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

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

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 ppm range Internal J&J OEL: 20 ppm IOHA London 2015, April 2015, Hilton London Metropole

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, April 2015, Hilton London Metropole

Identification Basic characterization: work stations & activities Isoflurane evaporator Surgical interventions (Masks) Induction Box IOHA London 2015, 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

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, April 2015, Hilton London Metropole

Control Induction box IOHA London 2015, 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

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

Control Workstations: correct use LEV IOHA London 2015, 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

Control Work practices & training IOHA London 2015, 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: ppm - With (5 times) : 1.7 – 6.8 ppm Manipulations - Opening lid induction box: 2 steps - Speed removal animals

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, April 2015, Hilton London Metropole