Pharmacologically active compounds including both legally used pharmaceuticals and illicit drugs are potent environmental contaminants. Extensive research has been undertaken over the recent years to ...understand their environmental fate and toxicity. The one very important phenomenon that has been overlooked by environmental researchers studying the fate of pharmacologically active compounds in the environment is their chirality. Chiral drugs can exist in the form of enantiomers, which have similar physicochemical properties but differ in their biological properties such as distribution, metabolism and excretion, as these processes (due to stereospecific interactions of enantiomers with biological systems) usually favour one enantiomer over the other. Additionally, due to different pharmacological activity, enantiomers of chiral drugs can differ in toxicity. Furthermore, degradation of chiral drugs during wastewater treatment and in the environment can be stereoselective and can lead to chiral products of varied toxicity. The distribution of different enantiomers of the same chiral drug in the aquatic environment and biota can also be stereoselective. Biological processes can lead to stereoselective enrichment or depletion of the enantiomeric composition of chiral drugs. As a result the very same drug might reveal different activity and toxicity and this will depend on its origin and exposure to several factors governing its fate in the environment. In this
critical review
a discussion of the importance of chirality of pharmacologically active compounds in the environmental context is undertaken and suggestions for directions in further research are made. Several groups of chiral drugs of major environmental relevance are discussed and their pharmacological action and disposition in the body is also outlined as it is a key factor in developing a full understanding of their environmental occurrence, fate and toxicity. This review will be of interest to environmental scientists, especially those interested in issues associated with environmental contamination with pharmacologically active compounds and chiral pollutants. As the review will outline current state of knowledge on chiral drugs, it will be of value to anyone interested in the phenomenon of chirality, chiral drugs, their stereoselective disposition in the body and environmental fate (212 references).
This review discusses the importance of chirality of pharmacologically active compounds in the environmental context and suggests further research directions.
Triclosan (TCS) and triclocarban (TCC) are antimicrobial agents formulated in a wide variety of consumer products (including soaps, toothpaste, medical devices, plastics, and fabrics) that are ...regulated by the U.S. Food and Drug Administration (FDA) and U.S. Environmental Protection Agency. In late 2014, the FDA will consider regulating the use of both chemicals, which are under scrutiny regarding lack of effectiveness, potential for endocrine disruption, and potential contribution to bacterial resistance to antibiotics. Here, we report on body burdens of TCS and TCC resulting from real-world exposures during pregnancy. Using liquid chromatography tandem mass spectrometry, we determined the concentrations of TCS, TCC, and its human metabolites (2′-hydroxy-TCC and 3′-hydroxy-TCC) as well as the manufacturing byproduct (3′-chloro-TCC) as total concentrations (Σ−) after conjugate hydrolysis in maternal urine and cord blood plasma from a cohort of 181 expecting mother/infant pairs in an urban multiethnic population from Brooklyn, NY recruited in 2007–09. TCS was detected in 100% of urine and 51% of cord blood samples after conjugate hydrolysis. The interquartile range (IQR) of detected TCS concentrations in urine was highly similar to the IQR reported previously for the age-matched population of the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2004, but typically higher than the IQR reported previously for the general population (detection frequency = 74.6%). Urinary levels of TCC are reported here for the first time from real-world exposures during pregnancy, showing a median concentration of 0.21 μg/L. Urinary concentrations of TCC correlated well with its phase-I metabolite ∑-2′-hydroxy-TCC (r = 0.49) and the manufacturing byproduct ∑-3′-chloro-TCC C (r = 0.79), and ∑-2′-hydroxy-TCC correlated strongly with ∑-3′-hydroxy-TCC (r = 0.99). This human biomonitoring study presents the first body burden data for TCC from exposures occurring during pregnancy and provides additional data on composite exposure to TCS (i.e., from both consumer-product use and environmental sources) in the maternal–fetal unit for an urban population in the United States.
Concerns are heightened from detecting environmentally persistent man-made per- and polyfluoroalkyl substances (PFAS) in drinking water systems around the world. Many PFAS, including perfluorooctane ...sulfonate (PFOS) and perfluorooctanoate (PFOA), remain in the human body for years. Since 1999–2000, assessment of exposure to PFOS, PFOA, and other select PFAS in the U.S. general population has relied on measuring PFAS serum concentrations in participants of the National Health and Nutrition Examination Survey (NHANES). Manufacturers have replaced select chemistries (“legacy” PFAS) with PFAS with shorter biological half-lives (e.g., GenX, perfluorobutanoate PFBA) which may efficiently eliminate in urine. However, knowledge regarding exposure to these compounds is limited. We analyzed 2682 urine samples for 17 legacy and alternative PFAS in 2013–2014 NHANES participants ≥6 years of age. Concentrations of some of these PFAS, measured previously in paired serum samples from the same NHANES participants, suggested universal exposure to PFOS and PFOA, and infrequent or no exposure to two short-chain PFAS, perfluorobutane sulfonate and perfluoroheptanoate. Yet, in urine, PFAS were seldom detected; the frequency of not having detectable concentrations of any of the 17 PFAS was 67.5%. Only two were detected in >1.5% of the population: PFBA (13.3%) and perfluorohexanoate (PFHxA, 22.6%); the 90th percentile urine concentrations were 0.1 μg/L (PFBA), and 0.3 μg/L (PFHxA). These results suggest that exposures to short-chain PFAS are infrequent or at levels below those that would result in detectable concentrations in urine. As such, these findings do not support biomonitoring of short-chain PFAS or fluorinated alternatives in the general population using urine, and highlight the importance of selecting the adequate biomonitoring matrix.
•No detectable extensive exposure to alternative PFAS in the U.S. general population•Choice of matrix influences the success of biomonitoring exposure assessments•Serum levels are best for biomonitoring of PFAS regardless of their biopersistence
The number of studies that have been published on the topic of nanosafety speaks for itself. We have seen an almost exponential rise over the past 15 years or so in the number of articles on ...nanotoxicology. Although only a couple of hundred papers had appeared on the topic of “Nanomaterials: environmental and health effects” before 2000, this number has exploded to over 10 000 since 2001. Most of these studies, however, do not offer any kind of clear statement on the safety of nanomaterials. On the contrary, most of them are either self‐contradictory or arrive at completely erroneous conclusions. Three years ago in this Journal we underscored the deficiencies in the way these studies were designed and pointed out the sources of error in the methods used. Now, on the basis of a comprehensive review of the literature and with the help of selected toxicological end points, we attempt to indicate where the significant weaknesses of these studies lie and what we must improve in the future.
A question of safety: This Review discusses how far the human toxicological evaluation of synthetic nanomaterials has come, for which over 10 000 publications have appeared since 2000. Four core themes have been analyzed: the uptake of nanomaterials by the three main pathways of the lungs, gastrointestinal tract, and skin as well as the assessment of the methods for lung exposure studies.
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The history of H2S – as an environmental toxin – dates back to 1700, to the observations of the Italian physician Bernardino Ramazzini, whose book “De Morbis Artificum Diatriba” ...described the painful eye irritation and inflammation of “sewer gas” in sewer workers. The gas has subsequently been identified as hydrogen sulfide (H2S), and opened three centuries of research into the biological roles of H2S. The current article highlights the key discoveries in the field of H2S research, including (a) the toxicological studies, which characterized H2S as an environmental toxin, and identified some of its modes of action, including the inhibition of mitochondrial respiration; (b) work in the field of bacteriology, which, starting in the early 1900s, identified H2S as a bacterial product – with subsequently defined roles in the regulation of periodontal disease (oral bacterial flora), intestinal epithelial cell function (enteral bacterial flora) as well as in the regulation of bacterial resistance to antibiotics; and (c), work in diverse fields of mammalian biology, which, starting in the 1940s, identified H2S as an endogenous mammalian enzymatic product, the functions of which – among others, in the cardiovascular and nervous system – have become subjects of intensive investigation for the last decade. The current review not only enumerates the key discoveries related to H2S made over the last three centuries, but also compiles the most frequently cited papers in the field which have been published over the last decade and highlights some of the current ‘hot topics’ in the field of H2S biology.
A study examined the oxidation of pollutants with organic photocatalysts, focusing on the biodegradation methods and alternatives. Some of these alternatives include ozonation, wet oxidation and ...photochemical oxidation.
Some heavy metals (e.g., arsenic, cadmium, lead, mercury) have been associated with obesity and obesity comorbidities. The analytical approach for those associations has typically focused on ...individual metals. There is a growing interest in evaluating the health effects of cumulative exposure to metal mixtures.
We utilized our Environmental Risk Score (ERS), a summary measure to examine the risk of exposure to multi-pollutants in epidemiologic research, to evaluate the associations of cumulative exposure to a mixture of correlated heavy metals with obesity and its comorbidities including hypertension, and type-2 diabetes mellitus (T2DM) while accounting for high degree correlations and interactions among metal mixtures components.
We examined blood and urinary markers of 18 heavy metals among 9537 adults in NHANES 2003–2014. We randomly split data into a training set for the construction of ERS (n = 6675) and a testing set for the evaluation of its statistical performance (n = 2862). ERS of heavy metal mixtures was computed for waist circumference using adaptive elastic-net (AENET) with 189 predictors including 18 main effects, 18 squared terms, and 153 pairwise interactions of heavy metals. Regression analyses with complex survey designs were performed to assess the associations of ERS with other obesity measures, hypertension and T2DM.
7 main effects (blood lead, blood cadmium, blood mercury, and urinary markers of monomethylarsonic acid (MMA), barium, mercury and thallium), 4 squared terms (blood cadmium, urinary cadmium, urinary antimony and urinary tungsten), and 7 pairwise interactions (blood lead & urinary cadmium, blood lead & urinary MMA, blood lead & urinary uranium, urinary cadmium & urinary MMA, urinary dimethylarsinic acid (DMA) & urinary tungsten, urinary MMA & urinary cobalt, and urinary lead & urinary antimony) were selected by AENET for construction of ERS of waist circumference-related metal mixtures. An increase in ERS from 10th percentile to 90th percentile in the overall study population was significantly associated with 4.50 kg/m2 (95% CI: 4.06, 4.94) higher BMI, 4.16 mm (95% CI: 3.56, 4.76) higher skinfold thickness, and 4.11 kg (95% CI: 0.83, 7.40) higher total body fat, independent of age, sex, race/ethnicity, education, smoking status, physical activity and NHANES cycle (Ps < 0.05). Significant associations of ERS with both hypertension and T2DM were also observed (Ps < 0.05).
Our study suggests that cumulative exposure to heavy metals as mixtures is associated with obesity and its related chronic conditions such as hypertension and T2DM. Additional research is needed to confirm these findings in longitudinal settings.
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•There is a growing interest in evaluating the health effects of cumulative exposure to metal mixtures.•Environmental Risk Score (ERS) is a summary measure to examine the risk of exposure to multi-pollutants.•We constructed an ERS of metal mixtures with 18 metals measured in blood and urine.•ERS of metal mixtures was significantly associated with obesity measures and hypertension and type-2 diabetes.•Cumulative exposure to metal mixtures may play a role in both obesity and its related chronic conditions.
The conversion of organic pollutants to value-added chemicals has been considered as a sustainable approach to solve environmental problems. However, it is still a challenge to construct a suitable ...heterogeneous catalyst that can synchronously achieve the enrichment and activation of organic pollutants (such as 4-nitrophenol, 4-NP). Here, an organic-inorganic hybrid catalyst (CeO
/Ni-MOF) was successfully fabricated for efficiently reducing 4-NP to 4-aminophenol (4-AP) with water as the hydrogen source. Based on the synergistic effect of Ni-MOF (adsorption action) and CeO
(active sites), CeO
/Ni-MOF could achieve a reaction rate of 1.102 μmol min
mg
with an ultrahigh Faraday efficiency (FE) (99.9%) and conversion (97.6%). In addition, the catalytic mechanism of 4-NP reduction over CeO
/Ni-MOF was elaborated in depth. This work presents a new avenue for the effective reduction of pollutants and provides a new strategy for designing high-performance catalysts for rare-earth metals.
Combined environmental exposures to the volatile organic compounds (VOCs) Benzene, Toluene, Ethylbenzene, and Xylene (BTEX) pose clear risks to public health. Research into these risks is ...under-studied even as BTEX levels in the atmosphere are predicted to rise. This review focuses on the available literature using single- and combined-BTEX component inhaled solvent exposures in animal models, necessarily also drawing on findings from models of inhalant abuse and occupational exposures. Health effects of these exposures are discussed for multiple organ systems, but with particular attention on neurobehavioral outcomes such as locomotor activity, impulsivity, learning, and psychopharmacological responses. It is clear that animal models have significant differences in the concentrations, durations and patterns of exposure. Experimental evidence of the deleterious health and neurobehavioral consequences of exposures to the individual components of BTEX were found, but these effects were typically assessed using concentrations and exposure patterns not characteristic of environmental exposure. Future studies with animal models designed appropriately to explore combined BTEX will be necessary and advantageous to discovering health outcomes and more subtle neurobehavioral impacts of long-term environmental exposures.
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