Safety and Health at Work

  • 제12권2호
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  • Pages.174-183
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  • 2021
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  • 2093-7911(pISSN)
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  • 2093-7997(eISSN)
산업안전보건연구원 (Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency)
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Risk Assessment for Toluene Diisocyanate and Respiratory Disease Human Studies

  • PARK, Robert M. (Division of Science Integration, Risk Evaluation Branch, National Institute for Occupational Safety and Health)
  • 투고 : 2020.07.10
  • 심사 : 2020.12.09
  • 발행 : 2021.06.30
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초록

Background: Toluene diisocyanate (TDI) is a highly reactive chemical that causes sensitization and has also been associated with increased lung cancer. A risk assessment was conducted based on occupational epidemiologic estimates for several health outcomes. Methods: Exposure and outcome details were extracted from published studies and a NIOSH Health Hazard Evaluation for new onset asthma, pulmonary function measurements, symptom prevalence, and mortality from lung cancer and respiratory disease. Summary exposure-response estimates were calculated taking into account relative precision and possible survivor selection effects. Attributable incidence of sensitization was estimated as were annual proportional losses of pulmonary function. Excess lifetime risks and benchmark doses were calculated. Results: Respiratory outcomes exhibited strong survivor bias. Asthma/sensitization exposure response decreased with increasing facility-average TDI air concentration as did TDI-associated pulmonary impairment. In a mortality cohort where mean employment duration was less than 1 year, survivor bias pre-empted estimation of lung cancer and respiratory disease exposure response. Conclusion: Controlling for survivor bias and assuming a linear dose-response with facility-average TDI concentrations, excess lifetime risks exceeding one per thousand occurred at about 2 ppt TDI for sensitization and respiratory impairment. Under alternate assumptions regarding stationary and cumulative effects, one per thousand excess risks were estimated at TDI concentrations of 10 - 30 ppt. The unexplained reported excess mortality from lung cancer and other lung diseases, if attributable to TDI or associated emissions, could represent a lifetime risk comparable to that of sensitization.

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과제정보

Robert Streicher, Dhimiter Bello, Kate Applebaum, and anonymous reviewers provided critical review and comments; Robert D. Daniels, Matthew Wheeler, and Randall J. Smith additionally provided critical comments and design of regression models.

참고문헌

  1. Bello D, Herrick CA, Smith TJ, Woskie SR, Streicher RP, Cullen MR, Liu Y, Redlich CA. Skin exposure to isocyanates: reasons for concern. Environ Health Persp 2007;115(3):328-35. https://doi.org/10.1289/ehp.9557
  2. Collins MA. Toxicology of toluene diisocyanate. Appl Occup Environ Hyg 2002;17(12):846-55. https://doi.org/10.1080/10473220290107048
  3. Ott MG, Diller WF, Jolly AT. Respiratory effects of toluene diisocyanate in the workplace: a discussion of exposure-response relationships. Crit Rev Toxicol 2003;33(1):1-59. https://doi.org/10.1080/713611031
  4. Verschoor L, Verschoor AH. Nonoccupational and occupational exposure to isocyanates. Curr Opin Pulm Med 2014;20(2):199-204. https://doi.org/10.1097/MCP.0000000000000029
  5. Brugsch H, Elkins H. Toluene di-isocyanate (TDI) toxicity. N Engl J Med 1963;268(7):353-7. https://doi.org/10.1056/NEJM196302142680705
  6. Diller W. Frequency and trends of occupational asthma due to toluene diisocyanate: a critical review. Appl Occup Environ Hyg 2002;17(12):872-7. https://doi.org/10.1080/10473220290107075
  7. Bakerly ND, Moore VC, Vellore AD, Jaakkola MS, Robertson AS, Burge PS. Fifteen-year trends in occupational asthma: data from the Shield surveillance scheme. Occup Med 2008;58(3):169-74. https://doi.org/10.1093/occmed/kqn007
  8. Sonny, Maher FJ, Sonny-Maher F. Health effects and worker exposure to toluene diisocyanate (TDI). Appl Occup Environ Hyg 2002;17(12):838-9. https://doi.org/10.1080/10473220290107020
  9. Redlich C, Karol M. Diisocyanate asthma: clinical aspects and immunopathogenesis. Int Immunopharm 2002;2(2):213-24. https://doi.org/10.1016/S1567-5769(01)00174-6
  10. Mikoczy Z, Welinder H, Tinnerberg H, Hagmar L. Cancer incidence and mortality of isocyanate exposed workers from the Swedish polyurethane foam industry: updated findings 1959-98. Occup Environ Med 2004;61(5):432-7. https://doi.org/10.1136/oem.2003.009712
  11. Sorahan T, Nichols L. Mortality and cancer morbidity of production workers in the UK flexible polyurethane foam industry: updated findings, 1958-98. Occup Environ Med 2002;59(11):751-8. https://doi.org/10.1136/oem.59.11.751
  12. Pinkerton LE, Yiin JH, Daniesl RD, Fent KW. Mortality among workers exposed to toluene diisocyanate in the US polyurethane foam industry: update and exposure-response analyses. Am J Ind Med 2016;59:630-43. https://doi.org/10.1002/ajim.22622
  13. Le Moual N, Kauffmann F, Eisen EA, Kennedy SM. The healthy worker effect in asthma: work may cause asthma, but asthma may also influence work. Am J Resp Crit Care Med 2008;177(1):4-10. https://doi.org/10.1164/rccm.200703-415PP
  14. Dharmarajan V, Rando ROY. Critical evaluation of continuous monitors for toluene diisocyanate. Am Ind Hyg Assn J 1980;41(12):869-78. https://doi.org/10.1080/15298668091425798
  15. Miller JA, Mueller FX. Evaluation of a continuous instrumental method for determination of isocyanates. Am Ind Hyg Assn J 1975;36(6):477-83. https://doi.org/10.1080/0002889758507274
  16. Momberg H, McCammon C. A comparison of two methods for the determination of Toluene diisocyanate in air. Cincinnati OH: National Institute for Occupational Safety and Health; 1976.
  17. Neilson A, Booth KS. A technique for dynamic calibration of a continuous toluene diisocyanate monitor. Am Ind Hyg Assn J 1975;36(3):169-71. https://doi.org/10.1080/0002889758507231
  18. Rando ROYJ, Rando ROY, Duvoisin P, Abdel Kader H, Hammad Y. A sequential tape monitor for toluene diisocyanate. Am Ind Hyg Assn J 1987;48(6):574-9. https://doi.org/10.1080/15298668791385237
  19. Redlich CA, Wisnewski AV, Gordon T. Mouse models of diisocyanate asthma. Am J Resp Cell Mol Bio 2002;27(4):385-90. https://doi.org/10.1165/rcmb.f249
  20. Long CM, Marshall NB, Lukomska E, Kashon ML, Meade BJ, Shane H, Anderson SE. A role for regulatory T cells in a murine model of epicutaneous toluene diisocyanate sensitization. Toxicol Sci 2016;152(1):85-98. https://doi.org/10.1093/toxsci/kfw074
  21. Nayak AP, Hettick JM, Siegel PD, Anderson SE, Long CM, Green BJ, Beezhold H. Toluene diisocyanate (TDI) disposition and Co-localization of immune cells in hair follicles. Toxicol Sci 2014;140(2):327-37. https://doi.org/10.1093/toxsci/kfu079
  22. Anderson SE, Beezhold K, Lukomska E, Richardson J, Long C, Anderson K, Franko J, Meade BJ, Beezhold DH. Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization. J Immunotox 2014;11(3):250-9. https://doi.org/10.3109/1547691X.2013.835891
  23. Pauluhn J. Development of a respiratory sensitization/elicitation protocol of toluene diisocyanate (TDI) in Brown Norway rats to derive an elicitation-based occupational exposure level. Toxicology 2014;319:10-22. https://doi.org/10.1016/j.tox.2014.02.006
  24. Karol MH. Concentration-dependent immunologic response to toluene diisocyanate (TDI) following inhalation exposure. Toxicol Appl Pharmacol 1983;68(2):229-41. https://doi.org/10.1016/0041-008X(83)90007-8
  25. Karol MH, Hauth BA, Riley EJ, Magreni CM. Dermal contact with toluene diisocyanate (TDI) produces respiratory tract hypersensitivity in Guinea pigs. Toxicol Appl Pharmacol 1981;58(2):221-30. https://doi.org/10.1016/0041-008X(81)90426-9
  26. Koschier FJ, Burden EJ, Brunkhorst CS, Friedman MA. Concentration-dependent elicitation of dermal sensitization in Guinea pigs treated with 2,4-toluene diisocyanate. Toxicol Appl Pharmacol 1983;67(3):401-7. https://doi.org/10.1016/0041-008X(83)90324-1
  27. Selgrade MK, Boykin EH, Haykal-Coates N, Woolhiser MR, Wiescinski C, Andrews DL, Farraj AK, Doerfler DL, Gavett SH. Inconsistencies between cytokine profiles, antibody responses, and respiratory hyperresponsiveness following dermal exposure to isocyanates. Toxicol Sci 2006;94(1):108-17. https://doi.org/10.1093/toxsci/kfl094
  28. Clark RL, Bugler J, McDermott M, Hill ID, Allport DC, Chamberlain JD. An epidemiology study of lung function changes of toluene diisocyanate foam workers in the United Kingdom. Int Arch Occup Environ Health 1998;71(3): 169-79. https://doi.org/10.1007/s004200050267
  29. Wang JD, Huang PH, Lin JM, Su SY, Wu MC. Occupational asthma due to toluene diisocyanate among velcro-like tape manufacturers. Am J Ind Med 1988;14(1):73-8. https://doi.org/10.1002/ajim.4700140109
  30. Gui W, Wisnewski AV, Neamtiu I, Gurzau E, Sparer JA, Stowe MH, Liu J, Slade MD, Rusu OA, Redlich CA. Inception cohort study of workers exposed to toluene diisocyanate at a polyurethane foam factory: initial one-year follow-up. Am J Ind Med 2014;57(11):1207-15. https://doi.org/10.1002/ajim.22385
  31. Adams WG. Long-term effects on the health of men engaged in the manufacture of tolylene di-isocyanate. Br J Ind Med 1975;32(1):72-8.
  32. Aoyama K, Huang J, Ueda A, Matsushita T. Provocation of respiratory allergy in Guinea pigs following inhalation of free toluene diisocyanate. Arch Environ Contam Toxicol 1994;26(3):403-7. https://doi.org/10.1007/BF00203570
  33. Arts JH, de Jong WH, van Triel JJ, Schijf MA, de Klerk A, van Loveren H, Kuper CF. The respiratory local lymph node assay as a tool to study respiratory sensitizers. Tox Sci 2008;106(2):423-34. https://doi.org/10.1093/toxsci/kfn199
  34. De Jong WH, Arts JHE, De Klerk A, Schijf MA, Ezendam J, Kuper CF, Van Loveran H. Contact and respiratory sensitizers can be identified by cytokine profiles following inhalation exposure. Toxicology 2009;261(3): 103-11. https://doi.org/10.1016/j.tox.2009.04.057
  35. Griem P, Goebel C, Scheffler H. Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data. Reg Toxicol Pharmacol 2003;38(3):269-90. https://doi.org/10.1016/j.yrtph.2003.07.001
  36. Hextall JM, Alagaratnam NJ, Glendinning AK, Holloway DB, Blaikie L, Basketter DA, McFadden JP. Dose-time relationships for elicitation of contact allergy to para-phenylenediamine. Contact Dermat 2002;47(2):96-9. https://doi.org/10.1034/j.1600-0536.2002.470207.x
  37. Belin L, Wass U, Audunsson G, Mathiasson L. Amines: possible causative agents in the development of bronchial hyperreactivity in workers manufacturing polyurethanes from isocyanates. Br J Ind Med 1983;40(3): 251-7.
  38. Bruckner HC, Avery SB, Stetson DM, Dodson VN, Ronayne JJ. Clinical and immunologic appraisal of workers exposed to diisocyanates. Arch Environ Health 1968;16(5):619-25. https://doi.org/10.1080/00039896.1968.10665117
  39. Huang J, Wang X, Chen B, Ueda A, Aoyama K, Matsushita T. Immunological effects of toluene diisocyanate exposure on painters. Arch Environ Con Tox 1991;21(4):607-11. https://doi.org/10.1007/bf01183884
  40. Jones RN, Rando RJ, Glindmeyer HW, Foster TA, Hughes JM, O'Neil CE, Weill H. Abnormal lung function in polyurethane foam producers. Weak relationship to toluene diisocyanate exposures. Am Rev Resp Dis 1992;146(4):871-7. https://doi.org/10.1164/ajrccm/146.4.871
  41. Kim H, Kim YD, Choi J. Seroimmunological characteristics of Korean workers exposed to toluene diisocyanate. Environ Res 1997;75(1):1-6. https://doi.org/10.1006/enrs.1997.3763
  42. Omae K. Two-year observation of pulmonary function in workers exposed to low concentrations of toluene diisocyanate. Int Arch Occup Environ Health 1984;55(1):1-12. https://doi.org/10.1007/BF00378062
  43. Ott MG, Klees JE, Poche SL. Respiratory health surveillance in a toluene diisocyanate production unit, 1967-97: clinical observations and lung function analyses. Occup Environ Med 2000;57(1):43-52. https://doi.org/10.1136/oem.57.1.43
  44. Porter C, Higgins R, Scheel L. A retrospective study of clinical, physiologic and immunologic changes in workers exposed to toluene diisocyanate. Am Ind Hyg Assn J 1975;36(3):159-68. https://doi.org/10.1080/0002889758507230
  45. Venables KM, Dally MB, Burge PS, Pickering CA, Newman Taylor AJ. Occupational asthma in a steel coating plant. Br J Ind Med 1985;42(8):517-24.
  46. White WG. Isocyanate-induced asthma in a car factory. The Lancet 1980;315(8171):756-60. https://doi.org/10.1016/S0140-6736(80)91247-7
  47. Williamson KS. Studies of diisocyanate workers. Occup Med 1964;14(1):81-8. https://doi.org/10.1093/occmed/14.1.81
  48. Bugler J, Clark RL, Hill ID, McDermott M. The acute and long-term respiratory effects of aromatic di-isocyanates. A five year longitudinal study of polyurethane foam workers. International Isocyanate Institute; 1991. Report No. 10848.
  49. Daftarian HS, Roegner KC, Reh CM. Health hazard evaluation report 98-0011-2801, Woodbridge Corporation, Brodhead, Wisconsin. Cincinnati, OH: National Institute for Occupational Safety and Health; July 2000. HETA Report # 98-0011-2801; 2000. Report No.: HETA Report # 98-0011-2801.
  50. Weill H, Butcher B, Dharmarajan V, Glindmeyer H, Jones R, Carr J, Salvaggio J. Respiratory and immunologic evalatuion of isocyanate expsoure in a new manufacturing plant. Morgantown, WV: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health; 1981. NIOSH Contract No. 210-75-0006.
  51. Bodner KM, Burns CJ, Randolph NM, Salazar EJ. A longitudinal study of respiratory health of toluene diisocyanate production workers. J Occup Environ Med 2001;43(10):890-7. https://doi.org/10.1097/00043764-200110000-00008
  52. Franzinelli A. Patologia respiratoria da isocianati in un'industria di frigoriferi. Medicina del lavoro 1978;69(2):163-71.
  53. Applebaum K, Malloy E, Eisen E. Left truncation, susceptibility, and bias in occupational cohort studies. Epidemiology 2011;22(4):599-606. https://doi.org/10.1097/EDE.0b013e31821d0879
  54. SAS Institute I. SAS Software version 9.3; 2011. Cary, NC.
  55. National Research Council. Health risks from exposure to low levels of ionizing radiation; BEIR VII phase 2. Washington DC: The National Academies Press. 2006. p. 277-8.. www.nap.edu.
  56. Alexandersson R, Hedenstierna G, Randma E, Rosen G, Swenson A, Tornling G. Symptoms and lung function in low-exposure to TDI by polyurethane foam manufacturing. Int Arch Occup Environ Health 1985;55(2):149-57. https://doi.org/10.1007/BF00378377
  57. Clark RL, Bugler J, Paddle GM, Chamberlain JD, Allport DC. A 17-year epidemiological study on changes in lung function in toluene diisocyanate foam workers. Int Arch Occup Environ Health 2003;76(4):295-301. https://doi.org/10.1007/s00420-002-0403-8
  58. Holness DL, Broder I, Corey PN, Booth N, Mozzon D, Nazar MA, Guirguis S. Respiratory variables and exposure-effect relationships in isocyanate-exposed workers. J Occup Med 1984;26(6):449-55. https://doi.org/10.1097/00043764-198406000-00018
  59. Jang AS, Choi IS, Koh YI, Moon JD, Lee KJ. Increase in airway hyper-responsiveness among workers exposed to methylene diphenyldiisocyanate compared to workers exposed to toluene diisocyanate at a petrochemical plant in Korea. Am J Ind Med 2000;37(6):663-7. https://doi.org/10.1002/(SICI)1097-0274(200006)37:6<663::AID-AJIM11>3.0.CO;2-H
  60. Omae K, Higashi T, Nakadate T, Tsugane S, Nakaza M, Sakurai H. Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. II. Four-year changes in the effects on the respiratory system. Int Arch Occup Environ Health 1992;63(8):565-9. https://doi.org/10.1007/BF00386347
  61. Wegman DH, Musk AW, Main DM, Pagnotto LD. Accelerated loss of FEV- in polyurethane production workers: a four-year prospective study. Am J Ind Med 1982;3(2):209-15. https://doi.org/10.1002/ajim.4700030212
  62. Diem JE, Jones RN, Hendrick DJ, Glindmeyer HW, Dharmarajan V, Butcher BT, Salvaggio JE, Weill H. Five-year longitudinal study of workers employed in a new toluene diisocyanate manufacturing plant. Am Rev Resp Dis 1982;126(3): 420-8.
  63. Musk AW, Peters JM, Berstein L. Absence of respiratory effects in subjects exposed to low concentrations of TDI and MDI: a reevaluation. J Occup Med 1985;27(12):917-20.
  64. Musk AW, Peters JM, DiBerardinis L, Murphy RL. Absence of respiratory effects in subjects exposed to low concentrations of TDI and MDI. J Occup Med 1982;24(10):746-50.
  65. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Resp Crit Care Med 1999;159(1): 179-87. https://doi.org/10.1164/ajrccm.159.1.9712108
  66. Park RM, Gilbert SJ. Pulmonary impairment and risk assessment in a diacetylexposed population - microwave popcorn workers. J Occup Environ Med 2018;60:496-506. https://doi.org/10.1097/JOM.0000000000001303
  67. Bang KM, Gergen PJ, Kramer R, Cohen B. THe effect of pulmonary impairment on all-cause mortality in a national cohort. Chest 1993;103(2):536-40. https://doi.org/10.1378/chest.103.2.536
  68. Hole DJ, Watt GC, Davey-Smith G, Hart CL, Gillis CR, Hawthorne VM. Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. Br Med J 1996;313(7059): 711-5 discussion 5-6. https://doi.org/10.1136/bmj.313.7059.711
  69. Ryan G, Knuiman MW, Divitini ML, James A, Musk AW, Bartholomew HC. Decline in lung function and mortality: the busselton health study. J Epid Community Health 1999;53(4):230-4. https://doi.org/10.1136/jech.53.4.230
  70. Schunemann H, Dorn J, Grant BJB, Winkelstein W, Trevisan M. Pulmonary function is a long-term predictor of mortality in the general population. Chest 2000;118(3):656-64. https://doi.org/10.1378/chest.118.3.656
  71. Sin D, Wu L, Man SFP. The relationship between reduced lung function and cardiovascular mortality. Chest 2005;127(6):1952-9. https://doi.org/10.1378/chest.127.6.1952
  72. Park RM, Maizlish NA, Punnett L, Moure-Eraso R, Silverstein MA. A comparison of PMRs and SMRs as estimators of occupational mortality. Epidemiology 1991;2(1):49-59. https://doi.org/10.1097/00001648-199101000-00008
  73. Schubauer-Berigan MK, Raudabaugh WR, Ruder AM, Hein MJ, Silver SR, Chen B, Laber P, Spaeth S, Steenland K. LTAS.NET: a NIOSH Life Table Analysis System for the windows environment. Ann Epidemiol 2005;15(8):656.
  74. Lee HS, Phoon WH. Diurnal variation in peak expiratory flow rate among workers exposed to toluene diisocyanate in the polyurethane foam manufacturing industry. Br J Ind Med 1992;49(6):423-7.
  75. Littorin M, Amon A, Broberg K, Sennbro CJ, Tinnerberg H. Eye and airway symptoms in low occupational exposure to toluene diisocyanate. Scand J Work Env Health 2007;33(4):280-5. https://doi.org/10.5271/sjweh.1144
  76. Peters JM, Murphy RL, Pagnotto LD, Van Ganse WF. Acute respiratory effects in workers exposed to low levels of toluene diisocyanate (TDI). Arch Environ Health 1968;16(5):642-7. https://doi.org/10.1080/00039896.1968.10665121
  77. Soderlund N, Rees D, Wasserfall C, Roodt L. A survey of a small-group of workers exposed to toluene diisocyanate. S Afr Med J 1993;83(2):100-3.
  78. Gamble J, Kellie S, Petersen M, Hodgson M. Health hazard evaluation report, Ford Motor company. Utica, MI. Cincinnati, OH: National Institute of Occupational Safety and Health; 1986. HETA Report # 82-181-1720.
  79. Collins JJ, Anteau S, Conner PR, Cassidy LD, Doney B, Wang ML, Kurth L, Carson M, Molenaar D, Redlich CA, Storey E. Incidence of occupational asthma and exposure to toluene diisocyanate in the United States toluene diisocyanate production industry. J Occup Environ Med 2017;59:S22-7. https://doi.org/10.1097/JOM.0000000000000890
  80. Middendorf P, Miller W, Feeley T, Doney B. Toluene diisocyanate exposure. J Occup Environ Med 2017;59:S1-12. https://doi.org/10.1097/JOM.0000000000001117
  81. Cassidy LD, Doney B, Wang ML, Kurth L, Conner PR, Collins JJ, Carson M, Molenaar D, Redlich CA, Storey E. Medical monitoring for occupational asthma among toluene diisocyanate production workers in the United States. J Occup Environ Med 2017;59:S13-21. https://doi.org/10.1097/JOM.0000000000001197
  82. Daniels RD. Occupational asthma risk from exposures to toluene diisocyanate: a review and risk assessment. Am J Ind Med 2018;61(4):282-92. https://doi.org/10.1002/ajim.22815
  83. Austin S. Biological monitoring of TDI-derived amines in polyurethane foam production. Occup Med 2007;57(6):444-8. https://doi.org/10.1093/occmed/kqm085
  84. Ban M, Morel G, Langonne I, Huguet N, Pepin E, Binet S. TDI can induce respiratory allergy with Th2-dominated response in mice. Toxicology 2006;218(1):39-47. https://doi.org/10.1016/j.tox.2005.09.013
  85. Pollaris L, Van Den Brouckc S, Decaesteker T, Cremer J, Seys S, Devos FC, Provoost S, Maes T, Verbeken E, Velde GV, Nemery B, Hoet PHM, Vanoirbeek JAJ. Dermal exposure determines the outcome of repeated airway exposure in a long-term chemical-induced asthma-like mouse model. Toxicology 2019;421:84-92. https://doi.org/10.1016/j.tox.2019.05.001
  86. ECHA. ECHA Scientific report for evaluation of limit values for diisocyanates at the workplace; October 17, 2019.. https://echa.europa.eu/documents/10162/db15bfdf-eec8-c10a-67c4-f65166c5110a.
  87. Lau A, Tarlo SM. Update on the management of occupational asthma and work-exacerbated asthma. Allergy Asthma Immunol Res 2019;11(2):188-200. https://doi.org/10.4168/aair.2019.11.2.188