The effect of low doses of chlorpyrifos on blood and bone marrow cells in Wistar rats

1Preston BL. Indirect effects in aquatic ecotoxicology: Implications for ecological risk assessment Environ Manage 2002;29:311–23. doi: 10.1007/s00267-001-0023-1 Preston BL Indirect effects in aquatic ecotoxicology: Implications for ecological risk assessment Environ Manage 200229311 23 10.1007/s00267-001-0023-1Open DOISearch in Google Scholar

2Damalas CA, Eleftherohorinos IG. Pesticide exposure, safety issues, and risk assessment indicators. Int J Environ Res Public Health 2011;8:1402–19. doi: 10.3390/ijerph8051402 Damalas CA Eleftherohorinos IG Pesticide exposure, safety issues, and risk assessment indicators Int J Environ Res Public Health 201181402 19 10.3390/ijerph8051402Open DOISearch in Google Scholar

3Bagchi D, Bagchi M, Hassoun EA, Stohs SJ. In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides. Toxicology 1995;140:129–40. doi: 10.1016/0300-483x(95)03156-a Bagchi D Bagchi M Hassoun EA Stohs SJ In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides Toxicology 1995140129–40 10.1016/0300-483x(95)03156-aOpen DOISearch in Google Scholar

4Li AP, Long TJ. An evaluation of the genotoxic potential of glyphosate. Fundam Appl Toxicol 1988;10:537–46. doi: 10.1016/0272-0590(88)90300-4 Li AP Long TJ An evaluation of the genotoxic potential of glyphosate Fundam Appl Toxicol 198810537 46 10.1016/0272-0590(88)90300-4Open DOISearch in Google Scholar

5Ali T, Ismail M, Asad F, Ashraf A, Waheed U, Khan QM. Pesticide genotoxicity in cotton picking women in Pakistan evaluated using comet assay. Drug Chem Toxicol 2018;41:213–20. doi: 10.1080/01480545.2017.1343342 Ali T Ismail M Asad F Ashraf A Waheed U Khan QM Pesticide genotoxicity in cotton picking women in Pakistan evaluated using comet assay Drug Chem Toxicol 201841213 20 10.1080/01480545.2017.1343342Open DOISearch in Google Scholar

6Bolognesi C, Creus A, Ostroski-Wegman P, Marcos R. Micronuclei and pesticide exposure. Mutagenesis 2011;26:19–26. doi: 10.1093/ mutage/geq070 Bolognesi C Creus A Ostroski-Wegman P Marcos R Micronuclei and pesticide exposure Mutagenesis 20112619 26 10.1093/mutage/geq070Open DOISearch in Google Scholar

7Bolognesi C. Genotoxicity of pesticides: a review of human biomonitoring studies. Mutat Res 2003;543:251–72. doi: 10.1016/ S1383-5742(03)00015-2 Bolognesi C Genotoxicity of pesticides: a review of human biomonitoring studies Mutat Res 2003543251 72 10.1016/S1383-5742(03)00015-2Open DOISearch in Google Scholar

8Goldoni A, Klauck CR, Puffal J, Ardenghi PG, da Silva LB. DNA damage in Wistar rats exposed to organophosphate pesticide fenthion. J Environ Pathol Toxicol Oncol 2017;36:277–81. doi: 10.1615/ JEnvironPatholToxicolOncol.2017024241 Goldoni A Klauck CR Puffal J Ardenghi PG da Silva LB DNA damage in Wistar rats exposed to organophosphate pesticide fenthion J Environ Pathol Toxicol Oncol 201736277 81 10.1615/JEnvironPatholToxicolOncol.201702424129431060Open DOISearch in Google Scholar

9Hutter H-P, Poteser M, Lemmerer K, Wallner P, Shahraki Sanavi S, Kundi M, Moshammer H, Weitensfelder L. Indicators of genotoxicity in farmers and laborers of ecological and conventional banana plantations in Ecuador. Int J Environ Res 2020;17(4):1435. doi: 10.3390/ijerph17041435 Hutter H-P Poteser M Lemmerer K Wallner P Shahraki Sanavi S Kundi M Moshammer H Weitensfelder L Indicators of genotoxicity in farmers and laborers of ecological and conventional banana plantations in Ecuador Int J Environ Res 20201741435 10.3390/ijerph17041435706856332102275Open DOISearch in Google Scholar

10Islas-Gonzalez K, Gonzalez-Hortal C, Sánchez -Ramirez B, Reyes-Aragon E, Levario-Carrillo M. In vitro assessment of the genotoxicity of ethyl paraoxon in newborns and adults. Hum Exp Toxicol 2005;24:319–24. doi: 10.1191/0960327105ht534oa Islas-Gonzalez K Gonzalez-Hortal C Sánchez -Ramirez B Reyes-Aragon E Levario-Carrillo M In vitro assessment of the genotoxicity of ethyl paraoxon in newborns and adults Hum Exp Toxicol 200524319 24 10.1191/0960327105ht534oa16004199Open DOISearch in Google Scholar

11Kaur K, Kaur R. Occupational exposure, impaired DNA repair, and diseases. Indian J Occup Environ Med 2018;22:74–81. doi: 10.4103/ ijoem.IJOEM_45_18 Kaur K Kaur R Occupational exposure, impaired DNA repair, and diseases Indian J Occup Environ Med 20182274 81 10.4103/ijoem.IJOEM_45_18617670330319227Open DOISearch in Google Scholar

12Khodabandeh Z, Etebari M, Aliomrani M. Study of the probable genotoxic effects of Zolone (Phosalone) exposure in mice bone marrow derived cells. Genes Environ 2021;43:18. doi: 10.1186/s41021-021-00191-5 Khodabandeh Z Etebari M Aliomrani M Study of the probable genotoxic effects of Zolone (Phosalone) exposure in mice bone marrow derived cells Genes Environ 20214318 10.1186/s41021-021-00191-5811758533985589Open DOISearch in Google Scholar

13Kocaman AY, Topaktaş M. Genotoxic effects of a particular mixture of acetamiprid and alpha-cypermethrin on chromosome aberration, sister chromatid exchange, and micronucleus formation in human peripheral blood lymphocytes. Environ Toxicol 2010;25:157–68. doi: 10.1002/tox.20485 Kocaman AY Topaktaş M Genotoxic effects of a particular mixture of acetamiprid and alpha-cypermethrin on chromosome aberration, sister chromatid exchange, and micronucleus formation in human peripheral blood lymphocytes Environ Toxicol 201025157 68 10.1002/tox.2048519319990Open DOISearch in Google Scholar

14Moshou H, Karakitsou A, Yfanti F, Hela D, Vlastos D, Paschalidou AK, Kassomenos P, Petrou I. Assessment of genetic effects and pesticide exposure of farmers in NW Greece. Environ Res 2020;186:109558. doi: 10.1016/j.envres.2020.109558 Moshou H Karakitsou A Yfanti F Hela D Vlastos D Paschalidou AK Kassomenos P Petrou I Assessment of genetic effects and pesticide exposure of farmers in NW Greece Environ Res 2020186109558 10.1016/j.envres.2020.10955832361259Open DOISearch in Google Scholar

15Paz-y-Miño C, Sánchez M-E, Arevalo M, Munoz MJ, Witte T, De-la-Carrera GO, Leone PE. Evaluation of DNA damage in an Equadorian population exposed to glyphosate. Genet Mol Biol 2007;30:456–60. doi: 10.1590/S1415-47572007000300026 Paz-y-Miño C Sánchez M-E Arevalo M Munoz MJ Witte T De-la-Carrera GO Leone PE Evaluation of DNA damage in an Equadorian population exposed to glyphosate Genet Mol Biol 200730456 60 10.1590/S1415-47572007000300026Open DOISearch in Google Scholar

16Sánchez-Alarcón J, Milić M, Kašuba V, Tenorio-Arvide MG, Montiel-González JMR, Bonassi S, Valencia-Quintana R. A systematic review of studies on genotoxicity and related biomarkers in populations exposed to pesticides in Mexico. Toxics 2021;9(11):272. doi: 10.3390/ toxics9110272 Sánchez-Alarcón J Milić M Kašuba V Tenorio-Arvide MG Montiel-González JMR Bonassi S Valencia-Quintana R A systematic review of studies on genotoxicity and related biomarkers in populations exposed to pesticides in Mexico Toxics 2021911272 10.3390/toxics9110272862420034822663Open DOISearch in Google Scholar

17Želježić D, Žunec S, Bjeliš M, Benković V, Mladinić M, Lovaković Tariba B, Pavičić I, Marjanović Čermak AM, Kašuba V, Milić M, Pizent A, Lucić Vrdoljak A, Kopjar N. Effects of the chloro-s-triazine herbicide terbuthylazine on DNA integrity in human and mouse cells. Environ Sci Pollut Res Int 2018;25:19065–81. doi: 10.1007/s11356-018-2046-7 Želježić D Žunec S Bjeliš M Benković V Mladinić M Lovaković Tariba B Pavičić I Marjanović Čermak AM Kašuba V Milić M Pizent A Lucić Vrdoljak A Kopjar N Effects of the chloro-s-triazine herbicide terbuthylazine on DNA integrity in human and mouse cells Environ Sci Pollut Res Int 20182519065 81 10.1007/s11356-018-2046-729721798Open DOISearch in Google Scholar

18Ezzi L, Salah IB, Haouas Z, Sakly A, Grissa I, Chakroun S, Kerkeni E, Hassine M, Mehdi M, Ben Cheikh, H. Histopathological and genotoxic effects of chlorpyrifos in rats. Environ Sci Pollut Res 2016;23:4859–67. doi: 10.1007/s11356-015-5722-x Ezzi L Salah IB Haouas Z Sakly A Grissa I Chakroun S Kerkeni E Hassine M Mehdi M Ben Cheikh H Histopathological and genotoxic effects of chlorpyrifos in rats Environ Sci Pollut Res 2016234859 67 10.1007/s11356-015-5722-x26545888Open DOISearch in Google Scholar

19Kopjar N, Žunec S, Mendaš G, Micek V, Kašuba V, Mikolić A, Lovaković BT, Milić M, Pavičić I, Čermak AMM, Pizent A, Lucić Vrdoljak A, Želježić D. Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats. Chem Biol Interact 2018;279:51–63. doi: 10.1016/j.cbi.2017.10.029 Kopjar N Žunec S Mendaš G Micek V Kašuba V Mikolić A Lovaković BT Milić M Pavičić I Čermak AMM Pizent A Lucić Vrdoljak A Želježić D Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats Chem Biol Interact 201827951–63 10.1016/j.cbi.2017.10.02929108776Open DOISearch in Google Scholar

20Muller M, Hess L, Tardivo A, Lajmanovich R, Attademo A, Poletta G, Simoniello MF, Yodice A, Lavarello S, Chialvo D, Scremin O. Neurologic dysfunction and genotoxicity induced by low levels of chlorpyrifos. Neurotoxicology 2014;45:22–30. doi: 10.1016/j. neuro.2014.08.012 Muller M Hess L Tardivo A Lajmanovich R Attademo A Poletta G Simoniello MF Yodice A Lavarello S Chialvo D Scremin O Neurologic dysfunction and genotoxicity induced by low levels of chlorpyrifos Neurotoxicology 20144522 30 10.1016/j.neuro.2014.08.01225196089Open DOISearch in Google Scholar

21Okonko LE, Ikpeme EV, Udensi OU. Genotoxic effect of chlorpyrifos and cypermethrin in Albino rats. Res J Mut 2016;6:31–5. doi: 10.3923/ rjmutag.2016.31.35 Okonko LE Ikpeme EV Udensi OU Genotoxic effect of chlorpyrifos and cypermethrin in Albino rats Res J Mut 2016631 5 10.3923/rjmutag.2016.31.35Open DOISearch in Google Scholar

22Sandhu MA, Saeed AA, Khilji MS, Ahmed A, Latif MS, Khalid N. Genotoxicity evaluation of chlorpyrifos: a gender related approach in regular toxicity testing. J Toxicol Sci 2013;38:237–44. doi: 10.2131/ jts.38.237 Sandhu MA Saeed AA Khilji MS Ahmed A Latif MS Khalid N Genotoxicity evaluation of chlorpyrifos: a gender related approach in regular toxicity testing J Toxicol Sci 201338237 44 10.2131/jts.38.237Open DOISearch in Google Scholar

23Želježić D, Mladinić M, Žunec S, Lucić Vrdoljak A, Kašuba V, Tariba B, Živković T, Marjanović AM, Pavičić I, Milić M, Rozgaj R, Kopjar N. Cytotoxic, genotoxic and biochemical markers of insecticide toxicity evaluated in human peripheral blood lymphocytes and an HepG2 cell line. Food Chem Toxicol 2016;96:90–106. doi: 10.1016/j. fct.2016.07.036 Želježić D Mladinić M Žunec S Lucić Vrdoljak A Kašuba V Tariba B Živković T Marjanović AM Pavičić I Milić M Rozgaj R Kopjar N Cytotoxic, genotoxic and biochemical markers of insecticide toxicity evaluated in human peripheral blood lymphocytes and an HepG2 cell line Food Chem Toxicol 20169690 106 10.1016/j.fct.2016.07.036Open DOISearch in Google Scholar

24Yin X, Zhu G, Li XB, Liu S. Genotoxicity evaluation of chlorpyrifos to amphibian Chinese toad (Amphibian: Anura) by comet assay and micronucleus test. Mutat Res 2009;680:2–6. doi: 10.1016/j. mrgentox.2009.05.018 Yin X Zhu G Li XB Liu S Genotoxicity evaluation of chlorpyrifos to amphibian Chinese toad (Amphibian: Anura) by comet assay and micronucleus test Mutat Res 20096802 6 10.1016/j.mrgentox.2009.05.018Open DOISearch in Google Scholar

25Akhtar N, Srivatsava MK, Raizada RB. Transplacental disposition and teratogenic effects of chlorpyrifos in rats. J Tox Sci 2006;31:521–7. doi: 10.2131/jts.31.521 Akhtar N Srivatsava MK Raizada RB Transplacental disposition and teratogenic effects of chlorpyrifos in rats J Tox Sci 200631521 7 10.2131/jts.31.521Open DOISearch in Google Scholar

26Farag AT, El Okazy AH, El Aswed AF. Developmental toxicity study of chlorpyrifos in rats. Reprod Toxicol 2003;17:203–8. doi: 10.1016/ S0890-6238(02)00121-1 Farag AT El Okazy AH El Aswed AF Developmental toxicity study of chlorpyrifos in rats Reprod Toxicol 200317203 8 10.1016/S0890-6238(02)00121-1Open DOISearch in Google Scholar

27Upadhyay J, Rana M, Tiwari N, Nazam Ansari M. Teratogenic effect of chlorpyrifos and glyphosate on pregnant rats: Biochemical and morphological evaluations. J Pharm Res Int 2020;32:133–45. doi: 10.9734/jpri/2020/v32i2330800 Upadhyay J Rana M Tiwari N Nazam Ansari M Teratogenic effect of chlorpyrifos and glyphosate on pregnant rats: Biochemical and morphological evaluations J Pharm Res Int 202032133 45 10.9734/jpri/2020/v32i2330800Open DOISearch in Google Scholar

28Breslin WJ, Liberacki AB, Dittenber DA, Quast JF. Evaluation of the developmental and reproductive toxicity of chlorpyrifos in the rat. Fund Appl Toxicol 1996;29:119–30. doi: 10.1006/faat.1996.0013 Breslin WJ Liberacki AB Dittenber DA Quast JF Evaluation of the developmental and reproductive toxicity of chlorpyrifos in the rat Fund Appl Toxicol 199629119 30 10.1006/faat.1996.00138838647Open DOISearch in Google Scholar

29Mansour SA, Mossa A-TH. Oxidative damage, biochemical and histopathological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc. Pest Biochem Physiol 2010;96:14–23. doi: 10.1016/j.pestbp.2009.08.008 Mansour SA Mossa A-TH Oxidative damage, biochemical and histopathological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc Pest Biochem Physiol 20109614 23 10.1016/j.pestbp.2009.08.008Open DOISearch in Google Scholar

30Raina R, Baba NA, Verma PK, Sultana M, Singh M. Hepatotoxicity induced by subchronic exposure of fluoride and chlorpyrifos in Wistar rats: Mitigating effect of ascorbic acid. Biol Trace Elem Res 2015;166:157–62. doi: 10.1007/s12011-015-0263-1 Raina R Baba NA Verma PK Sultana M Singh M Hepatotoxicity induced by subchronic exposure of fluoride and chlorpyrifos in Wistar rats: Mitigating effect of ascorbic acid Biol Trace Elem Res 2015166157 62 10.1007/s12011-015-0263-125669166Open DOISearch in Google Scholar

31Ambali S, Ayo JO, Esievo KAN, Ojo SA. Hemotoxicity induced by chronic chlorpyrifos exposure in Wistar rats: mitigating effect of vitamin C. Vet Med Int 2011;2011:945439. doi: 10.4061/2011/945439 Ambali S Ayo JO Esievo KAN Ojo SA Hemotoxicity induced by chronic chlorpyrifos exposure in Wistar rats: mitigating effect of vitamin C Vet Med Int 20112011945439 10.4061/2011/945439Open DOISearch in Google Scholar

32Ambali SF, Ayo JO, Ojo SA, Esievo KA. Ameliorative effect of vitamin C on chronic chlorpyrifos-induced erythrocyte osmotic fragility in Wistar rats. Hum Exp Toxicol 2011;30:19–24. doi: 10.1177/0960327110368415 Ambali SF Ayo JO Ojo SA Esievo KA Ameliorative effect of vitamin C on chronic chlorpyrifos-induced erythrocyte osmotic fragility in Wistar rats Hum Exp Toxicol 20113019 24 10.1177/0960327110368415Open DOISearch in Google Scholar

33Uchendu C, Ambali S, Ayo J, Esievo K. Body weight and hematological changes induced by chronic exposure to low levels of chlorpyrifos and deltamethrin combination in rats: the effect of alpha-lipoic acid. Comp Clin Pathol 2018;27:1383–8. doi: 10.1007/s00580-018-2750-1 Uchendu C Ambali S Ayo J Esievo K Body weight and hematological changes induced by chronic exposure to low levels of chlorpyrifos and deltamethrin combination in rats: the effect of alpha-lipoic acid Comp Clin Pathol 2018271383 8 10.1007/s00580-018-2750-1Open DOISearch in Google Scholar

34Deacon MM, Murray JS, Pilny MK, Rao KS, Dittenber DA, Hanley TR Jr, John JA. Embryotoxicity and fetotoxicity of orally administered chlorpyrifos in mice. Toxicol Appl Pharmacol 1980;54:31–40. doi: 10.1016/0041-008x(80)90005-8 Deacon MM Murray JS Pilny MK Rao KS Dittenber DA Hanley TR Jr John JA Embryotoxicity and fetotoxicity of orally administered chlorpyrifos in mice Toxicol Appl Pharmacol 19805431 40 10.1016/0041-008x(80)90005-8Open DOISearch in Google Scholar

35Farag AT, Radwan AH, Sorour F, El Okazy A, El-Sayed El-Agamy, El-Khaliek El-Sebae A. Chlorpyrifos induced reproductive toxicity in male mice. Reprod Toxicol 2010;29:80–5. doi: 10.1016/j. reprotox.2009.10.003 Farag AT Radwan AH Sorour F El Okazy A El-Sayed El-Agamy El-Khaliek El-Sebae A Chlorpyrifos induced reproductive toxicity in male mice Reprod Toxicol 20102980 5 10.1016/j.reprotox.2009.10.003Open DOISearch in Google Scholar

36Muto MA, Lobelle F Jr, Bidanset JH, Wurpel JN. Embryotoxicity and neurotoxicity in rats associated with prenatal exposure to DURBASAN (active ingredient chlorpyrifos). Vet Hum Toxicol 1992;34:498–501. PMID: 1283795 Muto MA Lobelle F Jr Bidanset JH Wurpel JN Embryotoxicity and neurotoxicity in rats associated with prenatal exposure to DURBASAN (active ingredient chlorpyrifos) Vet Hum Toxicol 199234498 501 PMID: 1283795Search in Google Scholar

37Moser VC, Phillips PM, McDaniel KL, Marshall RS, Hunter DL, Padilla S. Neurobehavioral effects of chronic dietary and repeated high-level spike exposure to chlorpyrifos in rats. Toxicol Sci 2005;86:375–86. doi: 10.1093/toxsci/kfi199 Moser VC Phillips PM McDaniel KL Marshall RS Hunter DL Padilla S Neurobehavioral effects of chronic dietary and repeated high-level spike exposure to chlorpyrifos in rats Toxicol Sci 200586375 86 10.1093/toxsci/kfi199Open DOISearch in Google Scholar

38Pope CN, Chakraborti TK, Chapman ML, Farra JD. Long-term neurochemical and behavioral effects induced by acute chlorpyrifos treatment. Pharm Biochem Behav 1992;42:251–6. doi: 10.1016/0091-3057(92)90523-I Pope CN Chakraborti TK Chapman ML Farra JD Long-term neurochemical and behavioral effects induced by acute chlorpyrifos treatment Pharm Biochem Behav 199242251 6 10.1016/0091-3057(92)90523-IOpen DOISearch in Google Scholar

39Attia AA, El Mazoudy RH, El Shenawy NS. Antioxidant role of propolis extract against oxidative damage of testicular tissue induced by insecticide chlorpyrifos in rats. Pest Biochem Physiol 2012;103:87–93. doi: 10.1016/j.pestbp.2012.04.002 Attia AA El Mazoudy RH El Shenawy NS Antioxidant role of propolis extract against oxidative damage of testicular tissue induced by insecticide chlorpyrifos in rats Pest Biochem Physiol 201210387–93 10.1016/j.pestbp.2012.04.002Open DOISearch in Google Scholar

40Elsharkawy E, Yahia D, El-Nisr N. Chlorpyrifos induced testicular damage in rats: Ameliorative effect of glutathione antioxidant. Environ Toxicol 2014;29:1011–9. doi: 10.1002/tox.21831 Elsharkawy E Yahia D El-Nisr N Chlorpyrifos induced testicular damage in rats: Ameliorative effect of glutathione antioxidant Environ Toxicol 2014291011 9 10.1002/tox.2183123172834Open DOISearch in Google Scholar

41Joshi SC, Mathur R, Gulati NT. Testicular toxcity of chlorpyrifos (an organophosphate pesticide) in albino rat. Toxicol Ind Health 2007;23:439–44. doi: 10.1177/0748233707080908 Joshi SC Mathur R Gulati NT Testicular toxcity of chlorpyrifos (an organophosphate pesticide) in albino rat Toxicol Ind Health 200723439 44 10.1177/074823370708090818536496Open DOISearch in Google Scholar

42Directive 2009/128/EC of the European Parliament and of the Council of 21 October 2009 establishing a framework for Community action to achieve the sustainable use of pesticides [displayed 16 September 2022]. Available at https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:32009L0128&from=EN Directive 2009/128/EC of the European Parliament and of the Council of 21 October 2009 establishing a framework for Community action to achieve the sustainable use of pesticides [displayed 16 September 2022] Available at https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:32009L0128&from=ENSearch in Google Scholar

43Langie SAS, Koppen G, Desaulniers D, Al-Mulla F, Al-Temaimi R, Amedei A, Azqueta A, Bisson WH, Brown DG, Brunborg G, Charles AK, Chen T, Colacci AM, Darroudi F, Forte S, Gonzalez L, Hamid RA, Knudsen LE, Leyns L, de Cerain Salsamendi AL, Memeo L, Mondello C, Mothersill C, Olsen A-K , Pavanello S, Raju J, Rojas E, Roy R, Ryan EP, Ostrosky-Wegman P, Salem HK, Scovassi AI, Singh N, Vaccari M, Van Schooten FJ, Valverde M, Woodrick J, Zhang L, van Larebeke N, Kirsch-Volders M, Collins AR. Causes of genome instability: the effect of low dose chemical exposures in modern society. Carcinogenesis 2015:36(Suppl 1):S61–88. doi: 10.1093/carcin/ bgv031 Langie SAS Koppen G Desaulniers D Al-Mulla F Al-Temaimi R Amedei A Azqueta A Bisson WH Brown DG Brunborg G Charles AK Chen T Colacci AM Darroudi F Forte S Gonzalez L Hamid RA Knudsen LE Leyns L de Cerain Salsamendi AL Memeo L Mondello C Mothersill C Olsen A-K Pavanello S Raju J Rojas E Roy R Ryan EP Ostrosky-Wegman P Salem HK Scovassi AI Singh N Vaccari M Van Schooten FJ Valverde M Woodrick J Zhang L van Larebeke N Kirsch-Volders M Collins AR Causes of genome instability: the effect of low dose chemical exposures in modern society Carcinogenesis 201536Suppl 1S61–88 10.1093/carcin/bgv031Open DOISearch in Google Scholar

44Azqueta A, Collins AR. The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch Toxicol 2013;87:949–68. doi: 10.1007/s00204-013-1070-0 Azqueta A Collins AR The essential comet assay: a comprehensive guide to measuring DNA damage and repair Arch Toxicol 201387949 68 10.1007/s00204-013-1070-0Open DOISearch in Google Scholar

45Hayashi H, Imai M, Shindo Y. Discrimination between DNA-protein and DNA-DNA crosslinks using proteinase K in the alkaline single cell gel (SCG) assay. Environ Mutagen Res 2005;27:39–44. doi: 10.3123/jems.27.39 Hayashi H Imai M Shindo Y Discrimination between DNA-protein and DNA-DNA crosslinks using proteinase K in the alkaline single cell gel (SCG) assay Environ Mutagen Res 20052739 44 10.3123/jems.27.39Open DOISearch in Google Scholar

46Merk O, Speit G. Detection of crosslinks with the comet assay in relationship to genotoxicity and cytotoxicity. Environ Mol Mutagen 1999;33:167–72. doi: 10.1002/(SICI)1098-2280(1999)33:2<167::AID-EM9>3.0.CO;2-D Merk O Speit G Detection of crosslinks with the comet assay in relationship to genotoxicity and cytotoxicity Environ Mol Mutagen 199933167 72 10.1002/(SICI)1098-2280(1999)33:2<167::AID-EM9>3.0.CO;2-DOpen DOISearch in Google Scholar

47Mitchelmore CL, Chipman JK. DNA strand breakage in aquatic organisms and the potential value of the comet assay in environmental monitoring. Mutat Res 1998;399:135–47. doi: 10.1016/s0027-5107(97)00252-2 Mitchelmore CL Chipman JK DNA strand breakage in aquatic organisms and the potential value of the comet assay in environmental monitoring Mutat Res 1998399135 47 10.1016/s0027-5107(97)00252-2Open DOISearch in Google Scholar

48Pfuhler S, Wolf H. Detection of DNA-crosslinking agents with the alkaline comet assay. Environ Mol Mutagen 1996;27:196–201. doi: 10.1002/(SICI)1098-2280(1996)27:3<196::AID-EM4>3.0.CO;2-D Pfuhler S Wolf H Detection of DNA-crosslinking agents with the alkaline comet assay Environ Mol Mutagen 199627196 201 10.1002/(SICI)1098-2280(1996)27:3<196::AID-EM4>3.0.CO;2-DOpen DOISearch in Google Scholar

49Collins AR. The comet assay for DNA damage and repair. Mol Biotechnol 2004;26:249–61. doi: 10.1385/MB:26:3:249 Collins AR The comet assay for DNA damage and repair Mol Biotechnol 200426249 61 10.1385/MB:26:3:249Open DOISearch in Google Scholar

50Nickson CM, Parsons JL. Monitoring regulation of DNA repair activities of cultured cells in-gel using the comet assay. Front Genet 2014;5:232. doi: 10.3389/fgene.2014.00232 Nickson CM Parsons JL Monitoring regulation of DNA repair activities of cultured cells in-gel using the comet assay Front Genet 20145232 10.3389/fgene.2014.00232Open DOISearch in Google Scholar

51Collins AR, Dušinská M, Horská A. Detection of alkylation damage in human lymphocyte DNA with the comet assay. Acta Biochim Pol 2001;48:611–4. PMID: 11833769 Collins AR Dušinská M Horská A Detection of alkylation damage in human lymphocyte DNA with the comet assay Acta Biochim Pol 200148611 4 PMID: 1183376910.18388/abp.2001_3895Search in Google Scholar

52Yahia D, Ali MF. Cytogenetic and genotoxic effects of penconazole and chlorpyrifos pesticides in bone marrow of rats. J Adv Vet Res 2019;9:29–38. Yahia D Ali MF Cytogenetic and genotoxic effects of penconazole and chlorpyrifos pesticides in bone marrow of rats J Adv Vet Res 2019929 38Search in Google Scholar

53Mavournin KH, Blakey DH, Cimino MC, Salamone MF, Heddle JA. The in vivo micronucleus assay in mammalian bone marrow and peripheral blood. A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat Res 1990;239:29–80. doi: 10.1016/0165-1110(90)90030-f Mavournin KH Blakey DH Cimino MC Salamone MF Heddle JA The in vivo micronucleus assay in mammalian bone marrow and peripheral blood A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat Res 199023929 80 10.1016/0165-1110(90)90030-fOpen DOISearch in Google Scholar

54OECD. OECD Guidelines for the Testing of Chemicals, Section 4. Test No. 474: Mammalian Erythrocyte Micronucleus Test, 2016 [displayed 16 September 2022]. Available at https://doi.org/10.1787/9789264264762-en OECD OECD Guidelines for the Testing of Chemicals, Section 4. Test No. 474: Mammalian Erythrocyte Micronucleus Test, 2016 [displayed 16 September 2022]. Available at https://doi.org/10.1787/9789264264762-en10.1787/9789264264762-enSearch in Google Scholar

55Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes [displayed 16 September 2022]. Available at https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:02010L0063-20190626&from=EN Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes [displayed 16 September 2022] Available at https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:02010L0063-20190626&from=ENSearch in Google Scholar

56World Health Organization. WHO Specifications and Evaluations for Public Health Pesticides. Chlorpyrifos OO-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate. Geneva: WHO; 2009. World Health Organization WHO Specifications and Evaluations for Public Health Pesticides. Chlorpyrifos OO-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate Geneva WHO 2009Search in Google Scholar

57European Food Safety Authority (EFSA). Conclusion on the peer review of the pesticide human health risk assessment of the active substance chlorpyrifos. EFSA J 2014;12(4):3640. doi: 10.2903/j. efsa.2014.3640 European Food Safety Authority (EFSA) Conclusion on the peer review of the pesticide human health risk assessment of the active substance chlorpyrifos EFSA J 20141243640 10.2903/j.efsa.2014.3640Open DOISearch in Google Scholar

58Pant K, Springer S, Bruce S, Lawlor T, Hewitt N, Aardema MJ. Vehicle and positive control values from the in vivo rodent comet assay and biomonitoring studies using human lymphocytes: Historical database and influence of technical aspects. Environ Mol Mutagen 2014;55:633–42. doi: 10.1002/em.21881 Pant K Springer S Bruce S Lawlor T Hewitt N Aardema MJ Vehicle and positive control values from the in vivo rodent comet assay and biomonitoring studies using human lymphocytes: Historical database and influence of technical aspects Environ Mol Mutagen 201455633–42 10.1002/em.21881Open DOISearch in Google Scholar

59Hayashi M, Morita T, Kodama Y, Sofuni T, Ishidate Jr M. The micronucleus assay with mouse peripheral blood reticulocytes using acridine orange-coated slides. Mutat Res 1990;245:245–9. doi: 10.1016/0165-7992(90)90153-b Hayashi M Morita T Kodama Y Sofuni T Ishidate Jr M The micronucleus assay with mouse peripheral blood reticulocytes using acridine orange-coated slides Mutat Res 1990245245 9 10.1016/0165-7992(90)90153-bOpen DOISearch in Google Scholar

60Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988;175:184–91. doi: 10.1016/0014-4827(88)90265-0 Singh NP McCoy MT Tice RR Schneider EL A simple technique for quantitation of low levels of DNA damage in individual cells Exp Cell Res 1988175184 91 10.1016/0014-4827(88)90265-0Open DOISearch in Google Scholar

61Hartmann A, Schumacher M, Plappert-Helbig U, Lowe P, Willi Suter W, Mueller L. Use of the alkaline in vivo comet assay for mechanistic genotoxicity investigations. Mutagenesis 2004;19:51–9. doi: 10.1093/ mutage/geg038 Hartmann A Schumacher M Plappert-Helbig U Lowe P Willi Suter W Mueller L Use of the alkaline in vivo comet assay for mechanistic genotoxicity investigations Mutagenesis 20041951 9 10.1093/mutage/geg03814681313Open DOISearch in Google Scholar

62Asahi J, Kamo H, Baba R, Doi Y, Yamashita A, Murakami D, Hanada A, Hirano T. Bisphenol A induces endoplasmic reticulum stress-associated apoptosis in mouse non-parenchymal hepatocytes. Life Sci 2010;87:431–8. doi: 10.1016/J. LFS.2010.08.007 Asahi J Kamo H Baba R Doi Y Yamashita A Murakami D Hanada A Hirano T Bisphenol A induces endoplasmic reticulum stress-associated apoptosis in mouse non-parenchymal hepatocytes Life Sci 201087431 8 10.1016/J.LFS.2010.08.007Open DOISearch in Google Scholar

63McNamee JP, Belllier PV. Use of a standardized JaCVAM in vivo rat comet assay protocol to assess the genotoxicity of three coded test compounds; ampicillin trihydrate, 1,2-dimethylhydrazine dihydrochloride, and N-nitrosodimethylamine. Mutat Res 2015;786–788:158–64. doi: 10.1016/j.mrgentox.2015.02.005 McNamee JP Belllier PV Use of a standardized JaCVAM in vivo rat comet assay protocol to assess the genotoxicity of three coded test compounds; ampicillin trihydrate, 1,2-dimethylhydrazine dihydrochloride, and N-nitrosodimethylamine Mutat Res 2015 786–788158 64 10.1016/j.mrgentox.2015.02.00526212307Open DOISearch in Google Scholar

64Lorenzo Y, Costa S, Collins AR, Azqueta A. The comet assay, DNA damage, DNA repair and cytotoxicity: hedgehogs are not always dead. Mutagenesis 2013;28:427–32. doi: 10.1093/mutage/get018 Lorenzo Y Costa S Collins AR Azqueta A The comet assay, DNA damage, DNA repair and cytotoxicity: hedgehogs are not always dead Mutagenesis 201328427 32 10.1093/mutage/get01823630247Open DOISearch in Google Scholar

65Oller AR, Erexson G. Lack of micronuclei formation in bone marrow of rats after repeated oral exposure to nickel sulfate hexahydrate. Mutat Res 2007;626:102–10. doi: 10.1016/j.mrgentox.2006.09.001 Oller AR Erexson G Lack of micronuclei formation in bone marrow of rats after repeated oral exposure to nickel sulfate hexahydrate Mutat Res 2007626102 10 10.1016/j.mrgentox.2006.09.00117052950Open DOISearch in Google Scholar

66Giannotti E, Vandin L, Repeto P, Comelli R. A comparison of the in vitro Comet assay with the in vitro chromosome aberration assay using whole human blood or Chinese hamster lung cells: validation study using a range of novel pharmaceuticals. Mutagenesis 2002;17:163–70. doi: 10.1093/mutage/17.2.163 Giannotti E Vandin L Repeto P Comelli R A comparison of the in vitro Comet assay with the in vitro chromosome aberration assay using whole human blood or Chinese hamster lung cells: validation study using a range of novel pharmaceuticals Mutagenesis 200217163 70 10.1093/mutage/17.2.163Open DOISearch in Google Scholar

67Krishna G, Hayashi M. In vivo rodent micronucleus assay: protocol, conduct and data interpretation. Mutat Res 2000;455:155–66. doi: 10.1016/s0027-5107(00)00117-2 Krishna G Hayashi M In vivo rodent micronucleus assay: protocol, conduct and data interpretation Mutat Res 2000455155 66 10.1016/s0027-5107(00)00117-2Open DOISearch in Google Scholar

68Meggs WJ, Brewer KL. Weight gain associated with chronic exposure to chlorpyrifos in rats. J Med Toxicol 2007;3:89–93. doi: 10.1007/ BF03160916 Meggs WJ Brewer KL Weight gain associated with chronic exposure to chlorpyrifos in rats J Med Toxicol 2007389 93 10.1007/BF03160916Open DOISearch in Google Scholar

69Slotkin TA. Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity? Reprod Toxicol 2011;31:297–301. doi: 10.1016/j.reprotox.2010.07.012 Slotkin TA Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity? Reprod Toxicol 201131297 301 10.1016/j.reprotox.2010.07.012Open DOISearch in Google Scholar

70Christensen K, Harper B, Luukinen B, Buhl K, Stone D. Chlorpyrifos technical fact sheet; National Pesticide Information Center, Oregon State University Extension Services [displayed 16 September 2022]. Available at http://npic.orst.edu/factsheets/archive/chlorptech.html Christensen K Harper B Luukinen B Buhl K Stone D Chlorpyrifos technical fact sheet; National Pesticide Information Center, Oregon State University Extension Services [displayed 16 September 2022] Available at http://npic.orst.edu/factsheets/archive/chlorptech.htmlSearch in Google Scholar

71Smegal DC; US Environmental Protection Agency, Office of Pesticide Programs, Health Effects Division (7509C). Human Health Risk Assessment Chlorpyrifos, 2000 [displayed 16 September 2022]. Available at https://archive.epa.gov/scipoly/sap/meetings/web/pdf/hed_ra.pdf Smegal DC; US Environmental Protection Agency, Office of Pesticide Programs, Health Effects Division (7509C) Human Health Risk Assessment Chlorpyrifos, 2000 [displayed 16 September 2022] Available at https://archive.epa.gov/scipoly/sap/meetings/web/pdf/hed_ra.pdfSearch in Google Scholar

72Jayusman PA, Budin SB, Ghazali AR, Taib IS, Louis SR. Effects of palm oil tocotrienol-rich fraction on biochemical and morphological alterations of liver in fenitrothion-treated rats. Pak J Pharm Sci 2014;27:1873–80. PMID: 25362611 Jayusman PA Budin SB Ghazali AR Taib IS Louis SR Effects of palm oil tocotrienol-rich fraction on biochemical and morphological alterations of liver in fenitrothion-treated rats Pak J Pharm Sci 2014271873 80 PMID: 25362611Search in Google Scholar

73Kalender Y, Uzunhisarcikli M, Ogutcu A, Acikgoz F, Kalender S. Effects of diazinon on pseudocholinesterase activity and haematological indices in rats: The protective role of Vitamin E. Environ Toxicol Pharmacol 2006;22:46–51. doi: 10.1016/j.etap.2005.11.007 Kalender Y Uzunhisarcikli M Ogutcu A Acikgoz F Kalender S Effects of diazinon on pseudocholinesterase activity and haematological indices in rats: The protective role of Vitamin E Environ Toxicol Pharmacol 20062246 51 10.1016/j.etap.2005.11.007Open DOISearch in Google Scholar

74OECD Guidelines for Testing of Chemicals, Mammalian Erythrocyte Micronucleus Test, 1997 [displayed 16 September 2022]. Available at https://www.oecd.org/chemicalsafety/risk-assessment/1948442.pdf OECD Guidelines for Testing of Chemicals, Mammalian Erythrocyte Micronucleus Test 1997 [displayed 16 September 2022]. Available at https://www.oecd.org/chemicalsafety/risk-assessment/1948442.pdfSearch in Google Scholar

75Cicchetti R, Bari M, Argentin G. Induction of micronuclei in bone marrow by two pesticides and their differentiation with CREST staining: an in vivo study in mice. Mutat Res 1999;439:239–48. doi: 10.1016/s1383-5718(98)00185-5 Cicchetti R Bari M Argentin G Induction of micronuclei in bone marrow by two pesticides and their differentiation with CREST staining: an in vivo study in mice Mutat Res 1999439239 48 10.1016/s1383-5718(98)00185-5Open DOISearch in Google Scholar

76Sarabia L, Maurer I, Bustos-Obregón E. Melatonin prevents damage elicited by the organophosphorous pesticide diazinon on mouse sperm DNA. Ecotoxicol Environ Saf 2009;72:663–8. doi: 10.1016/j. ecoenv.2008.04.023 Sarabia L Maurer I Bustos-Obregón E Melatonin prevents damage elicited by the organophosphorous pesticide diazinon on mouse sperm DNA Ecotoxicol Environ Saf 200972663 8 10.1016/j.ecoenv.2008.04.023Open DOISearch in Google Scholar

77Hariri AT, Moallem SA, Mahmoudi M, Hosseinzadeh H. The effect of crocin and safranal, constituents of saffron, against subacute effect of diazinon on hematological and genotoxicity indices in rats. Phytomedicine 2011;18:499–504. doi: 10.1016/j.phymed.2010.10.001 Hariri AT Moallem SA Mahmoudi M Hosseinzadeh H The effect of crocin and safranal, constituents of saffron, against subacute effect of diazinon on hematological and genotoxicity indices in rats Phytomedicine 201118499 504 10.1016/j.phymed.2010.10.001Open DOISearch in Google Scholar

78Saleha Banu B, Danadevi K, Rahman MF, Ahuja YR, Kaiser J. Genotoxic effect of monocrotophos to sentinel species using comet assay. Food Chem Toxicol 2001;39:361–6. doi: 10.1016/S0278-6915(00)00141-1 Saleha Banu B Danadevi K Rahman MF Ahuja YR Kaiser J Genotoxic effect of monocrotophos to sentinel species using comet assay Food Chem Toxicol 200139361 6 10.1016/S0278-6915(00)00141-1Open DOISearch in Google Scholar

79Ojha A, Yaduvanshi SK, Pant SC, Lomash V, Srivastava N. Evaluation of DNA damage and cytotoxicity induced by three commonly used organophosphate pesticides individually and in mixture, in rat tissues. Environ Toxicol 2013;28:543–52. doi: 10.1002/tox.20748 Ojha A Yaduvanshi SK Pant SC Lomash V Srivastava N Evaluation of DNA damage and cytotoxicity induced by three commonly used organophosphate pesticides individually and in mixture, in rat tissues Environ Toxicol 201328543 52 10.1002/tox.2074821786386Open DOISearch in Google Scholar