Evaluation of the Potential Effects of Three Chemicals on the Hypothalamic–Pituitary–Thyroid (HPT) and Hypothalamic–Pituitary–Gonadal (HPG) Axes Using the Larval Amphibian Growth and Development Assay (LAGDA)

ABSTRACT Three chemicals, 2‐ethylhexyl 4‐hydroxybenzoate (2‐EHHB), 5‐chloro‐2‐(2,4‐dichlorophenoxy) phenol (triclosan), and 4‐nonylphenol, branched (4‐NP), were evaluated using the larval amphibian growth and development assay (LAGDA) to investigate potential endocrine‐mediated effects. Xenopus laevis larvae at Nieuwkoop and Faber (NF) developmental Stage 8–10 were nominally exposed to 2‐EHHB, triclosan (at 3.6, 10.9, 33.0, and 100 μg/L), or 4‐NP (at 1.8, 5.5, 16.5, and 50 μg/L) until 10 weeks after the median time to metamorphosis (TTM). Each chemical increased the median TTM (NF Stage 62) at all tested concentrations, but the times between NF Stages 62 and 66 were less than the controls, resulting in similar times to NF Stage 66 for all treatments, including the controls. Exposure to 2‐EHHB increased body weight at NF Stage 62, while 4‐NP and triclosan reduced body weight at NF Stage 66. For juveniles at 10 weeks post metamorphosis, none of the test substances affected phenotypic sex ratios, consistency between phenotype and genotype, or liver‐somatic index. An increase in body weight in juveniles was observed in male and female frogs exposed to 4‐NP, and exposure to 2‐EHHB increased snout‐to‐vent length. Exposure to 4‐NP resulted in a marked acceleration of Müllerian duct development in male and female frogs. Gonadal ducts were also affected in 2‐EHHB and triclosan‐exposed frogs. No treatment‐related pathological liver effects were observed. Triclosan and 2‐EHHB exacerbated background findings in the kidney including mineralization, tubule dilation, interstitial fibrosis, and mononuclear cell infiltrates.