6:2 Fluorotelomer alcohol

6:2 Fluorotelomer alcohol (6:2 FTOH) is an orally active, blood-brain barrier-permeable modulator of cyclin D1 and ETS1. 6:2 Fluorotelomer alcohol downregulates cyclin D1 expression, upregulates ETS1 via the TNF-α/ERK 1/2 pathway, impairs mitochondrial membrane potential and respiratory function, increases reactive oxygen species levels, disrupts calcium homeostasis and activates endoplasmic reticulum stress markers, and induces cell proliferation inhibition and endothelial-mesenchymal transition. Furthermore, 6:2 Fluorotelomer alcohol induces morphological abnormalities in zebrafish embryos and liver developmental damage, while disrupting the brain immune microenvironment in mice, causing systemic toxicity and delayed pup maturation in CD-1 mice. 6:2 Fluorotelomer alcohol also induces cortical neuron apoptosis, glial cell activation, synaptic abnormalities, colonic barrier damage, intestinal dysbiosis and autism spectrum disorder-like symptoms in mice. 6:2 Fluorotelomer alcohol shows no mutagenic, clastogenic, primary skin/eye irritation or skin sensitizing effects, exhibits no selective reproductive toxicity in CD-1 mice, and is classified as GHS Category 4 for acute oral toxicity. 6:2 Fluorotelomer alcohol can be used in studies of neurodevelopmental disorders and autism spectrum disorders^{[1][2][3][4][5]}. In Vitro:6:2 FTOH (50-200 µg/mL) dose-dependently inhibits proliferation and downregulates cyclin D1 expression in HaCaT human keratinocytes and HDF human dermal fibroblasts, with cyclin D1 reduced at 200 µg/mL in HaCaT cells and at 100 and 200 µg/mL in HDF cells^[1].
6:2 FTOH (50-200 µg/mL) activates ER stress signaling in HaCaT human keratinocytes and HDF human dermal fibroblasts, with dose-dependent increases in GRP78/BiP and CHOP in both cell types, and cell-specific phospho-eIF2α regulation^[1].
6:2 Fluorotelomer alcohol (0.1-1 μM; 24 h) significantly increases the viability of mouse cerebral microvascular endothelial bEnd.3 cells^[2].
6:2 Fluorotelomer alcohol (0.1-1 μM) significantly increases the proliferation rate of mouse cerebral microvascular endothelial bEnd.3 cells, as measured by EdU incorporation^[2].
6:2 Fluorotelomer alcohol (0.1-1 μM) reduces tight junction protein (ZO-1) expression, increases Occludin degradation, upregulates mesenchymal marker (N-cadherin) expression, and downregulates endothelial marker (VE-cadherin) expression in mouse cerebral microvascular endothelial bEnd.3 cells, indicating EndMT induction and tight junction disruption^[2].
6:2 Fluorotelomer alcohol (0.1-1 μM) increases the expression of glycolysis-related proteins (GLUT1, GLUT3, LDHA) in mouse cerebral microvascular endothelial bEnd.3 cells, confirming enhanced glycolysis^[2].
6:2 Fluorotelomer alcohol (0.1-1 μM) significantly upregulates the mRNA expression of inflammation-related genes (IL-1β, TNF-α, COX-2, iNOS) in mouse cerebral microvascular endothelial bEnd.3 cells^[2]. In Vivo:6:2 FTOH (aqueous exposure; continuous exposure; 24 hours to 96 hpf) induces dose-dependent developmental toxicity in zebrafish (Danio rerio) embryos, including morphological defects, apoptosis, oxidative stress, and impaired liver development. Significant effects are observed at doses as low as 50 µg/mL, with strong toxicity observed at 200 µg/mL^[1]
6:2 Fluorotelomer alcohol (5-125 mg/kg, oral administration daily; from gestational day 8.5 to delivery) impairs blood-brain barrier function in male BALB/c mouse offspring, alters the brain immune microenvironment, and induces endothelial-mesenchymal transition in brain microvascular endothelial cells via upregulating ETS1^[2].
The no-observed-adverse-effect level (NOAEL) for systemic toxicity of 6:2 fluorotelomer alcohol (100 mg/kg/day; oral administration daily) is 25 mg/kg/day in male mice, 5 mg/kg/day in female mice, >100 mg/kg/day for reproductive toxicity, and 25 mg/kg/day for offspring survival and growth. Its primary target organ is the liver^[3].
6:2 Fluorotelomer alcohol (25 mg/kg/day; oral gavage; once daily; from gestational day 8.5 to parturition) induces autism spectrum disorder-like behaviors, brain histopathological damage, intestinal barrier dysfunction, and gut microbiota dysbiosis in male mouse offspring via the microbiota-gut-brain axis^[4].
6:2 Fluorotelomer alcohol (175-5000 mg/kg; p.o./dermal; single or 90-day exposure) exhibits acute oral toxicity with an LD₅₀ of 1750 mg/kg; its acute dermal LD₅₀ is >5000 mg/kg; subchronic oral toxicity occurs in brown rats at ≥25 mg/kg/day; its no-observed-adverse-effect level (NOAEL) is 5 mg/kg/day^[5].
6:2 Fluorotelomer alcohol (up to 100%) does not induce skin sensitization in mice^[5].