180 Day Repeated-Dose Toxicity Study on Forchlorfenuron in Sprague-Dawley Rats and Its Effects on the Production of Steroid Hormones.

Forchlorfenuron (FCF) is a synthetic plant cytokine-like growth regulator that is massively used in agriculture to increase fruit size and weight. There is an insufficiency of published data on the safety profile of FCF, especially as it is involved in ovarian function. In our study, a chronic toxicity study on FCF was conducted and designed by feeding at dosage levels of 0, 0.6, and 60 mg/kg body weight in Sprague-Dawley rats for 180 days. During the 180 day FCF administration, no biologically relevant changes were observed in the body weight, clinical signs, food consumption, organ weight, hematology, and clinical biochemistry of the tested animals. However, macroscopic and microscopic evaluations revealed the presence of severe hydrometra in the uterus and pathological changes in the ovaries. In addition, it was found that FCF inhibited the proliferation of granulosa cells (GCs) and H295R cells, as well as downregulated the expression of CYP17A1 and CYP19A1 in estradiol and progesterone production, resulting in decreased steroidogenesis in GCs and H295R cells. Taken together, our findings suggest that FCF has potential adverse effects on the ovaries and on steroidogenesis.