Reproductive toxicity of lead,cadmium, and phthalate exposure in men

Environmental toxicants viz lead or cadmium and phthalate esters (di(2-ethylhexyl) phthalate [DEHP], dibutyl phthalate [DBP], and diethyl phthalate [DEP]) widely found in different environmental strata are linked to deteriorating male reproductive health. The objective was to assess the relationships between the seminal lead, cadmium, and phthalate (DEHP, DBP, DEP) concentrations at environmental level and serum hormone levels and semen quality in non-occupationally exposed men and specify the effect of individual and combined exposure of toxicants on semen quality. A study of 60 male partners of couples attending the Andrology Laboratory of the Reproductive Biology Department, All India Institute of Medical Sciences (AIIMS), New Delhi, India for semen analysis to assess their inability to achieve a pregnancy was selected for the study. The results of univariate and stepwise multiple regression analysis in the unadjusted model showed a significant correlation between lead or cadmium and phthalates DEHP/DBP/DEP and sperm motility, sperm concentration, and DNA damage. After adjusting for potential confounders, an association with lead or DEHP was only observed. The present data shows that lead (Pb) or cadmium (Cd) or phthalates might independently contribute to decline in semen quality and induce DNA damage. Phthalates might influence reproductive hormone testosterone. These findings are significant in light of the fact that men are exposed to a volley of chemicals; however, due to the small sample size, our finding needs to be confirmed in a larger population.     

Mechanistic insights into the specificity of human cytosolic sulfotransferase 2A1 (hSULT2A1) for hydroxylated polychlorinated biphenyls through the use of fluoro-tagged probes

Determining the relationships between the structures of substrates and inhibitors and their interactions with drug-metabolizing enzymes is of prime importance in predicting the toxic potential of new and legacy xenobiotics. Traditionally, quantitative structure activity relationship (QSAR) studies are performed with many distinct compounds. Based on the chemical properties of the tested compounds, complex relationships can be established so that models can be developed to predict toxicity of novel compounds. In this study, the use of fluorinated analogues as supplemental QSAR compounds was investigated. Substituting fluorine induces changes in electronic and steric properties of the substrate without substantially changing the chemical backbone of the substrate. In vitro assays were performed using purified human cytosolic sulfotransferase hSULT2A1 as a model enzyme. A mono-hydroxylated polychlorinated biphenyl (4-OH PCB 14) and its four possible mono-fluoro analogues were used as test compounds. Remarkable similarities were found between this approach and previously published QSAR studies for hSULT2A1. Both studies implicate the importance of dipole moment and dihedral angle as being important to PCB structure in respect to being substrates for hSULT2A1. We conclude that mono-fluorinated analogues of a target substrate can be a useful tool to study the structure activity relationships for enzyme specificity.     

Oxidative potential and chemical composition of PM2.5 in office buildings across Europe – The OFFICAIR study

In the frame of the OFFICAIR project, indoor and outdoor PM_2.5 samples were collected in office buildings across Europe in two sampling campaigns (summer and winter). The ability of the particles to deplete physiologically relevant antioxidants (ascorbic acid (AA), reduced glutathione (GSH)) in a synthetic respiratory tract lining fluid, i.e., oxidative potential (OP), was assessed. Furthermore, the link between particulate OP and the concentration of the PM constituents was investigated.The mean indoor PM_2.5 mass concentration values were substantially lower than the related outdoor values with a mean indoor/outdoor PM_2.5 mass concentration ratio of 0.62 and 0.61 for the summer and winter campaigns respectively. The OP of PM_2.5 varied markedly across Europe with the highest outdoor OP^AA m⁻³ and OP^GSH m⁻³ (% antioxidant depletion/m³ air) values obtained for Hungary, while PM_2.5 collected in Finland exhibited the lowest values. Seasonal variation could be observed for both indoor and outdoor OP^AA m⁻³ and OP^GSH m⁻³ with higher mean values during winter. The indoor/outdoor OP^AA m⁻³ and OP^GSH m⁻³ ratios were less than one with 4 and 17 exceptions out of the 40 cases respectively. These results indicate that indoor air is generally less oxidatively challenging than outdoors. Correlation analysis revealed that trace elements play an important role in determining OP, in particular, the Cu content. Indoor air chemistry might affect OP since weaker correlations were obtained for indoor PM_2.5. Our findings also suggest that office workers may be exposed to health relevant PM constituents to a different extent within the same building.     

Dioxins and PCBs in game animals: Interspecies comparison and related consumer exposure

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DL-PCB) and non-dioxin-like polychlorinated biphenyls (NDL-PCB) are ubiquitous, persistent toxic compounds that are highly bioaccumulative in nature. Wild-living animals are vulnerable to the negative impacts of human activity. Dioxins and PCBs enter the animal organisms through foraging. Due to the toxicological threat, much attention is paid to these compounds worldwide. The aim of this study was to determine the dioxin contamination status of three game animal species (red deer, roe deer, and wild boar) and compare the PCDD/F and PCB congener bioaccumulation in the muscles, abdominal fat and liver. The chemical analysis was performed by the isotope dilution technique (IDMS) with high-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC/HRMS). Dioxins and PCBs were found in specimens collected from all studied species, suggesting the presence of the test compounds in the environment of the animals. The highest concentrations were found in the livers of all animals. The toxic equivalent (TEQ) levels in the muscles, adipose tissue and liver were in the order red deer > roe deer > wild boar. PCDD/Fs were the dominant congeners in TEQ value. For all tested species, the dominant contributors to the total WHO-TEQ were PCB-126, 2,3,4,7,8-PeCDF and 1,2,3,7,8-PeCDD. Among the PCDD/F congeners in the deer tissues, OCDD, OCDF and 2,3,4,7,8-PeCDF were dominant, while in wild boar, OCDD, 1,2,3,4,6,7,8-HpCDD and 1,2,3,4,6,7,8-HpCF occurred in the highest amounts. Among PCBs, PCB-105, 118, 156, 138, 153 and 180 were dominant in all species, but with different levels. The regular consumption of muscle meat from game animals should not cause unacceptable dioxin intake above the Tolerable Weekly Intake (TWI) value for children and adults. However, liver consumption should be avoided, especially by children and pregnant or lactating women. High consumption of contaminated liver may cause dioxin intake at levels up to 300% of TWI for adults and up to 700% TWI for children.     

Implementing systematic review techniques in chemical risk assessment: Challenges,opportunities and recommendations

Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question. Taking as a comparator the use of SR in synthesising research in healthcare, we argue that SR methods could also pave the way for a “step change” in the transparency, objectivity and communication of chemical risk assessments (CRA) in Europe and elsewhere. We suggest that current controversies around the safety of certain chemicals are partly due to limitations in current CRA procedures which have contributed to ambiguity about the health risks posed by these substances. We present an overview of how SR methods can be applied to the assessment of risks from chemicals, and indicate how challenges in adapting SR methods from healthcare research to the CRA context might be overcome. Regarding the latter, we report the outcomes from a workshop exploring how to increase uptake of SR methods, attended by experts representing a wide range of fields related to chemical toxicology, risk analysis and SR. Priorities which were identified include: the conduct of CRA-focused prototype SRs; the development of a recognised standard of reporting and conduct for SRs in toxicology and CRA; and establishing a network to facilitate research, communication and training in SR methods. We see this paper as a milestone in the creation of a research climate that fosters communication between experts in CRA and SR and facilitates wider uptake of SR methods into CRA.     

Evaluation of metals in several varieties of sweet potatoes (Ipomoea batatas L.): comparative study

Sweet potatoes are a staple in the diet of some people and an excellent source of minerals. Metal monitoring in food, like sweet potatoes, provides basic information on safety aspects in regulatory processes as well as nutritional values. One hundred five samples of three varieties of sweet potatoes were randomly obtained from supermarkets, farmers markets, and farmers' plots in Tenerife (Canary Islands, Spain). The edible portion (pulp) was the only part considered for analysis. Flame atomic absorption spectrometry was used to determine the contents of sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), copper (Cu), iron (Fe), manganese (Mn), and zinc (Zn), while the levels of chromium (Cr), nickel (Ni), cadmium (Cd), and lead (Pb) were determined using graphite furnace atomic absorption spectrometry. The mean concentrations were 500 Na, 4409 K, 564 Ca, 609 Mg, 1.291 Cu, 6.554 Fe, 2.324 Mn, 2.348 Zn, 0.028 Cr, 0.048 Ni, 0.001 Cd, and 0.003 Pb mg/kg, respectively. Potassium presented the highest contents in all varieties of sweet potatoes. Iron was the most abundant microelement. The orange fleshed sweet potato variety offered greater nutritional contributions to the recommended intakes than the rest of the varieties studied. The estimated mean daily intake of Ni (0.72 mg/day) detected in our samples was highly consistent with other studies. Average daily intakes of Cd (0.015 μg/day) and Pb (0.045 μg/day) were below toxicological reference values. In conclusion, the levels of Cd and Pb detected in the sweet potatoes analyzed do not represent any toxicological risk to consumers.     

Nail polish as a source of exposure to triphenyl phosphate

Triphenyl phosphate (TPHP) is primarily used as either a flame retardant or plasticizer, and is listed as an ingredient in nail polishes. However, the concentration of TPHP in nail polish and the extent of human exposure following applications have not been previously studied. We measured TPHP in ten different nail polish samples purchased from department stores and pharmacies in 2013–2014. Concentrations up to 1.68% TPHP by weight were detected in eight samples, including two that did not list TPHP as an ingredient. Two cohorts (n = 26 participants) were recruited to assess fingernail painting as a pathway of TPHP exposure. Participants provided urine samples before and after applying one brand of polish containing 0.97% TPHP by weight. Diphenyl phosphate (DPHP), a TPHP metabolite, was then measured in urine samples (n = 411) and found to increase nearly seven-fold 10–14 h after fingernail painting (p < 0.001). To determine relative contributions of inhalation and dermal exposure, ten participants also painted their nails and painted synthetic nails adhered to gloves on two separate occasions, and collected urine for 24 h following applications. Urinary DPHP was significantly diminished when wearing gloves, suggesting that the primary exposure route is dermal. Our results indicate that nail polish may be a significant source of short-term TPHP exposure and a source of chronic exposure for frequent users or those occupationally exposed.     

Using GRADE to respond to health questions with different levels of urgency

Increasing interest exists in applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to environmental health evidence. While ideally applied to evidence synthesized in systematic reviews and corresponding summary tables, such as evidence profiles, GRADE's correct application requires that “the evidence that was assessed and the methods that were used to identify and appraise that evidence should be clearly described.” In this article, we suggest that GRADE could be applied to evidence assembled from narrative reviews, modelled (indirect) evidence, or evidence assembled as part of a rapid response, if the underlying judgments about the certainty in this evidence are based on the relevant GRADE domains and provided transparently. Health questions that require assessing the certainty in a body of evidence to provide trustworthy answers may range from hours, to days or weeks, to a few months to scenarios that allow assessing evidence without short-term time pressures. Time frames of emergent, urgent or rapid evidence assessments will often require relying on existing summaries or rapidly compiling the available evidence and making assessments. Even without available full systematic reviews, expressing the certainty in the evidence can provide useful guidance for users of the evidence and those who evaluate certainty in effects. The ratings also help clarifying disagreement between organizations tackling similar questions about the evidence. Using the structured GRADE domains, narrative or other summaries of the evidence can be presented transparently.     

Preferential sorption of some natural organic matter fractions to titanium dioxide nanoparticles: influence of pH and ionic strength

Natural organic matter (NOM) sorption to nanoparticles (NPs) can influence their transport and bioavailability in the aquatic environment. The sorption affinity of NOM to surfaces including NPs is size dependent, and depending on environmental conditions, NOM may enhance or mitigate NPs toxicity. The aim of this study was to investigate the preferential sorption of different-sized fractions of NOM to titanium dioxide (TiO₂) NPs. We specifically investigated the influence of pH, ionic strength, and NOM concentration on the extent of this preferential sorption using a constant sorbent concentration (400 mg/L TiO₂ NPs). Additionally, sorption of NOM to TiO₂ NPs at varying pH was investigated. The nonsorbed NOM was separated from the sorbed, by 50 nm polycarbonate membrane filters and ultracentrifugation. High-performance size exclusion chromatography (HPSEC) was used to determine the average molecular weights of NOM (MWw). Corroborative evidence of preferential sorption of different-sized molecular weight fractions of NOM was obtained from optical techniques such as absorbance and fluorescence spectrophotometry. The total organic carbon was measured by the Total Organic Carbon Analyzer—Shimadzu (TOC-VCPH). The results indicated that there is preferential sorption of larger sized fractions of NOM to TiO₂ NPs irrespective of NOM concentration. It was observed that the sorption of larger sized fractions of NOM was much enhanced at lower pH and at higher ionic strength. Both absorbance and fluorescence spectrophotometric techniques gave credible corroborative evidence on the extent of preferential sorption of lager sized fractions of NOM with respect to pH and ionic strength. The sorption results demonstrated higher sorption at lower pH than at higher pH. Overall, the results of this study suggest that the environmental conditions are key factors that can contribute to NOM’s fractional preferential sorption to NPs in the aquatic environment.     

Persistence and dissipation of flubendiamide and its risk assessment on gherkin (Cucumis anguria L.)

A supervised open field trial was conducted to evaluate the dissipation pattern and risk assessment of flubendiamide in gherkin fruits following foliar application of Fame 480 SC at 60 and 120 g a.i.?ha^?1. Samples of gherkin fruits were drawn at different time intervals and quantified by HPLC-DAD. The maximum initial deposits of flubendiamide on gherkin were found to be 0.79 and 1.52 mg kg^?1, respectively, at recommended and double the recommended doses. The dissipation pattern of flubendiamide followed a first-order kinetics with half-lives of 1.87 to 2.16 days at 60 and 120 g a.i.?ha^?1, respectively. The limit of quantification of flubendiamide and desiodo flubendiamide was observed to be 0.01 mg kg^?1 for gherkin fruit and soil substrates. Theoretical maximum residue contribution (TMRC) for flubendiamide was calculated and found to be well below the maximum permissible intake (MPI) on gherkin fruits. Thus, the application of flubendiamide at the recommended dose on gherkin fruits presents no human health risks and safe to consumers.