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6. Summary Report, Conclusions and Recommendations

Author

Notten, Wilfried R. F., Hunter, William J., Herber, Rob F. M., Monster, Aart C., Zielhuis, Reinier L., Notten, Wilfried R. F., editor, Hunter, William J., editor, Herber, Rob F. M., editor, Monster, Aart C., editor, and Zielhuis, Reinier L., editor

Published
1988
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10. Estimation of the VA/(Q+VTIS) Distribution from Single-Breath Alkane Uptake

Author

van den Aardweg, Joost G., Kezic, Sanja, Bosch, Job A., and Monster, Aart C.

Subjects
Emphysema, Pulmonary -- Research, Biomedical engineering -- Models, Biological sciences, Business, Computers, Health care industry
Abstract

In this paper, it was investigated if the ventilation-perfusion distribution can be estimated from the uptake (U) of inert gases with different solubilities during the single-breath maneuver. A model was implemented that describes U as a function of solubility for inhomogeneously distributed alveolar volume (VA) versus blood and tissue volume (Q + VTIS). The VA / (Q + VTIS) distribution describes the relative contribution of gas-exchange units with different VA/(Q + VTIS) ratios to the expiratory volume. U was derived as the sum of uptakes corresponding to different modes in the distribution, weighted with the relative contribution to the expiratory volume. This permits an estimation of the distribution parameters by fitting U as a function of solubility. The n alkanes were used because of their different solubilities. Analysis of the sensitivity of the estimated VA / (Q + VTIS) distribution parameters to measurement errors showed that mostly two modes can be discerned. The influence of fixed model parameters appeared relatively small. The model could well explain U in normal and emphysematous subjects, with a larger contribution of high VA/(Q + VTIS) ratios in the emphysematous subjects. It was concluded that the VA/(Q + VTIS) distribution can be estimated noninvasively from single-breath alkane uptake. Index Terms--Alkanes, emphysema, pulmonary gas exchange, respiratory dead space, ventilation-perfusion distribution.

Published
2001

12. Percutaneous Absorption of Neat and Water Solutions of 2-Butoxyethanol in Man

Author

Kezic, Sanja, Mohammadi, Nadira, Jakasa, Ivone, Kruse, Jacob, Monster, Aart C, and Verberk, Maarten M

Subjects
integumentary system, Percutaneous Absorption, butoxyethanol, biological monitoring
Abstract

Aims To determine percutaneous absorption of 2-butoxyethanol (BE) dermally applied as a neat liquid and in 50 and 90 % solutions. Methods Six male volunteers were dermally exposed for 4 hr on the volar forearm over an area of 40 cm &sup2 ; . An inhalation exposure with a known input rate served as a reference. Dermal absorption was assessed for each individual from the concentration courses of BE in blood and butoxyacetic acid in urine, measured after both inhalation and dermal exposure. The Medical Ethics Committee of the Academic Medical Centre, University of Amsterdam approved the experimental protocol. Each subject signed an informed consent form. Results The amount of BE that was absorbed after skin exposure to 50 and 90 % BE was one order of magnitude higher than that of neat BE. The average absorption rate of 50 % BE amounted to 0.8 mg/cm &sup2 ; /hr. Inter-individual differences in dermal absorption rates of 50 % BE were moderate, the coefficient of variation (CV) amounted to 30 %. This was significantly lower than the variation previously reported for neat BE (Johanson et al 1988). Conclusions Dermal uptake of BE increases in the presence of water. This has already been reported in vivo in guinea pigs (Johanson et al 1988) and in vitro studies with human skin, however this is the first time that it has been shown also in humans in vivo. These findings should therefore be considered in the health risk assessment of occupational dermal exposure to BE where water-based products containing glycol ethers are used. Comparing the dermal uptake with the respiratory uptake at the occupational exposure limit (OEL, currently 100 mg/m &sup3 ; ), BE showed substantial skin absorption. Assuming 60 min skin contact of both hands (skin area of about 1000 cm &sup2 ; ) with 50 % BE, dermal uptake would equal the pulmonary uptake of the 8-hr occupational exposure. Therefore, in monitoring exposure at the work place, biological monitoring (BM) is to be preferred over environmental monitoring. For the purpose of BM, both BE in blood or BAA in urine can be used.

Published
2002

14. Gas chromatography-electron capture determination of styrene-7, 8-oxide enantiomers

Author

Kežić, Sanja, Jakaša Ivone, Wenker Mira, Boogaard, Peter J., Monster, Aart C., and de Wolff, Freik A.

Subjects
Styrene, Phenyloxirane, Enantiomer separation
Abstract

The enantiomers of styrene-7, 8-oxide (phenyloxirane, SO) were determined using a method based on base catalysed hydrolysis with sodium methoxide. The oxirane ring opening resulted in formation, without racemisation, of the enantiomeric pairs of the two regional isomers, 2-methoxy-1-phenylethanol and 2-methoxy-2-phenylethanol. The structure of these regional isomers was confirmed by gas chromatography– mass spectrometry (GC– MS) and proton nuclear magnetic resonance (1H-NMR). To improve sensitivity of determination, the formed methoxy alcohols were subsequently derivatised with pentafluoropropionic anhydride enabling electron capture detection. This derivatization proceeded also without racemisation and the formed pentafluoropropionyl derivatives were separated on two serially coupled columns, a non-chiral AT 1705 and a chiral CP Chirasil-Dex-CB. As internal standard 2S, 3S-(− )-2-methyl-3-phenyloxirane was used. The limit of quantitation of the method was 0.2 μ M. The repeatability of the method was assessed at two concentration levels (2.5 and 25 μ M) and ranged from 6 to 9% for both enantiomers. The method was applied to the determination of the rate and enantioselectivity of the cytochrome P-450 dependent oxidation of styrene to SO enantiomers in human liver microsomes.

Published
2000

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