Pharmacokinetics and toxicity evaluation following oral exposure to bisphenol F

Abstract

Bisphenol F is a substitute material for bisphenol A and is widely used in household products as a raw material for polycarbonate resin, epoxy resin, and plastic reinforcement. It is known to be mainly used in food containers, thermal paper for receipts, and coatings for water pipes. In some countries, bisphenol F has been detected in drinking water and human urine samples. However, due to the lack of safety evaluation data on bisphenol F, it is difficult to establish appropriate guidelines for the proper use of the substance, and social anxiety is increasing accordingly. This study investigated the use, exposure route, and distribution flow of bisphenol F, a household chemical. To determine the no-observed-adverse-effect level (NOAEL) and target organ of bisphenol F after exposure, a single-dose oral toxicity, dose-range finding (28 day oral), repeated dose toxicity (90 day oral), and genotoxicity (reverse mutation, chromosomal abnormality, in vivo micronucleus test) tests were performed. The pharmacokinetic profile was also obtained. The test results are as follows: in the pharmacokinetic study, it was confirmed that single oral exposure to BPF resulted in systemic exposure; in single oral dose toxicity test, the approximate lethal dose was found to be 4000 mg/kg and confusion and convulsion was shown in the test animals; NOAEL was determined to be 2 mg/kg/day for male and 5 mg/kg/day for female, and the no-observed-effect level (NOEL) was determined to be 2 mg/kg/day for males and 1 mg/kg/day for females, and the target organ was the small intestine; genotoxicity tests confirmed that BPF does not induce genotoxicity.

Omega 3 fatty acid improves sexual and erectile function in BPF-treated rats by upregulating NO/cGMP signaling and steroidogenic enzymes activities

“…Additionally, the observed decrease in AChE could account for the BPF-induced sexual dysfunction. The finding from this study that BPF decreased AChE is similar to previous studies that reported similar observations following BPF exposure 35 and its analog 36 , 37 . Although, it is expected that a decline in AChE should improve sexual function since AChE activities have been shown to breaks down or hydrolyzes acetylcholine (ACh), which is also responsible for penile erection 38 .…”

Bisphenol AF Induces Alterations in the Plasma Lipidome of Rats: An Untargeted Lipidomics Approach

“…15 Moreover, a toxicity test conducted with a single dose of BPF revealed symptoms like confusion and convulsions following oral administration. 16 Perinatal exposure to bisphenol AF did not induce adverse effects on oxidative damage; however, it led to alterations in the levels of β-glucose and glycogen in the livers of male mouse offspring. Gu et al investigated bisphenol AF exposure in zebrafish, revealing increased oxidative stress, apoptosis, and suppressed cardiac development gene expression.…”

“…Recent studies have demonstrated the detrimental effects of BPA and its structural congeners, including bisphenol AF, bisphenol G, bisphenol M, and bisphenol X, on microalgae species like Chlorella vulgaris and Desmodesmus armatus . Moreover, a toxicity test conducted with a single dose of BPF revealed symptoms like confusion and convulsions following oral administration . Perinatal exposure to bisphenol AF did not induce adverse effects on oxidative damage; however, it led to alterations in the levels of β-glucose and glycogen in the livers of male mouse offspring.…”

Report of the Scientific Committee of the Spanish Agency for Food Safety and Nutrition (AESAN) on the prospection of chemical hazards of interest in food safety in Spain (2)

“…With regard to BPF, it has been considered as a "substance requiring regulation" by the International Chemical Secretariat (ChemSec). Lee et al (2022) conducted recently a long-term toxicity study (90-day repeat-dose toxicity test), genotoxicity, and BPF pharmacokinetic studies in rats. The authors determined a NOAEL of 2 mg bisphenol F/kg b.w./day for male animals and 5 mg bisphenol F/kg b.w./day for females, and a NOEL (No Observed Effect Level) of 2 mg bisphenol F/kg b.w./day for male rats and 1 mg bisphenol F/kg b.w./day for females, with the target organ being the small intestine.…”