This investigator described, "Thimerosal is an organic compound that contains mercury and has been used historically as a preservative in vaccines and pharmaceutical products. The breakdown product, ethylmercury, in thimerosal-preserved childhood vaccines has been suggested to be neurotoxic and to contribute to the etiology of neurodevelopmental disorders, including autism; however, this supposition is highly controversial."

The researchers were "doing an unrelated study that was testing only for the maximum tolerated dose (MTD) levels for thimerosal in a mouse model to be subsequently used in a study of reversal of immune-mediated platelet destruction (Rampersad et al., 2005). However, during our MTD studies, we serendipitously discovered that thimerosal shows a differential toxicity that depends upon whether the test animals are male or female."

This investigator then went on to describe, "An important consideration when trying to evaluate the possible role of thimerosal toxicity is that autism occurs approximately four times more frequently in males compared to females (MMWR, 2007). Thus, if males have an increased sensitivity to thimerosal, this would have to be taken into account with analyses of any outcomes. Our results that demonstrate a significant difference in the MTD of thimerosal depending upon whether the test animal is male or female is, thus, an important finding. Indeed, in mice, we found when using 10% DMSO to completely dissolve the thimerosal prior to injection that the MTD of thimerosal in males was only 25.6 mg/kg; whereas, in females, the MTD was 76.8 mg/kg. Thus, thimerosal has a 3-fold increased toxicity in males compared to females."

Further, he postulated, "Although the in vivo levels of thimerosal used in our studies are far higher than what would be expected in humans, this may not preclude the impact of our findings as we were using mortality as our outcome. Although our study is not extensive as the group sizes are small, nevertheless, we clearly found that male mice were more susceptible to the toxic effects of thimerosal than were female mice."

In addition, he stated, "recently, it has been argued that prenatal and neonatal testosterone exposures may be risk factors for autism (Knickmeyer and Baron-Cohen, 2006). Furthermore, it has been reported that estrogens are protective against neurotoxic effects (Wang et al., 2006) and may protect against certain neurodegenerative diseases, such as Parkinson's disease (Benedetti et al., 2001; Dean and McCarthy, 2007). Thus, our findings that thimerosal has increased toxicity in males compared to female mice suggest that estrogens produced in female mice may have some protective effect on the toxicity of thimerosal, while testosterone may have no effect or, perhaps, accelerate these toxic effects."

In conclusion, the investigator stated, "In summary, this is the first report of gender-selective toxicity of thimerosal. As autism occurs much more frequently in males than in females (MMWR, 2007), our findings may relate to a potential selectivity of thimerosal for toxic effects in some male children..."

Sincerely,
Dr. Mark Geier
David Geier