Chlorinated paraffin metabolism and its importance for understanding CP toxicity

Abstract

Chlorinated paraffins (CPs) are industrial chemicals with broad use as plasticizers and components in paints, cutting and drilling oil additives. The research interest in CPs has recently increased, not least due to the progress in analytical techniques and the globally reported large production volumes of CPs. The adverse effects on CPs in biota and in man are being reported in an increasing number of articles and the mechanism of toxicity is being discussed. Whether the metabolism of CPs could increase their toxicity is, however, still an unsolved question. In this Perspective paper, CP metabolism is discussed and arguments pointing to the important role of metabolic enhancement in CP toxicity are highlighted.

Keywords

Chlorinated paraffins / metabolism / carbon chain length / chlorine content / bioactivation

References

[1] UNEP Candidate POPs chlorinated paraffins with carbon chain lengths in the rang C14-17 and chlorination levels at or exceeding 45 per cent Chlorine by Weight. Available from: https://chm.pops.int/TheConvention/POPsReviewCommittee/Meetings/POPRC17/MeetingDocuments/tabid/8918/Default.aspx [Last accessed on 10 Nov 2023]

[2] UNEP Report on the conference of parties to the stockholm convention on persistent organic pollutants on the work of its eight meeting. Available from: https://chm.pops.int/theconvention/conferenceoftheparties/meetings/cop8/tabid/5309/default.aspx [Last accessed on 10 Nov 2023]

[3] Chen W,Hou X.A review on biological occurrence, bioaccumulation, transmission and metabolism of chlorinated paraffins.Crit Rev Env Sci Tec2023;online ahead of print

[4] Mu YW,Zhang CL,Zeng T.The potential health risks of short-chain chlorinated paraffin: a mini-review from a toxicological perspective.Sci Total Environ2023;872:162187

[5] EFSA. Risk assessment of chlorinated paraffins in feed and food. Available from: https://www.efsa.europa.eu/en/efsajournal/pub/5991 [Last accessed on 10 Nov 2023]

[6] Yuan B,Macleod M.Methods for trace analysis of short-, medium-, and long-chain chlorinated paraffins: critical review and recommendations.Analytica Chimica Acta2019;1074:16-32.

[7] Chen L,Luo X.Bioaccumulation and biotransformation of chlorinated paraffins.Toxics2022;10:778

[8] Darnerud PO.Critical review on disposition of chlorinated paraffins in animals and humans.Environ Int2022;163:107195.

[9] Yuan S,Lv B.Transformation pathways of chlorinated paraffins relevant for remediation: a mini-review.Environ Sci Pollut Res2021;28:9020-8.

[10] Biessmann A,Brandt I.Chlorinated paraffins: disposition of a highly chlorinated polychlorohexadecane in mice and quail.Arch Toxicol1983;53:79-86.

[11] Darnerud PO,Brandt I.Metabolic fate of chlorinated paraffins: degree of chlorination of [1-14C]-chlorododecanes in relation to degradation and excretion in mice.Arch Toxicol1982;50:217-26.

[12] Darnerud PO.Chlorinated paraffins: effect of some microsomal enzyme inducers and inhibitors on the degradation of 1-14C-chlorododecanes to ¹⁴CO₂ in mice.Acta Pharmacol Toxicol1984;55:110-5

[13] Ahlman M,Darnerud PO,Sjövall J.Chlorinated paraffins: formation of sulphur-containing metabolites of polychlorohexadecane in rats.Xenobiotica1986;16:225-32.

[14] Omori T,Kodama T.Bacterial cometabolic degradation of chlorinated paraffins.Appl Microbiol Biotechnol1987;25:553-7

[15] Bucher JR,Montgomery CA.Comparative toxicity and carcinogenicity of two chlorinated paraffins in F344N rats and B6C3F1 mice.Fundam Appl Toxicol1987;9:454-68.

[16] Serrone DM,Weigand W.Toxicology of chlorinated paraffins.Food Chem Toxicol1987;25:553-62

[17] IARC Chlorinated paraffins. IARC monogr eval carcinog risks hum. Available from: https://publications.iarc.fr/_publications/media/download/1716/0355080f19678d0a827e62ad130467568c603bb1.pdf [Last accessed on 10 Nov 2023]

[18] Gong Y,Geng N.Short-chain chlorinated paraffins (SCCPs) induced thyroid disruption by enhancement of hepatic thyroid hormone influx and degradation in male Sprague Dawley rats.Sci Total Environ2018;625:657-66.

[19] Sprengel J,Besselink H,Vetter W.In vitro human cell-based TTR-TRβ CALUX assay indicates thyroid hormone transport disruption of short-chain, medium-chain, and long-chain chlorinated paraffins.Arch Toxicol2021;95:1391-6.

[20] Wyatt I,Elcombe CR.The effect of chlorinated paraffins on hepatic enzymes and thyroid hormones.Toxicology1993;77:81-90.

[21] Zhang Q,Zhu J,Zhang J.Assessment of the endocrine-disrupting effects of short-chain chlorinated paraffins in in vitro models.Environ Int2016;94:43-50

[22] Geng N,Cao R.Effect of short-chain chlorinated paraffins on metabolic profiling of male SD rats.Sci Total Environ2021;750:141404

[23] Geng N,Gong Y.Integration of metabolomics and transcriptomics reveals short-chain chlorinated paraffin-induced hepatotoxicity in male Sprague-Dawley rat.Environ Int2019;133:105231.

[24] Liu L,Coelhan M,Ma W.Relative developmental toxicity of short-chain chlorinated paraffins in Zebrafish (Danio rerio) embryos.Environ Pollut2016;219:1122-30

[25] Wang X,Kong B.C(9-13) chlorinated paraffins cause immunomodulatory effects in adult C57BL/6 mice.Sci Total Environ2019;675:110-21.

[26] Hallgren S.Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats-testing interactions and mechanisms for thyroid hormone effects.Toxicology2002;177:227-43

[27] Lundstedt-enkel K,Darnerud PO.Interaction study with rats given two flame retardants: polybrominated diphenyl ethers (Bromkal 70-5 DE) and chlorinated paraffins (Cereclor 70L).J Chemometr2010;24:710-8

[28] Wang F,Geng N.A metabolomics strategy to assess the combined toxicity of polycyclic aromatic hydrocarbons (PAHs) and short-chain chlorinated paraffins (SCCPs).Environ Pollut2018;234:572-80

[29] Heeb NV,Lehner S.Biotransformation of short-chain chlorinated paraffins (SCCPs) with LinA2: A HCH and HBCD converting bacterial dehydrohalogenase.Chemosphere2019;226:744-54.

[30] Knobloch MC,Schilling I.Transformation of short-chain chlorinated paraffins by the bacterial haloalkane dehalogenase LinB - Formation of mono- and di-hydroxylated metabolites.Chemosphere2021;262:128288.

[31] Li Y,Chen W.Carbon chain decomposition of short chain chlorinated paraffins mediated by pumpkin and soybean seedlings.Environ Sci Technol2019;53:6765-72.

[32] Li Y,Yu M.Dechlorination and chlorine rearrangement of 1,2,5,5,6,9,10-heptachlorodecane mediated by the whole pumpkin seedlings.Environ Pollut2017;224:524-31

[33] Chen W,Zhang Q.Metabolism of SCCPs and MCCPs in suspension rice cells based on paired mass distance (PMD) analysis.Environ Sci Technol2020;54:9990-9

[34] Huang X,Lyu L,Zhao Y.Identification and yield of metabolites of chlorinated paraffins incubated with chicken liver microsomes: Assessment of their potential to convert into metabolites.J Hazard Mater2023;455:131640

[35] Lin L,Chen LJ,Mai BX.Comparative in vitro metabolism of short chain chlorinated paraffins (SCCPs) by human and chicken liver microsomes: first insight into heptachlorodecanes.Sci Total Environ2022;851:158261.

[36] He C,Tang S.In vitro biotransformation and evaluation of potential transformation products of chlorinated paraffins by high resolution accurate mass spectrometry.J Hazard Mater2021;405:124245

[37] Ren X,Zhang H.Comparing the disrupting effects of short-, medium- and long-chain chlorinated paraffins on cell viability and metabolism.Sci Total Environ2019;685:297-307.

[38] Wang X,Xue Z,Jin Y.The environmental distribution and toxicity of short-chain chlorinated paraffins and underlying mechanisms: Implications for further toxicological investigation.Sci Total Environ2019;695:133834.

[39] Geng N,Zhang B.Effects of short-chain chlorinated paraffins exposure on the viability and metabolism of human hepatoma HepG2 cells.Environ Sci Technol2015;49:3076-83.

[40] Liang Y,Lin Q.Research progress on signaling pathway-associated oxidative stress in endothelial cells.Oxid Med Cell Longev2017;2017:7156941.

[41] Chen JW,Li B,Jiang SD.The responses of autophagy and apoptosis to oxidative stress in nucleus pulposus cells: implications for disc degeneration.Cell Physiol Biochem2014;34:1175-89.

[42] Spickett CM.Chlorinated lipids and fatty acids: an emerging role in pathology.Pharmacol Ther2007;115:400-9

[43] Wang M,Li G.Increased adverse effects during metabolic transformation of short-chain chlorinated paraffins by cytochrome P450: a theoretical insight into 1-chlorodecane.J Hazard Mater2021;407:124391.

[44] Gong Y,Geng N.Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor α (PPARα).Ecotoxicol Environ Saf2019;181:164-71

[45] Sun Y,Li T,Hu J.Protein-affinity guided identification of chlorinated paraffin components as ubiquitous chemicals.Environ Int2020;145:106165.