A review of cosmetic ingredients in terms of nitrosamine presence

Nitrozamini so znane rakotvorne in genotoksične snovi, katerih prisotnost so v kozmetičnih izdelkih prvič potrdili leta 1977. Nastanejo kot produkt reakcije predhodnikov nitrozaminov, najpogosteje sekundarnih aminov, in nitrozirajočih sredstev. Snovi, ki lahko vodijo v nastanek nitrozaminov, v kozmetični izdelek pridejo kot sestavina oziroma nečistota sestavine. Reakcijo nitrozacije dodatno vzpodbudi/zavre prisotnost katalizatorjev/zaviralcev nitrozacije. V Sloveniji področje nitrozaminov v kozmetičnih izdelkih ureja Uredba o kozmetičnih izdelkih. Ta določa, da so lahko nitrozamini prisotni le v sledovih do 50 µg/kg. V diplomski nalogi smo na podlagi pregleda znanstvenih objav ovrednotili v katerih kozmetičnih izdelkih so nitrozamini najpogosteje prisotni, kateri so ti nitrozamini in katere sestavine lahko vodijo v nastanek nitrozaminov. Ugotovili smo, da je N-nitrozodietanolamin najpogostejši nitrozamin v kozmetičnih izdelkih, ki ob prisotnosti nitrozirajočega sredstva nastane iz dietanolamina. Nitrozamine so najpogosteje zaznali v šamponih, kjer so glavne sestavine površinsko aktivne snovi, ki so po strukturi pogosto predhodniki nitrozaminov. Na podlagi rezultatov pregleda znanstvenih objav smo se odločili, da pregledamo sestavo šamponov na slovenskem trgu. V pregled smo vključili šampone iz slovenske spletne drogerije in slovenske spletne lekarne. Med sestavinami smo iskali predhodnike nitrozaminov, nitrozirajoča sredstva ter katalizatorje in zaviralce nitrozacije. Približno 9 % od 391 pregledanih šamponov je med sestavinami vsebovalo predhodnik nitrozamina oziroma nitrozirajoče sredstvo. Izmed teh jih je večina vsebovala hkrati tudi zaviralce nitrozacije, nobeden pa katalizatorja nitrozacije. Ugotovili smo, da nobeden izmed šamponov ni vseboval hkrati predhodnika nitrozamina in nitrozirajočega sredstva. Prav tako ni nobeden vseboval prepovedanih sekundarnih aminov in sestavin, ki so v kozmetičnih izdelkih prepovedane zaradi nevarnosti tvorbe nitrozaminov. Nazadnje smo v sistemu RAPEX, ki služi hitri izmenjavi informacij o nevarnih proizvodih namenjenih potrošnikom v Evropski uniji, poiskali kozmetične izdelke, ki so bili zaradi previsoke vsebnosti nitrozaminov odpoklicani s trga. V večini primerov je šlo za preseženo vsebnost N-nitrozodietanolamina, največkrat odpoklicanimi izdelki pa so bili šamponi. Nizko število odpoklicanih kozmetičnih izdelkov (10) ni v skladu z rezultati znanstvenih objav, kar nakazuje, da je preverjanje varnosti izdelkov na trgu pomanjkljivo in terja večji nadzor.Nitrosamines are known carcinogens and genotoxins that were first detected in cosmetics in 1977. They are formed as a reaction product of a nitrosamine precursor, usually a secondary amine, and a nitrosating agent. Substances that can lead to the formation of nitrosamines enter the cosmetic product as an ingredient or impurity of an ingredient. The nitrosation reaction is further catalysed/inhibited by the presence of nitrosation catalysts/inhibitors. In Slovenia, the field of nitrosamines in cosmetic products is regulated by the EU Cosmetic Directive. It specifies that nitrosamines may be present as impurities only up to 50 µg/kg. In our thesis, we have evaluated which cosmetic products are most likely to contain nitrosamines, which nitrosamines are present and which ingredients may lead to the formation of nitrosamines, based on a review of scientific publications. We found that N-nitrosodiethanolamine is the most common nitrosamine in cosmetics, forming from diethanolamine in the presence of a nitrosating agent. Nitrosamines were most frequently detected in shampoos whose main ingredients are surfactants, which are often precursors of nitrosamines. Based on the results of a review of scientific publications, we decided to investigate the composition of shampoos on the Slovenian market, including shampoos from a Slovenian online drugstore and a Slovenian online pharmacy. Among the ingredients, we looked for nitrosamine precursors, nitrosating agents as well as catalysts and inhibitors of nitrosation. About 9% of the 391 shampoos studied contained a nitrosamine precursor or nitrosating agent. The majority of them also contained nitrosation inhibitors and none contained a nitrosation catalyst. We found that none of the shampoos contained both a nitrosamine precursor and a nitrosating agent. None of the shampoos contained banned secondary amines and ingredients banned in the EU Cosmetic Directive. Finally, we used the RAPEX system, which is used for the rapid exchange of information on dangerous products intended for consumers in the European Union, to identify cosmetic products that were recalled from the market due to excessive nitrosamine levels. Most of the cases involved excessive levels of N-nitrosodiethanolamine. Shampoos were among the most frequently recalled products. The low number of recalled cosmetic products (10) is not in line with the results of scientific publications, indicating that the verification of the safety of products on the market is insufficient and needs to be more controlled