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1.
Environ Health Prev Med ; 25(1): 83, 2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33308136

RESUMO

BACKGROUND: Glyphosate and its salt formulations are nonselective herbicides that have been extensively used worldwide, both for residential and agricultural purposes. The possible carcinogenicity and teratogenicity of glyphosate remain to be elucidated. We developed a sensitive and high-throughput analytical method for urinary glyphosate using liquid chromatography-tandem mass spectrometry with the aim of contributing to glyphosate exposure assessment in epidemiological studies. METHODS: After urine dilution (creatinine matching dilution to 0.05 g creatinine/L), glyphosate was extracted using two types of solid phase extraction columns (SCX and NH2) with automated sample preparation instruments. The eluate was dried and dissolved in the mobile phase, followed by liquid chromatography-tandem mass spectrometry analysis. The optimized method was applied to urine samples obtained from 54 Japanese adults and children. RESULTS: The results from the validation study demonstrated good recoveries (91.0-99.6%), within- and between-run precisions (< 15%), low detection limits (0.1 µg/L), and lower limit of quantification (0.3 µg/L). The detection frequency and median concentration of the urinary glyphosate in Japanese subjects were 59% and 0.25 µg/L (0.34 µg/g creatinine). CONCLUSIONS: Our reliable determination method was successful in measuring urinary glyphosate concentration. Moreover, this is the first biomonitoring report of urinary glyphosate levels in the Japanese general population.


Assuntos
Cromatografia Líquida/métodos , Glicina/análogos & derivados , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Adulto , Idoso , Feminino , Glicina/urina , Humanos , Masculino , Pessoa de Meia-Idade
2.
Nutr Metab Cardiovasc Dis ; 30(11): 2051-2062, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-32669241

RESUMO

BACKGROUND AND AIMS: Increased left ventricular mass is an independent predictor for cardiovascular events, and shown to be higher in black than white populations. To gain a better understanding of early factors contributing to increased left ventricular mass in young black adults, we investigated metabolomic profiles, identified and compared metabolites that associated with left ventricular mass index in healthy black and white adults. METHODS AND RESULTS: We included normotensive black and white participants from the African-PREDICT study, with data on urinary metabolomics and echocardiography. Urinary metabolites were measured using three different analytical platforms. Univariate statistical analyses, including independent t-test (adjusted for multiple comparisons), effect size (d ≥ 0.3) and single regression analyses were used to identify metabolites. When comparing the black and white groups, the black group had higher central systolic blood pressure (p > 0.005), whereas left ventricular mass index was similar between the groups (p = 0.97). Three from a total of 192 metabolites were identified to be more abundant (p < 0.046) and inversely associated with left ventricular mass index in the black group only: hydroxyproline (ß = -0.22; p = 0.045), glycine (ß = -0.20; p = 0.049) and trimethylamine (ß = -0.21; p = 0.037). CONCLUSION: Higher urinary levels of hydroxyproline, glycine and trimethylamine were inversely associated with left ventricular mass index in the black adults only. Hydroxyproline and glycine are important in maintaining healthy collagen turnover and stability in the heart. Our results may reflect an increase in collagen biosynthesis and collagen deposition in the left ventricle due to higher central systolic blood pressure in the black population.


Assuntos
Grupo com Ancestrais do Continente Africano , Grupo com Ancestrais do Continente Europeu , Glicina/urina , Hidroxiprolina/urina , Metabolômica , Metilaminas/urina , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Fatores Etários , Biomarcadores/urina , Ecocardiografia , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores Raciais , África do Sul/epidemiologia , Urinálise , Adulto Jovem
3.
Artigo em Inglês | MEDLINE | ID: mdl-32344631

RESUMO

Background: There are few published studies concerning occupational exposure to glyphosate (GLY), and these are limited to spraying, horticulture and other agricultural aspects. Therefore, the concentration of glyphosate and its metabolite aminomethylphosphonic acid (AMPA), in the urine of workers exposed to glyphosate during glyphosate production was determined, and the relationship between internal (urinary glyphosate and AMPA concentration) and external exposure dose (time weighted average (TWA) value of glyphosate in the air of workplace) was analyzed. Methods: To avoid the influence of preparations, we selected people who were only involved in GLY production (without exposure to its preparations) as our research subjects. We collected 134 urine samples of workers exposed to GLY (prototype, not preparation). The urinary concentrations of GLY and AMPA (internal exposure dose) were detected by gas chromatography-mass spectrometry. The subjects' exposure to the amount of GLY in the air (external dose) was determined using ion chromatography. Conventional statistical methods, including quartiles, t-tests and regression analysis, were applied for data processing. Results: An on-site investigation revealed that the workers involved in centrifugation, crystallization, drying, and packaging and feeding were exposed to GLY. The TWA value of GLY in the workshop air was <0.02 mg/m3-34.58 mg/m3. The detection rates of GLY and AMPA in the urine samples were 86.6% and 81.3%, respectively. The concentration of urinary GLY was <0.020-17.202 mg/L (median, 0.292 mg/L). The urinary AMPA concentration was <0.010 mg/L-2.730 mg/L (median, 0.068 mg/L). The geometric means were 0.262 mg/L and 0.072 mg/L for GLY and AMPA, respectively. There was a correlation between the urinary concentration of GLY and AMPA and the TWA value of exposed workers (correlation coefficient [r] = 0.914 and 0.683, respectively; p < 0.01). Furthermore, there was a correlation between the urinary concentration of GLY and AMPA in the exposure group (r = 0.736, p < 0.01). Conclusions: The urinary concentration of GLY and AMPA of workers was correlated with the TWA value of workers' exposure, which could reflect the actual exposure of the workers.


Assuntos
Agricultura , Glicina/análogos & derivados , Herbicidas , Exposição Ocupacional , Adulto , China , Feminino , Glicina/urina , Herbicidas/urina , Humanos , Masculino , Pessoa de Meia-Idade , Local de Trabalho
4.
Ecotoxicol Environ Saf ; 195: 110467, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32182532

RESUMO

Heavy metals and pesticides can be easily enriched in food chains and accumulated in organisms, thus pose significant threat to human health. However, their combined effects for long-term exposure at low dose has not been thoroughly investigated; especially there was no biofluid biomarker available to noninvasively diagnose the toxicosis of the combined exposure of the two chemicals at their low levels. In this study, we investigated the change of urine metabolites of rats with 90-day exposure to heavy metal cadmium (Cd) and/or organophosphorus pesticide chlorpyrifos (CPF) using gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach. Our results showed that the interaction of Cd and CPF mainly displayed an antagonistic effect. We identified the panels of metabolite biomarkers in urine: benzoic acid and mannose were unique biomarkers for Cd exposure; creatinine and N-phenylacetyl glycine were unique biomarkers for CPF exposure; anthranilic acid, ribitol, and glucose were unique biomarkers for Cd plus CPF exposure. Our results suggest that 90-day exposure to Cd and/or CPF could cause a disturbance in energy and amino acid metabolism. And urine metabolomics analysis can help understand the toxicity of low dose exposure to mixed environmental chemicals.


Assuntos
Cádmio/toxicidade , Clorpirifos/toxicidade , Inseticidas/toxicidade , Animais , Ácido Benzoico/urina , Biomarcadores/urina , Creatinina/urina , Interações Medicamentosas , Cromatografia Gasosa-Espectrometria de Massas , Glicina/análogos & derivados , Glicina/urina , Masculino , Manose/urina , Metabolômica , Ratos
5.
Environ Pollut ; 256: 113334, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31677874

RESUMO

The goal of this study was to assess biomarkers of exposure to glyphosate and assess potential associations with renal function in children. Glyphosate is used ubiquitously in agriculture worldwide. While previous studies have indicated that glyphosate may have nephrotoxic effects, few have examined potential effects on kidney function in children. We leveraged three cohorts across different phases of child development and measured urinary levels of glyphosate. We evaluated associations of glyphosate with three biomarkers of kidney injury: albuminuria (ACR), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury marker 1 (KIM-1). Multivariable regression analyses examined associations of glyphosate with kidney injury biomarkers controlling for covariates. We identified glyphosate in 11.1% of the total participants. The herbicide was detected more frequently in the neonate population (30%). Multivariable regression models failed to identify significant associations of log-transformed glyphosate with any of the kidney injury biomarkers, controlling for covariates age, sex, and maternal education. While we confirm detectability of glyphosate in children's urine at various ages and stages of life, there is no evidence in this study for renal injury in children exposed to low levels of glyphosate. Further studies of larger sample size are indicated to better understand putative deleterious effects of the herbicide after different levels of exposure.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/urina , Glicina/análogos & derivados , Nefropatias/urina , Biomarcadores/urina , Criança , Pré-Escolar , Estudos de Coortes , Creatinina/urina , Estudos Transversais , Feminino , Glicina/urina , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Lactente , Recém-Nascido , Nefropatias/epidemiologia , Lipocalina-2/urina , Estudos Longitudinais , Masculino , Prevalência , Albumina Sérica Humana/urina
7.
Am J Emerg Med ; 37(8): 1600.e5-1600.e6, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31053371

RESUMO

INTRODUCTION: This report describes changes in blood and urine concentrations of glyphosate potassium over time and their correlations with clinical symptoms in a patient with acute glyphosate potassium poisoning. CASE REPORT: A 67-year-old man visited the emergency center after ingesting 250 mL of a glyphosate potassium-based herbicide 5 h before. He was alert but presented with nausea, vomiting, and bradyarrhythmia with atrial fibrillation (tall T waves). Laboratory findings revealed a serum potassium level of 6.52 mEq/L. After treatment with an injection of calcium gluconate, insulin with glucose, bicarbonate, and an enema with polystyrene sulfonate, the patient's serum potassium level normalized and the bradyarrhythmia converted to a normal sinus rhythm. During admission, the blood and urine concentration of glyphosate and urine aminomethylphosphonic acid (AMPA, a glyphosate metabolite) was measured at regular time intervals. The patient's glyphosate blood concentration on admission was 11.48 mg/L, and it had decreased rapidly by 16 h and maintained about 1mgl/L by 70 h after admission. Urine glyphosate and AMPA levels had also decreased rapidly by 6 h after admission. DISCUSSION: Glyphosate potassium poisoning causes hyperkalemia. Blood concentrations of glyphosate were decreased rapidly by 16 h after admission, and urine concentrations were also decreased by 6 h after admission.


Assuntos
Glicina/análogos & derivados , Herbicidas/sangue , Herbicidas/envenenamento , Hiperpotassemia/induzido quimicamente , Idoso , Arritmias Cardíacas/induzido quimicamente , Glicina/sangue , Glicina/envenenamento , Glicina/urina , Herbicidas/urina , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/tratamento farmacológico , Masculino , Náusea/induzido quimicamente , Potássio/sangue , Tentativa de Suicídio , Resultado do Tratamento , Vômito/induzido quimicamente
8.
Sci Total Environ ; 659: 790-795, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31096409

RESUMO

Glyphosate is one of the most widely used herbicides in the United States, which has led to its ubiquitous occurrence in food and water and regular detection in human urine at concentrations of 1-10 µg/L. Data pertaining to health risks arising from the ingestion of glyphosate are limited and are the subject of much debate, which demands the need for more exposure information for this herbicide. Very little is known about glyphosate exposure in pets. In this study, we determined concentrations of glyphosate (Glyp) and its derivatives, methyl glyphosate (Me-Glyp) and aminomethylphosphonic acid (AMPA), in urine collected from 30 dogs and 30 cats from New York State, USA. Glyp was the most predominant compound found in pet urine followed by AMPA and Me-Glyp. The mean urinary concentration of ∑Glyp (sum of Glyp + Me-Glyp + AMPA) in cats (mean: 33.8 ±â€¯46.7 ng/mL) was 2-fold higher than that in dogs (mean: 16.8 ±â€¯24.4 ng/mL). Cumulative daily intakes (CDI) of Glyp in dogs and cats estimated from the urinary concentrations were, on average, 0.57 and 1.37 µg/kg bw/d, respectively. The exposure doses were two to four orders of magnitude below the current acceptable daily intake (ADI) suggested by several international health organizations for humans.


Assuntos
Poluentes Ambientais/urina , Glicina/análogos & derivados , Herbicidas/urina , Fatores Etários , Animais , Gatos , Cães , Feminino , Glicina/urina , Masculino , New York , Fatores Sexuais
9.
Environ Health ; 18(1): 42, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064415

RESUMO

In response to the recent review by Gillezeau et al., The evidence of human exposure to glyphosate: A review, Environmental Health 1/19/19, here we report additional glyphosate biomonitoring data from a repository of urine samples collected from United States farmers in 1997-98. To determine if glyphosate exposure could be identified historically, we examined urine samples from a biorepository of specimens collected from US dairy farmers between 1997 and 98. We compared samples from farmers who self-reported glyphosate application in the 8 h prior to sample collection to samples from farm applicators who did not report using glyphosate. Of 18 applicator samples tested, 39% showed detectable levels of glyphosate (mean concentration 4.04 µg/kg; range:1.3-12) compared to 0% detections among 17 non glyphosate applicator samples (p-value < 0.01). One of the applicator samples that tested positive for glyphosate also tested positive for AMPA. Concentrations of glyphosate were consistent with levels reported in the prior occupational biomonitoring studies reviewed by Gillezeau et al.Accurately detecting both glyphosate and AMPA in this small sample of Wisconsin farmers demonstrates a) glyphosate exposures among farmers were occurring 20 years ago, which was prior to the widespread planting of genetically engineered glyphosate tolerant crops first approved in 1996; and b) liquid chromatography tandem mass spectrometry (LC-MS/MS) can be used for sensitive characterization in cryopreserved urine samples. These data offer an important historical benchmark to which urinary levels from current and future biomonitoring studies can be compared.


Assuntos
Indústria de Laticínios , Glicina/análogos & derivados , Herbicidas/urina , Exposição Ocupacional/análise , Estudos de Coortes , Monitoramento Ambiental , Glicina/urina , Humanos , Wisconsin
10.
Clin Chim Acta ; 493: 148-155, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30858092

RESUMO

BACKGROUND: Cerebral Creatine deficiency syndromes (CCDS) include three hereditary diseases affecting the metabolism of creatine (Cr): arginine glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency and disorders of creatine transporter. These pathologies cause a brain creatine deficiency responsible of non-specific neurological impairments with mental retardation. LC-MS/MS measurements of guanidinoacetic acid (GAA) and creatine in urine and plasma are an important screening test to identify the deficit. Analysis of this polar and basic molecules not hold on standard column requires a derivatization step to butyl-esters. To overcome this long and fastidious derivatization, an ion pairing (IP) method was chosen in this study. METHOD: IP method was validated using Comité francais d'accréditation (COFRAC) recommendations. Then, urine GAA and creatine of 15 patients with a CDS deficiency suspected were tested y LC-MS/MS using IP technique, and performances were assessed with reference laboratory method (butylation method). Moreover, references values were suggested y the study of 100 urines samples of healthy patients. RESULTS: The method developed provided a good accuracy and precision with intra and inter-day coefficients of variation (CVs) <15%. The curve was linear for the biological and pathological concentrations. The comparison with the reference method did not reveal any significant difference for analytical performances but showed a simplification of the preparation of samples. CONCLUSION: The use of IP technique that we have developed demonstrated a good correlation with the butylation method. Moreover, this new method not only allows a simplification of the technique, but also decreases in run time.


Assuntos
Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Creatina/urina , Glicina/análogos & derivados , Guanidinoacetato N-Metiltransferase/deficiência , Transtornos do Desenvolvimento da Linguagem/urina , Transtornos dos Movimentos/congênito , Cromatografia Líquida de Alta Pressão , Glicina/urina , Guanidinoacetato N-Metiltransferase/urina , Humanos , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/urina , Espectrometria de Massas em Tandem
11.
Cancer Chemother Pharmacol ; 83(5): 837-848, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30758648

RESUMO

PURPOSE: Pharmacokinetics, absorption, metabolism, and excretion of ivosidenib, a mutant isocitrate dehydrogenase-1 inhibitor, were determined in healthy male subjects. METHODS: In this open-label phase I study, a single dose of [14C]ivosidenib (500 mg, 200 µCi/subject) was orally administered to eight subjects (CYP2D6 extensive, intermediate, or poor metabolizers) under fasted conditions. Blood, plasma, urine, and fecal samples were assayed for radioactivity and profiled for metabolites. Ivosidenib plasma concentrations were determined using LC-MS/MS. Metabolites were separated using reverse-phase HPLC and analyzed using high-resolution LC-MS and LC-MS/MS. RESULTS: Ivosidenib was readily absorbed and slowly eliminated from plasma. Median Tmax of both unchanged ivosidenib and radioactivity in plasma was 4 h. Plasma t½ values for total radioactivity and ivosidenib were 71.7 and 53.4 h, respectively. The mean AUC0-72 blood-to-plasma total radioactivity concentration ratio was 0.565, indicating minimal partitioning to red blood cells. CYP2D6 genotype had no effect on ivosidenib exposure. The mean recovery of radioactivity in excreta was 94.3% over 360 h post-dose; the majority was excreted in feces (77.4 ± 9.62%) with a low percentage recovered in urine (16.9 ± 5.62%), suggesting fecal excretion is the primary route of elimination. Unchanged [14C]ivosidenib accounted for 67.4% of the administered radioactivity in feces. Only [14C]ivosidenib was detected in plasma, representing 92.4% of the total plasma radioactivity. Thirteen metabolites were structurally identified in excreta. CONCLUSION: Ivosidenib was well-absorbed, slowly metabolized to multiple oxidative metabolites, and eliminated by fecal excretion, with no CYP2D6 effect observed. Unchanged ivosidenib was the only circulating species in plasma.


Assuntos
Glicina/análogos & derivados , Isocitrato Desidrogenase/antagonistas & inibidores , Piridinas/farmacocinética , Administração Oral , Adulto , Área Sob a Curva , Radioisótopos de Carbono , Cromatografia Líquida , Fezes/química , Glicina/administração & dosagem , Glicina/sangue , Glicina/farmacocinética , Glicina/urina , Voluntários Saudáveis , Humanos , Limite de Detecção , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Piridinas/sangue , Piridinas/urina , Espectrometria de Massas em Tandem , Distribuição Tecidual
12.
Artigo em Inglês | MEDLINE | ID: mdl-30781414

RESUMO

The use of pesticides in agricultural activities has increased significantly during the last decades. Several studies have reported the health damage that results from exposure to pesticides. In Mexico, hundreds of communities depend economically on agricultural activities. The participation of minors in this type of activity and their exposure to pesticides represents a potential public health problem. A cross-sectional study was conducted, in which urine samples (first-morning urine) were taken from children under 15 years of age in both communities. A total of 281 urine samples obtained in both communities were processed for the determination of pesticides with high-performance liquid chromatography together with tandem mass spectrometry. In 100% of the samples, at least two pesticides of the 17 reported in the total samples were detected. The presence of malathion, metoxuron, and glyphosate was remarkable in more than 70% of the cases. Substantial differences were detected regarding the other compounds. It is necessary to carry out long-term studies to determine the damage to health resulting from this constant exposure and to inform the health authorities about the problem in order to implement preventive measures.


Assuntos
Praguicidas/urina , Adolescente , Agricultura , Criança , Pré-Escolar , Monitoramento Ambiental , Feminino , Glicina/análogos & derivados , Glicina/urina , Humanos , Malation/urina , Masculino , Compostos de Metilureia/urina , México , População Rural
13.
PLoS One ; 14(2): e0211698, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30721263

RESUMO

Atypical myopathy (AM) in horses is caused by ingestion of seeds of the Acer species (Sapindaceae family). Methylenecyclopropylacetyl-CoA (MCPA-CoA), derived from hypoglycin A (HGA), is currently the only active toxin in Acer pseudoplatanus or Acer negundo seeds related to AM outbreaks. However, seeds or arils of various Sapindaceae (e.g., ackee, lychee, mamoncillo, longan fruit) also contain methylenecyclopropylglycine (MCPG), which is a structural analogue of HGA that can cause hypoglycaemic encephalopathy in humans. The active poison formed from MCPG is methylenecyclopropylformyl-CoA (MCPF-CoA). MCPF-CoA and MCPA-CoA strongly inhibit enzymes that participate in ß-oxidation and energy production from fat. The aim of our study was to investigate if MCPG is involved in Acer seed poisoning in horses. MCPG, as well as glycine and carnitine conjugates (MCPF-glycine, MCPF-carnitine), were quantified using high-performance liquid chromatography-tandem mass spectrometry of serum and urine from horses that had ingested Acer pseudoplatanus seeds and developed typical AM symptoms. The results were compared to those of healthy control horses. For comparison, HGA and its glycine and carnitine derivatives were also measured. Additionally, to assess the degree of enzyme inhibition of ß-oxidation, several acyl glycines and acyl carnitines were included in the analysis. In addition to HGA and the specific toxic metabolites (MCPA-carnitine and MCPA-glycine), MCPG, MCPF-glycine and MCPF-carnitine were detected in the serum and urine of affected horses. Strong inhibition of ß-oxidation was demonstrated by elevated concentrations of all acyl glycines and carnitines, but the highest correlations were observed between MCPF-carnitine and isobutyryl-carnitine (r = 0.93) as well as between MCPA- (and MCPF-) glycine and valeryl-glycine with r = 0.96 (and r = 0.87). As shown here, for biochemical analysis of atypical myopathy of horses, it is necessary to take MCPG and the corresponding metabolites into consideration.


Assuntos
Acer/efeitos adversos , Ciclopropanos/metabolismo , Glicina/análogos & derivados , Doenças dos Cavalos/metabolismo , Doenças Musculares/veterinária , Intoxicação por Plantas/veterinária , Animais , Cromatografia Líquida de Alta Pressão , Ciclopropanos/sangue , Ciclopropanos/urina , Feminino , Glicina/sangue , Glicina/metabolismo , Glicina/urina , Doenças dos Cavalos/sangue , Doenças dos Cavalos/etiologia , Doenças dos Cavalos/urina , Cavalos/sangue , Cavalos/urina , Masculino , Redes e Vias Metabólicas , Doenças Musculares/etiologia , Doenças Musculares/metabolismo , Intoxicação por Plantas/etiologia , Intoxicação por Plantas/metabolismo , Sementes/efeitos adversos , Espectrometria de Massas em Tandem
14.
Environ Health ; 18(1): 2, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30612564

RESUMO

BACKGROUND: Despite the growing and widespread use of glyphosate, a broad-spectrum herbicide and desiccant, very few studies have evaluated the extent and amount of human exposure. OBJECTIVE: We review documented levels of human exposure among workers in occupational settings and the general population. METHODS: We conducted a review of scientific publications on glyphosate levels in humans; 19 studies were identified, of which five investigated occupational exposure to glyphosate, 11 documented the exposure in general populations, and three reported on both. RESULTS: Eight studies reported urinary levels in 423 occupationally and para-occupationally exposed subjects; 14 studies reported glyphosate levels in various biofluids on 3298 subjects from the general population. Average urinary levels in occupationally exposed subjects varied from 0.26 to 73.5 µg/L; environmental exposure urinary levels ranged from 0.16 to 7.6 µg/L. Only two studies measured temporal trends in exposure, both of which show increasing proportions of individuals with detectable levels of glyphosate in their urine over time. CONCLUSIONS: The current review highlights the paucity of data on glyphosate levels among individuals exposed occupationally, para-occupationally, or environmentally to the herbicide. As such, it is challenging to fully understand the extent of exposure overall and in vulnerable populations such as children. We recommend further work to evaluate exposure across populations and geographic regions, apportion the exposure sources (e.g., occupational, household use, food residues), and understand temporal trends.


Assuntos
Exposição Ambiental/análise , Glicina/análogos & derivados , Herbicidas/urina , Glicina/urina , Humanos
15.
Drug Test Anal ; 11(5): 638-648, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30408836

RESUMO

Reliable detection of urine adulteration attempts to circumvent positive drug testing represents a critical step for laboratories in abstinence control settings. An ideal workflow for high-throughput testing would involve simultaneous detection of adulteration attempts in the same run with drug detection. Monitoring of degraded or oxidized endogenous urinary compounds as indirect markers has been previously evaluated for that purpose exemplified for the adulterant potassium nitrite (KNO2 ). Fifteen, previously identified endogenous markers should now be evaluated for their general applicability to detect adulteration attempts for the adulterants hypochlorite-based bleach (NaOCl), peroxidase and peroxide (H2 O2 ), pyridinium chlorochromate (PCC), and iodine (I2 ). Initial experiments revealed similar results for the tested adulterants regarding degradation of indolylacryloylglycine (IAG), uric acid (UA), or UA derivatives. 5-Hydroxyisourate (HIU), the oxidation product of UA, was however only formed by KNO2 , PCC, and H2 O2 . Amino acids showed larger adulterant-dependent differences. All reactions were shown to be influenced by the adulterant concentration and the urinary pH with large variances depending on compound and adulterant. Except for HIU/PCC, all markers were stable within +/- 30% variation for all adulterants at -20°C. Receiver operating characteristics indicated best sensitivity and specificity over all adulterants for IAG (specificity 0.9, sensitivity 1.0) and UA (specificity 1.0, sensitivity 0.9). HIU gave best results for KNO2 , PCC, and H2 O2 and N-acetylneuraminic acid for PCC and H2 O2 , respectively. When integrating a limited number of targets into existing screening methods, monitoring of UA, IAG, N-acetylneuraminic acid, and HIU is recommended.


Assuntos
Biomarcadores/urina , Espectrometria de Massas/métodos , Nitritos/química , Detecção do Abuso de Substâncias/métodos , Urinálise/métodos , Cromatografia Líquida de Alta Pressão/métodos , Glicina/análogos & derivados , Glicina/urina , Humanos , Concentração de Íons de Hidrogênio , Ácido N-Acetilneuramínico/urina , Ácido Úrico/análogos & derivados , Ácido Úrico/urina , Coleta de Urina/métodos
16.
J Chromatogr A ; 1587: 73-78, 2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30471790

RESUMO

Recently, the phenomenon of acute poisoning events caused by glyphosate (GLY) had frequently occurred all over the world. The present work reported a simple liquid chromatography-high resolution mass spectrometry (LC-HRMS) method for direct determination of GLY and its metabolite aminomethylphosphonic acid (AMPA) in human urine by combining cold-induced phase separation (CIPS) with hydrophilic pipette tip solid-phase extraction (PTSPE). First, a urine sample was mixed with acetonitrile at a 80% concentration to precipitate proteins. After centrifugation, the mixture was performed a CIPS at -20 °C to enrich GLY and AMPA (six-fold) in the lower water phase which was further performed PTSPE procedure. PTSPE as a miniaturized procedure of SPE, combined with a manual accu-jet® Pro Pipette Controller, was used to extract GLY and AMPA, in which a new type of hydrophilic adsorbent (HILIC powder) based on amide-modified silica was selected as the adsorption of GLY and AMPA. The key factors including the type and the amount of adsorbent, the loading extraction solution, the type and volume of eluent, and the number of aspirating/dispensing cycles were investigated in detail. Meanwhile, the selectivity and sensitivity of GLY and AMPA analysis were improved by the use of LC-HRMS based on targeted single ion monitoring (tSIM) mode without tedious derivatization. This method made a full use of the advantages of these techniques by combining efficient enrichment, effective extraction and selective separation in a simple way. Finally, a comprehensive validation of the method was rigorously executed and the results indicated that the validated method afforded desired linearity, precision, accuracy, and sensitivity.


Assuntos
Cromatografia Líquida , Glicina/análogos & derivados , Compostos Organofosforados , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Urinálise/métodos , Temperatura Baixa , Glicina/análise , Glicina/urina , Humanos , Interações Hidrofóbicas e Hidrofílicas , Isoxazóis , Compostos Organofosforados/análise , Compostos Organofosforados/urina , Tetrazóis
17.
J Pharm Biomed Anal ; 162: 82-90, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30227356

RESUMO

Systemic Sclerosis (SSc) is a chronic autoimmune disease whose origin and pathogenesis are not yet well known. Recent studies are allowing a better definition of the disease. However, few studies have been performed based on metabolomics. In this way, this study aims to find altered metabolites in SSc patients in order to improve their diagnosis, prognosis and treatment. For that, 59 SSc patients and 28 healthy volunteers participated in this study. Urine and plasma samples were analysed by a fingerprinting metabolomic approach based on HPLC-ESI-QTOF-MS. We observed larger differences in urine than plasma metabolites. The main deregulated metabolic families in urine were acylcarnitines, acylglycines and metabolites derived from amino acids, specifically from proline, histidine and glutamine. These results indicate perturbations in fatty acid beta oxidation and amino acid pathways in scleroderma patients. On the other hand, the main plasma biomarker candidate was 2-arachidonoylglycerol, which is involved in the endocannabinoid system with potential implications in the induction and propagation of systemic sclerosis and autoimmunity.


Assuntos
Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Metabolômica/métodos , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/urina , Espectrometria de Massas por Ionização por Electrospray , Acilação , Adulto , Idoso , Ácidos Araquidônicos/sangue , Ácidos Araquidônicos/urina , Carnitina/análogos & derivados , Carnitina/sangue , Carnitina/urina , Estudos de Casos e Controles , Endocanabinoides/sangue , Endocanabinoides/urina , Feminino , Glicerídeos/sangue , Glicerídeos/urina , Glicina/sangue , Glicina/urina , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Escleroderma Sistêmico/diagnóstico , Urinálise
18.
Int J Hyg Environ Health ; 222(2): 205-210, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30293930

RESUMO

BACKGROUND: The International Agency for Research on Cancer (IARC) has recently classified glyphosate as a Group 2A 'probably carcinogenic to humans'. Due to this carcinogenic classification and resulting international debate, there is an increased demand for studies evaluating human health effects from glyphosate exposures. There is currently limited information on human exposures to glyphosate and a paucity of data regarding glyphosate's biological half-life in humans. OBJECTIVE: This study aims to estimate the human half-life of glyphosate from human urine samples collected from amenity horticulture workers using glyphosate based pesticide products. METHODS: Full void urine spot samples were collected over a period of approximately 24 h for eight work tasks involving seven workers. The elimination time and estimation of the half-life of glyphosate using three different measurement metrics: the unadjusted glyphosate concentrations, creatinine corrected concentrations and by using Urinary Excretion Rates (UER) (µg L-1, µmol/mol creatinine and UER µg L-1) was calculated by summary and linear interpolation using regression analysis. RESULTS: This study estimates the human biological half-life of glyphosate as approximately 5 ½, 10 and 7 » hours for unadjusted samples, creatinine corrected concentrations and by using UER (µg L-1, µmol/mol creatinine, UER µg L-1), respectively. The approximated glyphosate half-life calculations seem to have less variability when using the UER compared to the other measuring metrics. CONCLUSION: This study provides new information on the elimination rate of glyphosate and an approximate biological half-life range for humans. This information can help optimise the design of sampling strategies, as well as assisting in the interpretation of results for human biomonitoring studies involving this active ingredient. The data could also contribute to the development or refinement of Physiologically Based PharmacoKinetic (PBPK) models for glyphosate.


Assuntos
Poluentes Ambientais/urina , Glicina/análogos & derivados , Herbicidas/urina , Adulto , Monitoramento Biológico , Feminino , Glicina/urina , Meia-Vida , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade
19.
Int J Hyg Environ Health ; 221(7): 1012-1022, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30078418

RESUMO

BACKGROUND: Glyphosate has recently received much public attention following its 'Group 2A - probably carcinogenic to humans' classification from the International Agency for Research on Cancer. Despite the widespread use of glyphosate, there is limited data on potential exposures during common occupational uses. OBJECTIVE: The study aimed to characterise occupational exposures to glyphosate among amenity horticulturists through the collection and analysis of urine samples following pesticide application. The impact of work practices on personal exposure, as well as suitability of collecting multiple spot urine samples as a sampling strategy for the assessment of occupational exposure for glyphosate were also examined. METHODS: A minimum of three spot urine samples were collected per work task; before the work task began, after the work task completion and the following first morning void. All samples were analysed separately for glyphosate using liquid chromatography tandem mass spectrometry and for creatinine. Differences in urinary glyphosate concentrations between the pre-task samples versus the post-task and the peak urinary samples were both analysed using paired Student t-tests. Determinants of exposure on glyphosate urine concentrations were evaluated using Pearson's correlation coefficients and linear regression. A multivariate mixed effect model were elaborated to compare the glyphosate concentrations between post-task and following first morning void samples. In these models, worker identity was entered as a random effect to account for the presence of correlations between repeated measurements from the same individuals. RESULTS: Peak urine glyphosate concentrations measured for work tasks were 2.5, 1.9, 1.9 and 7.4 µg L-1 (arithmetic mean, geometric mean, median and maximum value, respectively). Concentrations were highest in samples taken up to 3 h after completing the work task. Regression analysis showed that workers who sprayed the day before the sampling task had higher glyphosate concentrations in pre-task samples than those who did not spray the day before (p < 0.01). Similarly, workers who took breaks during the work task had higher peak urinary glyphosate concentrations (p < 0.01). The multivariate mixed effect model showed that the following first morning void samples were approximately a factor 0.7 lower than post-task values. CONCLUSION: Occupational exposures to glyphosate among amenity horticulturalists are greater than those reported in environmental studies and comparable with previously reported agricultural studies. A suitable sampling strategy for occupational exposures to glyphosate is the collection of a spot urine sample up to 3 h after completing the application of a glyphosate based pesticide product, which provides a reliable marker of peak exposure.


Assuntos
Agricultura , Glicina/análogos & derivados , Herbicidas/urina , Exposição Ocupacional/análise , Adulto , Monitoramento Ambiental , Feminino , Glicina/urina , Humanos , Masculino , Pessoa de Meia-Idade
20.
Cancer Chemother Pharmacol ; 82(5): 803-814, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30128949

RESUMO

PURPOSE: This metabolite profiling and identification analysis (part of a phase I absorption, distribution, metabolism, and excretion study) aimed to define biotransformation pathways and evaluate associated inter-individual variability in four patients with advanced solid tumors who received [14C]-ixazomib. METHODS: After administration of a single 4.1-mg oral dose of [14C]-ixazomib (total radioactivity [TRA] ~ 500 nCi), plasma (at selected timepoints), urine, and fecal samples were collected before dosing and continuously over 0-168-h postdose, followed by intermittent collections on days 14, 21, 28, and 35. TRA analysis and metabolite profiling were performed using accelerator mass spectrometry. Radiolabeled metabolites were identified using liquid chromatography/tandem mass spectrometry. RESULTS: Metabolite profiles were similar in plasma, urine, and feces samples across the four patients analyzed. All metabolites identified were de-boronated. In AUC0-816 h time-proportional pooled plasma, ixazomib (54.2% of plasma TRA) and metabolites M1 (18.9%), M3 (10.6%), and M2 (7.91%), were the primary components identified. M1 was the major metabolite, contributing to 31.1% of the 76.2% of the total dose excreted in urine and feces over 0-35-day postdose. As none of the identified metabolites had a boronic acid moiety, they are unlikely to be pharmacologically active. CONCLUSIONS: Hydrolytic metabolism in conjunction with oxidative deboronation appears to be the principal process in the in vivo biotransformation pathways of ixazomib. The inference of formation-rate-limited clearance of ixazomib metabolites and the inferred lack of pharmacologic activity of identified circulating metabolites provides justification for use of parent drug concentrations/systemic exposure in clinical pharmacology analyses.


Assuntos
Antineoplásicos/sangue , Antineoplásicos/urina , Compostos de Boro/sangue , Compostos de Boro/urina , Fezes/química , Glicina/análogos & derivados , Neoplasias/metabolismo , Administração Oral , Antineoplásicos/administração & dosagem , Área Sob a Curva , Biotransformação , Compostos de Boro/administração & dosagem , Radioisótopos de Carbono , Feminino , Glicina/administração & dosagem , Glicina/sangue , Glicina/urina , Humanos , Masculino , Metaboloma/efeitos dos fármacos , Neoplasias/tratamento farmacológico
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