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Potestà dei genitori, responsabilità genitoriale e protezione dei minori nel diritto internazionale privato e processuale.
Get PDFThe purpose of the thesis is to give an overview on the rules of private international law existing at national and at international level and concerning relationships between parents and children, regardless of other conditions. In fact the thesis deals with jurisdiction, applicable law, recognition and enforcement of judgements in the field of parental authority, parental responsibility and child protection.
Whereas the relevant legislation on parents – children relationships does not consider this topic as an unicuum, but takes into account differently the abovementioned categories, the thesis focuses on each of them separately.
As a consequence, the first topic to be addressed is the relationship between the different relevant legislations, with reference to their material scope.
The legislations taken into account are hereafter listed:
- Council Regulation (EC) No 2201/2003 of 27 November 2003 concerning jurisdiction and the recognition and enforcement of judgments in matrimonial matters and the matters of parental responsibility, repealing Regulation (EC) No 1347/2000;
- Hague Convention of 5 October 1961 concerning the powers of authorities and the law applicable in respect of the protection of infants;
- Hague Convention of 19 October 1996 on jurisdiction, applicable law, recognition, enforcement and co-operation in respect of parental responsibility and measures for the protection of the child, that is expected to repeal the 1961 Hague Convention;
- Articles 36, 37 and 42 of Italian Private International Law, n. 218/1995.
After explaining the relationship among the abovementioned legislations, the thesis deals with jurisdiction, focusing on the fundamental principle ruling jurisdiction - the best interest of the child - and on the general criterion for determining jurisdiction: the habitual residence of the child, which is increasingly used in international acts.
On the other hand, nationality is relevant under the 1961 Hague Convention and under Art. 36 of the Italian private international law, as a connecting factor for determining the applicable law. As far as connecting factors in the field of parents - children relationships, the research focuses on several topics, such as the problems arising from the discrimination based on nationality, and on multiple nationalities.
Finally, the research explores the recognition as well as the enforcement of judgments: procedures differ from each other on the basis of where decisions are held, whether in a Member State or not. Also the object of the decision could lead to a different proceeding: for example, a judgment concerning access rights is directly recognized and enforceable in another Member State provided it is accompanied by a certificate, which shall be issued by the judge of origin who stated the judgment. The certificate guarantees that some procedural safeguards have been respected during the procedure in the State where the decision has been adopted. Finally, some recent aspects about public order exception are described.
Parental responsibility is considered by Art. 2 of the Council Regulation (EC) No 2201/2003, and by Art. 1 of the 1996 Hague Convention, which both widely define the concept: in fact “parental responsibility” covers all rights and duties of a parent, guardian or legal representative, relating to the person or the property of the child. This encompasses not only rights of custody and rights of access, but also matters such as the guardianship and the placement of a child in a foster family or in institutional care and child protection.
It is worth underlining that: i) the list of matters qualified as “parental responsibility” pursuant to the Regulation in Art. 2 is not exhaustive, but merely illustrative; ii) it includes also measures for the protection of the child; iii) the concept of parental responsibility pursuant to the 1996 Hague Convention includes parental authority.
As a consequence, parental responsibility may be considered the only relevant category in the field of parents – children relations. This hypothesis may lead to a uniform private international law regulations on family relations
Qualità di vita e alessitimia nel trattamento con antidepressivi.
No full textPremesse e obiettivi : Gli studi sull' impatto del trattamento con antidepressivi sulla qualità della vita hanno segnalato la necessità di non trascurare questo parametro nella valutazione a medio e lungo-termine dei disturbi ansioso-depressivi. La soddisfazione e il benessere sono esperienze soggettive che risultano fondamentali per comprendere l’atteggiamento del paziente verso la terapia. Scopo del progetto di ricerca è quello di valutare l’impatto del trattamento con antidepressivi sulla qualità della vita dei pazienti e di indagare l’eventuale influenza su tale parametro della presenza di alessitimia.
Metodi : Il presente progetto si configura come uno studio naturalistico osservazionale prospettico. I pazienti inclusi nello studio sono stati sottoposti ad una valutazione iniziale (T0), prima dell’introduzione del farmaco antidepressivo, e successivamente a 8 settimane (T1) e a 6 mesi (T2). In ciascuna valutazione sono state somministrate le seguenti scale: Hamilton Depression Rating Scale (HDRS); Toronto Alexythimia Scale 20 items (TAS-20); WHO Quality of Life versione breve di 26 items (WHOQOL-BREF).
Risultati : I pazienti che hanno accettato di partecipare allo studio sono 50, di cui 32 donne e 18 uomini con un’età media di 45.28 ± 12.16 anni. I pazienti che hanno effettuato la seconda valutazione sono 35 (70.0%) e quelli che ad oggi hanno completato lo studio sono 19 (38.0%).
Il punteggio medio della HDRS decresce (19±5,45 a T0 e 11.00 ± 8.69 a T2) evidenziando come l’introduzione della terapia farmacologica consenta di ottenere un miglioramento clinico. Invece il punteggio medio della scala TAS-20 rimane sostanzialmente stabile nel tempo (55,12±14,70 a T0 e 53.68 ± 13.52 a T2). Per quanto concerne la WHOQOL-BREF è possibile valutare un miglioramento di circa il 10% (cioè da 48,40% a 57.25%) da T0 a T2, in particolare nelle aree inerenti le componenti Fisica (da 48,56% a T0 a 61.44% a T2) e Psicologica (da 41,58% a T0 a 52.48 a T2).
Si è rilevata una correlazione negativa fra le scale HDRS e WHOQOL, che indica un miglioramento della QoL al ridursi della severità dei sintomi depressivi. Sia in acuto, che dopo parziale remissione della sintomatologia depressiva, i soggetti alessitimici tendono a percepire una peggiore QoL.
In base ai dati emersi dalla regressione logistica si può desumere che la presenza di HDRS <16 (p=0,040), l’assenza di tratti alessitimici (p=0,05) e l’assenza di patologie croniche (p=0,05) sono variabili in grado di influenzare positivamente la percezione della QoL.
Conclusioni: Il presente studio evidenzia come un corretto trattamento antidepressivo sia incisivo sulla QoL che rappresenta pertanto un paramentro indispensabile per una adeguata valutazione dell’esito a lungo termine dei disturbi dell’umore. La presenza di alessitimia sembra influenzare negativamente la QoL e potrebbe pertanto essere utile considerare anche tale variabile al fine di individuare strategie più mirate nel trattamento
Analysis of the interaction between the IGF system and HIF: rationale for cotargeting the two systems in breast cancer.
Get PDFThe observation that several RTKs can act as promoters of tumor development and growth has brought a revolution in the study of new targets, in the hope of developing more specific anticancer drugs: the Insulin-like Growth Factors system is among the most studied.
The role of this system in the development and progression of a large number of malignancies is well documented. Hence the development of different classes of compounds that can affect this system, in particular directly targeting the type 1 receptor (IGF-1R). Some of these compounds, both monoclonal antibodies (mAbs) against the receptor or small molecules that inhibit the TK activity of IGF-1R, are already undergoing clinical trials, because of their effectiveness in inhibiting the signal.
Unfortunately, cancer cells show a high degree of plasticity and redundancy in the proliferative and anti-apoptotic signals, which may contribute to the creation of resistance to specific inhibitors: the identification of these mechanisms, and their overcome, are two key goals in the development of these drugs.
Within this study, we encountered a similar problem: our experiments show that the compound in use, NVP-AEW541 (a specific, low molecular weight inhibitor of IGF-1R catalytic activity), is perfectly capable of inhibiting the signal transduced by the receptor following stimulation with IGF-1, but it appears to lose effectiveness following stimulation with IGF-2. Starting from the observation that IGF- 2 seems to be the key factor in this resistance, literature search showed us a growing number of experimental evidences in support of the role of variant A of the insulin receptor (IR-A) in the maintenance of a proliferative signal similar to that classically attributed to IGF-1R: our experiments confirmed the activation of this receptor following exposure to IGF-2, justifying the loss of effectiveness of NVP-AEW541 in regard of the migratory potential of MDA-231 cell line. While the dual inhibition of IGF-1R and IR could overcome this redundancy in the signal, it remains to consider the problems that may occur due to the inhibition of a receptor as essential for cellular metabolism as IR.
A different and probably more practicable strategy would be the inhibition of the key player in the dual activation, IGF-2. The one proposed is a strategy that reflects the physiological mechanism of controlling the levels of IGF-2: in fact normal cells are able to control the levels of circulating IGF-2 by binding the ligand to IGF-2R, followed by its subsequent transport to lysosomes for degradation.
During this study we then concentrated also on IGF-2R, observing no significative differences between the cell lines in study.
Following the ligand-based targeting of the IGF system, which effectiveness seems to be proven by an ongoing phase I clinical trial using MEDI-573, actually the only mAb in clinical testing that exerts its effects by neutralizing not only IGF-2 but also IGF-1, we used a neutralizing antibody against IGF- 2 (MAB292), making it impossible for it to bind both IGF-1R and IR-A. The use of MAB292 proved to be effective both in combination with NVP-AEW541 and alone: MDA-231 cells seem in fact unable to respond to stimulation with IGF-2 and almost completely lose the ability to migrate.
This strategy could be particularly effective especially considering that, in hypoxic conditions (pO2 <2.5%), stabilization of HIF-1α leads to an increase in the levels of IGF-2. This increase in fact results in the resistance of MDA-231 to NVP-AEW541, while MAB292 still retain its effectiveness. We also observed the lack of a direct and defined relationship between HIF-1α and IGF-2R levels: cells seemed not able to compensate to IGF-2 increase by increasing also the receptor levels.
From this observation it’s therefore evident that another strategy to overcome the resistance to IGF-1R inhibitors may be the combination with HIF-1α inhibitors. At the present days, the fundamental problem is the lack of specific inhibitors: many chemotherapic drugs, in fact, have a complete or partial inhibitory activity of HIF-1α, that is however accompanied by a number of off-target effects.
One of these compounds is Topotecan, a Top-1 poison in use in the treatment of ovarian and small cell lung cancer that inhibits HIF-1α translation by a Top1-dependent but DNA damage-independent mechanism, suggesting that its effect as HIF-1α inhibitor could be mechanistically distinguished from those characterizing its cytotoxic activity. In our case the dual inhibition was obtained with success through the use of Topotecan in combination with NVP-AEW541.
We also introduced the combination between NVP-AEW541 and Luteolin, a compound of natural origin belonging to the flavonoid class that possess anti-proliferative and anti-migratory activity.
Despite the more complex comprehension of its effect on HIF-1, which resulted only slightly decreased, the most interesting feature of this compound resulted to be its anti-migratory potential: the use of Luteolin in fact completely inhibited migration in MDA-231.
As a last point in our study, we focused our attention on the metabolic alteration determined by the modulation of insulin/IGF system. Since deregulation of cellular energy metabolism is considered an increasingly important hallmark of cancer, IR and its related metabolic syndromes have become another major focus in the breast cancer research and treatment field. Preliminary analysis of the oxidative and glycolitic profiles of three cell lines showed in first stance an interesting difference at the basal level as well as a modulation of the two processes after treatment with NVP-AEW541 together with MAB292 or with Luteolin. Further experiments would be needed to assess the effective impact of these compounds on cellular metabolism, as well as the metabolic processes and responses in hypoxia.
In conclusion we can say that the dual targeting of IGF-1R and HIF-1 appears to be an interesting therapeutic strategy in breast cancer, especially given the close relationship between these two systems
Utilizzo del nuovo antidepressivo agomelatina in pazienti affetti da disturbo depressivo maggiore: efficacia, tollerabilità, adesione al trattamento.
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Corbicula fluminea invasion in Lake Maggiore: a three years ecological study.
Get PDFThe number of reports of non-indigenous species (NIS) of the aquatic environments are increasing rapidly worldwide. The rate of invasions of freshwater environments is rising in many countries, mainly caused by an increase in human activities. The growing interest in invasive species is due to their negative impact on biodiversity and ecosystem functioning.
Some species are recognized among the most dangerous invasive species of freshwater ecosystems (eg C. fluminea, D. polymorpha and A. woodiana).
This study aims to evaluate the C. fluminea invasion in Lake Maggiore, inspecting different chraracteristics of populations settled in southern littoral part. Field and semi-natural condition observations are carried out to evaluate growth and reproductive rate of Corbicula in the environment recently colonized. Lab experiments were performed to measure filtration rate. To evaluate possible competitive interactions between alien and native species, dietary sources and trophic niche overlap were determined through measurements of the stable isotope compositions of C (δ13C) and N (δ15N) respectively.
Lake Maggiore offers a favorable environment for the establishment of the Asian clam Corbicula fluminea. The picture that emerges from the study of C. fluminea populations is quite complex, with differences among the five sampling sites. Larger size class organisms are well represented in Angera and Arona (southern sites), while are (still) almost absent in Feriolo and Monvalle (northern sites).
The density and biomass of C. fluminea observed are rather high, with peaks reaching up to 3000 ind.m-2 and 2500 g m-2.
The populations size structure provides clues to understand the process of invasion and its phases. The populations size structure in the different sites presents wide differences, indicative of different demographic dynamics. The timing of colonization of Lake Maggiore seems to follow this order: Monvalle <Feriolo <Brebbia <Angera <Arona. It is also possible to assume that the colonization of this environment began in 2007, for expansion of the population already established in its effluent, the river Ticino.
The reproductive period of C. fluminea in Lake Maggiore showed a single reproductive peak, from late Spring to Autumn. The recruitment of new organisms is scarce at the site of Arona, while the opposite situation is observed in Feriolo.
The number of larvae produced by each adult is highly variable, with values ranging from a few hundred to 16000 larvae per individual.
Generally in the sites of Angera, Brebbia, Feriolo and Monvalle mortality is rather low, while at Arona is considerably higher. At Angera was observed a phenomenon of mass mortality in Autumn 2012.
C. fluminea has a high growth rate and in this environment there are no factors able to limit the growth and spread of this species. The growth rates are affected by seasonal variations in temperature: in Summer and Autumn organisms show higher growth rate values than in the other seasons (almost 2 times higher). The growth rate is higher for small size organisms, as expected comparing young and adults organisms of the same species.
In spite of similar functional roles, Unionids and C. fluminea are likely to differ in filtering efficiency and trophic niche. Our preliminary results suggest that Corbicula has a noticeably higher filtration capacity than the most abundant Unionid species (U. elongatulus) and is able to shift its diet along the year. The results of stable isotope analysis highlight a niche overlap between C. fluminea and native species of bivalves, indicating that C. fluminea has lower trophic fidelity than native Unionids. Feeding plasticity of C. fluminea is likely of major importance for competing successfully indigenous bivalves in Lake Maggiore, thus promoting the overdomination of the alien species in the area. Indeed, Corbicula seems to stand already as a keystone littoral species in Lake Maggiore, likely being a strong competitor for space and food to native mussels.
However, besides the competition with bivalve invasive species the decline observed for the native species of Lake Maggiore (U. elongatulus abundance decreases about 90 % from 2004 and 2012) is likely due to several factors. Severe drought is responsible for periodical mass mortalities which affect both native Unionids and invasive clams, but these latter can recover and recolonize the environment more rapidly than native species.
The specimens that moving from one environment to another can bring along their parasites, which can find the conditions necessary to establish a new population. In the course of this study two new species of parasites of Unionids (cercariae of Bucephalidae and Rhodeus amarus) have been found. The infection of the gonads due to cercariae leads to the castration of bivalves and can be fatal, while the presence of the larvae of R. amarus in the gills reduces the rate of respiration and filtration.
The presence of D. polymorpha is recognized in the lake since the 1990’s and is often found anchored to the shell of other bivalve species. High infestation of Dreissena can cause the death by asphyxia.
The combination of all these factors provides sufficient explanation for the observed decline of native species, however, the invasion of C. fluminea appears to be a worrying phenomenon. After 3-4 years from the entry into the lake this clam had already colonized a third of the shoreline. To date, this bivalve is found in all suitable habitats distributed along the entire perimeter of the lake.
It is possible to conclude that eradication is an expensive solution and the methodologies used often have negative impacts on native species. Moreover, it is not possible to eradicate a species from the environment, in addiction the high growth rate and the plasticity of the alien species recorded in Lake Maggiore favour them respect native species. Mass mortality events can promote the replacement of the native by alien species
Ridurre l'area infartuale nello STEMI a costo zero!
Get PDFBackground – Postconditioning, i.e. cycles of ischaemia and reperfusion following a prolonged ischaemic insult, applied either intracoronary (culprit lesion) or on a remote organ, is an effective way to reduce infarct size.
Objectives – The aim of this study was to compare 2 different methods in use to achieve cardiac postconditioning: myocardial and remote. Primary end point was the reduction in infarct size, measured by ST-segment deviation resolution and Troponin I (TnI) release curve; secondary end point was the improvement in cardiac ejection fraction evaluated by means of echocardiography at 3 months.
Methods – We enrolled 78 pts randomized in 3 arms as follow: A myocardial postconditioning (29 pts), B remote postconditioning (29 pts), C control group (20 pts). Measures of efficacy were: ST-segment deviation recovery and peak TnI during hospitalization, LVEF and LVWMSI evaluated at 3 months.
Results – No statistically significant differences were found between group A and B, in terms of full ST-segment deviation recovery and reduction of ST-segment deviation score (62% e 78±14% vs 55% e 78±14%, p=NS respectively) and peak TnI (130±41 vs 134±42, p=NS). The LVEF and LVWMSI differences did not achieve statistical significance (46±10% vs 47±9% b, p=NS; 51±9% vs 52±10% a, p=NS; 1.6±0.4 vs 1.6±0.4 b, p=NS; 1.3±0.3 vs 1.3±0.3 a, p=NS, group A and B respectively). All efficacy measurers were statistically significant different when both groups A and B were compared to group C.
Conclusions – This study shows that remote postconditioning is non-inferior to myocardial for the prevention of reperfusion injury, and is even a safer, easier to do and faster method (no procedural time prolonged).
Introduzione – Il postcondizionamento, applicando dopo ischemia prolungata cicli di ischemia e riperfusione, sia a livello della coronaria riaperta che di un organo remoto, è in grado di ridurre l’area infartuale.
Scopo - Confronto di efficacia tra le 2 metodiche di postcondizionamento attualmente applicate in letteratura, miocardico e remoto: end point primario la riduzione dell’area infartuale, valutata mediante risoluzione della deviazione del tratto ST e curva di dismissione di Troponina I (TnI); end point secondario il miglioramento della funzione contrattile valutata mediante ecocardiografia a 3 mesi.
Metodi – Sono stati arruolati 78 pz, randomizzati in 3 gruppi: A postcondizionamento miocardico (29 pz), B postcondizionamento remoto (29 pz), C controllo (20 pz). Le misure di efficacia considerate sono: risoluzione della deviazione del tratto ST e picco di TnI durante l’ospedalizzazione, FEVS e LVWMSI a 3 mesi.
Risultati – Non vi sono differenze statisticamente significative tra i gruppi A e B in termini di risoluzione, assoluta e percentuale, della deviazione del tratto ST (rispettivamente 62% e 78±14% vs 55% e 78±14%, p=NS) e di picco di TnI (130±41 vs 134±42, p=NS). Anche la differenza in termini di FEVS e LVWMSI non è risultata statisticamente significativa (rispettivamente 46±10% vs 47±9% pre, p=NS; 51±9% vs 52±10% post, p=NS; 1.6±0.4 vs 1.6±0.4 pre, p=NS; 1.3±0.3 vs 1.3±0.3 post, p=NS). Tutte le misure di efficacia considerate differiscono significativamente tra i gruppi A e B quando confrontati con il gruppo C.
Conclusioni – I dati dimostrano la non inferiorità del postcondizionamento remoto, più sicuro, facile da applicare e veloce (nessun allungamento dei tempi procedurali), rispetto al miocardico
Prescription of phytotherapy diets and supplements in unconventional medicine of ambulatory department: epidemiologist and clinician aspects.
No full textThe object of this plan is to investigate and to describe the modalities of MNC use, regarding the treatments that imply the employment of pharmacologic therapies, near an MNC ambulatory department that conducted in Local Sanitary Company.
The greater attention has been turned use of phytotherapy in the ambulatory department of bioactive herbal medicines, through the characterization of natural principles produced from plants and on the putting to point of therapeutic outlines of association between allopathic medicines and formulated alimentary integrators with extracted vegetables.
It’s been estimated the prescription of alimentary and phytotherapic supplements near a MNC ambulatory department, with detail attention to the prescription frequency, It has been had with regard to the subjective appraisal of the satisfaction in relation to the attended effects. Every patient has been included in the study only after they are informed of the purposes of the plan. The data have been collected through the employment of a card purposely predisposed.
They have been enlisted participants, 59.5% women with avarage age of 44,6 years. The use of herbal products for cured pathologies came declared of 67.2% of the cases.
Herbalist and pharmacist that advice to the people to use MNC, and physician with their conventional medicine, are the main interlocutors and point of reference I use for it of not conventional Medicines. Moreover, the medical officer usually get information from the patients about their use of the herbal medicine.At The same time use of conventional medicine and herbal medicine could give possibilities of drugs adverse effects
QSAR models for the (eco-)toxicological characterization and prioritization of emerging pollutants: case studies and potential applications within REACH.
Get PDFUnder the European REACH regulation (Registration, Evaluation, Authorisation and Restriction of Chemical substances - (EC) No 1907/2006), there is an urgent need to acquire a large amount of information necessary to assess and manage the potential risk of thousands of industrial chemicals.
Meanwhile, REACH aims at reducing animal testing by promoting the intelligent and integrated use of alternative methods, such as in vitro testing and in silico techniques. Among these methods, models based on quantitative structure-activity relationships (QSAR) are useful tools to fill data gaps and to support the hazard and risk assessment of chemicals.
The present thesis was performed in the context of the CADASTER Project (CAse studies on the Development and Application of in-Silico Techniques for Environmental hazard and Risk assessment), which aims to integrate in-silico models (e.g. QSARs) in risk assessment procedures, by showing how to increase the use of non-testing information for regulatory decision-making under REACH. The aim of this thesis was the development of QSAR/QSPR models for the characterization of the (eco-)toxicological profile and environmental behaviour of chemical substances of emerging concern. The attention was focused on four classes of compounds studied within the CADASTER project, i.e. brominated flame retardants (BFRs), fragrances, prefluorinated compounds (PFCs) and (benzo)-triazoles (B-TAZs), for which limited amount of experimental data is currently available, especially for the basic endpoints required in regulation for the hazard and risk assessment.
Through several case-studies, the present thesis showed how QSAR models can be applied for the optimization of experimental testing as well as to provide useful information for the safety assessment of chemicals and support decision-making.
In the first case-study, simple multiple linear regression (MLR) and classification models were developed ad hoc for BFRs and PFCs to predict specific endpoints related to endocrine disrupting (ED) potential (e.g. dioxin-like activity, estrogenic and androgenic receptor binding, interference with thyroxin transport and estradiol metabolism). The analysis of modelling molecular descriptors allowed to highlight some structural features and important structural alerts responsible for increasing specific ED activities. The developed models were applied to screen over 200 BFRs and 33 PFCs without experimental data, and to prioritize the most hazardous chemicals (on the basis of ED potency profile), which have been then suggested to other CADASTER partners in order to focus the experimental testing.
In the second case-study, MLR models have been developed, specifically for B-TAZs, for the prediction of three key endpoints required in regulation to assess aquatic toxicity, i.e. acute toxicity in algae (EC50 72h Pseudokirchneriella subcapitata), daphnids (EC50 48h Daphnia magna) and fish (LC50 96h Onchorynchus mykiss). Also in this case, the developed QSARs were applied for screening purposes. Among over 350 B-TAZs lacking experimental data, 20 compounds, which were predicted as toxic (EC(LC)50 ≤ 10 mg/L) or very toxic (EC(LC)50 ≤ 1 mg/L) to the three aquatic species, were prioritized for further experimental testing.
Finally, in the third case-study, classification QSPR models were developed for the prediction of ready biodegradability of fragrance materials. Ready biodegradation is among the basic endpoints required for the assessment of environmental persistence of chemicals. When compared with some existing models commonly used for predicting biodegradation, the here proposed QSPRs showed higher classification accuracy toward fragrance materials. This comparison highlighted the importance of using local models when dealing with specific classes of chemicals.
All the proposed QSARs have been developed on the basis of the OECD principles for QSAR acceptability for regulatory purposes, paying particular attention to the external validation procedure and to the statistical definition of the applicability domain of the models. QSAR models based on molecular descriptors generated by both commercial (DRAGON) and freely-available (PaDELDescriptor, QSPR-Thesaurus) software have been proposed. The use of free tool allows for a wider applicability of the here proposed QSAR models.
Concluding, the QSAR models developed within this thesis are useful tools to support hazard and risk assessment of specific classes of emerging pollutants, and show how non-testing information can be
used for regulatory decisions, thus minimizing costs, time and saving animal lives.
Beyond their use for regulatory purposes, the here proposed QSARs can find application in the rational design of new safer compounds that are potentially less hazardous for human health and environment