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

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

“…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.…”

“…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.…”

“…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.…”

“…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.…”

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)

“…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).…”