ToxSci Advance Access originally published online on October 31, 2007
Toxicological Sciences 2008 101(2):294-309; doi:10.1093/toxsci/kfm265
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Published by Oxford University Press 2007.
Low-Level Neonatal Thimerosal Exposure: Further Evaluation of Altered Neurotoxic Potential in SJL Mice
* Department of Neurological Surgery and the Center for Children's Environmental Health
Center for Children's Environmental Health and Department of Molecular Biosciences, University of California Davis, California 95616
Laboratory of Experimental Gerontology NIA/NIH, Baltimore, Maryland 21224
Constella Group, LLC, Durham, North Carolina 27713
¶ Neurotoxicology Group, Laboratory of Neurobiology, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709
1 To whom correspondence should be addressed at Department of Neurological Surgery, University of California Davis, 1515 Newton Court, Room 502C, Davis, CA 95616. Fax: (530) 754-5125. E-mail: rfberman{at}ucdavis.edu.
Received July 15, 2007; accepted October 17, 2007
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Abstract |
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Ethylmercury in thimerosal-preserved childhood vaccines has been suggested to be neurotoxic and to contribute to the etiology of neurodevelopmental disorders, including autism. Immune system function may be an important factor influencing vulnerability of the developing nervous system to thimerosal. This possibility is based in part on a report by Hornig et al. (2004, Mol. Psychiatry 9, 833–845) of neurodevelomental toxicity in SJL/J mice that develop autoantibodies when exposed to organic mercury. The present study reexamined this possibility by injecting neonatal SJL/J mice with thimerosal, with and without combined HiB and DTP vaccines. Injections modeled childhood vaccination schedules, with mice injected on postnatal days 7, 9, 11, and 15 with 14.2, 10.8, 9.2, and 5.6 µg/kg mercury from thimerosal, respectively, or vehicle. Additional groups received vaccine only or a 10 times higher thimerosal + vaccine dose. Low levels of mercury were found in blood, brain, and kidneys 24 h following the last thimerosal injection. Survival, body weight, indices of early development (negative geotaxis, righting) and hippocampal morphology were not affected. Performance was unaffected in behavioral tests selected to assess behavioral domains relevant to core deficits in neurodevelopmental disorders such as autism (i.e., social interaction, sensory gating, anxiety). In an open-field test the majority of behaviors were unaffected by thimerosal injection, although thimerosal-injected female mice showed increased time in the margin of an open field at 4 weeks of age. Considered together the present results do not indicate pervasive developmental neurotoxicity following vaccine-level thimerosal injections in SJL mice, and provide little if any support for the hypothesis that thimerosal exposure contributes to the etiology of neurodevelopmental disorders.
Key Words: thimerosal; mercury; SJL mice; locomotor behavior; social behavior; hippocampus; stereology.
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