Projects / Metabolic disorders / DEHP metabolites

Di-(2-ethylhexyl) phthalate and autism spectrum disorders


In collaboration with:

Child Neuropsychiatry Unit, University Hospital AOUS of Siena, Italy

Joussef Hayke

Neonatal Intensive Care Unit, University Hospital AOUS of Siena,  Italy

Carlo De Felice

Clinical Physiology Institute (IFC-CNR), National Research Council of Italy, Lecce Section,  &  Division of Neonatology, Perrino Hospital, Brindisi, Italy

Giuseppe Latini

ASDs (autism spectrum disorders) are a complex group of neurodevelopment disorders, still poorly understood, steadily rising in frequency and treatment refractory. Extensive research has been so far unable to explain the aetiology of this condition, whereas a growing body of evidence suggests the involvement of environmental factors. Phthalates, given their extensive use and their persistence, are ubiquitous environmental contaminants. They are EDs (endocrine disruptors) suspected to interfere with neurodevelopment. Therefore they represent interesting candidate risk factors for ASD pathogenesis. The aim of this research is to evaluate the levels of the primary and secondary metabolites of DEHP, [di-(2-ethylhexyl) phthalate], in children with ASD in comparison to HCs (healthy controls). A diagnostic methodology, based on the determination of urinary concentrations of primary and secondary DEHP metabolites by HPLC-ESI-MS (HPLC electrospray ionization MS), has been set up. For the first time we correlated different levels of the primary and secondary metabolites with ASDs compared with HC children. These data generate the idea that either current exposure is higher in children with ASD, or alternatively, and more likely, ASD children may differ in their ability to metabolize phthalates. Therefore a prenatal/postnatal screening for urinary DEHP metabolites in the population at high risk for ASDs could have an important social impact.


Differences between groups: scatterplots for 5-oxo-MEHP values in ASDs urine samples (ASDs, n548; HC, n545) Data are medians and inter-quartile range.


F. Nuti, S. Hildenbrand, M. Chelli, R. Wodarzb, and A.M. Papini


Synthesis of DEHP metabolites as biomarkers for GC-MS evaluation of phthalates as endocrine disrupters

Bioorg. Med. Chem. 13, pp 3461-3465.



Di(2-ethylhexyl)phthalate and Autism Spectrum Disorders.

C. Testa, F. Nuti, J. Hayek, C. De Felice, M. Chelli, P. Rovero, G. Latini, A.M. Papini. ASN NEURO (American Society for Neurochemistry) (2012) 4(4), 223-229. Open Access.