Behaviour of urinary 2,5-hexanedione in occupational co-exposure to n-hexane and acetone

Abstract

We analysed the relationship between free 2,5-hexanedione (2,5-HD) and total 2,5-HD in the urine of 87 workers exposed to n-hexane and other solvents (hexane isomers, acetone and toluene), in relation to different working conditions. The concentration of free 2,5-HD in urine of workers exposed to n-hexane was about 12% of total urinary 2,5-HD. The most significant correlation (r = 0.936) was that of total 2,5-HD in urine with environmental n-hexane and exhaled air. With equal exposure to n-hexane, the concentrations in urine of free and total 2,5-HD increased when cutaneous absorption was involved (gloves not used), during the working week and with co-exposure to acetone. An analysis of the relationship between combined exposure to acetone and urinary concentrations of the various forms of 2,5-HD suggests that acetone might influence the toxicokinetics of n-hexane, increasing the proportion of free 2,5-HD.

Changes in n -hexane toxicokinetics in short-term single exposure due to co-exposure to methyl ethyl ketone in volunteers

“…Because of large variations in HD recovery ratios with and without acid hydrolysis [20], comparisons between the referred studies and our study is difficult. However, Cardona et al [5] analyzed HD both with and without acid hydrolysis. Taking into account the difference between their study and ours in the duration and type of n-hexane exposure, the levels of urinary HD in our n-hexane-alone condition seems to be consistent with the correlation between HD in urine and n-hexane in the breathing-zone air reported by them.…”

“…However, urinary HD was analyzed without acid hydrolysis which would have converted conjugated 4, 5-dihydroxy-2-hexanone to HD [11]. A substantial number of workplace studies reporting correlation between HD in urine and n-hexane in ambient air have been reported so far [5,8,12,18,19]. In most of those reports, urinary HD was analyzed with acid hydrolysis.…”

Urinary 2,5-hexanedione in workers exposed to n-hexane: influence of the sample treatment

“…Neuropathy is caused by the main HEX metabolite, 2,5-hexanedione (2,5-HD), which binds to DNA, RNA and axon proteins [5][6][7] . The most widely used bioindicator in the monitoring of workers exposed to HEX is urinary 2,5-HD due to its high correlation with environmental exposure to HEX as reported by various investigators [8][9][10] . Biological monitoring of HEX was done by the determination of total urinary 2,5-HD after acid hydrolysis, with the recommended limits being 5 mg 2,5-HD/g creatinine for exposure to the Threshold Limit Value-Time Weight Average (TLV-TWA) of 50 ppm HEX in air 11 .…”

Determinação da 2,5-hexanodiona em amostras de urina submetidas à hidrólise ácida: importância da coluna cromatográfica e do pH do meio

“…Quando esta hidrólise é realizada, os níveis deste biomarcador podem ser de 3 a 6 vezes maiores do que os encontrados nas mesmas amostras analisadas sem hidrólise, não só pela liberação do composto da forma conjugada mas, também, pela transformação in vitro de outros metabólitos urinários do n-hexano, como por exemplo o 4,5-diidroxi-2-hexanona (4,5-DH-2-H) em 2,5-HD [1][2][3] . Embora este fato aumente de maneira importante a sensibilidade e a especificidade da análise, é essencial que as condições analíticas sejam bem definidas, evitando-se resultados super ou subestimados do biomarcador.…”

“…Embora este fato aumente de maneira importante a sensibilidade e a especificidade da análise, é essencial que as condições analíticas sejam bem definidas, evitando-se resultados super ou subestimados do biomarcador. Sabe-se que, em hidrólises ácidas realizadas em pH próximos a 2,0, a 4,5-diidroxi-2-hexanona se transforma em 2,5 dimetilfurano (2,5-DF), subestimando a concentração total da 2,5-HD encontrada 1,2 . Outro ponto importante a ser considerado é a formação do composto 2-acetilfurano (2-AF), quando amostras de urina são submetidas à hidrólise ácida.…”