Exposome-Explorer (http://exposome-explorer.iarc.fr) is the first database dedicated to biomarkers of exposure to environmental risk factors. It contains detailed information on the nature of ...biomarkers, their concentrations in various human biospecimens, the study population where measured and the analytical techniques used for measurement. It also contains correlations with external exposure measurements and data on biological reproducibility over time. The data in Exposome-Explorer was manually collected from peer-reviewed publications and organized to make it easily accessible through a web interface for in-depth analyses. The database and the web interface were developed using the Ruby on Rails framework. A total of 480 publications were analyzed and 10 510 concentration values in blood, urine and other biospecimens for 692 dietary and pollutant biomarkers were collected. Over 8000 correlation values between dietary biomarker levels and food intake as well as 536 values of biological reproducibility over time were also compiled. Exposome-Explorer makes it easy to compare the performance between biomarkers and their fields of application. It should be particularly useful for epidemiologists and clinicians wishing to select panels of biomarkers that can be used in biomonitoring studies or in exposome-wide association studies, thereby allowing them to better understand the etiology of chronic diseases.
Abstract Introduction The other two presentations in this session highlight examples of IARC Monographs evaluations in which studies in exposed workers provided important evidence on cancer in humans ...or mechanisms of carcinogenesis. Since the update of the Preamble in 2019, the IARC Monographs contain a formal critical appraisal of the exposure assessment quality in human cancer and mechanistic studies. This presentation describes the workflow of this procedure and applications to some examples. Materials and Methods The steps of the exposure assessment critique as outlined by the IARC Monographs Preamble are presented. Former Monographs evaluations were used as case studies to identify the exposure assessment domains that were most informative for judging study quality. Results A common approach was used to evaluate the exposure assessment quality in the Monographs on (i) 1,1,1 trichloroethane, (ii) antimony and (iii) occupational exposure as a firefighter. Some criteria were adjusted for different agents, such as the studies’ definition of the exposure, information on exposure routes, and the assessment of co-exposures. Agent-specific knowledge is required concerning exposure assessment methods and potential co-exposures to identify the strengths and limitations of the exposure assessments performed in human cancer and mechanistic studies. Conclusions Evaluating the quality of exposure assessment methods in studies with exposed humans is a critical step needed to judge the studies’ quality and informativeness. The structured process formally introduced since the new Preamble can improve transparency and consistency in the application of evidence synthesis frameworks for future IARC working groups and other scientific review panels.
Acylcarnitines (ACs) play a major role in fatty acid metabolism and are potential markers of metabolic dysfunction with higher blood concentrations reported in obese and diabetic individuals. Diet, ...and in particular red and processed meat intake, has been shown to influence AC concentrations but data on the effect of meat consumption on AC concentrations is limited.
To investigate the effect of red and processed meat intake on AC concentrations in plasma and urine using a randomized controlled trial with replication in an observational cohort.
In the randomized crossover trial, 12 volunteers successively consumed 2 different diets containing either pork or tofu for 3 d each. A panel of 44 ACs including several oxidized ACs was analyzed by LC-MS in plasma and urine samples collected after the 3-d period. ACs that were associated with pork intake were then measured in urine (n = 474) and serum samples (n = 451) from the European Prospective Investigation into Cancer and nutrition (EPIC) study and tested for associations with habitual red and processed meat intake derived from dietary questionnaires.
In urine samples from the intervention study, pork intake was positively associated with concentrations of 18 short- and medium-chain ACs. Eleven of these were also positively associated with habitual red and processed meat intake in the EPIC cross-sectional study. In blood, C18:0 was positively associated with red meat intake in both the intervention study (q = 0.004, Student’s t-test) and the cross-sectional study (q = 0.033, linear regression).
AC concentrations in urine and blood were associated with red meat intake in both a highly controlled intervention study and in subjects of a cross-sectional study. Our data on the role of meat intake on this important pathway of fatty acid and energy metabolism may help understanding the role of red meat consumption in the etiology of some chronic diseases. This trial was registered at Clinicaltrials.gov as NCT03354130.
We performed a meta-analysis of epidemiological results for the association between occupational exposure as a firefighter and cancer as part of the broader evidence synthesis work of the ...IARCMonographs program.
A systematic literature search was conducted to identify cohort studies of firefighters followed for cancer incidence and mortality. Studies were evaluated for the influence of key biases on results. Random-effects meta-analysis models were used to estimate the association between ever-employment and duration of employment as a firefighter and risk of 12 selected cancers. The impact of bias was explored in sensitivity analyses.
Among the 16 included cancer incidence studies, the estimated meta-rate ratio, 95% confidence interval (CI), and heterogeneity statistic (I2) for ever-employment as a career firefighter compared mostly to general populations were 1.58 (1.14–2.20, 8%) for mesothelioma, 1.16 (1.08–1.26, 0%) for bladder cancer, 1.21 (1.12–1.32, 81%) for prostate cancer, 1.37 (1.03–1.82, 56%) for testicular cancer, 1.19 (1.07–1.32, 37%) for colon cancer, 1.36 (1.15–1.62, 83%) for melanoma, 1.12 (1.01–1.25, 0%) for non-Hodgkin lymphoma, 1.28 (1.02–1.61, 40%) for thyroid cancer, and 1.09 (0.92–1.29, 55%) for kidney cancer. Ever-employment as a firefighter was not positively associated with lung, nervous system, or stomach cancer. Results for mesothelioma and bladder cancer exhibited low heterogeneity and were largely robust across sensitivity analyses.
There is epidemiological evidence to support a causal relationship between occupational exposure as a firefighter and certain cancers. Challenges persist in the body of evidence related to the quality of exposure assessment, confounding, and medical surveillance bias.
Coffee drinking has been associated with a lower risk of certain chronic diseases and overall mortality. Its effects on disease risk may vary according to the type of coffee brew consumed and its ...chemical composition. We characterized variations in the chemical profiles of 76 coffee brew samples representing different brew methods, roast levels, bean species, and caffeine types, either prepared or purchased from outlets in Rockville, Maryland, United States of America. Samples were profiled using liquid chromatography coupled with high-resolution mass spectrometry, and the main sources of chemical variability identified by the principal component partial R-square multivariable regression were found to be brew methods (R
² = 36%). A principal component analysis (PCA) was run on 18 identified coffee compounds after normalization for total signal intensity. The three first principal components were driven by roasting intensity (41% variance), type of coffee beans (29%), and caffeine (8%). These variations were mainly explained by hydroxycinnamoyl esters and diketopiperazines (roasting), N-caffeoyltryptophan, N-
coumaroyltryptophan, feruloylquinic acids, and theophylline (coffee bean variety) and theobromine (decaffeination). Instant coffees differed from all coffee brews by high contents of diketopiperazines, suggesting a higher roast of the extracted beans. These variations will be important to consider for understanding the effects of different coffee brews on disease risk.
This study examines the occurrence of the artificial sweetener aspartame (E951) in foods and beverages sampled by food control authorities in Germany between 2000 and 2022. The dataset was obtained ...through the Consumer Information Act. Out of 53,116 samples analyzed, aspartame was present in 7331 samples (14%), of which 5703 samples (11%) in nine major food groups were further evaluated. The results showed that aspartame was most commonly found in powdered drink bases (84%), flavored milk drinks (78%), chewing gum (77%), and diet soft drinks (72%). In the solid food groups, the highest mean aspartame content was detected in chewing gum (1543 mg/kg,
= 241), followed by sports foods (1453 mg/kg,
= 125), fiber supplements (1248 mg/kg,
= 11), powdered drink bases (1068 mg/kg,
= 162), and candies (437 mg/kg,
= 339). Liquid products generally had the highest aspartame content in diet soft drinks (91 mg/L,
= 2021), followed by regular soft drinks (59 mg/L,
= 574), flavored milk drinks (48 mg/kg,
= 207), and mixed beer drinks (24 mg/L,
= 40). These results suggest that aspartame is commonly used in some foods and beverages in Germany. The levels of aspartame found were generally within the legal limits set by the European Union. These findings provide the first comprehensive overview of aspartame in the German food market and may be particularly useful in informing the forthcoming working groups of the WHO International Agency for Research on Cancer (IARC) and the WHO/FAO Joint Expert Committee on Food Additives (JECFA), which are in the process of evaluating the human health hazards and risks associated with the consumption of aspartame.
The intake of processed meat has been associated with several adverse health outcomes such as type II diabetes and cancer; however, the mechanisms are not fully understood. A better knowledge of the ...metabolite profiles of different processed and non-processed meat products from this heterogeneous food group could help in elucidating the mechanisms associated with these health effects. Thirty-three different commercial samples of ten processed and non-processed meat products were digested in triplicate with a standardized static in vitro digestion method in order to mimic profiles of small molecules formed in the gut upon digestion. A metabolomics approach based on high-resolution mass spectrometry was used to identify metabolite profiles specific to the various meat products. Processed meat products showed metabolite profiles clearly distinct from those of non-processed meat. Several discriminant features related to either specific ingredients or processing methods were identified. Those were, in particular, syringol compounds deposited in meat during smoking, biogenic amines formed during meat fermentation and piperine and related compounds characteristic of pepper used as an ingredient. These metabolites, characteristic of specific processed meat products, might be used as potential biomarkers of intake for these foods. They may also help in understanding the mechanisms linking processed meat intake and adverse health outcomes such as cancer.
Under the current EU chemicals legislation, in vitro test methods became the preferred methods to identify and classify the skin irritation potential of chemicals and mixtures. Among these, ...especially in vitro skin models are widely used. For surfactants, a well-known group of typically irritating chemicals, it is a long-standing experience that the irritation potential of a mixture of surfactants is typically lower than the irritation potential of the single surfactants, an effect usually described as surfactant antagonism. In order to evaluate if this effect can be observed in skin model systems as well, the irritation potential of the surfactants and of their mixtures was determined in the Open Source Reconstructed Epidermis (OS-REp) models. Combinations of sodium dodecyl sulfate or linear alkylbenzene sulfonate with cocoamidopropyl betain and alkyl polyglycosid, respectively, resulted in a clear decrease of the irritation potential compared to the irritation exerted by the single surfactants. The effect appeared to be primarily driven by the mixture's lower ability to damage the skin model's barrier, as shown by a reduced fluorescein permeation.
•Surfactant antagonism was demonstrated with the Open Source Reconstructed Epidermis (OS-REp) model•Mixing a skin irritating surfactant with a milder one decreases barrier disintegration of epidermis models and increases tissue viability•No surfactant antagonism was detected in keratinocyte 2D cultures, suggesting a role of the skin barrier for this effect
Applications for fluoropolymers and PFOA include surface coatings for stain, oil, and water resistance on household products, carpets, textiles, and food packaging; personal care products; seals; ...coatings for cables and wires; and construction materials. Since the previous classification of PFOA (as “possibly carcinogenic to humans”, Group 2B) by the IARC Monographs in 2014,2 many new studies have investigated the association between exposure to PFOA and cancer in experimental animals and humans, as well as mechanistic endpoints relevant to the key characteristics of carcinogens. ...PFOA induces oxidative stress, modulates receptor-mediated effects (via PPARα, CAR/PXR, and PPARγ), and alters cell proliferation, cell death, and nutrient and energy supply in human primary cells and experimental systems. For testicular cancer, additional evidence was a positive association in an ecological analysis conducted by the Working Group of available data on orchiectomies from the Veneto region of Italy, and a US study finding no associations.9 For all other cancers, the evidence was “inadequate”, as there were only sporadic positive findings.
In June, 2022, 25 scientists from eight countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to finalise their evaluation of the carcinogenicity of occupational ...exposure as a firefighter. Firefighters can be exposed to combustion products from fires (eg, polycyclic aromatic hydrocarbons PAHs and particulates), building materials (eg, asbestos), chemicals in firefighting foams (eg, perfluorinated and polyfluorinated substances PFAS), flame retardants, diesel exhaust, and other hazards (eg, night shift work and ultraviolet or other radiation). Dermal absorption of chemicals can occur even in firefighters wearing PPE due to limitations of its design, fit, maintenance, or decontamination. Since the previous classification of firefighting (as “possibly carcinogenic to humans,” Group 2B) by the IARC Monographs in 2007,2 many new studies have investigated the association between occupational exposure as a firefighter and cancer risk in humans. Airway and systemic inflammatory markers, such as IL-6 and IL-8, were associated with firefighting-related exposures. ...declines in lung function associated with changes in inflammatory markers and exposure-associated bronchial hyperreactivity were reported in firefighters.
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