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-
ON THE TOXICITY OF SODIUM PERBORATE 299 mogeneity of the cell nuclei and a darker staining coagulation of the cytoplasm. There were various de- grees of cloudy swelling and slight vacuolization of the cytoplasm. However, our untreated control rats also showed moderate albu- minous degeneration of the central and midzonal liver cells with slight focal peripheral cytonecrosis. Therefore, the change in liver mor- phology may be described as a worsening of the control finding, being one in degree rather than one of basic change. From the larger doses of SPM, the most severe lesions occurred between 24 and 48 hours after the dose. The severity of the lesions diminished to become minimal be- tween the 7th and the 10th days. (c) The kidney weights aver- aged 1.73 gin. (1.3 to 2.15) which was within normal limits. Mi- croscopic examination revealed no change from the untreated controls. (d) Careful examination was made of the gastric mucosa of all of the animals autopsied. In only one of the rats receiving the 1.3 per cent strength of SPM solution was there a change, a slight hy- perhemic condition of the mucosa. Of the rats receiving the 2.6 per cent strength 60 per cent of those autopsied after 24 hours had nor- mal stomachs. Of those autopsied at 48 hours after the administra- tion 45 per cent showed slight but definite hyperemia. There were grossly no frank ulcerations and no free blood in the gastric or intestinal cavities. In two cases where 2.6 per cent solution has been given, postmortem examination at 24 hours revealed that the fundic mucosa had epithelial degeneration, while one was associated with frank ulceration. Evidently, theselesions were uncommon and healed promptly since they were not found when autopsy was delayed several days. (e) Examination of heart, lungs, spleen, the adrenal, thymus and thyroid glands, the intestinal and genito-urinary tracts, and the brain and pituitary gland revealed no gross abnormalities. 2. Intravenously administered SPM to cats: Sodium perborate monohydrate, in 1.3 per cent solu- tion was injected into cats anes- thetized with nembutal. The blood pressure and heart rate of each ani- mal were recorded by a mercury manometer connected with a carotid artery in the usual manner. A 3 per cent SPM solution was injected intravenously from a buret at a rate of 1 cc. per minute. There was no effect on either blood pres- sure or heart rate. As the dose in- creased, the blood in the carotid artery canula became increasingly cyanotic. After a dose of 600 mg. per kilo given over a period of 30 minutes, the blood pressure then began to fall until the animal died from asphyxia with total doses of 700 to 90C rag. per kilo. At this time, artificial respiration did not avail. Five cats were run in this series. Lethal doses varied from 20 to 30 cc. of the 3.0 per cent solution of
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