Structure-specific variation in per- and polyfluoroalkyl substances toxicity among genetically diverse Caenorhabditis elegans strains.
Abstract — Entities Highlighted
Gene/ProteinChemicalDiseasePhenotypeAnatomyDev. Stage
There are >14,500 structurally diverse per- and polyfluoroalkyl substances (PFAS). Despite knowledge that these "forever chemicals" are in 99% of humans, mechanisms of toxicity and adverse health effects are incompletely known. Furthermore, the contribution of genetic variation to PFAS susceptibility and health consequences is unknown.
We determined the toxicity of a structurally distinct set of PFAS in twelve genetically diverse strains of the genetic model system Caenorhabditis elegans.
Dose-response curves for four perfluoroalkyl carboxylic acids (PFNA, PFOA, PFPeA, and PFBA), two perfluoroalkyl sulfonic acids (PFOS and PFBS), two perfluoroalkyl sulfonamides (PFOSA and PFBSA), two fluoroether carboxylic acids (GenX and PFMOAA), one fluoroether sulfonic acid (PFEESA), and two fluorotelomers (6:2 FCA and 6:2 FTS) were determined in the C. elegans laboratory reference strain, N2, and eleven genetically diverse wild strains. Body length was quantified by image analysis at each dose after 48 hr of developmental exposure of L1 arrest-synchronized larvae to estimate effective concentration values (EC50).
There was a significant range in toxicity among PFAS: PFOSA > PFBSA ≈ PFOS ≈ PFNA > PFOA > GenX ≈ PFEESA > PFBS ≈ PFPeA ≈ PFBA. Long-chain PFAS had greater toxicity than short-chain, and fluorosulfonamides were more toxic than carboxylic and sulfonic acids. Genetic variation explained variation in susceptibility to PFBSA, PFOS, PFBA, PFOA, GenX, PFEESA, PFPeA, and PFBA. There was significant variation in toxicity among C. elegans strains due to chain length, functional group, and between legacy and emerging PFAS.
C. elegans respond to legacy and emerging PFAS of diverse structures, and this depends on specific structures and genetic variation. Harnessing the natural genetic diversity of C. elegans and the structural complexity of PFAS is a powerful New Approach Methodology (NAM) to investigate structure-activity relationships and mechanisms of toxicity which may inform regulation of other PFAS to improve human and environmental health.
Relation Network
Specialists Used
deepseek: 45
All Extracted Relations (45)
| Entity 1 | Relation | Entity 2 | Confidence | Specialist | Direction |
|---|---|---|---|---|---|
| genetic variation | associated with | PFBA susceptibility | 85% | deepseek | supports |
| genetic variation | associated with | PFOA susceptibility | 85% | deepseek | supports |
| genetic variation | associated with | GenX susceptibility | 85% | deepseek | supports |
| genetic variation | associated with | PFEESA susceptibility | 85% | deepseek | supports |
| genetic variation | associated with | PFPeA susceptibility | 85% | deepseek | supports |
| long-chain PFAS | positively regulates | toxicity | 85% | deepseek | supports |
| fluorosulfonamides | positively regulates | toxicity | 85% | deepseek | supports |
| PFAS | associated with | C. elegans | 85% | deepseek | supports |
| PFNA | associated with | C. elegans | 85% | deepseek | supports |
| PFOA | associated with | C. elegans | 85% | deepseek | supports |
| genetic variation | associated with | PFOS susceptibility | 85% | deepseek | supports |
| PFPeA | associated with | C. elegans | 85% | deepseek | supports |
| PFBA | associated with | C. elegans | 85% | deepseek | supports |
| PFOS | associated with | C. elegans | 85% | deepseek | supports |
| PFBS | associated with | C. elegans | 85% | deepseek | supports |
| PFOSA | associated with | C. elegans | 85% | deepseek | supports |
| PFBSA | associated with | C. elegans | 85% | deepseek | supports |
| GenX | associated with | C. elegans | 85% | deepseek | supports |
| PFMOAA | associated with | C. elegans | 85% | deepseek | supports |
| PFEESA | associated with | C. elegans | 85% | deepseek | supports |
| 6:2 FCA | associated with | C. elegans | 85% | deepseek | supports |
| 6:2 FTS | associated with | C. elegans | 85% | deepseek | supports |
| PFOSA | causes phenotype | body length | 85% | deepseek | supports |
| PFBSA | causes phenotype | body length | 85% | deepseek | supports |
| PFOS | causes phenotype | body length | 85% | deepseek | supports |
| PFNA | causes phenotype | body length | 85% | deepseek | supports |
| PFOA | causes phenotype | body length | 85% | deepseek | supports |
| GenX | causes phenotype | body length | 85% | deepseek | supports |
| PFEESA | causes phenotype | body length | 85% | deepseek | supports |
| PFBS | causes phenotype | body length | 85% | deepseek | supports |
| PFPeA | causes phenotype | body length | 85% | deepseek | supports |
| PFBA | causes phenotype | body length | 85% | deepseek | supports |
| PFMOAA | causes phenotype | body length | 85% | deepseek | supports |
| 6:2 FCA | causes phenotype | body length | 85% | deepseek | supports |
| 6:2 FTS | causes phenotype | body length | 85% | deepseek | supports |
| genetic variation | associated with | PFBSA susceptibility | 85% | deepseek | supports |
| C. elegans strains | associated with | toxicity variation | 85% | deepseek | supports |
| chain length | associated with | toxicity variation | 85% | deepseek | supports |
| functional group | associated with | toxicity variation | 85% | deepseek | supports |
| legacy PFAS | associated with | toxicity variation | 85% | deepseek | supports |
| emerging PFAS | associated with | toxicity variation | 85% | deepseek | supports |
| C. elegans | associated with | legacy PFAS | 85% | deepseek | supports |
| C. elegans | associated with | emerging PFAS | 85% | deepseek | supports |
| specific structures | associated with | PFAS response | 85% | deepseek | supports |
| genetic variation | associated with | PFAS response | 85% | deepseek | supports |