How TolRx Works
Where the data comes from, how the known trigger database was built, and the research behind each flagged ingredient.
About TolRx
What is TolRx?
TolRx is a personal reference tool for people managing conditions like MCAS, EDS, POTS, and Celiac disease. It pulls ingredient data from FDA and DailyMed databases so you can track which inactive ingredients (excipients) are confirmed triggers, suspected triggers, or safe for you specifically.
Is this medical advice?
No. TolRx is an informational reference tool, not a diagnostic system or substitute for medical advice. The known trigger database reflects published research and patient community reports - associations are not diagnoses and individual reactions vary significantly. Always verify medications and ingredients with your pharmacist or doctor before making any health decisions.
Why do some medications show no ingredient data?
Ingredient data depends on what manufacturers submit to the FDA. Some products have incomplete, missing, or outdated labels in the FDA database. When this happens TolRx shows "No ingredient data available." You can use the "Report incorrect ingredients" feature on any medication to flag this, or search the medication directly on DailyMed for the most current label.
What does the severity rating mean?
HIGH, MODERATE, and LOW ratings reflect the strength and consistency of documented associations between an ingredient and a condition in the published literature, not the severity of any individual reaction. A LOW rated ingredient can still cause a severe reaction in a specific person and a HIGH-rated one may be completely tolerated by someone else. The ratings are a starting point for your own review, not a clinical verdict.
Medication Data Sources
The primary source for medication ingredient data. OpenFDA is the FDA's public API providing structured data from drug Structured Product Labels (SPLs) submitted by manufacturers. Covers most prescription and OTC medications sold in the United States.
open.fda.gov/apis/drug/labelThe National Library of Medicine's DailyMed database hosts current drug label information submitted to the FDA. TolRx queries DailyMed as a supplementary source when OpenFDA returns sparse or incomplete ingredient data.
dailymed.nlm.nih.govIngredient data is cached and periodically refreshed. Because label data is self-reported by manufacturers, some products may have incomplete or outdated information. Always verify directly with a pharmacist or the manufacturer for the most accurate current formulation.
Known Trigger Database
The known trigger database is a curated list of inactive ingredients (excipients) with documented associations to specific conditions. It is based on patient advocacy literature, clinical research, and publications from condition-specific organizations. These associations are informational only. An ingredient appearing in this list does not mean you will react to it, and absence from the list does not mean it is safe for you.
Primary sources used to build the database:
- The Mast Cell Disease Society (TMS) - Patient advocacy literature on MCAS excipient triggers
- Celiac Disease Foundation - Guidance on gluten-containing medication excipients
- Published peer-reviewed research (cited per ingredient category below)
Artificial dyes (FD&C colors)
FD&C Red 40, Yellow 5 (tartrazine), Yellow 6, Blue 1, Blue 2, and D&C Red 33 are synthetic petroleum-derived dyes used as colorants in tablets and capsules. Tartrazine (Yellow 5) has been associated with hypersensitivity reactions in aspirin sensitive individuals and is among the most commonly reported dye triggers in MCAS patients. Hypersensitivity reactions range from urticaria and flushing to anaphylaxis.
- The Mast Cell Disease Society - excipient trigger guidance: tmsforacure.org
- FDA color additive information: fda.gov/industry/color-additives
Preservatives (benzoate, benzyl alcohol, parabens)
Sodium benzoate is associated with worsening histamine intolerance in some patients; the precise mechanism is not fully established and research is ongoing. Benzyl alcohol has documented associations with hypersensitivity reactions; at high doses it is associated with serious toxicity, and sensitive individuals may react at lower exposures used in pharmaceutical formulations. Parabens (methylparaben, propylparaben, butylparaben) are associated with hypersensitivity reactions and have estrogenic activity that may affect mast cell behavior.
- Maintz L, Novak N. "Histamine and histamine intolerance." Am J Clin Nutr. 2007 May;85(5):1185-96. PubMed 17490952
- FDA Drug Safety Communication - benzyl alcohol toxicity in neonates: fda.gov
Emulsifiers and thickeners (PEG, polysorbates, carrageenan, CMC)
Polyethylene glycol (PEG) is increasingly recognized as a cause of IgE-mediated and mast-cell-mediated hypersensitivity reactions, including anaphylaxis. Its use in COVID-19 vaccine formulations brought significant attention to this association. Polysorbate 80 is an emulsifier with well-documented associations to mast cell activation and non-immunologic anaphylactoid reactions. Carrageenan, a seaweed-derived thickener, has documented pro-inflammatory effects in animal studies. Regulatory agencies have not restricted food-grade carrageenan, but it remains a commonly reported trigger in the MCAS patient community. Carboxymethylcellulose (CMC) and polysorbate 80 together have been shown in mouse studies to disrupt gut microbiota in ways that promote intestinal inflammation; human evidence is more limited.
- Tobacman JK. "Review of harmful gastrointestinal effects of carrageenan in animal experiments." Environ Health Perspect. 2001 Oct;109(10):983-94. PMC1242073
- Chassaing B, et al. "Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome." Nature. 2015 Mar 5;519(7541):92-6. PubMed 25731162
- Coors EA, et al. "Polysorbate 80 in medical products and nonimmunologic anaphylactoid reactions." Ann Allergy Asthma Immunol. 2005 Jun;95(6):593-9. PubMed 16400901
- Bruusgaard-Mouritsen MA, et al. "Clinical presentation and mechanisms of hypersensitivity reactions to polyethylene glycols." Clin Exp Allergy. 2021 Jul;51(7):933-942. PubMed 33394522
Solvents and vehicles (propylene glycol, ethanol)
Propylene glycol is widely used as a solvent in liquid medications. While generally recognized as safe by the FDA, documented cases of hypersensitivity reactions and contact dermatitis exist in sensitive individuals. Ethanol is a known histamine liberator and vasodilator, making it particularly problematic for MCAS and POTS patients where histamine burden and vascular instability are already elevated.
- Maintz L, Novak N. "Histamine and histamine intolerance." (Covers ethanol as histamine liberator.) Am J Clin Nutr. 2007. PubMed 17490952
Colorants (titanium dioxide)
Titanium dioxide is used as a white colorant in tablet coatings. The European Food Safety Authority (EFSA) concluded in 2021 that it can no longer be considered safe as a food additive due to evidence of potential genotoxicity and intestinal inflammation effects. The FDA has not banned it in the US, but it is flagged as a moderate-risk ingredient due to its potential gut inflammatory effects relevant to MCAS patients.
- EFSA Panel on Food Additives and Flavourings. "Titanium dioxide (E171) as a food additive." EFSA Journal. 2021;19(5):6585. efsa.europa.eu
Gluten-containing excipients (Celiac disease)
Celiac disease is an autoimmune condition in which gluten ingestion causes intestinal damage. Even trace amounts from excipients like wheat starch, barley malt, or hydrolyzed wheat protein can trigger a response. The FDA's 20 ppm gluten-free standard applies to food labeling, not medications - there is no finalized binding rule for drugs. Medications making a "gluten-free" claim may follow the food standard voluntarily, but medications without that claim may contain undisclosed gluten-derived excipients.
Ingredients like pregelatinized starch, dextrin, and modified starch are flagged at MODERATE severity because their source (corn vs. wheat) is often not specified on the label. Patients with Celiac disease should verify the source with the manufacturer for any medication containing these excipients.
- Celiac Disease Foundation: celiac.org
- FDA - Gluten-Free Labeling of Foods: fda.gov
- Green PHR, Cellier C. "Celiac Disease." N Engl J Med. 2007 Oct 25;357(17):1731-43. PubMed 17960014
Conditions
MCAS
Mast Cell Activation Syndrome - a condition in which mast cells inappropriately release chemical mediators, causing symptoms affecting multiple organ systems. Inactive medication excipients are a common trigger source.
The Mast Cell Disease SocietyEDS
Ehlers-Danlos Syndrome - a group of connective tissue disorders. Many EDS patients have comorbid MCAS and may react to excipients that affect connective tissue or trigger mast cells.
The EDS SocietyPOTS
Postural Orthostatic Tachycardia Syndrome - a form of dysautonomia. Ethanol and histamine releasing excipients are particularly problematic due to their vasodilatory effects on an already dysregulated autonomic nervous system.
Dysautonomia InternationalCeliac disease
An autoimmune condition triggered by gluten ingestion. TolRx flags gluten-containing and potentially-gluten-containing excipients. MODERATE-severity ingredients have unspecified sources that may or may not be wheat-derived. This flag is also useful for non-celiac gluten sensitivity, though the two conditions differ significantly in mechanism and severity.
Celiac Disease Foundation