Kinetics of distribution and elimination of DDE in rats

Mühlebach, Stefan; Moor, Markus; Wyss, P.; Bickel, Marcel H.

doi:10.3109/00498259109039455

Cited by 15 publications

(8 citation statements)

References 15 publications

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“…This value contrasts with values of Ͼ6%, 53.03%, 50 to 70%, and 10 to 20%, respectively, for lipophilic compounds such as dieldrin, DDT (DDE), PCB, and TCDD (Hayes, 1974;Matthews and Tuey, 1980;Abraham et al, 1988;Mühlebach et al, 1991). Although elimination of these lipophilic compounds from adipose tissue was similar, relatively high residue of these compounds in adipose tissue might be the result of metabolic stability.…”

Section: Nagahori Et Alcontrasting

confidence: 45%

“…Residual 14 C in adipose tissue 7 days after administration of pyridalyl was 2% of the dose, in contrast to values for lipophilic compounds such as dieldrin, DDT (DDE), PCB, and TCDD of Ͼ6%, 53.03%, 50 to 70%, and 10 to 20%, respectively (Hayes, 1974;Matthews and Tuey, 1980;Abraham et al, 1988;Mühlebach et al, 1991). Pyridalyl has an ether bond that is easily cleaved, whereas dieldrin, DDT (DDE), and PCB are more resistant to degradation.…”

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confidence: 97%

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Metabolism of 2,6-Dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl Ether (Pyridalyl) in Rats after Repeated Oral Administration and a Simple Physiologically Based Pharmacokinetic Modeling in Brown and White Adipose Tissues

Nagahori

Matsunaga²,

Tomigahara³

et al. 2010

Drug Metab Dispos

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in perirenal adipose tissue and lungs was pyridalyl, accounting for greater than 90 and 60%, respectively, of the total, whereas a major metabolite in whole blood, kidneys, and liver was a dehalogenated metabolite. The experimental data were simulated with simple physiologically based pharmacokinetics using fourcompartment models with assumption of lymphatic absorption and membrane permeability in adipose tissues. The different kinetics in brown and white adipose tissues was reasonably predicted in this model, with large distribution volume in adipose tissues and high hepatic clearance in liver. Sex-related difference of pyridalyl concentration in liver was considered to be a result of different unbound fraction times the hepatic intrinsic clearance (f ؋ CL int ) of 1.8 and 12 l/h for male and female, respectively.

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Section: Nagahori Et Alcontrasting

confidence: 45%

mentioning

confidence: 97%

Metabolism of 2,6-Dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl Ether (Pyridalyl) in Rats after Repeated Oral Administration and a Simple Physiologically Based Pharmacokinetic Modeling in Brown and White Adipose Tissues

Nagahori

Matsunaga²,

Tomigahara³

et al. 2010

Drug Metab Dispos

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“…DDE has an approximate 400–450:1 adipose to blood partition coefficient in the rodent, thus we anticipated that the primary depot of DDE would be the adipose tissue (Muhlebach et al 1991; You et al 1999). The current data do indeed indicate that adipose tissue concentrations increase from 1438.7 ng/g at 7 days to 1906.2 ng/g at 21 days following DDE administration and these data support the role of adipose as the primary storage depot of DDE.…”

Section: Discussionmentioning

confidence: 99%

Exposure to p,p′-dichlorodiphenyldichloroethylene (DDE) induces fasting hyperglycemia without insulin resistance in male C57BL/6H mice

et al. 2014

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Approximately 8.3% of the United States (U.S.) population have either diagnosed or undiagnosed diabetes mellitus. Out of all the cases of diabetes mellitus, approximately 90–95% of these cases are type 2 diabetes mellitus (T2D). Although the exact cause of T2D remains elusive, predisposing factors include age, weight, poor diet, and a sedentary lifestyle. Until recently the association between exposure to environmental contaminants and the occurrence of diabetes had been unexplored. However, recent epidemiological studies have revealed that elevated serum concentrations of certain persistent organic pollutants (POPs), especially organochlorine pesticides, are positively associated with increased prevalence of T2D and insulin resistance. The current study seeks to investigate if this association is causative or coincidental. Male C57BL/6H mice were exposed to DDE (2.0 mg/kg or 0.4 mg/kg) or vehicle (corn oil; 1 ml/kg) for five days via oral gavage; fasting blood glucose, glucose tolerance, and insulin challenge tests were performed following a seven day resting period. Exposure to DDE caused significant hyperglycemia compared to vehicle and this hyperglycemic effect persisted for up to 21 days following cessation of DDE administration. Intraperitoneal glucose tolerance tests and phosphorylation of Akt in the liver, skeletal muscle, and adipose tissue following insulin challenge were comparable between vehicle and DDE treated animals. To determine the direct effect of exposure to DDE on glucose uptake, in vitro glucose uptake assays following DDE exposure were performed in L6 myotubules and 3T3-L1 adipocytes. In summary, subacute exposure to DDE does produce fasting hyperglycemia, but this fasting hyperglycemia does not appear to be mediated by insulin resistance. Thus, the current study reveals that subacute exposure to DDE does alter systemic glucose homeostasis and may be a contributing factor to the development of hyperglycemia associated with diabetes.

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“…Although we see bioaccumulation of such lipophilic compounds as a problem, pyridalyl has a different nature. Residual 14 C in fat 7 days after administration of pyridalyl was 2% of the dose, but that of lipophilic compounds such as dieldrin, DDT (DDE), PCB, and dioxin was found to be Ͼ6, 53.03, 50 to 70, and 10 to 20%, respectively (Hayes, 1974;Matthews and Tuey, 1980;Abraham et al, 1988;Mühlebach et al, 1991). The difference may depend on metabolic stability.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of Pyridalyl in Rats

Nagahori

Saito²,

Tomigahara³

et al. 2009

Drug Metab Dispos

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ABSTRACT:Metabolism of pyridalyl [2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether] was examined in male and female Sprague-Dawley rats. After a single oral administration of [dichlorophenyl-14 C]pyridalyl at 5 or 500 mg/kg, the 14 C concentration in blood reached maxima at 2 to 10 h and then decreased rapidly with a biological half-life of approximately 11 to 12 h. 14 C concentrations in liver, fat, adrenal gland, and spleen were relatively high at a low dose, reaching 2.3 to 2.7, 1.9 to 2.3, 1.1 to 1.9, and 1.4 ppm, respectively, in these tissues at 2 to 24 h after administration. Although 14 C elimination from fat and hair and skin was relatively slow compared with that from other tissues, the total residue on the 7th day was low, in the range of 1.3 to 2.3% of the dose. The 14 C distribution in tissues with a high dose, as examined by whole-body autoradiography, was similar to that observed for the low dose. Results revealed that more than 88% of the dosed radiocarbon was excreted within 1 day after administration, with cumulative 14 C excretion into urine and feces 7 days after administration of 1.7 to 2.6 and 98.7 to 101.7%, respectively. One urinary and fecal major metabolite (resulting from O-dealkylation) and two minor metabolites were identified by NMR and mass spectrometry. Residual 14 C in fat was extracted, and analysis by thin-layer chromatography showed it to be due to pyridalyl itself. No marked sex-related differences were observed in 14 C elimination, 14 C distribution, and metabolites.Pyridalyl [2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether; S-1812] is a new class of insecticide for Lepidoptera and Thysanoptera (Sakamoto et al., 2004;Isayama et al., 2005). It has dichloropropenyl, phenyl and pyridyl groups in its structure but does not share structural similarity with other insecticides. Toxicity studies, including acute, chronic, oncogenicity, developmental, mutagenicity, and reproductive studies, have all been conducted previously with low acute toxicity, no oncogenicity and mutagenicity, and no teratogenicity observed (US Environmental Protection Agency, 2008).In the present study, metabolism of [dichlorophenyl-14 C]pyridalyl in rats was investigated in conjunction with toxicological studies for safety evaluation.14 C excretion, 14 C tissue distribution, and metabolites were investigated in support of rodent toxicology studies. The present report deals with metabolism ( 14 C excretion into feces, urine, and expired air, 14 C concentrations in tissues, and amounts of metabolites in excreta) of pyridalyl in rats. Materials and Methods Chemicals. [Dichlorophenyl-14 C]pyridalyl was prepared at the Environmental Health Science Laboratory of Sumitomo Chemical Co., Ltd. (Osaka, Japan) with a specific activity of 4.37 GBq/mmol. Labeled compound was purified with thin-layer chromatography (TLC) before use, and the radiochemical purity was Ͼ96.2%. Unlabeled pyridalyl (purity 98.4%) was also obtained from our co...

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Kinetics of distribution and elimination of DDE in rats

Cited by 15 publications

References 15 publications

Metabolism of 2,6-Dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl Ether (Pyridalyl) in Rats after Repeated Oral Administration and a Simple Physiologically Based Pharmacokinetic Modeling in Brown and White Adipose Tissues

Metabolism of 2,6-Dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl Ether (Pyridalyl) in Rats after Repeated Oral Administration and a Simple Physiologically Based Pharmacokinetic Modeling in Brown and White Adipose Tissues

Exposure to p,p′-dichlorodiphenyldichloroethylene (DDE) induces fasting hyperglycemia without insulin resistance in male C57BL/6H mice

Metabolism of Pyridalyl in Rats

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