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TOXINS CREATING AUTOIMMUNITY

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Top 25 environmental exposures associated with autoimmunity

Rank Exposure Autoimmune associations Evidence

1

 Crystalline silica SSc, RA, SLE, ANCA vasculitis ★★★★★

2

 Cigarette smoke RA, SLE, MS, Graves disease ★★★★★

3

 Trichloroethylene (TCE) Systemic sclerosis, SLE/autoimmune responses ★★★★½

4

 Organic solvents SSc, SLE, MS, systemic autoimmune disease ★★★★

5

 Mercury/methylmercury ANA/autoantibodies; autoimmune dysregulation ★★★★

6

 PM2.5/air pollution RA, CTD, IBD, psoriasis, possibly SLE ★★★★

7

 Agricultural pesticides RA, SLE, Sjögren syndrome ★★★★

8

 PFAS—especially PFOA/PFOS Celiac/IBD; immune dysregulation; emerging thyroid/RA evidence ★★★½

9

 Tetrachloroethylene/PCE Systemic sclerosis/autoimmune associations ★★★½

10

 PCBs Thyroid autoimmunity/immune dysregulation; possible MS/RA links ★★★

11

 Dioxin/TCDD Autoimmune immune modulation ★★★

12

 Organochlorine pesticides RA/SLE/autoantibody associations ★★★

13

 Organophosphate pesticides RA/systemic autoimmune associations ★★★

14

 Chlorpyrifos Immunotoxicity; autoimmune evidence developing ★★½

15

 Cadmium RA, autoantibodies, inflammatory immune dysregulation ★★½

16

 Arsenic Autoimmune/inflammatory immune dysregulation ★★½

17

 Lead Autoantibody/immune alterations; human autoimmune evidence limited ★★½

18

 Bisphenol A Thyroid/lupus/RA mechanisms; human evidence emerging ★★½

19

 Phthalates/DEHP Autoimmune/endocrine-immune dysregulation ★★½

20

 PBDE flame retardants Thyroid autoimmunity/immune disruption ★★

21

 Benzene Profound immunotoxicity; autoimmune associations less established ★★

22

 PAHs RA/SLE inflammatory and autoimmune pathways ★★

23

 DDT/DDE Autoimmune/endocrine immune effects ★★

24

 Formaldehyde Immune activation/occupational inflammatory disease; systemic autoimmunity uncertain ★½–★★

25

 Styrene Immune dysregulation; limited direct autoimmune epidemiology ★½

1. CRYSTALLINE SILICA — strongest toxicant association

This belongs at or near the top because human occupational studies repeatedly associate silica exposure with:

systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus and ANCA-associated small-vessel vasculitis.

A huge Danish occupational cohort demonstrated a dose-dependent association between respirable crystalline silica and autoimmune rheumatic disease, especially systemic sclerosis and RA.

Mechanisms

Silica particles can produce:

  • macrophage injury
  • inflammasome activation
  • oxidative stress
  • chronic pulmonary inflammation
  • release of intracellular autoantigens
  • loss of immune tolerance
  • ANA/autoantibody production

Full references

Boudigaard SH, Schlünssen V, Vestergaard JM, et al. Occupational exposure to respirable crystalline silica and risk of autoimmune rheumatic diseases: a nationwide cohort study. International Journal of Epidemiology. 2021;50(4):1213-1226.
Gómez-Puerta JA, Gedmintas L, Costenbader KH. The association between silica exposure and development of ANCA-associated vasculitis: systematic review and meta-analysis. Autoimmunity Reviews. 2013;12(12):1129-1135.
Parks CG, Conrad K, Cooper GS. Occupational exposure to crystalline silica and autoimmune disease. Environmental Health Perspectives. 1999;107 Suppl 5:793-802.

2. CIGARETTE SMOKE

Smoking is one of the best-established environmental risk factors for seropositive rheumatoid arthritis, particularly ACPA-positive RA.
The interaction between smoking and genetic susceptibility, especially certain HLA-DRB1 shared-epitope alleles, is particularly important.

Smoking promotes pulmonary protein citrullination, potentially facilitating ACPA formation.
It has also been associated with:

  • systemic lupus erythematosus
  • Graves disease
  • multiple sclerosis
  • poorer outcomes in several autoimmune diseases

A recent causal-risk analysis continues to identify smoking as an important modifiable RA risk factor.

Full reference

Morotti A, Sollaku I, Franceschini F, et al. Systematic review and meta-analysis on the association of occupational exposure to free crystalline silica and tobacco smoking with rheumatoid arthritis. Clinical Reviews in Allergy & Immunology. 2022.

3. TRICHLOROETHYLENE — TCE

TCE is one of the most interesting individual chemicals in environmental autoimmunity.

Associations have particularly concerned:

  • systemic sclerosis
  • lupus-like autoimmunity
  • increased ANA
  • autoimmune hepatitis-like processes

Experimental lupus-prone models provide unusually extensive mechanistic evidence.

Mechanisms

TCE or its metabolites may alter:

  • CD4+ T-cell regulation
  • oxidative stress
  • protein modification
  • cytokine balance
  • IFN-γ pathways
  • regulatory T-cell function

 

Full references

Cooper GS, Makris SL, Nietert PJ, Jinot J. Evidence of autoimmune-related effects of trichloroethylene exposure from studies in mice and humans. Environmental Health Perspectives. 2009;117(5):696-702. doi:10.1289/ehp.11782.
Cai P, Konig R, Boor PJ, et al. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL+/+ mice. Toxicology and Applied Pharmacology. 2008;228(1):68-75.

4. ORGANIC SOLVENTS

This includes occupational exposure to mixtures containing chemicals such as:

  • TCE
  • PCE
  • aromatic hydrocarbons
  • paint/degreasing solvents

A systematic review and meta-analysis found an association between solvent exposure and autoimmune diseases.

Particularly notable is systemic sclerosis. A systematic review concluded that silica and solvents were among the occupational exposures most consistently related to SSc.

Full references

Barragán-Martínez C, Speck-Hernández CA, Montoya-Ortiz G, et al. Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis. PLoS ONE. 2012;7(12):e51506. doi:10.1371/journal.pone.0051506.
Rubio-Rivas M, Moreno R, Corbella X. Occupational and environmental scleroderma: systematic review and meta-analysis. Clinical Rheumatology. 2017;36:569-582.

5. MERCURY / METHYLMERCURY

Mercury has one of the most developed experimental models of chemical-induced autoimmunity.

Human evidence is particularly interesting for autoantibody formation rather than proven clinical autoimmune disease.

In U.S. NHANES women, mercury exposure was associated with increased odds of high-titer ANA positivity.

Mechanisms

Mercury may promote:

  • polyclonal B-cell activation
  • ANA formation
  • nucleolar autoantibodies
  • altered T-cell signaling
  • increased inflammatory cytokines
  • breakdown of self-tolerance

 

Full references

Somers EC, Ganser MA, Warren JS, et al. Mercury exposure and antinuclear antibodies among females of reproductive age in the United States: NHANES. Environmental Health Perspectives. 2015;123(8):792-798. doi:10.1289/ehp.1408751.
Pollard KM, Cauvi DM, Toomey CB, Morris KV, Kono DH. Mercury-induced inflammation and autoimmunity. Biochimica et Biophysica Acta—General Subjects. 2019;1863(12):129299. doi:10.1016/j.bbagen.2019.02.001.

6. PM2.5 AND AIR POLLUTION

Increasing epidemiologic evidence associates chronic air-pollution exposure with:

  • rheumatoid arthritis
  • connective-tissue diseases
  • inflammatory bowel disease
  • psoriasis
  • possibly systemic lupus

A large study found long-term pollution exposure associated with increased autoimmune-disease risk.

Full reference

Adami G, Pontalti M, Cattani G, et al. Association between long-term exposure to air pollution and immune-mediated diseases: a population-based cohort study. RMD Open. 2022;8:e002055.

7. AGRICULTURAL PESTICIDES

Pesticide exposure has been associated with rheumatoid arthritis, SLE and Sjögren syndrome, although risks differ greatly by individual pesticide.

The Agricultural Health Study provides some of the best human data.

Full references

Parks CG, Walitt BT, Pettinger M, et al. Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women’s Health Initiative Observational Study. Arthritis Care & Research. 2011.
Parks CG, Meyer A, Beane Freeman LE, et al. Pesticide use and risk of systemic autoimmune diseases in the Agricultural Health Study. Environment International. 2022.

8. PFAS — PFOA/PFOS/PFHxS/PFNA

PFAS are unquestionably immunotoxic, but direct evidence for causing classic systemic autoimmunity is less developed than the evidence for silica or smoking.

Current evidence is strongest for:

  • altered antibody responses
  • immune-cell alterations
  • celiac disease/IBD associations
  • possible thyroid autoimmune effects
  • emerging RA/MS associations

A new systematic/scoping evaluation found the strongest autoimmune-related evidence for gastrointestinal immune-mediated diseases, while RA and other associations remain less certain.

Full references

Holm-Larsen CE, et al. Exposure to per- and polyfluoroalkyl substances (PFAS) and development of autoimmunity: a systematic evidence review. 2026. PubMed PMID 42034718.
Rudzanova B, et al. Impact of PFAS exposure on prevalence of immune-mediated diseases in adults. Environmental Research. 2023.

9. TETRACHLOROETHYLENE — PCE

PCE is a chlorinated solvent historically associated particularly with:

  • dry cleaning
  • metal degreasing
  • groundwater contamination

Solvent-exposure studies implicate chlorinated solvents in systemic sclerosis and other systemic autoimmune diseases, although evidence for PCE individually is weaker than TCE.

Full reference

Barragán-Martínez C, Speck-Hernández CA, Montoya-Ortiz G, et al. Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis. PLoS ONE. 2012;7:e51506. doi:10.1371/journal.pone.0051506.

10. POLYCHLORINATED BIPHENYLS — PCBs

PCBs are persistent, lipophilic pollutants with endocrine and immunological effects.

Potential associations include:

  • thyroid autoimmunity
  • altered immunoglobulin production
  • altered T-cell/B-cell function
  • emerging MS associations

The evidence for immune toxicity is stronger than the evidence for causation of specific autoimmune diseases.

Full reference

Khan MF, Wang H. Environmental exposures and autoimmune diseases: contribution of gut microbiome. Frontiers in Immunology. 2020;10:3094. doi:10.3389/fimmu.2019.03094.

11. DIOXIN / TCDD

TCDD acts primarily through the aryl hydrocarbon receptor (AhR) and can dramatically alter immune differentiation.

Potential effects include changes in:

  • Treg cells
  • Th17 cells
  • dendritic cells
  • B-cell responses
  • cytokine signaling

 

Full reference

Huang RG, et al. Endocrine-disrupting chemicals and autoimmune diseases. 2023. PubMed PMID 37224951.

12. ORGANOCHLORINE PESTICIDES

Examples include:

  • DDT
  • DDE
  • chlordane
  • heptachlor
  • lindane

They are persistent and can disrupt endocrine and immune signaling.

Associations with autoimmune diseases are intriguing but less consistent than silica/TCE.

Full reference

Parks CG, De Roos AJ. Pesticides, chemical and industrial exposures in relation to systemic lupus erythematosus. Lupus. 2014.

13. ORGANOPHOSPHATE PESTICIDES

Organophosphates are best known for acetylcholinesterase inhibition, but chronic exposure also influences:

  • inflammatory cytokines
  • oxidative stress
  • T-cell activity
  • immune regulation

Some agricultural studies associate pesticide use with RA and systemic autoimmune illness.

Full reference

Parks CG, Hoppin JA, De Roos AJ, et al. Rheumatoid arthritis in Agricultural Health Study spouses: associations with pesticides and other farm exposures. Environmental Health Perspectives. 2016.

14. CHLORPYRIFOS

Chlorpyrifos deserves separate consideration because of widespread historical use and substantial neuro/immunotoxicology.
However, the evidence for direct human autoimmune disease causation remains limited.

Full reference

Mostafalou S, Abdollahi M. Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Toxicology and Applied Pharmacology. 2013;268(2):157-177.

15. CADMIUM

Cadmium exposure comes from:

  • tobacco
  • diet
  • industrial emissions
  • batteries
  • occupational exposure

It can alter macrophage and lymphocyte function and generates substantial oxidative stress.

Modern reviews identify cadmium among toxic metals potentially involved in autoimmune pathogenesis, although direct epidemiological evidence remains incomplete.

Full reference

Bjørklund G, Wallace DR, Kangarlou K, Hossain F, Peana M. Environmental toxins and toxic metals in autoimmune diseases: sex differences, hormonal influences, and immune dysregulation. Autoimmunity Reviews. 2026;25(1):103955. doi:10.1016/j.autrev.2025.103955.

16. ARSENIC

Chronic arsenic exposure produces profound changes in:

  • oxidative stress
  • epigenetic regulation
  • inflammatory cytokines
  • T-cell signaling
  • innate immunity

Evidence linking arsenic to specific autoimmune diseases remains suggestive rather than definitive.

Full reference

Bjørklund G, Wallace DR, Kangarlou K, Hossain F, Peana M. Environmental toxins and toxic metals in autoimmune diseases: sex differences, hormonal influences, and immune dysregulation. Autoimmunity Reviews. 2026;25(1):103955. doi:10.1016/j.autrev.2025.103955.

17. LEAD

Lead clearly affects immune function, particularly at substantial or chronic exposure.

Reported mechanisms include:

  • altered cytokine production
  • oxidative stress
  • T-cell dysregulation
  • altered antibody production

But epidemiologic evidence for specific autoimmune disease caused by lead is considerably weaker than its neurodevelopmental, renal and cardiovascular toxicity.

Full reference

Bjørklund G, Wallace DR, Kangarlou K, Hossain F, Peana M. Environmental toxins and toxic metals in autoimmune diseases: sex differences, hormonal influences, and immune dysregulation. Autoimmunity Reviews. 2026;25(1):103955. doi:10.1016/j.autrev.2025.103955.

18. BISPHENOL A — BPA

BPA interacts with estrogen receptors and other endocrine pathways capable of influencing immunity.

Experimental evidence suggests effects on:

  • B-cell activation
  • antibody production
  • Th17/Treg balance
  • inflammatory cytokines

Human autoimmune evidence remains emerging.

Full reference

Huang RG, et al. Endocrine-disrupting chemicals and autoimmune diseases. 2023. PubMed PMID 37224951.

19. PHTHALATES / DEHP

Phthalates have widespread exposure through plastics and consumer products.

They can affect:

  • endocrine signaling
  • oxidative stress
  • inflammatory cytokines
  • immune-cell differentiation

Evidence linking them to specific autoimmune diseases remains less robust than for silica, smoking or TCE.

Full reference

Bjørklund G, Wallace DR, Kangarlou K, Hossain F, Peana M. Environmental toxins and toxic metals in autoimmune diseases: sex differences, hormonal influences, and immune dysregulation. Autoimmunity Reviews. 2026;25(1):103955. doi:10.1016/j.autrev.2025.103955.

20. PBDE FLAME RETARDANTS

PBDEs are persistent flame retardants formerly used heavily in:

  • furniture foam
  • electronics
  • textiles

They can alter thyroid hormone and immune signaling. Research into autoimmune thyroid disease is biologically plausible but remains developing.

Full reference

Kosarek NN, et al. Contributions of synthetic chemicals to autoimmune disease development. 2024. PubMed PMID 38653907.

21. BENZENE

Benzene is a potent bone-marrow and immune-system toxicant.

It alters:

  • hematopoietic stem cells
  • lymphocyte populations
  • oxidative pathways
  • immune competence

However, benzene’s strongest established human effect is hematologic toxicity and leukemia, not classic autoimmune disease.

Full reference

Khan MF, Wang H. Environmental exposures and autoimmune diseases: contribution of gut microbiome. Frontiers in Immunology. 2020;10:3094. doi:10.3389/fimmu.2019.03094.

22. POLYCYCLIC AROMATIC HYDROCARBONS — PAHs

PAHs occur in:

  • tobacco smoke
  • diesel exhaust
  • wildfire smoke
  • traffic pollution
  • charred foods

Possible autoimmune mechanisms include oxidative stress, AhR activation and epigenetic alteration.
Their contribution is difficult to separate from the overall effects of particulate air pollution and smoking.

Full reference

Celen H, et al. Airborne pollutants as potential triggers of systemic autoimmune rheumatic diseases: a narrative review. Clinical Rheumatology. 2022.

23. DDT / DDE

DDT and its persistent metabolite DDE can remain in humans for years.

Potential effects include:

  • endocrine disruption
  • altered cytokine signaling
  • immune modulation

Evidence for specific autoimmune diseases remains limited/emerging.

Full reference

Parks CG, De Roos AJ. Pesticides, chemical and industrial exposures in relation to systemic lupus erythematosus. Lupus. 2014.

24. FORMALDEHYDE

Formaldehyde is clearly capable of producing:

  • mucosal inflammation
  • sensitization
  • occupational respiratory disease
  • immune activation

But evidence that ordinary formaldehyde exposure produces a systemic autoimmune disease such as lupus or RA remains weak.

Full reference

Cooper GS, Miller FW, Germolec DR. Occupational exposures and autoimmune diseases. International Immunopharmacology. 2002;2:303-313.

25. STYRENE

Styrene can influence oxidative and inflammatory pathways, but direct human evidence for systemic autoimmune disease is limited.
It belongs toward the bottom rather than the top of an evidence-ranked autoimmune list.

Full reference

Barragán-Martínez C, Speck-Hernández CA, Montoya-Ortiz G, et al. Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis. PLoS ONE. 2012;7(12):e51506. doi:10.1371/journal.pone.0051506.

The 10 I would take most seriously

For a physician evaluating environmentally associated autoimmunity, I would prioritize the history around:

crystalline silica → cigarette smoke → TCE → occupational organic solvents → mercury → chronic particulate air pollution → agricultural pesticides → PFAS → PCE/chlorinated solvents → persistent organochlorines/PCBs.

This ranking reflects quality of evidence, not merely theoretical biochemical effects. A modern review identifies solvents, crystalline silica, mercury, pesticides and cigarette smoking among the environmental exposures with particularly substantial evidence for autoimmune involvement.

An especially important example is silica: a cohort covering more than 3 million Danish workers found exposure-dependent increases in systemic autoimmune rheumatic diseases, with the clearest relationships for systemic sclerosis and rheumatoid arthritis.

Likewise, a meta-analysis found a significant association between organic solvent exposure and autoimmune disease, while TCE possesses both human epidemiologic evidence and unusually strong mechanistic animal evidence.

Two clinical cautions

A positive ANA is not proof of toxin-induced autoimmune disease. For example, the mercury-NHANES study is important because methylmercury exposure correlated with high-titer ANA, but that represents subclinical autoimmunity, not proof that mercury caused lupus or another diagnosed autoimmune disease in those subjects.

Likewise, immunotoxicity is not synonymous with autoimmunity. PFAS are a good illustration: evidence that PFAS can impair vaccine-antibody responses and alter immune function is strong, whereas evidence tying individual PFAS directly to specific autoimmune diseases is considerably less settled.

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