1. Biological agents: Need for Occupational Exposure Limits (OELs) and feasibility of OEL setting Rafal Górny Department of Biohazards Institute of Occupational Medicine and Environmental Health WHO Collaborating Centre Sosnowiec Poland

2. Biological agents (BA) – is it a problem? Epidemiological studies: in world scale a few hundred million people are exposed to BA Putting non-occupational indoor environment aside, exposure to BA is registered for 148 specialist work professional groups in 22 main branches of industry Important issue for occupational medicine and public health Adverse health effects: allergic reactions, infections, toxic reactions, and nonspecific symptoms

3. Biological agents at work bioaerosols - airborne transport of biological particles penetration of biological agents through the skin, mucous membrane or with a bite of bloodsucker arthropoda less frequently through the alimentary tract (such way is rather atypical for occupational infections) Conditio sine qua non of proper hygienic regime of occupational settings and health comfort is correct control of worker exposure and control of crucial parameters determining contamination of work environment by BA

4. Necessary needs Elaboration of widely accepted guidelines, standards or limit values enabling proper interpretation of environmental situations or measurement results, at least Evaluation criteria Chemical/physical hazards Biohazards The higher concentration/intensity, the longer time of exposure the more severe health outcome (body damage, occupational disease) Unproportionality of human body answer to risk factor

5. Lack of standards/limit values dose-response relationship is still indeterminate and controversial in many aspects it is not possible to identify individual species of microorganisms or other specific BA responsible for health effects (except some common allergies attributed to specific agents or exposure) susceptibility as an individual feature of each organism source data regarding environmental/occupational concentrations of biological agents are still insufficient lack of standardization of sampling methods (lack of standard samplers) and experimental procedures (lack of commonly approved criteria for assessing exposure to biological agents)

6. Status quo ante Standards or limit values, if established, base on clinical picture of disease caused by biological agent, taking into account only presence of the reliable factor in some element of the studied environment (qualitative approach) Status praesens Nevertheless, quantitative standards, reference or limit values do exist to facilitate interpretation of measurement data

7. Strategy of hygienic standard elaboration ENVIRONMENT DWELLINGSOCCUPATIONAL ENVIRONMENT INDOOROUTDOOR INDUSTRIAL NON INDUSTRIAL AIR SURFACES 1. 2.

8. Quantitative standards/limit values ARBITRARYRELATIVE/COMPARATIVE Concentration of biological agent, which is acceptable or non-acceptable Usually for total microbial flora, their groups or certain species Proposed by individual investigators, expert groups or as a result of cross- sectional/large-scale research study Not related to the specific health outcome (do not precise dose- response relationship) Often equal or close to the detection level of particular analytical method Usually based on simultaneously measured concentration of biological agent in indoor and outdoor environments If indoor/outdoor relationship is below 1, it shows that hygienic conditions of indoor environment is good or acceptable Identification of indoor sources of biological agent(s) Suitable for qualitative or frequency of appearance comparisons

9. To ensure the reliability of bioaerosol measurement methods and their proper interpretation, in the first place, it is necessary to unify the methodology, i.e., to recommend the use of proper methods. The active air sampling (e.g., volumetric methods) should allow the measurement of a concentration of microorganisms and describe their taxonomical origin. Sampling method as immanent component of proposed standard/limit value Various technological and lifestyle recommendations and guidance allow to control the work environment contaminated with biological agents using a few different methods (e.g., Recommended limits for microbiological monitoring of clean areas for sterile processing according to the EUs Good Manufacturing Practice (GMP) guideline)

10. History of standards for BA Type of premises, biological agent Limit value proposal, author(s), year of publication Dwellings Bacteria and fungi (CFU/l) Bacteria (#/liter) Total microorganisms (CFU/m 3 ) 600 - Carnelley et al. (1887) 50 - Bujwid (1894) 1,8 10 3 - Bourdillon et al. (1941) Occupational premises Total microorganisms (CFU/m 3 ) 4,3 10 5 - Donham et al. (1988) 5 10 4 - Erman et al. (1989) 5 10 3 -1 10 4 - Malmros et al. (1992) Gram-negative bacteria (CFU/m 3 ) 1 10 3 - Clark (1985) 2 10 4 - Buyanov et al. (1990) 1 10 3 - Malmros et al. (1992) Fungi (CFU/m 3 ) 1 10 7 - Clark (1985) Endotoxins (µg/m 3 ) 0,1 - Clark (1985) 0,1-0,2 - Rylander (1987) 0,1-0,2 - Malmros et al. (1992) 0,005 - DECOS (1998) 0,025 - Laitinen et al. (1999)

11. Quantitative standard/limit value examples CULTURABLE OR VIABLE EVALUATION STANDARDS FOR HOME & COMMERICAL BUIDLINGS Governmental Bodies 1. Brazil 2. Canadian Mortgage and Housing Company (CMHC) 3. Commission of European Communities 4. Czech Republic 5. Finland 6. Netherlands and Research Institute 7. New York City Department of Health (NYCDH) 8. Nordic Council 9. Poland 10. World Health Organization (WHO) Trade Associations Indoor Air Quality Standard 11. American Conference of Governmental Industrial Hygienists Trade Associations 12. American Industrial Hygiene Association 13. Indoor Air Quality Association (AIHA) 14. International Society of Indoor Air Quality and Climate (IAQA) TOTAL SPORE EVALUATION STANDARDS GOVERNMENTAL BODIES 15. Russian Federation Standard 16. Texas Department of Health Trade Associations (TDH) 17. American Academy of Allergy, Asthma & Immunology 18. American College of Occupational and Environmental Medicine CULTURABLE OR VIABLE SPORE LIMITS FOR MEDICAL DEVICE & PHARMACEUTICAL CLEAM ROOMS Governmental Bodies 19. European Union Clean Room Standard 20. U. S. Pharmacopoeia clean room standard

12. Quantitative standard/limit value examples Functional Grouping of Mold and Bacteria Standards A. Permissible or Acceptable Exposure Levels B. Action Levels (Warranting Investigation) C. Ceiling Limit or IDLH Levels (Immediately dangerous to life and health) D. Clearance Levels Exposure Guidelines (Post Remediation) E. The Inside Versus Outside Concentration Rank Order Guidelines F. Ceiling Limits for Hospitals & Other Susceptible Occupant Environments G. Bacteria Standards H. Application of the Standards - The Issue of Open Windows

13. Quantitative standard/limit value examples Total bacteria: 1,0 10 3 ÷ 7,0 10 3 CFU/m 3 for dwellings and non- occupational indoor environment as well as 7,5 10 2 ÷ 1,0 10 7 CFU/m 3 for occupational environment (in all these indoor spaces no safe level for pathogens (0 CFU/m 3 ) Gram-neg. bacteria: 1,0 10 3 ÷ 2,0 10 4 CFU/m 3 for occupational environment Endotoxins: 0,005 ÷ 0,2 µg/m 3 for occupational environment Total fungi: 1,0 10 1 ÷ 1,0 10 4 CFU/m 3 for dwellings and non-occupational indoor environment as well as <1,0 10 2 ÷ 1,0 10 7 CFU/m 3 for occupational environment (in all these indoor spaces no safe level for pathogens (0 CFU/m 3 ) Subtilisins: 0,06 µg/m 3 for occupational environment House dust allergens: mite Der p I: 2,0 ÷ <15,0 µg/g cat Fel d I: <1,0 10 4 ng/g dog Can f I: <1,0 10 5 ng/g

14. Special environments, i.e., hospital premises and clean areas for sterile processing: 1,0 10 0 ÷ 4,0 10 3 CFU/m 3 and <1,0 10 0 ÷ 1,0 10 3 CFU/m 3 Clean areas for sterile processing: the microbial quality of the air is accompanied by the control of a quality of the surfaces. The proposed limits are as follows: <1,0 10 0 ÷ 4,0 10 2 CFU/24 cm 2, if concentration is related to the surface (usually equal to the surface of Petri dish), <1,0 10 0 ÷ 2,0 10 1 CFU/glow, if the certain quality of the worker hands is required, or 3,23 10 5 CFU/m 2, if microorganisms sediment on the surface within 1 week or up to 10 6 CFU/g of dust, if the concentration is related to the amount of settled dust Quantitative standard/limit value examples

15. Directive 2000/54/EC of the European Parliament and of the Council of 18 September 2000 on the protection of workers from risks related to exposure to biological agents at work. 2000 Qualitative approach Defines employers obligations in terms of the protection of workers against risks to their health and safety, including the prevention of such risks, arising or likely to arise from exposure to biological agents at work Annex III – Community classification (the list of classified BA)

16. European standards (EN) – Workplace atmospheres: 13098: Guidelines for measurement of airborne micro-organisms and endotoxin 14031: Determination of airborne endotoxins 14042: Guide for the application and use of procedures for the assessment of exposure to chemical and biological agents 14583: Volumetric bioaerosol sampling devices – requirements and test methods German standards (VDI) – Measurements of airborne microorganisms and viruses in ambient air 4252: Active sampling of bioaerosols 4253: Culture based method for the determination of the concentrations of moulds in the air 4255: Bioaerosols and biological agents - Source of emissions and control measures - Overview Life after... Directive 2000/54/EC No way of interpretation of quantitative results is given

17. 2004 Establishment of Biological Agents Expert Group as a part of the Interdepartmental Commission for Maximum Admissible Concentrations and Intensities for Agents Harmful to Health in the Working Environment Central Institute for Labor Protection - NRI Warsaw, Poland

18. Biological Agents Expert Group Scientific approach If a solid link between the concentration of investigated parameters and resulting adverse health effect cannot be effectively established, then, based on the biological agent concentration measurements, the reference values should enable evaluation of the quality of the environment, as well as determination of what is typical and acceptable and what is atypical or not acceptable for a specific type of setting

19. *) For respirable fraction the proposed limits should be twice as low, i.e., 50000 CFU/m 3 for total mesophilic bacteria, 10000 CFU/m 3 for both Gram- negative bacteria and thermophilic actinomycetes, and 25000 CFU/m3 for fungi Polish proposals for OEL and PSLV/RLV for bioaerosols (volumetric methods) Microbial agent Limit value Industrial settings polluted with organic dust Public service and residential buildings Mesophilic bacteria100.000 CFU/m 3 *5.000 CFU/m 3 Gram-negative bacteria 20.000 CFU/m 3 * 200 CFU/m 3 Thermophilic actinomycetes 20.000 CFU/m 3 * 200 CFU/m 3 Fungi50.000 CFU/m 3 *5.000 CFU/m 3 BA from the risk group 3 & 4 0 CFU/m 3 Bacterial endotoxin200 ng/m 3 (2.000 EU/m 3 ) *5 ng/m 3 (50 EU/m 3 )

20. Decision making when standards/limit values are not available Understanding of the nature of phenomenon and adequate measurement of biological agent (usually in the air) Understanding and defining of health effects as a result of such exposure Elaboration of the real hypothesis, which should be tested