Search

Phthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors and lead to metabolic diseases. During the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di(2-ethylhexyl)phthalate (DEHP) metabolites in 900 Italian women representative of the Italian female adult population (living in the north, centre, and south of Italy in both rural and urban areas). The whole cohort was exposed to DEHP and BPA with measurable levels above limit of detection in more than 99% and 95% of the samples, respectively. The exposure patterns differed for the two chemicals in the three macro-areas with the highest urinary levels for DEHP in south compared to central and northern Italy and for BPA in northern compared to central and southern Italy. BPA levels were higher in women living in urban areas, whereas no difference between areas was observed for DEHP. The estimated daily intake of BPA was 0.11 μg/kg per day, about 36-fold below the current temporary tolerable daily intake of 4 μg/kg per day established by the EFSA in 2015. The analysis of cumulative exposure showed a positive correlation between DEHP and BPA. Further, the reduction of exposure to DEHP and BPA, through specific legislative measures, is necessary to limit the harmfulness of these substances.

Humans are exposed to residues of organophosphate and neonicotinoid pesticides, commonly used in agriculture. Children are particularly vulnerable and, among possible adverse outcomes, the increased incidence of premature mammary gland development (thelarche) has raised concern. We evaluated the toxicological effects of chlorpyrifos (CPF), imidacloprid (IMI) and glyphosate (GLY) at exposure concentrations occurring in children on the tumorigenic MCF-7 and non-tumorigenic MCF-12A breast cell lines, as representative of the target organ model, assessing cytotoxicity, apoptosis, necrosis, intracellular reactive oxygen species (ROS) and ATP levels, 17β-estradiol secretion and gene expression of nuclear receptors involved in mammary gland development. The pesticides decreased cell vitality in MCF-7 and cell proliferation in MCF-12A cells. ATP levels were decreased in MCF-7 cells by pesticides and apoptosis was increased in MCF-12A cells only by GLY (2.3 nM). ROS production was decreased by pesticides in both cell lines, except IMI (1.6 nM) in MCF-7 cells. Endocrine disrupting activity was highlighted by induction of 17β-estradiol secretion and modulation of the gene expression of estrogen alpha and beta, progesterone, androgen, and aryl hydrocarbon receptors in both cell lines. The use of MCF-7 and MCF-12A cells highlighted dissimilar modes of action of each pesticide at low human relevant concentrations.

The Bis(2-ethylhexyl)phthalate (DEHP), a widespread plasticizer, is considered an endocrine disrupting chemical with main toxicological effects on reproductive and metabolic systems. Human biomonitoring (HBM) studies are promoted to evaluate the background exposure levels. In the frame of LIFE PERSUADED project, the HBM study measured DEHP main metabolites (mono-(2-ethylhexyl) phthalate, MEHP; 2-ethyl-5-hydroxy-hexylphthalate, MEHHP; 2-ethyl-5-oxo-hexylphthalate, MEOHP) in Italian children and adolescent (4–14 years old) according to geographical macro-areas and areas, age and sex. Children from the South and the Centre of Italy showed higher median levels of DEHP, as a sum of its metabolites (48.14 and 47.80 μg/L), than those from the North (39.47 μg/L; p = 0.0090 and 0.0004, respectively). Considering the total population, boys are more exposed than girls (only as urinary volume), and children aged 4–6 years have higher median levels than those 7–10 and 11–14 years old. The derived reference values (RV95) for DEHP in children is 168 μg/L. The relative metabolic rates of DEHP, the background levels and, thus, the RV95, vary with the geographical area, age and sex, indicating that all these parameters should be considered in the risk assessment.

Several pesticides are recognized as endocrine-disrupting chemicals (EDCs) since they can interfere with the dysregulation of sexual, thyroid and neuro-endocrine hormones. Children are particularly vulnerable to the adverse effects of EDCs due to their developmental stage, peculiar lifestyle and dietary habits. In this context, the exposure to pesticides represents an important risk factor associated with early development. This study deals with the possible association between exposure to pesticides and idiopathic premature thelarche in girls from areas of intensive agriculture practice in the Centre of Italy. An integrated approach was set up, including: (i) a case-control study on girls with idiopathic premature thelarche; (ii) the evaluation of multiple pesticides exposure in girls; (iii) the evaluation of multiple pesticides in food; (iv) the dietary intake of pesticide residues; (v) the assessment of toxicological effects of widely used pesticides by in vitro model. Data integration will provide an estimate of the predictive risk of potential effects on girls’ health, linked to dietary intake.

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.

A multicenter, randomized, double-blind, placebo-controlled, cross-over clinical study was performed to determine the effects of systemic flunisolide on the symptoms of 20 children with chronic severe atopic dermatitis. The study lasted 5 weeks. Ten of the 20 patients received flunisolide for 2 weeks followed by placebo for 2 weeks; the other 10 patients received placebo for 2 weeks and then flunisolide for 2 weeks. A 1-week washout period separated the administration of each treatment. Clinical symptoms were assessed at baseline (week 0) and weeks 2, 3, and 5. Total clinical severity scores indicated a significant improvement of symptoms in patients after 2 weeks of flunisolide treatment, compared with the placebo group. After treatment with flunisolide, no worsening of symptoms or relapse occurred. In the placebo group, no significant reduction in clinical scores was observed and, moreover, three patients demonstrated worsening of symptoms during the washout period that followed the placebo treatment. However, this group had a prompt reduction in clinical scores after administration of flunisolide. No side effects were observed during the study. The data suggest that, in children with severe atopic dermatitis, short courses of flunisolide can provide relief while awaiting response to other agents or during severe exacerbations of symptoms. Thus flunisolide is an alternative to traditional oral steroids and has no noticeable side effects.

A report is given of a newborn girl with situs inversus and Turner syndrome that presented respiratory distress. The patient had a mosaic karyotype 45,X/46,X + mar (80%/20%). Ciliary motion analysis demonstrated a total absence of ciliary motion whereas, ultrastructural studies revealed typical features of primary ciliary dyskinesia (PCD) (absence or short outer/inner dynein arms in 90% of the cilia). We regard this rare combination (PCD, situs inversus and Turner syndrome) as a coincidental occurrence.

Changes in time course of blood partial pressures of oxygen (PtcO2) and carbon dioxide (PtcCO2) before, during and after challenge with ultrasonically nebulized distilled water (UNDW) were evaluated in 22 children with mild asthma in basal conditions, and after 8 weeks of therapy with inhaled nedocromil sodium at a daily dosage of 8 or 16 mg. PtcO2 and PtcCO2 were followed using transcutaneous O2 and CO2 monitoring system. All asthmatic subjects presented a significant decrease in PtcO2 and/or PtcCO2 (20% basal value) during or after challenge. After therapy, the decrease in PtcO2 and PtcCO2 was normalized in the group treated with 16 mg/day, whereas only a partial yet significant reduction in the decrease of O2 and CO2 was observed in the group assuming 8 mg/-day. These data indicate that inhaled nedocromil is effective in treating bronchial hyperresponsiveness in childhood and that the dose required to achieve this effect is of 16 mg/day.