Plutonium and environmental and health effects

 TOXICOLOGICAL PROFILE FOR PLUTONIUM , Agency for Toxic Substances and Disease Registry Division of Toxicology and Environmental Medicine/Applied Toxicology Branch,  Atlanta, Georgia“……….HOW CAN PLUTONIUM AFFECT MY HEALTH? Plutonium may remain in the lungs or move to the bones, liver, or other body organs. It generally stays in the body for decades and continues to expose the surrounding tissues to radiation. Lung, liver, and bone cancer You may develop cancer depending on how much plutonium is in your body and for how long it remains in your body. The types of cancers you would most likely develop are cancers of the lung, bones, and liver. These types of cancers have occurred in workers who were exposed to plutonium in air at much higher levels than is in the air that most people breathe. Affect ability to fight infections In laboratory animals, plutonium affected the animal’s ability to resist disease (immune system). More information on the health effects of plutonium is presented in Chapters 2 and 3………

  2.2 SUMMARY OF HEALTH EFFECTS Risks for adverse outcomes of plutonium exposures are strongly dependent on radiation doses received by specific tissues and organ systems. Most of the body burden of plutonium resides in the skeleton and liver, and following inhalation exposures, in the lung and lung-associated lymph nodes. As a result, these tissues receive relatively high radiation doses following exposures to plutonium. Radiation-induced toxicity to these tissues has been documented in human epidemiological studies and in animal models. The relatively high radiation doses received by bone, liver, and lung lend greater credibility to the epidemiological findings for these tissues than for outcomes in other tissues that receive much smaller radiation doses. All epidemiological studies that have reported adverse outcomes in these tissues have studied populations (i.e., workers in plutonium production and processing facilities) that experienced exposures and radiation doses that greatly exceed those experienced by the general public. Accordingly, risks for these outcomes in the general population are substantially lower than reported for these more highly exposed worker populations.
Death. Possible associations between exposure to plutonium and mortality have been examined in studies of workers at the U.S. plutonium production and/or processing facilities (Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (e.g., Mayak) and the United Kingdom (e.g., Sellafield). The Mayak studies provide relatively strong evidence for an association between cancer mortality (bone, liver, lung) and exposure to plutonium. Plutonium dose-response relationships for lung cancer mortality have been derived from studies of Mayak workers, who received much higher uptakes of plutonium compared to other epidemiological cohorts (i.e., mean body burdens 0.09–9.2 kBq, with much higher individual exposures [up to 470 kBq] in relatively large numbers of these workers). Excess relative risk (ERR) estimated in three studies (adjusted for smoking) were 3.9 per Gy (95% confidence interval [CI]: 2.6– 5.8) in males, and 19 per Gy (95% CI: 9.5–39) in females (attained age 60 years), 4.50 per Gy (95% CI: 3.15–6.10) in males, and 0.11 per Sv (95% CI: 0.08–0.17) or 0.21 per Sv (95% CI: 0.15–0.35), depending on the smoking-radiation interaction model that was assumed (these estimates per Sv correspond to 2.2 or 4.3 per Gy, respectively, assuming a radiation weighting factor of 20 for -radiation). The ERR per Gy in Mayak workers declined strongly with attained age. In a recent cohort mortality study of the Mayak workers, significant plutonium dose-response relationships (p<0.001) were found for deaths due to lung or liver cancer, and for deaths in which bone cancer was considered a contributing cause. At attained age of 60 years, ERRs for lung cancer were 7.1 per Gy (95% CI: 4.9–10) in males and 15 per Gy (95% CI: 7.6–29) in females. Averaged-attained age ERRs for liver cancer were 2.6 per Gy (95% CI: 0.7–6.9) for males and 29 per Gy (95% CI: 9.8–95) for females, and averaged-attained age ERRs for bone cancer were 0.76 per Gy (95% CI: <0–5.2) for males and 3.4 per Gy (95% CI: 0.4–20) for females. Elevated risks for bone cancer were observed only for workers with plutonium doses exceeding 10 Gy. For lung and bone cancer, the ERR declined with attained age, and for lung cancer, the ERR declined with age at first plutonium exposure.
Decreased survival was noted in beagle dogs exposed to plutonium aerosols (238PuO2, 239PuO2, or 239Pu(NO3)4) at levels resulting in initial lung burdens in the range of ≥1 kBq/kg body weight. Early deaths were attributed to radiation pneumonitis and decreased survival late in life was typically associated  with tumor development.
 Cancer. Possible associations between exposure to plutonium and cancer mortality and morbidity have been examined in studies of workers at the U.S. plutonium production and/or processing facilities (Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (Mayak) and the United Kingdom (e.g., Sellafield). Compared to studies of U.K. and U.S. facilities, the Mayak cohorts had relatively high uptakes of plutonium (i.e., mean body burdens as high as 9.2 kBq, with much higher individual uptakes [up to 470 kBq] in relatively large numbers of these workers). Collectively, the Mayak studies provide evidence for an association between cancer mortality (lung, liver, bone) and uptake of plutonium. Studies of U.K. and U.S. facilities have examined cohorts of workers who had substantially lower estimated plutonium uptakes and corresponding internal radiation doses than the Mayak cohorts (e.g., Sellafield: ≤1 kBq in 97% of the assessed workers; Los Alamos: mean body burden 0.970 kBq, range 0.05– 3.18 kBq). Although a significantly higher incidence of cancer mortality in certain groups of plutonium workers has been found in some studies, higher cancer incidence and/or risks for tissues that received the highest plutonium radiation doses (i.e., lung, liver, bone) have not been found, making causal connections of these outcomes to plutonium exposure more uncertain. The Sellafield study is by far the strongest of these studies and did not find associations between plutonium exposure and cancers to tissues receiving the highest radiation doses from plutonium.
  Plutonium dose-response relationships for lung cancer mortality and morbidity have been corroborated in four Mayak studies. Estimated excess relative risk in these four studies (adjusted for smoking) were as follows: (1) 3.9 per Gy (95% CI: 2.6–5.8) in males and 19 per Gy (95% CI: 9.5–39) in females; (2) 7.1 per Gy (95% CI: 4.9–10) in males and 15 per Gy (95% CI: 7.6–29) in females at attained age of 60 years; (3) 4.50 per Gy (95% CI: 3.15–6.10) in males; and (4) 0.11 per Sv (95% CI: 0.08–0.17) or 0.21 per Sv (95% CI: 0.15–0.35), depending on the smoking-radiation interaction model that was assumed (these estimates per Sv correspond to 2.2 or 4.3 per Gy, respectively, assuming a radiation weighting factor of 20 for “-radiation).
  The risks of mortality and morbidity from bone and liver cancers have also been studied in Mayak workers. Increasing estimated plutonium body burden was associated with increasing liver cancer mortality, with higher risk in females compared to males. Relative risk for liver cancer for a cohort of males and females was estimated to be 17 (95% CI: 8.0–26) in association with plutonium uptakes >7.4 kBq; however, when stratified by gender, the relative risk estimates for females was 66 (95% CI: 16–45) and higher than for males, 9.2 (95% CI: 3.3–23). Risk of bone cancer mortality in this same cohort (n=11,000) was estimated to be 7.9 (95% CI: 1.6–32) in association with plutonium uptakes >7.4 kBq (males and females combined). Risks of leukemia mortality, in the same cohort, were not associated with internal plutonium exposure. In a case control study of Mayak workers, the odds ratio for liver cancer was 11.3 (95% CI: 3.6–35.2) for subjects who received doses >2.0–5.0 Gy (relative to 0– 2.0 Gy) and the odds ratios for hemangiosarcomas were 41.7 (95% CI: 4.6–333) for the dose group >2.0– 5.0 Gy, and 62.5 (95% CI: 7.4–500) for the dose group >5.0–16.9 Gy; doses were estimated based on periodic urine sampling. A study reported averaged-attained age ERRs for liver cancer of 2.6 per Gy (95% CI: 0.7–6.9) for males and 29 per Gy (95% CI: 9.8–95) for females, and averaged-attained age ERRs for bone cancer of 0.76 per Gy (95% CI: <0–5.2) for males and 3.4 per Gy (95% CI: 0.4–20) for females. Elevated risks for bone cancer were observed only for workers with plutonium doses exceeding 10 Gy. For lung and bone cancer, the ERR declined with attained age, and for lung cancer, the ERR declined with age at first plutonium exposure. …….
Studies in Animals. Radiation pneumonitis has been observed following plutonium (primarily insoluble) aerosol exposure of dogs, nonhuman primates (monkeys and baboons), and rodents. As discussed in Section 3.2.1.1, radiation pneumonitis was identified as primary, major contributing, or incidental cause of death in some dogs and nonhuman primates that inhaled 238PuO2, 239PuO2, or 239Pu(NO3)4 aerosols.
Muggenburg et al. (2008) studied the effect of plutonium ILB and radiation dose on radiation pneumonitis in beagles as part of a plutonium lifespan composite study. The relationship between pneumonitis induction and the cause of death was reported to be a function of the plutonium ILB, the resulting cumulative radiation dose, and the particle size to some extent. Increased ILB and plutonium dose rate were associated with the fraction of animals with radiation pneumonitis as primary, major contributing, or incidental cause of death. A trend was observed for the induction of radiation pneumonitis at lower ILBs in the 0.75 and 1.5 µm AMAD groups than in the 3 µm AMAD group. At radiation doses sufficient to produce radiation pneumonitis, the resulting inflammation was a chronic symptom due to long-term retention of 239PuO2 in the lung.
As a result, 239PuO2-induced radiation pneumonitis was always associated with pulmonary fibrosis. The radiation pneumonitis/pulmonary fibrosis progressively impaired lung function, including alveolar-capillary gas exchange, resulting in increases in respiratory rate, minute volume, arterial CO2 pressure, and lung stiffness, along with decreases in tidal volume and arterial O2 pressure. Symptoms in order of decreasing frequency were tachypnea, increased breath sounds, body weight loss, anorexia, dyspnea, cyanosis, bradycardia, and discharge from the nose, eyes, or mouth. Increasing radiation dose and dose rate corresponded to progressively shorter times to onset of symptoms and increased severity of effects (Muggenburg et al. 2008). …….
Exposure of Dogs to 238PuO2. In the ITRI 238PuO2 dog studies, the first symptom of radiation pneumonitis (tachypnea) was observed at approximately 600 days after initial exposure (Muggenburg et al. 1996). …… Radiation pneumonitis was the primary cause of death in eight dogs with initial lung burdens of 8.3–45 kBq/kg (Muggenburg et al. 1996).
 Similar observations were reported in the PNL studies on 238PuO2, with chronic radiation pneumonitis observed in dogs with initial lung burdens ≥0.28 kBq/kg (Park et al. 1997). Exposure of Dogs to 239PuO2. Chronic radiation pneumonitis also was observed in the ITRI and PNL dogs exposed to 239PuO2 aerosols   ……  Radiation pneumonitis was observed in dogs dying from 0.3 to 11.7 years after inhaling 239PuO2, with the time to death inversely related to initial lung burden (Hahn et al. 1999; Muggenburg et al. 1999, 2008). The lowest initial lung burden causing fatal radiation pneumonitis was 1.0 kBq/kg (Muggenburg et al. 1999, 2008). The time to death from radiation pneumonitis was not different in ITRI dogs administered a single exposure (initial lung burden of 3.9 kBq/kg) or repeated exposures (7–10 semiannual exposures for a mean total lung burden of 5.3 kBq/kg) (Diel et al. 1992). Death due to radiation pneumonitis was observed in 239PuO2-exposed PNL dogs at mean initial lung burdens ≥1 kBq/kg (DOE 1988a; Weller et al. 1995b) …..
Exposure of Other Laboratory Animal Species. Baboons ….. Higher initial lung burdens resulted in earlier death from radiation pneumonitis accompanied by pulmonary edema. Radiation pneumonitis and pulmonary fibrosis were also reported in Rhesus monkeys…..
  Cardiovascular Effects. Epidemiological Studies in Humans. Possible associations between exposure to plutonium and cardiovascular disease have been examined in studies of workers at production and/or processing facilities in the United Kingdom (Sellafield) (McGeoghegan et al. 2003; Omar et al. 1999). These studies are summarized in Table 3-2 and study outcomes for mortality from cardiovascular disease are described in Section 3.2.1.1. Omar et al. (1999) compared mortality rates between plutonium workers and other radiation workers within a cohort of Sellafield workers and found that the mortality rate ratios were significantly elevated for cerebrovascular disease (1.27, p<0.05) in a cohort of Sellafield workers. The cumulative internal uptakes of plutonium in the cohort were estimated to range from 0 to 12 kBq, with approximately 75% of the cohort having cumulative uptakes ≤250 Bq. McGeoghegan et al. (2003) compared mortality rates between plutonium workers and other radiation workers within a cohort of Sellafield workers and found that morality rate ratios for plutonium workers were significantly elevated for deaths from circulatory disease (2.18, p<0.05) and ischemic heart disease (4.46, p<0.01). ….
Cancer.  Epidemiological Studies in Humans. Possible associations between exposure to plutonium and cancer mortality and morbidity have been examined in studies of workers at the U.S. plutonium production and/or processing facilities (Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (Mayak) and the United Kingdom (e.g., Sellafield). The most recent findings from these studies are summarized in Table 3-2. Compared to studies of U.K. and U.S. facilities, the Mayak cohorts had relatively high PLUTONIUM 55 3. HEALTH EFFECTS exposures to plutonium (i.e., mean body burdens ranging from 0.09 to 9.2 kBq, with individual exposures as high as 470 kBq (Krahenbuhl et al. 2005). Collectively, the Mayak studies provide evidence for an association between cancer mortality and exposure to plutonium. Plutonium dose-response relationships for lung cancer mortality have been corroborated in three Mayak studies (Gilbert et al. 2004; Jacob et al. 2005; Kreisheimer et al. 2003). ……
Collectively, the Mayak studies provide evidence for increased risk of cancer mortality (bone, liver, lung) in association with increased internal plutonium-derived radiation dose and/or body burden, with approximately 4-fold higher risks in females compared to males. Four studies estimated lung cancer mortality risk among Mayak workers and yielded similar estimates of excess relative risk per Gy of internal lung dose. Gilbert et al. (2004) estimated the excess lung cancer mortality risk (per Gy attained at age 60 years) for essentially the entire cohort of Mayak workers (n=21,790) to be approximately 4.7 per Gy (95% CI: 3.3–6.7) in males, and 19 per Gy (95% CI: 9.5–39) in females. Adjustment for smoking, based on risk estimates in subgroups for which smoking data were available, decreased these estimates only slightly: males, 3.9 per Gy (95% CI: 2.6–5.8); and females, 19 (95% CI: 7.7–51). Cancer mortality risk was linearly related to plutonium radiation dose. ……
Risks of mortality and morbidity from bone and liver cancers have also been studied in Mayak workers (Gilbert et al. 2000; Koshurnikova et al. 2000; Shilnikova et al. 2003; Sokolnikov et al. 2008; Tokarskaya et al. 2006). Increasing estimated plutonium body burden was associated with increasing cancer mortality, with higher risk in females compared to males. Gilbert et al. (2000) examined liver cancer mortality in a cohort of Mayak workers (n=11,000). …….
U.K. Atomic Energy Authority and Atomic Weapons Establishment Workers. ………..The mortality rate ratio was significantly elevated for breast cancer (7.66, p<0.01) and cerebrovascular disease (1.27, p<0.05). McGeoghegan et al. (2003) examined cancer mortality in a cohort of female Sellafield workers (n=6,376), from which a subset (n=837) of women who had been monitored for plutonium exposure was identified as plutonium workers. This cohort overlapped considerably with that studied by Omar et al. 1999). Effective dose equivalents to the lung from plutonium were estimated to have ranged up to 178 mSv (mean: 3.45 mSv, 5th–95th percentile range: 0.36–8.89 mSv). Comparisons of mortality rates between plutonium workers and other radiation workers yielded significantly elevated mortality rate ratios for all deaths (2.20, p<0.01), all cancers (3.30, p<0.01), breast cancer (3.77, p<0.05), circulatory disease (2.18, p<0.05), and ischemic heart disease (4.46, p<0.01).
……p. 66   3.3 GENOTOXICITY Abundant information is available regarding the genotoxicity of ionizing radiation (refer to the Toxicological Profile for Ionizing Radiation for a detailed discussion of the genotoxic effects of various forms of ionizing radiation). The genotoxicity of alpha radiation from plutonium sources has been investigated in various groups of plutonium workers, as well as in vivo animal studies and a variety of in vitro test systems. Tables 3-4 and 3-5 present the results of in vivo and in vitro genotoxicity studies, respectively. Although epidemiological studies do not provide conclusive evidence that plutonium produces genetic damage in humans, results of some studies provide suggestive evidence of dose-related increases in chromosomal aberrations in plutonium workers with measurable internalized plutonium. For example, Livingston et al. (2006) examined relationships between external radiation dose, internal radiation dose, and frequencies of chromosomal aberrations and micronuclei in peripheral blood lymphocytes of a group of 30 retired plutonium workers with dosimetrically-estimated internal and external radiation doses >0.5 Sv, another 17 workers with predominantly external radiation doses <0.1 Sv, and 21 control subjects with no history of occupational radiation exposure. Frequency of chromosomal aberrations was positively correlated with the bone marrow dose (alpha radiation from internalized plutonium; 168 mSv  median dose to the bone marrow), but not with the external radiation dose. Frequency of micronuclei did not differ significantly among the three study groups.
Significantly increased frequencies of symmetrical and asymmetrical chromosomal aberrations were reported among workers at the Sellafield (United Kingdom) plutonium facility with internalized plutonium in excess of 20% of the maximum permissible body burden (Tawn et al. 1985). Frequencies of symmetrical aberrations were significantly higher at retesting 10 years later, although no significant external radiation exposure had occurred during the 10-year interim (Whitehouse et al. 1998). This finding is consistent with the hypothesis that internally-deposited plutonium irradiates hemopoietic precursor cells (Whitehouse et al. 1998).
  Internal plutonium dose-related increased frequencies in chromosomal aberrations have also been reported in peripheral blood lymphocytes of plutonium workers with estimated plutonium body burdens as high as 15.5 kBq from exposure at the Mayak plutonium facilities in Russia (Hande et al. 2003, 2005; Mitchell et al. 2004; Okladnikova et al. 2005). The increased frequencies of chromosomal aberrations in the Mayak workers persisted many years following the cessation of exposure (Hande et al. 2003, 2005; Mitchell et al. 2004).
 Significantly increased frequencies of chromosomal aberrations were observed among Rocky Flats (Colorado) plutonium workers with internal plutonium burdens >740 Bq (Brandom et al. 1990; IAEA 1979). Conversely, among Manhattan Project plutonium workers followed for up to 32 years, no apparent correlation was found between the frequency of chromosomal aberrations and plutonium body burdens in the range of 0.185–15.4 kBq (Hempelmann et al. 1973; Voelz et al. 1979).
Open wounds represent a significant route through which plutonium workers might be exposed to plutonium alpha particles. Chromosomal aberrations were observed in lymphocytes among eight plutonium workers in the United Kingdom occupationally exposed to plutonium with the primary routes of exposure through wounds, punctures, or abrasions (estimated plutonium body burdens from 0.78 to 1.5 kBq). In exposed individuals, the number of dicentric aberrations averaged 5 per 500 cells, while the natural population background frequency of this aberration is 1 per 4,000 cells (Schofield 1980; Schofield et al. 1974).
Results of in vivo genotoxicity studies in laboratory animals consistently reveal alpha radiation-induced dose-related increases in the frequency of chromosomal aberrations following internalization of   plutonium. Chromosomal aberrations were observed in monkeys and hamsters following inhalation exposure to plutonium. Increases in chromosomal aberrations in blood lymphocytes were seen in immature Rhesus monkeys exposed to 239PuO2 at concentrations resulting in initial lung burdens of 1.9– 19 kBq 239Pu/kg body weight (LaBauve et al. 1980) and Cynomolgus monkeys exposed to 239Pu(NO3)4 at a concentration resulting in a projected initial lung burden of 40 kBq (Brooks et al. 1992), but not at lower levels. ……
  Consistently positive genotoxicity results have been reported in various test systems exposed to the alpha radiation from plutonium compounds in vitro (see Table 3-5). Chromosomal aberrations were reported in human peripheral blood lymphocytes and lymphoblasts (DOE 1980h; Purrott et al. 1980)  ……https://www.atsdr.cdc.gov/toxprofiles/tp143.pdf?fbclid=IwAR1iffNMF8xj33aBhDW-zhtFzPejF0eNlQ5QUaIgxBhCcujUKU0XRC8NvMc     Agency for Toxic Substances and Disease Registry Division of Toxicology and Environmental Medicine/Applied Toxicology Branch 1600 Clifton Road NE Mailstop F-62 Atlanta, Georgia 30333

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s


%d bloggers like this: