1. Case Study: Controlling exposure to isoflurane used in animal surgical procedures in Research & Development Michel Vangeel, Janssen Campus Belgium IOHA London 2015, 25-30 April 2015 Hilton London Metropole

2. Introduction Janssen Research & Development All stages of Discovery 1800 employees Beerse, Belgium Johnson & Johnson IOHA London 2015, 27-30 April 2015, Hilton London Metropole

3. Anticipation Reports acute adverse health effects During animal surgical procedures Headaches, dizziness, loss of concentration, numbness fingers; 3 Janssen R&D sites J&J Isoflurane exposures 10-23 ppm range Internal J&J OEL: 20 ppm IOHA London 2015, 27-30 April 2015, Hilton London Metropole

4. Identification Basic characterization: isoflurane Boiling point: 48.5 °C (1013 mbar) - Vapor pressure: 440 hPa (25°C) - Relative Density: 1.45 g/cm 3 Routes of entry: Inhalation - may provoke: Headache, dizziness, loss of concentration, unconsciousness In case of contact with eyes: irritation, redness Occupational Exposure Limits (IFA - GESTIS databank) - Canada: 2 ppm - Sweden, Finland, Austria: 10 ppm – 20 ppm (STEL) - J&J: 20 2 ppm IOHA London 2015, 27-30 April 2015, Hilton London Metropole

5. Identification Basic characterization: work stations & activities Isoflurane evaporator Surgical interventions (Masks) Induction Box IOHA London 2015, 27-30 April 2015, Hilton London Metropole Filled with mixture of air and 2-5 volume % isoflurane minimum 30% O 2 (till 100%), flow rate 1l/min

6. Evaluation Exposure monitoring Identification work stations & sampling plan Personal & area monitoring: - SKC Anasorb 747 (100/50 mg) - flow rate: 200 cc/min. Continuous monitoring: - Thermo SaphIRe MIRAN - detection limit 0.04 ppm Statistical Analysis results - IDHA – Bayesian stats UCL 95,75 IOHA London 2015, 27-30 April 2015, Hilton London Metropole

7. Control Induction box IOHA London 2015, 27-30 April 2015, Hilton London Metropole = creates under pressure Controlled supply Adjusted diameters & position supply & exhaust Glide lid in 2 steps Adjusted sizes/animal Speed removing Additional exhaust

8. Control Anesthetic masks IOHA London 2015, 27-30 April 2015, Hilton London Metropole Supply isoflurane inside Exhaust outside Avoid to cover whole table Controlled supply isolfurane with indication on screen

9. Control Workstations: correct use LEV IOHA London 2015, 27-30 April 2015, Hilton London Metropole Correct use of supply & exhaust - No disturbances flow pattern = recipients & equipment / covers (sheets) - Close valve supply on time - Proper connections tubing Isoflurane filters - Saturated filters = source of exposure - Good maintenance & follow up - Evaluate removal & connection with LEV Expansion LEV - No improvisation/bad connections

10. Control Work practices & training IOHA London 2015, 27-30 April 2015, Hilton London Metropole Wipe of fur - Wipe off fur animal in front of extraction unit - Reduction of 10 times the concentration - Without wiping: 60- 88 ppm - With (5 times) : 1.7 – 6.8 ppm Manipulations - Opening lid induction box: 2 steps - Speed removal animals

11. Conclusion Connection & teamwork OH, IH, toxicology, EHS colleagues, business Respect pillars of Industrial Hygiene Control: combination of engineering controls, good work practices and training & awareness Reduce exposure < 2 ppm (new J&J OEL) IOHA London 2015, 27-30 April 2015, Hilton London Metropole