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As a result of proposed global restrictions and regulations on current-use per-and polyfluoroalkyl substances (PFAS), research on possible alternatives is highly required. In this study, phase I in vitro metabolism of two novel prototype PFAS in human and rat was investigated. These prototype chemicals are intended to be safer-by-design and expected to mineralize completely, and thus be less persistent in the environment compared to the PFAS available on the market. Following incubation with rat liver S9 (RL-S9) fractions, two main metabolites per initial substance were produced, namely an alcohol and a short-chain carboxylic acid. While with human liver S9 (HL-S9) fractions, only the short-chain carboxylic acid was detected. Beyond these major metabolites, two and five additional metabolites were identified at very low levels by non-targeted screening for the ether- and thioether-linked prototype chemicals, respectively. Overall, complete mineralization during the in vitro hepatic metabolism of these novel PFAS by HL-S9 and RL-S9 fractions was not observed. The reaction kinetics of the surfactants was determined by using the metabolite formation, rather than the substrate depletion approach. With rat liver enzymes, the formation rates of primary metabolite alcohols were at least two orders of magnitude higher than those of secondary metabolite carboxylic acids. When incubating with human liver enzymes, the formation rates of single metabolite carboxylic acids, were similar or smaller than those experienced in rat. It also indicates that the overall metabolic rate and clearance of surfactants are significantly higher in rat liver than in human liver. The maximum formation rate of the thioether congener exceeded 10-fold that of the ether in humans but were similar in rats. Overall, the results suggest that metabolism of the prototype chemicals followed a similar trend to those reported in studies of fluorotelomer alcohols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and some organochlorine pesticides (OCPs) were determined in serum of Egyptian colorectal cancer patients (n = 35) and compared to a healthy control group (n = 32). p,p'-DDE (the major metabolite of DDT) was the most frequently detected contaminant with the highest concentration (median = 131 ng/g lw) in all studied serum samples. BDE-209 was the least frequently detected contaminant with a median concentration <0.3 ng/g lw. The contamination profile in patients and controls was almost identical with p,p'-DDE showing the highest median contribution (77%) and oxychlordane the lowest (1%). The low p,p'-DDT/p,p'-DDE ratio (3.7%) in serum implies bioaccumulation and past exposure to DDT (c.f. recent and ongoing intake). Statistical analysis revealed no significant differences (P > 0.05) between the levels of target contaminants in serum of patients and the control group. Gender, age and body mass index (BMI) were investigated as potential factors influencing serum contaminant levels. ΣDDT, hexachlorobenzene and pentachlorophenol concentrations showed significant positive associations with age and/or BMI of the participants. Comparison with other countries revealed concentrations of PBDEs and PCBs in Egyptian serum among the lowest reported worldwide., (Copyright © 2017 Elsevier Ltd. All rights reserved.)