Characterizing perchlorate exposure and effects in mammals
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Perchlorate contamination in the U.S. appears to be more widespread than originally thought. Perchlorate is naturally occurring, in addition to its anthropogenic sources. Animals including humans have been exposed to perchlorate through drinking water and/or trophic transfer; perchlorate has been detected in dairy milk, some food items, human milk, and urine. Perchlorate exposure and effects in mammals were characterized in the current study. The ability to detect perchlorate in exposed animals is critical for effects studies and risk assessments; perchlorate residues in biological fluids such as plasma, urine, and milk can serve as biomarkers for perchlorate exposure. A well-developed method for perchlorate determination in these matrices would contribute greatly to perchlorate exposure assessment. In this study, analytical methods for perchlorate determination in these matrices were explored. Alumina-neutral cartridges combined with C18 cartridges and NAX combined with alumina-neutral provided the best cleanup with significantly reduced background signal of plasma and urine, respectively, and relatively high recovery of perchlorate using conventional ion chromatography with suppressed conductivity detection (IC-SCD). However, the cleanup method was not robust enough to be used on some urine matrices such as deer mouse urine collected in perchlorate excretion and elimination experiments. As an alternative to IC-SCD, IC-MS/MS provides an excellent method with high selectivity and sensitivity for part per trillion perchlorate determination in both aqueous and deer mice urine matrices. A study on perchlorate exposure and absorption in beef cattle showed that constant exposure to 25 ng/mL perchlorate in water over 14 weeks did not result in measurable residues in blood plasma or edible tissues of cattle at the first test site (McLennan County, Texas). However, perchlorate was detected in 4 of 33 and 17 of 26 cattle at the two Kansas farms with the highest plasma perchlorate concentrations of 43 and 32 ng/mL, respectively. Compared to perchlorate residues in urine, perchlorate residues in plasma may not be a proper biomarker for perchlorate exposure assessment. A study on perchlorate distribution, excretion, and depuration in rodents showed that urine was the major pathway for perchlorate fate in the body. Higher levels of perchlorate exposure corresponded well to high levels of perchlorate excreted in the urine. Perchlorate excretion via urine reached a steady state after one day in the 28-day exposure experiment. An average of 46, 46, and 61% of perchlorate was recovered in urine over the exposure period in high, medium, and low dose groups, respectively. Metabolism of perchlorate may occur in the body based in part on the 40% perchlorate unaccounted for in this study. Endogenous perchlorate may also exist. Perchlorate exposure through dosed drinking water for 28 days increased sodium-iodide symporter (NIS) gene expression in the kidney and stomach, and pendrin gene expression in the kidney, without significant difference. No significant difference was observed neither between the low and high dose groups in the depuration experiment regarding either gene expression in the kidney or stomach. No significant linear relationship was found between perchlorate urinary excretion and either gene expressions in the kidney. A partial sequence of deer mice NIS gene cDNA with 425 bps was discovered in the current study for the first time. Quantitative analysis of NIS mRNA expression in various tissues was also studied for the first time in the current study with expression levels from highest to lowest in deer mice tissues in the following order: stomach, testes, brain, large intestine, and barely expression in the lung, kidney, heart, and liver. The effect of perchlorate exposure on the fatty acid profile in milk was observed in lactating goats dosed with perchlorate from Monday to Friday each week for 4.5 weeks. Omega-6 fatty acids and total polyunsaturated fatty acids (PUFA) at the 1 mg/kg treatment were significantly reduced at day 10 (p = 0.0113 and 0.0053, respectively), day 17 (p < 0.001), and day 24 (p < 0.05), but not at day 2 and 31. Monounsaturated fatty acid (MUFA) was significantly reduced only at day 17 (p = 0.0130). Significant reductions in short- and long-chain fatty acids were observed at day 24 only (p = 0.0431 and 0.0097, respectively) in the high and low dose groups, respectively. Additionally, a weak negative correlation between milk perchlorate concentrations and total PUFA levels was found in human breast milk samples collected from Lubbock, TX or nearby counties. To our knowledge, this is the first report on the effect of perchlorate exposure on fatty acid profiles in milk. Further study is urged to investigate mechanistic aspects of the effect. This work will contribute to the human risk assessment of perchlorate, particularly for the development of infants with maternal exposure to perchlorate.