In vivo binding of the flame retardantsTris(2,3-dibromopropyl) phosphate andTris(1,3-dichloro-2-propyl) phosphate to macromolecules of mouse liver, kidney and muscle

Early Zebrafish Embryogenesis Is Susceptible to Developmental TDCPP Exposure

“…Moreover, TDCPP exposure did not result in obvious effects on the cell cycle, overall embryo size, or cell morphology during cleavage (Figure 5), suggesting that TDCPP mediates toxicity at the subcellular or genomic level during this stage of embryogenesis. Because TDCPP-specific genotoxicity assays have, for the most part, been negative in vivo (Bloom 1984; Brusick et al 1980; Cifone 2005; Morales and Matthews 1980) and because zygotic genome remethylation is a key biological event during cleavage (Mhanni and McGowan 2004), we investigated whether TDCPP altered the status of gDNA methylation, and observed that normal gDNA methylation at the end of cleavage (2 hpf) was absent in TDCPP-treated embryos (Figure 6). Overall, our findings suggest that the cleavage period during zebrafish embryogenesis is susceptible to TDCPP-induced delays in remethylation of the zygotic genome, a mechanism that may be associated with enhanced developmental toxicity following initiation of TDCPP exposure at the start of cleavage.…”

“…Because most TDCPP-specific genotoxicity assays have been negative in vivo (Bloom 1984; Brusick et al 1980; Cifone 2005; Morales and Matthews 1980), we used a screening-level, genome-wide restriction analysis approach to determine whether the susceptibility of cleavage was associated with adverse effects on zygotic genome methylation. We found that gDNA within TDCPP-treated embryos—but not vehicle-treated embryos—at the end of cleavage was completely digested by methylation-sensitive restriction endonucleases, suggesting that normal gDNA methylation was absent in TDCPP-treated embryos at 2 hpf.…”

“…To evaluate uptake and elimination during these exposure scenarios, we quantified concentrations of TDCPP and bis(1,3-dichloro-2-propyl) phosphate (BDCPP, the primary metabolite of TDCPP) within whole embryos using liquid chromatography/tandem mass spectrometry (LC/MS-MS). Finally, because TDCPP-specific genotoxicity assays have, for the most part, been negative in vivo (Bloom 1984; Brusick et al 1980; Cifone 2005; Morales and Matthews 1980) and zygotic genome remethylation is a key biological event during cleavage (Mhanni and McGowan 2004), we investigated whether TDCPP altered the status of zygotic genome methylation during early zebrafish embryogenesis.…”

Quantitative evaluation of DNA binding data for risk estimation and for classification of direct and indirect carcinogens

“…CBI values from Lutz (1979) unless stated otherwise in the list of abbreviations arranged below in increasing carcinogenic potency. Bz, benzene; CCI 4 , carbon tetrachloride (Levy and Brabec 1984); Ani, aniline (McCarthy et al 1985); AcrN, acrylonitrile (Farooqui and Ahmed 1983); VC, vinyl chloride (Bergman 1982); Safr, safrole (Randerath et al 1984); TCE, 1,1,2-trichloroethane ; tBPP, tris(2,3-dibromopropyl)phosphate (Morales and Matthews 1980); Ure, urethane; CMAni, 4-chloro-2-methylaniline (unpublished); NMAni, nitrosomethylaniline; DCE, 1 ,2-dichloroethane ; DNT, 2,4-dinitrotoluene (Kedderis et al 1984); NPyrr, nitrosopyrrolidine (Hunt and Shank 1982); BP, benzo[a]pyrene (Shertzer 1983); DMAAB, N,N-dimethyl-4-aminoazobenzene FANFT, N-[5-nitro-2-furyl)-2-thiazolyl]formamide (Morton 1982); CPh, cyclophosphamide; Bzd, benzidine (Martin and Ekers 1980); DBE, 1,2-dibromoethane; AAF, 2-acetylaminofluorene; Aza, azaserine (Zurlo et al 1982); NDMA, nitrosodimethylamine; Strtoz, streptozotocin (Bennett and Pegg 1981); DMH, 1,2-dimethylhydrazine; Steri, sterigmatocystine ; Pcz, procarbazine (Wiestler et al 1984); NDEA, nitrosodiethylamine; AFB 1 , aflotoxin B 1 potency with DNA binding ability. Firstly, most sturlies have concentrated on the Ievel of DNA binding at the time ofmaximum DNA darnage after a single administration.…”

Organophosphate Ester Contaminants in Herring Gulls (Larus argentatus) from the Great Lakes of North America: Bioaccumulation, Exposure, Pharmacokinetics and Trends

“…It has also been shown that TCEP has a weak binding affinity for acetylcholinesterase (Matthews et al, 1990). Multiple studies have examined the phenotypic effects of OPEs in rodents, birds and fish Liu et al, 2012;Farhat et al, 2013;Liu et al, 2013;Umezu et al, 1998;Morales et al, 1980). In most of these studies, even though valuable information has been gained regarding phenotypic changes upon exposure to OPEs (such as endocrine disruption, developmental toxicity, and mRNA expression changes), very little is known regarding direct interactions between OPEs and specific biomolecules.…”