Studies for a genotoxic potential of some endogenous and exogenous sex steroids. II. Communication: examination for the induction of cytogenetic damage using the chromosomal aberration assay on human lymphocytes in vitro and the mouse bone marrow micronucleus test in vivo.

The cytogenetic potential of 10 sex steroids (cyproterone acetate, drospirenone, gestodene, cyclodiol, cyclotriol, ethinylestradiol, atamestane, lilopristone, onapristone and propylmesterolone) with various medical indications was determined using the chromosomal aberration test in human lymphocytes in vitro and the mouse bone marrow micronucleus test in vivo. Nine of these sex steroids (gestodene was omitted) were investigated in the human lymphocyte assay and found to be negative with respect to the induction of chromosomal aberrations either with or without metabolic activation. In all assays the highest concentration evaluated was either clearly cytotoxic or, in case of noncytotoxicity, resulted in visible precipitates in the culture medium. Evaluation of the data from the mouse bone marrow micronucleus test indicated that the seven steroids (cyproterone acetate, drospirenone, gestodene, ethinylestradiol, atamestane, onapristone and propylmesterolone) investigated failed to induce enhanced frequencies of micronucleated polychromatic erythrocytes in male and female mice. The steroids were tested up to dose levels which induced signs of toxicity in the experimental animals or, in the case of non toxic compounds, the animals were treated up to the maximum recommended dose of 2 g/kg body weight. Evaluation of all data indicates that the investigated estrogens, progestins and other sex steroids had no genotoxic potential detectable with the chromosomal aberration assay on cultured human lymphocytes or the mouse bone marrow micronucleus test.