TERATOGENIC EFFECTS OF TOPICALLY APPLIED PARAPHENYLENEDIAMINE ON THE RAT FOETUS
Background: Paraphenylenediamine (PPD) is an organic compound used in hair dye. It causes local and systemic side-effects. Not much is known regarding its foetotoxic effects. This study aimed at determining the teratogenic effects of topically applied PPD. Methods: This experimental study was carried out at IBMS, Khyber Medical University, and Peshawar Medical College, Peshawar over a period of 6 months. Twenty healthy Sprague Dawely female pregnant rats were divided into 5 groups, i.e., positive control (Group A), control (Group B), and 3 experimental groups (C, D, and E). For group A, 0.1 ml of distilled water was applied topically on back of each rat. For positive control group B, 0.5 ml of dye containing 3% PPD was applied, while for group C, D and E, 1, 2 and 3 mg/Kg dose of PPD respectively was applied for 30 minutes daily. Skin was washed followed by rats mating. After successful fertilization, same doses were repeated for 20 days. Animals were sacrificed and foetuses were examined for skeletal abnormalities and hepatic changes. Skin biopsy of adult rats was examined for any changes. Result: Topically applied PPD resulted in significant teratogenic effects on foetal liver in a dose dependent manner. However, no significant teratogenic effect was observed on foetal skeleton (p=0.075). Topical PPD showed increased epidermal thickening and keratinization on adult rats skin. Conclusion: PPD has significant dermal effects on adult rats and teratogenic effects on liver of rat foetuses but no significant effects were observed on foetal skeleton.
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Devi M. Toxicological effects of hair dye paraphenylene diamine: A threat to cosmetic world. Int J Res Anal Rev 2016;3(2):19–23.
Khaskheli MS, Shaikh S, Meraj M, Raza H, Aslam I. Paraphenylenediamine poisoning: clinical features, complications and outcome in a tertiary care institute. Anaesth Pain Intensive Care 2019;22(3):343–7.
Abd-ElZaher MA, Fawzy IA, Ahmed HM, Abd-Allah AM, Gayyed MF. Some toxicological health hazards associated with subchronic dermal exposure to paraphenylene-diamine (PPD): An experimental study. Egypt J Forensic Sci 2012;2(3):105–11.
Kawakubo Y, Merk HF, Al Masaoudi T, Sieben S, Blömeke B. N-Acetylation of paraphenylenediamine in human skin and keratinocytes. J Pharmacol Exp Ther 2000;292(1):150–5.
Zahm SH, Weisenburger DD, Babbitt PA, Saal RC, Vaught JB, Blair A. Use of hair coloring products and the risk of lymphoma, multiple myeloma, and chronic lymphocytic leukemia. Am J Public Health 1992;82(7):990–7.
Ziadat AH. Disabilities of children in correlation to the usage of hair dye among pregnant women. Int J Pharmacol 2010;6(4):487–93.
Al-Suwaidi A, Ahmed H. Determination of para-phenylenediamine (PPD) in henna in the United Arab Emirates. Int J Environ Res Public Health 2010;7(4):1681–93.
Chaudhary SC, Sawlani KK, Singh K. Paraphenylenediamine poisoning. Niger J Clin Pract 2013;16(2):258–9.
Beshir L, Kaballo B, Young D. Attempted suicide by ingestion of hair dye containing p-phenylenediamine: a case report. Ann Clin Biochem 2017;54(4):507–10.
Abidi K, Himdi B, Cherradi N, Lamalmi N, Alhamany Z, Zeggwagh A, et al. Myocardial lysis in a fetus induced by maternal paraphenylenediamine poisoning following an intentional ingestion to induce abortion. Hum Exp Toxicol 2008;27(5):435–8.
Saad AH, Mousa HM, Ali BH. Some toxicological observations on phenylenediamine (hair dye) in rats and chickens. Pak J Biol Sci 2000;3(6):953–6.
Malik S, Noor U, Baqar A, Qamar K. Medullary congestion in ovary of topically applied paraphenylene diamine effected rat. Pak Armed Forces Med J 2019;69(1):187–91.
Picciano JC, Schnetzinger RW, Morris WE, Wolf BA, Rodwell DE. Evaluation of the teratogenic potential of the oxidattve dye N-phenyl-para-phenylenediamine. Drug Chem Toxicol 1984;7(2):167–76.
Erbagci H, Erbagci I, Sari I, Kizilkan N, Bagci C, Saygili O, Gumusburun E, et al. Histopathological effects of maternal hair dye use on the cornea. Afr J Biotechnol 2010;9(25):3944–8.
Bharali MK, Basumatary R, Rahman T, Dutta K. Repeated topical application of para-phenylenediamine induces renal histopathological changes in rats. Toxicol Int 2012;19:132–7.
Bharali MK, Dutta K. Hepatic histopathological abnormalities in rats treated topically with para-phenylene diamine (PPD). J Pharmacol Toxicol 2009;4(6):221–8.
Malik S, Qamar K, Abbasi S, Kiani RB, Fatima M, Ahmad S. Topically applied paraphenylene diamond induces decrease in primary and secondary ovarian follicles in rat. Rawal Med J 2019;44(2):410–3.
Bharali MK, Dutta K. Testicular toxicity of para-phenylenediamine after subchronic topical application in rat. Int J Environ Res Public Health 2012;22(3):270–8.
Lee S, Cho H, Lee S-II. Effect of p-phenylenediamine to rat skin. J Korean Soc Food Sci Nutr 2005;34(9):1330–5.
El-Nagdy SA, Etewa RL, Mohamed EM, El-fakharany YM. Possible toxicological effects associated with chronic dermal exposure to para-phenylenediamine (PPD on pancreas of adult male albino rats. Egyp J Forensic Sci Appl Toxicol 2020;20(3):77–88.
Bharali M, Dutta K, Hill R. Hematotoxic and genotoxic effect of para-phenylenediamine after subchronic topical application in rats. Bioscan 2010;5(4):585–90.
Brent RL, Fawcett LB. Developmental toxicology, drugs, and fetal teratogenesis. In: Reece EA, John C. Hobbins JC. (Eds). Clinical Obstetrics the Fetus and Mother. 3rd ed. UK: Blackwell; 2007.p. 26.
Bowen SE, Irtenkauf S, Hannigan JH, Stefanski AL. Alterations in rat fetal morphology following abuse patterns of toluene exposure. Reprod Toxicol 2009;27(2):161–9.
Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995;19(12):1409–17.
Abdelhalim MA, Jarrar BM. Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration. J Nanobiotechnology 2012;10:5.
Mohammadi Z, Azarnia M, Mirabolghasemi G, Shiravi A, Mohammadi Z. Histological changes in the liver of fetuses of pregnant rats following citalopram administration. Indian J Pharmacol 2013;45(5):517–21.
Ngan V. Allergy to paraphenylenediamine [Internet]. Dermnet 2002. Available from: https://dermnetnz.org/topics/allergy-to-araphenylenediamine [cited 2022 Jan 15].
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