Abstract
Forchlorfenuron (CPPU) is a plant growth regulator extensively used in agriculture. However, studies on CPPU pharmacokinetics are lacking. We established and validated a rapid, sensitive, and accurate liquid chromatography–mass spectrometry method for CPPU detection in rat plasma. CPPU pharmacokinetics was evaluated in adult and juvenile rats orally treated with 10, 30, and 90 mg/kg of the compound. The area under the plasma drug concentration–time curve from 0 to 24 h (AUC), at the final time point sampled (AUC0–t), and the maximum drug concentration of CPPU increased in a dose-dependent manner. The pharmacokinetic parameters AUC0–t and absolute bioavailability were higher in the juvenile rats than in adult rats. The mean residence time and AUC0–t of juvenile rats in the gavage groups, except for the 10 mg/kg dose, were significantly higher in comparison to those observed for adult rats (p < 0.001). The plasma clearance of CPPU in juvenile rats was slightly lower than that in the adult rats. Taken together, juvenile rats were more sensitive to CPPU than adult rats, which indicates potential safety risks of CPPU in minors.
Highlights
Forchlorfenuron, known as 1-(2-chloro-4-pyridyl)-3-phenylurea (CPPU), is a synthetic phenyl urea-derived cytokinin extensively used as a plant growth regulator in agriculture
Data are presented as the mean ±SD (n = 6). i.v.—intravenous; p.o.—per oral; Cmax—the maximum drug concentration; T1/2—the time taken for half the initial drug concentration to be eliminated; CLz—plasma clearance; MRT0–t—mean residence time; AUC0–t— the area under the plasma drug concentration–time curve from 0 to 24 h, the final time point sampled; AUC0–∞—the area under the plasma drug concentration–time curve from 0 to infinity; comparison between the doses in adult and juvenile rats; F—bioavailability, CPPU—1-(2-chloro-4-pyridyl)-3-phenylurea, forchlorfenuron. ** p < 0.01 and *** p < 0.001. Both the AUC0–t and maximum drug concentration (Cmax) in adult and juvenile rats treated with CPPU at 10–90 mg/kg increased in a dose-dependent manner
We studied the PK characteristics of CPPU in adult and juvenile rats and found that AUC0–t and absolute bioavailability were higher in juvenile than in adult rats, which may be due to metabolic differences
Summary
Forchlorfenuron, known as 1-(2-chloro-4-pyridyl)-3-phenylurea (CPPU), is a synthetic phenyl urea-derived cytokinin extensively used as a plant growth regulator in agriculture. A previous study demonstrated that juvenile animals are more susceptible to the acute effects of some organophosphorus insecticides than adults [10]. Based on these reports, pesticide exposure is expected to induce a more toxic response in children. While the PK characteristics of CPPU in juvenile rats are currently unclear, understanding these may provide a basis for the further study of pesticide exposure in children. We applied the method to compare the PK characteristics of CPPU in adult and juvenile rats. Our findings provide evidence for the risks of CPPU exposure in children as well as a scientific basis for the understanding of its metabolism in humans
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