Association between Polymorphisms of Hemochromatosis (HFE), Blood Lead (Pb) Levels, and DNA Oxidative Damage in Battery Workers.

Occupational exposure to lead (Pb) continues to be a serious public health concern and may pose an elevated risk of genetic oxidative damage. In Brazil, car battery manufacturing and recycling factories represent a great source of Pb contamination, and there are no guidelines on how to properly protect workers from exposure or to dispose the process wastes. Previous studies have shown that Pb body burden is associated with genetic polymorphisms, which consequently may influence the toxicity of the metal. The aim of this study was to assess the impact of Pb exposure on DNA oxidative damage, as well as the modulation of hemochromatosis (HFE) polymorphisms on Pb body burden, and the toxicity of Pb, through the analysis of 8-hydroxy-2'-deoxyguanosine (8-OHdG), in subjects occupationally exposed to the metal. Male Pb-exposed workers (n = 236) from car battery manufacturing and recycling factories in Brazil participated in the study. Blood and plasma lead levels (BLL and PLL, respectively) were determined by ICP-MS and urinary 8-OHdG levels were measured by LC-MS/MS, and genotyping of HFE SNPs (rs1799945, C → G; and 1800562, G → A) was performed by TaqMan assays. Our data showed that carriers of at least one variant allele for HFE rs1799945 (CG + GG) tended to have higher PLL than those with the non-variant genotype (ß = 0.34; p = 0.043); further, PLL was significantly correlated with the levels of urinary 8-OHdG (ß = 0.19; p = 0.0060), while workers that carry the variant genotype for HFE rs1800562 (A-allele) showed a prominent increase in 8-OHdG, as a function of PLL (ß = 0.78; p = 0.046). Taken together, our data suggest that HFE polymorphisms may modulate the Pb body burden and, consequently, the oxidative DNA damage induced by the metal.

Advanced data mining approaches in the assessment of urinary concentrations of bisphenols, chlorophenols, parabens and benzophenones in Brazilian children and their association to DNA damage.

Human exposure to endocrine disrupting chemicals (EDCs) has received considerable attention over the last three decades. However, little is known about the influence of co-exposure to multiple EDCs on effect-biomarkers such as oxidative stress in Brazilian children. In this study, concentrations of 40 EDCs were determined in urine samples collected from 300 Brazilian children of ages 6-14 years and data were analyzed by advanced data mining techniques. Oxidative DNA damage was evaluated from the urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8OHDG). Fourteen EDCs, including bisphenol A (BPA), methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), 3,4-dihydroxy benzoic acid (3,4-DHB), methyl-protocatechuic acid (OH-MeP), ethyl-protocatechuic acid (OH-EtP), triclosan (TCS), triclocarban (TCC), 2-hydroxy-4-methoxybenzophenone (BP3), 2,4-dihydroxybenzophenone (BP1), bisphenol A bis(2,3-dihydroxypropyl) glycidyl ether (BADGE·2H2O), 2,4-dichlorophenol (2,4-DCP), and 2,5-dichlorophenol (2,5-DCP) were found in >50% of the urine samples analyzed. The highest geometric mean concentrations were found for MeP (43.1 ng/mL), PrP (3.12 ng/mL), 3,4-DHB (42.2 ng/mL), TCS (8.26 ng/mL), BP3 (3.71 ng/mL), and BP1 (4.85 ng/mL), and exposures to most of which were associated with personal care product (PCP) use. Statistically significant associations were found between urinary concentrations of 8OHDG and BPA, MeP, 3,4-DHB, OH-MeP, OH-EtP, TCS, BP3, 2,4-DCP, and 2,5-DCP. After clustering the data on the basis of i) 14 EDCs (exposure levels), ii) demography (age, gender and geographic location), and iii) 8OHDG (effect), two distinct clusters of samples were identified. 8OHDG concentration was the most critical parameter that differentiated the two clusters, followed by OH-EtP. When 8OHDG was removed from the dataset, predictability of exposure variables increased in the order of: OH-EtP > OH-MeP > 3,4-DHB > BPA > 2,4-DCP > MeP > TCS > EtP > BP1 > 2,5-DCP. Our results showed that co-exposure to OH-EtP, OH-MeP, 3,4-DHB, BPA, 2,4-DCP, MeP, TCS, EtP, BP1, and 2,5-DCP was associated with DNA damage in children. This is the first study to report exposure of Brazilian children to a wide range of EDCs and the data mining approach further strengthened our findings of chemical co-exposures and biomarkers of effect.

Urinary concentrations of 25 phthalate metabolites in Brazilian children and their association with oxidative DNA damage.

Exposure of humans to phthalates has received considerable attention due to the ubiquitous occurrence and potential adverse health effects of these chemicals. Nevertheless, little is known about the exposure of the Brazilian population to phthalates. In this study, concentrations of 25 phthalate metabolites were determined in urine samples collected from 300 Brazilian children (6-14years old). Further, the association between urinary phthalate concentrations and a biomarker of oxidative stress, 8-hydroxy-2'-deoxyguanosine (8OHDG), was examined. Overall, eleven phthalate metabolites were found in at least 95% of the samples analyzed. The highest median concentrations were found for monoethyl phthalate (mEP; 57.3ngmL-1), mono-(2-ethyl-5-carboxypentyl) phthalate (mECPP; 52.8ngmL-1), mono-isobutyl phthalate (mIBP; 43.8ngmL-1), and mono-n-butyl phthalate (mBP; 42.4ngmL-1). The secondary metabolites of di(2-ethylhexyl) phthalate (DEHP), and mEP, mIBP, and mBP were the most abundant compounds, accounting for >90% of the total concentrations. On the basis of the measured concentrations of urinary phthalate metabolites, we estimated daily intakes of the parent phthalates, which were 0.3, 1.7, 1.8, 2.1, and 7.2µg/kg-bw/day for dimethyl phthalate, di-n-butyl phthalate, diisobutyl phthalate, diethyl phthalate, and DEHP, respectively. Approximately one-quarter of the Brazilian children had a hazard index of >1 for phthalate exposures. Statistically significant positive associations were found between 8OHDG and the concentration of the sum of phthalate metabolites, sum of DEHP metabolites, mEP, mIBP, mBP, monomethyl phthalate, mono(3-carboxypropyl) phthalate, monobenzyl phthalate, monocarboxyoctyl phthalate, monocarboxynonyl phthalate, monoisopentyl phthalate, and mono-n-propyl phthalate. To the best of our knowledge, this is the first study to report the exposure of a Brazilian population to phthalates.

Occurrence of perchlorate in indoor dust from the United States and eleven other countries: implications for human exposure.

Perchlorate is a widespread environmental contaminant and potent thyroid hormone disrupting compound. Despite this, very little is known with regard to the occurrence of this compound in indoor dust and the exposure of humans to perchlorate through dust ingestion. In this study, 366 indoor dust samples were collected from 12 countries, the USA, Colombia, Greece, Romania, Japan, Korea, Pakistan, Kuwait, Saudi Arabia, India, Vietnam, and China, during 2010-2014. Dust samples were extracted by 1% (v/v) methylamine in water. Analyte separation was achieved by an ion exchange (AS-21) column and analysis was performed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The overall concentrations of perchlorate in dust were in the range of 0.02-104µg/g (geometric mean: 0.41µg/g). The indoor dust samples from China contained the highest concentrations (geometric mean: 5.38µg/g). No remarkable differences in perchlorate concentrations in dust were found among various microenvironments (i.e., car, home, office, and laboratory). The estimated median daily intake (EDI) of perchlorate for toddlers through dust ingestion in the USA, Colombia, Greece, Romania, Japan, Korea, Pakistan, Kuwait, Saudi Arabia, India, Vietnam, and China was 1.89, 0.37, 1.71, 0.74, 4.90, 7.20, 0.60, 0.80, 1.55, 0.70, 2.15, and 21.3ng/kgbodyweight (bw)/day, respectively. Although high concentrations of perchlorate were measured in some dust samples, the contribution of dust to total perchlorate intake was <5% of the total perchlorate intake in humans. This is the first multinational survey on the occurrence of perchlorate in indoor dust.