Uptake, Deposition, and Metabolism of Triphenyl Phosphate in Embryonated Eggs and Chicks of Japanese Quail (Coturnix japonica)

Abstract

The toxicokinetics of triphenyl phosphate (TPHP) in vivo including the uptake, deposition, and biotransformation into the metabolite diphenyl phosphate (DPHP) is presently reported in embryonated eggs and chicks of Japanese quail. Quail were dosed with TPHP at 3 concentrations by air cell egg injection on embryonic day 0, followed by daily oral dosing after chicks hatched (5 d). Vehicle‐only exposed controls were also used. In dosed eggs, only 33% of the TPHP remained 2 d after injection (no hepatic development); after 10 d (post‐hepatogenesis), only 2% remained. The estimated TPHP half‐lives in the eggs ranged from 1.1 to 1.8 d for the 3 dosed groups. In all exposed eggs and chicks, DPHP significantly increased with dose (0.001 < p < 0.044). It appears that DPHP is an important metabolite in quail, making up 41 to 74% of all metabolites formed in embryonated eggs. In chicks, at medium and high doses, DPHP concentrations significantly exceeded those of TPHP (p ≤ 0.007), making up 67 and 76% of the total burden, respectively. Our findings suggest that rapid TPHP metabolism occurred in chicks and embryonated quail eggs but that this may vary with the age of the embryonated egg and the stage of embryo development, which should be considered when evaluating concentrations of TPHP and DPHP measured in eggs of wild birds. Environ Toxicol Chem 2020;39:565–573. © 2019 Her Majesty the Queen in Right of Canada. Environmental Toxicology and Chemistry © 2019 SETAC

Uptake, Accumulation, and Biomarkers of PM2.5-Associated Organophosphate Flame Retardants in C57BL/6 Mice after Chronic Exposure at Real Environmental Concentrations

“…The average recovery rate of the internal standard BDCPP- d 10 in the spiked samples was 58.5%, which could basically meet the requirements of the target metabolite extraction (Figure S5). Of these metabolites, DPhP, the hydrolyzed metabolite of TPhP, has been most frequently detected in animal and human samples and is widely accepted as a biomarker of TPhP exposure. ,− DnBP was the main end product of TnBP biotransformation in the body and was identified as the major TnBP metabolite in recent human and animal biomonitoring studies. − Interestingly, although TCrP was not detected in any tissue, its main metabolite DCrP was found in H-group urine samples. Unlike the other two metabolites mentioned above, DCrP has rarely been detected in biological samples.…”

Developmental exposure to the flame retardant, triphenyl phosphate, causes long‐lasting neurobehavioral and neurochemical dysfunction

“…TPPs and diphenyl phosphate) (Marteinson et al, 2020;Su, Crump, Letcher, & Kennedy, 2014), which may contribute to neurotoxicity in distinct ways.…”

“…For example, OP insecticides generate toxic oxon‐forms through metabolism (Mutch & Williams, 2006; Poet, Wu, Kousba, & Timchalk, 2003), which are believed to contribute to the overall neurotoxicity of these compounds and their anti‐cholinesterase properties (Betancourt & Carr, 2004). TPP, by contrast, is primarily metabolized into intermediate phenyl phosphates (e.g., hydroxylated TPPs and diphenyl phosphate) (Marteinson et al, 2020; Su, Crump, Letcher, & Kennedy, 2014), which may contribute to neurotoxicity in distinct ways.…”

Biotransformation, Physico-Chemical Properties and Environmental Fate of Bisphenol A Bis(Diphenyl Phosphate): In Slico, In Vitro and Non-Target Metabolites using a Wister-Han Rat Liver Microsomal Model

“…The importance of CYP450s is also supported by in vitro study of human liver metabolites following exposure to TPHP (Zhang et al, 2018). Biotransformation and metabolism of TPHP into DPHP via dealkylation was reported within embryonated quail eggs and chick carcasses (Marteinson et al, 2020). In vitro metabolism of TPHP has been studied in chicken embryonic hepatocytes, where phase I metabolites and phase II conjugates were quantified, and hydroxylation was identified as a biotransformation pathway of particular importance (Su et al, 2015a).…”