Biological agents Need for Occupational Exposure Limits OELs

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

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

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

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 The higher concentration/intensity, the longer time of exposure the more severe health outcome (body damage, occupational disease) Biohazards Unproportionality of human body answer to risk factor

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)

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

Strategy of hygienic standard elaboration 1. ENVIRONMENT INDOOR DWELLINGS OCCUPATIONAL ENVIRONMENT INDUSTRIAL 2. OUTDOOR AIR NON INDUSTRIAL SURFACES

Quantitative standards/limit values ARBITRARY 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 crosssectional/large-scale research study Not related to the specific health outcome (do not precise doseresponse relationship) Often equal or close to the detection level of particular analytical method RELATIVE/COMPARATIVE 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

Sampling method as immanent component of proposed standard/limit value 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. 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 EU’s Good Manufacturing Practice (GMP) guideline)

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 50 1, 8 103 - Carnelley et al. - Bujwid - Bourdillon et al. (1887) (1894) (1941) Occupational premises - Donham et al. - Erman et al. - Malmros et al. (1988) (1989) (1992) 1 103 Gram-negative bacteria (CFU/m 3) 2 104 1 103 - Clark - Buyanov et al. - Malmros et al. (1985) (1990) (1992) Fungi (CFU/m 3) 1 107 - Clark (1985) Endotoxins (µg/m 3) 0, 1 -0, 2 0, 005 0, 025 - Clark - Rylander - Malmros et al. - DECOS - Laitinen et al. (1985) (1987) (1992) (1998) (1999) Total microorganisms (CFU/m 3) 4, 3 105 5 104 5 103 -1 104

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

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

Quantitative standard/limit value examples Total bacteria: 1, 0 103 ÷ 7, 0 103 CFU/m 3 for dwellings and nonoccupational indoor environment as well as ≤ 7, 5 102 ÷ 1, 0 107 CFU/m 3 for occupational environment (in all these indoor spaces no safe level for pathogens (0 CFU/m 3) Gram-neg. bacteria: 1, 0 103 ÷ 2, 0 104 CFU/m 3 for occupational environment Endotoxins: 0, 005 ÷ 0, 2 µg/m 3 for occupational environment Total fungi: 1, 0 101 ÷ 1, 0 104 CFU/m 3 for dwellings and non-occupational indoor environment as well as <1, 0 102 ÷ 1, 0 107 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, 0 104 ng/g dog Can f I: <1, 0 105 ng/g

Quantitative standard/limit value examples Special environments, i. e. , hospital premises and clean areas for sterile processing: 1, 0 100 ÷ 4, 0 103 CFU/m 3 and <1, 0 100 ÷ 1, 0 103 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, 0 100 ÷ 4, 0 102 CFU/24 cm 2, if concentration is related to the surface (usually equal to the surface of Petri dish), <1, 0 100 ÷ 2, 0 101 CFU/glow, if the certain quality of the worker hands is required, or 3, 23 105 CFU/m 2, if microorganisms sediment on the surface within 1 week or up to 106 CFU/g of dust, if the concentration is related to the amount of settled dust

2000 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. 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) Qualitative approach

„Life after. . . Directive 2000/54/EC” 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 No way of interpretation of quantitative results is given

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

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

Polish proposals for OEL and PSLV/RLV for bioaerosols (volumetric methods) Limit value Microbial agent Industrial settings polluted with organic dust Public service and residential buildings 100. 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 Mesophilic bacteria Fungi BA from the risk group 3 & 4 Bacterial endotoxin 50. 000 CFU/m 3 * 0 CFU/m 3 200 ng/m 3 (2. 000 EU/m 3) * 5. 000 CFU/m 3 5 ng/m 3 (50 EU/m 3 ) *) 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 Gramnegative bacteria and thermophilic actinomycetes, and 25000 CFU/m 3 for fungi

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