Perfluorododecanoic acid

Danio rerio (adult female)^[1]

20 μg/g body weight; 40 μg/g body weight; 80 μg/g body weight

i.p.; single injection

Caused hepatocyte swelling at 7 days post-injection (20 μg/g dose).
Caused obscured cell borders and vacuolar degeneration at 7 days post-injection (40 μg/g dose).
Caused severe hepatic lesions including nuclei enlargement, pycnosis, hepatocyte necrosis, cytolysis, and near-collapse of cellular structure at 7 days post-injection (80 μg/g dose).
Induced dose-dependent decreases in GSH content of 14%, 26%, 29% respectively at 48 h post-injection.
Caused 14% and 12% decreases in GSH content at 96 h post-injection (20 μg/g and 80 μg/g doses respectively).
Caused significant depletion of GSH content at 7 days post-injection (80 μg/g dose).
Caused significant decreases in SOD activity at 48 h post-injection (all doses).
Caused significant elevations in SOD activity compared to controls at 7 days post-injection (40 μg/g and 80 μg/g doses).
Showed time-related increases in SOD activity across all doses at 96 h and 7 days relative to 48 h.
Caused significant decreases in CAT activity at 48 h post-injection (all doses).
Caused a significant 1.4-fold reduction in CAT activity at 96 h post-injection (20 μg/g dose).
Induced significant dose-dependent increase in GPx activity at 48 h post-injection.
Caused a significant 1.6-fold increase in GPx activity at 7 days post-injection (80 μg/g dose).
Showed significantly decreased GPx activity at 7 days relative to 48 h (all doses).
Caused a significant 7-fold increase in hepatic lipid peroxidation (MDA) at 7 days post-injection (80 μg/g dose).
Caused a significant 2.8-fold decrease in L-FABP gene expression at 7 days post-injection (20 μg/g dose).
Induced dose-dependent significant decreases in PPARα gene expression of 1.6-fold, 2.2-fold, 2.5-fold respectively at 7 days post-injection.
Caused significant decreases in CPT-I gene expression of 2.0-fold, 1.6-fold, 2.2-fold respectively at 7 days post-injection.
Caused a significant 2.0-fold induction in MCAD gene expression at 7 days post-injection (40 μg/g dose); caused an elevation in MCAD gene expression at 7 days post-injection (80 μg/g dose).
Induced dose-dependent significant decreases in UCP-2 gene expression of 1.5-fold, 2.0-fold, 2.3-fold respectively at 7 days post-injection.
Caused significant decreases in Bcl-2 gene expression of 1.8-fold, 1.6-fold, 2.1-fold respectively at 7 days post-injection.

Wistar (male, 8 weeks old)^[3]

5 mg/kg; 20 mg/kg; 50 mg/kg

p.o.; single dose

Reached a brain concentration of 44.4 μg/g tissue and serum concentration of 24.4 μg/mL 9 days post-dosing at 50 mg/kg.
Reached a brain concentration of 28.6 μg/g tissue 30 days post-dosing at 50 mg/kg.
Induced a significant decrease in discrimination index at doses ≥20 mg/kg on Days 6-7 post-dosing.
Caused a persistent discrimination index deficit through Day 30 post-dosing at 50 mg/kg, with no change in total exploration time at any dose or time point.
Triggered a decrease in discrimination index when brain concentrations exceeded 20 μg/g tissue.
Significantly increased time spent in open arms at 50 mg/kg, with no changes in distance traveled, total arm entries, or percentage of open arm entries.
Showed no significant differences in alternation percentage, total arm entries, distance traveled, number of crossings, time spent in the central area, or immobility time between 50 mg/kg and vehicle-treated rats.