Table 1.
Brain Region-Specific Accumulation of PFAS in Humans, Polar Bears, and Ratsa
| study description | human 202265 | polar bear 20069 | polar bear 2011–201244 | rat 1 mg/kg/d 200323 | rat 10 mg/kg/d 200323 | rat dams 1 mg/kg/d 201740 | rat dams 2 mg/kg/d 201740 | rat pups 1 mg/kg/d 201740 | rat pups 2 mg/kg/d 201740 |
|---|---|---|---|---|---|---|---|---|---|
| blood or serum (ng/mL)b | |||||||||
| total PFAS | 291.9 | 158.4 | – | 10 480.0 | 45 446.0 | 20 400.0 | 38 200.0 | 19 300.0 | 37 200.0 |
| PFOS | 0.8 | 135.6 | – | 10 480.0 | 45 446.0 | 20 400.0 | 38 200.0 | 19 300.0 | 37 200.0 |
| PFOA | 217.4 | 3.7 | – | – | – | – | – | – | – |
| PFHxS | 71.0 | 19.1 | – | – | – | – | – | – | – |
| PFHxA | 2.6 | n.d. | – | – | – | – | – | – | – |
| Brain Subregions (ng/g) | |||||||||
| cerebral cortexc | |||||||||
| total PFAS | 29.6 | 32.2–34.2 | 22.2–31.3 | 294.0 | 4487.0 | 1500.0 | 3100.0 | 6100.0 | 11 200.0 |
| PFOS | n.d. | 30.5–32.8 | 20.5–29.7 | 294.0 | 4487.0 | 1500.0 | 3100.0 | 6100.0 | 11 200.0 |
| PFOA | 22.2 | 0.2–0.3 | 0.6 | – | – | – | – | – | – |
| PFHxS | 4.6 | 1.4–1.5 | 1.0–1.2 | – | – | – | – | – | – |
| PFHxA | 2.8 | n.d. | 0.0–0.1 | – | – | – | – | – | – |
| hypothalamus | |||||||||
| total PFAS | 206.9 | 60.1 | 23.2 | <50 | 15 706.0 | – | – | – | – |
| PFOS | n.d. | 58.8 | 20.5 | <50 | 15 706.0 | – | – | – | – |
| PFOA | 158.9 | n.d | 1.5 | – | – | – | – | – | – |
| PFHxS | 31.6 | 1.3 | 1.0 | – | – | – | – | – | – |
| PFHxA | 16.4 | n.d. | 0.2 | – | – | – | – | – | – |
| hippocampus | |||||||||
| total PFAS | – | – | 28.2 | 115.0 | 8966.0 | 1200.0 | 2300.0 | 5000.0 | 9800.0 |
| PFOS | – | – | 23.7 | 115.0 | 8966.0 | 1200.0 | 2300.0 | 5000.0 | 9800.0 |
| PFOA | – | – | 2.6 | – | – | – | – | – | – |
| PFHxS | – | – | 1.6 | – | – | – | – | – | – |
| PFHxA | – | – | 0.4 | – | – | – | – | – | – |
| brain stem (midbrain, pons/medulla)d | |||||||||
| total PFAS | 23.0 | 48.6 | 35.7 | 363.0 | 5346.0 | – | – | – | – |
| PFOS | n.d. | 46.9 | 33.4 | 363.0 | 5346.0 | – | – | – | – |
| PFOA | 13.3 | 0.2 | 0.9 | – | – | – | – | – | – |
| PFHxS | 8.6 | 1.3 | 1.2 | – | – | – | – | – | – |
| PFHxA | 1.1 | n.d. | 0.1 | – | – | – | – | – | – |
| cerebellum | |||||||||
| total PFAS | 54.4 | 38.6 | 26.3 | 289.0 | 5540.0 | 1700.0 | 3100.0 | 7600.0 | 14 600.0 |
| PFOS | n.d. | 36.5 | 24.5 | 289.0 | 5540.0 | 1700.0 | 3100.0 | 7600.0 | 14 600.0 |
| PFOA | 32.3 | 0.3 | 0.6 | – | – | – | – | – | – |
| PFHxS | 8.7 | 1.8 | 1.2 | – | – | – | – | – | – |
| PFHxA | 13.4 | n.d. | 0.0 | – | – | – | – | – | – |
| striatume | |||||||||
| total PFAS | 45.3–109.2 | 33.7 | 21.6 | 396.0 | 4256.0 | – | – | – | – |
| PFOS | n.d. | 31.9 | 19.2 | 396.0 | 4256.0 | – | – | – | – |
| PFOA | 31.1–93.3 | 0.2 | 1.4 | – | – | – | – | – | – |
| PFHxS | 8.4–12.1 | 0.9 | 0.8 | – | – | – | – | – | – |
| PFHxA | 2.1–7.4 | n.d. | 0.2 | – | – | – | – | – | – |
| caudate nucleus | |||||||||
| total PFAS | 109.2 | – | – | – | – | – | – | – | – |
| PFOS | n.d. | – | – | – | – | – | – | – | – |
| PFOA | 93.3 | – | – | – | – | – | – | – | – |
| PFHxS | 8.4 | – | – | – | – | – | – | – | – |
| PFHxA | 7.4 | – | – | – | – | – | – | – | – |
| lenticular nucleus | |||||||||
| total PFAS | 45.3 | – | – | – | – | – | – | – | – |
| PFOS | n.d. | – | – | – | – | – | – | – | – |
| PFOA | 31.1 | – | – | – | – | – | – | – | – |
| PFHxS | 12.1 | – | – | – | – | – | – | – | – |
| PFHxA | 2.1 | – | – | – | – | – | – | – | – |
| thalamuse | |||||||||
| total PFAS | 19.7 | 41.2 | 23.7 | 396.0 | 4256.0 | – | – | – | – |
| PFOS | n.d. | 38.8 | 21.5 | 396.0 | 4256.0 | – | – | – | – |
| PFOA | 14.4 | 0.9 | 1.1 | – | – | – | – | – | – |
| PFHxS | 2.7 | 1.3 | 1.0 | – | – | – | – | – | – |
| PFHxA | 2.7 | n.d. | 0.2 | – | – | – | – | – | – |
| brain average or whole brainf | |||||||||
| total PFAS | 97.5 | 37.5 | 25.2 | 247.0 | 12821.0 | 1900.0 | 3310.0 | 8400.0 | 15 100.0 |
| PFOS | n.d. | 35.2 | 22.9 | 247.0 | 12821.0 | 1900.0 | 3310.0 | 8400.0 | 15 100.0 |
| PFOA | 73.0 | 0.3 | 1.1 | – | – | – | – | – | – |
| PFHxS | 18.5 | 1.4 | 1.1 | – | – | – | – | – | – |
| PFHxA | 6.1 | n.d. | 0.1 | – | – | – | – | – | – |
The PFAS included PFOS, PFOA, PFHxS, and PFHxA because these are the only PFAS included in brain region-specific quantification in the human study. The human study by Di Nisio et al. in 2022 analyzed samples taken from five Caucasian males that were non-occupationally exposed (exposure characterized by Pitter et al.) to elevated levels of PFASs (especially PFOA) in Veneto Region, Italy.12,65 The polar bear studies collected samples from East Greenland in 20069 and 2011–2012.44 The PFAS totals in the table are only for the PFAS PFOS, PFOA, PFHxS, and PFHxA to compare with the human levels, although the polar bear studies included many additional PFAS. The polar bear and human studies only received environmental exposure to PFAS mixtures.9,44 The female adult rat study conducted by Austin et al. in 2003 and Ishida et al. in 2017 (gestational rat study) were the only controlled exposure laboratory studies that analyzed brain region-specific PFAS accumulation. These studies only assessed PFOS exposure; therefore, PFOS levels are equal to the total PFAS levels.23,40 The adult rat study dosed female rats with 1 or 10 mg/kg/d for 14 days, and tissue samples were immediately collected at the end of the exposure.23 The gestational rat study exposed pregnant female rats (dams) to 1 or 2 mg/kg/d from gestation day (GD) 11–20 (10 days total).40 PFOS was quantified on postnatal day 4 in the dams and pups.40 For both rat studies, control rat PFOS serum brain levels were below the limit of detection and not represented in the table.23,40 Quantities are given as average PFAS levels in the table, and average ranges are given if multiple subregions were samples in one study. Blood or serum levels are presented as ng/ mL, and all brain and brain levels are presented as ng/g. “n.d.” = below the detection limit; “–” = not quantified in the study.
Human and polar bear studies used whole blood, whereas the rat study used serum. Polar bear PFAS blood levels were converted from ng/g to ng/mL using 1 g wet blood = 0.9434 mL blood volume.72
The polar bear study quantified many subregions of the cerebral cortex including frontal, occipital, and temporal regions separately; the human study only quantified the frontal cortex, and the rat study quantified the cortex in its entirety.
The adult rat study was the only study to quantify the brain stem altogether. The human study only quantified the midbrain portion of the brainstem, and the polar bear studies only quantified the pons/medulla together.
The adult rat study quantified the rest of the brain together, which included the striatum and thalamus. The striatum and thalamus were individually quantified in the human and polar bear studies. The human study only quantified subregions of the dorsal striatum, whereas the polar bear studies quantified the entire striatum. Both the polar bear and human studies quantified the thalamus separately.
The 2017 gestational rat study quantified PFOS in the whole brain instead of averaging the measured regions.