A Pathology Review of the Lower Gastrointestinal Tract in Relation to Ulcerative Colitis in Rats and Cynomolgus Macaques Treated With Ammonium Perfluorooctanoate

Abstract

Among many short-term, subchronic, and chronic toxicology studies with ammonium perfluorooctanoate (PFOA), the gastrointestinal tract has not been identified as a target organ for PFOA-related toxicity in laboratory animals where the corresponding serum PFOA concentrations typically approach several orders of magnitude higher than the general human population. These lack of gastrointestinal tract-related findings were in direct contrast to an epidemiological observation where a positive trend was observed for ulcerative colitis, an idiopathic chronic inflammatory condition of the gut, in a Mid-Ohio River community whose drinking water contained higher levels of PFOA. This study was conducted to perform a histological reevaluation of large intestine sections in laboratory animals from 2 long-term toxicological studies: one was with Sprague Dawley rats that received ammonium PFOA in their diet for 2 years and the other one was with cynomolgus macaques that received daily capsules of ammonium PFOA for 6 months. In both studies, there was a lack of histological evidence of treatment-related inflammatory lesions that was suggestive of the occurrence of ulcerative colitis in these laboratory animals even under the most rigorous treatment schedules. These findings do not offer support for the biological plausibility of the epidemiological associations reported.

Perfluorooctane sulfonate exerts inflammatory bowel disease-like intestinal injury in rats

“…Notably, PFCs have long half-life once absorbed into the blood, ranging from several weeks to a few years in humans (Olsen et al, 2007). Studies have shown that both professional and nonprofessional exposure sources contribute to the body burden of PFOS for people (Chang et al, 2020;Wang et al, 2018). Available data from the Environmental Protection Agency (EPA) on the US population exposure to PFCs have been estimated as 6 million individuals affected by PFOS, PFOA from public drinking water at levels above the 70 pg/ml dose recommended by the EPA (Hu et al, 2016).…”

Figure 5: PFOS exposure induced inflammatory factors infiltration in the proximal jejunum of rats.

“…Notably, PFCs have long half-life once absorbed into the blood, ranging from several weeks to a few years in humans (Olsen et al, 2007). Studies have shown that both professional and nonprofessional exposure sources contribute to the body burden of PFOS for people (Chang et al, 2020;Wang et al, 2018). Available data from the Environmental Protection Agency (EPA) on the US population exposure to PFCs have been estimated as 6 million individuals affected by PFOS, PFOA from public drinking water at levels above the 70 pg/ml dose recommended by the EPA (Hu et al, 2016).…”