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12 2788 Biochemical Research Laboratory The Dow Chemical Company SUITABILITY OF METHYL CHLOROFORM AND METHYLENE CHLORIDE FOR USE IN AEROSOL HAIR SPRAY FORMULATIONS File Ref. Charge Sub. By Kept. By T2.43-148-2 See below 2505 T. Anthony K. J. Olson T 2.43-148-2 Signed , Checked 0 4- COPIED IN MIDLAND Gftt i. SEP 2 0 1999 DISTRIBUTION The Dow Chemical Company, R. H. Boundy Central Research Index H* H. McIntyre T. R. Norton A.Hart N. Wright G. E. Lynn (2) G. D. Jones O. R. MeIntire T. Anthony (6) A. L. Steinhauer K. J. Olson Midland Pitman-Moore Division R. D. Moss Midland Division B. B. Holder, M. D. A. W. Wilson E. N. Luce S. A. Shrader Texas Division Central Research Index D. J. Kilian, M. D. Western Division Central Research Index D. Elshere J. F. Kagy 'Si ` i > ' sjl ,, A 1QGR CENTRAL RESEARCH INDEX RESTRICTED: for use within The Dow Chemical Company only. - R&Sl 68054 SUITABILITY OF METHYL CHLOROFORM AND METHYLENE CHLORIDE FOR USE IN AEROSOL HAIR SPRAY FORMULATIONS Biochemical Research Laboratory The Dow Chemical Company Midland, Michigan June 1, 1966 I. INTRODUCTION The purpose of this study was to evaluate the toxicological properties from inhalation, eye irritation, and skin irri tation viewpoints of several proprietary hair sprays in comparison with Dow Experimental Formulations containing methyl chloroform and methylene chloride in varying concen trations. Nitrous oxide was also evaluated as a propellant. Vinyl chloride was incorporated in two of the experimental formulations. II. GENERAL SUMMARY AND CONCLUSIONS A. All Dow experimental formulations studied produced some degree of corneal injury as a result of direct spray applications to the rabbit eye. In general the effects were comparable to those produced by the proprietary products. The formulations would likely not produce permanent effects in the human eye. B. None of the Dow or proprietary formulations studied would be likely to produce skin irritation under conditions of recommended use. C. Laboratory rats exposed to approximately 800 times the atmospheric concentration of aerosol mist and vapor that would result under consumer use conditions showed signs of toxicity, including death, which was attributable to suffocation resulting from oxygen depletion. It is most unlikely that any untoward effects would result from normal use of any of the formulations tested. D. It is recommended that formulations containing vinyl chloride be subjected to further study in order to insure safety. R&Sl 68055 Ill- MATERIALS AND FORMULATIONS TESTED A. Proprietary Products Proprietary Product Trade Name 1 New Lustre Cream 2 Super Natural 3 Alberto V05 4 Breck 5 Sudden Beauty 6 Just Wonderful 7 New Halo 8 Hidden Magic 9 Spray Net 10 Aqua Net 11 Adorn Manufacturer Colgate-Palmolive Reylon, Incorporated Alberto-Culver Company Breck Whitehall Laboratories Caryl Richards, Inc. Colgate-Palmolive Co. Proctor and Gamble Helene Curtis Ind.' Helene Curtis Ind. Toni Co. (Gillette) R&S168056 R&S168057 Dow Experimental Formulations (Percentages) P-12 Vinyl Chloride P-11 Methyl Chloroform Methylene Chloride 1 25 2 25 25 3 25 4 15 5 15 6 15 7 8 15 15 9 15 10 25 15 25 15 50 40 50 40 40 30 10 10 10 10 10 Resin fvpAa 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 Ethanol 47-5 47-5 47.5 30.0 30.0 30.0 30.0 40.0 40.0 47.5 Nitrous Oxide (60 psig) 2.5 2.5 2.5 2.5 2.5 2.5 P-12, P-11 from DuPont Vinyl chloride, methyl chloroform {tech.), and methylene chloride (tech.) all from Dow. ' Ethanol is anhydrous formula 40-2 PVP/VA from General Aniline and Film Corporation 60:40 ratio IV. INHALATION OF AEROSOL MIST A. General Comment As a result of extensive studies which have been conducted In the laboratory and also Judging by human exposure experience from manufacturer and customer use It Is known that the toxicity of the solvents (methyl chloroform and methylene chloride) used in the Dow formulations is very low. In light of this knowledge It was recognized that in order to assess any possible toxicological effects which might result from exposure to hair spray mist, a laboratory method would have to be devised which would afford drastic exposure conditions to laboratory animals. The method described below was designed with the intent of providing atmospheric concentrations of the mist and vapor Just slightly below that which would produce death in laboratory rats caused by asphyxia or suffocation. In other words, the oxygen level in the exposure chamber as a result of vapor and mist displacement would be barely sufficient to support life. B. Laboratory Method A total of 138 rats (69 males and 69 females) were used on the experiment. Young male rats were chosen in the weight range of 170-300 grams. The female rats weighed between 140-190 grams. The exposure chamber consisted of a wire mesh cage, 7" x 7" x 14M in dimensions, which was enveloped in a polyethylene bag secured tightly to the walls of the cage with tape. Six rats (three males, three females) were placed in the chamber immediately prior to the exposure. The aerosol can was then introduced into the neck of the bag and the aerosol mist was delivered directly into the chamber for exactly ten seconds. The bag was then sealed and the animals were allowed to remain in the air-tight chamber for an exposure period of fifteen minutes. At the termination of the experimental period the plastic bag was removed from the cage, the animals were then returned to holding cages where they were allowed to eat and drink ad libitum. This procedure was repeated three times per day A.M., 1:00 P.M., and 4:00 P.M.) five days per week for two weeks. The exposure amounted to 45 minutes per day or a total exposure time of 450 minutes (7*5 hours) over the two week period. R&SI 68058 All animals were observed dally during and after the exposure period for signs of untoward physiological responses, abnormal behavior or stress of any kind. During the two week experimental period all animals were weighed three times per week. Animals which failed to survive the procedure were autopsied, when practical, to determine the cause of death. At the end of the two week period.all surviving animals were sacrificed and internal organs were examined from a gross pathological viewpoint. At the sacrifice time, blood samples were taken for the purpose of determining serum urea nitrogen (SUN) and glutamic pyruvic transaminase values (SGPT) in the serum. Serum urea nitrogen is reported as mg.$ and SGPT in unlts/ml. An enzyme unit is defined as the amount of enzyme which catalyzes 1 mp mole change of reactants per minute at 37C and pH 7*4. The volume of the exposure chamber was 7^4 cu. in. or approximately 12.8 liters. The total volume occupied by the six rats was calculated to be 1.8 liter. The unoccupied volume of the experimental chamber, therefore, was about 11 liters. Assuming uniform dispersion of mist, the animals, then, were exposed to about 815 times the atmospheric concentration of hair spray ingredients that would be encountered in normal human use in a powder room of dimensions of 5' x 8' x 81 (320 cu. ft. or 8900 liters). In addition to concentration differential it should be appreciated that a powder room is subjected to some degree of ventilation which would afford a continuous dilution factor in the case of human use. The rat exposure chamber was air-tight. C. Results and Conclusions From inspection of the mortality ratio data presented in Table 1 it is apparent that several animals failed to survive the drastic exposure conditions imposed by the test procedure. Dow Sample 6 which contained 50# methyl chloroform and 15# vinyl chloride afforded the highest mortality ratio as none of the six rats exposed survived. Four of these animals died following the very first exposure. In the case of Dow Sample 4 which contained 5056 methyl chloroform and 15# Freon-12, only half of the animals (all females) survived. Attention is called to the data recorded for Dow Sample 1 (control) which contained Freons 11 and 12. While there R&S168059 was no mortality in the Dow Sample 1 Control group, half of the animals gained weight and half lost. In the case of the air controls, all animals except one showed a normal weight gain pattern. The mortality data pertaining to the remaining Dow experimental materials is not appreciably different from those of the proprietary materials. Prom gross pathological examination of deceased animals, death was attributed to suffocation resulting from oxygen displacement by the excessive mist In the exposure chambers. Serum urea nitrogen values (Table 2) were normal in all animals at the time of sacrifice. SGPT values (Table 2) were likewise judged normal except for two questionably high values; one animal of three on Proprietary 5 and one of three on Proprietary 8. It is apoarent from the data presented that the major physiological effect caused by exposing rats to aerosol hair spray mist was that resulting from oxygen depletion in the atmosphere. In view of the fact that the exposure concentration of mist approximated 800 times that likely to be experienced by humans, it Is very unlikely that any untoward effects would result from normal use of any of the proprietary or experimental formulations. There appears to be no contra-indication for the use of methyl chloroform and methylene chloride in any of the combinations studied. Due to the results for Dow Sample 6 it is recommended that vinyl chloride not be considered for use in aerosol hair sprays until further investigated for this use in the laboratory. The highly acute effects (death) appear to have resulted from suffocation. Vinyl chloride has a very high vapor pressure and would be expected to rapidly contribute to oxygen depletion in such extremely confined quarters. V. EYE IRRITATION (TABLE 3) A. Method Three albino rabbits were used to evaluate eye irritating properties of each hair spray formulation. Prior to conducting the study, all eyes were established as being free of injury when the corneal tissue showed no response to aqueous fluorescein stain. The materials were sprayed directly into the conjunctival sacs by holding the spray nozzle 4 to 6 inches from the eye. The amount of material actually entering the conjunctival sac was regulated by the time required for the animal to blink, which was R&S168060 almost instantaneous in spite of an attempt by an attendant to hold the eye open. In no case were the materials washed from the eyes. Immediately follow ing the application, the exposed eyes were examined for signs of conjunctival irritation and corneal injury. The eyes were subsequently examined at intervals of one hour, twenty-four hours, forty-eight hours, one week and two weeks after instillation of the material. Here again, fluorescein stain was employed to assist in detecting corneal injury. The type and intensity of the reaction were rated according to the following index code. Index Reaction 1 No effect. 2 Very slight effect disappearing in 24 hours. May consist of appreciable pain Initially and some conjunctival Irritation. No corneal Injury. 3 Slight effect, disappearing within a week. May consist of appreciable conjunctival irritation and pain but no corneal or internal injury. 4 Moderate effect consisting of superficial corneal injury which cleared within a week. No loss of vision expected. Conjunctival Irritation may or may not be severe. 5 Moderate to severe effect, consisting of corneal injury from which recovery will be prolonged. Some IrTtTs may be observed" Permanent impairment of vision not likely. 6 Severe effects consisting of total loss of vision due to serious corneal injury and/or internal involvement. B. Results and Conclusions In Table 3 (bar graph) it will be noted that the eye reactions of each individual animal are recorded. It is further important to note that each formulation. Proprietary as well as Dow Experimental, is compared with the control formulation (Dow Sample 1), for each individual animal. The length of the line Is indicative of the degree of eye tissue reaction and in each case should be compared with the control dotted line. The length of the dotted lines vary considerably and reflect for the most part animal variation with respect to eye tissue reaction to the spray mist. R&S168061 In general, all of the formulations studied except two (Proprietaries 1 and 8) produced some degree of corneal injury when sprayed directly into the rabbit eye. While there are individual rabbits In which the experimental or proprietary formulation appears less irritating than the control, if an attempt Is made to average the reactions of the three animals used on any particular formulation in all cases except two (Proprietaries 1 and 8) the experimental or proprietary material is as toxic or more toxic as an eye irritant than the control. Even the most severe reactions produced in the rabbits are deemed not of a permanent nature. Considering the limits of animal variation and the limited number of animals employed on the study, it would be risky to attach much significance to proclaiming safety of one formulation over another, particularly where hazard relative to normal consumer use is the major consideration. The chemical exposure in these experimental studies was accomplished by holding the rabbit eye open which represents a much more extensive eye contamination than would likely occur incidental to spraying the hair. In addition to this, most investigators feel that the human cornea is appreciably more resistant to chemical irritation than is the rabbit cornea. In the opinion of the writer, none of the experimental Dow formulations would be expected to produce permanent effects in the human eye. VI. SKIN CONTACT IRRITATION The laboratory procedure was designed to evaluate Irritation potential of the hair spray formulations when applied under simulated use conditions as well as under conditions of exaggerated or rather drastic exposure. A. Method Three albino rabbits were employed on each formulation. Several days prior to starting the study, the hair was removed from the belly skin using a straight razor and barber soap. All animals were caged individually and allowed to eat and drink ad libitum throughout the experimental period of two weeks. The formulations were evaluated for irritation potential by applying the spray mist to the inner surface of the ear and to intact and abraded skin of the belly. In order to simulate the drastic exposure condition, the abdominal areas were fitted with a cloth bandage taped securely in place. This served to suppress evaporation and to render the R&S168062 material capable of exerting its maximum irritation effects. The application to the ear (unbandaged) served to more closely simulate use conditions. The materials were applied in the form of the spray mist to all exposure sites by holding the nozzle 4-6 inches from the skin surface and releasing the spray for 2-3 seconds. This procedure delivered an excessive amount of liquid concentrate to each exposure site. Fresh amounts were applied each day to each site; five days per week for two weeks to the ear and intact belly skin and for three consecutive days to freshly abraded skin. In the case of the intact areas, the test program represented continuous exposure for 14 days. The continuous exposure in the case of abraded skin was of three days' duration. The condition of the skin was assessed and the severity of the response was recorded 24 hours after each application. The animals were weighed at intervals during the exposure period and were observed frequently to detect any departure from normal insofar as general appearance and behavior were concerned. The estimated average response of the three animals employed is recorded in Table 4 for each formulation following application. The numerical rating code is as follows. Index 1 2 3 4 5 6 Reaction No perceptible reactions. Questionable to barely perceptible erythema and/or exfoliation. Definite but slight erythema and/or exfoliation. No burn. Slight or moderate erythema and/or exfoliation with slight or moderate superficial skin burn. Healing of abrasions normal. Slight scar may or may not result. Moderate to severe skin reaction Including deep burn resulting in appreciable scar formation. Extensive skin injury Including Impairment of healing. Extensive scar formation likely. R&S168063 B- Results and Conclusions All materials studied, when sprayed in copious amounts to the inner surface of the rabbit ear and allowed to remain for 24 hours, produced essentially no perceptible skin reaction. In all cases, continuous response to the ear for up to ten days produced only a slight perceptible erythema and/or exfoliation. In this regard all materials appear to possess the same properties as the control (Dow Sample 1) Insofar as skin irritation potential is concerned. When intimately confined under a bandage to intact skin (rabbit belly) for 24 hours, the materials produced, at the most, a slight erythema. These data represent results of skin exposure far in excess of what would likely occur under normal use of hair sprays. The Dow experimental formulations are comparable to the control (Dow Sample 1) and to several of the proprietary materials. None appeared to impair healing of freshly abraded skin. When confined to skin on a continuous basis for several days, Dow Sample 6 appeared to possess the greatest potential for irritating the skin of all formulations studied. After five days it produced a moderate to severe burn. Similar exposure resulted In superficial burns in the case of Dow formulations 4, 5, 7, and 8. It should be appreciated that under this condition of exposure solvent evaporation is greatly inhibited and that such conditions in no way resemble those of normal use. In the opinion of the writer, there are no contra indications, from a skin Irritation viewpoint, for further investigating the usefulness of the solvent systems represented by the Dow experimental formulations in hair spray preparation. R&S168064 R&S168065 Table 1 - INHALATION OP HAIR SPRAY MIST (RATS) Material No. Of Exposures (3/day) Exposure Time mln/day Total min Total Weight Material Used (grams) No. Of Rats Sex No. Died/ No. Exposed Av. Wt. Change Of Survivors (grams) Response-Remarks Proprietary 1 Proprietary 2 Proprietary 3 Proprietary 4 30 30 30 30 Proprietary 5 30 Proprietary 6 30 Proprietary 7 30 45 45 45 45 45 45 .45 450 450 450 450 450 450 450 350 234 . 254 214 276 289 350 3M 3P 3M 3P 3M 3F 3M 3P 3M 3F 3M 3P 3M 3F 1/3 + 7.5 Animal died after 6 exposures (2 days) 1/3 - 5-0 Animal died after 9 exposures (3 days) 1/3 +12.0 Animal died after 12 exposures (4 days) 1/3 - 3-0 Animal died after 9 exposures (3 days) 1/3 +14.0 Animal died after 9 exposures (3 days) 0/3 - 2,5 0/3 +14.3 0/3 - 1.3 1 rat gained 2 g., the others lo3t 5 g. and 1 g. 0/3 + 9-5 1 rat lost 1 g., the others gained 18 g. and 2 g. 0/3 -26.7 Animals lost 9, 26 and 45 g. 0/3 +17.4 Animals gained 13, 16 and 23 g. 0/3 - 2.0 One animal gained 3 g., the others lost 3 and 6 g. 0/3 -16.0 One rat gained 1 g., the others lost 11 g. and 38 g. 0/3 -19.7 Animals lost 1, 13 and 45 g. continued R&S168066 Table 1 - continued Material No. Of Exposures (3/day) Exposure Time min/day Total min Total Weight Material Used (grams) No. Of Rats Sex No. Died/ No. Exposed Av. Wt. Change Of (grams) Response-Remarks Proprietary 8 30 45 450 321 3M 1/3 - 2.0 Animal died after 6 exposures (2 days), one rat gained 2 g., the other lost 24 g. 3P 0/3 + 9.4 Rats gained 1, 7 and 20 g. Proprietary 9 30 45 450 365 3M 0/3 -21.4 Rats lost 14, 20 and 30 g. 3F 0/3 -11.0 Rats lost 9, 12 and 12 g. Proprietary 10 30 45 450 221 3M 3P 0/3 - 9.4 Rats lost 5, 11 and 12 g. 0/3 - 4.4 Two rats lost 3 and 13 g.j one gained 3 g- Proprietary 11 30 45 450 Air Control 30 45 450 234 3M 0/3 -22.7 Rats lost 16, 24 and 28 g. 3F 0/3 -12.7 Rats lost 12, 13 and 13 g. -- 3M 0/3 +20.4 Rats gained 14, 23 and 24 g. 3F 0/3 + 5-4 Two rats gained 11 and 19 g.j one lost 14 g. Dow Sample 1 30 45 450 (control) 209 3M 0/3 +15.7 Two rats gained 15 and 40 g., one rat lost 6 g. 3F 0/3 -13.0 Two rats lost 8 and 9 g., one rat gained 4 g. Dow Sample 2 30 45 450 196 3M 1/3 -15.7 Rats lost 15 and 32 g. 3F 0/3 -12.7 Rats lost 7, 15 and 16 g. continued R&S168067 Table 1 - continued Material No. Of Exposures (3/8ay) Exposure Time min/day Total min Total Weight Material Used ( grams) No. Of Rats No. Died/ Sex No. Exposed Av. Wt. Change Of Survivors (grams) Response-Remarks Dow Sample 3 30 45 450 198 3M 0/3 -27.7 Rats lost 19, 24 and 30 g. 3F 1/3 -14.0 Rats lost 13 and 15 B* Dow Sample 4 30 45 450 221 3M 3/3 Animals died after 3 exposures (1 day) 3F 0/3 - 7.0 Animals lost -3, -9 and -11 g. Dow Sample 5 30 45 450 246 3M 1/3 - 9-0 One rat gained 3 g.j one lost 30 g. 3F 1/3 -13.0 Animal3 lost 12 and 14 g. Dow Sample 6 129 3/3 Two males and two females died following very first exposure. Others died on fourth and seventh day of the experiment. Dow Sample 7 30 45 450 212 3M 1/3 -10.4 Rats lost 12 and 19 g. 3F 1/3 - 5-0 Rats lost 6 and 9 g. Dow Sample 8 30 45 450 228 3M 1/3 -22.0 Rats lost 20 and 24 g. 3F 1/3 -14-5 Rats lost 12 and 17 g. Dow Sample 9 30 45 450 Dow Sample 10 30 45 450 Air Control 30 45 450 218 3M 0/3 -17-7 Rats lost 5, 20 and 27 g. 3F 3/3 -- 205 3M 1/3 -12.0 Rats lost 9 and 15 g. 3F 0/3 -10.0 Rats lost 7, 11 and 12 g. -- 3M 0/3 -12.7 Two rats lost 11 and 29 g.; l gained 2 g. 3F 1/3 - 5-5 Rat3 lost 5 and 6 g. Table 2 - SERUM BLOOD UREA NITROGEN (BUN) AND SERUM GLUTAMIC PYRUVIC' TRANSAMINASE (SGPT) VALUES ON RATS EXPOSED TO HAIR SPRAY MIST Material Untreated (controls) Air (controls) Proprietary 1 Proprietary 2 Proprietary 3 Proprietary 4 Proprietary 5 Proprietary 6 Continued Animal Number 1 2 3 Av. 2220 2221 2222 Av. 2167 2168 Av. 2172 2173 Av. 2179 2180 Av. 2184 2185 2l86 Av. 2190 2191 2192 Av. 2196 2197 2198 Av. Males BUN SGPT (Mg. %) (unlts/ml.) 23 84.9 17 47.8 14 70.6 18 67.8 18 62.2 17 57-4 15 78.9 17 66.2 15 57.4 17 59.8 16 58.6 16 87.3 19 71-8 18 79-6 20 64.6 16 55-0 18 59-8 19 51.4 16 62.2 17 58.6 17 57.4 23 56.2 19 59.8 20 83.7 21 66.6 18 82.5 13 56.2 15 52.6 15 63.8 Animal Number 4 5 6 Av. 2223 2224 2225 Av. 2169 2170 Av. 2176 2177 Av. 2l8l 2183 Av. 2187 2188 2189 Av. 2193 2194 2195 Av. 2199 2200 2201 Av. Females BUN SGPT (Mg. %) (units/ml. 19 64 6 21 59-8 16 81.3 19 68.6 21 53.8 17 51-4 22 59-8 20 55-0 22 40.7 15 50.2 19 45.5 19 45-4 23 41.9 21 43.7 25 41.9 25 61.0 25 53-4 23 40.7 24 46.6 20 47.8 22 45.0 18 81.3 15 55*0 20 105-2 18 80.5 19 46.6 18 46.6 18 62.2 18 51.8 R&S168068 Tible 2 - Continued Material Proprietary 7 Proprietary 8 Proprietary 9 Proprietary 10 Proprietary 11 Dow Sample 1 (control) Dow Sample 2 Dow Sample 3 Continued oj > oCVJ oCVJ o <CVJ OJ OJ OJ Animal Number 2208 2209 Av. 2764 2765 2766 Av. 2770 2771 2772 Av. 2776 2777 2778 Av. 2214 2215 2216 Av. 2783 2784 Av. 2788 2789 2790 Av. Males BUN SGPT (Mg. %) (units/ml. ) 17 64.6 14 88.5 17 62.2 16 71.8 18 52.6 18 102.9 18 77-8 18 39-5 18 39-5 23 49-0 20 42.7 19 29.9 17 43-1 19 23.9 18 32.3 21 35-9 23 41.9 23 41.9 22 39-9 21 62.2 17 68.2 21 69.4 20 66.6 31 44.3 41 40.7 36 42.5 14 44.3 16 50.2 19 51.4 16 48.6 Animal Number 2205 2206 2207 Av. 2211 2212 2213 Av. 2767 2768 2769 Av. 2773 2774 2775 Av. 2779 2780 2781 Av. 2217 2218 2219 Av. 2785 2786 2787 Av. 2791 2792 Av. Females BUN SGPT (Mg. *) (units/ml.) 20 45.4 18 52.6 18 69.4 19 55.8 21 45.4 19 76.5 18 53-8 19 58.6 24 35.9 20 32.3 22 22.7 22 30.3 20 19.1 20 27.5 20 16.7 20 21.1 21 34.7 25 31.1 31 39.5 26 35-1 19 56.2 20 65.8 18 39-5 19 53.8 22 38.3 19 34.7 20 32.3 20 35-1 20 20.3 19 29.9 20 25.I R&S168069 Table 2 - Continued Material Animal Number Males BUN SGPT (Mg. %) (units/ml.) Dow Sample 4 NO MALE SURVIVORS Dow Sample 5 Dow Sample 6 2796 21 34.7 2797 23 41.9 Av. 22 38.3 NO MALE SURVIVORS Females (units/ml. 'IAnimal BUN Number (Mg. %) SGPT 2793 22 34.7 2794 16 29.9 2795 21 34.7 Av. 20 25.1 2798 25 32.3 2799 27 34.7 Av. 26 33.1 NO FEMALE SURVIVORS Dow Sample 7 Dow Sample 8 Dow Sample 9 Dow Sample 10 Air (control) 2800 2801 Av. 2804 2805 A v. 2808 2809 2810 Av. 2813 2814 A v. 28l8 2819 2820 Av. 14 41.9 19 41.9 17 41.9 18 43.1 20 95.7 19 69.4 18 51.4 18 37.1 22 52.6 19 47.0 17 49 19 49 18 49 19 39-5 21 40.7 16 39-5 19 39.5 2802 23 35.9 2803 20 25.1 Av. 22 30.5 2806 21 22.7 2807 22 34.7 A v. 22 28.7 NO FEMALE SURVIVORS 2815 2816 2817 Av. 35 26 19 27 2821 45 44.3 2822 34 40.7 Av. 40 42.5 R&St 68070 R&S168071 Table 3 - THE EFFECTS OF HAIR SPRAY FORMULATIONS WHEN SPRAYED DIRECTLY INTO THE RABBIT EYE Material Proprietary Sample 1 Proprietary Sample 2 Proprietary Sample 3 Proprietary Sample 4 ------------ Experimental formulation ------------- Control: F-12 F-ll PVP-VA Ethanol 25.056 25.056 2.556 47-556 Animal Number ConjunctivitisCorneal Injury Moderate- Very slight SlightModerate severe Severe 695 <nrrr: 699 <|rz:_.... 702 <j________ I --i------------------- --i-----------------------1------------------ ----1----------- ----------- 1-------------- ------- 698 700 701 704 703 <t~~_______ i <T- ' Jiit, s- - .. - L+t1 ..--...--.................... 1 --t .. (_ _ " --- 11111----------------111 11 t|111 -- - - *~ <r______ 1 t1 ---- 1l111 Ii1l ,1----------- ----------- 1111111111,-------------- ------- 11111 1i1 1l 705 710 706 4'-:-------------- ___1i_____________ <jm:-- <fi- -- - ~1l~ " -- -- __ --11i----------------------- __j__ 1 11j------------------ j --1111j----------1i * 1 ----------- f1 r1 ~ 111 11 707 4 -- 11 1 i 11 --.... jt 111 1111t1 11l 11 1i11111 i1111 11 111i ------------ i[1t11 _ 111111 1 2 -3 4 5+ INDEX Table 3 - continued Material Proprietary Sample 5 Proprietary Sample 6 Proprietary Sample 7 Proprietary Sample 8 R&S168072 Animal Number Conjunctivitis Very slight Slight 709 <1 708 <j 712 4 Corneal Injury Moderate 1 T I . JtII H Moderatesevere Severe 711 Ilk r1 ~ r 1AL- 713 715 720 4-- 1 --748 : r11 1---------- 746 <ir_ i1t .1 "T 111 ----1----------- -----,----------1t1 i <t----749 752 s\~'~ 1---- ----- 1 1 1 11 11 11 1 111 _11___------11-----------11------- 1 t i1 INDEX Table 3 - continued Material Proprietary Sample 9 Proprietary Sample 10 Proprietary Sample 11 R&S168073 Conjunctivitis Corneal Injury Animal Moderate- Number Very slight Slight Moderate severe Severe i753 756 758 759 761 763 721 728 727 1 1 /r~ ~ | - 1 nr *-- -- -4------------------ <!--------------------- i---------------- 11 11 4 : . .. . 1 ....................... 11 <!- -1 <11111____ 1f1i1 <T- - -If 1 "1 -J! t1 11 t 1 1tt 111 11 11 11 t111 ------------11t1T11!11-11lr1i111t_------------..--.--.---.---.--.--.--.--.------------------1111111r111111111111111---------------------------------------111111111111t1111111r1--------------------------------------- \1 1 _i111 ! 1 t111 i 1r 1f11 1 111t 11 1 1 rJ| 11 1| 1| Jt1 11t 1 1| 1| 11 |1 *| r 1t 1 i 1| 1 1 2 3 4 5 INDEX R&S168074 Table 3 - continued Dow Sample Number Hair Spray Formulation {%) Animal Number Conjunctivitis Very slight Slight Corneal Injury Moderate Moderatesevere Severe Freon-12 25.0 267 Methyl chloroform PVP-VA 25.0 2.5 263 Ethanol 47-5 248 --1--- --------1------------i-------- -- 1-----------1----------- 3 Freon-12 25.0 j 28l <!_ _ 1 ir................... 1 t1 Methyl chloroform - - .... .Methylene chloride _ --. -- - -j _ .PVP-VA i --------- -------- ----Ethanol 15.0 10.0 2.5 47.5 245' 251 t <tr__ - i i ! ..........* ( *1 1 1-------------------- --T1)11 ---- -- _ .4 Freon-12 Methyl chloroform PVP-VA -Ethanol j__ ___ _ _____Nitrous oxide 15.0 50.0 2.5 30.0 2.5 31 11-- 33 <11 . 35 <1-- i 1 --j -- 1 - 1 --~t11r1---~r------ 111 1 11 ----- 111------------ 111J11 i1 11 tj11111---------------------11 111 11 Freon-12 Methyl chloform Methylene chloride PVP-VA Ethanol Nitrous oxide 15.0 40.0 10.0 2.5 30.0 2.5 1 360 254 477 11 368 INDEX R&S168075 Table 3 - continued Dow Sample Number 6 7 8 Hair Spray Formulation (#) Vinyl chloride Methyl chloroform PVP-VA Ethanol Nitrous oxide 13.0 50.0 2.5 30.0 2.5 Vinyl chloride Methyl chloroform Methylene chloride PVP-VA Ethanol Nitrous oxide Freon-12 Methyl chloroform PVP-VA Ethanol Nitrous oxide 15.0 40.0 10.0 2.5 30.0 2.5 15.0 4o.o 2.5 40,0 2.5 , Conjunctivitis Corneal Injury Animal Moderate- Number Very slight Slight Moderate severe Severe 370 373 372 1 1 11--------- ______ t111------------------ -- 1_. _1 ____________ 1 r1t1 t1 ____ 1 ----------- .i------------------------ J---------- I i 1J 1 \1 j 11111 11111a 1 11111 111111 1 369 291 4____ i1 <J______ j ----------- j-1---- - -- -J r1 1 1j1 1 1111 t 11 295 11 11 297 377 379 </11L1j1--------- t 1j1 ______ l._1 ._________ 1 j11-------------------- i 7"-. 11 11 1 C --_il11t11il1L--------------- ------------------------*11I111t1t|111_--_--_-_--_-_~-~___"*__--_-1i111111111t111_-_' __-__~__- _____ ~i1111t1-----------------------1i11111-1 --------------------- 11 * 11 _Xl111111111 11 11 11t1t1111 1 2 3 4 T5 INDEX R&S) 68076 Table 3 - continued Dow Sample Number 9 10 Hair Spray Formulation (%) Freon-12 Methyl chloroform PVP-VA Ethanol Nitrous oxide 15-0 40.0 42o..5o 2.5 Freon-12 Freon-11 Methylene chloride PVP-VA Ethanol 25.0 15.0 10.0 2.5 47.5 Conjunctivitis Corneal Injury Animal Number Very slight <f i 385 <----- _________ j 381 <15-_ 1 1l 383 <TT" 1 387 4_ _ 11 382 <1 L_ 384 i1-- 1 t1 t 11 _ r1 11 i 1 i1t ' ii Moderate- Slight Moderate severe Severe i1 "rtL 111 11 t1111 1 t - 4- 1tr i1. _ 1 1111 1J11 1 11 11 J11 t T1 11l1 r 11111 11 1t 111111 11 iiiiiitiiti i iiii 12 3 4 5 INDEX R&S168077 Table 4 - SKIN IRRITATION PROPERTIES OP HAIR SPRAY FORMULATIONS WHEN APPLIED TO INTACT (i) AND ABRADED (a) RABBIT SKIN Material Proprietary 1 Proprietary 2 Proprietary 3 Proprietary 4 Proprietary 5 Proprietary 6 Proprietary 7 Site Ear (I) Belly (i) Belly (a) Ear (i) Belly (i) Belly (a) Ear (I) Belly (I) Belly (a) Ear (I) Belly (I) Belly (a) Ear (i) Belly (i) Belly (a) Ear (I)' Belly (I) Belly (a) Ear (i) Belly (1) Belly (a) Index of Response After Application Number 1 2 3 4 5 6 7 8 9 10 1 122333333 12 22 3 33 33 3 4 4 4 healed normally 1 3 3 3 3 3333 3 1233333 33 3 2 3 3 healed normally 2 22 3 333 33 3 2 2 3 3 3 33 3 3 3 2 3 3 healed normally 1 3 33333333 3333 333333 4 4 4 healed normally 1 122233333 2 2 3 3 3 33 33 3 4 4 4 healed with slight scar 2 2 3 3 333 33 3 2 2 2 3 3 33 3 33 2 3 3 healed normally 2233333333 1 2 3 3 333 3 3 3 3 3 3 healed normally continued R&S168078 Table 4 - continued Material Site Proprietary 8 Proprietary 9 Proprietary 10 Proprietary 11 Dow Sample 1 (Control) Freon-12 25.056 Freon-11 25.056 Ethanol 47.55 Resin (PVP/VA) 2.556 Dow Sample 2 Freon-12 25.056 Methyl chloroform 25.056 Ethanol 47.556 Resin (PVP/VA) 2.556 Ear (I) Belly (i) Belly (a) Ear (i) Belly (i) Belly (a) Ear (i) Belly (i) Belly (a) Ear (i) Belly (I) Belly (a) Ear (i) Belly (i) Belly (a) Ear (1) Belly (I) Belly (a) continued Index of Response After Application Number 1 2 3 4 5 6 7 8 9 10 2 3 3 3 3 33 3 3 3 3333333333 4 4 4 healed with slight scar 1 2 2 2 2 222 2 2 2' 2 2 3 3 3 3 3 3 3 3 3 4 healed normally 23 3 3 3 333 3 3 2233333333 3 4 4 healed with slight scar 233 3333333 333 3333333 3 4 4 healed with slight scar 1333333333 1 3 3 3 3 33 3 3 3 4 4 4 healed with slight scar 1 3 3 3 3 33 3 3 3 3333333333 4 4 4 healed with slight scar R&S160079 Table 4 - continued Material Dow Sample 3 Freon-12 Methyl chloroform Methylene chloride Ethanol Resin (PVP/VA) Dow Sample 4 Freon-12 Methyl chloroform Ethanol Nitrous oxide Resin (PVF/VA) Dow Sample 5 Freon-12 Methyl chloroform Methylene chloride Ethanol Nitrous oxide Resin (PVP/VA) Dow Sample 6 Vinyl chloride Methyl chloroform Ethanol Nitrous oxide Resin (PVP/VA) 25.056 15. (# 10.0% 47-556 2-5# 15 -0% 50.0% 30.0% 2-556 2.5# 15-056 40.0% 10.0% 30.0% 2.556 2-556 15-0# 50.056 30.0% 2.556 2.556 Site Ear (i) Belly (i) Belly (a) Ear (i) Belly (I) Belly (a) Ear (i) Belly (i) Belly (a) Ear (i) Belly (i) Belly (a) Index of Response After Application Number 1 2 3 4 5 6 7 8 9 10 1233333333 1 133333333 3 4 4 healed with slight scar 2 3 3 33 33 2 3 3 33 33 3 3 4 healed normally 333 444 2 3 3 33 3 3 3 44 3444444444 4 4 5 healed with scar 1 3 3 33 33 333 3 4 4 44 5 5 5 55 4 5 5 healed with moderate :3car continued R&St 68080 Table 4 - continued Material Dow Sample 7 Vinyl chloride Methyl chloroform Methylene chloride Ethanol Nitrous oxide Resin (FVFAa) Dow Sample 8 Freon-12 Methyl chloroform Ethanol Nitrous oxide Resin (FVP/VA) Dow Sample 9 Freon-12 Methyl chloroform Methylene chloride Ethanol Nitrous oxide Resin (PVP/VA) Dow Sample 10 Freon-12 Freon-11 Methylene chloride Ethanol Resin (PVPAa) 15.0% 40.0% 10.0% 30.0^ 2.556 2.5# 15.0% 40.0% 40.0% 2.5% 2.5% 15-0% 30.0% 10.0% 40.0% 2.5% 2.5% 25.0% 15.0% 10.0% 47.5% 2-5% Site Ear (i) Belly (i) Belly (a) Ear ' (i) Belly (i) Belly (a) Ear (i) Belly (I) Belly (a) Ear (i) Belly (!) Belly (a) Index of Response After Application Number 1 2 3 4 5 6 7 8 9 10 2 3 3 3 3 3 3 3 3 3 3 33 3 33 4 4 44 3 4 4 healed with slight scar 1 2 3 33 33333 2 3 3 33 33 344 3 4 4 healed with slight scar 1333333333 2 3 3 3 333 3 33 3 3 4 healed normally 1 2 3 3333 3 3 3 2333333333 3 3 4 healed normally