Ingredients in Victoria’s Secret Bombshell and Ivanka Trump eaux de parfums that repel mosquitoes

Insect repellents are widely used to fend off nuisance mosquitoes and, more importantly, to reduce or eliminate mosquito bites in areas where viruses and other vector-borne diseases are circulating. Synthesized more than six decades ago, DEET is the most widely used insect repellent. Plant-derived compounds are used in a plethora of commercial formulations and natural recipes to repel mosquitoes. They are also used as fragrances. We analysed Bombshell® to identify the constituent(s) eliciting a previously reported “off-label” repellence activity. The two major fragrance ingredients in Bombshell, i.e., methyl dihydrojasmonate and lilial, demonstrated strong repellence against the southern house mosquito, Culex quinquefasciatus, in laboratory assays. Both compounds activated a previously identified DEET-sensitive odorant receptor, CquiOR136. These compounds were also major constituents of Ivanka Trump eau de parfum. The methyl dihydrojasmonate content was higher in the Ivanka Trump perfume than in Bombshell, the reverse being true for lilial. Both Bombshell and Ivanka Trump eaux de parfums retained activity for as long as 6 hours in laboratory assays. Although wearing these perfumes may repel nuisance mosquitoes, their use as “off-label” repellents against infected mosquitoes is not recommended. A panel of 104 students (18-23 years old) conducted a blind test to compare the two eaux de parfums and showed a preference for Bombshell over Ivanka Trump’s brand, particularly among women.

repellents against infected mosquitoes is not recommended. A panel of 104 students (18-48 23 years old) conducted a blind test to compare the two eaux de parfums and showed a 49 preference for Bombshell over Ivanka Trump's brand, particularly among women. Additionally, a group of natural product aficionados embrace the misleading notion that 68 natural is safe and synthetic is harmful, so they too do not use DEET. As the old repellent 69 on the market, DEET has been scrutinized more than any of its counterparts and has a 70 remarkable safety record [5], but one has to consider that no chemicals are "absolutely 71 safe." One of the more modern alternatives to DEET is picaridin [5], which dermatologists 72 recommend as a second-line agent after concluding, based on peer-reviewed literature, 73 that DEET demonstrates a strong and consistent ability to reduce mosquito bites relative 74

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The laboratory colony of Cx. quinquefasciatus used in this study ("Davis colony') 100 originated from mosquitoes collected in Merced, California in the 1950s. The original 101 "Merced colony" has been maintained in the Kearney Agricultural Center (KAC), University 102 of California by Dr. Anthon Cornel. The "Davis colony" was initiated from eggs of the 103 "Merced colony" provided by Dr. Anthon Cornel and has been maintained at Davis for 104 more than six years under a photoperiod of 12:12 h (L:D), 27±1°C, and 75% relative 105 Technologies, Palo Alto, CA), which was equipped with an HP-5MS capillary column (30 122 m x 0.25 mm; 0.25 μm film; Agilent Technologies). The oven temperature was set at the 123 initial temperature of 70 o C, for 1 min then the temperature was raised at a rate of 10 o C/min 124 to 270 o C, and held at this final temperature for 10 min. After each run, the oven 125 Corporation, Parsippany, NJ, USA), the balance was zeroed, the capillary tube was filled 163 with the test perfume, and the amount weighted. To estimate the amount of perfume 164 dispensed per spray and the area of the body covered, a bottle of each perfume was held at about 10 cm from the forearm and the area covered by a single spray was measured. 166 Then, the same procedure was done at a short distance to collect the entire spray into a 4-167 ml glass vial, which was weighted in an analytical balance. (colour and temperature), but also to hold dental cotton rolls. Syringe needles on the top of 175 these tubes delivered carbon dioxide (at 50 ml/min) and held cotton rolls in place. Insect 176 pins placed 1.8 cm above the syringe needles held filter paper rings (width 4 cm; 25 cm; 177 overlapped 1 cm for stapling), which served as a spatial repellent source (and control). Serine/Histidine (SH, for Bombshell). Students were asked if they preferred one of these 220 two perfumes and were provided with an optional column to make "other remarks" and 221 disclose the tester's gender. To optimize the number of participants between classes, 222 aliquots of the two eaux de parfums were transferred to three bottles each. 223 224

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Gas chromatography-mass spectrometry analyses showed that the top four major 226 constituents of Bombshell ® were methyl dihydrojasmonate, lilial, galaxolide, and 227 isopropryl myristate (Fig. 1) Next, we tested whether these individual compounds were repellents in our surface 249 landing and feeding assay [13]. For this, we used DEET at 1% as a positive control and 250 the southern house mosquito, Culex quinquefasciatus, as test mosquitoes. Both methyl 251 dihydrojasmonate (MDJ) ( Fig. 2A) and lilial at 1% (Fig. 2B) showed strong repellence 252 activity. By contrast, neither isopropyl myristate (IM) (Fig. 2C) nor galaxolide (Fig. 2D) 253 repelled Culex mosquitoes. When tested in 2:1 mixtures at 1 and 5%, methyl 254 particularly with regard to the major constituents, except for isopropyl myristate that 289 appeared at much lower levels in the latter perfume (Fig. 1). They also differed in other 290 minor constituents that appeared in Ivanka Trump eau de parfum, but not in Bombshell. 291 Of note, a peak at 13.41 min in the former was identified as lyral based on comparison of 292 MS and retention time obtained with authentic lyral. In our surface landing and feeding 293 assay, lyral demonstrated no repellence activity (Fig. 2D). 294 Whereas Ivanka Trump eau de parfum has a significantly higher content of methyl 295 dihydrojasmonate than Bombshell has, the content of lilial in the latter was higher than in 296 the former (Fig. 5). Interestingly, the major constituent of these eaux de parfums does not 297 appear in their labels. It might be that the disclosure of constituents in their labels is meant 298 to comply with the Seventh Amendment to the European Cosmetic Directive demanding 299 that cosmetics on sale in Europe indicate whether certain compounds are present at any 300 level [8]. Various minor constituents in these perfumes, as well as lilial and lyral, make is no legal requirement to disclose this compound on labels, despite it being the major 303 constituent in these perfumes. 304 305

Fig. 5. Concentrations of MDJ and lilial in Bombshell (left, blue) and Ivanka Trump 306
(right, red) eaux de parfums. Amounts were estimated by gas chromatography after 307 calibrating the responses of the flame ionization detector with standards. Perfumes were 308 diluted 1,000x for injections (n=3). The data are expressed as mean ± SEM. 309

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A major concern about natural repellents is the complete protection time, i.e., how long 311 they would last as active repellents. Many compounds are misleadingly effective as 312 repellents when tested only at the time the samples are prepared, but not over a 313 reasonable period of time. As opposed to DEET and picaridin, many natural products 314 have an initial spike of activity, because their vapor pressures are very high (low boiling 315 points) thus releasing initially overwhelming doses, but they lose activity over time as the 316 sources are rapidly depleted. In short, even when testing repellents at the same nominal 317 doses, one must keep in mind that the more volatile compounds will have a higher vapor 318 dose initially, whereas the less volatile compounds have lower vapor doses, but they will 319 last longer. DEET has an optimal boiling point for a repellent (545 o F = 285 o C; PubChem), 320 which allows a steady vapor concentration at the skin surface for a long period of time. 321 Over time, DEET loses activity due to skin penetration and wash off, but loss due to 322 evaporation is minimal [13]. Because perfumes are notorious for depleting over a short 323 duration, despite the new technologies and the availability of fixatives, we asked whether 324 these two eaux de parfums would retain activity for a reasonable period of time.
Surprisingly, both Bombshell and Ivanka Trump eaux de parfums retained activity for as 326 long as 6 h (Fig. 6). 327 It is worth mentioning that our assays did not measure loses (e.g., wash off, skin 335 penetration) other than loss due to evaporation (from a filter paper; see Material and 336 Methods). Additionally, our tests were conducted with aliquots of 200 μl of each eau de 337 parfum to be consistent with the volume of repellents applied in our repellent assays [13]. 338 Of note, DEET 5% in our experimental setup is nearly equivalent to a commercial 339 formulation with 30% DEET [13]. In our behavioural measurements with 5% DEET, 10 340 mg of this repellent was used per test. Considering the amounts of methyl 341 dihydrojasmonate in Ivanka Trump eau de parfum, i.e., peak 1, 42.65±1.95 mg/ml and 342 peak 2, 12.26±0.58 mg/ml, we loaded in these comparative assays ≈11 mg of methyl 343 dihydrojasmonate and ≈0.5 mg of lilial (2.46±0.23 mg/ml). Likewise, from Bombshell 344 (peak 1, 30.29±0.49 mg/ml and peak 2, 5.35±0.07 mg/ml), we applied ≈7 mg of methyl 345 dihydrojasmonate and ≈1.8 mg of lilial (9.21±0.32 mg/ml). In short, as far as the amounts 346 of repellents were concerned, these compounds performed nearly equally. It is very applies perfume at levels comparable to repellent applications. Here, 200-μl solutions 349 were applied to approximately 20 cm 2 [13], but a standard application of DEET is 1 ml of 350 a 20% solution applied to 600 cm 2 [14]. Thus, in practical applications on the skin, DEET 351 is applied at approximately 0.34 mg/cm 2 . Since Ivanka Trump eau de parfum dispensed 352 50±2.6 mg of perfume/spray (n=3) and covered an area of the forearm of 24.7±1.5 353 cm 2 /spray (n=3) [similar results obtained with Bombshell were 55±1 mg/spray and 354 28.3±0.9 cm 2 /spray] and considering the estimated densities of these perfumes (Ivanka 355 Trump, 0.858±0.18 g/ml; Bombshell, 0.861±0.003 g/ml), the actual amounts of total active 356 repellents in these cosmetics applied to the skin were estimated to be 0.13 mg/cm 2 357 (Ivanka Trump) and 0.1 mg/cm 2 (Bombshell). In other words, even excessive users are 358 unlikely to apply perfume at doses comparable to that of repellents. They typically apply 359 three times lower doses of these perfume-derived mosquito repellents than DEET (from 360 repellent formulations). Although these perfume applications may suffice to fend off 361 nuisance mosquitoes, it might not be a wise prophylactic tool for preventing bites of 362 mosquitoes in areas with arboviruses or other mosquito-borne diseases. 363 Lastly, we performed a blind test to determine which, if any, of these eaux de parfums 364 would smell good to young people. A blind test was conducted with 18-to 23-year-old 365 students on the UC-Davis campus. They were presented with spray bottles labelled with 366 code names, i.e., Isoleucine/Threonine (IT for Ivanka Trump) and Serine/Histidine (SH, 367 for Bombshell) and asked if they prefer one of them; one column was provided for other 368 remarks. There were no responders that disliked both products; a woman student 369 indicated that "both smell like hand sanitizers," but she preferred IT. In general, the women than men (Fig. 7). Of the 104 students who responded, 62 did not make any 372 remarks, just selected one of the two choices. Some noteworthy remarks were "smell 373 like angel" (IT), "more refreshing" (SH), "love it!" (IT), "more pleasant to smell" (SH), "less 374 harsh" (IT), "sweet" and "sweeter smell" (both SH), "too sweet" (IT), "smell[s] less strong

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We have identified the active ingredients that make two eaux de parfums, Bombshell and 386 Ivanka Trump, repel blood-seeking Culex mosquitoes, i.e., methyl dihydrojasmonate and 387 lilial. Albeit not recommended by us, the "off-label" use of these eaux de parfums as 388 mosquito repellents might help fend off nuisance mosquitoes. However, they might not serve 389 as prophylactic tools against infected mosquitoes for which higher doses of repellents have 390