A method of determining a genotoxicity risk for a test population of cells, the method comprising the steps of: a) performing a directional genomic hybridization (dGH) reaction by contacting one or more pairs of single-stranded sister chromatids on at least four cells from the test population of cells, with a plurality of sets of dGH probes, wherein the dGH probes of each set of dGH probes binds to a different target DNA sequence on a same single-stranded sister chromatid, wherein each set of dGH probes binds to a corresponding set of target DNA sequences on a different single-stranded sister chromatid, and wherein each single-stranded sister chromatid can be assigned to a chromosome number based on a color of the set of dGH probes that binds thereto and other visual features of the single-stranded sister chromatid; b) assessing a presence or absence of two or more types of chromosome variants and/or repair events in each of the at least four cells of the test population of cells individually based on results of the dGH reaction; c) measuring the number and/or variability of each of the two or more chromosomal variant and/or repair event types in each of the at least four cells of the test population of cells; and d) comparing the number and/or variability of each of the two or more chromosomal variant and/or repair event types in the test population of cells to a number and/or variability for a corresponding type of chromosomal variant and/or repair event of a control cell or a population of control cells, wherein a weight is assigned to the number and/or variability for each type of chromosomal variant and/or repair event to provide a series of weighted factors, wherein the weight assigned to obtain each weighted factor of the series of weighted factors depends on a characteristic of and/or a type of cells of the test population of cells to determine a weighted chromosomal stability score, wherein the weighted chromosomal stability score is used to determine the genotoxicity risk of the test population of cells, and wherein an increased weighted chromosomal stability score in the test population of cells compared to the control cell or the population of control cells is indicative of an increased genotoxicity risk for the test population of cells. a) performing a directional genomic hybridization (dGH) reaction by contacting one or more pairs of single-stranded sister chromatids on at least four cells from the test population of cells, with a plurality of sets of dGH probes, wherein the dGH probes of each set of dGH probes binds to a different target DNA sequence on a same single-stranded sister chromatid, wherein each set of dGH probes binds to a corresponding set of target DNA sequences on a different single-stranded sister chromatid, and wherein each single-stranded sister chromatid can be assigned to a chromosome number based on a color of the set of dGH probes that binds thereto and other visual features of the single-stranded sister chromatid; b) assessing a presence or absence of two or more types of chromosome variants and/or repair events in each of the at least four cells of the test population of cells individually based on results of the dGH reaction; c) measuring the number and/or variability of each of the two or more chromosomal variant and/or repair event types in each of the at least four cells of the test population of cells; and d) comparing the number and/or variability of each of the two or more chromosomal variant and/or repair event types in the test population of cells to a number and/or variability for a corresponding type of chromosomal variant and/or repair event of a control cell or a population of control cells, wherein a weight is assigned to the number and/or variability for each type of chromosomal variant and/or repair event to provide a series of weighted factors, wherein the weight assigned to obtain each weighted factor of the series of weighted factors depends on a characteristic of and/or a type of cells of the test population of cells to determine a weighted chromosomal stability score, wherein the weighted chromosomal stability score is used to determine the genotoxicity risk of the test population of cells, and wherein an increased weighted chromosomal stability score in the test population of cells compared to the control cell or the population of control cells is indicative of an increased genotoxicity risk for the test population of cells.