Low levels of exposure to benzene: which biomarker is best for risk assessment ?

Introduction  The first biomarker for benzene exposure was phenol: because of its low specificity, benzene in exhaled breath was proposed by ACGIH when the  TLV was reduced to 0.5 ppm. In 1997 S-phenylmercapturic acid (SPMA) was adopted and then trans,trans-muconic acid (t,t-MA) was added. Both metabolites are questionable when levels of exposure to benzene are low: t,t-MA is also a metabolite of the food preservative sorbic acid, while SPMA  formation by conjugation of benzene epoxide with glutathione could be affected by the polymorphism of genes coding for glutathione-S-transferases. Smoking is an important confounding factor in the biomonitoring of benzene exposure.    

Methods  Quantitative determination of t,t-MA and SPMA in urine is performed using HPLC/MS/MS with isotopic dilution. The GSTT1, GSTM1 and GSTP1 genotype is assesed by means of real time PCR on DNA from blood samples.    

Results   Occupational exposure to benzene nowadays appears negligible in comparison with that from cigarette smoking, thanks to occupational prevention culture. The t,t-MA/SPMA ratio (R) is a variable value, higher than the BEI ratio, which is 20.    

Discussion and Conclusions  Sorbic acid  is rapidly metabolized, so if urine is collected a few hours after meals, all t,t-MA is attributable to benzene exposure. The modulating effect of the polymorphism of GSTT1 and GSTP1 on the SPMA excretion is confirmed,  and higher R values are associated with GSTT1 or GSTM1 null genotype subjects, considered at increased health risk (ref).  Therefore we suggest that,  in order to correctly  assess benzene occupational exposure at low levels, both t,t-MA and SPMA  are determined on the same subject and their ratio used  as a marker of individual susceptibility.    

Reference: Mansi, A., et al., Low occupational exposure to benzene in a petrochemical plant: Modulating effect of genetic polymorphisms and smoking habit on the urinary t,t-MA/SPMA ratio. Toxicol. Lett. (2011), doi:10.1016/j.toxlet.2011.02.001