Rationale for use of air-purifying respirators in most NTP toxicology studies

FEATURE

Rationale for use of air-purifying respirators in most NTP toxicology studies By Laura Hodson, Douglas B. Walters, and Brad Collins

T

he National Toxicology Program (NTP) was established in 1978 to coordinate various types of toxicology research and testing within the U.S. Department of Health and Human Services.1 Because the toxicology of NTP test chemicals is usually not completely understood prior to the completion of laboratory studies, it is prudent to ensure that workers handling these NTP test compounds are protected against possible exposure at all times. In addition to engineering controls, part of the protection includes the use of an air-purifying respirator (APR). This paper explains the rationale for using APRs equipped with organic vapor or combination cartridges for most NTP animal toxicology studies, and provides an insight to determining cartridge service life. All NTP test chemicals are evaluated in accordance with the National Institute for Occupational Safety and Health (NIOSH) Respirator Decision Logic and the NIOSH Respirator Use Laura Hodson is af®liated to Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709, USA (e-mail: [email protected]). Douglas B. Walters, Ph.D., CSP, is af®liated with KCP, Inc., 6807 Breezewood Road, Raleigh, NC 27607, USA (e-mail: [email protected]) (formerly National Toxicology Program, NIEHS, PO Box 12233, Research Triangle Park, NC 27709, USA). Brad Collins is af®liated to National Toxicology Program, NIEHS, PO Box 12233, Research Triangle Park, NC 27709, USA (e-mail: [email protected]). 1074-9098/02/$22.00 PII S1074-9098(02)00350-7

Policy for Protection Against Carcinogens.2,3 These NTP laboratories must implement a respiratory protection program which meets the requirements of the OSHA Respiratory Protection regulation, and all respirators must be certi®ed by NIOSH.4 Respira-

All NTP test chemicals are evaluated in accordance with the National Institute for Occupational Safety and Health (NIOSH) Respirator Decision Logic and the NIOSH Respirator Use Policy for Protection Against Carcinogens. tor selection considers two categories of respirators; air-purifying, and atmosphere-supplying respirators, which include types that operate under positive or negative pressure. An air-purifying respirator protects the user by removing the contaminant(s) from inhaled air, while a positive-pressure respirator delivers a steady stream of puri®ed air. A negative-pressure respirator is regulated so that air is delivered whenever the face-piece pressure drops below a certain preset level. NIOSH has provided Assigned Protection Factors (APFs) that speci®es each speci®c respirator class for protection against gas/vapor exposures. The APF assigned is 10 for any air-purifying half-mask, and 50 for any air-purifying full face respirator.

The APF increases to 10,000 for a self-contained respirator with a full facepiece operated in a pressure demand or other positive-pressure mode. Respirator recommendations are guided by the APF, the airborne concentration and the NIOSH Recommended Exposure Limit (REL), or other exposure limit (e.g., OSHA PEL, or ACGIH TLV when a REL is not available), for a speci®c chemical substance, as shown in the following formula: APF >

workplaceairborneconcentration REL

This formula states that the APF must be greater than the ratio of the workplace air concentration to the REL. The APF numerically represents the particular respirator's ability to reduce the concentration of a particular contaminant against which it is used. Respirator cartridge service life can be determined using software programs, provided an estimate of the chemical concentration exists.5 Estimates of potential human exposures in the laboratory to NTP test chemicals can be made using chemical monitoring, historical data, or prediction by analogy with structurally similar chemicals under similar conditions. If a comparison technique is used, it is critical that the physical and chemical properties of each chemical be carefully evaluated to ensure all conclusions are correct. Four examples are given illustrating different chemicals (trichloroethylene, cumene, o-cresol, and 2-butoxyethanol) with different administration routes, (gavage, inhalation, feed and dermal). These example calculations show that the use of APRs to protect animal-room workers in NTP studies

ß Division of Chemical Health and Safety of the American Chemical Society Elsevier Science Inc. All rights reserved.

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is justi®ed, and further provide a method to estimate the cartridge service life.

Example 1. Gavage study with

trichloroethylene (TCE) CAS number: Molecular formula: Molecular weight: Density: Vapor pressure: NIOSH REL: OSHA PEL: ACGIH TLV:

79-01-6 C2HCl3 131.40 1.46 g/mL 77 mmHg at 258C N/A, potential carcinogen 100 ppm 50 ppm

Step 1: Estimate worse-case airborne chemical concentrations:  Room air changes/hr ˆ 10/hr Room air changes over every 6 minutes  Room size ˆ …10 ft  15 ft  20 ft† ˆ 3000 ft3 3000 ft3  0:0283 m3 /ft3 ˆ 84:9 m3  Total number of animals …rats† ˆ 600/room

Conclusion: The use of an APR is justi®ed. Step 3: Determine the cartridge service life:

Is 10 > 100 ppm=50 ppm?

 The 3M ``2000 Respirator Selection Guide'' recommends an organic vapor (OV) respirator for TCE, provided the exposure not exceed 10 times the TLV of 50 ppm.  Using the TCE estimated exposure level of 48 ppm, and the 3M Cartridge Service Life software (http:// www.3m.com/occsafety/) and assuming work is performed at 32 to 1228F; 65% relative humidity; 0.8 to 12 atmospheres pressure, it is estimated that an organic vapor cartridge will last 47 to 85 hr (depending upon breakthrough of either 0:1 exposure or 0:5  the TLV, and if either light or medium work is being done).

Conclusion: The use of an APR is justi®ed.

Example 2. Inhalation study with cumene

 Dose ˆ 0:5 mL/animal  600 animals ˆ 300 mL total of TCE

CAS number: Molecular formula: Molecular weight: Vapor pressure:

 Assume 150 mL (1/2 the dose) is excreted over 1 hr and steady state exists

NIOSH REL: OSHA PEL: ACGIH TLV:

 …150 mL/60 minutes†  …6 minutes/ room change† ˆ 15 mL/room change 15 mL  1:46 g/mL …density† ˆ 21:9 g ˆ 2:19  104 mg 2:19  104 mg/84:9 m3 ˆ 257:9 mg/m3 257.9 mg/m3  24:45/131:4 ˆ 47:9 ppm TCE Step 2: Is the APF > …chemical concentration†/TLV?  For a half-mask air-purifying respirator, the APF ˆ 10. Under animal room conditions, the ambient TCE concentration is estimated to be 47.9 ppm, and the TLV is 50 ppm TCE. Is 10 > 47:9 ppm=50 ppm? Yes; 10 > 0:959 18

to be 100 ppm, and the REL is 50 ppm cumene.

98-82-8 C9H12 120.2 8 mmHg at 208C 50 ppm 50 ppm 50 ppm

Step 1: Estimate worse-case airborne chemical concentrations:  High dose ˆ 1000 ppm  Assume 10% of the chemical leaks from an inhalation chamber 10% of 1000 ppm ˆ 100 ppm  100 ppm is the potential personnel exposure concentration, without accounting for dispersion and dilution into the room. Step 2: Is the APF > chemical concentration/REL?  For a half-mask air-purifying respirator the APF ˆ 10. Under animal room conditions, the ambient cumene concentration is estimated

Yes; 10 > 2:0

Step 3: Determine the cartridge service life:  The 3M ``2000 Respirator Selection Guide'' recommends an organic vapor respirator for cumene, provided the exposure not exceed 10 times the TLV of 50 ppm.  Using the cumene estimated exposure level of 100 ppm, and the 3M Cartridge Service Life software (http://www.3m.com/occsafety/) and assuming work is performed at 32 to 1228F; 65% relative humidity; 0.8 to 12 atmospheres pressure, it is estimated that an organic vapor cartridge will last 33 to 64 hr (depending upon breakthrough of either 0:1  exposure or 0:5  the TLV, and if either light or medium work is being done). Example 3. Feed study with o-cresol CAS number: Molecular formula: Molecular weight: Density: Vapor pressure: NIOSH REL: OSHA PEL: ACGIH TLV:

95-48-7 C7H8O 108.14 1.048 g/mL NA 2.3 ppm (10 mg/m3) 5 ppm 5 ppm

Step 1: Estimate worse-case airborne chemical concentrations for a typical study:  Assume the concentration of airborne, respirable, particulate feed in a 84.9 m3 room is 24 mg/m3 (based upon housing 50 animals per sex, per dose, with 3 doses per study for rats and mice).  Assuming that the feed contains 0.03 to 3.0% of the chemical (o-cresol).  This results in a maximum concentration of 0.72 mg/m3 (or 0.16 ppm)

Chemical Health & Safety, September/October 2002

of o-cresol becoming airborne in the room. Step 2: Is the APF > chemical concentration/REL?  For a half-mask air-purifying respirator the APF ˆ 10. Under animal room conditions, the ambient o-cresol concentration is estimated to be 0.16 ppm, and the REL is 2.3 ppm o-cresol. Is 10 > 0:16 ppm=2:3 ppm? Yes; 10 > 0:07 Conclusion: The use of an APR is justi®ed. Step 3: Determine the cartridge service life:  The 3M ``2000 Respirator Selection Guide'' recommends an organic vapor respirator for o-cresol, provided the exposure not exceed 10 times the TLV of 5 ppm.  Using the o-cresol estimated exposure level of 0.16 ppm, and the 3M Cartridge Service Life software (http://www.3m.com/occsafety/) and assuming work is performed at 32 to 1228F; 65% relative humidity; 0.8 to 12 atmospheres pressure, it is estimated that an organic vapor cartridge will last nominally 999 hr before breakthrough (of 0:1  exposure for medium work being done).  It would be good practice to not wait until the respirator cartridge had reached 999 hr (or a life span of 6 months) with o-cresol, but rather to implement a more frequent changeout schedule as determined by the industrial hygienist or chemical hygiene officer (e.g., feed studies usually run for 90 days to 2 years, and at a minimum, new cartridges would be recommended at the beginning of each month).  Since the concentration is well below the REL and TLV, under normal laboratory practice a respirator would not be necessary, however, because the toxicology of NTP test chemicals is usually not completely understood prior to the completion of laboratory studies, it is prudent to ensure that workers handling these

NTP test compounds are protected against possible exposure at all times, and part of the protection includes the use of air-purifying respirators for all studies. Example 4. Dermal study with 2-butoxyethanol CAS number: Molecular formula: Molecular weight: Density: Vapor pressure: NIOSH REL: OSHA PEL: ACGIH TLV:

111-76-2 C6H14O2 118.2 0.903 g/mL 0.8 mmHg at 208C 5 ppm (24 mg/m3) 50 ppm (240 mg/m3) 20 ppm

Step 1: Estimate worse-case airborne chemical concentrations:  Room air changes/hr ˆ 10/hr Room changes over every 6 minutes

Is 10 > 10:6 ppm=5 ppm? Yes; 10 > 2:1 Conclusion: The use of an APR is justi®ed. Step 3: Determine the cartridge service life:  The 3M ``2000 Respirator Selection Guide'' recommends an organic vapor respirator for 2-butoxyethanol, provided the exposure not exceed 10 times the TLV of 20 ppm.  Using the 2-butoxyethanol estimated exposure level of 10.6 ppm, and the 3M Cartridge Service Life software (http://www.3m.com/occsafety/) and assuming work is performed at 32 to 1228F; 65% relative humidity; 0.8 to 12 atmospheres pressure, it is estimated that an organic vapor cartridge will last 346 to 586 hr (depending upon breakthrough of either 0:1  exposure or 0:5  the TLV, and if either light or medium work is being done).

 Room size ˆ …10 ft  15 ft  20 ft† ˆ 3000 ft3 3000 ft3  0:0283 m3 /ft3 ˆ 84:9 m3

CONCLUSIONS

 Total number of animals …rats† ˆ 600/room

Because the toxicology of NTP test chemicals is usually not completely

 Dose ˆ 0:1 mL/animal  600 ˆ 60 mL total Absorption through skin ˆ 20% 80% is vaporized and goes into the room atmosphere Constant steady evaporation rate

Because the toxicology of NTP test chemicals is usually not completely understood prior to the completion of laboratory studies, it is prudent to ensure that workers exposed to these NTP test compounds are protected against possible exposure at all times.

 0.1 mL/animal  600 animals ˆ 60 mL  80% ˆ 48 mL in air 48 mL  0:903 g/mL …density† ˆ 43:3 g ˆ 4:33  104 mg 4:33  104 mg/10 air changes/ hr ˆ 4:33  103 mg/air change 4:33  103 mg/84.9 m3/air change ˆ 51 mg/m3 51 mg/m3  24:45/118:2 ˆ 10:6 ppm Step 2: Is the APF > chemical concentration/REL?  For a half-mask air-purifying respirator the APF ˆ 10. Under animal room conditions, the ambient 2-butoxyethanol concentration is estimated to be 10.6 ppm, and the REL is 5 ppm 2-butoxyethanol.

Chemical Health & Safety, September/October 2002

understood prior to the completion of laboratory studies, it is prudent to 19

ensure that workers exposed to these NTP test compounds are protected against possible exposure at all times. Part of this protection includes requiring workers to wear air-purifying respirators while dosing animals. To provide validation of the selection of air-purifying respirators, examples were given of four different NTP toxicity study exposure chemicals (TCE, cumene, o-cresol, and 2-butoxyethanol) administered to test animals (rats and/or mice), by four different routes (gavage, inhalation, feed and dermal). These worse-case testing examples illustrate that the general use of airpurifying respirators was suitably protective in NTP laboratories.

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The cartridge service life estimates for the half face respirators was then obtained using an on-line software program, (http://www.3m.com/occsafety/), which demonstrated that cartridges may be used for 30 to 999 hr depending upon the chemical and it's known or estimated concentration. While the examples included only four NTP test chemical situations, predictions may also be made by valid comparison by analogy with structurally similar chemicals under similar conditions whose airborne concentrations have been determined by air monitoring. If a comparison technique is used, it is critical that the physical and chemical properties of each che-

mical be evaluated carefully to ensure all conclusions are valid. References

1. Soward, S. M.; Rowley, R. M.; Nicholoson, G. L.; Eastin, W. C. Chem. Health Safe., 2000, 7(4), 9. 2. NIOSH Respirator Decision Logic, May 1987, DHHS publication 87±108. 3. NIOSH Respirator Use Policy for Protection Against Carcinogens, September 1995; http://www.cdc.gov/niosh/ respuse.html 4. OSHA Respirator Protection Standard, 29 CFR 1910.134. 5. 3M Company, Occupational Health and Safety Division, PO Box 33275, St. Paul, MN 55133-3275; http:// www.3m.com/occsafety/

Chemical Health & Safety, September/October 2002