Baby tooth analysis shows that fetal and early postnatal zinc-copper metabolic rhythms predict autism risk.

The developing fetus is particularly vulnerable to adverse effects from pharmaceutical and exogenous chemical exposure. Deciduous teeth primarily form over specific periods from the second trimester in utero through the months after birth. We hypothesized that organic chemicals or their metabolites circulating in the bloodstream may sorb into forming dental tissues and remain stored in the tooth thereafter. Our aims were to devise analytical and preparation methods for potentially toxic or beneficial organic chemicals or metabolites in deciduous teeth and to estimate their detection frequencies. The analgesic acetaminophen was stored at greater concentration in a child's second molar than a first molar, consistent with intake, suggesting that acetaminophen concentration in molars may be a biomarker of acetaminophen exposure during molar formation. Chemicals detected by liquid chromatography/tandem mass spectrometry in molars of 21 typically developing children include the endocannabinoid anandamide (86% of children), acetaminophen (43%), and specific metabolites mono-2-ethylhexyl phthalate (MEHP, of plasticizer di-2-ethylhexyl phthalate, 29%), 3,5,6-trichloro-2-pyridinol (TCPy, of organophosphate (OP) insecticide chlorpyrifos, 10%), and 2-isopropyl-6-methyl-4-pyrimidinol (IMPy, of OP insecticide diazinon, 10%). None of these chemicals has previously been detected in human teeth. Molars from the two oldest subjects contained the largest concentrations of MEHP, TCPy, and IMPy. Potentially protective fatty acids detected by gas chromatography/mass spectrometry after derivatization include docosahexaenoic (19%), arachidonic (100%), and linoleic (100%). Validation studies are necessary to verify that each detected chemical in molars provides a biomarker of perinatal exposure.

Mitoplasticity occurs when mitochondria adapt to tolerate stressors. Previously we hypothesized that a subset of lymphoblastoid cell lines (LCLs) from children with autistic disorder (AD) show mitoplasticity (AD-A), presumably due to previous environmental exposures; another subset of AD LCLs demonstrated normal mitochondrial activity (AD-N). To better understand mitoplasticity in the AD-A LCLs we examined changes in mitochondrial function using the Seahorse XF96 analyzer in AD and Control LCLs after exposure to trichloroacetaldehyde hydrate (TCAH), an in vivo metabolite of the environmental toxicant and common environmental pollutant trichloroethylene. To better understand the role of reactive oxygen species (ROS) in mitoplasticity, TCAH exposure was followed by acute exposure to 2,3-dimethoxy-1,4-napthoquinone (DMNQ), an agent that increases ROS. TCAH exposure by itself resulted in a decline in mitochondrial respiration in all LCL groups. This effect was mitigated when TCAH was followed by acute DMNQ exposure but this varied across LCL groups. DMNQ did not affect AD-N LCLs, while it neutralized the detrimental effect of TCAH in Control LCLs and resulted in a increase in mitochondrial respiration in AD-A LCLs. These data suggest that acute increases in ROS can activate mitochondrial protective pathways and that AD-A LCLs are better able to activate these protective pathways.

Purpose: The aim of this study was to assess whether chemically intolerant women are at greater risk for having a child with autism spectrum disorders (ASD) or attention deficit hyperactivity disorder (ADHD).Methods: We conducted a case-control study of chemical intolerance among mothers of children with ASD (n ‫؍‬ 282) or ADHD (n ‫؍‬ 258) and children without these disorders (n ‫؍‬ 154). Mothers participated in an online survey consisting of a validated chemical intolerance screening instrument, the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Cases and controls were characterized by parental report of a professional diagnosis. We used a one-way, unbalanced analysis of variance to compare means across the 3 groups.Results: Both mothers of children with ASD or ADHD had significantly higher mean chemical intolerance scores than did mothers of controls, and they were more likely to report adverse reactions to drugs. Chemically intolerant mothers were 3 times more likely (odds ratio, 3.01; 95% confidence interval, 1.50 -6.02) to report having a child with autism or 2.3 times more likely (odds ratio, 2.3; 95% confidence interval, 1.12-5.04) to report a child with ADHD. Relative to controls, these mothers report their children are more prone to allergies (P < .02), have strong food preferences or cravings (P < .003), and have greater sensitivity to noxious odors (P < .04). Conclusion

Biological samples are an important part of investigating toxic exposures and disease outcomes. However, blood, urine, saliva, or hair can only reflect relatively recent exposures. Alternatively, deciduous teeth have served as a biomarker of early developmental exposure to heavy metals, but little has been done to assess organic toxic exposures such as pesticides, plastics, or medications. The purpose of our study was to determine if organic chemicals previously detected in a sample of typically developing children could be detected in teeth from a sample of children with autism. Eighty-three deciduous teeth from children with autism spectrum disorders (ASD) were chosen from our tooth repository. Organic compounds were assessed using liquid chromatography tandem mass spectrometry and gas chromatography methods. Consistent with a prior report from Camann et al., (2013), we have demonstrated that specific semivolatile organic chemicals relevant to autism etiology can be detected in deciduous teeth. This report provides evidence that teeth can be useful biomarkers of early life exposure for use in epidemiologic case-control studies seeking to identify differential unbiased exposures during development between those with and without specific disorders such as autism.