No abstract

In Brazil, gas station workers are occupationally exposed to the benzene present in gasoline. Brazilian law indicates the use of trans,trans-muconic acid(t,t-MA) as a biomarker of benzene exposure. The aim of this study was to evaluate the level of exposure to benzene in gas station workers, through the quantification of t,t-MA present in urine. A total number of 269 gas station workers divided into 179 filling station attendants exposed by inhalation and dermal route and 90 convenience store workers exposed only by inhalation were included. A control group was formed by 100 office workers, without occupational exposure to benzene. The urinary levels of t,t-MA were evaluated by HPLC with a UV detector. Gas station workers showed higher mean values of t,t-MA (0.204 mg/g creatinine; 95% CI 0.170–0.237) than office workers (0.126 mg/g creatinine; 95% CI 0.0817–0.1693). T,t-MA levels were higher in convenience store workers exposed to gasoline only by inhalation (0.221 mg/g creatinine; 95% CI 0.160–0.282), than in those exposed to gasoline by inhalation and dermal route—filling station attendants (0.195 mg/g creatinine; 95% CI 0.155–0.235). Gas station workers with a higher level of t,t-MA had epistaxis. T,t-MA values were higher in the Downtown (0.15 mg/g creatinine) region’s workers than in the more affluent South Zone region’s workers (0.07 mg/g creatinine). Smoking habits influenced the urinary t,t-MA values, while the frequency of consumption of industrialized and frozen foods showed no influence.

No abstract

Daidzein (DZ), an isoflavone with the potential to interfere with estrogen signaling, is found in soy products, which have gained popularity due to purported beneficial effects on the cardiovascular and skeletal systems and potential antineoplastic properties. However, the ingestion of phytoestrogens has been associated with impaired reproductive function in many species. The aim of this study was to determine the long-term effects on the ovaries of rat offspring exposed to DZ or ethinyl estradiol (EE) during prenatal development. Gravid rats were administered either vehicle or 5 or 60 mg DZ/kg body weight/d or 0.002 mg 17-α EE /kg body weight/d on gestational days 6-21. Ovarian-related endpoints were investigated during adulthood in female offspring. The mean cell height of the ovarian surface epithelium was significantly reduced in all treated groups. Alterations in folliculogenesis included increased follicular atresia, a reduction in secondary and tertiary follicle numbers, and cyst formation. An elevated prevalence of a slightly prolonged estrus phase was also observed. The morphological changes to the ovarian surface epithelium are consistent with an antiproliferative effect, while ovarian folliculogenesis was adversely affected. The effects of the high dose DZ were similar to those observed with 17-α EE.

Mouse cytochrome P450 (CYP) 2A5 is induced by inflammatory conditions and infectious diseases that down-regulate the expression and activity of most other CYP isoforms. Enhanced oxidative stress and nuclear factor (erythroid 2-related factor) 2 (Nrf2) transcription factor activation have been hypothesised to mediate up-regulation of CYP2A5 expression in the murine liver. The unique and complex regulation of CYP2A5, however, is far from being thoroughly elucidated. Sepsis and high doses of bacterial lipopolysaccharide (LPS) elicit oxidative stress in the liver, but depression, not induction, of CYP2A5 has been observed in studies of mice treated with LPS. The foregoing facts prompted us to evaluate the response of CYP2A5 liver activity in female DBA-2 mice over a broad range of LPS doses (0, 0.025, 0.05, 0.1, 0.2, 0.5, 1, 2, 5, 10, and 20 mg/kg). Cytokine levels (interleukin [IL]-2, IL-4, IL-6, IL-10, IL-17A, interferon gamma, tumour necrosis factor alpha) and nitric oxide (NO) were measured in the blood serum. Activities of CYP1A (EROD) and CYP2B (BROD) in the liver were also determined for comparative purposes. LPS depressed CYP2A5 at low doses (0.025–2.0 mg/kg) but not at doses (>2 mg/kg) that increased pro-inflammatory cytokines and NO serum levels, and depressed CYP1A and CYP2B activities. Blockade of pro-inflammatory cytokines and the overproduction of NO induced by co-treatment with pentoxifylline and LPS and iNOS inhibition with aminoguanidine both extended down-regulation of CYP2A5 to the high dose range while not affecting LPS-induced depression of CYP1A and CYP2B. Overall, the results suggested that NO plays a role in the reversal of the low-dose LPS-induced depression of CYP2A5 observed when mice were challenged with higher doses of LPS.

BackgroundCytochrome P450 2A5 (Cyp2a5), a mouse enzyme orthologous of human CYP2A6, catalyzes a number of toxicologically important reactions, including the metabolism of nicotine, aflatoxin B1, and several other xeno- and endobiotics. Cyp2a5 expression is complex and not yet fully understood. We investigated inter-strain differences in the activity and mRNA expression of hepatic Cyp2a5. Cyp1a1/2 and Cyp2b9/10 activities were evaluated for comparative purposes. Data on the interstrain differences in the expression and activity of Cyp2a5 are important to select a suitable mouse model for studying CYP2A6-mediated metabolism.ResultsActivity of Cyp2a5 (coumarin 7-hydroxylase) was highest in DBA-2 and DBA-1, intermediate in B6D2F1 (hybrid) and low in the remaining strains (C57BL/6, C57BL/10, CBA, BALB/cAn, SW). Contrasting with the activity, background levels of Cyp2a4/5 mRNA did not differ between high- and low-activity murine strains. Phenobarbital (PB, 80 mg/kg body weight/day × 3 days, i.p.) increased Cyp2a5, Cyp1a1/2 (ethoxyresorufin-O-deethylase) and Cyp2b9/10 (bezyloxyresorufin-O-debenzylase) activities while only Cyp2a5 was enhanced by pyrazole (PYR, 100 mg/kg body weight/day × 3 days, i.p.). Inductions of Cyp2a5 activity by PYR and PB were accompanied by increases of Cyp2a4/5 mRNA. PYR and PB did not upregulate heme oxygenase-1 (hmox-1) mRNA expression in any strain, a finding that is apparently at odds with the notion that Cyp2a5 and hmox-1 inductions are coordinated events.ConclusionsSince background levels of Cyp2a4/5 gene transcripts of high-activity strains did not differ from those of low-activity mice, distinct constitutive activities did not result from different transcription rates and/or mRNA half-lives. Results therefore suggested that interstrain differences in constitutive activity of Cyp2a5 possibly arise from distinct translation efficiencies, protein half-lives and/or enzyme kinetics toward the substrate. Data from this study indicated that all tested strains are suitable models for studying toxicants that are substrates for human CYP2A6; DBA-2, DBA-1 and the hybrid B62DF1, however, have the advantage of presenting high constitutive activities of Cyp2a5.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-017-2435-x) contains supplementary material, which is available to authorized users.

The main volatile organic compounds found at gasoline stations are benzene, toluene, ethylbenzene, and xylene isomers (BTEX). They cause several harmful effects on human health. Regulatory Norm 7 (1978) provides that, in Brazil, biological monitoring of toluene and xylene is carried out by measuring the urinary metabolites hippuric acid (HA) and methylhippuric acid (MHA), respectively. The objective of this study was to assess the exposure to toluene and xylene and to identify related signs and symptoms in gasoline station workers. A cross-sectional epidemiological study was conducted with workers occupationally exposed to fuels. These gasoline station workers were divided into two groups: 94 workers exposed mainly by inhalation (convenience store workers (CSWs)) and 181 workers exposed by inhalation and dermal route (filling station attendants (FSAs)). A comparison group was formed by 119 workers not occupationally exposed to fuels (office workers (OWs)). Workers exposed to fuels had higher average levels of these exposure biomarkers (HA and MHA), which were also higher in convenience store workers than in filling station attendants. In addition, individuals exposed to the solvents present in gasoline had altered mood/depression, cramps, dizziness, drowsiness, headaches, irritability/nervousness, weakness, weight loss, and other symptoms more frequently and had higher urinary levels of HA and MHA compared to the comparison group. Gasoline station workers showed high levels of HA and MHA, reflecting high occupational exposure to the solvents toluene and xylene present in gasoline, demonstrating that changes in the current legislation and in the work environment are necessary to ensure better health protection for these workers.

ResumoIntrodução: o benzeno, composto encontrado na gasolina, é reconhecido como agente cancerígeno e tem sido objeto de controle em âmbito mundial devido aos seus efeitos agudos e crônicos à saúde humana. No Brasil, trabalhadores de postos de revenda de combustíveis (PRC) são expostos ao benzeno durante suas atividades ocupacionais. A Vigilância Sanitária, ao monitorar a exposição dos trabalhadores ao benzeno, pode avaliar os riscos e implementar estratégias para estabelecer um ambiente de trabalho mais seguro. Objetivo: suscitar a discussão sobre as ações da Vigilância Sanitária em postos de combustíveis baseada na aplicação do modelo Força-Motriz/Pressão/Situação/Exposição/Efeito/ Ação (FPSEEA). Método: realização de uma ampla revisão da literatura com a finalidade de obter as informações necessárias para construção e desenvolvimento da matriz proposta no modelo. Discussão: foi possível identificar as deficiências existentes nos diferentes níveis institucionais que possuem suas ações voltadas à proteção da saúde do trabalhador e propor ações para avançar na reflexão sobre o modelo de desenvolvimento, modos de produção e exploração de recursos. Também foram identificadas as possíveis ações da Vigilância Sanitária a serem aplicadas no ambiente ocupacional de PRC para eliminação ou redução dos riscos à saúde aos quais os trabalhadores estão expostos. Palavras-chave: vigilância sanitária; benzeno; postos de combustíveis. Abstract