| Summary: | cC<sub>6</sub>O<sub>4</sub> is a new-generation perfluoroalkyl surfactant used in the chemical industry for the synthesis of perfluoroalkyl polymers. It was introduced as a less biopersistent substitute of traditional perfluoroalkyl surfactants such as PFOA, but its kinetics in humans was never investigated. This work is aimed to investigate the kinetics of elimination of cC<sub>6</sub>O<sub>4</sub> in exposed workers. Eighteen male individuals occupationally exposed to cC<sub>6</sub>O<sub>4</sub> in the production of fluoropolymers volunteered for the study. Blood and urine samples were collected from the end of a work-shift for the following 5 days off work. Serum and urinary cC<sub>6</sub>O<sub>4</sub> were measured by LC-MS/MS. Seventy-two samples with serum cC<sub>6</sub>O<sub>4</sub> ranging from 0.38 to 11.29 µg/L were obtained; mean levels were 3.07, 2.82, 2.67 and 2.01 µg/L at times 0, 18, 42 and 114 h. Two hundred and fifty-four urine samples with cC<sub>6</sub>O<sub>4</sub> ranging from 0.19 to 5.92 µg/L were obtained. A random-intercept multiple regression model was applied to serum data and a half-life of 184 (95% CI 162–213) h for a first-order kinetics elimination was calculated; a mean distribution volume of 80 mL/kg was also estimated. Pearson’s correlation between ln-transformed serum and daily urine concentrations was good, with r ranging from 0.802 to 0.838. The amount of cC<sub>6</sub>O<sub>4</sub> excreted daily in urine was about 20% of the amount present in serum. The study allowed calculating a half-life for cC<sub>6</sub>O<sub>4</sub> in blood of about 8 days in humans, supporting its much shorter biopersistence in comparison with legacy PFAS. The good correlation between urine and serum cC<sub>6</sub>O<sub>4</sub> suggests urine as a possible non-invasive matrix for biomonitoring. The amount of cC<sub>6</sub>O<sub>4</sub> excreted daily in urine suggests urine as the sole elimination route.
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