Abstract
There is a large demand of a human relevant in vitro test system suitable for assessing the cardiotoxic potential of cosmetic ingredients and other chemicals. Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we have already established an in vitro cardiotoxicity assay and identified genomic biomarkers of anthracycline-induced cardiotoxicity in our previous work. Here, five cosmetic ingredients were studied by the new hiPSC-CMs test; kojic acid (KJA), triclosan (TS), triclocarban (TCC), 2,7-naphthalenediol (NPT), and basic red 51 (BR51) based on cytotoxicity as well as ATP assays, beating rate, and genomic biomarkers to determine the lowest observed effect concentration (LOEC) and no observed effect concentration (NOEC). The LOEC for beating rate were 400, 10, 3, >400, and 3 µM for KJA, TS, TCC, NPT, and BR51, respectively. The corresponding concentrations for cytotoxicity or ATP depletion were similar, with the exception of TS and TCC, where the cardiomyocyte-beating assay showed positive results at non-cytotoxic concentrations. Functional analysis also showed that the individual compounds caused different effects on hiPSC-CMs. While exposure to KJA, TS, TCC, and BR51 induced significant arrhythmic beating, NPT slightly decreased cell viability, but did not influence beating. Gene expression studies showed that TS and NPT caused down-regulation of cytoskeletal and cardiac ion homeostasis genes. Moreover, TS and NPT deregulated genomic biomarkers known to be affected also by anthracyclines. The present study demonstrates that hiPSC-CMs can be used to determine LOECs and NOECs in vitro, which can be compared to human blood concentrations to determine margins of exposure. Our in vitro assay, which so far has been tested with several anthracyclines and cosmetics, still requires validation by larger numbers of positive and negative controls, before it can be recommended for routine analysis.
Highlights
Various kinds of cosmetic products overflow the market
The present study demonstrates that human-induced pluripotent stem cells (hiPSCs)-CMs can be used to determine lowest observed effect concentration (LOEC) and no observed effect concentration (NOEC) in vitro, which can be compared to human blood concentrations to determine margins of exposure
Since in vivo testing of cosmetics is no longer possible, the establishment of in vitro assays to predict cardiotoxic effects of cosmetic ingredients and critical concentration ranges is of high relevance
Summary
Various kinds of cosmetic products overflow the market. They are used by billions of people of different ages, often on a daily basis. This is the case for general-use cosmetics such as cleansing cosmetics (shower gel, hand wash liquid, shampoo, and toothpaste), general skin care products (moisturizing day and night creams, body lotions, sun protection, and shaving aids), underarm deodorants, and perfumes. More specific products with active ingredients such as antiaging creams, skin-bleaching products, and hair dyes have become increasingly popular. A whole market exists for baby cosmetics.
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