Physiologically based pharmacokinetic modelling of human exposure to 2-butoxyethanol.

Abstract:

:A physiologically based pharmacokinetic (PBPK) model describing the disposition of 2-butoxyethanol (2-BE) was developed in order to predict the urinary concentration of its major metabolite, butoxyacetic acid (BAA) under a range of exposure scenarios. Based on Corley et al. [Corley, R.A., Bormett, G.A., Ghanayem, B.I., 1994. Physiologically based pharmacokinetics of 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in rats and humans. Toxicol. Appl. Pharmacol. 129, 61-79], the model included such features as multiple entry routes into the body, varying workload conditions, metabolism in the liver and elimination of free BAA in urine by glomerular filtration and acid transport. A bladder compartment simulating the fluctuations in metabolite concentration in urine caused by micturition formed a novel aspect of the model. Good agreement between model predictions and existing experimental data of total BAA levels in the blood and urine over various exposure conditions were observed. The mechanistically based PBPK model allowed comparison of disparate studies and also enabled the prediction of urinary concentrations of BAA post-shift. By calculating the total amount of BAA, any inter-individual variability in conjugation is taken into account. This led us to conclude that a biological monitoring guidance value should be proposed for total rather than free BAA with a value of 250 mmol/mol of creatinine (post-shift), based on an 8h exposure to 25 ppm 2-BE at resting working conditions.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Franks SJ,Spendiff MK,Cocker J,Loizou GD

doi

10.1016/j.toxlet.2005.09.012

keywords:

subject

Has Abstract

pub_date

2006-04-10 00:00:00

pages

164-73

issue

2-3

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(05)00287-0

journal_volume

162

pub_type

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