The use of antibiotics in food-producing animals can induce the presence of residual substances in manure, which are then released into the environment and may contribute to soil and groundwater ...contamination. During the on-farm implementation of strategies to improve animal health and welfare in chicken and pig farms, the consequences of antibiotic use were evaluated in terms of the occurrence and levels of antibiotic residues in manure.
A set of 35 broiler farms from Cyprus, Greece, the Netherlands and 40 pig farms from France and Italy provided a total of 350 manure samples. The primary objective was to develop a specific LC/MS/MS method capable of quantifying antibiotic residues in both types of manure. The method was able to detect fifteen antibiotics belonging to nine classes, with validated limits of quantification of 10–20 μg/kg, and accuracies ranging from 81% to 138%.
With the exception of amoxicillin, which was never detected in any manure, all antibiotics used were detected in manure from treated animals with typical concentrations ranging from 10 to 99198 μg/kg for both chickens and pigs. The occurrence of residual antibiotics was higher in chicken than in pig manure, especially for fluoroquinolones and doxycycline which were detected in 89% and 100% of the chicken manure, respectively, and in 28% of the pig manure. The impact of the health plans on the antibiotic load manure was assessed by measuring for each farm the ratio of the sum of all antibiotic concentrations measured after and before the implementation of the plan. The results showed that, in addition to the frequency of treatments, the class of antibiotic used is an important factor to consider as it strongly influences the stability/instability of the compounds, i.e. their ability to persist in the manure of food-producing animals.
•15 antibiotics from 9 classes are quantified by LC/MS/MS in pig and broiler manure.•Amoxicillin mainly used both in pig and poultry farms is not detected in manure.•Fluoroquinolones and doxycycline are prevalent, particularly in poultry manure.•Antibiotic class is the main factor influencing its persistence in manure.
Bisphenol A (BPA), an endocrine disruptor, has been replaced by structural analogues including bisphenol S (BPS). BPA and BPS exhibited similar effects regarding reproductive functions. Moreover, ...metabolic status and lipid metabolism are related to female fertility and could worsen BPS effects. The objective was to determine BPS in vivo effects on folliculogenesis and embryo production after chronic exposure through diet, and the influence of metabolic status in adult ewes. Sixty primiparous 2.5 year-old ewes, undergoing a restricted or well fed diet, were exposed to BPS (0, 4 or 50 µg/kg/day) for at least three months. After hormonal oestrus synchronisation and ovarian stimulation, ewes were subjected to ovum pick-up (OPU) procedures to collect immature oocytes, that underwent in vitro maturation, fertilisation and embryo production. Body weight, body condition score and plasma glucose were higher in well-fed compared to restricted ewes, while plasma NEFA was lower during the 4–5 months after the beginning of the diets. Plasma progesterone levels increased on day 5 before OPU session in well-fed compared to restricted ewes. No effect of BPS dose was observed on follicle population, plasma AMH levels and embryo production numbers and rates. However, a significant diet x BPS dose interaction was reported for cleaved embryos, > 4-cell embryos, blastocyst and early blastocyst numbers, and plasma triiodothyronine levels. Our study showed that a contrasted diet did not affect follicle population nor embryo production in adult ewes but could affect the quality and progesterone secretion of the corpus luteum. Chronic low BPS exposure had no effect on follicular population and oocyte competence. Nevertheless, the significant diet x dose interactions observed on embryo production suggest that BPS effect is modulated by metabolic status. Further studies are required to assess the risk of BPS exposure for public reproductive health.
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•The metabolic status modulates bisphenol S effects on female ovarian parameters.•The metabolic status affects the progesterone secretion.•3-month bisphenol S low dose exposure had no effects on ovarian parameters.
Sewer biofilms are likely to constitute hotspots for selecting and accumulating antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). This study aimed to optimize culture ...conditions to obtain
biofilms, mimicking the biofilm collected in sewers, to study the impact of fluoroquinolones (FQs) on sewer biofilm microbiota. Biofilms were grown on coupons in CDC Biofilm Reactors®, continuously fed with nutrients and inoculum (1/100 diluted wastewater). Different culture conditions were tested: (i) initial inoculum: diluted wastewater with or without sewer biofilm, (ii) coupon material: concrete vs. polycarbonate, and (iii) time of culture: 7 versus 14 days. This study found that the biomass was highest when
biofilms were formed on concrete coupons. The biofilm taxonomic diversity was not affected by adding sewer biofilm to the initial inoculum nor by the coupon material.
and
dominated in the sewer biofilm composition, whereas
biofilms were mainly composed of
. The relative abundance of
and
genes was higher in
biofilms than sewer biofilm. The resistome of sewer biofilm showed the highest Shannon diversity index compared to wastewater and
biofilms. A PCoA analysis showed differentiation of samples according to the nature of the sample, and a Procrustes analysis showed that the ARG changes observed were linked to changes in the microbial community. The following growing conditions were selected for
biofilms: concrete coupons, initial inoculation with sewer biofilm, and a culture duration of 14 days. Then, biofilms were established under high and low concentrations of FQs to validate our
biofilm model. Fluoroquinolone exposure had no significant impact on the abundance of
genes, but high concentration exposure increased the proportion of mutations in
A (codons S83L and D87N) and
C (codon S80I). In conclusion, this study allowed the determination of the culture conditions to develop an
model of sewer biofilm; and was successfully used to investigate the impact of FQs on sewer microbiota. In the future, this setup could be used to clarify the role of sewer biofilms in disseminating resistance to FQs in the environment.
Bisphenol (BP) structural analogues of BPA are widely used. Previous studies showed similar effects of BPA and BPS on reproduction in several species including human. We hypothesised that the similar ...effects of several bisphenols (BPs) could accumulate in granulosa cells (GCs) and affects steroidogenesis. This study investigated the effects of seven BP analogues and their equimolar cocktail on human granulosa cells (hGC) and assessed BPA, BPS, BPF and BPAF level exposures in the follicular fluid of 277 women undergoing Assisted Reproductive Technology. The hGCs were recovered after women oocyte punctures and treated with the seven BP analogues (BPS, BPA, BPAF, BPF, BPAP, BPE and BPB) or their equimolar cocktail of 7 × 1.43 or 7 × 7.14 μM for each of the seven BPs, the sum of BPs reaching 10 (”∑BPs 10 μM”), or 50 μM (”∑BPs 50 μM”), respectively. Oestradiol and progesterone secretion, cell proliferation, viability and expression of steroidogenic enzymes were investigated. Progesterone secretion was decreased by 6 BPs 10 μM and the cocktail “∑BPs 10 μM”, (−17.8 to −41.3%) and by all seven BPs 50 μM and “∑BPs 50 μM” (−21.8 to −84.2%). Oestradiol secretion was decreased only by 50 μM BPAF and BPAP (−37.8% and −44%, respectively), with corresponding decreases in CYP17A1 and CYP19A1 gene expression. Cellular proliferation was decreased after treatment with 50 μM BPAF (−32.2%), BPAP (−29%), BPB (−24%) and the equimolar cocktail “∑BPs 50 μM” (−33.1%). BPB (50 μM) and the cocktail “∑BPs 50 μM” increased HSD3B2 mRNA expression. At least one BP was detected in 64 of 277 (23.1%) women follicular fluids.
Similar effects of the seven BPs or their cocktail were observed on progesterone secretion and/or on cell proliferation, suggesting cumulative effects of BPs. Our results highlight the urge to consider all BPs simultaneously and to further investigate the potential additive or synergistic effects of several BPs.
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•BPA, BPS and BPF were detected in 23.1% of 277 women follicular fluids.•BPA, BPS, BPF, BPAF, BPAP, BPB, BPE inhibited progesterone secretion.•Cumulative effects of bisphenols was observed on granulosa progesterone secretion.•Cumulative effects of bisphenols was observed on granulosa cellular proliferation.•BPAF and BPAP are more cytotoxic compared to other bisphenols.
•Oral kinetics of BPS-d8 and BPSG-d8 showed a rapid appearance and elimination.•There was a higher oral bioavailability of active BPS than BPA.•Major differences between BPS and BPA oral kinetics ...were evidenced.•Dermal absorption of BPS was limited.•Replacement of BPA by BPS could increase exposure to a hormonally active substance.
The measurement of bisphenol-S (BPS) and its glucurono-conjugate (BPSG) in urine may be used for the biomonitoring of exposure in populations. However, this requires a thorough knowledge of their toxicokinetics. The time courses of BPS and BPSG were assessed in accessible biological matrices of orally and dermally exposed volunteers. Under the approval of the Research Ethics Committee of the University of Montreal, six volunteers were orally exposed to a BPS-d8 deuterated dose of 0.1 mg/kg body weight (bw). One month later, 1 mg/kg bw of BPS-d8 were applied on 40 cm2 of the forearm and then washed 6 h after application. Blood samples were taken prior to dosing and at fixed time periods over 48 h after treatment; complete urine voids were collected pre-exposure and at pre-established intervals over 72 h postdosing. Following oral exposure, the plasma concentration–time courses of BPS-d8 and BPSG-d8 over 48 h evolved in parallel, and showed a rapid appearance and elimination. Average peak values (±SD) were reached at 0.7 ± 0.1 and 1.1 ± 0.4 h postdosing and mean (±SD) apparent elimination half-lives (t½) of 7.9 ± 1.1 and 9.3 ± 7.0 h were calculated from the terminal phase of BPS-d8 and BPSG-d8 in plasma, respectively. The fraction of BPS-d8 reaching the systemic circulation unchanged (i.e. bioavailability) was further estimated at 62 ± 5% on average (±SD) and the systemic plasma clearance at 0.57 ± 0.07 L/kg bw/h. Plasma concentration–time courses and urinary excretion rate profiles roughly evolved in parallel for both substances, as expected. The average percent (±SD) of the administered dose recovered in urine as BPS-d8 and BPSG-d8 over the 0–72 h period postdosing was 1.72 ± 1.3 and 54 ± 10%. Following dermal application, plasma levels were under the lower limit of quantification (LLOQ) at most time points. However, peak values were reached between 5 and 8 h depending on individuals, suggesting a slower absorption rate compared to oral exposure. Similarly, limited amounts of BPS-d8 and its conjugate were recovered in urine and peak excretion rates were reached between 5 and 11 h postdosing. The average percent (±SD) of the administered dose recovered in urine as BPS-d8 and BPSG-d8 was about 0.004 ± 0.003 and 0.09 ± 0.07%, respectively. This study provided greater precision on the kinetics of this contaminant in humans and, in particular, evidenced major differences between BPA and BPS kinetics with much higher systemic levels of active BPS than BPA, an observation explained by a higher oral bioavailability of BPS than BPA. These data should also be useful in developing a toxicokinetic model for a better interpretation of biomonitoring data.
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•The mixture approach used in this toxicokinetic study allows reducing animal testing.•Bisphenol S results in the highest systemic exposure compared to other bisphenols.•The urinary ...excretion differs greatly among 12 bisphenols.•Urine biomonitoring does not reflect the external exposure for some bisphenols.
Due to the restrictions of its use, Bisphenol A (BPA) has been replaced by many structurally related bisphenols (BPs) in consumer products. The endocrine disrupting potential similar to that of BPA has been described for several bisphenols, there is therefore an urgent need of toxicokinetic (TK) data for these emerging BPs in order to evaluate if their internal exposure could increase the risk of endocrine disruption. We investigated TK behaviors of eleven BPA substitutes (BPS, BPAF, BPB, BPF, BPM, BPZ, 3-3BPA, BP4-4, BPAP, BPP, and BPFL) by intravenous and oral administrations of mixtures of them to piglets and serial collection of blood over 72 h and urine over 24 h, to evaluate their disposition. Data were analyzed using nonlinear mixed-effects modeling and a comparison was made with TK predicted by the generic model HTTK package. The low urinary excretion of some BPs, in particular BPM, BPP and BPFL, is an important aspect to consider in predicting human exposure based on urine biomonitoring. Despite their structural similarities, for the same oral dose, all BPA analogues investigated showed a higher systemic exposure (area under the plasma concentration-time curve (AUC) of the unconjugated Bisphenol) than BPA (2 to 4 fold for 3-3BPA, BPAF, BPB and BPZ, 7–20 fold for BP4-4, BPAP, BPP, BPFL, BPF and BPM and 150 fold for BPS) due mainly to a considerable variation of oral bioavailability (proportion of BP administered by oral route that attains the systemic circulation unchanged). Given similarities in the digestive tract between pigs and humans, our TK data suggest that replacing BPA with some of its alternatives, particularly BPS, will likely lead to higher internal exposure to potential endocrine disruptive compounds. These findings are crucial for evaluating the risk of human exposure to these emerging BPs.
Given its hormonal activity, bisphenol S (BPS) as a substitute for bisphenol A (BPA) could actually increase the risk of endocrine disruption if its toxicokinetic (TK) properties, namely its oral ...availability and systemic persistency, were higher than those of BPA.
The TK behavior of BPA and BPS was investigated by administering the two compounds by intravenous and oral routes in piglet, a known valid model for investigating oral TK.
Experiments were conducted in piglets to evaluate the kinetics of BPA, BPS, and their glucuronoconjugated metabolites in plasma and urine after intravenous administration of BPA, BPS, and BPS glucuronide (BPSG) and gavage administration of BPA and BPS. A population semiphysiologically based TK model describing the disposition of BPA and BPS and their glucuronides was built from these data to estimate the key TK parameters that drive the internal exposure to active compounds.
The data indicated that almost all the BPS oral dose was absorbed and transported into the liver where only 41% of BPS was glucuronidated, leading to a systemic bioavailability of 57.4%. In contrast, only 77% of the oral dose of BPA was absorbed and underwent an extensive first-pass glucuronidation either in the gut (44%) or in the liver (53%), thus accounting for the low systemic bioavailability of BPA (0.50%). Due to the higher systemic availability of BPS, in comparison with BPA, and its lower plasma clearance (3.5 times lower), the oral BPS systemic exposure was on average about 250 times higher than for BPA for an equal oral molar dose of the two compounds.
Given the similar digestive tracts of pigs and humans, our results suggest that replacing BPA with BPS will likely lead to increased internal exposure to an endocrine-active compound that would be of concern for human health. https://doi.org/10.1289/EHP4599.
Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as BPAF, BPAP, BPB, BPF, BPP, BPS, and BPZ. However, these alternatives ...are under surveillance for potential endocrine disruption, particularly during the critical period of fetal development. Despite their structural analogies, these BPs differ greatly in their placental transport efficiency. For predicting the fetal exposure of this important class of emerging contaminants, quantitative structure-activity relationship (QSAR) studies were developed to model and predict the placental clearance indices (CI). The most usual input parameters were molecular descriptors obtained by modelling, but for bisphenols (BPs) with structural similarities or heteroatoms such as sulfur, these descriptors do not contrast greatly. This study evaluated and compared the capacity of QSAR models based either on molecular or chromatographic descriptors or a combination of both to predict the placental passage of BPs. These chromatographic descriptors include both the retention mechanism and the peak shape on columns that reflect specific molecular interactions between solute and stationary and mobile phases and are characteristic of the molecular structure of BPs. The chromatographic peak shape such as the asymmetry and tailing factors had more influence on predicting the placental passage than the usual retention parameters. Furthermore, the QSAR model, having the best prediction capacity, was obtained with the chromatographic descriptors alone and met the criteria of internal and cross validation. These QSAR models are crucial for predicting the fetal exposure of this important class of emerging contaminants.
In this study, the impact of infection stage on clinically and microbiologically efficacious doses and on antibiotic consumption was assessed during a naturally evolving infectious disease, using an ...original mouse model of pulmonary infection produced by air-borne contamination. When Pasteurella multocida was administered as pathogenic agent to immunocompetent mice, 60% of the animals exhibited clinical symptoms of pneumonia 2 to 4 days after bacterial contamination of the lungs. Two beta-lactam antibiotics were evaluated: amoxicillin and cefquinome, a fourth generation cephalosporin developed for food animals. First, a pharmacokinetic study was performed in infected mice to determine the exposure to amoxicillin or cefquinome required to treat clinically affected animals, based on the targeted values of PK/PD indices for beta-lactams. We then confirmed that these doses resulted in a 100% clinical cure rate in animals exhibiting clinical signs of infection and harboring a high pathogenic inoculum. More interestingly, we also showed that the same 100% clinical cure could be obtained in our model with 10-fold lower doses in animals at pre-patent stages of infection i.e. when harboring a low pathogenic inoculum. At the group level, antimicrobial drug consumption was reduced by treating animals at an early stage of the infection course with a pre-patent tailored dose. These results suggest that early treatment with a dose suitably adjusted to the stage of infection might help to reduce both overall antibiotic consumption and resistance selection pressure in the animals and in the environment.
Lipids are key molecules in various biological processes, thus their quantification is a crucial point in a lot of studies and should be taken into account in lipidomics development. This family is ...complex and presents a very large diversity of structures, so analyzing and quantifying all this diversity is a real challenge. In this review, the different techniques to analyze lipids will be presented: from nuclear magnetic resonance (NMR) to mass spectrometry (with and without chromatography) including universal detectors. First of all, the state of the art of quantification, with the definitions of terms and protocol standardization, will be presented with quantitative lipidomics in mind, and then technical considerations and limitations of analytical chemistry's tools, such as NMR, mass spectrometry and universal detectors, will be discussed, particularly in terms of absolute quantification.
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