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. 2020 Nov 1;178(1):36-43.
doi: 10.1093/toxsci/kfaa133.

2,4,6-Tribromophenol Disposition and Kinetics in Pregnant and Nursing Sprague Dawley Rats

Gabriel A Knudsen  1 , Margaret Chapman  1 , Andrew W Trexler  1   2 , Christopher T Juberg  1 , Linda S Birnbaum  1
Affiliations

2,4,6-Tribromophenol Disposition and Kinetics in Pregnant and Nursing Sprague Dawley Rats

Gabriel A Knudsen et al. Toxicol Sci. .

Abstract

2,4,6-Tribromophenol (TBP, CAS no. 118-79-6) is a brominated chemical used as a precursor, flame retardant, and wood antifungal agent. TBP is detected in environmental matrices and biota, including human breast milk, placenta, and serum. To address reports of TBP accumulation in human placenta and breast milk, studies were conducted to characterize TBP disposition and toxicokinetics in timed-pregnant or nursing Sprague Dawley rats following a single oral dose to the dam. Animals were administered [14C]-TBP (10 μmol/kg, 25 µCi/kg, 4 ml/kg) by gavage on gestation day 12 and 20, or postnatal day 12 and serially euthanized between 15 min and 24 h for collection of blood and tissues from the dam and fetuses/pups. Observed plasma TBP Cmax (3 and 7 nmol/ml) occurred at 15 min in both GD12 and GD20 dams while Cmax (3 nmol/ml) was observed at 30 min for PND12 dams. Concentrations in tissues followed plasma concentrations, with kidneys containing the highest concentrations at 30 min. GD12 litters contained a sustained 0.2%-0.3% of the dose (5-9 nmol/litter) between 15 min and 6 h while GD20 fetuses (2%-3%) and placentas (0.3%-0.5%) had sustained levels between 30 min and 12 h. The stomach contents (approx. 1 nmol-eq/g, 6-12 h), livers (0.04-0.1 nmol-eq/g) and kidneys (0.1-0.2 nmol-eq/g) of PND12 pups increased over time, indicating sustained exposure via milk. Systemic exposure to TBP and its metabolites occurs in both the directly exposed mother and the indirectly exposed offspring and is rapid and persistent after a single dose in pregnant and nursing rats.

Keywords: biotransformation; pharmacokinetics; toxicokinetics.

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Figures

Figure 1.
Figure 1.
Chemical structure for [14C]-radiolabeled TBP. *Radiolabel was uniformly distributed on the phenolic ring.
Figure 2.
Figure 2.
TBP in plasma after a single oral dose (10 µmol/kg). Data from nonpregnant/conventional animals replotted from Knudsen et al. (2019). Regression lines were generated using a 1-compartment model fit of the data (N = 4–5 samples/time-point). Inset: TBP plasma concentrations between 0 and 240 min.
Figure 3.
Figure 3.
Representative radiochromatograms of dam plasma extracts collected at 15 min, 30 min, or 3 h. A, Nonpregnant (data from Knudsen et al., 2019), B, pregnant, GD12, C: pregnant, GD20 D: nursing, PND12. Parent molecule (TBP) and/or a mixture of metabolites (TBP-glucuronide [TBP-G] and TBP-sulfate [TBP-S]) were detected (N = 4–5 samples/time-point).
Figure 4.
Figure 4.
Concentration versus time data for total chemical from select matrices between 0 and 24 h following a single oral dose to pregnant or nursing female SD rats. A, Concentration in embryos and dam plasma, liver, and kidney collected at GD12. B, Concentration in fetuses and placentas, and dam plasma, liver, and kidney collected at GD20. C, Concentration in dam plasma, liver, kidney, and mammary gland collected at PND12. D, Concentration in pup stomach contents, liver, and kidney collected at PND12 (dam mammary added for reference). Regression lines show predicted data from a 1-compartment model fit (N = 4–5 samples per time-point).
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References

    1. Andersson M., Ersson L., Brandt I., Bergstrom U. (2017). Potential transfer of neurotoxic amino acid beta-n-methylamino-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines. Toxicol. Appl. Pharmacol. 320, 40–50. - PubMed
    1. Ansari J., Carvalho B., Shafer S. L., Flood P. (2016). Pharmacokinetics and pharmacodynamics of drugs commonly used in pregnancy and parturition. Anesth. Analg. 122, 786–804. - PubMed
    1. Athanasiadou M., Cuadra S. N., Marsh G., Bergman A., Jakobsson K. (2008). Polybrominated diphenyl ethers (PBDEs) and bioaccumulative hydroxylated PBDE metabolites in young humans from Managua, Nicaragua. Environ. Health Perspect. 116, 400–408. - PMC - PubMed
    1. Bacq Y. (2000. –2013). The liver in normal pregnancy. Madame Curie Bioscience Database. Austin, TX: Landes Bioscience.
    1. Butt C. M., Miranda M. L., Stapleton H. M. (2016). Development of an analytical method to quantify PBDEs, OH-BDEs, HBCDs, 2,4,6-TBP, EH-TBB, and BEH-TEBP in human serum. Anal. Bioanal. Chem. 408, 2449–2459. - PMC - PubMed

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