Can Linalool Oxidation Products Elicit Eczema?

Linalool has a floral scent and is widely used in perfumes and cosmetics. When exposed to air, it oxidizes and forms substances different from the original linalool. Some of these oxidation products are called linalool hydroperoxides.

A study published by Sofia Botvid and colleagues in 2026 investigated the concentrations at which repeated skin exposure to these oxidation products elicited eczema in people who already had contact allergy to them. It did not investigate the probability of new sensitization in people without the allergy, or symptoms caused by inhaling a fragrance.

How do patch-test results relate to everyday use?

Sensitization means that the immune system has acquired the ability to respond to a substance. When a sensitized person encounters that substance again through the skin, allergic contact dermatitis, an allergic skin rash, may occur. Being sensitized does not mean that eczema will inevitably develop at every concentration.

Contact allergy is investigated using patch tests: a sample is placed against the skin and the reaction is read later. For linalool oxidation products, however, results may include doubtful or irritant reactions as well as clear positives. Relating test results to everyday symptoms has therefore been a challenge.

The researchers set three objectives: reassess the concentrations used for testing, explore the concentrations that elicit dermatitis during repeated application simulating use, and investigate the skin’s immune response.

Repeated application in 12 sensitized patients and 16 controls

Sixteen patients with a clear positive result on a previous patch test agreed to participate. Three subsequently withdrew, and one with an allergy to the aluminum in the testing equipment was excluded, leaving 12 patients for analysis.

Twenty healthy controls were recruited, but four with positive or doubtful reactions in the study’s confirmatory patch tests were excluded. Sixteen therefore underwent repeated application. It was not a group of 20 controls maintained unchanged throughout the study.

The repeated-application test used samples in an ethanol-and-water vehicle intended to simulate a leave-on perfume. Patients applied three concentrations of the oxidation products and the vehicle alone to separate eczema-free sites on their forearms. Controls tested only the highest concentration and the vehicle.

Samples were identified by color, with their contents concealed from both participants and the researchers assessing them. Assignment to application sites was also randomized. This was a medically supervised study with twice-daily application and observation for up to 21 days; application of a sample was stopped once a clear reaction occurred.

Fewer participants reacted at lower concentrations

At the highest concentration, 1630 ppm, or approximately 0.163%, four of the 12 patients developed positive dermatitis reactions. Two reacted at 538 ppm and one at 179 ppm. Parts per million refers here to the concentration of the oxidation products of interest, not the total amount of original linalool.

These groups of four, two, and one were not separate populations. The person who reacted at the lowest concentration also reacted at both higher concentrations. They therefore cannot be added together as seven cases. Four people reacted overall.

The time to reaction also varied. At the highest concentration, reactions appeared as early as day 4 in one person and on days 17 or 21 in others. The findings show that an absence of an immediate reaction after one use does not establish how someone will respond to repeated contact.

None of the 16 controls showed skin reactions or itching during repeated application. By contrast, all 12 patients reported localized or generalized itching during the trial. The four people with visible dermatitis should be distinguished from the number reporting itch.

The authors interpret these findings as supporting a relationship with existing contact allergy rather than irritation alone. However, the absence of reactions in these controls does not prove that irritation or allergy cannot occur in anyone else.

A 1% patch-test concentration helped confirm sensitization

Patch tests performed before repeated application compared several concentrations. With 1% of the oxidation products in the study’s ethanol-and-water vehicle, all 12 patients had clear positive reactions. With the standard 1% preparation in petrolatum, 11 had clear positive reactions and one had a doubtful reaction.

The researchers report that 1% was suitable for confirming sensitization in this small patient group. This concerns diagnostic testing conditions, not a claim that a concentration up to 1% is safe in cosmetics. Patch testing and repeated-application use tests differ in both concentration and contact conditions.

A small investigation of the skin’s immune response

Volunteers underwent additional patch tests, and small skin samples were collected from those sites on day 3. The samples were not taken from eczema elicited by repeated application. Samples from three patients and four controls could be analyzed.

The researchers measured the activity of genes involved in inflammation and immune responses. In patients’ skin, there were trends toward increased activity of genes related to early inflammatory responses and what is known as type 2 immunity, among others. This is consistent with the immune activity expected in contact allergy to fragrances.

However, because the sample was small, the researchers did not perform tests of whether between-group differences were statistically significant. The findings offer clues to immune-related changes, but do not by themselves establish the causal pathways behind each person’s eczema or itching.

How should the reaction at the lowest concentration be understood?

Because one person reacted even at 179 ppm, the researchers did not identify a concentration within the three tested levels at which all patients remained reaction-free. This does not show that every lower concentration is hazardous, nor does it measure the incidence of dermatitis in the general population of users.

The dose reaching the skin depends on the amount and frequency of application and the vehicle, not just concentration. The authors also discuss an earlier study that found fewer reactions with lower concentrations in a cream. They consider differences in vehicle, concentration, and patient reactivity as possible explanations for the different results.

The study used test solutions with confirmed concentrations. It did not examine how much the oxidation products increase as a bottle of perfume ages, or the safety of all commercial products. It is not a set of instructions for making test solutions or repeatedly applying a product that has caused symptoms to check the reaction. Concerning skin symptoms should be assessed with a healthcare professional.

The study was supported by Asthma and Allergy Denmark and Aage Bangs Fond. The authors declared no conflicts of interest.

Summary

Repeated skin contact elicited eczema in patients already sensitized to linalool oxidation products, with fewer patients reacting at lower concentrations within the range tested. Separate samples from patch-test sites also suggested changes in immune-related gene activity consistent with contact allergy.

The study’s contribution is its effort to connect a positive diagnostic test, symptoms arising during everyday-type exposure, and the underlying immune response. Verification in larger patient groups and with different vehicles could help make decisions about diagnosis, prevention of recurrence, and symptom management more specific.

References

Botvid, S., Bennike, N. H., Johansen, J. D., et al.(2026). Repeated Exposure to Hydroperoxides of Linalool Induces Immunologically Verified Allergic Contact Dermatitis. Contact Dermatitis, 94(6), 652–661. DOI: 10.1111/cod.70119. Full article / Full text at PMC. © 2026 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd. The original article is available under CC BY-NC-ND 4.0.