An animal model of marginal iodine deficiency during development: the thyroid axis and neurodevelopmental outcome.

Thyroid hormones (THs) are essential for brain development, and iodine is required for TH synthesis. Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the extent of neurological impairments associated with low-level TH disruption. This study examined the dose-response characteristics of marginal iodine deficiency (ID) on parameters of thyroid function and neurodevelopment. Diets deficient in iodine were prepared by adding 975, 200, 125, 25, or 0 µg/kg potassium iodate to the base casein diet to produce five nominal iodine levels ranging from ample (Diet 1: 1000 µg iodine/kg chow, D1) to deficient (Diet 5: 25 µg iodine/kg chow, D5). Female Long Evans rats were maintained on these diets beginning 7 weeks prior to breeding until the end of lactation. Dams were sacrificed on gestational days 16 and 20, or when pups were weaned on postnatal day (PN) 21. Fetal tissue was harvested from the dams, and pups were sacrificed on PN14 and PN21. Blood, thyroid gland, and brain were collected for analysis of iodine, TH, and TH precursors and metabolites. Serum and thyroid gland iodine and TH were reduced in animals receiving two diets that were most deficient in iodine. T4 was reduced in the fetal brain but was not altered in the neonatal brain. Neurobehavior, assessed by acoustic startle, water maze learning, and fear conditioning, was unchanged in adult offspring, but excitatory synaptic transmission was impaired in the dentate gyrus in animals receiving two diets that were most deficient in iodine. A 15% reduction in cortical T4 in the fetal brain was sufficient to induce permanent reductions in synaptic function in adults. These findings have implications for regulation of TH-disrupting chemicals and suggest that standard behavioral assays do not readily detect neurotoxicity induced by modest developmental TH disruption.

A comparison of clinical laboratory data for assigning a consensus value for manganese in a caprine blood reference material.

Biomonitoring for manganese (Mn) exposure is important due to its potential to cause adverse health effects. In this study, we investigate how different sample preparation methods (simple dilution, digestion, volumetric, gravimetric), calibration protocols (aqueous, blood-based, standard additions), and instrumental techniques affect Mn method bias and analytical imprecision. The techniques used included graphite furnace atomic absorption spectrometry (GFAAS), dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS), and sector field (SF-) ICP-MS. We analyzed NIST SRM 1643e Trace Elements in Water and SRM 1598a Inorganic Constituents in Animal Serum (both certified for Mn), and SRM 955c Toxic Metals in Caprine Blood - Level 1 (not certified for Mn). Various matrix effects in ICP-MS produced inaccurate results for SRM 1643e and discrepant results for SRM 955c. In the absence of a certified value for Mn in SRM 955c, we assigned a "consensus" value by combining data from the New York State Department of Health (NYS), the Centers for Disease Control and Prevention (CDC) and the Centre de toxicologie du Québec (CTQ). With this interlaboratory approach, we established an "all-lab" consensus value of 16.3 ± 0.8 µg L-1 based on data from DRC-ICP-MS with simple dilution sample preparation and blood-based calibration. We also assigned an "all-method" consensus value of 16.3 ± 0.9 µg L-1 based on GFAAS and SF-ICP-MS data from the NYS lab and the DRC-ICP-MS all-lab consensus value. Although the expanded uncertainty (U) calculated for the consensus values may not fully account for all sources of uncertainty, it does show the relative variation that might be expected from one study to the next for the determination of Mn in blood.