Evaluation of serum lipid, thyroid, and hepatic clinical chemistries in association with serum perfluorooctanesulfonate (PFOS) in cynomolgus monkeys after oral dosing with potassium PFOS

Abstract

An oral dose study with perfluorooctanesulfonate (PFOS) was undertaken to identify potential associations between serum PFOS and changes in serum clinical chemistry parameters in purpose-bred young adult cynomolgus monkeys (Macaca fascicularis). In this study, control group (n = 6/sex) was sham-dosed with vehicle (0.5% Tween 20 and 5% ethanol in water), low-dose group (n = 6/sex) received 1 single K+PFOS dose (9 mg/kg), and high-dose group (n = 4–6/sex) received 3 separate K+ PFOS doses (11–17.2 mg/kg). Monkeys were given routine checkups and observed carefully for health problems on a daily basis. Scheduled blood samples were drawn from all monkeys prior to, during, and after K+PFOS administration for up to 1 year and they were analyzed for PFOS concentrations and clinical chemistry markers for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. No mortality occurred during the study. All the monkeys were healthy, gained weight, and were released back to the colony at the end of the study. The highest serum PFOS achieved was approximately 165 μg/ml. When compared with time-matched controls, administration of K+PFOS to monkeys did not result in any toxicologically meaningful or clinically relevant changes in serum clinical measurements for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. A slight reduction in serum cholesterol (primarily the high-density lipoprotein fraction), although not toxicologically significant, was observed. The corresponding lower-bound fifth percentile benchmark concentrations (BMCL1sd) were 74 and 76 μg/ml for male and female monkeys, respectively. Compared to the 2013–2014 geometric mean serum PFOS level of 4.99 ng/ml (0.00499 μg/ml) in US general population reported by CDC NHANES, this represents 4 orders of magnitude for margin of exposure.

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

“…Chang et al () treated cynomolgus monkeys with a single dose of 9 mg PFOS/kg bw by gavage and reported on an insignificant reduction of serum cholesterol in the post‐treatment phase. No further alterations could be observed.…”

Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health

“…Several experimental animal studies (n=8) reported short-term clinical effects related to PFAS exposure, with most studies showing small changes in BUN and/or creatinine concentrations across a wide range of exposure doses (42,43,45,47,48,59,79,80). However, the short-term clinical effects were variable, with some animal studies (n=3) showing no changes in BUN or creatinine at exposure doses as high as 600 mg/kg for PFOA (41,44,46), and others showing increased concentrations of both BUN and creatinine at exposure doses as low as 0.05-1.00 mg/kg for perfluoroundecanoic acid and perfluorododecanoic acid (47).…”

A Probabilistic Approach to Evaluate the Risk of Decreased Total Triiodothyronine Hormone Levels following Chronic Exposure to PFOS and PFHxS via Contaminated Drinking Water

“…Disruption of the thyroid hormone system has been reported in both epidemiological (Dallaire et al 2009;Knox et al 2011;Wen et al 2013) and animal studies (Chang et al 2008;Curran et al 2008;Luebker et al 2005;Martin et al 2007;Seacat et al 2002;Thibodeaux et al 2003). However, not all epidemiological studies have found a negative correlation with PFOS levels in serum (Olsen et al 2003), nor all animal studies (Chang et al 2017). Nevertheless, PFOS has been identified as a thyroid hormone disruptor (ATSDR 2018;Coperchini et al 2017).…”

“…However, not all epidemiological studies have found a negative correlation with PFOS levels in serum ( Olsen et al. 2003 ), nor all animal studies ( Chang et al. 2017 ).…”