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In vivo percutaneous absorption of boric acid, borax, and disodium octaborate tetrahydrate in humans compared to in vitro absorption in human skin from infinite and finite doses

R C Wester, X Hui, T Hartway, H I Maibach, K Bell, M J Schell, D J Northington, P Strong, B D Culver
Toxicological Sciences: An Official Journal of the Society of Toxicology 1998, 45 (1): 42-51
Literature from the first half of this century report concern for toxicity from topical use of boric acid, but assessment of percutaneous absorption has been impaired by lack of analytical sensitivity. Analytical methods in this study included inductively coupled plasma-mass spectrometry which now allows quantitation of percutaneous absorption of 10B in 10B-enriched boric acid, borax, and disodium octaborate tetrahydrate (DOT) in biological matrices. This made it possible, in the presence of comparatively large natural dietary boron intakes for the in vivo segment of this study, to quantify the boron passing through skin. Human volunteers were dosed with 10B-enriched boric acid, 5.0%, borax, 5.0%, or disodium octaborate tetrahydrate, 10%, in aqueous solutions. Urinalysis, for boron and changes in boron isotope ratios, was used to measure absorption. Boric acid in vivo percutaneous absorption was 0.226 (SD = 0.125) mean percentage dose, with flux and permeability constant (Kp) calculated at 0.009 microgram/cm2/h and 1.9 x 10(-7) cm/h, respectively. Borax absorption was 0.210 (SD = 0.194) mean percentage of dose, with flux and Kp calculated at 0.009 microgram/cm2/h and 1.8 x 10(-7) cm/h, respectively. DOT absorption was 0.122 (SD = 0.108) mean percentage, with flux and Kp calculated at 0.01 microgram/cm2/h and 1.0 x 10(-7) cm/h, respectively. Pretreatment with the potential skin irritant 2% sodium lauryl sulfate had no effect on boron skin absorption. In vitro human skin percentage of doses of boric acid absorbed were 1.2 for a 0.05% solution, 0.28 for a 0.5% solution, and 0.70 for a 5.0% solution. These absorption amounts translated into flux values of, respectively, 0.25, 0.58, and 14.58 micrograms/cm2/h and permeability constants (Kp) of 5.0 x 10(-4), 1.2 x 10(-4), and 2.9 x 10(-4) cm/h for the 0.05, 0.5, and 5.0% solutions. The above in vitro doses were at infinite, 1000 microliters/cm2 volume. At 2 microliters/cm2 (the in vivo dosing volume), flux decreased some 200-fold to 0.07 microgram/cm2/h and Kp of 1.4 x 10(-6) cm/h, while percentage of dose absorbed was 1.75%. Borax dosed at 5.0%/1000 microliters/cm2 had 0.41% dose absorbed, flux at 8.5 micrograms/cm2/h, and Kp was 1.7 x 10(-4) cm/h. Disodium octaborate tetrahydrate (DOT) dosed at 10%/1000 microliters/cm2 was 0.19% dose absorbed, flux at 7.9 micrograms/cm2/h, and Kp was 0.8 x 10(-4) cm/h. These in vitro results from infinite doses (1000 microliters/cm2) were 1000-fold greater than those obtained in the companion in vivo study. The results from the finite (2 microliters/cm2) dosing were closer (10-fold difference) to the in vivo results. General application of infinite dose percutaneous absorption values for risk assessment is questioned by these results. These in vivo results show that percutaneous absorption of boron, as boric acid, borax, and disodium octaborate tetrahydrate, through intact human skin, is low and is significantly less than the average daily dietary intake. This very low boron skin absorption makes it apparent that, for the borates tested, the use of gloves to prevent systemic uptake is unnecessary. These findings do not apply to abraded or otherwise damaged skin.


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