In vivo animal studies help achieve international consensus on standards and guidelines for health risk estimates for chronic exposure to low levels of tritium in drinking water
Abstract:Existing and future nuclear fusion technologies involve the production and use of large quantities of tritium, a highly volatile, but low toxicity beta-emitting isotope of hydrogen. Tritium has received international attention because of public and scientific concerns over its release to the environment and the potential health impact of its internalization. This article provides a brief summary of the current state of knowledge of both the biological and regulatory aspects of tritium exposure; it also explore… Show more
“…These results suggest that the molecular changes detected for ferritin and iron are not linked to major histological changes in the intestinal wall. This confirms and extends previous results indicating the absence of major changes in apoptosis or in proliferation within intestinal epithelial cells, regardless of duration or group of exposure 26 .Figure 9Histological and immuno-histological analysis of the intestine. ( A ) HES staining of intestine section, showing a normal appearance of villi (large arrow) and crypts (thin arrows).…”
Section: Resultssupporting
confidence: 89%
“…This means that a TAA concentration of 10 kBq.l −1 in water should correspond to an overall concentration of tritium of <1000 GBq.l −1 . Since in the present study effects of a 20 MBq.l −1 HTO concentration produced only limited effects and recognizing that similar results were obtained in other studies in the same model 26,43,45,53 , it appears that the occurrence of biological effects attributable to an OBT form of tritium at the regulatory concentration level in drinking water is highly unlikely. Therefore, the current regulations about tritium in drinking water appear to be defendable as sufficiently protective.…”
Section: Discussionsupporting
confidence: 89%
“…However, one cannot exclude the possibility that damage was produced by the local concentration of TAA elsewhere in the organism. Nevertheless, we think that this is unlikely, since analyses of toxicity in various tissues of the same mice used in this study did not reveal any tissue or metabolic major specific effects 26 . It would be of interest to test this hypothesis using other forms of OBT with a different metabolic behaviour, such as polysaccharides or lipids.…”
Section: Discussionmentioning
confidence: 75%
“…The fact that hepcidin is decreased in the blood both after one month of exposure and that level of hemoglobin is compensated through increased life span of RBC suggests that the RBC decrease could originate either in a defect in iron capture in the intestine, or in an increase in iron elimination by the kidney. Previous results indicated that kidney function appears normal as assessed with urine biochemical parameters; however a definite increase in inflammation and oxidative stress were observed 26 . The normal renal function was consistent with our results showing a normal expression of EPO mRNA and a normal EPO level in the blood.…”
Section: Discussionmentioning
confidence: 93%
“…To fill the knowledge gap, a large-scale in vivo mouse study was conducted to study the biokinetics and non-cancerous/carcinogenic effects of tritium incorporation at low concentrations relevant to possible human exposures and current regulations. Details about this large-scale study have been published 26 . Two different forms of tritium were used, HTO and OBT (in the form of a mixture of three amino acids (AA), alanine, glycine and proline).…”
The increased potential for tritium releases from either nuclear reactors or from new facilities raises questions about the appropriateness of the current ICRP and WHO recommendations for tritium exposures to human populations. To study the potential toxicity of tritium as a function of dose, including at a regulatory level, mice were chronically exposed to tritium in drinking water at one of three concentrations, 10 kBq.l−1, 1 MBq.l−1 or 20 MBq.l−1. Tritium was administered as either HTO or as tritiated non-essential amino acids (TAA). After one month’s exposure, a dose-dependent decrease in red blood cells (RBC) and iron deprivation was seen in all TAA exposed groups, but not in the HTO exposed groups. After eight months of exposure this RBC decrease was compensated by an increase in mean globular volume - suggesting the occurrence of an iron deficit-associated anemia. The analysis of hematopoiesis, of red blood cell retention in the spleen and of iron metabolism in the liver, the kidneys and the intestine suggested that the iron deficit was due to a decrease in iron absorption from the intestine. In contrast, mice exposed to external gamma irradiation at equivalent dose rates did not show any change in red blood cell numbers, white blood cell numbers or in the plasma iron concentration. These results showed that health effects only appeared following chronic exposure to concentrations of tritium above regulatory levels and the effects seen were dependent upon the speciation of tritium.
“…These results suggest that the molecular changes detected for ferritin and iron are not linked to major histological changes in the intestinal wall. This confirms and extends previous results indicating the absence of major changes in apoptosis or in proliferation within intestinal epithelial cells, regardless of duration or group of exposure 26 .Figure 9Histological and immuno-histological analysis of the intestine. ( A ) HES staining of intestine section, showing a normal appearance of villi (large arrow) and crypts (thin arrows).…”
Section: Resultssupporting
confidence: 89%
“…This means that a TAA concentration of 10 kBq.l −1 in water should correspond to an overall concentration of tritium of <1000 GBq.l −1 . Since in the present study effects of a 20 MBq.l −1 HTO concentration produced only limited effects and recognizing that similar results were obtained in other studies in the same model 26,43,45,53 , it appears that the occurrence of biological effects attributable to an OBT form of tritium at the regulatory concentration level in drinking water is highly unlikely. Therefore, the current regulations about tritium in drinking water appear to be defendable as sufficiently protective.…”
Section: Discussionsupporting
confidence: 89%
“…However, one cannot exclude the possibility that damage was produced by the local concentration of TAA elsewhere in the organism. Nevertheless, we think that this is unlikely, since analyses of toxicity in various tissues of the same mice used in this study did not reveal any tissue or metabolic major specific effects 26 . It would be of interest to test this hypothesis using other forms of OBT with a different metabolic behaviour, such as polysaccharides or lipids.…”
Section: Discussionmentioning
confidence: 75%
“…The fact that hepcidin is decreased in the blood both after one month of exposure and that level of hemoglobin is compensated through increased life span of RBC suggests that the RBC decrease could originate either in a defect in iron capture in the intestine, or in an increase in iron elimination by the kidney. Previous results indicated that kidney function appears normal as assessed with urine biochemical parameters; however a definite increase in inflammation and oxidative stress were observed 26 . The normal renal function was consistent with our results showing a normal expression of EPO mRNA and a normal EPO level in the blood.…”
Section: Discussionmentioning
confidence: 93%
“…To fill the knowledge gap, a large-scale in vivo mouse study was conducted to study the biokinetics and non-cancerous/carcinogenic effects of tritium incorporation at low concentrations relevant to possible human exposures and current regulations. Details about this large-scale study have been published 26 . Two different forms of tritium were used, HTO and OBT (in the form of a mixture of three amino acids (AA), alanine, glycine and proline).…”
The increased potential for tritium releases from either nuclear reactors or from new facilities raises questions about the appropriateness of the current ICRP and WHO recommendations for tritium exposures to human populations. To study the potential toxicity of tritium as a function of dose, including at a regulatory level, mice were chronically exposed to tritium in drinking water at one of three concentrations, 10 kBq.l−1, 1 MBq.l−1 or 20 MBq.l−1. Tritium was administered as either HTO or as tritiated non-essential amino acids (TAA). After one month’s exposure, a dose-dependent decrease in red blood cells (RBC) and iron deprivation was seen in all TAA exposed groups, but not in the HTO exposed groups. After eight months of exposure this RBC decrease was compensated by an increase in mean globular volume - suggesting the occurrence of an iron deficit-associated anemia. The analysis of hematopoiesis, of red blood cell retention in the spleen and of iron metabolism in the liver, the kidneys and the intestine suggested that the iron deficit was due to a decrease in iron absorption from the intestine. In contrast, mice exposed to external gamma irradiation at equivalent dose rates did not show any change in red blood cell numbers, white blood cell numbers or in the plasma iron concentration. These results showed that health effects only appeared following chronic exposure to concentrations of tritium above regulatory levels and the effects seen were dependent upon the speciation of tritium.
For a more systematic understanding of the levels of environmental tritium and its behavior in East Asia, a database on environmental tritium was established based on the literature published in the past 30 years. Subsequently, the levels and behavior of the environmental tritium were further studied by statistical analyses. The results indicate that the distribution of environmental tritium is inhomogeneous and complex. In areas without nuclear facilities, the level of environmental tritium has decreased to its background level, even though a certain number of atmospheric nuclear tests were performed before 1980. In general, the level of atmospheric tritium was marginally higher than the levels in precipitation and surface water; the levels in shallow groundwater and seawater were considerably lower. Furthermore, the levels of tritium in the atmosphere, precipitation, and inland surface water were strongly correlated with latitude and distance from the coastline. In soil and living organisms, the level of tissue-free water tritium (TFWT) was comparable to the tritium levels in local rainfall, whereas the persistence of organically bound tritium (OBT) in the majority of organisms resulted in an OBT/TFWT ratio greater than one. Conversely, extremely high levels of environmental tritium were observed near certain nuclear power plants and the Fukushima accident sites. These results highlight the requirement to know the tritium baseline level and its behavior in the environment beforehand to better assess the impact of tritium discharge. Further investigations of environmental tritium in East Asia using more efficient and adequate monitoring methods are also required.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
