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The main objective was to develop a wipe sampling test to measure surface contamination of the most frequently used antineoplastic drugs (ADs) in Swedish healthcare and furthermore to develop an analysis method sensitive enough to assess low levels of contamination. Two wipe sampling tests with separate sample processing methods assessing i) cyclophosphamide (CP), ifosfamide (IF), 5-fluorouracil (5-FU), etoposide (ETO), gemcitabine (GEM) and cytarabine (CYT) (Wipe Test 1), and ii) GEM, CYT and methotrexate (MTX) (Wipe Test 2), respectively were developed by optimization of absorption and extraction efficiencies using different wipe tissue materials, tissue wetting solution and extraction solvents. A fast LC-MS/MS method was developed for simultaneous detection of the studied ADs. The limit of quantification for the method was between 0.04 to 2.4 ng/wipe sample (0.10 to 6.1 pg/cm2 for an area of 400 cm2) and at 50 ng/sample the within-day precision was between 1.3-15%, and the accuracy between 102-127%. Wipe Test 1 was applied in an assessment of cleaning efficiency of five different cleaning solutions (formic acid, water, sodium hydroxide, ethanol and sodium dodecyl sulfate (SDS) for removal of ADs from surfaces made of stainless steel or plastic. For CP, IF, 5-FU, GEM and CYT 92% of the AD were removed regardless of surface and cleaning solution. In conclusion, a user-friendly assessment method to measure low levels of seven ADs in the work environment was developed and validated. Assessment of the decontamination efficiency of cleaning solutions concerning removal of ADs from stainless steel showed that efficiencies differed depending on the AD with water being the least effective cleaning agent. The results suggests that a combination of different cleaning agents including detergent and a solution with an organic component would be optimal to efficiently remove the measured ADs from surfaces in the workplace.

Hexahydrophthalic anhydride (HHPA), an industrially important chemical, is a highly allergenic compound. The aim of this work was to identify proteins in nasal lavage fluid (NLF) that form adducts with HHPA. Such bindings may induce production of specific immunoglobulin E (IgE) or affect physiological mechanisms of the proteins. NLF was obtained from HHPA-exposed volunteers, workers and exposed guinea pigs. HHPA-binding proteins were visualized with immunoblotting using a polyclonal antiserum against HHPA. The proteins were excised from sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels, digested with trypsin and identified by tandem mass spectrometry (MS/MS) and database searches. The antiserum was found to be specific for HHPA-bound proteins. In vivo formed HHPA-binding proteins in humans were identified as antileukoproteinase, immunoglobulin G (IgG), immunoglobulin A (IgA), serum albumin and lactoferrin. In addition, several proteins binding to HHPA were found in NLFs from guinea pigs but these could not be identified from database searches. Hypotheses for development of airways diseases by adduction of this allergenic compound to the NLF proteins in humans were established.

Relationships between chemical structure and immunogenicity have been studied in 13 dicarboxylic acid anhydrides. Guinea-pigs were immunized intradermally by a single dose of 0.3 M solutions of succinic anhydride (SA), maleic anhydride (MA), methylmaleic anhydride (MMA), cis-cyclohexane-1,2-dicarboxylic anhydride (cis-HHPA), trans-cyclohexane-1, 2-dicarboxylic anhydride (trans-HHPA), 4-methylcyclohexane-1,2-dicarboxylic anhydride (MHHPA), cis-1,2,3,6-tetrahydrophthalic anhydride (THPA1236), cis-3,4,5,6-tetrahydrophthalic anhydride (THPA3456), cis-3-methylcyclohex-4-ene-1, 2-dicarboxylic anhydride (MTHPA34), cis-4-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA44), phthalic anhydride (PA), 4-methylphthalic anhydride (MPA), and trimellitic anhydride (TMA) in olive oil. Specific IgE, IgG, IgG1, and IgG2 antibodies against guinea-pig serum albumin conjugates of the anhydrides were determined by passive cutaneous anaphylaxis (PCA) tests and enzyme-linked immunoabsorbant assay (ELISA). Specific IgG was significantly increased in all animals, except those immunized with THPA3456 and SA, which sensitized only 3 9 and 7 9 animals, respectively. Furthermore, the specific IgG values were very low in the SA group. The titers of specific IgG, and IgG2 were increased in the IgG-positive animals. Specific IgE was positive in all animals immunized with MA, MHHPA, MTHPA (both isomers), and MPA, and in 6 9 and 5 9 guinea pigs immunized with TMA and MMA, respectively. The IgE titers were generally very low; PCA was negative after dilutions to 1:32, or less. The results indicate a considerable variation in the sensitizing potential between different organic acid anhydrides. The most marked general effect of the chemical structure on immunogenicity was the enhancement of antibody formation when a hydrogen atom in the anhydride was substituted with a methyl group.