The evaluation of potential toxic metal levels of various drugs used in children

Serkan Şahin; Vugar Ali Türksoy

doi:10.32322/jhsm.1356020

Research Article

Year 2024, Volume: 7 Issue: 1, 39 - 46, 15.01.2024

Serkan Şahin Vugar Ali Türksoy

https://doi.org/10.32322/jhsm.1356020

Abstract

References

Şenkal E, Toprak S, Özbörü Aşkan Ö, et al. Effectiveness of ımmunity supporting drugs in preventing respiratory ınfections in nursery children. Çocuk Derg. 2019;19(3):132-137. doi:10.5222/j.child.2019.76993
Legislation Information System. https://www.mevzuat.gov.tr/mevzuat?MevzuatNo=39102&MevzuatTur=7&MevzuatTertip=5. Accessed June 13, 2023.
Legislation Information System. https://www.mevzuat.gov.tr/mevzuat?MevzuatNo=1262&MevzuatTur=1&MevzuatTertip=3. Accessed June 13, 2023.
Thomas KJ, Nicholl JP, Coleman P. Use and expenditure on complementary medicine in England: a population based survey. Complement Ther Med. 2001;9(1):2-11. doi:10.1054/ctim.2000.0407
Cohen PA. Assessing supplement safety—the FDA’s controversial proposal. N Engl J Med. 2012;366(5):389-391. doi:10.1056/nejmp1113325
Ernst E. Prevalence of use of complementary/alternative medicine: a systematic review. Bull World Heal Organ. 2000;78(2):258-266.
Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF. Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000. Am J Epidemiol. 2004;160(4):339-349. doi:10.1093/aje/kwh207
Picciano MF, Dwyer JT, Radimer KL, et al. Dietary supplement use among infants, children, and adolescents in the United States, 1999-2002. Arch Pediatr Adolesc Med. 2007;161(10):978-985. doi:10.1001/archpedi.161.10.978
Atalay D, Erge SH. Dietary supplements and their effects on health. Food Heal. 2018;4(2):98-111. doi:10.3153/FH18010
Bailey RL, Gahche JJ, Miller PE, Thomas PR, Dwyer JT. Why US adults use dietary supplements. JAMA Intern Med. 2013;173(5):355-361. doi:10.1001/JAMAINTERNMED.2013.2299
Garvey GJ, Hahn G, Lee R V., Harbison RD. Heavy metal hazards of Asian traditional remedies. Int J Environ Heal Res. 2001;11(1):63-71. doi:10.1080/09603120020019656
Kákosy T, Hudák A, Náray M. Lead intoxication epidemic caused by ingestion of contaminated ground paprika. J Toxicol Clin Toxicol. 1996;34(5):507-511. doi:10.3109/15563659609028008
Markowitz SB, Nunez CM, Klitzman S, et al. Lead poisoning due to hai ge fen. The porphyrin content of individual erythrocytes. JAMA. 1994;271(12):932-934. doi:10.1001/jama.1994.03510360058037
Dunbabin DW, Tallis GA, Popplewell PY, Lee RA. Lead poisoning from Indian herbal medicine (Ayurveda). Med J Aust. 1992;157(11-12):835-836. doi:10.5694/j.1326-5377.1992.tb141305.x
Olujohungbe A, Fields PA, Sandford AF, Hoffbrand AV. Heavy metal intoxication from homeopathic and herbal remedies. Postgrad Med J. 1994;70(828):764. doi:10.1136/pgmj.70.828.764
Agency for Toxic Substances and Disease Registry. https://www.atsdr.cdc.gov/index.html. Accessed July 26, 2023.
US Pharmacopeia (USP). https://www.usp.org/ Accessed July 26, 2023.
Legislation Information System. https://www.mevzuat.gov.tr/mevzuat?MevzuatNo=18532&MevzuatTur=7&MevzuatTertip=5. Accessed July 26, 2023.
Turkozu D, Sanlier N. Current overview: heavy metal contamination of food. Selcuk J Agric Food Sci. 2012;26(4):73-80.
Yerli C, Cakmakcı T, Sahin U, Tufenkci S. The effects of heavy metals on soil, plant, water and human health. Turkish J Nat Sci. 2020;9(Special Issue):103-114. doi:10.46810/tdfd.718449
Costagliola G, Spada E, Comberiati P, Peroni DG. Could nutritional supplements act as therapeutic adjuvants in COVID-19? Ital J Pediatr. 2021;47(1):1-5. doi:10.1186/S13052-021-00990-0/TABLES/1
Turksoy VA, Yalvac ES, Simsek OT, et al. Impact of zinc on birth and placental weight in cadmium and lead exposure during pregnancy. Indian J Forensic Med Pathol. 2019;12(3):246-254. doi:10.21088/ijfmp.0974.3383.12319.15
Ministry of Food A and L. Turkish Food Codex Contaminants Regulation. https://www.resmigazete.gov.tr/eskiler/2011/12/20111229M3-8.htm. Published 2011. Accessed January 15, 2022.
Grzybowski A, Zülsdorff M, Wilhelm H, Tonagel F. Toxic optic neuropathies: an updated review. Acta Ophthalmol. 2015;93(5):402-410. doi:10.1111/AOS.12515
Renu K, Chakraborty R, Myakala H, et al. Molecular mechanism of heavy metals (lead, chromium, arsenic, mercury, nickel and cadmium) - induced hepatotoxicity - a review. Chemosphere. 2021;271:129735. doi:10.1016/J.CHEMOSPHERE.2021.129735
Arslanbaş E, Baydan E. Common toxicosis in swine 2. metal, vitamin, pharmaceutical, pesticide and plant toxicosis. J Lalahan Livest Res Inst. 2012;52(1):33-40.
Rani A, Kumar A, Lal A, Pant M. Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res. 2014;24(4):378-399. doi:10.1080/09603123.2013.835032
Al osman M, Yang F, Massey IY. Exposure routes and health effects of heavy metals on children. Biometals. 2019;32(4):563-573. doi:10.1007/S10534-019-00193-5
Sherief LM, Abdelkhalek ER, Gharieb AF, et al. Cadmium status among pediatric cancer patients in Egypt. Medicine. 2015;94(20):e740. doi:10.1097/MD.0000000000000740
Bose-O’Reilly S, McCarty KM, Steckling N, Lettmeier B. Mercury exposure and children’s health. Curr Probl Pediatr Adolesc Health Care. 2010;40(8):186-215. doi:10.1016/J.CPPEDS.2010.07.002
Bernhoft RA. Mercury toxicity and treatment: a review of the literature. J Environ Public Health. 2012;2012:460508. doi:10.1155/2012/460508
Trasande L, Schechter C, Haynes KA, Landrigan PJ. Applying cost analyses to drive policy that protects children: mercury as a case study. Ann N Y Acad Sci. 2006;1076(1):911-923. doi:10.1196/ANNALS.1371.034
Li Y, Lv H, Xue C, Dong N, Bi C, Shan A. Plant polyphenols: potential antidotes for lead exposure. Biol Trace Elem Res. 2020;199(10):3960-3976. doi:10.1007/S12011-020-02498-W
Qureshi MI, Abdin MZ, Qadir S, Iqbal M. Lead-induced oxidative stress and metabolic alterations in Cassia angustifolia Vahl. Biol Plant. 2007;51(1):121-128. doi:10.1007/S10535-007-0024-X
Gürer H, Özgünes H, Saygin E, Environmental NE-A of, 2001 U. Antioxidant effect of taurine against lead-induced oxidative stress. Arch Contam Environ Toxicol. 2001;41(4):397-402. doi:10.1007/s002440010265
Reuben A. Childhood lead exposure and adult neurodegenerative disease. J Alzheimer’s Dis. 2018;64(1):17-42. doi:10.3233/JAD-180267
Murata K, Iwata T, Dakeishi M, Karita K. Lead toxicity: Does the critical level of lead resulting in adverse effects differ between adults and children? J Occup Health. 2009;51(1):1-12. doi:10.1539/joh.K8003
Cohen MD, Kargacin B, Klein CB, Costa M. Mechanisms of chromium carcinogenicity and toxicity. Crit Rev Toxicol. 1993;23(3):255-281. doi:10.3109/10408449309105012
Chmatalova Z, Vyhnalek M, Laczo J, et al. Relation of plasma selenium and lipid peroxidation end products in patients with Alzheimer’s disease. Physiol Res. 2017;66(6):1049-1056. doi:10.33549/PHYSIOLRES.933601
Zhang ZW, Wang QH, Zhang JL, Li S, Wang XL, Xu SW. Effects of oxidative stress on immunosuppression induced by selenium deficiency in chickens. Biol Trace Elem Res. 2012;149(3):352-361. doi:10.1007/S12011-012-9439-0/FIGURES/9
Elango S, Samuel S, Khashim Z, Subbiah U. Selenium ınfluences trace elements homeostasis, cancer biomarkers in squamous cell carcinoma patients administered with cancerocidal radiotherapy. Asian Pacific J Cancer Prev. 2018;19(7):1785-1792. doi:10.22034/APJCP.2018.19.7.1785
Dinh QT, Cui Z, Huang J, et al. Selenium distribution in the Chinese environment and its relationship with human health: a review. Environ Int. 2018;112:294-309. doi:10.1016/J.ENVINT.2017.12.035
Nuttall KL. Evaluating selenium poisoning. Ann Clin Lab Sci. 2006;36(4):409-420.
Gardiner MR. Chronic selenium toxicity studies in sheep. Aust Vet J. 1966;42(12):442-448. doi:10.1111/J.1751-0813.1966.TB14470.X
Freake HC, Govoni KE, Guda K, Huang C, Zinn SA. Actions and interactions of thyroid hormone and zinc status in growing rats. J Nutr. 2001;131(4):1135-1141. doi:10.1093/JN/131.4.1135
Willoughby JL, Bowen CN. Zinc deficiency and toxicity in pediatric practice. Curr Opin Pediatr. 2014;26(5):579-584. doi:10.1097/MOP.0000000000000132
Prime Ministry Legislation Development and Publication General Directorate. https://www.resmigazete.gov.tr/eskiler/2011/12/2011 1229M3-8.htm. Accessed June 7, 2023.
Korfali SI, Hawi T, Mroueh M. Evaluation of heavy metals content in dietary supplements in Lebanon. Chem Cent J. 2013;7(1):10. doi:10.1186/1752-153X-7-10
Minimal Risk Levels for Hazardous Substances | ATSDR. https://wwwn.cdc.gov/TSP/MRLS/mrlslisting.aspx. Accessed June 9, 2023.

The evaluation of potential toxic metal levels of various drugs used in children

Year 2024, Volume: 7 Issue: 1, 39 - 46, 15.01.2024

Serkan Şahin Vugar Ali Türksoy

https://doi.org/10.32322/jhsm.1356020

Abstract

Aims: Medicines have been widely used in recent years to support the immune system. Exposure to toxic metals can occur at different stages, such as raw material procurement, production, and packaging of drugs designed to support the immune system. This exposure can lead to serious health problems. In this study, the aim was to determine the levels of toxic metals in drugs used to support the immune system in children.
Methods: Ten drug samples, available in pharmacies and intended for strengthening the immune system in children, were collected. Preliminary processes were conducted for the ICP-MS analysis of these collected drugs. Following the initial preparation, levels of Arsenic (As), Copper (Cu), Zinc (Zn), Manganese (Mn), Selenium (Se), Chromium (Cr), Mercury (Hg), Lead (Pb), Cadmium (Cd), Tin (Sn), Cobalt (Co), Aluminum (Al), Molybdenum (Mo), Antimony (Sb), Nickel (Ni) were determined using an ICP-MS device.
Results: In our study, we evaluated the levels of toxic metals in drugs used to support the immune system. The average levels of Cr, Zn, As, Se, Cd, and Sn in the samples were found to exceed the limits set by international organizations. However, the average levels of Al, Cu, and Hg were very close to these limit levels. On the other hand, the levels of Mo, Sb, and Pb in the analyzed products were well below the established limits.
Conclusion: The levels of toxic metals in immune-supporting drugs can lead to toxicity when the results of the study are evaluated. To inform consumers and safeguard their health, it would be appropriate for manufacturers to include information about the daily intake limits set by international organizations for toxic metals and trace elements. Conducting toxicological tests, especially during these inspections, will greatly contribute to protecting the health of children and fostering the development of healthy generations.

Keywords

Drug, child, toxic metals, immune system

Supporting Institution

The authors declared that this study has received no financial support

References

Şenkal E, Toprak S, Özbörü Aşkan Ö, et al. Effectiveness of ımmunity supporting drugs in preventing respiratory ınfections in nursery children. Çocuk Derg. 2019;19(3):132-137. doi:10.5222/j.child.2019.76993
Legislation Information System. https://www.mevzuat.gov.tr/mevzuat?MevzuatNo=39102&MevzuatTur=7&MevzuatTertip=5. Accessed June 13, 2023.
Legislation Information System. https://www.mevzuat.gov.tr/mevzuat?MevzuatNo=1262&MevzuatTur=1&MevzuatTertip=3. Accessed June 13, 2023.
Thomas KJ, Nicholl JP, Coleman P. Use and expenditure on complementary medicine in England: a population based survey. Complement Ther Med. 2001;9(1):2-11. doi:10.1054/ctim.2000.0407
Cohen PA. Assessing supplement safety—the FDA’s controversial proposal. N Engl J Med. 2012;366(5):389-391. doi:10.1056/nejmp1113325
Ernst E. Prevalence of use of complementary/alternative medicine: a systematic review. Bull World Heal Organ. 2000;78(2):258-266.
Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF. Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000. Am J Epidemiol. 2004;160(4):339-349. doi:10.1093/aje/kwh207
Picciano MF, Dwyer JT, Radimer KL, et al. Dietary supplement use among infants, children, and adolescents in the United States, 1999-2002. Arch Pediatr Adolesc Med. 2007;161(10):978-985. doi:10.1001/archpedi.161.10.978
Atalay D, Erge SH. Dietary supplements and their effects on health. Food Heal. 2018;4(2):98-111. doi:10.3153/FH18010
Bailey RL, Gahche JJ, Miller PE, Thomas PR, Dwyer JT. Why US adults use dietary supplements. JAMA Intern Med. 2013;173(5):355-361. doi:10.1001/JAMAINTERNMED.2013.2299
Garvey GJ, Hahn G, Lee R V., Harbison RD. Heavy metal hazards of Asian traditional remedies. Int J Environ Heal Res. 2001;11(1):63-71. doi:10.1080/09603120020019656
Kákosy T, Hudák A, Náray M. Lead intoxication epidemic caused by ingestion of contaminated ground paprika. J Toxicol Clin Toxicol. 1996;34(5):507-511. doi:10.3109/15563659609028008
Markowitz SB, Nunez CM, Klitzman S, et al. Lead poisoning due to hai ge fen. The porphyrin content of individual erythrocytes. JAMA. 1994;271(12):932-934. doi:10.1001/jama.1994.03510360058037
Dunbabin DW, Tallis GA, Popplewell PY, Lee RA. Lead poisoning from Indian herbal medicine (Ayurveda). Med J Aust. 1992;157(11-12):835-836. doi:10.5694/j.1326-5377.1992.tb141305.x
Olujohungbe A, Fields PA, Sandford AF, Hoffbrand AV. Heavy metal intoxication from homeopathic and herbal remedies. Postgrad Med J. 1994;70(828):764. doi:10.1136/pgmj.70.828.764
Agency for Toxic Substances and Disease Registry. https://www.atsdr.cdc.gov/index.html. Accessed July 26, 2023.
US Pharmacopeia (USP). https://www.usp.org/ Accessed July 26, 2023.
Legislation Information System. https://www.mevzuat.gov.tr/mevzuat?MevzuatNo=18532&MevzuatTur=7&MevzuatTertip=5. Accessed July 26, 2023.
Turkozu D, Sanlier N. Current overview: heavy metal contamination of food. Selcuk J Agric Food Sci. 2012;26(4):73-80.
Yerli C, Cakmakcı T, Sahin U, Tufenkci S. The effects of heavy metals on soil, plant, water and human health. Turkish J Nat Sci. 2020;9(Special Issue):103-114. doi:10.46810/tdfd.718449
Costagliola G, Spada E, Comberiati P, Peroni DG. Could nutritional supplements act as therapeutic adjuvants in COVID-19? Ital J Pediatr. 2021;47(1):1-5. doi:10.1186/S13052-021-00990-0/TABLES/1
Turksoy VA, Yalvac ES, Simsek OT, et al. Impact of zinc on birth and placental weight in cadmium and lead exposure during pregnancy. Indian J Forensic Med Pathol. 2019;12(3):246-254. doi:10.21088/ijfmp.0974.3383.12319.15
Ministry of Food A and L. Turkish Food Codex Contaminants Regulation. https://www.resmigazete.gov.tr/eskiler/2011/12/20111229M3-8.htm. Published 2011. Accessed January 15, 2022.
Grzybowski A, Zülsdorff M, Wilhelm H, Tonagel F. Toxic optic neuropathies: an updated review. Acta Ophthalmol. 2015;93(5):402-410. doi:10.1111/AOS.12515
Renu K, Chakraborty R, Myakala H, et al. Molecular mechanism of heavy metals (lead, chromium, arsenic, mercury, nickel and cadmium) - induced hepatotoxicity - a review. Chemosphere. 2021;271:129735. doi:10.1016/J.CHEMOSPHERE.2021.129735
Arslanbaş E, Baydan E. Common toxicosis in swine 2. metal, vitamin, pharmaceutical, pesticide and plant toxicosis. J Lalahan Livest Res Inst. 2012;52(1):33-40.
Rani A, Kumar A, Lal A, Pant M. Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res. 2014;24(4):378-399. doi:10.1080/09603123.2013.835032
Al osman M, Yang F, Massey IY. Exposure routes and health effects of heavy metals on children. Biometals. 2019;32(4):563-573. doi:10.1007/S10534-019-00193-5
Sherief LM, Abdelkhalek ER, Gharieb AF, et al. Cadmium status among pediatric cancer patients in Egypt. Medicine. 2015;94(20):e740. doi:10.1097/MD.0000000000000740
Bose-O’Reilly S, McCarty KM, Steckling N, Lettmeier B. Mercury exposure and children’s health. Curr Probl Pediatr Adolesc Health Care. 2010;40(8):186-215. doi:10.1016/J.CPPEDS.2010.07.002
Bernhoft RA. Mercury toxicity and treatment: a review of the literature. J Environ Public Health. 2012;2012:460508. doi:10.1155/2012/460508
Trasande L, Schechter C, Haynes KA, Landrigan PJ. Applying cost analyses to drive policy that protects children: mercury as a case study. Ann N Y Acad Sci. 2006;1076(1):911-923. doi:10.1196/ANNALS.1371.034
Li Y, Lv H, Xue C, Dong N, Bi C, Shan A. Plant polyphenols: potential antidotes for lead exposure. Biol Trace Elem Res. 2020;199(10):3960-3976. doi:10.1007/S12011-020-02498-W
Qureshi MI, Abdin MZ, Qadir S, Iqbal M. Lead-induced oxidative stress and metabolic alterations in Cassia angustifolia Vahl. Biol Plant. 2007;51(1):121-128. doi:10.1007/S10535-007-0024-X
Gürer H, Özgünes H, Saygin E, Environmental NE-A of, 2001 U. Antioxidant effect of taurine against lead-induced oxidative stress. Arch Contam Environ Toxicol. 2001;41(4):397-402. doi:10.1007/s002440010265
Reuben A. Childhood lead exposure and adult neurodegenerative disease. J Alzheimer’s Dis. 2018;64(1):17-42. doi:10.3233/JAD-180267
Murata K, Iwata T, Dakeishi M, Karita K. Lead toxicity: Does the critical level of lead resulting in adverse effects differ between adults and children? J Occup Health. 2009;51(1):1-12. doi:10.1539/joh.K8003
Cohen MD, Kargacin B, Klein CB, Costa M. Mechanisms of chromium carcinogenicity and toxicity. Crit Rev Toxicol. 1993;23(3):255-281. doi:10.3109/10408449309105012
Chmatalova Z, Vyhnalek M, Laczo J, et al. Relation of plasma selenium and lipid peroxidation end products in patients with Alzheimer’s disease. Physiol Res. 2017;66(6):1049-1056. doi:10.33549/PHYSIOLRES.933601
Zhang ZW, Wang QH, Zhang JL, Li S, Wang XL, Xu SW. Effects of oxidative stress on immunosuppression induced by selenium deficiency in chickens. Biol Trace Elem Res. 2012;149(3):352-361. doi:10.1007/S12011-012-9439-0/FIGURES/9
Elango S, Samuel S, Khashim Z, Subbiah U. Selenium ınfluences trace elements homeostasis, cancer biomarkers in squamous cell carcinoma patients administered with cancerocidal radiotherapy. Asian Pacific J Cancer Prev. 2018;19(7):1785-1792. doi:10.22034/APJCP.2018.19.7.1785
Dinh QT, Cui Z, Huang J, et al. Selenium distribution in the Chinese environment and its relationship with human health: a review. Environ Int. 2018;112:294-309. doi:10.1016/J.ENVINT.2017.12.035
Nuttall KL. Evaluating selenium poisoning. Ann Clin Lab Sci. 2006;36(4):409-420.
Gardiner MR. Chronic selenium toxicity studies in sheep. Aust Vet J. 1966;42(12):442-448. doi:10.1111/J.1751-0813.1966.TB14470.X
Freake HC, Govoni KE, Guda K, Huang C, Zinn SA. Actions and interactions of thyroid hormone and zinc status in growing rats. J Nutr. 2001;131(4):1135-1141. doi:10.1093/JN/131.4.1135
Willoughby JL, Bowen CN. Zinc deficiency and toxicity in pediatric practice. Curr Opin Pediatr. 2014;26(5):579-584. doi:10.1097/MOP.0000000000000132
Prime Ministry Legislation Development and Publication General Directorate. https://www.resmigazete.gov.tr/eskiler/2011/12/2011 1229M3-8.htm. Accessed June 7, 2023.
Korfali SI, Hawi T, Mroueh M. Evaluation of heavy metals content in dietary supplements in Lebanon. Chem Cent J. 2013;7(1):10. doi:10.1186/1752-153X-7-10
Minimal Risk Levels for Hazardous Substances | ATSDR. https://wwwn.cdc.gov/TSP/MRLS/mrlslisting.aspx. Accessed June 9, 2023.

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Details

Primary Language	English
Subjects	Pharmaceutical Toxicology
Journal Section	Original Article
Authors	Serkan Şahin 0000-0001-7000-6342 Vugar Ali Türksoy 0000-0002-3545-3945
Early Pub Date	January 7, 2024
Publication Date	January 15, 2024
Published in Issue	Year 2024 Volume: 7 Issue: 1

Cite

AMA	Şahin S, Türksoy VA. The evaluation of potential toxic metal levels of various drugs used in children. J Health Sci Med / JHSM. January 2024;7(1):39-46. doi:10.32322/jhsm.1356020

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