Monitoring for occupational exposure to 4,4'-methylenebis(2-chloroaniline) by gas chromatographic-mass spectrometric analysis of haemoglobin adducts, blood, plasma and urine.
The feasibility of using plasma, blood and haemoglobin adducts for monitoring occupational exposure to the suspected human carcinogen 4,4'-methylenebis(2-chloroaniline) (MOCA) was investigated. A method utilising capillary gas chromatography-negative-ion chemical-ionisation mass spectrometry (GC-MS) for the determination of pentafluoropropionyl (PFP) derivatives of MOCA, released by alkaline hydrolysis from protein adducts and conjugates, was both sensitive and selective. When selected ion monitoring was used, sub-femtomole amounts of PFP-MOCA could be measured. The detection limit for haemoglobin adducts of MOCA was below 10 fmol/g Hb, well below the levels found for occupationally exposed individuals. Capillary GC with electron-capture detection also had the required sensitivity for the determination of MOCA in blood samples, however, the presence of interfering compounds in some samples limited its use. The levels of MOCA in the blood and urine of five individuals who were exposed to MOCA during the manufacture of polyurethane elastomers were determined by the GC-MS method. The MOCA concentrations for the various blood fractions and urine were within the following ranges: haemoglobin adducts, 0.73-43.3 pmol MOCA/g Hb; plasma alkaline hydrolysate, 0.05-22.0 nmol/l; whole blood, 0.13-17.4 nmol/l; urine, 4.5-2390 nmol/l. Because the products of MOCA in the blood reflect metabolic activation of MOCA and integrate exposure over a period of weeks, the use of blood samples for monitoring exposure to MOCA offers advantages over the currently used urinary MOCA measurements.
Vaughan
G T
GT
Centre for Advanced Analytical Chemistry, CSIRO Division of Coal and Energy Technology, Bangor, NSW, Australia.
Kenyon
R S
RS
D004784:Environmental Monitoring; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008753:Methylenebis(chloroaniline) / Q000032:analysis*; D016273:Occupational Exposure; D010949:Plasma / Q000737:chemistry; D012680:Sensitivity and Specificity
D006454:Hemoglobins; D008753:Methylenebis(chloroaniline)