Toxicological Assessment of Oral Co-Exposure to Bisphenol A (BPA) and Bis(2-ethylhexyl) Phthalate (DEHP) in Juvenile Rats at Environmentally Relevant Dose Levels: Evaluation of the Synergic, Additive or Antagonistic Effects

BACKGROUND: The general population (including children) is exposed to chemical mixtures. Plasticizers such as Bisphenol A (BPA) and Phthalates (mainly Bis(2-ethylhexyl) phthalate-DEHP) are widespread contaminants classified as endocrine disrupters which share some toxicological profiles and coexist in food and environment. METHODS: To identify hazards of DEHP and BPA mixtures, the juvenile toxicity test-where rodents are in peripubertal phase of development, resembling childhood-was selected using exposure data from biomonitoring study in children. Biological activity and potential enhanced and/or reduced toxicological effects of mixtures due to common mechanisms were studied, considering endpoints of metabolic, endocrine and reproductive systems. The degree of synergy or antagonism was evaluated by synergy score calculation, using present data and results from the single compound individually administered. RESULTS: In metabolic system, synergic interaction predominates in female and additive in male rats; in the reproductive and endocrine systems, the co-exposure of BPA and DEHP showed interactions mainly of antagonism type. CONCLUSIONS: The present approach allows to evaluate, for all the endpoints considered, the type of interaction between contaminants relevant for human health. Although the mode of action and biological activities of the mixtures are not completely addressed, it can be of paramount usefulness to support a more reliable risk assessment.