ON THE TOXICITY OF SODIUM PERBORATE* By MICHAEL G. MULIIgOS, M.D., GEoP, cE K. HIGGINS,i M.D., and GEORGE J. CHKISTAKIS From the Departments of Pharmacology and Pathology, New York Medical College, New York A SEARCH OF the liter- ature has failed to reveal any extensive study concerning the sys- temic toxicity of sodium perborate. Its use has been primarily as an antiseptic and deodorant in super- ficial wounds and in dentistry. It is strongly alkaline and has in strong concentrations proved caustic to the mucous membranes of the mouth (1). Continued use has resulted in hypertrophy of the lingual papillae and darkening of the gums (2). Interest in the systemic effects of sodium perborate monohydrate (SPM) has been renewed recently through its employment as a "neu- tralizer" for the thioglycolate type of permanent hair waving lotions (3). It is used to replace so- dium bromate solution employed by many manufacturers of cold waving solutions which may be toxic on accidental oral ingestion (4). The alkalinity and oxidative power of sodium perborate render * Presented at the May 15, 1952, .Meeting, New York City. This investigation was supported in part by a grant from the Toni Company, Chicago, Ill. •Present address, the Pack Medical Group, New York, N.Y. it from slightly irritating to caustic to the mucous membrane of the stomach. The systemic toxicity and the degree of irritation would be dependent upon a number of factors: (a) the amount and con- centration of solution imbibed (b) the amount of hydrochloric acid and of food in the stomach at the time by which SPM would be rapidly decomposed (c) whether the irritation results in vomiting with loss of solution. It is con- sidered as unlikely, therefore, that any of the perborate or of the per- oxide would be absorbed from the digestive tract. Presumably, only metaborate would remain to be absorbed and to exert any toxic effects which it may possess. Solutions of boric acid have been found toxic to humans when taken in doses of from 5 to 6 gin. by chil- dren, and 15 to 20 gm. by adults (8). No data have been found concerning the systemic effect of metaborate or of perborate solu- tions. Borax (Na•BO410H20) has been administered internally as a urinary antiseptic in doses of from 297

298 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 0.6' to 1.3 gm. It is therefore not s,urprising that perborate and its reduction product metaborate should prove to possess a low order of toxicity. EXPERIMENTAL The toxicity of solutions of sodium perborate was assayed on rats and rabbits by the oral route and on cats and rabbits by the intravenous route. The peroral administration of the solution of the sodium perborate was made by stomach tube (5). The solutions were made up fresh immediately before injection, using both the chemically pure sodium perborate monohydrate crystals, as well as from the powder obtained from the "neutralizer" envelope of the manufacturer's permanent wave kit. The latter contains 4.2 gm. of sodium perborate mono- hydrate (SPM), together with 1.0 gm. of sodium hexametaphosphate which are to be dissolved in a pint of water, resulting in a concentra- tion of sodium perborate of ap- proximately 0.87 per cent. If a child were to drink the' whole pint of neutralizer solution, it would obtain at most 4.2 gin. of SPM, or 2.5 gm. of perborate. RESULTS 1. Per orallyadministeredsodium perborate to rats: The dose sched- ules and the effects are shown in Table 1. Doses of up to 0.65 gm. of SPM per kilo of body weight were given, but no deaths resulted. Groups of animals were autopsied TaBLe. 1--ToxIc•T¾ or Soriuta PE}tBoaaY•. MONOHYDRATES PERORAL ADMINISTRATION TO RATS* No. • - Dose of SPM Used Rats % Solution Cc. X Kg. Mg. X Kg. 10 1.3 10 130 16 1.3 2O 26O 10 1.3 25 325 10 2.6 10 260 18 2.6 20 520 33 2.6 25 650 * None of the 97 rats died. Some were allowed to live for at least one month follow- ing the dose others were sacrificed serially for gross and microscopic pathologic ex- amination. in order to obtain data on organ changes. Some were sacrificed at 24 and some at 48-hour intervals following the peroral administra- tion of the dose. A second group of rats received a dose of 25 cc. per kilo of the 1.3 per cent solution. Two rats were sacrificed on the 3rd 5th, 6th, 7th, and 10th days follow- ing the oral administration. The data showed no deviation from the controls and emphasized the low toxicity of SPM for 'the rat. (a) There was no loss in body weight, which averaged 186 gm. (132 to 238). The lighter animals gained in weight, showing that ap- petite had not been impaired. (b) The weight of the liver averaged 9.47 gm. (7.45 to 10.5) and was within normal limits for the weights of these animals. The liver appeared normal and except for occasional infestation showed no evidence of pathology. Micro- scopic section revealed a moderate degree of focal degeneration of a non-specific type. The histologic changes were evidenced by a ho-