Abstract
Percutaneous absorption of a lipophilic surfactant, dodecyl decaethoxylate, can be predicted using in vitro models. In vivo, dermal penetration of dodecyl decaethoxylate was found to be 22.9% in 48h. All of the absorbed dodecyl decaethoxylate in the rat was metabolised and excreted in expired air as carbon dioxide, or in the urine and faeces. Using rat skin mounted in the unoccluded flow-through diffusion cell with MEM as receptor fluid, in vivo absorption was predicted by the percentage of the applied dose recovered in the stratum corneum, epidermis, dermis and receptor fluid at 24 h (25%). Conversely, the penetration of dodecyl decaethoxylate was over-predicted in the unoccluded static diffusion cell using aqueous ethanol (50% v/v) as the receptor fluid where 49.4% recovered in the receptor fluid at 24 h. In vitro models may be used to predict percutaneous absorption and reduce animal use, provided a suitable receptor fluid is used in which the penetrant is soluble. Dermal metabolism of dodecyl decaethoxylate was low and not considered to influence dermal absorption.
This is a preview of subscription content, log in via an institution to check access.
References
Auton TR, Ramsey JD, Woollen BH (1993) Modelling dermal pharmackinetics using in vitro data. Part ii. Fluazifop butyl in man. Hum Exp Toxicol 12: 207–213
Blank IH, Griesemer RD, Gould E (1957) The penetration of an anticholinesterase agent (Sarin) into skin I. Rate of penetration into excised human skin. J Invest Dermatol 29: 299–309
Bronaugh RL, Stewart RF (1985) Methods for in vitro percutaneous absorption studies IV: the flow through diffusion cell. J Pharm Sci 74 [1]: 64–67
Bronaugh RL, Collier SW, Storm JE, Nathan DL, Stewart RF (1990) in vitro absorption metabolism studies in human and animal skin. Prediction of percutaneous penetration Vol. 1. Scott RC, Guy RH and Hadgraft J (eds). IBC Technical Services, London, pp 58–73
Clark NWE (1992) Cutaneous xenobiotic metabolism and its role in percutaneous absorption. PhD Thesis, University of Newcastleupon-Tyne
Clark NWE, Scott RC, Blain PG, Williams FM (1991) Maintenance of skin viability in skin absorption systems. In: Scott RC, Guy RH, Hadgraft J, Boddé HE (eds). Prediction of percutaneous penetration Vol. 2. IBC Technical Services, London, UK, pp 541–554
Clark NWE, Scott RC, Blain PG, Williams FM (1993) Fate of fluazifop butyl in rat and human skin in vitro. Arch Toxicol 67: 44–48
Dick IP, Scott RC (1992) The influence of different strains and age on in vitro rat skin permeability to water and mannitol. Pharm Res 9: 884–887
Dick IP, Blain PG, Williams FM (1993) The absorption and skin distribution of lindane following dermal exposure in man compared with in vitro model systems. In: Brain, James, Wolters (eds). Prediction of percutaneous penetration, Vol. 3b. STS Publishing, Cardiff, pp 609–614
Dugard PH, Walker M, Mawdsley SJ, Scott RC (1984) Absorption of some glycol ethers through human skin in vitro. Environ Health Perspec 57: 193–197
Feldmann RJ, Maibach HI (1974) Percutaneous penetration of some pesticides and herbicides in man. Toxicol Appl Pharmacol 28: 126–132
Franz TJ (1975) Percutaneous absorption. On the relevance of in vitro data. JID 64: 190–195
Graham MJ, Williams FM, Rettie AE, Rawlins MD (1987) Aldrin metabolism in skin. Pharmacology and the skin, Vol. 1, Karger, Basel pp 252–255
Grissom RE, Brownie C, Guthrie FE (1987) in vivo and in vitro dermal penetration of lipophilic and hydrophilic pesticides in mice. Bull Environ Contam Toxicol 38: 917–924
Holland JM, Kao JY, Whitaker MJ (1984) A multisample apparatus for kinetic evaluation of skin penetration in vitro. The influence of viability and metabolic status of the skin. Toxicol Appl Pharmacol 72: 272–280
Howes D (1988) Absorption and metabolism of 2-phenoxyethanol in rat and man. 15th International Federation of Societies of Cosmetic Chemists International Congress, Vol. 3
Kao J, Hall J (1987) Skin absorption and cutaneous first pass metabolism of topical steroids: in vitro studies with mouse skin in organ culture. J Pharmacol Exp Ther 241: 482–487
Kemppainen BW, Reifenrath WG, Stafford RG, Mehta M (1991) Methods for in vitro skin absorption studies of a lipophilic toxin produced by red tide. Toxicology 66: 1–17
Macpherson SE, Scott RC, Williams FM (1991a) Percutaneous absorption and metabolism of aldrin by rat skin in diffusion cells. Arch Toxicol 65: 599–602
Macpherson SE, Scott RC, Williams FM (1991b) Fate of carbaryl in rat skin. Arch Toxicol 65: 594–598
Rettie AE, Williams FM, Rawlins MD, Mayer RT, Burke MD (1986) Major differences between lung, skin and liver in the microsomal metabolism of a homologous series of resorufin and coumarin ethers. Biochem Pharmacol 35: 3495–3500
Richards DE, Begley KB, DeBord DG, Cheever KL, Weigel WW, Tirmenstein MA, Savage RE (1993) Comparative metabolism of bis(2-methoxyethyl) ether in isolated rat hepatocytes and in the intact rat: effects of ethanol on in vitro metabolism. Arch Toxicol 67: 531–537
Roper CS (1994) In vitro approaches to the prediction of percutaneous absorption and metabolism: a study of ethoxylates. PhD Thesis, University of Newcastle-upon-Tyne
Roper CS, Howes D, Blain PG, Williams FM (1993) Absorption and metabolism of 2-phenoxyethanol through rat and human skin in vitro. Hum Exp Toxicol 12: 427
Sabourin PJ, Medinsky MA, Thurmond F, Birnbaum LS, Henderson RF (1992) Effect of dose on the disposition of methoxyethanol, ethoxyethanol and butoxyethanol administered dermally to male F344/N rats. Fundam Appl Toxicol 19: 124–132
Scott RC (1989) Percutaneous absorption. In vitro technique as an alternative to in vivo assessments. In: Wang, Franklin, Honeycult, Reinert (eds). Biological monitoring for pesticide exposure. American Chemical Soc, Washington DC, pp 158–168
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Roper, C.S., Howes, D., Blain, P.G. et al. Prediction of the percutaneous penetration and metabolism of dodecyl decaethoxylate in rats using in vitro models. Arch Toxicol 69, 649–654 (1995). https://doi.org/10.1007/s002040050227
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s002040050227