Search

Chlorinated paraffins (CPs), a group of chlorinated alkane mixtures, are frequently detected in various environmental matrices and human bodies. Recently, CPs have garnered considerable attention owing to their potential to induce health hazards in wildlife and human. Several reviews have discussed short-chain CPs (SCCPs) induced ecological risk; however, a comprehensive understanding of the underlying toxic mechanisms and a comparison among SCCPs, medium-, and long-chain CPs (MCCPs and LCCPs, respectively) are yet to be established. This review summarizes the latest research progress on the toxic effects and the underlying molecular mechanisms of CPs. The main toxicity mechanisms of CPs include activation of several receptors, oxidative stress, disturbance of energy metabolism, and inhibition of gap junction-mediated communication. The sensitivity of different species to CP-mediated toxicities varies markedly, with aquatic organisms exhibiting the highest sensitivity to CP-induced toxicity. The toxicity comparison analysis indicated that MCCPs may be unsafe as potential substitutes for SCCPs., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Short-chain chlorinated paraffins (SCCPs) used in various industrial applications have been listed as new POPs. Previous studies based on high-dose exposures indicate their hepatotoxicity. However, their mechanisms of toxicity or adverse outcome pathways and health risks remain largely unknown., Objectives: This study aimed to evaluate metabolic consequences of chronic dietary exposure to SCCPs at low doses and reveal the molecular mechanisms underlying hepatotoxicity of SCCPs., Methods: A combination of transcriptomics and metabolomics, together with general pathophysiological tests were performed to assess the hepatic response of male rats exposed to SCCPs., Results: Our results highlight two major modes of action: Inhibition of energy metabolism and activation of the peroxisome proliferator-activated receptor α (PPARα). Exposure to SCCPs suppressed oxidative phosphorylation, glycolysis, gluconeogenesis and turnover of ATP-ADP-AMP and thus results in deficiencies of amino acids and nucleotides in liver of the rat. Exposure to SCCPs affected expression levels of 13 genes downstream of PPARα that encode proteins associated with metabolism of fatty acids. As a result, peroxisomal and mitochondrial fatty acid β-oxidation, microsomal fatty acid ω-oxidation, and lipogenesis were accelerated., Conclusions: Results of this work strongly support the conclusion that low-dose exposure to SCCPs can result in adverse outcomes in the rat model. Significant SCCP-induced inhibition of energy metabolism occurs at environmentally relevant dosages, which suggests that SCCPs exhibit metabolic toxicity. Interactions of SCCPs with PPARα signaling pathway can explain the disruption of lipids and amino acids metabolism., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Short-chain chlorinated paraffins (SCCPs), which are candidate persistent organic pollutants (POPs) according to the Stockholm Convention, are of great concern because of their persistent bioaccumulation, long-range transport and potential adverse health effects. However, data on the endocrine-disrupting effects of SCCPs remain scarce. In this study, we first adopted two in vitro models (reporter gene assays and H295R cell line) to investigate the endocrine-disrupting effects of three SCCPs (C10-40.40%, C10-66.10% and C11-43.20%) via receptor mediated and non-receptor mediated pathway. The dual-luciferase reporter gene assay revealed that all test chemicals significantly induced estrogenic effects, which were mediated by estrogen receptor α (ERα), in the following order: C11-43.20%>C10-66.10%>C10-40.40%. Notably, C10-40.40% and C10-66.10% also demonstrated remarkable anti-estrogenic activities. Only C11-43.20% showed glucocorticoid receptor-mediated (GR) antagonistic activity, with a RIC20 value of 2.6×10(-8)mol/L. None of the SCCPs showed any agonistic or antagonistic activities against thyroid receptor β (TRβ). Meanwhile, all test SCCPs stimulated the secretion of 17β-estradiol (E2). Both C10-66.10% and C11-43.20% increased the production of cortisol at a high level in H295R cell lines. In order to explore the possible mechanism underlying the endocrine-disrupting effects of SCCPs through the non-receptor pathway, the mRNA levels of 9 steroidogenic genes were measured by real-time polymerase chain reaction (RT-PCR). StAR, 17βHSD, CYP11A1, CYP11B1, CYP19 and CYP21 were upregulated in a concentration-dependent manner by all chemicals. The data provided here emphasized that comprehensive assessments of the health and ecological risks of emerging contaminants, such as SCCPs, are of great concern and should be investigated further., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Chlorinated paraffins (CPs), complex mixtures of polychlorinated alkanes, are widely used in various industries and are thus ubiquitous in the receiving environment. The present study comprehensively reviewed the occurrence, fate and ecological risk of CPs in various environmental matrices in Asia. Releases from the production and consumption of CPs or CP-containing materials, wastewater discharge and irrigation, sewage sludge application, long-range atmospheric transport and aerial deposition have been found to be most likely sources and transport mechanisms for the dispersion of CPs in various environmental matrices, such as air, water, sediment, soil and biota. CPs can be bioaccumulated in biota and biomagnified through food webs, likely causing toxic ecological effects in organisms and posing health risks to humans. Inhalation, dust ingestion and dietary intake are strongly suggested as the major routes of human exposure. Research gaps are discussed to highlight the perspectives of future research to improve future efforts regarding the analysis of CPs, the environmental occurrence and elimination of CPs, the total environmental pressure, and the risks to organisms and populations., (Copyright © 2016. Published by Elsevier Ltd.)

Caenorhabditis elegans is a free-living soil nematode that is commonly used as a model for toxicity tests. The aim of this study was to investigate the toxicity of seven organic pollutants: four azaarenes (quinoline, acridine, phenazine, and 1,10-phenanthroline), short-chain chlorinated paraffins, and two organochlorinated pesticides (toxaphene and hexachlorobenzene). The exposure to all chemicals was carried out in three test media (soil, agar, and aquatic medium), and adult mortality was evaluated after 24 and 48 h. Toxaphene was the most toxic substance with LC(50) (48 h) of 379 mg/kg in the soil and 0.2 mg/L in the aquatic medium. Quinoline was the most toxic chemical in agar test with LC(50) (48 h) of 10 mg/L. HCB showed a very low toxicity in all tests, maybe due to its very low water solubility. Longer than 24-h test duration was found necessary for getting more correct data on toxicity. In comparison with other studies, C. elegans was less sensitive than other soil invertebrates. Different response might be attributed to different exposure routes and shorter test duration. Equilibrium partitioning theory was used to calculate K(oc) from results of soil and aquatic tests but this approach was found not working. Our results suggest that the tests with nematode C. elegans should be included to the battery of tests for risk assessment of POPs in soil.