Biomonitoring of 4,4'-methylene dianiline by measurement in hydrolysed urine and plasma after epicutaneous exposure in humans

Abstract

Five healthy volunteers were dermally exposed for 1 h to 0.75-2.25 mumol 4,4'-methylene dianiline (MDA) dissolved in isopropanol, by use of a patch-test technique. Determination of MDA remaining in the patch units after exposure showed that a median of 28% (range 25-29%) was absorbed. By analysis of hydrolysed plasma, an initial accumulation of MDA could be shown, and then a decline. MDA was also detected in hydrolysed urine. The maximum rate of MDA excretion in urine was found 6-11 h after the onset of exposure. Within two subjects studied at three doses, the urinary excretion was proportional to the exposure. The elimination half-lives (elim-t1/2) in plasma and urine had medians of 13 and 7 h, respectively. In eight out of nine exposures, the elim-t1/2 was longer in plasma than in urine. Slow acetylation seemed to be associated with short elim-t1/2 in urine. The median of total MDA amount excreted in urine during 48 h, was 33 nmol for the five subjects exposed to 0.75 mumol, which corresponded to roughly 16% (range 2%-26%) of the absorbed dose while only a limited number of individuals were studied, the data still indicated that MDA in hydrolysed plasma or urine can be used for biological monitoring of occupational dermal exposure. However, the individual variation must be taken into account. Sampling should preferably be made several hours post shift. Urine is preferred before plasma at low exposures, because of its higher concentrations of MDA.