ANALYST FULL PAPER THE www.rsc.org/analyst Exposure to 4,4A-methylenediphenyl diisocyanate (MDI) during moulding of rigid polyurethane foam: determination of airborne MDI and urinary 4,4A-methylenedianiline (MDA) Katja Kääriä,† a Ari Hirvonen, a Hannu Norppa, a Päivi Piirilä, b Harri Vainio‡ a and Christina Rosenberg* a a Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, Finland. E-mail: Christina.Rosenberg@occuphealth.fi b Department of Occupational Medicine, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, Finland Received 28th November 2000, Accepted 9th February 2001 First published as an Advance Article on the web 5th March 2001 Occupational exposure to 4,4A-methylenediphenyl diisocyanate (MDI) was measured during moulding of rigid polyurethane foam. The aim of the study was to find out whether an MDI-derived urinary amine metabolite could be detected in the urine of workers exposed to apparently low levels of MDI. Airborne MDI was sampled on 1-(2-methoxyphenyl)-piperazine (2MP)-impregnated glass fibre filters and determined by high-performance liquid chromatography (HPLC) using ultraviolet (UV) and electrochemical (EC) detection. The limit of detection of MDI was 3 ng ml 21 for a 20 ml injection. The precision of sample preparation, expressed as relative standard deviation (RSD), was 1.3% with UV detection and 2.1% with EC detection at a concentration of 70 ng MDI ml 21 (n = 6). The 2MP-MDI derivative was stable at + 4 °C up to eight weeks. The accuracy of the method was validated in an international quality control programme. Workers (n = 57) from three different factories participated in the study. Urinary 4,4A-methylenedianiline (MDA) metabolite was determined after acid hydrolysis as heptafluorobutyric anhydride derivatives by gas chromatography-mass spectrometry using chemical ionisation and monitoring negative ions. The limit of detection in urine was 0.2 nmol l 21 . The precision of six analyses for a urine sample spiked to a concentration of 1nmol l 21 was 29% (RSD). The MDI concentrations were below the limit of detection in most (64%) of the air samples collected in the worker’s breathing zone. Still, detectable amounts of MDA were found in 97% of the urine samples. Monitoring of urinary MDA appears to be an appropriate method of assessing MDI exposure in work environments with low or undetectable MDI concentrations in the workplace air. Introduction Isocyanates are highly reactive chemicals used principally in the production of polyurethanes for rigid and flexible foams, elastomers, paints, lacquers and glues. The aromatic 4,4A- methylenediphenyl diisocyanate (MDI; C 15 H 10 N 2 O 2 ; M r 250.3) is largely used in the production of rigid foam for insulation materials. 1 Isocyanates are toxic and mucosal irritants, and their inhalation may adversely affect the respiratory tract. Diisocya- nates are today the most common chemical causes of occupa- tional asthma. 2–6 Analytical methods for determining iso- cyanates in workplace air include derivatisation of the NCO group, with subsequent chromatographic separation. Most techniques employ high-performance liquid chromatography (HPLC) combined with ultraviolet (UV), fluorescence (FL), electrochemical (EC) or mass spectrometric (MS) detection. Air is usually sampled either by bubbling it through an absorbent solution or by filtering it through solid sorbent media or reagent impregnated glass fibre filters. 7–11 In mammals exposed to isocyanates, the absorbed compounds undergo hydrolysis to corresponding amines which are then typically acetylated before urinary excretion. 12 Hydrolysed urine from rats exposed to MDI has been found to contain 4,4A-methylenedianiline (MDA; C 13 H 14 N 2 M r 198.3). 13,14 Isocyanate-derived amines have also been detected in the hydrolysed urine of workers occupationally exposed to the parent isocyanate. 15–20 This study assessed worker exposure to MDI during moulding of rigid polyurethane foam for insulation of re- frigerators and freezers. The results on airborne MDI and urinary MDA concentrations will form the basis of an occupational exposure profile to be used in studies of cytoge- netic effects and genetic susceptibility for developing bronchial asthma. Experimental Chemicals Acetonitrile (HPLC grade) and ethyl acetate (SupraSolv) were purchased from Merck (Darmstadt, Germany), dichlorome- thane from Rathburn (Walkerburn, Scotland, UK) and toluene from J. T. Baker (Deventer, Netherlands). Acetic acid, acetic acid anhydride, sodium sulfate, methanol, sulfuric acid, sodium hydroxide, sodium chloride, sodium acetate, potassium dihy- drogen phosphate, all p.a. grade, were from Merck. MDI was from Aldrich (Milwaukee, WI, USA) and MDA from Sigma (St. Louis, MO, USA). Heptafluorobutyric anhydride (HFBA) and 1-(2-methoxyphenyl)-piperazine (2MP) were from Fluka † Current address: Orion Corporation, Orion Pharma, P.O. Box 65, FIN- 02101 Espoo, Finland. ‡ Current address: Unit of Chemoprevention, International Agency for Research on Cancer, 150 cours Albert Thomas, F-69372 Lyon Cedex 08, France. This journal is © The Royal Society of Chemistry 2001 476 Analyst, 2001, 126, 476–479 DOI: 10.1039/b009549o