STINGING CAPACITY OF APPLIED SUBSTANCES 205 X. EFFECT OF VEHICLES ADP was evaluated in 5 stingers using 5 per cent concentrations in the following vehi- cles: ethanol, hydrophilic ointment USP, carbowax USP, ethanol: propylene glycol (1:1) and vanishing cream USP. The ethanol:propylene glycol solution stood out above all the others in stinging ca- pacity, followed closely by ethanol. The onset and intensity of stinging was markedly reduced by vanishing cream. Stinging was virtually abolished with carbowax and hy- drophilic ointment. Thus, solutions are more likely to cause stinging than creams and ointments. The effects are no doubt dependent on release from the vehicle. XI. DOSE RESPONSES ADP was tested at 1.0, 3.0, and 5.0 per cent concentrations in ethanol in 3 stingers. The 1 per cent concentration did not cause any stinging. Stinging was mild with 3 per cent in all 3 subjects. The 5 per cent solution produced intense stinging as usual in ad- dition, stinging came on earlier. Thus, clear-cut differences can be detected over a rather narrow concentration range. XII. ASSAY OF MATERIALS OF DEILMATOLOGIC INTEREST Stinging tests were carried out on panels of 5 stingers with a variety of familiar substances. Stinging.was not observed with 3 per cent hydrogen peroxide, 5 per cent ammonium hydroxide, saturated salt solution, vanishing cream USP, hydrophilic oint- ment USP, carbowax Ointment USP, "pool chlorine," and a variety of steroid creams and gels, 1 per cent aqueous neomycin sulfate, 5 per cent p-aminobenzoic acid in hydro-alcoholic vehicle*, 0.2 per cent Uvinul 539 in ethanol (2-ethylhexyl-2-cyano-3- 3-diphenyl-acrylate), 8 per cent homosMate'}'. All the materials in Table II induced de- layed stinging to varying degrees. These have been sorted into 3 groups (slight, mod- erate, and severe). The following agents caused transient but not delayed stinging: methanol, ethanol, 5 per cent concentrations of ascorbic, acetic, citric and sorbic acids, retinoic acid.:• DISCUSSION The essential features of our stinging test are: (1) selection of volunteers who exhibit sharp stinging to 5 per cent lactic acid and (2) application of the test agent to the nasolabial fold after sweating has been induced. The results are highly repeatable there is sufficient sensitivity to permit substances to be accurately rated as mild, moderate, or severe. *Pre-Sun, Westwood Pharmaceuticals, Inc., Buffalo, N.Y. 14213. 'l-Coppertone Cream, Plough Inc., Memphis, TN 38151. •Retin A solution, 0.05 per cent, Johnson & Johnson Co., East Brunswick, N.J.

206 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table II Agents That Induce Stinging Concentration Agent Per cent pH Vehicle Severity Benzene 1.0 7.5 Ethanol Phenol 1.0 5.9 Ethanol Salicylic acid 5.0 2.4 Ethanol Resorcinol 5.0 6.4 Water Phosphoric acid 1.0 2 1 Water Sodium carbonate 15.0 11.2 Water Trisodium phosphate 5.0 12.0 Water Propylene glycol a Neat 5.3 Propy[ene carbonate a Neat 8.05 Propylene glycol diacetate a Neat 3.8 Dimethylace tamid e Neat 7.8 Dimethylformamide Neat 10.2 Dlmethylsulfoxide Neat 14.0 Diethyltoluamide a (Deer) 50.0 8.8 Ethanol Dimethyl phthalate a 50.0 4.0 Ethanol 2-Ethyl- 1, 3-hexanediol a 50.0 10.5 Ethanol (Rutgers 612) Benzoyl peroxide lotion •' 5.0 9.9 Be nzo yl peroxide gel c 10.0 14.0 Crude coal tar a 5.0 10.0 Phosphoric acid 3.3 1.9 (1/3 mol) Hydrochloric acid a 1.2 1.3 (1/3 mol) -Sodium hydroxide 1.3 13.0 (1/3 mot) 2-e thoxyet hyl p-me thoxy- 2.0 7.4 cinnamate d Grease-free washable lotion base Polyoxyethylene laury[ ether gel D•methylformamide Water Water Water Ethanol Slight Slight Slight Slight Slight Moderate Moderate Moderate Moderate Moderate Moderate Moderate Moderate Moderate Moderate Moderate Moderate Moderate Severe Severe Severe Severe Severe aimmediate transient stinging as well'as delayed type. bBenoxyl 5 lotion, Stiefel Labs., Inc. ½Desquam-X 10 gel, Westwood Pharmaceuticals, Inc. dGiv-Tan F ©, Givaudan Corp. The stinging phenomenon-is peculiar to the face, particularly the nasolabial folds and cheeks, the latter being a little less sensitive. Our explanation for this localization relates to the high permeability of the nasolabial region (as determined by visible responses to vasoactive drugs), the high density of appendages (hair follicles and sweat glands), which can serve as penetration shunts into the dermis, and, not least, the elaborate sensory nerve network. In man, every veilus hair follicle is associated with specialized nerve endings these along with the abundant derreal nerve network on the face confer an exceptional sensitivity to touch and pain. Stinging seems to be a variant of pain and develops quickly after appropriate stimula- tion of sensory nerves. However, toxic and irritating chemicals, which can badly