case study: methylene chloride exposure in a pharmaceutical process

Exposure Risk Assessment

of

Methylene Chloride

Both Alone and in Combination

with Methanol in a

Pharmaceutical Plant

Presented by:

Bernard L. Fontaine, Jr., CIH, CSP

The Windsor Consulting Group, Inc.

Copyright© 2000 The Windsor Consulting Group, Inc.

Methylene Chloride and Methanol in a Pharmaceutical Plant

• Initial Investigation to Evaluate:– Weight and Mix Solvents in Solution Prep

Room – Purge Spray Nozzles - Coating Room– Spray Pills in Ventilated Chamber


• Sampling Methods

• MSA Escort sampling pumps calibrated at 100 cc/minute using silica gel tubes for methanol vapors

• MSA Escort sampling pumps calibrated with two charcoal tubes at 100 cc/minute for methylene chloride vapors


• Analytical Methods

• Methanol - NIOSH Method 2000 - Desorb in water - GC/FID - LOD is 0.01 mg.

• Methylene Chloride - NIOSH Method 1005 - Desorb in carbon disulfide (CS2) - GC/FID - LOD is 0.01 mg.


• Methylene Chloride Exposures (Initial)

• Weigh and transfer coating solution to mixing kettle - 140 ppm (86 minutes)

• Divide coating - 27 ppm (81 minutes)

• Purge spray nozzles - 62 ppm (87 mins.)

• Spray pills - 22 ppm (149 minutes)


• Methylene Chloride Exposures (Initial)

• 8-Hour TWA - 47.7 ppm

• OSHA SAE - 0.12

• 95% CI - (42.0 - 53.4 ppm)

• 8-Hour ACGIH TLV-TWA - 50 ppm

• 8-Hour OSHA PEL-TWA - 500 ppm


• Methanol Exposures (Initial)

• Blend and mix solvent - 71 ppm (87 minutes)

• Divide coating into two batches - 3.7 ppm (82 minutes)

• Purge spray nozzles - 13 ppm (85 mins.)

• Spray pills - 8.1 ppm (149 minutes)


• Methanol Exposures


• OSHA SAE - 0.22

• 95% CI - (16.1 - 22.3 ppm)




• ACGIH TLVs for Chemical Mixtures with Additive Effects

∀Σ = 47.4 ppm + 18.3 ppm = 1.05

50 ppm 200 ppm

• Methylene Chloride and Methanol

•


• Methylene Chloride 1st Follow-Up Survey

• Transfer solvent to mixing kettle - 16 - 30 ppm (38 - 41 minutes)

• Divide solvent coating into two batches 24 - 38 ppm (72 - 87 minutes)

• Spray pills - 16 - 29 ppm (81 - 83 mins.)


• Methylene Chloride Follow-Up Survey

• 8-Hour TWA - 8.4 ppm - 13.1 ppm

• OSHA SAE - 0.12




• OSHA Methylene Chloride Standard (29 CFR 1910.1052)

• New OSHA PEL-TWA - 25 ppm

• New OSHA STEL-TWA - 125 ppm

• ACGIH TLV-TWA - 50 ppm


• Methylene Chloride 2nd Follow-Up Survey

• Transfer solvent to mixing kettle - 83 ppm (23 minutes)

• Purge and calibrate spray nozzles - 140 ppm (37 minutes)


• Methylene Chloride Follow-Up Survey

• Assist calibration of nozzles - 190 ppm (13 minutes)

• Area sample above sprayer - 54 ppm (15 minutes)

• Loading tablets into sprayer - 17 ppm (42 minutes)


• Methylene Chloride 2nd Follow-Up Survey

• Spray dye coating on tablets - 2.8 ppm (20 minutes) - 2.9 (49 minutes)

• Loading tablets while spraying - 44 ppm (124 minutes)



• Methylene Chloride Sample Results

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05/26/9801/06/9711/11/96


• Methylene Chloride Sample Results

• Work task exposure - 46.8 ppm (171 minutes)




• Recommendations

• Engineer or administratively control 15-minute STEL exposure

• Use appropriate respiratory protection and PPE while implementing controls

• Inform workers of the test results and location of exposure data


• Recommendations

• Inform workers about health effects of methylene chloride alone and combined with methanol, isopropanol or n-butanol

• Monitor for methylene chloride along with other volatile organic compounds

• Upgrade levels of respiratory protection, surveillance, and written program


• Recommendations

• Upgrade electrical equipment and wiring to conform to NEC Class I, Division II

• Install area monitors to warn employees in the Solvent Prep room of elevated level

• Post warnings to regulate work area and prevent unauthorized entry


• Recommendations

• Re-monitor worker exposures to methylene chloride and methanol

• Implement medical surveillance program for affected workers


• Conclusions

• Consider chemical substitution for methylene chloride

• Improve ventilation in Solvent Prep room

• Supplement with air supplied respirators

• Improve employee work practices and procedures

case study: methylene chloride exposure in a pharmaceutical process

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