5 4.5 5.5 7.5 7.5 After statistical analysis of the test results (comparison of Q-test) the following conclusions could be drawn: Throughout the chosen concentration range, no significant difference appears between the standard bactericide and E, both being associated with strong cough stimulation even at low concentration, B and C did not irritate the respiratory tract at any concentration within the observation range, A is not irritant at concentrations up to 0.1 o; at higher concentrations the CF quickly rises to that associated with the standard formula, D is not irritant at concentrations up to 0.05; at higher concentrations the CF quickly increases to that associated with the standard formula. Influence of solvents and propellant In technically well-designed aerosols, the percentages of solvents and propellant cannot exceed certain practical limits. The sprays considered here sometimes had extreme compositions that could hardly be used in normal practice. The observed CF values clearly show, however, how cough-stimulating activity varied in such cases (Table Vl(a) and (b)). The results showed that ethanol and propellant only influence cough stimulation to a small extent. However, since high alcohol levels seemed slightly to reduce the irritant activity, the influence of alcohol was further investigated. A number of sprays with increasing alcohol levels was tested in two series with 0.1 and with 0.2 of bactericide respectively. In addition, each COUGH IRRITATION BY DEODORANT SPRAYS 519 of these formulae was used to prepare two aerosols' one with a standard valve (spray rate 1.0 g s-), and one with a valve ensuring a spray rate of 0.5 g s -. Table VI (a). Effect of varying solvents and propellants (bactericide present) Composition: lsopropyl myristate 0.3 0.3 0.3 0.3 0.3 Perfume 0.2 0.2 0.2 0.2 0.2 Bactericide 0.2 0.2 0.2 0.2 0.2 Ethanol -- -- 24.3 39.3 39.3 Fll -- 79.3 25.0 -- 50.0 F12 99.3 20.0 50.0 60.0 10.0 CF 5.0 5.5 6.0 5.0 3.5 Difference from standard not sign. not sign. -- not sign. sign. Table VI(b). Effect of varying solvents and propellants (in absence of bactericide) Composition: [sopropyl myristate 0.3 0.3 0.3 0.3 0.3 Perfume 0.2 0.2 0.2 0.2 0.2 Bactericide ..... Ethanol -- -- 24.5 39.5 39.5 Fll -- 79.5 25.0 -- 50.0 F12 99.5 20.0 50.0 60.0 10.0 CF 1.0 2.0 1.5 1.5 1.5 Difference from Formula D not sign. not sign. -- not sign. not sign. Each of these sprays contained 0.2o of perfume, 0.3 of isopropyl myristate and up to 100 propellant (F1 l/F12: 60/40). The CF values found are reported in Table VII(a) and (b). Table VII(a). Influence of ethanol concentration at different spray rates Bactericide 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Ethanol 3.0 3.0 6.0 6.0 12.0 12.0 25.0 25.0 50.0 50.0 Spray rate (g s -) 0.5 1.0 0.5 1.0 0.5 1.0 0.5 1.0 0.5 1.0 0.5 1.0 CF 3.0 3.0 4.5 4.5 4.0 4.0 4.0 4.5 4.5 4.0 3.0 2.5 520 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table VII(b). Influence of ethanol concentration at different spray rates with bactericide at increased concentration Bactericide 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Ethanol 3.0 3.0 6.0 6.0 12.0 12.0 25.0 25.0 50.0 50.0 Spray rate(gs -x) 0.5 1.0 0.5 1.0 0.5 1.0 0.5 1.0 0.5 1.0 0.5 1.0 CF 4.5 4.0 6.5 6.0 6.0 6.5 6.0 6.5 6.0 5.5 3.5 3.5 The recorded CF values led to the following conclusions: In deodorant sprays, concentrations of ethanol from 3.0 to 25o showed no influence on cough stimulation. At 50o concentration of ethanol, cough stimulation appears to have been slightly reduced; ethanol-free sprays also showed a slight reduction of CF. A 50o reduction of the spray rate of these deodorant sprays did not influence cough stimulation. DISCUSSION Before discussing the results, it should be clearly stated that these tests and measurements are not all-embracing. There is a wide range of other possible variations, e.g. other bactericides, influence of important perfume raw materials, formulae with other solvents, etc. When planning the tests, it was decided to remain within practical limits of importance to con- temporary cosmetic science. The main advantage of the Consumer Test Method is that it allows direct correlation between the properties of a product and the consumer's appraisal, thereby bypassing the necessity of converting a number, obtained by instrumental observation, into some kind of index corresponding to acceptance by the end consumer. In addition, the method is inexpensive and rapid. Each subject interrogated is expected to give a numerical appraisal expressed as 0, 1, 2, 3 or 4. As he or she does this, it is essential that no comparison material be made available; in daily use of a product--here a deodorant spray--no comparison material will actually be available. The absolute appraisal, in terms of these ratings, relates to a given property of the product, assessed as in daily use. COUGH IRRITATION BY DEODORANT SPRAYS 521 In our evaluations, a dispersion of values was noted in every test. In addition, the frequency distribution was not normal, thereby making it impossible to compare two series of measurements by t-test. In an evalua- tion like this, the most precise way is to use the (T) sign test in order to recognize significant differences. In interpreting the data obtained with the consumer test, we preferred, however, to use the Q-test of Wilcoxon. Here each segment of the data in a series is compared with the data obtained from another series. This yields a difference score, called Q-value, allowing the one-side overrun proba- bility to be determined by means of tables. Using the Q-test instead of the T-test has the advantage of allowing comparison between series of different length. Experience has shown that the average rating, as determined with the consumer test method, has a maximum value of 3 to 3.5. Not only when assessing cough stimulation due to deodorants, but in other tests, too, there appears to be some personal dislike for giving the maximum mark for a given effect. This finding is in accordance with the findings of several other investigators (7, 8, 9). The conclusions which can be drawn for the sources of cough stimula- tion by deodorant sprays are that this irritation is due to the type of bac- tericide used and the percentage of bactericide included in the formula. Other factors, like the spray pattern and spray rate, the concentrations of solvents and perfumes, appear to play a secondary role. That respiratory tract irritation appears not to depend on spray rate is quite logical if it is realized that a test subject feels irritation from an aerosol cloud no matter how this cloud has been formed. This statement is supported by the fact that the test procedure has no influence on the actual irritation felt by the subjects. Wide differences appear to exist between the cough-stimulating effect of different bactericides. No correlation could be deduced between the bac- tericidal and the irritant properties for the different compounds studied, so we have only reported our actual findings. (Received: 21st February 1975) REFERENCES (1) Kinkel, H. J. Inhalation and toxicity studies. J. Soc. Cosmet. Chem. 15 395 (1964). (2) Kiibler, H. Physiological properties of propellants. J. Soc. Cosmet. Chem. 14 341 (1963). (3) Gloxhuber, C. Zur Methodik der toxikologischen Prti lung von Kosmetika. J. Soc. Cosmet. Chem. 21 313 (1970). 522 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS (4) O'Connor Ward, C. Current perspectives on aerosol toxicity. J. Soc. Cosmet. Chem. 25 271 (1974). (5) Troy, W. R. Testing for inhalation toxicity. J. Soc. Cosmet. Chem. 25 283 (1974). (6) Joyner, B. D. and Holmes, C. L. Manufacturing Chemist p. 8l May 1970. (7) Amerine, M. A., Pangborn, R. M. and Roessler, E. B. Principles of Sensory Evahation of Food (1965) (Academic Press, New York). (8) Guilford, J.P. Psychometric Methods (1954) (MacGraw-Hill, New York). (9) Ough, C. S. and Baker, G. A. Small panel sensory evaluations of wines by scoring. ttilgardia 30 587 (1961).