Endocrine Disruptors and Prostate Cancer.

The role of endocrine disruptors (EDs) in the human prostate gland is an overlooked issue even though the prostate is essential for male fertility. From experimental models, it is known that EDs can influence several molecular mechanisms involved in prostate homeostasis and diseases, including prostate cancer (PCa), one of the most common cancers in the male, whose onset and progression is characterized by the deregulation of several cellular pathways including androgen receptor (AR) signaling. The prostate gland essentiality relies on its function to produce and secrete the prostatic fluid, a component of the seminal fluid, needed to keep alive and functional sperms upon ejaculation. In physiological condition, in the prostate epithelium the more-active androgen, the 5α-dihydrotestosterone (DHT), formed from testosterone (T) by the 5α-reductase enzyme (SRD5A), binds to AR and, upon homodimerization and nuclear translocation, recognizes the promoter of target genes modulating them. In pathological conditions, AR mutations and/or less specific AR binding by ligands modulate differently targeted genes leading to an altered regulation of cell proliferation and triggering PCa onset and development. EDs acting on the AR-dependent signaling within the prostate gland can contribute to the PCa onset and to exacerbating its development.

Application of a risk-based standardized animal biomonitoring approach to contaminated sites.

Biomonitoring has been used to disclose the public health impact of contaminated sites. This study aimed at setting up good practices to apply biomonitoring targeting animal matrixes to design risk-based surveillance and exposure assessment plans. A nine-step protocol targeting farmed animals was devised and tested in three case study areas including (1) a waste dump, (2) a waste incinerator, and (3) a secondary aluminum smelter. Between 2010 and 2012, in each study area, the following 9-step best practices were applied: hazard identification, GIS project creation, risk area delimitation, control area selection, receptors (livestock) identification, farms and matrixes selection, sampling study design, on-farm secondary sources exclusion, and statistical and geostatistical analysis. Dairy farms and free-range laying hens were the primary targets: eggs from both risk and control areas and milk from risk areas were sampled and submitted for detection of selected tracking contaminants compatible with the putative sources. Comparison data (risk vs. control) of heavy metal concentrations in eggs were available only for case study 2, whereas egg comparison data of persistent organic pollutants were available for all the risk-control pairs. After taking into account potential secondary sources, no concern from metals was arisen, whereas high concentrations of persistent organic pollutants were detected in all risk areas; however, only for the aluminum smelter case study, the contamination was broad and higher in the risk area compared with the control one. The protocol has proved to be easily applicable and flexible to varying contexts and able to provide helpful data to inform risk management decisions.

Individual methylmercury intake estimates from local seafood of the Mediterranean Sea, in Italy.

A Seafood Frequency Questionnaire (SFQ) broken down in more than 42 items with 8-week coverage was interview-administered to 278 adults aged 19-82years (167 women, 98 in the reproductive age 19-45years, and 111 men), resident on the Italian Mediterranean shore and frequent buyer at local fish markets. Methylmercury (MeHg) intake on individual basis was estimated for a selected occurrence equal to the median value+Median Absolute Deviation (MAD) in each seafood species reported (conservative scenario). MeHg occurrence was derived from an extensive seafood database referred to years 2009-2011. Accounting for an average body weight of 62.2kg, 24.6% of women resulted overexposed with respect to the European Food Safety Authority (EFSA) Tolerable Weekly Intake (TWI) for MeHg of 1.3µg/kg bw, with a mean of 0.92µg/kg bw. In the vulnerable group aged 19-45years, 29.6% exceeded the TWI. Rather than the amount of seafood consumed, the seafood choice appears to be the main determinant of the MeHg intake. Risk awareness was reported in the 49% of SFQs. Uncertainties related to such estimates from questionnaires are discussed, in order to give adequate health recommendations without compromising seafood consumption in the Mediterranean region.

Heavy metals and trace elements in milk and dairy products in the Lazio region (Central Italy).

A study was carried out to determine the concentration of heavy metals and trace elements in milk and dairy products collected from local farms, supermarkets, or food retailers in the region of Lazio (Central Italy). Persistent exposure to metal contamination is of particular concern for human health, as it can cause different serious disorders. The monitoring of the matrices studied is therefore important, given their high consumption in the daily diet. The elements determined by ICP-MS (Inductively Coupled Plasma - Mass Spectrometry) were lead (Pb), arsenic (As), mercury (Hg), cadmium (Cd), chromium (Cr), nickel (Ni), molybdenum (Mo) and thallium (Tl), for a total of 151 measurements in 98 samples. The results showed that 11.3% of the measurements were quantifiable but below the legal maximum limits (MLs) set by EU regulations. The data obtained may be useful for dietary exposure information, inter-regional comparisons and for planning regional surveillance strategies.

Overview of human health effects related to glyphosate exposure.

Glyphosate is a chemical compound derived from glycine, marketed as a broad-spectrum herbicide, and represents one of the most widely used pesticides in the world. For a long time, it was assumed that glyphosate was harmless, either due to its selective enzymatic acting method on plants, and because commercial formulations were believed to contain only inert chemicals. Glyphosate is widely spread in the environment, the general population is daily exposed to it via different routes, including the consumption of both plant, and non-plant based foods. Glyphosate has been detected in high amounts in workers' urine, but has been detected likewise in bodily fluids, such as blood and maternal milk, and also in 60%-80% of general population, including children. Considering its massive presence, daily exposure to glyphosate could be considered a health risk for humans. Indeed, in 2015, the IARC (International Agency for Research on Cancer) classified glyphosate and its derivatives in Group 2A, as probable human carcinogens. In 2022, nevertheless, EFSA (European Food Safety Authority) stated that the available data did not provide sufficient evidence to prove the mutagenic/carcinogenic effects of glyphosate. Therefore, the European Commission (EC) decided to renew the approval of glyphosate for another 10 years. The purpose of this review is to examine the scientific literature, focusing on potential risks to human health arising from exposure to glyphosate, its metabolites and its commercial products (e.g., Roundup®), with particular regard to its mutagenic and carcinogenic potential and its effects as endocrine disrupter (ED) especially in the human reproductive system.

Mercury occurrence in Italian seafood from the Mediterranean Sea and possible intake scenarios of the Italian coastal population.

Mercury (Hg) settlements in the Mediterranean Sea determine a potential toxicological relevance of seafood intakes for coastal populations. To assess this possibility, fish, molluscs, and crustaceans of commercial size of 69 different species were sampled and analyzed for total mercury (Hg(TOT)) from georeferenced areas and evaluated for their compliance with the European Union Maximum Residue Limits of 0.5 and 1.0 mg/kg wet weight (ww). Accounting for the weekly estimated seafood intake in the Italian coastal population (mean 469-626 g/person/week) it was then possible to recover threshold contamination values in seafood. Under a Tolerable Weekly Intake of 1.3 µg/kg/bw/week, a threshold seafood contamination <0.10 mg/kg ww has been derived for sensitive groups. A suitable algorithm based on the parallel MeHg and Hg(TOT) analysis on the most consumed species, helped to refine the uncertainties related to the conservative assumption in seafood all the Hg(TOT) present is in form of MeHg. This work aims to improve the link between the risk management and risk assessment strategies, with the identification of those fish and seafood species, that, when regularly consumed, could determine or prevent potential Hg(TOT)/MeHg overintakes in sensitive groups.

[Beta-hexachlorocyclohexane contamination in dairy farms of the Sacco River Valley, Latium, Italy, 2005. A retrospective cohort study]. / Contaminazione da beta-esaclorocicloesano delle aziende bovine da latte della Valle del Sacco (Lazio). Gestione dell'emergenza 2005 e conseguente studio di coorte retrospettivo.

OBJECTIVE: in March 2005, the Italian National Monitoring System on Chemical Residuals in Food of Animal Origin detected levels of the pesticide beta-hexachlorocyclohexane (ß-HCH) that were 20 times higher than the legal limit of 0.003 mg/kg in bulk milk from a dairy farm in the Sacco River valley. ß-HCH, a lindane isomer and possible human carcinogen, was subsequently found in milk from several neighboring farms. A study was therefore undertaken to evaluate the extent and risk factors for contamination. DESIGN: all dairy cattle farms in the valley were enrolled in a retrospective cohort study and their bulk milk analyzed for ß-HCH. A questionnaire was administered to farmers to evaluate possible exposure factors. SETTING AND PARTICIPANTS: cases: dairy farms with at least one result indicating ß-HCH ≥ 0.002 mg/kg in bulk milk during the period april-june 2005; exposure: feeding animals on fodder cultivated in soils watered with and/or flooded by river water; participants: IZSLT, RMG Local Health Unit, FR Local Health Unit. MAIN OUTCOME MEASURES: attack rate, relative risk, attributable proportion among exposed. RESULTS: of 244 farms tested, 34 met the case definition (attack rate 14%). The exposure to fodder cultivated in soils watered with and/or flooded by river water was observed in 33/34 (97%) case-farms and in 23/210 (10.9%) of those with contamination <0.002 mg/kg in bulk milk (RR 110.8; 95%CI 15.5- 792). Attributable proportion among exposed was more than 99%. CONCLUSION: fodder cultivated near a contaminated river was the main risk factor for ß-HCH contaminated milk. On the basis of the epidemiologic evidence and laboratory testing, watering local fields with river water and production of fodder in farms with contaminated soil was banned, and all the animals from positive farms were culled.

Monitoring honey bee health in five natural protected areas in Italy.

The health status of the honey bee populations has attracted a great amount of interest in recent years. We investigated honey bee health in five natural protected areas in Italy from October 2009 to December 2010. Areas were selected to represent a wide range of bio­geographical zones including alpine, continental, and Mediterranean. Within each of these natural protected areas, one apiary of 20 colonies near potential pollution sources (e.g., agricultural areas, industrial areas, or urban settlements) and another apiary of 20 colonies far from possible sources of pollutants have been placed. To monitor honey bee health, colony mortality was related to: honey bee pathologies, environment (Naturality Index, plant protection products and heavy metal exposure), and apiary management. Anthropogenic pollutants and pathogens did not have significant effects on colony mortality while environment and the poor colony management skills of the beekeepers did.

PCDD and PCDF depletion in milk from dairy cows according to the herd metabolic scenario.

High level of PCDD+PCDF contamination in bulk milk (9.7 pg WHO-TE g(-1) fat) from 1604 Holstein Fresian lactacting cows was observed just four weeks after the beginning of their exposure to a feed supplement contaminated at 10.4 ng WHO-TE kg(-1) dry matter. In-farm produced hay and silage showed levels not exceeding 0.2 ng WHO-TE kg(-1) dry matter. After the supplement withdrawal, it was possible to monitor the depletion phase for a following 75-day period in milk, until the levels dropped well below 3.0 pg WHO-TE g(-1) fat, the EU regulatory Maximum Residue Level for PCDD+PCDF. During this phase, the half-life was calculated as 17+/-3 days, on WHO-TEQ basis. The full availability of farm data on both cow nutrition and milk production allowed the calculation of the carry-over rate (COR) (PCDD+PCDF milk excretion vs. feed), which was 46% at the end of the exposure. This COR value is justified from the main TE contribution of Penta-CDD and -CDF congeners (63%), and the half-life is among the shortest of all those described in the literature both for experimental and naturally-exposed dairy cows. A fugacity-based model predicts a bulk milk contamination of 5 pg WHO-TE g(-1) fat, compared to the 10 pg WHO-TE g(-1) fat level observed. Such findings are discussed in light of the lactation and metabolic status of the herd for which the transition period, characterised by a negative metabolic energy balance and a consequent adipose tissue mobilization, could play a relevant role.

Intake estimates of dioxins and dioxin-like polychlorobiphenyls in the Italian general population from the 2013-2016 results of official monitoring plans in food.

The implementation of the European Union strategy for polychlorodibenzo-dioxins and -furans (PCDD/Fs), and dioxin-like polychlorobiphenyls (DL-PCBs) is determining a general reduction of their presence in the environment and in the food chain. The most important route for human exposure to these substances is food consumption and, as a consequence, a progressive decrease of their dietary intake has been observed in the last decades. In this context, it seemed worth updating the PCDD/F and DL-PCB intake estimation for the Italian population. A total of 2659 samples of food of animal and vegetable origin analyzed for PCDD/Fs and DL-PCBs in the period 2013-2016 by accredited official laboratories and the national food consumption database were considered for the dietary intake assessment in different age groups of the Italian general population The median cumulative intake estimates expressed as pg WHO-TEQ/kg body weight per day and computed with a deterministic and a probabilistic approach were 1.40-1.52 for children, 0.82-0.85 for adolescents, and 0.64-0.61 for adults, respectively. Such results confirm the decreasing trend of PCDD/F and DL-PCB dietary intake even though the Tolerable Daily Intake (TDI) value of 2 WHO-TEQ/kg body weight per day is exceeded at the 95th percentile for all age groups, with children as sensitive group. Most contributing food categories to the intake resulted fish, food of vegetable origin, and cheese. A sensitivity analysis was also performed to calculate the target contamination levels able to keep the dietary exposure below the TDI. Computed target levels fall between P50 and P97 of the occurrence distribution of the main food groups, meaning that most of the Italian food production can be considered safe.

Measurements of ß and α hexachlorocyclohexane in Juglans regia and Prunus spinosa trees in a contaminated area, central Italy.

Vegetables play an important role in the human diet, and the transfer of toxic contaminants from the soil to plants has been little studied for most tree species and their edible portions. In an area affected by hexachlorocyclohexane (HCH) contamination, in the Sacco River Valley (central Italy), measurements of ß- and α-HCH isomers were made on different parts of two tree species: Juglans regia and Prunus spinosa. Concentrations were analysed in roots, branches, leaves, fruits, and seeds. A spatial evaluation of the results highlighted an inverse association of contamination with distance from the river, which is the main route of transport in the environment. Results in J. regia showed decreasing values in this order: branches > leaves > husks > nutmeat. Results in P. spinosa showed decreasing values in the following order: branches > leaves > fruits. In J. regia, nutmeat values were all below limit of detection (LOD, 0.0005 mg/kg), except in one case in which a very low concentration of ß-HCH was found (0.006 mg/Kg), compliant with maximum residue limits (MRLs). The ability of J. regia to store large quantities of ß-HCH in wooden and leafy parts but not in edible kernels makes this plant a potential and precious tool in remediation and economical reconversion of polluted areas. It is also valuable for food and wood manufacturing.

Metals in Mediterranean aquatic species.

Metals such as arsenic (As), cadmium (Cd), copper (Cu), chromium (Cr), nickel (Ni), lead (Pb), vanadium (V), have been determined in species of Mediterranean marine organisms collected from areas supposed to be at background contamination levels. The Inductively Coupled Plasma Mass Spectrometry (ICP-MS) approach was adopted for the determination of all the metals. Arsenic, Cd and Pb determined in the 42 samples, do not exceed the pertinent maximum level except a sample of hake. In wild fish, the concentration range for Cr, Ni, V and Cu was, respectively: 0.07-0.09, 87.6-124, 0.022-0.075 and 0.79-1.74 µg/g fresh weight (fw). The farmed fish samples show concentration levels below the wild fish ones, except for Cr which range at the same levels. Cadmium and Pb show a high sample number under the quantification limit. The elements do not bio-magnify among the species considered and appear to show low variations in relation to organisms' position in the food chain and at sampling sites.

Data on milk dioxin contamination linked with the location of fodder croplands allow to hypothesize the origin of the pollution source in an Italian valley.

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) have similar toxic, endocrine-disrupting, and carcinogenic activity. They are classified as persistent organic pollutants accumulating in the environment and the tissues of living organisms. High concentrations of PCDD/F and dl-PCB have been detected in bovine milk collected in a Piedmont valley (Northwestern Italy) since 2004. This geographic study describes the local distribution of pollution from PCDD/Fs and dl-PCBs. Since their presence in animal products could be traced back to the ingestion of contaminated fodder, dioxin levels in cow milk were related to the distribution of fodder cropland parcels. Specifically, the aim of the study was to determine, through an exploratory approach, whether the contamination was consistent with one common point source of contamination or different scattered sources. Data for PCDD/F and dl-PCB concentrations in the bulk milk from 27 herds, sampled over a 4-year period (2004-2007), were matched to the georeferenced land parcels the dairy farmers used for growing fodder. Isopleth maps of dioxin concentrations were estimated with ordinary kriging. The highest level of pollution for both PCDD/Fs and dl-PCBs was geographically juxtaposed: in both instances, the location of the local steel plant was within this extremely highly polluted area. The study results support the hypothesis for one common point source of contamination in the valley. The exploratory spatial analysis applied in this research may provide a valuable, novel approach to straightforward identification of a highly likely source of dioxin contamination of dairy products (even in the absence of top soil contamination data).

Persistent toxic substances in Mediterranean aquatic species.

Fish and fishery products may represent one of the main sources of dietary exposure to persistent toxic substances (PTSs) such as polychlorinated dibenzodioxins, dibenzofurans, and biphenyls; polybromodiphenyl ethers; organochlorine pesticides; perfluorooctanoic acid and perfluorooctane sulfonate; and inorganic mercury and methyl mercury. In this study, PTS contamination of Mediterranean fish and crustaceans caught in Italian coastal waters was investigated in order to increase the representativeness of the occurrence database for wild species. The objectives were to verify the suitability of regulatory limits for PTSs, identify background concentrations values, if any, and examine the possible sources of variability when assessing the chemical body burdens of aquatic species. Twelve wild species of commercial interest and two farmed fish species were chosen. Excluding methyl mercury, chemical concentrations found in wild species fell generally towards the low ends of the concentration ranges found in Europe according to EFSA database and were quite lower than the tolerable maximum levels established in the European Union; farmed fish always showed contamination levels quite lower than those detected in wild species. The data obtained for wild species seemed to confirm the absence of local sources of contamination in the chosen sampling areas; however, species contamination could exceed regulatory levels even in the absence of specific local sources of contamination as a result of the position in the food web and natural variability in species' lifestyle. A species-specific approach to the management of contamination in aquatic organisms is therefore suggested as an alternative to a general approach based only on contaminant body burden. A chemical-specific analysis performed according to organism position in the food chain strengthened the need to develop this approach.

A spatial, statistical approach to map the risk of milk contamination by β-hexachlorocyclohexane in dairy farms.

In May 2005, beta-hexachlorocyclohexane (ß-HCH) was found in a sample of bovine bulk milk from a farm in the Sacco River valley (Latium region, central Italy). The primary source of contamination was suspected to be industrial discharge into the environment with the Sacco River as the main mean of dispersion. Since then, a surveillance programme on bulk milk of the local farms was carried out by the veterinary services. In order to estimate the spatial probability of ß- HCH contamination of milk produced in the Sacco River valley and draw probability maps of contamination, probability maps of ß-HCH values in milk were estimated by indicator kriging (IK), a geo-statistical estimator, and traditional logistic regression (LR) combined with a geographical information systems approach. The former technique produces a spatial view of probabilities above a specific threshold at non-sampled locations on the basis of observed values in the area, while LR gives the probabilities in specific locations on the basis of certain environmental predictors, namely the distance from the river, the distance from the pollution site, the elevation above the river level and the intrinsic vulnerability of hydro-geological formations. Based on the ß-HCH data from 2005 in the Sacco River valley, the two techniques resulted in similar maps of high risk of milk contamination. However, unlike the IK method, the LR model was capable of estimating coefficients that could be used in case of future pollution episodes. The approach presented produces probability maps and define high-risk areas already in the early stages of an emergency before sampling operations have been carried out.