Postnatal Evaluation of Cervical Ribs in Control Rats.

BACKGROUND: Cervical ribs in rat fetuses have been widely reported to occur in controls as well as in response to various maternal chemical exposures. However, few evaluations of cervical ribs have been reported in rats postnatally. The available literature has indicated that the postnatal incidences of cervical ribs in control rats are no higher than in perinatal fetuses. METHODS: In a developmental toxicity study in rats conducted by the inhalation route, a control group of 44 time-mated female rats was exposed to filtered air only from gestation day (GD) 6 to 20, and divided into two cohorts. For one cohort, fetuses were removed from dams by laparohysterectomy for skeletal evaluation on GD 21. The other cohort of dams was permitted to deliver, and adult offspring were euthanized on postnatal day 65 for a subsequent postnatal skeletal evaluation of cervical ribs. RESULTS: The incidence of cervical ribs (mean percentage of affected fetuses or adults per litter) was observed to increase during postnatal development, from 1.0% on GD 21 to 12.7% on postnatal day 65. Further evaluation is ongoing to determine whether these observations were attributable to the inhalation exposure conditions used in this study. CONCLUSION: These results, while limited to the evaluation of one skeletal alteration in control rats, support the need for additional research into the area of postnatal development of skeletal abnormalities observed in developmental toxicity studies and the relevance of these skeletal observations to human risk assessment. Birth Defects Research 109:1301-1304, 2017. © 2017 Wiley Periodicals, Inc.

Molecular characterization of thyroid toxicity: anchoring gene expression profiles to biochemical and pathologic end points.

Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants. Follicular cell hypertrophy and pale-staining colloid were present in thyroid glands from PB-treated rats, and more severe hypertrophy/colloid changes along with diffuse hyperplasia were present in thyroid glands from PTU-treated rats. In PB- and PTU-treated rats, thyroid-stimulating hormone (TSH) levels were significantly elevated, and both thyroxine and triiodothyronine hormone levels were significantly decreased. PB induced hepatic uridine diphosphate-glucuronyltransferase (UDPGT) activity almost 2-fold, whereas PTU reduced hepatic 5 -deiodinase I (5 -DI) activity to < 10% of control in support of previous reports regarding the mechanism of action of each chemical. NaI also significantly altered liver weights and UDPGT activity but did not affect thyroid hormone levels or thyroid pathology. Thyroid gene expression analyses using Affymetrix U34A GeneChips, a regularized t-test, and Gene Map Annotator and Pathway Profiler demonstrated significant changes in rhodopsin-like G-protein-coupled receptor transcripts from all chemicals tested. NaI demonstrated dose-dependent changes in multiple oxidative stress-related genes, as also determined by principal component and linear regression analyses. Differential transcript profiles, possibly relevant to rodent follicular cell tumor outcomes, were observed in rats exposed to PB and PTU, including genes involved in Wnt signaling and ribosomal protein expression.