Information resources in toxicology—Italy

Toxicology 190 (2003) 35 /54 www.elsevier.com/locate/toxicol

Information resources in toxicology* Italy /

Paolo Preziosi a,*, Adriana Dracos b, Ida Marcello b a

Department of Pharmacology, Catholic University of the Sacred Heart, Rome, Italy b National Health Institute, Rome, Italy

Abstract The purpose of the present paper is to provide an overview of current resources in the field of toxicology in Italy. The discussion will begin with a brief history of toxicology in this country, which includes the study of the toxicity of plants and other natural substances, and the birth of industrial and forensic toxicology. We will also provide information on research, education, and hazard control in the field of toxicology. Within this context we will examine the public bodies responsible for surveillance and regulatory activities, state-owned and private structures involved in toxicological research, and the educational programs and research activities of universities. Particular emphasis will be placed on the activities of the National Health Service, which plays an important role in areas such as clinical toxicology, food safety, and animal health, as well as those of national and regional agencies dedicated to the protection of the environment. The presentation will be organized as follows: 1) 2) 3) 4) 5)

A Brief History of Toxicology in Italy; Professional Societies; National Health Service; National Bodies; Resources for the Environment;

6) 7) 8) 9) 10)

Biomedical Websites; Recent Publications; Research Structures; Graduate and Postgraduate Programs; Legislation.

# 2003 Elsevier Ireland Ltd. All rights reserved.

1. A brief history of toxicology in Italy In Italy, the harmful effects that can be provoked by natural substances have long been recognized, and in the past many of these effects have been exploited for sinister purposes (cf. Agrippina, the Emperor Nero, the Borgias). The peninsula has produced legendary poisons (the famous ‘acquetta di Perugia’) and ‘toxic femmes’

* Corresponding author. E-mail address: [email protected] (P. Preziosi).

such as Locusta and Caterina dei Medici, who exported her skills to France. Information on toxic substances, as well as poisonous plants and animals, can be found in the works of Pietro d’Abano (1256 /1315): Liber de Venenis , published posthumously 1402; Pietro Andrea Gregorio Mattioli (1500 /1577), the father of modern botany: a textbook on herbs and a translation, with comments, of De Pedacio Dioscoride Anarzabeo Libri Quinque (1544); Francesco Redi (1626 /1698); and Felice Fontana (1720 /1805), whose treatise on viper poison was published in 1781.

0300-483X/03/$ - see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0300-483X(03)00195-1

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Professor Bernardo Ramazzini (1633 /1714) of the University of Bologna described numerous cases of industrial intoxication, outlining the health hazards of irritating chemicals, dust metals and other abrasive agents encountered by workers in 52 occupations. He is in fact considered the father of industrial toxicology and occupational medicine. Problems related to forensic toxicology are discussed in the texts of Paolo Zacchia (1584 / 1659) (Questiones medicolegales ), Fortunato Fedele (1551 /1630), Michele Bernardo Valentini (Corpus juris medico legale ), Francesco Rognetta (1800 /1857), whose main interest was arsenic poisoning, and Ranieri Bellini (1817 /1878), who also wrote the book entitled Lezioni sperimentali di Tossicologia . In the latter half of the 19th century, eminent professors of pharmacology in Italian universities also turned their attentions to mechanistic problems in toxicology: Pietro Albertoni (1849 /1933); Luigi Sabbatani (1863 /1928), who studied under Albertoni; and Pietro Giacosa (1853 /1928), who authored a textbook on medicine, pharmacology and toxicology. The scientific journal Annali di chimica applicata alla medicina, cioe` alla farmacologia, alla tossicologia ed alla terapeutica was widely read between 1845 and 1881. Giusto Coronedi, Professor of Pharmacology at the University of Florence from 1917 through 1935 expanded the University’s Pharmacology Institute to include a Division of Toxicology, which was later directed by the famous pharmaco-toxicologist Mario Aiazzi Mancini (1887 /1980) and is now headed by Professor Pierfrancesco Mannaioni. The two branches of toxicology that arose in Italy, forensic and industrial, developed in parallel, and in 1910 the first Department of Occupational Medicine was opened at the University of Milan by Professor Luigi Devoto (1864 /1936), one of the most highly respected figures in this field.

2. Professional societies The Italian Society of Toxicology (SITOX ) was founded in 1966 and currently has over 500 members. It is actively engaged in promoting the

value of scientific, professional and regulatory aspects of modern toxicology. SITOX sponsors an annual postgraduate course in toxicology, and a national congress is held every 3 years. Its official website (http://users.unimi/it /pharm/sit/ SIThome.html) includes a file with the names of all members as well as a summary of its activities (SITOX/Informa ), which is also available in a printed version. The Society includes sections dealing with specific aspects of toxicology (environmental, experimental and human toxicology ), each headed by its own coordinator. Some of these sections are listed on the web site, with news on events being organized and more detailed information on the section itself. SITOX is a member of the Federation of the European Societies of Toxicology (EUROTOX) and the International Union of Toxicology (IUTOX), and it contributed significantly to the VI International Congress of Toxicology held in Rome in 1992 (June 30 /July 3). In 1999, SITOX created the Register of Italian Certified Toxicologists (RENTIC ), aimed to evaluate toxicologist’s skills and institute a register with complete information about toxicology experts, available for public and private institutions. Cell Tox (The Italian Association of in vitro Toxicology) was founded in 1991 and currently has approximately 100 members. Its scope is to promote the use of in vitro systems in pharmacological and toxicological research and to develop methods and techniques for the study of toxic effects at the cellular and molecular levels. Its activities include biennial congresses, continuing education courses, and scientific meetings. The International Association of Forensic Toxicologists (TIAFT ), founded 39 years ago, has over 1400 members throughout the world, all of whom are actively engaged in the field of analytical toxicology or related areas. The TIAFT website (http://www.tiaft.org/) was designed to promote the cooperation and coordination of efforts among nations and to encourage research in forensic toxicology. Professor Davide Ferrara of the Forensic and Behavioural Toxicology Center of the University of Padua represents Italy on the TIAFT

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Executive Committee. The Italian delegate to the Committee on Systematic Toxicological Analysis and Guidelines is Professor Aldo Polettini from the Department of Legal Medicine and Public Health of the University of Pavia. The primary aims of this Committee are to reduce the probability of gaps in the identification and detection of unknown substances, to develop new analytical spectroscopic and chromatographic techniques, and to draw up an official set of TIAFT-approved Laboratory Guidelines.

7)

3. National health service1

. Department of Health care, Veterinary Health and International Affairs (which includes six offices dealing with activities such as disease prevention, drug surveillance, food and nutrition, etc.) . Department of Healthcare Systems, Research and Ministry Organization (with six offices that deal with healthcare planning, research, organization, budget issues, etc.)

3.1. Central structure Italy has a state-financed, regionally based public health care system. The Italian National Health Service (NHS) was established by the National Health Service Act in 1978. This system is composed of the following: 1)

2) 3) 4)

5)

6)

The Ministry of Health, supported by the Consiglio Superiore di Sanita` (National Health Council), which provides high-quality advisory services on technological and scientific issues. Several scientific/technical institutions that operate at the national level: Istituto Superiore di Sanita` (ISS, National Institute of Health); Istituto Superiore per la Prevenzione e la Sicurezza del Lavoro (ISPESL, National Institute of Occupational Safety and Prevention); Agenzia per i Servizi Sanitari Regionali (ASSR, Agency for Regional Health care Services); Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS, National Institutes for Care and Scientific Research);

1 Revised by U. Moscato, A.G. de Belvis and V. RomanoSpica. Institute of Hygiene, Health Safety, Technology and Drug-utilization Department, Catholic University, Rome.

8) 9) 10) 11)

Istituti Zooprofilattici Sperimentali (IIZZSS, Experimental Institutes of Zooprophylaxis). Scientific/technical institutions operating at the regional, provincial and municipal levels: Regioni e Province Autonome (Self-governing Regions and Provinces) Aziende Unita` Sanitarie Locali (ASL, Local Healthcare Corporations) Aziende Ospedaliere (AO, Public Hospitals)

The Healthcare Reform passed in 2001 established the following executive bodies within the Ministry of Health:

The Ministry of Health also receives input and support from a number of other ministries and institutions: . The Ministry of Social Affairs, which coordinates the social services provided through the NHS infrastructure; . The Ministry of the Treasury, which contributes to the establishment and control of the healthcare budget; . The Standing Committee on Relations between the State, the Regions and the Autonomous Provinces, established in 1988 and composed of the regional governors and representatives of the national government. The central structure is responsible for the following activities: . . . . . .

framework regulation; regional monitoring; healthcare planning; healthcare financing; research support; international relations;

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. general governance of IRCCS.

3.2. Local (regional and municipal) structures Structures at the regional level have legislative and executive functions and provide technical support and evaluation. Since 1999, efforts to federalize the public healthcare system have increased the roles played by the regions in healthcare legislation and financing. For many years, the national territory was divided into 659 local health units known as Unita` Sanitarie Locali (USL). Reforms introduced in 1992 profoundly reshaped the organizational structure and management of these units, reducing their number, widening their population bases, and increasing their autonomy. The result is a network of 228 Aziende Unita` Sanitarie Locali (ASL, local healthcare corporations), each serving an average population of 250,000. Within its area of jurisdiction, each ASL offers a full range of free or low-cost healthcare services (including outpatient visits by general practitioners and specialists, diagnostic procedures, acute and long-term hospitalization, and nursing home care). These services are provided through facilities owned and managed directly by the ASL, public hospitals, National Institutes for Scientific Research, and state-accredited private facilities and providers. The ASL also provide public health services related to: . hygiene and public health, including infectious and parasitic disease prophylaxis, health promotion and education, and elimination of environmental hazards; . food and nutrition (control of production, processing, preservation, commerce and transport; prevention of food-related disease and nutritional disorders such as obesity and malnutrition, etc.); . occupational safety (including work-site inspections and application of norms designed to prevent occupational diseases and accidents); . veterinary medicine (surveillance of animal herds, breeding practices, feeds, etc.).

Until recently, no formal provision had been made for the inclusion of toxicologists on ASL staffs or for the establishment of specialized toxicology services.

4. National bodies 4.1. National health institute (Istituto superiore di sanita` ), Viale Regina Elena 299, 00161 Rome, Italy, Tel.: /390649901, Fax: /390649388118, E-mail: [email protected]: http://www.iss.it. The Italian National Health Institute (Istituto Superiore di Sanita` -ISS) conducts scientific research and provides control and advisory services in the field of public health. In 1978, it became the technical and scientific body of the NHS, under the authority of the Ministry of Health. In 1999, the ISS was transformed into a public body with scientific, organizational, administrative and accounting autonomy. It continues to serve as the technical and scientific body of the NHS and collaborates with the Ministry of Health, regions, hospitals and other health organizations. The Institute has a staff of approximately 2000, including permanent staff members, research fellows and trainees. There are currently 20 laboratories, which are destined to be grouped into departments. Most of the work within the field of toxicology will be carried out in the Department of Pharmacology, whose responsibilities include drug safety and prevention of tuberculosis, and the Department for Primary Prevention of Environmental Hazards, which is responsible for the identification and control of different types and sources of chemical and biological risks. These departments will include the Laboratories of Applied Toxicology, Comparative Toxicology and Ecotoxicology, Environmental Hygiene, Pharmaceutical Chemistry and Pharmacology, which are already involved in the research, control and institutional activities related to chemical risk and safety assessment. Their work is supported by other laboratories (e.g. Clinical Biochemistry, Epidemiology and Biostatistics, Food, Veterinary Medicine) and the Institute’s Documentation

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Service. At this time, there are over 20 toxicological research projects dealing with pesticides, dangerous chemicals, bioelements in the environment, mineral fibers, genotoxicity, models and methods for the assessment of toxicological and ecotoxicological risks, air, water and soil quality, wastes and environmental epidemiology. A National Toxicology Advisory Committee (CCTN Committee) has been established within the ISS by the Ministry of Health. Its purpose is to evaluate the potential carcinogenic, mutagenic, reproductive and other toxic risks of human exposure to chemicals and to identify specific areas for toxicological research. The ISS is also responsible for maintaining and updating the National Inventory of Chemical Substances (INCS), a data bank on the hazards and risks related to existing chemicals. At an international level, the ISS takes part in scientific and technical activities organized by the European Union regarding classification, labeling, preparation of test guidelines and risk assessment for existing chemical substances, and activities concerning new chemical substances. The ISS, which oversees technical aspects of national directives on pesticides, serves as one of the four European Community Reference Laboratories for monitoring pesticide residues in food and environmental matrices. The ISS is the national coordinator of the OECD Toxicology Testing Guidelines Program. It serves as a reference point for the Complementary Information Exchange Procedure (CIEP) and the Screening Information Data Set. It is a WHO Collaborating Center for research and training in veterinary public health. ISS experts regularly participate, as temporary advisers, in WHO groups examining chemicals. The ISS contributes to activities and programs organized by the IARC, UNEP, IPCS and NATO-CCMS. A new website has recently been created by the ISS to provide information on environmental pollutants endowed with endocrine activity (endocrine disruptors) (http://www.endodistru. iss.it).

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4.2. National agency for new technologies, energy and the environment (Ente per le Nuove Tecnologie, l’Energia e l ’Ambiente ) (ENEA), Centro Ricerche Casaccia, BIOTEC MED, Via Anguillarese 301, 00060 S. Maria di Galeria (RM), Italy, Phone: /390630484016, Fax: /390630486559, E-mail: [email protected] The Agency for New Technologies, Energy and the Environment (Ente per le Nuove Tecnologie, l’Energia e l ’Ambiente -ENEA) is an obligatory reference point for national policies regarding the environment, energy-saving measures, development of renewable sources of energy and technological development. Its activities include research, development and industrial implementation of the projects it elaborates. The ENEA is headed by a President nominated by the President of the Republic and approved by the Council of Ministers. There is also a Director General, who is elected by the five members of the Administrative Council. The ENEA operates under the authority of the Ministry of Industry and works closely with the Ministry of Universities and Research and the Ministry of the Environment in carrying out its activities. Plans and projects are drawn up with the aid of an advisory board composed of internationally recognized experts. The structure is divided into departments, each equipped with its own laboratory. ENEA has eight research centers located in Rome and throughout the country. Universities and other research organizations are often involved in ENEA research activities. In the Department of Biotechnology, Health and Ecosystem Protection (Biotec Med ), there is a section on Toxicology involved in the following activities: Genetic toxicology: Evaluation of the genotoxic effects of environmental chemicals in rodents, with particular emphasis on cytogenetic damage, and biomonitoring of human populations exposed to radiation and/or chemicals. Reproductive toxicology: Evaluation of toxic effects on the reproductive functions, particularly those caused by endocrine disrupting chemicals, in experimental models and groups at risk for occupational or environmental exposure.

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Environmental toxicology: Development and validation of bionsensors for pesticides and other environmental pollutants. Estimation of levels of radionuclides and heavy metals in selected population groups. 4.3. Italian national research council (Consiglio Nazionale delle Ricerche ) (CNR), P.le Aldo Moro, 00100 Rome, Italy, Phone: /390649931, Fax: /390649933324, E-mail: [email protected], Web: http://cnr.it The structure of the Consiglio Nazionale delle Ricerche (CNR) was completely revised by a law passed in 1999. There is now a President, who is nominated by the Ministry of Universities and Scientific Research and Technology, and an Executive Committee consisting of eight members, four of whom are nominated by the Minister. The activities of the CNR were previously organized by 14 Scientific Committees, which have now been replaced by a single 20-member Scientific Committee. To ensure continuity, the remaining four members of the Executive Committee, as well as 10 of the members of the Scientific Committee, have been elected by these Committees. The other 10 members of the Scientific Committee are elected by the research staff itself. The CNR no longer provides funding for research conducted by individual research groups. It does not have laboratories specifically devoted to toxicological research, although it supports many toxicologically oriented research projects, and many of its laboratories are involved in basic research projects with relevance to toxicology. 4.3.1. National research council water research institute, department of applied hydrobiology (Consiglio Nazionale delle Ricerche, Istituto di Ricerca sulle Acque Sezione Territoriale di Idrobiologia Applicata */IRSA-CNR), 20047 Brugherio (MI), Italy, Phone: /390392004303, Fax: /390392004692, E-mail: [email protected] The ecotoxicology section of this CNR institute is in charge of monitoring and establishing quality standards for water. Studies have been conducted to determine the acute and long-term effects of

industrial chemicals and environmental contaminants (detergents, heavy metals, ammonia, amines, chlorobenzene, etc.) on aquatic organisms (both adult and developmental stages). The accumulation of persistent organic and inorganic chemicals in fish has also been studied in the field and laboratory. Recently, studies have been undertaken to forecast the distribution and fate of organic micropollutants in the environment based on their physicochemical properties. QSARs have been applied to aquatic toxicology to correlate bioaccumulation and its acute and chronic effects with simple molecular descriptors for homogenous series of organic chemicals. A toxicological approach has also been applied to field monitoring with the aim of detecting toxic organic micropollutants in surface waters.

4.4. Supranational centers located in Italy, European commission joint research center (JRC), Via E. Fermi 1, 21020 Ispra (VA), Italy, Phone: /390332789893, Fax: /390332785409, E-mail: [email protected], Web: http:// www.jrc.org/ The European Commission Joint Research Center (JRC) includes seven scientific institutes located in five separate areas of Europe. The JRC in Ispra (VA) hosts three of these institutes, as well as the Directorate for Resources, which is responsible for providing all seven institutes with the logistic support necessary to carry out their missions. The scientific institutes located in Ispra include: . The Institute for Health and Consumer Protection, which was created with the aim of reestablishing confidence in food production by providing analysis of food quality and safety and by supporting EU legislation on food. Activities are conducted in a wide range of fields, including analytical chemistry, molecular biology, pharmacology, and toxicology. Current research includes harmonization of tests for detecting the presence of BSE and GMOs. . The Institute for Environment and Sustainability, which is responsible for checking various

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forms of pollution and ensuring water and air quality. . The Institute for the Protection and the Security of the Citizen, which is concerned with cybersecurity, protection against natural, technological and economic risks, human safety and nuclear safeguards. The European Center for Validation of Alternative Methods (ECVAM), located in the JRC, is presently the international reference Center for the development, scientific and regulatory acceptance of alternative testing methods. Its work is aimed at reducing and/or improving the use of laboratory animals in biomedical research. To these ends, the ECVAM continuously reviews data on alternative testing methods for approved use in specific areas. 4.4.1. World health organization European Center for Environment and Health (ECEH) */Rome Division, Via Francesco Crispi 10, 00187 Rome, Italy, Switchboard: /3906487751, Fax: /39064877599, E-mail: [email protected], Web: http://www.who.it The Rome Division of the ECEH was established in 1991. Office accommodation, core staff and core activities are funded by the Italian Government. It has a staff of about 30 people. It hosts a Library specialized in environment and health topics that is open to internal and external users (holdings: about 5000 monographs, 65 international biomedical journals and electronic databases available for consultation). The ECEH-Rome focuses its attention on health aspects related to the environment, such as transport, energy or agriculture; policy and strategy development; health risks deriving from the exploitation, degradation or pollution of the environment; the impact of global environmental changes on health; assessment of the effects of globalization of the economy on health. Technical areas covered by the Rome office are: health impact assessment; food safety; water and sanitation; and waste management. Other active programs include Global Change and Health,

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Transport, Environment and Health, and Children’s Environment and Health. The ECEH-Rome also collaborates with the Ministers of Health and Environment of Europe and is involved in specific projects on Environment and Health in Italy. Its advice and assistance are available to member states of the WHO Regional Office for Europe.

5. Resources for the environment Monitoring and control of the national territory and human activities, evaluation of the environmental impact of programs and projects, and environmental advisory services for regions, provinces and municipalities are handled by the network of national, regional and local bodies described below. 5.1. Ministry for environmental protection (Ministero dell’Ambiente e della Tutela del Territorio) (http://www.minambiente.it) The activities of the Ministry are divided into the following sectors: development; preservation of the territory; pollution and industrial risks; international environmental protection; environmental impact assessment; nature preservation; waste and reclamation; marine and inland water protection. The website provides clear and complete information on each topic, oriented to both experts and laymen. Documents are available in full-text format. 5.2. National agency for environmental protection (Agenzia Nazionale per la Protezione dell ’Ambiente -APAT) (http://www.aicq.it/ampa/ manuale/present.html) The National Agency for Environmental Protection and for Technical Services (Agenzia per la Protezione dell ’Ambiente e per i servici technici ANPA) is one of the major Italian bodies involved in environmental control. It was created in 1994 to support governmental activities and is under the direct supervision of the Ministry for Environ-

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mental Protection (Ministero dell ’Ambiente e della Tutela del Territorio ). The ANPA coordinates the activities of the regional agencies (ARPA) and provincial agencies (APPA) through a network that allows exchange of information and knowledge to better analyze and control the state of health of Italy. The Agency plays important roles in environmental protection, contributing to the drafting of environmental norms, collecting and handling data on different environmental pollutants and emissions (INES), and providing information on nuclear safety and radioprotection. It is the National Focal Point for the collection of national data for the European Agency for the Environment. In this context, the ANPA has created six national centers that collaborate with regional agencies on environmental protection issues related to inland and coastal waters; physical agents; atmosphere; climate and emissions; nature preservation; waste disposal; soil and contaminated sites. Activities in each area are carried out by different structures operating in the environmental sector, such as universities, CNR institutes, the Istituto Superiore di Sanita` , the Istituto Centrale per la Ricerca Applicata al Mare . The objectives of these centers are to identify indexes and indicators of the state of health of different environmental matrices, and to identify and classify pollutants and dangerous substances based on their uses and effects on the environment.

6.1. TOX.IT */The world of Italian Clinical Toxicology on the Internet (http://www.tox.it)

5.2.1. Regional (ARPA) and provincial (APPA) agencies for environmental protection (http:// www.arpa.emr.it/chi.htm) The Regional Agencies for Environmental Protection were established between 1995 and 1998. Each agency has its own website, where a variety of activities on different environmental matrices and risks to the population are described in detail, such as plans for handling emergencies, industrial plants at risk for serious incidents, alerts regarding spills or leakages of toxic substances. Some sites also provide access to on-line journal searches, studies and research activities on topical environmental issues.

These web pages were created by the Poison Center (PC) of the National Institute of Health and several academic institutes to provide easy access to Italian toxicological resources for professionals and the public. Information is published in Italian and English. Non-professional users can find the addresses of PCs in Italy and a service called ‘The virtual toxicologist,’ which provides answers to questions on toxins, poisons, symptoms, and treatment. The service is maintained by the PC of the Catholic University of the Sacred Heart in Rome. In the near future, a link will be added for a search engine devoted exclusively to international toxicological information. Specialists can sign up for a mailing list dealing with various aspects of toxicology. Members can exchange

5.2.2. National system for environmental information (Sistema Informativo Nazionale Ambientale */SINAnet) (http://sinanet.anpa.it/) The SINAnet was designed to coordinate and standardize data from various environmental resources in Italy, to facilitate their use on the national and European levels. It is supervised by the ANPA. 5.3. The national register of pollutant emissions (INES) (http://www.sinanet.anpa.it/INES/default/ htm) The National Register of Pollutant Emissions (INES) was established at the beginning of 2002, and the website is still under development. Data on Integrated Pollution Prevention and Control (IPPC) are to be reported to the ANPA and other authorities on a yearly basis, specifying in detail the quantities of any single pollutant emitted by industrial plants. The statements will then be transmitted by the ANPA to the Ministry of Environment and to the European Commission and published on the Web.

6. Biomedical websites

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opinions, submit problems and ask for information. The site also contains a link to the EMER.CHEM databases (http://www.diesis.com/ cemec/emerchem), which contain information on industrial toxics (database available in English and Italian), past industrial accidents and industrial risk mapping. The databases were created as part of a European Council project directed by the European Center for Disaster Medicine in the Republic of San Marino. 6.2. Medical toxicology (http://www.toxy.net) The TOXY.NET website was created to provide information and support to specialists working in the field of toxicology. It is a nonprofit site that adheres to HON code principles, and it was set up by Dr Nicola Cadel, a medical toxicology specialist from the University of Padua. TOXY.NET offers access to the main toxicology information resources available online, with links to Poison and Tobacco Centers in Italy, centers providing information on drugs and alcohol and Italian and international food science institutes. It provides the latest news in the field, an online forum and access to scientific literature and legislative material related to the major topics in toxicology. It is connected to the Italian search engine Virgilio. 6.3. SITOX (http://www.sitox.org; E-mail: sitox@comm2000) Accessed through the home page of the SITOX (see Professional Societies), this site provides an overview of the Society’s activities, including the training courses it organizes in Italy. The Events section contains information on major toxicology conferences and meetings being organized in Italy and other parts of the world, including the Society’s National Congress (the 23rd will be held in 2003 in Florence, Italy) and the Eurotox Congress, which is usually held every 3 years. Links are also provided to the major international toxicology societies and institutes engaged in toxicological research. In the Clinical Medicine section, users can join workgroups and find

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information about meetings, training courses and guidelines, as well as a list of useful links.

6.4. MYCOLOGIC-NATURALISTIC Group (GRUPPO MICOLOGICO-NATURALISTICO ) (http://antares.fastnet.it/associazioni/gmn/) This site was created by the Environmental Education Center of the Mycologic-Naturalistic Group in Ancona. One of its prime objectives is to educate the public on the hazards of poisonous mushrooms. It also provides information and teaching materials on various aspects of mycology and ecology.

6.5. Mushrooms in Italy (FUNGHI IN ITALIA ) (http://www.funghiitaliani.it) Created by the National Mycological Association, this site also provides information on poisonous mushrooms found in Italy, guidelines for their recognition, growing seasons, habitats, shortand long-term latency syndromes and symptoms of probable intoxication. It also provides access to the Association’s online journal and an online forum.

6.6. Toxicology of hymenopterous poisons and their therapeutic USE (Bee Venom Therapy) [TOSSICOLOGIA DEI VELENI DI IMENOTTERI E LORO IMPIEGO TERAPEUTICO (apiterapia)] (http:// www.apicolturaonline.it/) The site is managed by the Orthopedic Division of the Azienda Ospedaliera of Cremona. It provides information on the properties of bee venoms, their composition and toxicology, and their therapeutic uses.

6.7. The international association of forensic toxicologists (http://www.tiaft.org) (see Professional Societies).

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6.8. Subject list of sites (http://pacs.unica.it/ siti.htm) This site, managed by the University of Cagliari, offers a wide variety of links related to different biomedical fields. The section on Toxicology includes useful links to international databases and databanks in the field. 6.9. ANESTIT (Italian anesthesia) [ANESTIT (ANESTesia ITaliana)] (http://anestit.unipa.it) The aim of the ANESTIT site (ANESTesia ITaliana), run and managed by the Anesthesia Department of the Buccheri La Ferla Fatebenefratelli Hospital of Palermo, is to provide specialized information for anesthesiologists and specialists and paramedical staff members working in critical care areas. The toxicology section provides information on the practical aspects of clinical toxicology and access to actual case reports taken from the electronic journal Educational Synopses in Anesthesia and Critical Care Medicine*/Italy of ANESTIT. A new service allows users to locate hospitals that can provide antidotes against poisoning caused by mushrooms or home products. For each type of toxic agent, illustrated technical cards are provided describing the composition, toxicity data, symptoms and treatment of intoxication. In the pharmacology section, users can find updated information on Anesthesiological Pharmacology in ‘Farmacologia online.’

Annuario DEA delle Universita` e Istituto di Studio e Ricerca in Italia (2000)DEA Editrice, Roma

Vighi, M. (1998)Ecotossicologia. pp. XIX/237, UTET, Torino

Lombardi, C. (1999)Norme e procedure per l’utilizzo di agenti cancerogeni nei laboratori di ricercaENEA, Dipartimento Ambiente, Roma

Capuano, A. Dugo, G. Restani, P. (1999)Tossicologia degli alimenti. In: Paoletti R, ed. Farmacologia e Terapia. ; pp. 227, UTET, Torino

Bertol, E. (1999)Trattato di tossicologia forense28 ed. pp. XVIII/527, Cedam, Padova

Hrelia P., Cantelli Forti G. (2001)La tossicologia per la qualita` e la sicurezza alimentare.pp. VIII/ 137, Patron ed., Bologna

Cantelli Forti, G.P. Hrelia, M. Marinovich, C.L. Galli (2000)Tossicologia molecolare e cellulare (In: Paoletti R. ed., Farmacologia e Terapia )pp. XVII260, UTET, Torino Froldi, R. (2001)Lezioni di tossicologia forensepp. X/143 Giappichelli, Torino

7. Recent publications (over the last 5 years) Toxicology is a broad field, and the literature is continuously being updated. It is impossible to provide a complete list of all recent publications in this field, but we have selected some of the more representative titles in certain branches. 7.1. Books Annuario Nazionale dell’Energia e dell’Ambiente (2001-XIX ed.)Inter-Ed, Roma

Farina M.L., Bacis G., Gattini A., Di Muzio M., Taddei G.C., Giuliani L. (2001)Antidoti. Prontuario terapeutico aggiornatopp. 165, Il Pensiero Scientifico Ed., Roma Gagliano-Candela, R. (2001)Tossicologia forense in schemi, tabelle e testoGiuffre`, Milano Gruppo micologico Bresadola (2001)Parliamo di funghi: tossicologia, commercializzazione, legisla-

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zione.Giunta della Provincia autonoma di Trento, pp. 206 7.2. ANPA-ARPA Monographs Cima F., Brema G. (1999)Il rischio in Italia da sostanze inorganiche: fondo naturale incontaminato e contaminatopp. 363 ANPA, Roma Cassoni, F. Buschini, AM. (2000)Test di mutagenesi e monitoraggio ambientale.pp. 127, Arpa, Bologna Istituto di Igiene e Medicina Preventiva (1998)Laboratorio di mutagenesi ambientalepp. 56 Quaderni Arpa, Universita` di Genova

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. The formation and metabolism of nitrosamines under different conditions . Development of short-term toxicity tests using isolated perfused organs and cells as models of target organ toxicity . The effects of glutamic acid on the central nervous system . Mechanisms and mediators of renal injury provoked by antibiotics and anticancer agents . Evaluation of chemical composition and toxicity of urban waste incinerator emissions . Immunotoxicology . Toxicokinetics In its 40 years of activity, the Institute has published approximately 7000 articles in international journals, 2500 transfer articles, and 180 books (monographs and Congress Proceedings).

8. Research structures The following is a partial list of some of the well known research centers involved in toxicological research in Italy.

8.1. Istituto di Ricerche Farmacologiche Mario Negri (Mario Negri Institute for Pharmacological Research), Via Eritrea 62, 20157 Milan, Italy, Phone: /3902390141, Fax: /39023546277/ 39001918, E-mail: [email protected], Web: http://www.marionegri.it The Mario Negri Institute for Pharmacological Research is a scientific nonprofit foundation for biomedical research and higher education that opened in 1963. The Institute is equipped with 44 research laboratories and employs more than 800 people (researchers, laboratory technicians, postgraduate trainees, supporting staff, etc.). There are also three extension laboratories located in Bergamo, Ranica (Bergamo) and S. Maria Imbaro (Chieti). The following lines of toxicological research are currently being pursued: . Relations among toxic effects, metabolism, and disposition of xenobiotics in animals . Influences of polychlorinated aromatic hydrocarbons on the hepatic heme pathway

8.2. Toxicology Unit, Department of Pharmacology, University of Bologna, Phone: / 390512091798 or 2091799 or 253548, Fax: / 39051248862, E-mail: [email protected]; [email protected]; [email protected] The Toxicology Unit is headed by Professor Giorgio Cantelli Forti, and its professional staff is made up of five faculty members and six Ph.D. students. Between 10/15 undergraduate students are working on their theses in the Unit’s laboratories. The Toxicology Unit works closely with other national and international scientific centers, including the Karolinska Institut in Stockholm, the GSF Center in Munich, the University of Texas Medical Branch in Galveston (TX), and the Kimmel Cancer Center in Philadelphia (PA). The research group’s work on critical biological events in the expression of toxicity by drugs, natural substances and environmental contaminants has provided new insights into the potential hazards related to exposure to these substances. Emphasis has been placed on the investigation of mechanisms underlying mutagenesis and carcinogenesis and the development of methods to improve assessment of human exposure, susceptibility and risk. The Unit promotes a multidisci-

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plinary approach to research in the field of environmental toxicology, food toxicology, and toxic drug interactions. Its main objectives are to increase our understanding of the following issues: 1) Toxic stress response in human cell lines, as an indicator of carcinogenic potential of xenobiotics 2) Biomarkers and genetic/carcinogenic risk in human populations 3) Phenotypic studies on drug-metabolizing enzymes 4) Natural substances in the chemoprevention of cancer

8.3. Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 2, 16132 Genoa, Italy, Phone: /390103538801 or 3538850, Fax: / 390103538232, E-mail: [email protected]; [email protected] In the last two decades, the research activity of the Pharmacology and Toxicology Unit, headed by Professor Giovanni Brambilla, has been focused primarily on the identification of genotoxic/ carcinogenic activity of drugs and other chemical agents and on the development and validation of sensitive in vitro and in vivo assays for detecting such effects. Over 180 original articles in peerreviewed journals, review articles and book chapters have been published in this period. Important studies within the field of genotoxicity have been conducted on the high-order structure of native chromatin DNA, the physicochemical bases for DNA alkaline elution, the genotoxic risk to humans linked to the intragastric nitrosation of amine drugs, and the inhibitory effects on nitrosation reactions of a series of phenols and hydroxybenzoic acid. A new extremely sensitive viscometric method has also been developed for the detection of DNA breaks. These studies have led to the identification of the DNA-damaging activity of drugs, lipid peroxidation products, and industrial chemicals.

8.4. Unit of Toxicology, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy, Phone: / 390250318315, Fax: /390250318260, E-mail: [email protected] or [email protected] The Laboratory of Toxicology, headed by Professor Corrado Galli, was created in 1979 to study toxicological aspects of food additives. Over the last two decades, research has been focused on the cellular and molecular mechanism(s) of action of toxic substances (mainly environmental contaminants) and their relevance to human risk assessment. Main research activities and expertise include the identification and characterization of biochemical mechanisms involved in cell response to toxic agents, focused on: a) the central nervous system; and b) immune system, and possible interactions between them. In the Unit of Toxicology is also active the Center of Evaluation of Toxicological Risk . The activity of the Center deals with the scientific evaluation of known potential adverse health effects resulting from human exposure to toxic agents. The process consists of the following steps: (i) hazard identification, i.e. the identification of biological, chemical, and physical agents capable of causing adverse helath effects; (ii) hazard characterization, the qualitative and/or quantitative evaluation of the nature of the adverse effects associate with biological, chemical and physical agents; (iii) exposure assessment; and (iv) risk characterization.

8.5. Department of Pharmacology, Chemotherapy and Medical Toxicology, Faculty of Medicine, University of Milan, Via Vanvitelli 32, 20129Milan, Italy, Phone: /390250317080, Fax: / 390250317079, E-mail: [email protected] The research conducted in the Department of Pharmacology, Chemotherapy and Medical Toxicology, involves various fields of environmental and clinical toxicology. The toxicological unit is chaired by Professor Enzo Chiesara.

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In vitro studies have been carried out on isolated hepatocytes from humans (HepG2), mice, and rainbow trout to identify the mechanisms of action and biochemical changes underlying the toxic effects of water pollutants and the protective mechanisms they trigger in these cells. These studies have focused on the general toxic effects of pollutants, as well as their specific actions, such as endocrine disruption and the effects of byproducts formed by the interaction of natural substances and pollutants (e.g. disinfectants). Genetically engineered cells are also being constructed as biomarkers of water pollution by specific elements. Other toxicological studies are being conducted on the behavioral effects of repeated administration of psychoactive drugs as part of a broader project in the field of neuropharmacology. In the field of clinical toxicology, studies are being conducted to evaluate the risk/benefit ratio of hyperbaric oxygen treatment for carbon monoxide intoxication. While this approach undoubtedly has a positive impact on survival rates, it also produces serious secondary effects in the lungs, heart and brain. Experimental data appear to confirm that the toxic effects of hyperbaric oxygen therapy are mediated by the production of free radicals that can cause direct damage to vascular endothelial cells. 8.6. Toxicological Unit, Department of Pharmacology, Faculty of Medicine, University of Turin, Via Pietro Giuria 13, 10125 Torino, Italy, Phone: /390116707792, Fax: 0116707788, E-mail: [email protected] The research conducted by the Toxicological Unit, headed by Professor Francesco de Matteis, focuses on the roles of heme and hemoproteins in toxicological reactions. The following aspects are currently being studied: 1) Mechanisms underlying the induction of hepatic uroporphyria by polyhalogenated chemicals . Evidence collected thus far suggests that these chemicals activate a cytochrome-P-(CYP)-dependent oxidative stress mechanism in the liver.

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2) Mechanisms underlying the resistance to digestion of the malarial pigment (hemozoin, a polymeric form of heme) after phagocytosis by human monocytes. The results suggest that the lysosome is unable to de-polymerize hemozoin and release free heme from it, accounting for the pigment’s inability to induce heme oxygenase in monocytes and to act as a substrate for the enzyme. 3) The modulation of cerebellar and hepatic nitric oxide synthase (NOS ) activities by exogenous arginine and endotoxin has also been studied. The results indicate that LPS stimulates NOS expression/activity in both the cerebellum and the liver and suggest a complex pattern of modulation of iNOS by arginine. 4) The role of CYP forms in the metabolic transformation of halocarbons to neoantigens and the selective olfactory CYP inactivation by haloethanes. 8.7. Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy Operative Unit for Clinical Toxicology and Drug Addiction, University of Florence, Azienda Ospedaliera di Careggi, Viale G.B. Morgagni 85, Phone: /390554277238 (Inpatient Ward), Phone: / 390554277819 (Poison Center), Phone: / 390554277244 (Outpatient Clinic), Fax: / 390554277925, E-mail: [email protected], Web: http://www.pharm.unifi.it (Dipartimento di Farmacologia) The Department of Preclinical and Clinical Pharmacology of the Florence University School of Medicine is chaired by Professor Pier Francesco Mannaioni. Its research groups are active in both experimental and clinical toxicology. In the last 5 years, two research issues have been addressed experimentally: 1) The conversion into free radicals of drugs of abuse . Results indicate that morphine, methadone and cocaine can be converted into radical species by prostaglandin-H -synthase

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and by the S-10-mix fraction of CYP450, causing membrane lipoperoxidation and cell damage. 2) The pathophysiological involvement of carbon monoxide in the modulation of the response of the immune system. It has been demonstrated that both the induction of heme oxygenase 1 and exposure to exogenous carbon monoxide down-regulate the IgE-dependent activation of isolated or tissue-resident mast cells, with consequent implications in the carbon monoxide toxicity. Since 1917, the medical staff of the Department has been involved in the diagnosis and treatment of acute poisoning in the Florence General Hospital (Azienda Ospedaliera Careggi ), and since 1972, it has also been responsible for the care of patients with opioid addiction and alcohol-related syndromes. The Clinical Toxicology Unit is equipped with a 22-bed inpatient ward, an outpatient clinic, facilities for blood studies and urinalysis, and a poison control and treatment center with access to the Micromedex System database. The Unit, which provides 24-h coverage, has a staff of 25 nurses and nursing assistants and 14 physicians. Consultations can be requested from social workers, psychologists, psychiatrists and neurologists. The Unit evaluates guidelines and protocols for the treatment of opioid and alcohol addiction and collects epidemiological data on drug addiction and poisoning, which are reported on a yearly basis to the Ministry of Health. 8.8. Institute of Toxicology and National Toxicology Information Center, University of Pavia and Maugeri Foundation, Via Ferrara 8, 27100 Pavia, Italy, Phone: /39038224444 (Poison Center) (24-h), Phone: /390382556600 (Research Center), Fax: /390382592782, E-mail: [email protected] or [email protected] Headed by Prof. Luigi Manzo, the Institute includes the National Toxicology Information Center, with an associated clinical unit, and the Toxicology Research Center. It has a staff of about 30 scientists, clinicians and post-graduate students operating within the Medical School of

the University of Pavia and the ‘Salvatore Maugeri’ Foundation, a national nonprofit organization devoted to research and clinical activities in the fields of occupational health and rehabilitation medicine. A series of training programs in toxicology are offered in the Institute, as part of graduate courses, by the Medical Faculty and the Postgraduate Schools of Internal Medicine, Pharmacology, Occupational Medicine, Anesthesiology and Intensive Care. The National Toxicology Information Center serves as the coordinator of a nation-wide network of approximately 300 hospitals providing toxicological services. It is operated by a 24-h poison control staff of qualified professionals with expertise in the fields of clinical toxicology, emergency medicine, anesthesiology, pharmacology, analytical chemistry, occupational and environmental health. It also collaborates with several governmental bodies and public interest groups on programs related to chemical accidents, industrial toxicology and the production of the National Inventory of Chemical Substances. Resources include advanced technology for chemical hazard communications, bibliographic tools, electronic journals, and a variety of computerized databases for emergency medicine, clinical and industrial toxicology. Special consultancy systems are used for first-aid treatment, chemical emergencies and hazard monitoring in the workplace. Clinical activities include the management of poisoning and overdose, drug and alcohol dependence, and the diagnosis and treatment of disorders caused by prescribed drugs and other chemicals. Research activities . In collaboration with academic and research institutes in other European countries and the United States, the Toxicology Research Center is conducting studies on the molecular mechanisms of neurotoxicity, biomarkers, the effects of metals and industrial solvents, and novel in vitro toxicity assays. Over the last 5 years (1996 /2001), the Institute has produced about 200 articles, books, monographs and special documents, most of which have been published in international journals.

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9. Graduate and postgraduate programs 9.1. University programs This section contains information on institutions offering officially approved courses related to the disciplines of pharmacology and toxicology, postgraduate specialization courses in toxicology or pharmacotoxicology, and Ph.D. programs in pharmacotoxicology. Further details are available in the 3rd Edition of Information Resources in Toxicology */Italy, pp. 677 /693. Thirty-five Italian Universities offer courses in pharmacotoxicology as part of the undergraduate curricula of the following faculties: Medicine and Surgery, Dentistry, Pharmacy, Veterinary Medicine and Science. In the Faculties of Medicine and Surgery , toxicology is now considered an obligatory part of the course work in pharmacology (which also includes basic pharmacology, pharmacology of organ systems, neuropsycopharmacology and chemotherapy). Approximately 100 /120 h are allotted for the course work in pharmacology. Most are divided between the fourth and fifth years of medical school, and a few hours are dedicated to toxicology. The concepts formerly covered in clinical, industrial and forensic toxicology courses are included in courses of anesthesiology and intensive care, occupational medicine and forensic medicine, respectively. Toxicology is also taught in the Faculties of Dentistry . It accounts for approximately 50 of the teaching hours dedicated to pharmacology. The course concentrates on areas with specific relevance to dentistry, such as the toxic effects of local anesthetics, fluorine and mercury. In the Faculties of Pharmacy , one or two of the three semesters dedicated to pharmacology are focused on toxicology. There are also other courses dealing with topics in the field of toxicology and toxicological analysis, e.g. complementary concepts in toxicological chemistry and analysis of drugs (analytical and chemical toxicology). During the 5th year students are enrolled in professionoriented courses that increase their understanding of previously acquired concepts of pharmacotoxicology. Since 2000, Faculty of Pharmacy of Milan

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activated a degree (3 years ) in Environmental Toxicology. The Faculties of Veterinary Medicine and Science have revised their curriculum in conformity with recent decrees issued in 2000 /2001 by the Ministry of Universities and Scientific/Technical Research. Courses in toxicology and veterinary pharmacology are now included in the last 4 years of the graduate program and include Veterinary Pharmacology, Veterinary Chemotherapy, Drug Surveillance, Veterinary Toxicology, and Toxicology of Residues in Foods of Animal Origin. In the Faculties of Biological Science (5 years of study). Toxicology courses are currently optional. When offered, they represent one semester of study for a total of 90 teaching hours. Topics in environmental toxicology and ecotoxicology are covered in different courses. 9.2. Postgraduate programs Postgraduate training in toxicology includes: a) Postgraduate Schools of Specialization b) Ph.D. Programs c) Research Fellowships 9.2.1. Postgraduate Schools of Specialization Postgraduate Schools of Specialization related to toxicology are operated by the Medical Faculties of Universities and include 17 programs leading to postdoctoral degrees in medical toxicology (4 years) or pharmacology (option toxicology) (4 years) and two programs in forensic toxicology (4 years). Within the Faculties of Pharmacy, there are also three postdoctoral programs in toxicology (3 years). These programs generally require 800 h/ year, half of which are dedicated to practical training and activities. Each school admits from 8 to 20 students each year, and one of these students is selected to receive a State Scholarship. The curricula of these schools are currently being revised by the Ministry for Universities and Scientific Research. The main change is expected to be a greater emphasis on practical experiences rather than theory/lectures.

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9.2.2. Ph.D. Programs Programs leading to a Ph.D. in areas related to toxicology include six focused on Pharmacology and Toxicology, one on Drug Addiction, one on Drug Addiction and Alcoholism, one on Neuropsychopharmacology and Drug Addiction, three on the Medico-Forensic Sciences, one on Forensic Toxicology, two in Occupational Medicine and Industrial Toxicology, 11 in Environmental Sciences, five in Veterinary Pharmacology and Toxicology, and five in Veterinary Clinical and Pharmacotoxicology. The programs are offered by universities, and admission is granted on the basis of competitive testing. Students are expected to complete 3 /4 years of study and research (depending on the individual program); specific activities are established by the program coordinator. The student receives a monthly salary from the university during the entire period of study. This salary is increased by 50% for study periods abroad, which can last 1 or 2 years. At the end of the course of studies the student is expected to present a complete dissertation regarding his or her research. This work is evaluated by a randomly selected Commission of Examiners composed by two full professors from other Italian universities with expertise in the student’s field of research.

9.2.3. Research fellowships Research fellowships dealing with specific topics are proposed by individual faculty members of a university. Candidates are evaluated by a commission nominated by the faculty that includes the person that proposed the fellowship. Fellowships are granted for 2 years (with possible renewal for an additional 2 years) or 4 years. The salary assigned to the fellow, which is roughly equivalent to that of a Ph.D. candidate, is paid with funds administered by the department in which the research is conducted. At the discretion of the research tutor, the research fellow may be allowed to conduct part of the research in laboratories outside Italy. Also SITOX has an annual program of fellowships.

10. Legislation Article 10 of Legislative Decree no. 285 (16 July 1988) was passed in accordance with the EEC Directive (88/379/EEC) concerning classification, packaging and labeling of dangerous preparations. The Article provides for the creation of a computerized database of dangerous substances or products. The ISS Laboratory of Applied Toxicology is responsible for maintenance of the database, which contains relevant information on all dangerous preparations placed on the Italian market. The Archivio preparati pericolosi (database of dangerous preparations) can be accessed through in the ISS website (http://www.iss.it) or directly through the dangerous preparations website (http://www.preparatipericolosi.iss.it). At present, 148,632 preparations (of the 542,657 existing ones) are included in the database. Italy has extensive national legislation in the field of chemicals. These Acts are first of all adopted from European Union Directives and are also national Acts. In addition to EU Directives and national Acts, Italy is guided by a number of international treaties as the Convention on Long-Range Transboundary Air Pollution (LRTAP), adopted in 1979 under the auspices of the United Nations Economic Commission for Europe (UNECE) and the voluntary Prior Informed Consent (PIC) procedure developed by UNEP and the Food and Agriculture Organization (FAO) of the United Nations. The Italian legislation may be regarded within the framework of hazard identification, risk assessment and risk management, according to well known EU criteria.

10.1. Hazard identification (dangerous properties of chemicals) / A key directive in this field is Council Directive 67/548/EEC (O.J. L. 19, 8/16/197) on classification, packaging and labeling of dangerous substances and its subsequent amendments. The 7th amendment of Directive 67/548/EEC (Directive 92/32/EEC) (O.J. L. 154 5/6/1992) is currently in force. The basic directive was

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implemented in Italy by Law no. 256 of 29 May 1974, and the 7th amendment was adopted by Legislative Decree No. 52 of 3 February 1997. Throughout Europe, a clear distinction is made between the regulation of existing and new chemicals. The latter are defined as substances placed (manufactured or imported) on the market for the first time after September 18, 1981 and, therefore, not included in the European Inventory of Existing Commercial Chemical Substances. The 6th amendment to Directive 67/548/EEC requires that all new substances manufactured or marketed in the EU must be reported to the competent authority. The 7th amendment to Directive 67/548/EEC (Directive 92/32/EEC, O.J. L. 258, 15.10.1979) was adopted in April 1992 and implemented in Italy by Legislative Decree No. 52 of 3 February 1997. Coordination of the notification procedure is the responsibility of the Ministry of Health. A Notification Unit, which is in charge of the technical and scientific aspects of the procedure, has been set up in the ISS. Directive 67/ 548/EEC was most recently amended (for the 28th time) by Directive 2001/59/EC, which is the only amendment that has yet to be implemented in Italy. An Italian version of Annex I of Directive 67/548/EEC can be accessed at the following website: http:// www.spp.iss.it/. / Another key directive in this field is Directive 88/379/EEC regarding the classification, packaging and labeling of dangerous preparations, which was implemented in Italy through Ministerial Decree 28/I/1992. The recently adopted Directive 1999/45/EC abrogates Directive 88/379 and extends the scope of Directive 88/379/EEC to cover plant protection products and preparations and is going to be in force. / The two previously mentioned key directives provide the basis for a cascade of actions, which at the Italian level constitute risk management instruments for the definition of intrinsic dangerous properties of substances and/or preparations.

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10.2. Risk assessment (health risks represented by exposure to chemicals) / In 1993 a European Regulation was adopted on the evaluation and control of the risks related to exposure to existing chemicals (EEC Council regulation N. 793/93 of March 23, 1993, O.J. L. 84, 5/4/1993). It requires industrial plants to provide all available data on tonnage, use, physicochemical properties, toxicological and ecotoxicological effects, human exposure and environmental fate for all high production volume (HPV) substances (produced within the EU market in quantities of /1000 tons/ year). Member States were required to draw up lists of priority substances representing potential risks to human health and/or the environment. Four priority lists have been published as Commission Regulations [1179/94 (O.J. N. 131, 26.5.1994), 2268/95 (O.J. N. 231, 28.9.1995) 143/97 (O.J. N. 25, 28.1.1997 and 2364/2000 (O. J. N. 273, 26.10.2000)]. All data provided by producers and importers of the substances are stored in the International Uniform Chemical Information Database (IUCLID), and this program of activity is fully coordinated within the OECD program on existing HPV chemicals. Nonconfidential data stored in the IUCLID and Risk Assessment Reports can be accessed through the website of the European Chemical Bureau (ECB) of the Commission’s Joint Research Center located in Ispra, Varese, Italy (http://ecb.jrc.it/existing-chemicals/) Risk assessment required by Council Regulation 93/ 793 is carried out according to the principles laid down in Commission Regulation 1488/94 of June 28, 1994 (O.J. L. 161). In Italy, the Ministry of Health, with the technical cooperation of the ISS, is the designated national competent authority responsible for the application of Regulation 93/793 for existing chemicals according to the Decree of November 29, 1994. Italy was rapporteur to Member States for four substances present in the first three lists. Risk assessment required for new chemicals according to Directive 92/32/EC is carried out in accordance with the principles set out by Commission Directive 93/67/EEC (O.J. N. L.

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227 8.9.1993). Directive 93/67/EEC was incorporated into Italian legislation by Decree No. 52 of 3.2.1997. A detailed Technical Guidance Document has been issued by the European Commission in support of Directive 93/67/EEC. In Italy, the Ministry of Health and the ISS are the designated national authorities responsible for the risk assessment of new chemicals. / Directive 91/414/EEC concerning the marketing of Plant Protection Products was implemented by Decree No. 194 of 17/3/1995. The directive sets up the criteria for a harmonized system of authorization for marketing the active substances used in plant protection products at the EU level. Member States may then approve products containing such substances for use in their own territories. Annex VI of Directive 91/ 414 provides uniform principles for the authorization of plant protection products. In Italy, the Ministry of Health is responsible for the authorization of preparations containing pesticides. The directive provides for priority lists of active substances that are subject to risk assessment procedures. / Directive 98/8/EC provides for risk assessment of active substances contained in biocidal products. This directive was implemented in Italy in February 2000. In Italy, products of this type can be marketed or utilized only with ministerial authorization; conditions that must be met for authorization vary according to the risk associated with the biocide and other factors. There is a system of reciprocal recognition between Member States, but it is not automatic. For example, a substance whose use is authorized in Scandinavia might not be safe in another area with different climatic characteristics. The decree also provides guidelines on advertising of biocidal substances. In Italy, the Ministry of Health and the Ministry of Environment, with the technical collaboration of the ISS, are responsible for the application of the set of rules for biocidal products. / Directive 76/769/EEC relates to restrictions on marketing and use of certain dangerous substances and preparations. The basic Directive 76/769 was enforced in Italy, quite literally, by Decree No. 904 of the President of the Republic

/

/

/ /

/

No. 904 (1982); the most recent amendments were adopted at the beginning of 2002. In addition, the following specific national regulations related to dangerous substances are in force: Aromatic amines. Ministerial Memorandum no. 46 of 12 June 1979 and no. 61 of 4 June 1981 of the Ministry of Labor Asbestos. Law no. 257 of 27 March 1992 Chlorofluorocarbons (CFC) and other ozonedepleting substances, other fully halogenated CFC; halons; carbon tetrachloride; 1,1,1-trichloroethane; methyl bromide; hydrobromofluorocarbons (HBFC); hydrochlorofluorocarbons (HCFC). Law no 549 of 28 December 1993 (notification 94/0013/I) prohibited the production, use, marketing, import and export of the following substances (with exemptions provided by the government) after 31 December 1999: methylchloride, methylbromide, hydrobromofluorocarbons and hydrochlorofluorocarbons. Lead and lead compounds [Lead carbonates (neutral anhydrous carbonate, PbCO3, and lead hydrocarbonate, 2PbCO3 Pb(OH)2), and lead sulphates (PbSO4 and Pbx SO4)]. Law no. 706 of July 19 1961 fixed the level of lead and its compounds (expressed as metal lead) contained in paints.

10.3. Risk management Directive 76/769/EEC mentioned above is directly linked to Directive 67/548/EEC concerning substances classified as carcinogenic, mutagenic or toxic for reproduction (category 1 or 2). / The basic Directive 79/117/EEC prohibited marketing and use of plant protection products containing certain active substances. / Directive 91/414/EEC (mentioned above) states that Italy, and other Member States, may authorize plant protection products only when their use has been demonstrated to be safe, and authorization must be revoked when these conditions are no longer satisfied. / In Italy substances and preparations are regulated by the decrees cited above, which implement EC directives (Legislative Decree 52/1997,

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Legislative Decree 285/1998) and EEC Regulation no. 793/93. Marketing and sale of substances and preparations must be controlled by competent institutions at the national, regional and local levels. Sites of production, storage and sale may be inspected at any time and specimens and information collected. Violations noted during such inspections are subject to sanctions. This control is put into practice through No. 13 of 10 September 2000 (G. U. No. 229, 30 September 2000). Like other Member States, Italy is required to present an annual report on these controls to the EC Commission. / Final laws, rules, regulations and all official acts concerning toxic substances are published in the GU , which is issued daily (http://www. gazzettaufficiale.it/index.jsp). The following website provides information concerning Italian implementations of European Community Directives: http://www.parlamento.it/parlam/leggi/ deleghe/dlattcee.htm In 1978 the ISS established a computerized Inventario Nazionale delle Sostanze Chimiche (INSC), (or National Inventory of Chemical Substances-INCS), which is a factual data bank on chemicals (in Italian language) that can be consulted for routine and emergency needs. For risk assessment, the INSC is used for hazard identification, providing extensive information on chemical identification, toxicological and ecotoxicological data, occupational health and safety, environmental fate, standards, evaluation and classification for about 3000 entries. The INSC is available at http://www.insc.iss.it.

Table (Continued )

Acronym

Full Name

ARPA

Agenzia Regionale per la Protezione dell’Ambiente , Regional Agency for Environmental Protection Bovine spongiform encephalopathy Commissione Consultiva Tossicologica Nazionale, National Toxicology Advisory Committee Chlorofluorocarbons Complementary Information Exchange Procedure Consiglio Nazionale delle Ricerche , Italian National Research Council European Center for Environment and Health Ente per le Nuove Tecnologie, l ’Energia e l ’Ambiente , Agency for New Technologies, Energy and the Environment European Topic Centers European Union Food and Agriculture Organization Genetically modified organism Gazzetta ufficiale della Repubblica Italiana, Official Gazette of the Italian Republic Hydrobromofluorocarbons Hydrochlorofluorocarbons High production volume (substances) International Agency for Research on Cancer Inventario Nazionale delle sostanze chimiche , National Inventory of Chemical Substances International Program on Chemical Safety Istituti di ricovero e cura a carattere scientifico, National for Care and Scientific Research Istituto Superiore di Sanita` , National Health Institute Joint Research Center Convention on Long-Range Transboundary Air Pollution

BSE CCTN

CFC CIEP CNR ECEH ENEA

ETC EU FAO GMO GU

HBFC HCFC HPV IARC INCS

Lists of acronyms IPCS Acronym

Full Name

APT

Agenzia per la Protezione dell’Ambiente e per i servici tecnici , Agency for Environment Protection and for Technical Services Agenzia Provinciale per la Protezione dell’Ambiente , Provincial Agency for Environmental Protection

APPA

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IRCCS

ISS JRC LRTAP

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Table (Continued )

Table (Continued )

Acronym

Full Name

Acronym

Full Name

NATOCCMS NHS OECD

NATO-Committee on the Challenges of Modern Society Italian National Health Service Organization for Economic Cooperation and Development Prior Informed Consent Quantitative Structure/Activity Relationship

RENTIC

Register of Italian toxicologists Certified Italian Society of Toxicology The International Association of Forensic Toxicologists United Nations Economic Commission for Europe

PIC QSAR

SITOX TIAFT UNECE