Document nN5z8BeJ1BOk0e6BBQpRQE806

aJPme ASSOCIATION OF PLASTICS MANUFAC.TUB.aRS iN EUROPE Protocol for the maintenance of a register of cases of angiosarcoma related to PVC production. Association of Plastics Manufacturers of Europe ABOUT APME The Association of Plastics Manufacturers of Europe represents the interests ofthe industry at European level andpromotes the benefits of plastics in every aspect oflife. It co-operates with other industry sectors to provide effective solutions to plastics-related issues through scientificfact and environmental and economic data. The Association has a full time secretariat with a range of steering and working groups made up of experts from member companies. The APME Vinyls Medical and Toxicological Working Group monitors and advises the Vinyls Committee ofAPME and its other working groups on medical and toxicological aspects ofvinyls materials and substances used in the production ofvinyl materials and initiates and co-ordinates any studies or submissions required on medical and toxicological aspects ofthe materials ofinterest. Revision 1 July 8, 1996 Avenue E. Van Nieuwenhuyse 4 Box 3 B - J 1 6 0 Brussei.s Telephone ( 32-2 ) 675 3 2 97 Facsimile ( 32-2 ) 675 3 9 3 5 NGC35778 Introduction The knowledge of the toxicity of Vinyl Chloride Monomer (VCM) developed during three well defined periods: In the first, between the 30's and 40's the acute effects on man, above all on the Central Nervous System, with euphoria, dizziness, headaches, narcosis, due to the inhalation of high concentrations of VCM were pointed out. However the substance was considered moderately toxic. The effects, both experimental and human, of repeated exposure to VCM were described following the great industrial development of the 50's, in the production of VCM and its derivatives, mostly polymers (Polyvinyl Chloride - PVC). These effects, characterised by s a specific alterations of the liver, digestive and respiratory systems, and Raynaud like phenomenon to the hands with sclerodermic lesions and osteolytic bone alterations of distal phalanges, are part of the so-called "Vinyl Chloride Illness". At the beginning of the 70's, following the experimental studies begun by Prof. Viola and continued by Prof Maltoni, the carcinogenic effect of VCM was discovered. In particular. Prof. Maltoni's studies indicated that VCM was responsible for a very rare tumour of the liver, the angiosarcoma. At the same time, the clinical confirmation on man of this effect came from the United States. VCM has probably been the only case, in environmental toxicology, in which the experimental evidence on animats, was confirmed, almost at the same time, by clinical data on man. The measures taken by Industry following these discoveries, show that it is possible to continue the production of chemical substances, even carcinogenic, using such technologies as to minimise the risk for workers and users. Regarding the possibility that VCM is the cause, even in man, of other tumours, the studies carried out up to now do not give certain results. The International Agency for Research on Cancer (IARC) has recently published the results of a multi-centric collaborative European study on workers of different industries producers of VCM/PVC which indicate: an important increase in liver cancer and above all angiosarcoma. no significant excess of mortality for cancer of other sites, although there is a slight increase in the incidence of lung and brain cancer and lymphosarcoma. Revision 1 July 8, 1996 2 NGC35779 an increased risk of bladder cancer and melanoma of the skin not related to exposure. no increased mortality has been observed for the other main causes of death The following sentence appeared in the important magazine 'The Lancet" in June of 1974: "Vinyl Chloride is a milestone in Occupational Hygiene" DR P Bonetti - Solvay S.A. Revision 1 July 8, 1996 3 NGC35780 Purpose To as far as reasonably practical maintain and make available a register of cases of angiosarcoma associated with the production ofvinyl chloride and polyvinyl chloride world-wide in order to: Assess the impact ofthe technological, organisational and hygiene improvements on the occurrence of angiosarcoma ofthe liver. Collect data for the epidemiological investigation of cases. - Maximise our understanding of the disease with a view to its eradication. Scope This protocol applies to the Custodian and the APME secretariat responsible for the maintenance of the register and associated files. Definitions APME - The Association ofPlastic Manufacturers ofEurope ASL Register - A register of cases of angiosarcoma ofthe liver known to have occurred world-wide. Secretariat - The secretary ofthe APME Vinyls Committee Medical and Toxicological Work Group and their supporting staff within APME. Angiosarcoma - A malignant tumour composed of spindle or pleomorphic cells with inconspicuous nuclei that line, or grow into, the lumina ofpreexisting vascular spaces, such as liver sinusoids and small veins (from - "Histological Typing of Tumours of the Liver" by K.G Ishak, P.P. Anthony, and L.H. Sobin in collaboration with Pathologists in 6 countries, WHO, 1994) Case - A histologically confirmed case of angiosarcoma of the liver occurring in a patient who has previously been employed in the manufacture of vinyl chloride monomer or polyvinyl chloride for more than 6 months and more 1 year after starting work Vinyls Medical and Toxicological Working Group - A working group consisting of medical officers representing member companies of the APME as well as other professionals who may from time to time be co-opted for the consideration of particular problems. Custodian - The Occupational Physician appointed by the Medical and Toxicological Working Group to be responsible on their behalf for all aspects of management of the Register and in particular to ensure confidentiality of the clinical data and ethical operation of the Protocol. The Custodian shall normally be a member ofthe Group. At all times the Custodian is acting as an Revision 1 July 8, 1996 4 NGC35781 agent ofthe Vinyls Medical and Toxicological Working Group. Security undertaking - The Secretary ofthe Medical Working Group shall ensure that all staff who may work with or have access to the files associated with the register prior to its publication sign the security undertaking laid out in appendix 1. General Administrative Arrangements APME regards the security and confidentiality of any clinical information related to the maintenance ofthe register as the single most important feature of its operation and has made the following arrangements to address this issue. Accordingly ONLY the Chairperson ofthe Medical and Toxicological Working Group, the Custodian and the Secretariat will have access to any information used in the preparation ofthe Register within APME. The Chairperson, the Custodian and all staff in the Secretariat shall be required to sign the security undertaking in appendix I before they start any work related to the Register. All files associated with the maintenance ofthe Register and its publication will be kept at the APME's offices in Brussels under the day to day charge ofthe Secretariat. Files not actually in use will be kept in locked storage at all times. The published Register shall not contain personal identifiers ofeach case including Name, initials, or exact date of birth. This information will only be sent out for checking to those making the initial case report. Arrangements will be maintained by the Secretariat that at least one copy is maintained by the Custodian of all papers relating to the Register at a location remote from APME. The Custodian shall ensure that all these copies are kept in locked storage when not in use. Archival of documents will be arranged by the Secretariat and will involve the scanning of documents onto CD-ROM. Copies will be strictly controlled with two copies being held by the Secretariat and one by the Custodian. In the event of a change in Custodian all papers, copies and computer media related to the register shall be returned by the Custodian to APME for use by the new Custodian. No disclosure of data other than that specified in the Protocol shall be made by the Custodian without the authority of the Vinyls Medical and Toxicological Working Group. This would require a formal written agreement as to the purpose of the study and include adequate security undertakings. In the event that the Register is wound up all documentation relating to the register will be lodged with a suitable Academic Unit identified by the Medical and Toxicological Working Group and no copies retained in APME. Revision 1 July 8, 1996 5 NGC35782 The System Once per year the Custodian and the Secretariat will arrange a search of a suitable Commercial Database in order to establish as far as reasonably practicable a list all sites involved in the manufacture of vinyl chloride monomer or polyvinyl chloride world-wide. This list will be used to update the list of existing and previous manufacturing sites already identified. This list will form the basis for an annual mailing to explain the Register and solicit the further identification of cases. The updated list shall be reviewed by the Vinyls Committee of APME to further check its accuracy. A note will be kept of any changes suggested by the Vinyls Committee. The Custodian and the Secretariat will then arrange the mailing of each site on the list. The mailing shall include this protocol together with a request for the notification ofnew cases, a case input form, and a request will also be included to check the record of production dates at that plant. A nil return will be requested. Contact details for any Occupational Physician attending the plant will also be requested. One follow up mailing shall be made to each plant not responding within two calendar months. Details of previous European cases will be circulated to the APME Vinyls Medical Work Group for checking. Where plants outside Europe identify Occupational Physicians then details of cases previously notified from those plants will be sent to the relevant Occupational Physician for checking. It is anticipated that general correspondence relating to cases or plant records will continue to arrive at other times during the year. The Custodian and the Secretariat shall meet on a regular basis at the APME in Brussels. At these meetings all correspondence will be reviewed and arising actions agreed and minuted. The Register itself shall be maintained by the Custodian and Secretariat as an appropriate computerised database copies ofwhich shall exist on one personal computer at APME and the personal computer of the Custodian. Alterations to the database shall only be made in the presence ofboth the Secretariat and the Custodian and a record ofEVERY amendment will be kept in a paper amendment record and as an appendix to the computer file. The Secretariat shall establish the following files for correspondence related to the Register. 1) A file for each case 2) A file for each plant 3) A database amendment file Revision 1 July 8, 1996 6 A ME NGC35783 4) A general correspondence file. 5) A file for cases that have been notified but not included in the Register. 6) A review file to contain the annual security and epidemiological reviews. 7) A pending file for information received and not yet evaluated for inclusion in Register A key word index shall be established for the general correspondence file. Amendments to the plant records shall only be made at the discretion ofthe Custodian and the Secretariat based on correspondence received. Amendments to the case file shall be made by the Custodian when the criteria are met which are: Patient worked at least six months on vinyl chloride monomer or polyvinyl chloride production starting more than one yearpreviously. There is histological confirmation of the diagnosis. When the custodian does not feel that the above criteria have not been met, he will inform the person who notified the case. For surviving cases the Custodian shall establish the progress of the case by letter each three months. A panel ofpathologists has been established to help with advice on diagnosis. The Custodian shall establish and update the pathological criteria for diagnosis. The Custodian and the Secretariat shall establish with the agreement ofthe Vinyls Medical Work Group the routine analyses ofthe data to be included in the Register. These will be checked with an independent epidemiologist to ensure that they are appropriate and valid on this database. The Custodian shall present a review of all matters relating to the Register at each meeting ofthe Medical and Toxicological Working Group. The Register shall be published at intervals determined by the volume of cases notified but not normally less than once every three years. The Custodian and Secretariat shall arrange for a triennial review by an independent Revision 1, January 21,1997 Ensures case details only released to relevant Occupational Physicians for checking Ensures notifier told where criteria not met 7 NGC35784 epidemiologist, approved by the Medical and Toxicological Working Group, ofthe data collection and analyses, as well as the security aspects of the system. Each such review will be included as an appendix to the next edition of the Register. Revision I, January 21,1997 Ensures case details only released to relevant Occupational Physicians for checking Ensures noti/ier told where criteria not met 8 NGC35785 Appendix 1 Security undertaking It has been explained to me that during the course of my employment with APME either directly or under contract that I may gain knowledge of or be entrusted with sensitive, personal or medical information. I understand that APME regards such medical information as the most confidential and expects me to take all practical steps to prevent its untimely disclosure. Signature of staff member/contractor Signature of APME supervisor Date Date JCP 17/4/96 - version 5 9 NGC35786