scholarly journals Human metabolism and urinary excretion of seven neonicotinoids and neonicotinoid-like compounds after controlled oral dosages

2021 ◽  
Author(s):  
Sonja A. Wrobel ◽  
Daniel Bury ◽  
Heiko Hayen ◽  
Holger M. Koch ◽  
Thomas Brüning ◽  
...  
Keyword(s):  
Exposure Assessment ◽  
High Resolution Mass Spectrometry ◽  
Daily Intake ◽  
Human Biomonitoring ◽  
Human Metabolism ◽  
Post Dose ◽  
Important Group ◽  
Glycine Derivatives ◽  
Insight Into ◽  
Signal Intensities

AbstractFew human data on exposure and toxicity are available on neonicotinoids and neonicotinoid-like compounds (NNIs), an important group of insecticides worldwide. Specifically, exposure assessment of humans by biomonitoring remains a challenge due to the lack of appropriate biomarkers. We investigated the human metabolism and metabolite excretion in urine of acetamiprid (ACE), clothianidin (CLO), flupyradifurone (FLUP), imidacloprid (IMI), sulfoxaflor (SULF), thiacloprid (THIAC) and thiamethoxam (THIAM) after single oral dosages at the currently acceptable daily intake levels of the European Food Safety Authority. Consecutive post-dose urine samples were collected up to 48 h. Suspect screening of tentative metabolites was carried out by liquid chromatography–high-resolution mass spectrometry. Screening hits were identified based on their accurate mass, isotope signal masses and ratios, product ion spectra, and excretion kinetics. We found, with the exception of SULF, extensive metabolization of NNIs to specific metabolites which were excreted next to the parent compounds. Overall, 24 metabolites were detected with signal intensities indicative of high metabolic relevance. Phase-I metabolites were predominantly derived by mono-oxidation (such as hydroxy-FLUP, -IMI, and -THIAC) and by oxidative N-desalkylation (such as N-desdifluoroethyl-FLUP and N-desmethyl-ACE, -CLO and -THIAM). IMI-olefin, obtained by dehydration of hydroxylated IMI, was identified as a major metabolite of IMI. SULF was excreted unchanged in urine. Previously reported metabolites of NNIs such as 6-chloronicotinic acid or 2-chlorothiazole-4-carboxylic acid and their glycine derivatives were detected either at low signal intensities or not at all and seem less relevant for human biomonitoring. Our highly controlled approach provides specific insight into the human metabolism of NNIs and suggests suitable biomarkers for future exposure assessment at environmentally relevant exposures.

Exposure assessment of Spanish lactating mothers to acrylamide via human biomonitoring

2021 ◽  
pp. 111832
Author(s):  
Sandra F. Fernández ◽  
Olga Pardo ◽  
Clara Coscollà ◽  
Vicent Yusà
Keyword(s):  
Exposure Assessment ◽  
Human Biomonitoring ◽  
Lactating Mothers

scholarly journals Pharmacokinetics and Safety of Rifamycin SV after Single and Multiple Doses of MMX® Modified Release Tablets in Healthy Male and Female Volunteers

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 167
Author(s):  
Andrea Francesco Daniele Di Stefano ◽  
Milko Massimiliano Radicioni ◽  
Angelo Vaccani ◽  
Alessandro Mazzetti ◽  
Luigi Maria Longo ◽  
...  
Keyword(s):  
Dose Regimen ◽  
Multiple Dose ◽  
Daily Intake ◽  
Pharmacokinetic Profile ◽  
Primary Objective ◽  
Systemic Absorption ◽  
Modified Release ◽  
Post Dose ◽  
Rifamycin Sv ◽  
Study Results

The primary objective of this single- and multiple-dose pharmacokinetic study was the investigation of rifamycin SV’s pharmacokinetic profile in plasma and urine. All the 18 enrolled healthy men and post-menopausal women received modified release tablets containing 600 mg of the oral non-absorbable antibiotic, rifamycin SV, according to a multiple dose regimen: one tablet three times a day (daily intake: 1800 mg) for 14 consecutive days. Blood sampling and urine collection were performed up to 24 h post-dose after the first dose on Days 1 and 7. On average, on Day 1, Cmax,0–24 was 5.79 ± 4.24 ng/mL and was attained in a median time of 9 h. On Day 7, all the subjects had quantifiable levels of rifamycin SV in plasma at each sampling time. After a peak concentration attained 2 h post-dose (mean ± SD concentration: 10.94 ± 16.41 ng/mL), rifamycin SV decreased in plasma to levels similar to those of Day 1. The amounts of rifamycin SV excreted in urine paralleled the plasma concentration at the corresponding times. On Day 1, the total amount excreted in urine was 0.0013%, and was 0.0029% on Day 7. The study results confirmed those of the previous Phase I study: the systemic absorption of rifamycin SV was also proved negligible after 7 days of the 600 mg t.i.d. dose regimen of the newly formulated tablets, currently under development for the treatment of several small and large intestinal pathologies, including diarrhea-predominant irritable bowel syndrome, hepatic encephalopathy, and others. Registered at ClinicalTrials.gov with the identifier NCT02969252, last updated on 26JAN18.

scholarly journals Levels of Polychlorinated Dibenzo-p-Dioxins/Furans (PCDD/Fs) and Dioxin-Like Polychlorinated Biphenyls (DL-PCBs) in Human Breast Milk in Chile: A Pilot Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4825
Author(s):  
Claudia Foerster ◽  
Liliana Zúñiga-Venegas ◽  
Pedro Enríquez ◽  
Jacqueline Rojas ◽  
Claudia Zamora ◽  
...  
Keyword(s):  
High Resolution ◽  
Breast Milk ◽  
Polychlorinated Biphenyls ◽  
High Resolution Mass Spectrometry ◽  
Daily Intake ◽  
Human Breast Milk ◽  
International Studies ◽  
Cross Sectional ◽  
Pooled Samples ◽  
Chilean Women

Persistent organic pollutants (POPs) are organic compounds that resist biochemical degradation, moving long distances across the atmosphere before deposition occurs. Our goal was to provide up-to-date data on the levels of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in breast milk from Chilean women and to estimate the exposure of infants due to breast milk consumption. In Chile, we conducted a cross-sectional study based on methodologies proposed by the WHO, with a sample of 30 women recruited from three defined areas: 10 from the Arica Region (urban; Arica and Parinacota Region), 10 from Coltauco (rural; O’Higgins Region), and 10 from Molina (40% rural; Maule Region). High-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC/HRMS) was performed on pooled samples from each area. We calculated equivalent toxic concentrations (WHO-TEQ) based on the current WHO Toxic Equivalency Factors (TEF). The minimum and maximum values of ∑ PCDDs/Fs + DL-PCBs-TEQ were 4.317 pg TEQ/g fat in Coltauco and 6.31 pg TEQ/g fat in Arica. Molina had a total TEQ of 5.50 pg TEQ/g fat. The contribution of PCDD/Fs was approximately five-fold higher than that of DL-PCBs. The Estimated Daily Intake (EDI) of ∑ PCDDs/Fs + DL-PCBs based on the three pooled samples ranged between 6.71 and 26.28 pg TEQ/kg body weight (bw)/day, with a mean intake of 16.11 (±6.71) pg TEQ/kg bw/day in breastfed children from 0 to 24 months old. These levels were lower than those reported in international studies. Despite the fact that the observed levels were low compared to those in most industrialized countries, the detection of a variety of POPs in breast milk from Chilean women indicates the need for follow-up studies to determine whether such exposures during childhood could represent a health risk in adulthood.

scholarly journals An Insight into Saponins from Quinoa (Chenopodium quinoa Willd): A Review

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1059 ◽  
Author(s):  
Khadija El Hazzam ◽  
Jawhar Hafsa ◽  
Mansour Sobeh ◽  
Manal Mhada ◽  
Moha Taourirte ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Bitter Taste ◽  
Biological Activities ◽  
Chenopodium Quinoa ◽  
Toxic Effects ◽  
Mechanical Abrasion ◽  
Important Group ◽  
The Past ◽  
Wide Range ◽  
Insight Into

Saponins are an important group found in Chenopodium quinoa. They represent an obstacle for the use of quinoa as food for humans and animal feeds because of their bitter taste and toxic effects, which necessitates their elimination. Several saponins elimination methods have been examined to leach the saponins from the quinoa seeds; the wet technique remains the most used at both laboratory and industrial levels. Dry methods (heat treatment, extrusion, roasting, or mechanical abrasion) and genetic methods have also been evaluated. The extraction of quinoa saponins can be carried out by several methods; conventional technologies such as maceration and Soxhlet are the most utilized methods. However, recent research has focused on technologies to improve the efficiency of extraction. At least 40 saponin structures from quinoa have been isolated in the past 30 years, the derived molecular entities essentially being phytolaccagenic, oleanolic and serjanic acids, hederagenin, 3β,23,30 trihydroxy olean-12-en-28-oic acid, 3β-hydroxy-27-oxo-olean-12en-28-oic acid, and 3β,23,30 trihydroxy olean-12-en-28-oic acid. These metabolites exhibit a wide range of biological activities, such as molluscicidal, antifungal, anti-inflammatory, hemolytic, and cytotoxic properties.

scholarly journals Analysis of Crowdsourced Metformin Tablets from Individuals Reveals Widespread Contamination with N-Nitrosodimethylamine (NDMA) in the United States

2020 ◽  
Author(s):  
Qian Wu ◽  
Evgenia Kvitko ◽  
Amber Jessop ◽  
Shannon Williams ◽  
Ryan C. Costantino ◽  
...  
Keyword(s):  
United States ◽  
High Resolution Mass Spectrometry ◽  
Daily Intake ◽  
The United States ◽  
Product Recalls ◽  
Acceptable Daily Intake ◽  
Drug Products ◽  
Post Market ◽  
United States Food ◽  
States Food

AbstractRecent reports of metformin drug products contaminated with unacceptable levels of the probable human carcinogen N-Nitrosodimethylamine (NDMA) prompted a national sampling of post-market metformin drug products. To most broadly sample the market and minimize supply chain bias, metformin medication samples were crowdsourced directly from individuals across many states in the United States. 128 samples were received, and liquid chromatography-high resolution mass spectrometry tests for a panel of nitrosamines revealed significant levels of NDMA that trend with labeling company. 42% of all medication samples contained detectable levels of NDMA and, when scaled to maximum daily tablet dose, 36% of all medication samples contained NDMA levels exceeding the FDA daily acceptable intake limit. The highest NDMA detection from the tested samples was 1565 ng per tablet, which, when commonly taken four times a day, is 65 times the United States Food and Drug Administration (FDA) acceptable daily intake limit. Results underscore the need for immediate product recalls of tainted medications and an overall investigation of metformin manufacturing practices.

scholarly journals Human Biomonitoring of T-2 Toxin, T-2 Toxin-3-Glucoside and Their Metabolites in Urine through High-Resolution Mass Spectrometry

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 869
Author(s):  
Alfonso Narváez ◽  
Luana Izzo ◽  
Noelia Pallarés ◽  
Luigi Castaldo ◽  
Yelko Rodríguez-Carrasco ◽  
...  
Keyword(s):  
High Performance ◽  
High Resolution Mass Spectrometry ◽  
Human Biomonitoring ◽  
Italian Population ◽  
South Italy ◽  
Almost All ◽  
Low Prevalence ◽  
Frequent Exposure ◽  
Mean Concentration

The metabolic profile of T-2 toxin (T-2) and its modified form T-2-3-glucoside (T-2-3-Glc) remain unexplored in human samples. Therefore, the present study aimed to investigate the presence of T-2, T-2-3-Glc and their respective major metabolites in human urine samples (n = 300) collected in South Italy through an ultra-high performance liquid chromatography (UHPLC) coupled to Q-Orbitrap-HRMS methodology. T-2 was quantified in 21% of samples at a mean concentration of 1.34 ng/mg Crea (range: 0.22–6.54 ng/mg Crea). Almost all the major T-2 metabolites previously characterized in vitro were tentatively found, remarking the occurrence of 3′-OH-T-2 (99.7%), T-2 triol (56%) and HT-2 (30%). Regarding T-2-3-Glc, a low prevalence of the parent mycotoxin (1%) and its metabolites were observed, with HT-2-3-Glc (17%) being the most prevalent compound, although hydroxylated products were also detected. Attending to the large number of testing positive for T-2 or its metabolites, this study found a frequent exposure in Italian population.

scholarly journals Acetaminophen Metabolism Revisited Using Non-Targeted Analyses: Implications for Human Biomonitoring

2020 ◽  
Author(s):  
Arthur David ◽  
Jade Chaker ◽  
Thibaut Léger ◽  
Raghad Al-Salhi ◽  
Marlene Danner Dalgaard ◽  
...  
Keyword(s):  
Phase Ii ◽  
Enterohepatic Circulation ◽  
High Resolution Mass Spectrometry ◽  
Parent Compound ◽  
Human Biomonitoring ◽  
Relevant Information ◽  
Point Of View ◽  
Internal Exposure ◽  
Current Standard ◽  
Excretion Rates

The analgesic paracetamol (N-acetyl-4-aminophenol, APAP) is commonly used to relieve pain, fever and malaise. While sales have increased worldwide, a growing body of experimental and epidemiological evidence has suggested APAP as a possible risk factor for various health disorders. To perform internal exposure-based risk assessment, the use of accurate and optimized biomonitoring methods is criticical. However, retrospectively assessing pharmaceutical use of APAP in humans is challenging because of its short half-life. The objective of this study was to address the key biomonitoring issues with APAP using current standard analytical methods based on urinary analyses of free APAP and its phase II conjugates. Using non-targeted analyses based on high-resolution mass spectrometry, we identified in a controlled longitudinal exposure study with male volunteers, unrecognized APAP metabolites with delayed formation and excretion rates. We postulate that these metabolites are formed via the thiomethyl shunt after the enterohepatic circulation as already observed in rodents. Importantly, the conjugated thiomethyl metabolites were (i) of comparable diagnostic sensitivity as the free APAP and its phase II conjugates detected by current methods; (ii) had delayed peak levels in blood and urine compared to other APAP metabolites and therefore potentially extend the window of exposure assessment; and (iii) provide relevant information regarding metabolic pathways of interest from a toxicological point of view. Including these metabolites in future APAP biomonitoring methods provide an option to decrease potential underestimation of APAP use and challenges the notion that the standard methods in biomonitoring based exclusively on the parent compound and its phase II metabolites are adequate for human biomonitoring of non-persistant chemical such as APAP. <br>

Exposure Assessment of Artificial Sweeteners among Type 2 Diabetic, Overweight and Obese Individuals

2016 ◽  
Vol 53 (3) ◽  
pp. 268
Author(s):  
A. Bhagyasri ◽  
R. Naveen Kumar ◽  
N. Balakrishna ◽  
V. Sudershan Rao
Keyword(s):  
Exposure Assessment ◽  
Daily Intake ◽  
Cross Sectional Study ◽  
Consumption Pattern ◽  
Cross Sectional ◽  
Significant Difference ◽  
Overweight Group ◽  
The Mean ◽  
Type 2 Diabetic

In recent years consumption of artificially sweetened foods and beverages became popular in India, with the regulatory formulations to use them in selected foods; their inclusion especially in sweets, biscuits and beverages has increased. There are many concerns rising regarding their safety and is becoming an area of controversy. So an exposure assessment has been carried out to evaluate intake levels among type II diabetic, overweight and obese individuals. A cross-sectional study design was applied and a food frequency questionnaire was used to obtain the information on consumption pattern. Range, standard deviation and mean daily intake levels were calculated and the values were compared with an appropriate Acceptable Daily Intake (ADI). Results indicated that, the mean daily intake levels of aspartame (0.85±0.75) were found to be high among type 2 diabetic individuals whereas sucralose (0.41±0.41) and acesulfame-k (0.07±0.02) were high among overweight group. There was a significant difference (p&lt;0.0001) observed in intake levels among both groups and all the sweeteners were found to be well within the ADI levels.

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