Percutaneous penetration and dermal metabolism of triclosan (2,4,4′-trichloro-2′-hydroxydiphenyl ether)

Phase II Metabolism in Human Skin: Skin Explants Show Full Coverage for Glucuronidation, Sulfation,N-Acetylation, Catechol Methylation, and Glutathione Conjugation

“…Cutaneous enzyme activities were rarely measured in the past, usually with a single substrate or in an experimental model that may poorly reflect the metabolic activity of the in vivo human skin-for example, skin microsomes or reconstructed threedimensional skin models (Table 2). Skin explants were also used previously (Moss et al, 2000;Goebel et al, 2009;Zalko et al, 2011), but dermatomed to 230-500 mM, effectively minimizing the possible contribution of skin dermis to drug biotransformation.…”

“…Although few phase II biotransformation reactions were reported in the skin models previously (Table 2), such as in the case of 4-methylumbelliferone (Jackh et al, 2011;Gotz et al, 2012), minoxidil (Anderson et al, 1998), triclosan (Moss et al, 2000), and p-toluidine Results are presented as the mean value and S.D. To prepare explants with skin after freezing, full-thickness skin from the same donor was snap-frozen in liquid N 2 , kept at -80°C for 7 days, and then thawed at room temperature.…”

“…Since previous skin metabolism studies used different experimental models (e.g., split-thickness explants, cells, or subcellular fractions), a wide range of test substrate concentrations [e.g., 500 mM of 4-methylumbelliferone in Jäckh et al (2011) versus 10 mM in the present study], or even different administration routes [topical triclosan in Moss et al (2000) versus media inclusion in the present study], direct comparison of the measured activity rates is challenging. If substrate depletion only is taken into account (i.e., conversion rate percentage), our results on triclosan glucuronidation and sulfation correlate well with the values published previously (Moss et al, 2000).…”

“…Use of three-dimensional reconstructed skin models and immortalized cell lines (e.g., HaCaT cells) raises concerns of altered gene expression, even if existing studies are mostly encouraging (Bonifas et al, 2010b;Jackh et al, 2011;Gotz et al, 2012). Skin explants were rarely used in the past and mostly dermatomed to thickness below 500 mm (Ademola et al, 1993;Moss et al, 2000;Goebel et al, 2009;Zalko et al, 2011), thus minimizing the potential metabolic contributions of skin dermis. Taken together, difficulties in accessing fresh human tissue, lack of alternative and simpler model validation against the full-thickness human skin, limited selection of test substrates, and potential enzyme inactivation in skin subcellular Blacker et al, 1991;Raza et al, 1991;Luu-The et al, 2009;Hu et al, 2010;van Eijl et al, 2012 a Enzymes with higher reported expression.…”

4-Nonylphenol, bisphenol-A and triclosan levels in human urine of children and students in China, and the effects of drinking these bottled materials on the levels

“…It is different to the findings of Calafat et al (2008b) that the concentrations of urinary TCS (≥6 years old) in the 20-29 age groups were the highest. Since oral route (by ingesting toothpaste or other oral health care products) and dermal route (by contact with soap, skin cleanser, shower gel or other skin-care products) are recognized as two major routes of human exposure to TCS (Moss et al, 2000;Sandborgh-Englund et al, 2006), kindergarten children and pupils (b12 years old) might use more personal care products under the care of their parents, thus having higher exposure to TCS. The present study also observed that the females had a significant higher LSGM concentration of TCS than the males (p = 0.031) ( Table 3).…”