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

Abstract

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.

Identity, Synthesis, and Cytotoxicity of Forchlorfenuron Metabolites in Kiwifruit

“…There have been many residue studies on CPPU itself, among which Sharma et al studied CPPU residues in grapes, as well as in environmental samples from soil and water . Much progress has been made toward the quick and accurate quantification of CPPU in fruits and vegetables. ,− In addition, hyperspectral imaging technology and hand-held detector have been developed that can be used to nondestructively distinguish between CPPU treated and untreated kiwifruit. , Repeated-dose toxicity study of CPPU in rats indicate the danger that CPPU has potential adverse effects on the ovaries and steroid production . In addition, animal studies in zebrafish indicate that CPPU adversely affects cardiac morphology and function …”

Residue Analysis and the Effect of Preharvest Forchlorfenuron (CPPU) Application on On-Tree Quality Maintenance of Ripe Fruit in “Feizixiao” Litchi (Litchi chinensis Sonn.)

“…Because of the very low concentrations of CPPU applied, residue of CPPU in the fruit flesh is generally below the maximum residue limit (MRL; Chen et al, 2013;Li et al, 2020). However, the potential health risk of CPPU is still under evaluation (Bu et al, 2019). Available reports have shown that the dissipation rate of CPPU residue in fruit differs greatly among species (Zhang et al, 2011;Chen et al, 2013;Li et al, 2020).…”

“…In practice, CPPU is generally applied at very low concentration due to its strong cytokinin activity, and residue of CPPU in the fruit flesh is generally below maximum residue limit (MRL; Chen et al, 2013;Li et al, 2020). However, the potential health risk of CPPU is still under evaluation (Bu et al, 2019). Therefore, in this study, residues of CPPU in the pericarp and aril tissues were analyzed following application to provide reference about food safety related to preharvest application of CPPU.…”

A Sensitive Monoclonal-Antibody-Based ELISA for Forchlorfenuron Residue Analysis in Food Samples

“…Gong et al [ 7 , 8 ] found that CPPU can induce cardiac morphology deformation and validated the cardiotoxicity of CPPU in a different experimental model. A chronic toxicity study on CPPU revealed its potentially negative effects on the ovaries [ 9 ]. In addition, long-term exposure to CPPU can induce acute and chronic intoxication and irritation to the eyes and skin [ 10 ].…”