Biomonitoring of glyphosate and aminomethylphosphonic acid: Current insights and future perspectives.

Glyphosate is one of the most widely used herbicides globally, raising concerns about its potential impact on human health. Biomonitoring studies play a crucial role in assessing human exposure to glyphosate and providing valuable insights into its distribution and metabolism in the body. This review aims to summarize the current trends and future perspectives in biomonitoring of glyphosate and its major degradation product of aminomethylphosphonic acid (AMPA). A comprehensive literature search was conducted, focusing on studies published between January 2000 and December 2022. The findings demonstrated that glyphosate and AMPA have been reported in different human specimens with urine as the dominance. Sample pretreatment techniques of solid-phase and liquid-liquid extractions coupled with liquid/gas chromatography-tandem mass spectrometry have achieved matrix elimination and accurate analysis. We also examined and compared the exposure characteristics of these compounds among different regions and various populations, with significantly higher levels of glyphosate and AMPA observed in Asian populations and among occupational groups. The median urinary concentration of glyphosate in children was 0.54 ng/mL, which was relatively higher than those in women (0.28 ng/mL) and adults (0.12 ng/mL). It is worth noting that children may exhibit increased susceptibility to glyphosate exposure or have different exposure patterns compared to women and adults. A number of important perspectives were proposed in order to further facilitate the understanding of health effects of glyphosate and AMPA, which include, but are not limited to, method standardization, combined exposure assessment, attention for vulnerable populations, long-term exposure effects and risk communication and public awareness.

Neonicotinoid insecticides and their metabolites: Specimens tested, analytical methods and exposure characteristics in humans.

The use of neonicotinoid insecticides (NEOs) has been rising globally due to their broad-spectrum insecticidal activity, unique mode of neurotoxic action and presumed low mammalian toxicity. Given their growing ubiquity in the environment and neurological toxicity to non-target mammals, human exposure to NEOs is flourishing and now becomes a big issue. In the present work, we demonstrated that 20 NEOs and their metabolites have been reported in different human specimens with urine, blood and hair as the dominance. Sample pretreatment techniques of solid-phase and liquid-liquid extractions coupled with high performance liquid chromatography-tandem mass spectrometry have successfully achieved matrix elimination and accurate analysis. We also discussed and compared exposure characteristics of these compounds among types of specimens and different regions. A number of important knowledge gaps were also identified in order to further facilitate the understanding of health effects of NEO insecticides, which include, but are not limited to, identification and use of neuro-related human biological samples for better elucidating neurotoxic action of NEO insecticides, adoption of advanced non-target screening analysis for a whole picture in human exposure, and expanding investigations to cover non-explored but NEO-used regions and vulnerable populations.

Phthalate metabolites: Characterization, toxicities, global distribution, and exposure assessment.

Phthalates are plasticizers in various products and regarded as endocrine disruptors due to their anti-androgen effects. Environmental occurrence and toxicities of parent phthalates have been widely reported, while the current state of knowledge on their metabolites is rarely summarized. Based on the available literature, the present review mainly aims to 1) characterize the potential metabolites of phthalates (mPAEs) using the pharmacokinetics evidences acquired via animal or human models; 2) examine the molecular and cellular mechanism involved in toxicity for mPAEs; 3) investigate the exposure levels of mPAEs in different human specimens (e.g., urine, blood, seminal fluid, breast milk, amniotic fluid and others) across the globe; 4) discuss the models and related parameters for phthalate exposure assessment. We suggest there is subtle difference in toxic mechanisms for mPAEs compared to their parent phthalates due to their alternative chemical structures. Human monitoring studies performed in Asia, America and Europe have provided the population exposure baseline levels for typical phthalates in different regions. Urine is the preferred matrix than other specimens for phthalate exposure study. Among ten urinary mPAEs, the largest proportions of di-(2-ethylhexyl) phthalate (DEHP) metabolites (40%), monoethyl phthalate (mEP) (43%) and DEHP metabolites/mEP (both 29%) were observed in Asia, America and Europe respectively, and mono-5-carboxy-2-ethypentyl phthalate was the most abundant compounds among DEHP metabolites. Daily intakes of phthalates can be accurately calculated via urinary mPAEs if the proper exposure parameters were determined. Further work should focus on combining epidemiological and biological evidences to establish links between phthalates exposure and biological phenotypes. More accurate molar fractions (FUE) of the urinary excreted monoester related to the ingested diesters should be collected in epidemiological or pharmacokinetic studies for different population.

Exposure Profile of Severe Acute Respiratory Syndrome Coronavirus 2 in Canadian Food Sources.

ABSTRACT: A new coronavirus strain known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. This virus is the causative agent for coronavirus disease 2019 (COVID-19) and spreads primarily through human-to-human transmission via infected droplets and aerosols generated by infected persons. Although COVID-19 is a respiratory virus, the potential for transmission of SARS-CoV-2 via food is considered theoretically possible and remains a concern for Canadian consumers. We have conducted an exposure assessment of the likelihood of exposure of SARS-CoV-2 in Canadian food sources at the time of consumption. This article describes the exposure routes considered most relevant in the context of food contamination with SARS-CoV-2, including contaminated food of animal origin, other contaminated fresh foods, fomites, and SARS-CoV-2-contaminated feces. The likelihood of foodborne infection of SARS-CoV-2 via the human digestive tract also was considered. Our analysis indicates that there is no evidence that foodborne transmission of SARS-CoV-2 has occurred, and we consider the likelihood of contracting COVID-19 via food and food packaging in Canada as low to remote. Adherence to safe food practices and cleaning procedures would in any case prevent a potential foodborne infection with SARS-CoV-2.

Exposure to benzylpenicillin after different dosage regimens in growing pigs.

BACKGROUND: Penicillin is important for treatment of pigs, but data on its absorption and disposition in pigs are sparse. This is reflected by the variation in recommended dosages in the literature. Inadequate dosage may lead to treatment failure and selection of resistant bacteria. To optimize treatment regimens, plasma exposure to benzylpenicillin for two sustained release formulations of procaine benzylpenicillin for intramuscular administration was studied in growing pigs by means of tandem mass spectrometry (UPLC-MS/MS). One formulation was an aqueous suspension, Ethacilin® vet (ETH), and the other an oily suspension, Ultrapen vet (UPA). Benzylpenicillin exposure after intravenous administration of potassium benzylpenicillin was also explored. Exposure profiles were first studied after single administrations of the approved dosages in healthy pigs and then after repeated administration of different dosages in pigs inoculated intranasally with an Actinobacillus pleuropneumoniae serotype 2 strain. RESULTS: After intravenous administration of benzylpenicillin (n = 6), maximum plasma concentration (Cmax), 1860-9318 µg/L, was observed after 15 min. At four h, plasma concentrations decreased to 15-76 µg/L. After intramuscular administration of ETH (n = 6) Cmax, 1000-4270 µg/L, was observed within one h (tmax) in 5 pigs but at four h in one pig. Cmax for UPA (n = 6), 910-3220 µg/L, was observed within one h in three pigs, but at four or 24 h in three pigs. For both ETH and UPA, the terminal phase was characterized by slow decline compared with intravenous administration. Repeated administration of different dosages of ETH and UPA in pigs inoculated with A. pleuropneumoniae (n = 54) showed that the approved dose for UPA (30 mg/kg, qd) but not for ETH (20 mg/kg, qd) gave adequate plasma exposure for bacteria with a penicillin MIC of 500 µg/L. However, more frequent dosing of ETH (bid) or increased dosage gave an adequate exposure. CONCLUSIONS: The approved dosage of ETH provided insufficient plasma exposure for adequate therapy of infections caused by A. pleuropneumoniae or other bacteria with a penicillin MIC of 500 µg/L. More frequent ETH dosing (bid) or an increased dosage would improve exposure. The approved dosage of UPA however provided adequate exposure.

Cluster analysis of urinary tobacco biomarkers among U.S. adults: Population Assessment of Tobacco and Health (PATH) biomarker study (2013-2014).

Tobacco use delivers nicotine, tobacco-specific nitrosamines (TSNAs), volatile organic compounds (VOCs), and polycyclic aromatic hydrocarbons (PAHs), which are metabolized and excreted in urine offering useful biomarkers of exposure. Previous studies compared individual toxicants across tobacco users. Based on a group of biomarkers, cluster analysis was used to define tobacco toxicant exposure profiles. Clusters with distinct exposure profiles, were determined and described, based on levels of urinary biomarkers of exposure to nicotine, TSNAs, VOCs, and PAHs among a national sample of current, established, adult tobacco users, and examine the association of use behavior and cluster membership. The PATH Biomarker Wave 1 data were analyzed. Current established tobacco users with complete urinary biomarker data were included (N = 6724). User groups included cigarette smokers, users of electronic cigarette (ECIG), smokeless tobacco (SLT), and dual and poly tobacco users. Cluster analysis, pairwise comparisons, and multinomial logistic regression were conducted. Cigarette smokers were primarily in clusters with high biomarker concentrations across all groups, but actual concentrations were associated with smoking quantity. A cluster with high TSNAs but low levels of PAHs and VOCs was heavily populated by SLT users. Exclusive ECIG users, depending on use frequency, were predominantly in clusters with low biomarker concentrations, except for one cluster that had relatively high TSNAs. Clusters heavily populated by dual and poly tobacco users were the same as those heavily populated by cigarette smokers. Ten exposure profiles (clusters) were determined and linked to tobacco use behavior. Findings could inform future research and policy initiatives.

Profiles, variability and predictors of concentrations of blood trihalomethanes and urinary haloacetic acids along pregnancy among 1760 Chinese women.

Blood trihalomethanes (THMs) and urinary haloacetic acids (HAAs) are the leading candidate biomarkers for disinfection byproduct (DBP) exposure. However, no studies have assessed the exposure profiles, temporal variability, and potential predictors of these biomarkers during pregnancy. Here we collected blood (n = 4304) and urine samples (n = 4165) from 1760 Chinese pregnant women during early, mid-, and late pregnancy, which were separately analyzed for 4 THMs and 2 HAAs. We calculated the intraclass correlation coefficients (ICCs) to assess the variability of these biomarkers and estimated their correlations with sociodemographic, water-use behavioral, dietary and sample collection factors using mixed models. The median concentrations of TCM, BDCM, Br-THMs [sum of BDCM, dibromochloromethane (DBCM), bromoform (TBM)], total THMs (TTHMs, sum of TCM and Br-THMs), DCAA and TCAA in the water distribution system were 4.2 µg/L, 1.7 µg/L, 2.9 µg/L, 7.1 µg/L, 3.4 µg/L and 8.2 µg/L, respectively. Chloroform (TCM), bromodichloromethane (BDCM), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected in > 75% of the biospecimens. Repeated measurements of blood TCM, BDCM, Br-THMs and TTHMs and urinary DCAA and TCAA uniformly exhibited high variability (ICCs = 0.01-0.13); the use of a single measurement to classify gestational average exposure resulted in a high degree of exposure misclassification. The sampling season was a strong predictor of all analyzed DBPs. Additionally, we detected a positive association of blood TCM and BDCM with household income, urinary DCAA with age, and urinary TCAA with tap water usage, education level and amount of tap water consumed. Inverse associations were found between blood BDCM and vegetable consumption, and between blood Br-THM and TTHM and time interval since the last bathing/showering. Afternoon samples had lower DCAA concentrations than did early morning samples. Our results indicate that blood THM and urinary HAA concentrations vary greatly over the course of pregnancy and are affected by sampling season, time of day of blood/urine collection, sociodemographic factors, recent water-use activities and dietary intake.

Impact of Internal and External Factors on EBC-pH and FeNO Changes in Humans Following Challenge with Ethyl Acrylate.

Acute effects of ethyl acrylate exposure at 5 ppm for 4 h include changes of pH in exhaled breath condensate (EBC-pH) and exhaled nitric oxide (FeNO). So far, few data have been reported for atopic persons or the impact of the exposure conditions on biomarkers, e.g., constant versus variable application of irritants. Nine atopic and eighteen healthy volunteers without bronchial hyperresponsiveness were exposed for 4 h to ethyl acrylate concentrations of 0.05 ppm (sham), 5 ppm (constant concentration), and 0-10 ppm (variable, mean concentration of 5 ppm) in an exposure laboratory. A positive atopic status was defined according to specific IgE concentrations to common inhalant allergens (sx1 ≥ 0.35 kU/L). Biomarker levels were assessed before and after challenge and adjusted for levels after sham exposure (net response). Ethyl acrylate at constant, but not at variable concentrations induced a significant change in the net responses of EBC-pH and FeNO. Concerning FeNO, this could be observed only for atopic persons. The changes of biomarker levels were related to their baseline values. Biomarker responses to challenge with ethyl acrylate may be influenced by the patterns of application as well as baseline airway inflammation and atopic status of the volunteers.