Environmental Science and Pollution Research

, Volume 25, Issue 10, pp 9371–9379 | Cite as

Teratogenic effects induced by chitosan oligosaccharide in Wistar female rat Rattus norvegicus

  • Amal Abdel Aziz Eisa
  • Gamal El-Sayed Aboelghar
  • Ibrahim Mahmoud Ammar
  • Hala Gabr Metwally
  • Samah Saied Arafa
Research Article


The aim of this research is to investigate the teratogenic effects of chitosan oligosaccharide in Wistar female rats (Rattus norvegicus). Chitosan LD50 value was calculated by probit analysis. High dose, 1/10 LD50 which equal to 150 mg/kg body weight, and low dose, 1/30 LD50 which equal to 50 mg/kg body weight, were administrated orally to Wistar female rats to examine the teratogenic effect during organogenesis period from 6th day to 15th day of gestation. Treated and control rats were sacrificed and their foetuses were examined for external, skeletal and visceral anomalies, number and length of foetuses and their weights. Obtained results showed toxicity and teratogenic effects of chitosan on treated rats and their progenies, i.e. high fetal mortality, offspring’s weight and length reduction, and high incidence of fetal external, skeletal and visceral abnormalities. This suggested that chitosan is a teratogenic compound, restricted to current results from orally treated Wistar rats.


Wistar rat Rattus norvegicus Teratogenic Chitosan oligosaccharide 


  1. Abou-Amer LW, Ali FA, Rady MI, Abdelmonem AE (2010) Teratological effects induced by three pesticides in pregnant rats. Alex J Pharm Sci 24Google Scholar
  2. Abu-Qare AW, Abdel-Rahman A, Kishk AM, Abou-Donia M (2000) Placental transfer and pharmcokinetic of a single dermal dose of [14 C] methyl parathion rats. Toxicol Sci 53:1096–6080CrossRefGoogle Scholar
  3. Ali, I. Omina, Hanaa, M.R. Hegazy and Fatma, M. Fakhry (2011). Amendment effect of antioxidants of barley and oat against teratogenicity induced by amitraz. J Amer Sci, 7(5)Google Scholar
  4. Andrews JE, Gray LE (1990) The effects of lindane and linuron on calcium metabolism, bone morphometry and the kidney in rats. Toxicology 60(1-2):99–107. CrossRefGoogle Scholar
  5. Bradman A, Barr DB, Claus-Henn BG, Drumheller T, Curry C, Eskenazi B (2003) Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: a validation study. Environ HealthGoogle Scholar
  6. Chanda SM, Harp P, Liu J, Pope CN (1995) Comparative developmental and maternal neurotoxicity following acute gestational exposure to chlorpyrifos in rats. J Toxicol Enviro Health 44(2):189–202. CrossRefGoogle Scholar
  7. Chandy T, Sharma C (1990) Chitosan–as a biomaterial. Biomat Art Cells Art Org 18(1):1–24. CrossRefGoogle Scholar
  8. Dewan P, Jain V, Gupta P, Banerjee BD (2013) Organochlorine pesticide residues in maternal blood, cord blood, placenta and breastmilk and their relation to birth size. Chemosphere 5:1704–1079.
  9. El Ghareeb AEW, Hamdi H, Taha ESF, Ali H (2015) Evaluation of teratogenic potentials of bronchodilator drug on offsprings of albino rats. Int J Sci Eng Res 6:534–542Google Scholar
  10. FDA (1970) Advisory committee on protocols for safety evaluation, panel on reproduction: report on reproduction studies in the safety evaluation of food additives and pesticide residues. Toxicol Appl Pharma 16:264–296.
  11. Finney DJ (1971) Probit Analysis. 3rd ed. Cambridge University Press. Fird Food Chem Toxicol 42:1269–1277.
  12. Goel A, Dani V, Dhawan DK (2005) Protective effects of zinc on lipid peroxidation, antioxidant enzymes and hepatic histoarchitecture in chlorpyrifos-induced toxicity. Chem Biol Interact 156(2-3):131–140. CrossRefGoogle Scholar
  13. Goy CR, De Britto D, Odilio ABG (2009) A review of the antimicrobial activity of chitosan. Polímeros: Ciência e Tecnologia 19:241–247.
  14. Harbison RD (1980) Teratogens, Chapter 8 in Toxicology, the basic science of poisons, 2nd . Ed. Edited by Doull, Klaassen and Amdur. Macmillan publishing Co.Google Scholar
  15. Kim SS, Kwack SJ, Lee RD, Lim KJ, Rhee GS, Seok JH, Kim BH, Won YH, Lee GS, Jeung EB, Lee BM, Park KL (2005) Assessment of estrogenic and androgenic activities of tetramethrin in vitro and in vivo assays. J Toxicol Enviro Health, Part A 68:2277–2289.
  16. Lozano AMA, Manzanilla CM, Alvarez LR, Reyes RE (1989) Mutagenic and teratogenic effects of diazinon. Revi InternatDecont Ambien 24:137–150Google Scholar
  17. Lu FC (1996) Basic toxicology: fundamentals, target organs and risk assessment. 3rd Ed., Taylor and Francis, Washington, DC., USA., 13: 358Google Scholar
  18. Madu PE (2015) Teratogenic and embryotoxic effects of orally administered cypermethrin in pregnant albino rats. J Toxi Enviro H Sci 7:60-67.
  19. Manel A, Fadoua N, Wahiba D, Lamia K, Mohamed Fadhel N, Abderraouf K, Zohra H (2016) Toxic effects of methamidophos on paraoxonase 1 activity and on rat kidney and liver and ameliorating effects of alpha-tocopherol. Environ Toxicol 31:842–854CrossRefGoogle Scholar
  20. Manson JM, Kang YJ (1989) Test methods for assessment of female reproductive and developmental toxicology. In: Hayes AW, editor. Raven Press, Prin.and Meth. of Toxicol.. New York, pp 72–83Google Scholar
  21. Mansour SA (2004) Pesticide exposure-Egyptian scene. J Toxicol 198(1-3):91–115. CrossRefGoogle Scholar
  22. Mansour SA, Mossa ATH (2010) Oxidative damage, biochemical and histopathological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc. Pesticide Biochem Physiol 96:14-23.
  23. Mansour SA, Mossa ATH (2011) Adverse effects of exposure to low doses of chlorpyrifos in lactating rats. Toxicol Ind Health 27(3):213–224. CrossRefGoogle Scholar
  24. Mirkin BL (1973) Maternal and fetal distribution of drugs in pregnancy. ClinPharma Therap 14(4part2):643–647. CrossRefGoogle Scholar
  25. Mossa ATH, Refaie AA, Ramadan A (2011) Effect of exposure to mixture of four organophosphate insecticides at no observed adverse effect level dose on rat liver: the protective role of vitamin C. Res J Environ Toxic 5(6):323–335. CrossRefGoogle Scholar
  26. Murray FJ, Staples RE, Schwetz BA (1979) Teratogenic potential of carbaryl given to rabbits and mice by gavage or by dietary inclusion. Toxicol Applied Pharmacol 51(1):81–89. CrossRefGoogle Scholar
  27. Nafstad I, Berge G, Sannes E, Lyngest A (1983) Teratogenic effects of the organophosphorus compound fenchlorphos in rabbits. Acta Vet Scand 3:295–304Google Scholar
  28. Nau H, Scott WJ (1985) Weak acids may act as human teratogen by accumulation in the young mammalian embryo. Nature 332:276–278Google Scholar
  29. Nittin SD, Sharma AK, Dwivedi PR, Patil D and Kumar M (2007) Citrinin and endosulfan induced teratogenic effects in Wistar rats. J Applied Toxicol 27:143–151.
  30. Omara AE, Aly HF, Nada SA (2012) Chitosan induced hepato-nephrotoxicity in mice with special reference to gender effect in glycolytic enzymes activities. Regul Toxicol Pharmacol 62(1):29-40.
  31. Organisation for Economic Co-operation and Development Guidelines for Testing of Chemicals section 4 (2001) Test no. 414, prenatal and developmental toxicity study [website on the Internet]. Paris: OECD. Available from:
  32. Pant N, Prasad AK, S C, Srivastava RS, and Srivastava SP (1995) Effect of oral administration of carbofuran on male reproductive system of rat. Hum Experi Toxicol (11):889-894.
  33. Saxena MC, Siddiqui MKJ, Bhargava AK, Murti CRK, Kutty D (1981) Placental transfer of pesticides in humans. Arch Toxicol 48(2-3):127–134. CrossRefGoogle Scholar
  34. Sharma Y, Bashir SB, Irshad M, Gupta s d, Dogra TD (2005) Effects of acute dimethoate administration on antioxidant status of liver, brain of expermintal rats. Toxicology 20:49-57.
  35. Soni I, Bhatngar P (1989) Embryotoxic and teratogenic studies of phosphamidon in Swiss albino mice. Teratog Carcinog Mutagen 4:253–257CrossRefGoogle Scholar
  36. Srivastava MK, Raizada RB (1996) Development effect of technical dimethoate in rats: maternal and fetal toxicit evaluation. Indian J Exp Biol 39:1023–1027Google Scholar
  37. Staples RE, Schnell VL (1964) Refinements in rapid clearing technique in the KOH-alizarin red S method for fetal bone. Stain Technal 39:251–277Google Scholar
  38. Tanaka Y, Tanioka S, Tanaka M, Tanigawa T, Kitamura Y, Minami S, Okamoto Y, Miyashita M, Nanno M (1997) Effects of chitin and chitosan particles on BALB/c mice by oral and parenteral administration. Biomaterials 18(8):591–595. CrossRefGoogle Scholar
  39. Teo S, Stirling D, Thomas S, Hoberman A, Kiorpes A, Khetani V (2002) A 90-days oral gavage toxicity study of D-methylphenidate and d, l-methylphenidate in Sprage-Dawley rats. Toxicology 179(3):183–196. CrossRefGoogle Scholar
  40. Tezak Z, Simic B, Kniewald J (1992) Effect of pesticides on oestradiol-receptor complex formation in rat uterus cytosol. Fd Chem Toxic 30:879–885CrossRefGoogle Scholar
  41. Tuchmann H (1975) Drug effects on faetus ADIS press. USA, New York, 7(4)Google Scholar
  42. Vasil’ev LA, Dzyubinskaya EV, Zinovkin RA, Kiselevsky DB, Lobysheva NV, Samuilov VD (2009) Chitosan-induced programmed cell death in plants. Biochem-Moscow 74(9):1035–1043. CrossRefGoogle Scholar
  43. Wang GM (1988) Regulatory decision making and the need for the exposure data on pesticide determined to be teratogenic in test animals. Teratog Carcinog Mutagen 8:117–126CrossRefGoogle Scholar
  44. Weber M (1990) The effect of dimethoate and vibration on fetal development in the rat. Anat Anz 170(3-4):221–226Google Scholar
  45. Weis SJ, Weis P (1977) J Fish Biol 11:49CrossRefGoogle Scholar
  46. Whyatt RM, Camann DE, Kinney PL, Reyes A, Ramirez J, Dietrich J, Diaz D, Holmes D, Perera FD (2002) Residential pesticide use during pregnancy among a cohort of urban minority women. EnvironHealth Perspect 110:507–514Google Scholar
  47. Wilson JG (1972) Embryological consideration in teratology in Wilson, J.G. and WarKany, J. (eds) Teratology: principles and techniques the University of Chicago press. Chicageo & London , 251–277Google Scholar
  48. Yan Y, Yang Y, Zhao X, Liu X, Xue J, Zhang J, and Yang A, (2015) Exposure to the mixture of organophosphorus pesticides is embryotoxic and teratogenic on gestational rats during the sensitive period. Wiley Period, Inc. Environ Toxicol.

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Amal Abdel Aziz Eisa
    • 1
  • Gamal El-Sayed Aboelghar
    • 1
  • Ibrahim Mahmoud Ammar
    • 1
  • Hala Gabr Metwally
    • 2
  • Samah Saied Arafa
    • 1
  1. 1.Pesticides Department, Faculty of AgricultureMenoufia UniversityShibin El KomEgypt
  2. 2.Clinical Pathology Department, Faculty of MedicineCairo UniversityGizaEgypt

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