Placental transfer of ruthenium in rat and guinea-pig.

Ruthenium-106 in citrate solution was administered intravenously to rat at different stages of pregnancy and to guinea-pig either before conception or in late pregnancy. The results for rat showed that retention in the embryo/foetus measured at 3-5 days after administration increased from about 0.0002% of injected activity per embryo/foetus on day 12 of gestation to about 0.05% at birth. The relative concentrations of 106Ru in embryo/foetus and mother (Cf/Cm ratio) were about 0.1 in each case. Concentrations in the yolk sac on day 12 were about 1% g-1 compared with 0.01% g-1 in the foetus. Retention in the guinea-pig foetus in late gestation at 7 days after administration (days 50-57) was about 0.2% injected activity per foetus, corresponding to a Cf/Cm = 0.2. Retention in each foetoplacental unit was 2% of injected 106Ru with 50% in the yolk sac, 35% in the placenta and 10% in the foetus. For administration 4 weeks prior to conception, the level of 106Ru retained in the foetus on day 57 of gestation was two orders of magnitude lower than after short-term administration, with a Cf/Cm about 0.004.

Induction of osteosarcoma and acute myeloid leukaemia in CBA/H mice by the alpha-emitting nuclides, uranium-233, plutonium-239 and amercium-241.

PURPOSE: To compare tumour induction in CBA/H mice, principally osteosarcoma and acute myeloid leukaemia, resulting from exposure to the alpha-emitting nuclides, uranium-233, plutonium-239 and americium-241, and to relate differences between the three nuclides to the pattern of dose delivery within tissues. MATERIALS AND METHODS: Each nuclide was administered intraperitoneally in citrate solution to three groups of adult male CBA/H mice at levels of activity which gave estimated life-time average skeletal doses of about 0.25-0.3 Gy, 0.5-1 Gy and 1-2 Gy. Animals were carefully monitored and sacrificed as soon as they showed signs of ill health; tumours were identified by standard histopathological techniques. RESULTS: Statistical modelling by Cox regression showed that, considering all three nuclides together, there was a highly significant increase in risk of death from osteosarcoma or myeloid leukaemia with increasing dose rate. For osteosarcoma, the effect was significantly greater for 239Pu than 241Am, while separate analysis for 233U showed no significant increase with increasing dose rate. For example, the increase in relative risk of death from osteosarcoma for an increase in life-time average dose rate to bone of 1 mGyd(-1) was 4.2 (2.7-6.5) for 239Pu, 2.3 (1.4-3.4) for 241Am and 1.1 (0.4-3.1) for 233U. For myeloid leukaemia, there was no significant difference between 239Pu and 241Am in the effect of dose rate. The increase in relative risk from myeloid leukaemia for an increase in average dose rate of 1 mGyd(-1) was 1.8 (1.1-2.8) for 239Pu, 2.0 (1.4-2.9) for 241Am and 1.5 (0.8-2.7) for 233U. Significant increases in renal and hepatic carcinomas were also recorded in animals exposed to 233U and 241Am, respectively. Studies of the distribution of the nuclides within the skeleton, published separately, have shown differences in their retention in individual bones and within bone. The proportions of decays occurring near to endosteal bone surfaces and throughout bone marrow were in the order: 239Pu> 241Am>233U. CONCLUSIONS: For osteosarcoma, the relative effectiveness of the nuclides in terms of average bone dose, in the order 239Pu>241Am>233U, is consistent with the proportion of dose delivered near to endosteal surfaces. For myeloid leukaemia, the greater effectiveness of 239Pu and 241Am than 233U is consistent with their accumulation in marrow.

Gastrointestinal absorption and retention of polonium in adult and newborn rats and guinea pigs.

The gastrointestinal absorption of 210Po was determined by comparing tissue retention after oral and systemic administration. The results indicate an increase in absorption in adult rats for 210Po administered in liver compared with 210Po nitrate with estimated absorption of 5 and 13%, respectively. For 210Po citrate, values of about 7% were obtained in 1-day-old neonate and adult rats while absorption in guinea pigs was estimated to be about 23% in 1-day-old neonates, 17% in 5-day-old neonates, and 9% in adults. Gut retention of ingested 210Po in neonates was high in rats but not guinea pigs. In adult animals, but not neonates, the liver accounted for a greater proportion of 210Po reaching the bloodstream after ingestion than after systemic injection. The significance of these results is discussed in relation to current assumptions made in the calculation of doses from 210Po.

Transfer of polonium to the embryo and foetus of rat and guinea pig.

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.