Integration of proteomic and metabolomic analyses: New insights for mapping informal workers exposed to potentially toxic elements.

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.

Home-based outsourced informal work by children and adolescents impacts sleep and leisure-a preliminary study.

Child labor is a serious and controversial issue. Despite governments establishing health policies prohibiting or restricting the age of entry to the job market, there is still a large number of working children and adolescents worldwide, particularly informal workers. This study aimed to evaluate the living and working conditions of adolescents. Work activities were home-based involving the production of jewelry and fashion jewelry, in a Brazilian city, Limeira, São Paulo. Participants were 11-17-year-old workers and non-workers, who answered a comprehensive questionnaire on their living and working conditions and filled out a time-budget protocol for 10 consecutive days. Both instruments were applied twice during both school and vacation terms. Chi-square/Fisher and Student's t tests were used, and Bonferroni corrections were performed in the significance levels of the statistical methods. During school time, working children/adolescents had lower mean sleep duration (p < 0.01) than non-working ones. During vacation, non-working youths enjoyed longer leisure time (p < 0.04). Comparing school and vacation times, working youths showed no significant difference in daily routine (p > 0.05), while non-workers spent more time on leisure activities during the vacation period (p = 0.005). In summary, this study found that working at home had a deleterious effect on the sleep and leisure of the youths studied. These data should be considered as an exposome component (specific external exposure) in evaluations of long-term health endpoints and their possible causes.

Brazilian preschool children attending day care centers show an inadequate micronutrient intake through 24-h duplicate diet.

Inadequate micronutrient intake in childhood harms growth and development, and it is related to increased rates of morbidity and mortality. The aim of this study is to evaluate the dietary intake and prevalence of inadequate micronutrient intake in preschool children (1-4 years old) attending two-day care centers. To assess children's dietary micronutrient intake, 24-h duplicate diets (n = 64) were collected for one week-day, including everything the children ate and drank both at home and in kindergarten. Anthropometric measurements were carried out to evaluate the children's nutritional status. The micronutrients copper, iron, calcium, magnesium, selenium, zinc, potassium, sodium, and manganese were determined by inductively coupled plasma mass spectrometry or graphite furnace atomic absorption spectrometry. Calcium and selenium were found with high inadequate intake rates: 50% and 42%, respectively, for children aged 1-3 years old, and 93% and 90% for children aged 4 years. Potassium was consumed in very low amounts, 13% and 5% of children aged 1-3 and 4 years old, respectively, achieved the adequate intake for the nutrient. Sodium intakes were excessive: 23% of the 1-3-year old and 42% of the 4-year-old children, respectively, had an intake higher than the tolerable upper levels. Regarding the nutritional status, overweight and obesity prevalence was 17%. Therefore, considering the damaging health effects for children of micronutrient deficiency and overweight and obesity status, it is necessary that government authorities be aware and update public policies and educational programs in order to promote healthy eating habits in early childhood.

The human exposome unraveling the impact of environment on health: promise or reality?

Considering the innovative nature of the approach to human exposome, we present the state of the art of studies on exposome, and discuss current challenges and perspectives in this area. Several reading and discussion activities were conducted by the Expossoma e Saúde do Trabalhador (eXsat - Group Exposome and Worker's Health), with systematization of the literature in the area published between January 2005 and January 2017, available in the databases PubMed and Web of Science. This comment brings a thematic analysis to encourage the dissemination of the exposome approach for studies in the Public Health area.

The human exposome unraveling the impact of environment on health: promise or reality? / O expossoma humano desvendando o impacto do ambiente sobre a saúde: promessa ou realidade?

ABSTRACT Considering the innovative nature of the approach to human exposome, we present the state of the art of studies on exposome, and discuss current challenges and perspectives in this area. Several reading and discussion activities were conducted by the Expossoma e Saúde do Trabalhador (eXsat - Group Exposome and Worker's Health), with systematization of the literature in the area published between January 2005 and January 2017, available in the databases PubMed and Web of Science. This comment brings a thematic analysis to encourage the dissemination of the exposome approach for studies in the Public Health area.

RESUMO Levando em consideração a natureza inovadora da abordagem do expossoma humano, apresentamos o estado da arte dos estudos sobre expossoma, e discutimos os desafios e perspectivas atuais nessa área. Foram realizadas diversas atividades de leitura e discussão pelo grupo eXsat (Expossoma e Saúde do Trabalhador), com sistematização da literatura da área publicada entre janeiro de 2005 e janeiro de 2017, disponíveis nas bases de dados PubMed e Web of Science. O presente comentário traz uma análise da temática de forma a incentivar a disseminação da abordagem do expossoma nos estudos da área de Saúde Pública.

Lead exposure from households and school settings: influence of diet on blood lead levels.

Lead is known as a potent toxicant to human health, particularly for children while their central nervous system is developing. The aim of this study was to investigate the associations between blood lead levels (BLLs) and lead exposure in the children's diet, home, and school environments. A cross-sectional study was conducted with 153 children aged 1-4 years, in four day care centers (DCCs), where a high prevalence of lead exposure was previously found. Lead determination by graphite furnace atomic absorption spectrometry (GF-AAS) was performed for venous blood, drinking water collected in the DCCs, and the 24-h diet (n = 64). Environmental screenings were conducted to evaluate lead concentrations in the tableware, buildings, and playground items in all DCCs and children's homes (n = 18) by using a field-portable X-ray fluorescence analyzer (FP-XRF). The BLL mean was 2.71 µg dL-1. Means for 24-h lead concentrations in the diet were 1.61 and 2.24 µg kg-1 of body weight (BW) in two DCCs. Lead concentrations in the water supply were lower than 2 µg L-1. More than 11% of the DCCs' environmental analyses presented lead concentrations higher than or equal to 1 mg cm-2, as defined by the USEPA. The diet was not found to be a risk factor for lead exposure, but households and DCC settings raised concern. Children's exposure to lead in DCC environments, where they spend the most part of their weekdays, appeared to be relevant. Graphical abstract ᅟ.

Lead, Cadmium, and Arsenic Bioaccessibility of 24 h Duplicate Diet Ingested by Preschool Children Attending Day Care Centers in Brazil.

Lead, known as a metal with high neurotoxicity to children, cadmium, which is a carcinogenic and bioaccumulative contaminant, and arsenic, a class 1 carcinogenic according to the International Agency for Research on Cancer, are toxic elements (TEs) whose relevant route of exposure may be diet. We determined the bio-accessible fraction of lead, cadmium, and arsenic from the diet of preschool children from two day care centers (DCC). A cross-sectional study was conducted with 64 one⁻four-year-old children from two DCCs where the 24-h duplicate diet samples were collected. The diet samples were analyzed by ICP-MS for lead, cadmium, and arsenic total concentrations (n = 64) and their bio-accessibility were analyzed for a subsample (n = 10). The dietary intake (DI) mean for lead, cadmium, and arsenic were 0.18 ± 0.11 µg kg-1 bw, 0.08 ± 0.04 µg kg-1 bw, and 0.61 ± 0.41 µg kg-1 bw, respectively. All DI calculated for TEs, considering total intake, were found lower than the tolerable limits (TL) (European Union, or World Health Organization, WHO, when applicable) except for one child's Pb intake. Bio-accessibilities ranged between 0% to 93%, 0% to 103%, and 0% to 69%, for lead, cadmium, and arsenic, respectively. Although DI for TEs has been found lower than TL, these reference values have been recently decreased or withdrawn since it was for lead and arsenic whose TL were withdrawn by WHO.

Famílias inseridas no arranjo produtivo informal da produção de jóias e bijuterias de Limeira, SP: a exposição ocupacional a contaminantes químicos em ambiente domiciliar / Families inserted in local productive arrangement of the productive chain of jewelry and fashion jewelry from Limeira, SP the occupational exposure to chemical contaminants in a home setting

Introdução: A informalidade no mercado de trabalho assola muitas economias em desenvolvimento e é uma característica notável da produção de joias e bijuterias em Limeira, São Paulo, um dos maiores polos de produção de joias e bijuterias do Brasil. A produção de joias e bijuterias envolve o manuseio de produtos que podem ter em sua composição elementos com potencial tóxico à saúde humana. Em Limeira, a atividade de produção ocorre dentro dos domicílios, o que significa que o trabalhador e seus familiares podem estar expostos a elementos potencialmente tóxicos (EPT) oriundos da atividade ocupacional. Objetivos: Este estudo investigou a exposição ocupacional aos EPTs Cromo (Cr), Manganês (Mn), Níquel (Ni), Cobre (Cu), Zinco (Zn), Arsênio (As) Cádmio (Cd), Antimônio (Sb), Estanho (Sn), Mercúrio (Hg) e Chumbo (Pb), dos trabalhadores domiciliares e de seus familiares inseridos no arranjo produtivo de joias e bijuterias na cidade de Limeira - SP e discutiu os riscos identificados no ambiente de trabalho domiciliar versus a legislação ocupacional vigente. Métodos: Este estudo incluiu 52 famílias (n=165 indivíduos), divididas em grupo Exposto (n=112) e grupo Controle (n=53). Foram coletadas amostras de sangue (n=165) dos trabalhadores e seus familiares, e amostras de ar da zona de respiração de soldadores (n=9). As concentrações de EPTs foram determinadas por espectrometria de massas com plasma indutivamente acoplado (ICP-MS). Questionários foram aplicados para obter informações sociodemográficas, detalhes das condições do local de trabalho e dos materiais utilizados. As informações relevantes para compor a avaliação do ambiente de trabalho frente aos requisitos legais vigentes foram obtidas a partir destes questionários. Além disso, a análise de componentes principais (PCA), formação de clusters e regressão logística foram realizadas. Resultados: Os elementos Cd, Ni e Cu apresentaram concentração no ar maiores do que as diretrizes ocupacionais americanas. Foi encontrada diferença estatisticamente significativa para a concentração de Pb entre os grupos Exposto e Controle e entre os sexos (p <0,05), já para o Cu e Sb foram encontradas diferenças apenas entre os sexos (p <0,05). Conclusões: As concentrações de EPTs encontradas no ar são preocupantes, uma vez que os familiares dos trabalhadores, incluindo as crianças, estão no mesmo cenário de exposição. Condições inadequadas de trabalho foram observadas nas residências, revelando a necessidade de implementar ações públicas urgentes para proteger essas famílias de trabalhadores. A avaliação do cenário de exposição revelou que os trabalhadores e familiares estão sob os mesmos riscos de exposição, uma vez que a produção de joias é realizada sem nenhuma proteção do trabalhador e em ambiente geralmente compartilhado dentro das casas. Ações públicas e remodelagem do fluxo produtivo são necessárias para proteção social e de saúde destes trabalhadores e seus familiares com foco em melhoria das condições de trabalho e regularização profissional.

Introduction: Informality in the occupational segment devastated many developing economies and is a notable feature of the production of jewelry and fashion jewelry in Limeira city, São Paulo, one of the largest poles of jewelry and fashion jewelry production in Brazil. The production of jewelry and fashion jewelry involves the manipulation of chemical products that may have in their composition potentially toxic elements (PTE) to human health. In Limeira, the production activity occurs inside the households, which means that worker and family members could be exposed to PTE from the occupational activity. Objective: This study investigated occupational exposure to PTE Chromium (Cr), Manganese (Mn), Nickel (Ni), Copper (Cu), and Zinc (Zn), Arsenic (As), Cadmium (Cd), Antimony (Sb), Tin (Sn), Mercury (Hg), and Lead (Pb), household workers and their families included in the production of jewelry and fashion jewelry in Limeira, and discussed the risks identified in the households\' occupational environment assessment versus the current occupational legislation. Methods: This study included 52 families (n = 165 individuals), divided into Exposed group (n = 112) and Control group (n = 53). Blood samples (n = 165) were collected from the workers and their relatives, and air samples from the breathing zone of welders (n = 9). Concentrations of EPTs were determined by ICP-MS. Questionnaires were applied to collect sociodemographic information, details of the workplace conditions and the materials used. The relevant information to compose the occupational environment assessment against the current legal requirements were obtained from these questionnaires. In addition, the principal component analysis (PCA), clusters formation and logistic regression were performed. Results: Cd, Ni, and Cu elements presented higher air concentration than the American occupational guidelines limits. A statistically significant difference was found for the Pb concentration between the exposed and control groups and between the sexes (p <0.05), whereas for Cu and Sb only differences between the sexes were found (p <0.05). Conclusions: Concentrations of EPT found in the air raise concern, since workers' relatives, including children, are in the same exposure scenario. Inadequate working conditions were observed in the houses, revealing the need to implement urgent public actions to protect these families and the workers. The exposure assessment revealed that workers and family members are at the same risk of exposure as the production of jewelry is carried out without any individual protection and, generally, is performed in the shared environment inside the houses. Public actions and remodeling the productive flow are necessary for the social and health protection of these workers and the families with a focus on improving working conditions and professional regularization.

What are the blood lead levels of children living in Latin America and the Caribbean?

INTRODUCTION: Information on the prevalence of lead exposure is essential to formulate efficient public health policies. Developed countries have implemented successful public policies for the prevention and control of lead poisoning. In the United States, Canada, Japan and the European Union, for instance, periodically repeated prevalence studies show that blood lead levels (BLLs) in children have decreased overall. Although BLL of Latino children in the U.S. have also dropped in recent years, the geometric mean remains higher than that of white children. Little is known about lead exposure in children in Latin America and the Caribbean (LAC). In this review, we responded to two questions: What is currently known about lead sources and levels in children in LAC? Are there public policies to prevent children's exposure to lead in LAC? METHOD: We conducted a literature review covering the period from January 2000 to March 2014 in the PubMed and Lilacs databases to obtain English, Portuguese and Spanish language studies reporting the prevalence of BLLs in children aged 0-18years living in LAC countries. No specific analytical method was selected, and given the scarcity of data, the study was highly inclusive. RESULTS: Fifty-six papers were selected from 16 different LAC countries. The children's BLLs found in this review are high (≥10µg/dL) compared to BLLs for the same age group in the U. S. However, most studies reported an association with some type of "lead hot spot", in which children can be exposed to lead levels similar to those of occupational settings. Only Peru and Mexico reported BLLs in children from population-based studies. CONCLUSIONS: Most BLLs prevalence studies carried out in LAC were in areas with known emission sources. The percentage of children at risk of lead poisoning in LAC is unknown, and probably underestimated. Thus, there is an urgent need to establish public health policies to quantify and prevent lead poisoning, specifically by prioritizing the identification and control of "hot spots".