THE INDIA RUBBER WORLD 



[XuVKMHI-.R 1, 1919. 



severely for nearly two months, the hands, wrists, forearms, 

 face and neck all being involved. The part selected for the test 

 with the concentrated accelerator was the arm above the elbow, 

 where the skin was perfectly clear and where the patient said he 

 had never had any rash. An application of a SO per cent water 

 solution of hexamcthylene-tctramine was made by moistening 

 six plies of sterile gauze bandage with the solution and secur- 

 ing it with bandage and adhesive tape. This method of applica- 

 tion was selected to insure constant contact with the skin and 

 at the same time protect the treated spot from contamination 

 with other substances. In the course of twenty-four hours, an 

 eruption developed on the treated surface having all the char- 

 acteristics typical of the "rubber rash." The other arm above 

 the elbow was similarly treated, with the same result at the end 

 of twenty-four hours. During these tests the forearms, face 

 and neck on which the patient had previously had the rash were 

 clearing up showing that the rash above the elbow was not due 

 to spreading from the forearms. No more applications were 

 made for a period of eight days, at the end of which time the 

 skin above the elbows had returned to its normal condition. 

 Again, hexamethylene-tetramine was applied in SO per cent solu- 

 tion and again the rash was reproduced above the elbows. Tw<- 

 other patients susceptible to rash were similarly treated with 

 this SO per cent solution ; in both cases a rash was produced. All 

 these tests were conducted while the weather was warm and the 

 patients perspired freely while working. These results were so 

 clean cut that they left little doubt as to the irritating action of 

 hexamethylene-tetramine. 



The absence of any rash, even on the hottest days, among 

 those who handled the cured stock was very pronounced ; as far 

 as the writers are aware, not a single case was reported. In 

 view of the recent work of Bedford and Scott on the "Reactions 

 of Accelerators During Vulcanization,"" this is readily explained. 

 These investigators have shown that hexamethylene-tetramine 

 reacts with sulphur at the vulcanization temperature, forming 

 among other things, hydrogen sulphide, carbon bisulphide, 

 ammonia and a sulphocyanate. 



In order to determine a suitable substance to use as a pre- 

 ventive, an explanation of the mechanism of the action of hexa- 

 methylene-tetramine was sought. As the occurrence of rash is 

 closely associated with the excretion of perspiration, the possible 

 chemical changes which might result from its action on hexa- 

 methylene-tetramine were investigated. According to Scham- 

 berg° the perspiration is normally acid ; this has also been 

 demonstrated by actual tests by the writers. It is well known 

 that hexamethylene-tetramine is readily decomposed by acids. 

 Hartung' has shown that warming with strong acids results in 

 the formation of formaldehyde, and more recently, Ischidzu and 

 Inouye* have demonstrated that the weaker acids such as acetic, 

 lactic and succinic acid bring about the same result ; these in- 

 vestigators also showed that hexamethylene-tetramine is decom- 

 posed to some extent even on boiling the aqueous solution. Its 

 use as a bladder antiseptic depends on the liberation of formalde- 

 hyde in the bladder due to the presence of acids in the urine; 

 Suder' has shown that when the urine is alkaline this decom- 

 position does not take place. It seems a logical conclusion, 

 therefore, that when hexamethylene-tetramine is absorbed by 

 the skin, formaldehyde will be produced in the pores under the 

 influence of the sweat acids. 



The corrosive and toxic action of formaldehyde has long been 

 known. Remington and Wood" state that formalin is an intense 

 local irritant both to the mucous membrane and, if in sufficient 

 concentration, to the skin. It has been the writer's experience, 



= Presented at the fall meeting of the American Chemical Society, Sep- 

 tember, 1919. 



" "Diseases of the Skin and Eruptive Fevers," paee 26. 



'T. Prakt. Chem. (2). 46, 16. 



'J. Pharm. Sec. Taran. January, 1906. 



•United States Dispensatory, 15th Edition, page 611. 



™ United btates liispensatory, 20th Edition, page 638. 



however, that the action of a solution of formaldehyde is quite 

 different from that produced by hexamethylene-tetramine. Ap- 

 plication of 40 per cent formalin produced a hardening of the 

 skin followed by a scaly appearance due to cracking of the sur- 

 face. This eventually peels off leaving the lower skin perfectly 

 clear. There is no reddening of the skin, nor any itching 

 sensation. 



Formic acid on the other hand is extremely irritative to the 

 skin. On making an application of the strong acid, severe 

 smarting and itching occurs almost immediately, followed 

 shortly by the production of a blister. After twenty-four hours 

 the blister subsides and the affected spot has a pus-like appear- 

 ance. A thick scab slowly forms and quite a perceptible scar 

 remains after the sore has healed, showing that the acid burns 

 quite deeply. The action of the formic acid resembles very 

 much that of hexamethylene-tetramine, only very much 

 intensified. 



This study of the respective effects of formaldehyde and 

 formic acid on the skin has led the writers to believe that the 

 action of hexamethylene-tetramine is due to the formation of 

 formaldehyde in the pores under the influence of the sweat 

 acids, followed by subsequent oxidation of the aldehyde in the 

 pores to formic acid, and that the latter is the active irritant. 

 Though there is no proof that such an oxidation does occur in 

 the pores of the skin such an action seems- not so improbable, 

 when it is considered that formaldehyde has been shown to be 

 rapidly oxidized in the system, appearing in the urine as formic 

 acid." The reason for the difference in action of formaldehyde 

 as such and formaldehyde generated from hexamethylene- 

 tetramine may be attributed to difference in absorption. Hexa- 

 methylene-tetramine is extremely soluble in water (1 part dis- 

 solves in 1.2 parts of water at 12 degrees C.) which permits of 

 rapid absorption through the pores. Formaldehyde, on the 

 other hand, though very soluble in water, when applied to the 

 skin quickly hardens the surface, making it impervious to 

 further absorption. In fact, the property of formaldehyde has 

 been utilized for the purpose of checking excessive perspiration." 



On the assumption then that the acid of the perspiration is 

 the primary cause of the rash, neutralization of this acid should 

 prove an effective preventive, and furthermore, if the actual 

 irritant is formic acid, neutralization of this would prevent its 

 action, if it were formed. Any substance used to obtain this 

 result should be itself non-irritating to the skin, preferably 

 neutral in character, and sufficiently soluble in water to be easily 

 absorbed by the skin. Sodium bicarbonate or "baking soda" 

 meets all these requirements. It is neutral, quite soluble in 

 water (one hundred parts of water dissolve 9.6 parts of tlie salt 

 at 20 degrees C.) and non-irritating, and consequently was se- 

 lected for experimentation as a preventive means. 



In applying the sodium bicarbonate, the method of treatment 

 employed consisted in first thoroughly washing the affected part 

 with soap and water, drying and then applying a saturated solu- 

 tion of the bicarbonate, allowing this to dry without wiping. 

 The thorough washing opens the pores of the skin and allows 

 better penetration of the bicarbonate wash. On drying, a white 

 film of the salt remains as a thin coating which adheres with 

 surprising tenacity. Two applications daily were made, at the 

 beginning and at the middle of the shift. Before leaving the 

 factory the affected parts were washed and no further applica- 

 tion made at that time. 



The first patient on whom this treatment was tried responded 

 rapidlj'. The solution was applied to the arms, face and neck, 

 all of which parts were affected. In the course of a week all the 

 rash had completely disappeared, and what was of chief interest, 

 no new eruptions had developed. Since the weather was fairly 

 cool during this period, it might be concluded that this was the 

 cause of the rapid disappearance of the rash. To prove other- 

 " Remington and Wood, toe. cit. 



