Cocktails of endocrine disruptors in the different diets of French consumers.

With a view to identifying main endocrine disruptors (ED) mixtures to which French consumers are exposed through food, their main diets were modelled using an adapted dimension reduction method. Seven specific diets could be modelled for adults while only one overall diet was considered for children aged 3-17 years. The knowledge of the contamination levels of 78 known or suspected endocrine disrupting compounds in the foods constituting these diets, collected in the frame of the second French Total Diet Study, made it possible to explore the mixtures of EDs to which consumers are exposed. We have thus shown that the ED substances most present in mass concentration are comparable for the whole population, whatever the diet considered. However, a second approach made it possible to highlight, for a given diet, the substances whose exposure is statistically higher than in the diet of the general population. Thus, significantly different ED mixtures could be established for each diet. For example, diets with a high proportion of animal-based foods induce significantly higher exposures to some persistent organic pollutants (e.g., PCDD/F, brominated flame retardants), whereas these exposures are lower for Mediterranean-type diet. On the other hand, the latter, richer in fruits and vegetables, is the one for which pesticides represent a specific signature.These results now pave the way for studying the specific effects of these cocktails of endocrine disruptors, each of which is representative of a type of chronic exposure linked to specific diets.

Sensitivity of fecal immunochemical test and risk factors for interval colorectal cancer in a French population.

BACKGROUND: Colorectal cancer (CRC) screening using fecal immunochemical testing (FIT) aims to detect pre-symptomatic colorectal lesions and reduce CRC mortality. AIMS: The objectives of this study were to determine the FIT sensitivity for diagnosis of CRC, the impact of diagnostic circumstances on treatment and survival, and risk factors for interval cancer (IC). METHODS: This population-based study evaluated the 2016-2017 CRC screening campaign in Finistère, France. CRCs were classified according to diagnostic circumstances: screen-detected CRC (SD-CRC), CRC with delayed diagnosis, IC after negative FIT (FIT-IC), post-colonoscopy CRC, CRC in non-responders and CRC in the excluded population. RESULTS: This study included 909 CRCs: 248 SD-CRCs (6% of positive FIT) and 60 FIT-ICs (0.07% of negative FIT). The FIT sensitivity for CRC was 80.5% (CI95%: 76.1-84.9) at the threshold of 30 µg hemoglobin/g feces used in France. In multivariate analysis, proximal (OR:6.73) and rectal locations (OR:7.52) were associated with being diagnosed with FIT-IC rather than SD-CRC. The FIT positivity threshold maximizing the sum of sensitivity and specificity was found to be 17 µg/g, with 14 additional CRCs diagnosed compared to the current threshold. CONCLUSIONS: Our study confirms the good sensitivity of FIT. A decrease of the FIT detection threshold could optimize sensitivity.

Factors associated with non-presentation in a multidisciplinary team meeting for colon cancer: A matched retrospective cohort study in a French area.

BACKGROUND: Survival of patients with colon cancer has increased in recent years due to advances in treatment and the implementation of multidisciplinary team meetings (MDTm). However, the organization of MDTm can be improved. The objectives of this work were to characterize patients with colon cancer who were not presented in MDTm and to analyse the reasons for their non-presentation. METHODS: The study was based on a retrospective cohort including patients with colon cancer diagnosed between 2014 and 2016. Risk factors for non-presentation in MDTm were investigated after 1:1 matching on age, gender and tumour location, using multivariate analysis. RESULTS: amongst 1616 patients diagnosed with colon cancer, 20.5% were not presented in MDTm. The most common reasons for non-presentation were 'advanced age or poor general condition' (22.6%) and 'superficial tumour' (20.5%), while 20.8% of non-presentation remained unexplained. Non-presentation in MDTm was associated with ECOG PS of 2 (OR 0.51, 95%CI 0.32-0.81, p = 0.005), best supportive care (OR 0.05, 95%CI 0.00-0.38, p = 0.016) and early death (OR 0.09, 95%CI 0.04-0.19, p<0.001). By contrast, patients with symptomatic tumours were more likely to be presented in MDTm than patients participating in mass screening (OR 2.16, 95%CI 1.09-4.32, p = 0.028). Presentation was significantly associated with diagnosis by a digestive surgeon (OR 2.16, 95%CI 1.22-3.92, p = 0.01) and a high UICC stage. CONCLUSIONS: This study identified factors associated with non-presentation in a multidisciplinary team meeting for colon cancer such as an advanced age or a superficial tumour, paving the way for targeted improvements.

Impact of sociodemographic profile, generation and bioaccumulation on lifetime dietary and internal exposures to PCBs.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants triggering numerous adverse effects. Because they are present in various food, dietary exposure of the population to these contaminants must be estimated to assess the related health risk. However, the classical risk assessment approach allows only short-term estimates of exposure and does not account for dietary changes, evolution of food contaminations and bioaccumulation of PCBs through life. The approach presented here assesses lifetime PCB exposure trajectories according to birth year and individual sociodemographic profiles. Moreover, a physiologically based toxicokinetic model was developed to simulate lifetime PCB plasma concentrations, while considering physiological changes with age. A focus on the long-term impact of breastfeeding is also presented in order to consider the risk related to PCBs and due to the mother-to-child transfer. For example, the exposure of an individual born in 1972 exceeds the critical value of 20 ng PCB/kg bw/day half as often as an individual born in 1932 throughout their lifetime but 13 times more often than an individual born in 2012, according to our simulations. In addition, even if breastfeeding clearly leads to much higher dietary exposures than formula feeding, the long-term impact on PCB body burden remains negligible. Risk assessment related to PCB lifetime trajectories is described and discussed.

Lifetime dietary exposure to bisphenol A in the general population and during pregnancy: Foetal exposure and health risk assessment.

Bisphenol A is a well-known chemical substance triggering reprotoxic and endocrine disruptor effects. Pregnancy is considered as a critical period of exposure to BPA because of the foetal sensitivity to endocrine disruption. Because of its wide use in food packaging, BPA is found in common foods and in infant formulae. We used a lifetime approach to simulate dietary exposure trajectories of a French population and to assess the associated health risk. Moreover, a semi-physiological based toxicokinetic model was used to simulate the maternal-foetal exchanges of BPA during pregnancy. Metabolism was taken into account by considering the glucuronidation of BPA by the foetal-placental unit, as well as the reactivation of BPA-glucuronide into BPA in the foetal compartment. From maternal critical daily exposures defined by ANSES based on effects for different endpoints of BPA in the unborn child (i.e. 0.083, 0.17, 0.29 and 0.33 µg/kg bw/d, respectively based on effects on mammary gland, brain and behaviour, metabolism and obesity and female reproductive system), resulting concentrations of BPA in the foetal compartment were estimated and health risk was assessed for the sub-population of unborn children. This work leads to the conclusion that while a health risk due to dietary exposures of the general population can be excluded, this is not the case for the sub-population of pregnant women, in view of the levels of foetal exposure to BPA.

Impact of dietary guidelines on lifetime exposure to chemical contaminants: Divergent conclusions for two bioaccumulative substances.

Food based dietary guidelines (FBDGs) are developed to promote appropriate nutrients intake. However, FBDGs may trigger higher exposure to some food chemical contaminants while recommending the consumption of specific food groups that are more contaminated than others. In some cases, the balance between benefits and risks is difficult to achieve. In the present article, we describe the long-term impact of some FBDGs on the exposure to food contaminants. Two examples of bioaccumulative substances were studied: cadmium and PCBs. To this aim, lifetime dietary exposure trajectories were simulated for two populations: the first representing the general French population, the second generated using virtual individuals following national FBDGs during their entire life. Exposure trajectories were then converted into lifetime cadmium and PCB internal concentrations using physiologically based toxicokinetic models. Finally, trajectories were compared with reference values to assess the health risk related to dietary exposures to cadmium and PCBs, for both simulated populations. This work highlights that FBDGs may have a major impact on PCB dietary exposures and lead to significantly higher PCB plasma concentrations than those observed in the general population. In contrast, cadmium exposure is only slightly impacted when FBDGs are followed. This underscores the relevance of taking into account lifetime exposures when establishing FBDGs.

Dietary risk assessment methodology: how to deal with changes through life.

Chemicals are present in food and numerous methods have been developed to assess dietary risk associated with these substances, but mainly by studying short periods of exposure. Usually, consumption data used to assess the risk are collected over a short period-of-time. The aim of this paper was to compile existing methods to assess dietary risk and identify their limitations in terms of lifetime risk assessment. To this end, we reviewed the different methods currently used at each step of risk assessment (i.e. methods to collect consumption data, to compute dietary exposures, and then to interpret these exposures in terms of risk for the consumer). Numerous methodologies exist to collect consumption data, contamination data collection, as well as for data treatment and interpretation. These methods consider different hypotheses and therefore lead to numerous uncertainties and discrepancies in the estimation of the exposure. Moreover, changes in eating habits through life, evolutions of food contamination, as well as health risk induced by fluctuating exposures, are rarely studied. A scientific consensus on the current risk assessment approaches is needed between national regulatory authorities. Moreover, additional research activities appear needed to take the evolution of consumption and contamination through time into account and to be able to assess the dietary health risk over the entire life.

A method to assess lifetime dietary risk: Example of cadmium exposure.

Usually health risk related to food contaminants is assessed based on consumption data collected on a few days. Consequently, this approach considers neither the evolution of exposures over time nor the potential accumulation of the substance. The aim of the present study was to develop a method to assess lifetime dietary risk due to cadmium exposure. Three methods were compared, respectively based on age, dietary pattern and sociodemographic characteristics. Additionally, exposure trajectories were converted into cadmium body burden trajectories using a PBTK-TD model ultimately predicting the occurrence of renal effects. It was shown that dietary exposures to cadmium, as well as exceedances of health based guidance values, greatly vary with age and individual profiles. The developed methods allowed identifying parameters affecting dietary exposure to cadmium and distinguishing at-risk subpopulations. Furthermore, this study demonstrated that it is necessary to consider individual changes through life and kinetic of the substance to assess risk properly.