AbstractSex reversal of early life stage tilapia (approximately 7–12 d post‐hatch, total length averaging 9–11 mm, and total weight averaging 10–15 mg) is used commonly to produce populations of fish comprised of > 5% phenotypic females. The synthetic androgen, 17α‐methyl testosterone (MT), is used to effect sex reversal in tilapia. This paper evaluates environmental impact and human food safety aspects of MT use for tilapia sex reversal based on a review of the scientific literature and on dilution models of farm discharge.Effect of MT treatment on human food safety was evaluated by regression analysis of radioactivity depletion data and by dilution through growth analysis. Results show that the proposed use of MT for sex reversal of early life stage tilapia presents no negative effects on human food safety. Regression analysis of available depletion data from tilapia shows that whole‐body concentrations of MT and metabolites in tilapia attain levels of <100 pg/g after 8 to 40 d of withdrawal, and that achievement of <10 pg/g of MT and metabolites in carcass tissue occurs after 6 to 50 d of withdrawal. These concentrations are attained well before completion of the FDA‐required 120‐d withdrawal period following MT treatment.Standardized calculations were made to estimate MT concentration in effluents based on stocking rate and water exchange. Guidelines are provided for management of farms to ensure that effluent MT concentration remains < 1 μg/L. Given the expected concentration of MT in any farm effluents, the rapid dilution of effluent MT to very low levels in receiving waters, the sensitivity of MT to photo‐oxidation, the expected rapid bacterial degradation of MT, and the limited total use of MT in the United States, we concluded that the use of MT‐treated feed according to the proposed protocol will not cause significant adverse environmental effects.