Summary
There have been very few published studies that have evaluated exposure to myelotoxic drugs among production workers in pharmaceutical plants. Previous studies have focussed mainly on nurses and evaluated exposure to cytotoxic drugs using urine mutagenicity as a marker of exposure. The aim of this study was to evaluate the exposure of workers involved in the production of chloramphenicol and azathioprine. Exposure was evaluated utilising biological monitoring, biological effect monitoring and environmental monitoring. Biological monitoring included plasma chloramphenicol levels, plasma 6-mercaptopurine and urine 6-thiouric acid levels. These were analysed using high performance liquid chromatography. Myelotoxic effect was assessed by measuring the haematological indices of bone. marrow function. The exposed 17 workers were compared to matched controls of equal numbers. Neither substance could be detected in serum nor urine by the analytical methods employed. However, haematological indices demonstrated a significantly decreased mean reticulocyte and neutrophil count in the azathioprine exposed group. Industrial hygiene measurements demonstrated contamination of the air inside the airhood of exposed workers. In conclusion, it is evident that workers involved in the production of both these drugs are at risk of developing adverse health effects. Furthermore, more sensitive analytical methods need to be developed to evaluate absorption of myelotoxic chemicals among occupationally exposed workers.
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References
Agius R. Occupational exposure limits for therapeutic substances. Ann Occup Hyg 1989;33:555–562
Aksoy M, Erdem S, Dincol G, Bakioglu I, Kutlar A. Aplastic anaemia due to chemicals and drugs. Sex Transm Dis Oct–Dec 1984:347–350
Farina GF, Alessio L, Fomi A. Haematological changes in 2 workers occupationally exposed to chloramphenicol. Med Lav 1972;63:1/2:52–56
Yunus AA. Chloramphenicol induced bone marrow suppression. Semin Hematol 1973;10:225–234
Oski FA. Haematological consequences of chloramphenicol therapy. J Pediatr 1979;94:515–516
Martindale. The Extra Pharmacopoeia 29th ed. 1989, pp 186–192
Wood AJJ, Oates JA. Adverse reactions to drugs. Harrison's Principles of Internal Medicine 12th ed. 1991;1:376
Martìndale. The Extra Pharmacopoeia 29th ed. 1989, pp 635–636
Thiringer G, Granung G, Holmen A, Hogstedt B, Jarvholm B, Jonsson D, Persson L, Wahlstrom J, Westin J. Comparison of methods for the biomonitoring of nurses handling antitumor drugs. Scand J Work Environ Health 1991;17:133–8
Anastas MY. Health Hazard Controls in the Pharmaceutical Tablet Making Process. Industrial Hygiene News Report 1984;27:5
Lennard L, Keen D, Lilleyman JS. Oral 6-MP in childhood leukaemia: Parent drug pharmacokinetics and active metabolite concentrations. Clin Pharmacol Ther 1986;40:287–292
Bruunshuus I, Schmiegelow K. Analysis of 6-MP, 6-TGN, and 6-TU in biological fluids by high performance liquid chromatography. Scan J Clin Lab Invest 1989;49:779–784
Lennard L. Assay of 6-MP in human plasma. J Chromatogr 1985;345:441–6
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Jeebhay, M., Mbuli, S. & Uebel, R. Assessment of exposure to chloramphenicol and azathioprine among workers in a South African pharmaceutical plant. Int. Arch Occup Environ Heath 65 (Suppl 1), S119–S122 (1993). https://doi.org/10.1007/BF00381321
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DOI: https://doi.org/10.1007/BF00381321