Reference values for basic human anatomical and physiological characteristics for use in radiation protection.

A new publication prepared by the ICRP Task Group on Reference Man, Basic anatomical and physiological data for use in radiological protection: reference values, is focused on those human characteristics that are important for dosimetric calculations. Moving from the past emphasis on a Reference Man, the new report presents a series of reference values for both male and female subjects of six different ages--newborn, 1, 5, 10, 15 y, and adult. In selecting reference values, the task group has used data on Western Europeans and North Americans because these populations have been well studied with respect to anatomy, body composition and physiology. When appropriate, comparisons are made between the chosen reference values and data from several Asian populations. The reference values for height and body mass are higher than those reported for various Asian populations. However, the reported masses of individual organs and tissues, particularly for China and Japan, are similar to the reference values.

The toxicity of insoluble cerium-144 inhaled by beagle dogs: non-neoplastic effects.

The biological effects of inhaled beta-particle-emitting radionuclides are not well known. The non-neoplastic diseases induced by an inhaled, relatively insoluble form of cerium-144 ((144)Ce) were studied in beagle dogs exposed to graded activity levels of (144)Ce in fused aluminosilicate particles by a single, brief inhalation exposure and observed for their life span. The initial lung burdens (ILBs) achieved ranged from 0.000093-7.6 MBq (144)Ce/kg body weight. The (144)Ce was retained in the lung with an effective half-life of about 190 days. Significant (144)Ce was translocated to the tracheobronchial lymph nodes, and the concentration exceeded that of the lung at about 400 days after inhalation exposure. Significant radiation doses were delivered to the lung and tracheobronchial lymph nodes and to the heart adjacent to the tracheobronchial lymph nodes. Radiation pneumonitis was the predominant non-neoplastic disease. The dose response for radiation pneumonitis indicated that an ILB of 1.4 MBq/kg would cause death from radiation pneumonitis in 50% of the exposed dogs. This ILB resulted in a pulmonary dose to death of about 350 Gy. The tracheobronchial lymph nodes developed lesions in dogs with ILBs lower than those causing radiation pneumonitis. The overall results of this study, however, showed that (144)Ce, inhaled in an insoluble form, did not cause any unique or inexplicable biological effects in dogs or cause effects at unusually low doses that might call current radiation protection guidelines into question.

Deterministic effects from occupational radiation exposures in a cohort of Mayak PA workers: data base description.

Project 2.3 of the Joint Coordinating Committee on Radiation Effects Research (JCCRER) is a study of deterministic health effects among a cohort of Russia nuclear workers. The preliminary study population includes a stratified random sample of 221 radiation workers who were employed in a cohort of 8,055 workers at the Mayak PA facilities for at least one year during the period from 1948 to 1958. High annual doses, approaching 1 Gy per year from external and internal radiation sources, were reported for a significant proportion of the workers in this cohort. The present data set includes 96 cases of chronic radiation sickness (CRS), 14 cases of acute radiation syndrome (ARS) and 13 cases of plutonium pneumosclerosis (PPn). The remainder of the sample consists of "uninjured workers" who had no known history of radiation illness or injury; however, the uninjured workers are not "controls" for radiation exposure. The data base is currently being expanded to 600 individuals sampled from the cohort of workers from 1948 to 1958 to allow a more complete analysis of the deterministic health effects and comparisons with existing health effect models. The final data base will be used with state-of-the-art modeling techniques to determine threshold doses and dose-response relationships for key clinical diagnostic variables.

Comparative stochastic effects of inhaled alpha- and beta-particle-emitting radionuclides in beagle dogs.

The stochastic effects of inhaled, insoluble particles of alpha- or beta-particle-emitting radionuclides were compared in dogs. Male and female beagle dogs were exposed briefly by nasal inhalation to relatively insoluble aerosols of (239)PuO(2) or (144)Ce in fused aluminosilicate particles (FAP) and observed for cancer for their lifetimes. The initial lung burden and retention of each radionuclide was determined by whole-body counting of the emissions from (144)Ce-(144)Pr- or (169)Yb-labeled (239)PuO(2). Lung doses were calculated for each dog from these data. The lung doses ranged from 0.21 to 1200 Gy for (144)Ce FAP and 1.6 to 58 Gy for (239)PuO(2). Dogs with doses to the lung of about 60 Gy or greater from (144)Ce or about 2 Gy or greater from (239)PuO(2) had an increased incidence of lung carcinomas. In dogs exposed to (144)Ce FAP, three organs were targets for neoplasia: lung, tracheobronchial lymph nodes, and heart. The insoluble FAP carried to the lymph nodes draining the lung delivered high radiation doses to the nodes and adjacent heart, resulting in hemangiosarcomas of these organs. In the lung, high radiation doses induced hemangiosarcomas and carcinosarcomas. At lower doses, carcinomas of various histological patterns were induced in the lung. In dogs exposed to (239)PuO(2), the lung was the sole target organ for neoplasia. Nearly all of these neoplasms were carcinomas of various histological patterns. These results indicated that relatively low doses of alpha-particle radiation can induce pulmonary cancers, but relatively large doses of beta-particle radiation are required. In addition, inhaled beta-particle emitters can also induce cancers in lung-associated lymph nodes and heart at these larger absorbed radiation doses.

Comparative deterministic effects of inhaled, insoluble alpha- and beta-particle-emitting radionuclides in dogs.

This report compares the deterministic effects from an alpha-particle-emitting radionuclide, (239)PuO(2), and a beta-particle emitter, (144)Ce in fused aluminosilicate particles (FAP). The studies were conducted in beagle dogs of both genders exposed by inhalation to aerosols of the radionuclides. The initial lung burdens of (239)Pu and (144)Ce were determined by whole-body counting of the (169)Yb added to the plutonium aerosol during its preparation or the (144)Ce and its progeny (144)Pr. In addition, organ retention data were obtained from parallel serial sacrifice studies with the same aerosols. After exposure, the dogs were observed for health effects over their lifetime. The deterministic effects observed for both of these relatively insoluble aerosols were lymphopenia, fibrosis, atrophy of the lung-associated lymph nodes, and radiation pneumonitis. Due to the longer half-life of plutonium, the lymphopenia was more prolonged and the clinical course of the radiation pneumonitis more chronic than that resulting from cerium. The greater tissue penetration of the beta-particle emissions from the cerium resulted in more uniform dose distribution over the lung and the atria of the heart than from the alpha-particle emissions from plutonium.

Toxicity of inhaled 91YCl3 in dogs.

This study was conducted in dogs to determine the toxicity of inhaled 91YCl3, which is of interest because 91Y is a fission-product radionuclide that is abundant in a reactor inventory after sustained operation. Yttrium-91 has a short half-life, 59 days, and decays with the emission of beta particles and low-yield gamma rays. The study was conducted in 58 beagle dogs with equal numbers of males and females. Forty-six dogs inhaled the 91YCl3 aerosol, while 12 served as controls. Four exposure levels were used. To determine the long-term retained burden (LTRB) of 91Y, each dog was periodically whole-body counted and its excreta were analyzed radiochemically. Over time, the 91Y transferred from the lung primarily to the skeleton and liver. The dogs were observed over their life spans for biological effects. Fatal hematological dyscrasia occurred from 12 to 33 days after exposure in the dogs with the highest LTRBs. Bone-associated tumors of the nasal and oral mucosae occurred in 5 dogs from 2000 to 5800 days after they inhaled the 91YCl3 aerosols. Five dogs died with malignant lung tumors and 2 dogs with malignant liver tumors. The results of this study were compared to those from similar studies in beagles that inhaled 90SrCl2 or 144CeCl3 or were injected with 137CsCl. The comparison showed that the biological effects in each study were clearly dependent on the cumulative doses to critical organs.

Statistical modeling of carcinogenic risks in dogs that inhaled 238PuO2.

Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest National Laboratory (PNNL) were conducted. The hazard functions (age-specific risks) for incidence of lung, bone and liver tumors were modeled as a function of cumulative radiation dose, and estimates of lifetime risks based on the combined data were developed. For lung tumors, linear-quadratic functions provided an adequate fit to the data from both laboratories, and linear functions provided an adequate fit when analyses were restricted to doses less than 20 Gy. The estimated risk coefficients for these functions were significantly larger when based on ITRI data compared to PNNL data, and dosimetry biases are a possible explanation for this difference. There was also evidence that the bone tumor response functions differed for the two laboratories, although these differences occurred primarily at high doses. These functions were clearly nonlinear (even when restricted to average skeletal doses less than 1 Gy), and evidence of radiation-induced bone tumors was found for doses less than 0.5 Gy in both laboratories. Liver tumor risks were similar for the two laboratories, and linear functions provided an adequate fit to these data. Lifetime risk estimates for lung and bone tumors derived from these data had wide confidence intervals, but were consistent with estimates currently used in radiation protection. The dog-based lifetime liver tumor risk estimate was an order of magnitude larger than that used in radiation protection, but the latter also carries large uncertainties. The application of common statistical methodology to data from two studies has allowed the identification of differences in these studies and has provided a basis for common risk estimates based on both data sets.

Biological effects of inhaled 144CeCl3 in beagle dogs.

The biological effects of 144Ce were studied in beagle dogs that were exposed to graded activity levels of 144CeCl3 via a single, brief inhalation exposure and observed for their life span. The long-term retained body burdens ranged from 0.06 to 13 MBq/kg with a median of 1.2 MBq/kg. After a short residence time in the lung, most of the 144Ce was translocated to liver and skeleton, where the 144Ce was retained with a half-time approaching the physical half-life of 144Ce, 284 days. Significant radiation doses were delivered to the lung, 28 Gy (median) and 2.5-370 Gy (range); liver, 68 Gy (median) and 6.1-250 Gy (range); and skeleton, 21 Gy (median) and 1.9-100 Gy (range). Lesions induced by the beta-particle radiation were noted in the lung, liver, skeleton, bone marrow, and oral and nasal mucosae closely associated with bone. Early deaths (within 2.5 years) were generally related to hematological dyscrasia, radiation pneumonitis, or hepatocellular degeneration and atrophy. Neoplasms that occurred relatively early, from 2.2-6.8 years after exposure, were noted in the liver, bone, bone marrow and oral mucosa closely associated with bone. Neoplasms that occurred later, beyond 7 years after exposure, were noted in the liver, lung and nasal mucosa closely associated with bone. Increased numbers of neoplasms were not found in two other organs that had relatively high radiation doses, namely the thyroid and kidney. Only one primary bone tumor was noted, but 11 tumors of bone-associated tissues (oral and nasal mucosae and bone marrow) were found. Radiation doses and effects in tissues adjacent to bone, especially those of epithelial or marrow origin, should be considered when determining risks from internally deposited bone-seeking radionuclides, such as 144Ce. The property of 144Ce in depositing on and remaining associated with bone surfaces for long times may be an important factor in the radiation dose to bone marrow and epithelium adjacent to bone.

Pulmonary carcinogenicity of relatively low doses of beta-particle radiation from inhaled 144CeO2 in rats.

This study was conducted to examine the carcinogenic effects of inhaled beta-particle-emitting radionuclides, particularly in lower dose regions in which there were substantial uncertainties associated with available information. A total of 2751 F344/N rats (1358 males and 1393 females) approximately 12 weeks of age at exposure were used. Of these, 1059 rats were exposed to aerosols of 144CeO2 to achieve mean desired initial lung burdens (ILBs) of 18 kBq (low level), 247 rats to achieve mean ILBs of 60 kBq (medium level) and 381 rats to achieve mean ILBs of 180 kBq (high level). Control rats (total of 1064) were exposed to aerosols of stable CeO2. Based on the 95% confidence intervals of the median survival times and the cumulative survival curves, there were no significant differences in the survival of groups of female and male exposed rats relative to controls. The mean lifetime beta-particle doses to the lungs of the rats in the four groups were: low level, 3.6 +/- 1.3 (+/-SD) Gy; medium level, 12 +/- 4.5 Gy; and high level, 37 +/- 5.9 Gy. The crude incidence of lung neoplasms increased linearly with increasing doses to the lungs (controls, 0.57%; low level, 2.0%; medium level, 6.1%; and high level, 19%). The estimated linear risk coefficients for lung neoplasms per unit of dose to the lung were not significantly different for the three dose levels studied. The risk coefficient at the lower level was 39 +/- 14 (+/-SE) excess lung neoplasms per 10(4) rat Gy; at the medium level the risk was 47 +/- 12; and at the higher level the risk was 50 +/- 9.0. The relationship of beta-particle dose to the lung and the crude incidence of lung neoplasms was described adequately by a linear function. We concluded that the risk of lung neoplasms in rats per unit of radiation dose did not increase with decreasing mean beta-particle dose to the lung over the range of 3.6 to 37 Gy. The weighted average of these three values was 47 +/- 6.4 (+/-SE) excess lung neoplasms per 10(4) rat Gy. To extend the risk coefficients for lung neoplasms to lower doses by experimentation will require much larger numbers of rats than used in this study.

Biological effects of 137CsCl injected in beagle dogs of different ages.

The toxicity of 137Cs in the beagle dog was investigated at the Inhalation Toxicology Research Institute (ITRI) and Argonne National Laboratory (ANL) as part of programs to evaluate the biological effects of both radionuclides in atomic bomb fallout and internally deposited fission-product radionuclides. In the ITRI study, young adult dogs were exposed once by intravenous injection to a range of 137Cs concentrations; the results have recently been published (Nikula et al., Radiat. Res. 142, 347-361, 1995). The purpose of the present report is to summarize the ANL study and to compare the results of the two studies. At ANL, 63 dogs in three age groups (15 juveniles, 142-151 days old; 38 young adults, 388-427 days old; and 10 middle-aged dogs, 1387-2060 days old) were given 137Cs intravenously at levels (61-162 MBq/kg) near those expected to be lethal within 30 days after injection. There were 17 control dogs from the same colony. Twenty-three of the dogs injected with 137Cs, including all middle-aged dogs, died within 52 days after injection due to hematopoietic cell damage resulting in severe pancytopenia that led to fatal hemorrhage and/or septicemia. The other significant early effect was damage to the germinal epithelium of the seminiferous tubules of all male dogs. These early effects are the same as those reported for the dogs injected with 137Cs at ITRI. In addition, the design of the ANL study revealed an age- and gender-related differential radiosensitivity for early effects: The middle-aged dogs died significantly earlier due to complications of hematological dyscrasia compared to the juvenile and young adult dogs, and the middle-aged females died significantly earlier than the middle-aged males. The most significant non-neoplastic late effects in the 137Cs-injected dogs from ANL and ITRI were atrophy of the germinal epithelium of seminiferous tubules with azoospermia, and a significant dose-dependent decrease in survival. However, the survival of the ANL dogs was decreased more than that of the ITRI dogs at similar radiation doses from 137Cs. Numerous neoplasms occurred at many different sites in the dogs injected with 137Cs at ANL and ITRI. Two differences in the findings of the two studies were that (1) there was an increased risk for malignant thyroid neoplasms in the ANL male dogs injected with 137Cs, but not the ITRI dogs of either gender, and (2) there was an increased relative risk for benign neoplasms excluding mammary neoplasms in the ITRI dogs injected with 137Cs, but not the ANL dogs. In both groups, there were dose-related increased incidences of malignant neoplasms, malignant neoplasms excluding mammary neoplasms, all sarcomas considered as a group, all non-mammary carcinomas considered as a group and malignant liver neoplasms. In summary, the similarity of the findings between the two studies and the dose-response relationships for survival and for large groupings of neoplasms suggests that these results are consistent findings in 137Cs-injected dogs and might be dose-related late effects in humans exposed to sufficient amounts of internally deposited 137Cs.

The biological effects of radium-224 injected into dogs.

A life-span study was conducted in 128 beagle dogs to determine the biological effects of intravenously injected 224Ra chloride. The 224Ra chloride was prepared by the same method used for intravenous injections in humans who were treated for ankylosing spondylitis and tuberculosis. Thus the results obtained from dogs can be compared directly to the population of treated humans, both for the elucidation of the effect of exposure rate and for comparison with other radionuclides for which data for humans are unavailable. Using equal numbers of males and females, the dogs were injected with one of four levels of 224Ra resulting in initial body burdens of approximately 13, 40, 120 or 350 kBq of 224Ra kg-1 body mass. A control group of dogs was injected with diluent only. All dogs were divided further into three groups for which the amount of injected 224Ra (half-life of 3.62 days) or diluent was given in a single injection or divided equally into 10 or 50 weekly injections. As a result of these three injection schedules, the accumulation of dose from the injected 224Ra was distributed over approximately 1, 3 or 12 months. Each injection schedule included four different injection levels resulting in average absorbed alpha-particle doses to bone of 0.1, 0.3, 1 and 3 Gy, respectively. The primary early effect observed was a hematological dyscrasia in the dogs receiving either of the two highest injection levels. The effect was most severe in the dogs receiving a single injection of 224Ra and resulted in the death of three dogs injected at the highest level. The late-occurring biological effects were tumors. Bone tumors were the most common followed by tumors in the nasal mucosa. The occurrence of bone tumors was highest in the dogs given the highest dose in 50 injections. The age-specific incidence rate for mammary tumors was increased in all three injection groups. The results of this study revealed two important exposure-rate effects. Hematological dyscrasia was amplified by delivery of relatively high doses at a high exposure rate. In contrast, bone tumors were amplified by delivery of relatively high doses at a lower exposure rate (i.e. dose delivered over 1 year rather than 1-3 months). There was a dose-response relationship for the induction of nasal mucosal tumors and mammary tumors. These findings in dogs are similar to those in humans injected with 224Ra, except for the nasal tumors. The calculated risk of developing a bone tumor was about 40 times higher in dogs than reported for humans.

Hepatic neoplasms from internally deposited 144CeCl3.

Fifty-five dogs were exposed by inhalation to graded activity levels of 144CeCl3, a relatively soluble form of the beta-emitting radionuclide. A large portion of the 144Ce translocated from lung to liver and skeleton. Significant radiation doses were delivered to the respiratory tract, liver, and skeleton; however, the liver received the greatest cumulative absorbed dose. Liver tumors were the most frequently observed neoplasms in these exposed dogs and included 7 primary hepatic hemangiosarcomas, 1 cholangiocarcinoma, 1 hepatocellular carcinoma, 1 fibrosarcoma, 4 biliary cystadenomas, and 1 fibroma. The dose to the liver in these dogs ranged from 11 to 250 Gy with a median of 57 Gy. Autoradiographs showed a relative uniform distribution of beta dose to the liver. All the malignant tumors and 1 cystadenoma were primary causes of death. The morphologic features of the hemangiosarcomas and associated hepatic lesions were similar to those described for hemangiosarcomas induced in people exposed to Thorotrast. Biliary cystadenomas were associated with degenerative lesions in the liver but not with other neoplasms in the liver. These results indicate that the liver is an important target organ for effects from internally deposited 144Ce.

Toxicity of inhaled plutonium dioxide in beagle dogs.

This study was conducted to determine the biological effects of inhaled 238PuO2 over the life spans of 144 beagle dogs. The dogs inhaled one of two sizes of monodisperse aerosols of 238PuO2 to achieve graded levels of initial lung burden (ILB). The aerosols also contained 169Yb to provide a gamma-ray-emitting label for the 238Pu inhaled by each dog. Excreta were collected periodically over each dog's life span to estimate plutonium excretion; at death, the tissues were analyzed radiochemically for plutonium activity. The tissue content and the amount of plutonium excreted were used to estimate the ILB. These data for each dog were used in a dosimetry model to estimate tissue doses. The lung, skeleton and liver received the highest alpha-particle doses, ranging from 0.16-68 Gy for the lung, 0.08-8.7 Gy for the skeleton and 0.18-19 for the liver. At death all dogs were necropsied, and all organs and lesions were sampled and examined by histopathology. Findings of non-neoplastic changes included neutropenia and lymphopenia that developed in a dose-related fashion soon after inhalation exposure. These effects persisted for up to 5 years in some animals, but no other health effects could be related to the blood changes observed. Radiation pneumonitis was observed among the dogs with the highest ILBs. Deaths from radiation pneumonitis occurred from 1.5 to 5.4 years after exposure. Tumors of the lung, skeleton and liver occurred beginning at about 3 years after exposure. Bone tumors found in 93 dogs were the most common cause of death. Lung tumors found in 46 dogs were the second most common cause of death. Liver tumors, which were found in 20 dogs but were the cause of death in only two dogs, occurred later than the tumors in bone and lung. Tumors in these three organs often occurred in the same animal and were competing causes of death. These findings in dogs suggest that similar dose-related biological effects could be expected in humans accidentally exposed to 238PuO2.

Biological effects of 137CsCl injected in beagle dogs.

The toxicity of intravenously administered 137CsCl in the beagle dog was investigated as part of a program to evaluate the biological effects of internally deposited fission-product radionuclides. The intravenous route of exposure was chosen for simplicity and accuracy because it was known that after intravenous injection, inhalation or ingestion, internally deposited 137CsCl is rapidly absorbed and distributed throughout the body, exposing the whole body to beta-particle and gamma radiations. Fifty-four dogs were injected intravenously with 137Cs to provide one group of six dogs with mean initial body burdens of 141 MBq 137Cs/kg body mass and four groups of 12 dogs each with mean initial body burdens of 104, 72, 52 and 36 MBq 137Cs/kg. Twelve dogs were injected with isotonic saline as study controls. Because the number of study control dogs was small, data from an additional 49 control dogs from other studies at the Inhalation Toxicology Research Institute that were performed over a similar span of years were also used. There was a significant, dose-dependent decrease in survival of the 137Cs-injected dogs. Eleven 137Cs-injected dogs, including all six in the highest initial body burden group, died within 81 days after injection, primarily due to hematopoietic cell damage resulting in severe pancytopenia. An additional 25 dogs had transient hematological dyscrasia but survived for long times. All 137Cs-injected male dogs had marked damage to the germinal epithelium of the testicular seminiferous tubules with azoospermia in the long-term survivors. Benign and malignant neoplasms occurred in a variety of organs in 137Cs-injected dogs, rather than in a single target organ. When individual organs were considered, the incidence of malignant neoplasms was increased in the liver and in the nasal cavity and paranasal sinuses of the 137Cs-injected dogs. There was a 137Cs treatment effect in the incidence of malignant neoplasms (P < 0.001) in male dogs but no 137Cs-related treatment effect in female dogs. However, when malignant mammary neoplasms were excluded from the analysis, there was no gender difference, and there was a dose-related response (P < 0.001) in both males and females for the incidence of malignant neoplasms.

Skeletal malignancies among beagles injected with 241Am.

Seventy skeletal malignancies in 44 dogs were identified among 117 beagles injected as young adults with graded dosages of approximately 0.07 to 104 kBq 241Am kg-1 and maintained for lifetime observation. All of these tumors were osteosarcomas except four fibrosarcomas of bone and four chondrosarcomas of bone. Of these 117 animals, 114 survived beyond the minimum age (of 2.79 y) for radiation-induced bone cancer, and all are now dead. An expression was derived that described the dependence of percent occurrence of bone sarcoma on skeletal radiation dose of A = 0.76 + 30D, where A = percent of dogs with skeletal malignancy within any dosage group, D = average skeletal dose (< 3 Gy) at 1 y before death (average skeletal dose was calculated to the presumed start of tumor growth, which we have taken to be 1 y before death), and 0.76 represents the lifetime percent malignant bone tumor response among 132 suitable control dogs in our colony not given any radioactivity. All dosage groups with skeletal doses of > 3 Gy at 1 y before death exhibited close to 100% occurrence and appeared to be beyond the region of linearity. Therefore, they were excluded from the derivation of this expression. Similar analysis of corresponding data for beagles given 226Ra as young adults, excluding the two highest dosage groups in which the bone tumor response was approximately 100%, yielded the expression, A = 0.76 + 4.7D, (D < 20 Gy). A ratio of the coefficients in these two expressions indicates the effectiveness at low radiation doses for bone-cancer induction of 241Am relative to 226Ra, or (30 +/- 2.6)(4.7 +/- 0.47)-1 = 6 +/- 0.8. This compares to the relative effectiveness at low radiation doses that was obtained earlier for a 239Pu:226Ra toxicity ratio of about 16 +/- 5.

Strontium-90 induced bone tumours in beagle dogs: effects of route of exposure and dose rate.

Bone tumours from beagles exposed by inhalation to 90SrCl2 at the Inhalation Toxicology Research Institute (ITRI), by chronic ingestion of 90Sr at the Laboratory of Energy-Related Health Research (LEHR), and by injection of 90Sr citrate at the University of Utah were analysed to determine if the bone tumour characteristics differed among the three studies. The range of average skeletal doses at which the bone tumours occurred was similar in all three studies, but differences in the skeletal distribution, histological phenotype, and time to death were observed. The differences observed were attributed to the difference in dose-rate pattern obtained in the chronic ingestion study, in contrast to the inhalation and injection studies. In general, however, the differences noted in bone tumour characteristics were subtle, and would be unlikely to make an impact on models developed to assess the risk of human exposure to 90Sr.

Detection of serum alpha-fetoprotein in dogs with hepatic tumors.

Serum alpha-fetoprotein (AFP) concentration was detected by use of 2 commercially available kits containing antibodies to human AFP--a radioimmunoassay and an enzymetric test. Using neonatal canine serum (a source high in AFP), it was determined that reagents from both kits were able to bind to canine AFP, but a significant difference was detected in AFP concentration. The enzymetric test was superior in detecting canine AFP. Sera from dogs were classified into 6 groups: from dogs with primary hepatic tumors only (group 1); from dogs with primary hepatic tumors and other tumors (group 2); from dogs with normal liver but with other types of neoplasia (group 3); from dogs with nonneoplastic hepatic disease and tumors originating in other organs (group 4); from dogs with nonneoplastic hepatic disease only (group 5); and from clinically normal dogs (group 6). Serum biochemical determinations (alkaline phosphatase, alanine transaminase, albumin, total protein, total bilirubin, and serum bile acids) and values from the 2 AFP assays were obtained for all dogs. Serum AFP concentration detected by the enzymetric test was significantly higher in dogs with hepatocellular carcinoma and cholangiocarcinoma. Values greater than 250 ng/ml were detected in 5 of 9 dogs with cholangiocarcinoma and in 3 of 4 dogs with hepatocellular carcinoma. High serum AFP concentration also was indicative of liver involvement in 2 of 3 dogs with primary hepatic lymphosarcoma; 2 dogs had values greater than 225 ng/ml. Serum AFP concentration in dogs with other types of hepatic tumors was less than 250 ng/ml, and serum AFP concentration could not be correlated with such tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

An optimization strategy for a biokinetic model of inhaled radionuclides.

Models for material disposition and dosimetry involve predictions of the biokinetics of the material among compartments representing organs and tissues in the body. Because of a lack of human data for most toxicants, many of the basic data are derived by modeling the results obtained from studies using laboratory animals. Such a biomathematical model is usually developed by adjusting the model parameters to make the model predictions match the measured retention and excretion data visually. The fitting process can be very time-consuming for a complicated model, and visual model selections may be subjective and easily biased by the scale or the data used. Due to the development of computerized optimization methods, manual fitting could benefit from an automated process. However, for a complicated model, an automated process without an optimization strategy will not be efficient, and may not produce fruitful results. In this paper, procedures for, and implementation of, an optimization strategy for a complicated mathematical model is demonstrated by optimizing a biokinetic model for 144Ce in fused aluminosilicate particles inhaled by beagle dogs. The optimized results using SimuSolv were compared to manual fitting results obtained previously using the model simulation software GASP. Also, statistical criteria provided by SimuSolv, such as likelihood function values, were used to help or verify visual model selections.

Predicted and observed early effects of combined alpha and beta lung irradiation.

The nonstochastic radiobiological effects of combined alpha and beta irradiation of the lungs of rats from inhaled radionuclides were studied. Both respiratory functional morbidity at 18 mo and mortality from radiation pneumonitis within 18 mo after exposure were examined for rats exposed to the beta-emitter 147Pm, the alpha-emitter 238Pu, or both combined. The results were used to validate hazard-function models that were developed (1) for respiratory functional morbidity at 18 mo and (2) for lethality from radiation pneumonitis within 18 mo. Both models were found to adequately predict the experimental observations for chronic alpha plus beta irradiation of the lung. Based on this 18-mo study, a relative biological effectiveness of approximately seven was obtained for 238Pu alpha radiation compared to 147Pm beta radiation for both respiratory functional morbidity and lethality from radiation pneumonitis. However, the relative biological effectiveness for the alpha radiation is likely to increase with longer follow-up.

Lung lavage therapy to lessen the biological effects of inhaled 144Ce in dogs.

To evaluate the therapeutic effects of removal of an internally deposited radionuclide on long-term biological effects, lung lavage was used to treat dogs that had inhaled 144Ce in a relatively insoluble form, in fused aluminosilicate particles. Either 10 lung lavages were performed between Days 2 and 56 after exposure or 20 lung lavages were performed between Days 2 and 84 after exposure. Approximately one-half of the 144Ce was removed by the lavages, resulting in a corresponding reduction in the total absorbed beta dose to lung. The mean survival time of the treated dogs was 1270 days compared to 370 days for untreated dogs whose initial pulmonary burdens of 144Ce were similar. Treated dogs died late from cancers of the lung or liver, whereas the untreated dogs died at much earlier times from radiation pneumonitis. Dogs treated with lung lavage but not exposed to 144Ce had a mean survival of 4770 days. We concluded that removal of 144Ce from the lung by lavage resulted in increased survival time and in a change in the biological effects from inhaled 144Ce from early-occurring inflammatory disease to late-occurring effects, principally cancer. In addition, the biological effects occurring in the treated dogs could be better predicted from the total absorbed beta dose in the lung and the dose rate after treatment rather than from the original dose rate to the lung. Therefore, we concluded that prompt treatment to remove radioactive materials could be of significant benefit to persons accidentally exposed to high levels of airborne, relatively insoluble, radioactive particles.