Determination of glucuronide conjugates of hydroxyl triphenyl phosphate (OH-TPHP) metabolites in human urine and its use as a biomarker of TPHP exposure

• A method was developed for determination of para(p)- and meta(m)-OH TPHP glucuronides in urine.
• Both p- and m-OH-TPHP glucuronides were detected in urine samples.
• Concentration ranges of p- and m-OH-TPHP glucuronides were • p-OH-TPHP glucuronide and DPHP concentrations in urine were strongly and positively correlated.
• This is first known report demonstrating TPHP hydroxylation occurs in TPHP exposed humans.

In vitro studies using avian hepatocytes or human liver microsomes suggest that hydroxylation is an important pathway in the metabolism of triphenyl phosphate (TPHP), a chemical used as a flame retardant and plasticizer. TPHP metabolism can lead to the formation of para(p)- and meta(m)-hydroxyl-(OH-)TPHP products as well as their glucuronide conjugates. To determine whether the TPHP hydroxylation and depuration pathway also occurs in vivo in humans, the present study developed a sensitive method for quantification of p- and m-OH-TPHP glucuronides in human urine samples. In n = 1 pooled urine sample and n = 12 individual urine samples collected from four human volunteers from Ottawa (ON, Canada), p- and m-OH-TPHP glucuronides were detectable in 13 and 9 of the 13 analyzed samples and at concentrations ranging from

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