Human – Environment QSAR Studies of Radioactive Chemicals by Online Prediction Websites

Diagnosis, therapy, and research – development are main targets in radioactive materials issues that took huge places in medical sector of radio-molecular imaging and nuclear medicine where adsorbed radionuclide by the target(s) with high selectivity and minimum duration management compared to chemotherapy. In this study, three online websites created by various scientific groups in Baker Institute, university of Queensland, and School of Computing and Information Systems, University of Melbourne as a computed base to predict toxicity of various radiopharmaceuticals having Sm-153; Ga-68; F-18; Hg-197; I-131; I-123; Tc-99m: In-111, or Se-75. Prediction of forty – five radio-chemicals targeted embryo, cardio-: Arrhythmia, heart block, Cardiac Failure, hERG, Myocardial Infarction, and hypertension. Herbicidal activity and environmental safety represented by Honey Bee, Avian, Minnow , as well as human toxicity that include Ames, rat acute (LD 50 ) and chronic (LOAEL) toxicities were additionally evaluated by these three online websites. Here first Iraqi attempt showed that these tested materials had a toxic site to one or more of human (embryo or pregnant mother), cardio-(Arrhythmia, Cardiac Failure, Heart Block, hERG, Hypertension, or Myocardial Infarction) or rat acute (LD 50 ) – chronic (LOAEL), as well as environment (


Introduction
Diagnosis, therapy, and researchdevelopment are main targets in radioactive materials issues that took huge places in published scientific sources especially in medical sector named as radio-molecular imaging and nuclear Iraqi Journal of Industrial Research (IJOIR) Journal homepage: http://ijoir.gov.iqmedicine [1].In the part of radio-chemicals therapies, early starts were begin in 20th centenary after Becquerel and Curie discoveries in the subject followed limited experiments done by Danlos, Bloch, Proescher, and Bell testing radium effect on skin lesion, tumor, and other diseases.Huge expansion in radionuclide therapy was noticed via delivering adsorbed dose to the target(s) with high selectivity and minimum duration management compared to chemotherapy (see Table 1) [2,3,4].
From these beginnings, nuclear medicine become a functionalized branch in molecular imaging by utilizing radiopharmaceutical as a visualizing biomaterial enabling highly accurate metabolic, chemical, biological, and functional characterizations.These characterizations may be achieved at molecularcellular levels to measure and treat living systems depending upon defined linkage between radioactive atom(s) and organic carrier (Table 1, Figures 1, 2, & 3) that directly reacts with human body after intravenous step [5,6,7,8].So, molecular imaging in diagnosis, therapy, and research fields mainly based upon radioactive atom decay as diagnostic tool that transforms detected radioactive pharmaceutical to visualized image as well as enabling characterization and measurement of the particle emission (Tables 1 and 2) [8,9].

Experimental Procedure 2.1. Chemicals under Testing
Studied radioactive chemicals were tested via three online websites [10,11,12].Studied toxicological properties were embryo, cardio-: Arrhythmia, heart block, Cardiac Failure, hERG Toxicity, Myocardial Infarction, and hypertension.Herbicidal activity and environmental safety represented by Honey Bee, Avian, Minnow, as well as human toxicity that includes Ames, rat acute (LD50) and chronic (LOAEL) toxicological characters.Each radiopharmaceutical symbolizes as Code: Name.
. This isomeric or canonical SMILES with copy-paste in any online website that mentioned in [10, 11, or 12] article present the full accurate molecular structure of the molecule under test then pressing predict to get the needed information.

Results and Discussion
Various radiopharmaceuticals were studied in this paper where their actual actions according to the mentioned references in introduction section, https://pubchem.ncbi.nlm.nih.gov/website with its cited references beside recent references related to cancers are limited as Antineoplastic, Radio-conjugate in somatostatin receptor imaging in conjunction with Positron Emission Tomography (PET), Radioactive Imaging Agent or Diagnostic aid in (renal function, hypoalbuminemia, or Lung scintigraphy), Radiotracer, Probe for primary and metastatic melanoma imaging or as a diagnosis agent in malignant Melanoma, Parkinson' disease detector, and labeled form as a tumor-targeting agent [13,14,15,16] .These radiopharmaceuticals contains radioactive elements or ions of Sm-153; Ga-68; F-18; Hg-197; I-131; I-123; Tc-99m: In-111, and Se-75.
Here, a new toxicological evaluation was done with in Silico prediction via various online websites to evaluate different toxicity of each radio-compound against embro-, cardio, and environmental: avian, honey bee, Minnow fish, Ames, rat, and herbicidal as shown in Tables (3 & 4, Figure 4).

Figure (4). Rat Acute (LD50) and Rat Chronic (LOAEL) toxicities of all tested radiopharmaceuticals
In medical section, irregular heartbeat (Arrhythmia) during any physical activity by human categories into brady and tachy-arrhythmia according to heart rate (too quick, too slow, or irregular rhythm).In brady-type, heart rate is lower than 60 beats / minute (bpm) while beating excesses than 180 bpm classifies as tach-type.Deviation in rate may be resulted by many factors including toxic material(s) that may led to sudden death.Also, structural defect can cause heart failure especially in foetus then intrauterine death with absence of transplacental controlling or anti-arrhythmic drug treatment [17,18].
 This prediction showed that Tc5-99m, Tc10 -99m, Tc12-99m, Tc24-99m, Tc26-99m, Tc29-99m, and Tc32-99m were toxic in heart block issue (15.56% were toxic). Myocardio-infraction prediction found in Hg-197, I-123, Tc5-99m, Tc8-99m, Tc9-99m, Tc11-99m, Tc13-99m, and Tc29-99m (as 17.78% Myocardio-infraction in tested radiopharmaceuticals). It can be noticed that Tc29-99m was unsafe in three cardio-toxicological subjects: Arrhythmia, heart block, and Myocardio-infraction.This toxic radiopharmaceutical may cause birth defects such as disruption, malformation, deformation, dysplasia, delayed mental development, growth, or other disorders as a result of its embryotoxicity. While Tc32-99m may cause Arrhythmia, heart block, and hypertension beside embryo toxicological effects. Table (3) presented Tc12-99m and Tc29-99m had the same toxicological actions to embryo as well as Arrhythmia and heart block.Also, Tc17-99m and In111 may cause Embryo, Arrhythmia and hERG. Table (4) shows attractive results about Honey Bee, Avian, Minnow, as well as human toxicity that includes rat acute (LD50) and chronic (LOAEL) toxicological characters (Figure 4) where only Tc11-99m and Tc25-99m (Figure 3) had a serious toxicological effect on honey bee. Also, Table (4) showed that Tc11-99m had an additional toxicological effect on avian beside honey bee that mentioned above. Minnow fish that is used as toxicological indicator may be influences by these radiopharmaceuticals under prediction with a toxicity range (-1.567 to 4.071) while rat acute (LD50) and chronic (LOAEL) ranges (Table 4, Figure 4) were (111.9 to 6603.9) and (5.2 to 1629.3) respectively. Ames test was with No response to all radiochemicals under prediction. Table (4) showed that Tc12-99m the lowest value but most dangerous effect on Minnow fish (-1.567) between all tested materials.This toxic influence may be related to the presence of poly-ol and poly (N-COOH) in its molecular structure (Figure 2)  Also, Tc24-99 (Figure 3) had a highly toxic with the lowest LD50 as a rat acute toxicity indication (Figure 4). Presence of Iodine -123 in the chemical structure of the secondary amine (I123) radio-substance (Figure 1) showed a dark image in this prediction study with the lowest rat chronic dose.
For more understanding of prediction efficiency, Tc11-99m (Figure 3 Heart attack or Myocardial Infarction is a silent -serious medical situation caused by depriving of blood flow to myocardium as a catastrophic occurrence.This may drive to death after hemodynamic deterioration [19].For example, Tc11-99m may impulse irreversible cardiac damage of the muscular fibers or intense stress that induced spasms in the vessel walls and shorten blood supply to the smooth muscle.Also, this radioactive material is in Silico considered safe from being sick with cardiac failure, heart failure, hypertension, or hERG medical issue.