Beyond Pesticides | April 5, 2024

Exposure to chemical toxicants, molds, and algae contributes to autism and attention disorders in children, according to research that bolsters earlier findings. The exposures may be most relevant, not in the children, but one generation back—in the parents. The study, “Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children,” was published in the March issue of the Journal of Xenobiotics.

Led by Claudia S. Miller, MD, an immunologist at the University of Texas at San Antonio noted for her work on chemical intolerance (CI), the authors build on previous work published in 2015 establishing parental CI as a risk factor for autism and ADHD. Dr. Miller participated in Beyond Pesticides’ 2022 Forum Series. Recordings of her presentation are available on YouTube here and here.

In 1996, Dr. Miller concluded that CI is induced by Toxicant-Induced Loss of Tolerance (TILT). For further details, see Beyond Pesticides’ Daily News Blog. Three years later Dr. Miller developed the Quick Environmental Exposure and Sensitivity Inventory (QEESI), a questionnaire for individuals tracing their toxicant exposures and symptom histories. QEESI was first developed with groups exposed to organophosphate pesticides, volatile organic compounds in reconstruction and remodeling, various military chemicals used in the Gulf War, and breast implants. QEESI has been used in 16 countries, and the Miller team believes it offers “high sensitivity and specificity for differentiating individuals with CI from the general population.”

The concept behind TILT is that either a short-duration acute exposure to a chemical or biological agent or a low-dose chronic exposure can sensitize the immune system so that further exposures at much lower doses, or even exposures to previously tolerated substances, set off a cascade of immune responses leading to CI. CI often involves symptoms in multiple body systems and may be triggered not only by environmental chemicals, but also by foods and drugs. The prevalence of CI, if clinically diagnosed, is estimated at 0.5-6.5%; if self-diagnosed, the average is 20%.

Autism globally is estimated to occur in about one percent of children. It increased by 6-15 percent a year between 2002 and 2020. Less than a fifth of autism cases can be attributed to a specific cause. The rest, the authors write, are termed “idiopathic autism,” for which interactions between genes and the environment are thought to be the best explanation.

Attention Deficit Hyperactivity Disorder (ADHD) affects about 6% of youth and 2.5% of adults, according to the authors, and there is “substantial overlap” between autism and ADHD, estimated at 28-78%. The research team published work in 2015 showing that mothers with CI have three times the likelihood of reporting a child with autism and 2.3 times the odds of reporting a child with ADHD. The current study reinforces the association between CI and children’s behavioral problems, finding that the top 10 percent of parents with CI had 5.7 times the risk of having a child with autism and/or ADHD as the bottom 10%.

They also suggest that toxicant exposures, such as heavy metals, organophosphate pesticides, and tobacco smoke, probably stimulate epigenetic changes in gene expression.

Epigenetics refers to the process by which various molecules grant or deny access to genes by other cellular components, which in turn determines whether the genes are active. Epigenetic configurations have been shown to be heritable, although there is controversy regarding whether this applies to direct offspring that were gestating at the time of the mother’s exposure. The children in the current study would have been influenced both by their mother’s exposures and directly by any environmental substance that could penetrate the placental barrier.

The Miller team drew a random sample representing all 50 states from nearly three million people who completed an 80-question QEESI questionnaire through a SurveyMonkey online portal.

Nearly 23 percent of the respondents report high levels of CI. Of those, 13 percent report having a child with an autism spectrum disorder, and nearly 29 percent have a child with an attention disorder.  

The initiating exposures reported by respondents fall into two categories: fossil fuel-derived toxicants and biogenic toxicants such as particles and volatile organic compounds from mold or algae. The scientists note that regulatory standards for “safe exposure levels” to these substances are derived from animal tests. They rely on establishing “No Observed Adverse Effect Levels” (NOAELs). For people with CI, the level of exposure sufficient to trigger symptoms is usually far below established NOAELs. Nor do those levels capture the effects of mixtures or address carcinogenicity or mutagenicity, the authors note.

When CI, TILT, and QEESI were first developed, the theory did not include a specific mechanism for how the immune cascade develops. In 2021 Miller and colleagues proposed that toxic exposures trigger mast cells—part of the immune system—to change their behaviors and overreact to chemical signals.

Mast cells were discovered more than a century ago, but their role in CI has only recently been explored by Dr. Miller and colleagues. Mast cells are highly conserved in animal physiology, having appeared some 500 million years ago in early bony fish. Generally, they are deployed near an organism’s interface with the outside world (skin, digestive, and respiratory tracts), ready to defend against allergens, toxins, and pathogens. They are usually the first immune system responders to external invasion and release several kinds of inflammatory markers, including cytokines and histamine. They contribute to wound healing, tissue regeneration, and blood vessel formation. They also communicate with the nervous system, suggesting an involvement with responses to stress. Their roles in diseases associated with highly industrialized societies are the focus of intense scientific interest. Beyond Pesticides covered Dr.Miller’s examination of petrochemicals’ influence on mast cells in 2023.

One limitation of the current study is that QEESI is a subjective measure based on self-reporting from a self-selected population, and thus provides only anecdotal information. Further, there is no standard clinical protocol or a suite of laboratory tests for diagnosing CI. Nor is there a widely accepted method for diagnosing mast cell activation syndrome, a condition thought to underlie many disorders ranging from allergies to irritable bowel syndrome and possibly including CI.

Yet there is no doubt that environmental exposures contribute to many diseases and evidence of their influence on gene expression is mounting. What can be done? Mitigating environmental exposures by avoiding pesticides and industrial chemicals in fabrics, furniture, kitchen and bathroom cleaners, personal care products, traffic fumes, smoke, and the like, may help. But for chemical sensitivity, once the problem is established, it is very difficult to alleviate.

In order to really address the problem, it must be confronted at scale. That means reducing the presence in the ambient environment of the culprit chemicals, such as everything derived from fossil fuels—pesticides, plastics, internal combustion pollution, and the myriad compounds used in commerce, such as flame retardants and surfactants. Even biological triggers like mold and algae are often connected to human activities, especially those exacerbating climate change. Earth’s biosphere is being overwhelmed with these substances’ disruptions, impelling organisms to overamp their defense mechanisms, with the results we see about us—inflammation in every physiological system, leading to many health consequences ranging from heart disease, arthritis, depression, Alzheimer’s disease, cancer—and hair-trigger chemical sensitivities, autism and ADHD. Expecting the patients with CI/TILT, autism, and ADHD to cope individually by restricting their lifestyles to the point of absurdity, such as never being able to open a window or even go outside, is again, blaming the victim and will never result in overall improvement in public health.

All unattributed positions and opinions in this piece are those of Beyond Pesticides.

Sources:

Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children
Raymond F Palmer, David Kattari, Rodolfo Rincon, Claudia S Miller
J Xenobiot, 2024 Mar 5;14(1):350-367
https://www.mdpi.com/resolver?pii=jox14010022 

Chemical Intolerance and Mast Cell Activation: A Suspicious Synchronicity
by Raymond F. Palmer, J Xenobiot, 2023 Nov 12;13(4):704-718. doi: 10.3390/jox13040045 
https://www.mdpi.com/2039-4713/13/4/45

Drug Intolerances: Potential Risk Factors for Autism and Attention Deficit Hyperactivity Disorder
Heilbrun, L.P.; Palmer, R.F.; Jaen, C.R.; Svoboda, M.; Perkins, J.; Miller, C.S. Maternal Chemical and (ADHD). J. Am. Board Fam. Med. 2015, 28, 461–470
https://www.jabfm.org/content/28/4/461

Multiple chemical sensitivity/idiopathic environmental intolerance: A disability-rights, patient-led perspective
Sophia Jaworski, Comment J Allergy Clin Immunol Pract, 2024 Jan;12(1):265-266. doi: 10.1016/j.jaip.2023.11.023
https://linkinghub.elsevier.com/retrieve/pii/S2213-2198(23)01265-5

Mast cell activation may explain many cases of chemical intolerance
Claudia S. Miller, Raymond F. Palmer, Tania T. Dempsey, Nicholas A. Ashford & Lawrence B. Afrin, Environmental Sciences Europe, Volume 33, Article number: 129 (2021)
https://enveurope.springeropen.com/articles/10.1186/s12302-021-00570-3

Multiple Chemical Sensitivity
Review Brain Sci, Gesualdo M Zucco, Richard L Doty
2021 Dec 29;12(1):46. doi: 10.3390/brainsci12010046.
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/35053790/

The Dilemma of Mast Cell Activation Syndrome: Overdiagnosed or Underdiagnosed?
Cem Akin, MD, PhD, The Journal of Allergy and Clinical Immunology: In Practice
https://www.jaci-inpractice.org/article/S2213-2198(24)00065-5/fulltext

Parental avoidance of toxic exposures could help prevent autism, ADHD in children, new study shows
Press Release, March 28, 2024, University of Texas Health Science Center at San Antonio
https://www.sciencedaily.com/releases/2024/03/240328111021.htm#:~:text=A%20population%2Dbased%20survey%20of,in%20the%20bottom%20tenth%20percentile

The mast cell: an evolutionary perspective, Enrico Crivellato and Domenico Ribatti, Biol. Rev. (2010), 85, pp. 347 – 360.347