RESUMO
The aim of the present study was to investigate the in vitro metabolism of two emerging organophosphate flame retardants, namely tetrekis(2-chlorethyl)dichloroisopentyldiphosphate (V6) and bisphenol-A bis-diphenyl phosphate (BDP) in human liver microsomes (HLMs), HLM S9 fractions and in human serum. In particular, the role of cytochrome P450 (CYPs) enzymes and/or paraoxonases (PONs) in the formation of V6 and BDP phase I metabolites was studied. Mono-, di-hydroxylated and hydrolytic phase I metabolites of V6 were mainly formed by CYPs in HLMs, while hydrolytic and O-dealkylated phase I metabolites of BDP were generated by PONs mainly in serum experiments. Limited number of glucuronidated and sulfated phase II metabolites were also identified for the two chemicals. The activity of seven recombinant CYPs (rCYPs) including rCYP1A2, rCYP2B6, rCYP2C9, rCYP2C19, rCYP2D6, rCYP2E1 and rCYP3A4 in the in vitro phase I metabolism of V6 and BDP was investigated. The formation of V6 metabolites was catalyzed by several enzymes, especially rCYP1A2 that was responsible for the exclusive formation of two metabolites, one primary (M1) and its secondary metabolite (M9). For BDP, only one phase I metabolite (MM1) was catalyzed by the seven rCYPs. Collectively, these results indicate that CYPs have a predominant role in the metabolism of V6, while PONs have a predominant role in BDP in vitro metabolism. These results are a starting point for future studies involving the study of the toxicity, bioaccumulation and in vivo biomonitoring of V6 and BDP.
Assuntos
Retardadores de Chama/análise , Microssomos Hepáticos/metabolismo , Arildialquilfosfatase/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Monitoramento Ambiental , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Humanos , Espectrometria de Massas/métodos , Organofosfatos/metabolismo , Organofosfatos/toxicidadeRESUMO
As many people spend a large part of their life indoors, the quality of the indoor environment is important. Data on contaminants such as flame retardants, pesticides and plasticizers are available for indoor air and dust but are scarce for consumer products such as computers, televisions, furniture, carpets, etc. This review presents information on semi-volatile organic compounds (SVOCs) in consumer products in an attempt to link the information available for chemicals in indoor air and dust with their indoor sources. A number of 256 papers were selected and divided among SVOCs found in consumer products (nâ¯=â¯57), indoor dust (nâ¯=â¯104) and air (nâ¯=â¯95). Concentrations of SVOCs in consumer products, indoor dust and air are reported (e.g. PFASs max: 13.9⯵g/g in textiles, 5.8⯵g/kg in building materials, 121â¯ng/g in house dust and 6.4â¯ng/m3 in indoor air). Most of the studies show common aims, such as human exposure and risk assessment. The main micro-environments investigated (houses, offices and schools) reflect the relevance of indoor air quality. Most of the studies show a lack of data on concentrations of chemicals in consumer goods and often only the presence of chemicals is reported. At the moment this is the largest obstacle linking chemicals in products to chemicals detected in indoor air and dust.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Compostos Orgânicos Voláteis/análise , Poluição do Ar , Materiais de Construção/análise , Qualidade de Produtos para o Consumidor , Poeira/análise , Pisos e Cobertura de Pisos , Humanos , Instituições AcadêmicasRESUMO
BACKGROUND: Diet is a major source of human exposure to hazardous environmental chemicals, including many perfluoroalkyl acids (PFAAs). Several assessment methods of dietary exposure to PFAAs have been used previously, but there is a lack of comparisons between methods. AIM: To assess human exposure to PFAAs through diet by different methods and compare the results. METHODS: We studied the dietary exposure to PFAAs in 61 Norwegian adults (74% women, average age: 42 years) using three methods: i) by measuring daily PFAA intakes through a 1-day duplicate diet study (separately in solid and liquid foods), ii) by estimating intake after combining food contamination with food consumption data, as assessed by 2-day weighted food diaries and iii) by a Food Frequency Questionnaire (FFQ). We used existing food contamination data mainly from samples purchased in Norway and if not available, data from food purchased in other European countries were used. Duplicate diet samples (n=122) were analysed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to quantify 15 PFAAs (11 perfluoroalkyl carboxylates and 4 perfluoroalkyl sulfonates). Differences and correlations between measured and estimated intakes were assessed. RESULTS: The most abundant PFAAs in the duplicate diet samples were PFOA, PFOS and PFHxS and the median total intakes were 5.6ng/day, 11ng/day and 0.78ng/day, respectively. PFOS and PFOA concentrations were higher in solid than liquid samples. PFOS was the main contributor to the contamination in the solid samples (median concentration 14pg/g food), while it was PFOA in the liquid samples (median concentrations: 0.72pg/g food). High intakes of fats, oils, and eggs were statistically significantly related to high intakes of PFOS and PFOA from solid foods. High intake of milk and consumption of alcoholic beverages, as well as food in paper container were related to high PFOA intakes from liquid foods. PFOA intakes derived from food diary and FFQ were significantly higher than those derived from duplicate diet, but intakes of PFOS derived from food diary and FFQ were significantly lower than those derived from duplicate diet. We found a positive and statistically significant correlation between the PFOS intakes derived from duplicate diet with those using the food diary (rho=0.26, p-value=0.041), but not with the FFQ. Additionally, PFOA intakes derived by duplicate diet were significantly correlated with estimated intakes from liquid food derived from the food diary (rho=0.34, p=0.008) and estimated intakes from the FFQ (rho=0.25, p-value=0.055). CONCLUSIONS: We provide evidence that a food diary or a FFQ-based method can provide comparable intake estimates to PFOS and PFOA intakes derived from a duplicate diet study. These less burdensome methods are valuable and reliable tools to assess dietary exposure to PFASs in human studies.
Assuntos
Bebidas/análise , Exposição Ambiental , Poluentes Ambientais/análise , Fluorocarbonos/análise , Contaminação de Alimentos/análise , Adulto , Cromatografia Líquida , Dieta/estatística & dados numéricos , Monitoramento Ambiental , Feminino , Humanos , Pessoa de Meia-Idade , Noruega , Avaliação Nutricional , Espectrometria de Massas em TandemRESUMO
Alternative plasticizers and flame retardants (FRs) have been introduced as replacements for banned or restricted chemicals, but much is still unknown about their metabolism and occurrence in humans. We identified the metabolites formed in vitro for four alternative plasticizers (acetyltributyl citrate (ATBC), bis(2-propylheptyl) phthalate (DPHP), bis(2-ethylhexyl) terephthalate (DEHTP), bis(2-ethylhexyl) adipate (DEHA)), and one FR (2,2-bis (chloromethyl)-propane-1,3-diyltetrakis(2-chloroethyl) bisphosphate (V6)). Further, these compounds and their metabolites were investigated by LC/ESI-Orbitrap-MS in urine and finger nails collected from a Norwegian cohort. Primary and secondary ATBC metabolites had detection frequencies (% DF) in finger nails ranging from 46 to 95%. V6 was identified for the first time in finger nails, suggesting that this matrix may also indicate past exposure to FRs as well as alternative plasticizers. Two isomeric forms of DEHTP primary metabolite were highly detected in urine (97% DF) and identified in finger nails, while no DPHP metabolites were detected in vivo. Primary and secondary DEHA metabolites were identified in both matrices, and the relative proportion of the secondary metabolites was higher in urine than in finger nails; the opposite was observed for the primary metabolites. As many of the metabolites present in in vitro extracts were further identified in vivo in urine and finger nail samples, this suggests that in vitro assays can reliably mimic the in vivo processes. Finger nails may be a useful noninvasive matrix for human biomonitoring of specific organic contaminants, but further validation is needed.