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Jordi To-Figueras,¹ Maria Sala,² Raquel Otero,³ Carme Barrot,¹ Mary Santiago-Silva,³ Miquel Rodamilans,¹

Carme Herrero,⁴ Joan Grimalt,³ Jordi Sunyer²

Abstract

Serum and urine from 100 subjects of a general population highly exposed to airborne hexachlorobenzene (HCB) were analyzed to obtain new insights into the metabolism of this ubiquitous compound. HCB was detected in all serum samples with concentrations ranging between 1.1 and 953 ng/ml. The major known metabolites of HCB were investigated in urine collected over 24 hr. Pentachlorophenol (PCP) was detected in all urines with values ranging between 0.58 and 13.9 10 g excreted in 24 hr [mean +/- standard deviation (SD) , 2.52 +/- 2.05 ; geometric mean, 2.05]. A sulfur derivative that, after hydrolysis, yielded pentachlorobenzenethiol (PCBT) could also be identified and quantified in all the urines with values ranging between 0.18 and 84.0 10 g of PCBT excreted in 24 hr (mean +/- SD, 3.47 +/- 10.8 ; geometric mean, 1.39) . The sulfur derivative assessed as PCBT appeared to be the main metabolite, with urinary concentrations surpassing those of PCP in the subjects with higher HCB accumulation (HCB in serum >32 ng/ml) . PCBT concentration in urine collected over 24 hr showed a very strong association with HCB concentration in serum ; the association was stronger in males than in females. An increase of 1 ng/ml of HCB in serum led to an increase of 2.12 10 g of PCBT excreted in urine collected over 24 hr in males (95% CI, 1.82-2.44) and to an increase of 0.67 10 g of PCBT in females (CI, 0.33-1.09) . A weaker association was found between PCP in urine and HCB in serum, which was only statistically significant in males (an increase of 1 ng/ml of HCB in serum led to an increase of 0.63 10 g of PCP excreted in urine collected over 24 hr ; (CI, 0.34-0.95) . These results show that the formation of the cysteine conjugate is a quantitatively more important metabolic pathway in humans than the formation of PCP. Moreover, the association found suggests that PCBT is a good urinary marker of HCB internal dose and glutathione-mediated metabolism. Key words: exposed population, hexachlorobenzene, metabolism, pentachlorobenzenethiol, pentachlorophenol, urine. Environ Health Perspect 105:78-83 (1997)

Address correspondence to J. To-Figueras, Toxicology Unit, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.

The collaboration of C. Camps and the Health Care Center of Flix is highly appreciated. We also thank J.M. Antó and M. Kogevinas for their contribution to the study. This work was supported by Spanish "Fondo de Investigación Sanitaria," grant 93/0006-01.

Received 9 July 1996 ; accepted 26 September 1996.