Effects of nonylphenols on embryonic development and metamorphosis of Xenopus laevis: FETAX and amphibian metamorphosis toxicity test (OECD TG231)

Nonylphenols (NPs) are a group of endocrine-disrupting surfactants that mimic estrogen. To determine the developmental toxicity and thyroid-disrupting effect of NPs, the effects of exposure to nonylphenol (NP), 4-nonylphenol (4-NP), and nonylphenol ethoxylate (NP-12) were examined according to the frog embryo teratogenesis assay-Xenopus (FETAX) and Organization for Economic Co-operation and Development test guidelines 231 (TG231). In FETAX, the LC50 values of NP, 4-NP, and NP-12 were 59.14 mg/L, 10.13 mg/L, and 14.60 mg/L, respectively. At 10.0 mg/L, NP, 4-NP, and NP-12 significantly decreased the total length of tadpoles, and NP and 4-NP increased gut malformation and bent tails. In surviving tadpoles, the EC50 values for malformation of NP, 4-NP, and NP-12 were 4.66, 6.51, and 13.08 mg/L, respectively. The teratogenic indices of NP, 4-NP, and NP-12 were 12.69, 1.56, and 1.08, respectively, suggesting the teratogenic potential of NP and 4-NP. In a range-finder assay for TG231, the 96-h LC50 values of NP, 4-NP, and NP-12 were 2.0, 2.0, and 10.57 mg/L, respectively. When NF stage 51 larvae were exposed for 21 days, larval growth was inhibited by NP, 4-NP, and NP-12 at 0.67, 0.07, and 0.37 mg/L, respectively. 4-NP at 0.07 mg/L accelerated the developmental stage and significantly increased hind limb length, while 0.67 mg/L 4-NP delayed the developmental stage and decreased hind limb length, suggesting a bimodal effect of 4-NP on metamorphosis. NP and NP-12 at test concentrations did not alter the larval stage, but NP-12 at 0.37 mg/L significantly decreased total length and tail length, suggesting growth inhibition in larvae. The total colloid area of thyroid follicles was significantly increased by 0.07 mg/L 4-NP but not by NP and NP-12, suggesting that 4-NP may interfere with thyroid function. Together, the developmental toxicity of NPs was in the following order: 4-NP, NP-12, and NP. 4-NP may alter metamorphosis driven by thyroid hormones in X. laevis.