Subacute oral toxicity study of bisphenol F based on the draft protocol for the “Enhanced OECD Test Guideline no. 407”

Abstract

Since bisphenol F (4,4'-dihydroxydiphenylmethane) has been reported to exhibit estrogen agonistic properties in the uterotrophic assay, we performed a 28-day repeated-dose toxicity study (enhanced OECD test guideline No. 407) on bisphenol F based on the OECD draft protocols to determine whether it has endocrine-mediated properties. Bisphenol F was orally administered at doses 0, 20, 100 and 500 mg/kg per day for at least 28 days, but no clear endocrine-mediated changes were detected, and it was concluded to have no endocrine-mediated effects in young adult rats. On the other hand, the main effect of bisphenol F was concluded to be liver toxicity based on clinical biochemical parameters and liver weight, but without histopathological changes. The no-observed-effect level for bisphenol F is concluded to be under 20 mg/kg per day since decreased body weight accompanied by decreased serum total cholesterol, glucose, and albumin values were observed in the female rats given 20 mg/kg per day or higher doses of bisphenol F.

Exposure to endocrine disruptors during adulthood: consequences for female fertility

“…ATBC (5 and 10 mg/kg/day), a phthalate alternative, decreased the numbers of primordial, primary, and secondary follicles, but did not alter the numbers of corpora lutea or atretic follicles in mouse ovaries (Rasmussen et al 2016). In contrast the BPA analogue, BPF (20 – 500 mg/kg/day), did not cause histopathological changes in the rat ovary (Higashihara et al 2007). …”

“…One study showed that the BPA alternative, BPF (20 – 500 mg/kg/day), did not alter histopathology in the rat pituitary (Higashihara et al 2007). …”

Genotoxic and endocrine activities of bis(hydroxyphenyl)methane (bisphenol F) and its derivatives in the HepG2 cell line

“…In a recent publication, Higashara et al (2007) concluded no estrogens mediated effects of BPF in young adult rats, in a subacute oral toxicity study. Furthermore, we showed that in the rat, BPF was highly metabolized but also excreted as sulfate and glucuronide conjugates (Cabaton et al, 2006).…”

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing

“…Following the OeCD tG 407 which includes endpoints for thyroid hormone disruption, Higashihara et al found effects on thyroid hormone level in addition to changes in thyroid and pituitary weight (Higashihara et al, 2007). While the exact mechanism of action is not yet elucidated, BPF did not affect cell proliferation in both the t-screen and the tSH-screen, suggesting that its main mechanism of acwith other pathways (Roy and Mugesh, 2006b;Cao et al, 2010;Gayrard et al, 2011;Zabka et al, 2011;Kosuda et al, 1997;Grover et al, 2007;liu and Brent, 2010).…”