Table I.1.
In vitro genotoxicity studies
| Test system | Cells/animals | Concentration/Treatment for genotoxicity endpoints | Result | Comment | Reference |
|---|---|---|---|---|---|
| In vitro | |||||
| Bacterial reverse mutation assay (Ames test) | S. Typhimurium TA98,TA100, TA1535, TA1537, TA1538 |
PFBA: 20 μmol/plate (+/−S9) PFHxA: 20 μmol/plate (+/−S9) PFHpA: 10 μmol/plate (+/−S9) PFNA: 5 μmol/plate (+/−S9) PFDA: 5 μmol/plate (+/−S9) PFDoDA: 1 μmol/plate (+/−S9) |
Negative Negative Negative Negative Negative Negative |
Only highest applied non‐cytotoxic dose shown; two independent experiments Only highest applied non‐cytotoxic dose shown; independent experiments Only highest applied non‐cytotoxic dose shown; independent experiments Only highest applied non‐cytotoxic dose shown; independent experiments Only highest applied non‐cytotoxic dose shown; independent experiments Only highest applied non‐cytotoxic dose shown; independent experiments |
Buhrke et al. (2013) |
| Bacterial reverse mutation assay (Ames test) | S. Typhimurium TA98,TA100, TA1535, TA1537, WP2uvrA | PFHxA: 0, 333–5,000 μg/plate (+/−S9) | Negative | Loveless et al. (2009) | |
| Bacterial reverse mutation assay (Ames test) | S. Typhimurium TA98,TA100, E. Coli WP2 uvrA pKM 101 |
PFHxA: 10–750 μg/plate (TA98, TA100, +/−S9) PFHxA: 100–2,000 μg/plate E. Coli WP2 uvrA pKM 101, +/−S9) PFNA: 50–500 μg/plate (TA98, TA100, +/−S9) PFNA: 500–5,000 μg/plate E. Coli WP2 uvrA pKM 101, +/−S9) PFDA: 100–1,000 μg/plate (TA98, TA100, +/−S9) PFDA: 500–5,000 μg/plate E. Coli WP2 uvrA pKM 101, +/−S9) PFBS: 50–5,000 μg/plate (TA98, +/−S9) PFBS: 50–5,000 μg/plate (TA100, +/−S9) PFBS: 50–1,000 μg/plate E. Coli WP2 uvrA pKM 101, +/−S9) |
Negative Negative Negative Negative Negative Negative Equivocal Negative Negative |
NTP (2019a) NTP (2019b) |
|
| Chromosomal aberration assay | Human peripheral blood lymphocytes |
PFHxA: 0, 2000–3,860 μg/mL (−S9), 4 h PFHxA: 0, 250–1,000, (+S9), 4 h PFHxA: 0, 250–1,000, (−S9), 22 h |
Negative Negative Negative |
No significant increase of structural or numerical chromosome aberrations activated test systems | Loveless et al. (2009) |
| DNA strand breaks and FPG sensitive sites (Comet assay) | HepG2 cells |
PFHxA: 0, 100–400 μM, 24 h PFNA: 0, 100–400 μM, 24 h PFBS: 0, 100–400 μM, 24 h |
Negative Positive ≥ 200 μM Negative |
No significant increase in ROS production (DCFH‐DA), 0.4–2,000 μM, 3h; 400 μM for 24 h resulted in a LDH release of ≤ 5% No significant increase in ROS production (DCFH‐DA), 0.4‐2,000 μM, 3 h; 400 μM for 24 h resulted in a LDH release of 66%. No significant increase in ROS production (DCFH‐DA), 0.4‐2,000 μM, 3h; 400 μM for 24 h resulted in a LDH release of ≤ 5% |
Eriksen et al. (2010) |
| DNA strand breaks (Comet assay | HepG2 cells |
PFHxS: 0, 0.2–20 μM, 24 h PFNA: 0, 0.2–20 μM, 24 h PFDA: 0, 0.2–20 μM, 24 h PFUnDA: 0, 0.2–20 μM, 24 h PFDoDA: 0, 0.2–20 μM, 24 h |
Positive 1, ≥ 10 μM Positive 2, 20 μM Negative Negative Negative |
Cytotoxicity > 200 μM, 24 h; no clear dose dependency, positive for ROS (DCFDA fluorescence) ≥ 0.2 μM Cytotoxicity > 200 μM, 24 h; no clear dose dependency, positive for ROS (DCFDA fluorescence) 0.2, ≥ 20 μM Cytotoxicity > 200 μM, 24 h; positive for ROS (DCFDA fluorescence) 0.2, ≥ 20 μM Cytotoxicity > 200 μM, 24 h; positive for ROS (DCFDA fluorescence) ≥ 2 μM Cytotoxicity > 20 μM, 24 h; positive for ROS (DCFDA fluorescence) ≥ 2 μM |
Wielsøe et al. (2015) |
| DNA strand breaks (Comet assay) | Human lymphoblastoid (TK6) cells | PFNA: 0, 125, 250 ppm, 2 h |
Positive 125, 250 μg/mL |
The authors state that cells are viable (as measured by trypan blue). However, data are not shown. | Yahia et al. (2014) |
|
8‐OHdG (LC‐MS/MS) |
Human lyphoblastoid (TK6) cells | PFNA: 0, 125, 250 ppm, 2 h |
Positive 125, 250 μg/mL |
The authors state that cells are viable (as measured by trypan blue). However, data are not shown. 8‐OHdG induction was greater than that produced by PFOA. | Yahia et al. (2014) |
|
Micronuclei (OECD 487) |
V79 cells |
PFBA: 100 μM (–/+S9), 3 h (+21 h) PFHxA: 100 μM (–/+S9), 3 h (+21 h) PFHpA: 100 μM (–/+S9), 3 h (+21 h) PFNA: 10 μM (–/+S9), 3 h (+21 h) PFDA: 10 μM (–/+S9), 3 h (+21 h) PFDoDA: 1 μM (–/+S9), 3 h (+21 h) |
Negative Negative Negative Negative Negative Negative |
IC50 (neutral red) > 1,000 μM, 72 h IC50 (neutral red): 344 μM, 72 h IC50 (neutral red): 128 μM, 72 h IC50 (neutral red): 28 μM, 72 h IC50 (neutral red): 15 μM, 72 h IC50 (neutral red): 7 μM, 72 h |
Buhrke et al. (2013) |
DCFDA: dichlorodihydrofluorescein diacetate; IC50: half maximal inhibitory concentration; ROS: reactive oxygen species.