FTOH & Dental Fluorosis

There are over 8000 perfluorinated compounds manufactured today...
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FTOH & Dental Fluorosis

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Fluorotelomer alcohols, or FTOHs, are fluorotelomers with an alcohol functional group. They are volatile precursors to perfluorinated carboxylic acids, such as PFOA and PFNA, and other compounds.

Commonly, an individual fluorotelomer alcohol molecule is named by the number of carbons that are fluorinated versus the number that are hydrocarbon-based. For example, 8:2 fluorotelomer alcohol would represent a molecule with 8 fluorinated carbons and a 2 carbon ethyl alcohol group.

Structure: (CnF2n+1CH2CH2OH, where n = 6, 8, 10, 12)

FTOH & Dental Fluorosis

The followings studies show elevated fluoride blood levels, as well as dental fluorosis, in the animals tested. [Please note that all were conducted by Dupont staff - toxicity is downplayed throughout.]

Anand SS, Serex TL, Carpenter C, Donner EM, Hoke R, Buck RC, Loveless SE - "Toxicological assessment of tridecafluorohexylethyl methacrylate (6:2 FTMAC) Toxicology 292(1):42-52 (2012)
"The changes noted in teeth (altered mineralization; retention of basophilic material) and femur (increased mineralization) in all treated groups were not associated with clinical signs or microscopic changes and were likely related to free fluoride formed from 6:2 FTMAC metabolism. Plasma (3-4-fold) and urine (30-50-fold) fluoride was higher in treated groups versus controls."

Ladics GS, Kennedy GL, O'Connor J, Everds N, Malley LA, Frame SR, Gannon S, Jung R, Roth T, Iwai H, Shin-Ya S - "90-day oral gavage toxicity study of 8-2 fluorotelomer alcohol in rats" Drug Chem Toxicol 31(2):189-216 (2008)
https://pubmed.ncbi.nlm.nih.gov/18330782/
"In both males and females, plasma fluorine levels were increased at 125 mg/kg and urinary fluorine was elevated at > or =5 mg/kg. Degeneration/disorganization of enamel organ ameloblast cells was observed at 125 mg/kg in males, but not females."

Ladics GS, Stadler JC, Makovec GT, Everds NE, Buck RC -"Subchronic toxicity of a fluoroalkylethanol mixture in rats" Drug Chem Toxicol 28(2):135-58 (2005)
https://pubmed.ncbi.nlm.nih.gov/15865257/
"Thyroid follicular hypertrophy was present at 100 and 250 mg kg(-1) day(-1) but was not present after recovery....microscopic tooth lesions (ameloblast degeneration/disorganization) occurred at 100 and 250 mg kg(-1) day(-1) and persisted with decreased severity throughout recovery...Under the conditions of the study, the no-observed adverse effect level for this mixture was 25 mg kg(-1) day(-1) for subchronic toxicity."

Mukerji P, Rae, JC, Buck RC - "Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice" Toxicology Reports 2:130–143 (2015)
https://pubmed.ncbi.nlm.nih.gov/28962345/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598097/
"While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth....6:2 FTOH-related changes in the incisor teeth, consistent with fluoride exposure, were present in males and females at 100 mg/kg/day. These changes included degeneration and atrophy of ameloblastic epithelium, accentuation of the normal laminar pattern of dentin and an increase in observed incomplete decalcification of enamel and/or dentin. Degeneration and atrophy of ameloblasts was characterized by segmental disorganization and attenuation of ameloblastic epithelium of the incisor teeth. Lamination of dentin was characterized by the presence of concentric basophilic rings within the dentin of these teeth. Incomplete decalcification of enamel and dentin was characterized by an increase in the observed presence of basophilic, mineralized debris in the enamel space of the incisor between the dentin and the gingiva."

Serex T, Anand S, Munley S, Donner EM, Frame SR, Buck RC, Loveless SE - "Toxicological evaluation of 6:2 fluorotelomer alcohol" Toxicology 319: 1–9 (2014)

6:2 FTOH has been shown to rapidly metabolize with formation of fluoride (Mukerji et al., 2015; Gannon et al., 2010, 2012).

Finlay C, Jepson G, Kennedy G, Stadler J - "Development of a mammalian screen to evaluate absorption and persistence of fluorinated chemicals" Toxicologist 60:291 (2001)

Gannon SA, Mawn MP, Munley SM, Buck RC, Serex TL - "Toxicokinetic evaluation of 6:2 fluorotelomer alcohol and metabolites in rats following 90-days of oral exposure" Toxicologist 126 (1) (2012) 402.

Gannon SA, Nabb DL, Snow TA, Mawn MP, Serex TL, Buck RC - "In vitro metabolism of 6–2 fluorotelomer alcohol in rat, mouse and human hepatocytes" Toxicologist 114 (97) (2010)

THYROID

Shi G, Cui Q, Zhang H, Cui R, Guo Y, Dai J - "Accumulation, Biotransformation, and Endocrine Disruption Effects of Fluorotelomer Surfactant Mixtures on Zebrafish" Chem Res Toxicol (2019) 32(7):1432-1440
https://pubmed.ncbi.nlm.nih.gov/31251046/
(T3 and T4 levels decreased in the 50 and 500 μg/L females and increased T4 level in 500 μg/L exposed males.)
Last edited by admin on Mon Nov 30, 2020 4:14 pm, edited 1 time in total.
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Thyroid - PFAS

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"Several PFASs, including perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), were positively associated with TSH concentrations when modeled individually. PFOS and PFNA were significantly associated with free T3 and PFNA was significantly associated with total T3 in models with PFAS*sex interactive terms; these associations suggested negative associations in men and positive associations in women. PFASs were not significantly associated with concentrations of free or total T4."

Byrne SC, Miller P, Seguinot-Medina S, Waghiyi V, Buck CL, von Hippel FA, Carpenter DO - "Exposure to perfluoroalkyl substances and associations with serum thyroid hormones in a remote population of Alaska Natives" Environ Res 166:537-543 (2018) doi: 10.1016/j.envres.2018.06.014. Epub 2018 Jun 27. PMID: 29958161; PMCID: PMC6932630.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932630/

Xie W, Zhong W, Appenzeller BMR, et al. - "Nexus between perfluoroalkyl compounds (PFCs) and human thyroid dysfunction: A systematic review evidenced from laboratory investigations and epidemiological studies" Critical Reviews in Environmental Science and Technology (2020)
https://www.tandfonline.com/doi/full/10 ... 20.1795052
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Danish Ministry of the Environment, EPA - "Short-chain Polyfluoroalkyl Substances (PFAS) - "A literature review of information on human health effects and environmental fate and effect aspects of short-chain PFAS" Environmental Project No. 1707 (2015)
https://www2.mst.dk/Udgiv/publications/ ... 2-15-5.pdf

"A subchronic oral study in rats of a commercial FTOH mixture (CnF2n+1CH2CH2OH, where n = 6, 8, 10, 12) at doses of 0, 25, 100 and 250 mg/kg/day showed effects from fluorosis on teeth to elevated liver and kidney weights and thyroid follicular hypertrophy, with a no observed adverse effect level (NOAEL) of 25 mg/kg b. w. per day (Ladics et al. 2005)."

"In various animal and in vitro studies PFAS have shown effects on thyroidea hormones and decreased the levels. The mechanism may be a competitive binding to the thyroid hormone plasma transport protein transthyretin (TTR) that will alter/decrease the free thyroxine (T4) in blood. Of the short-chain PFAS only PFHxS and 6:2 FTOH seem to be potent endocrine disruptors.

In human population studies it is difficult to assess effects of the single PFAS, since most populations are exposed to a mixture of PFAS, in which PFOA and/or PFOS dominate, and where levels of most short-chain PFAS often are below the quantitation limit. However, there are studies showing associations between PFHxS and effects on lipid metabolism, fertility, thyroidea hormones, asthma, and children’s behaviour.

Data from National Health and Nutrition Examination Survey (NHANES) for the years 2007–2008 were used to evaluate the effect of PFOS, PFOA, PFNA, PFDA, PFHxS, and 2-(N-methyl-perfluorooctane sulfonamide) acetic acid on the levels of six thyroid function variables (Jain et al. 2013). Levels of triiodothyronine were found to increase with the levels of PFOA (p=0.01), and total thyroxine levels were found to increase with increase in PFHxS levels (p<0.01).

PFBA has been tested in a 90 days gavage study with rats (Bjork and Wallace 2009). At the highest dose (30 mg/kg bw/day) there was an increase in liver weight and reduced thyroid hormone in males. In that study PFBA was surprisingly more toxic than PFHxA but five times less toxic than PFOA."
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Jain RB - "Association between thyroid profile and perfluoroalkyl acids: data from NHNAES 2007-2008" Environ Res 126:51-9 (2013)
https://pubmed.ncbi.nlm.nih.gov/24053974/
"TSH levels increased with increase in levels of PFOA (p<0.01)."
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