A 90-day repeated dose oral (gavage) toxicity study of perfluorohexanoic acid (PFHxA) in rats (with functional observational battery and motor activity determinations)

Chengelis, Christopher P.; Kirkpatrick, Jeannie B.; Radovsky, Ann; Shinohara, Motoki

doi:10.1016/j.reprotox.2009.01.006

Cited by 55 publications

(58 citation statements)

References 19 publications

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“…Bodyweights were not affected by treatment in either study. In contrast, significantly decreased bodyweights were noted in the subchronic studies conducted with PFHxA in males at doses of ≥50 mg/kg for the free acid and 500 mg/kg for the Na salt [33,35], with no mortality noted.…”

Section: Systemic and Reproductive Toxicologymentioning

confidence: 82%

“…Hepatocellular hypertrophy with increased liver weight parameters was one of the most sensitive effects noted in the subchronic studies [33,35,36••] and in the 14-day study [24•]; lowest observed effect levels (LOELs) from 90-day studies for this effect were 25 mg/kg/day for C6-FTOH and 100-200 mg/kg/day for PFHxA in males and 125 mg/kg/day for C6-FTOH and 500 mg/kg/day for PFHxA in females. In the chronic study [34••], hepatocellular hypertrophy was not evident at doses of up to 100 mg/kg/day (males) and 200 mg/kg/day (females); however, hepatocellular necrosis and hepatic congestion were noted in high-dose males and females.…”

Section: Systemic and Reproductive Toxicologymentioning

confidence: 99%

“…For PFHxA, 90-day [33] subchronic and 2-year [34••] oral toxicity studies have been conducted in rats with the free acid, at dose ranges of 0, 10, 50, and 200 mg/kg/day for the subchronic study and doses of 0, 2.5, 15, and 100 mg/kg/day (males) and 0, 5, 30, and 200 mg/kg/day (females) in the chronic study. Ninety-day oral studies have also been conducted in rats with sodium PFHxA [35] and C6-FTOH [36••] at dose ranges of 0, 20, 100, and 500 mg/kg/day for Na PFHxA and 0, 5, 25, 125, and 250 mg/kg/day of C6-FTOH.…”

Section: Systemic and Reproductive Toxicologymentioning

confidence: 99%

“…The subchronic [33,35,36••] and developmental/ reproductive toxicity [35, 37••, 38••] studies demonstrate that the C6 compounds share some similarities in their toxicological profiles with the C8 compounds (see below), except that PFHxA appears to be at least an order of magnitude less potent than perfluorooctanoate (PFOA). Common findings in the above-cited 90-day studies included mortality and/or decreased bodyweights, hepatocellular hypertrophy and increased liver weights, increased kidney weights, and hematological changes indicative of mild anemia at the high doses tested in these studies.…”

Section: Systemic and Reproductive Toxicologymentioning

confidence: 99%

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C6-Perfluorinated Compounds: The New Greaseproofing Agents in Food Packaging

Rice

2015

Curr Envir Health Rpt

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Due to their oleophobic and hydrophobic properties and stability, perfluorinated compounds (PFCs) are used in many applications, particularly as greaseproofing agents for food contact. However, PFCs 8-carbons in length or greater (C8-PFCs) have raised concerns regarding environmental biopersistence, bioaccumulation in humans, and potent toxicity that have resulted in their gradual phase-out for food contact use. Industry has replaced C8-PFCs with shorter-chained C6-based greaseproofing agents, which are intended to have the same favorable physicochemical properties without the problematic toxicological effects in humans and wildlife. Compared with the large body of data available for C8 compounds, however, the available database on toxicity and exposure to the C6 compounds is fairly limited. This article summarizes the information in this database, focusing on aspects of human exposure and potential health risks associated with two types of C6 PFCs found in food packaging: perfluorohexanoic acid (PFHxA) and 6-2 fluorotelomer alcohol (C6-FTOH).

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Section: Systemic and Reproductive Toxicologymentioning

confidence: 82%

Section: Systemic and Reproductive Toxicologymentioning

confidence: 99%

Section: Systemic and Reproductive Toxicologymentioning

confidence: 99%

Section: Systemic and Reproductive Toxicologymentioning

confidence: 99%

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C6-Perfluorinated Compounds: The New Greaseproofing Agents in Food Packaging

Rice

2015

Curr Envir Health Rpt

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“…Global regulatory efforts have led to a reduction in the emission of PFOS-related and long-chain PFASs; however, introduction of replacement chemicals results in perfluorinated end-products such as perfluorohexanoic acid (PFHxA) (Scheringer et al, 2014). To the best of our knowledge previous reports did not identify toxic effects in mammals or teleosts (Chengelis et al, 2009;Iwai and Hoberman, 2014;Loveless et al, 2009). Contrary to PFOS, PFHxA presents low bioconcentration capacities which make it difficult to detect and study in animal tissues after assimilation (Martin et al, 2003a;Martin et al, 2003b).…”

Section: Introductionmentioning

confidence: 89%

Mixture-specific gene expression in zebrafish ( Danio rerio ) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126)

Blanc

Kärrman

Kukučka

et al. 2017

Science of The Total Environment

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Short‐Chain Per/Polyfluoroalkyl Acids (C7 and Below)

Lasee,

Dourson,

Onyema

2024

Patty's Toxicology

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This chapter is about a series of short‐chain per‐ and polyfluoroalkyl substances (PFAS). In the past, PFAS were described as fluorinated fatty acids or sulfonates. The overall structure of PFAS is a carbon chain with fluorine atoms substituting for hydrogen atoms. The resulting chemicals are chemically stable, water and oil resistant, and useful for many industrial applications, such as in the formation of polymers. The most notorious in this group are the fluorinated fatty acids (carboxylates) or sulfonates. In biological systems, these chemicals are generally well‐absorbed by the oral route and resistant to metabolism but also have the unusual property of having drastically different elimination kinetics between mammalian species. The available literature on this group of PFAS (C7 and below) is modest. This chapter will not attempt to review all this literature. Rather, human studies will be emphasized. Since human studies often suggest associations between PFAS exposure and health outcomes, these studies will be followed by definitive experimental animal studies that give insights into the human evidence. Afterward, a summary of attempts to estimate potential human risk by various international agencies will be described. What will become obvious, however, is that the overall uncertainty in the database of some of these chemicals has led to widely divergent risk assessment positions that need to be resolved. Risk management decisions on specific members of this class of chemistries are seen to be premature without such scientific resolution.

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A 90-day repeated dose oral (gavage) toxicity study of perfluorohexanoic acid (PFHxA) in rats (with functional observational battery and motor activity determinations)

Cited by 55 publications

References 19 publications

C6-Perfluorinated Compounds: The New Greaseproofing Agents in Food Packaging

C6-Perfluorinated Compounds: The New Greaseproofing Agents in Food Packaging

Mixture-specific gene expression in zebrafish ( Danio rerio ) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126)

Short‐Chain Per/Polyfluoroalkyl Acids (C7 and Below)

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