Tissue distribution and excretion of tritiated tetrachlorodibenzo-p-dioxin in non-human primates and rats

Miller, John P.; Marlar, R. J.; Allen, James

doi:10.1016/s0015-6264(76)80360-4

Cited by 82 publications

(9 citation statements)

References 15 publications

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“…This result is confirmed in our studies using a smaller dose. In adult rhesus monkeys van Miller et al (1976) reported a percentage of 10.4% of a given dose in the whole liver 7 days following a single administration of the extremely high (and probably lethal) dose of 400 lag 2,3,7,8-T4CDD/kg body wt. In the same Macaca mulatta species Birnbaum et al (1981) found about 1% of the dose in whole liver 21 days after treatment with 30.7 ~g 2,3,7,8-T4CDF/kg body wt.…”

Section: Tissue Distributionmentioning

confidence: 99%

Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys

et al. 1990

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A defined mixture of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) was subcutaneously administered to marmoset monkeys (Callithrix jacchus). Tissue concentrations in hepatic and adipose tissue were measured at different times after treatment (1-28 weeks). One week after application high concentrations could be detected for the 2,3,7,8-substituted congeners only. The percent of the administered dose in whole liver differed for the various 2,3,7,8-substituted congeners, ranging from 24.5 +/- 4.5% for 2,3,7,8-TCDD to 74.1 +/- 4.9% for 2,3,4,6,7,8-H6CDF. Therefore, the concentration ratio (liver/adipose tissue) was also very different, ranging from about 1 (2,3,7,8-T4CDD or 2,3,7,8-T4CDF) to greater than 10 in the case of some higher chlorinated PCDDs and PCDFs. Half-lives of PCDDs and PCDFs were very different for the various 2,3,7,8-substituted congeners. For the most toxic compound (2,3,7,8-T4CDD) a t/2 of about 8 weeks in hepatic tissue and about 11 weeks in adipose tissue was found when calculated from data obtained later than 6 weeks after injection. For 2,3,7,8-T4CDD and 1,2,3,7,8-P5CDD the decreases in hepatic concentrations were much faster during the first 6 weeks after administration (t/2 of 4 weeks). This was apparently due to redistribution phenomena. Half-life increased with increasing degrees of chlorination. In some cases (e.g. OCDD, OCDF) no significant decrease in tissue concentrations could be observed after 28 weeks. The shortest t/2 was determined for 2,3,7,8-T4CDF: shorter than 6 days in hepatic tissue and about 10 days in adipose tissue. Calculation of the body burden of the non-2,3,7,8-substituted PCDDs/PCDFs 1 week after injection revealed that all groups of isomers were present at less than 5%. Consequences of these findings for the use of TCDD-toxic-equivalency factors are discussed and a change in strategy is suggested.

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Section: Tissue Distributionmentioning

confidence: 99%

Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys

et al. 1990

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“…15) In rhesus monkeys, the urinary elimination was reported to be 28% of that in feces. 16) Further, daily intake from meals and daily excretion from feces have been studied in German people who had been with and without occupational exposure, and it has been suggested that the level of daily excretion from feces exceeded that of daily intake in both cases. 7,17) However, it has been demonstrated that sebum plays an important role in excretion in addition to feces.…”

Section: Introductionmentioning

confidence: 99%

Balance of Intake and Excretion of 20 Congeners of Polychlorinated Dibenzo-p-dioxin, Polychlorinated Dibenzofuran and Coplanar Polychlorinated Biphenyl in Healthy Japanese Men.

Kitamura

Nagahashi

Sunaga

et al. 2001

JOURNAL OF HEALTH SCIENCE

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Daily intake from meals, and excretion from feces and sebum of 20 congeners of polychlorinated dibenzo-pdioxin (PCDD), polychlorinated dibenzofuran (PCDF) and coplanar polychlorinated biphenyl (Co-PCB) were analyzed in healthy Japanese men who are considered to be a standard for the Japanese. Daily intake of these congeners was 84.2 ± 12.5 pg toxic equivalent (TEQ) and daily excretion from feces and sebum were 18.3 ± 5.9 and 23. 8 ± 5.6 pg TEQ, respectively, indicating 22% the daily intake of dioxins from meals is excreted from feces and 29% from sebum. 1,2,3,7,8-Pentachlorodibenzo-p-dioxin (1,2,3,7,2,3,4,7,3,4,7, and 3,3′,4,4′,5-pentachlorobiphenyl (3,3′, 4,4′,5-PeCB) were most abundant in TEQ, in meals, feces, sebum and blood. Co-PCBs were most efficiently excreted among three congener groups in TEQ, especially from sebum. Octachlorodibenzo-p-dioxin (OCDD), 2,3,7,3,7, and 3,3′,4,4′-tetrachlorobiphenyl (3,3′,4,4′-TCB) were well absorbed from intestine and excreted at more than 100% of intake, mainly from the sebum. In contrast, 1,2,3,4,7,2,3,4,7,2,3,7,8,2,3,7,8, were excreted at relatively low levels from sebum, although well absorbed from the intestine, and the excretion ratios were lowest among the 20 congeners. It was suggested that 80.5-85.2% TEQ of each congener-group might be absorbed from the intestine, after taking bile excretion into consideration.

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“…Early kinetic studies on TCDD suggested that in contrast to differences in sensitivity, the fate of TCDD in the body seemed to be notably similar in all species, with the possible exception of the primates (Van Miller et al 1976). The halflife of excretion, for example, was determined to be 17-31 days in the rat (Piper et al 1973;Allen et al 1975; al.…”

mentioning

confidence: 99%

Tissue Distribution, Metabolism, and Excretion of ¹⁴C‐TCDD in a TCDD‐Susceptible and a TCDD‐Resistant Rat Strain^a

Pohjanvirta

Vartiainen

Uusi-Rauva

et al. 1990

Pharmacology & Toxicology

110

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A comparative study was carried out in the most TCDD-resistant [Han/Wistar (H/W), LD50 greater than 3000 micrograms/kg] and the most TCDD-susceptible [Long-Evans (L-E), LD50 about 10 micrograms/kg] rat strain to assess the significance of kinetic factors in TCDD toxicity. Young adult males of both strains were administered 5 micrograms/kg (1.9 microCi/kg) 14C-TCDD intraperitoneally. Four rats per strain were killed at 4 hr, 1, 4, 8, 16, and 32 days after exposure. A total of 22 tissues along with blood and serum were sampled for liquid scintillation counting. From half of the animals, daily urine and faeces were also analyzed. In addition, 3 rats per strain were given 50 micrograms/kg (19 microCi/kg) 14C-TCDD and prepared for whole-body autoradiography after 1, 4 or 8 days. The livers of two rats per strain killed at 4 hr, 4 or 16 days, and the excreta from two rats of both strains collected on days 1-4, 5-8, 13-16, and 29-32 after exposure were analyzed for metabolites of TCDD by high pressure liquid chromatography. The label was mainly excreted in faeces as metabolites of TCDD, and the half-life of elimination was 20.8 (L-E) or 21.9 (H/W) days. A very similar overall distribution pattern was observed in both strains irrespective of dose, and the liver was the major site of accumulation. Practically all liver 14C-activity was found as the parent compound. Moderate strain-related differences were observed in the thyroid, thymus, prostate, adrenals, and brown and white fat, where lower values were recorded in H/W rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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Tissue distribution and excretion of tritiated tetrachlorodibenzo-p-dioxin in non-human primates and rats

Cited by 82 publications

References 15 publications

Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys

Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys

Balance of Intake and Excretion of 20 Congeners of Polychlorinated Dibenzo-p-dioxin, Polychlorinated Dibenzofuran and Coplanar Polychlorinated Biphenyl in Healthy Japanese Men.

Tissue Distribution, Metabolism, and Excretion of ¹⁴C‐TCDD in a TCDD‐Susceptible and a TCDD‐Resistant Rat Strain^a

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Tissue distribution and excretion of tritiated tetrachlorodibenzo-p-dioxin in non-human primates and rats

Cited by 82 publications

References 15 publications

Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys

Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys

Balance of Intake and Excretion of 20 Congeners of Polychlorinated Dibenzo-p-dioxin, Polychlorinated Dibenzofuran and Coplanar Polychlorinated Biphenyl in Healthy Japanese Men.

Tissue Distribution, Metabolism, and Excretion of 14C‐TCDD in a TCDD‐Susceptible and a TCDD‐Resistant Rat Straina

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Tissue Distribution, Metabolism, and Excretion of ¹⁴C‐TCDD in a TCDD‐Susceptible and a TCDD‐Resistant Rat Strain^a