Tissue toxicokinetics of perfluoro compounds with single and chronic low doses in male rats

Abstract

-To examine the kinetics of low doses of perfluoro compounds (PFCs), we administered perfluorohexanoic acid (C6A), perfluorooctanoic acid (C8A), perfluorononanoic acid (C9A) and perfluorooctane sulfonate (C8S) with a single oral dose (50-100 μg/kg BW), and in drinking water at 1, 5, and 25 μg/L for one and three months to male rats; and examined the distribution in the brain, heart, liver, spleen, kidney, whole blood and serum. C6A was very rapidly absorbed, distributed and eliminated from the tissues with nearly the same tissue t 1/2 of 2-3 hr. Considering serum Vd, and the tissue delivery, C6A was mainly in the serum with the lowest delivery to the brain; and no tissue accumulation was observed in the chronic studies as estimated from the single dose study. For the other PFCs, the body seemed to be an assortment of independent one-compartments with a longer elimination t 1/2 for the liver than the serum. The concentration ratio of liver/serum increased gradually from C 0 to a steady state. The high binding capacity of plasma protein may be the reason for the unusual kinetics, with only a very small fraction of free PFCs moving gradually to the liver. Although the tissue specific distribution was time dependent and different among the PFCs, the Vd and k e of each tissue were constant throughout the study. The possibility of extremely high C6A accumulation in the human brain and liver was suggested, by comparing the steady state tissue concentration of this study with the human data reported by Pérez et al. (2013).

Risk to human health related to the presence of perfluoroalkyl substances in food

“…Iwabuchi et al. () administered PFNA to male rats either as a single dose (gavage, 50 μg/kg bw) or in drinking water (1, 5 or 25 μg/L) for 1 or 3 months. After a 3‐month exposure period, PFNA was found to accumulate mainly in the liver: at the highest dose tested (25 μg/L), the concentration in this organ was 2.4 mg/kg.…”

“…After gavage administration or iv injection, PFHxA was not detected in the serum at any sampling time (LOD = 0.2 nmol/g). Iwabuchi et al (2017) administered PFHxA to male rats either as a single dose (gavage, 100 lg/kg bw) or in drinking water (1, 5 or 25 lg/L) for 1 or 3 months. PFHxA was very rapidly and completely absorbed, distributed and eliminated from the body with a half-life ranging from 2 to 4 h (Table C.3).…”

“…For males and females treated by gavage, urinary elimination and faecal excretion were close to, or below 1% of the administered dose and the distribution pattern was similar to that found in animals exposed by iv injection. Iwabuchi et al (2017) administered PFNA to male rats either as a single dose (gavage, 50 lg/kg bw) or in drinking water (1, 5 or 25 lg/L) for 1 or 3 months. After a 3-month exposure period, PFNA was found to accumulate mainly in the liver: at the highest dose tested (25 lg/L), the concentration in this organ was 2.4 mg/kg.…”

A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior

“…While PFAS are most concentrated in protein rich tissues of the body, primarily the liver and serum, they have also been detected in nervous tissues of humans, experimentally exposed laboratory animals, and diverse taxa of environmentally exposed wildlife. In addition to humans, PFAS have been detected in the brains of numerous organisms, including mice, rats, frogs, fish, birds, and marine and arctic mammals ( Ahrens et al, 2009 ; Bogdanska et al, 2011 ; Rubarth et al, 2011 ; Shi et al, 2012 ; Greaves et al, 2013 ; Iwabuchi et al, 2017 ; Foguth R. M. et al, 2020 ). The concentrations of PFAS in the brain vary appreciably depending on duration and route of exposure, however, for the most well studied PFAS (PFOA and PFOS), accumulation in the brain is proportional to exposure dose ( Austin et al, 2003 ; Kudo et al, 2007 ; Cui et al, 2009 ; Cao and Ng, 2021 ).…”

Predicting risks in an increasingly complex world

“…After 5 days, tissue:blood ratios (excluding stomach and small intestine) were >1 for liver (tissue:blood=1.6), kidney (tissue:blood=1.3), whole bone (tissue:blood=1.1), and cartilage (tissue:blood=1.1). At all-time points, approximately 90% of the ingested 35 S was recovered in combined blood, liver, bone, skin, and muscle Iwabuchi et al (2017). compared tissue distribution following single doses or 3-month dosing of PFOS…”