TOXICOLOGY OF NEURODEVELOPMENTAL DISORDERS The role of mercury in the pathogenesis of autism

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder of unknown etiology in most cases. Studies of monozygotic twins report an average 60% concordance rate, indicating a role for both genetic and environmental factors in disease expression. Recent reviews in environmental health have suggested that early exposure to hazardous substances may underlie some cases of neurodevelopmental disorders, including ADHD, learning disabilities, and speech/language difficulties. In 1999, thimerosal used as a vaccine preservative was identified as a widespread source of organic mercury exposure in infants. Mercury (Hg), a heavy metal, is considered highly neurotoxic. The amount of mercury in vaccines, while small, exceeded USEPA safety guidelines on a cumulative basis. Certain individuals may exhibit severe adverse reactions to low doses of Hg which are otherwise largely benign to the majority of those exposed. Some individuals with idiopathic autism spectrum disorder may represent such a sensitive population. As summarized in this paper, disease characteristics suggest this possibility: (a) ASD traits are known to arise from mercury exposure; (b) onset of ASD symptoms is temporally associated with administration of immunizations; (c) the reported increase in the prevalence of autism in the 1990s closely follows the introduction of two mercurycontaining vaccines; and (d) elevated mercury has been detected in biological samples of autistic patients. Since ASD may now affect as many as one in 150 US children, and since thimerosal is still used in many products worldwide, confirmation of thimerosal as an environmental agent in autism pathogenesis has important societal and patient implications. Thimerosal is comprised of 49.6% ethylmercury (EtHg) by weight. Until early 2001, it was a component of most Hepatitis B, Haemophilus influenzae type B (HiB), and Diphtheria/Tetanus/Pertussis (DTP or DTaP) vaccines. These vaccines were routinely administered to infants at birth and at ages 2, 4, 6, and 15–18 months. The cumulative amount of mercury injected in the first 6 months of life was 187.5 g. Although the pharmacokinetics of EtHg have not been well studied, its toxicity is believed to be similar to MeHg, for which pharmacokinetic models have been developed to estimate the risk of adverse outcomes based on Hg levels in standard biomarkers of hair or blood. Using such a model,