The teratogenicity and behavioral teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-butyl Phthalate (DBP) in a chick model
Date
2011-10-13
Authors
Abdul-Ghani, Safa
Yanai, Joseph
Abdul-Ghani, Rula
Pinkas, Adi
Abdeen, Ziad
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
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 maternalneonatal
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.
Description
Keywords
DNA damage , Embryonic development , Gastroschisis , Neurobehavioral teratogenicity , Omphalocele , Phthalates