title: Assessing the safety of cosmetic chemicals: Consideration of a flux decision tree to predict dermally delivered systemic dose for comparison with oral TTC (Threshold of Toxicological Concern).
abstract: Threshold of Toxicological Concern (TTC) aids assessment of human health risks from exposure to low levels of chemicals when toxicity data are limited. The objective here was to explore the potential refinement of exposure for applying the oral TTC to chemicals found in cosmetic products, for which there are limited dermal absorption data. A decision tree was constructed to estimate the dermally absorbed amount of chemical, based on typical skin exposure scenarios. Dermal absorption was calculated using an established predictive algorithm to derive the maximum skin flux adjusted to the actual 'dose' applied. The predicted systemic availability (assuming no local metabolism), can then be ranked against the oral TTC for the relevant structural class. The predictive approach has been evaluated by deriving the experimental/prediction ratio for systemic availability for 22 cosmetic chemical exposure scenarios. These emphasise that estimation of skin penetration may be challenging for penetration enhancing formulations, short application times with incomplete rinse-off, or significant metabolism. While there were a few exceptions, the experiment-to-prediction ratios mostly fell within a factor of 10 of the ideal value of 1. It can be concluded therefore, that the approach is fit-for-purpose when used as a screening and prioritisation tool.
authors.affiliation: Newcastle University, Newcastle upon Tyne, UK. Electronic address: publications@ilsieurope.be.
authors.forename: Faith M
authors.initials: FM
authors.lastname: Williams
authors.affiliation: Procter & Gamble Service GmbH, Schwalbach, DE, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Rothe
authors.affiliation: Health Canada, Ottawa, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Barrett
authors.affiliation: ILSI Europe, Brussels, Belgium.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Chiodini
authors.affiliation: ILSI Europe, Brussels, Belgium.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Whyte
authors.affiliation: Liverpool John Moore University, Liverpool, UK.
authors.forename: Mark T D
authors.initials: MT
authors.lastname: Cronin
authors.affiliation: Kansas State University, Manhattan, KS, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Monteiro-Riviere
authors.affiliation: DSM Nutritional Products, Basel, CH, Switzerland.
authors.forename: James
authors.initials: J
authors.lastname: Plautz
authors.affiliation: Charles River Laboratories, Edinburgh, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Roper
authors.affiliation: TNO, Zeist, NL, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Westerhout
authors.affiliation: Altamira LLC, Columbus, OH, USA.
authors.forename: Chihae
authors.initials: C
authors.lastname: Yang
authors.affiliation: University of Bath, Bath, UK.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Guy
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D001682:Biological Availability; D003257:Consumer Product Safety; D003358:Cosmetics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D003663:Decision Trees; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007408:Intestinal Absorption; D008954:Models, Biological; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D003358:Cosmetics
keywords: Cosmetic chemical; Decision tree; Dermal; Flux; Prediction; Systemic bioavailability; Threshold of Toxicological Concern (TTC)