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increased risk of airway and throat infections and diarrhea in children of 10 years or below is associated 427

with PFAS as measured in the cord-blood PFAS [111]. Exposure to PFAS at an early age also resulted 428

in an immunosuppressive effect with an increased incidence of lower respiratory tract infection and 429

atopic dermatitis [112]. Childhood allergy and asthma are not associated with PFAS [112]. The 430

down-regulation of C-reactive protein is also associated with perfluorooctanoic acid (PFOA) blood 431

levels [113]. Thyroid, an autoimmune disease, can be induced in children and women due to PFOA 432

and PFAS exposure. 433

b. Liver dysfunction - PFAS disrupts hepatic metabolism, increases bile acid reuptake, and lipid 434

accumulation in the liver promoting advanced liver disease and liver cancer in humans [114]. 435

c. Insulin dysregulation - PFAS increases resistance to human insulin and is associated with dysregulated 436

lipogenesis activity [115]. PFAS activates G protein-coupled receptor 40 which is a free fatty acid- 437

regulated membrane receptor on islet ß cells that stimulate insulin secretion [116]. 438

d. Kidney diseases - PFAS exposure leads to diminished glomerular filtration and chronic kidney disease 439

in adults and children [117]. Uric acid, a biomarker of renal disease is also associated with PFAS [118]. 440

e. Reproductive outcomes - PFOA exposure leads to impairment of motility of human sperm and its 441
penetration into viscous media [119] and is associated with lower sperm count and concentration and 442

higher levels of luteinizing and follicle-stimulating hormones in young men [120]. 443

4.4 Effects on Wildlife 444

Of all the PFAS studied, PFOS followed by PFOA has the highest toxicological data obtained from the toxicity 445

reference values for mammalian wildlife [121]. PFAs show effects in neurological, immunological, and 446

histopathological endpoints. The least toxicity was associated with PFCAs with fluorocarbons of chain length 447

of C6 or less and the greatest toxicity was observed for C8 to C12 compounds but C14 was less toxic than C8 448

to C12 PFCAs [106]. For PFAS, fluorocarbon chain length also influenced toxicity, with PFOS (C8) being 449

the most toxic followed by PFHxS (C6) and then PFBS (C4). Exposure to PFOS adversely affects innate and 450

cellular immunity in different rodents. Bioassays using the peripheral blood leukocytes of bottlenose dolphins 451

show that PFOS exposure is associated with an increase in pro‐inflammatory interferon‐γ and an increased 452

susceptibility to diseases [122]. 453

4.5 Toxicity Assessment of PFAs 454