Exposure assessment of titanium dioxide via drugs available on the French market: A nationwide descriptive study.

PURPOSE: Based on potential adverse health effects including genotoxicity concerns, the European Union banned titanium dioxide (TiO2) as a food additive in 2022, but food-grade TiO2 can still be used in pharmaceutical products. METHODS: This study described the presence of TiO2 in drugs available on the French market and estimated the population exposure to TiO2 through drug consumption. We used annual drug claim data aggregated at the national level together with data on the TiO2 content of pharmaceutical products available on the French market in 2001-2020. RESULTS: Of the 17 171 pharmaceutical specialties identified on the French market between 2001 and 2020, 38% contained TiO2. That figure reached 95% for capsules, 92% for film-coated tablets, 74% for coated tablets and 66% for soft capsules. Only 1% of non-oral specialties contained TiO2. The median TiO2 amount in one common dispensing unit was 1.5mg for oral specialties containing TiO2. We estimated that the mean exposure to TiO2 per inhabitant through the consumption of reimbursed drugs between 2012 and 2020 was 1.71mg per day, with women (1.81mg/d) slightly more exposed than men (1.54mg/d) and people older than 59 years (4.00mg/d) much more exposed than younger people (1.24 and 0.21mg/d for 20-59 and<20 years old individuals, respectively). CONCLUSION: This study highlights a widespread presence of TiO2 in drugs on the French market. The health impact of exposure to TiO2 through drug consumption should be evaluated in future epidemiological studies.

The mode of action of different organochlorine pesticides families in mammalians.

Organochlorine pesticides (OCPs) show differences in their chemical structure, mechanism of toxicity, and target organisms. However, OCPs also have some common characteristics such as high persistence in the environment, bioaccumulation, and toxicity which lead to health issues. Nowadays, the toxicity of OCPs is well known, but we still do not know all the specific molecular mechanisms leading to their toxicity in mammalians. Therefore, this review aims to collect data about the mode of action of various classes of OCPs, highlighting their differences and common behavioural reactions in the human and animal body. To discuss the OCPs molecular pathways and fate in different systems of the body, three organochlorine insecticides were selected (Dichlorodiphenyltrichloroethane, Hexachlorocyclohexane and Chlordecone), regarding to their widespread use, with consequent effects on the ecosystem and human health. Their common biological responses at the molecular scale and their different interactions in human and animal bodies were highlighted and presented.

Educational level and characteristics of invasive breast cancer: findings from a French prospective cohort.

PURPOSE: Breast cancer (BC) characteristics are known to influence patients survival. Social differences have been reported by previous studies for those characteristics but questions persist because of inconsistent conclusions. We aimed to investigate the impact of education on BC stage, grade, and hormone receptor (HR) status, while adjusting for potential confounders including a broad set of health behaviors, anthropometric measures, and reproductive factors. METHODS: In the French E3N cohort, 5236 women developed a primary invasive BC for which there was available information on stage, grade, and HR status. No multivariate analyses was performed for BC stage based on the lack of association in bivariate analyses. Odds ratios and confidence intervals were estimated using multinomial logistic regression models for BC grade or binomial logistic regression models for HR status of BC. RESULTS: Women with a lower education were diagnosed with higher grade BC compared to women with a higher education (1.32 [1.12; 1.57]). This association was slightly attenuated after adjustment for covariates independently and more strongly affected in the fully adjusted model (1.20 [0.99; 1.45]). A significant association was observed between lower education and HR- status of BC (1.20 [1.02; 1.42]) attenuated after adjustment for age at first childbirth (1.12 [0.95; 1.33]). CONCLUSION: In this cohort, education was associated with BC grade and HR status but not stage at diagnosis. The link between education and BC grade was not entirely explained by the different adjustments. A specific mechanism could be at play and deserves further investigations.

BMI and breast cancer risk around age at menopause.

BACKGROUND: A high body mass index (BMI, kg/m2) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology. METHODS: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy. RESULTS: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO. CONCLUSION: The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.

Lifestyle changes in middle age and risk of cancer: evidence from the European Prospective Investigation into Cancer and Nutrition.

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers-including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others-using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95-0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07-1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65-0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.