Ethylene Oxide Residues in Fumigated Books a First

Ethylene Oxide Residues in Fumigated Books - a First Result of the Project Men and Books : EU grant 2012 -0920/001 -001 Patricia Engel & Katja Sterflinger

In every archive/library in Europe we find - microorganisms - acidic paper - ink corrosion - vegetabil tanned leather Horn I conference 2011 confirmed the need for research in these subjects and defined even more urgent research subjects

Mould on paper, leather, siels, etc.

Reasons l New infestation l l l Environment not clean enough Environment too wet Environment too warm Microclimate Old infestation

Recommendation for the museum/library/archive l l l Good, i. e. individual house keeping policy Stop sorce: Renovation of building / wet areas etc. Cleaning of books by conservators or staff advised by conservators (health and safety measures!) Repacking Regular control in future - climate monitoring etc.

Active measures l l l Dry cleaning (HEPA Filter) Alcohol Gamma rays l l Energy Ethylene oxide l l l But ethylene oxide treatment of paper is not allowed anymore in the EU since 1 st September 2006. from 1 st September 2013 on EO may only be used according to Article 56 of the BPR (research and development) If the use of EO as book fumigant on a regular basis is intended, ethylene oxide has to be included in. Annex I of the BPD and authorised as biocidal product first.

I Questions in this project Does EO stay in the books, if so how long? l Does off fuming dose pose a risk in readers? l Did EO kill the mold? l Did EO damage the material? l

Compilation of Publications on Ethyleneoxide in Paper Conservation l l l l Hanus, J. , Mináriková, J. , Ďurovič, M. , Bacílková, B. : Influence of ethylene oxide fumigation on some properties of different types of paper. La Conservation: Une Science en evolution - Bilan et Perspectives. Actes des troisiémes journées internationales d'études de l'ARSAG, Paris, 21 - 25 April 1997, p. 193 -203. Richardin, P. , Hanus, J. , Bonnassies-Termes, S. : Rétention de l'oxyde d'ethylene dans les documents graphiques et photographiques désinfectés. Colloque Huilles essentielles et conservation des oeuvres d'art. Musée National des Arts et Traditions Populaires, Paris, 2 -3 décembre 1998. Abstracts of presentations, p. 11. Hanus, J. : Determination of residual ethylene oxide and its desorption from different types of sterilized papers. Final Report. Centre de Recherches sur la Conservation des Documents Graphiques, Paris 1998, 100 p. Hanus, J. , Richardin, P. , Bonnassies-Termes, S. : Influence of ethylene oxide sterilisation on some photographic papers. ICOM Committee for Conservation, 12 th Triennial Meeting Lyon, 29 August - 3 September 1999, Preprints Volume II, p. 550 -554. th Triennial Meeting Lyon, 29 August - 3 September 1999, Preprints Volume II, p. 507 -512. Hanus, J. , Richardin, P. , Bonnassies-Termes, S. , Ďurovič, M. , Kubelka, V. : Comparison of two different methods by head space gas chromatography for determination of residual ethylene oxide in sterilized papers. ICOM Committee for Conservation, 12 Christina Meier; Karin Petersen: Schimmelpilze auf Papier. Ein Handbuch , 2006 Christina Meier; Karin Petersen: Schimmelpilze auf Papier. Ein Handbuch fur Restauratoren, biologische Grundlagen, Erkennung, Behandlung und Pravention, Tonning [a. o. ]: Der Andere Verlag, 2006 Flavia Pinzari, Katja Sterflinger, The revenge of time: fungal deterioration of cultural heritage with particular reference to books, Environmental Microbiology (2011) cultural heritage with particular reference to books, paper and parchmentemi. Environmental Microbiology (2011) Diplomarbeit Wien l l l l l l l l l l l l l l l l l l l l l l l l l l l Abrahams, R. H. Recent studies with workers exposed to ethylene oxide, in: Jorkasky J. F. , ed. , Safe use of ethylene oxide, Proceedings of the Educational Seminar, Washington DC, Health Industries Manufacturers Association, 27 -38, pp. 211 -220, HIMA Report No. 80 -4, 1980 Adkins B jr, Van Stee EW, Simmons JE, Eustis SL (1986) Oncogenic response of strain A/J mice to inhaled chemicals. J Toxicol Environ Health 17: 311 -322 AGS - Ausschuss fur Gefahrstoffe (2011): ERB (Exposition-Risiko-Beziehung)-Begrundung zu Ethylenoxid (CAS-Nr. : 75 -21 -8). Begrundung zur ERB zu Ethylenoxid in Bek. GS 910. ANAND, V. P. , COGDILL, C. P. , KLAUSNER, K. A. , LISTER, L. , BARBOLT, T. , PAGE, B. F. J. , URBANSKI, P. , WOSS CASIMIR, J. , BOYCE, J. Reevaluation of ethylene oxide hemolysis and irritation potential, J. Biomed. Mater. Res. 64 A, pp. 648 -654, 2003 Alomar A, Camarasa JMG, Noguera J, Aspinolea F (1981) Ethylene oxide dermatitis. Contact Dermatitis 7: 205 -207 ATSDR –Agency of Toxic Substances and Disease Registry (1990) Toxicological Profile for Ethylene Oxide- December 1990. CAS#: 75 -21 -8 Basketter, D. A. , Griffiths, H. A. , Wang, X. M. , Wilhelm, . K. P. , Mc Fadden, J. (1996) Individual, ethnic and seasonal variability in irritant susceptibility of skin: the implications for a predictive human patch test. Contact Dermatitis 35, 208 -213; Bokkers BG, Slob W. 2005. A comparision of ratio distributions based on the NOAEL and the benchmark approach for subchronic-to-chronic extrapolation. Toxicological Sciences 85, 1033 -1040 Bokkers BG, Slob W. 2007. Deriving a data-based interspecies assessment factor using the NOAEL and the benchmark dose approach. Crit Rev Toxicol. 2007 37(5): 355 -73. Bommer J, Barth HP, Wilhelms OH, Schindele H, Ritz E (1985). Anaphylactoid reactions in dialysis patients: role of ethylene-oxide. Lancet 28: 1382 -1384. Bruch CW. 1973. Factors determining choice of sterilizing procedure. In: Phillips GB, Miller WS, eds. Industrial sterilization. Durham, NC: Duke University Press, 119 -123. (reviewed in ATSDR 1990) CEN ISO/TS 11135 -2: 2008/AC: 2009, Sterilization of health care products - Ethylene oxide - Part 2: Guidance on the application of ISO 11135 -1 (ISO/TS 11135 -2: 2008/Cor 1: 2009) Chapman J, Lee W, Youkilis E, Martis L (1986). Animal model for ethylene oxide (Et. O) associated hypersensitivity reactions. Trans Am Soc Artif Intern Organs 32: 482485. CICAD Concise International Chemical Assessment Document 54. Ethylene oxide. WHO 2003. Csanady GA, Denk B, Putz C, Kreuzer PE, Kessler W, Baur C, Gargas ML, Filser JG (2000): A Physiological Toxicokinetic Model for Exogenous and Endogenous Ethylene and Ethylene Oxide in Rat, Mouse, and Human: Formation of 2 -Hydroxyethyl Adducts with Hemoglobin and DNA. Toxicology and Applied Pharmacology 165, 1– 26 (2000) 43 DFG –Deutsche Forschungsgemeinschaft (1984) Ethylenoxid. 1984. DFG –Deutsche Forschungsgemeinschaft (1993) Ethylenoxid. 1993. DFG –Deutsche Forschungsgemeinschaft (1996) Ethylenoxid Nachtrag 1996. DFG –Deutsche Forschungsgemeinschaft (2002) Ethylenoxid MAK-Werte. 34. Lieferung. DGAUM (2008) Toxische Gefahrdung durch Hautresorption; Deutsche Gesellschaft fur Arbeitsmedizin und Umweltmedizin e. V. (DGAUM) http: //www. dgaum. de/index. php/publikationen/leitlinienarbeitsmedizin/251 -leitliniearbeitsmedizintox-haut. html Drager (2012) Analysenbericht 20121412, unpublished Dunkelberg H (1982) Carcinogenicity of ethylene oxide and 1, 2 -propylene oxide upon intragastric administration to rats. Brit J Cancer 46: 924 -933 Dunkelberg H (1981) Carcinogenic activity of ethylene oxide and its reaction products 2 chloroethanol, 2 -bromoethanol, ethylene glycol and diethylene glycol. I. Carcinogenicity of ethylene oxide in comparison with 1, 2 -propylene oxide after subcutaneous administration in mice. Zbl Bakt I, Abt Orig B 174: 383 -404 Dunkelberg H (1979) On the oncogenic activity of ethylene oxide and propylene oxide in mice. Brit J Cancer 39: 588 -589 ECETOC (1982) Technical Report Nr 5. Toxicity of Ethylene Oxide and its Relevance to Man. European Chemical Industry, Brussels. ECETOC (1982) Technical Report Nr 11. Toxicity of Ethylene Oxide and its Relevance to Man. An updating of ECETOC Technical Report Nr 5. European Chemical Industry, Brussels. ECETOC (1986) ECETOC document Nr 26 ECETOC statement on Ethylene Oxide toxicology and its Relevance to Man. October 1986. European Chemical Industry, Brussels. ECHA (2008): Guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation http: //echa. europa. eu/documents/10162/13632/information_requirements_part_e_en. pdf ECHA (2009): Evaluation & Reporting of data: How to provide a (robust) study summary http: //echa. europa. eu/documents/10162/13566/evaluation_of_available_information_en. pdf ECHA (2010 a): Guidance on information requirements and chemical safety assessment, Chapter R 8 – Characterisation of dose [concentration]-response for human health. http: //echa. europa. eu/documents/10162/13632/information_requirements_r 8_en. pdf ECHA (2010 b): Guidance on information requirements and chemical safety assessment, Chapter R 19 – Uncertainty analysis, http: //echa. europa. eu/documents/10162/13632/information_requirements_r 19_en. pdf EMEA (2006) Committee for medicinal products for human use. Guideline on the Limits of Genotoxic impurities. CPMP/SWP/5199/02. 44 http: //www. ema. europa. eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC 500 002903. pdf EN ISO 10993 -7 (2009): Biological evaluation of medical devices Part 7: Ethylene oxide sterilization residuals (ISO 10993 -7: 200 + Cor 1: 2009) (consolidated version) EU, (2008) SCHER/SCCP/SCENIHR (2008) Scientific opinion on use of the Threshold of Toxicological Concern (TTC) Approach for the Safety Assessment of Chemical Substances. SCCP/1171/08 EU (2012) SCHER/SCCP/SCENIHR (2012) Scientific opinion on Toxicity and Assessment of Chemical Mixtures. ISBN 978 -92 -79 - DG for Health and Consumers. European Union. European Chemicals Bureau (ECB) (2003) Technical Guidance Document on Risk Assessment. EN ISO 11135 -1: 2007, Sterilization of health care products - Ethylene oxide - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices (ISO 111351: 2007) Fennell T. R, Brown C. D. A Physiologically based Pharmacokinetic Model for Ethylene Oxide in Mouse, Rat and Human. Toxicol. Appl. Pharmocology 173, 161 -175, 2001. Fluhr JW, Darlenski R, Angelova-Fischer I, Tsankov N, Basketter D. (2008) Skin Irritation and Sensitization: Mechanisms and New Approaches for Risk Assessment. Skin Pharmacology and Physiology 2008, 21: 124 -135. GESTIS Stoffdatenbank: www. dguv. de/ifa/stoffdatenbank Ginsberg G. , Foss B, Brown Dzubow R, Firestone M. Options for incorporating children´s inhaled dose into human health risk assessment. Inhalation Toxicology 22(8): 627 -647. Graeter, L. , Mortensen M. E. (1996) Kids are different: developmental variability in toxicology. Toxicology , 111, 1– 3, 15– 20. Grammer LC, Roberts M, Nicholls AJ, Platts MM, Patterson R (1984). Ig. E against ethylene oxidealtered human serum albumin in patients who have had acute dialysis reactions. J Allergy Clin Immunol 74: 544 -546. Greaves-Walker WJ, Greeson CE (1932). The toxicity of ethylene oxide. J. Hygiene 32, 409. Hallier E, Langhof T, Dannappel D, Leutbecher M, Schroder K, Goergens HW, Muller A, Bolt HM (1993) Polymorphism of glutathione conjugation of methyl bromide, ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchange (SCE) in lymphocytes. Arch Toxicol 67: 173 -178 Hardt J. , Schromer M. L. , Angerer J. Untersuchung zur Exposition bei der Verwendung Ethylenoxidsterilisierter Medizinprodukte im Krankenhaus. Arbeitsmed. Sozialmed. Umweltmed. 41, 5, 2006. Hasegawa, R. ; Hirata-Koizumi, M. ; Dourson, M. L. ; Parker, A. ; Sweeney, L. M. ; Nishikawa, A. ; Yoshida; M. ;

Report by Prof. Dr. habil. A. Strzelczyk Torun l l l April – Aug. 1994 346, 2 meter in total (261, 2 m, 85 m in foulders, 13 m notes) The following measures were taken: l 1. sources of damage were analysed, l The books were stored in wet/very humid conditions l The books were dusty, there are spores in the dust, a risk for human health l 10 years ago (1984) the books were brought to dry rooms, but due to tight packing they dryed slowly l Humidiy and temperature were measured in 50 books in Junly 1994, the r. H was between 59 and 71 and the Temp. Between 19, 5 and 23, 4^C l The humidity of the air in the room was between 57 -62 % and the temperatureat 22, 6 Centigrades l 2. 9 books and 15 groups of archival documents were selected according to various criteria (sort of damage, , aterial composition, content) and model restoration was made, l 3. Microorganisms were analysed by microscopic observation directly on the books or in complicated cases on growth medium. The following species were found: Streptomyces, Geotrichum, Chaetomium, Acremoniella, Stachybotrys, Epicoccum, Stemphylium, Botrytis. Streptomyces and Geotrichum were found more often. l 4. the entire collection plus the 9 books and 15 groups of archival material was packed and prepared for desinfection l Chamber for 20 m 3, 10 kg Petrox, 5 days fumigation, then airwashing until EO detector did not show EO any more l The rooms were desinfected with 2% Aseptin M solution and treatment repeated after 10 days l 5. Fumigation with 90% EO and 10% CO 2 (Petrox gas) l 6. books were air washed and climatized, l In Swidnica l 7. dust and microorganism spores were removed from the books in Sept. 1994 (after the report was written) l 8. the effectivity of the desinfection was evaluated (report Nov. 1994)

15 years later 2009 in Ossolineum alle alten Drucke (Signaturgruppe SD) und Handschriften (Signaturgruppe R) begast worden. l „ 2010 durch Adam Wilga, der eine solche Begasungskammer erfunden hat, die übrigen Bücher begast (Signaturen 1, 2, 8000). “ l „Wenn es um die Signaturen geht, nach denen Sie gefragt haben, handelt es sich um fortlaufende Signaturen (gemäß Katalog Dr. Górski). “ l l Waiting for data from Ossolineum

MEN AND BOOKS - 2012 For the selection of books several parameters were relevant: (1) moment of fumigation (17 fumigated in 2009, 11 fumigated in 2010) (2) material composition (11 printed books, 7 ms iron gall ink, 10 modern dye ink, 15 leather involved, 3 parchment involved, 11 textile involved, all book blocks paper of their time) (3) age of the book (2 18 th cent. , 12 from 19 th cent. Rest 20 th cent. ) (4) size of book (folio to octav) The books for ethylene oxide measurement were chosen aiming to get a representative average of all these features. This is especially important when it comes to transfer data into application Europe-wide and on an “average archive” at the end of the project. 28 volumes bound in leather, parchment, paper and textiles, dating from the 18 th, 19 th and 20 th century, thus representing also different sorts of paper as book block, ranging from folio to quart were selected by the Parish in Swidnica and brought to the European Research Centre for Book and Paper Conservation-Restoration in Horn. There these books were put into a chamber of inert synthetic material of 1 qm volume and stored under closed conditions for 60 days at 20 °C and 50%rel. H.

Books brought to Horn off gasing measured

Two different analysis methods were chosen to detect the off gassing ethylene oxide, a digital handheld device, Dräger X-am 5000, which turned out to be too rough (measuring range 0 - 200 ppm, resolution 0. 5 ppm, smallest possible detection 1 ppm; expected concentration below) and a GC/FID. For the later the measurement was passive with ORSA-tubes filled with activated carbon. The measurement lasted for 336 hours. Then the tubes were taken out, closed and sent to gas chromatography. The analysis was made with GC/FID with retention time catalogues and quantification via external calibration function. This standard working instruction is a modified NIOSH 1612. Working conditions: Gaschromatograph “Doppelsäulengerät Sichromat 1 -4”; Injektion: split/splitless; 2. 5µL splitted auf 2 wide-bore colums, 250°C, Colums: 30 m OPTIMA-WAX; 0. 53 mm * 1. 0 µm and 30 m OPTIMA 1; 0. 53 mm *1. 0 µm, Both detectors FID (250°C), Carrier gas Nitrogen: 2. 5 m. L/min, burning gas synth. air: 300 m. L/min, Hydrogen: 25 m. L/min, stove temperature 45°C isotherm 10 min, 45°C to 180°C in 5°C/min; 180°C isotherm 13 min, 180°C to 200°C in 10°C/min, 200°C isotherm 13 min. The method is based on the international method NIOSH 1612 (http: //www. cdc. gov/n iosh/docs/2003 -154/pdfs/1612. pdf)

Umweltbundesamt l l l Takes the influence via inhalation for the gratest risk Not so much touching Not so much oral About Material I suggest to add several book blocks to the fumigation of dummies, as to have more substance to catch the EO gas possibly and get more realistic and controlled measurement for our conclusions.

Workflow Dummies Dummy A 1 Nach der Herstellung direkt für Ethylenoxidbe gasung ohne Zwischenschri tte Dummy A 1 Dummy A 2 Nach der Herstellung direkt für Mikroorganismen beimpfung ohne Zwischenschritte Dummy A 3 Dummy A 4 Nach der Referenz Herstellung direkt für Mikroorganismen beimpfung ohne Zwischenschritte Dummy A 2 Direkt vom ERC kommend zum Beimpfen Dummy A 3 Direkt vom ERC kommend zum Beimpfen Beiter zum Ethylenoxid begasen Dummy A 3 Kommt direkt aus dem ERC ohne Vorbehandlun g Ist nicht gealtert, sondern Nur beimpft Dummy A 5 Nach der Herstellung direkt für Alterung Dummy A 6 Nach der Herstellung direkt für Alterung Dummy A 7 Nach der Herstellung direkt für Alterung Dummy 8 Nach der Herstellung direkt für Alterung Dummy A 5 Dummy A 6 Dummy A 7 Dummy A 8 Alterung Referenz Alterung Weiter zur Ethylenoxid begasung Alterung Weiter zur Mikro Organismen beimpfung Dummy A 6 Dummy A 7 Von der TU Graz kommend zum Beimpfen Referenz Dummy A 8 Von der TU Graz kommend zum Beimpfen Weiter zum Ethylen oxid Dummy 8 Kommt direkt aus der TU Graz Ist nur gealtert Kommt von der BOKU ist gealtert Und beimpft

Suggestion book block for more volume l !

Aims ERC took over in the project: l l l l - measuring off-gassing ethylene oxide - evaluation of toxicity(Umweltbundesamt) - provide dummies - analysis of the parchment&leather - interpretation of analyse-data - development of guidelines for the restoration - develop recommendations for the handling of mouldy heritage&handling of ethylene oxide-fumigated heritage on paper, parchment and leather - suggestions of alternative methods to disinfect mouldy written/printed heritage - disseminate the project results (website, journals, etc. ) - organise the joint exhibition in coop. with the other partners - organise the final conference in coop. with P 5 - organise the publication material in coop. with the partners (translation, distribution, etc. ) - distribution of results: professional journals, special meetings, conference, webpage, movable exhibition for specialists & laymen, local newspapers, TV, radio, underlining the benefit of EU funding; ERASMUS-students - workshops beyond project runtime

Next steps - Work flow Graz BOKU Ossolineum - Shrinkage Temperature Measurement - Graz: Paper tests - Umweltbundesamt Results - BOKU results on fungi - Question: is the paper more disposed to new attack by the ethylene Oxide treatment or not?

HW Step 6 together with ICARUS: Digitization(50000 files) of the material for research work in the project & making it accessible for all on the internet Start on 11 th March 2013 l

Acknowlegement For the information about the books: Bozena Pytel, Reverend Waldemar Pytel, Sonja Stankowski, Dr. Stephan Aderhold Umweltbundesamt: Dr. Elisabeth Fassold, DI Isabel Peißl, Dr. Maximilian Kinzl, Dr. Martin Paparella Dräger Safety AG & Co. KGa. A: Thomas Krebs and Dr. Dirk Rahn-Marx ERC: Shirin Jacoby, Bogna Gorniak, Marta Cieplinska, Cristina Cicero