Tissue distribution of 35S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose

Bogdanska, Jasna; Borg, Daniel; Sundström, Maria; Bergström, Ulrika; Halldin, Krister; Abedi‐Valugerdi, Manuchehr; Bergman, Åke; Nelson, Bruce R.; DePierre, Joseph W.; Nobel, Stefan

doi:10.1016/j.tox.2011.03.014

Cited by 78 publications

(60 citation statements)

References 135 publications

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“…The surfactants perfluorooctanesulfonate (PFOS) and perfluorononanoic acid, and a pharma compound identified as a glycine transporter inhibitor showed cytotoxicity unique to BECs (BE3C). Notably, PFOS is known to affect lung development prenatally 20 , and studies have shown preferential distribution of the chemical to the lung in pharmacokinetic studies 21 . It is intriguing that this cell model may possibly recapitulate some of the chemical's complex in vivo toxicity.…”

Section: Overview Of Activities Measuredmentioning

confidence: 99%

Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms

et al. 2014

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Addressing the safety aspects of drugs and environmental chemicals has historically been undertaken through animal testing. However, the quantity of chemicals in need of assessment and the challenges of species extrapolation require the development of alternative approaches. Our approach, the US Environmental Protection Agency's ToxCast program, utilizes a large suite of in vitro and model organism assays to interrogate important chemical libraries and computationally analyze bioactivity profiles. Here we evaluated one component of the ToxCast program, the use of primary human cell systems, by screening for chemicals that disrupt physiologically important pathways. Chemical-response signatures for 87 endpoints covering molecular functions relevant to toxic and therapeutic pathways were generated in eight cell systems for 641 environmental chemicals and 135 reference pharmaceuticals and failed drugs. Computational clustering of the profiling data provided insights into the polypharmacology and potential off-target effects for many chemicals that have limited or no toxicity information. The endpoints measured can be closely linked to in vivo outcomes, such as the upregulation of tissue factor in endothelial cell systems by compounds linked to the risk of thrombosis in vivo. Our results demonstrate that assaying complex biological pathways in primary human cells can identify potential chemical targets, toxicological liabilities and mechanisms useful for elucidating adverse outcome pathways.

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Section: Overview Of Activities Measuredmentioning

confidence: 99%

Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms

et al. 2014

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“…Earlier studies have shown that PFOS accumulates to bone and bone marrow 10, 11 . Rib bone samples taken from twenty cadavers in Catalonia, Spain, showed significant amounts of PFOA and PFOS, and the concentrations of PFOA in rib bone exceeded those in liver, lung, brain, and kidney 12 .…”

Section: Introductionmentioning

confidence: 99%

Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation

Koskela

Koponen

Lehenkari

et al. 2017

Sci Rep

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Perfluoroalkyl substances (PFAS), including two most commonly studied compounds perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are widely distributed environmental pollutants, used extensively earlier. Due to their toxicological effects the use of PFAS is now regulated. Based on earlier studies on PFOA’s distribution in bone and bone marrow in mice, we investigated PFAS levels and their possible link to bone microarchitecture of human femoral bone samples (n = 18). Soft tissue and bone biopsies were also taken from a 49-year old female cadaver for PFAS analyses. We also studied how PFOA exposure affects differentiation of human osteoblasts and osteoclasts. PFAS were detectable from all dry bone and bone marrow samples, PFOS and PFOA being the most prominent. In cadaver biopsies, lungs and liver contained the highest concentrations of PFAS, whereas PFAS were absent in bone marrow. Perfluorononanoic acid (PFNA) was present in the bones, PFOA and PFOS were absent. In vitro results showed no disturbance in osteogenic differentiation after PFOA exposure, but in osteoclasts, lower concentrations led to increased resorption, which eventually dropped to zero after increase in PFOA concentration. In conclusion, PFAS are present in bone and have the potential to affect human bone cells partly at environmentally relevant concentrations.

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“…Levels in liver and lung were four times and two times, respectively, those in blood, whereas levels in kidney were similar to those in blood. At higher concentrations, PFOS exhibited a different distribution profile and there was a shift to higher concentrations in tissues at higher doses (Bogdanska et al, 2011, Borg et al, 2010.…”

Section: Experimental Animal Studiesmentioning

confidence: 99%

Extensive literature search and provision of summaries of studies related to the oral toxicity of perfluoroalkylated substances (PFASs), their precursors and potential replacements in experimental animals and humans. Area 1: Data on toxicokinetics (absorption, distribution, metabolism, excretion) in in vitro studies, experimental animals and humans. Area 2: Data on toxicity in experimental animals. Area 3: Data on observations in humans

Bull

Burnett

Vassaux

et al. 2014

EFS3

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Tissue distribution of 35S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose

Cited by 78 publications

References 135 publications

Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms

Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms

Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation

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