Methylisothiazolinone: How "Allergen of the Year" Changed the Industry

The Rise: A Preservative That Actually Worked

Methylisothiazolinone is devastatingly effective at killing microbes. Part of the isothiazolinone family, it disrupts bacterial and fungal cellular processes at remarkably low concentrations - parts per million level.

For decades, it was used primarily in combination with Methylchloroisothiazolinone (MCI) in a 3:1 MCI/MI ratio, famously known as Kathon CG. This combination was restricted to 15 ppm early on due to sensitization concerns with MCI.

Then came the innovation that would prove disastrous: using MIT alone at higher concentrations. The theory was sound - MIT by itself appeared less sensitizing than the MCI/MI combination. Regulators approved it at 100 ppm (0.01%) for all cosmetic products.

Formulators loved it. Finally, a broad-spectrum preservative that worked in challenging systems - high water activity, difficult pH ranges, heavy botanical loads. MIT became ubiquitous.

The Fall: Epidemic of Sensitization

By 2010, dermatologists started noticing something alarming. Patch test positivity rates for MIT were climbing. Fast.

In 2013, the American Contact Dermatitis Society named MIT their "Allergen of the Year" - a distinction meant to alert clinicians to emerging sensitization epidemics.

The pattern was clear: widespread use of MIT in leave-on products (moisturizers, lotions, wet wipes) was sensitizing the population at an alarming rate.

The SCCS Verdict: No Safe Concentration

The EU's Scientific Committee on Consumer Safety delivered their final opinion (SCCS/1647/15) in December 2015. The conclusions were damning:

The phrase "no safe concentration" is regulatory death for an ingredient. It means even trace amounts could pose risk to sensitized individuals.

The Regulatory Response

The EU moved quickly after the SCCS opinion:

The reduction from 100 ppm to 15 ppm represents an 85% reduction in permitted concentration. Combined with the leave-on ban, MIT's cosmetic applications were decimated.

The Science: Why MIT Sensitizes So Effectively

MIT is classified as a strong sensitizer in the Local Lymph Node Assay (LLNA):

Dermal absorption compounds the problem. Studies show MIT absorption is dose-dependent and substantial:

• 25 ppm: 21.4% absorption
• 75 ppm: 33.7% absorption
• 150 ppm: 51.2% absorption

At 100 ppm in a leave-on product applied repeatedly, significant amounts of MIT reach the viable epidermis - exactly where sensitization occurs.

The Elicitation Problem

Perhaps the most troubling aspect is the elicitation threshold - the concentration that triggers a reaction in someone already sensitized.

The EU's 15 ppm limit for rinse-off sits exactly at the elicitation threshold. There's essentially zero safety margin for already-sensitized individuals.

The SCCS explicitly noted: "no information available to evaluate potential for MIT to elicit contact allergy" at 15 ppm. They're hoping rinse-off use provides enough additional protection through short contact time and wash-off.

EU vs. Rest of World

The regulatory divergence is stark:

Notably, the US never approved MIT for cosmetic use at all - it's not in any OTC monograph and isn't considered GRAS (Generally Recognized As Safe). The US skipped MIT entirely while the EU learned the hard way.

The CIR Disagreement

In a rare divergence, the Cosmetic Ingredient Review (CIR) Expert Panel's 2020 amended assessment reached a different conclusion than the SCCS:

• CIR position: MIT safe for rinse-off ≤100 ppm; safe for leave-on when "formulated to be non-sensitizing" (QRA-based)
• SCCS position: MIT safe for rinse-off ≤15 ppm (induction only); NOT safe for leave-on at any concentration

The CIR allows leave-on use if quantitative risk assessment demonstrates non-sensitizing potential. The EU takes the precautionary approach: no amount is acceptable in products that stay on skin.

Did the Restrictions Work?

The European multicenter data suggests yes:

• 2015: 4.5% sensitization prevalence
• 2017: 2.96% sensitization prevalence
• Reduction: ~34% decrease in 2 years

The leave-on ban and rinse-off restriction appear to have measurably reduced population sensitization rates. This is rare real-world validation of regulatory intervention.

The Bottom Line

Methylisothiazolinone's story is a cautionary tale about the dangers of extrapolating safety data:

• MIT alone seemed safer than MCI/MI - it wasn't, just at higher concentrations
• 100 ppm seemed reasonable - it caused an epidemic
• Widespread use revealed the problem - lab tests hadn't predicted it
• Leave-on products were the primary driver - continuous exposure maximized sensitization
• Restrictions appear effective - sensitization rates dropped after regulatory action

For formulators, the lesson is clear: a preservative that works brilliantly in the lab may fail catastrophically at population scale. The isothiazolinone class is now approached with extreme caution, even where still permitted.

For consumers, MIT's story shows that regulatory systems can respond to emerging safety signals - even if it takes years and an epidemic to trigger action.

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References

1. SCCS (2015). Opinion on Methylisothiazolinone (P94) - Sensitisation. SCCS/1647/15 FINAL. European Commission.
2. Bergfeld WF, Belsito DV, Cohen DE, et al. (2020). Amended Safety Assessment of Methylisothiazolinone as Used in Cosmetics. International Journal of Toxicology, 39(Suppl 3):3S-18S. DOI: 10.1177/1091581820965830
3. European Commission (2016). Regulation (EU) 2016/1198 - Amending Annex V to Regulation (EC) No 1223/2009. Official Journal of the European Union, L198:7-9.
4. European Commission (2017). Regulation (EU) 2017/1224 - Amending Annex V to Regulation (EC) No 1223/2009. Official Journal of the European Union, L176:16-18.
5. Geier J, Lessmann H, Brasch J, et al. (2012). Contact allergy to methylisothiazolinone - epidemic or endemic? British Journal of Dermatology. DOI: 10.1111/j.1469-7610.2012.01203.x
6. Uter W, Gefeller O, Geier J, et al. (2016). Contact dermatitis caused by methylisothiazolinone in cosmetics and non-cosmetic products. Contact Dermatitis. DOI: 10.1111/cod.12658
7. American Contact Dermatitis Society (2013). Allergen of the Year 2013: Methylisothiazolinone. ACDS Official Announcement.