Alberto Mantovani - Academia.edu (original) (raw)

Papers by Alberto Mantovani

Annali dell'Istituto superiore di sanità, 2015

The development of in vitro testing strategies may achieve a cost-effective generation of compreh... more The development of in vitro testing strategies may achieve a cost-effective generation of comprehensive datasets on a large number of chemicals, according to the requirements of the European Regulation REACH. Much emphasis is placed on in vitro methods based on subcellular mechanisms (e.g., nuclear receptor interaction), but it is necessary to define the predictive value of molecular or biochemical changes within an adverse outcome pathway (AOP). AOP pivots on the description of the flow from a molecular initiating event through a cascade of intermediate events needed to produce a specific adverse effect at organism level: downstream responses at cell level are, therefore, essential to define an AOP. Several in vitro assays are based on human cell lines representative of endocrine-targeted tissues (e.g., prostate) and on functional biomarkers of clinical relevance (e.g., PSA secretion in human prostate epithelial cells). We discuss the implementation of such functional biomarkers in...

NeuroToxicology, 2011

The present study was designed to investigate the adverse reproductive effects of acetamiprid, be... more The present study was designed to investigate the adverse reproductive effects of acetamiprid, besides the possible protective role of Nigella sativa oil (NSO), as a potential antioxidant agent. Thirty-two male Wistar rats were allocated into four equal groups of eight, control (CRL), acetamiprid (ACMP, 27 mg/kg), Nigella sativa oil (NSO, 0.5 ml/kg) and in combination (ACMP þ NSO). The experimental animals were dosed by gavage (5 days per week) for 45 consecutive days. Body weight gain, reproductive organs weights, sperm characteristics, testosterone, and thiobarbutiric acid-reactive substances (TBARS) levels were investigated. The obtained results showed that ACMP decreased significantly (p < 0.001) the body weight gain and the absolute weights of reproductive organs (testes, epididymis, and seminal vesicles). Furthermore, significant alterations at least (p < 0.01) in semen characteristics were noted in ACMP group as evidenced by a decline in spermatids number, sperm count, sperm motility, and testosterone level with an increase in abnormal and dead sperm and TBARS level. Treatment with NSO alone may stimulate spermatogenesis, increased significantly (p < 0.001) spermatids number and the weight of seminal vesicles. On the other hand, the co-administration of NSO along with ACMP can mitigate more efficiently and modulate in certain cases the adverse effects induced by ACMP on reproductive organs weights, semen quality, testosterone, and TBARS levels (at least p < 0.001). This obvious protective role of NSO against ACMP induced reproductive toxicity may be due to its antioxidant properties and ability to reduce TBARS levels as shown in this work.

Environmental Health and Preventive Medicine, 2003

Objective: The aim of this study was to explore the association between exposure to specific pest... more Objective: The aim of this study was to explore the association between exposure to specific pesticides (including endocrine disrupters) of greenhouse workers and spontaneous abortion in their spouses. Methods: A group of exposed workers was compared with a non-exposed group. The risk of spontaneous abortion was evaluated using a logistic regression model. Results: A significantly higher rate of spontaneous abortion was observed among spouses of workers exposed to specific compounds (atrazine, benomyl-carbendazim, carbaryl and DDT) in comparison with spouses of the unexposed group. The logistic regression model confirmed the increased risk of spontaneous abortion (OR=11.8; 95% CI 2.3-59.6). Conclusions: These findings suggest that occupational exposure to pesticides might have an adverse effect on the partner's reproductive health.

EFSA Journal, 2008

Following a request from the European Commission, the European Food Safety Authority was asked to... more Following a request from the European Commission, the European Food Safety Authority was asked to deliver a scientific opinion on the safety and efficacy of a manganese chelate of the hydroxy analogue of methionine (Mintrex ® Mn) as a feed additive for all species.

Oncology Reports, 2015

Pollutants altering the endocrine system, known as endocrine disruptors (ED), may modify the risk... more Pollutants altering the endocrine system, known as endocrine disruptors (ED), may modify the risk of female cancers. The carcinogenic effect of ED on humans has been confirmed by experimental studies for various substances including pesticides, DDT, dioxins, phthalates, bisphenol A, diethylstilbestrol, as well as heavy metals, but it is difficult to quantify precisely for several reasons hereby reviewed. Carcinogenesis is a complex and multifactorial mechanism that manifests itself over a long period of time, making difficult the detection of the specific contribution of the pollutants, whose absorbed dose is often unknown. The combined effect of various substances leads to complex interactions whose outcome is difficult to predict. These substances may accumulate and carry out their harmful effect on critical periods of life, probably also at doses considered harmless to an adult. ED can also have epigenetic adverse effects on the health of future generations. In conclusion, the carcinogenic effects of endocrine disruptors on female cancer types is plausible although additional studies are needed to clarify their mechanisms and entities. In the last part of the review we suggest ways to reduce ED exposure as it is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as the embryonic period and puberty.

Following a request from European Commission, the Panel on Additives and Products or Substances u... more Following a request from European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of 25-hydroxycholecalciferol (E 670 a) as feed additive for poultry and pigs. This additive is already authorised for use without a time limit in chickens for fattening, turkeys and laying hens. The applicant is now asking for a re-evaluation of the existing authorisation and for an extension of the authorisation to all poultry and pigs. The additive ROVIMIX ® Hy•D ® 1.25% contains 12.5 g 25-OH-D 3 kg-1 as active substance, which is a physiological precursor of the vitamin D 3 active hormone. 25-OH-D 3 from ROVIMIX ® Hy•D ® 1.25% is efficacious in all poultry species and pig categories when substituting for vitamin D 3 in feed. ROVIMIX ® Hy•D ® 1.25% is considered safe for the target animals at maximum contents of 0.100 mg 25-OH-D 3 kg-1 complete feed for chickens and turkeys for fattening, of 0.080 mg 25-OH-D 3 kg-1 complete feed for all other poultry species and of 0.050 mg 25-OH-D 3 kg-1 for all pig categories. After reassessing the in vivo toxicological studies on laboratory animals submitted, the FEEDAP Panel confirms its earlier conclusions that the 'effects seen in the toxicity studies 1 For citation purposes: Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) on a request from European Commission on the safety and efficacy of 25-hydroxycholecalciferol as feed additive for poultry and pigs. The EFSA Journal (2009) 969, 1-32 * One member of the Panel did not participate in the discussion on the subject referred to above because of possible conflicts of interest.

SUMMARY The emergence and the spread of resistance to antimicrobials in bacteria pose a threat to... more SUMMARY The emergence and the spread of resistance to antimicrobials in bacteria pose a threat to human and animal health and present a major financial cost. In an effort to decrease the development of resistance various actions have been taken at Community level, including the removal of all antibiotics used for growth promotion purposes from animal feed in 2006. With

Reproductive Toxicology, 2006

Maturation of neuroendocrine regulations is an extremely complex process made up of several stage... more Maturation of neuroendocrine regulations is an extremely complex process made up of several stages, that can be permanently affected by any exogenous substances able to interfere with the hormonal signalling at various levels. The Endocrine Disrupting Chemicals (EDCs) are a heterogeneous group of xenobiotics with potential endocrine activities which have been identified as priority risk factors in toxicological research. The present review is aimed at suggesting a number of endocrine and behavioural endpoints to be used in experimental studies to: (i) characterize more thoroughly the functional effects of developmental exposure to agents known to act as endocrine disruptors and (ii) unmask possible interferences with the maturation of the hypothalamus-hypophysis-gonad/thyroid (HHG/Th) axis by different class of xenobiotics not considered as EDCs. A combined testing strategy, considering both markers of endocrine/hormonal maturation and behavioural endpoints under hormonal control in laboratory rodents, may evidence even subtle perturbations of the neuroendocrine homeostasis, that often go undetected.

Reproductive Toxicology, 2009

Experimental and Toxicologic Pathology, 2009

EFSA Journal, 2008

Following a request from the European Commission, the European Food Safety Authority was asked to... more Following a request from the European Commission, the European Food Safety Authority was asked to deliver a scientific opinion on the safety and efficacy of a zinc chelate of the hydroxy analogue of methionine (Mintrex ® Zn) as a feed additive for all species. Mintrex ® Zn contains a minimum of 16 % zinc and 80 % hydroxy methionine analogue ((2hydroxy-4-methylthio)butanoic acid, HMTBa), as shown from analyses of the product. It is intended to be used as a source of the essential trace element zinc. Zinc (in several forms) and HMTBa are already separately authorised as nutritional feed additives in the European Union. Mintrex ® Zn can be considered as a bioavailable zinc source, comparable to another authorised inorganic source of zinc, for all animal species.

Reproductive Toxicology, 2008

reseArch from AnImAl testIng to clInIcAl experIence Summary. Diet is a significant source of expo... more reseArch from AnImAl testIng to clInIcAl experIence Summary. Diet is a significant source of exposure to endocrine disrupting chemicals (EDC); health risks cannot be excluded, in particular long-term effects in vulnerable groups such as children. However, food safety assessment must also consider the effects of natural food components modulating the endocrine system. The scientific evidence on the complex interactions between EDC and food components is still limited. The new EDC-Diet Interactions Database (EDID) within the ISS EDC area (www.iss.it/inte/) aims to stimulate further research in the field of food toxicology: a database on international literature's studies, either on experimental systems and on animal population and humans, easy to consult and periodically updated. Examples of studies contained in EDID are provided concerning EDC with iodine, vitamins and phytoestrogens.

Frontiers in public health, 2017

Current Hazard Analysis Critical Control Points (HACCP) approaches mainly fit for food industry, ... more Current Hazard Analysis Critical Control Points (HACCP) approaches mainly fit for food industry, while their application in primary food production is still rudimentary. The European food safety framework calls for science-based support to the primary producers' mandate for legal, scientific, and ethical responsibility in food supply. The multidisciplinary and interdisciplinary project ALERT pivots on the development of the technological invention (BEST platform) and application of its measurable (bio)markers-as well as scientific advances in risk analysis-at strategic points of the milk chain for time and cost-effective early identification of unwanted and/or unexpected events of both microbiological and toxicological nature. Health-oriented innovation is complex and subject to multiple variables. Through field activities in a dairy farm in central Italy, we explored individual components of the dairy farm system to overcome concrete challenges for the application of translatio...

Frontiers in Public Health, 2017

One Health involves the multifaceted environment-animal-human web: nevertheless, the role of toxi... more One Health involves the multifaceted environment-animal-human web: nevertheless, the role of toxicological issues has yet to be fully explored in this context. Aflatoxin B1 (AFB1) contamination of feeds is a risk for the health of several farm animals, including fishes; milk is the only food of animal origin where a significant feed-food carry over may occur. The main AFB1-related compound present in milk is the hydroxy-metabolite aflatoxin M1 (AFM1). Besides contamination of raw milk, AFM1 is of concern for the whole dairy chain; AFM1 may also contaminate the milk of several other ruminants used for milk/dairy production. In a One Health perspective, milk represents a sentinel matrix for AFB1 vulnerability of the agro-food system, that is crucial in a phase when food/nutritional security becomes a global issue and climatic changes may affect agricultural productions. In the global setting, food chain exposure to long-term toxicants, such as AFM1, is a growing concern for economically developing countries, whereas global trade and climatic change makes AFM1 an emerging hot issue in economically developed countries as well. We critically review the state of the art on AFM1 risk assessment and risk management using two scenarios as case studies: a European Union country where the health system aims at ensuring a high-level protection of food chain (Italy) and the world's largest (and economically developing) producer of dairy products by volume (India). The case studies are used to provide building blocks for a global One Health framework.

Journal of Agricultural Chemistry and Environment, 2014

Community is the foundation of public health: the present paper reports the approach and strategy... more Community is the foundation of public health: the present paper reports the approach and strategy for intervention on the dairy production community developed by the Italian project ALERT (www.alert2015.it), which implements the transfer of technical innovation and technological know-how from public research. Starting from the local role of primary producers, North-South and South-South networking (www.noodlesonlus.org) is needed to share solutions for transnational problems like climatic change, contaminated agro-farming sites and food waste and losses in the era of food crisis. Based on risk analysis, science-society dialogue and global health, the main drivers of this experience of translational research are One Health, i.e. the web of interrelationships among environment, farm animals and human health, and sustainable food safety (prevention actions on diet of young women, today, to protect next generation's health) to increase population life expectancy in good health.

Pure and Applied Chemistry, 2010

Essential trace elements (TEs) are major nutritional feed additives, required for the health and ... more Essential trace elements (TEs) are major nutritional feed additives, required for the health and welfare of farm animals, especially under intensive husbandry conditions. Within the European Food Safety Authority (EFSA), risk assessment of feed additives is carried out by the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), which is increasingly confronted with additives based on organic forms of TEs. Organic forms are expected to have higher bioavailability, hence, lower levels in feeds may be needed to meet farm animal requirements. On the other hand, higher bioavailability might also lead to enhanced deposition in edible tissues, hence, increased consumer exposure; specific organic forms might also have a different distribution in edible tissues or products. Higher consumer exposure is especially relevant to TEs with recognized health risks at excess levels (e.g., Se); exposure scenarios should take into account background dietary levels and other intak...

Translational Oncology, 2009

Liver cancers in children are rare representing only 1.1% of malignancies, with an annual inciden... more Liver cancers in children are rare representing only 1.1% of malignancies, with an annual incidence rate of 1.5 cases per million. Hepatoblastoma and hepatocellular carcinomas are the most common malignancies of the liver occurring in young people aged 15 years or younger. Molecular basis of both tumors are still unclear, and common markers (i.e., CTNNB1, APC, IGF-2) are not always useful in the characterization of sporadic forms; in this respect, microRNA recently associated with carcinogenesis could play a pivotal role in their onset. CTNNB1 and APC were analyzed by sequencing, and IGF-2 promoter methylation status was assessed by methylation-specific polymerase chain reaction. MicroRNA expression was assayed by microarray and quantitative reverse transcription-polymerase chain reaction in hepatoblastoma samples. Although few genomic alterations were detected in ours samples, an altered expression of some microRNA in hepatoblastoma was observed. Unsupervised clustering shows that microRNA profile can distinguish tumor from nontumor tissues. Further analyses of microRNA contents in hepatoblastoma compared with hepatocellular carcinoma highlighted four upregulated microRNA (miR-214, miR-199a, miR-150 [P < .01], and miR-125a [P < .05]) and one downregulated microRNA (miR-148a [P < .01]). In conclusion, although our samples were poorly informative from a genetic point of view, they showed a peculiar microRNA expression pattern compared with nontumor tissues and hepatocellular carcinoma. MicroRNA could represent valid markers for the classification of pediatric liver tumors.

Toxicological Sciences, 2009

Organophosphorus insecticides, as Chlorpyrifos (CPF), are widely used in agriculture and against ... more Organophosphorus insecticides, as Chlorpyrifos (CPF), are widely used in agriculture and against household pests; these compounds receive an increasing consideration as potential endocrine disrupters. The aim of the present study was to examine the potential short-and long-term effects of CPF on thyroid and adrenal glands in CD1 mice following exposure at dose levels not inducing brain acetyl cholinesterase (AchE) inhibition, during gestational and/or postnatal vulnerable phases. Pregnant dams were treated with 0, 3, 6 mg/kg bw/day of CPF on gestational days 15-18. After delivery, pups were treated subcutaneously on postnatal days (PND) 11-14 with: 0, 1, 3 mg/kg bw/day of CPF. Serum thyroxin (T4), thyroid and adrenals histology and histomorphometry were evaluated in dams and in F1 mice. In dams at 6 mg/kg, decreased T4 levels and increased cell height in thyroid were observed, and adrenal histology showed a slightly increased vacuolization in the X-zone. In the F1, shortterm morphological modifications (reduced follicular size at PND 2) and long-term morphological (increased necrotic follicular cells) and biochemical alterations (reduced serum T4 levels) were found at PND 150 with an apparent higher vulnerability of males. For the first time these results indicate that CPF exposure at dose levels not inducing brain AchE inhibition causes thyroid alterations in dams and in F1 CD1 mice. Thyroid may be a sensitive target to CPF developmental exposure possibly leading to long-term effects on thyroid function. Because thyroid plays a pivotal role in mammalian development, these findings can be relevant to humans.

Annali dell'Istituto superiore di sanità, 2015

The development of in vitro testing strategies may achieve a cost-effective generation of compreh... more The development of in vitro testing strategies may achieve a cost-effective generation of comprehensive datasets on a large number of chemicals, according to the requirements of the European Regulation REACH. Much emphasis is placed on in vitro methods based on subcellular mechanisms (e.g., nuclear receptor interaction), but it is necessary to define the predictive value of molecular or biochemical changes within an adverse outcome pathway (AOP). AOP pivots on the description of the flow from a molecular initiating event through a cascade of intermediate events needed to produce a specific adverse effect at organism level: downstream responses at cell level are, therefore, essential to define an AOP. Several in vitro assays are based on human cell lines representative of endocrine-targeted tissues (e.g., prostate) and on functional biomarkers of clinical relevance (e.g., PSA secretion in human prostate epithelial cells). We discuss the implementation of such functional biomarkers in...

NeuroToxicology, 2011

The present study was designed to investigate the adverse reproductive effects of acetamiprid, be... more The present study was designed to investigate the adverse reproductive effects of acetamiprid, besides the possible protective role of Nigella sativa oil (NSO), as a potential antioxidant agent. Thirty-two male Wistar rats were allocated into four equal groups of eight, control (CRL), acetamiprid (ACMP, 27 mg/kg), Nigella sativa oil (NSO, 0.5 ml/kg) and in combination (ACMP þ NSO). The experimental animals were dosed by gavage (5 days per week) for 45 consecutive days. Body weight gain, reproductive organs weights, sperm characteristics, testosterone, and thiobarbutiric acid-reactive substances (TBARS) levels were investigated. The obtained results showed that ACMP decreased significantly (p < 0.001) the body weight gain and the absolute weights of reproductive organs (testes, epididymis, and seminal vesicles). Furthermore, significant alterations at least (p < 0.01) in semen characteristics were noted in ACMP group as evidenced by a decline in spermatids number, sperm count, sperm motility, and testosterone level with an increase in abnormal and dead sperm and TBARS level. Treatment with NSO alone may stimulate spermatogenesis, increased significantly (p < 0.001) spermatids number and the weight of seminal vesicles. On the other hand, the co-administration of NSO along with ACMP can mitigate more efficiently and modulate in certain cases the adverse effects induced by ACMP on reproductive organs weights, semen quality, testosterone, and TBARS levels (at least p < 0.001). This obvious protective role of NSO against ACMP induced reproductive toxicity may be due to its antioxidant properties and ability to reduce TBARS levels as shown in this work.

Environmental Health and Preventive Medicine, 2003

Objective: The aim of this study was to explore the association between exposure to specific pest... more Objective: The aim of this study was to explore the association between exposure to specific pesticides (including endocrine disrupters) of greenhouse workers and spontaneous abortion in their spouses. Methods: A group of exposed workers was compared with a non-exposed group. The risk of spontaneous abortion was evaluated using a logistic regression model. Results: A significantly higher rate of spontaneous abortion was observed among spouses of workers exposed to specific compounds (atrazine, benomyl-carbendazim, carbaryl and DDT) in comparison with spouses of the unexposed group. The logistic regression model confirmed the increased risk of spontaneous abortion (OR=11.8; 95% CI 2.3-59.6). Conclusions: These findings suggest that occupational exposure to pesticides might have an adverse effect on the partner's reproductive health.

EFSA Journal, 2008

Following a request from the European Commission, the European Food Safety Authority was asked to... more Following a request from the European Commission, the European Food Safety Authority was asked to deliver a scientific opinion on the safety and efficacy of a manganese chelate of the hydroxy analogue of methionine (Mintrex ® Mn) as a feed additive for all species.

Oncology Reports, 2015

Pollutants altering the endocrine system, known as endocrine disruptors (ED), may modify the risk... more Pollutants altering the endocrine system, known as endocrine disruptors (ED), may modify the risk of female cancers. The carcinogenic effect of ED on humans has been confirmed by experimental studies for various substances including pesticides, DDT, dioxins, phthalates, bisphenol A, diethylstilbestrol, as well as heavy metals, but it is difficult to quantify precisely for several reasons hereby reviewed. Carcinogenesis is a complex and multifactorial mechanism that manifests itself over a long period of time, making difficult the detection of the specific contribution of the pollutants, whose absorbed dose is often unknown. The combined effect of various substances leads to complex interactions whose outcome is difficult to predict. These substances may accumulate and carry out their harmful effect on critical periods of life, probably also at doses considered harmless to an adult. ED can also have epigenetic adverse effects on the health of future generations. In conclusion, the carcinogenic effects of endocrine disruptors on female cancer types is plausible although additional studies are needed to clarify their mechanisms and entities. In the last part of the review we suggest ways to reduce ED exposure as it is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as the embryonic period and puberty.

Following a request from European Commission, the Panel on Additives and Products or Substances u... more Following a request from European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of 25-hydroxycholecalciferol (E 670 a) as feed additive for poultry and pigs. This additive is already authorised for use without a time limit in chickens for fattening, turkeys and laying hens. The applicant is now asking for a re-evaluation of the existing authorisation and for an extension of the authorisation to all poultry and pigs. The additive ROVIMIX ® Hy•D ® 1.25% contains 12.5 g 25-OH-D 3 kg-1 as active substance, which is a physiological precursor of the vitamin D 3 active hormone. 25-OH-D 3 from ROVIMIX ® Hy•D ® 1.25% is efficacious in all poultry species and pig categories when substituting for vitamin D 3 in feed. ROVIMIX ® Hy•D ® 1.25% is considered safe for the target animals at maximum contents of 0.100 mg 25-OH-D 3 kg-1 complete feed for chickens and turkeys for fattening, of 0.080 mg 25-OH-D 3 kg-1 complete feed for all other poultry species and of 0.050 mg 25-OH-D 3 kg-1 for all pig categories. After reassessing the in vivo toxicological studies on laboratory animals submitted, the FEEDAP Panel confirms its earlier conclusions that the 'effects seen in the toxicity studies 1 For citation purposes: Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) on a request from European Commission on the safety and efficacy of 25-hydroxycholecalciferol as feed additive for poultry and pigs. The EFSA Journal (2009) 969, 1-32 * One member of the Panel did not participate in the discussion on the subject referred to above because of possible conflicts of interest.

SUMMARY The emergence and the spread of resistance to antimicrobials in bacteria pose a threat to... more SUMMARY The emergence and the spread of resistance to antimicrobials in bacteria pose a threat to human and animal health and present a major financial cost. In an effort to decrease the development of resistance various actions have been taken at Community level, including the removal of all antibiotics used for growth promotion purposes from animal feed in 2006. With

Reproductive Toxicology, 2006

Maturation of neuroendocrine regulations is an extremely complex process made up of several stage... more Maturation of neuroendocrine regulations is an extremely complex process made up of several stages, that can be permanently affected by any exogenous substances able to interfere with the hormonal signalling at various levels. The Endocrine Disrupting Chemicals (EDCs) are a heterogeneous group of xenobiotics with potential endocrine activities which have been identified as priority risk factors in toxicological research. The present review is aimed at suggesting a number of endocrine and behavioural endpoints to be used in experimental studies to: (i) characterize more thoroughly the functional effects of developmental exposure to agents known to act as endocrine disruptors and (ii) unmask possible interferences with the maturation of the hypothalamus-hypophysis-gonad/thyroid (HHG/Th) axis by different class of xenobiotics not considered as EDCs. A combined testing strategy, considering both markers of endocrine/hormonal maturation and behavioural endpoints under hormonal control in laboratory rodents, may evidence even subtle perturbations of the neuroendocrine homeostasis, that often go undetected.

Reproductive Toxicology, 2009

Experimental and Toxicologic Pathology, 2009

EFSA Journal, 2008

Following a request from the European Commission, the European Food Safety Authority was asked to... more Following a request from the European Commission, the European Food Safety Authority was asked to deliver a scientific opinion on the safety and efficacy of a zinc chelate of the hydroxy analogue of methionine (Mintrex ® Zn) as a feed additive for all species. Mintrex ® Zn contains a minimum of 16 % zinc and 80 % hydroxy methionine analogue ((2hydroxy-4-methylthio)butanoic acid, HMTBa), as shown from analyses of the product. It is intended to be used as a source of the essential trace element zinc. Zinc (in several forms) and HMTBa are already separately authorised as nutritional feed additives in the European Union. Mintrex ® Zn can be considered as a bioavailable zinc source, comparable to another authorised inorganic source of zinc, for all animal species.

Reproductive Toxicology, 2008

reseArch from AnImAl testIng to clInIcAl experIence Summary. Diet is a significant source of expo... more reseArch from AnImAl testIng to clInIcAl experIence Summary. Diet is a significant source of exposure to endocrine disrupting chemicals (EDC); health risks cannot be excluded, in particular long-term effects in vulnerable groups such as children. However, food safety assessment must also consider the effects of natural food components modulating the endocrine system. The scientific evidence on the complex interactions between EDC and food components is still limited. The new EDC-Diet Interactions Database (EDID) within the ISS EDC area (www.iss.it/inte/) aims to stimulate further research in the field of food toxicology: a database on international literature's studies, either on experimental systems and on animal population and humans, easy to consult and periodically updated. Examples of studies contained in EDID are provided concerning EDC with iodine, vitamins and phytoestrogens.

Frontiers in public health, 2017

Current Hazard Analysis Critical Control Points (HACCP) approaches mainly fit for food industry, ... more Current Hazard Analysis Critical Control Points (HACCP) approaches mainly fit for food industry, while their application in primary food production is still rudimentary. The European food safety framework calls for science-based support to the primary producers' mandate for legal, scientific, and ethical responsibility in food supply. The multidisciplinary and interdisciplinary project ALERT pivots on the development of the technological invention (BEST platform) and application of its measurable (bio)markers-as well as scientific advances in risk analysis-at strategic points of the milk chain for time and cost-effective early identification of unwanted and/or unexpected events of both microbiological and toxicological nature. Health-oriented innovation is complex and subject to multiple variables. Through field activities in a dairy farm in central Italy, we explored individual components of the dairy farm system to overcome concrete challenges for the application of translatio...

Frontiers in Public Health, 2017

One Health involves the multifaceted environment-animal-human web: nevertheless, the role of toxi... more One Health involves the multifaceted environment-animal-human web: nevertheless, the role of toxicological issues has yet to be fully explored in this context. Aflatoxin B1 (AFB1) contamination of feeds is a risk for the health of several farm animals, including fishes; milk is the only food of animal origin where a significant feed-food carry over may occur. The main AFB1-related compound present in milk is the hydroxy-metabolite aflatoxin M1 (AFM1). Besides contamination of raw milk, AFM1 is of concern for the whole dairy chain; AFM1 may also contaminate the milk of several other ruminants used for milk/dairy production. In a One Health perspective, milk represents a sentinel matrix for AFB1 vulnerability of the agro-food system, that is crucial in a phase when food/nutritional security becomes a global issue and climatic changes may affect agricultural productions. In the global setting, food chain exposure to long-term toxicants, such as AFM1, is a growing concern for economically developing countries, whereas global trade and climatic change makes AFM1 an emerging hot issue in economically developed countries as well. We critically review the state of the art on AFM1 risk assessment and risk management using two scenarios as case studies: a European Union country where the health system aims at ensuring a high-level protection of food chain (Italy) and the world's largest (and economically developing) producer of dairy products by volume (India). The case studies are used to provide building blocks for a global One Health framework.

Journal of Agricultural Chemistry and Environment, 2014

Community is the foundation of public health: the present paper reports the approach and strategy... more Community is the foundation of public health: the present paper reports the approach and strategy for intervention on the dairy production community developed by the Italian project ALERT (www.alert2015.it), which implements the transfer of technical innovation and technological know-how from public research. Starting from the local role of primary producers, North-South and South-South networking (www.noodlesonlus.org) is needed to share solutions for transnational problems like climatic change, contaminated agro-farming sites and food waste and losses in the era of food crisis. Based on risk analysis, science-society dialogue and global health, the main drivers of this experience of translational research are One Health, i.e. the web of interrelationships among environment, farm animals and human health, and sustainable food safety (prevention actions on diet of young women, today, to protect next generation's health) to increase population life expectancy in good health.

Pure and Applied Chemistry, 2010

Essential trace elements (TEs) are major nutritional feed additives, required for the health and ... more Essential trace elements (TEs) are major nutritional feed additives, required for the health and welfare of farm animals, especially under intensive husbandry conditions. Within the European Food Safety Authority (EFSA), risk assessment of feed additives is carried out by the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), which is increasingly confronted with additives based on organic forms of TEs. Organic forms are expected to have higher bioavailability, hence, lower levels in feeds may be needed to meet farm animal requirements. On the other hand, higher bioavailability might also lead to enhanced deposition in edible tissues, hence, increased consumer exposure; specific organic forms might also have a different distribution in edible tissues or products. Higher consumer exposure is especially relevant to TEs with recognized health risks at excess levels (e.g., Se); exposure scenarios should take into account background dietary levels and other intak...

Translational Oncology, 2009

Liver cancers in children are rare representing only 1.1% of malignancies, with an annual inciden... more Liver cancers in children are rare representing only 1.1% of malignancies, with an annual incidence rate of 1.5 cases per million. Hepatoblastoma and hepatocellular carcinomas are the most common malignancies of the liver occurring in young people aged 15 years or younger. Molecular basis of both tumors are still unclear, and common markers (i.e., CTNNB1, APC, IGF-2) are not always useful in the characterization of sporadic forms; in this respect, microRNA recently associated with carcinogenesis could play a pivotal role in their onset. CTNNB1 and APC were analyzed by sequencing, and IGF-2 promoter methylation status was assessed by methylation-specific polymerase chain reaction. MicroRNA expression was assayed by microarray and quantitative reverse transcription-polymerase chain reaction in hepatoblastoma samples. Although few genomic alterations were detected in ours samples, an altered expression of some microRNA in hepatoblastoma was observed. Unsupervised clustering shows that microRNA profile can distinguish tumor from nontumor tissues. Further analyses of microRNA contents in hepatoblastoma compared with hepatocellular carcinoma highlighted four upregulated microRNA (miR-214, miR-199a, miR-150 [P < .01], and miR-125a [P < .05]) and one downregulated microRNA (miR-148a [P < .01]). In conclusion, although our samples were poorly informative from a genetic point of view, they showed a peculiar microRNA expression pattern compared with nontumor tissues and hepatocellular carcinoma. MicroRNA could represent valid markers for the classification of pediatric liver tumors.

Toxicological Sciences, 2009

Organophosphorus insecticides, as Chlorpyrifos (CPF), are widely used in agriculture and against ... more Organophosphorus insecticides, as Chlorpyrifos (CPF), are widely used in agriculture and against household pests; these compounds receive an increasing consideration as potential endocrine disrupters. The aim of the present study was to examine the potential short-and long-term effects of CPF on thyroid and adrenal glands in CD1 mice following exposure at dose levels not inducing brain acetyl cholinesterase (AchE) inhibition, during gestational and/or postnatal vulnerable phases. Pregnant dams were treated with 0, 3, 6 mg/kg bw/day of CPF on gestational days 15-18. After delivery, pups were treated subcutaneously on postnatal days (PND) 11-14 with: 0, 1, 3 mg/kg bw/day of CPF. Serum thyroxin (T4), thyroid and adrenals histology and histomorphometry were evaluated in dams and in F1 mice. In dams at 6 mg/kg, decreased T4 levels and increased cell height in thyroid were observed, and adrenal histology showed a slightly increased vacuolization in the X-zone. In the F1, shortterm morphological modifications (reduced follicular size at PND 2) and long-term morphological (increased necrotic follicular cells) and biochemical alterations (reduced serum T4 levels) were found at PND 150 with an apparent higher vulnerability of males. For the first time these results indicate that CPF exposure at dose levels not inducing brain AchE inhibition causes thyroid alterations in dams and in F1 CD1 mice. Thyroid may be a sensitive target to CPF developmental exposure possibly leading to long-term effects on thyroid function. Because thyroid plays a pivotal role in mammalian development, these findings can be relevant to humans.