Developmental toxicity in rat fetuses exposed to the benzimidazole netobimin

Navarro, Marc; Canut, Lourdes; Carretero, Ana; Cristòfol, Carles; Pérez-Aparicio, Fco Javier; Arboix, M.; Ruberte, Jesús

doi:10.1016/s0890-6238(99)00013-1

Cited by 26 publications

(20 citation statements)

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“…Since, they inhibit cell growth and differentiation of micromass culture of rat embryo midbrain and limb bud cells. In agreement with our result, Capece et al [39], Navarro et al [40] reported that benzimidazole induces a significant increase of resorptions, a decrease of fetal body weights and an increase in skeletal malformation. Mantovni [41] and Teruel et al [42] indicated that the benzimidazole anthelmintic, albendazole, shows a dose related increase in embryolethality, growth reduction and a reduction in the ossification process in the rat.…”

Section: Discussionsupporting

confidence: 94%

Genotoxical, teratological and biochemical effects of anthelmintic drug oxfendazole Maximum Residue Limit (MRL) in male and female mice

et al. 2006

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-Oxfendazole, methyl-5 (6)-phenylsulfinyl-2-benzimidazole carbamate, is a member of the benzimidazole family of anthelmintics. Anthelmintic benzimidazoles are widely used in meat producing animals (cattle, sheep and pigs) for control of endoparasites. The extensive use of veterinary drugs in food-producing animals can cause the presence of small quantities of the drug residues in food. Maximum residue limit or "MRL" means the maximum concentration of residue resulting from the use of a veterinary medicinal product which may be legally permitted recognized as acceptable in food. The FAO/WHO Expert Committee on Food Additives (1999) evaluations of toxicological and residue data, reported that oxfendazole (MRL) has toxicological hazards on human health. The toxicity of oxfendazole (MRL) was tested in male and female mice and their fetuses. Chromosomal aberrations, teratological examination and biochemical analysis were the parameters used in this study. The results show that oxfendazole MRL induced a mutagenic effect in all tested cell types. Also, oxfendazole exhibit embryotoxicity including teratogenicity. The biochemical results show that oxfendazole induced a disturbance in the different biochemical contents of all tested tissues. So, we must increase the attention paid to the potential risk of oxfendazole residues in human beings and should stress the need for careful control to ensure adherence to the prescribed withdrawal time of this drug.anthelmintic / oxfendazole / maximum residue limit / genotoxicity / embryotoxicity / teratogenicity / biochemical changes

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Section: Discussionsupporting

confidence: 94%

Genotoxical, teratological and biochemical effects of anthelmintic drug oxfendazole Maximum Residue Limit (MRL) in male and female mice

et al. 2006

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“…El ABZ y el SOABZ han sido usados como modelos para elucidar la inducción de dismorfogénesis provocadas por los benzimidazoles, habiendo sido demostrado en ovinos (Marriner, 1986;Fabre et al, 1989;McKellar & Scott, 1990), vacunos (Delatour et al, 1981;Piscopo & Smoak, 1997) y ratas (Mantovani et al, 1995;Cristófol et al,1997;Piscopo & Smoak;Navarro et al, 1999;Teruel et al, 2003). La actividad teratógena del ABZ in vivo es atribuida al SOABZ, debido a su mayor concentración sistémica cuando es comparada a la del ABZ (Delatour et al, 1984).…”

Section: Introductionunclassified

Efectos del Albendazol en el Hígado de Feto de Rata: Estudios Morfológico y Morfométrico

et al. 2005

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RESUMEN:El objetivo del presente trabajo fue caracterizar morfológica, morfométrica y estereológicamente las alteraciones causadas por la administración de albendazol en ratas preñadas en el hígado de los fetos. Fueron usadas ratas Wistar, que recibieron entre los días 9 y 11 de la preñez, una dosis diaria de 5 mg/kg de peso de albendazol. Las ratas control recibieron volumen semejante de suero fisiológico en los mismos días. Al 20º día, las ratas fueron sacrificadas por inhalación de éter, siendo retirados los fetos e inmediatamente fijados en alfac por 24 h. Los fetos, úteros y placentas, luego de fijados, fueron secados en papel de filtro y pesados en balanza de precisión, siendo medidos los cordones umbilicales con nonio. Los cuerpos de los fetos fueron seccionados longitudinalmente e incluidos en parafina. Los cortes seriados de 6 µ m de espesor, fueron teñidos con hematoxilina y eosina. Además del examen histopatológico, fueron utilizadas técnicas histométricas. Los resultados obtenidos, en las condiciones experimentales, sugieren que la exposición prenatal al albendazol actúa directamente en la embriogénesis, causando malformaciones como agenesia del rabo y fetos hidrópicos. En los fetos sin malformaciones, la droga causó retardo del desarrollo fetal, caracterizado por reducción de peso corporal, peso de la placenta y longitud del cordón umbilical, así como alteraciones estructurales hepáticas, reflejadas en hepatocitos menores con núcleos menores y citoplasma más escaso y aumento de la densidad numérica. Los megacariocitos eran mayores, con núcleos lobulados grandes, con mayor volumen relativo. Los sinusoides ocuparon un volumen relativo semejante en los fetos de los dos grupos estudiados. Los fetos tratados, además de las malformaciones, mostraron aspectos que sugieren inmadurez al ser comparados con los controles. El ABZ y el SOABZ han sido usados como modelos para elucidar la inducción de dismorfogénesis provocadas por los benzimidazoles, habiendo sido demostrado en ovinos (Marriner, 1986;Fabre et al., 1989;McKellar & Scott, 1990), vacunos (Delatour et al., 1981Piscopo & Smoak, 1997) y ratas (Mantovani et al., 1995;Cristófol et al.,1997;Piscopo & Smoak;Navarro et al., 1999;Teruel et al., 2003). La actividad teratógena del ABZ in vivo es atribuida al SOABZ, debido a su mayor concentración sistémica cuando es comparada a la del ABZ (Delatour et al., 1984). PALABRAS CLAVE: HígadoEl objetivo de este trabajo es evaluar y cuantificar las alteraciones hepáticas presentes en fetos de ratas sometidas a la acción del ABZ. 112 MATERIAL Y MÉTODOFueron usadas 14 ratas, variedad Wistar, con peso medio de 170 g. Las ratas fueron alojadas en jaulas individuales y alimentadas con ración comercial y agua ad libitum.Las ratas fueron colocadas para cruzarse con los machos durante la noche, considerándose como el primer día de la preñez, si se verificada la presencia de espermatozoides en el frotis vaginal.En los días 9, 10 y 11 de la preñez, 7 ratas recibieron 5 mg/kg/día de Albendazol (Zolben®, Sanofi Pharma do Brasil)...

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“…3,4 Further ABZ-SO is oxidized to ABZ sulphone (ABZ-SO 2 ), 3,5 in a process catalyzed by cytochrome P450 and, finally, to ABZ 2-aminosulphone (ABZ-SO 2 NH 2 ), the N-deacetylation product of ABZ sulphone. 6 Of all three metabolites, pharmacokinetics studies indicate that ABZ-SO exhibit anthelmintic activity 7 and toxic effects, 8 whereas ABZ-SO 2 and ABZ-SO 2 NH 2 are considered biologically inactive. 8,9 Chemical structures of ABZ and its metabolites are displayed in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

Spectrophotometric Determination of Albendazole Drug in Tablets: Spectroscopic Characterization of the Charge‐transfer Solid Complexes

Refat

Fathi

2011

Chin. J. Chem.

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Simple, rapid and reliable method for the determination of albendazole (ABZ) was described. This includes the utility of some Π‐acceptors such as 2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone (DDQ) and 3,6‐dichloro‐2,5‐dihy‐ droxy‐p‐benzoquinone (p‐CLA) for estimation of ABZ drug (act as donor). The experimental conditions were optimized and the system obeys Beer's law for 7.50–80 and 10.00–85.00 µg·mL−1 of ABZ using DDQ and p‐CLA, respectively. The molar absorptivity and Sandell sensitivity were calculated to be 1.83×103 and 1.12×103 L·mol−1·cm−1, and 2.60 and 3.40 ng·cm−2 using DDQ and p‐CLA, respectively. The limits of detection and quantification were calculated to be (7.42 and 6.73) and (9.94 and 4.13) µg·mL−1 using DDQ and p‐CLA, respectively. The proposed methods were successfully applied to the determination of ABZ in commercially available dosage forms. The reliability of the assays was established by parallel determination by the official method and recovery studies. The chemical structures of the solid charge‐transfer (CT) complexes formed via reaction between ABZ under study and Π‐acceptors, have been elucidated using elemental analyses (C, H and N), IR, 1H NMR and mass spectra.

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Developmental toxicity in rat fetuses exposed to the benzimidazole netobimin

Cited by 26 publications

References 26 publications

Genotoxical, teratological and biochemical effects of anthelmintic drug oxfendazole Maximum Residue Limit (MRL) in male and female mice

Genotoxical, teratological and biochemical effects of anthelmintic drug oxfendazole Maximum Residue Limit (MRL) in male and female mice

Efectos del Albendazol en el Hígado de Feto de Rata: Estudios Morfológico y Morfométrico

Spectrophotometric Determination of Albendazole Drug in Tablets: Spectroscopic Characterization of the Charge‐transfer Solid Complexes

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