In vivo distribution and biotransformation of Tris (1,3-dichloro-2-propyl) phosphate in mice

Abstract

Phosphorus flame retardants (PFRs) have been widely detected in environmental media and human samples. Understanding the distribution and biotransformation of PFRs is important for toxicological research of PFRs in humans. C57BL/6 mice were administered with 300 mg/kg body weight/day of tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) for 35 consecutive days. The liver, kidney, muscle, feces, urine and hair samples were collected to investigate the distribution of TDCIPP and its diester, bis (1,3-dichloro-2-propyl) phosphate (BDCIPP), as well as other potential metabolites of TDCIPP. Concentrations of TDCIPP in muscle (535.7 ± 192.2 ng/g wet weight) were significantly higher than those in liver (186.9 ± 55.0 ng/g wet weight) and kidney (43.5 ± 12.0 ng/g wet weight) (p < 0.05), while concentrations of BDCIPP were higher in kidney (2189.2 ± 420.7 ng/g wet weight) and liver (1337.1 ± 249.6 ng/g wet weight) than other tissues. The distribution of TDCIPP and BDCIPP in mice is tissue-specific, TDCIPP tends to accumulate in muscle, while BDCIPP tends to enrich in kidney and liver. BDCIPP was prone to be eliminated by urine, which may result in the high levels of BDCIPP in urine. Urine and feces had significantly higher concentrations of BDCIPP than TDCIPP (p < 0.05), which demonstrated that BDCIPP is an important metabolite of TDCIPP. Hair could serve as a suitable and reliable biomarker for TDCIPP and also metabolites of TDCIPP. Multifarious metabolites of TDCIPP were identified in various matrices of mice, especially urine. Seven novel metabolites of TDCIPP were identified for the first time. TDCIPP metabolic pathways involved oxidative dealkylation, oxidative dehalogenation, reoxidation, dehalogenation with dehydrogenation. The metabolites identified in the present study could serve as candidate biomarkers for future human biomonitoring studies.