History
The Collaborative Radiological Health Laboratory (CRHL) was conceived in 1962 as a joint operation between the Division of Biological Effects, BRH, FDA, and the Department of Radiology and Radiation Biology, Colorado State University, to conduct a study of the long-term effects in the beagle from low-level whole-body gamma irradiation.[1]
In August 1962, the breeding program for beagles began to provide the first generation of subjects to be tested within the Collaborative Radiological Health Laboratory (CRHL) at Colorado State University. At that time the state of the art database system was also enacted on site to manage the data, an IBM-1620 computer that used Fortran programming and punch cards.
IBM-1620 computer that used Fortran programming and punch cards
The Biometry Section for CRHL was solely responsible for generating and maintaining the data and analysis with a relational database system.
Their early studies in the1960’s involved implants of plutonium in the paws of beagle dogs. The aim was to determine the relative translocation of Pu of known Am content from simulated puncture wounds contaminated with PuO2 in beagle dogs. Test validity of 241Am as tracer for Pu burden assessment.[2]
In December of 1967, a major study was initiated with 1,680 beagle dogs to determine the lifetime effects associated with invitro and invivo radiation exposures.[3] Sponsored by the U.S. Food and Drug Administration, these studies sought to understand the effects of ionizing radiation using Co60, to mirror medical treatments during early human development. There were three main segments of scientific research conducted: (I) Long-Term Study, Segment I. Study of prenatal development and short-term prenatal radiosensitivity in the beagle, (II) Long-Term Study, Segment II. To determine the radiosensitivity in terms of lethal dose and delayed effects within short time ( a few years) following exposure within LD50 range. These animals received a single whole-body expo of 60Co gamma radiation.; (III) Long-Term Study effects in beagles of a single whole-body radiation exposure given at different periods of development.[4],[5]
For an in depth read of the Cobalt-60 studies and the respective data, please read the 1992 Final Report:
“Health Effects of Low Level Irradiation During Development of the Dog”
Summary of Studies
Plutonium Implant Injection Study (not lifelong) 1960’s
Aim: To determine the relative translocation of Pu of known Am content from simulated puncture wounds contaminated with PuO2 in beagle dogs. Test validity of 241Am as tracer for Pu burden assessment. Measure the effects of chelation therapy within this test.[6]
Isotopes: 239Pu(NO3)4; 239PuO2 (high fired) with known amounts of 241Am. The plutonium oxide used in implants was provided by the Rocky Flats Division of Dow Chemical Company.
Delivery Method: Air oxidized Pu, 239Pu(NO3)4 Implants: subcutaneous injections over left metacarpus. This location was chosen as most accidental wound contaminations of industrial plutonium incidents were located on the hands and fingers of workers.[7]
Methods: The two insoluble oxides were suspended in aqueous media and the nitrate was in a solution of 0.02 N in HNO3.[8] Implanting procedures can be found in report COO-1787-6
Species: Beagle Dog, 40 adult males divided into ten study groups. Half of each group received DTPA therapy.
Additional studies: The effect of DTPA therapy was greater for the nitrate than for the air oxidized plutonium implants.[9] Half of each group received DTPA therapy.
1968 Report: “In Vivo evaluation of internal deposition and translocation of plutonium in the body is primarily based on the gamma emission of americium-241, the daughter of plutonium-241, which is present in the reactor produced plutonium.” It was believed that americium is metabolized in a similar way with plutonium once implanted inside the body.
Cobalt-60 Gamma Exposure Studies on Early Development
Long-Term Study Segment I
Isotope: 60Co gamma exposures
Delivery Method: Whole body exposure
Species: Beagle Dog, 1680 animals exposed (combined for all segments)
Method: This segment is designed to characterize prenatal development and short- term prenatal radiosensitivity of the beagle during period of interest to the major study ( see Segment III ) . The emphasis on early development in the major study and the paucity of published information on the dog dealing with prenatal sensitivity created an urgent need for work on canine embryology and teratology . Utilizing females which had previously fulfilled their role as suppliers of experimental stock , the experimental portion of this segment is now largely completed . The understanding of prenatal effects including developmental malformations , growth retardation and increased rates of prenatal and neonatal mortality will form a basis for evaluating late -developing permanent effects at various exposure ages.[10]
Long-Term Study Segment II
Isotope: 60Co gamma exposures
Delivery Method: Whole body exposure
Species: Beagle Dog, 1680 animals exposed (combined for all segments)
Method: Animals received a single whole – body exposure to 60Co gamma radiation at 8 days postcoitus ( dpc ) , 28 dpc , or 55 dpc or at 2 days postpartum ( dpp ) . Females used to provide prenatally irradiated pups were previously unirradiated animals that had contributed their second litters to Segment III ; 2 – day – old pups were from first litters of their bitches . Exposure conditions were similar to those used in Segment III except that the range of exposures used at each age was designed to bracket the LD50 . Animals surviving the first 60 days of postnatal life were assigned to one of four subgroups , and were respectively scheduled for necropsy at 70 days , 2 years , or 4 years , or available for physiological testing procedures . The circumstances of irradiation , management procedures , ages – at – exposure , and genetic background of the dogs in Segments II and III are identical . Therefore , Segment II serves as an extension of the major study by providing data over an extended dose range and making animals available for necropsy prior to the initial 5 – year sacrifice time specified in Segment III .[11]
Long-Term Study Segment III
Isotope: 60Co gamma exposures
Delivery Method: Whole body exposure
Species: Beagle Dog, 1680 animals exposed (combined for all three segments)
Method: Animals received a single , bilateral , whole – body exposure to 60Co gamma radiation at 8 dpc , 28 dpc , or 55 dpc , or at 2 dpp , 70 dpp , or 365 dpp . experimental design called for either 20 R ( limited to animals exposed in utero or at 2 dpp ) or 100 R midline in- air exposures . The exposure time was 10 minutes . Control animals were sham-irradiated . Exposure and dose statistics for Segment III beagles are given in Table 3 .[12]
From the 1980 annual report
Method: Eight groups of 120 dogs each received Mean doses of 16 or 83 cGy at 8 (preimplantation)2,8 (embryonic)o, r 55 (late fetal) days postcoitus( dpc), or 2 (neonatal) days postpartum( dpp). One group of 120 dogs received 83 cGy at 70 dpp (juvenile),and one group of 240 dogs received 83 cGy at 365 dpp (young adult).[13]
Data
The data from the Cobalt 60 studies was accessible in two forms: Rbase or Acess Database. We are providing the database sheets in the form of Excel sheets derived from the Access MDB entitled CRHL2002. This mdb was most likely constructed within the NRA based on the Rbase spreadsheets. In order to understand these data, it is imperative that you read the documentation provided that explains the abbreviated field headers and understand that these are relational database sheets that rely on multiple relationships to gain comprehensive understanding. Plainly said, you will benefit from joining several sheets together in a program such as Rscript to best understand these data and reading the header descriptions in the documentation “CRHL Database I”.
Documentation
Database notes (*this is formatted as a letter written to the person receiving the data)
Data
Annual Reports
References
References
[1] Bureau of Radiological Health, Rockville, Md. (USA). Div. of Biological Effects (1974). CSU-PHS collaborative radiological health laboratory annual report, 1974 (PB–246722). United States
[2] Johnson, L.J. Relative Translocation and Distribution of Pu and Am From Experimental PuO2 Subcutaneous Implants in Beagles. Special Report to AEC. 1969. Report COO-1787-6
[3] United States, Collaborative Radiological Health Laboratory. CSU-FDA Collaborative Radiological Health Laboratory annual report. CSU-FDA Collaborative Radiological Health Laboratory annual report. 1972. FDA 74-8017
[4] United States, Collaborative Radiological Health Laboratory. CSU-FDA Collaborative Radiological Health Laboratory annual report. CSU-FDA Collaborative Radiological Health Laboratory annual report. 1989.
[5] United States, Collaborative Radiological Health Laboratory. CSU-FDA Collaborative Radiological Health Laboratory annual report. CSU-FDA Collaborative Radiological Health Laboratory annual report. 1980. FDA 82-8042.
[6] Johnson, L.J. Relative Translocation and Distribution of Pu and Am From Experimental PuO2 Subcutaneous Implants in Beagles. Special Report to AEC. 1969. Report COO-1787-6
[7] Johnson, LJ (1969)
[8] Watters, R. L. & Lebel, J. L. (1972). Progress in the Beagle Studies at Colorado State University. Health Physics, 22 (6), 811-814.
[9] Watters, R. L. & Lebel, J. L. (1972).
[10] United States, Collaborative Radiological Health Laboratory. CSU-FDA Collaborative Radiological Health Laboratory annual report. CSU-FDA Collaborative Radiological Health Laboratory annual report. 1972. FDA 74-8017
[11] United States, Collaborative Radiological Health Laboratory. CSU-FDA Collaborative Radiological Health Laboratory annual report. CSU-FDA Collaborative Radiological Health Laboratory annual report. 1980. FDA 82-8042.
[12] United States, Collaborative Radiological Health Laboratory. CSU-FDA Collaborative Radiological Health Laboratory annual report. CSU-FDA Collaborative Radiological Health Laboratory annual report. 1980. FDA 82-8042.
[13] Benjamin SA, Saunders WJ, Angleton GM, Lee AC. Radiation carcinogenesis in dogs irradiated during prenatal and postnatal development. Journal of radiation research. 1991;32 Suppl 2:86-103.