Low-level neonatal thimerosal exposure: further evaluation of altered neurotoxic potential in SJL mice.
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 mug/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.
Berman
Robert F
RF
Department of Neurological Surgery and the Center for Children's Environmental Health, University of California Davis, CA 95616, USA. rfberman@ucdavis.edu.
Pessah
Isaac N
IN
Mouton
Peter R
PR
Mav
Deepak
D
Harry
Jean
J
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000097:blood / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D020258:Neurotoxicity Syndromes / Q000097:blood / Q000209:etiology*; D011310:Preservatives, Pharmaceutical / Q000493:pharmacokinetics / Q000633:toxicity*; D013849:Thimerosal / Q000493:pharmacokinetics / Q000633:toxicity*; D014018:Tissue Distribution
D011310:Preservatives, Pharmaceutical; D013849:Thimerosal; D008628:Mercury