Human percutaneous absorption

In vitro testing is carried out on excised pig or human skin, according to OECD guideline 428 (OECD, 2004b). In general animal skin (e.g. rat skin) is more permeable and therefore may overestimate human percutaneous absorption (Diembeck et al, 1999). 

Alcohol and alcohol ether sulfates have also been studied to determine their toxicity by percutaneous absorption in rats and guinea pigs [354-356]. Alcohol ether sulfates penetrate in the order of 1 ng/cm2/day and alcohol sulfates are less penetrant by a factor of 10. The surfactant absorbed was metabolized. Since it is known that human skin is less permeable than animal skin, only very small amounts of alcohol or alcohol ether sulfates can be absorbed even in the case of complete body exposure. 

Taking into account the low oral toxicity and the low intestinal and percutaneous absorption of alcohol sulfates and alcohol ether sulfates, the possibility of systemic toxic effects in humans is extremely unlikely [344]. 

Moore MR, Meredith PA, Watson WS, et al. 1980. The percutaneous absorption of lead-203 in humans from cosmetic preparations containing lead acetate, as assessed by whole-body counting and other techniques. Food Cosmet Toxicol 18 399-405. 

Skin tape stripping can be used to determine the concentration of chemical in the stratum comeum at the end of a short application period (30 min) and by linear extrapolation predict the percutaneous absorption of that chemical for longer application periods. The chemical is applied to skin of animals or humans, and after a 30-minute skin contact application time, the stratum comeum is blotted and then removed by successive tape applications. The tape strippings are assayed for chemical content. There is a linear relationship between this stratum comeum reservoir content and percutaneous absorption. The major advantages of this method are (1) the elimination of urinary and fecal excretion to determine absorption and (2) the applicability to nonradiolabeled determination of percutaneous absorption, because the skin strippings contain adequate chemical concentrations for nonlabeled assay methodology. 

Hydrogen cyanide is moderately lipid-soluble, which, along with its small size, allows it to rapidly cross mucous membranes, to be taken up instantly after inhalation, and to penetrate the epidermis. In addition, some cyanide compounds, such as potassium cyanide, have a corrosive effect on the skin that can increase the rate of percutaneous absorption (NIOSH 1976). Information regarding dermal absorption in animals and evidence that cyanide can be absorbed through the skin of humans is provided in Sections 2.3.1.3 and 2.2.3, respectively. 

R. C. Wester, J. Christoffel, T. Hartway, N. Poblete, H. I. Maibach, and J. Forsell. Human cadaver skin viability for in vitro percutaneous absorption Storage and detrimental effects of heat-separation and freezing. Pharm. Res. 15 82-84 (1998). 

R. L. Bronaugh, R. E Stewart, and E. R. Congdon. Methods for in vitro percutaneous absorption studies. II. Animal models for human skin. Toxicol. Appl. Pharmacol. 62 481 188 (1982). 

S. A. Hotchkiss, P. Hewitt, J. Caldwell, W. L. Chen, and R. R. Rowe. Percutaneous absorption of nicotinic acid, phenol, benzoic acid and triclopyr butoxyethyl ester through rat and human skin in vitro Further validation of an in vitro model by comparison with in vivo data. Food Chern. Toxicol. 30 891-899 (1992). 

F. P. Schmook, J. G. Meingassner, and A. Billich. Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. Int. J. Pharm. 215 51-56 (2001). 

Keywords Skin permeability Percutaneous absorption Skin penetration Mathematical model Quantitative structure-activity relationships Permeability coefficient Human skin... 

Chloroform can also permeate the stratum comeum of rabbit skin (Torkelson et al. 1976) and mouse skin (Tsuruta 1975). Percutaneous absorption of chloroform across mouse skin was calculated to be approximately 38 pg/min/cm, indicating that the dermal absorption of chloroform occurs fairly rapidly in mice. No reliable studies report the percutaneous absorption of chloroform in humans however, a few clinical reports indicate that chloroform is used as a vehicle for drug delivery (King 1993). Islam et al. (1995) investigated the fate of topically applied chloroform in male hairless rats. For exposures under 4 minutes, chloroform-laden water was applied to shaved back skin for exposures of 4-30 minutes, rats were submerged in baths containing chloroform-laden water. Selected skin areas were tape-stripped a various number of times after various delay periods. It appeared that there was an incremental build-up of ehloroform in the skin over the first four minutes. When compared to uptake measured by bath concentration differences, approximately 88% of lost chloroform was not accounted for in the stratum comeum and was assumed to be systemically absorbed. 

Dick D, Sauder DN, Chu 1. 1995. In vitro and in vivo percutaneous absorption of 14C-chloroform in humans. Human Experimental Toxicology 14 260-265. 

Bronaugh RL, Maibach Fll. 1985. Percutaneous absorption of nitroaromatic compounds In vivo and in vitro studies in the human and monkey. J Invest Dermatol 84 180-183. 

Wester, R.C., T. Hartway, H.I. Maibach, M.J. Schell, D.J. Northington, B.D. Culver, and PL. Strong. 1998a. In vitro percutaneous absorption of boron as boric acid, borax, and disodium octaborate tetrahydrate in human skin. A summary. Biol. Trace Elem. Res. 66 111-120. 

Bronaugh, R.L., Steward, R.F., Wester, R.C., Bucks, D., Mailbach, H I. Anderson, J. (1985) Comparison of percutaneous absorption of fragrances by humans and monkeys. Food chem. Toxicol., 23, 111-114... 

Toxicokinetic studies in humans have demonstrated that coumarin is rapidly absorbed from the gastrointestinal tract after oral administration and extensively metabolized by the liver in the first pass, with only 2-6% reaching the systemic circulation intact (Ritschel etal., 1977, 1979 Ritschel Hofimann, 1981).The elimination of coumarin from the systemic circulation is rapid, the half-lives following intravenous doses of 0.125, 0.2 and 0.25 mg/kg bw being 1.82, 1.46 and 1.49 h [109, 88 and 89 min], respectively (Ritschel et a/., 1976). Coumarin is also extensively absorbed after dermal application. In one study with human subjects, some 60% of a 2.0-mg dose applied for 6 h was absorbed (reviewed in Lake, 1999). The percutaneous absorption of coumarin has also been demonstrated in vitro with human skin (Beckley-Kartey et al, 1997 Yourick Bronaugh, 1997). 

Human volunteers were exposed for 24 hours to 2-pyrimidinyl ring-labeled [14C] -diazinon applied to either the forearm or abdomen in either an acetone solution or a lanolin wool grease at doses of approximately 15-20 pg/dose for each application method to test the percutaneous absorption of diazinon. Daily complete void urine samples were collected and analyzed for levels of radioactivity for 7 days after dosing. Percutaneous absorption, calculated from the amount of radioactivity present in the urine, was reported as 2.9-3.85% of the administered dose (Wester et al. 1993). 

Wester RC, Sedik L, Melendres J, et al. 1993. Percutaneous absorption of diazinon in humans. Fd Chem Toxic 31 569-572. 

Wester RC, Maibach Hl, Bucks DA, et al. 1990. Percutaneous absorption and skin decontamination of PCBs In vitro studies with human skin and in vivo studies in the Rhesus monkey. J Toxicol Environ Health 31 235-246. 

Zhong WZ. Application of solid-phase extraction in the method development for determination of SEP A, an acronym for soft enhancement of percutaneous absorption in human, rat and rabbit serum using GC-FID method. J Pharm Biomed Anal 1998 16(7) 1179. 

Since mini-pig skin is similar to human skin particularly as it pertains to percutaneous absorption, the percutaneous absorption of tazarotene (2) has been carried out using mini-pigs. In mini-pigs, high topical doses of tazarotene (2) produced only... 

Mraz, J. Nohova, H. (1992a) Percutaneous absorption of W-dimethylformamide in humans. Int. Arch, occup. environ. Health, 64, 79-83... 

Rates of percutaneous absorption of hydroquinone in 5% aqueous solution through human stratum comeum in vitro were approximately half those through full-thickness rat skin the human skin penetration rate was classified as slow (Barber et al., 1995). The data allowed calculation of skin absorbance in workers in photographic development. 

Percutaneous absorption of hydroquinone from an aqueous solution was studied in full-thickness rat skin in vitro-, the permeability constant was 2.3 x 10 cm/h, which was approximately two-fold faster than that of human skin (Barber et al., 1995). 

Barber, E.D., Hill, T. Schum. D.B. (1995) The percutaneous absorption of hydroquinone (HQ) through rat and human skin in vitro. Toxicol. Lett., 80, 167-172... 

Garnett. A.. Hotclrkiss. S.A.M. Caldwell, J. (1994) Percutaneous absorption of benzyl acetate through rat skin in vitro. 3. Comparison with human skin. Food chem. Toxicol., 32, 1061-1065... 

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