Biomarker For Assessment Of Exposure Research Articles

Quantitative Metabolism and Urinary Elimination Kinetics of Seven Neonicotinoids and Neonicotinoid-Like Compounds in Humans.

Reverse dosimetry, i.e., calculating the dose of hazardous substances that has been taken up by humans based on measured analyte concentrations in spot urine samples, is critical for risk assessment and requires metabolic and kinetic data. We quantitatively studied the metabolism of seven major neonicotinoid and neonicotinoid-like compounds (NNIs) after single oral doses in male volunteers and determined key kinetic parameters and urinary elimination for NNIs together with their metabolites. Complete and consecutive urine samples were collected over 48 h. All samples were analyzed by tandem mass spectrometry, following liquid or gas chromatographic separation. Single- and group-specific NNI metabolites were quantified, i.e., hydroxylated and N-dealkylated NNIs and NNI-associated carboxylic acids and their glycine derivatives. Large, substance-dependent variations of key toxicokinetic parameters were observed. Mean times of concentration maxima (tmax) in urine varied between 2.0 (imidacloprid) and 25.8 h (N-desmethyl-clothianidin), whereas mean urinary elimination half-times (t1/2) were between 2.5 (acetamiprid) and 49.5 h (sulfoxaflor). Mean 48 h excretion fractions (Fue's) were between 0.03% (2-chloro-1,3-thiazole-5-carboxylic acid glycine) and 84% (clothianidin). In contrast, the interindividual differences of Fue's between the volunteers for each of the NNIs and their metabolites remained low (below a factor of 2 between the maximum and minimum derived Fue with the exception of 6-chloronicotinic acid in the acetamiprid dose study). The obtained quantitative data enabled choosing appropriate biomarkers for exposure assessment and, at the same time, for risk assessment by reverse dosimetry at current environmental exposures, i.e., comparing the calculated doses that have been taken up to currently available acceptable daily intakes of NNIs.

A high-throughput LC-MS Method for Urinary Transportation- and Petrochemical-Related VOC Metabolites as Biomarkers for Exposure Assessment

A high-throughput LC-MS Method for Urinary Transportation- and Petrochemical-Related VOC Metabolites as Biomarkers for Exposure Assessment

Exposures to pesticides and risk of cancer: Evaluation of recent epidemiological evidence in humans and paths forward.

Knowledge of the role in cancer etiology of environmental exposures as pesticides is a prerequisite for primary prevention. We review 63epidemiological studies on exposure to pesticides and cancer risk in humans published from 2017 to 2021, with emphasis on new findings, methodological approaches, and gaps in the existing literature. While much of the recent evidence suggests causal relationships between pesticide exposure and cancer, the strongest evidence exists for acute myeloid leukemia (AML) and colorectal cancer (CRC), diseases in which the observed associations were consistent across several studies, including high-quality prospective studies and those using biomarkers for exposure assessment, with some observing dose-response relationships. Though high-quality studies have been published since the IARC monograph on organophosphate insecticides in 2017, there are still gaps in the literature on carcinogenic evidence in humans for a large number of pesticides. To further knowledge, we suggest leveraging new techniques and methods to increase sensitivity and precision of exposure assessment, incorporate multi-omics data, and investigate more thoroughly exposure to chemical mixtures. There is also a strong need for better and larger population-based cohort studies that include younger and nonoccupationally exposed individuals, particularly during developmental periods of susceptibility. Though the existing evidence has limitations, as always in science, there is sufficient evidence to implement policies and regulatory action that limit pesticide exposure in humans and, hence, further prevent a significant burden of cancers.

Variability of lead in urine and blood in healthy individuals

BackgroundLead is a non-essential toxic trace element. Lead in blood (BPb) is the most common biomarker of lead exposure but lead in urine (UPb) has also been used. There is, however, limited data on the variability of UPb in the general population and the association with BPb. ObjectivesOur aims were to assess variability of lead in repeated blood and urine samples. The diurnal variation of UPb was also examined as well as associations with BPb. MethodsWe established an openly available biobank including 60 healthy non-smoking individuals, 29 men and 31 women, 21–64 years of age (median 31 years), with repeated sampling of blood and urine. Timed urine samples were collected at six fixed time points in two 24 h periods, about one week apart, and adjusted for creatinine and specific gravity (SG). BPb and UPb were analyzed by inductively coupled plasma mass spectrometry. The within- and between-individual variabilities and intra-class correlation coefficients (ICCs; ratios of the between-individual to total observed variances) were calculated using mixed-effects models. ResultsThe ICCs for UPb samples were mostly above 0.5, when adjusted for creatinine or SG, and higher for overnight samples compared with daytime samples. The highest ICCs were obtained for BPb (ICC = 0.97) and for urine samples corrected for dilution by SG or creatinine. The ICC was 0.66 for overnight samples adjusted for creatinine. High correlations with BPb were found for 24 h UPb (rs = 0.77) and overnight samples, e.g. rs = 0.74 when adjusted for SG. There was diurnal variation of UPb with lowest excretion rate in overnight samples. There was also a significant association between the Pb excretion rate and urinary flow rate. ConclusionsIn addition to BPb, UPb adjusted for creatinine or SG seems to be a useful biomarker for exposure assessment in epidemiological studies.

Recent advances in heterocyclic aromatic amines: An update on food safety and hazardous control from food processing to dietary intake.

Heterocyclic aromatic amines (HAAs) as probable carcinogenic substances are mainly generated in meat products during thermal processing. Numerous studies have contributed to the analysis, formation, and mitigation of HAAs during food processing. However, few articles have comprehensively reviewed food safety aspects from both food processing and dietary intake regarding the formation, mitigation, metabolism, biomarkers for exposure, hazard control, and risk assessment of HAAs, and related food safety researches. Several factors may influence the generation of HAAs, including processing temperature, processing time, and chemical composition of the meat. Nonetheless, these mutagenic compounds are attenuated to different levels by the addition of natural or synthetic flavorings and antioxidant-rich marinades, as well as pretreatments using technique such as microwave heating. After dietary intake, different types of HAAs are metabolized in humans by several enzymes, including cytochrome P450s, peroxidases, N-acetyltransferases, sulfotransferases, uridine diphosphate-glucuronosyltransferases, and glutathione S-transferases. Their primary metabolites are further conjugated with DNA or ultimately excreted in urine and feces. The 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in hair as well as DNA, hemoglobin, and serum albumin adducts has been considered as biomarkers for exposure assessment. Dietary intake information obtained from questionnaires and the results of epidemiological investigations have shown a positive relationship between the intakes of red meat and processed meat and high risk of cancer incidence. As several cancers have been reported to be associated with HAAs, HAAs should be both effectively reduced during food processing and controlled from dietary intake to facilitate human health.

Passive smoking as a stress factor in diabetic children

ObjectiveThis study aimed to measure urinary cotinine level and urinary cotinine/creatinine ratio as a biomarker of passive smoking in diabetic children.DNA damage was estimated in peripheral leukocytes by a DNA fragmentation assay in diabetic children.BackgroundExposure to passive smoking is associated with a number of health hazards such as prenatal damage to the fetus, poor growth, respiratory illness, atopy and asthma, coronary heart disease, and sudden infant death syndrome.Patients and methodsThis study was carried out on 54 diabetic children attending the Genetic and Endocrine Unit of the Pediatric Department, Faculty of Medicine, Menoufia University.The children were divided into two groups: group I (34 children exposed to passive smoking) and group II (20 children not exposed to passive smoking).The studied groups were subjected to a detailed assessment of history, thorough clinical examination, investigations, and family counseling.ResultsSignificantly higher urinary cotinine levels and urinary cotinine/creatinine ratios were found in children with a history of exposure to passive tobacco smoke (120.4 ± 86.2 and 173.7 ± 130.1, respectively) in comparison with children with no history of exposure (2901.5 ± 1423.2 and 3284.7 ± 2322.8, respectively, P ≤ 0.000), and the urinary cotinine levels were found to be dependent on the daily exposure to tobacco smoke as indicated by the number of cigarettes consumed by the smoker in the presence of the child. Also, significantly higher positive gel electrophoresis results (DNA damage) were found in children with a history of exposure to passive tobacco smoke (29.4%) in comparison with children with no history of exposure (0%).ConclusionPassive smoking is a risk factor for many health hazards and cotinine is a valuable biomarker for assessment of exposure to second-hand smoking, especially among children. Also, passive smoking is a cause of enhanced apoptotic changes in diabetic children.

Diet & Nutrition: Acrylamide Study Suggests Breast Cancer Link

The International Agency for Research on Cancer classifies acrylamide as a probable human carcinogen. It has only been in recent months that an epidemiologic study first found a link between dietary acrylamide and human cancer risk. Now Danish researchers report that acrylamide adduct levels in blood are associated with an increased risk of breast cancer in postmenopausal women. This is the first epidemiologic study to use blood biomarkers to assess acrylamide exposure. The findings, says first author Pelle Thonning Olesen, emphasize the importance of using biomarkers for exposure assessment. “Biomarkers are a more trustworthy indicator for exposure,” he says. Before 2002, people were known to be exposed to acrylamide in certain industries and through smoking tobacco. That year, the Swedish National Food Administration discovered that acrylamide also forms in fried or baked starchy foods such as french fries, coffee, and baked goods. Diet is now thought to be the major source of exposure among nonsmokers, but the cancer risk posed by acrylamide in food is unknown. All previous epidemiologic trials estimated acrylamide consumption from food frequency questionnaires. Olesen, a toxicologist at the Technical University of Denmark, Soborg, and colleagues instead measured levels of acrylamide and a key metabolite, glycidamide, bound to hemoglobin. The subjects included 374 postmenopausal women with breast cancer and 374 controls who participated in the Danish Cancer Society’s Diet, Cancer, and Health Study. Adduct levels of acrylamide among smokers reflect both dietary and smoking intake of the compound. After statistical adjustments for smoking behavior, women with the highest acrylamide-hemoglobin levels showed a 2.7 times higher risk of estrogen receptor–positive breast cancer compared with women with the lowest acrylamide-hemoglobin levels. The risk rose with increasing acrylamide exposure. Acrylamide-hemoglobin levels were not linked to estrogen receptor–negative breast cancer, and glycidamide-hemoglobin levels showed no connection with any breast cancer. The finding that only acrylamide-hemoglobin was associated with breast cancer suggests that the compound may induce cancer by nongenotoxic routes such as alkylation of proteins that could alter estrogen receptor function. The findings were reported in the 1 May 2008 issue of the International Journal of Cancer. “This is an important study because it’s the first to measure acrylamide adducts,” says epidemiologist Lorelei Mucci, an assistant professor at the Harvard School of Public Health. Nonetheless, the study should be repeated in larger numbers of nonsmoking women, according to Mucci, because more than half the cases and controls were current or former smokers. “The big public health question here is whether the amount of acrylamide in foods is enough to lead to cancer,” Mucci says. It is possible that other chemical compounds formed along with acrylamide may be the culprit in any cancer link. “Acrylamide-hemoglobin may be a biomarker for other carcinogenic chemicals formed during the heating of foods,” cautions Olesen.

Epidemiologic Methods Developments: A Look Forward to the Year 2032

This article responds to a request by the Editors for a perspective on potential epidemiologic methods developments between now and the year 2032 when the American College of Epidemiology will have its 50th Annual Meeting. The response begins by describing the need for enhanced methods in epidemiologic research and goes on to suggest some approaches to satisfying such needs. The suggested approaches include the more extensive use of biomarkers for exposure assessment, the greater standardization of data analysis and reporting methods, and enhancement of the interplay between observational studies and randomized controlled trials. It is argued that a phased approach to epidemiologic hypothesis evaluation may often be needed, with hypotheses that are promising in observational studies subjected to controlled trials having well-selected intermediate outcomes. It is also argued that a multidisciplinary, coordinated community of scientists interested in disease risk estimation and disease prevention will be needed for epidemiologic research to fulfill its potential over the next 25 years.

Identification and Quantification of 1-Nitropyrene Metabolites in Human Urine as a Proposed Biomarker for Exposure to Diesel Exhaust

1-nitropyrene (1-NP) is one of the most abundant nitrated polycyclic aromatic hydrocarbons (NPAHs) in diesel exhaust particulate matter (DEP) and is a main contributor of direct-acting mutagenicity in DEP. Therefore, the metabolites of 1-NP are expected to be a biomarker for assessment of exposure to DEP. In this study, a highly specific and sensitive analytical method using liquid chromatography with tandem mass spectrometry (LC-MS/MS) was developed to determine urinary 1-NP metabolites. After enzymatic hydrolysis of the conjugated metabolites, the analytes were selectively extracted from the urine matrix with blue rayon. The eluate from the rayon was further purified on an acidic alumina cartridge. Hydroxy-N-acetyl- 1-aminopyrenes (6- and 8-OHNAAP) and hydroxy-1-nitropyrenes (3-, 6-, and 8-OHNP) in human urine were identified by their retention times and MS/MS spectra and quantified by using deuterated internal standards. 1-NP metabolites were quantified in urine from all healthy, nonoccupationally exposed subjects. 6-OHNAAP, 8-OHNAAP, 6-OHNP, and 8-OHNP (means of 117, 109, 203, and 137 pmol/mol creatinine, respectively) were the most abundant isomers in human urine. This report is the first to demonstrate the presence of OHNAAPs and OHNPs in human urine, in agreement with previous in vivo and in vitro studies that predicted that these metabolites should be excreted into human urine. This method for determining urinary 1-NP metabolites should be useful for the surveillance of exposure to NPAHs and DEP and will facilitate the study of cancer risk associated with these exposures.