RESUMO
Occupational exposure to potentially toxic elements (PTEs) is a concerning reality of informal workers engaged in the jewelry production chain that can lead to adverse health effects. In this study, untargeted proteomic and metabolomic analyses were employed to assess the impact of these exposures on informal workers' exposome in Limeira city, São Paulo state, Brazil. PTE levels (Cr, Mn, Ni, Cu, Zn, As, Cd, Sn, Sb, Hg, and Pb) were determined in blood, proteomic analyses were performed for saliva samples (n = 26), and metabolomic analyses in plasma (n = 145) using ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole-time-of-flight (Q-TOF) mass spectrometry. Blood PTE levels of workers, controls, and their family members were determined by inductively coupled plasma-mass spectrometry (ICP-MS). High concentration levels of Sn and Cu were detected in welders' blood (p < 0.001). Statistical analyses were performed using MetaboAnalyst 4.0. The results showed that 26 proteins were upregulated, and 14 proteins downregulated on the welder group, and thirty of these proteins were also correlated with blood Pb, Cu, Sb, and Sn blood levels in the welder group (p < 0.05). Using gene ontology analysis of these 40 proteins revealed the biological processes related to the upregulated proteins were translational initiation, SRP-dependent co-translational protein targeting to membrane, and viral transcription. A Metabolome-Wide Association Study (MWAS) was performed to search for associations between blood metabolites and exposure groups. A pathway enrichment analysis of significant features from the MWAS was then conducted with Mummichog. A total of 73 metabolomic compounds and 40 proteins up or down-regulated in welders were used to perform a multi-omics analysis, disclosing seven metabolic pathways potentially disturbed by the informal work: valine leucine and isoleucine biosynthesis, valine leucine and isoleucine degradation, arginine and proline metabolism, ABC transporters, central carbon metabolism in cancer, arachidonic acid metabolism and cysteine and methionine metabolism. The majority of the proteins found to be statistically up or downregulated in welders also correlated with at least one blood PTE level, providing insights into the biological responses to PTE exposures in the informal work exposure scenario. These findings shed new light on the effects of occupational activity on workers' exposome, underscoring the harmful effects of PTE.
Assuntos
Isoleucina , Chumbo , Humanos , Leucina , Proteômica , Brasil , ValinaRESUMO
The city of Limeira presents a relevant productive chain of jewelry and fashion jewelry, including a scenario of outsourcing informal home practices. It is highly complex to understand the potentially toxic elements (PTE: Cr, Mn, Ni, Cu, Zn, As, Cd, Sn, Sb, Hg, and Pb) exposures of the workers because this productive chain encompasses households. This study aimed to investigate the associations between blood PTE levels and informal work in the home environment. Fifty-two families divided into Exposed group (nâ¯=â¯112) and Control group (nâ¯=â¯53) were included. Families' blood (nâ¯=â¯165) and welder's breathing zone air samples (nâ¯=â¯9) were collected and PTEs concentrations were determined by ICP-MS. Questionnaires were applied to collect sociodemographic information and workplace details. Principal component analysis, Mann-Whitney test, cluster and a logistic regression analysis based on environment-wide association studies (EWAS) were carried out. Ni, Cu, Zn, Cd and Pb concentrations in the air samples were higher than occupational guidelines. Eighty percent of the workers were female, and 43.5% of those females then worked as welder. A significant difference was found for Pb concentration between the exposed and control group (pâ¯<â¯0.0001) and between sexes (pâ¯=â¯0.0046). For Cu (pâ¯<â¯0.0001) and Sb (pâ¯=â¯0.0434), differences were found between the sexes. The receiver operating characteristic of the EWAS was 0.80, providing evidence of a potential model to associate exposure levels and occupational factors. PTEs concentrations in the air samples raised concerns, particularly for children, who were in the same exposure scenario. Inadequate work conditions were observed in the houses, revealing the need of public actions to protect these families.