Our team at the Toxicant-Induced Loss of Tolerance (TILT) Research Program at UT Health San Antonio wanted to share this important external letter from Dr. Peter Spencer of the World Federation of Neurology:
Distinguished Colleagues,
I write as a biomedical scientist with five decades of experience in experimental and human neurotoxicology [1] to encourage you to consider including the TILT hypothesis in your toxicology training courses.
TILT, Toxicant-Induced Loss of Tolerance, is a concept coined in the late 1990s by Dr. Claudia Miller (Professor Emeritus at University of Texas Health Science Center at San Antonio) that built on experience with Chemical Intolerance, which describes medically unexplained, multisystem symptoms resulting from a newly acquired intolerance to chemicals, foods, and drugs.
TILT is characterized by a two-stage process in which, first, an acute or chronic exposure to a variety of environmental agents sets the second stage in which symptoms result from exposure to extremely small concentrations of previously tolerated substances that are often unrelated to the original exposure. The biomechanism underlying TILT is thought to involve the alteration, activation, and subsequent sensitization of mast cells [2], the body’s first line of defense against exposures to xenobiotics.
Recent studies have suggested that a diagnosis of TILT may have second-generation outcomes, since parents with chemical intolerance scores in the top versus bottom tenth percentile had 5.7 times the risk of reporting a child with autism and 2.1 times for Attention Deficit/Hyperactivity Disorder [3].
Details are provided in the following presentations, which may prove useful educational materials for your toxicology students. These modules also provide background for further research on the molecular and cellular mechanisms underlying the not uncommon clinical presentation of chemical intolerance.
TILT Tutorial for Chemical Intolerance, Autism/ADHD
Thank you for your consideration.
Sincerely,
Peter S. Spencer, PhD, FANA, FRCPath
Chair
World Federation of Neurology
Environmental Neurology Specialty Group
Professor
Department of Neurology, School of Medicine
Oregon Institute of Occupational Health Science;
Oregon Health & Science University
Portland, Oregon 97239, USA
About the Author: Dr. Peter S. Spencer is a Professor at the Department of Neurology, Oregon Health & Science University, where he has also served as the Founding Director (1988–2009) of both the Center for Research on Occupational and Environmental Toxicology (renamed Oregon Institute of Occupational Health Sciences) and the OHSU Global Health Center (2009–2013). He obtained a Ph.D. in Pathology from the University of London in 1972 and undertook post-doctoral study in Neuroscience from Albert Einstein College of Medicine in 1974. Prior to joining OHSU in 1988, he was a Professor of Neuroscience, Neurology, and Pathology (Neuropathology), and a Director at the Institute of Neurotoxicology of New York’s Albert Einstein College of Medicine, which he joined after leaving the Royal Free Hospital School of Medicine in 1971. He specializes in neurotoxicology, occupational and environmental neurology, and global health. He has received continuous federal research grant support for more than 45 years. His continuously funded research, which is published in ~500 papers, has been recognized by numerous international awards and honorary professorial appointments. He is a member of the American Association of Neuropathologists, European Association of Neurology, Peripheral Nerve Society, Royal College of Pathologists, and Society of Toxicology – Neurotoxicology, and he serves as the 2024 Chair of the Environmental Neurology Specialty Group of the World Federation of Neurology.
References
[1] Spencer PS, Schaumburg HH. Experimental and Clinical Neurotoxicology. Oxford, 2000, 1310p.
[2] Miller CS, Palmer RF, Dempsey TT, Ashford NA, Afrin LB. Mast call activation may explain many cases of chemical intolerance. Environ Sci Eur 33, 129 (2021). https://doi.org/10.1186/s12302-021-00570-3.
[3] Palmer RF, Kattari D, Rincon R, Miller CS. Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children. J Xenobiot. 2024 Mar 5;14(1):350-367. doi: 10.3390/jox14010022.