Gender-selective toxicity of thimerosal

Departments of Medicine and Laboratory Medicine and Pathobiology, University of Toronto, 67 College St., Toronto, Ontario, Canada M5G 2M1
Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie (Impact Factor: 1.86). 03/2009; 61(2):133-136. DOI: 10.1016/j.etp.2008.07.002


A recent report shows a correlation of the historical use of thimerosal in therapeutic immunizations with the subsequent development of autism; however, this association remains controversial. Autism occurs approximately four times more frequently in males compared to females; thus, studies of thimerosal toxicity should take into consideration gender-selective effects. The present study was originally undertaken to determine the maximum tolerated dose (MTD) of thimersosal in male and female CD1 mice. However, during the limited MTD studies, it became apparent that thimerosal has a differential MTD that depends on whether the mouse is male or female. At doses of 38.4–76.8 mg/kg using 10% DMSO as diluent, seven of seven male mice compared to zero of seven female mice tested succumbed to thimerosal. Although the thimerosal levels used were very high, as we were originally only trying to determine MTD, it was completely unexpected to observe a difference of the MTD between male and female mice. Thus, our studies, although not directly addressing the controversy surrounding thimerosal and autism, and still preliminary due to small numbers of mice examined, provide, nevertheless, the first report of gender-selective toxicity of thimerosal and indicate that any future studies of thimerosal toxicity should take into consideration gender-specific differences.

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Available from: Donald R Branch, Sep 23, 2014
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    • "( 1973 ) observed no marked difference in Hg distribution when administering either thimerosal or etHg . With reference to gender and strain of mice , Branch ( 2009 ) and Ekstrand et al . ( 2010 ) reported male mice were more susceptible to thimerosal toxicity than females . "
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    • "The aim of this study was to find the MTD value for acute exposure of TQ and address the possible mechanism of TQ toxicity using IP and oral routes. In preclinical and clinical toxicology, the gender issue is becoming an important investigation aspect [8,9] , therefore, the effect of gender on TQ toxicity will be an investigation point in our study. Anatomical and biochemical analysis were implemented to achieve the aim set for our study. "
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    • "This is an interesting phenomenon in relation to the toxicology of Hg. Studies in rats showed male rats to be significantly more susceptible to the adverse effects of inorganic Hg (Ekstrand et al. 2010) and also, more recently, to thimerosal (Branch 2009). The mechanisms underlying this gender disparity seem to be linked to differences in testosterone and estrogen levels, as testosterone was found to increase the toxicity of Hg, while estrogen was reported to be protective against Hg damage (Muraoka and Itoh 1980). "
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