`Toxicant-induced loss of tolerance' (or TILT) describes a two-step disease process in which (1) certain chemical exposures, e.g., indoor air contaminants, chemical spills, or pesticide applications, cause certain susceptible persons to lose their prior natural tolerance for common chemicals, foods, and drugs (initiation); (2) subsequently, previously tolerated exposures trigger symptoms. Responses may manifest as addictive or abdictive (avoidant) behaviors. In some affected individuals, overlapping responses to common chemical, food, and drug exposures, as well as habituation to recurrent exposures, may hide (mask) responses to particular triggers. Accumulating evidence suggests that this disease process might underlie a broad array of medical illnesses including chronic fatigue, fibromyalgia, migraine headaches, depression, asthma, the unexplained illnesses of Gulf War veterans, multiple chemical sensitivity, and attention deficit disorder.
Ashford N., and Miller C.Chemical Exposures: Low Levels and High Stakes. Wiley and Sons, New York, 1998.
3.
Ashford N., Heinzow B., Lütjen K., Marouli C., Mølhave L., Mönch B., Papadopoulos S., Rest K., Rosdahl D., Siskos P., and Velonakis E.Chemical sensitivity in selected European countries: an exploratory study. A report to the European Commission, 1995.
4.
Association of Occupational and Environmental Clinics (AOEC). Advancing the understanding of multiple chemical sensitivity. Tox. Ind. Health1992: 8 (4): 1-1.
5.
Bell I., Miller C., Schwartz G., Peterson J., and Amend D.Neuropsychiatric and somatic characteristics of young adults with and without self-reported chemical odor intolerance and chemical sensitivity. Arch. Environ. Health1996: 51 (1): 9-21.
6.
Carter K.Ignaz Semmelweiss, Carl Mayrhofer, and the rise of the germ theory. Med. Hist.1985: 29: 33-53.
7.
Cone J., and Sult T.Acquired intolerance to solvents following pesticide exposure in a buildingTox. Ind. Health1992: 8 (4): 29-39.
8.
Davidoff A., and Fogarty L.Psychogenic origins of multiple chemical sensitivity syndrome: a critical review of the research literature. Arch. Environ. Health1994: 49 (5): 316-325.
9.
Environmental Protection Agency (EPA). Report to Congress on Indoor Air Quality, Vol. II. Assessment and Control of Indoor Air Pollution, 1989.
10.
Fiedler N., Kipen H., Natelson B., and Ottenweller J.Chemical sensitivities and the Gulf War: department of veterans affairs research center in basic and clinical science studies of environmental hazards. Regul. Toxicol. Pharmacol.1996: 24: S129-S138.
11.
Fukuda K., Nisenbaum R., Stewart G., Thompson W., Robin L., Washko R., Noah D., Barrett D., Randall B., Herwaldt B., Mawle A., and Reeves W.Chronic multi-system illness affecting Air Force veterans of the Gulf War. JAMA1998: 280 (11): 981-988.
12.
Genton M.Shedding light on darkroom disease—progress and challenges in understanding radiology workers' occupational illness. Can. J. Med. Radiat. Technol.1998: 2 (2): 60-66.
13.
Health Canada. Multiple chemical sensitivities and their relevance to psychiatric disorders. Workshop Proceedings. Ottawa, Canada, December 7, 1992.
14.
Hill A.The environment and disease: association or causation?Proc. R. Soc. Med.1965: 58: 295-300.
15.
Hirzy J., and Morrison R.Carpet/4-Phenylcyclohexene toxicity: the EPA headquarters case. Presented at the Annual Meeting of the Society for Risk Analysis, San Francisco, 1989.
16.
Johnson A.MCS Information Exchange. Brunswick, ME, 1996.
17.
Kruetzer R., and Neutra R.Evaluating individuals reporting sensitivities to multiple chemicals. Agency for Toxic Substances and Disease Registry, National Technical Information Service, Springfield, VA. Publication #P896-187646, 1996.
18.
Kuhn T.The Structure of Scientific Revolutions, 3rd edn.University of Chicago Press, Chicago, IL, 1970.
19.
Lax M., and Henneberger P.Patients with multiple chemical sensitivities in an occupational health clinic: presentation and follow-up. Arch. Environ. Health1995: 50 (6): 425-431.
20.
Leroy J., Davis T., and Jason L.Treatment efficacy: a survey of 305 MCS patients. The CFIDS Chronicle Winter 1996: 52-53.
21.
Meggs W., Dunn K., Bloch R., Goodman P., and Davidoff L.Prevalence and nature of allergy and chemical sensitivity in a general population. Arch. Environ. Health1996: 51 (4): 275-282.
22.
Miele F.The ionian instauration. An interview with E.O. Wilson. Skeptic1998: 6 (1): 76-85.
23.
Miller C.Multiple chemical sensitivity syndrome (letter to the Editor). J. Occup. Environ. Med.1995: 37 (12): 1323-1323.
24.
Miller C.Chemical sensitivity: symptom, syndrome or mechanism for disease?Toxicology1996a: 11: 69-86.
25.
Miller C.Invited Presentation before the Presidential Advisory Committee on Gulf War Veteran's Illnesses. San Antonio, Texas, 1996b.
26.
Miller C.Toxicant-induced loss of tolerance—an emerging theory of disease?Environ. Health Perspect.1997: 105 (suppl 2): 445-453.
27.
Miller C., and Prihoda T.A controlled comparative study of chemical intolerances among MCS patients, implant recipients and Gulf War veterans. Tox. Ind. Health1999: 386-398.
28.
Miller C., Ashford N., Doty R., Lamielle M., Otto D., Rahill A., and Wallace L.Empirical approaches for the investigation of toxicant-induced loss of tolerance. Environ. Health Perspect.1997: 105 (suppl 2): 515-519.
29.
Monk J.Farmers fight chemical war. Chemistry and Industry February 5, 1996: 108-108.
30.
National Research Council (NRC). Multiple chemical sensitivities: addendum to biologic markers in immunotoxicology. National Research Council, National Academy of Sciences. National Academy Press, Washington, DC, 1992.
31.
Newlin D.A behavior-genetic approach to multiple chemical sensitivity. Environ. Health Perspect.1997: 105 (suppl 2): 505-508.
32.
Overstreet D., Miller C., Janowsky D., and Russell R.Potential animal model of multiple chemical sensitivity with cholinergic supersensitivity. Toxicology1996: 111: 119-134.
33.
Randolph T.Human Ecology and Susceptibility to the Chemical Environment. Charles C. Thomas, Springfield, IL, 1962.
34.
Randolph T., and Moss R.An Alternative Approach to Allergies. Lippincott & Crowell, New York, 1980.
35.
Rogers W., Miller C., and Bunegin L.A rat model of neurobehavioral sensitization to toluene. Tox. Ind. Health1999: 356-369.
36.
Silverman K., Evans S., Stain E., and Griffiths R.Withdrawal syndrome after the double-blind cessation of caffeine consumption. NEJM1992: 327 (16): 1109-1114.
37.
Sorg B.Proposed animal model for multiple chemical sensitivity in studies with formalin. Toxicology1996: 111: 135-145.
38.
Stephens R., Spurgeon A., Calvert I., Beach J., Levy L., Berry H., and Harrington J.et al.Neuropsychological effects of long-term exposure to organophosphates in sheep dip. Lancet1995: 345: 1135-1139.
39.
Waddell W.The science of toxicology and its relevance to MCS. Regul. Toxicol. Pharmacol.1993: 18: 13-22.
