Urinary and faecal excretion of pyrene and hydroxypyrene by rats after oral, intraperitoneal, intratracheal or intrapulmonary application

Jacob, Jürgen; Brune, H.; Gettbarn, G.; Grimmer, Donna; Heinrich, Uwe; Mohtashamipur, E.; Norpoth, K.; Pott, F.; Wenzel-Hartung, R.

doi:10.1016/0304-3835(89)90209-7

Cited by 47 publications

(17 citation statements)

References 15 publications

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“…It is not uncommon for any orally ingested chemical compound, that the unmetabolized component is transported into the lumen of the GI tract and eliminated through feces. Similar to the present study, several other studies have reported unchanged PAHs such as BaP [17], chrysene [18] and pyrene [19] in rats orally exposed to these chemicals. The differences in the levels of unchanged FLA among the vehicles noticed in the present study suggests that the presence of unchanged FLA depend on the bioavailability of the administered dose and lipid content in the vehicle.…”

Section: Discussionsupporting

confidence: 91%

Vehicle-Dependent Disposition Kinetics of Fluoranthene in Fisher-344 Rats

Harris

Hood

Ramesh

2008

IJERPH

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The objective of this study was to evaluate how the vehicles of choice affect the pharmacokinetics of orally administered Fluoranthene [FLA] in rats. Fluoranthene is a member of the family of polycyclic aromatic hydrocarbon chemicals. Fluoranthene exposure to humans may occur as a result of cigarette smoking, consumption of contaminated food and water, heating woods in stoves and boilers, industrial sources such as coal gasification, carbon and graphite electrode manufacturing. Adult male Fisher-344 rats were given single oral doses of 25 and 50 μg/kg FLA in tricaprylin, peanut oil, cod liver oil, tween 80/isotonic saline (1:5) and 2% Alkamuls-EL620 through gavage. After administration, the rats were housed individually in metabolic cages and sacrificed at 2, 4, 6, 8, 10 and 12 hours post FLA exposure. Blood, lung, liver, small intestine, adipose tissue samples, urine, and feces were collected at each time point. Samples were subjected to a liquid-liquid extraction using methanol, chloroform, and water. The extracts were analyzed by a reverse-phase HPLC, equipped with a fluorescence detector. The results revealed a dose-dependent increase in FLA concentrations in plasma and tissues for all the vehicles used. Plasma and tissue FLA concentrations were greater for peanut oil; cod liver oil, and tricaprylin vehicles compared to Alkamuls (p < 0.05), and tween 80/isotonic saline (1:5). Most of the FLA administered through peanut oil, cod liver oil and tricaprylin was cleared from the body by 8 hours (90%) and 12 hours (80%) post administration for the 25 μg/kg and 50 μg/kg dose groups, respectively. With both doses employed, the metabolism of FLA was highest when cod liver oil was used as a vehicle and lowest in vehicles containing detergent/water [cod liver oil > peanut oil > tricaprylin > alkamuls > tween 80/isotonic saline (1:5)]. These findings suggest that uptake and elimination of FLA is accelerated when administered through oil-based vehicles. The low uptake of FLA from alkamuls and tween 80/isotonic saline may have been a result of the poor solubility of the chemical. In summary, our findings reiterate that absorption characteristics of FLA were governed by the dose as well as the dosing vehicle. The vehicle-dependent bioavailability of FLA suggests a need for the judicious selection of vehicles in evaluating oral toxicity studies for risk assessment purposes.

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Section: Discussionsupporting

confidence: 91%

Vehicle-Dependent Disposition Kinetics of Fluoranthene in Fisher-344 Rats

Harris

Hood

Ramesh

2008

IJERPH

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“…If there are no significant differences between the two routes of administration, an oral dose will be used, because it is simpler and more practical. Several previous studies have examined the bioavailability and urinary excretion of BaP and pyrene metabolites after oral, intravenous, cutaneous, intraperitoneal, or intrapulmonary administration to rats (Jacob et al, 1989;Van de Wiel et al, 1993;Bouchard and Viau, 1997). They found that the formation of metabolites varied greatly after different administration routes.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of [D₁₀]Phenanthrene to Tetraols in Smokers for Potential Lung Cancer Susceptibility Assessment: Comparison of Oral and Inhalation Routes of Administration

Zhong¹,

Wang²,

Carmella³

et al. 2011

J Pharmacol Exp Ther

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Polycyclic aromatic hydrocarbons (PAHs) are believed to be among the causative agents for lung cancer in smokers. PAHs require metabolic activation for carcinogenicity. One pathway produces diol epoxides that react with DNA, causing mutations. Because diol epoxides are converted to tetraols, quantitation of tetraols can potentially be used to identify smokers who may be at higher risk for lung cancer. Our approach uses [D 10 ]phenanthrene, a labeled version of phenanthrene, a noncarcinogenic PAH structurally analogous to carcinogenic PAH. Although smokers are exposed to PAH by inhalation, oral dosing would be more practical for phenotyping studies. Therefore, we investigated [D 10 ]phenanthrene metabolism in smokers after administration by inhalation in cigarette smoke or orally. Sixteen smokers received 10 g of [D 10 ]phenanthrene in a cigarette or orally. Plasma and urine samples were analyzed for [D 10 ]r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene ([D 10 ]PheT), the major end product of the diol epoxide pathway, by gas chromatography-negative ion chemical ionization-tandem mass spectrometry. The ratios of [D 10 ]PheT (oral dosing/inhalation) in 15 smokers were 1.03 Ϯ 0.32 and 1.02 Ϯ 0.35, based on plasma area under the concentrationtime curve (0-ϱ) and total 48-h urinary excretion, respectively. Overall, there was no significant difference in the extent of [D 10 ]PheT formation after the two different routes of exposure in smokers. A large interindividual variation in [D 10 ]PheT formation was observed. These results demonstrate that the level of [D 10 ]PheT in urine after oral dosing of [D 10 ]phenanthrene can be used to assess individual capacity of PAH metabolism by the diol epoxide pathway.

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“…The extensive formation of DNA adducts in lung, an organ distant from the site of exposure, indicates that lung is particularly susceptible to genotoxicity induced by chemical components of complex mixtures. Studies have also demonstrated the usefulness of 1-hydroxypyrene excretion in urine as a biological marker of exposure to PAHs (Jongeneelen et al, 1985(Jongeneelen et al, , 1986Jacob et al, 1989). Clonfero and co-workers (1990) recently determined that urinary 1-hydroxypyrene levels correlated in humans treated with pharmaceutical coal tar.…”

Section: Discussionmentioning

confidence: 96%

Biochemical effects of manufactured gas plant residue following ingestion by B6C3F1 mice

Weyand

Patel

et al. 1994

Journal of Toxicology and Environmental Health

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The toxic potential of manufactured gas plant residue (MGP) given in the diet to male and female B6C3F1 mice was evaluated. In addition, the bioavailability of chemical components of MGP were also investigated by monitoring polycyclic aromatic hydrocarbon (PAH) metabolites in urine and DNA adduct formation in forestomach and lung tissue. Basal gel diets containing 0.05, 0.25, 0.50% MGP or 0.005% benzo[a]pyrene (BaP) were fed to animals for 94 and 185 d. Mice readily consumed adulterated diets without any evidence of acute toxicity. The total amount of MGP and BaP consumed by mice ranged from 118 to 2604 mg and from 12 to 29 mg, respectively. Male mice fed a control or BaP diet and female mice fed a 0.05% MGP diet had the highest body weight gains. Male and female mice fed a 0.50% MGP diet had the lowest body weight gains. The bioavailability of chemical components of MGP was evaluated by monitoring the urinary excretion of PAH metabolites by male mice fed a 0.25% MGP diet. 1-Hydroxypyrene was determined by high-performance liquid chromatography analysis to be the major fluorescent metabolite excreted by mice throughout the 185 d of diet administration. At necropsy, no chemical-related gross lesions were detected. In addition, no treatment-related microscopic lesions were evident in tissues obtained from animals fed a 0.50% MGP- or BaP-adulterated diet. The 32P-postlabeling assay was used to evaluate MGP- and BaP-induced DNA adduct formation in lung and forestomach tissue. The level of DNA adducts formed from the chemical components of MGP paralleled the amount of material ingested by animals. Lung DNA adduct levels were considerably higher than forestomach levels when mice ingested a 0.25% or 0.50% MGP diet. These studies demonstrate that the continuous ingestion of MGP or BaP for 185 d does not result in acute toxicity or chemical-related lesions at doses up to 0.50% MGP or 0.005% BaP.

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Urinary and faecal excretion of pyrene and hydroxypyrene by rats after oral, intraperitoneal, intratracheal or intrapulmonary application

Cited by 47 publications

References 15 publications

Vehicle-Dependent Disposition Kinetics of Fluoranthene in Fisher-344 Rats

Vehicle-Dependent Disposition Kinetics of Fluoranthene in Fisher-344 Rats

Metabolism of [D₁₀]Phenanthrene to Tetraols in Smokers for Potential Lung Cancer Susceptibility Assessment: Comparison of Oral and Inhalation Routes of Administration

Biochemical effects of manufactured gas plant residue following ingestion by B6C3F1 mice

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Urinary and faecal excretion of pyrene and hydroxypyrene by rats after oral, intraperitoneal, intratracheal or intrapulmonary application

Cited by 47 publications

References 15 publications

Vehicle-Dependent Disposition Kinetics of Fluoranthene in Fisher-344 Rats

Vehicle-Dependent Disposition Kinetics of Fluoranthene in Fisher-344 Rats

Metabolism of [D10]Phenanthrene to Tetraols in Smokers for Potential Lung Cancer Susceptibility Assessment: Comparison of Oral and Inhalation Routes of Administration

Biochemical effects of manufactured gas plant residue following ingestion by B6C3F1 mice

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Metabolism of [D₁₀]Phenanthrene to Tetraols in Smokers for Potential Lung Cancer Susceptibility Assessment: Comparison of Oral and Inhalation Routes of Administration