Gastrointestinal Absorption and Retention of Polonium in Adult and Newborn Rats and Guinea Pigs

Haines, Jackie; Naylor, G P; Pottinger, H.; Harrison, John

doi:10.1080/09553009314551181

Cited by 16 publications

(8 citation statements)

References 9 publications

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“…Evidence also suggests that milk in the GI tract enhances absorption of certain xenobiotics and may contribute to the age differences in bioavailability (Kostial et al, 1978;NRC, 1993). Increased GI absorption in developing animals has been observed after exposure to lead (Bowers and Cohen, 1998;NRC, 1993; United States Environmental Protection Agency (U.S. EPA), 1994) polonium nitrate (Haines et al, 1993), mercuric chloride (Walsh, 1982), and for select pharmaceuticals (Hoffman, 1982;NRC, 1993).…”

Section: Discussionmentioning

confidence: 99%

Differences in Tissue Distribution of HBCD Alpha and Gamma between Adult and Developing Mice

Szabo¹,

Diliberto²,

Huwe³

et al. 2011

Toxicological Sciences

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Hexabromocyclododecane (HBCD) is a mixture of three stereoisomers alpha (α), beta (β), and gamma (γ). γ-HBCD dominates the mixture (∼70%), and despite α-HBCD's minor contribution to global HBCD production and usage (∼10%), it is the dominant congener found in most biotic samples worldwide. Evidence of toxicity and lack of stereoisomer studies drives the importance of understanding HBCD toxicokinetics in potentially susceptible populations. The majority of public health concern has focused on hazardous effects resulting from exposure of infants and young children to HBCD due to reports on adverse developmental effects in rodent studies, in combination with human exposure estimates suggesting that nursing infants and young children have the highest exposure to HBCD. This study was designed to investigate differences in the disposition of both γ-HBCD and α-HBCD in infantile mice reported to be susceptible to the HBCD commercial mixture. The tissue distribution of α-[(14)C]HBCD- and γ-[(14)C]HBCD-derived radioactivity was monitored in C57BL/6 mice following a single oral dose of either compound (3 mg/kg) after direct gavage at postnatal day 10. Mice were held up to 7 days in shoebox cages after which pups were sacrificed, tissue collected, and internal dosimetry was measured. Developing mice exposed to α-HBCD had an overall higher body burden than γ-HBCD at every time point measured; at 4 days postexposure, they retained 22% of the α-HBCD administered dose, whereas pups exposed to γ-HBCD retained 10%. Total body burden in infantile mice after exposure to γ-HBCD was increased 10-fold as compared with adults. Similarly, after exposure to α-HBCD, infantile mice contained 2.5-fold higher levels than adult. These differences lead to higher concentrations of the HBCD diastereomers at target tissues during critical windows of development. The results indicate that the toxicokinetics of the two HBCD diastereomers differ between developing and adult mice; whereas distribution patterns are similar, concentrations of each HBCD diastereomer's-derived radioactivity are higher in the pup's liver, fat, kidney, brain, blood, muscle, and lungs than in the adult's. This study suggests that developmental stage may be a risk factor for the harmful effects of α-HBCD and γ-HBCD, when developing animals may be more sensitive to effects and have increased body burden.

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Section: Discussionmentioning

confidence: 99%

Differences in Tissue Distribution of HBCD Alpha and Gamma between Adult and Developing Mice

Szabo¹,

Diliberto²,

Huwe³

et al. 2011

Toxicological Sciences

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“…The fraction of 210 Po absorbed from the digestive tract into the blood (f1) ranges from 3% to 80% (Harrison et al 2007). Experimental data indicate greater absorption of biologically incorporated 210 Po than of inorganic 210 Po (Haines et al 1993). In some areas, caribou and shellfish are important sources of 210 Po in the diet of humans.…”

Section: Po Biokinetics and Biodistribution After Ingestionmentioning

confidence: 99%

Occurrence of ²¹⁰ Po and Biological Effects of Low-Level Exposure: The Need for Research

Seiler

2012

Environ Health Perspect

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Background: Polonium-210 (210Po) concentrations that exceed 1 Bq/L in drinking-water supplies have been reported from four widely separated U.S. states where exposure to it went unnoticed for decades. The radionuclide grandparents of 210Po are common in sediments, and segments of the public may be chronically exposed to low levels of 210Po in drinking water or in food products from animals raised in contaminated areas.Objectives: We summarized information on the environmental behavior, biokinetics, and toxicology of 210Po and identified the need for future research.Methods: Potential linkages between environmental exposure to 210Po and human health effects were identified in a literature review.Discussion: 210Po accumulates in the ovaries where it kills primary oocytes at low doses. Because of its radiosensitivity and tendency to concentrate 210Po, the ovary may be the critical organ in determining the lowest injurious dose for 210Po. 210Po also accumulates in the yolk sac of the embryo and in the fetal and placental tissues. Low-level exposure to 210Po may have subtle, long-term biological effects because of its tropism towards reproductive and embryonic and fetal tissues where exposure to a single alpha particle may kill or damage critical cells. 210Po is present in cigarettes and maternal smoking has several effects that appear consistent with the toxicology of 210Po.Conclusions: Much of the important biological and toxicological research on 210Po is more than four decades old. New research is needed to evaluate environmental exposure to 210Po and the biological effects of low-dose exposure to it so that public health officials can develop appropriate mitigation measures where necessary.

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“…Owing to the volatility of Po, the tissue samples were wet ashed using a variation of published techniques (Fink 1950, Stannard 1964, as described previously (Haines et al 1993) . Aliquots of the digest solutions were added to PCS scintillation cocktail (Amersham Corp ., USA) and counted using a liquid scintillation counter (LKB-Wallac 1219 Rackbeta) .…”

Section: 4 Measurement Of 210pomentioning

confidence: 99%

Transfer of Polonium to the Embryo and Foetus of Rat and Guinea Pig

Haines¹,

Harrison²,

Pottinger³

et al. 1995

International Journal of Radiation Biology

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Transfer of 210Po to the foetus measured 3 days after administration in rat and 7 days later in guinea pig increased with increasing gestational age to about 0.1% injected activity per rat foetus at birth and 0.6% per guinea pig foetus on day 57, corresponding to whole-body foetus:mother concentration ratios of about 0.1:1 in both species. The greatest concentrations of 210Po were measured in the rat yolk sac during its haemopoietic stage, an order of magnitude greater than concentrations in the placenta and two orders of magnitude greater than foetal concentrations. The results obtained have been used to estimate in utero doses to haemopoietic tissues, taking account of transfer to the blastocyst/egg cylinder, yolk sac, liver and bone marrow. The concentration ratios relative to maternal liver for these tissues were taken to be 1, 3, 0.1 and 0.05 respectively and were applied to periods of human gestation of 0-2.5, 2.5-6, 6-12 and 12-38 weeks respectively. For chronic maternal intake by ingestion of 210Po during the year of pregnancy giving a committed effective dose (CED) to the mother of 1 mSv, the total in utero dose to haemopoietic tissue was about 340 microSv compared with a maternal red bone marrow dose of 2.2 mSv. The yolk sac and bone marrow accounted for 66 and 27% of the in utero dose respectively. In addition, the total CED to the offspring was calculated assuming a whole-body foetus:mother concentration ratio of 0.1:1 and that the distribution of 210Po between tissues was the same in the foetus as in adults and children. For chronic intake of 210Po during the year of pregnancy as assumed above, the CED to the offspring was estimated to be 8% of that to the mother.

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Gastrointestinal Absorption and Retention of Polonium in Adult and Newborn Rats and Guinea Pigs

Cited by 16 publications

References 9 publications

Differences in Tissue Distribution of HBCD Alpha and Gamma between Adult and Developing Mice

Differences in Tissue Distribution of HBCD Alpha and Gamma between Adult and Developing Mice

Occurrence of ²¹⁰ Po and Biological Effects of Low-Level Exposure: The Need for Research

Transfer of Polonium to the Embryo and Foetus of Rat and Guinea Pig

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Gastrointestinal Absorption and Retention of Polonium in Adult and Newborn Rats and Guinea Pigs

Cited by 16 publications

References 9 publications

Differences in Tissue Distribution of HBCD Alpha and Gamma between Adult and Developing Mice

Differences in Tissue Distribution of HBCD Alpha and Gamma between Adult and Developing Mice

Occurrence of 210 Po and Biological Effects of Low-Level Exposure: The Need for Research

Transfer of Polonium to the Embryo and Foetus of Rat and Guinea Pig

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Occurrence of ²¹⁰ Po and Biological Effects of Low-Level Exposure: The Need for Research