6 diﬀerent evaluator for the ADOS (assessed by a professional certiﬁed in the ADOS) versus the ATEC, modiﬁed PDD-BI, and SAS which were assessed by the same person (the parent who was the primary care giver). The various correlation analyses found that overall there were multiple positive correlations between the severity of autism and the urinary excretion of some toxic metals (both before and after taking DMSA). Lead (after DMSA) and antimony (at baseline) had the most consistent eﬀect, but other metals were also important. The existence of multiple positive correlations suggested that a regression analysis was appropriate. The regression analysis found that the body burden of toxic metals (as assessed by urinary excretion before and after DMSA) was signiﬁcantly related to the variations in the severity of autism, for each of the four scales. The metals of greatest inﬂuence were lead (Pb), antimony (Sb), mercury (Hg), tin (Sn), and aluminum (Al). Diﬀerent metals are signiﬁcant for the diﬀerent scales, and this partial dis- agreement is probably due to two factors. First, the severity scales are not identical, having somewhat diﬀerent questions and evaluating symptoms somewhat diﬀerently; as pointed out in Table 3, the correlations between the scales are good but not identical. Second, it should be noted that the high correlation between urinary excretion of many of the metals (see Adams et al. [10]) makes it diﬃcult to separate the eﬀect of one metal from another. This makes it improper to assign too much meaning to speciﬁc regression variables and their coeﬃcients. Thus, it is probably best to not overinterpret the results in terms of a particular metal, but to instead interpret them as evidence of the general role of toxic metals in relation to the severity of autism. Since oxidative stress and thiol metabolic disturbances have both been described in the autism population [12, 13], it is likely that these play a role in both relative burden and susceptibility to heavy metals. And since heavy metal exposure generates oxidative stress and thiol depletion, the potential etiological role of metal cations in generating autism symptoms should be further studied. Similarly, prior depletion of thiols and increased oxidative stress makes it more likely the individual will accumulate metals. It should also be noted that each severity scale assesses a somewhat diﬀerent aspect of autism; for example, the ATEC has a major section on physical health, which is not assessed by the other scales. So, that may also explain why the diﬀerent scales have somewhat diﬀerent relationships with diﬀerent metals. The ADOS had the highest adjusted R2 value, suggesting that it is a very useful scale for assessing the severity of autism and for inclusion in correlation and regression analyses with biological factors. This may be due to the fact that, of the four tools we used, only the ADOS involves a trained professional making a quantitative assessment of many children, whereas the other tools are assessments by parents of only their child. The strong correlation of the SAS with the other scales, and the high adjusted R2 value (0.36), suggests that the SAS is a useful tool for simple assessment of the severity of autism. Journal of Toxicology We are aware of two other studies which found a relationship between the severity of autism and a biomarker related to heavy metal toxicity. One study by Geier et al. [14] found that elevations in urinary porphyrins (associated with mercury or lead and mercury toxicity) were signiﬁcantly associated with Childhood Autism Rating (CARS) scores. A second paper to report a relationship of the severity of autism with a biomarker was a study which found a strong inverse relationship of the severity of autism with the amount of mercury in the baby hair of the subjects [15]. However, a replication study [16] did not reproduce that correlation with severity. So, while two studies [14, 15] do support a possible relationship of variations in the severity of autism with body burden of toxic metals, as was found in this paper, additional research is needed to conﬁrm this ﬁnding. This paper has focused on the possible relationship between toxic metals and the severity of autism. It has not included an examination of the source of those metals. Mercury, lead, and other toxic metals come from many sources. There has been particular interest in the possible relationship of autism and thimerosal (a mercury-based preservative once used in many childhood vaccines, but removed from most vaccines after 2003). However, this study was not designed to determine the sources of the toxic metals found in children with autism. 4.1. Limitations of this Study. The original study was designed primarily for evaluating the safety and eﬃcacy of DMSA therapy. It was not primarily designed for investigat- ing the relationship of the severity of autism to toxic metals, but that was an interesting outcome, so we felt it worth while to report it. Some limitations of the study design include the following. (1) The PDD-BI, SAS, and ADOS were assessed 2– 4 weeks after the ﬁrst round of DMSA, whereas the ATEC was assessed before. However, the strong correlation of the ATEC and PDD-BI suggests that this was a minor issue, and that the initial round of DMSA did not signiﬁcantly aﬀect the assessment. (2) The ATEC involved the largest number of partic- ipants (n = 63), whereas the other assessments involved somewhat smaller numbers (n = 49). 5. Conclusions Overall, the correlation analysis found multiple signiﬁcant correlations of severity of autism and the urinary excretion of toxic metals, such that a higher body burden of toxic metals was associated with more severe autistic symptoms. The results of the regression analyses (P < .005 in all cases) indicate that variations in the severity of autism may be partially explained in terms of toxic metal body burden. However, the ﬁnding of a relationship does not establish causality.