Abstract
Abstract:
This article is an update of our previous review of propolis published in Dermatitis in 2013. It provides brief general information on propolis and a full update of the literature published between March 2013 and May 2025 on contact allergy to propolis, including results of testing in consecutive patients, data on testing in groups of selected patients, case reports, and case series. In addition, coreactivity to fragrances, fragrance-markers, and other compounds is presented and assessed, recent analyses of the components of the propolis materials used for patch testing are detailed, the allergens in propolis are briefly discussed, and data on the frequency of propolis used in cosmetics are provided. Special attention is paid to the sudden appearance of Brazilian propolis (Allergeaze) as patch test allergen, which caught us (and many others) by surprise. We try to elucidate the nature of positive patch tests to this material (allergic, false-positive, both?) and find an explanation for the extremely large number of positive reactions seen in various studies. We argue that propolis is used in few cosmetics and that these products are an infrequent cause of sensitization and allergic contact dermatitis. Rather, the majority may represent cross- or pseudo-cross-reactions in patients previously sensitized to fragrances. It is imperative that in the publication of all studies in which contact allergy to propolis was investigated, the source of propolis test material is specified: Chemotechnique (Chinese propolis) or Allergeaze (propolis = Chinese propolis; propolis [B] = Brazilian propolis).
Capsule Summary
This article provides a full 2013–2025 review of contact allergy and allergic contact dermatitis to Chinese and Brazilian propolis, their ingredients, coreactivity, composition of patch test materials, and frequency of use in cosmetics. Testing with Brazilian propolis yields significantly more positive reactions than with Chinese propolis. No adequate explanation has been put forward for the extremely high rates (>20%) reported in some studies; most appear to be allergic, but irritant and false-positive reactions from other causes have not been excluded.
INTRODUCTION
In 2013, an article reviewing properties, applications, chemical composition, contact allergy, and other adverse effects of propolis, covering the period 1987–2012, was published in Dermatitis. 1 The literature from before 1987 has been thoroughly reviewed and presented by Hausen et al. 2 Here, we review literature data on this intriguing botanical substance, published between March 2013 and May 2025. All issues of Contact Dermatitis were fully screened for relevant articles from volume 68, issue 2 (February 2013) to and including volume 93, issue 1 (July 2025), as were the articles of “Early view,” the online version of records before inclusion in an issue (accessed June 10, 2025). All issues of Dermatitis were fully screened for relevant articles from volume 24, issue 2 (March/April 2013) to and including volume 36, issue 2 (March/April 2025), as were the articles of “Online now,” the Online publications Ahead of print (accessed May 5, 2025). Literature lists of journal publications thus identified were searched for other relevant articles. In addition, a PubMed search was conducted with “propolis” as single search term and “propolis” combined with “allergy” and “dermatitis.” The focus of this review is on an update of contact allergy and allergic contact dermatitis (ACD) and on recent investigations into the composition of propolis used for preparing commercial patch test preparations. However, some useful general information on propolis is, in abbreviated and updated format, reproduced from the 2013 review article. 1
GENERAL INFORMATION
What Is Propolis?
Propolis (bee glue) is formed from a resinous material that honeybees (Apis mellifera L.) collect from living plants. The materials are mixed with the enzyme β-glycosidase present in the bees’ saliva, partially digested and added to beeswax to form the final product (raw propolis, propolis in natura). Raw propolis is hard and wax-like when cool, but soft and very sticky when warm, hence the name bee glue. The material has a pleasant aromatic smell; its color varies from yellow, green, or red to dark brown, depending on its source and age. The bees use propolis in the construction and adaptation of their nests and apply it in a thin layer on the internal walls of their hive or other cavity they inhabit, for example, to block holes and cracks, to repair combs, and to strengthen the thin borders of the comb and as a thermal insulator. 1
Botanical Sources
It is generally accepted and has been chemically demonstrated that, in temperate zones, the bud exudates of species and their hybrids of the genus Populus (poplars) are the main source of propolis, notably P. nigra L. (black poplar) and to a lesser extent P. deltoides L. and P. fremontii. Poplars being the main source for propolis (“poplar-type propolis”) are true for Europe (except some Mediterranean parts such as southern Greece, Crete, Malta, Cyprus, southern Italy), North America, Canada, New Zealand, and the nontropical regions of Asia, including China, which is the main producer of commercial propolis. Despite the honeybees’ preference for these poplars, exudates are also collected from other trees, for example, eucalyptus, birch, beech, alder, oak, willow, horse chestnut, pine, various conifers, and fruit trees. 1
In tropical regions there are no poplars and birches, and bees use other plant sources of bee glue. These can be identified by comparing the chemical profiles of the propolis in the region concerned and the suspected plant sources by chromatographic investigations. Examples of plant species that serve as botanical source for tropical propolis include Baccharis species, predominantly Baccharis dracunculifolia DC (Brazil; green propolis), Dalbergia species (Cuba, Brazil, Mexico; red propolis), Clusia major and Clusia minor (Venezuela, Cuba), Macaranga tanarius (Pacific region), Cistus species (Tunisia), Ambrosia deltoidea (Sonora desert [United States, Mexico]), Larrea nitida Cav. (Argentinian Andean propolis), Acacia paradoxa DC (Kangaroo Island, Australia), and Mangifera indica L. (Indonesia). The main source of Mediterranean propolis may be Cupressus sempervirens. As a consequence, there is a wide variation in the composition of “propolis,” depending (among others) on the geographic location where it was produced. 1
Properties and Applications
Propolis has been used by humans for thousands of years for its pharmaceutical properties. Raw propolis is washed with water, solubilized in 95% ethanol, and repeatedly filtered to remove the wax and organic debris, creating “propolis balsam” or “propolis tincture.” The balsam possesses antibacterial, antifungal, and antiviral properties and is claimed to have a wide range of other beneficial biological activities including wound-healing.3-5 Propolis is widely used as a popular remedy in folk medicine (especially in the Balkan States, the former USSR, Germany and Austria), and in apitherapy, which is the medical use of honey bee products. It is also a constituent of “biocosmetics” and is sold in many health food stores as a dietary supplement, as “over-the-counter” products for the protection of health and prevention of diseases, and as biopharmaceuticals for self-treatment of various diseases.3-5
Many producers of propolis claim their products to be “all natural,” which consumers often equate with safety. However, propolis and some of its constituents, notably the caffeates, are strong sensitizers, 1 and the use of propolis products not infrequently leads to sensitization and ACD, both from occupational contact in beekeepers (also called apiarists) and from the use of propolis products in consumers, especially from topical administration to the skin and oral mucosae. 1
CONTACT ALLERGY
General
The first description of contact dermatitis due to propolis was published in 1915. Such cases began to emerge with increasing frequency in the 1970s, and at that time, it was already predicted that the incidence of allergy to propolis would rise with the increasing use of propolis-containing biocosmetics and biopharmaceuticals for self-treatment of various diseases. 1 Occupational contact allergy to propolis in beekeepers is well known (mainly from collecting honey and cleaning hives, where contact with propolis is inevitable) and may lead to both contact dermatitis and airborne ACD. Airborne contact dermatitis may sometimes also be observed in neighbors of beekeepers. Occupational contact allergy to propolis also occurs, albeit far less frequently, in musicians and people who make stringed musical instruments 6 and has been observed in farmers and several other occupations. 1
Currently, most reported cases of ACD from propolis are caused by the topical use of propolis for medicinal purposes. Other sources of sensitization include cosmetics, “biocosmetics” or “natural cosmetics.” Candies, chewing gum, and the use of toothpastes, lozenges, powders, mouthwashes and various remedies for intraoral use containing propolis have been reported to cause allergic stomatitis (sometimes with ulcers), labial and oral swelling, dyspnea, cheilitis and perioral eczema. Oral administration of propolis-adulterated honey or propolis-containing products (capsules, tablet, powders, sprays) by patients allergic to propolis may cause generalized skin eruptions. 1
It should be realized that occupational contact allergy in beekeepers may still be a problem.7,8 In India, of 40 beekeepers with dermatitis, 6 (15%) had positive reactions to propolis. 111 With 2008, over 3.5% of German beekeepers suffered from occupational propolis allergy. 7 However, they did not seem to recognize the problem and continued their hobby without protecting themselves from contact with the substance. On the contrary, many used propolis as a medication for other disorders. This means that very few will be seen by a dermatologist, and the problem goes unrecognized and unreported. 7
A New and Unexpected Player in the Field: Brazilian Propolis
In January 2019, the European Society of Contact Dermatitis included propolis 10% pet. in the European baseline series (EBS) for routine testing, 9 which was prolonged in 2023. 10 The decision for inclusion was largely based on the results of patch test studies performed by the European Surveillance System on Contact Allergy network (ESSCA) in 2013–2014 in 7 countries. Five (Switzerland, Germany, Austria, Poland, Italy) showed a high prevalence of positive patch test reactions (2.1–6.3%), and 2 had low rates: the United Kingdom (0.3%) and Lithuania (0.7%). 11 Early 2024, our group in Amsterdam decided to investigate the usefulness of the addition of propolis to the EBS for The Netherlands. 12 Of 3134 consecutive patients patch tested with propolis 10% pet. in the EBS from 2019 to 2023, 299 (9.5%) had positive reactions. The rates by year were 3.4% (2019, 5.5 months), 2.8% (2020), 6.1% (2021), 16.1% (2022), and 16.4% (2023, 11 months), showing a significant rise from 2020 to 2023. The striking increase in the prevalence of positive reactions to propolis in this period could not be explained by (apparent) increased exposure to propolis-containing products. Therefore, we looked at possible changes in the patch test material from Allergeaze we used. It was found that Chinese propolis (coded NA71) had been discontinued in October 2019 because of supplier problems. It was substituted with a newly created propolis patch test material, propolis [B] (company code NH400), originating from Brazil, which came available as patch test hapten in November 2019. Brazilian propolis Allergeaze (from here on mostly termed propolis B) was used from that moment on (or early 2020) in the EBS and (most likely) other series including the American core baseline series (North American Contact Dermatitis Group [NACDG] recommended) and the Pediatric series. From checking ordering data with our distributor of Allergeaze test materials, we could reconstruct that, up to the end of 2020, >90% of patients had been tested with the Chinese propolis, and that from the end of 2021 on, probably all patch tests had been performed with propolis B. Therefore, we assumed that the high percentages in 2022 and 2023 (both >16%) were related to the switch from Chinese propolis to propolis B, of which we were not aware (and neither were all colleagues from large university centers whom we contacted). Apparently, the rise in positive reactions from propolis B was known to the manufacturer, who wrote, “We have seen higher rates in our own clinics and reports of higher prevalence for propolis in the literature” (Email from SmartPractice, March 19, 2024).
To verify our assumption that the rise observed by us was caused by the use of propolis B, in 2024, we performed a prospective study, in which consecutive patients were patch tested with propolis B and with Chinese propolis from both Allergeaze and Chemotechnique. 13 Of 239 patients, 57 (23.8%) had a positive reaction to propolis B and 9 (3.8%) to Chinese propolis. Of the 57 reactions to propolis B, only 2 (3.5%) were found to be clinically relevant, versus 3/9 (33.3%) for Chinese propolis. These results confirmed our hypothesis that the observed increase in positive patch tests to propolis between 2020 and 2023 had been the result of the switch from Chinese to Brazilian propolis. The rates of reactions to both propolis samples from China were significantly lower than to propolis B.
At that time, there were only 2 other studies in which patients had been tested with both Brazilian and Chinese propolis.14,15 In February and March 2023, at the Floridsdorf Allergy Center in Vienna, Austria, 143 consecutive patients were simultaneously patch tested with propolis B and Chinese propolis from Chemotechnique, yielding 9 (6.3%) positive reactions to propolis B and zero to Chinese propolis. 14 In the second study, performed in Genova, Italy, from February to July 2023, 257 adult consecutive dermatitis patients were patch tested with propolis B and Chinese propolis Chemotechnique. Fifteen (5.8%) had positive reactions to propolis B, of whom 2 coreacted to the Chinese variety. There were 3 reactions to Chinese propolis (1.2%), of whom 2 coreacted to propolis B. The difference between the rate of reactions to propolis B and that of the Chinese variety was statistically significant.15,16
Previously, in 2021 and 2022, researchers in 3 Informationsverbund Dermatologischer Kliniken (IVDK [Germany, Switzerland, Austria]) clinics in Switzerland had patch tested 1290 consecutive patients with propolis B, resulting in 303 (23.5%) positive reactions. 14 Data on clinical relevance were available in 181 of these patients. Current and past clinical relevance were documented in 29 (16.0%) and 2 (1.1%) of the patients, respectively. 14
The most recent data on patch testing with Brazilian and Chinese propolis come from the United States.17,18 At the University of North Carolina Contact Dermatitis Clinic in Chapel Hill, North Carolina, the reaction rate to propolis B NH400 purchased from Allergeaze increased from 3% in 2018 to 30% in 2022 (which cannot be correct, as NH400 only became available in November 2019). Chinese propolis purchased from Chemotechnique was added in 2021 and 2022 for comparison, with a reaction rate of 0% and 3%, respectively.17,18 Thus, this study also showed very high rates of positive reactions to propolis B (30% in 2022) and far lower reaction rates to Chinese propolis.
Our requests to the first author of these studies to provide more information remained unanswered.
Based on these studies, it can be concluded that the use of Brazilian propolis for routine patch testing resulted in high (>6%) to very high (>20%) rates of positive reactions, and that testing with Chinese propolis, both from Chemotechnique13B14 -18 and from Allergeaze, 13 yields significantly lower scores.
Interestingly, it appears that other investigators have also been testing with propolis B, who were, just as us, unaware of the switch from Chinese to Brazilian propolis by SmartPractice. These included the members of the NACDG. 19 In the 2019–2020 study period of the NACDG, propolis became a top 10 allergen with a prevalence of 8.6%. This was a statistically significant increase both for 2019–2020 versus 2017–2018 (4.7%) and versus 2009–2018. However, no explanation for this sudden rise was provided. 19
Very recently, the 2021–2022 NACDG data were published. 20 Of 3052 patients patch tested, 68 (2.2%) now reacted to propolis. The authors noted that the frequency of positive patch tests had significantly decreased compared with the previous study period, from 8.6% in 2019–2020 to 2.2% in 2021–2022; this was considered to be “back to normal.” 20 We suggested to one of the authors that the sudden rise in 2019–2020 could be explained by the use of propolis B in 2020. It was verified that SmartPractice had indeed provided the NACDG with propolis B in November 2019 for the 2020 study period. However, for the 2021–2022 test cycle, the NACDG had replaced all of the Allergeaze branded products within their Baseline Series with Chemotechnique products (mail correspondence with Joel DeKoven, June 15, 2025). Chemotechnique uses Chinese propolis, the composition of which is similar to that of the Chinese propolis from Allergeaze. 21 This conveniently explained the subsequent fall back to normal in 2021–2022. 20
In a study from Hungary, the results of testing propolis from 1992 to 2021 were analyzed and presented in 2022 (in Hungarian). In the 30-year period, the frequency of sensitization to propolis was relatively stable at on average 2.6%. However, in the period 2019–2021, there was a sudden increase to 6.2%, 8.4%, and 6.9%. 22 In the publication Abstract, it was stated that “The general need for biocosmetics, complementary and alternative medicine raises the exposure of propolis,” but no sound explanation for the sudden rise was given. We have suggested to the authors by email that the use of propolis B may have been responsible for this rise in 2020 and 2021 and asked whether the patch test material they had used was indeed propolis [B] Allergeaze, which specific question remained unanswered. They did use Allergeaze material, though, so it is likely that Brazilian propolis had been used.
What Can Explain the High Reactivity Rates of Brazilian Propolis?
How can such extremely high rates of 16.1–16.4%, 12 23.8%, 13 28%, 23 and a staggering 30%17,18 positive patch tests be explained? Increased and massive exposure is very unlikely.12,14 The second option is that a number of these reactions are false-positive, not indicating sensitization. Then the question arises whether the propolis B test material induces irritant reactions. This possibility has been investigated in the IVDK study. 14 The authors assessed the diagnostic performance of propolis B based on the evaluation of the reaction index (0.7 [95% confidence interval (CI) 0.6–0.8]) and the positivity ratio (77.6 [95% CI 72.4–82.1]) of their patch test results, which suggested that the preparation is not very irritating per se. The share of irritant or doubtful reactions was low, and strong (++) or extreme (+++) reactions to propolis B were observed, which is indicative for a patch test preparation with a good discriminatory power. In addition, a D2–D3/D4 crescendo reaction was observed in 75% of the patients with positive reactions, with 50% still negative on D2, favoring allergic patch test reactions. However, as current clinical relevance was ascertained in only a small number of patients, the authors acknowledged that positive patch test reactions to propolis B should be interpreted with caution. 14 We suggested that the potential irritancy of propolis B be further investigated, for example, by retesting in patients with a positive reaction, testing propolis in a dilution series, and/or control testing in individuals without dermatitis. 13
Another explanation for false-positive reactions was suggested in the IVDK study. 14 The raw material batch for the patch test preparation used in the 3 Swiss IVDK departments was characterized by a high total aerobic microbial count (TAMC; 130.000), which is an indicator of microbial contamination. Information from the manufacturer showed that ethanolic extraction was applied to the Chinese Allergeaze propolis raw material for purification purposes, but not to the propolis B material due to its lower share of waxes. The authors hypothesized that bacteria in the propolis B test material modulated the skin response during patch testing, thereby eliciting false-positive reactions. This was also suggested as an explanation for the lack of clinical relevance in most cases. 14 However, communications with SmartPractice have shown that in 2024 and 2025, in which we have had very high rates of positive reactions,13,23 our propolis B was prepared from a batch of which the TAMC was not elevated (<10.000). Therefore, microbial contamination cannot have played a role in the many positives we observed.
These authors had yet another theory for false-positive reactions to propolis B. 14 They found frequent coreactivity to nickel sulfate (28.9%) and to a lesser degree to cobalt chloride (13.2%) in propolis B-reactive individuals. Percentages in propolis B-negative individuals were not given, but the reaction rates to the metals were significantly higher than in a group of patients tested previously with Chinese propolis from Allergeaze. 24 Based on these data and the finding of the presence of nickel in 106 crude Brazilian propolis samples in quantities ranging from 0.10 to 42.50 mg/kg in a study from Brazil, 25 it was suggested that metal impurities in the patch test preparation might have been causative for positive patch test reactions rather than propolis constituents. However, the authors presented no evidence for the presence of nickel in propolis B. Also, in the Brazilian study, all nickel had disappeared after alcoholic extraction, which is always done with crude propolis for purification and removal of the fatty materials. 1 And finally, the maximum concentration of nickel in the crude propolis was nearly a factor 1.200 lower than the currently used 5% concentration for nickel patch testing, which may be far too low to detect sensitization. Therefore, we feel that this hypothesis 14 is rather unlikely. 13
Alternatively, the positive reactions to propolis B—or at least a portion thereof—could actually represent contact allergic reactions. In our study, 13 60% of the patients reacting to propolis B coreacted to at least one fragrance (linalool hydroperoxides, limonene hydroperoxides) or/and indicators of fragrance allergy (fragrance mixes 1 and 2, colophonium, Myroxylon pereirae resin [balsam of Peru]). There was a significant overrepresentation of coreactions to fragrance mixes 1 and 2 and to limonene hydroperoxides in propolis B-reactive individuals, which may indicate a relationship with fragrance allergy, as previously suggested. 12 The fact that a crescendo patch test reaction was observed in over 80% of the patients was also suggestive for allergic reactions. In the Vienna study, 14 7 of 9 (78%) patients positive to propolis B coreacted to fragrance materials (in particular Myroxylon pereirae resin) or colophony, again suggestive for a relationship with fragrance allergy.
When assuming that many of the positive reactions to propolis B are indeed allergic, it is obvious that their frequency far exceeds that of reactions to propolis from China. A difference in composition has been suggested as explanation.13,14 Indeed, it is well known that the composition of Brazilian propolis is significantly different from propolis found in the temperate zones, such as the Chinese propolis. 1 For the latter, bud exudate of poplars, mainly Populus nigra L. (black poplar), is the main source, whereas Baccharis species, predominantly Baccharis dracunculifolia DC, is the major source for bees producing Brazilian (green) propolis. 1 Our group has investigated the composition of the raw propolis materials used by SmartPractice to produce their Brazilian and Chinese propolis test allergens, as well as a sample used by Chemotechnique for producing their Chinese propolis patch test hapten. The results, which are detailed in the section “Analyses of propolis used for preparing patch test allergens,” confirmed that, whereas the Chinese samples were quite similar in composition, the Brazilian sample had an entirely different spectrum of constituents. 21
Finally, United States researchers found that the number of haptens in propolis B from Allergeaze is far greater than in Chinese propolis from Chemotechnique (detailed in section “Analyses of propolis used for preparing patch test allergens—Chinese propolis.”) 17 Therefore, they consider it possible that the greater percentage of terpenes, flavonoids, chalcones, phenolic, and aromatic compounds in propolis B is responsible for the greater sensitization rates to propolis B seen in all comparative studies with Chinese propolis.11,14B15 -18 These authors also suggested that the greater presence of fungal metabolites in propolis B and the presence of monocillin VI and istamycin C1, compounds with an antibiotic-like nature, may contribute to increased sensitization rates. 17
In the meantime, we have followed our own advice previously given 13 to test propolis in a dilution series, to further investigate the potential irritancy of propolis B. 23 Two hundred consecutive patients were patch tested with 10%, 3.3%, and 1% propolis B in petrolatum. Fifty-six (28%) had one or more positive patch tests. Eighteen propolis-allergic individuals (32%) reacted only to the 10% concentration, 21 individuals (38%) to all 3 concentrations, 13 (23%) to 2 concentrations, and 4 (7%) to a lower concentration only. A D2–D3 crescendo reaction to propolis B 10% was observed in 43/50 (86%) patients, of whom 24 (24/43, 56%) had been negative at D2. There was a strong association with fragrances, especially with the fragrance mixes 1 and 2. We concluded that our data seem to indicate that the positive patch test reactions to propolis B 10% pet., or at least a large part thereof, are allergic in nature. We also suggested that previous fragrance sensitization may play an important role in the large number of positive patch tests. 23
For the moment, it remains unknown how the very high rates of positive reactions to propolis B observed by several investigators12-14,17,18 can be explained. Although irritancy of the test material and false-positive patch tests from other causes have not been completely excluded, there are strong indications from testing with a dilution series, 23 a very large share of D2-D3 crescendo reactions,13,14,23 and strong association with fragrance sensitization,12-14,23 that the majority of positive patch tests to propolis B may in fact be allergic. Previous fragrance sensitization may play an important role in the large number of positive patch tests to propolis B, and the discrepancy between reactions to propolis from Brazil and from China may well be caused by their different composition.17,21
PATCH TESTING IN GROUPS OF PATIENTS
Patch Testing in Consecutive Patients Suspected of Contact Dermatitis: Routine Testing
Results of studies testing propolis in consecutive patients suspected of contact dermatitis (routine testing) back to January/February 2013 (publication date) are shown in Table 1. In the 31 studies reviewed, prevalences of positive patch test reactions have ranged from 0.1% in Israel in 2019–2022 42 to 30% in the United States in 2022. 18 Comparison between studies is difficult. Up to October 2019, both the test material from Chemotechnique and from SmartPractice (Allergeaze) contained Chinese propolis. However, in October 2019, the Chinese propolis from Allergeaze was replaced by Brazilian propolis, which yields far higher rates of positive reactions. Therefore, in Table 1, there are subsections for studies from the period 2019–2025 and studies from 2013 to 2018. To complicate things further, in most North American studies from 2019 to 2025 it was not mentioned which type of propolis had been used.19,20,26,27 Sensitization rates far higher than usual in some investigations19,26 may have been caused by using the Brazilian variety of propolis, which was confirmed for the NACDG study for 2020. 19
Patch Testing in Groups of Patients: Routine Testing
Study of the North American Contact Dermatitis Group (NACDG).
Study of the ESSCA (European Surveillance System on Contact Allergy network).
study of GEIDAC (Spanish Contact Dermatitis and Skin Allergy Research Group).
ACD, allergic contact dermatitis; IVDK, Informationsverbund Dermatologischer Kliniken (Germany, Switzerland, Austria).
In the European studies performed between 2019 and 2025, it was clearly indicated which propolis was used, with the exception of studies from Hungary, 22 the ESSCA, 35 and Spain. 36 In 2 investigations, a sudden increase in positive patch tests from 2019/2020 on suggested the switch from Chinese to Brazilian propolis12,22 This includes our own 2019–2023 investigation, where the hidden use of Brazilian propolis was first noticed and reported. 12
The results of patch testing with propolis B are discussed in more detail in section “A new and unexpected player in the field: Brazilian propolis.”
2013–2018
In the United States, rates of sensitization to Chinese propolis up to 2016 were in the range of 1.7–2.3% in the NACDG studies29,32,33 and somewhat higher (3.5%) in other US clinics.30,31 “Definite + probable relevance” was never more than 20% in the NACDG studies and relevance was not mentioned by the other clinics. In the 2017–2018 NACDG study period, in which there was a significant increase to a 4.7% rate of positive reactions, relevance was slightly higher (29%). 28
In Europe, large datasets of routine testing with propolis in 5–9 countries were reported by the ESSCA.11,32,37,41 Percentages of positive reactions for all countries and clinics together ranged from 2.48% to 3.26%. For individual countries, sensitization rates ranged from 0% to 6.54%. In the study with the highest rate of 3.26%, the 5 participating countries included Austria, Switzerland, and Germany, where propolis is frequently used and rates of sensitization are high. 38 Data on relevance were not available. In a large study performed by the IVDK, the frequency of sensitization rose from 2.35% in 2007–2010 to 3.94% in 2015–2018. No data on relevance were provided. 39 In a clinic in Spain, in 2003–2017, 41 (2.1%) of 1927 patient reacted to propolis. Sources in 17 patients with relevant reactions were nearly always topical remedies for treating skin disease. 40
In Israel, sensitization to propolis was very infrequent. 42 A 3% reaction rate was found in Australia between 2001 and 2010, but with only 14% relevant reactions. 44 In a small study from Singapore, there were 11 positives in 216 patients (5.1%). Two reactions were considered to be relevant, as these patients had used lip cosmetics containing beeswax, probably on the assumption that these products were polluted with propolis (bee glue). 43 Contamination of beeswax with propolis is indeed often assumed, but has very rarely been verified by chemical analysis. 45
Patch Testing in Groups of Selected Patients
Results of patch testing propolis in groups of selected patients back to January/February 2013 (publication date) are shown in Table 2. Selected groups have included patients with (allergic) contact cheilitis,45,50,57,60,70 frontal fibrosing alopecia (FFA)/lichen planopilaris,47,54 eyelid, 59 periorbital 71 or perianal 61 dermatitis, stasis dermatitis/chronic leg ulcers, 63 airborne contact dermatitis, 65 and individuals with a positive reaction to the fragrance-mix I. 56 Other studies have investigated propolis allergy in beekeepers with dermatitis, 8 nurses with occupational contact dermatitis, 68 hairdressers/cosmetologists, 72 children,48,51,67 individuals suspected of cosmetic intolerance, 69 female patients with facial dermatitis, 49 rosacea, 53 or allergic contact stomatitis, 55 individuals tested with botanical allergens,58,66 patients aged 65 years or older, 64 and in individuals tested with an antimicrobials, vehicles, and cosmetics series. 73
Patch Testing in Groups of Patients: Selected Patient Groups
Study of the North American Contact Dermatitis Group (NACDG).
IVDK, Informationsverbund Dermatologischer Kliniken (Germany, Switzerland, Austria); MP, Myroxylon pereirae resin.
In 28 studies, frequencies of sensitization to propolis have ranged from 2.1%71,73 to 50% in a small study of 12 patients with lichen planopilaris or FFA. 47 It may be expected that the observed frequencies heavily depend on the mode of selection of patients. Relatively low rates of reactions to propolis (≤3.8%) were seen in 12/28 studies.50,51,58,59,63-65,67-69,71,73 In one, the frequency was not specified 72 ; in another, the selection procedure was not described, 62 and 2 were considered to be of poor quality or unreliable.48,61 In the remaining 12 studies, the relevance of the observed positive propolis patch tests was not mentioned in 58,52,55-57 and insufficiently described in another 2.53,54 In patients with cheilitis, frequencies of positive patch tests were 6.6% 57 (relevance not mentioned), 8.3% 70 very small study; culprit products not mentioned), and 19%. 45 In the latter study, patients were selected on the basis of suspected allergic contact cheilitis, eczema around the lips or on the face, or suspicion of contact allergy to beeswax-containing products. 45
Sixteen patients had a positive patch test to propolis. These individuals did not use lip balms or other cosmetic products containing propolis (one could argue that sensu stricto; these reactions therefore were not relevant).
However, 14/16 propolis-positive patients were also allergic to beeswax, which was nearly always clinically relevant.
It was suggested that the beeswax in the lip balms that caused most reactions was contaminated with propolis (bee glue), from which product beeswax is obtained. Indeed, some caffeic acid, caffeic acid phenethyl ester, and caffeic acid 1,1-dimethylallyl ester, which may be allergens in propolis, were found on the surface of 8 beeswax samples, but whether the amounts were sufficient to cause ACD and whether these caffeates were actually the allergens in these patients is unknown. 45
For some studies, the high frequencies of sensitization to propolis are easy to explain, for example, 15% positives in beekeepers with dermatitis. 8 In others, where high frequences of positive patch tests to fragrances and fragrance-markers were found, the patch test reactions to propolis were almost certainly (pseudo-)cross-reactions, for example, in women with rosacea and suspected ACD, 46 massage therapists with occupational contact dermatitis, 52 female patients with FFA/lichen planopilaris, 54 patients with a positive reaction to the fragrance-mix I, 55 women with chronic vulvar complaints, 46 and possibly also the group of patients with cheilitis in which the reactions to propolis were ascribed to the use of beeswax in lip balms. 45
The 50% positive reactions in 12 patients with clinically and biopsy-proven lichen planopilaris (n = 9) or FFA (n = 3) are puzzling. 47 Why was propolis (tested as Brazilian propolis) by far the most frequent allergen? All 6 reactions were considered to be relevant. Why did the authors not mention which propolis-containing products the patients had used? Or did they also consider these reactions relevant, when cosmetics with fragrances were used? Without such information, the data of this study cannot be properly assessed and correctly interpreted.
CASE REPORTS AND CASE SERIES
Case Series
Propolis was stated to be the (or an) allergen in 3 patients in a group of 603 individuals suffering from cosmetic dermatitis, seen in the period 2010–2015 in Leuven, Belgium. 74 In the period 1996–2013, in a tertiary referral center in Valencia, Spain, 5419 patients were patch tested. Of these, 628 individuals had ACD to cosmetics. Propolis was the responsible allergen in 4 cases. 75
Case Reports
In the literature from the period 2013 to May 2025, only 18 case reports of ACD from propolis-containing products were identified by the authors. Their main features are summarized in Table 3. Topical62,76,79,85,86,88 and oral propolis-containing remedies78,84 were the most frequent culprits, followed by cosmetics.78,80,82,89,90 Throat candies were implicated in 2 patients79,87 and propolis-enriched honey in another 2,83,91 of whom one had used honey topically for soothing the irritation from a sinecatechins-containing ointment used to treat genital warts. 83 A beekeeper was allergic to his own propolis (but not to commercial Chinese propolis for patch testing) and had occupational ACD.
Case Reports of Contact Allergic Reactions to Propolis-Containing Products
Beeswax is said to be frequently contaminated with small amounts of propolis, but very few analytical investigations have been performed to verify this, 45 so some such reports may not have been accurate; these cases are presented here, as the authors in the title ascribed the dermatitis of the 2 reported patients as having been caused by propolis (bee glue), not beeswax.
ACD, allergic contact dermatitis.
Most had “plain” ACD (of whom one “consort ACD” 76 ), 2 had stomatitis from throat candies,79,87 one erythema multiforme-like ACD 88 and another systemic allergic dermatitis from oral intake of propolis. 84 The 2 patients in the 2013 case report from the United States, 92 in whom the positive patch tests to propolis (bee glue) were scored as relevant because the patients had used products containing beeswax (and not propolis), are shown in Table 3 only, as the title of the article suggested propolis to be the culprit (which remained unproven).
Other Clinical Studies on Contact Allergy to Propolis
During 2016–2017, in a multicenter study performed in western Sweden, 722 consecutive patients were patch tested with propolis samples from China, Lithuania, North America, and Sweden, all 10% pet. 93 45 of the 722 patients (6.2%) had positive patch test reactions to one or more propolis types. The most frequent reaction was to the propolis originating from China (3.6%), followed by North America (3.2%) and Lithuania (3.0%). The least frequent were reactions to the propolis sample from western Sweden (2.2%). Of the 45 patients with a positive patch test to propolis, 23 (51%) had a reaction to only 1 of the 4 origins of propolis. Eight patients (18%) reacted to 2 and 3 types of propolis, respectively, and 6 patients (13%) reacted to all 4 types of propolis. Evaluation of relevance was recorded in 33 (73%) of the patients. Current relevance was found in 9 (27%) of these, earlier relevance in 2 (6%), and unclear relevance in 22 individuals (67%). In total, there were 37 (5.1%) doubtful reactions to any type of propolis, the highest number (n = 18) to Chinese propolis. 93
During 2017–2019, 1,470 consecutive patients with dermatitis from Denmark, Lithuania, and Spain were patch tested with propolis from China, Lithuania, North America, and Sweden.94,95 In the total study population, frequencies of positive reactions to the 4 propolis types ranged from 1.2% (Swedish propolis) to 1.8% (Lithuanian and Chinese propolis). In the study populations of individual countries, 1.3–5.8% of the patients had positive patch test reactions to any of the propolis types. Positive reactions to propolis from Lithuania were significantly more frequent than propolis originating from Sweden. Apart from this, no statistically significant differences were seen in the number of positive reactions between the 4 different types of propolis in any of the 3 countries, individually or together. Of the 54 patients with a positive patch test to propolis, 29 (54%) reacted to only 1 of the 4 origins of propolis. Sixteen patients (30%) reacted to 2 types of propolis, 7 patients (13%) reacted to 3 types and 2 patients (4%) reacted to all 4 types of propolis. Concomitant reactions to 2 types of propolis were most frequent to those of Lithuanian and Swedish origin, 16 out of 26 (62%) and 18 out of 26 (69%) patients, respectively. Overall, 38% of propolis reactions were considered to have current relevance, whereas 16% were thought to have past relevance.94,95 An important finding of this study was that the 2 commercially available propolis test preparations using propolis originating from China (Chemotechnique) and North America (Allergeaze) detected, respectively, only approximately half (48%) and one-third (35%) of all patients with a positive reaction to propolis. 94
Comment
In the Materials and Methods section of both studies,93,94 it was stated that the test material containing propolis from North America was a commercial test preparation obtained from SmartPractice (brand Allergeaze). However, the Allergeaze test material contained Chinese propolis, not North American propolis (email correspondence with Kristine Schreiber, Global Marketing & Sales Director of SmartPractice, May 29, 2025). Thus, “North American propolis” in this 94 and the previous 93 study was in fact Chinese propolis.
CROSS-REACTIONS, PSEUDO-CROSS-REACTIONS, AND COREACTIONS
Coreactivities to Myroxylon pereirae resin (balsam of Peru) in groups of patients allergic to Chinese propolis have been noted for decades (summarized in ref. 1 ) Both substances are extremely complex materials, and patch testing with (some of) their ingredients is rarely performed. At least 26 chemicals may be present in both propolis and Myroxylon pereirae resin, 1 and at least 9 of these have caused positive patch test reactions both in patients allergic to propolis and in patients allergic to Myroxylon pereirae resin: benzoic acid, benzyl benzoate, benzyl cinnamate, benzyl isoferulate, benzyl salicylate, cinnamic acid, cinnamyl alcohol, coniferyl benzoate, and cinnamyl cinnamate. 1 Thus, there are ample opportunities for positive patch test reactions to both propolis and Myroxylon pereirae resin to be caused by common ingredients (pseudo-cross-reactions).
Other coreactivities observed before 2013 in patients allergic to Chinese propolis included fragrance-mix 1, fragrance-mix 2, colophonium, beeswax, poplar-bud extracts and various essential oils. 1
2013–2025 Update
The rates of coreactions to fragrances and fragrance-markers in patients with positive patch tests to propolis in studies from 2013 to 2025 are shown in Table 4 (Myroxylon pereirae resin), Table 5 (colophonium), Table 6 (fragrance-mix 1), and Table 7 (fragrance-mix 2 and limonene and linalool hydroperoxides). The correct interpretation of these data is complicated by several factors: (a) there are currently 2 types of propolis in use, Chinese and Brazilian propolis, which have different compositions (see section “Ingredients of propolis”); (b) the 2 types cannot always be differentiated: in one study, 12 and likely also in another, 22 both types of propolis were used for patch testing; (c) in a large ESSCA investigation, 35 the source of propolis was not mentioned, but because of the large number of participating centers in different countries, it is very likely that here too both Chinese and Brazilian propolis have been used; (d) in many of the studies, there was no control group of propolis-negative patients, making it impossible to calculate whether the observed rates of coreactivities in propolis-positive groups are significantly increased (although very high percentages probably are); and (e) there are strong indications that (at least a large part) of the observed positive patch tests to Brazilian propolis are allergic in nature. 23 However, it cannot be excluded that there are also false positives, either from irritancy of the test material or from other causes (see section “A new and unexpected player in the field: Brazilian propolis”). For optimal clarity, we have divided the studies into 3 categories: “Brazilian propolis,” “Chinese + Brazilian propolis or unknown,” and “Chinese propolis.”
Coreactivity to Myroxylon Pereirae Resin in Patients with Positive Patch Tests to Propolis
ESSCA, European Surveillance System on Contact Allergy network; IVDK, Informationsverbund Dermatologischer Kliniken (Germany, Switzerland, Austria); MP: Myroxylon pereirae resin; NACDG, North American Contact Dermatitis Group; OR, odds ratio.
Coreactivity to Colophonium in Patients with Positive Patch Tests to Propolis
IVDK, Informationsverbund Dermatologischer Kliniken (Germany, Switzerland, Austria); NACDG, North American Contact Dermatitis Group.
Coreactivity to Fragrance-Mix I in Patients with Positive Patch Tests to Propolis
ESSCA, European Surveillance System on Contact Allergy network; FM1, fragrance-mix 1; IVDK, Informationsverbund Dermatologischer Kliniken (Germany, Switzerland, Austria); NACDG, North American Contact Dermatitis Group; OR, Odds ratio.
Coreactivity to Fragrance-Mix 2, Linalool-OOH and Limonene-OOH in Patients with Positive Patch Tests to Propolis
FM2, fragrance-mix 2; IVDK, Informationsverbund Dermatologischer Kliniken (Germany, Switzerland, Austria); NACDG, North American Contact Dermatitis Group; OOH, hydroperoxides.
When evaluating the data in Tables 4–7, we conclude that, in patients who have positive patch tests to Chinese propolis, there are significant associations with Myroxylon pereirae resin, colophonium, and the fragrance mixes 1 and 2 (Table 8). These are likely the result of cross-reactions or reactions to common constituents. As to Brazilian propolis: at this moment, we consider significant associations with fragrance mixes 1 and 2 very likely, with limonene hydroperoxides probable, and with Myroxylon pereirae resin, colophonium, and linalool hydroperoxides to be uncertain (Table 8). Further large-scale patch test studies with Brazilian propolis (propolis [B] Allergeaze) should be performed to clarify these issues.
Evaluation of Coreactivities
P = 0.056, almost significant.
MP, Myroxylon pereirae; OOH, hydroperoxides.
Associations Between Propolis and Other Compounds
Essential oils and Compositae-mix II of 13 patients with positive reactions to propolis investigated in Belgium, 4 (30.8%) coreacted to lavender oil. 62
In an NACDG study, in a group of 627 patients allergic to propolis, 96 (15.3%) coreacted to Compositae-mix II and 78 (12.4%) to ylang-ylang oil; there were no control groups. 96 In a study of the IVDK performed in 2013–2019, of 2598 patients reacting to propolis, 13.4% coreacted to ylang-ylang oil, 8.1% to jasmine absolute, 7.6% to sandalwood oil and 7.4% to Compositae-mix II. These percentages were significantly higher than in the control group of 61,032 individuals with negative patch tests to propolis. 24
In a study performed by Swiss members of the IVDK in 2021 and 2022, in a group of 303 patients reacting to Brazilian propolis, 5.9% coreacted to ylang-ylang oil and 2.6% to Jasmine absolute. These percentages were lower than in a previous study with patients allergic to Chinese propolis, but there was no control group of propolis B-negative individuals. 14
Shellac
In a group of 21 patients with positive patch tests to shellac (20% alc.), 4 (19%) coreacted to colophonium and 3 (14%) to propolis. These results indicated, according to the authors, an association between shellac and markers of fragrance allergy. Unfortunately, there was no control group of shellac-negative individuals tested with propolis and colophonium. 97
In a study of the IVDK, in a group of 76 patients with positive reactions to shellac 20% alc. 9 (11.8%) coreacted to propolis. In the control group of 1906 shellac-negative individuals, the percentage positives to propolis were only 1.6; the difference was statistically significant, suggesting a relationship between allergy to shellac and to propolis. Reactions to colophonium, Myroxylon pereirae resin, the fragrance mixes, and 2 essential oils, with which propolis is known to coreact, were also significantly more frequent in shellac-positive patients. 98
Beeswax
Before 2013, of 72 patients in 5 studies who were allergic to propolis and who were tested with yellow beeswax (cera flava), white beeswax (cera alba), or both, 14 (19.4%) coreacted to beeswax. 1 This was conveniently explained by contamination of the beeswax with propolis, although analytical investigations to prove this in actual cases of contact allergy had not been performed. In a recent study, of 16 patients with positive patch tests to propolis, 14 coreacted to beeswax, which was relevant for most as they had used beeswax-containing lip balms. 45 Some caffeic acid, caffeic acid phenethyl ester and caffeic acid 1,1-dimethylallyl ester, which may be allergens in propolis, was found on the surface of 8 beeswax samples, but whether the amounts were sufficient to cause ACD and whether these caffeates were actually the allergens in these patients is unknown. 45
Other Compounds
In Spain, 36 patients with FFA, of who 25 (69.4%) had had a history of dermatitis (frequently the face) were patch tested. The most frequently positive allergens were benzyl salicylate (n = 8, 22.2%), gallates (n = 6, 16.7%), propolis (n = 6, 16.7%), and limonene hydroperoxides (n = 5, 13.9%). Benzyl salicylate was likely relevant to the dermatitis (labeled on personal care products and most patients reporting clinical improvement with allergen avoidance). Five of the patients reacting to propolis coreacted to benzyl salicylate. According to the authors, this could be explained by the fact that benzyl salicylate is a known (possible) ingredient of propolis. The reactions to benzyl salicylate were stronger than those to propolis. 99
Also in Spain, in a group of 33 patients with FFA patch tested, 9 (27.3%) had positive reactions to ethylhexyl salicylate 10% pet. Of these 9, 3 (33.3%) coreacted to propolis 10% pet. 100
Of 14 patients who had ACD from Mastisol, a liquid adhesive containing gum mastic (Pistacia lentiscus), gum storax (styrax, Liquidambar styraciflua), methyl salicylate, and ethanol, 6 (42.8%) coreacted to propolis. There were also high frequencies of coreactions to Myroxylon pereirae resin (39%), fragrances (majantol, hydroperoxides of limonene and linalool), essential oils (sandalwood oil, ylang-ylang oil) and other botanical products. 101
INGREDIENTS OF PROPOLIS
Chemical Composition of Poplar-Type Propolis
The chemical composition of propolis is highly variable, mainly due to the variability of plant species growing around the hive, from which the bees collect the exudates. Geographic location therefore is a major determinant of the composition. Propolis from temperate regions (poplar-type propolis), for example, differs considerably from Brazilian green and red propolis. 1 Generally speaking, crude propolis is composed of 50% resin and vegetable balsam (which contains the biologically active compounds), 35% waxes (mainly beeswax, some vegetable waxes), 5–10% aromatic oils, 5% pollen, and minor other substances, including organic debris.
Poplar propolis is the most widely used and the most investigated type of propolis. Up to 2014, over 340 constituents have been identified in this type of propolis from various geographical locations. They included (in order of declining numbers in each category): 44 aromatic acid esters; 42 terpenoids; 37 aromatic acids; 25 aliphatic fatty acids (long-chain) and their esters; 25 aliphatic hydrocarbons and wax esters; 25 amino acids; 22 flavones and flavonols; 17 aliphatic acids (short-chain); 16 glycerol derivatives; 14 flavanones; 13 aldehydes; 12 alcohols; 10 aliphatic acid esters; 9 chalcones; 9 sugars and sugar alcohols; 8 acetophenones and other ketones; 5 dihydrochalcones; 4 steroids and 7 miscellaneous ingredients. A full list of the constituents of poplar-type propolis reported before 2014, written and published by De Groot et al in June 2014, 102 is available and can be downloaded from the author’s website at https://www.antondegroot.com/downloads. For more recent chemical analyses and reviews of poplar-type propolis data, in some of which additional ingredients were identified, please refer to refs.103B104 -108 The composition of Chinese propolis from Chemotechnique was analyzed in refs.17,21 and that of Chinese propolis from SmartPractice (Allergeaze) in ref. 21 ; the results are (partly) presented in the next section.
Analyses of Propolis Used for Preparing Patch Test Allergens
Allergeaze (www.smartpracticeeurope.com) produces test haptens of Chinese propolis (propolis, catalog number NA71) and Brazilian propolis (propolis [B], catalog number NH400). Chemotechnique (www.chemotechnique.se) provides a test hapten with Chinese propolis (propolis, catalog number P-022). Their compositions have recently been studied with chemical analyses.17,21 While the Chinese propolis samples have great compositional similarities, 21 the spectrum of ingredients in Brazilian propolis appears to be quite different from the Chinese varieties.17,21
Chinese Propolis
In the United States, a Chemotechnique propolis test hapten sample, after extraction with ethanol to obtain the crude extract, was analyzed using electrospray ionization mass spectrometry, and compounds were identified via the mzCloud, ChemSpider, and MassList databases. 17 The 6 most abundant compounds identified were prenylgermacrene B, pinocembrin, 16-([ethylcarbamoyl]amino)hexadecanoic acid, (4E)−6-hydroxy-4-octadecenoic acid/bee glue, linoleamide, and MFCD00083068 (which may be propylene glycol dilaurate). A large number of other identified ingredients (too many to reproduce here) were tabulated in Table 4 of the publication. 17 The compositional match between this sample of Chinese propolis and Brazilian propolis (Allergeaze, NH400), which was also investigated with this technique, was low. Only prenylgermacrene B was present in the top 6 of compounds in both Chinese and Brazilian propolis. 17
In Germany/The Netherlands, chemical analyses were performed of 2 raw propolis samples used for preparing Chinese propolis 10% pet. test haptens by Chemotechnique and SmartPractice Europe (brand: Allergeaze). 21 They were analyzed using gas chromatography–mass spectrometry/flame ionization detection (GC-MS/FID) of the volatile components obtained by headspace solid phase microextraction (SPME). In the chromatogram of the Allergeaze sample, the number of detected peaks was 178, of which 74 were identified, accounting for 90.29% of the total peak area. The 15 main components are shown in Table 9, left column. In the chromatogram of the Chemotechnique sample, the number of detected peaks was 195, of which 59 were identified, accounting for 88.58% of the total peak area. The 15 main components are shown in Table 9, right column. 21
Main Components of Chinese Propolis from Allergeaze and Chemotechnique 21
The compositions of the 2 Chinese propolis samples show great similarities. In both preparations, the 4 components with the largest peak areas are the same: (E)-cinnamyl alcohol, 2-phenethyl alcohol, α-curcumene, and guaiol. In addition to these 4, 7 other chemicals are present in the top 15 of both samples: α-bisabolol, bulnesol, α-eudesmol, selinene (one α-, one β-), β-bisabolene, β-eudesmol, and (E)-cinnamaldehyde.
The data of all chemicals identified in the 2 samples with retention times and retention indices, percentages of peak areas, and CAS numbers, are shown in the supporting information accompanying this open access publication. 21
Whereas the compositions of the 2 Chinese propolis samples were very similar, they were very different from the composition of Brazilian propolis, which was also investigated. 21 Please refer to the next section.
Brazilian Propolis
In the United States, a sample of Brazilian propolis patch test material from Allergeaze (catalog number NH400), after extraction with ethanol to obtain the crude extract, was analyzed using electrospray ionization mass spectrometry, and compounds were identified via the mzCloud, ChemSpider, and MassList databases. 17 The 6 most abundant compounds identified were lauryldimethylamine oxide, prenylgermacrene B, (9Z)−9-octadecenamide, an unknown compound (listed as “unknown compound” in Table 2 of this publication, but in the text and the summary is was termed trioctylmethylammonium cation), monocillin VI, and istamycin C1. A large number of other identified ingredients (too many to reproduce here) are tabulated in Table 3 in this publication. 17
The compositional match between this sample of Brazilian propolis and Chinese propolis (Chemotechnique, catalog number P-022), which was also investigated with this technique, was low. Only prenylgermacrene B was present in the top 6 of compounds in both Brazilian and Chinese propolis. Compared with Chinese propolis, the Brazilian sample contained a larger number of flavonoids, chalcones, phenolic and aromatic compounds, terpenes and terpenoid derivatives, alkaloids, and nitrogen-containing and heterocyclic compounds. 17
In Germany/The Netherlands, chemical analysis was performed of a raw propolis sample used for preparing Brazilian propolis 10% pet. by SmartPractice Europe (brand: Allergeaze). 21 The material was analyzed using GC-MS/FID of the volatile components obtained by headspace SPME. In the chromatogram of the Brazilian propolis sample, the number of detected peaks was 245, of which 98 were identified, accounting for 83.98% of the total peak area. The 15 main components are shown in Table 10.
Main Components of Brazilian Propolis Allergeaze 21
The data of 98 chemicals identified in the Brazilian propolis sample with retention times and retention indices, percentages of peak areas, and CAS numbers, are shown in the supporting information accompanying this open access publication. 21 As clearly shows from these data, the composition of Brazilian propolis (Table 10) shows little similarity with that of the Chinese varieties (Table 9).
THE ALLERGENS IN PROPOLIS
In a (limited) number of studies, patients allergic to poplar-type propolis have been tested with a (limited) number of its ingredients. The most important sensitizers — at least of the ones that have been tested—were found to be the esters of caffeic acid: “LB1” (a mixture of 3-methyl-2-butenyl caffeate, 3-methyl-3-butenyl caffeate, 2-methyl-2-butenyl caffeate, phenethyl caffeate, caffeic acid and benzyl caffeate); phenethyl caffeate; benzyl caffeate; 3-methyl-2-butenyl caffeate; and geranyl caffeate. In general, the terpenoids—conform their weak or absent sensitizing potential in animal experiments—appear not to be important sensitizers in propolis. This subject has been fully reviewed in ref. 1 Since 2013, no new studies aimed at identifying the sensitizers in Chinese propolis have been published. The nature of the sensitizers in Brazilian green and red propolis and propolis from other regions has not been investigated.
PRESENCE OF PROPOLIS IN COSMETIC PRODUCTS
To be able to assess the role of cosmetics in sensitization to propolis, it is important to know how frequent the substance is present in these products. The available data is summarized in this section.
Results of Searches in Cosmetics Databases
In the United States, in June 2025, propolis cera was present in 35 products (scored as 0% of all products on file), propolis wax in 23 cosmetics (also scored as 0%), and propolis extract in 819 products on file with the SkinSort database (www.skinsort.com). The latter was scored as 0.9% of all products in the database, which means that the total number of products was around 90,000.
Also in the United States, in February 2025, propolis cera was present in 3, propolis wax in 18, and propolis extract in 178 (0.14%) of 123,000 cosmetic products of which the composition is known in EWG’s Skin Deep Cosmetics Database (http://www.ewg.org/skindeep/).
In the United States, in March 2022, propolis wax was present in 9 and propolis extract in 178 (0.5%) of 35,000 cosmetic products of which the composition is known in FDA’s Voluntary Cosmetic Registration Program (VCRP). 109
In Denmark, in 2017, propolis was present in 25 of 10,067 (0.25%) cosmetic products, of which full compositions were available in the database of the Kemiluppen app. 110
Studies Reported in Dermatitis
In Dermatitis, in the past 12 years, a large number of studies from the United States have been reported investigating the presence of potential allergens in specific products, mostly cosmetics. The results on the presence of propolis in these products are summarized in Table 11. With the exception of beard moisturizers (with a staggering 29% presence of propolis), 120 and 1 propolis hit in 100 body washes/bar soaps, 124 none of the other investigated products categories, of which full data was available, contained products in which propolis was present. In 3, it remained unclear because propolis was not screened for in 1 study 123 and in 2 other publications only the more common allergens were listed.126,127
Frequency of Use of Propolis in Cosmetics, Medical Hand Cleansers, and Diaper Products
Not screened for the presence of propolis.
Propolis was also termed “cera alba,” which is incorrect (propolis cera is correct).
Only ingredients that were present in >10% of the products were listed.
Only the “most common” ingredients were listed.
Other Reports
In a US study, in 2024, propolis was present in 0 of 50 baby cleansers. 129 In another investigation from the United States, performed in 2021, propolis was present in 0 of 209 shampoos. 130 In Brazil, in 2016, propolis was identified in the ingredient list of 9 of 236 (3.8%) cosmetic products and repellents for children. 131
In the United States, in November 2009, the full ingredient lists of 5,416 skin, hair, and cosmetic products marketed by the CVS pharmacy chain were screened by the American Contact Alternatives Group. Their results for propolis are shown below.132B133 -135 However, “beeswax” was also counted as “propolis” (because of alleged adulteration of beeswax with propolis). Therefore, all percentages shown below for “propolis” (except 0%) are unreliable and (grossly) overestimate the actual use of propolis per se in cosmetic products.
In 2009, in the United States, the ingredient lists of 1591 facial cosmetics from one company were screened for the presence of propolis. Propolis was present in 0% of 132 blushers and 38 bronzers, in 11% of 90 concealers, in 0% of 174 eyeliners, in 5% of 304 eyeshadows, in 0% of 457 foundations, in 0% of 140 loose and pressed powders, and in 61% of 256 mascaras. 132 In 2009, in the United States, the ingredient lists of 796 hair products from one company were screened for the presence of propolis. Propolis was present in 3% of 279 shampoos, in 3% of 231 conditioners, and in 2% of 286 styling products. 133 In 2009, in the United States, the ingredient lists of 730 lip cosmetics and dental care products from one company were screened for the presence of propolis. Propolis was present in 42% of 31 lip liners, in 21% of 429 lipsticks, in 61% of 92 lip moisturizers (probably all or nearly all beeswax/cera alba in these lip cosmetics), in 0% of 153 toothpastes, and in 0% of 25 mouth washes. 134 In 2009, in the United States, the ingredient lists of 657 miscellaneous cosmetics from one company were screened for the presence of propolis. Propolis was present only in 13% of 201 sunblocks. 135
From the data shown here and our own unpublished observations on the presence of propolis in cosmetic products in The Netherlands, we feel it can be safely stated that the use of propolis in cosmetics in the United States and Europe is (very) limited. The origin of propolis in these products (Chinese, Brazilian, other) is always unknown. Chinese propolis (poplar-type) is considered to be the most widely used type. Indeed, in Germany, in the period 2013–2019, propolis from Brazil consistently had a relatively small share in imported propolis (maximum 16.9% in 2015). 24
From the results of searching in the 3 cosmetics databases (SkinSort, EWG’s Skin Deep Cosmetics Database, FDA’s VCRP), it is clear that “propolis” is most often used in cosmetics as “propolis extract.” Whether such extracts contain the same haptens as those that induce positive propolis patch test reactions is unknown.
The Role of Cosmetics in Sensitization to Propolis
When comparing the very limited presence of propolis in cosmetic products with frequencies of positive patch test reactions to Chinese propolis observed in the United States and Europe (roughly 2–3.5%; Table 1), we conclude that few sensitizations to propolis are caused by contact with bee glue in cosmetics. Other propolis-containing products may be involved, but the majority of cases of positive patch test reactions to propolis are very likely the result of (pseudo-)cross-reactions in patients previously sensitized to fragrances, which also applies to Brazilian propolis.12,13,23
OTHER INFORMATION
Late Positive Patch Test Reactions
In the United States, the Mayo Clinic Contact Dermatitis Group (3 hospitals) in the period 2007–2013 patch tested 166 patients with propolis 10% (selection process not entirely clear) and 4 (2.4%) had a negative reaction at D5 but macular erythema at D7 or later. Although macular erythema (?+) is generally not considered to be a positive (allergic) response, these reactions were scored as relevant. Whether there were also patients with positive reactions at D5 who were negative before the D5 reading was not mentioned. It was concluded that a patch test reading schedule that includes late readings (day 7 or later) is particularly useful for propolis. Somewhat curiously, the authors considered propolis to be a preservative. 136
Five years later, investigators from the Mayo Clinic from Scottsdale presented data of “late delayed” positive reactions from 2001 to 2020 (probably overlap with the study presented in ref.136,137). “Late delayed” positive reactions were defined as any patch tests that were initially negative from days 4 to 7 yet became positive after day 8. Now, of 416 patients patch tested with propolis whose reactions had been read >day 7, 2 (0.5%) had delayed weak positive reactions, which were not relevant. 137
In 2019–2021, in Slovenia, 748 consecutive patients were patch tested with Chinese propolis 10% pet., and 30 (4.0%) had a positive reaction. In 7 of the 30 patients, the patch tests were first positive at D6/D7. 34 This means, when the results can be confirmed by others, that >20% of sensitizations to propolis may be missed when late readings at D6 or D7 are not performed.
Patch Test Sensitization
Patch test sensitization to propolis 10% pet. appears to be very rare. During 2016–2017, in a multicenter study performed in western Sweden, 722 consecutive patients were patch tested with propolis from China, Lithuania, North America (which recently proved in fact to be Chinese propolis) and Sweden, all 10% pet. 93 45 of the 722 patients (6.2%) had positive patch test reactions to any of the types of propolis. Two late reactions were recorded. The first patient reacted on day 24 after the application of patch tests to propolis from China (Chemotechnique) and North America (Allergeaze). Three months later, the patient was retested and now had positive reactions on D3 to both propolis types. The second patient reacted on day 11 after application to propolis from Sweden and Lithuania and to Myroxylon pereirae resin. Retesting 5 months later yielded positive reactions on day 3 to all 3 test materials. 93 These data are very suggestive of patch test sensitization to propolis in the first patient and in the second patient to propolis (with cross-reaction to Myroxylon pereirae), to Myroxylon pereirae resin (with cross-reactions to the propolis samples), or to both.
