Elemental impurities in lipsticks: Results from a survey of the Portuguese and Brazilian markets Edgar Pinto a,b,* , Kainá Paiva a,c , Ana Carvalhido a , Agostinho Almeida a a LAQV, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal b Department of Environmental Health, School of Health, Polytechnic Institute of Porto, CISA/Research Center in Environment and Health, R. Dr. António Bernardino de Almeida 400, 4200-072 Porto, Portugal c Department of Pharmaceutical Sciences, Health Sciences Centre – Vitória, Federal University of Espírito Santo, Avenida Fernando Ferrari 514, 29075-910 Vitória, Espírito Santo, Brazil Keywords: Metals Lipsticks ICP-MS Safety assessment Limits European regulation ABSTRACT For safety reasons, European regulations prohibit the use of a long list of metal(loid)s as ingredients of cosmetic products. However, their presence as impurities in finished products is virtually unavoidable, even under GMP conditions. This study aimed at determining the elemental profile of lipsticks available in the Portuguese and Brazilian markets. A total of 96 lipsticks were purchased in Brazil (n = 53; 9 brands) and Portugal (n = 43; 7 brands) and the content of 44 elements was determined. Results ranged from < 1 μg/g to several tens of μg/g (e.g., Sn, Mn, Zn). Significant differences were found between Portuguese and Brazilian products for several elements, particularly for Pb. For the elements of major toxicological concern (Pb, Cd, As, Sb, Hg), mean values were always below the current limits set by the German competent authority. However, a significant percentage of exceedances were observed for Pb (24%) and Cd (21%). A safety assessment was carried out for the tox- icologically relevant elements. Results showed that, except for Pb, the systemic exposure resulting from lipstick use represents less than 0.2% (ca. 3% for Pb) of the respective permitted daily exposure even in the worst-case scenario (i.e., ingestion of the total amount of product applied). 1. Introduction Cosmetics are highly regulated products in most developed coun- tries. Lipsticks, in particular, because of the potential for systemic ex- posure through oral ingestion beyond the exposure due to dermal contact, are subject to special attention (European Regulation, 2009; Food and Drugs Act, 2017; U.S Government Publishing Office, 1974). Regarding elemental species, several metallic elements (e.g., Fe, Zn, Ti, Bi, Cu, Mn) may be present in important amounts in cosmetic pro- ducts, including lipsticks, since they enter in the composition of in- gredients commonly used in the manufacturing of these products. Many others metals and metalloids, on the contrary, due to their well-known toxicity, are strictly prohibited by international regulations. According to the European Regulation No. 1223/2009, a long list of substances (listed in the Annex II) are prohibited in cosmetic products, which in- cludes, in the case of lipsticks, all the compounds of Sb, As, Be, Cd, Cr, Pb, Au, Nd, Te, Tl, Hg and Se (European Regulation, 2009). However, due to their ubiquitous and persistent nature, the pre- sence of trace amounts of those elements in cosmetic products is vir- tually unavoidable even under conditions of good manufacturing practices (GMP). In accordance with article 17 of the European Regulation No. 1223/2009, the non-intended presence of small quan- tities of the prohibited substances (stemming from impurities of natural or synthetic ingredients, the manufacturing process, migration from packaging, etc.) must be limited to the amounts that are technically unavoidable under GMP and, according to article 3 of the same Regulation, cannot compromise the product safety for human health under normal or reasonably foreseeable conditions of use. The safety of each individual cosmetic product has to be demonstrated in the Safety Report, a mandatory component of the respective Product Information File (European Regulation, 2009). Lead is the element that gave rise to these concerns and has received most of the attention. In 2007, the Campaign for Safe Cosmetics, a coalition of different US entities that works to eliminate substances linked to adverse health impacts from the cosmetics, raised a warning flag when Pb at levels up to 0.65 ppm were found in 61% of the 33 most popular lipstick brands available in the US market (Campaign for Safe Cosmetics, 2007). In 2009, Al-Saleh et al. evaluated the Pb content in lipsticks (n = 26) available in Saudi Arabia market but imported from countries with a low level of regulatory oversight, and identified several T