Application of imaging MALDI-MS to the determination of hazardous compounds in skin.

PRIDEAUX, Brendan. (2007). Application of imaging MALDI-MS to the determination of hazardous compounds in skin. Doctoral, Sheffield Hallam University (United Kingdom)..

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Abstract

The overall aim of this work described in this thesis was to apply MALDI-MS and imaging MALDI-MS (MALDI-MSI) to the analysis of compounds of interest in occupational hygiene monitoring.Isocyanates are highly reactive compounds with a wide variety of industrial uses. MALDI-MS and MS/MS were used to investigate diisocyanate stability and reactivity. A monoisocyanate intermediate product was observed from the hydrolysis of both an aromatic and also an aliphatic diisocyanate. The stability of this product was assessed over a 14 day experimental period. Ethanol was used to derivatise hexamethylene diisocyanate (HDI) and the resulting urethane was observed to be stable over 14 days. This derivatisation method was incorporated into a surface swab technique for sampling of HDI from work surfaces.Industrial diisocyanates have been reported to penetrate through skin and to be excreted as diamine metabolites in urine. A LC-MS method for the determination of free toluene diamine (TDA) monomer formed by biotransformation of toluene diisocyanate (TDI) when applied to HaCaT cells was developed. In the two experiments performed, TDA was only observed at low levels after spiking with high concentrations of TDI. This appeared to be due to most of the isocyanate becoming conjugated to proteins within the cell and thus not being extracted during the extraction procedure.A novel ethanol-saturated cellulose membrane blotting technique was developed for the extraction and ethanol-derivatisation of HDI from the surface of skin. However, not all of the HDI present on the membrane reacted with the ethanol. Increasing the amount of ethanol on the membrane did increase the amount of derivatised HDI monomer observed although this occurred at the expense of spatial information. The technique was also applied for analysis of the insecticide chlorpyrifos, for both skin surface sampling and permeation studies. From the images obtained, chlorpyrifos was observed to readily penetrate through the stratum corneum and reach a depth of 1.7mm. The highest amount was located in the dermis after the 1 hour exposure time.The dermal absorption of HDI was monitored after 1 hour exposure by mapping HDI monoamine penetration through the skin via indirect blotting and novel direct skin analysis methods. Similar profiles were observed from both methods. Penetration depths of 2.3 and 2.6 mm were observed for the direct skin and indirect blotting methods respectively. The highest level of HDI monoamine was located in the dermis.

Item Type: Thesis (Doctoral)
Additional Information: Thesis (Ph.D.)--Sheffield Hallam University (United Kingdom), 2007.
Research Institute, Centre or Group: Sheffield Hallam Doctoral Theses
Depositing User: EPrints Services
Date Deposited: 10 Apr 2018 17:21
Last Modified: 30 May 2018 13:19
URI: http://shura.shu.ac.uk/id/eprint/20249

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