Microbial Contamination on Disposable Hypodermic Syringes Prior to Sterilization by Ionizing Radiation

A large number of syringes were taken from the production lines of three independent manufacturers; the numbers and types of microorganisms contaminating these randomly sampled syringes were assessed in the laboratories maintained by each of these manufacturers for routine sterility testing, according to a standard protocol devised by the Research Committee of the UK Panel on Gamma and Electron Irradiation, which coordinated the investigation and analyzed the results. Items produced by a manufacturer were assessed for microbiological contamination both in their own laboratories and in the laboratories of the other manufacturers. The level of “false-positive” results was determined independently for each laboratory by the testing of “known sterile” items which had been subjected to the radiation-sterilization process. Both the percentage of syringes initially sterile and the average number of organisms per contaminated syringe differed among the three manufacturers. When corrected for interlaboratory differences, the number of syringes initially sterile ranged from 16 to 48%, and the mean number of organisms per contaminated syringe was 20 to 70. Of 964 syringes tested by all three laboratories, only one contained over 1,000 aerobic organisms (1,133). The most common organisms found were coagulase-negative, gram-positive cocci. Two manufacturers assessed contamination by anaerobic organisms; of 610 syringes, 1 contained 4,275 organisms and 3 more had 100 to 1,000 organisms, but 488 (80%) were uncontaminated by anaerobes. The results are discussed in the context of the choice of radiation dose necessary for the sterilization of medical products manufactured under controlled hygienic conditions.     

Stability of a second-generation cephalosporin veterinary mastitis formulation after electron beam irradiation

This study focused on the chemical stability of the cephalosporin {ie28-1} acid, sodium salt (cephem 1) formulation after electron beam (e-beam) irradiation. The cephem 1 concentrations of samples irradiated at 5, 10, and 15 kilograys for glass vials and low-density polyethylene (LDPE) cannula syringes were not statistically different from the concentrations of the nonirradiated control samples. Samples from each irradiation dose stored in controlled-temperature chambers at 5°C and 30°C for 24 months did not show any concentration changes within statistical limits compared with the nontreated samples. Samples from each irradiation dose stored at 40°C for 12 months also did not show any concentration changes within statistical limits compared with the nontreated samples. The percentage of related substances increased slightly with the increase in ebeam irradiation level and storage temperature, but this increase was within the proposed label claim of 90% to 110% (45–55 mg/g). In conclusion, e-beam sterilization did not affect the chemical stability of cephem 1 intramammary formulation in LDPE cannula syringes, suggesting that e-beam irradiation may be a feasible method for terminal sterilization of this cephem 1 formulation.     

The rationale and a computer evaluation of a gamma irradiation sterilization dose determination method for medical devices using a substerilization incremental dose sterility test protocol

The experimental procedure described is designed to allow calculation of the radiation sterilization dose for medical devices to any desired standard of sterility assurance. The procedure makes use of the results of a series of sterility tests on device samples exposed to doses of radiation from 0.2 to 1.8 Mrad in 0.2 Mrad increments. From the sterility test data a 10^-2 sterility level dose is determined. A formula is described that allows a value called DS Mrad to be calculated. This is an estimate of the effective radiation resistance of the heterogeneous microbial population remaining in the tail portion of the inactivation curve at the 10^-2 dose and above. DS Mrad is used as a D ₁₀ value and is applied, in conjunction with the 10^-2 sterility level dose, to an extrapolation factor to estimate a sufficient radiation sterilization dose. A computer simulation of the substerilization process has been carried out. This has allowed an extensive evaluation of the procedure, and the sterilization dose obtained from calculation to be compared with the actual dose required. Good agreement was obtained with most microbial populations examined, but examples of both overdosing and underdosing were found with microbial populations containing a proportion of organisms displaying pronounced shoulder inactivation kinetics. The method allows the radiation sterilization dose to be derived from the natural resistance of the microbial population to gamma sterilization.     

Validating a Low Dose Gamma Irradiation Process for Sterilizing Allografts Using ISO 11137 Method 2B

This paper describes the validation of an allograft sterilization method specifically designed for the processing methods used at AlloSource in Centennial, CO. The methods used for this validation followed ISO Standard 11137, Method 2B. Three hundred allografts, collected from three defined production batches were dosed using a series of five incremental doses, beginning at 1 kGy and increasing by 1 kGy until 5 kGy was achieved. Following sterilization dosing, each allograft test article was analyzed using a sterility test to identify any viable microorganisms. The number of positive sterility samples was used to calculate the verification dose (1.27 kGy), which was then verified by an additional batch of 100 allografts. The results from this validation indicate that sterility (10⁻⁶ SAL) on human allograft tissue using gamma ⁶⁰Co radiation can be achieved when a dose of at least 9.2 kGy is employed.     

Thermoradiation Inactivation of Naturally Occurring Bacterial Spores in Soil

Samples of soil collected from the Kennedy Space Center near the spacecraft assembly facilities were found to contain microorganisms very resistant to conventional sterilzation techniques. The inactivation kinetics of the naturally occurring spores in soil were investigated by using dry heat and ionizing radiation, first separately and then simultaneously. Dry-heat inactivation kinetics of spores was determined at 105 and 125 C; radiation inactivation kinetics was determined for dose rates of 660 and 76 krads/h at 25 C. Simultaneous combinations of heat and radiation were then investigated at 105, 110, 115, 120, and 125 C, with a dose rate of 76 krads/h. Combined treatment was found to be highly synergistic, requiring greatly reduced radiation doses to accomplish sterilization of the population.     

Studies on the sterilization of pharmaceutical base materials with ionizing radiation and ethylene oxide.

The use of ionizing radiation and ethylene oxide for the sterilization of pharmaceutical base materials of animal origin, used to produce organopreparations, was studied. The materials included liver extract, pancreas extract, dried thyroid and intrinsic factor. The effective sterilizing doses for the examined materials and dependence between effective ionizing radiation dose and primary contamination were determined.     

Fecundity,fertility and reproductive recovery of irradiated Queensland fruit fly Bactrocera tryoni

Pupae of the Queensland fruit fly or Q‐fly Bactrocera tryoni (Froggatt) are irradiated routinely to induce reproductive sterility in adults for use in sterile insect technique programmes. Previous studies suggest that adult sexual performance and survival under nutritional and crowding stress are compromised by the current target dose of radiation for sterilization (70–75 Gy), and that improved mating propensity and survival under stress by irradiated males may be achieved by reducing the target sterilization dose without reducing the level of induced sterility. This raises the question of the amount by which the irradiation dose can be reduced before residual fertility becomes unacceptable. The present study measures the levels of residual fertility in male and female irradiated Q‐flies at different irradiation doses (20, 30, 40, 50, 60 and 70 Gy), and investigates the possibility that fecundity and fertility increase between 10–15 and 30–35 days post emergence. Male flies require a higher dose than females to induce sterility, with no residual fertility found in females irradiated at doses of 50 Gy or above, and no residual fertility found in males irradiated at doses of 60 Gy or above. Irradiated females are more fecund at 30–35 days post emergence than at 10–15 days. However, fertility does not increase between 10 and 15 days post emergence and 30–35 days, even at doses below 50 Gy. The present study shows that there is scope to reduce the target sterilization dose for Q‐flies below that of the current dose range (70–75 Gy) at the same time as retaining an adequate safety margin above radiation doses at which residual fertility can be expected.     

Gamma radiation resistance of Bacillus anthracis spores

The aim of the presented study was determined the effectiveness of action the gamma radiation on water suspension B. anthracis spores. The irradiation was performed using a Cobalt 60 (Co 60) source, by using single and fractionary irradiation doses. In the investigations was used B. anthracis stain "Sterne" 34F2. The obtained results show, that gamma radiation effectively inactivates B. anthracis spores. On the efficiency of sterilization process influence the irradiation's method and the number of spores in 1 ml suspension. In the suspension 1.5 x 10(9) spore in 1 ml, sporicidal doses gamma radiation amount to 25.0 kGy (single dose) or 41.5 kGy (fractionary dose). The volume suspension about definite inoculum of spores, subjected working the gamma rays has not influence on sporicidal effectiveness of radiation sterilization.     

Radiation Resistance of the Microflora Associated with Amniotic Membranes

Summary Amniotic membrane is widely used in the treatment of burn wounds and ulcers of various etiology. As it comes into contact with open wounds, it needs to be perfectly sterile to avoid the transmission of any disease. Accordingly, amniotic membrane needs to bear a high sterility assurance level (SAL). Conventionally, a radiation dose of 25 kGy is the generally accepted dose for sterilization. But to keep intact the biomechanical and other properties, it is sometimes proposed to use a lower dose without compromising an SAL of 10⁻⁶. The initial microbial contamination level and the radiation resistance of the contaminants determine the dose required for sterilization. The microbial species associated with the amniotic membrane from about 70 different batches were isolated. Twenty-two representative bacterial isolates were characterized and tested for survival in an incremental series of radiation doses from 0.5 to 5.0 kGy. The radiation decimal reduction dose (D₁₀) values for the strains were determined. Relatively higher D₁₀ values were recorded for the gram-positive isolates. The D₁₀ values of microbial isolates ranged from 0.16 to 1.3 kGy, and most resistant Bacillus strain had a D₁₀ value of 2.1 kGy. The radiation dose necessary to achieve an SAL of 10⁻⁶ was calculated based on the D₁₀values of the isolated strains. For a bioburden of 1000 Bacillus organism, the sterilization dose of 18.9 kGy is obtained. However, based on the experimental determination of D₁₀ of the radiation-resistant reference strain Bacillus pumilus, the adequate dose for radiation sterilization is found to be 19.8 kGy if bioburden level of 1000 is granted. The results substantiate that radiation dose of 25 kGy assures sterilization of amniotic membranes with bioburden level of 1000 colony forming units.     

Validation of Radiation Sterilization Dose for Lyophilized Amnion and Bone Grafts

A limited number of grafts produced in one batch is the main constrain to validate radiation sterilization dose of amnion and bone grafts according to ISO standard. The validation experiments done were according to ISO 13409 with a slight modification in sampling method. The experiments were carried out three times by using 20 samples each, 10 for bio-burden enumeration and 10 for sterility test at verification dose. The average bio-burden with sample item portion (SIP) = 1 for amnion membranes were 98, 50 and 69 cfu respectively and 0 cfu for bone grafts. Verification dose experiments, were done at doses of 2.90kGy for bone grafts and 5.13kGy for amnion grafts and the results of sterility tests showed that amnion grafts got one positive and bone grafts got 0 positive. The results met the requirements of ISO 13409 so that the radiation sterilization dose, at sterility assurance level of 10^-6 was 25kGy for both amnion and bone grafts. Viral contamination was excluded in this experiment.     

Sterilization of Allograft Bone: is 25 kGy the Gold Standard for Gamma Irradiation?

For several decades, a dose of 25 kGy of gamma irradiation has been recommended for terminal sterilization of medical products, including bone allografts. Practically, the application of a given gamma dose varies from tissue bank to tissue bank. While many banks use 25 kGy, some have adopted a higher dose, while some choose lower doses, and others do not use irradiation for terminal sterilization. A revolution in quality control in the tissue banking industry has occurred in line with development of quality assurance standards. These have resulted in significant reductions in the risk of contamination by microorganisms of final graft products. In light of these developments, there is sufficient rationale to re-establish a new standard dose, sufficient enough to sterilize allograft bone, while minimizing the adverse effects of gamma radiation on tissue properties. Using valid modifications, several authors have applied ISO standards to establish a radiation dose for bone allografts that is specific to systems employed in bone banking. These standards, and their verification, suggest that the actual dose could be significantly reduced from 25 kGy, while maintaining a valid sterility assurance level (SAL) of 10⁻⁶. The current paper reviews the methods that have been used to develop radiation doses for terminal sterilization of medical products, and the current trend for selection of a specific dose for tissue banks.     

Effect of low dose rate radiation on cell growth kinetics.

Experimental determinations were made of cell number as a function of time for two strains of L5178Y mammalian cells maintained continuously in various environments of radiation. One strain possessed a shoulder in its dose response curve whereas the other did not. Neither strain showed any significant difference in growth rate for interdivision doses on the order of the median lethal dose or less delivered continuously at a low dose rate or pulsed every 4 h at a high instantaneous dose rate. It was also shown that large numbers of dead cells have little effect on growth rate and that these dead cells last as discrete entities for many days. A simple theory of growth rate in the presence of radiation is presented, and the agreement with the observations implies that there is no effect of any sublethal low dose rate radiation received in one generation on the growth rate or radiation sensitivity of the succeeding generation. Further analysis of the data also showed that for the no-shoulder cells at 37 degrees C, tritiated water had a relative biological effect close to unity for cell sterilization.     

Radiation biology of mosquitoes

There is currently renewed interest in assessing the feasibility of the sterile insect technique (SIT) to control African malaria vectors in designated areas. The SIT relies on the sterilization of males before mass release, with sterilization currently being achieved through the use of ionizing radiation. This paper reviews previous work on radiation sterilization of Anopheles mosquitoes. In general, the pupal stage was irradiated due to ease of handling compared to the adult stage. The dose-response curve between the induced sterility and log (dose) was shown to be sigmoid, and there was a marked species difference in radiation sensitivity. Mating competitiveness studies have generally been performed under laboratory conditions. The competitiveness of males irradiated at high doses was relatively poor, but with increasing ratios of sterile males, egg hatch could be lowered effectively. Males irradiated as pupae had a lower competitiveness compared to males irradiated as adults, but the use of partially-sterilizing doses has not been studied extensively. Methods to reduce somatic damage during the irradiation process as well as the use of other agents or techniques to induce sterility are discussed. It is concluded that the optimal radiation dose chosen for insects that are to be released during an SIT programme should ensure a balance between induced sterility of males and their field competitiveness, with competitiveness being determined under (semi-) field conditions. Self-contained ⁶⁰Co research irradiators remain the most practical irradiators but these are likely to be replaced in the future by a new generation of high output X ray irradiators.     

Assessment of radiation-induced DNA damage in human blood lymphocytes using the single-cell gel electrophoresis technique.

The ability of the alkaline single-cell gel (SCG) electrophoresis technique to detect single-strand breaks and alkali-labile DNA damage in human cells induced by low doses of radiation was evaluated. Peripheral blood lymphocytes were irradiated with gamma-rays from a 137Cs source at doses from 0.01 to 1 Gy and exposed to alkali (pH greater than 13) for 20, 40 or 60 min and then electrophoresed at 25 V and 300 mA for either 20 or 40 min. The extent of DNA damage that was expressed and detected as DNA migration depended directly on the dose of radiation, the duration of exposure to alkali and the length of electrophoresis. At all experimental conditions tested, it was possible to detect a significant increase in DNA damage induced by a radiation dose as low as 0.05 Gy. Based on an analysis of the ratio of the range to the standard deviation for each radiation dose and experimental condition, the distribution of damage among cells for all doses was neither excessively homogeneous nor heterogeneous. Furthermore, the distribution was independent of radiation treatment. The SCG technique is rapid and sensitive, and useful for investigations concerned with effects of low doses of radiation.     

SOME EFFECTS OF RADIUM RADIATIONS ON WHITE MICE

It has been estimated that 92 per cent of the total radiation emitted by radium in equilibrium with its subsequent products is given off in the form of α-rays. This, however, cannot be utilized when the source is enclosed in an ordinary container, because the α-rays are absorbed completely by even a small thickness of glass. About 3.2 per cent of the total radiation is emitted in the form of β-rays, and 4.8 per cent as gamma radiation. The effects produced on the radiated mice of these experiments were due mainly to the β-rays, which are easily absorbed by tissue. The γ-rays, being only slightly absorbed by organic matter, probably contributed very little to the observed effects. It is interesting to correlate the different effects produced by the same dose of radiation. The mice which received a dose of 1.9 millicurie hours showed no local effects on the skin or hair. Neither females nor males were sterilized, and the time at which they opened their eyes or reached sexual maturity was not affected, as far as we could tell. The only difference noted between the radiated animals and the controls was in the body weight. This dose accelerated the growth of the young mice, that is, while initially of the same weight, soon after irradiation they became distinctly bigger than the controls, but finally the animals of each group had substantially the same average weight. That this variation in body weight should be accidental is unlikely, since it was observed also in the animals treated by a slightly larger dose (2.4 millicurie hours). The number of animals (seven) which showed this effect is too small to prove conclusively the accelerating effect of small doses of radiation on the body growth of mice. But considering that similar results have been. obtained by radiating plants and beetles, it is reasonable that the observed increase in weight might be attributed, at least in part, to the effects of radiation. Since this paper was first written Russ, Chambers, and Scott have shown that small doses of x-rays accelerate the body growth of rats. In view of this additional evidence there can be little doubt that the increase in weight observed in our experiments was due to the radiation. A dose of 2.4 millicurie hours applied over the backs of the animals produced no local skin effects, but it accelerated the growth of the mice as in the previous case. In addition it caused permanent sterilization of all the females. A similar result was obtained with 4.9 millicurie hours, except that the effect on the rate of growth was uncertain. A dose of 6.8 millicurie hours produced a definite but mild skin erythema and retarded the development of lanugo hair. But since in this instance the emanation was applied over the heads of the animals, the dose reaching the ovaries was not sufficient to cause sterilization, as already explained. No other definite effect was noted. In connection with the sterilization of the females it should be noted that a dose of radiation which produced no visible skin changes was sufficient to cause permanent sterility. On account of the greater distance of the ovaries from the source of radiation as compared with that of the skin directly below the tube, and the depth of tissue which the rays had to traverse to reach the ovaries, the amount of radiation acting on the latter was much smaller than the amount falling on the skin. The radiation emitted by the emanation tube is reduced to about 50 per cent of its initial value after traversing 1 mm. of tissue. Still, while the skin was not visibly affected, the mice were sterilized. This shows that the ovaries are influenced very easily by radiation of this type. We can estimate the amount of radiation reaching the ovaries which is sufficient to cause sterility to be less than 25 per cent of the amount necessary to produce visible skin changes in the mice. It should be noted also that whenever sterility of the female mice was induced, it was permanent. Furthermore, those mice which were not rendered sterile by radiation were, as far as the experiments enable us to say, as prolific as the controls. Remembering that a dose of 1.9 millicurie hours had no apparent effect on the ovaries, while a slightly larger dose, 2.4 millicurie hours, caused permanent sterility, it might be concluded that it is not possible to produce temporary sterility by radiation. We know, however, that temporary sterility can be produced, at least when the animals are radiated at a later stage in their development. The mice in our experiments were radiated for the first time soon after birth, and it is not improbable that under these conditions temporary sterility cannot be obtained. Large sublethal doses produced severe skin burns, retarded the body growth of the animals, but failed to sterilize the males. About one-third of the total skin area of the mice showed marked effects from the radiation. The animals were very sick for a time, and their growth was temporarily stunted. But nevertheless they recovered and finally became apparently normal except for the narrow hairless strip of skin which had been closest to the emanation tube. Only the females were rendered permanently sterile. The males did not show even temporary sterility when the doses of radiation were close to the lethal dose. While the testes of mammals are known to be very easily affected by radiation, still they are more resistant than the ovaries. In addition, in these experiments they were at a greater distance from the source of radiation than the ovaries, and they were better protected by the thicker layer of tissue in the path of the rays. The fact that no sublethal dose in these experiments sterilized the males shows that under the conditions of irradiation adopted the amount of radiation reaching the testes was not sufficient to affect them noticeably. If the source of radiation had been applied closer to the reproductive organs of the males, they would have been sterilized by millicurie hour doses much smaller than the lethal dose. Some of the radiated animals were killed with ether, and macroscopic and microscopic examinations of the reproductive organs were made. The ovaries of the sterile females were generally atrophied and colored yellow. The normal histological structure was altered. The characteristic findings were the destruction of the Graafian follicles, with absence of ovum cells. The testes and the epididymis of the radiated mice of the present experiment appeared macroscopically and histologically normal, with the presence of abundant spermatozoa. Owing to the method adopted for the irradiation of the mice, the testes were too far from the source of radiation, and too well protected by the intervening tissue to be definitely affected by the rays.     

Prediction of growth of Bacillus megaterium spores as affected by gamma radiation dose and spore load

AIMS: To provide data on the interaction of radiation dose (x1) and microbial contamination load (x2), as predictor variables, on the percentage of vials exhibiting growth of Bacillus megaterium spores (y). METHODS AND RESULTS: The influence of a wide range of spore loads (1-50 000 spores of B. megaterium vial-1) and gamma radiation doses (0.2-10 kGy) on the contaminated samples was determined. Each contamination load was studied by adding the specified number of spores to 100 vials containing nutrient broth and exposing them to various doses of gamma radiation. Curves representing the number of contaminated vials against the dose of radiation were sigmoidal in shape and the data showed an indirect relationship. Data were analysed by regression analysis which revealed a significant correlation (R2=0.85). The relationship among the tested variables is exponential and can be described by the following equation: y = 1 - (1 - e(0.0173x(1)))(x(2)) It was also estimated that, for each increase of 1 in the number of spores per vial, there is an increase of 1 in the number of contaminated vials. CONCLUSION: The two variables (x1 and x2) have great influence on the radiation sterilization efficiency and the proposed mathematical model is valid for the prediction of this efficiency. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present investigation can be of useful industrial application and can help to set acceptance and rejection limits for the production of materials vulnerable to microbial contamination.     

Radiation Sterilization of Prototype Military Foods: II. Cured Ham

Ten lots of diced cured ham, packed in cans, were inoculated with approximately 10(6)Clostridium botulinum spores per can. Each lot was seeded with a different strain (five type A and five type B strains). All cans were irradiated to various dose levels with Co(60). Evidence provided by swelling, toxicity, and recoverable C. botulinum with 6,350 cans demonstrated that: (i) 4.5 Mrad was more than adequate as a sterilization dose; (ii) the minimal experimental sterilizing dose (ESD) based on nonswollen nontoxic endpoints was 2.0 < ESD 相似文献   

Prolongation of the effective copulation period by fractionated‐dose irradiation in the sweet potato weevil,Cylas formicarius

The sterile insect technique (SIT), based on the principles of population and behavioral ecology, is widely used to suppress or eradicate target pest insect populations. The effectiveness of SIT depends on the ability of released sterile males to mate with and inseminate wild females; however, the use of gamma radiation to induce sterility negatively affects both somatic cells as well as reproductive cells. Consequently, sterilization by irradiation drastically diminishes mating performance over time. It is well known that fractionated‐dose irradiation, in which a sterilizing dose is delivered via a series of smaller irradiations, reduces radiation damage. In the present study, we evaluated the effect of fractionated‐dose irradiation on fertility, longevity, and mating propensity in Cylas formicarius (Summers) (Coleoptera: Brentidae) for 16 days after irradiation. Fractionated‐dose irradiation with 200 Gy induced full sterility regardless of the number of radiation doses. Although the mating propensity of males sterilized by a single 200 Gy dose (the current standard of the Okinawa Prefecture SIT program) was equal to that of non‐irradiated weevils for the first 6 days, the mating propensity of males sterilized by a series of three doses was maintained for at least the first 12 days. These results demonstrated that fractionated‐dose irradiation can be highly advantageous in C. formicarius eradication programs.     

A novel fast kilovoltage switching dual-energy CT with deep learning: Accuracy of CT number on virtual monochromatic imaging and iodine quantification

PurposeA novel fast kilovoltage switching dual-energy CT with deep learning [Deep learning based-spectral CT (DL-Spectral CT)], which generates a complete sinogram for each kilovolt using deep learning views that complement the measured views at each energy, was commercialized in 2020. The purpose of this study was to evaluate the accuracy of CT numbers in virtual monochromatic images (VMIs) and iodine quantifications at various radiation doses using DL-Spectral CT.Materials and methodsTwo multi-energy phantoms (large and small) using several rods representing different materials (iodine, calcium, blood, and adipose) were scanned by DL-Spectral CT at varying radiation doses. Images were reconstructed using three reconstruction parameters (body, lung, bone). The absolute percentage errors (APEs) for CT numbers on VMIs at 50, 70, and 100 keV and iodine quantification were compared among different radiation dose protocols.ResultsThe APEs of the CT numbers on VMIs were <15% in both the large and small phantoms, except at the minimum dose in the large phantom. There were no significant differences among radiation dose protocols in computed tomography dose index volumes of 12.3 mGy or larger. The accuracy of iodine quantification provided by the body parameter was significantly better than those obtained with the lung and bone parameters. Increasing the radiation dose did not always improve the accuracy of iodine quantification, regardless of the reconstruction parameter and phantom size.ConclusionThe accuracy of iodine quantification and CT numbers on VMIs in DL-Spectral CT was not affected by the radiation dose, except for an extremely low radiation dose for body size.     

Acute biological effects of simulating the whole-body radiation dose distribution from a solar particle event using a porcine model

In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses.