In an article published on February 2, 2018 in the peer-reviewed journal The Journal of Steroid Biochemistry and Molecular Biology, Valentina Pomatto and colleagues from the University of Turin, Italy, reported on adipogenic effects of several plasticizers increasingly used in food contact materials (FCM) as “safer alternatives” to several phthalates restricted as substances of very high concern (SVHC) under REACH. These plasticizers are diisononyl phthalate (DiNP, CAS 28553-12-0), diisodecyl phthalate (DiDP, CAS 26761-40-0), diethylene glycol dibenzoate (DEGDB, CAS 120-55-8), and tri-m-cresyl phosphate (TMCP, CAS 563-04-2). Bisphenol A (BPA, CAS 80-05-7) and rosiglitazone (CAS 122320-73-4) were used as reference compounds. Rosiglitazone is a well-known pro-adipogenic agonist of peroxisome proliferator activated receptor gamma (PPARγ). The researchers used 3T3-L1 cells to test the above compounds at a wide range of concentrations.
All four tested plasticizers enhanced lipid accumulation and were shown to bind to PPARγ in silico, with TMCP having the greatest potency in both assays. BPA also enhanced lipid accumulation, but likely through other pathways not involving PPARγ. The tested plasticizers were also found to modulate the expression of several adipogenesis-related genes.
The authors conclude that their results “suggest that exposure to low, environmentally relevant doses [(low nanomolar concentrations)] of the plasticizers DiNP, DiDP, DEGDB and TMCP increase lipid accumulation in 3T3-L1 adipocytes, an effect likely mediated through activation of PPARγ.” This shows that “these four plasticizers may not be harmless substitute[s] of currently restricted compounds.” The scientists further point out that, although individual chemicals showed a “moderate” effect on lipid accumulation, their global effect “could be significantly higher in mixtures.” Importantly, FCMs are known to often contain multiple plasticizers. This calls for further studies evaluating the effects of mixtures of these plasticizers.
Pomatto, V., et al. (2018). “Plasticizers used in food-contact materials affect adipogenesis in 3T3-L1 cells.” The Journal of Steroid Biochemistry and Molecular Biology (published February 2, 2018).