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Regul Toxicol Pharmacol
2022 Oct 01;134:105241. doi: 10.1016/j.yrtph.2022.105241.
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Amphibian Metamorphosis Assay: Investigation of the potential effects of five chemicals on the hypothalamic-pituitarythyroid axis of Xenopus laevis.
Kamel A
,
Matten SR
,
Lynn SG
,
Wolf JC
,
Fort DJ
.
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2-Ethylhexyl 4-hydroxybenzoate (2-EHHB), 4-tert-octylphenol (4-OP), 4-nonylphenol-branched (4-NP), benzyl butyl phthalate (BBP) and dibutyl phthalate (DBP) were evaluated using a 21-day Amphibian Metamorphosis Assay (AMA). Xenopus laevis larvae were exposed nominally to each chemical at 3.6, 10.9, 33.0, and 100 μg/L, except 4-NP concentrations were 1.8, 5.5, 16.5 and 50 μg/L. Endpoints included mortality, developmental stage, hind limb length (HLL), snout-vent length (SVL), body weight (BW), and thyroid histopathology. BBP and 4-OP accelerated development compared to controls at the mean measured concentration of 3.5 and 39.8 μg/L, respectively. An increase in developmental stage frequency distribution was observed for 4-OP at 39.8 and 103 µg/L, BBP at all concentrations and DBP at 143 µg/L. Normalized HLL was increased on study day (SD) 21 for all tested substances except 4-NP. Histopathology revealed accelerated development and mild thyroid follicular cell hypertrophy at all BBP concentrations, but moderate severity at 105 μg/L. Increased BW occurred for all chemicals except 4-OP. Increased SVL was observed for 4-NP, BBP and DBP on SD 21. There was insufficient evidence that 4-NP and 2-EHHB affected the hypothalamic-pituitarythyroid axis, however, BBP, DBP and 4-OP showed potential effects on amphibian metamorphosis and thyroid activity, albeit through different lines of evidence.
Fig. 2. Effect of exposure to the tested chemicals on Body Weight (BW) at Study Days 7 and 21.*Significantly different from control (Jonckheere-Terpstra p<0.5).aMean measured concentrations for the tested chemicals are listed in Table 1.bSEM: Standard error of the mean.
Fig. 3. Photomicrographs of transverse sections through the head/neck region of frogs exposed to BBP A) Cross section of head from a control frog. Internal gills and thyroid glands (arrows) are located at the level of the eyes and telencephalon brain region. B) Higher magnification of a thyroid gland from a control frog. Note that follicles are lined by cuboidal cells. C) High magnification of a thyroid gland from a frog exposed to 105 μg/L BBP. This was diagnosed as moderate follicular cell hypertrophy, which is characterized by the lining of most follicles by medium-height columnar cells. D) Cross section of head from a frog exposed to 105 μg/L BBP. The thyroid glands (arrows) are located at the level of the diencephalon and inner ears (caudal migration), the internal gills are in the process of resorption, and there is no laryngeal development as yet. E) Cross section of head from a frog exposed to 3.6 μg/L BBP, obtained at approximately the same axial level as in D. In this instance, caudal migration of the thyroids (arrows) is apparent, but in this case the internal gills have been completely resorbed, and there is accelerated laryngeal development relative to controls. F) Cross section of head from a frog exposed to 105 μg/L BBP. Note the single small cluster of thyroid follicles (arrow). Recorded diagnoses for the thyroids in this animal included caudal migration (here located at the level of the myelencephalon), hypoplasia/atrophy, and bilateral fusion. Key: di = diencephalon, ie = inner ears, ig = internal gills, te = telencephalon, la = larynx, my = melencephalon. Bar sizes: A, E, D, F = 500 mm; B, C = 50 mm.
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