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Di(2-ethylhexyl)phthalate and Autism Spectrum Disorders

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http://www.asnneuro.org/an/imps/abs/AN20120015.htm

open access:

Di(2-ethylhexyl)phthalate and Autism Spectrum Disorders

Chiara Testa, Francesca Nuti, Joussef Hayek, Claudio De Felice,

Chelli, Paolo Rovero, Giuseppe Latini and Papini

Polo Scientifico e Tecnologico of the University of Florence, Sesto

Fiorentino, Italy. annamaria.papini2@...

Autism spectrum disorders (ASDs) 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 endocrine-disrupting chemicals

suspected to interfere with neurodevelopment. Therefore, they represent

interesting candidate risk factors for ASDs pathogenesis. Aim of this

study was to evaluate the levels of the primary and secondary

metabolites of the di(2-ethylhexyl)phthalate (DEHP) in children with

ASDs. A total of 48 children with ASDs [M: 36, F: 12; mean age: 11 years

± 5 years] and 45 age and sex comparable healthy controls (HCs, M: 25,

F: 20; mean age: 12 years± 5 years) were enrolled. A diagnostic

methodology, based on the determination of urinary concentrations of

DEHP metabolites by HPLC-ESI-MS, was applied to urine spot samples.

MEHP, 6-OH-MEHP, 5-OH-MEHP, and 5-oxo-MEHP were measured and compared to

unequivocally characterised, pure synthetic compounds (<98%) taken as

standards. In ASDs patients, significantly increased 5-OH-MEHP (52.1%,

median 0.18) and 5-oxo-MEHP (46.0%, median 0.096) urinary concentrations

were detected, with a significant positive correlation between 5-OH-MEHP

and 5-oxo-MEHP (r_s = 0.668, p < 0.0001). The fully oxidised form

5-oxo-MEHP showed 91.1% specificity in identifying patients with ASDs.

Our findings, demonstrate for the first time an association between

phthalates exposure and ASDs, thus suggesting a previously unrecognized

role for these ubiquitous environmental contaminants in the pathogenesis

of autism.

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