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Isaac J. Asiedu-Gyekye, Abdulai Seidu Mahmood, Charles Awortwe and Alexander K. Nyarko


Polyhexamethylene biguanide (PHMB) is an antiseptic with antiviral and antibacterial properties used in a variety of products including wound care dressings, contact lens cleaning solutions, perioperative cleansing products, and swimming pool cleaners. There are regulatory concerns with regard to its safety in humans for water treatment. We decided to assess the safety of this chemical in Sprague-Dawley rats. PHMB was administered in a single dose by gavage via a stomach tube as per the manufacturer’s instruction within a dose range of 2 mg/kg to 40 mg/kg. Subchronic toxicity studies were also conducted at doses of 2 mg/kg, 8 mg/kg and 32 mg/kg body weight and hematological, biochemical and histopathological findings of the major organs were assessed. Administration of a dose of 25.6 mg/kg, i.e. 1.6 mL of 0.4% PHMB solution (equivalent to 6.4×103 mg/L of 0.1% solution) resulted in 50% mortality. Histopathological analysis in the acute toxicity studies showed that no histopathological lesions were observed in the heart and kidney samples but 30% of the animals had mild hydropic changes in zone 1 of their liver samples, while at a dosage of 32 mg/kg in the subchronic toxicity studies, 50% of the animals showed either mild hepatocyte cytolysis with or without lymphocyte infiltration and feathery degeneration. Lymphocyte infiltration was, for the first time, observed in one heart sample, whereas one kidney sample showed mild tubular damage. The acute studies showed that the median lethal dose (LD50) is 25.6 mg/kg (LC50 of 1.6 mL of 0.4% PHMB. Subchronic toxicological studies also revealed few deleterious effects on the internal organs examined, as seen from the results of the biochemical parameters evaluated. These results have implications for the use of PHMB to make water potable.

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Mazyar Yazdani

’ principles and methods of toxicology Taylor & Francis Group, LLC, Boca Raton, FL. Hedges S, Blair J, Venturi M, Shoe J (2004). A molecular timescale of eukaryote evolution and the rise of complex multicellular life. BMC Evol Biol 4: 2. Kidambi S, Yarmush RS, Novik E, Chao P, Yarmush ML, Nahmias Y (2009). Oxygen- mediated enhancement of primary hepatocyte metabolism, functional polarization, gene expression, and drug clearance. Proceedings of the National Academy of Sciences 106: 15714-15719. Malda J, Dawson R, Kairuz E

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Pavel Anzenbacher and Eva Anzenbacherová

I. (1998) Isolation and purification of constitutive forms of microsomal cytochrome P450. Meth Mol Biol   107 : 55-67 (Cytochrome P450 Protocols). Jančová P, Anzenbacherová E, Papoušková B, Lemr K, Lužná P, Veinlichová A, Anzenbacher P, Šimánek V. (2007) Silybin is metabolized by cytochrome P450 2C8 in vitro. Drug Metab Dispos   35 : 2035-2039. Ferrini JB, Ourlin JC, Pichard L, Fabre G, Maurel P. (1998) Human hepatocyte culture. Meth Mol Biol   107 : 341-52 (Cytochrome P450 Protocols).

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A. Valdovska and M. Pilmane

Guelph, Ontario, pp 21-27. Hsu SM, Raine L, Fanger H ( 1981 ) The use of antiavidin antibody and avidin-biotin - peroxidase complex in immunoperoxidase technics. Am J Clin Pathol 75: 816-821. Ishikawa KS, Masui T, Ishikawa K, Shiojiri N ( 2001 ) Immunolocalization of hepatocyte growth factor and its receptor (c-Met) during mouse liver development. Histochem Cell Biol 116: 453-462. Issa R, Williams E, Trim N, Kendall T, Arthur MJ, Reichen J, Benyon RC, Iredale JP ( 2001 ) Apoptosis of hepatic

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Madalina Iliescu, R. L. Craciun and Angelica Nela Stavar

. & Konig, J. (2000). Hepatic secretion of conjugated drugs and endogenous substances. Semin Liver Dis, 20(3), 265-272. doi: 10.1055/s-2000-9391 7. Lecureur, V., Courtois, A., Payen, L., Verhnet, L., Guillouzo, A. & Fardel, O. (2000). Expression and regulation of hepatic drug and bile acid transporters. Toxicology, 153(1-3), 203-219. 8. Lee, J. & Boyer, J.L. (2000). Molecular alterations in hepatocyte transport mechanisms in acquired cholestatic liver disorders. Semin Liver Dis, 20(3), 373-384. doi: 10.1055/s-2000-9390

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O. Naseer, J.A. Khan, M.S. Khan, M.O. Omer, G.A. Chishti, M.L. Sohail and M.U. Saleem

References Abdel-Wahhab MA, Nada SA, Khalil FA ( 2002 ) Physiological and toxicological responses in rats fed aflatoxin-contaminated diet with or without sorbent materials. Anim Feed Sci Tech 97: 209-219. Akhtar R, Sardar M, Saima N, Saleem G, Imran S, Aslam A ( 2014 ) Response of Nili-Ravi buffalo to aflatoxins B 1 with and without toxin adsorbents. J Anim Feed Sci 23: 317-323. Albright CD, Lui R, Bethea TC, Da Costa KA, Salganik RI, Zeisel SH ( 1996 ) Choline deficiency induces apoptosis in SV40-immortalized CWSV-1 rat hepatocytes in culture

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L. Radko, W. Cybulski and W. Rzeski

(lasalocid-A). Biochim Biophys Acta 1056: 250-258. Avizeh R, Najafzadeh H, Razijalali M, Shirali S ( 2009 ) Evaluation of prophylactic and therapeutic effects of silymarin and N-acetylcysteine in acetaminophen-induced hepatotoxicity in cats. J Vet Pharmacol Ther 33: 95-99. Bolkent S, Zierold K ( 2002 ) Effects of the ionophores valinomycin, ionomycin and gramicidin A on the element compartmentation in cultured rat hepatocytes. Toxicol In Vitro 16: 159-165. Bradford MM ( 1976 ) A rapid and sensitive method for the quantitation

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Jin-ling Dong, Shun-ai Liu, Qi Wang, Jin-qian Zhang and Jun Cheng

References 1. Waheed Y, Shafi T, Safi SZ, Qadri I. Hepatitis C virus in Pakistan: A systematic review of prevalence, genotypes and risk factors. World J Gasteroenterol 2009;15:5647-5653. 2. Berenguer M, Lopez-Labrador FX, Wright TL. Hepatitis C and liver transplantation. J Hepatol 2001;35:666-678. 3. Chen H, Wu M, Yu SY, Chen JL, Yuan ZH. Interferon-β induction and related signaling pathways in human hepatocyte. Wei Sheng Wu Yu Gan Ran(Chin) 2009;4:81-87. 4. Eylan E, Curran J, Hofmann K

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Aleksandra Zyska and Jolanta Jasik-Ślęzak

cyanobacteria: What can we learn from experiments? Water Res. 2012;46:1420-9. 12. Rinehart KL, Namikoshi M, Choi BW. Structure and Biosynthesis of toxins from blue-green algae (cyanobacteria). J Appl Physiol. 1994;6:159-76. 13. Botes DP, Kruger H, Viljoen CC. Isolation and characterisation of four toxins from the blue green alga Microcystis aeruginosa. Toxicon. 1982a;20:945-54. 14. Eriksson JE, Toivola D, Meriluo'o JAO, et al. Hepatocyte deformation induced by cyanobacterial toxins reflects inhibition of protein phosphst-sses. Biochem Biophys Res Commun. 1990

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Rumyana Simeonova, Vessela Vitcheva and Mitka Mitcheva

-681. Cohen LH, van Leeuwen REW, van Thiel GCF, van Pelt JF and Yap SH. (2000) Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P 450 enzymes. Biopharm Drug Dispos   21 : 353-364. Council of Europe (1991) European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes. CETS No. 123 . Deby C and Goutier R. (1990) New perspectives on the biochemistry of superoxide anion and the efficiency of SOD