Y-isomer of Hexachlorocyclohexane (C6H6Cl6) in Modern Human Life and Its Influence on the Processes of Oncogenesis
Mata Uvaysovna Razhaeva1, Linda Ahmedovna Khuchieva1, Said-Akhmed AlMirzoevich Musaev2, Alder Kamilevich Rustamov3*, Khadizhat Shepaevna Bicherkaeva4, Khava Saidkhuseinovna Usmanova4
1Department of Therapy, Medical Faculty of the Medical Institute of the Chechen State University, Grozny, Republic of Chechnya, Russia. 2Department of Therapy, Medical Faculty of Saratov State Medical University named after V.I. Razumovsky, Saratov, Russia. 3Department of Therapy, Medical Faculty of Rostov State Medical University, Rostov-on-Don, Russia. 4Department of Therapy, Faculty of Medicine of North Ossetian State Medical Academy, Vladikavkaz, Republic of North Ossetia-Alania, Russia.
Today, more than two and a half thousand compounds are known that are used in the production of food products. This is usually done to increase the preservation and storage period and improve organoleptic parameters. However, some of these toxic compounds may inadvertently enter food through packaging material and technological additives. Residues of toxic chemicals and industrial pollutants in food are a serious problem for a healthy body, which can lead to oncogenetic processes. Among such persistent organic pollutants are organochlorine pesticides, polychlorinated biphenyls, as well as by-products of chemical production and combustion processes, such as dioxins and furans. One of the most toxic pesticides is the organochlorine pesticide γ-isomer of hexachlorocyclohexane (C6H6Cl6). Pure hexachlorocyclohexane is a hydrophobic white powder with a crystalline structure that has strong acid-resistant parameters. To date, it is known for sure that hexachlorocyclohexane is a polytropic toxic chemical that primarily affects the central and autonomic nervous system of mammals. Hexachlorocyclohexane has been widely used in agriculture for pest control. Now the substance is banned everywhere. This article is devoted to the effect of hexachlorocyclohexane on the human body.
Keywords: Hexachlorocyclohexane, Toxicity, Health, Oncogenesis
Pesticides are an extensive heterogeneous group consisting of organochlorine, organometallic, phosphoorganic substances and alkaloids, differing in mechanism and degree of action on target cells. An important and unambiguous axiom applies to this group of substances: the long-term effect of using pesticides is equivalent to a decrease in species diversity, since one of the most striking properties of pesticides is their total reproductive toxicity for all animals, including humans.[2-4]
In 2017, the United Nations declared the falsity of the statement about the need to use pesticides to ensure food safety. Data on more than two hundred thousand cases of deaths due to pesticide poisoning were given as proof. It was noted that constant contact with toxic chemicals is subsequently associated with oncological diseases, Alzheimer's and Parkinson's diseases, endocrine pathologies, disorders of physical and mental development in children and reduced fertility.[5, 6] High levels and/or prolonged exposure to hexachlorocyclohexane may also affect an increase in the frequency of miscarriages in women. In particular, there is information that hexachlorocyclohexane lindanes have an antiandrogenic effect on men, which leads to insufficient development of the reproductive system: from a decrease in the size of the testicles and normal production of sperm fluid to a violation of the production of sex hormones.
Today, there is indisputable evidence that pesticides play a role in the development of cancer. For example, in February 2019, researchers found that the accumulation of dichlorodiphenyltrichloroethane compounds in young women dramatically increases the likelihood of developing breast cancer at a more mature age due to the pathotransformation of cell physiology. In addition, dichlorodiphenyl trichloroethane is very stable and is almost not excreted from the tissue structures of the body, for which it was also banned in many states at one time. There are whole lists compiled by doctors about the correlative relationship between certain substances and side effects caused by them.[10, 11] Thus, the use of pesticides in the food industry should be clearly and smoothly controlled at the legislative level in order to avoid mass poisoning of people.
Organochlorine pesticide γ-isomer of hexachlorocyclohexane (C6H6Cl6) was widely used early in agriculture to control harmful insects of feed stocks, now banned everywhere. The famous scientist Michael Faraday obtained hexachlorocyclohexane under laboratory conditions in 1825. Almost a century later, another researcher G. Bender discovered insecticidal properties in one of the isomers of hexachlorocyclohexane. Thus, the now famous hexachlorocyclohexane was discovered, whose mass production began in 1949. According to some data, hexachlorocyclohexane still ranks second in terms of production and use after dichlorodiphenyltrichloroethane.
Pure hexachlorocyclohexane is a hydrophobic white powder with a crystalline structure that has strong acid-resistant parameters. It was usually obtained by the chemical reaction of benzene chlorination and the chlorination reaction of cyclohexane and cyclohexene.
Technical lindane hexachlorocyclohexane (Figure 1) has a persistent smell of musty mold, dirty yellow color due to impurities of pentachlorocyclohexene and tetrachlorocyclohexadiene. It is hydrophobic, but it dissolves quite effectively in organic nonpolar solvents, such as acetone, benzene, kerosene, etc.
Figure 1. Model of lindane hexachlorocyclohexane.
This pesticide served as one of the main means of combating some insects and was widely used for fumigation of warehouses, because its lindane has powerful insecticidal properties, being a strong contact, systemic, intestinal and fumigant poison. To date, it is known for sure that hexachlorocyclohexane is a polytropic toxic chemical that primarily affects the central and autonomic nervous system of mammals. Back in 1985, the Soviet scientist Professor Melnikov wrote that "all isomers of hexachlorocyclohexane have pronounced cumulative properties, especially α-, β- and γ-isomers of hexachlorocyclohexane, therefore they are characterized by chronic poisoning, which in the future may be complicated by the appearance and growth of malignant neoplasms".[13, 14]
Hexachlorocyclohexane was produced (and is still being produced in some countries with agricultural economies) in the form of dust (12% content), powder on phosphorous flour (25% content), emulsions, aerosols and smoke bombs. In industrially developed countries, hexachlorocyclohexane and its lindanes are considered as extremely dangerous compounds that cause total harm to the environment and the health of living organisms.[15, 16] As a result, they are either prohibited in production and use, or severely restricted.
The effect of large amounts of hexachlorocyclohexane can harm the central and autonomic nervous system, causing a whole symptom complex: from headaches and dizziness to convulsions and convulsions. Also, the most common side effects are a burning sensation, itching, dryness and the appearance of a skin rash. There was no clear evidence in animal experiments that hexachlorocyclohexane affects immunity, and it is not considered genotoxic. Prenatal exposure to β-hexachlorocyclohexane and a by-product of production is associated with changes in thyroid hormone levels and may affect the development of the central nervous system. It is reported that people can be exposed to hexachlorocyclohexane in the workplace by inhalation, contact, ingestion and contact with mucous membranes, and up to 50 mg/m3 it does not pose too serious a danger at the moment.
Based mainly on the results of animal studies, most assessments of lindane have concluded that it may still be capable of causing cancer. In 2001, experts from the US Environmental Protection Agency concluded that there was "suggestive evidence of carcinogenicity, but insufficient to assess the carcinogenic potential of humans". And almost 15 years later, WHO has accurately classified hexachlorocyclohexane as a strong carcinogen.
Researchers have found associations with oncopathologies such as leukemia, brain cancer, lymphoma and melanoma of the skin. Also, the kidneys, mammary gland in women, prostate in men, and digestive tract organs become target organs for oncopathogenesis. An increased level of carcinogenicity has been found among agricultural workers who still use these hexachlorocyclohexane, in some countries. Studies suggest a link between the effects of hexachlorocyclohexane on the central nervous system with the development of glioma and meningioma, diffuse large-cell B-cell lymphoma. Occupational exposure to pesticides on a woman during her pregnancy is associated with an increased risk of leukemia, Wilms tumor and brain cancer in a child.
The putative molecular mechanism of hexachlorocyclohexane action and carcinogenesis is damage to genetic materials at the chromosome level: DNA and histone proteins. There is evidence of damage to cellular organelles, such as the endoplasmic reticulum, the mitochondrial complex and nuclear receptors in cells.
If we talk about the prevention of cancer risks induced by the gamma-isomer of hexachlorocyclohexane, then the "precautionary principle" in the use of pesticides plays a significant role here, which is directly regulated by environmental law. WHO recommends limiting the use of pesticides, in particular hexachlorocyclohexane has proven its oncotoxicity and therefore the global agricultural industry should completely remove it from use in work. It is also important to increase literacy among the population in the field of nutrition, food hygiene and epidemiology.[25-27]
Today, there is indisputable evidence that pesticides play a role in the development of cancer, and the gamma isomer of hexachlorocyclohexane is involved in carcinogenesis (damage to genetic materials at the chromosome level). However, some of these toxic compounds may inadvertently enter food through packaging material and technological additives. If we talk about the prevention of cancer risks induced by the gamma-isomer of hexachlorocyclohexane, then the "precautionary principle" in the use of pesticides plays a significant role here, which is directly regulated by environmental law. WHO recommends limiting the use of pesticides, in particular, hexachlorocyclohexane has proven its oncotoxicity and therefore the global agricultural industry should completely remove it from use in work. It is also important to increase literacy among the population in the field of nutrition, food hygiene and epidemiology.
Residues of toxic chemicals and industrial pollutants in food are a serious problem for a healthy body, which can lead to oncogenetic processes. Among such persistent organic pollutants are organochlorine pesticides, polychlorinated biphenyls, as well as by-products of chemical production and combustion processes, such as dioxins and furans. One of the most toxic pesticides is the organochlorine pesticide γ-isomer of hexachlorocyclohexane (C6H6Cl6). hexachlorocyclohexane has been widely used in agriculture for pest control. now the substance is banned everywhere.
Thus, the use of pesticides in the food industry should be clearly and smoothly controlled at the legislative level in order to avoid mass poisoning of people.
1. Golshani R, Zafarani GG, Rebezov M, Karbalaei S, Walker TR. Assessment of Organophosphorus Pesticide Residues in Water and Sediment Collected from the Southern Caspian Sea. Appl Environ Res. 2022;44(2):18-31. doi:10.35762/AER.2022.44.2.2
2. Kumar N, Pathera AK, Saini P, Kumar M. Harmful effects of pesticides on human health. Ann Agri Bio Res. 2012;17(2):165-8.
3. Meka W, Dubiwak AD. Environmental Impact of Pesticide and its Adverse Effect on Human Health: A Narrative Review. EC Pharmacol Toxicol. 2021;9(11):10.
4. Osipchuk GV, Povetkin SN, Simonov AN, Verevkina MN, Karatunov VA, Yakovets MG. On the Issue of Non-Hormonal Stimulation of the Reproductive Function of Rams. Pharmacophore. 2020;11(2):73-6.
5. Agnihotri A, Aruoma OI. Alzheimer's Disease and Parkinson's Disease: A Nutritional Toxicology Perspective of the Impact of Oxidative Stress, Mitochondrial Dysfunction, Nutrigenomics and Environmental Chemicals. J Am Coll Nutr. 2020;39(1):16-27. doi:10.1080/07315724.2019.1683379
6. Khandia R, Ali Khan A, Alexiou A, Povetkin SN, Verevkina MN. Codon Usage Analysis of Pro-Apoptotic Bim Gene Isoforms. J Alzheimers Dis. 2022;86(4):1711-25. doi:10.3233/JAD-215691
7. Yuksel H, Ispir Ü, Ulucan A, Turk C, Taysı MR. Effects of Hexachlorocyclohexane (HCH-γ-Isomer, Lindane) on the Reproductive System of Zebrafish (Danio rerio). Turkish J Fish Aquat Sci. 2016;16(4):917-21. doi:10.4194/1303-2712-v16419
8. Anjanapriya S, SulaimanMumtaz M, Mohideen MHAK, Radha A, Sasirekha N, Sawicka B, et al. Pharmaceutical Pollution Crisis in the World: A Menace to Ecosystem. Entomol Appl Sci Lett. 2021;8(1):77-89. doi:10.51847/iUGgphofKK
9. Gilden RC, Huffling K, Sattler B. Pesticides and health risks. J Obstet Gynecol Neonatal Nurs. 2010;39(1):103-10. doi:10.1111/j.1552-6909.2009.01092.x
10. van't Veer P, Lobbezoo IE, Martín-Moreno JM, Guallar E, Gómez-Aracena J, Kardinaal AF, et al. DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study. BMJ. 1997;315(7100):81-5. doi:10.1136/bmj.315.7100.81
11. Areshidze DA, Mischenko DV, Makartseva LA, Rzhepakovsky IV, Nagdalian AA. Some functional measures of the organism of rats at modeling of ischemic heart disease in two different ways. Entomol Appl Sci. 2018;5(4):2349-864.
12. Li YF, Zhulidov AV, Robarts RD, Korotova LG. Hexachlorocyclohexane use in the former Soviet Union. Arch Environ Contam Toxicol. 2005;48(1):10-5. doi:10.1007/s00244-004-0047-7
13. Nayyar N, Sangwan N, Kohli P, Verma H, Kumar R, Negi V, et al. Hexachlorocyclohexane: persistence, toxicity and decontamination. Rev Environ Health. 2014;29(1-2):49-52. doi:10.1515/reveh-2014-0015
14. Maslova AY, Bazaeva KL, Abdullaeva ZA, Khazamova SO, Zeusheva KA, Grechkina TA, et al. Astrocytes and their Phenomenal Possibilities in the Treatment of Various Neurodegenerative Disorders: An Overview. J Pharm Res Int. 2021;33(33A):60-8. doi:10.9734/jpri/2021/v33i33A31772
15. Davies JE, Dedhia HV, Morgade C, Barquet A, Maibach HI. Lindane poisonings. Arch Dermatol. 1983;119(2):142-4. doi:10.1001/archderm.1983.01650260050017
16. Sergeevna LM, Ivanovich KV, Sergey P, Viktorovich PS, MarinaPetrovna M, Viktorovich SV, et al. 5% Suspension of albendazole echinacea magenta (echinacea purpurea) toxicometric evaluation. Entomol Appl Sci Lett. 2018;5(4):30-4.
17. Melnikov NN. Pesticide and the environment: Gamma hexachlorocyclohexane. Khim Sel'sk.Khoz. 1974;12:631-5. (In Russian)
18. Willett KL, Ulrich EM, Hites RA. Differential toxicity and environmental fates of hexachlorocyclohexane isomers. Environ Sci Technol. 1998;32(15):2197-207. doi:10.1021/es9708530
19. Rubini E, Paglia G, Cannella D, Macone A, Di Sotto A, Gullì M, et al. β-Hexachlorocyclohexane: A Small Molecule with a Big Impact on Human Cellular Biochemistry. Biomedicines. 2020;8(11):505. doi:10.3390/biomedicines8110505
20. Olivero-Verbel J, Guerrero-Castilla A, Ramos NR. Biochemical effects induced by the hexachlorocyclohexanes. Rev Environ Contam Toxicol. 2011;212:1-28. doi:10.1007/978-1-4419-8453-1_1
21. Alshareef AA, Ibrahim M. Neuroprotective effect of virgin coconut oil against hydrocarbon induced neurotoxicity. Pharmacophore. 2020;11(2):95-9.
22. Sandu MA, Virsta A. Preliminary study on hexachloro-cyclohexane concentration in a historically contaminated industrial site. J Environ Prot Ecol. 2018;19(1):55-61.
23. Alvarez-Pedrerol M, Ribas-Fitó N, Torrent M, Carrizo D, Garcia-Esteban R, Grimalt JO, et al. Thyroid disruption at birth due to prenatal exposure to beta-hexachlorocyclohexane. Environ Int. 2008;34(6):737-40. doi:10.1016/j.envint.2007.12.001
24. Curl CL, Spivak M, Phinney R, Montrose L. Synthetic Pesticides and Health in Vulnerable Populations: Agricultural Workers. Curr Environ Health Rep. 2020;7(1):13-29. doi:10.1007/s40572-020-00266-5
25. Ayivi R, Ibrahim SA, Colleran H, Silva R, Williams L, Galanakis C, et al. COVID-19: human immune response and the influence of food ingredients and active compounds. Bioact Compd Health Dis. 2021;4(6):100-48.
26. Kalyabina VP, Esimbekova EN, Kopylova KV, Kratasyuk VA. Pesticides: formulants, distribution pathways and effects on human health - a review. Toxicol Rep. 2021;8:1179-92. doi:10.1016/j.toxrep.2021.06.004
27. Kim KH, Kabir E, Jahan SA. Exposure to pesticides and the associated human health effects. Sci Total Environ. 2017;575:525-35. doi:10.1016/j.scitotenv.2016.09.009