The estimation of permitted daily exposure (PDE) values for Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms, balsamum (balsam of Peru) for regulatory toxicology purposes: application of various toxicological strategies.

Myroxylon pereirae resin (MP; balsam of Peru) is a botanical balsam which is derived from a tree known as Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms, balsamum. This natural substance has a long history of medicinal use (antiseptic and for wound healing) but surprisingly there is a lack of toxicological data. The medicinal application of Peru balsam has been documented throughout a period of at least 30 years, however, due to the high risk of sensitisation and other treatment options available in the proposed indication, the medicinal use of MP in EU today is limited. The aim of this article is deriving Permitted Daily Exposure (PDE) values for MP for regulatory purposes using various toxicological strategies due to the problems with toxicological data. The results described in this article fills a gap in the literature on toxicological aspects of MP for the first time.

Patch testing with aluminium Finn Chambers could give false-positive reactions in patients with contact allergy to aluminium.

BACKGROUND: Earlier laboratory studies have shown that sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride trigger the release of aluminium (Al) from Finn Chambers (FC). OBJECTIVES: To investigate whether aluminium realease from FC could influence the diagnostic outcome of patch testing with FC. METHOD: A retrospective analysis of patch test results from 2010 to 2019 was performed. A two-sided Fisher's exact test was used to calculate any overrepresentation of contact allergy to Al among patients with positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride. RESULTS: A total of 5446 patients had been tested with FC during the study period. There was a significant overrepresentation of contact allergy to Al among patients with positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride. Patients with a strong Al allergy had significantly higher amounts of concomitant reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride compared to patients with weak Al allergy. These results were not seen for patients tested with Finn Chambers AQUA. CONCLUSION: In patients with contact allergy to Al, patch testing with Finn chambers could give false-positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride.

Fragrance- and Botanical-Related Allergy and Associated Concomitant Reactions: A Retrospective Analysis of the North American Contact Dermatitis Group Data 2007-2016.

IMPORTANCE: When fragrance- and botanical-related (F/BR) allergy is identified, concomitant reaction (CR) frequencies can help direct avoidance recommendations. OBJECTIVE: This study aimed to determine the CR rates for F/BR allergens. DESIGN: A retrospective cross-sectional analysis of the North American Contact Dermatitis Group data 2007-2016 was conducted. Frequencies of demographics, positive reactions, strength of reactions, trends, and CR rates were calculated. RESULTS: A total of 5504 (22.7%) of 24,246 patients had F/BR allergic reactions. The F/BR-sensitive patients were more likely to be female, older than age 40 years, and White and have face, leg, or anal/genital dermatitis. Top allergens included fragrance mix I (FMI, 10.6%), Myroxylon pereirae (balsam of Peru [BOP], 8%), and fragrance mix II (FMII, 4.9%). There were increasing trends for FMI, FMII, cinnamic aldehyde, and Compositae mix and decreasing trends for BOP and propolis. When patients were positive to any F/BR allergen, they were likely to be positive to FMI, FMII, and BOP. Concomitant reactions were bidirectional between multiple fragrance allergens and propolis, colophony, and Compositae mix. CONCLUSIONS: Concomitant reactions were identified between fragrances, between fragrances and BR allergens, and between BR allergens and fragrances. If CRs of greater than 10% suggest cross-reactivity, then all patients with fragrance sensitivity should avoid BR allergens and vice versa.

Molecular profiling of Peru Balsam reveals active ingredients responsible for its pharmaceutical properties.

Peru Balsam, a resinous substance derived from Myroxylon balsamum var. pereirae, has historically been used as a topical ointment for various skin conditions such as scabies, poorly healing wounds, eczema, and haemorrhoids. The ingredients responsible for these properties are not fully elucidated. We investigated the chemical composition of two Peru Balsam samples, one historical and one modern, using gas chromatography/mass spectrometry to identify the active ingredients responsible for its pharmaceutical properties. Both Peru Balsam specimens investigated had similar compositions, showing the stability of the substance. Components identified are effective against scabies, exhibit antimicrobial activity and aid skin penetration. These properties are consistent with historical uses of Peru Balsam. Several ingredients are also known allergens. This study, combining chemical information with scientific literature related to pharmaceutical properties of natural substances, represents a breakthrough in the elucidation of active ingredients in Peru Balsam.

"Peruvian balsam": an example of transoceanic transfer of medicinal knowledge.

BACKGROUND: Connections between China and the new Spanish colonies in America are known for an exchange of silver for silks and porcelains. That also medicinal drugs and medicinal knowledge crossed the Pacific Ocean is hardly known or discussed. Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms ("New World" or "Peruvian balsam") is a botanical balsam that has a long history of medicinal use, particularly as antiseptic and for wound healing. Except for a Chinese article discussing the reception of balsam in China and Japan, no scientific studies on its impact in China and Japan and the channels of transfer from the Americas to Asia exist. METHODS: Description: (1) This section provides a general introduction into Commiphora gileadensis ("Old World" balsam) as a medicinal category and discusses the specific medicinal properties of Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms. The section "Historical research and uses" provides a brief survey on some historical analyses of balsam. Aim, design, setting: (2) Applying a comparative textual and archaeological analysis the article critically examines Chinese and Japanese sources (texts, maps) to show (i) what Chinese and Japanese scholars knew about balsam, (ii) where and how it was used, and (iii) to identify reasons why the "digestion" of knowledge on balsam as a medicinal developed so differently in China and Japan. RESULTS AND DISCUSSION: This chapter discusses the introduction of "Peruvian balsam" into, its uses as a medicinal as well as its scholarly reception in early modern China and Japan and introduces the channels of transmission from Spanish America to Asia. It is shown that Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms was partly a highly valued substance imported from the Americas into China and Japan. But the history of the reception of medicinal knowledge on Peruvian balsam was significantly different in China and Japan. CONCLUSIONS: In Japan, the knowledge on Myroxylon balsamum was continuously updated, especially through mediation of Dutch physicians; Japanese scholars, doctors and pharmacists possessed a solid knowledge on this balsam, its origin and its medicinal uses. In China, on the contrary, there was no further "digestion" or development of the knowledge on either Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms or Commiphora gileadensis. By the late nineteenth century, related medicinal and even geographic knowledge had mostly been lost. The interest in "balsam" in late Qing scholarship was pure encyclopaedic and philosophic.

FEMA GRAS assessment of natural flavor complexes: Cinnamomum and Myroxylon-derived flavoring ingredients.

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a program for the re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, third in the series, considers NFCs composed primarily of constituents with the 3-phenyl-2-propenyl or a cinnamyl functional group, using the procedure outlined in 2005 and updated in 2018 to evaluate the safety of naturally-occurring mixtures for their intended use as flavor ingredients. The procedure relies on a complete chemical characterization of the NFC intended for commerce and organization of each NFC's chemical constituents into well-defined congeneric groups. The safety of the NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of members of the congeneric groups and the NFC under evaluation. Six NFCs from the Myroxylon and Cinnamomum genera, Balsam Oil, Peru (FEMA 2117), Tolu Balsam Extract (FEMA 3069), Cassia Bark Extract (FEMA 2257), Cassia Bark Oil (FEMA 2258), Cinnamon Bark Extract (FEMA 2290) and Cinnamon Bark Oil (FEMA 2291) were evaluated and affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients.

Evaluation of the antimicrobial and antioxidant activity of 7-hydroxy-4', 6-dimethoxy-isoflavone and essential oil from Myroxylon peruiferum L.f.

This study evaluated the antibacterial, antifungal, and antioxidant effect of 7-hydroxy-4',6-dimethoxy-isoflavone and essential oil of Myroxylon peruiferum. The compound was isolated and its structure elucidated by NMR. The chemical composition of essential oil determined by GC-MS analysis. To evaluation of antimicrobial activity, the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC) were performed. In addition to analysis of antioxidant activity, DPPH radical scavenging tests, iron chelating assay (FIC), antioxidant reducing power assay (FRAP) and ß-carotene bleaching assay (BCB) were performed. For the essential oil were identified 24 organized compounds having as main constituents; Germacrene D (17.2%), α-pinene (14.8%) and E-caryophyllene (10.8%). The results showed that isoflavone (2000 to 156 µg/mL) and essential oil (5.0 to 1.25%) present antibacterial and antifungal activity against Gram-positive bacteria and filamentous fungi. The isoflavone and the essential oil also presented antioxidant activity in all the tests, mainly on inhibition of the oxidation of ß-carotene test concentrations ranging from 60 to 100%. In conclusion, isoflavone and essential oil from M. peruiferum present an antimicrobial alternative against Gram-positive bacteria, especially of the genus Staphylococcus and dermatophyte fungi of the genus Trichophyton, as well as a natural compound antioxidant.

Prevalence of contact allergy in the general population: A systematic review and meta-analysis.

BACKGROUND: Contact allergy and allergic contact dermatitis are frequent conditions in the general population. OBJECTIVES: To provide an updated estimate of the prevalence of contact allergy in the general population based on data from our previous review combined with new data from an updated search for relevant studies published between 2007 and 2017. METHODS: Two authors independently searched PubMed for studies reporting on the prevalence of contact allergy in samples of the general population. Proportion meta-analyses were performed to calculate the pooled prevalence estimates of contact allergy. RESULTS: A total of 28 studies were included in the analysis, covering 20 107 patch tested individuals from the general population. Overall, the pooled prevalence of contact allergy was 20.1% (95% confidence interval [CI]: 16.8%-23.7%). In children and adolescents (<18 years), the prevalence was 16.5% (95%CI: 13.6%-19.7%). The prevalence was significantly higher in women (27.9% [95%CI: 21.7%-34.5%]) than in men (13.2% [95%CI: 9.3%-17.6%]). The most common allergen was nickel (11.4% [95%CI: 9.4%-13.5%]), followed by fragrance mix I (3.5% [95%CI: 2.1%-5.4%]), cobalt (2.7% [95%CI: 2.1%-3.4%]), Myroxylon pereirae (1.8% [95%CI: 1.0%-2.7%]), chromium (1.8% [95%CI: 1.3%-2.6%]), p-phenylenediamine (1.5% [95%CI: 1.0%-2.1%]), methylchloroisothiazolinone/methylisothiazolinone (1.5% [95%CI: 0.8%-2.5%]), and colophonium (1.3% [95%CI: 1.0%-1.6%]). CONCLUSIONS: This meta-analysis confirmed that at least 20% of the general population are contact-allergic to common environmental allergens. It highlights the need for more effective preventive strategies for common allergens in consumer goods, cosmetics, and the workplace.

Sensitization to fragrances in Spain: A 5-year multicentre study (2011-2015).

BACKGROUND: Fragrance chemicals constitute the second most frequent cause of contact allergy in Spain. There are no data available concerning the individual fragrances that are most frequently involved. OBJECTIVES: To describe the diagnostic contribution provided by specific fragrance series to the results obtained with baseline series fragrance markers by correlating the results of both series. MATERIALS AND METHODS: We performed a 5-year retrospective study of fragrance marker-positive patients tested with specific fragrance series in 23 Spanish centres. We collected the demographic and clinical characteristics, and compared the results of patch tests obtained from different suppliers. RESULTS: Of 19 588 patients patch tested with the Spanish baseline series, 1590 (8.1%) reacted positively to a fragrance marker. Of these, 1013 (63.7%) were patch tested with a fragrance series, and 664 patients reacted positively to at least one individual fragrance other than hydroxyisohexyl 3-cyclohexene carboxaldehyde. Geraniol was the most frequent allergen. Positive reactions to substances not included in fragrance mix (FM) I or FM II were found in 230 patients. Of the 436 FM I-positive patients and the 419 FM II-positive patients, 184 (42%) and 64 (39.1%), respectively, had no positive reactions to fragrance series. In the case of FM I, negative results were more common when individual fragrances were patch tested at low concentrations. CONCLUSIONS: We recommend patch testing all patients positive for any fragrance marker with a specific fragrance series. The correlation between the results of baseline series and fragrance series could be improved by increasing the concentrations of individual fragrances.

Mating System and Effective Population Size of the Overexploited Neotropical Tree (Myroxylon peruiferum L.f.) and Their Impact on Seedling Production.

The reproductive system of a tree species has substantial impact on genetic diversity and structure within and among natural populations. Such information, should be considered when planning tree planting for forest restoration. Here, we describe the mating system and genetic diversity of an overexploited Neotropical tree, Myroxylon peruiferum L.f. (Fabaceae) sampled from a forest remnant (10 seed trees and 200 seeds) and assess whether the effective population size of nursery-grown seedlings (148 seedlings) is sufficient to prevent inbreeding depression in reintroduced populations. Genetic analyses were performed based on 8 microsatellite loci. M. peruiferum presented a mixed mating system with evidence of biparental inbreeding (t^m-t/ = 0.118). We found low levels of genetic diversity for M. peruiferum species (allelic richness: 1.40 to 4.82; expected heterozygosity: 0.29 to 0.52). Based on Ne(v) within progeny, we suggest a sample size of 47 seed trees to achieve an effective population size of 100. The effective population sizes for the nursery-grown seedlings were much smaller Ne = 27.54-34.86) than that recommended for short term Ne ≥ 100) population conservation. Therefore, to obtain a reasonable genetic representation of native tree species and prevent problems associated with inbreeding depression, seedling production for restoration purposes may require a much larger sampling effort than is currently used, a problem that is further complicated by species with a mixed mating system. This study emphasizes the need to integrate species reproductive biology into seedling production programs and connect conservation genetics with ecological restoration.

Patch testing with the European baseline series fragrance markers: a 2016 update.

BACKGROUND: Fragrance contact allergy is common and is currently screened for using the following European baseline series fragrance markers: fragrance mix (FM)I, FMII, Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde. OBJECTIVES: To investigate the validity of patch testing using these fragrance markers in detecting fragrance allergy to 26 individual fragrance substances for which cosmetic ingredient labelling is mandatory within the European Union. METHODS: We conducted a retrospective review of the patch test records of all patients with eczema who underwent testing using the European baseline series, extended with the individual fragrance substances during the period from 2015 to 2016. RESULTS: Overall, 359 patients (17·2%) reacted to one or more allergens from the labelled fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were oxidized linalool [n = 154; 7·4%, 95% confidence interval (CI) 6·3-8·6], oxidized limonene (n = 89; 4·3%, 95% CI 3·4-5·2) and Evernia furfuracea (n = 44; 2·1%, 95% CI 1·5-2·8). Of the 319 patients who reacted to any of the labelled fragrance substances, only 130 (40·8%) also reacted to a baseline series fragrance marker. The sensitivity of our history-taking for detecting fragrance allergy was 25·7%. CONCLUSIONS: Given the evolving trends in fragrance allergy, patch testing with FMI, FMII, M. pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde is no longer sufficient for screening for fragrance allergy.

The current spectrum of contact sensitization in patients with chronic leg ulcers or stasis dermatitis - new data from the Information Network of Departments of Dermatology (IVDK).

BACKGROUND: Patients with lower leg dermatitis, chronic venous insufficiency or chronic leg ulcers have a high prevalence of contact sensitization. OBJECTIVES: To identify the current spectrum of contact allergens in these patients. PATIENTS AND METHODS: Data of the Information Network of Departments of Dermatology on 5264 patients with the above diagnoses from the years 2003 to 2014 (study group) were compared with data on 4881 corresponding patients from 1994 to 2003 (historical control group) and with a current control group without these diagnoses (n = 55 510). RESULTS: Allergic contact dermatitis was diagnosed less frequently in the study group than in the historical control group (25.9% versus 16.9%; p < 0.001), and contact sensitization to most allergens had declined. The allergen spectrum, however, was largely unchanged. Important allergens are Myroxylon pereirae (balsam of Peru) (14.8% positive reactions), fragrance mix I (11.4%), lanolin alcohol (7.8%), colophonium (6.6%), neomycin sulfate (5.0%), cetearyl alcohol (4.4%), oil of turpentine (3.1%), and paraben mix (2.6%). Patch testing with additional series showed sensitization to Amerchol L-101 (9.7%), tert-butyl hydroquinone (8.7%), framycetin sulfate (5.0%), and gentamicin sulfate (3.1%). CONCLUSIONS: Topical preparations for treating the above-mentioned conditions should not contain fragrances, Myroxylon pereirae, and colophonium. The special allergen spectrum has to be considered in patch testing.

Time trends of contact allergy to the European baseline series in Lithuania.

BACKGROUND: Monitoring trends of positive patch test reactions is useful for epidemiological surveillance and contact allergy prevention, and has not previously been reported in Lithuania. OBJECTIVES: To examine and compare changes in the prevalence of contact allergy to European baseline series allergens in adults with suspected contact dermatitis during a 9-year period. METHODS: In this retrospective study, patch test results of 297 consecutive patients, tested with the European baseline series in 2014-2015, were analysed and compared with the data published earlier in Lithuania. RESULTS: The most common allergens were nickel sulfate (30.6%), methylisothiazolinone (MI) (13.5%), methylchloroisothiazolinone (MCI)/MI (7.4%), potassium dichromate (6.1%), cobalt chloride (6.1%), Myroxylon pereirae resin (5.4%), p-phenylenediamine (5.4%), fragrance mix I (4.7%), formaldehyde (4.4%), and methyldibromo glutaronitrile (3.7%). Increases in the prevalence of sensitization to MCI/MI (2.3% in 2006-2008 and 7.4% in 2014-2015; p < 0.0001) and nickel sulfate (16.4% in 2006-2008 and 30.6% in 2014-2015; p < 0.0001) and decreases in the prevalence of sensitization to paraben mix (3.2% in 2006-2008 and 0.3% in 2014-2015; p = 0.006) were observed. Prevalences for the other allergens remained stable or showed a decreasing trend (Myroxylon pereirae resin; p = 0.06). CONCLUSION: This study provides current information on the prevalence of contact allergy in Lithuania. Changing trends in sensitivity to some allergens probably reflect changes in exposure.

Fragrance allergy could be missed without patch testing with 26 individual fragrance allergens.

BACKGROUND: In 2003, the EU Cosmetics Directive stated that 26 fragrance substances must be listed on the cosmetic product ingredient labels. Not all of these 26 fragrance substances are detected by the usual screening markers comprising fragrance mix I, fragrance mix II, and Myroxylon pereirae. OBJECTIVES: To evaluate the usefulness of testing with the 26 individual fragrance substances in addition to the standard fragrance screening markers. MATERIALS AND METHODS: Three hundred and twelve consecutive patients were patch tested with our baseline series and the 26 specific fragrance substances required to be declared on cosmetic product ingredient labels in accordance with the EU Cosmetics Directive. RESULTS: Positive reactions to at least either one of the 26 individual fragrance substances or the usual fragrance screening markers were seen in 84 of 312 patients (26.9%). Fifteen of these 84 patients (17.8%) reacted negatively to the fragrance screening markers. The most common individual fragrance allergens were cinnamyl alcohol (11.2%), cinnamal (9%), and hydroxycitronellal (3.8%). Sixty-two of 312 patients (19.8%) had at least one positive reaction to the fragrance screening markers. CONCLUSION: Additional patch testing with the 26 individual fragrance allergens, or with the commonest fragrance allergens identified within these 26, should be performed to optimize the detection of fragrance allergy. Cinnamyl alcohol and cinnamal are important fragrance allergens in Thailand.

Contact allergy to essential oils cannot always be predicted from allergy to fragrance markers in the baseline series.

BACKGROUND: Essential oils are fragrance substances that are labelled on cosmetic products by their INCI names, potentially confusing consumers. OBJECTIVES: To establish whether contact allergy to essential oils might be missed if not specifically tested for. METHODS: We tested 471 patients with 14 essential oils and 2104 patients with Melaleuca alternifolia oil between January 2008 and June 2014. All patients were tested with fragrance mix I, fragrance mix II, hydroxyisohexyl 3-cyclohexene carboxaldehyde, and Myroxylon pereirae. Three hundred and twenty-six patients were tested with hydroperoxides of limonene and linalool. RESULTS: Thirty-four patients had a +/++/+++ reaction to at least one essential oil. Eleven had no reaction to any of the six marker fragrance substances. Thus, 4 of 11 positive reactions to M. alternifolia oil, 2 of 7 reactions to Cymbopogon flexuosus oil, 1 of 5 reactions to Cananga odorata oil, 3 of 4 reactions to Santalum album oil and 2 of 3 reactions to Mentha piperita oil would have been missed without individual testing. CONCLUSION: A small number of patients who are allergic to essential oils could be missed if these are not specifically tested. Labelling by INCI names means that exposure may not be obvious. Careful inspection of so-called 'natural' products and targeted testing is recommended.

Multicenter Patch Testing With a Resol Resin Based on Phenol and Formaldehyde Within the International Contact Dermatitis Research Group.

BACKGROUND: Contact allergy to phenol-formaldehyde resins (PFRs) based on phenol and formaldehyde is not detected by a p-tertiary-butylphenol-formaldehyde resin included in most baseline patch test series. OBJECTIVE: The aims of this study were to investigate the contact allergy rate to PFR-2 in an international population and to investigate associated simultaneous allergic reactions. METHODS: Thirteen centers representing the International Contact Dermatitis Research Group included PFR-2 into their patch test baseline series during a period of 6 months in 2012. RESULTS: Of 2259 patients tested, 28 (1.2%) reacted to PFR-2. Of those 28 individuals, one had a positive reaction to formaldehyde and 2 to p-tertiary-butylphenol-formaldehyde resin. Simultaneous allergic reactions were noted to colophonium in 3, to Myroxylon pereirae in 5, and to fragrance mix I in 8. CONCLUSIONS: The contact allergy frequency in the tested population (1.2%) merits its inclusion into the international baseline series and possibly also into other baseline series after appropriate investigations. Significantly, overrepresented simultaneous allergic reactions were noted for M. pereirae and fragrance mix I.