[From the selection of priority pollutants to the analysis of health data in the SENTIERI Project]. / Dalla selezione degli inquinanti prioritari alla lettura dei dati sanitari nel Progetto SENTIERI.

OBJECTIVES: evaluation of mortality and hospitalization of residents in five Italian National Priority Contaminated Sites, studied in the SENTIERI Project, for those pathologies which, on the basis of the assessments of international agencies and bodies, are known to have an aetiological connection with exposure to specific environmental pollutants. DESIGN: ecological study. SETTING AND PARTICIOANTS: resident population in the sites of Trieste and Piombino (steel plants), and Falconara, Livorno, and the industrial area of Milazzo (petrochemical plants and/or refineries). Data extracted from the Sixth SENTIERI Report. MAIN OUTCOME MEASURES: mortality (2013-2017) and hospitalization (2014-2018) for associated causes by exposure to specific pollutants detected in the soil and water matrices. RESULTS: the results obtained do not show common patterns between the excesses found in Trieste and Piombino Sites (steel plants) nor among Livorno, Falconara, and Milazzo (petrochemicals and/or refineries). Livorno and Trieste sites, having a larger population, show the greatest number of excesses. CONCLUSIONS: the proposed approach can be a useful tool, in addition to others, for the study of the health profile of residents in contaminated sites, being also the basis for aetiological epidemiological studies.

Determination and risk assessment of phthalates in face masks. An Italian study.

Serious human health concerns have been recently raised from daily use of face masks, due to the possible presence of hazardous compounds as the phthalic acid esters (PAEs). In this study, the content of 11 PAEs in 35 commercial masks was assessed by applying a specific and accurate method, using Gas Chromatography/Mass Spectrometry. Surgical, FFP2 and non-surgical models, for both adults and children were collected from the Italian market. Analyses showed that four of the target analytes were detected in all tested samples with median total concentrations ranging between 23.6 mg/kg and 54.3 mg/kg. Results obtained from the experimental analysis were used in the risk assessment studies carried out for both carcinogenic and non-carcinogenic effects. Doses of exposure (Dexp) of PAEs ranged from 6.43 × 10-5 mg/kg bw/day to 1.43 × 10-2 mg/kg bw/day. Cumulative risk assessment was performed for non-carcinogenic and carcinogenic effects. No potential risk was found for non-carcinogenic effects, yet the 20% of the mask samples showed potential carcinogenic effects for humans. A refined exposure assessment was performed showing no risk for carcinogenic effects. This paper presents a risk assessment approach for the identification of potential risks associated to the use of face masks.

Cancer incidence in Priolo, Sicily: a spatial approach for estimation of industrial air pollution impact.

The territory around the industrial Sicilian area of Priolo, Italy, has been defined as a contaminated site (CS) of national priority for remediation because of diffuse environmental contamination caused by large industrial settlements. The present study investigates the spatial distribution of cancer into the CS territory (period 1999-2006). Different geographical methods used for the evaluation of the impact of industrial air pollutants were adopted. Using the database of Syracuse Province Cancer Registry, gender-specific standardised incidence ratios were calculated for 35 tumour sites for the CS overall and for each municipality included in the CS. A cluster analysis for 17 selected neoplasms was performed at micro-geographical level. The identification of the priority index contaminants (PICs) present in environmental matrices and a review of their carcinogenicity have been performed and applied in the interpretation of the findings. The area has a higher cancer incidence with respect to the provincial population, in particular excess is registered among both genders of lung, bladder and breast cancers as well as skin melanoma and pleural mesothelioma and there is an a priori evidence of association with the exposure to PICs. The study highlights the need to provide different approaches in CSs where several exposure pathways might be relevant for the population. The presence of potential sources of asbestos exposure deserves specific concern.

[Index contaminants and target organs]. / Inquinanti indice e organi bersaglio.

SENTIERI Project evaluates the health impact of environmental exposures on residential population of National Priority Contaminated Sites (NPCSs). It takes into account a priori etiological hypotheses, based on the epidemiological evidence of an association between those exposures and selected diseases or causes of death. Building on the previous chapter, this one acts as a blueprint for future causal inferences based on scientific evidence relating to the health effects of exposure to specific pollutants present in the sites. In order to select the relevant pollutants, we make use of data concerning soil, aquifers, the food chain and the atmosphere. For each pollutant, we indicate cancer site and target organs, for non-neoplastic diseases, based on scientific assessment by international Agencies. We have chosen to focus on two sites: Brescia-Caffaro and Priolo. This method may conceivably be used by SENTIERI in the future to carry out more specific studies and provides the basis for a systematic analysis of contaminated sites.

The Italian Helpdesk under the Regulation (EC) No. 1272/2008 (CLP): three-year activity and experience (2009-2011).

INTRODUCTION: The Regulation (EC) No. 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) sets further obligations for manufacturers, importers, distributors, downstream users of substances either on their own or in mixtures. According to the European mandate, each Member State has constituted its National Helpdesk to provide advice to the interested parties on their duties under this Regulation. In Italy, the contact point for questions has been established at the National Centre for Chemical Substances of the Istituto Superiore di Sanità. FUNCTIONS: The responders of the Italian CLP Helpdesk process the requests that have been submitted by the dedicated website. Applicants are asked to complete the form with all the required information. The Helpdesk staff also take part in the European network of CLP, REACH and ECHA Helpdesks together with the European Commission and other parties, that is the HelpNet. RESULTS: The present paper describes the results of the three-year activity of the Italian CLP Helpdesk (2009-2011).

Information gathering for CLP classification.

Regulation 1272/2008 includes provisions for two types of classification: harmonised classification and self-classification. The harmonised classification of substances is decided at Community level and a list of harmonised classifications is included in the Annex VI of the classification, labelling and packaging Regulation (CLP). If a chemical substance is not included in the harmonised classification list it must be self-classified, based on available information, according to the requirements of Annex I of the CLP Regulation. CLP appoints that the harmonised classification will be performed for carcinogenic, mutagenic or toxic to reproduction substances (CMR substances) and for respiratory sensitisers category 1 and for other hazard classes on a case-by-case basis. The first step of classification is the gathering of available and relevant information. This paper presents the procedure for gathering information and to obtain data. The data quality is also discussed.

[A cluster of methanol-related poisonings in Sicily: case characterization and identification of unexpected sources of exposure]. / Un cluster di intossicazioni da metanolo in Sicilia: descrizione dei casi e identificazione delle fonti di esposizione.

OBJECTIVE: To describe methanol poisoning exposures in Italy and to investigate a cluster of methanol-related deaths due to abuse occurred in Sicily among immigrants from East Europe. DESIGN: the human methanol exposures handled by the Poison Control Centre of Milan, the major national centre for toxicological advise active in Italy, were reviewed retrospectively (January 2004-September 2006) and prospectively (October 2006-October 2008). SETTING: For each case of managed human exposure, the Poison Control Centre of Milan uses a standard format to collect patient information, substance/exposure information, clinical effects, therapy, outcomes. The database arising from that procedure was searched for all cases exposed to methanol and/or reporting selected clinical signs (i.e., metabolic acidosis with ocular effects and/or central nervous system depression and/or respiratory depression). Each case was reviewed and classified according to standard criteria. MAIN OUTCOMES: Three commercial products containing more than 70% methanol available on the market in Sicily and associated with lethal exposures due to abuse among immigrants were identified. RESULTS: In the period under study, the Poison Control Centre of Milan examined 29 methanol poisoning exposures (none in 2004, 6 in 2005, 6 in 2006, 15 in 2007, and 2 in 2008). Among them, 17 occurred in Sicily, with a peak of 11 cases in 2007, and 12 in other regions. The patients included 16 men and 13 women with a median age of 49,5 years (range 1-81 years). Fifteen cases were immigrants from East Europe (14 Rumanian and one Polish). Eleven cases reported minor effects, two cases moderate effects, four cases major effects, and 12 cases died. Twelve cases were accidental exposures (5 occurred at work, 3 at home and 4 in other places), while 17 cases were intentional exposures (14 due to abuse, 2 to attempted suicide and 1 to misuse). Minor effects were reported in 11 cases, moderate effects in two cases, major effects in four cases and death in 12 cases. The most frequently reported clinical effects included: coma (13 cases), metabolic acidosis (10 cases), mydriasis (4 cases), visual loss (3 cases), gastric pyrosis (2 cases), constriction of the visual field (2 cases), and vertigo (2 cases). Blood methanol level was reported for 15 cases (< 50 mg/dL in 2 cases; 50-99 mg/dL in 2 cases; 100-499 mg/dL in 4 cases; >500 mg/dL in 1 case; positive, unknown value in 6 cases). All cases due to abuse (n. 14) and, among them, lethal (n. 12) occurred in Sicily and involved immigrants. On the other hand, all methanol poisonings occurring in the other Italian regions involved Italian citizens unintentionally exposed and with minor effects, except for one case of attempted suicide with consequent major effects. The investigations performed in Sicily lead to identifying three locally produced and marketed detergents containing more than 70% methanol, improperly labelled and packaged. Furthermore, a detergent for domestic use was identified containing 25-30% methanol without any labelling information. Two of the detergents containing more than 70% methanol were withdrawn from the market in November 2007, while the other, that was identified later, was withdrawn in July 2008. The detergent for domestic use, containing 25-30% methanol was withdrawn in December 2007. Starting from July 2008, no new cases of methanol poisonings were observed. CONCLUSION: The availability in Sicily of products containing high concentrations of methanol, improperly packaged and labelled, determined a generalised risk of accidental exposures and favoured voluptuary assumption of methanol among selected groups. The observations highlight the importance of a surveillance system of toxic exposures based on the information collected by the Poison Control Centres and its ability to provide timely identification of unexpected and dangerous events and to support preventive actions.

Prevention, ethics and science: lessons from Lorenzo Tomatis.

This paper is dedicated to Lorenzo Tomatis, former director of the International Agency for Research on Cancer (IARC), promoter of prevention principles with a precautionary approach, supported by an important scientific foundation. He has recommended an appropriate consideration of both "false negatives" and "false positives" errors in the evaluation of epidemiological and experimental data on toxicological and carcinogenic risk. The current rules for IARC Monographs preparation include both a full transparency of the data used and of the possible conflicts of interest of the experts involved. Tomatis has also underlined that "Dismissing animal carcinogenicity findings would lead to human cases as the only means of demonstrating carcinogenicity of environmental agents. This is an unacceptable public health policy". The main role of experimental studies is presently included in both the new preamble of IARC Monographs and the method adopted for the World Health Organization Air Quality Guidelines for low-dose carcinogenic risk assessment.

Exponential growth of new chemicals and evolution of information relevant to risk control.

The number of new chemicals synthesized and marketed increases exponentially. The database CAS REGISTRY at present contains more than 33 million organic and inorganic substances. However, the little information regarding the potential hazard associated with a large amount of chemicals is an old known problem in the European Union and also in the United States. This critical problem may find a solution in the collaboration of the different involved countries and in a planned task setting at international level. Both in the United States (e.g., the "Gore Initiative") and in European Union (the REACH policy) a big effort has been dedicated to this solution, within standardized procedures and an appropriate collaboration.

The ISS National Inventory of Chemical Substances (INSC).

The INSC (Inventario Nazionale delle Sostanze Chimiche), a factual data bank, produced by Istituto Superiore di Sanità (ISS), consists of an electronic tool on chemical information developed for routine and emergency purposes. Historical background, current status and future perspectives of INSC are discussed. The structure and the feature of INSC are briefly examined. Aspects of information retrieval and the criteria for inclusion of data and priority selection are also considered.

The ISS Carcinogens Data Bank (BDC).

The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanità website, aimed at supporting the risk management decision making of central and local administrators. It can also represent a valuable tool for industry. The available information on carcinogenicity evaluations/classifications produced by European Union and by other institutions (IARC, USEPA, NTP, CCTN) is presented in a concise form accompanied by bibliographic references enabling the users to consult the original sources and, in some cases, to be directly connected to the relevant website. The classifications carried out by each organization in accordance with its own criteria assign the examined agents to specific qualitative categories and do not include quantitative assessment. BDC intends to provide an easy tool for experts, researchers and risk managers dealing with carcinogenic agents.

The ISS Sensitizing Agents Data Bank (BDS).

The Istituto Superiore Sanità has developed a data bank on sensitizing substances (Banca Dati Sensibilizzanti, BDS), available on website (www.iss.it/bdse/), sharing complete, controlled and updated information coming from different sources, such as scientific publications, international agencies and governmental or non governmental organizations. It is worthwhile that the main objective of the BDS is not the classification of sensitizing or potentially sensitizing agents within specific risk classes, but it is essentially to provide concise and non confidential information related to this endpoint. At present, the BDS includes: all the substances officially classified by European Union, (Annex I to Directive 67/548/EEC), some substances listed in I (Directive 67/548/EEC) for endpoints different than "sensitization" but indicated as sensitizers by other relevant institutions, all the substances indicated as sensitizers by relevant agencies or institutions (ACGIH, DFG), some substances indicted as sensitizers by industry and other non-governmental organizations (ETAD and HERA), all the substances regarded as "potentially sensitizing dyes" by the Commission of the European Community for the award of the eco-label to textile products, some substances for which, even in the absence of any categorization by Union, ACGIH or DFG, it is not possible to exclude a sensitizing potential on the basis of reliable documents.

The ISS Reclamation Data Bank.

Since the issue of the first regulations concerning the remediation of contaminated sites, the Istituto Superiore di Sanità, on the basis of specific requests, has drawn up various technical opinions regarding the proposed reference values (quality standards) for soils and underground waters, to be achieved when remediating contaminated sites, for substances for which no standard limit values did not exist at that time. These reference values, widely used throughout the country and accepted and adopted as "remediation aim" values by various territorial bodies responsible for the approval and monitoring of remediation projects, have been collected in a specific reclamation oriented data bank known as the "Banca Dati Bonifiche (BDB)" (Reclamation Data Bank). The BDB contains the related standardized "rationale" for each reference value, in order to serve as a useful reference for the national bodies concerned with the remediation of contaminated sites.

Low-dose risk, hormesis, analogical and logical thinking.

The hormesis theory proposes the low-dose beneficial and high-dose detrimental pattern, existing for specific conditions, as a "general default assumption" for toxicology and carcinogenicity. Crump and Kitchin and Drane underline that in a post hoc retrospective scientific literature searching for hormetic dose-response patterns, the consideration of the whole available relevant studies is necessary and, for statistical testing purposes, for instance at a 0.05 standard level, a P value obtained from 1 - (1 - P)(n) = 0.05 (i.e., P = 0.0005 for 100 examined cases) should be used (otherwise, by definition, 5 "positive" results are expected by chance over 100 cases). The hypothesis, based on some experimental data on rodents, by Calabrese and Baldwin, of an hormetic effect of 2,3,7,8-TCDD at the 1-10 ng/kgbw/day dose, of Na-saccharine in the < or = 1% of diet exposure range, of Cadmium Chloride in the 0-5 micromol/kg dose range, single injection, and of neutrons in the 0- to 2-rad dose range, are not confirmed, and, rather, are contradicted, when the whole relevant data presented by international and national agencies are considered. As far as the radiation risk is in particular concerned, a recently published epidemiological study on more than 400,000 nuclear plant workers, co-ordinated by the IARC has indicated a small, but significant risk, at the current exposure limits, and possibly below them. Therefore, the hormesis theory-based criticism of current radiation protection criteria, assumed to be excessively conservative, is not justified. Also not justified is the assumption that "by dismissing hormesis, regulatory agencies such as U.S. EPA deny the public the opportunity for optimal health and avoidance of diseases;" rather, the contrary is here considered true. Analogical considerations are not necessarily logical ones and the single result should be considered in its whole context.

Development of carcinogenicity classifications and evaluations: the case of formaldehyde.

In this paper carcinogenicity classification and evaluations case of formaldehyde made by national and international agencies and organizations (such as European Union, International Agency for Research on Cancer, World Health Organization) both in occupational (such as American Conference of Government Industrial Hygienists, National Institute of Occupational Safety and Health and Occupational Health and Safety Administration) and non occupational environment (such as United States Environmental Protection Agency) are proposed. The differences in the database and consequently in the conclusion are described in a short historical review since formaldehyde was considered for the first time as regard as health effects.

Some non neoplastic effects of ELF magnetic fields in experimental animals.

This study has been addressed to the non neoplastic effects observed in experimental animals exposed to the ELF magnetic fields exposure, giving particular attention to the large and comprehensive data of the two-year NTP (National Toxicology Program) studies. The statistical analysis of non neoplastic incidences, whenever not presented by the study authors, has been carried out in the present study. Only the effects coherently emerging for both the animal genders have been considered; gender specific effects have obviously been separately analysed. The trend analysis has been carried out over the 4 exposure levels (0, 2, 200 microT, and 1000 microT -microTesla) and on the first 3 ones. For 28 dose-response relationships, non neoplastic effects significantly emerged (6 for hyperplasia, 4 for cyst, 4 for inflammation, 3 for focus, 3 for atrophy, 2 for cellular infiltration, and 1 for each of other 6 effects). This number is much higher than the one of neoplastic effects indicated by the NTP as significant. For many of these dose-response relationships, the trend was significant only over the first 3 treatment levels (excluding the highest one, 1000 microT/1 mT), in agreement with the results of some other studies indicating a response reduction, or even a possible anticarcinogenic effects, at considerably high exposures (mT range). The obtained results suggest a complex effect modulation pattern.

[Agricultural pesticide-related poisonings in Italy: cases reported to the Poison Control Centre of Milan in 2000-2001]. / Intossicazioni acute da antiparassitari di uso agricolo in Italia: i casi esaminati dal Centro antiveleni di Milano nel 2000 e 2001.

OBJECTIVE: Aim of the present study is to provide a preliminary description of agricultural pesticide-related poisonings in Italy. DESIGN: The study focuses on the cases with at least one sign or symptom due to exposure to agricultural pesticides occurred in 2000-2001 and referred to the Poison control centre of Milan, the Italian centre more frequently consulted nationwide. RESULTS: During the study period, 872 agricultural pesticide-related poisonings were identified. Most of the observed cases occurred in Sicily (n=199), Lombardy (n=100), Apulia (n=99), Veneto (n=75), Emilia-Romagna (n=67) and Campania (n=59). About 86% of the observed cases were unintentional and about 76% of them were men. Children aged 10 or less accounted for about 6% of the total. The poisonings occurred more frequently at home (about 38%) than at workplace (about 24%). The chemical classes of agents more frequently reported were: organophosphates (233 cases), copper and sulphur compounds (140 cases), carbamates (126 cases) and pyrethrins/pyrethroids (102 cases). The top six pesticides associated with poisonings were methomyl (97 cases), dimethoate (59 cases), copper sulfate (58 cases), glyphosate (53 cases), sulphur compounds other than copper sulfate (47 cases), and paraquat dichloride (41 cases). CONCLUSION: The data here presented provide an initial support to identify priorities for prevention in agricultural settings.

Information resources in toxicology--Italy.

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) A Brief History of Toxicology in Italy; (2) Professional Societies; (3) National Health Service; (4) National Bodies; (5) Resources for the Environment; (6) Biomedical Websites; (7) Recent Publications; (8) Research Structures; (9) Graduate and Postgraduate Programs; (10) Legislation.