US EPA

1249807 

Journal Article 

The teratogenicity and behavioral teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-butyl Phthalate (DBP) in a chick model 

Abdul-Ghani, S; Yanai, J; Abdul-Ghani, R; Pinkas, A; Abdeen, Z 

2012 

1 

Neurotoxicology and Teratology
ISSN: 0892-0362
EISSN: 1872-9738 

PERGAMON-ELSEVIER SCIENCE LTD 

OXFORD 

34 

1 

56-62 

English 

22019469 

10.1016/j.ntt.2011.10.001 

WOS:000301037100007 

http://www.sciencedirect.com/science/article/pii/S089203621100198X
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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 100mg/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. 

DNA damage; Embryonic development; Gastroschisis; Neurobehavioral teratogenicity; Omphalocele; Phthalates