Human toxicokinetics of inhaled monochlorobenzene: latest experimental findings regarding re-evaluation of the biological tolerance value

Objective: The aim of this study was to obtain toxicokinetic data on the ab sorption and elimination of monochlorobenzene (MCB) in blood and its main m etabolite 4-chlorocatechol (4-ClCat) as well as on the isomeric chloropheno ls (o-ClPh, m-ClPh, and especially p-ClPh as the main ClPh metabolite) in u rine for reevaluation of the biological tolerance (BAT) value of MCB. Metho ds: Eight subjects performed 8-h inhalation tests daily over five successiv e days in an exposure chamber, at a maximum allowable concentration at the workplace (MAK) value of 10 ppm MCB. Five and two probands carried out the test series during physical activity levels of 75 and 50 W, respectively, f or 10 min/h on a bicycle ergometer, and one subject was exposed continuousl y while at rest. MCB and its metabolites were analyzed by gas chromatograph y in combination with mass spectrometry. Results: The mean MCB blood concen tration of the five subjects exposed during physical activity of 75 W was 2 17 +/- 42 mug/l. The relationship of the mean blood concentration measured under the conditions of rest or 50 and 75 W activity levels was in a ratio of about 1:1.7.2.8. The half-life values in the first hour after ending the exposures were 53 min and 150 min for the ensuing period, with steady-stat e being reached after 45 min. The mean 4-ClCat concentration in urine at th e end of the five days was 150 +/- 13 mg/g creatinine in the case of the su bjects exposed at 75 W, which decreased to 25 mg/g creatinine at the beginn ing of the next exposure. The analogous p-ClPh concentrations were 25 +/- 2 and 9 +/- 2 mg/g creatinine. The elimination half-life values of the ClPh isomers ranged from 12.4 to 16.5 h, and the half-life of 4-ClCat was 6.4 h. There was no apparent tendency for MCB and its metabolites to accumulate i n blood or urine. Conclusions: The results are in accordance with relevant field and laboratory studies. Taken into consideration with the 95th percen tile, the evaluated BAT values should be set at levels of 300 mug MCB/l blo od, 175 mg 4-ClCat/g creatinine or alternatively at 30 mg p-ClPh/g creatini ne in urine after the end of a shift. At the beginning of the next shift, t he BAT values of the metabolites should be 35 and 15 mg/g creatinine, respe ctively.