Assessment of urinary aromatic amines in Brazilian pregnant women and association with DNA damage: Influence of genetic diversity, lifestyle, and environmental and socioeconomic factors.

Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p-aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential.

Urinary levels of 30 metal/metalloids in the Brazilian southeast population: Findings from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The assessment of risks associated with environmental exposure to metals/metalloids requires well-established reference values for each population since it varies considerably according to distinct local/regional characteristics. However, very few studies establish baseline values for these elements (essential and toxic) in large population groups, especially in Latin American countries. This study was aimed at establishing urinary reference levels of 30 metals/metalloids: aluminum (Al), antimony (Sb), arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), cerium (Ce), cesium (Cs), chromium (Cr), cobalt (Co), copper (Cu), lanthanum (La), lead (Pb), lithium (Li), strontium (Sr), manganese (Mn), mercury (Hg), molybdenum (Mo), nickel (Ni), platinum (Pt), rubidium (Rb), selenium (Se), silver (Ag), tin (Sn), tellurium (Te), thallium (Tl), thorium (Th), tungsten (W), uranium (U) and zinc (Zn) in a Brazilian southeast adult population. This pilot study is a cross-sectional analysis conducted with the first wave of the ELSA-Brasil cohort (baseline examination). A total of 996 adults (45.5% men, N = 453, mean age: 50.5, and 54.5% women, N = 543, mean age: 50.6) were included in the study. Sample analyses were performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Percentiles (2.5, 10, 25, 50, 75, 95 (CI95%), and 97.5) of each element (µg/g of creatinine) in the study are presented according to sex. Moreover, differences in the mean metal/metalloid urinary levels according to age, education, smoking, and alcohol intake are also presented. Finally, median found values were compared to established values of large human biomonitoring surveys previously conducted in North America and France. This is the first comprehensive and systematic human biomonitoring study that established population reference ranges for 30 (essential and/or toxic elements) in a Brazilian population group.

Screening of regulated aromatic amines in clothing marketed in Brazil and Spain: Assessment of human health risks.

Azo dyes used in textile products contain aromatic amines (AAs), which may be released into the environment after skin bacteria cleavage the azo bond. In Europe, 22 carcinogenic AAs are regulated. Unfortunately, no information is available in many non-European countries, including Brazil. This study aimed to determine the concentrations of 20 regulated AAs in clothes marketed in Brazil and Spain. Generally, higher levels of regulated AAs were found in samples sold in Brazil than in Spain, which is linked to the lack of regulation. Sixteen AAs showed concentrations above 5 mg/kg in samples commercialized in Brazil, while 11 exceeded that threshold in Spain. Regulated AAs with levels above 5 mg/kg were more found in synthetic clothes of pink color. Concentrations in clothing were also used to evaluate the dermal exposure to AAs in 3 vulnerable population groups. The highest exposure corresponded to 2,4-diaminoanisole for toddlers in Brazil and 4,4-oxydianiline for newborns in Spain. Non-cancer risks associated with exposure to 4,4-benzidine by Brazilian toddlers was 14.5 (above the threshold). On the other hand, 3,3-dichlorobenzidine was associated with potential cancer risks for newborns and toddlers in Brazil. Given this topic's importance, we recommend conducting continuous studies to determine the co-occurrence of carcinogenic substances.

Legacy and emerging pollutants in Latin America: A critical review of occurrence and levels in environmental and food samples.

The increase and indiscriminate use of personal care products, food products, fertilizers, pesticides, and health products, among others, have resulted/are resulting in extensive environmental contamination. Most of these products contain traces of widespread chemicals, usually known as emerging pollutants (EPs) or pollutants of emerging concern (PEC). The Latin American (LA) region comprises 20 countries with different social and cultural aspects, with 81 % of the population living in urban areas. The LA region has some countries on the top list of users/consumers of EPs, from pesticides and fertilizers to personal care products. However, there is a gap in information related to the distribution of EPs in the environment of this region, with very few existing review texts exploring this issue. Therefore, this present paper advances this approach. An exhaustive literature review, with the selection of 176 documents, provided unique up-to-date information on the presence/distribution of 17 classes of legacy or emerging pollutants in different food and environmental matrices (soil, sediment, water, and air). The study shows that the wide distribution and recorded levels of these pollutants in the continental environment are potential risks to human health, mainly through food and drinking water ingestion. Polycyclic aromatic hydrocarbons are pollutants of deep public concern since they show carcinogenic properties. Several classes of pollutants, like endocrine disruptors, have caused harmful effects on humans and the environment. Besides that, pharmaceutical products and pesticides are compounds of high consumption worldwide, being environmental contamination a real and ongoing possibility. Finally, gaps and future research needs are deeply pointed out.

Oxidative stress in testes of rats exposed to n-butylparaben.

This study was aimed at determining if oxidative stress imbalance in testes of rats occurs after n-butylparaben (n-ButP) exposure. Young male Sprague-Dawley rats were subcutaneously treated with n-ButP during one spermatogenic cycle (57 days) at 0 (control-oil), 150, 300 and 600 mg/kg/d with peanut oil as vehicle. A non-vehicle control group was also included. Antioxidant enzyme activities (superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase) and levels of reduced and oxidized glutathione were measured in testes. Lipid peroxidation and H2O2 concentrations were also assessed. Results showed an increase of oxidative stress in oil-treated groups, excepting 600 mg/kg/d, suggesting oxidative stress due to peanut oil. A possible antioxidant effect due to n-ButP and its metabolites was suggested at 600 mg/kg/d, the only group not showing oxidative stress. An increase of calcium concentration in testes was also observed. On the other hand, a physiologically-based pharmacokinetic (PBPK) model was developed and the concentrations of n-ButP and its metabolites were simulated in plasma and testes. The peak concentration (Cmax) in testes was found slightly higher than that in plasma. The current results indicate that peanut oil can cause oxidative stress while high doses of n-ButP can act as antioxidant agent in testes.

Trace element concentrations in breast cancer patients.

Alterations in the circulating levels of trace elements have been observed in breast cancer (BC) patients. However, the relationships between these alterations and the metabolic and clinical consequences of BC are unknown. The treatment-of-choice of BC is surgery followed by radiation therapy (RT). The present study was aimed at investigating: 1) the concentrations of several trace elements in BC patients, and their relationships with the intrinsic molecular subtypes of tumors; 2) the toxicological effect of RT. We studied 49 women with BC who were scheduled to receive RT following excision of the tumor. Plasma samples were obtained before and after the irradiation procedure. The control group was composed of 49 healthy women. Patients had significantly lower pre-RT concentrations of B, Cu, and Zn, and significantly higher concentrations of Sr than the control group. Irradiation was associated with a striking increase in plasma B concentrations, while Cu, Fe, Sr and Zn concentrations were not significantly different from pre-RT levels, albeit Sr and Zn showed non-significant trends towards increases. The plasma concentrations of B, Cu, Fe, Sr, and Zn were associated with the tumor expression of hormone receptors, epidermal growth factor receptor 2, Ki67 antigen, as well as dermatitis and asthenia, all of which represent the main toxicological responses to RT.

Environmental exposure to low-doses of ionizing radiation. Effects on early nephrotoxicity in mice.

Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium (137Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-ß-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation (137Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137Cs). Further investigations are required to clarify the mechanisms involved in the internal IR-induced nephrotoxicity.

Seasonal surveillance of airborne PCDD/Fs, PCBs and PCNs using passive samplers to assess human health risks.

This study aimed at determining the air concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) near a municipal solid waste incinerator (MSWI) in Tarragona (Catalonia, Spain) by means of passive air sampling. Seasonal trends in airborne levels were also assessed by comparing the results of 6-month surveys conducted between spring of 2010 and autumn of 2011. These data were used to estimate exposure for the population living nearby and to evaluate the non-carcinogenic and carcinogenic risks associated to inhalation of those persistent organic pollutants (POPs). No seasonal differences were noted in POP concentrations among the sampling campaigns. The highest levels of PCDD/Fs were found in the 3rd campaign, while significantly lower levels of PCNs were found in the 4th survey. The concentrations of PCDD/F and PCB congeners, as well as those of PCN homologues, did not change significantly with time, which indicates that the MSWI does not have an important influence on the surrounding environment. The levels of POPs near the facility are at the lower part of the range, when compared with data from the scientific literature. Consequently, the current levels of POPs in ambient air around the MSWI are associated to a low human exposure to PCDD/Fs, PCBs and PCNs, which means a lack of additional health risks for the local population. In addition, passive samplers have been confirmed to be a good tool for local environmental monitoring, as well as a good method to study seasonal trends in POP concentrations in air.

Aluminum, calcium ion and radiofrequency synergism in acceleration of lymphomagenesis.

This study that was done on lymphomagene-bearing mice indicates a synergism aluminum-radiofrequency which induces an early increase in mortality that is in concomitance with lymphoid elements proliferation and infiltration of spleen and liver. These two last phenomena were assessed by determination of the hypertrophic index (Growth Index) which is the organ weight to to the body weight ratio, as well as by the histopathological examination of the organ tissue. The importance of this synergism appears to be determined by the ionization at the physiological pH of the used aluminum complexes: much higher with lactate complex than with the citrate one. On the other hand, this dissociation appears to induce a remarkable acceleration of the mortality and the lymphoid elements-related hypertrophy of the spleen and liver at early age. Aluminum complexes are known as modifiers of the intracellular calcium homeostasis, and to verify if such process could be implicated in this synergism, the effects of calcium chloride were assayed, in this case the calcium-overload had no effects in the presence of a workable cellular control of intracellular calcium homeostasis. This finding support the hypothesis that ionized aluminum provided by lactate may be implicated in the inhibition of the buffering and extruding extracellular calcium system.