{"text_format":"1","workbook":"xlsx","n_sheets":8,"sheets":["ReadMe","Main","Abstract","Log","Notes","Pathway_queries","Sample_queries","Landscape"],"not_rendered":{"charts":0,"images":0,"macros":1,"external_links":0,"defined_names":7,"comments":1,"pivot_tables":0},"unopened":[],"bounds":{"document_bytes":16777216,"sheet_cells":100000,"rows_first":2000,"rows_last":500,"rows_between":2000,"halvings":0,"cell_chars":16384,"cell_head_chars":4096},"cells_cut":0,"cells_raw":0,"read":"whole","date_system":"1900"}

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["Read Me"]
["Abstract Sifter v3",null,"Note:  because of changes expected to PubMed web services, it is important to use a newer version (v3 or above) of the Abstract Sifter.  In the future, you can find new versions here: ftp://newftp.epa.gov/COMPTOX/Sustainable_Chemistry_Data/Chemistry_Dashboard/Abstract_Sifter/"]
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["Recent enhancements:"]
["Filters and Notes work."]
["You can now select many rows and apply the same Note to all of them."]
["Notes now include tags and yes/no/maybe."]
["Blank sifter terms won't cause error."]
["Double-clicking on an article in Notes will bring user to the abstract page. "]
["09/07/2017 - Landscape page col A value changed."]
["09/07/2017 - Can select notes to send to PubMed (instead of all)."]
["09/11/2017 - Fixed formatting on Landscape"]
["10/20/2017 - Some cleanup; changed yes/no/maybe on Notes to string; No author to blanks."]
["10/23/2017 - reformatting"]
["11/2/2017 - toggle for viewing queries on Landscape"]
["11/12/2017 - Review column formatting fix; loop structure on heatmap; form renames"]
["11/14/2017 - Error control on Landscape sheet and entity query expansion"]
["04/24/2018 - Added wrap text to query on row 3, Landscape sheet"]
["04/24/2018 - Row counts on Main changed to avoid 0 in column headers"]
["04/24/2018 - Now records query counts for not-run queries (0 recs and >5000)  on Log sheet"]
["05/02/2018 - added occupational exposure to sample queries"]
["05/30/2018 check on blank sifter terms added"]
["09/20/2018 Lots of changes to the export function and AOP queries"]
["9/26/2018 On Abstract sheet, added button and fuctionality for finding like articles or finding articles citing this article"]
["09/27/2018 Send queries to landscape simplified."]
["10/17/2018  Error control on PubMed retrieval (0 out of headers from bad PubMed … like this over 300?)"]
["10/19/2018  Like this limited to 200 pmids in order to bypass error"]
["10/30/2018  Added superheading to Pathway_queries and Sample_queries sheets; colorization transfers to Landscape."]
["11/05/2018  modified formatting on Sample_queries to Landscape; "]
["11/06/2018  query run updated only if query is run to completion (2 changes); autofilter corrections on Landscape; ReadMe updates."]
["11/09/2018  set title and abstract to null before iteration"]
["11/19/2018  added a timer to slow down Landscape retrieval to come under NLM limits"]
["11/21/2018  note on ReadMe pointing to ftp site"]
["12/19/2018  Landscape page fix - select area for update counts button checked"]
["Version 3"]
["01/29/2019  Colorize PMIDs immediately when taking notes / 2"]
["02/01/2019  PubMed DOM rewrite. Added keywords and PMC flag."]
["02/05/ 2019  works fast - can't add perc notes … like not fixed"]
["02/06/2019  trim abstract AND clean up formatting on Notes sheet"]
["02/08/2019  Fixed log entries for like/citing"]
["02/08/2019  Added nowrap on authors (example 25905296) and citation to ReadMe"]
["02/12/2019 Formatting on pathway queries; font size on query boxes reduced."]
["02/21/2019  Fixed problem with pubyr like Spring 2019 and unwrap Journal title: 24943998[uid] OR 28139124[uid]"]
["02/21/2019  Started reworking pathway_queries to have KE by number when possible"]
["03/06/2019  Pathway queries send col A and B to landscape, not C."]
["07/08/2019  Landscape sheet - no error msg if blank chem/subject cells selected"]
["07/08/2019  Pathway and Sample queries - send only selected AND visible rows to Landscape"]
["08/19/2019  Fixed problem with copy to clipboard from Notes sheet"]
["09/05/2019  Enhanced some sample_queries"]
[]
["HAWC video documentation is available here:   ",null,null,null,"https://www.youtube.com/watch?v=VIgstH82cL0&index=3&list=PLNPQFGpE48NcDKnWBs8eoFZhoQXud-cR3"]

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["Abstract Sifter",null,null,null,null,null,"Query run: (Linalool) AND ((\"allergic\" AND \"contact\" And dermatitis) OR Dermatitis, Allergic Contact[mh])",null,null,"Provided by the USEPA's National Center for Computational Toxicology"]
["v3","Your sifter terms and frequency counts"]
["PMID","linaloo","skin","dermatit","Total","Pub Yr","Title","Review","PMC","Authors","Journal","tiab","LinkPMID"]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M4,M4)","v":24588367},{"$f":"IF(ISBLANK(B$3),0,(LEN($L4) - LEN(SUBSTITUTE(LOWER($L4),LOWER(B$3),\"\")))/LEN(B$3))","v":16},{"$f":"IF(ISBLANK(C$3),0,(LEN($L4) - LEN(SUBSTITUTE(LOWER($L4),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L4) - LEN(SUBSTITUTE(LOWER($L4),LOWER(D$3),\"\")))/LEN(D$3))","v":3},{"$f":"SUM(B4:D4)","v":19},2014,"Air-oxidized linalool elicits eczema in allergic patients - a repeated open application test study.",0,0,"Andersch Björkman, Hagvall, Siwmark, Niklasson, Karlberg, Bråred Christensson","Contact dermatitis","Air-oxidized linalool elicits eczema in allergic patients - a repeated open application test study.    Abstract:  Title:  Linalool is a commonly used fragrance terpene that forms potent sensitizers upon oxidation. In a recent multicentre study, we found that 7% of 2900 patients showed positive patch test reactions to oxidized linalool at 6.0%. No elicitation studies have been performed. To identify threshold concentrations for elicitation of allergic contact dermatitis caused by oxidized linalool in allergic individuals with repeated exposures. Repeated open application tests were performed in 6 participants previously diagnosed with contact allergy to oxidized linalool. Creams containing 3.0%, 1.0% and 0.30% oxidized linalool (corresponding to 0.56%, 0.19% and 0.056% linalool hydroperoxides, respectively) and 'fine fragrance' containing 1.0%, 0.30% and 0.10% oxidized linalool (corresponding to 0.19%, 0.056% and 0.019% linalool hydroperoxides, respectively) were used twice daily for up to 3 weeks. Patch testing with a dilution series of oxidized linalool was performed. Five of 6 participants reacted to the cream containing 3% oxidized linalool. With 1% oxidized linalool, a reaction was seen in 3 (cream) and 4 (fine fragrance) participants, respectively. With 0.3% oxidized linalool, 2 (cream) and 1 (fine fragrance) participants reacted. Repeated exposure to low concentrations of oxidized linalool can elicit allergic contact dermatitis in previously sensitized individuals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS: Allergens, Monoterpenes, Perfume, linalool, Adult, Allergens/administration & dosage/metabolism, Dermatitis, Allergic Contact/diagnosis/etiology, Female, Humans, Male, Medication Adherence, Middle Aged, Monoterpenes/administration & dosage/metabolism, Oxidation-Reduction, Patch Tests/methods, Perfume/adverse effects, Young Adult  allergic eczema, autoxidation, contact allergy, fragrance terpenes, hydroperoxides, linalool, oxidation products, repeated open application test",24588367]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M5,M5)","v":12492549},{"$f":"IF(ISBLANK(B$3),0,(LEN($L5) - LEN(SUBSTITUTE(LOWER($L5),LOWER(B$3),\"\")))/LEN(B$3))","v":13},{"$f":"IF(ISBLANK(C$3),0,(LEN($L5) - LEN(SUBSTITUTE(LOWER($L5),LOWER(C$3),\"\")))/LEN(C$3))","v":3},{"$f":"IF(ISBLANK(D$3),0,(LEN($L5) - LEN(SUBSTITUTE(LOWER($L5),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B5:D5)","v":17},2002,"Investigation of the skin sensitizing activity of linalool.",0,0,"Basketter, Wright, Colson, Patlewicz, Pease","Contact dermatitis","Investigation of the skin sensitizing activity of linalool.    Abstract:  Title:  An increasing range of chemicals appears to be capable of causing skin sensitization as a result of their capacity to undergo air oxidation (autoxidation) with the consequent formation of reactive species such as epoxides and hydroperoxides. In this small investigation, the ability of linalool, a common fragrance ingredient, to cause such effects was quantified using the local lymph node assay before and after careful purification by vacuum distillation. The commercially available grade of linalool (97% purity) was shown to be a weak skin sensitizer. Various impurities, including linalool oxide, dihydrolinalool, epoxylinalool, 3-hexenyl butyrate and 3,7-dimethyl-1,7-octadiene-3,6-diol were identified and were completely removed (except for the dihydrolinalool remaining at 1.4%) and the re-purified linalool retested. Neither linalool or dihydrolinalool are protein-reactive compounds. The sensitization potency of the re-purified linalool sample was considerably reduced, but not entirely eliminated, suggesting either that an allergenic impurity could be very quickly reformed by mechanisms of activation or that certain potent undetectable allergens remained. Both possibilities are consistent with what is understood of the chemistry and composition of commercially available linalool.  KEYWORDS: Monoterpenes, Perfume, linalool, Dermatitis, Allergic Contact/diagnosis/etiology, Dose-Response Relationship, Drug, Humans, Immunization, Monoterpenes/adverse effects/chemistry, Patch Tests/methods, Perfume/adverse effects, Sensitivity and Specificity",12492549]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M6,M6)","v":26918793},{"$f":"IF(ISBLANK(B$3),0,(LEN($L6) - LEN(SUBSTITUTE(LOWER($L6),LOWER(B$3),\"\")))/LEN(B$3))","v":12},{"$f":"IF(ISBLANK(C$3),0,(LEN($L6) - LEN(SUBSTITUTE(LOWER($L6),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L6) - LEN(SUBSTITUTE(LOWER($L6),LOWER(D$3),\"\")))/LEN(D$3))","v":5},{"$f":"SUM(B6:D6)","v":17},2016,"Oxidized limonene and oxidized linalool - concomitant contact allergy to common fragrance terpenes.",0,0,"Bråred Christensson, Karlberg, Andersen, Bruze, Johansen, Garcia-Bravo, Giménez Arnau, Goh, Nixon, White","Contact dermatitis","Oxidized limonene and oxidized linalool - concomitant contact allergy to common fragrance terpenes.    Abstract:  Title:  Limonene and linalool are common fragrance terpenes. Both oxidized R-limonene and oxidized linalool have recently been patch tested in an international setting, showing contact allergy in 5.2% and 6.9% of dermatitis patients, respectively. To investigate concomitant reactions between oxidized R-limonene and oxidized linalool in consecutive dermatitis patients. Oxidized R-limonene 3.0% (containing limonene hydroperoxides 0.33%) and oxidized linalool 6% (linalool hydroperoxides 1%) in petrolatum were tested in 2900 consecutive dermatitis patients in Australia, Denmark, Singapore, Spain, Sweden, and the United Kingdom. A total of 281 patients reacted to either oxidized R-limonene or oxidized linalool. Of these, 25% had concomitant reactions to both compounds, whereas 29% reacted only to oxidized R-limonene and 46% only to oxidized linalool. Of the 152 patients reacting to oxidized R-limonene, 46% reacted to oxidized linalool, whereas 35% of the 200 patients reacting to oxidized linalool also reacted to oxidized R-limonene. The majority of the patients (75%) reacted to only one of the oxidation mixtures, thus supporting the specificity of the reactions. The concomitant reactions to the two fragrance allergens suggest multiple sensitizations, which most likely reflect the exposure to the different fragrance materials in various types of consumer products. This is in accordance with what is generally seen for patch test reactions to fragrance materials. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS: Cyclohexenes, Monoterpenes, Perfume, Terpenes, Limonene, linalool, Australia/epidemiology, Cohort Studies, Cyclohexenes/adverse effects, Denmark/epidemiology, Dermatitis, Allergic Contact/diagnosis/epidemiology/etiology, Humans, Limonene, Monoterpenes/adverse effects, Oxidation-Reduction, Patch Tests, Perfume/adverse effects, Singapore/epidemiology, Spain/epidemiology, Sweden/epidemiology, Terpenes/adverse effects, United Kingdom/epidemiology  allergic contact dermatitis, autoxidation, concomitant reactions, fragrance allergy, hydroperoxides, limonene, linalool, oxidation products, patch test concentration, patch testing",26918793]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M7,M7)","v":22906042},{"$f":"IF(ISBLANK(B$3),0,(LEN($L7) - LEN(SUBSTITUTE(LOWER($L7),LOWER(B$3),\"\")))/LEN(B$3))","v":12},{"$f":"IF(ISBLANK(C$3),0,(LEN($L7) - LEN(SUBSTITUTE(LOWER($L7),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L7) - LEN(SUBSTITUTE(LOWER($L7),LOWER(D$3),\"\")))/LEN(D$3))","v":4},{"$f":"SUM(B7:D7)","v":16},2012,"Air-oxidized linalool: a frequent cause of fragrance contact allergy.",0,0,"Bråred Christensson, Andersen, Bruze, Johansen, Garcia-Bravo, Gimenez Arnau, Goh, Nixon, White","Contact dermatitis","Air-oxidized linalool: a frequent cause of fragrance contact allergy.    Abstract:  Title:  Linalool is a common fragrance terpene that, in pure form, is not allergenic or is a very weak allergen. However, linalool autoxidizes on air exposure, and the oxidation products can cause contact allergy. In a Swedish study, oxidized linalool 6.0% in petrolatum (pet.) gave 5% positive patch test reactions in 2500 dermatitis patients. To investigate whether oxidized linalool 6%, with a stable concentration of the main haptens, the linalool hydroperoxides (Lin-OOHs) in pet., could be a useful tool for the detection of contact allergy in an international setting. Methods. Oxidized linalool 6.0% (Lin-OOHs 1%) pet. was tested in 2900 consecutive dermatitis patients in Denmark, the United Kingdom, Singapore, Spain, Sweden, and Australia. Overall, 6.9% (range 3-13%) of the patients showed positive patch test reactions to oxidized linalool. Doubtful reactions were found in 9.2% of the patients (range 0-36%). Few irritant reactions were seen. In an international setting, oxidized linalool has been shown to be a common allergen. Oxidized linalool 6.0% (Lin-OOHs 1%) pet. is a useful, standardized and stable tool for the detection of contact allergy in dermatitis patients. Many patients showing positive patch test reactions to oxidized linalool would not have been informed of their fragrance allergy if this specific test had not been performed. © 2012 John Wiley & Sons A/S.  KEYWORDS: Haptens, Monoterpenes, Perfume, linalool, Adult, Air, Australia, Dermatitis, Allergic Contact/diagnosis/etiology, Dose-Response Relationship, Drug, Europe, Female, Haptens/adverse effects/chemistry, Humans, Male, Middle Aged, Monoterpenes/adverse effects/chemistry, Oxidation-Reduction, Patch Tests, Perfume/adverse effects/chemistry, Singapore",22906042]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M8,M8)","v":15606147},{"$f":"IF(ISBLANK(B$3),0,(LEN($L8) - LEN(SUBSTITUTE(LOWER($L8),LOWER(B$3),\"\")))/LEN(B$3))","v":12},{"$f":"IF(ISBLANK(C$3),0,(LEN($L8) - LEN(SUBSTITUTE(LOWER($L8),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L8) - LEN(SUBSTITUTE(LOWER($L8),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B8:D8)","v":14},2004,"Contact allergens formed on air exposure of linalool. Identification and quantification of primary and secondary oxidation products and the effect on skin sensitization.",0,0,"Sköld, Börje, Harambasic, Karlberg","Chemical research in toxicology","Contact allergens formed on air exposure of linalool. Identification and quantification of primary and secondary oxidation products and the effect on skin sensitization.    Abstract:  Title:  Linalool (3,7-dimethyl-1,6-octadien-3-ol) is an important fragrance chemical, frequently used in scented products because of its fresh, flowery odor. Linalool is an unsaturated hydrocarbon and is therefore susceptible to oxidation in the presence of air. The primary oxidation products, that is, hydroperoxides, formed in the autoxidation process, are reactive compounds that can be suspected to act as sensitizers. In the present investigation, we studied the autoxidation of linalool with emphasis on the formation of hydroperoxides. The oxidation products were isolated using flash chromatography and preparative HPLC and were identified with NMR and GC/MS, using synthesized reference compounds. Two hydroperoxides and several different secondary oxidation products were identified, among which some contain structural features that make them potential allergens. The amounts of linalool and the major oxidation products were quantified over time, using GC and an HPLC-method, suitable for the analysis of thermolabile primary oxidation products. The hydroperoxide 7-hydroperoxy-3,7-dimethylocta-1,5-diene-3-ol was found to be present in 15% in an oxidized sample. The local lymph node assay (LLNA) was used to investigate the sensitizing potential of pure linalool, two samples of air-exposed linalool, and oxidation products of linalool (an alpha,beta-unsaturated aldehyde, a mixture of two hydroperoxides, and an alcohol). Pure linalool showed no sensitizing potential. The air-exposed samples of linalool produced clearly positive responses, and the hydroperoxides were the strongest allergens of the tested oxidation products. The study demonstrates the importance of autoxidation on the sensitizing potential of linalool. We also conclude that the sensitizing potential differs with the composition of the oxidation mixture and thus with the air exposure time.  KEYWORDS: Allergens, Monoterpenes, Perfume, Hydrogen Peroxide, linalool, Allergens/chemistry/immunology, Chromatography, High Pressure Liquid, Dermatitis, Allergic Contact/immunology, Humans, Hydrogen Peroxide/analysis, Local Lymph Node Assay, Monoterpenes/chemistry/immunology/metabolism, Oxidation-Reduction, Perfume/chemistry, Time Factors",15606147]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M9,M9)","v":12084079},{"$f":"IF(ISBLANK(B$3),0,(LEN($L9) - LEN(SUBSTITUTE(LOWER($L9),LOWER(B$3),\"\")))/LEN(B$3))","v":12},{"$f":"IF(ISBLANK(C$3),0,(LEN($L9) - LEN(SUBSTITUTE(LOWER($L9),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L9) - LEN(SUBSTITUTE(LOWER($L9),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B9:D9)","v":14},2002,"Studies on the autoxidation and sensitizing capacity of the fragrance chemical linalool, identifying a linalool hydroperoxide.",0,0,"Sköld, Börje, Matura, Karlberg","Contact dermatitis","Studies on the autoxidation and sensitizing capacity of the fragrance chemical linalool, identifying a linalool hydroperoxide.    Abstract:  Title:  Fragrances are among the most common causes of allergic contact dermatitis. The two monoterpenes linalool and d-limonene are the most frequently incorporated fragrance chemicals in scented products. Previous studies on d-limonene show that this monoterpene oxidizes on air exposure (autoxidation) and that allergenic oxidation products are formed. Due to structural similarities, linalool might also form allergenic oxidation products on air exposure. The aim of the present study was to study the autoxidation of linalool and to investigate the sensitizing potential of linalool before and after air exposure. Linalool was oxidized for 10 weeks and gas chromatographic analyses showed that the content of linalool decreased to about 80%. The chromatograms revealed the formation of other compounds during oxidation. One of the major oxidation products was isolated and identified as 7-hydroperoxy-3,7-dimethyl-octa-1,5-diene-3-ol. This substance is, to the best of our knowledge, described for the first time. In sensitization studies in guinea pigs, linalool of high purity gave no reactions, while linalool that had been oxidized for 10 weeks sensitized the animals. It is concluded that autoxidation of linalool is essential for its sensitizing potential.  KEYWORDS: Monoterpenes, Perfume, Terpenes, linalool, Animals, Chromatography, Gas, Dermatitis, Allergic Contact/etiology, Guinea Pigs, Monoterpenes, Perfume/adverse effects/chemistry, Terpenes/adverse effects/chemistry",12084079]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M10,M10)","v":20136877},{"$f":"IF(ISBLANK(B$3),0,(LEN($L10) - LEN(SUBSTITUTE(LOWER($L10),LOWER(B$3),\"\")))/LEN(B$3))","v":11},{"$f":"IF(ISBLANK(C$3),0,(LEN($L10) - LEN(SUBSTITUTE(LOWER($L10),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L10) - LEN(SUBSTITUTE(LOWER($L10),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B10:D10)","v":13},2010,"Linalool--a significant contact sensitizer after air exposure.",0,0,"Christensson, Matura, Gruvberger, Bruze, Karlberg","Contact dermatitis","Linalool--a significant contact sensitizer after air exposure.    Abstract:  Title:  Linalool is a widely used fragrance terpene. Pure linalool is not allergenic or a very weak allergen, but autoxidizes on air exposure and the oxidation products can cause contact allergy. Oxidized (ox.) linalool has previously been patch tested at a concentration of 2.0% in petrolatum (pet.) in 1511 patients, and 1.3% positive patch test reactions were observed. To investigate the optimal patch test concentration for detection of contact allergy to ox. linalool. Four concentrations of ox. linalool (2.0%, 4.0%, 6.0%, 11.0% pet.) were tested in 3418 consecutive dermatitis patients. Ox. linalool 2.0%, 4.0%, 6.0%, and 11.0% pet. detected positive patch test reactions in 0.83%, 3.2%, 5.3%, and 7.2% of the tested patients, respectively. The doubtful reactions increased with rising concentrations but relatively less, giving 5.1%, 6.4%, and 7.3% doubtful reactions, respectively, for ox. linalool 4.0%, 6.0%, and 11.0% pet. Few irritative reactions were seen. Raising the patch test concentration for ox. linalool gave a better detection of contact allergy, as many as 5-7% positive patch test reactions were detected. We suggest a patch test concentration of ox. linalool 6.0% pet. for future patch testing, giving a dose per unit area of 2.4 mg/cm(2) when 20 mg test substance is tested in small Finn Chambers.  KEYWORDS: Haptens, Monoterpenes, Perfume, Petrolatum, linalool, Air, Dermatitis, Allergic Contact/diagnosis/epidemiology/etiology, Dose-Response Relationship, Drug, Female, Haptens/adverse effects/chemistry, Humans, Male, Monoterpenes/adverse effects/chemistry, Oxidation-Reduction, Patch Tests, Perfume/adverse effects, Petrolatum/chemistry, Sweden/epidemiology",20136877]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M11,M11)","v":28885310},{"$f":"IF(ISBLANK(B$3),0,(LEN($L11) - LEN(SUBSTITUTE(LOWER($L11),LOWER(B$3),\"\")))/LEN(B$3))","v":9},{"$f":"IF(ISBLANK(C$3),0,(LEN($L11) - LEN(SUBSTITUTE(LOWER($L11),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L11) - LEN(SUBSTITUTE(LOWER($L11),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B11:D11)","v":10},2017,"Contact Allergy to Hydroperoxides of Linalool and D-Limonene in a US Population.",0,0,"Nath, Liu, Green, Atwater","Dermatitis : contact, atopic, occupational, drug","Contact Allergy to Hydroperoxides of Linalool and D-Limonene in a US Population.    Abstract:  Title:  Linalool and D-limonene are common fragrance ingredients that readily oxidize on exposure to air. The resulting hydroperoxides of linalool and D-limonene have been shown to have high frequencies of positive patch test reactions in several European and international studies. The aim of the study was to investigate the prevalence of contact allergy to the hydroperoxides of linalool and D-limonene in a US population. In this retrospective study, 103 patients with suspected fragrance allergy were patch tested to linalool 10% petrolatum (pet), hydroperoxides of linalool 1% pet, D-limonene 10% pet, and/or the hydroperoxides of D-limonene 0.3% pet between July 9, 2014, and October 25, 2016. In this study, the frequency of positive patch test reactions to the hydroperoxides of linalool is 20% (19/96), and the frequency of positive reactions to the hydroperoxides of D-limonene is 8% (7/90). These high frequencies suggest that patch testing to the hydroperoxides of linalool and limonene should be performed in all patients with suspected fragrance allergy.  KEYWORDS: Cyclohexenes, Monoterpenes, Peroxides, Terpenes, Limonene, linalool, Adult, Aged, Aged, 80 and over, Cyclohexenes/adverse effects, Dermatitis, Allergic Contact/etiology, Female, Humans, Limonene, Male, Middle Aged, Monoterpenes/adverse effects, Patch Tests, Peroxides/adverse effects, Retrospective Studies, Terpenes/adverse effects, United States, Young Adult",28885310]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M12,M12)","v":24702129},{"$f":"IF(ISBLANK(B$3),0,(LEN($L12) - LEN(SUBSTITUTE(LOWER($L12),LOWER(B$3),\"\")))/LEN(B$3))","v":9},{"$f":"IF(ISBLANK(C$3),0,(LEN($L12) - LEN(SUBSTITUTE(LOWER($L12),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L12) - LEN(SUBSTITUTE(LOWER($L12),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B12:D12)","v":11},2014,"Allergy to oxidized limonene and linalool is frequent in the U.K.",0,0,"Audrain, Kenward, Lovell, Green, Ormerod, Sansom, Chowdhury, Cooper, Johnston, Wilkinson, King, Stone, Horne, Holden, Wakelin, Buckley","The British journal of dermatology","Allergy to oxidized limonene and linalool is frequent in the U.K.    Abstract:  Title:  The oxidized forms of the fragrance terpenes limonene and linalool are known to cause allergic contact dermatitis. Significant rates of contact allergy to these fragrances have been reported in European studies and in a recent worldwide study. Patch testing to oxidized terpenes is not routinely carried out either in the U.K. or in other centres internationally. To investigate the prevalence of contact allergy to oxidized limonene and linalool in the U.K. Between 1 August 2011 and 31 December 2012, 4731 consecutive patients in 13 U.K. dermatology departments were tested for hydroperoxides of limonene 0·3% pet., hydroperoxides of linalool 1·0% pet., stabilized limonene 10·0% pet. and stabilized linalool 10·0% pet. Doubtful (?+) and equivocal (±) reactions were grouped together as irritant reactions. Two hundred and thirty-seven patients (5·0%) had a positive patch test reaction to hydroperoxides of limonene 0·3% pet. and 281 (5·9%) to hydroperoxides of linalool 1·0% pet. Irritant reactions to one or both oxidized terpenes were found in 242 patients (7·3%). Eleven patients (0·2%) had a positive patch test reaction to the stabilized terpenes alone. This large, multicentre U.K. audit shows a significant rate of allergy to the hydroperoxides of limonene and linalool plus a high rate of irritant reactions. Testing to the oxidized forms alone captures the majority (97·0%; 411 of 422) of positive reactions; testing to nonoxidized terpenes appears to be less useful. We recommend that the hydroperoxides of limonene and linalool be added to an extended baseline patch test series. © 2014 British Association of Dermatologists.  KEYWORDS: Allergens, Cyclohexenes, Irritants, Monoterpenes, Perfume, Terpenes, Limonene, linalool, Adolescent, Adult, Aged, Aged, 80 and over, Allergens/toxicity, Child, Child, Preschool, Cyclohexenes/toxicity, Dermatitis, Allergic Contact/epidemiology, Female, Humans, Irritants/toxicity, Limonene, Male, Middle Aged, Monoterpenes/toxicity, Patch Tests, Perfume/toxicity, Terpenes/toxicity, United Kingdom/epidemiology, Young Adult",24702129]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M13,M13)","v":30378131},{"$f":"IF(ISBLANK(B$3),0,(LEN($L13) - LEN(SUBSTITUTE(LOWER($L13),LOWER(B$3),\"\")))/LEN(B$3))","v":8},{"$f":"IF(ISBLANK(C$3),0,(LEN($L13) - LEN(SUBSTITUTE(LOWER($L13),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L13) - LEN(SUBSTITUTE(LOWER($L13),LOWER(D$3),\"\")))/LEN(D$3))","v":3},{"$f":"SUM(B13:D13)","v":11},2019,"Contact sensitization to hydroperoxides of limonene and linalool: Results of consecutive patch testing and clinical relevance.",0,1,"Dittmar, Schuttelaar","Contact dermatitis","Contact sensitization to hydroperoxides of limonene and linalool: Results of consecutive patch testing and clinical relevance.    Abstract:  Title:  Hydroperoxides of limonene and linalool are potent sensitizers. To investigate the prevalence of contact allergy to both hydroperoxides of limonene and hydroperoxides of linalool, to report clinical relevance, and to investigate patient demographics. A total of 821 patients (35.6% male, mean age 42.4 years ± 17.8 years) were consecutively patch tested with our departmental baseline series and our fragrance series, including hydroperoxides of limonene 0.3% pet. and hydroperoxides of linalool 1.0% pet. The clinical relevance was assessed for all positive reactions. Positive patch test reactions to hydroperoxides of limonene and to hydroperoxides of linalool were observed in 77 patients (9.4%, 95% confidence interval [CI]: 7.4%-11.4%) and in 96 patients (11.7%, 95%CI: 9.5%-13.9%), respectively; 38 of these patients (4.6%, 95%CI: 3.2%-6.0%) reacted to both. Most reactions were considered to be possibly or probably clinically relevant (66.3% and 68.8%, respectively), and a small proportion were deemed to be of certain clinical relevance (18.2% and 19.8%, respectively). As compared with previous studies, high numbers of positive reactions to both hydroperoxides of limonene and hydroperoxides of linalool were observed, the majority of which were clinically relevant, supporting their inclusion in the European baseline series. © 2018 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.  KEYWORDS: Monoterpenes, Peroxides, Limonene, linalool, Adult, Dermatitis, Allergic Contact/epidemiology/etiology, Female, Humans, Limonene/adverse effects, Male, Middle Aged, Monoterpenes/adverse effects, Patch Tests, Peroxides/adverse effects, Prevalence  allergic contact dermatitis, clinical relevance, contact allergy, fragrances, hydroperoxides of limonene, hydroperoxides of linalool, patch testing",30378131]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M14,M14)","v":19125719},{"$f":"IF(ISBLANK(B$3),0,(LEN($L14) - LEN(SUBSTITUTE(LOWER($L14),LOWER(B$3),\"\")))/LEN(B$3))","v":8},{"$f":"IF(ISBLANK(C$3),0,(LEN($L14) - LEN(SUBSTITUTE(LOWER($L14),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L14) - LEN(SUBSTITUTE(LOWER($L14),LOWER(D$3),\"\")))/LEN(D$3))","v":3},{"$f":"SUM(B14:D14)","v":12},2009,"Air oxidation increases skin irritation from fragrance terpenes.",0,0,"Bråred Christensson, Forsström, Wennberg, Karlberg, Matura","Contact dermatitis","Air oxidation increases skin irritation from fragrance terpenes.    Abstract:  Title:  Linalool and limonene are common fragrance terpenes that autoxidize on air exposure. The pure compounds are not allergenic but their oxidation products can cause contact allergy. Little has been investigated regarding the irritancy of oxidized terpenes. The aim of this study was to investigate the irritating effect of pure and oxidized R-limonene and linalool in concentration series and to study the MNIC (Maximum Non Irritant Concentration) of autoxidized linalool and limonene. Patch testing was performed in dermatitis patients and controls with sequentially diluted concentrations of oxidized and non-oxidized linalool, and oxidized and non-oxidized R-limonene. Readings were made with visual assessment and using laser Doppler imaging. The non-oxidized terpenes were non-irritating in all tested concentrations. Both linalool and especially R-limonene were more irritating after oxidation compared with the pure compounds. No difference in response was seen between dermatitis patients and controls. Autoxidation of the fragrance terpenes linalool and R-limonene increases irritation. Oxidized linalool is less irritating than oxidized R-limonene. In this study, we found no advantages in using laser Doppler technique compared with visual assessment.  KEYWORDS: Allergens, Cyclohexenes, Monoterpenes, Perfume, Terpenes, Limonene, linalool, Adult, Air, Allergens/chemistry/toxicity, Case-Control Studies, Cyclohexenes/chemistry/toxicity, Dermatitis, Allergic Contact/diagnosis/etiology, Female, Humans, Laser-Doppler Flowmetry, Limonene, Male, Middle Aged, Monoterpenes/chemistry/toxicity, Oxidation-Reduction, Patch Tests, Perfume/toxicity, Probability, Statistics, Nonparametric, Terpenes/chemistry/toxicity, Young Adult",19125719]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M15,M15)","v":27896835},{"$f":"IF(ISBLANK(B$3),0,(LEN($L15) - LEN(SUBSTITUTE(LOWER($L15),LOWER(B$3),\"\")))/LEN(B$3))","v":5},{"$f":"IF(ISBLANK(C$3),0,(LEN($L15) - LEN(SUBSTITUTE(LOWER($L15),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L15) - LEN(SUBSTITUTE(LOWER($L15),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B15:D15)","v":7},2017,"Contact sensitization to limonene and linalool hydroperoxides in Spain: a GEIDAC* prospective study.",0,0,"Deza, García-Bravo, Silvestre, Pastor-Nieto, González-Pérez, Heras-Mendaza, Mercader, Fernández-Redondo, Niklasson, Giménez-Arnau","Contact dermatitis","Contact sensitization to limonene and linalool hydroperoxides in Spain: a GEIDAC* prospective study.    Abstract:  Title:  Limonene and linalool are common fragrance terpenes widely used in cosmetic, household and hygiene products. Their primary oxidation products formed after air exposure, the hydroperoxides, have been recognized as important contact haptens. To investigate the prevalence of contact allergy to hydroperoxides of limonene (Lim-OOHs) and hydroperoxides of linalool (Lin-OOHs) in Spain, and to define the optimal concentration for screening in consecutive patients. Three different concentrations of Lim-OOHs (0.1%, 0.2% and 0.3% pet.) and Lin-OOHs (0.25%, 0.5% and 1.0% pet.) were simultaneously tested in 3639 consecutive patients at 22 departments of dermatology in Spain. Lim-OOHs at 0.1%, 0.2% and 0.3% yielded positive patch test reactions in 1.4%, 3.4% and 5.1% of the tested patients, respectively; and Lin-OOHs at 0.25%, 0.5% and 1.0% yielded positive reactions in 1.3%, 2.9% and 4.9% of the tested patients, respectively. Few irritant (1.5-1.9%) and doubtful reactions (0.4-0.5%) to both terpene hydroperoxides were registered at the highest concentrations tested. Lim-OOHs and Lin-OOHs can be considered as common causes of contact allergy, and their inclusion in an extended baseline patch test series therefore seems to be appropriate. The patch test preparations of Lim-OOHs 0.3% pet. and Lin-OOHs 1.0% pet. are useful tools for screening of contact sensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS: Cyclohexenes, Monoterpenes, Perfume, Terpenes, Limonene, Hydrogen Peroxide, linalool, Adolescent, Adult, Aged, Aged, 80 and over, Cyclohexenes/adverse effects, Dermatitis, Allergic Contact/diagnosis/epidemiology/etiology, Female, Humans, Hydrogen Peroxide/adverse effects, Limonene, Male, Middle Aged, Monoterpenes/adverse effects, Oxidation-Reduction, Patch Tests, Perfume/adverse effects, Prevalence, Prospective Studies, Spain/epidemiology, Terpenes/adverse effects, Young Adult  allergic contact dermatitis, fragrance allergy, hydroperoxides, limonene, linalool",27896835]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M16,M16)","v":26671837},{"$f":"IF(ISBLANK(B$3),0,(LEN($L16) - LEN(SUBSTITUTE(LOWER($L16),LOWER(B$3),\"\")))/LEN(B$3))","v":5},{"$f":"IF(ISBLANK(C$3),0,(LEN($L16) - LEN(SUBSTITUTE(LOWER($L16),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L16) - LEN(SUBSTITUTE(LOWER($L16),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B16:D16)","v":7},2016,"Patch Testing with Main Sensitizers Does Not Detect All Cases of Contact Allergy to Oxidized Lavender Oil.",0,0,"Hagvall, Christensson","Acta dermato-venereologica","Patch Testing with Main Sensitizers Does Not Detect All Cases of Contact Allergy to Oxidized Lavender Oil.    Abstract:  Title:  Lavender oil is an essential oil obtained from lavender (Lavendula angustifolia). The main components linalool and linalyl acetate have been shown to autoxidize in contact with oxygen in the air, forming sensitizing hydroperoxides. Patients with suspected allergic contact dermatitis were consecutively patch-tested with oxidized lavender oil 6% pet., oxidized linalyl acetate 6% pet., and oxidized linalool 6% pet. to investigate the frequency of contact allergy to oxidized lavender oil, and the pattern of concomitant reactions to oxidized linalool and oxidized linalyl acetate. Positive reactions to oxidized lavender oil were found in 2.8% of the patients. Among those, 56% reacted to oxidized linalool and/or oxidized linalyl acetate, while 52% reacted to the fragrance markers of the baseline series. Oxidized lavender oil showed among the highest frequencies of contact allergy to studied essential oils. A well-standardized preparation of oxidized lavender oil could be a useful tool for diagnosis of contact allergy to fragrances.  KEYWORDS: Monoterpenes, Oils, Volatile, Plant Oils, linalyl acetate, linalool, lavender oil, Dermatitis, Allergic Contact/diagnosis/immunology, Female, Humans, Male, Middle Aged, Monoterpenes/immunology, Oils, Volatile/chemistry, Oxidation-Reduction, Patch Tests, Plant Oils/chemistry, Sweden",26671837]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M17,M17)","v":15144499},{"$f":"IF(ISBLANK(B$3),0,(LEN($L17) - LEN(SUBSTITUTE(LOWER($L17),LOWER(B$3),\"\")))/LEN(B$3))","v":5},{"$f":"IF(ISBLANK(C$3),0,(LEN($L17) - LEN(SUBSTITUTE(LOWER($L17),LOWER(C$3),\"\")))/LEN(C$3))","v":4},{"$f":"IF(ISBLANK(D$3),0,(LEN($L17) - LEN(SUBSTITUTE(LOWER($L17),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B17:D17)","v":10},2004,"Cytotoxicity of lavender oil and its major components to human skin cells.",0,0,"Prashar, Locke, Evans","Cell proliferation","Cytotoxicity of lavender oil and its major components to human skin cells.    Abstract:  Title:  Lavender (Lavandula angustifolia) oil, chiefly composed of linalyl acetate (51%) and linalool (35%), is considered to be one of the mildest of known plant essential oils and has a history in wound healing. Concerns are building about the potential for irritant or allergenic skin reactions with the use of lavender oil. This study has demonstrated that lavender oil is cytotoxic to human skin cells in vitro (endothelial cells and fibroblasts) at a concentration of 0.25% (v/v) in all cell types tested (HMEC-1, HNDF and 153BR). The major components of the oil, linalyl acetate and linalool, were also assayed under similar conditions for their cytotoxicity. The activity of linalool reflected that of the whole oil, indicating that linalool may be the active component of lavender oil. Linalyl acetate cytotoxicity was higher than that of the oil itself, suggesting suppression of its activity by an unknown factor in the oil. Membrane damage is proposed as the possible mechanism of action.  KEYWORDS: Monoterpenes, Oils, Volatile, Plant Oils, linalyl acetate, linalool, lavender oil, Cell Line, Cell Membrane/drug effects, Cell Survival/drug effects, Dermatitis, Allergic Contact/etiology, Dose-Response Relationship, Drug, Endothelial Cells/drug effects/pathology, Fibroblasts/drug effects/pathology, Humans, Lavandula, Monoterpenes/toxicity, Oils, Volatile/toxicity, Plant Oils/toxicity, Skin/cytology",15144499]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M18,M18)","v":28511284},{"$f":"IF(ISBLANK(B$3),0,(LEN($L18) - LEN(SUBSTITUTE(LOWER($L18),LOWER(B$3),\"\")))/LEN(B$3))","v":4},{"$f":"IF(ISBLANK(C$3),0,(LEN($L18) - LEN(SUBSTITUTE(LOWER($L18),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L18) - LEN(SUBSTITUTE(LOWER($L18),LOWER(D$3),\"\")))/LEN(D$3))","v":3},{"$f":"SUM(B18:D18)","v":7},2017,"Non-mix fragrances are top sensitizers in consecutive dermatitis patients - a cross-sectional study of the 26 EU-labelled fragrance allergens.",0,0,"Bennike, Zachariae, Johansen","Contact dermatitis","Non-mix fragrances are top sensitizers in consecutive dermatitis patients - a cross-sectional study of the 26 EU-labelled fragrance allergens.    Abstract:  Title:  For cosmetics, it is mandatory to label 26 fragrance substances, including all constituents of fragrance mix I (FM I) and fragrance mix II (FM II). Earlier reports have not included oxidized R-limonene [hydroperoxides of R-limonene (Lim-OOH)] and oxidized linalool [hydroperoxides of linalool (Lin-OOH)], and breakdown testing of FM I and FM II has mainly been performed in selected, mix-positive patients. To report the prevalence of sensitization to the 26 fragrances, and to assess concomitant reactivity to FM I and/or FM II. A cross-sectional study on consecutive dermatitis patients patch tested with the 26 fragrances and the European baseline series from 2010 to 2015 at a single university clinic was performed. Of 6004 patients, 940 (15.7%, 95%CI: 14.7-16.6%) were fragrance-sensitized. Regarding the single fragrances, most patients were sensitized to Lin-OOH (3.9%), Evernia furfuracea (3.0%), Lim-OOH (2.5%), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (2.1%). Significantly fewer patients were 'FM I-positive and constituent-positive' than 'FM II-positive and constituent-positive' (32.7% versus 57.0%, p < 0.0001). Additionally, significantly more patients were 'FM II-negative but constituent-positive' than 'FM I-negative but constituent-positive' (12.4% versus 3.2%, p = 0.0008). Non-mix fragrances are the most important single fragrance allergens among consecutive patients. The test concentration of the single FM I constituents should be increased when possible. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS: Aldehydes, Allergens, Cyclohexanols, Cyclohexenes, Monoterpenes, Perfume, Terpenes, Trityl Compounds, linalool oxide, Limonene, hydroxyisohexyl 3-cyclohexene carboxaldehyde, Adult, Aldehydes/adverse effects, Allergens/adverse effects, Cross-Sectional Studies, Cyclohexanols/adverse effects, Cyclohexenes/adverse effects, Denmark/epidemiology, Dermatitis, Allergic Contact/epidemiology/etiology, Female, Humans, Lichens, Limonene, Male, Middle Aged, Monoterpenes/adverse effects, Perfume/adverse effects, Prevalence, Terpenes/adverse effects, Trityl Compounds/adverse effects  26 fragrances, clinical relevance, concomitant reactivity, contact allergy, fragrance mix, non-mix fragrances, oxidized limonene, oxidized linalool",28511284]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M19,M19)","v":28095632},{"$f":"IF(ISBLANK(B$3),0,(LEN($L19) - LEN(SUBSTITUTE(LOWER($L19),LOWER(B$3),\"\")))/LEN(B$3))","v":4},{"$f":"IF(ISBLANK(C$3),0,(LEN($L19) - LEN(SUBSTITUTE(LOWER($L19),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L19) - LEN(SUBSTITUTE(LOWER($L19),LOWER(D$3),\"\")))/LEN(D$3))","v":4},{"$f":"SUM(B19:D19)","v":8},2017,"Severe intractable eyelid dermatitis probably caused by exposure to hydroperoxides of linalool in a heavily fragranced shampoo.",0,1,"Elliott, Ramzy, Nilsson, Moffat, Suzuki","Contact dermatitis","Severe intractable eyelid dermatitis probably caused by exposure to hydroperoxides of linalool in a heavily fragranced shampoo.    Abstract:  Title:  NOABSTRACT. No abstract found.  KEYWORDS: Hair Preparations, Monoterpenes, Perfume, Hydrogen Peroxide, linalool, Child, Dermatitis, Allergic Contact/diagnosis/etiology, Eyelid Diseases/diagnosis/etiology, Facial Dermatoses/diagnosis/etiology, Female, Hair Preparations/adverse effects, Humans, Hydrogen Peroxide/adverse effects, Monoterpenes/adverse effects, Patch Tests, Perfume  allergic contact dermatitis, case report, eyelid dermatitis, fragrances, hydroperoxides of linalool, linalool oxidation products, liquid chromatography-mass spectrometry, patch testing, static headspace gas chromatography-mass spectrometry",28095632]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M20,M20)","v":27251025},{"$f":"IF(ISBLANK(B$3),0,(LEN($L20) - LEN(SUBSTITUTE(LOWER($L20),LOWER(B$3),\"\")))/LEN(B$3))","v":4},{"$f":"IF(ISBLANK(C$3),0,(LEN($L20) - LEN(SUBSTITUTE(LOWER($L20),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L20) - LEN(SUBSTITUTE(LOWER($L20),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B20:D20)","v":6},2017,"Can contact allergy to p-phenylenediamine explain the high rates of terpene hydroperoxide allergy? - An epidemiological study based on consecutive patch test results.",0,0,"Bennike, Lepoittevin, Johansen","Contact dermatitis","Can contact allergy to p-phenylenediamine explain the high rates of terpene hydroperoxide allergy? - An epidemiological study based on consecutive patch test results.    Abstract:  Title:  Contact allergy to linalool hydroperoxides (Lin-OOHs) and limonene hydroperoxides (Lim-OOHs) is common. Similarly to what occurs with the terpene hydroperoxides, reactive intermediates formed from p-phenylenediamine (PPD) can cause oxidative modifications of tryptophan residues on proteins in mechanistic studies. To test the hypothesis that patients sensitized to PPD are at increased risk of concomitant reactivity to either of the terpene hydroperoxides, owing to a 'common pathway' of skin protein oxidation. A database study of consecutively patch tested eczema patients (n = 3843) from 2012 to 2015, tested concomitantly with PPD, Lim-OOHs and Lin-OOHs, was performed. Associations were examined by level of concordance and odds ratios (ORs) adjusted for age, sex, and contact allergy to fragrance mix I and fragrance mix II. Concomitant reactions to PPD were seen in 2.2% of Lim-OOH-positive patients and in 4.9% of Lin-OOH-positive patients. Neither proportion was higher than expected by chance. No association existed between PPD and Lim-OOH patch test reactivity. In a multiple logistic regression analysis, PPD allergy was associated with an insignificantly increased risk (OR 2.11, 95%CI:0.92-4.80) of a positive patch test reaction to Lin-OOHs. PPD sensitization cannot explain the high rates of sensitization to Lin-OOHs and/or Lim-OOHs. Contact allergy to oxidized linalool is more strongly associated with fragrance allergy than with PPD allergy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS: Coloring Agents, Cyclohexenes, Monoterpenes, Phenylenediamines, Terpenes, Limonene, Hydrogen Peroxide, linalool, 4-phenylenediamine, Adult, Coloring Agents/adverse effects, Cyclohexenes/adverse effects, Dermatitis, Allergic Contact/epidemiology/etiology, Epidemiologic Studies, Female, Humans, Hydrogen Peroxide/adverse effects, Limonene, Logistic Models, Male, Middle Aged, Monoterpenes/adverse effects, Multivariate Analysis, Oxidation-Reduction, Patch Tests, Phenylenediamines/adverse effects, Retrospective Studies, Risk Factors, Terpenes/adverse effects  concomitant reactivity, contact allergy, d-limonene, linalool, p-phenylenediamine, patch testing, terpene hydroperoxides",27251025]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M21,M21)","v":18154552},{"$f":"IF(ISBLANK(B$3),0,(LEN($L21) - LEN(SUBSTITUTE(LOWER($L21),LOWER(B$3),\"\")))/LEN(B$3))","v":4},{"$f":"IF(ISBLANK(C$3),0,(LEN($L21) - LEN(SUBSTITUTE(LOWER($L21),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L21) - LEN(SUBSTITUTE(LOWER($L21),LOWER(D$3),\"\")))/LEN(D$3))","v":3},{"$f":"SUM(B21:D21)","v":8},2008,"Autoxidation of linalyl acetate, the main component of lavender oil, creates potent contact allergens.",0,0,"Sköld, Hagvall, Karlberg","Contact dermatitis","Autoxidation of linalyl acetate, the main component of lavender oil, creates potent contact allergens.    Abstract:  Title:  Fragrances are among the most common causes of allergic contact dermatitis. We have in previous studies shown that linalool, present in lavender oil, autoxidizes on air exposure, forming allergenic oxidation products. Oxidized linalool was found to be a frequent cause of contact allergy in a patch test study on consecutive dermatitis patients. Linalyl acetate, the main component of lavender oil is commonly used as a fragrance chemical in scented products. Because of structural similarities, linalyl acetate should also be susceptible to oxidation on air exposure, forming similar oxidation products as linalool. The aim of the present study was to investigate the autoxidation of linalyl acetate and the influence of oxidation on its sensitizing potency. Analyses were performed using gas chromatography, nuclear magnetic resonance spectrometry and mass spectrometry. Sensitizing potencies of compounds were determined using the local lymph node assay (LLNA) in mice. Analyses showed that the content of linalyl acetate decreased over time on air exposure and other compounds were formed. Hydroperoxides, an epoxide and an alcohol were identified as oxidation products from linalyl acetate. In the LLNA, linalyl acetate of high purity showed a weak sensitizing potency (EC3 25%). Autoxidation increased the sensitizing potency of linalyl acetate, and a 10 weeks oxidized sample gave an EC3 value of 3.6%. As for linalool, the hydroperoxides were shown to be the oxidation products with the highest sensitizing potency. It is concluded that autoxidation of the weakly allergenic linalyl acetate leads to formation of allergenic oxidation products.  KEYWORDS: Allergens, Monoterpenes, Oils, Volatile, Plant Oils, linalyl acetate, Hydrogen Peroxide, lavender oil, Air, Allergens/adverse effects/chemistry/metabolism, Animals, Chromatography, Gas, Dermatitis, Allergic Contact/etiology/immunology, Hydrogen Peroxide/adverse effects/chemistry/metabolism, Lymph Nodes/immunology, Magnetic Resonance Spectroscopy, Mass Spectrometry, Mice, Monoterpenes/adverse effects/chemistry/metabolism, Oils, Volatile/adverse effects/chemistry, Oxidation-Reduction, Plant Oils/adverse effects/chemistry, Skin/immunology, Time Factors",18154552]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M22,M22)","v":30912148},{"$f":"IF(ISBLANK(B$3),0,(LEN($L22) - LEN(SUBSTITUTE(LOWER($L22),LOWER(B$3),\"\")))/LEN(B$3))","v":3},{"$f":"IF(ISBLANK(C$3),0,(LEN($L22) - LEN(SUBSTITUTE(LOWER($L22),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L22) - LEN(SUBSTITUTE(LOWER($L22),LOWER(D$3),\"\")))/LEN(D$3))","v":3},{"$f":"SUM(B22:D22)","v":6},2019,"Allergic contact dermatitis caused by oxidized linalool in a deodorant.",0,0,"Isaksson, Karlberg, Nilsson","Contact dermatitis","Allergic contact dermatitis caused by oxidized linalool in a deodorant.    Abstract:  Title:  NOABSTRACT. No abstract found.  KEYWORDS:   allergic contact dermatitis, armpit dermatitis, case report, chemical analysis, fragrances, hydroperoxides of linalool, linalool oxidation products, patch testing",30912148]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M23,M23)","v":30905868},{"$f":"IF(ISBLANK(B$3),0,(LEN($L23) - LEN(SUBSTITUTE(LOWER($L23),LOWER(B$3),\"\")))/LEN(B$3))","v":3},{"$f":"IF(ISBLANK(C$3),0,(LEN($L23) - LEN(SUBSTITUTE(LOWER($L23),LOWER(C$3),\"\")))/LEN(C$3))","v":2},{"$f":"IF(ISBLANK(D$3),0,(LEN($L23) - LEN(SUBSTITUTE(LOWER($L23),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B23:D23)","v":6},2019,"Exposure source for skin sensitizing hydroperoxides of limonene and linalool remains elusive: An analytical market surveillance.",0,0,"Natsch, Nägelin, Leijs, van Strien, Giménez-Arnau, Vey, González","Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association","Exposure source for skin sensitizing hydroperoxides of limonene and linalool remains elusive: An analytical market surveillance.    Abstract:  Title:  Positive patch test reactions of dermatological patients to oxidized samples of linalool and limonene are frequently reported. The sensitizing ingredients in the oxidation mixtures are hydroperoxides (HP). It is not clear whether fragranced consumer products are a relevant exposure source for HP. Analytical methodologies had been validated, allowing quantification of HP in different consumer products. The analytical approach was used to analyse 104 consumer products. Samples included aged and new samples from the same brand, products suspected by patients to elicit their symptoms and products containing essential oils. Only four samples contained >50 μg/g of at least one of the HP by the screening method. Confirmatory analysis by LC-MS methods indicated that levels are even below those observed by the conservative screening method. The samples retrieved from patch-test positive patients were below detection limit for all target analytes. This market surveillance indicates that concentrations of HP in consumer products and patient products are orders of magnitude below sensitizing doses in animal tests. No evidence for hydroperoxide accumulation in aged products or products used by patients was found. The nature and source of the inducing agent responsible for the frequent positive patch test reactions to oxidized terpenes remains elusive. Copyright © 2019 Elsevier Ltd. All rights reserved.  KEYWORDS: Monoterpenes, Limonene, Hydrogen Peroxide, linalool, Chromatography, Liquid/methods, Dermatitis, Allergic Contact/diagnosis/etiology, Gas Chromatography-Mass Spectrometry/methods, Humans, Hydrogen Peroxide/adverse effects/analysis/chemistry, Limit of Detection, Limonene/chemistry, Luminescent Measurements, Mass Spectrometry/methods, Monoterpenes/chemistry, Product Surveillance, Postmarketing  Consumer products, Market surveillance, Quantification, Skin allergy, Terpene hydroperoxides",30905868]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M24,M24)","v":29940212},{"$f":"IF(ISBLANK(B$3),0,(LEN($L24) - LEN(SUBSTITUTE(LOWER($L24),LOWER(B$3),\"\")))/LEN(B$3))","v":3},{"$f":"IF(ISBLANK(C$3),0,(LEN($L24) - LEN(SUBSTITUTE(LOWER($L24),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L24) - LEN(SUBSTITUTE(LOWER($L24),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B24:D24)","v":5},2018,"Fragrance allergens in household detergents.",0,0,"Wieck, Olsson, Kümmerer, Klaschka","Regulatory toxicology and pharmacology : RTP","Fragrance allergens in household detergents.    Abstract:  Title:  Consumers are confronted with a large number of fragrance allergens from various sources. Until now, the discussion of exposure sources has mainly addressed cosmetic products and neglected other scented products in households. For the first time, fragrance allergens were evaluated in a complete set of detergents in households. In 131 households, we investigated the prevalence of detergents and searched their lists of ingredients for 26 fragrance allergens liable to be indicated on products according to the European Detergents Regulations. On the ingredient lists of 1447 products, these 26 fragrance substances were named almost 2000 times, most often limonene, linalool and hexyl cinnamal. Benzyl salicylate was used frequently in all-purpose cleaners. Linalool and limonene, hexyl cinnamal and butylphenyl methylpropional and citronellol and linalool co-occurred most often together in products. Fragrance allergens co-occurring together most frequently within households were eugenol, coumarin and cinnamyl alcohol. The study shows that detergents could play a relevant role for the exposure of consumers towards fragrance allergens and that they should not be underestimated as an exposure source during the exposure assessment. Copyright © 2018. Published by Elsevier Inc.  KEYWORDS: Allergens, Detergents, Perfume, Adult, Allergens/administration & dosage/adverse effects/analysis, Child, Dermatitis, Allergic Contact/prevention & control, Detergents/administration & dosage/adverse effects/analysis, Germany, Humans, Perfume/administration & dosage/adverse effects/analysis, Skin/drug effects  Aggregated exposure, Co-exposure, Contact allergy, Detergents, Fragrance allergens, Product inventory, Washing and cleaning agents",29940212]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M25,M25)","v":29029310},{"$f":"IF(ISBLANK(B$3),0,(LEN($L25) - LEN(SUBSTITUTE(LOWER($L25),LOWER(B$3),\"\")))/LEN(B$3))","v":3},{"$f":"IF(ISBLANK(C$3),0,(LEN($L25) - LEN(SUBSTITUTE(LOWER($L25),LOWER(C$3),\"\")))/LEN(C$3))","v":2},{"$f":"IF(ISBLANK(D$3),0,(LEN($L25) - LEN(SUBSTITUTE(LOWER($L25),LOWER(D$3),\"\")))/LEN(D$3))","v":4},{"$f":"SUM(B25:D25)","v":9},2018,"Editor's Highlight: Fragrance Allergens Linalool and Limonene Allylic Hydroperoxides in Skin Allergy: Mechanisms of Action Focusing on Transcription Factor Nrf2.",0,0,"Raffalli, Clouet, Kuresepi, Damiens, Lepoittevin, Pallardy, Ferret, Giménez-Arnau, Kerdine-Römer","Toxicological sciences : an official journal of the Society of Toxicology","Editor's Highlight: Fragrance Allergens Linalool and Limonene Allylic Hydroperoxides in Skin Allergy: Mechanisms of Action Focusing on Transcription Factor Nrf2.    Abstract:  Title:  Allergic contact dermatitis is regarded as the most frequent expression of immunotoxicity in humans. Many odorant terpenes commonly used in fragrance compositions are considered as weak skin sensitizers, whereas some of their autoxidation products, allylic hydroperoxides, are classified as strong sensitizers according to the local lymph node assay. However, the mechanism of their effects on the immune system remains unclear. Since dendritic cells play a key role in allergic contact dermatitis, we studied their activation by the frequently used linalool (LINA) and limonene (LIMO), and their respective sensitizing allylic hydroperoxides (LINA-OOH, LIMO-OOH). The THP-1 cell-line was used as a surrogate for dendritic cells, the model currently employed in the validated h-CLAT in vitro test. Our data showed that allylic hydroperoxides behave differently. Both LINA-OOH and LIMO-OOH oxidized cell surface thiols 30 min after stimulation. However, the oxidative stress induced by LINA-OOH was stronger, with a higher decreased GSH/GSSG ratio and a stronger reactive species production. Moreover, LINA-OOH induced a stronger Nrf2 accumulation in correlation with nqo1 and ho-1 gene expression, 2 Nrf2 target genes. Regarding signaling pathways involved in these effects, P38 mitogen-activated protein kinase and P-ERK were activated in response to LINA-OOH but not with LIMO-OOH. CD54 and CD86 were induced 24-h postexposure. In contrast, LINA and LIMO did not modify THP-1 phenotype. This work underlies that autoxidation forming allylic hydroperoxide (ROOH) does not lead to equal chemical reactivity since LINA-OOH appears to be a stronger activator than LIMO-OOH, in regard to oxidative stress and Nrf2 pathway activation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.  KEYWORDS: Allergens, Monoterpenes, NF-E2-Related Factor 2, Perfume, Limonene, Hydrogen Peroxide, linalool, Allergens/chemistry/immunology, Cell Culture Techniques, Cell Line, Cell Survival/drug effects/immunology, Dermatitis, Allergic Contact/etiology/immunology/metabolism, Humans, Hydrogen Peroxide/chemistry, Limonene/chemistry/immunology, Monocytes/drug effects/immunology/metabolism, Monoterpenes/chemistry/immunology, NF-E2-Related Factor 2/metabolism, Perfume/chemistry  Nrf2, allergic contact dermatitis, allylic hydroperoxides, cell surface thiol, sensitizers, terpenes",29029310]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M26,M26)","v":18759894},{"$f":"IF(ISBLANK(B$3),0,(LEN($L26) - LEN(SUBSTITUTE(LOWER($L26),LOWER(B$3),\"\")))/LEN(B$3))","v":3},{"$f":"IF(ISBLANK(C$3),0,(LEN($L26) - LEN(SUBSTITUTE(LOWER($L26),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L26) - LEN(SUBSTITUTE(LOWER($L26),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B26:D26)","v":6},2008,"Lavender oil lacks natural protection against autoxidation, forming strong contact allergens on air exposure.",0,0,"Hagvall, Sköld, Bråred-Christensson, Börje, Karlberg","Contact dermatitis","Lavender oil lacks natural protection against autoxidation, forming strong contact allergens on air exposure.    Abstract:  Title:  Lavender oil is an essential oil frequently used as a fragrance ingredient and in traditional herbal medicine. We have previously studied the effect of air oxidation on the skin sensitizing potency of the monoterpenes linalyl acetate, linalool and beta-caryophyllene, the main constituents of lavender oil. The aim of this study was to investigate if the autoxidation observed for the single synthetic terpenes, resulting in strong contact allergens, will take place also in lavender oil. Lavender oil was exposed to air and the autoxidation was followed by chemical analysis. The sensitizing potency before and after air exposure was investigated in mice using the local lymph node assay. Patients with patch test reactions to oxidized linalool were tested to investigate if air-exposed lavender oil could elicit dermatitis in these individuals. The terpenes oxidized in air-exposed lavender oil at the same rates as the pure compounds exposed to air, and the same oxidation products were identified. The sensitizing potency of lavender oil increased accordingly on air exposure. Patch testing showed positive reactions to air-exposed lavender oil and also to oxidized linalyl acetate in patients with contact allergy to oxidized linalool. This study shows that lavender oil lacks natural protection against autoxidation, and that air-exposed lavender oil can be an important source of exposure to allergenic hydroperoxides.  KEYWORDS: Air Pollutants, Allergens, Oils, Volatile, Plant Oils, Terpenes, lavender oil, Adult, Air Pollutants/analysis/toxicity, Allergens/analysis/toxicity, Animals, Dermatitis, Allergic Contact/diagnosis/etiology, Female, Humans, Local Lymph Node Assay, Lymph Nodes/drug effects, Male, Mice, Oils, Volatile/analysis/toxicity, Oxidation-Reduction, Patch Tests/methods, Plant Oils/analysis/toxicity, Terpenes/analysis/toxicity, Time Factors",18759894]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M27,M27)","v":17428070},{"$f":"IF(ISBLANK(B$3),0,(LEN($L27) - LEN(SUBSTITUTE(LOWER($L27),LOWER(B$3),\"\")))/LEN(B$3))","v":3},{"$f":"IF(ISBLANK(C$3),0,(LEN($L27) - LEN(SUBSTITUTE(LOWER($L27),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L27) - LEN(SUBSTITUTE(LOWER($L27),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B27:D27)","v":6},2007,"Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization.",0,0,"Hagvall, Bäcktorp, Svensson, Nyman, Börje, Karlberg","Chemical research in toxicology","Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization.    Abstract:  Title:  Fragrances are common causes of contact allergy. Geraniol (trans-3,7-dimethyl-2,6-octadiene-1-ol) is an important fragrance terpene. It is considered a weak contact allergen and is used for fragrance allergy screening among consecutive dermatitis patients. Analogous to other monoterpenes studied, such as limonene and linalool, geraniol has the potential to autoxidize on air exposure and form highly allergenic compounds. The aim of the present study was to investigate and propose a mechanism for the autoxidation of geraniol at room temperature. To investigate whether allergenic compounds are formed, the sensitizing potency of geraniol itself, air-exposed geraniol, and its oxidation products was determined using the local lymph node assay in mice. The results obtained show that the allylic alcohol geraniol follows an oxidation pattern different from those of linalool and limonene, which autoxidize forming hydroperoxides as the only primary oxidation products. The autoxidation of geraniol follows two paths, originating from allylic hydrogen abstraction near the two double bonds. From geraniol, hydrogen peroxide is primarily formed together with aldehydes geranial and neral from a hydroxyhydroperoxide. In addition, small amounts of a hydroperoxide are formed, analogous to the formation of the major linalool hydroperoxide. The autoxidation of geraniol greatly influenced the sensitizing effect of geraniol. The oxidized samples had moderate sensitizing capacity, quite different from that of pure geraniol. The hydroperoxide formed is believed to be the major contributor to allergenic activity, together with the aldehydes geranial and neral. On the basis of the present study and previous experience, we recommend that the possibility of autoxidation and the subsequent formation of contact allergenic oxidation products are considered in risk assessments performed on fragrance terpenes.  KEYWORDS: Allergens, Perfume, Terpenes, Hydrogen Peroxide, geraniol, Air, Allergens/chemistry/toxicity, Animals, Dermatitis, Allergic Contact/etiology/pathology, Hydrogen Peroxide/analysis/toxicity, Immunization, Local Lymph Node Assay, Lymph Nodes/drug effects/metabolism/pathology, Mice, Oxidation-Reduction, Perfume/chemistry/toxicity, Terpenes/chemistry/toxicity",17428070]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M28,M28)","v":16226832},{"$f":"IF(ISBLANK(B$3),0,(LEN($L28) - LEN(SUBSTITUTE(LOWER($L28),LOWER(B$3),\"\")))/LEN(B$3))","v":3},{"$f":"IF(ISBLANK(C$3),0,(LEN($L28) - LEN(SUBSTITUTE(LOWER($L28),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L28) - LEN(SUBSTITUTE(LOWER($L28),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B28:D28)","v":6},2006,"The fragrance chemical beta-caryophyllene-air oxidation and skin sensitization.",0,0,"Sköld, Karlberg, Matura, Börje","Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association","The fragrance chemical beta-caryophyllene-air oxidation and skin sensitization.    Abstract:  Title:  Fragrances are common causes of allergic contact dermatitis. beta-Caryophyllene is a sesquiterpene that is used as a fragrance chemical. Analogous to the monoterpenes R-limonene and linalool, it can be expected to autoxidize when air exposed. The aim of the present study was to investigate the autoxidation of beta-caryophyllene and to evaluate the effect on the contact allergenic activity. beta-Caryophyllene started to oxidize immediately when air exposed and after 5 weeks almost 50% of the original compound was consumed. Caryophyllene oxide was found to be the major oxidation product. Hydroperoxides of beta-caryophyllene could not be detected in the oxidation mixture. Caryophyllene oxide was shown to be an allergen of moderate strength and beta-caryophyllene air exposed for 10 weeks showed a weak sensitizing capacity in the local lymph node assay. The study reveals that the allergenic activity of beta-caryophyllene is affected by autoxidation, but to a lesser extent when compared to R-limonene and linalool. The present findings support our results in clinical studies showing oxidized beta-caryophyllene to be a rather rare sensitizer compared to oxidized R-limonene and linalool.  KEYWORDS: Perfume, Sesquiterpenes, caryophyllene, Air, Animals, Dermatitis, Contact/etiology/pathology, Female, Guinea Pigs, Mice, Mice, Inbred CBA, Oxidation-Reduction, Perfume/adverse effects/chemistry, Sesquiterpenes/adverse effects/chemistry",16226832]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M29,M29)","v":15932583},{"$f":"IF(ISBLANK(B$3),0,(LEN($L29) - LEN(SUBSTITUTE(LOWER($L29),LOWER(B$3),\"\")))/LEN(B$3))","v":3},{"$f":"IF(ISBLANK(C$3),0,(LEN($L29) - LEN(SUBSTITUTE(LOWER($L29),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L29) - LEN(SUBSTITUTE(LOWER($L29),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B29:D29)","v":5},2005,"Selected oxidized fragrance terpenes are common contact allergens.",0,0,"Matura, Sköld, Börje, Andersen, Bruze, Frosch, Goossens, Johansen, Svedman, White, Karlberg","Contact dermatitis","Selected oxidized fragrance terpenes are common contact allergens.    Abstract:  Title:  Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, linalool and caryophyllene are not allergenic themselves but readily form allergenic products on air-exposure. This study aimed to determine the frequency and characteristics of allergic reactions to selected oxidized fragrance terpenes other than limonene. In total 1511 consecutive dermatitis patients in 6 European dermatology centres were patch tested with oxidized fragrance terpenes and some oxidation fractions and compounds. Oxidized linalool and its hydroperoxide fraction were found to be common contact allergens. Of the patients tested, 1.3% showed a positive reaction to oxidized linalool and 1.1% to the hydroperoxide fraction. About 0.5% of the patients reacted to oxidized caryophyllene whereas 1 patient reacted to oxidized myrcene. Of the patients reacting to the oxidized terpenes, 58% had fragrance-related contact allergy and/or a positive history for adverse reaction to fragrances. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations.  KEYWORDS: Allergens, Perfume, Terpenes, Allergens/adverse effects, Dermatitis, Allergic Contact/diagnosis/epidemiology/etiology/pathology, Europe/epidemiology, Female, Humans, Male, Oxidation-Reduction, Patch Tests, Perfume/adverse effects, Predictive Value of Tests, Surveys and Questionnaires, Terpenes/adverse effects",15932583]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M30,M30)","v":30201159},{"$f":"IF(ISBLANK(B$3),0,(LEN($L30) - LEN(SUBSTITUTE(LOWER($L30),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L30) - LEN(SUBSTITUTE(LOWER($L30),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L30) - LEN(SUBSTITUTE(LOWER($L30),LOWER(D$3),\"\")))/LEN(D$3))","v":5},{"$f":"SUM(B30:D30)","v":7},2019,"A Patch Testing Initiative for the Investigation of Allergic Contact Dermatitis in a UK Allergy Practice: A Retrospective Study.",0,0,"Watts, Watts, Thursfield, Haque","The journal of allergy and clinical immunology. In practice","A Patch Testing Initiative for the Investigation of Allergic Contact Dermatitis in a UK Allergy Practice: A Retrospective Study.    Abstract:  Title:  Patch testing is the gold standard diagnostic tool for investigating allergic contact dermatitis (ACD). In the United Kingdom, patch testing has been historically confined to the dermatologist's office. Furthermore, detailed studies on patch testing by allergists are significantly underrepresented at the international level. The objective of this study was to undertake a comprehensive evaluation of a patch testing initiative from an allergy practice; we report on various patient characteristics, prevalence and relevance data, in addition to immediate hypersensitivity testing. We undertook a retrospective analysis of 156 patients suspected of having contact dermatitis seen in our UK allergy practice between October 2016 and April 2018. Of the 156 patients patch tested (mean age 36.9 years, female 88%, white ethnicity 71.8%, atopy 68.6%), ACD was diagnosed overall in 49% of the cohort and ACD of current relevance was assigned to 31%. Our extended British standard series alone detected the responsible allergen in 87% of patients, and the remaining 13% were detected from supplementary or own material testing alone. Most prevalent contact allergens were nickel (28.2%), p-phenylenediamine (8.3%), cobalt (8.3%), methylisothiazolinone (5.8%), and hydroperoxides of linalool (4.5%) and limonene (4.5%). A history of occupationally related dermatitis (P = .004) and initial (pretest) diagnosis of ACD (P < .001) were both significantly associated with relevant positive patch test reactions (atopy status was not associated P > .05). ACD was detected in almost 50% of assessed patients, and we highlight the importance of assessing relevance. Hydroperoxides of limonene and linalool are notable additions to the prevalence data. Patch testing should be incorporated into more allergy practices, although availability of training is a limiting factor. Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.  KEYWORDS:   Allergic contact dermatitis, Allergy practice, British standard series, Clinical relevance, Patch testing",30201159]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M31,M31)","v":28960261},{"$f":"IF(ISBLANK(B$3),0,(LEN($L31) - LEN(SUBSTITUTE(LOWER($L31),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L31) - LEN(SUBSTITUTE(LOWER($L31),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L31) - LEN(SUBSTITUTE(LOWER($L31),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B31:D31)","v":3},2018,"Patch testing with the European baseline series fragrance markers: a 2016 update.",0,0,"Ung, White, White, Banerjee, McFadden","The British journal of dermatology","Patch testing with the European baseline series fragrance markers: a 2016 update.    Abstract:  Title:  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. 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. 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. 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%. 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. © 2017 British Association of Dermatologists.  KEYWORDS: Aldehydes, Allergens, Biomarkers, Cosmetics, Cyclohexanols, Cyclohexenes, Monoterpenes, Perfume, Trityl Compounds, limonene-1,2-epoxide, linalool oxide, hydroxyisohexyl 3-cyclohexene carboxaldehyde, Aldehydes, Allergens/adverse effects, Biomarkers, Cosmetics/adverse effects, Cyclohexanols/adverse effects, Cyclohexenes, Dermatitis, Allergic Contact/diagnosis, Humans, Monoterpenes/adverse effects, Myroxylon, Odorants, Patch Tests/methods/standards, Perfume/adverse effects, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Trityl Compounds/adverse effects",28960261]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M32,M32)","v":28796916},{"$f":"IF(ISBLANK(B$3),0,(LEN($L32) - LEN(SUBSTITUTE(LOWER($L32),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L32) - LEN(SUBSTITUTE(LOWER($L32),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L32) - LEN(SUBSTITUTE(LOWER($L32),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B32:D32)","v":4},2018,"Fragrance contact allergens in 5588 cosmetic products identified through a novel smartphone application.",0,0,"Bennike, Oturai, Müller, Kirkeby, Jørgensen, Christensen, Zachariae, Johansen","Journal of the European Academy of Dermatology and Venereology : JEADV","Fragrance contact allergens in 5588 cosmetic products identified through a novel smartphone application.    Abstract:  Title:  More than 25% of the adult European population suffers from contact allergy, with fragrance substances recognized as one of the main causes. Since 2005, 26 fragrance contact allergens have been mandatory to label in cosmetic products within the EU if present at 10 ppm or above in leave-on and 100 ppm or above in wash-off cosmetics. To examine exposure, based on ingredient labelling, to the 26 fragrances in a sample of 5588 fragranced cosmetic products. The investigated products were identified through a novel, non-profit smartphone application (app), designed to provide information to consumers about chemical substances in cosmetic products. Products registered through the app between December 2015 and October 2016 were label checked according to International Nomenclature of Cosmetic Ingredients (INCI) for the presence of the 26 fragrance substances or the wording 'fragrance/parfum/aroma'. The largest product categories investigated were 'cream, lotion and oil' (n = 1192), 'shampoo and conditioner' (n = 968) and 'deodorants' (n = 632). Among cosmetic products labelled to contain at least one of the 26 fragrances, 85.5% and 73.9% contained at least two and at least three of the 26 fragrances, respectively. Linalool (49.5%) and limonene (48.5%) were labelled most often among all investigated products. Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC/Lyral® ) was found in 13.5% of deodorants. Six of the 26 fragrance substances were labelled on less than one per cent of all products, including the natural extracts Evernia furfuracea (tree moss) and Evernia prunastri (oak moss). A total of 329 (5.9%) products had one or more of the 26 fragrance substances labelled but did not have 'parfum/fragrance/aroma' listed on the label. Consumers are widely exposed to, often multiple, well-established fragrance contact allergens through various cosmetic products intended for daily use. Several fragrance substances that are common causes of contact allergy were rarely labelled in this large sample of cosmetic products. © 2017 European Academy of Dermatology and Venereology.  KEYWORDS: Aldehydes, Cyclohexenes, Deodorants, Hair Preparations, Monoterpenes, Perfume, Plant Extracts, Terpenes, Limonene, linalool, hydroxyisohexyl 3-cyclohexene carboxaldehyde, Aldehydes/analysis, Cyclohexenes/analysis, Deodorants/chemistry, Dermatitis, Allergic Contact/etiology, Hair Preparations/chemistry, Humans, Limonene, Mobile Applications, Monoterpenes/analysis, Perfume/adverse effects/analysis, Plant Extracts/analysis, Skin Cream/chemistry, Smartphone, Terpenes/analysis",28796916]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M33,M33)","v":27427817},{"$f":"IF(ISBLANK(B$3),0,(LEN($L33) - LEN(SUBSTITUTE(LOWER($L33),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L33) - LEN(SUBSTITUTE(LOWER($L33),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L33) - LEN(SUBSTITUTE(LOWER($L33),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B33:D33)","v":3},2016,"Essential Oils, Part III: Chemical Composition.",1,0,"de Groot, Schmidt","Dermatitis : contact, atopic, occupational, drug","Essential Oils, Part III: Chemical Composition.    Abstract:  Title:  Data on the chemistry of essential oils which have caused contact allergy are provided. The largest group of chemicals found in essential oils consists of terpenes. The number of identified components usually ranges from 100 to 250, but in some oils (lavender, geranium, rosemary) 450 to 500 chemicals have been found. Many chemicals are present in a large number of oils, up to 98% for β-caryophyllene and 97% for limonene. Chemicals that are important constituents of >20 oils are limonene, linalool, and α-pinene. In many essential oils, there are 2 to 5 components which together constitute over 50% to 60% of the oil. In some oils, however, there is one dominant ingredient, making up more than 50% of the oil, including (E)-anethole in aniseed and star anise oil, carvone in spearmint oil, 1,8-cineole (eucalyptol) in Eucalyptus globulus oil, and (E)-cinnamaldehyde in cassia oil. The most important chemicals in 93 individual oils are specified.  KEYWORDS: Cyclohexenes, Monoterpenes, Oils, Volatile, Sesquiterpenes, Terpenes, Limonene, caryophyllene, linalool, alpha-pinene, Cyclohexenes/adverse effects/chemistry, Dermatitis, Allergic Contact/etiology, Humans, Limonene, Monoterpenes/adverse effects/chemistry, Oils, Volatile/adverse effects/chemistry, Sesquiterpenes/adverse effects/chemistry, Terpenes/adverse effects/chemistry",27427817]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M34,M34)","v":26806578},{"$f":"IF(ISBLANK(B$3),0,(LEN($L34) - LEN(SUBSTITUTE(LOWER($L34),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L34) - LEN(SUBSTITUTE(LOWER($L34),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L34) - LEN(SUBSTITUTE(LOWER($L34),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B34:D34)","v":4},2016,"Contact allergy to essential oils cannot always be predicted from allergy to fragrance markers in the baseline series.",0,0,"Sabroe, Holden, Gawkrodger","Contact dermatitis","Contact allergy to essential oils cannot always be predicted from allergy to fragrance markers in the baseline series.    Abstract:  Title:  Essential oils are fragrance substances that are labelled on cosmetic products by their INCI names, potentially confusing consumers. To establish whether contact allergy to essential oils might be missed if not specifically tested for. 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. 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. 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. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS: Aldehydes, Allergens, Cosmetics, Cyclohexenes, Monoterpenes, Oils, Volatile, Perfume, Plant Oils, Terpenes, Tea Tree Oil, Limonene, peppermint oil, linalool, hydroxyisohexyl 3-cyclohexene carboxaldehyde, Aldehydes/adverse effects, Allergens/adverse effects, Cananga/adverse effects, Cosmetics/adverse effects/chemistry, Cyclohexenes/adverse effects, Cymbopogon/adverse effects, Dermatitis, Allergic Contact/etiology, Humans, Limonene, Monoterpenes/adverse effects, Myroxylon/adverse effects, Oils, Volatile/adverse effects, Patch Tests, Perfume/adverse effects, Plant Oils/adverse effects, Product Labeling, Retrospective Studies, Santalum/adverse effects, Tea Tree Oil/adverse effects, Terpenes/adverse effects  allergic contact dermatitis, cosmetic reactions, essential oils, fragrances",26806578]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M35,M35)","v":24673435},{"$f":"IF(ISBLANK(B$3),0,(LEN($L35) - LEN(SUBSTITUTE(LOWER($L35),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L35) - LEN(SUBSTITUTE(LOWER($L35),LOWER(C$3),\"\")))/LEN(C$3))","v":2},{"$f":"IF(ISBLANK(D$3),0,(LEN($L35) - LEN(SUBSTITUTE(LOWER($L35),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B35:D35)","v":5},2014,"Characterization of skin sensitizers from autoxidized citronellol - impact of the terpene structure on the autoxidation process.",0,0,"Rudbäck, Hagvall, Börje, Nilsson, Karlberg","Contact dermatitis","Characterization of skin sensitizers from autoxidized citronellol - impact of the terpene structure on the autoxidation process.    Abstract:  Title:  Citronellol is a frequently used fragrance compound in consumer products. It is present in fragrance mix II, which is used for screening of contact allergy to fragrances. Because of its chemical structure, citronellol could be susceptible to autoxidation. To compare the behaviour of citronellol with that of the structurally similar compounds linalool and geraniol, in terms of ability to autoxidize, the products formed, and the sensitization potencies of these. Citronellol was exposed to air, and autoxidation was followed by gas chromatography-mass spectrometry (GC-MS) analysis after derivatization of thermolabile compounds. The sensitizing potencies of the oxidation mixture and its major oxidation compounds were examined with the local lymph node assay. The concentration of citronellol decreased while the sensitization potency increased in air-exposed samples over time, with hydroperoxides being identified as the major oxidation products and main skin sensitizers. The present study shows the impact of the absence of the 2,3-double bond in the citronellol structure on the oxidation pathways for formation of oxidation products. The study also shows the usefulness of our new GC-MS method for quantification of the citronellol oxidation products, especially the hydroperoxides. The investigated citronellol hydroperoxides could be important allergens, owing to the high concentrations detected and frequent exposure to citronellol in the population. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS: Allergens, Monoterpenes, Perfume, Terpenes, Hydrogen Peroxide, linalool, geraniol, citronellol, Allergens/chemistry, Animals, Dermatitis, Allergic Contact/diagnosis, Female, Gas Chromatography-Mass Spectrometry, Hydrogen Peroxide/chemistry, Local Lymph Node Assay, Mice, Inbred CBA, Monoterpenes/chemistry, Oxidation-Reduction, Perfume/chemistry, Rosa/chemistry, Structure-Activity Relationship, Terpenes/chemistry  FM II, GC-MS, autoxidation, citronellol, contact allergy, fragrances, prehapten, structure-activity relationships, trimethyl silyl (TMS) derivatives",24673435]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M36,M36)","v":24102121},{"$f":"IF(ISBLANK(B$3),0,(LEN($L36) - LEN(SUBSTITUTE(LOWER($L36),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L36) - LEN(SUBSTITUTE(LOWER($L36),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L36) - LEN(SUBSTITUTE(LOWER($L36),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B36:D36)","v":3},2013,"Coupled exposure to ingredients of cosmetic products: I. Fragrances.",0,0,"Uter, Yazar, Kratz, Mildau, Lidén","Contact dermatitis","Coupled exposure to ingredients of cosmetic products: I. Fragrances.    Abstract:  Title:  The use of cosmetics exposes consumers to mixtures of ingredients, many of which are contact allergens. Fragrances in particular are mostly used in combination; combinations of fragrances have been shown to enhance sensitization and elicitation. To examine the pattern of co-exposure to fragrances in different categories of cosmetics, addressing the 26 fragrances that need to be identified on the label according to the Cosmetics Directive 76/768/EEC amended by 2003/15/EC. A survey of products marketed in Germany, conducted in 2006-2009 by the Chemical and Veterinary Investigation Office in Karlsruhe, identified 4991 products with information on the presence of fragrances. The products were categorized according to Annex I to the Cosmetics Directive. The occurrence and co-occurrence of fragrances were analysed in tabular form and as social network diagrams. The median number of fragrances in products varied greatly between categories, ranging up to nine in perfumes. Limonene and linalool were the most commonly identified fragrances, often used together, but also with other fragrances. Thirty per cent of all products were not declared to contain any fragrances. For the first time, the pattern of co-exposure to fragrance ingredients in important categories of cosmetic products has been described. The observations illustrate and quantify the 'cocktail' of fragrance allergens that may facilitate sensitization. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS: Allergens, Cyclohexenes, Monoterpenes, Perfume, Terpenes, Limonene, linalool, Allergens/adverse effects/analysis, Cyclohexenes/analysis, Dermatitis, Allergic Contact/etiology, Environmental Exposure/adverse effects/analysis, Germany, Humans, Limonene, Monoterpenes/analysis, Perfume/adverse effects/analysis/chemistry, Product Labeling, Risk Assessment, Terpenes/analysis  cosmetics, exposure analysis, fragrances, ingredient label",24102121]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M37,M37)","v":21392034},{"$f":"IF(ISBLANK(B$3),0,(LEN($L37) - LEN(SUBSTITUTE(LOWER($L37),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L37) - LEN(SUBSTITUTE(LOWER($L37),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L37) - LEN(SUBSTITUTE(LOWER($L37),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B37:D37)","v":3},2011,"Allergy to oxidized linalool in the UK.",0,0,"Buckley","Contact dermatitis","Allergy to oxidized linalool in the UK.    Abstract:  Title:  NOABSTRACT. No abstract found.  KEYWORDS: Monoterpenes, Perfume, linalool, Adult, Aged, Dermatitis, Allergic Contact/epidemiology/etiology, Female, Humans, Male, Middle Aged, Monoterpenes/adverse effects/chemistry, Oxidation-Reduction, Patch Tests, Perfume/chemistry, United Kingdom/epidemiology",21392034]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M38,M38)","v":18949810},{"$f":"IF(ISBLANK(B$3),0,(LEN($L38) - LEN(SUBSTITUTE(LOWER($L38),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L38) - LEN(SUBSTITUTE(LOWER($L38),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L38) - LEN(SUBSTITUTE(LOWER($L38),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B38:D38)","v":4},2008,"Evaluation of ionization techniques for mass spectrometric detection of contact allergenic hydroperoxides formed by autoxidation of fragrance terpenes.",0,0,"Nilsson, Carlberg, Abrahamsson, Hulthe, Persson, Karlberg","Rapid communications in mass spectrometry : RCM","Evaluation of ionization techniques for mass spectrometric detection of contact allergenic hydroperoxides formed by autoxidation of fragrance terpenes.    Abstract:  Title:  Hydroperoxides formed by autoxidation of common fragrance terpenes are strong allergens and known to cause allergic contact dermatitis (ACD), a common skin disease caused by low molecular weight chemicals. Until now, no suitable methods for chemical analyses of monoterpene hydroperoxides have been available. Their thermolability prohibits the use of gas chromatography and their low UV-absorption properties do not promote sensitive analytical methods by liquid chromatography based on UV detection. In our study, we have investigated different liquid chromatography/mass spectrometry (LC/MS) ionization techniques, electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photoionization (APPI), for detection of hydroperoxides from linalool and limonene.Flow injection analysis was used to evaluate the three different techniques to ionize the monoterpene hydroperoxides, linalool hydroperoxide and limonene hydroperoxide, by estimating the signal efficacy under experimental conditions for positive and negative ionization modes. The intensities for the species [M+H]+ and [M+H-H2O]+ in positive ionization mode and [M-H]- and [M-H-H2O]- in negative ionization mode were monitored. It was demonstrated that the mobile phase composition and instrumental parameters have major influences on the ionization efficiency of these compounds. ESI and APCI were both found to be appropriate as ionization techniques for detection of the two hydroperoxides. However, APPI was less suitable as ionization technique for the investigated hydroperoxides.  KEYWORDS: Allergens, Terpenes, Hydrogen Peroxide, Allergens/chemistry, Chromatography, Liquid/methods, Hydrogen Peroxide/chemistry, Mass Spectrometry/methods, Oxidation-Reduction, Terpenes/chemistry",18949810]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M39,M39)","v":16958922},{"$f":"IF(ISBLANK(B$3),0,(LEN($L39) - LEN(SUBSTITUTE(LOWER($L39),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L39) - LEN(SUBSTITUTE(LOWER($L39),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L39) - LEN(SUBSTITUTE(LOWER($L39),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B39:D39)","v":4},2006,"Hydroperoxides form specific antigens in contact allergy.",0,0,"Bråred Christensson, Matura, Bäcktorp, Börje, Nilsson, Karlberg","Contact dermatitis","Hydroperoxides form specific antigens in contact allergy.    Abstract:  Title:  Concomitant positive reactions to colophonium, oxidized limonene, and/or oxidized linalool are recorded in patch test studies. The main allergens in these patch test mixtures are hydroperoxides, which form antigens by a radical pathway. Theoretically, concomitant reactions can be explained not only by concomitant sensitization or by true cross-reactions but also by the hydroperoxides acting as oxidizing agents on skin proteins to form non-specific antigens without hapten-protein binding. The aim of this study was to explore concomitant reactions and cross-reactivity patterns among hydroperoxide haptens. We investigated whether individuals allergic to the main allergen in colophonium, 15-hydroperoxyabietic acid, would also react to limonene hydroperoxide or linalool hydroperoxide. Only 1 of 29 individuals reacted to more than 1 hydroperoxide. The cross-reactivity pattern among cumene hydroperoxide, limonene hydroperoxide, 1-(1-hydroperoxy-1-methylethyl) cyclohexene (cyclohexene hydroperoxide), and 15-hydroperoxydehydroabietic acid was investigated in guinea-pigs. No general cross-reactivity was observed. Cross-reactions between cumene hydroperoxide and cyclohexene hydroperoxide show that similarity in the overall structure and the way of antigen formation are needed. Quantum calculations were used to determine the formation energies of the intermediary radicals. We concluded that hydroperoxides form specific antigens and that formation of non-specific antigens is unlikely. The concomitant patch test reactions described in the literature are best explained as a result of multiple sensitizations.  KEYWORDS: Allergens, Antigens, Benzene Derivatives, Cyclohexenes, Terpenes, cyclohexene, cumene, Limonene, Hydrogen Peroxide, Allergens/adverse effects/chemistry/immunology, Animals, Antigens/biosynthesis, Benzene Derivatives/chemistry, Cross Reactions, Cyclohexenes/chemistry, Dermatitis, Allergic Contact/etiology, Female, Guinea Pigs, Humans, Hydrogen Peroxide/adverse effects/chemistry/immunology, Limonene, Male, Middle Aged, Patch Tests, Terpenes/chemistry",16958922]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M40,M40)","v":15206687},{"$f":"IF(ISBLANK(B$3),0,(LEN($L40) - LEN(SUBSTITUTE(LOWER($L40),LOWER(B$3),\"\")))/LEN(B$3))","v":2},{"$f":"IF(ISBLANK(C$3),0,(LEN($L40) - LEN(SUBSTITUTE(LOWER($L40),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L40) - LEN(SUBSTITUTE(LOWER($L40),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B40:D40)","v":3},2004,"Inhibition of the sensitizing effect of carvone by the addition of non-allergenic compounds.",0,0,"Nilsson, Jonsson, Luthman, Nilsson, Karlberg","Acta dermato-venereologica","Inhibition of the sensitizing effect of carvone by the addition of non-allergenic compounds.    Abstract:  Title:  We have previously reported a reduction of sensitization to carvone in guinea pigs when adding non-allergenic, structurally related compounds simultaneously at induction. This study investigates the criteria needed to obtain a reduction of sensitization in contact allergy. Linalool, a non-sensitizer structurally unrelated to carvone, significantly reduced the sensitizing capacity of carvone in guinea pigs. The effect of different concentrations of inhibitors in mixtures with carvone was investigated. No significant differences in response were obtained between the concentrations explored. A possible anti-inflammatory effect from the inhibitory chemicals was investigated in vitro. No suppression of the immune system was seen. This study shows that a non-allergenic compound with a structure not resembling the hapten can reduce the sensitizing effect of the hapten. It indicates that reduction of an allergenic effect might occur in consumer products that are mixtures of different chemicals. Further studies with chemically unrelated compounds with and without allergenic effect are needed.  KEYWORDS: Allergens, Cytokines, Monoterpenes, Terpenes, carvone, linalool, Allergens/adverse effects, Analysis of Variance, Animals, Cross Reactions, Cytokines/metabolism, Dermatitis, Allergic Contact/etiology/immunology, Disease Models, Animal, Female, Guinea Pigs, Immunization/methods, Lymphocyte Activation, Monoterpenes/pharmacology, Patch Tests, Probability, Sensitivity and Specificity, Terpenes/pharmacology",15206687]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M41,M41)","v":31433384},{"$f":"IF(ISBLANK(B$3),0,(LEN($L41) - LEN(SUBSTITUTE(LOWER($L41),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L41) - LEN(SUBSTITUTE(LOWER($L41),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L41) - LEN(SUBSTITUTE(LOWER($L41),LOWER(D$3),\"\")))/LEN(D$3))","v":4},{"$f":"SUM(B41:D41)","v":5},2019,"Contact Allergy to and Other Adverse Effects of Fragrances: A Brief Overview.",0,0,"de Groot","Dermatitis : contact, atopic, occupational, drug","Contact Allergy to and Other Adverse Effects of Fragrances: A Brief Overview.    Abstract:  Title:  This article gives an overview of fragrance allergy. The following subjects are discussed: composition of perfumes, contact with fragrances, diagnosing fragrance allergy, frequency of allergy, clinical picture of allergic contact dermatitis, culprit products, occupational contact dermatitis, and other adverse effects of fragrances. For diagnosing fragrance sensitization, personal products and a fragrance series may need to be tested in addition to the baseline series. In the general adult population, up to 4.5% may be allergic to fragrance materials, and in consecutive patients patch tested for suspected contact dermatitis, the frequency may reach 20% to 25%. More than 150 fragrances have caused contact allergy. The most frequent sensitizers are linalool and limonene hydroperoxides, hydroxyisohexyl 3-cyclohexene carboxaldehyde, treemoss and oakmoss absolute, isoeugenol, cinnamyl alcohol, and cinnamal. Culprit products for induction of sensitization are often deodorants, fine fragrances, and aftershaves. Occupational contact dermatitis from fragrances is seen occasionally. Other adverse effects are all discussed but occur infrequently.  KEYWORDS: ",31433384]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M42,M42)","v":31145193},{"$f":"IF(ISBLANK(B$3),0,(LEN($L42) - LEN(SUBSTITUTE(LOWER($L42),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L42) - LEN(SUBSTITUTE(LOWER($L42),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L42) - LEN(SUBSTITUTE(LOWER($L42),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B42:D42)","v":3},2019,"Highlights in allergic contact dermatitis 2018/2019.",0,0,"Johansen, Werfel","Current opinion in allergy and clinical immunology","Highlights in allergic contact dermatitis 2018/2019.    Abstract:  Title:  The purpose was to highlight recent findings especially concerning new and old allergens, trends, diagnosis and causes of contact allergy. Nickel is still the most frequent cause of contact allergy in women and piercings remain an important risk factor. Countries with a long history of regulation of contact allergens have the lowest level of contact allergy to nickel and chromium in Europe. Among the most frequent causes of fragrance contact allergy is terpenes, which are oxidized such as limonene, linalool and in some countries: geraniol. Methylisothiazolinone is still causing considerable problems due to hidden exposures. Acrylates are emerging allergens and 2-hydroxyethyl methacrylate has been included in the 2019 update of the baseline series, as many new cases are seen due to long-lasting nail polish based on acrylates and glue (isobornyl acrylate) in insulin pumps. More than 10 new allergens have been described, which need to be considered in diagnosing contact allergy. Allergic contact dermatitis is a frequent problem, it also constitutes a challenge to diagnose due to many potential contact allergens. The main culprit allergens remain the same, new significant causes are found especially within acrylates.  KEYWORDS: ",31145193]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M43,M43)","v":31136355},{"$f":"IF(ISBLANK(B$3),0,(LEN($L43) - LEN(SUBSTITUTE(LOWER($L43),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L43) - LEN(SUBSTITUTE(LOWER($L43),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L43) - LEN(SUBSTITUTE(LOWER($L43),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B43:D43)","v":2},2019,"Fragrance Allergens in Hair Removal Cosmetic Products.",0,0,"Nanyan","Dermatitis : contact, atopic, occupational, drug","Fragrance Allergens in Hair Removal Cosmetic Products.    Abstract:  Title:  Fragrances are the most common cause of contact allergy in cosmetics. The aim of this study was to identify fragrance allergens in hair removal products based on the list of ingredients. Hair removal products found in the French market were checked for the 26 allergens classified in accordance with Directive 2003/15/EC through information on the packages using the Web site of the manufacturer, vendor, or supermarket. A total of 662 hair removal products were checked. Fragrance allergens were present in 318 (48%) of the products, with an average of 4 allergens per product. Linalool and limonene were the most common fragrances present in 67% and 50.3%, respectively. Strip and spray formulations contained significantly more allergens than cream/lotion or wax products. To prevent allergic contact dermatitis, the formulation of hair removal products should be considered, because fragrance allergens are more often present in strip and spray formulations.  KEYWORDS: ",31136355]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M44,M44)","v":31041411},{"$f":"IF(ISBLANK(B$3),0,(LEN($L44) - LEN(SUBSTITUTE(LOWER($L44),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L44) - LEN(SUBSTITUTE(LOWER($L44),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L44) - LEN(SUBSTITUTE(LOWER($L44),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B44:D44)","v":3},2019,"Skin safety and health prevention: an overview of chemicals in cosmetic products.",0,1,"Panico, Serio, Bagordo, Grassi, Idolo, DE Giorgi, Guido, Congedo, DE Donno","Journal of preventive medicine and hygiene","Skin safety and health prevention: an overview of chemicals in cosmetic products.    Abstract:  Title:  Cosmetic products contain a wide range of chemicals to which we are exposed every day. The aim of the study was to determine the presence of potential dangerous substances which can cause adverse health effects by examining product labels. A total of 283 products were collected from various shops in Lecce (Italy) and divided into 3 categories: rinse-off, leave-on and make-up. The label of every product was examined and a list including fragrances, preservatives and other chemicals of concern was created. Fragrances were present in 52.3% of the examined products, mostly limonene (76.9%) and linalool (64.6%) but also citronellol (34.1%), geraniol (31.5%), coumarin (30%) and hexyl cinnamal (29.2%). Preservatives showed a rate of 60% and the most frequently identified were phenoxyethanol (48.7%), sodium benzoate (35.6%), potassium sorbate (22%), methylparaben (15.2%) and MI/MCI (9.9%). The other chemicals of concern were detected in 58% of products; included PEGs (62.3%), acrylate copolymer (34%), petrolatum (17.2%), polysorbates (14,8%), BHT (14.7%), ethylhextyl methoxycinnamate (13.6%), benzophenone-1 (3.7%), benzophenone-3 (4.9%), BHA (1.6%), cocamide DEA and toluene (1.2%). The use of many of these substances is allowed within certain limits, due to their toxicity at higher concentrations. Other important aspects should be considered as, for instance, the possibility of long-term effects. On the other hand, other substances may induce several acute adverse side-effects, i.e. contact dermatitis and allergic reactions. For these reasons, an enhancement of the criteria used for cosmetics formulation is required since many chemicals used singularly or combined are potentially unsafe.  KEYWORDS:   Additive Effect, Cocktail Effect, Cosmetics, Health Prevention",31041411]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M45,M45)","v":30802323},{"$f":"IF(ISBLANK(B$3),0,(LEN($L45) - LEN(SUBSTITUTE(LOWER($L45),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L45) - LEN(SUBSTITUTE(LOWER($L45),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L45) - LEN(SUBSTITUTE(LOWER($L45),LOWER(D$3),\"\")))/LEN(D$3))","v":5},{"$f":"SUM(B45:D45)","v":6},2019,"Quality of life and disease severity in dermatitis patients with fragrance allergy-A cross-sectional European questionnaire study.",0,0,"Bennike, Heisterberg, White, Mahler, Silvestre-Salvador, Giménez-Arnau, Johansen","Contact dermatitis","Quality of life and disease severity in dermatitis patients with fragrance allergy-A cross-sectional European questionnaire study.    Abstract:  Title:  Fragrance contact allergy is common, but few studies on quality of life (QoL) in affected patients exist. Recently, the disease-specific Fragrance Quality of Life Index (FQLI) was developed. To characterize QoL in European dermatitis patients with fragrance contact allergy at the time of diagnosis. This was a cross-sectional study, in which 2011 Danish, British, Spanish and German adult consecutive dermatitis patients were invited to complete a questionnaire on self-reported disease severity, the Dermatology Life Quality Index (DLQI), and the FQLI immediately prior to being patch tested. One thousand seven hundred and fifty-eight patients responded, and 259 (14.7%; country range 11.7%-18.5%) were fragrance-positive. Among these, the total (SD) DLQI score was 6.2 (5.6) and the total (SD) FQLI score was 60 (25), with both estimates being comparable to those in fragrance-negative patients. Adjusting the total FQLI score for age, sex and self-rated disease severity showed a higher (ie, worse) score in fragrance-positive patients (3.6-point increase; 95% confidence interval: 0.30-6.8 points; P = 0.03). Specifically, contact allergy to oxidized linalool was associated with greater impairment in QoL. QoL in patients with fragrance contact allergy is impaired at a level comparable to that in other patch tested dermatitis patients, at the time of diagnosis, across several European countries. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS:   European, allergic contact dermatitis, contact allergy, cross-sectional questionnaire, fragrance allergy, patch testing, patient-reported outcomes, quality of life",30802323]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M46,M46)","v":30570579},{"$f":"IF(ISBLANK(B$3),0,(LEN($L46) - LEN(SUBSTITUTE(LOWER($L46),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L46) - LEN(SUBSTITUTE(LOWER($L46),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L46) - LEN(SUBSTITUTE(LOWER($L46),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B46:D46)","v":3},2019,"Airborne Contact Dermatitis Caused by Essential Oils in a Child.",0,0,"Shah, Goldman, Agim","Dermatitis : contact, atopic, occupational, drug","Airborne Contact Dermatitis Caused by Essential Oils in a Child.    Abstract:  Title:  NOABSTRACT. No abstract found.  KEYWORDS: Monoterpenes, Oils, Volatile, Particulate Matter, linalool, Child, Dermatitis, Allergic Contact/etiology, Humans, Male, Monoterpenes/adverse effects, Oils, Volatile/adverse effects, Particulate Matter/adverse effects, Patch Tests",30570579]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M47,M47)","v":30415634},{"$f":"IF(ISBLANK(B$3),0,(LEN($L47) - LEN(SUBSTITUTE(LOWER($L47),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L47) - LEN(SUBSTITUTE(LOWER($L47),LOWER(C$3),\"\")))/LEN(C$3))","v":2},{"$f":"IF(ISBLANK(D$3),0,(LEN($L47) - LEN(SUBSTITUTE(LOWER($L47),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B47:D47)","v":4},2018,"Determination of fragrance allergens and their dermal sensitization quantitative risk assessment (QRA) in 107 spray perfumes.",0,0,"Soo Lim, Min Choi, Kim, Yoon, Kacew, Sik Kim, Lee","Journal of toxicology and environmental health. Part A","Determination of fragrance allergens and their dermal sensitization quantitative risk assessment (QRA) in 107 spray perfumes.    Abstract:  Title:  Cutaneous allergy occurs primarily as a result of using cosmetic, household, and laundry products available on the market that contain fragrances. The aim of this study was to develop a rapid and specific high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method for quantification of 25 fragrance allergens (amyl cinnamyl alcohol, benzyl alcohol, benzyl benzoate, benzyl cinnamate, benzyl salicylate, citronellol, cinnamyl alcohol, citral, coumarin, eugenol, farnesol, geraniol, hydroxycitronellal, HICC (4-(4-hydroxy-4-methylpentyl)-3-cyclohexene-1-carboaldehyde), isoeugenol, isoeugenyl acetate, lilial (butyl phenyl methyl propional), limonene, linalool, methyl 2-octynoate, etc.). In addition, an exposure-based quantitative risk assessment (QRA) was performed to determine safe levels of fragrance ingredients in 107 perfumes. In 76 women's and 31 men's fragrances, 25 allergens were identified at concentrations ranging from undetectable (N.D.) to 8,997.68 mg/kg, and from N.D. to 17,352.34 mg/kg, respectively. An exposure-based sensitization QRA revealed that the ratios of acceptable exposure level (AEL) to consumer exposure level (CEL) of fragrance ingredients were greater than 1, suggesting an absence of skin sensitizing potential. However, the maximum level used in the exposure scenario was determined by the product purpose and application type, and AEL/CEL ratios of lilial, HICC, citral, isoeugenol, and methyl 2-octynoate analyzed in women's perfume were 0.53, 0.67 0.19, 0.13, and 0.57, respectively. As the ratios of AEL:CEL of these fragrance ingredients were below 1, the utilization of these potential skin sensitizers is not considered safe. Our findings indicate that the sensitization risk of allergens with AEL:CEL ratios below 1 detected in fragrances needs to be reduced to the appropriate human safety level for risk management.  KEYWORDS: Allergens, Perfume, Allergens/analysis, Dermatitis, Allergic Contact, Environmental Exposure/analysis, Female, Humans, Male, Odorants/analysis, Perfume/analysis, Prevalence, Republic of Korea, Risk Assessment",30415634]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M48,M48)","v":30000851},{"$f":"IF(ISBLANK(B$3),0,(LEN($L48) - LEN(SUBSTITUTE(LOWER($L48),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L48) - LEN(SUBSTITUTE(LOWER($L48),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L48) - LEN(SUBSTITUTE(LOWER($L48),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B48:D48)","v":3},2006,"Drugs and Lactation Database (LactMed)",0,0,null,"Book: National Library of Medicine (US)","Drugs and Lactation Database (LactMed)    Abstract:  Title:  Coriander (Coriandrum sativum) seeds contain a volatile oil, consisting mainly of linalool, which is responsible for its odor and taste. It also contains 1,8-cineole (eucalyptol). Coriander is a purported galactogogue, and has been included in some mixtures promoted to increase milk supply;[1][2] however, no scientifically valid clinical trials support this use. Galactogogues should never replace evaluation and counseling on modifiable factors that affect milk production.[1] Coriander is \"generally recognized as safe\" (GRAS) as a food by the U.S. Food and Drug Administration. However, allergic reactions and photosensitivity have been reported and it can cause contact dermatitis. One case of excessive use possibly caused endocrine disruption in a nursing mother. A woman nursing her 10-month-old infant had drunk 200 mL of about a 10% aqueous extract of Coriandrum sativa (method of verification and possible presence of contaminants not stated) daily for 7 consecutive days to enhance her milk supply when she was admitted to the hospital with severe diarrhea and stomach pain. The patient had no abnormal serum or urine tests and recovered with palliative therapy. Fifteen days later the patient was complaining of skin darkness, depressed mood, a loss of body fluids, and amenorrhea, which was diagnosed as an adrenal dysfunction. The patient said that she did not have any history of such a condition. She was treated with adrenocorticoids and an oral contraceptive. She was well and healthy 10 days later.[2] Elevated liver enzymes occurred in a woman taking Mother's Milk Tea, which contains coriander.[3] Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible to ensure the safety, but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. A manufacturer may contract with an independent organization to verify the quality of a product or its ingredients, but that does not certify the safety or effectiveness of a product. Because of the above issues, clinical testing results on one product may not be applicable to other products. More detailed information about dietary supplements is available elsewhere on the LactMed Web site.  KEYWORDS: ",30000851]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M49,M49)","v":29882592},{"$f":"IF(ISBLANK(B$3),0,(LEN($L49) - LEN(SUBSTITUTE(LOWER($L49),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L49) - LEN(SUBSTITUTE(LOWER($L49),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L49) - LEN(SUBSTITUTE(LOWER($L49),LOWER(D$3),\"\")))/LEN(D$3))","v":7},{"$f":"SUM(B49:D49)","v":8},2018,"Is a specific eyelid patch test series useful? Results of a French prospective study.",0,0,"Assier, Tetart, Avenel-Audran, Barbaud, Ferrier-le Bouëdec, Giordano-Labadie, Milpied, Amsler, Collet, Girardin, Soria, Waton, Truchetet, Bourrain, Gener, Bernier, Raison-Peyron","Contact dermatitis","Is a specific eyelid patch test series useful? Results of a French prospective study.    Abstract:  Title:  Eyelids are frequent sites of contact dermatitis. No prospective study focused on eyelid allergic contact dermatitis (EACD) has yet been published, and this topic has never been studied in French patients. To prospectively evaluate the usefulness of an eyelid series in French patients patch tested because of EACD, and to describe these patients. We prospectively analysed standardized data for all patients referred to our departments between September 2014 and August 2016 for patch testing for suspected EACD as the main reason. All patients were patch tested with an eyelid series, the European baseline series (EBS), the French additional series, and their personal products. Patch testing with additional series and repeated open application tests (ROATs) or open tests were performed if necessary. A standardized assessment of the relevance was used, and the analysis of the results was focused on patients having positive test results with a current certain relevance. Two-hundred and sixty-four patients (238 women and 26 men) were included. Three-hundred and twenty-two tests gave positive results in 167 patients, 84 of whom had currently relevant reactions: 56 had currently relevant positive test reactions to the EBS, 16 had currently relevant positive test reactions to their personal products, 8 had currently relevant positive test reactions to the French additional series, and 4 had currently relevant positive test reactions to the eyelid series. Sixty-seven per cent of all relevant cases were related to cosmetic products. The most frequent allergens with current relevance were methylisothiazolinone (10.2%), fragrance mix I (3%), nickel (2.7%), hydroxyperoxides of linalool (2.7%) and limonene (2.3%), and Myroxylon pereirae (2.3%). Current atopic dermatitis was found in 9.5% of patients. The duration of dermatitis was shorter (23.2 vs 34.2 months; P = .035) in patients with currently relevant test reactions. The percentage of currently relevant tests remained the same when atopic patients or dermatitis localized only on the eyelids were taken into account. In French patients, testing for EACD with the extended baseline series and personal products, also including ROATs and use tests, appears to be adequate, considering the currently relevant positive test reactions. The regular addition of an eyelid series does not seem to be necessary. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.  KEYWORDS: Allergens, Cosmetics, Adult, Allergens/administration & dosage/adverse effects, Cosmetics/administration & dosage/adverse effects, Dermatitis, Allergic Contact/diagnosis/etiology, Eyelid Diseases/chemically induced, Facial Dermatoses/chemically induced, Female, France, Humans, Male, Patch Tests/methods, Prospective Studies, Young Adult  French population, eyelid dermatitis, eyelid series, patch test, prospective study",29882592]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M50,M50)","v":29430711},{"$f":"IF(ISBLANK(B$3),0,(LEN($L50) - LEN(SUBSTITUTE(LOWER($L50),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L50) - LEN(SUBSTITUTE(LOWER($L50),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L50) - LEN(SUBSTITUTE(LOWER($L50),LOWER(D$3),\"\")))/LEN(D$3))","v":3},{"$f":"SUM(B50:D50)","v":4},2018,"Methotrexate does not impede the development of contact allergy.",0,0,"Yfanti, Nosbaum, Berard, Nicolas","Contact dermatitis","Methotrexate does not impede the development of contact allergy.    Abstract:  Title:  NOABSTRACT. No abstract found.  KEYWORDS: Immunosuppressive Agents, Monoterpenes, nickel sulfate, Nickel, linalool, Methotrexate, Adult, Dermatitis, Allergic Contact/etiology/prevention & control, Dermatitis, Atopic/drug therapy, Female, Humans, Immunosuppressive Agents/therapeutic use, Methotrexate/therapeutic use, Monoterpenes/adverse effects, Nickel/adverse effects, Patch Tests  allergic contact dermatitis, case report, methotrexate, patch tests",29430711]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M51,M51)","v":28927722},{"$f":"IF(ISBLANK(B$3),0,(LEN($L51) - LEN(SUBSTITUTE(LOWER($L51),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L51) - LEN(SUBSTITUTE(LOWER($L51),LOWER(C$3),\"\")))/LEN(C$3))","v":4},{"$f":"IF(ISBLANK(D$3),0,(LEN($L51) - LEN(SUBSTITUTE(LOWER($L51),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B51:D51)","v":6},2018,"Chemical stability and in chemico reactivity of 24 fragrance ingredients of concern for skin sensitization risk assessment.",0,0,"Avonto, Wang, Chittiboyina, Vukmanovic, Khan","Toxicology in vitro : an international journal published in association with BIBRA","Chemical stability and in chemico reactivity of 24 fragrance ingredients of concern for skin sensitization risk assessment.    Abstract:  Title:  Twenty-four pure fragrance ingredients have been identified as potential concern for skin sensitization. Several of these compounds are chemically unstable and convert into reactive species upon exposure to air or light. In the present work, a systematic investigation of the correlation between chemical stability and reactivity has been undertaken. The compounds were subjected to forced photodegradation for three months and the chemical changes were studied with GC-MS. At the end of the stability study, two-thirds of the samples were found to be unstable. The generation of chemically reactive species was investigated using the in chemico HTS-DCYA assay. Eleven and fourteen compounds were chemically reactive before and after three months, respectively. A significant increase in reactivity upon degradation was found for isoeugenol, linalool, limonene, lyral, citronellol and geraniol; in the same conditions, the reactivity of hydroxycitronellal decreased. The non-reactive compounds α-isomethyl ionone, benzyl alcohol, amyl cinnamal and farnesol became reactive after photo-oxidative degradation. Overall, forced degradation resulted in four non-reactive fragrance compounds to display in chemico thiol reactivity, while ten out of 24 compounds remained inactive. Chemical degradation does not necessarily occur with generation of reactive species. Non-chemical activation may be involved for the 10 stable unreactive compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.  KEYWORDS: Oxidants, Perfume, Proteins, Dermatitis, Allergic Contact, Molecular Structure, Oxidants, Perfume/chemistry, Protein Binding, Proteins/chemistry/metabolism, Skin/metabolism, Toxicity Tests  DCYA, Fragrance ingredients, In chemico methods, Skin sensitization, Stability studies",28927722]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M52,M52)","v":28508257},{"$f":"IF(ISBLANK(B$3),0,(LEN($L52) - LEN(SUBSTITUTE(LOWER($L52),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L52) - LEN(SUBSTITUTE(LOWER($L52),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L52) - LEN(SUBSTITUTE(LOWER($L52),LOWER(D$3),\"\")))/LEN(D$3))","v":11},{"$f":"SUM(B52:D52)","v":12},2017,"Diagnosing Allergic Contact Dermatitis Through Elimination, Perception, Detection and Deduction.",1,0,"Pongpairoj, Puangpet, Thaiwat, McFadden","American journal of clinical dermatology","Diagnosing Allergic Contact Dermatitis Through Elimination, Perception, Detection and Deduction.    Abstract:  Title:  Several authors have commented upon the skills of detection required in making a diagnosis of allergic contact dermatitis. Here, we emphasise the search for clues in a systematic manner. We describe four stages as part of a systematic method for diagnosing allergic contact dermatitis. Firstly, elimination (or inclusion) of non-allergic diagnoses. Secondly, perception: the pre-patch test diagnosis and the 'three scenarios' principle. Thirdly, detection: optimising the sensitivity of the patch test process. Fourthly, deduction: diagnosing allergic contact dermatitis by associating the dermatitis with the allergen exposure. We further compare and contrast the pre-patch test history and examination with the markedly different one ('microhistory' and 'microexamination') used after patch testing. The importance of knowledge of contact dermatitis literature is emphasised with a review of recent publications. Finally, we also highlight the use of contact allergy profiling as an investigative tool in the diagnosis of allergic contact dermatitis.  KEYWORDS: , Clinical Competence, Dermatitis, Allergic Contact/diagnosis, Dermatology/methods, Diagnosis, Differential, Humans, Patch Tests/methods/standards, Practice Guidelines as Topic  Allergic Contact Dermatitis, Contact Dermatitis, Dermatitis, Linalool, Patch Testing",28508257]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M53,M53)","v":27957756},{"$f":"IF(ISBLANK(B$3),0,(LEN($L53) - LEN(SUBSTITUTE(LOWER($L53),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L53) - LEN(SUBSTITUTE(LOWER($L53),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L53) - LEN(SUBSTITUTE(LOWER($L53),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B53:D53)","v":3},2017,"Allergic contact dermatitis caused by exfoliating socks.",0,0,"Millelid, Isaksson","Contact dermatitis","Allergic contact dermatitis caused by exfoliating socks.    Abstract:  Title:  NOABSTRACT. No abstract found.  KEYWORDS: Cosmetics, Monoterpenes, Perfume, linalool, Cosmetics/adverse effects, Dermatitis, Allergic Contact/etiology, Female, Foot Dermatoses/chemically induced, Humans, Middle Aged, Monoterpenes/adverse effects, Perfume/adverse effects  case report, fragrance material, heel fissures, keratolytic",27957756]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M54,M54)","v":27040875},{"$f":"IF(ISBLANK(B$3),0,(LEN($L54) - LEN(SUBSTITUTE(LOWER($L54),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L54) - LEN(SUBSTITUTE(LOWER($L54),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L54) - LEN(SUBSTITUTE(LOWER($L54),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B54:D54)","v":2},2016,"Contact allergens in 'natural' hair dyes.",0,0,"Thorén, Yazar","Contact dermatitis","Contact allergens in 'natural' hair dyes.    Abstract:  Title:  NOABSTRACT. No abstract found.  KEYWORDS: Allergens, Aminophenols, Anthraquinones, Benzenesulfonates, Cyclohexenes, Ethylene Glycols, Hair Dyes, Monoterpenes, Terpenes, Acid Violet 43, Limonene, linalool, phenoxyethanol, 3-aminophenol, Allergens/adverse effects/analysis, Aminophenols/adverse effects, Anthraquinones/adverse effects, Benzenesulfonates/adverse effects, Cyclohexenes/adverse effects, Dermatitis, Allergic Contact/etiology, Ethylene Glycols/adverse effects, Hair Dyes/analysis/chemistry, Humans, Limonene, Monoterpenes/adverse effects, Terpenes/adverse effects  cosmetics, hair dye, organic",27040875]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M55,M55)","v":24603515},{"$f":"IF(ISBLANK(B$3),0,(LEN($L55) - LEN(SUBSTITUTE(LOWER($L55),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L55) - LEN(SUBSTITUTE(LOWER($L55),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L55) - LEN(SUBSTITUTE(LOWER($L55),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B55:D55)","v":2},2014,"European Directive fragrances in natural products.",0,0,"Scheman, Scheman, Rakowski","Dermatitis : contact, atopic, occupational, drug","European Directive fragrances in natural products.    Abstract:  Title:  Information on the presence of European Directive fragrance (EUF) allergens in plants and foods is important for numerous reasons. If an individual is allergic to an EUF and is avoiding fragrance, it is possible that they may still be exposed to the allergen in a natural product. In addition, because many of these allergens are also found in foods, it is possible that ingestion of a food containing the allergen may induce systemic contact allergy. Finally, individuals with lip dermatitis may react to contact with foods that contain the allergen. In this article, we have used the data available to identify which plants and foods contain EUF. When available, concentrations of EUF in natural products are provided. The goal of this article is to narrow down the list of botanicals to avoid for specific EUF allergies.  KEYWORDS: Allergens, Anisoles, Benzoates, Biological Products, Coumarins, Cyclohexenes, Flavoring Agents, Monoterpenes, Perfume, Propanols, Salicylates, Terpenes, Eugenol, Farnesol, isoeugenol, Acrolein, anisyl alcohol, hydroxycitronellal, Limonene, coumarin, linalool, geraniol, Benzyl Alcohol, benzyl benzoate, citronellol, cinnamic aldehyde, cinnamyl alcohol, citral, benzyl salicylate, Acrolein/analogs & derivatives/analysis, Allergens/analysis, Anisoles/analysis, Benzoates/analysis, Benzyl Alcohol/analysis, Biological Products/chemistry, Coumarins/analysis, Cyclohexenes/analysis, Eugenol/analogs & derivatives/analysis, European Union, Farnesol/analysis, Flavoring Agents/analysis, Food, Limonene, Monoterpenes/analysis, Perfume/chemistry, Plants/chemistry, Propanols/analysis, Salicylates/analysis, Terpenes/analysis",24603515]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M56,M56)","v":17577350},{"$f":"IF(ISBLANK(B$3),0,(LEN($L56) - LEN(SUBSTITUTE(LOWER($L56),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L56) - LEN(SUBSTITUTE(LOWER($L56),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L56) - LEN(SUBSTITUTE(LOWER($L56),LOWER(D$3),\"\")))/LEN(D$3))","v":3},{"$f":"SUM(B56:D56)","v":4},2007,"Sensitization to 26 fragrances to be labelled according to current European regulation. Results of the IVDK and review of the literature.",1,0,"Schnuch, Uter, Geier, Lessmann, Frosch","Contact dermatitis","Sensitization to 26 fragrances to be labelled according to current European regulation. Results of the IVDK and review of the literature.    Abstract:  Title:  To study the frequency of sensitization to 26 fragrances to be labelled according to current European regulation. During 4 periods of 6 months, from 1 January 2003 to 31 December 2004, 26 fragrances were patch tested additionally to the standard series in a total of 21 325 patients; the number of patients tested with each of the fragrances ranged from 1658 to 4238. Hydroxymethylpentylcyclohexene carboxaldehyde (HMPCC) was tested throughout all periods. The following frequencies of sensitization (rates in %, standardized for sex and age) were observed: tree moss (2.4%), HMPCC (2.3), oak moss (2.0), hydroxycitronellal (1.3), isoeugenol (1.1), cinnamic aldehyde (1.0), farnesol (0.9), cinnamic alcohol (0.6), citral (0.6), citronellol (0.5), geraniol (0.4), eugenol (0.4), coumarin (0.4), lilial (0.3), amyl-cinnamic alcohol (0.3), benzyl cinnamate (0.3), benzyl alcohol (0.3), linalool (0.2), methylheptin carbonate (0.2), amyl-cinnamic aldehyde (0.1), hexyl-cinnamic aldehyde (0.1), limonene (0.1), benzyl salicylate (0.1), gamma-methylionon (0.1), benzyl benzoate (0.0), anisyl alcohol (0.0). 1) Substances with higher sensitization frequencies were characterized by a considerable number of '++/+++' reactions. 2) Substances with low sensitization frequencies were characterized by a high number of doubtful/irritant and a low number of stronger (++/+++) reactions. 3) There are obviously fragrances among the 26 which are, with regard to contact allergy, of great, others of minor, and some of no importance at all.  KEYWORDS: Allergens, Perfume, Adult, Allergens/adverse effects, Dermatitis, Allergic Contact/diagnosis/epidemiology/etiology, Dermatitis, Atopic/epidemiology, Dermatitis, Occupational/epidemiology, Female, Humans, Male, Middle Aged, Patch Tests, Perfume/adverse effects/chemistry/standards, Prevalence, Product Labeling/legislation & jurisprudence, Retrospective Studies",17577350]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M57,M57)","v":16930231},{"$f":"IF(ISBLANK(B$3),0,(LEN($L57) - LEN(SUBSTITUTE(LOWER($L57),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L57) - LEN(SUBSTITUTE(LOWER($L57),LOWER(C$3),\"\")))/LEN(C$3))","v":2},{"$f":"IF(ISBLANK(D$3),0,(LEN($L57) - LEN(SUBSTITUTE(LOWER($L57),LOWER(D$3),\"\")))/LEN(D$3))","v":4},{"$f":"SUM(B57:D57)","v":7},2006,"Skin diseases in workers at a perfume factory.",0,0,"Schubert","Contact dermatitis","Skin diseases in workers at a perfume factory.    Abstract:  Title:  The aim of this study is to find out the causes of skin diseases in one-third of the staff of a perfume factory, in which 10 different perfume sprays were being manufactured. Site inspection, dermatological examination and patch testing of all 26 persons at risk with 4 perfume oils and 30 ingredients of them. The results showed 6 bottlers were found suffering from allergic contact dermatitis, 2 from irritant contact dermatitis, 12 workers showed different strong reactions to various fragrances. The main causes of allergic contact dermatitis were 2 perfume oils (12 cases) and their ingredients geraniol (12 cases), benzaldehyde(9), cinnamic aldehyde (6), linalool, neroli oil, terpenes of lemon oil and orange oil (4 each). Nobody was tested positive to balsam of Peru. Job changes for office workers, packers or printers to other rooms, where they had no longer contact with fragrances, led to a settling. To conclude, automation and replacement of glass bottles by cartridges from non-fragile materials and using gloves may minimize the risk.  KEYWORDS: Oils, Perfume, Beauty Culture, Dermatitis, Occupational/etiology, Facial Dermatoses/etiology, Hand Dermatoses/etiology, Humans, Oils/adverse effects/analysis, Patch Tests, Perfume/adverse effects/chemistry",16930231]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M58,M58)","v":14996046},{"$f":"IF(ISBLANK(B$3),0,(LEN($L58) - LEN(SUBSTITUTE(LOWER($L58),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L58) - LEN(SUBSTITUTE(LOWER($L58),LOWER(C$3),\"\")))/LEN(C$3))","v":1},{"$f":"IF(ISBLANK(D$3),0,(LEN($L58) - LEN(SUBSTITUTE(LOWER($L58),LOWER(D$3),\"\")))/LEN(D$3))","v":1},{"$f":"SUM(B58:D58)","v":3},2003,"Allergenic activity of an air-oxidized ethoxylated surfactant.",0,0,"Karlberg, Bodin, Matura","Contact dermatitis","Allergenic activity of an air-oxidized ethoxylated surfactant.    Abstract:  Title:  Ethoxylated surfactants are used in household and industrial cleaners, topical pharmaceuticals, cosmetics and laundry products. Polyethers, e.g. ethoxylated surfactants and polyethylene glycols, are oxidized by atmospheric oxygen (autoxidized) when stored and handled. We have previously shown that a chemically well-defined non-ionic surfactant, the ethoxylated alcohol penta-ethylene glycol mono-n-dodecyl ether (C12E5), forms a complex mixture of autoxidation products when exposed to air. Predictive testing in guinea pigs showed that the surfactant itself is a non-sensitizer, but that oxidation products formed are skin sensitizers. The aim of this study was to investigate the sensitizing capacity of a total oxidation mixture of C12E5 obtained after autoxidation. The allergenic activity of different oxidation products is discussed as well as the clinical importance of the findings. This study shows that the non-ionic surfactant C12E5 containing 20% oxidation products is a sensitizing mixture. The result accords with what is observed for other compounds that are unstable when in contact with air, e.g. limonene and linalool, major fragrance terpenes. Studies regarding the clinical relevance of our findings should be performed. However, it is already clear from this study that precautions must be taken in handling and storage of ethoxylated surfactants to avoid formation of allergenic mixtures.  KEYWORDS: Allergens, Detergents, Surface-Active Agents, Polyethylene Glycols, Allergens/adverse effects, Animals, Dermatitis, Allergic Contact/etiology, Detergents/adverse effects, Disease Models, Animal, Dose-Response Relationship, Immunologic, Environmental Exposure/adverse effects, Female, Guinea Pigs, Oxidation-Reduction, Patch Tests, Polyethylene Glycols/adverse effects, Probability, Reference Values, Sensitivity and Specificity, Surface-Active Agents/adverse effects/pharmacology",14996046]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & M59,M59)","v":11683833},{"$f":"IF(ISBLANK(B$3),0,(LEN($L59) - LEN(SUBSTITUTE(LOWER($L59),LOWER(B$3),\"\")))/LEN(B$3))","v":1},{"$f":"IF(ISBLANK(C$3),0,(LEN($L59) - LEN(SUBSTITUTE(LOWER($L59),LOWER(C$3),\"\")))/LEN(C$3))","v":0},{"$f":"IF(ISBLANK(D$3),0,(LEN($L59) - LEN(SUBSTITUTE(LOWER($L59),LOWER(D$3),\"\")))/LEN(D$3))","v":2},{"$f":"SUM(B59:D59)","v":3},2001,"Fragrance chemicals in domestic and occupational products.",0,0,"Rastogi, Heydorn, Johansen, Basketter","Contact dermatitis","Fragrance chemicals in domestic and occupational products.    Abstract:  Title:  Epidemiological studies have described an increasing prevalence of fragrance allergy and indicated an association with hand eczema. 59 domestic and occupational products intended for hand exposure were subjected to gas chromatography-mass spectrometric (GC-MS) analyses to test the hypothesis that fragrance chemicals known to have the potential to cause contact allergy but not included in fragrance mix (FM) may be common ingredients in these products. A quantitative analysis of 19 selected fragrances was performed by GC-MS. Further analysis of GC-MS data revealed the presence of 43 other fragrance chemicals/groups of fragrance chemicals in the products investigated. Among the 19 target substances the most commonly detected were limonene in 78%, linalool in 61% and citronellol in 47% of the products investigated. The FM ingredients were present in these products with the following frequencies: oak moss (evernic acid methylester) 2%, cinnamic alcohol 2%, cinnamic aldehyde (cinnamal) 3%, isoeugenol 5%, alpha-amylcinnamic aldehyde (amyl cinnamal) 8%, hydroxycitronellal 12%, eugenol 27%, and geraniol 41%. Thus, the chemical analyses of domestic and occupational products indicates that investigation of potential contact allergy related to these products types should consider fragrance allergens additional to those in the FM, since these may occur with high frequency.  KEYWORDS: Detergents, Perfume, Dermatitis, Allergic Contact/etiology, Dermatitis, Occupational/etiology, Detergents/adverse effects/chemistry, Europe, Gas Chromatography-Mass Spectrometry, Hand Dermatoses/etiology, Humans, Industrial Oils/adverse effects, Occupational Exposure/adverse effects, Perfume/adverse effects/chemistry",11683833]

{"sheet":"Abstract","index":2,"n_rows":5,"n_cols":6,"rows_kept":5,"cut":false,"hidden":false,"merged":[[0,0,0,1]]}
["Abstract with highlights"]
["Article:",{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & C2,C2)","v":28508257},28508257,"PubYr","Authors","Journal"]
["RowonMain:",52]
["Title:","Diagnosing Allergic Contact Dermatitis Through Elimination, Perception, Detection and Deduction.",null,2017,"Pongpairoj, Puangpet, Thaiwat, McFadden","American journal of clinical dermatology"]
["Title and Abstract:","Diagnosing Allergic Contact Dermatitis Through Elimination, Perception, Detection and Deduction.    Abstract:  Title:  Several authors have commented upon the skills of detection required in making a diagnosis of allergic contact dermatitis. Here, we emphasise the search for clues in a systematic manner. We describe four stages as part of a systematic method for diagnosing allergic contact dermatitis. Firstly, elimination (or inclusion) of non-allergic diagnoses. Secondly, perception: the pre-patch test diagnosis and the 'three scenarios' principle. Thirdly, detection: optimising the sensitivity of the patch test process. Fourthly, deduction: diagnosing allergic contact dermatitis by associating the dermatitis with the allergen exposure. We further compare and contrast the pre-patch test history and examination with the markedly different one ('microhistory' and 'microexamination') used after patch testing. The importance of knowledge of contact dermatitis literature is emphasised with a review of recent publications. Finally, we also highlight the use of contact allergy profiling as an investigative tool in the diagnosis of allergic contact dermatitis.  KEYWORDS: , Clinical Competence, Dermatitis, Allergic Contact/diagnosis, Dermatology/methods, Diagnosis, Differential, Humans, Patch Tests/methods/standards, Practice Guidelines as Topic  Allergic Contact Dermatitis, Contact Dermatitis, Dermatitis, Linalool, Patch Testing"]

{"sheet":"Log","index":3,"n_rows":22,"n_cols":6,"rows_kept":22,"cut":false,"hidden":false,"merged":[[0,5,0,10]]}
["Log of activity",null,null,null,null,"Note: Feel free to delete rows, but not columns. Some queries are displayed here as samples."]
["Date","Record Ct","Query Used (double-click on query to rerun)","Src","PMID"]
["2019-09-05T14:19:08",56,"(Linalool) AND ((\"allergic\" AND \"contact\" And dermatitis) OR Dermatitis, Allergic Contact[mh])","Main"]
["2019-09-05T14:12:49",37,"(Dronabinol) AND ((emergency OR emergencies OR spill OR spills OR disaster OR disasters or hurricane OR hurricanes OR flood OR flood OR explosion OR forest fire OR fires OR wildfire OR climate change OR Mass casualty incidents OR Chemical Hazard Release))","Main"]
["2019-09-05T14:07:35",1,"(ethyldichlorosilane) AND ((emergency OR emergencies OR spill OR spills OR disaster OR disasters or hurricane OR hurricanes OR flood OR flood OR explosion OR forest fire OR fires OR wildfire OR climate change OR Mass casualt*))","Main"]
["2019-09-05T14:04:47",11,"(Linalool) AND ((decontamination OR Environmental Restoration and Remediation))","Main"]
["2019-09-05T14:03:15",197,"Articles like 16233935","like",16233935]
["2019-09-05T14:01:31",13,"(Tetrachloroethylene[majr]) AND ((emergency OR emergencies OR spill OR spills OR disaster OR disasters or hurricane OR hurricanes OR flood OR flood OR explosion OR forest fire OR fires OR wildfire OR climate change OR Mass casualt*))","Main"]
["2019-09-05T13:57:27",10,"(Cyperquat OR 1-Methyl-4-phenylpyridinium OR \"1-Methyl-4-phenylpyridinium Chloride\" OR \"N-Methyl-4-phenylpyridinium\") AND ((emergency OR emergencies OR spill* OR disaster OR disasters or hurricane OR flood OR explosion OR forest fire OR fires OR wildfire OR climate change OR Mass casualt*))","Main"]
["2019-09-05T13:56:47",21,"(Triphenyl phosphate) AND ((emergency OR emergencies OR spill* OR disaster OR disasters or hurricane OR flood OR explosion OR forest fire OR fires OR wildfire OR climate change OR Mass casualt*))","Main"]
["2019-09-05T13:43:12",7,"(pentabrominated diphenyl ether 100 OR BDE-100 OR 5436-43-1 OR 2,2',4,4'-Tetrabromodiphenyl ether OR PBDE) AND ((decontamination OR Environmental Restoration and Remediation)) AND emergency","Main"]
["2019-09-05T13:41:43",149,"(pentabrominated diphenyl ether 100 OR BDE-100 OR 5436-43-1 OR 2,2',4,4'-Tetrabromodiphenyl ether OR PBDE) AND ((decontamination OR Environmental Restoration and Remediation))","Main"]
["2019-09-05T13:40:00",4874,"pesticides AND (decontamination OR Environmental Restoration and Remediation[mh])","Main"]
["2019-09-05T13:34:52",300,"OECD AND skin","Main"]
["2019-08-19T15:28:59",54,"(Linalool) AND ((\"allergic\" AND \"contact\" And dermatitis) OR Dermatitis, Allergic Contact[mh])","Main"]
["2019-07-10T16:54:42",72,"((1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine OR MPTP)) AND ((Respiratory hypersensitivity OR respiratory sensitization OR Bronchial Hyperreactivity OR Respiration Disorders OR Respiratory Tract Diseases OR (Drug hypersensitivity AND lung) OR (irritants AND lung) OR (occupational diseases AND lung) OR ((asthma OR rhinitis) AND chemically induced) OR Respiration/drug effects OR Bronchoconstriction OR Respiratory Mechanics))","Main"]
["2019-07-10T16:50:39",2,"(5370-41-2 OR Pridefine) AND ((neurotoxicity OR (Nervous system diseases and chemically induced) OR ((neurons OR brain OR behavior) AND drug effects))","Main"]
["2019-07-09T11:14:32",118,"(Styrene) AND ((cochlea AND drug effects) OR (ear AND drug effects) OR  (Neurons, Afferent OR auditory hair cells OR organ of corti OR lateral line system[mh]) OR deafness OR hearing loss OR hearing disorders OR ear diseases  or ototoxicity OR tinnitus))","Main"]
["2019-07-08T13:21:16",5,"(Tetrabromobisphenol A OR TBBPA) AND ((selenoproteins OR selenium) OR Thioredoxins OR glutathione peroxidase)","Main"]
["2019-07-08T13:20:28",11,"(Linalool) AND ((Cognition Disorders OR Memory Disorders OR Learning Disorders OR ((Learning OR Maze Learning OR Memory OR Mental Recall OR Spatial Learning OR Spatial Memory) AND (drug effects OR toxicity)))","Main"]
["2019-07-08T13:15:13",121,"(Styrene) AND ((ccl2 or cxcl10 or il-1 or tnf-alpha or chemokine))","Main"]
["2019-07-08T11:07:41",25,"(pentabrominated diphenyl ether 100 OR BDE-100 OR 5436-43-1 OR 2,2',4,4'-Tetrabromodiphenyl ether OR PBDE) AND ((Fatty liver OR steatosis))","Main"]

{"sheet":"Notes","index":4,"n_rows":5,"n_cols":14,"rows_kept":5,"cut":false,"hidden":false,"merged":[]}
["My Notes",null,null,null,null,null,null,null,null,"Note: Feel free to delete rows after Row 2, but not columns. Some sample Notes may be displayed. "]
["PMID ","yes","no","maybe","total","Tag","Note ","PubYr","Title","Authors","Journal","LinkID","tiab","When Noted"]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & L3,L3)","v":15606147},1,0,0,null,"Linalool and skin",null,2004,"Contact allergens formed on air exposure of linalool. Identification and quantification of primary and secondary oxidation products and the effect on skin sensitization.","Sköld, Börje, Harambasic, Karlberg","Chemical research in toxicology",15606147,"Contact allergens formed on air exposure of linalool. Identification and quantification of primary and secondary oxidation products and the effect on skin sensitization.    Abstract:  Title:  Linalool (3,7-dimethyl-1,6-octadien-3-ol) is an important fragrance chemical, frequently used in scented products because of its fresh, flowery odor. Linalool is an unsaturated hydrocarbon and is therefore susceptible to oxidation in the presence of air. The primary oxidation products, that is, hydroperoxides, formed in the autoxidation process, are reactive compounds that can be suspected to act as sensitizers. In the present investigation, we studied the autoxidation of linalool with emphasis on the formation of hydroperoxides. The oxidation products were isolated using flash chromatography and preparative HPLC and were identified with NMR and GC/MS, using synthesized reference compounds. Two hydroperoxides and several different secondary oxidation products were identified, among which some contain structural features that make them potential allergens. The amounts of linalool and the major oxidation products were quantified over time, using GC and an HPLC-method, suitable for the analysis of thermolabile primary oxidation products. The hydroperoxide 7-hydroperoxy-3,7-dimethylocta-1,5-diene-3-ol was found to be present in 15% in an oxidized sample. The local lymph node assay (LLNA) was used to investigate the sensitizing potential of pure linalool, two samples of air-exposed linalool, and oxidation products of linalool (an alpha,beta-unsaturated aldehyde, a mixture of two hydroperoxides, and an alcohol). Pure linalool showed no sensitizing potential. The air-exposed samples of linalool produced clearly positive responses, and the hydroperoxides were the strongest allergens of the tested oxidation products. The study demonstrates the importance of autoxidation on the sensitizing potential of linalool. We also conclude that the sensitizing potential differs with the composition of the oxidation mixture and thus with the air exposure time.  KEYWORDS: Allergens, Monoterpenes, Perfume, Hydrogen Peroxide, linalool, Allergens/chemistry/immunology, Chromatography, High Pressure Liquid, Dermatitis, Allergic Contact/immunology, Humans, Hydrogen Peroxide/analysis, Local Lymph Node Assay, Monoterpenes/chemistry/immunology/metabolism, Oxidation-Reduction, Perfume/chemistry, Time Factors","2019-08-19T15:29:43"]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & L4,L4)","v":18154552},1,0,0,null,"Linalool and skin",null,2008,"Autoxidation of linalyl acetate, the main component of lavender oil, creates potent contact allergens.","Sköld, Hagvall, Karlberg","Contact dermatitis",18154552,"Autoxidation of linalyl acetate, the main component of lavender oil, creates potent contact allergens.    Abstract:  Title:  Fragrances are among the most common causes of allergic contact dermatitis. We have in previous studies shown that linalool, present in lavender oil, autoxidizes on air exposure, forming allergenic oxidation products. Oxidized linalool was found to be a frequent cause of contact allergy in a patch test study on consecutive dermatitis patients. Linalyl acetate, the main component of lavender oil is commonly used as a fragrance chemical in scented products. Because of structural similarities, linalyl acetate should also be susceptible to oxidation on air exposure, forming similar oxidation products as linalool. The aim of the present study was to investigate the autoxidation of linalyl acetate and the influence of oxidation on its sensitizing potency. Analyses were performed using gas chromatography, nuclear magnetic resonance spectrometry and mass spectrometry. Sensitizing potencies of compounds were determined using the local lymph node assay (LLNA) in mice. Analyses showed that the content of linalyl acetate decreased over time on air exposure and other compounds were formed. Hydroperoxides, an epoxide and an alcohol were identified as oxidation products from linalyl acetate. In the LLNA, linalyl acetate of high purity showed a weak sensitizing potency (EC3 25%). Autoxidation increased the sensitizing potency of linalyl acetate, and a 10 weeks oxidized sample gave an EC3 value of 3.6%. As for linalool, the hydroperoxides were shown to be the oxidation products with the highest sensitizing potency. It is concluded that autoxidation of the weakly allergenic linalyl acetate leads to formation of allergenic oxidation products.  KEYWORDS: Allergens, Monoterpenes, Oils, Volatile, Plant Oils, linalyl acetate, Hydrogen Peroxide, lavender oil, Air, Allergens/adverse effects/chemistry/metabolism, Animals, Chromatography, Gas, Dermatitis, Allergic Contact/etiology/immunology, Hydrogen Peroxide/adverse effects/chemistry/metabolism, Lymph Nodes/immunology, Magnetic Resonance Spectroscopy, Mass Spectrometry, Mice, Monoterpenes/adverse effects/chemistry/metabolism, Oils, Volatile/adverse effects/chemistry, Oxidation-Reduction, Plant Oils/adverse effects/chemistry, Skin/immunology, Time Factors","2019-08-19T15:29:43"]
[{"$f":"HYPERLINK(\"https://www.ncbi.nlm.nih.gov/pubmed/\" & L5,L5)","v":12492549},1,0,0,null,"Linalool and skin",null,2002,"Investigation of the skin sensitizing activity of linalool.","Basketter, Wright, Colson, Patlewicz, Pease","Contact dermatitis",12492549,"Investigation of the skin sensitizing activity of linalool.    Abstract:  Title:  An increasing range of chemicals appears to be capable of causing skin sensitization as a result of their capacity to undergo air oxidation (autoxidation) with the consequent formation of reactive species such as epoxides and hydroperoxides. In this small investigation, the ability of linalool, a common fragrance ingredient, to cause such effects was quantified using the local lymph node assay before and after careful purification by vacuum distillation. The commercially available grade of linalool (97% purity) was shown to be a weak skin sensitizer. Various impurities, including linalool oxide, dihydrolinalool, epoxylinalool, 3-hexenyl butyrate and 3,7-dimethyl-1,7-octadiene-3,6-diol were identified and were completely removed (except for the dihydrolinalool remaining at 1.4%) and the re-purified linalool retested. Neither linalool or dihydrolinalool are protein-reactive compounds. The sensitization potency of the re-purified linalool sample was considerably reduced, but not entirely eliminated, suggesting either that an allergenic impurity could be very quickly reformed by mechanisms of activation or that certain potent undetectable allergens remained. Both possibilities are consistent with what is understood of the chemistry and composition of commercially available linalool.  KEYWORDS: Monoterpenes, Perfume, linalool, Dermatitis, Allergic Contact/diagnosis/etiology, Dose-Response Relationship, Drug, Humans, Immunization, Monoterpenes/adverse effects/chemistry, Patch Tests/methods, Perfume/adverse effects, Sensitivity and Specificity","2019-08-19T15:29:43"]

{"sheet":"Pathway_queries","index":5,"n_rows":102,"n_cols":5,"rows_kept":102,"cut":false,"hidden":false,"merged":[]}
["Pathway Queries",null,null,"Note: these are starting points … please expand and customize","How to use: select rows and click on button"]
[]
["Header1: Pathway","Header2: KeyEvent","More data","Query (double-click to see how the query looks to PubMed)","Notes / titles"]
["aop07","1_mie",408,"((Aromatase OR Cyp19) AND (inhibition or antagonism)) OR Aromatase Inhibitors ","Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female"]
["aop07","2_ke",219,"(estrogen AND synthesis AND drug effects) OR Estrogen antagonists","Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female"]
["aop07","3_ao1",406,"((fertility  OR impaired fertility ) AND  female AND drug effects )  OR infertility, female[mh]","Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female"]
["aop07","3_ao2",406,"(ovarian cycle OR menstrual cycle OR menstruation AND (disrupt* OR disregulat*))","Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female"]
[{"$f":"HYPERLINK(\"https://aopwiki.org/aops/126\",\"aop126\")","v":"aop126"},"1_ mie",849,"Adrenergic alpha-2 Receptor Antagonists OR (Receptors, Adrenergic, alpha-2 AND inhibit)","Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation"]
["aop126","2_ke1",null,"(LHRH Receptor* OR Gonadotropin-Releasing Hormone OR Gonadotropin) AND adrenergic receptor ","Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation"]
["aop126","3_ke?",null,"(Proto-Oncogene Proteins c-fos OR fos gene* OR c-fos) AND (decrease OR down-regulate OR inhibit)","Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation"]
["aop126","7_ke4",532,"ovulation AND delay*","Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation"]
["aop126","8_KE",532,"ovulation AND delay*","Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation"]
["aop126","9_AO",null,"fertility AND drug effects ","Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation"]
["aop126","9_KE ",null,"(chromosome  AND drug effects) OR polyploid*  OR chromosome aberrations ","Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation"]
["aop17","10_AO",341,"(Cognition Disorders OR Memory Disorders OR Learning Disorders OR ((Learning OR Maze Learning OR Memory OR Mental Recall OR Spatial Learning OR Spatial Memory) AND (drug effects OR toxicity))","Oxidative stress and Developmental impairment in learning and memory"]
["aop17","1_mie",1487,"(selenoproteins OR selenium) OR Thioredoxins OR glutathione peroxidase","Oxidative stress and Developmental impairment in learning and memory"]
["aop17","2_KE",1538,"(oxidative stress )","Oxidative stress and Developmental impairment in learning and memory"]
["aop17","3_KE",1392,"reactive oxygen species ","Oxidative stress and Developmental impairment in learning and memory"]
["aop17","4_KE",1488,"(glutamate OR glutamic acid OR  Glutamate Plasma Membrane Transport Proteins OR  Amino Acid Transport System X-AG) AND (homeostasis OR drug effects OR toxicity) ","Oxidative stress and Developmental impairment in learning and memory"]
["aop17","5_KE",55,"apoptosis OR cell death ","Oxidative stress and Developmental impairment in learning and memory"]
["aop17","6_KE",188,"neuroinflammation OR ((nervous system OR brain) AND inflammation) ","Oxidative stress and Developmental impairment in learning and memory"]
["aop17","7_KE",1492,"(microglia OR astrocytes OR neuroglia OR glial OR Glial Fibrillary Acidic Protein OR gfap)  AND (activation OR drug Effects)","Oxidative stress and Developmental impairment in learning and memory"]
["aop17","8_KE",1493,"(inflammation mediators OR NF-kappa B OR Map Kinase OR JNK Mitogen-Activated Protein Kinases)","Oxidative stress and Developmental impairment in learning and memory"]
["aop17","9_KE",386,"(Nerve net OR Neural Pathways OR hippocampus)","Oxidative stress and Developmental impairment in learning and memory"]
[{"$f":"HYPERLINK(\"https://aopwiki.org/aops/23\",\"aop23\")","v":"aop23"},"1_mie",25,"(Agonism, Androgen receptor OR androgens ) AND fish","Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)"]
["aop23","2_ke",129," (Receptors, Gonadotropin AND antagonists & inhibitors AND fish)","Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)"]
["aop23","3_ke",274,"testosterone AND  (down-regulation OR antagonist OR antagonism OR reduction) AND fish","Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)"]
["aop23","4_ke",3,"Estradiol AND (down-regulation OR antagonist OR antagonism OR reduction) AND fish","Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)"]
["aop23","5_ke",309,"vitellogenin AND oocytes AND fish","Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)"]
["aop23","6_ao",360,"((population AND decrease) OR (mortality AND increase) AND Fish)","Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)"]
["aop40","1_mie",396,"(covalent binding AND protein) OR (protein binding) OR adducts OR haptens OR IL-18 OR OR caspase-1 OR electrophile OR hapten-protein complex or nrf2 OR  NADPH-quinone oxidoreductase 1  OR glutathione S-transferase","Covalent Protein binding leading to Skin Sensitisation"]
["aop40","2_ke",826,"((Keratinocytes OR Keratin) AND (drug effects OR toxicity)) ","Covalent Protein binding leading to Skin Sensitisation"]
["aop40","3_ke",398,"(dendritic cells OR  cell-mediated immunity OR antigen-presenting cells  OR  major histocompatibility complex)","Covalent Protein binding leading to Skin Sensitisation"]
["aop40","4_ke ",272,"Antigens, Differentiation, T-Lymphocyte[mh] OR T-Lymphocytes  OR \"memory T-cells\"[tiab]","Covalent Protein binding leading to Skin Sensitisation"]
["aop40","5_ao",827,"\"skin sensitization\" OR \"skin sensitisation\" OR Drug Eruptions[mh] OR Dermatitis, Allergic Contact OR Drug Hypersensitivity OR Dermatitis, Contact OR Dermatitis, Atopic","Covalent Protein binding leading to Skin Sensitisation"]
["aop42","1_mie",279,"((thyroperoxidase OR Iodide Peroxidase OR TPO) AND (inhibition OR inhibit OR decrease)) ","Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"]
["aop42","2_ke",277,"(thyroid hormone OR t3 OR t4) AND (synthesis or inhibition)","Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"]
["aop42","3_ke",281,"(thyroid hormone OR t3 OR t4) AND (serum or blood or plasma) and  (decrease OR inhibition OR down-regulate)","Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"]
["aop42","4_ke",280,"((thyroid hormone OR t3 OR t4) AND (brain or cortex or hippocampus))","Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"]
["aop42","5_ke",756,"((hippocampus) and (gene expression) and (development))","Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"]
["aop42","6_ke",757,"((hippocampus AND (anatomy) and (development))","Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"]
["aop42","7_ke",758,"((hippocampus AND (physiology) and (development))","Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"]
["aop42","8_ao",402,"((memory or learning) and (spatial or temporal or contextual))","Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"]
["aop42","8ao_broad",402,"(Cognition Deficits OR cognition/drug effects OR Cognitive Dysfunction OR Intelligence/drug effects OR (brain AND embryonic development))","Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"]
[{"$f":"HYPERLINK(\"https://aopwiki.org/aops/43\",\"aop43\")","v":"aop43"},"1_mie",305,"(Vascular Endothelial Growth Factor Receptor-2 OR Vascular Endothelial Growth Factor) AND (inhibition  OR inhibit OR antagonism OR inhibitor OR antagonist)","Disruption of VEGFR Signaling Leading to Developmental Defects"]
["aop43","2_ke",28,"((angiogenesis OR vasculogenesis) AND (reduce OR inhibit)) OR (Neovascularization, Physiologic AND (drug effects OR toxicity))","Disruption of VEGFR Signaling Leading to Developmental Defects"]
["aop43","3_ke",110,"endothelium OR endothelial AND (damage OR impair OR impairment)","Disruption of VEGFR Signaling Leading to Developmental Defects"]
["aop43","4_ke",298,"Blood circulation AND (drug effects AND toxicity)","Disruption of VEGFR Signaling Leading to Developmental Defects"]
["aop43","5_ao1",1001,"birth defects OR Congenital Abnormalities","Disruption of VEGFR Signaling Leading to Developmental Defects"]
["aop43","6_ao2",1001,"(bone OR bone development OR calcification OR osteogenesis OR limb bud/drug effects OR limb deformity) AND (embryo OR embryonic development OR fetus OR fetal development)","Disruption of VEGFR Signaling Leading to Developmental Defects"]
["aop57","1_mie",18,"(ahr OR (Aryl Hydrocarbon AND receptor)) AND (upregulat* OR agonism OR agonist OR increase)"]
["aop57","2_ke",450,"(very-low-density lipoprotein OR Lipoproteins, VLDL) AND  (downregulat* OR antagonists OR inhibitors)"]
["aop57","3_ke",451," (Mitochondrial fatty acid beta-oxidation OR Mitochondrial Trifunctional Protein)"]
["aop57","4_ke",327,"(Fatty acids OR fatty acid) And (accum* OR increase)"]
["aop57","5_ke",216,"(PCK1 protein OR Phosphoenolpyruvate Carboxykinase (GTP))"]
["aop57","6_ke",291,"(Triglycerides AND (increase OR agonis*))"]
["aop57","7_ke",54,"(CD36 Antigens OR Fatty Acid Transport Proteins)"]
["aop57","8_ke",465,"(fatty acid transport AND influx)"]
["aop57","9_ke",466,"(Receptors, LDL AND (agonis* OR up-regulat* OR upregulat*)"]
[{"$f":"HYPERLINK(\"https://aopwiki.org/aops/126\",\"aop57\")","v":"aop57"},"10_ke",467,"(Lipoproteins, VLDL OR \"very low density lipoproteins\"[tiab] OR Receptors, LDL OR VLDL receptor) AND (up-regulation OR increase) AND uptake","AhR activation leading to hepatic steatosis"]
[{"$f":"HYPERLINK(\"https://aopwiki.org/aops/126\",\"aop57\")","v":"aop57"},"11_ke",80,"(cyp1a1 OR Cytochrome P-450 CYP1A1) AND (up-regulat* OR increase)","AhR activation leading to hepatic steatosis"]
[{"$f":"HYPERLINK(\"https://aopwiki.org/aops/126\",\"aop57\")","v":"aop57"},"12_ke",462,"(Stearoyl-CoA Desaturase AND (increase or accumulation) ","AhR activation leading to hepatic steatosis"]
[{"$f":"HYPERLINK(\"https://aopwiki.org/aops/57\",\"aop57\")","v":"aop57"},"13_ke",455,"(Fatty liver OR steatosis)","AhR activation leading to hepatic steatosis"]
["aop8","1_mie",239,"(Pregnane X Receptor OR NR1I2 protein) AND (activate OR activation OR agonism)","Nuclear receptor induced TH Catabolism and Developmental Hearing Loss"]
["aop8","2_ke",280,"((thyroid hormone OR t3 OR t4) AND (brain or cortex or hippocampus))","Nuclear receptor induced TH Catabolism and Developmental Hearing Loss"]
["aop8","3_ke",281,"(thyroid hormone OR t3 OR t4) AND (serum or blood or plasma) and  (decrease OR inhibition OR down-regulate)","Nuclear receptor induced TH Catabolism and Developmental Hearing Loss"]
["aop8","4_ke",295,"(glucuronyltransferase AND (upregulation OR agonism OR increase))","Nuclear receptor induced TH Catabolism and Developmental Hearing Loss"]
["aop8","5_ke",401,"(glucuronide OR glucuronides) AND (increase OR upregulat*) AND (bile OR bilary OR urine OR excrete OR urinalysis)","Nuclear receptor induced TH Catabolism and Developmental Hearing Loss"]
["aop8","6_ke",757,"((hippocampus AND (anatomy) and (development))","Nuclear receptor induced TH Catabolism and Developmental Hearing Loss"]
["aop8","7_ke",758,"((hippocampus AND (physiology) and (development))","Nuclear receptor induced TH Catabolism and Developmental Hearing Loss"]
["aop8","8_ke",756,"((hippocampus AND gene expression) AND drug effects)"]
["aop8","9_ao",319,"(cochlea AND drug effects) OR (ear AND drug effects) OR  (Neurons, Afferent OR auditory hair cells OR organ of corti OR lateral line system[mh]) OR deafness OR hearing loss OR hearing disorders OR ear diseases  or ototoxicity OR tinnitus)","Nuclear receptor induced TH Catabolism and Developmental Hearing Loss"]
["HeartDev putative AOP","1_mie",null,"(\"bone morphogenic protein 2\" OR bmp2 OR vegf-A OR ephrin)","putative AOP for valvuloseptal defects caused by chemical exposure (TCE)"]
["HeartDev putative AOP","2_mie",null,"(Wnt Signaling Pathway OR Wnt Proteins OR WNT Receptors )","putative AOP for valvuloseptal defects caused by chemical exposure (TCE)"]
["HeartDev putative AOP","3_ke",null,"(endothelial mesenchymal transition OR Endothelial-Mesenchymal Transition)","putative AOP for valvuloseptal defects caused by chemical exposure (TCE)"]
["HeartDev putative AOP","4_ke",null,"(Cell Adhesion OR Cell Proliferation OR Extracellular Matrix OR  Basement Membrane OR Mesenchymal Stromal Cells OR Myocytes, Cardiac OR (neural crest cells AND heart ) AND drug effects","putative AOP for valvuloseptal defects caused by chemical exposure (TCE)"]
["HeartDev putative AOP","5_ke",null,"(Mesoderm OR Myocardium OR Endocardium) AND drug Effects","putative AOP for valvuloseptal defects caused by chemical exposure (TCE)"]
["HeartDev putative AOP","6_ke",null,"(Endocardial Cushions OR Atrial Septum OR Ductus Arteriosus OR Fetal Heart OR Heart OR Heart Atria OR Heart Septum OR Heart Valves OR Heart Ventricles OR Mitral Valve OR Tricuspid Valve OR Truncus Arteriosus OR Ventricular Septum) AND (toxicity OR drug effects)","putative AOP for valvuloseptal defects caused by chemical exposure (TCE)"]
["HeartDev putative AOP","9_ao",null,"(Endocardial Cushion Defects OR Arteriovenous Malformations OR Heart Septal Defects OR Heart Valve Diseases OR endocardial cushions OR \"Heart Defects, Congenital\") AND (drug effects OR toxicity OR Abnormalities, Drug-Induced OR chemically induced) AND (embryology OR embryonic heart OR pregnancy OR embryo OR fetus)","putative AOP for valvuloseptal defects caused by chemical exposure (TCE)"]
["KCC","Adducts",null,"protein Adducts OR dna adducts OR epoxides OR quinones OR aldehydes","IARC Key characteristics of cancer"]
["KCC","Cancer",null,"(cancer OR neoplasms OR precancerous OR carcinogen OR carcinoma) AND (toxicity OR poisoning OR adverse effects)","IARC Key characteristics of cancer"]
["KCC","Cell immortalization",null,"(cell immortalization OR cell division OR hayflick limit OR Aging/genetics OR Cellular Senescence)","IARC Key characteristics of cancer"]
["KCC","DNA",null," (dna/drug effects OR DNA Damage OR chromosome aberrations OR genotoxicity OR micronucleus   OR mutagenicity tests OR mutagens OR mutagenicity OR mutagenic or \"gene mutation\" OR \"ames \" OR \"comet assay\")","IARC Key characteristics of cancer"]
["KCC","DNA break/repair",null,"(topoisomerase OR DNA Repair/drug effects OR double-strand break repair)","IARC Key characteristics of cancer"]
["KCC","Epigenetics",null,"(DNA methylation OR histone modification OR Histone Code OR Chromatin Assembly and Disassembly OR microRNAs OR Epigenesis, Genetic)","IARC Key characteristics of cancer"]
["KCC","Immunosuppress",null,"(immunosuppressive OR immune system dysfunction)","IARC Key characteristics of cancer"]
["KCC","Inflammation",null,"(inflammation OR macrophages)","IARC Key characteristics of cancer"]
["KCC","Oxidative stress",null,"(oxidative stress OR reactive oxygen species OR mitochondria/drug effects )","IARC Key characteristics of cancer"]
["KCC","Proliferation",null,"(cell proliferation OR cell death OR apoptosis OR Neovascularization, Pathologic)","IARC Key characteristics of cancer"]
["KCC","Receptors",null,"receptors AND (antagonism OR agonism OR drug effects)","IARC Key characteristics of cancer"]
["vascular dev","1mie",null,"(hypoxia OR Reactive Oxygen Species OR Hif1a OR ahr OR Aryl Hydrocarbon ","putative expanded AOP for vascular development"]
["vascular dev","2mie",null,"(Vegf OR fgf OR notch OR dll4 )  ","putative expanded AOP for vascular development"]
["vascular dev","3mie",null,"(ccl2 or cxcl10 or il-1 or tnf-alpha or chemokine)","putative expanded AOP for vascular development"]
["vascular dev","4mie",null,"(extracellular matrix OR upar Or pai-1 OR mmp OR intg)","putative expanded AOP for vascular development"]
["vascular dev","5ke_Cell",null,"(angioblast OR \"blood island\"[tiab] OR  Hemangioblasts)","putative expanded AOP for vascular development"]
["vascular dev","6ke_Organ",null,"(endothelial cells AND cytoskeleton AND sprout*)","putative expanded AOP for vascular development"]
["vascular dev","7ke3_Cell",null,"(macrophage AND (motility OR movement OR growth factor))","putative expanded AOP for vascular development"]
["vascular dev","vdc_ao1",null,"((placenta OR Chorionic Villi OR decidua or trophoblasts) AND (nutrient OR blood supply) AND (toxicity OR drug effects))","putative expanded AOP for vascular development"]
["vascular dev","vdc_ao2",null,"(Fetal Growth Retardation OR (abnormalities AND embryonic development))","putative expanded AOP for vascular development"]
["vascular dev","vdc_ao3",null,"((Infant, Low Birth Weight OR malformation OR Fetal Mortality OR Infant mortality) AND (toxicity OR drug effects))","putative expanded AOP for vascular development"]
["vascular dev","vdc_ke4",null,"((Myocytes, Smooth Muscle OR pericytes  OR Muscle, Smooth, Vascular OR \"mural cell\"[tiab]) AND (vessel stabilization OR recruitment))","putative expanded AOP for vascular development"]
["vascular dev","vdc_ke5",null,"(Neovascularization, Pathologic  OR Neovascularization, Physiologic  OR blood vessels\\development)","putative expanded AOP for vascular development"]

{"sheet":"Sample_queries","index":6,"n_rows":37,"n_cols":5,"rows_kept":37,"cut":false,"hidden":false,"merged":[]}
["Sample Queries",null,null,"Note: these are starting points … please expand and customize"]
[]
["Category","Heading ","MoreInfo","Query (double-click to see how the query looks to PubMed)","Comments"]
["Ecological","Algae",null,"\"algal bloom\" OR eutrophication OR algae","any relationship"]
["Epidemiology","Epi",null,"epidemiology"]
["Exposure","Dust exposure",null,"environmental exposure AND dust"]
["Exposure","Food exposure",null,"environmental exposure AND food"]
["Exposure","Water exposure",null,"environmental exposure AND (water OR groundwater OR drinking water)"]
["Exposure","Occupational",null,"(occupational exposure OR Air Pollutants, Occupational OR  ((worker OR workers OR employee OR workplace OR industry) AND exposure))"]
["Emergency/disaster","Emergency / disaster",null,"(emergency OR emergencies OR spill OR spills OR disaster OR disasters or hurricane OR hurricanes OR flood OR flood OR explosion OR forest fire OR fires OR wildfire OR climate change OR Mass casualty incidents OR Chemical Hazard Release)"]
["Decontamination","Decontamination",null,"(decontamination OR Environmental Restoration and Remediation)"]
["Mechanism","Oxidative stress",null,"\"oxidative stress\" OR \"free radicals\" OR \"reactive oxygen species\" OR peroxides","needs work "]
["Metabolism","Metabolism",null,"(metabolism OR metabolite OR tissue distribution OR pharmacokinetics OR pharmacodynamics)"]
["Methods","Analytical chemistry",null,"\"Chemistry Techniques, Analytical\" OR analytical chemistry"]
["Methods","Statistical",null,"Statistics as Topic[mh] OR statistics OR statistical"]
["Methods ","In vitro",null,"In Vitro Techniques[mh] OR cell culture or \"in vitro\""]
["Mixtures ","Mixtures",null," (Drug synergism[mh] OR cocarcinogenesis OR  pesticide synergists[mh] OR mixture[tiab] OR mixtures[tiab] OR Drug Antagonism[mh] OR Drug Interactions[mh] OR drug agonism)"]
["Medicine","Clinical trials",null,"((clinical[Title/Abstract] AND trial[Title/Abstract]) OR clinical trial[Publication Type] )"]
["Medicine","Clinical trials in children",null,"((children OR child OR infants) AND human) AND ((clinical[Title/Abstract] AND trial[Title/Abstract]) OR clinical trial[Publication Type] )"]
["Medicine","Obesity",null,"(obesity OR obese OR adipose OR overweight Or adipogenesis OR adipose tissue)"]
["Toxicity","Genetox",null," (dna/drug effects OR DNA Damage OR chromosome aberrations OR genotoxicity OR micronucleus  OR DNA Repair OR mutagenicity tests OR mutagens OR mutagenicity OR mutagenic or \"gene mutation\" OR \"ames \" OR \"comet assay\")"]
["Toxicity","Cancer",null,"neoplasms or cancer "]
["Toxicity ","ReproTox",null,"(reproduction AND (toxicity OR abnormal OR adverse effects))"]
["Toxicity","NeuroTox",null,"(neurotoxicity OR (Nervous system diseases and chemically induced) OR ((neurons OR brain OR behavior) AND drug effects)"]
["Toxicity","DevTox",null,"((toxicity OR congenital abnormalities OR Prenatal Exposure Delayed Effects) AND (fetus OR embryo OR embryonic development OR larva OR eggs)) or embryotoxicity "]
["Toxicity","Skin sensitization",null,"(\"allergic\" AND \"contact\" And dermatitis) OR Dermatitis, Allergic Contact[mh]"]
["Toxicity","Respiratory sensitisation",null,"(Respiratory hypersensitivity OR respiratory sensitization OR Bronchial Hyperreactivity OR Respiration Disorders OR Respiratory Tract Diseases OR (Drug hypersensitivity AND lung) OR (irritants AND lung) OR (occupational diseases AND lung) OR ((asthma OR rhinitis) AND chemically induced) OR Respiration/drug effects OR Bronchoconstriction OR Respiratory Mechanics)"]
["Use","Pharmaceutical",null,"\"therapeutic use\" OR \"therapeutic use\"[subheading]\" OR pharmacologic actions[mh] OR drug therapy"]
["Use","Pesticide",null,"pesticide OR insecticide OR rodenticide OR fungicide "]
["Use","Cosmetics ",null,"cosmetics OR beauty "]
["Use","Explosive Agents",null,"Explosive Agents OR explosive OR explosives"]
["Use","Food   ",null,"food OR diet OR beverage OR nutrition"]
["Use","Surface-acting ",null,"Antifoaming OR Anti-foaming OR detergent OR detergents OR soap OR detergent  OR surfactant"]
["Use","Dye/coloring",null,"dye OR \"coloring agent\" OR pigment OR pigments"]
["Use ","Fertilizer",null,"fertilizer OR fertilize "]
["Use ","Solvents",null,"solvents OR solvent"]
["Use","Flame retardant",null,"flame retardant OR flame retardants OR fire suppression"]

{"sheet":"Landscape","index":7,"n_rows":20,"n_cols":12,"rows_kept":20,"cut":false,"hidden":false,"merged":[]}
["Abstract Sifter","Landscape View"]
[]
[null,null,"Subject queries:",null," (dna/drug effects OR DNA Damage OR chromosome aberrations OR genotoxicity OR micronucleus  OR DNA Repair OR mutagenicity tests OR mutagens OR mutagenicity OR mutagenic or \"gene mutation\" OR \"ames \" OR \"comet assay\")","neoplasms or cancer ","(reproduction AND (toxicity OR abnormal OR adverse effects))","(neurotoxicity OR (Nervous system diseases and chemically induced) OR ((neurons OR brain OR behavior) AND drug effects)","((toxicity OR congenital abnormalities OR Prenatal Exposure Delayed Effects) AND (fetus OR embryo OR embryonic development OR larva OR eggs)) or embryotoxicity ","(\"allergic\" AND \"contact\" And dermatitis) OR Dermatitis, Allergic Contact[mh]","(Respiratory hypersensitivity OR respiratory sensitization OR Bronchial Hyperreactivity OR Respiration Disorders OR Respiratory Tract Diseases OR (Drug hypersensitivity AND lung) OR (irritants AND lung) OR (occupational diseases AND lung) OR ((asthma OR rhinitis) AND chemically induced) OR Respiration/drug effects OR Bronchoconstriction OR Respiratory Mechanics)","(emergency OR emergencies OR spill OR spills OR disaster OR disasters or hurricane OR hurricanes OR flood OR flood OR explosion OR forest fire OR fires OR wildfire OR climate change OR Mass casualty incidents OR Chemical Hazard Release)"]
[null,null,"Summary heading",null,"Toxicity","Toxicity","Toxicity ","Toxicity","Toxicity","Toxicity","Toxicity","Emergency/disaster"]
["DSSTOX link to Dashboard","Preferred Name","Chemical / Entity query","Link","Genetox","Cancer","ReproTox","NeuroTox","DevTox","Skin sensitization","Respiratory sensitisation","Emergency / disaster"]
[null,"PERC/TCE","Tetrachloroethylene[majr]",null,42,76,38,68,14,0,22,15]
[null,"Tripropylene glycol","Tripropylene glycol OR 24800-44-0 ",null,4,3,0,0,0,5,0,0]
[null,"Tetrachlorophthalic anhydride","Tetrachlorophthalic anhydride",null,1,0,0,1,0,0,11,0]
[null,"Linalool","Linalool",null,41,58,5,154,24,56,20,3]
[null,"TBBPA","Tetrabromobisphenol A OR TBBPA",null,16,46,45,77,57,0,3,16]
[null,"Dronabinol / THC","Dronabinol",null,60,441,131,2625,57,2,125,37]
[null,"TPHP","Triphenyl phosphate",null,9,12,22,26,27,3,3,22]
[null,"BDE-100 / PBDE","pentabrominated diphenyl ether 100 OR BDE-100 OR 5436-43-1 OR 2,2',4,4'-Tetrabromodiphenyl ether OR PBDE",null,94,160,341,347,230,0,13,125]
[null,"Styrene","Styrene",null,1032,1083,99,524,76,12,242,116]
[null,"PCB126","3,4,5,3',4'-pentachlorobiphenyl",null,22,53,58,53,73,0,6,0]
[null,"MPTP","(1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine OR MPTP)",null,200,325,31,5270,57,0,72,31]
[null,"MPTP transformation product","Cyperquat OR 1-Methyl-4-phenylpyridinium OR \"1-Methyl-4-phenylpyridinium Chloride\" OR \"N-Methyl-4-phenylpyridinium\"",null,103,199,27,1600,65,0,16,10]
[null,"Ethyldichlorosilane","ethyldichlorosilane",null,0,0,0,0,0,0,0,1]
[null,"4-methylcyclohexanemethanol","4-methylcyclohexanemethanol",null,1,0,1,0,1,1,0,20]
[null,"methyldithiocarbamate","methyldithiocarbamate",null,2,3,7,5,6,2,4,8]