1. H ARMONIZATION OF C ATEGORIZATION S YSTEMS FOR A GENTS - F IRST D ATA FROM G ERMAN P OISONS C ENTRES XXVII I NTERNATIONAL C ONGRESS OF THE EAPCCT A THENS 2 M AY 2007 A. S TÜRER 1, G. H ÜLLER 2, HJ. R EINECKE 3, C. S EIDEL 4, U. S TEDTLER 5, R. W AGNER 6, M. G ANZERT 7, D. W URM 8, A. H AHN 9, H. D ESEL 6, PC S : 1) Z URICH 2) E RFURT 3) M AINZ 4) B ONN 5) F REIBURG 6) G ÖTTINGEN 7) M UNICH 8) H OMBURG 9) B F R B ERLIN

2. O BJECTIVE  Categorization Systems for Agents => Central part in PC EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

3. Cate- gorization System for Agents (CSA) R OLE OF THE CSA Identification of Agents (consulting) Recording of Agents (case collection) Index (Names) of Agents EAPCCT P RAGUE 20. A PRIL 2006 - C ATEGORIZATION S YSTEM FOR S UBSTANCES IN PC‘s - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

4. processing of new product information O BJECTIVE: U SE OF CSA categorization system names of agents recording of cases providing of substance / product info. retrieval of cases for scientific evaluations 1 st registration of agents annual reports EAPCCT P RAGUE 20. A PRIL 2006 - C ATEGORIZATION S YSTEM FOR S UBSTANCES IN PC‘s - A. S TÜRER „ G ROUP IT OR L OSE IT“ A. S TÜRER - 200 7  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

5.  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS O BJECTIVE: CSA – A NNUAL R EP. EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER

6. O BJECTIVE  Categorization Systems for Agents => central part in PC  TDI Project (1999 – 2006) => Electronic product data exchange => Harmonization of CSA in Germany  TDI Project (2006) => Collection of harmonized data of Human Exposure 2005 in German PC EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

7. A IMS  Steps of the harmonization process  Situation before using the TDI-CSA  Current state of TDI-CSA integration  Make TDI-CSA more familiar  Presentation of the first common data collection grouped by TDI-CSA  Future steps of CSA harmonization EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

8. M ETHODS 1.Evaluation of the preceding situation in German PC => Ques. EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

9. M ETHODS 1.Evaluation of the preceding situation in German PC => Ques. 2.Developement of a harmon. CSA (1999 – 2006) => TDI-CSA EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

10. S TRUCTURE OF TDI-CSA L-1 L-2 L-3 L-4 L-5 L-6 L-7 L-8 L-9 Plants Cosmetics (COLIPA+ EAPCCT) Drugs (ATC-code) Pesticides SECTOR LEVEL EAPCCT P RAGUE 20. A PRIL 2006 - C ATEGORIZATION S YSTEM FOR S UBSTANCES IN PC‘s - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

11. S TRUCTURE OF TDI-CSA technical link (non-ambiguous) retrieval (daily work) hierachcal structure (tree) EAPCCT P RAGUE 20. A PRIL 2006 - C ATEGORIZATION S YSTEM FOR S UBSTANCES IN PC‘s - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

12. S TRUCTURE OF TDI-CSA – „TREE“ = products = remedies = human drugs = cardiovascular system  hum. Drugs  Metoprolol ATC-Code 2007 (n = 5410) (Vet-ATC; n=5900 ) WHO Collaborating Centre for Drug Statistics Methodology, Oslo EAPCCT P RAGUE 20. A PRIL 2006 - C ATEGORIZATION S YSTEM FOR S UBSTANCES IN PC‘s - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

13. S TRUCTURE OF TDI-CSA – „TREE“ = natural environment = plants >>> taxonomical classification >>>  Plants  Golden Chain Tree Taxonomical classification according to: Zander, ed.: Dictionary of plant names, Kater pupl. 2000, 16th edition (n = 2‘700) EAPCCT P RAGUE 20. A PRIL 2006 - C ATEGORIZATION S YSTEM FOR S UBSTANCES IN PC‘s - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

14. S TRUCTURE OF TDI-CSA – „TREE“ = products =products of daily demand = cosmetics = cosmetics for nails  Cosmetics  Nail Polish = nail polish and -remover = nail polish = nail polish remover Cosmetic Frame Formulations EAPCCT & COLIPA, 2000 completed by some own categories (n = 180) EAPCCT P RAGUE 20. A PRIL 2006 - C ATEGORIZATION S YSTEM FOR S UBSTANCES IN PC‘s - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

15. M ETHODS 1.Evaluation of the preceding situation in German PC => Ques. 2.Developement of a harmon. CSA (1999 – 2006) => TDI-CSA 3.Test period in 2 PC (Erfurt+Mainz) (2001 – 2005), completion EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

16. M ETHODS 1.Evaluation of the preceding situation in German PC => Ques. 2.Developement of a harmon. CSA (1999 – 2006) => TDI-CSA 3.Test period in 2 PC (Erfurt+Mainz) (2001 – 2005), completion 4.Distribution 1 st version TDI-CSA (Sept. 2006) to German PC (n = 15‘029) EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

17. M ETHODS 5.Data Collection (2006)  Inclusion criteria:  Exposure of humans in 2005  Grouping criteria:  First 3 levels of TDI-CSA  Age groups (Children <18y=< Adult; unknown)  Course (Poisoning severity score; most serious known situation of the course; +/- follow up)  => FORM EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

18. M ETHODS 40 Sectors x 3 Age Groups x 6 Severity Grading = 720 fields per PC x 7 PC = 5‘040 primary data EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

19. M ETHODS 6.Data collection and pooling in independent PC (9-11/2006) 7.Returning complete data set to participating PC (11/2006) 8.Common evaluation and quality control (since 11/2006) 9.Questionnaire: „Depth of use“ (Jan. 2007) EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

20. Q UESTIONNAIRE- 1 : BEFORE TDI-CSA  7/10 participating PC  4 different CSA, regional extensions  Existing CSA used since 6 – 27 y  6/7 maintain CSA, mostly infrequent  7/7 categorization of new agents  4/7 immediately with case recording, mostly 2 nd pass before annual report  Maintenance of CSA: 1-5 person (1.5)  Categorization of Agents: 1-20 p. (1.0) EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

21. I MPLEMENTATION OF TDI- CSA  7 of 10 PC integrated TDI-CSA at least up to first 3 levels, 2 month  Parallel use of regional CSA and TDI-CSA  First 3 levels cover 40 categories („Sectors“: hum. drugs, cosmetics, …)  4/7 integrated complete TDI-CSA  2/7 complete categorization of the regional index of agents (cases) EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

22. D ATA C OLL.: H UM. E XPO. 2005  7/10 PCs 137‘689 cases 1‘270-27‘952 (Median 23‘220) cases/PC  78% of all Exposures in German PC EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

23. H UMAN E XPOSURE 2005 EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER AdultChildrenunknown Cases60'38671'3615'941 %44%52%4% Range40 - 68%24 - 59%1 - 13%  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

24. H UMAN E XPOSURE 2005 DATA EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

25. L EVEL 1 C ATEGORIES EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS

26. L EVEL 2-3 C ATEGORIES EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS SECTOR:

27. T OP 10 C ATEGORIES EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS TOP 10 CATEGORIES (ADULT)% Human Drugs57.9 Cleaning Agents, Detergents and Care Products7.3 Foods and Food-Additives6.0 Products - unclassified3.7 Plants3.3 Chemicals for Technical Tools, Processes and Products2.9 Basic Materials2.9 Drugs of Abuse2.6 Pesticides and Exterminator2.2 Civilisation Remnants, Inherited Waste1.8 TOP 10 CATEGORIES (CHILDREN)% Human Drugs25.3 Plants20.3 Cleaning Agents, Detergents and Care Products14.4 Cosmetics7.2 Chemicals for Technical Tools, Processes and Products4.4 Foods and Food-Additives3.6 Products - unclassified3.0 Illuminant Fuels, Inflammable Matters, Scents, Decorations and similar Agents2.5 Paints, Varnish and Dyers2.4 Objects of daily Demand (except Cleaning and Room Air Conditioning Agents)2.1

28. GER = USA ? EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS N°MOST FREQUENT CATEGORIES (ADULT >= 18y)) GER [%] ComparabilityComparison USA [%] MOST FREQUENT CAT. (ADULT > 19y) 1Human Drugs57.9==59.8several Groups of drugs 2Cleaning Agents, Detergents and Care Products7.3=<9.1Cleaning substances (household) 3Foods and Food-Additives6.0(=)>4.2Food products/food poisoning 4Products - unclassified3.7<>-- 5Plants3.3?-? 6Chemicals for Technical Tools, Processes and Products2.9?-? 7Basic Materials2.9(=)=3.3Chemicals 8Drugs of Abuse2.6(=)=2.7Stimulants and street drugs 9Pesticides and Exterminator2.2=<5.0Pesticides 10Civilisation Remnants, Inherited Waste1.8?<3.1Fumes/gases/vapors 11Animals1.7(=)<<6.8Bites and envenomations 12Fungi1.7?-? 13Cosmetics1.4=<<4.5Cosmetics/personal care products 14Paints, Varnish and Dyers1.2?-? 15Chemical / Physicochemical Articles - unclassified0.9<>-- different groups <>-3.3Hydrocarbons within Food <>-5.2Alcohols SUM97.6 107.0SUM

29. H IGH R ISC C ATEGORIES EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS CHILDREN / PSS asymptminormoder.severefatalunkn. Drugs of Abuse (n=293) 15.047.419.53.80.014.3 Human Drugs (n=18'051) 71.121.62.10.40.14.8 Foods and -Additives (n=2541) 70.521.32.80.40.05.0 TOTAL (68'878) 76.318.21.30.20.04.0

30. H IGH R ISC C ATEGORIES EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS ADULT / PSSasymptminormoder.severefatalunkn. Drugs of Abuse (n=1'594) 9.157.518.66.80.17.8 Human Drugs (n=34'989) 23.052.012.74.60.27.5 Pesticides (n=1'347) 26.748.76.34.00.813.4 TOTAL (68'878) 27.849.510.53.60.28.4

31. L IMITATIONS EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS  In about 5-10% of the cases data attribution to the TDI-CSA is not completely reliable (incompatibility)  Currently categorization of cases down to the deepest level is only in 2 PC obtainable  There is probably a bias towards lower severity grades (follow up is performed in only 8%)

32. C ONCLUSION EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS  In 7/10 German PC the first step to a harmonized CSA was successful.  The procedure for a multi-centre maintenance and update is running.  A dataset of over 130‘000 cases is ready to be subjected to internal quality control measurements and benchmarking between PC.

33. C ONCLUSION EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS  For the first time within the 40-year history of the German PC common data of human exposure and poisonings in Germany are available for preliminary risk assessment and epidemiological analysis.

34. F UTURE EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS  A complete integration of the TDI- CSA in all German PC will take about another 5 years.  A new working group within the Society of Clinical Toxicology of German speaking PC (7/11) ensure the maintenance of the TDI-CSA => www.klinitox.de -> WG V – “categories” (next meeting Sept. 2007)www.klinitox.de

35. F UTURE EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER  O BJECTIVE O BJECTIVE  M ETHODS M ETHODS  R ESULTS R ESULTS  C ONCLUSION C ONCLUSION  F UTURE F UTURE  L IMITATIONS L IMITATIONS  A first federal institute (BVL) will use one sector of the TDI-CSA (cosmetics) and will share the System with the cosmetic industry.  The experience of harmonisation as well as the TDI-CSA may serve as a basis for further harmonization on a European level.

36. T HANKS  TDI-Team  PC  Erfurt: G. Hüller  Mainz: HJ. Reinecke, I. Weilemann, H. Zeimentz  Bonn: C. Seidel  Freiburg: U. Stedtler  Göttingen: R. Wagner, H. Desel  Homburg: S. Meier, D. Wurm  Munich: M. Ganzert  BfR  K. Begemann, A. Hahn, G. Heinemeyer  PC Zurich Team  H. Kupferschmidt, C. Rauber-Lüthy EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER

37. THE E ND EAPCCT A THENS 2 M AY 2007 - H ARMONIZATION OF CSA – F IRST D ATA FROM PC S - A. S TÜRER FURTHER I NFORMATION: www.klinitox.de/129.0.html > TKS