High-Fat Diet Enhances Accumulation of Hexachlorobenzene in Rat Dams and Delays Its Transfer from Rat Dams to Suckling Pups through Milk

Nakashima, Yoko; Ohsawa, Saeko; Ikegami, Sachie

doi:10.1021/jf980831c

Cited by 5 publications

(7 citation statements)

References 19 publications

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“…This regimen could potentially provide a safe method for reducing the body burden of lipophilic xenobiotics by minimizing concentrations in sensitive tissues. The observation by Nakashima et al (34) of a high-fat diet reducing excretion of hexachlorobenzene in milk lends support to this approach.…”

Section: Summary Of Interventions That Alter Storage and Elimination mentioning

confidence: 88%

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Factors affecting the storage and excretion of toxic lipophilic xenobiotics

Jandacek

Tso

2001

Lipids

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Lipophilic toxins have been introduced into the environment both as functional compounds, such as pesticides, and as industrial waste from incineration or the manufacture of electrical transformer components. Among these substances are compounds that are carcinogenic and that affect the endocrine system. Accidental high exposures of humans to some lipophilic toxins have produced overt disease symptoms including chloracne and altered liver function. These toxic materials have been the recent focus of international effort to reduce or eliminate classes of halogenated hydrocarbons from the environment. Evidence of the widespread distribution of lipophilic toxins in the biosphere has been obtained by analyses of human tissues and human milk. The principal route of entry of lipophilic toxins into humans is through the food chain, and most of them are stored in adipose tissue. A common route of excretion is in bile, but there is also evidence of nonbiliary excretion into the intestine. Enterohepatic circulation of many of these compounds slows their removal from the body. Substances that interrupt the enterohepatic circulation of compounds that enter the intestine by the biliary and nonbiliary routes increase the rate of their removal from the body and reduce their storage half-lives. Reduction in body fat, along with these dietary substances that interrupt enterohepatic circulation, further enhances the excretion rate. Areas for further research include optimizing regimens for body burden reductions, understanding the nature of nonbiliary excretion, and following the effects of tissue redistribution during loss of body fat.

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Section: Summary Of Interventions That Alter Storage and Elimination mentioning

confidence: 88%

“…Contrasted with the studies of energy deprivation, Nakashima et al (34) studied the effect of a high-fat diet on the elimination of hexachlorobenzene in lactating rats. Pregnant rats fed a high-fat diet transferred hexachlorobenzene more slowly in milk to pups than those fed a low-fat diet.…”

Section: Amount and Type Of Absorbable Dietary Fatmentioning

confidence: 99%

Factors affecting the storage and excretion of toxic lipophilic xenobiotics

Jandacek

Tso

2001

Lipids

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“…1; 21 HCB has been shown to readily transfer to the fetus, concentrate in milk, and transfer to neonates in rhesus monkeys and Sprague Dawley rats. [22][23][24][25][26] Metabolites found in rats after exposure to HCB include pentachlorophenol, tetrachloro-1,4-hydroquinone, and diverse tetra-and tri-chlorophenols. 27 Another major metabolic pathway is the conjugation of HCB with glutathione.…”

Section: Experimental Animalsmentioning

confidence: 99%

NTP Technical Report on the Toxicity Studies of Hexachlorobenzene (CASRN 118-74-1) Administered by Gavage to Female Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats

2021

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Despite the cessation of its production and use in many parts of the world, hexachlorobenzene (HCB) remains highly persistent in the environment, and chronic, low-dose exposure to HCB in humans continues. Its structural resemblance to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), ability to activate the aryl hydrocarbon (Ah) receptor, TCDD-like toxicities, and bioaccumulative nature suggest HCB be included in the toxic equivalency factor (TEF) methodology. Consequently, the National Toxicology Program conducted this subchronic study of HCB, including measurement of a variety of toxicological and biochemical endpoints, to allow comparison to TCDD data obtained in a previous 2-year bioassay. Groups of 10 female Sprague Dawley (Hsd:Sprague Dawley ® SD ®) rats (core study) were administered doses of 0.03, 0.1, 0.3, 1, 3, 10, or 25 mg HCB/kg body weight/day (mg/kg/day) in corn oil:acetone (99:1) by gavage, 5 days/week for 13 weeks (3 months). Elimination of HCB after repeated dosing was evaluated in a group of 10 female rats (elimination study) administered 0.03 or 25 mg/kg/day for 13 weeks (3 months) and then held without dosing until necropsy at 21 (5 rats) or 29 (5 rats) weeks. Vehicle control female rats (10 core study and 10 elimination study) were administered the corn oil:acetone vehicle only. Genotoxicity in Salmonella typhimurium was also evaluated.

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“…For example, a high-fat diet significantly decreased the accumulation of 2,2′,3,3′,6,6′-hexachlorobiphenyl (PCB136) in mouse adipose tissue (8.6 ± 1.4%) compared to a normal diet (11.5 ± 0.7%), which was attributed to the higher excretion of nonabsorbed PCB 136 with undigested fat in faeces . In contrast, Nakashima et al suggested that a high-fat diet could alter the fat tissue mass and further enhance the accumulation of hexachlorobenzene in rat fat tissue . The studies mentioned above mainly focused on the bioavailability of pure contaminants under the influence of food; however, information regarding coingested food effects on HOC bioavailability in soil is limited.…”

Section: Introductionmentioning

confidence: 99%

“…5 In contrast, Nakashima et al suggested that a high-fat diet could alter the fat tissue mass and further enhance the accumulation of hexachlorobenzene in rat fat tissue. 6 The studies mentioned above mainly focused on the bioavailability of pure contaminants under the influence of food; however, information regarding coingested food effects on HOC bioavailability in soil is limited. Some soil ingestion bioaccessibility assays have incorporated food into in vitro tests to mimic digestive tract conditions as a "fed" state.…”

Section: ■ Introductionmentioning

confidence: 99%

The Influence of Food on the In Vivo Bioavailability of DDT and Its Metabolites in Soil

Chen

Juhasz

et al. 2020

Environ. Sci. Technol.

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Incidental soil ingestion is considered to be an important route of exposure to hydrophobic organic contaminants (HOCs), such as dichlorodiphenyl-trichloroethane (DDT). Contaminant ingestion often occurs during food consumption; however, knowledge on the influence of food on DDT bioavailability remains limited. In this study, the relative bioavailability (RBA) of soil DDTr (i.e., DDT and metabolites) was determined using an in vivo mouse model in the presence of eight kinds of food including rice, egg, pork, pear, soybean, bread, spinach, and milk powder. The values of DDTr-RBA ranged from 19.8 ± 10.9 to 114 ± 25.1%. DDTr-RBA was positively correlated with fat (r = 0.71) and negatively correlated with fiber (r = 0.63) content in food. A mechanistic study showed that fat enhanced micellarization and promoted the formation of chylomicron, which facilitated the dissolution and transport of DDTr in the intestinal tract. Bioaccessibility of DDTr was determined using a physiologically based in vitro method. The addition of lipase significantly improved the ability of the method to predict DDTr-RBA, indicating that the "fasted state" in vitro method required optimization for food scenarios. To the best of our knowledge, this is the first study to explore the mechanistic influence of food on DDTr-RBA and provide important knowledge on dietary approaches for reducing exposure to HOCs.

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High-Fat Diet Enhances Accumulation of Hexachlorobenzene in Rat Dams and Delays Its Transfer from Rat Dams to Suckling Pups through Milk

Cited by 5 publications

References 19 publications

Factors affecting the storage and excretion of toxic lipophilic xenobiotics

Factors affecting the storage and excretion of toxic lipophilic xenobiotics

NTP Technical Report on the Toxicity Studies of Hexachlorobenzene (CASRN 118-74-1) Administered by Gavage to Female Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats

The Influence of Food on the In Vivo Bioavailability of DDT and Its Metabolites in Soil

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