Physiologically Based Pharmacokinetics and the Dermal Absorption of 2-Butoxyethanol Vapor by Humans

Corley, Richard A.; Markham, Dan A.; Banks, Colin; Delorme, Pierre; Masterman, A. T.; Houle, Jean-Marie

doi:10.1006/faat.1997.2363

Cited by 70 publications

(21 citation statements)

References 22 publications

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“…In most of the studies, only the free urinary fraction of BAA was measured. However, recent studies by Corley et al [3], Rettenmeier et al [14] and Sakai et al [15] have shown that a substantial amount of BAA is excreted in human urine as a glutamate conjugate (on average 48, 71 and 66%, respectively), and that the conjugated BAA fraction is highly variable. This was the reason why, in the present study, we measured the excretion of the total (i.e.…”

Section: Discussionmentioning

confidence: 96%

“…Values are means ± SD. ND not determined: blood concentrations were below limit of quantitation a Each subject was exposed twice to 50% BE a Each subject was exposed twice to 50% BE [3]. This half-life implies that the excretion of BAA was almost completed by 24 h. The 24-h cumulative amount of BAA excreted in urine measured after inhalation accounted for 57% of the respiratory uptake of BE (range 42 to 70%).…”

Section: Discussionmentioning

confidence: 99%

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Percutaneous absorption of neat and aqueous solutions of 2-butoxyethanol in volunteers

Jakaša

Mohammadi

Krüse

et al. 2004

International Archives of Occupational and Environmental Health

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The percutaneous absorption of BE from aqueous solution increased markedly when compared with neat BE. Even water content as low as 10% led to an approximate fourfold increase in the permeation rates. These findings are important for the health risk assessment of occupational exposure to BE, since BE is commonly used in mixtures that contain water. Exposure to aqueous solutions of 50% and 90% of BE may result in substantial skin absorption: if a 60-min skin contact of 1,000 cm(2) is assumed, dermal uptake would be four-times higher than the pulmonary uptake of an 8-h occupational exposure at a TLV of 100 mg m(-3). This clearly justifies the skin notation for BE. For the purpose of biological monitoring, both BE in blood and BAA in urine were shown to be reliable indicators of exposure.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Percutaneous absorption of neat and aqueous solutions of 2-butoxyethanol in volunteers

Jakaša

Mohammadi

Krüse

et al. 2004

International Archives of Occupational and Environmental Health

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“…Transdermal uptake of vapor has also shown for other low-volatile compounds such as NMP (Bader et al 2008) and glycol ethers (Corley et al 1997;Johanson and Boman 1991).…”

Section: Mass Of Pyrene + Metabolites (In µMol)mentioning

confidence: 95%

Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model

Jongeneelen¹,

Berge²

2011

Int Arch Occup Environ Health

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Introduction A physiologically based toxicokinetic (PBTK) model can predict blood and urine concentrations, given a certain exposure scenario of inhalation, dermal and/or oral exposure. The recently developed PBTK-model IndusChemFate is a unified model that mimics the uptake, distribution, metabolism and elimination of a chemical in a reference human of 70 kg. Prediction of the uptake by inhalation is governed by pulmonary exchange to blood. Oral uptake is simulated as a bolus dose that is taken up at a first-order rate. Dermal uptake is estimated by the use of a novel dermal physiologically based module that considers dermal deposition rate and duration of deposition. Moreover, evaporation during skin contact is fully accounted for and related to the volatility of the substance. Partitioning of the chemical and metabolite(s) over blood and tissues is estimated by a Quantitative Structure-Property Relationship (QSPR) algorithm. The aim of this study was to test the generic PBTK-model by comparing measured urinary levels of 1-hydroxypyrene in various inhalation and dermal exposure scenarios with the result of model simulations. Experimental In the last three decades, numerous biomonitoring studies of PAH-exposed humans were published that used the bioindicator 1-hydroxypyrene (1-OHpyrene) in urine. Longitudinal studies that encompass both dosimetry and biomonitoring with repeated sampling in time were selected to test the accuracy of the PBTK-model by comparing the reported concentrations of 1-OHP in urine with the model-predicted values. Two controlled human volunteer studies and three field studies of workers exposed to polycyclic aromatic hydrocarbons (PAH) were included. Results The urinary pyrene-metabolite levels of a controlled human inhalation study, a transdermal uptake study of bitumen fume, efficacy of respirator use in electrode paste workers, cokery workers in shale oil industry and a longitudinal study of five coke liquefaction workers were compared to the PBTK-predicted values. The simulations showed that the model-predicted concentrations of urinary pyrene and metabolites over time, as well as peak-concentrations and total excreted amount in different exposure scenarios of inhalation and transdermal exposure were in all comparisons within an order of magnitude. The model predicts that only a very small fraction is excreted in urine as parent pyrene and as free 1-OH-pyrene. The predominant urinary metabolite is 1-OH-pyrene-glucuronide. Enterohepatic circulation of 1-OH-pyrene-glucuronide seems the reason of the delayed release from the body. Conclusions It appeared that urinary excretion of pyrene and pyrene-metabolites in humans is predictable with the PBTK-model. The model outcomes have a satisfying accuracy for early testing, in so-called 1st tier simulations and in range finding. This newly developed generic PBTKmodel IndusChemFate is a tool that can be used to do early explorations of the significance of uptake of pyrene in the human body following industrial or environmental exposure scenarios...

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“…Recent research, however, found that only a small percentage of total exposure to airborne EGBE would be derived by dermal absorption from vapors (Corley et al 1997). The OECD (1997) concluded that the potential for absorption of EGBE from dermal contact with liquids would also be a minor part of the expected dose in most settings.…”

Section: Glycol Ethersmentioning

confidence: 99%

Occupational exposure to glycol ethers and human congenital malformations

Maldonado

Delzell

Tyl³

et al. 2003

International Archives of Occupational and Environmental Health

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Physiologically Based Pharmacokinetics and the Dermal Absorption of 2-Butoxyethanol Vapor by Humans

Cited by 70 publications

References 22 publications

Percutaneous absorption of neat and aqueous solutions of 2-butoxyethanol in volunteers

Percutaneous absorption of neat and aqueous solutions of 2-butoxyethanol in volunteers

Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model

Occupational exposure to glycol ethers and human congenital malformations

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