TY - JOUR
T1 - The teratogenicity and behavioral teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-butyl Phthalate (DBP) in a chick model
AU - Abdul-Ghani, Safa
AU - Yanai, Joseph
AU - Abdul-Ghani, Rula
AU - Pinkas, Adi
AU - Abdeen, Ziad
N1 - Funding Information:
This study was supported by a grant from the Al-Quds Nutrition & Health Research Institute . The authors would like to thank Mr. Rateb Hussein and Mr. Munther Metani for their technical assistance, and Dr. Tamer Essawi and Mr. Firas Hassan for their help in performing the biochemical measurements.
PY - 2012/1
Y1 - 2012/1
N2 - Phthalates are industrial chemicals widely used in consumer products, plastics and children toys, and the risk of exposure to phthalates, especially prenatal exposure, is a growing concern justifying the development of an animal model to better understand their effect. The present study was designed to evaluate the suitability of a chick model for phthalate DEHP teratogenicity and neurobehavioral teratogenicity, a model which is simple and devoid of potential confounding factors such as maternal toxicity, maternal-fetal unit and maternal-neonatal interactions; major findings were confirmed in the DBP study. Prehatch exposure to DEHP in doses ranging from 20 to 100. mg/kg, reduced the percent hatching from 80% in control eggs to 65%, and increased late hatchings from 12.5% in control eggs to 29.4%. In addition it induced developmental defects characterized by an opening or weakening of abdominal muscles allowing internal organs to protrude externally with or without a sac, omphalocele or gastroschisis, respectively. The effect was dose dependent ranging from 8% with DEHP (20. mg/kg) to 22% (100. mg/kg). Similar treatment with DBP 100. mg/kg has reduced percentage hatching to 57% and increased late hatching to 37.5%, with a 14% increase in gastroschisis. Biochemical evaluation revealed elevated levels of alkaline phosphatase, which reflects non-specific toxicity of DEHP at such a high dose. Behavioral evaluation using an imprinting test and locomotor activity on chicks pretreated with DEHP (100. mg/kg) has shown an abolishment of imprinting performance from the control (0.65) preference ratio. DNA damage measurements of the metabolite 8-hydroxydeoxyguanosine (8-OH-dG) in blood samples showed an increase of 39.7% after prehatch exposure to phthalates. This was statistically significant for DEHP and indicates genetic toxicity, since part of the teratogenic activity is associated with oxidative stress and DNA damage.
AB - Phthalates are industrial chemicals widely used in consumer products, plastics and children toys, and the risk of exposure to phthalates, especially prenatal exposure, is a growing concern justifying the development of an animal model to better understand their effect. The present study was designed to evaluate the suitability of a chick model for phthalate DEHP teratogenicity and neurobehavioral teratogenicity, a model which is simple and devoid of potential confounding factors such as maternal toxicity, maternal-fetal unit and maternal-neonatal interactions; major findings were confirmed in the DBP study. Prehatch exposure to DEHP in doses ranging from 20 to 100. mg/kg, reduced the percent hatching from 80% in control eggs to 65%, and increased late hatchings from 12.5% in control eggs to 29.4%. In addition it induced developmental defects characterized by an opening or weakening of abdominal muscles allowing internal organs to protrude externally with or without a sac, omphalocele or gastroschisis, respectively. The effect was dose dependent ranging from 8% with DEHP (20. mg/kg) to 22% (100. mg/kg). Similar treatment with DBP 100. mg/kg has reduced percentage hatching to 57% and increased late hatching to 37.5%, with a 14% increase in gastroschisis. Biochemical evaluation revealed elevated levels of alkaline phosphatase, which reflects non-specific toxicity of DEHP at such a high dose. Behavioral evaluation using an imprinting test and locomotor activity on chicks pretreated with DEHP (100. mg/kg) has shown an abolishment of imprinting performance from the control (0.65) preference ratio. DNA damage measurements of the metabolite 8-hydroxydeoxyguanosine (8-OH-dG) in blood samples showed an increase of 39.7% after prehatch exposure to phthalates. This was statistically significant for DEHP and indicates genetic toxicity, since part of the teratogenic activity is associated with oxidative stress and DNA damage.
KW - DNA damage
KW - Embryonic development
KW - Gastroschisis
KW - Neurobehavioral teratogenicity
KW - Omphalocele
KW - Phthalates
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U2 - 10.1016/j.ntt.2011.10.001
DO - 10.1016/j.ntt.2011.10.001
M3 - Article
C2 - 22019469
AN - SCOPUS:82655189525
SN - 0892-0362
VL - 34
SP - 56
EP - 62
JO - Neurotoxicology and Teratology
JF - Neurotoxicology and Teratology
IS - 1
ER -