Abordagem integrada de metodologias in vitro e in silico para avaliação da segurança de conservantes antimicrobianos utilizados em cosméticos
Carregando...
Data
2021-08-17
Autores
Corrêa, Gabriela de Oliveira Prado
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Os cosméticos, assim como outros produtos que contêm água e compostos orgânicos/inorgânicos, exigem proteção contra a contaminação microbiológica, sendo de grande importância o uso de conservantes antimicrobianos, para prolongar a vida útil dos produtos e garantir a segurança do consumidor. A avaliação de segurança dos cosméticos é, geralmente, determinada a partir do conhecimento da toxicidade dos ingredientes e da compatibilidade dos produtos com a pele. A combinação de métodos in vitro e in silico, além de aplicável à área cosmética, vem ganhando maior espaço na avaliação de parâmetros toxicológicos. Deste modo, o objetivo desse trabalho foi avaliar a segurança dos conservantes propilparabeno (PP), metilparabeno (MP), fenoxietanol (FE), mistura de metilcloroisotiazolinona e metilisotiazolinona (CMI/MI), DMDM hidantoína (DMDMH), imidazolidinil ureia (IMU), dehidroacetato de sódio (SD), álcool benzílico (BA), cloreto de benzalcônio (BAC), caprilil glicol (CG), benzoato de sódio (SB) e etilhexilglicerina (EEG) por meio de uma abordagem integrada de métodos in vitro e in silico. Foram realizados testes in vitro de citotoxidade e avaliação do potencial de irritação ocular, análise in silico dos desfechos de sensibilização da pele, fototoxicidade, toxicidade oral aguda, carcinogenicidade, mutagenicidade, genotoxicidade e atividade endócrina. Os resultados obtidos foram plotados em uma matriz toxicológica para a avaliação do perigo, na qual os conservantes foram classificados em níveis de toxicidade definidos como baixo (B) e alto (A). Na avaliação da exposição, foi estabelecida a concentração máxima segura e a caracterização do risco, que permitiram a integração dos dados e uma conclusão de segurança. Considerando a abordagem de avaliação do perigo, os desfechos mais preocupantes, nos quais grande parte dos conservantes receberam classificação de nível alto de toxicidade, foram a irritação da pele (PP, MP, FE, CMI, MI, DMDMH, IMU, BAC, CG e EEG), sensibilização da pele (MP, FE, CMI, MI, DMDMH, IMU, SD e BA) e toxicidade oral aguda (FE, CMI, MI, DMDMH, SD, BA e BAC). Na avaliação da exposição, apenas dois conservantes (SB e EEG) ficaram com a margem de segurança (MoS) abaixo de 100; contudo, reduzindo a concentração utilizada foi possível chegar em uma concentração segura. Considerando os ensaios realizados, é necessária uma abordagem holística que englobe os resultados obtidos in vitro e in silico, pois dados isolados não configuram uma avaliação de segurança. Apesar dos desafios na utilização de métodos in silico, a abordagem integrada de testes proposta permitiu a robustez na avaliação da segurança. Os conservantes antimicrobianos estão presentes em praticamente todos os produtos; portanto, as substâncias que tenham potencial para causar qualquer efeito adverso, devem ser incorporadas, nos cosméticos, em condições consideradas seguras, para garantir a integridade da saúde humana.
Cosmetics, like other products containing water and organic/inorganic compounds, require protection against microbiological contamination. It is important to use antimicrobial preservatives to prolong the shelf life of products and ensure consumer safety. The safety assessment of cosmetics is generally determined from knowledge of the toxicity of the ingredients and the compatibility of the products with the skin. The combination of in vitro and in silico methods, in addition to being applicable to cosmetic purposes, has been gaining more space in the assessment of toxicological parameters. Thus, the aim of this work was to evaluate the safety of preservatives: propylparaben (PP), methylparaben (MP), phenoxyethanol (FE), mixture of methylisothiazolinone and methylchloroisothiazolinone (CMI/MI), DMDM hydantoin (DMDMH), imidazolidinyl urea (IMU), sodium dehydroacetate (SD), benzyl alcohol (BA), benzalkonium chloride (BAC), caprylyl glycol (CG), sodium benzoate (SB) and ethylhexylglycerine (EEG) through an integrated approach of in vitro and in silico methods. In vitro cytotoxicity tests, evaluation of eye irritation potential and in silico analysis of skin sensitization, phototoxicity, acute oral toxicity, carcinogenicity, mutagenicity, genotoxicity, and endocrine activity endpoints were performed. The results obtained were plotted in toxicological matrices for hazard assessment, where preservatives were classified into toxicity levels defined as low (B) and high (A), exposure assessment, where the maximum safe concentration was established and risk characterization, which allowed for data integration and a safety conclusion. Considering the hazard assessment approach, the endpoints in which most preservatives were rated as high toxicity level were skin irritation (PP, MP, FE, CMI, MI, DMDMH, IMU, BAC, CG and EEG), skin sensitization (MP, FE, CMI, MI, DMDMH, IMU, SD and BA), and acute oral toxicity (FE, CMI, MI, DMDMH, SD, BA and BAC). In the exposure assessment, only two preservatives (SB and EEG) had a safety of margin (MoS) below 100, however, by reducing the concentration used, it was possible to reach a safe concentration. Considering the tests performed, a holistic approach that encompasses the results obtained in vitro and in silico is necessary, as isolated data do not constitute a safety assessment. Despite the challenges in using in silico methods, the proposed integrated testing approach allowed for robustness in the safety assessment. Antimicrobial preservatives are present in virtually all products; therefore, substances that have the potential to cause any adverse effect must be incorporated into cosmetics under conditions considered safe to ensure the integrity of human health.
Cosmetics, like other products containing water and organic/inorganic compounds, require protection against microbiological contamination. It is important to use antimicrobial preservatives to prolong the shelf life of products and ensure consumer safety. The safety assessment of cosmetics is generally determined from knowledge of the toxicity of the ingredients and the compatibility of the products with the skin. The combination of in vitro and in silico methods, in addition to being applicable to cosmetic purposes, has been gaining more space in the assessment of toxicological parameters. Thus, the aim of this work was to evaluate the safety of preservatives: propylparaben (PP), methylparaben (MP), phenoxyethanol (FE), mixture of methylisothiazolinone and methylchloroisothiazolinone (CMI/MI), DMDM hydantoin (DMDMH), imidazolidinyl urea (IMU), sodium dehydroacetate (SD), benzyl alcohol (BA), benzalkonium chloride (BAC), caprylyl glycol (CG), sodium benzoate (SB) and ethylhexylglycerine (EEG) through an integrated approach of in vitro and in silico methods. In vitro cytotoxicity tests, evaluation of eye irritation potential and in silico analysis of skin sensitization, phototoxicity, acute oral toxicity, carcinogenicity, mutagenicity, genotoxicity, and endocrine activity endpoints were performed. The results obtained were plotted in toxicological matrices for hazard assessment, where preservatives were classified into toxicity levels defined as low (B) and high (A), exposure assessment, where the maximum safe concentration was established and risk characterization, which allowed for data integration and a safety conclusion. Considering the hazard assessment approach, the endpoints in which most preservatives were rated as high toxicity level were skin irritation (PP, MP, FE, CMI, MI, DMDMH, IMU, BAC, CG and EEG), skin sensitization (MP, FE, CMI, MI, DMDMH, IMU, SD and BA), and acute oral toxicity (FE, CMI, MI, DMDMH, SD, BA and BAC). In the exposure assessment, only two preservatives (SB and EEG) had a safety of margin (MoS) below 100, however, by reducing the concentration used, it was possible to reach a safe concentration. Considering the tests performed, a holistic approach that encompasses the results obtained in vitro and in silico is necessary, as isolated data do not constitute a safety assessment. Despite the challenges in using in silico methods, the proposed integrated testing approach allowed for robustness in the safety assessment. Antimicrobial preservatives are present in virtually all products; therefore, substances that have the potential to cause any adverse effect must be incorporated into cosmetics under conditions considered safe to ensure the integrity of human health.
Descrição
Palavras-chave
cosméticos, conservantes antimicrobianos, in vitro, in silico, avaliação de segurança, safety assessment