title: What happens in the skin? Integrating skin permeation kinetics into studies of developmental and reproductive toxicity following topical exposure.
abstract: Animal-based developmental and reproductive toxicological studies involving skin exposure rarely incorporate information on skin permeation kinetics. For practical reasons, animal studies cannot investigate the many factors which can affect human skin permeation and systemic uptake kinetics in real-life scenarios. Traditional route-to-route extrapolation is based on the same types of experiments and requires assumptions regarding route similarity. Pharmacokinetic modeling based on skin physiology and structure is the most efficient way to incorporate the variety of intrinsic skin and exposure-dependent parameters occurring in clinical and occupational settings into one framework. Physiologically-based pharmacokinetic models enable the integration of available in vivo, in vitro and in silico data to quantitatively predict the kinetics of uptake at the site of interest, as needed for 21st century toxicology and risk assessment. As demonstrated herein, proper interpretation and integration of these data is a multidisciplinary endeavor requiring toxicological, risk assessment, mathematical, pharmaceutical, biological and dermatological expertise.
authors.affiliation: Clinical Research Unit for Skin, Allergy and Regeneration & Experimental Dermatology Laboratory, Institute of Medical Biology, A*STAR, Singapore. Electronic address: yuri.dancik@imb.a-star.edu.sg.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Dancik
authors.affiliation: Clinical Research Unit for Skin, Allergy and Regeneration & Experimental Dermatology Laboratory, Institute of Medical Biology, A*STAR, Singapore.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Bigliardi
authors.affiliation: Clinical Research Unit for Skin, Allergy and Regeneration & Experimental Dermatology Laboratory, Institute of Medical Biology, A*STAR, Singapore. Electronic address: mei.bigliardi@gmail.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Bigliardi-Qi
mesh_terms: D000279:Administration, Cutaneous; D000367:Age Factors; D000818:Animals; D006801:Humans; D023421:Models, Animal; D008954:Models, Biological; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010599:Pharmacokinetics; D012098:Reproduction / Q000187:drug effects*; D018570:Risk Assessment; D012307:Risk Factors; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013045:Species Specificity; D014116:Toxicology / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations
keywords: Alternative methods; Dermal exposure; Exposure scenario; Occupational toxicology; PBPK; Skin penetration