- Title
- Comparative toxicity studies of short- and long- chain perfluorocarboxylic acids (PFCA) on Caenorhabditis elegans
- Creator
- Sana, Tanmoy
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2022
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Perfluorocarboxylic acids (PFCAs) are man-made chemicals that are increasingly detected in the environmental matrix of all the continents. Continuous unveiling of toxicity reports on environmentally available long-chain PFCAs led the industries to adopt short-chain PFCAs analogues (e.g., perfluorobutanoic acid, PFBA; perfluorohexanoic acid, PFHxA) as a substitute for toxic long-chain PFCAs (PFOA). However, toxicity information of these newly introduced short-chain PFCAs is very scarce. Therefore, further research is needed to assess the environmental risk of these chemical groups as they are very mobile and water-soluble and can readily enter into different environmental compartments in a short time. The literature review has focused on the available PFCAs induced toxicity studies on invertebrate species, including median lethality, genotoxicity, reproductive toxicity, oxidative stresses, cellular apoptosis, and neurotoxicity parameters. The species sensitivity distribution (SSD) analysis was performed for eight available PFCAs causing 50% toxic effects in 14 invertebrate species from published literature (R2 = 0.84; N = 40), which revealed Perna viridis as the highly sensitive species to PFCAs (EC50 of genotoxicity at 0.08 mg L-1 perfluorodecanoic acid, PFDA). The literature review also illustrated Caenorhabditis elegans as an outstanding toxicity model animal. Therefore, it is crucial to gain essential information about the environmental PFCAs concentrations, their adverse effects on living biota, impacts on ecological food cycles, and their environmental risk assessment. This current study examined PFOA (perfluorooctanoic acid), PFHxA and PFBA induced acute and chronic trans- and multigenerational toxicological impacts on C. elegans, differential gene expression and metabolomic changes. The median lethal concentrations (LC50) of PFBA, PFHxA, and PFOA in exposed C. elegans were found to be 2.86 mM (612.15 mg L-1), 1.66 mM (521.3 mg L-1), and 0.0044 mM (1.83 mg L-1), respectively. Thus, PFHxA showed 285 times, and PFBA showed 334 times less toxicity than PFOA. The current study also revealed different acute behavioural endpoints including alteration in nematodes' fecundity, growth, lifespan, chemotaxis plasticity, and locomotion behaviour after exposure to three PFCAs. Present study results demonstrated that PFOA was highly bioaccumulative in C. elegans compared to PFHxA and PFBA, with a bioaccumulation factor (BAF) of 520 following its exposure to 0.00041 mg L-1 PFOA. Chemotaxis plasticity was significantly altered by the exposure to 0.41 mg L-1 PFOA, 3.14 mg L-1 PFHxA and 2.14 mg L-1 PFBA. Acute developmental toxicity was also observed afterexposure to 0.41 mg L-1 PFOA, 0.31 mg L-1 PFHxA, and 2.14 mg L-1 PFBA. This study explored the comparative multi- and transgenerational toxicity (P0 – F5; 6 generations) of PFBA, PFHxA, and PFOA in C. elegans using the lifespan, reproduction, and locomotion behaviour (head thrashing and body-bending) as toxicity parameters. Study outcomes demonstrated that PFCAs impacted the locomotor behaviour and altered the fecundity in C. elegans, and these effects were carried on to the next generations. PFHxA and PFOA but not PFBA caused a reduction in the lifespan of nematodes. Continuous exposure to PFHxA and PFOA at environmentally relevant concentrations demonstrated toxicity from two generations onwards. Thus, PFCAs exhibited trans- and multigenerational effects in C. elegans, with the toxicity depending on exposure concentration and carbon chain length. Based on the coefficient of distribution values (𝐾𝑑) of PFCAs in five experimented soils, sorption patterns followed the trend, PFOA >> PFHxA > PFBA. The present study also examined the influences of different soils and sediment waters' physicochemical properties on PFCA-induced C. elegans toxicity. Total organic carbon (TOC), 𝐾𝑑, and clay content of experimented soils were the important influencers of PFCAs induced C. elegans lethality in soil. The electrical conductivity value (EC) also played a vital role in the sediment lethality assay. This study also conducted gene expression and metabolomics on PFCAs exposed to nematodes. Results demonstrated that 0.1 mg L-1 PFOA upregulated sod-3, gst-4, apl-1, 1 mg L-1 PFOA upregulated che-12, and 5 mg L-1 PFOA upregulated cat-2, eat-1, egl-2. Whereas PFHxA 0.1 mg L-1 upregulated gst-4, apl-1, che-12, 1 mg L-1 PFHxA upregulated egl-2, and 10 mg L-1 PFHxA upregulated sod-3 and cat-2. PFBA 1 mg L-1 upregulated che-12 and 10 mg L-1 upregulated sod-3, gst-4, and apl-1. Whereas both 0.1 mg L-1 PFOA and PFHxA upregulated ace-1 but significantly downregulated after the exposure of 10 mg L-1 PFHxA and 5 mg L-1 PFOA. These genes are accountable for various vital roles in C. elegans, such as behavioural changes in locomotion, oxidative stress, chemotaxis learning, neurotransmitter secretion, and fecundity. Furthermore, perturbation of C.elegans metabolomes, especially crucial metabolic pathways, is also significantly affectedby PFCAs exposure. Aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine, tyrosine, tryptophan biosynthesis, and propanoate metabolism were affected by PFBA, PFHxA, and PFOA after 24 h exposure. Whereas D-glutamine and D-glutamate metabolism pathways were affected by both PFBA and PFOA, and conversely, ubiquinone and other terpenoid-quinone biosynthesis pathways were affected by both PFHxA and PFOA. To our knowledge, this is the first report on PFOA, PFHxA, and PFBA induced toxicity to C. elegans. The findings are important for environmental risk assessment and management of PFCAs.
- Subject
- perfluorocarboxylic acids; caenorhabditis elegans; toxicity studies; chemotaxis plasticity
- Identifier
- http://hdl.handle.net/1959.13/1507522
- Identifier
- uon:56027
- Rights
- Copyright 2022 Tanmoy Sana, This thesis is under embargo and will be released 30.06.2025.
- Language
- eng
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