The Xenopus laevis teratogenesis assay for developmental toxicity of phthalate plasticizers and alternatives

Contamination of phthalate ester plasticizers threatens the wildlife as well as human health. To evaluate the developmental toxicity of commonly used phthalate esters and emerging alternatives, the frog embryo teratogenesis assay-Xenopus (FETAX) was conducted for dibutyl-phthalate (DBP), benzyl-butyl-phthalate (BBP), dioctyl-terephthalate (DOTP), di(2-propylheptyl)-phthalate (DPHP), diisononyl-phthalate (DINP), diisodecyl-phthalate (DIDP), diethyl hexyl cyclohexane (DEHCH), and diisononyl-cyclohexane-1,2-dicarboxylate (DINCH). The 96-hrs LC₅₀ for DBP, BBP, DOTP, DIDP, DINCH, DINP, DPHP, and DEHCH were 18.3, 20.1, 588.7, 718.0, 837.5, 859.3, 899.0, and 899.0 mg/L, respectively. The 96-hrs EC₅₀ of developmental abnormality of DBP, BBP, DPHP, DOTP, DINP, DEHCH, DINCH, and DIDP were 7.5, 18.2, 645.1, 653.6, 664.4, 745.6, 813.7, and 944.5 mg/L, respectively. The lowest observed effective concentration for embryonic survival, malformation, and growth was DINP, DBP, BBP, DIDP, DPHP, DINCH, DEHCH, and DOTP in increasing order. In tadpoles, DBP, BBP, DEHCH, DINP, and DIDP caused inositol-requiring enzyme 1 or protein kinase R-like endoplasmic reticulum kinase pathway endoplasmic reticulum stress (ERS) in order, and BBP, DBP, DOTP, DPHP, DINP, and DIDP caused long term ERS-related apoptosis or mitochondrial apoptosis in order. Together, in Xenopus embryos, the developmental toxicity and the cellular stress-inducing potential of tested plasticizers were DEHCH, DINCH, DPHP, DIDP, DINP, DOTP, BBP, and DBP in increasing order. In consideration of public as well as environmental health this information would be helpful for industrial choice of phthalate ester plasticizers and their alternatives.