What the evidence shows
MCS was defined in an occupational clinic. Mark Cullen’s 1987 description came from workers whose solvent exposure was documented by their jobs. The strongest onset evidence remains the cohorts where exposure was recorded before illness: Gulf War veterans, whose pesticide, pyridostigmine and oil-fire exposures were logged by the military and who developed chronic multisystem illness at rates well above unexposed troops; the EPA headquarters employees sensitized after the building’s 1987 re-carpeting. Claudia Miller’s toxicant-induced loss of tolerance describes the same two-step pattern across hundreds of cases: an initiating exposure, then loss of tolerance to unrelated things.
The chemicals that start MCS and the chemicals that most strongly activate TRPV1 and TRPA1 are largely the same list. Pesticides, solvents, aldehydes and combustion products are among the strongest known agonists of the receptors found sensitized in MCS. Patient histories and receptor pharmacology point at the same substances from two directions.
Susceptibility is real and not yet explained. Not everyone exposed develops MCS. In Gulf War veterans, those with a low-activity variant of the PON1 gene were most affected. In civilian MCS, a Toronto study of 203 women and 162 controls found associations with the active and rapid variants of CYP2D6 and NAT2 — faster metabolism, not slower — and those and other candidate-gene findings have not replicated consistently; they support investigating susceptibility and do not establish a cause. Familial clustering is reported and unmeasured.
Looking backward has limits. People search for a cause and find one. That is why the documented-exposure cohorts carry the weight, and why the registry asks about chronology before it asks about blame.