Fragrance material review on methyl jasmonate

Food and Chemical Toxicology 50 (2012) S572–S576

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Review

Fragrance material review on methyl jasmonate J. Scognamiglio a,⇑, L. Jones b, C.S. Letizia a, A.M. Api a a b

Research Institute for Fragrance Materials, Inc. 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA Leah Jones Consulting, 55 W 14th Street, New York , NY 10011, USA

a r t i c l e

i n f o

Article history: Available online 17 March 2012 Keywords: Fragrance material Methyl jasmonate Review

a b s t r a c t A toxicologic and dermatologic review of methyl jasmonate when used as a fragrance ingredient is presented. Methyl jasmonate is a member of the fragrance structural group Ketones Cyclopentanones and Cyclopentenones. The common characteristic structural element of the group members is a cyclopentanone or cyclopentenone ring with a straight or branched chain alkane or alkene substituent. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for methyl jasmonate were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, phototoxicity, and photoallergy data. A safety assessment of the entire Ketones Cyclopentanones and Cyclopentenones will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Ketones Cyclopentanones and Cyclopentenones in fragrances. Ó 2012 Elsevier Ltd. All rights reserved.

Contents 1. 2. 3. 4.

5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Physical properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Usage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Exposure assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Existing authorizations and evaluations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Toxicology data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Acute toxicity (See Table 2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1.1. Oral studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1.2. Dermal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Skin irritation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2.1. Human studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2.2. Animal studies (See Table 3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3. Mucous membrane (eye) irritation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4. Skin sensitization and elicitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4.1. Sensitization studies in humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4.2. Elicitation studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4.3. Allergic contact dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5. Photoirritation and photoallergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5.1. Phototoxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5.2. Photoallergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6. Toxicokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7. Repeated dose toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.8. Reproductive toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.9. Genotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.10. Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

⇑ Corresponding author. Tel.: +1 201 689 8089; fax: +1 201 689 8090. E-mail address: [email protected] (J. Scognamiglio). 0278-6915/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.fct.2012.03.035

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Conflict of Interest Appendix A . . . . . . Appendix B . . . . . . References . . . . . . .

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1. Introduction This document provides a comprehensive summary of the human health toxicological data currently available pertaining to the safety evaluation of methyl jasmonate (See Fig. 1) when used as a fragrance ingredient. All safety data on methyl jasmonate were compiled with due diligence including published and unpublished data. In 2008, a complete literature search was conducted on methyl jasmonate. On-line toxicological databases were searched including those from the Chemical Abstract Services, [e.g. ToxCenter [which in itself contains 18 databases including Chemical Abstracts)], and the National Library of Medicine [e.g. Medline, Toxnet (which contains 14 databases)] as well as 26 additional sources (e.g. BIOSIS, Embase, RTECS, OSHA, ESIS). In addition, all RIFM sponsored studies and studies from fragrance companies are included in this summary. Data from all relevant references are summarized in this FMR. Commonly used terms and their abbreviations are listed in Appendix A. References that are not included are listed in Appendix B. More details have been provided for unpublished data. The number of animals, sex and strain are always provided unless they are not given in the original report or paper. Papers in which the vehicles and/or the doses are not given were included and noted in this summary because either they demonstrated an adverse effect or there were limited to no data on this fragrance ingredient. 2. Identification 2.1. Synonyms: Cyclopentaneacetic acid, 3-oxo-2-(2-pentenyl)-, methyl ester (1R,2bZ); methyl (1R-(1a,2b(Z)))-3-oxo-2(pent-2-enyl)cyclopentaneacetate; methyl 3-oxo-2-(2-pentenyl)cyclopentyl acetate; methyl (3-oxo-2-pent-2-en-1ylcyclopentyl)acetate; methyl (2-pent-2-enyl-3-oxo-1cyclopentyl) acetate 2.2. CAS registry number: 1211-29-6 2.3. EINECS number: 214-918-6 2.4. Formula: C13H20O3 2.5. Molecular weight: 224.3 3. Physical properties 3.1. Physical form: Colorless oily liquid with powerful floral-herbaceous, sweet-tenacious odor representing typical background notes of Jasmin absolute

O

O

O

Fig. 1. Methyl jasmonate.

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3.2. 3.3. 3.4. 3.5. 3.6. 3.7. 3.8. 3.9.

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Boiling point: 314 °C Flash point: >200 °F; CC Henry’s law (calculated): 0.000000441 atm m3/mol @ 25 °C Log Kow (calculated): 2.76 Specific gravity: 1.02 Vapor pressure (calculated): <0.001 mm Hg @ 25 °C Water solubility (calculated): 143.5 mg/l @ 25 °C UV spectra not available at RIFM

4. Usage Methyl jasmonate is a fragrance ingredient used in many fragrance mixtures. It may be found in fragrances used in decorative cosmetics, fine fragrances, shampoos, toilet soaps and other toiletries as well as in non-cosmetic products such as household cleaners and detergents. It is a colorless oily liquid with powerful floral-herbaceous, sweet-tenacious odor representing typical background notes of Jasmin absolute (Arctander, 1969). The worldwide volume of use for methyl jasmonate is in the region of 0.01–0.1 metric tons per year (IFRA, 2008). This reported volume is for its use as a fragrance ingredient in fragrance compounds (mixtures) found in all finished consumer product categories. The volume of use is surveyed by IFRA approximately every 4 years through a comprehensive survey of IFRA and RIFM member companies. As such the volume of use data from this survey provide volume of use of fragrance ingredients for the majority of the fragrance industry. 4.1. Exposure assessment The dermal systemic exposure in cosmetic products (see Table 1) is calculated based on the concentrations of the same fragrance ingredient in 10 types of the most frequently used personal care and cosmetic products (anti-perspirant, bath products, body lotion, eau de toilette, face cream, fragrance cream, hair spray, shampoo, shower gel, and toilet soap). The concentration of the fragrance ingredient in fine fragrances is obtained from examination of several thousand commercial formulations and the upper 97.5th percentile concentration is calculated from the data obtained. This upper 97.5th percentile concentration is then used for all 10 consumer products. These concentrations are multiplied by the amount of product applied, the number of applications per day for each product type, and a ‘‘retention factor’’ (ranging from 0.001 to 1.0) to account for the length of time a product may remain on the skin and/or likelihood of the fragrance ingredient being removed by washing. The resultant calculation represents the total consumer exposure (mg/kg/day) (Cadby et al., 2002; Ford et al., 2000). This is a conservative calculation of dermal systemic exposure because it makes the unlikely assumption that a consumer will use these 10 products which are all perfumed with the upper 97.5th percentile level of the fragrance ingredient from a fine fragrance type of the product (Cadby et al., 2002; Ford et al., 2000). The 97.5th percentile use level in formulae for use in cosmetics in general has been reported to be 0.06% (IFRA, 2007), which would result in a maximum daily exposure on the skin of 0.00153 mg/kg for high end users (see Table 1). A maximum skin level is then determined for consideration of potential sensitization. The exposure is calculated as the percent

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Table 1 Calculation of the total human skin exposure from the use of multiple cosmetic products containing methyl jasmonate. Product type

Grams applied

Applications per day

Retention factor

Mixture/product (%)

Ingredient/mixturea

Ingredient mg/kg/dayb

Antiperspirant Bath products Body lotion Eau de toilette Face cream Fragrance cream Hair spray Shampoo Shower gel Toilet soap

0.50 17.0 8.00 0.75 0.80 5.00 5.00 8.00 5.00 0.80

1.00 0.29 0.71 1.00 2.00 0.29 2.00 1.00 1.07 6.00

1.000 0.001 1.000 1.000 1.000 1.000 0.010 0.010 0.010 0.010

0.010 0.020 0.004 0.080 0.003 0.040 0.005 0.005 0.012 0.015

0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06

0.0000 0.0000 0.0002 0.0006 0.0000 0.0006 0.0000 0.0000 0.0000 0.0000

–

–

–

–

0.0014

Total a b

–

Upper 97.5 percentile levels of the fragrance ingredient in the fragrance mixture used in these products. Based on a 60 kg adult.

concentration of the fragrance ingredient applied to the skin based on the use of 20% of the fragrance mixture in the fine fragrance consumer product (IFRA, 2007). The average maximum use level in formulae that goes into fine fragrances has been reported to be 0.08% (IFRA, 2007); assuming use of the fragrance oil at levels up to 20% in the final product.

patch removal and evaluation. There were no reactions (RIFM, 1980c). Subjects were observed for irritation in another HRIPT using 1% methyl jasmonate in alcohol SDA 39C. Forty-four volunteers received 0.4 ml on the upper arms for 24 h using occluded patches three times per week until 9 applications were made. No irritation was observed (RIFM, 1978a).

4.2. Existing authorizations and evaluations 4.2.1. Council of Europe: No statement 4.2.2. FDA: No statement 4.2.3. FEMA (1973): Flavor and Extract Manufacturers’ Association: Generally Recognized as Safe as a flavor ingredient GRAS 7 (3410) 4.2.4. JECFA (2006): The Joint FAO/WHP Expert Committee on Food Additives (JECFA No. 1400) concluded that the substance does not present a safety concern at current levels of intake when used as a flavoring agent 5. Toxicology data 5.1. Acute toxicity (See Table 2) 5.1.1. Oral studies The LD50 was >5 g/kg when methyl jasmonate was administered by oral gavage to Sherman Wistar rats (5/sex) at 5 g/kg followed by a 14-day observation period. Mortality was seen in one animal on day 1. Clinical signs of toxicity included CNS depression and ruffled fur. Gross necropsy was normal (RIMF, 1980a). 5.1.2. Dermal Studies Methyl jasmonate was administered topically to albino rabbits (5/sex) at a dose of 2 g/kg followed by a 14-day observation period. The LD50 was >2 g/kg. There was no mortality or clinical signs of toxicity. Gross necropsy was normal (RIFM, 1980b). 5.2. Skin irritation 5.2.1. Human studies In the induction phase of a Human Repeated Insult Patch Test (HRIPT), 10% methyl jasmonate (vehicle not reported) was applied to the upper arms of 50 volunteers three times per week for 3 successive weeks. Each application lasted 24 h and was followed by Table 2 Summary of acute toxicity studies. Route

Species

No. Animals/dose group

LD50

References

Oral Dermal

Rat Rabbit

10 10

>5.0 >2.0

RIFM (1980a) RIFM (1980b)

5.2.2. Animal studies (See Table 3) Methyl jasmonate was administered topically to albino rabbits (5/sex) at a dose of 2 g/kg followed by a 14-day observation period. There was no irritation observed (RIFM, 1980b). A single application of 0.5 ml of 10% methyl jasmonate in alcohol was administered topically to six albino rabbits for a period of 24 h. The sites were evaluated immediately upon removal of the patch and 48 h later. Scoring was done according to the Draize scale. The test material was not irritating (RIFM, 1980d). Guinea pig maximization tests according to the Kligman (1969) method were conducted in 10% methyl jasmonate in alcohol SDA 39C. Induction consisted nine applications of the test article three times per week under occlusive conditions for 24 h. No irritation was observed in any of the 10 animals tested (RIFM, 1980f). Six albino New Zealand rabbits received 0.5 ml of 1% methyl jasmonate in alcohol for 24 h under occlusion. Half of the test sites were intact and half were abraded. Evaluations took place at 24 and 48 h after patch removal. None to well-defined erythema and very slight edema occurred in both intact and abraded skin (RIFM, 1978b). 5.3. Mucous membrane (eye) irritation A volume of 0.1 ml of neat methyl jasmonate was instilled into the right eye of six New Zealand white rabbits followed by examination on days 1, 2, 3, 5 and 7. The left eye served as the control. Scoring was done according to the Draize scale. The test material was not irritating (RIFM, 1980e). In another eye irritation test, six albino New Zealand rabbits received 0.1 ml of 1% methyl jasmonate in propylene glycol in the right eyes followed by examination on days 1, 2, 3, 4 and 7. The left eyes served as controls. Conjunctival irritation, which cleared within 72 h, was observed. The mean ocular irritation scores were 2.0, 0.33, 0, 0, and 0 at 1, 2, 3, 4, and 7 days, respectively (RIFM, 1979a). Six albino New Zealand rabbits were tested with 0.1 ml of 1% methyl jasmonate in alcohol SDA 39C in the right eyes. Left eyes were controls. Slight corneal opacity and moderate conjunctive redness, chemosis, and discharge were observed, with all symptoms clearing in all but one animal by day 10. Similar irritation was seen when the vehicle was tested alone (RIFM, 1978c).

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J. Scognamiglio et al. / Food and Chemical Toxicology 50 (2012) S572–S576 Table 3 Summary of animal irritation studies. Method

Dose (%)

Species

Reactions

References

Acute dermal 24-h patch test Guinea pig maximization pretest Primary irritation

100 10 10 1

10 Rabbits 6 Rabbits 10 Guinea Pigs 6 Rabbits

Not Not Not Not

RIFM RIFM RIFM RIFM

irritating irritating irritating irritating

(1980b) (1980d) (1980f) (1978b)

5.4. Skin sensitization and elicitation

5.5. Photoirritation and photoallergy

5.4.1. Sensitization studies in humans 5.4.1.1. Human repeated insult patch test. An HRIPT was conducted in 50 volunteers to determine if 10% methyl jasmonate (vehicle not reported) would induce dermal sensitization in human volunteers. During the induction phase, methyl jasmonate was applied to the upper arm of each volunteer for 24 h. Induction applications were made to the same site on every 48 h for a total of nine applications during a 3-week period. Following a 14-day rest period, a challenge patch was applied to the same site and a site previously unexposed. Patches were applied as in the induction phase, kept in place for 24 h, and then removed. Reactions to the challenge application were scored at 24 and 48 h after application. No sensitization reactions occurred (RIFM, 1980c). Forty-three volunteers were observed in another HRIPT using 0.4 ml 1% methyl jasmonate in alcohol SDA 39C (1000 lg/cm2). Patches were applied on the upper arms for 24 h using occluded patches and replaced every 48 h for a total of nine applications during a 3-week period. Following a two week rest period, challenge patches were applied to a site already exposed and a naïve site on each subject. No sensitization was observed (RIFM, 1978a).

5.5.1. Phototoxicity 5.5.1.1. Human studies. A photosensitization study as part of an HRIPT was conducted to determine if a 10% concentration of methyl jasmonate (vehicle not reported) would induce sensitization in human volunteers. During the induction phase, methyl jasmonate was applied to the upper arm of each volunteer for 24 h. Induction applications were made to the same site on every 48 h for a total of nine applications during a 3-week period. The volunteers were exposed to 365 nm light (Spectroline Model B100, Black Light Flood lamp) for 15 min at a distance of 15 in. following induction applications 1, 4, 7 and 9. There were no reactions in 20 volunteers (RIFM, 1980c). 5.5.2. Photoallergy 5.5.2.1. Human studies. A photosensitization study as part of an HRIPT was conducted to determine 10% methyl jasmonate (vehicle not reported) would induce sensitization in volunteers. During the induction phase, methyl jasmonate was applied to the upper arm of each volunteer for 24 h. Induction applications were made to the same site every 48 h for a total of nine applications during a 3-week period. The volunteers were exposed to 365 nm light (Spectroline Model B-100, Black Light Flood lamp) for 15 min at a distance of 15 in. following induction applications 1, 4, 7 and 9. After a 10–14-day rest period, a challenge patch was applied to the same skin site and a site previously unexposed. Patches were applied as in the induction phase and kept in place for 24 h after which time they were removed. Both sites were then exposed to light as in the induction phase. Reactions to the challenge doses were scored at 24 and 48 h after application. There were no reactions in 20 volunteers (RIFM, 1980c).

5.4.1.2. Maximization studies. There are no data available on this material.

5.4.1.3. Sensitization studies in animals (see Table 4). Guinea pig maximization tests according to the Kligman (1969) method were conducted in 10% methyl jasmonate in alcohol SDA 39C. Induction consisted nine applications of the test article three times per week under occlusive conditions for 24 h. Animals were challenged 17 days later with a 24-h occluded patch application. Reactions were read 24 and 48 h after patch removal. No sensitization reactions were observed in any of the 10 animals tested (RIFM, 1980f).

5.6. Toxicokinetics There are no data available on this material.

5.4.1.4. Patch test sensitization (‘‘active sensitization’’). There are no data available on this material.

5.7. Repeated dose toxicity There are no data available on this material.

5.4.1.5. Cross-sensitization. There are no data available on this material.

5.8. Reproductive toxicity 5.4.2. Elicitation studies There are no data available on this material.

There are no data available on this material. 5.9. Genotoxicity

5.4.3. Allergic contact dermatitis There are no data available on this material.

There are no data available on this material.

Table 4 Summary of guinea pig sensitization studies. Method

Induction concentration (%)

Challenge concentration (%)

Reactions

References

Guinea pig maximization

10

10

No reactions

RIFM (1980f)

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5.10. Carcinogenicity

Appendix B

There are no data available on this material. This individual fragrance material review is not intended as a stand-alone document. Please refer to the toxicologic and dermatologic assessment of ketones cyclopentanones and cyclopentenones (Belsito et al., submitted for publication) for an overall assessment of this material. Conflict of Interest Joseph Scognamiglio, Leah Jones, Charlene Letizia, and Anne Marie Api are employees of the Research Institute for Fragrance Materials, an independent research institute supported by the manufacturers of fragrances and consumer products containing fragrances. Appendix A A glossary of commonly used terms and their abbreviations. Toxicological terms Freund’s Complete Adjuvant Test Gestation Day Human Repeated Insult Patch Test Local Lymph Node Assay Lowest Observed Adverse Effect Level Lowest Observed Effect Level Maximization Test Maximum Tolerated Dose No Observed Adverse Effect Level No Observed Effect Level Open Epicutaneous Test

FCAT GD HRIPT LLNA LOAEL LOEL MAX MTD NOAEL NOEL OET

Solvents Diethyl phthalate Diisopropylene glycol Dimethyl sulfoxide Dodecylbenzene sulfonate Ethanol Polyethylene glycol Sodium lauryl sulfate

DEP DIPG DMSO DOBS EtOH PEG SLS

Organizations Council of Europe Environmental Protection Agency Flavor and Extract Manufacturers’ Association Food and Drug Association International Fragrance Association Joint Expert Committee on Food Additives

COE EPA FEMA FDA IFRA JECFA

Consulted but not included in the review of methyl jasmonate. Placzek, M., Fromel, W., Eberlein, B., Gilbertz, K.P., Przybilla, B., 2007. Evaluation of phototoxic properties of fragrances. Acta Dermato-Venereologica, 87(4), 312–316 References Arctander, S., 1969. Perfume and Flavor Chemicals (Aroma Chemicals). Volume II, No. 2093. S. Arctander, Montclair, New Jersey. Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Hanifin, J.H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2012. A toxicologic and dermatologic assessment of cyclopentanones and cyclopentenones when used as fragrance ingredients. Food and Chemical Toxicology 50 (Suppl.3), S517–S556. Cadby, P., Troy, W., Vey, M., 2002. Consumer exposure to fragrance ingredients: providing estimates for safety evaluation. Regulatory Toxicology and Pharmacology 36, 246–252. FEMA (Flavor and Extract Manufacturers Association), 1973. Recent progress in the consideration of flavoring ingredients under the Food Additives Amendment 7. GRAS substances. Food Technology, 27(11), 56–57. Ford, R., Domeyer, B., Easterday, O., Maier, K., Middleton, J., 2000. Criteria for development of a database for safety evaluation of fragrance ingredients. Regulatory Toxicology and Pharmacology 31, 166–181. JECFA (Joint Expert Committee on Food Additives), 2006. Safety evaluation of certain food additives. Who Food Additives Series:54. Prepared by the 63rd meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). World Health Organization, Geneva 2006. IFRA (International Fragrance Association), 2007. Use Level Survey, June 2007. IFRA (International Fragrance Association), 2008. Volume of Use Survey, December 2008. RIFM (Research Institute for Fragrance Materials, Inc.), 1978a. Repeated insult patch test with methyl jasmonate. RIFM report number 54078, January 9. RIFM, Woodcliff Lake, NJ, USA. RIFM (Research Institute for Fragrance Materials, Inc.), 1978b. Primary dermal irritation study with methyl jasmonate in rabbits. RIFM report number 54081, January 19. RIFM, Woodcliff Lake, NJ, USA. RIFM (Research Institute for Fragrance Materials, Inc.), 1978c. Rabbit eye irritation study with methyl jasmonate. RIFM report number 54080, January 10. RIFM, Woodcliff Lake, NJ, USA. RIFM (Research Institute for Fragrance Materials, Inc.), 1979a. Primary ocular irritation study with methyl jasmonate in rabbits. RIFM report number 54079, May 11. RIFM, Woodcliff Lake, NJ, USA. RIFM (Research Institute for Fragrance Materials, Inc.), 1980a. Acute oral toxicity of methyl jasmonate in rats. RIFM report number 38752, April 9. RIFM, Woodcliff Lake, NJ, USA. RIFM (Research Institute for Fragrance Materials, Inc.), 1980b. Acute dermal toxicity of methyl jasmonate in rabbits. RIFM report number 38753, April 10. RIFM, Woodcliff Lake, NJ, USA. RIFM (Research Institute for Fragrance Materials, Inc.), 1980c. Repeated insult patch test/photosensitization study of methyl jasmonate in human subjects. RIFM report number 38756, June 11. RIFM, Woodcliff Lake, NJ, USA. RIFM (Research Institute for Fragrance Materials, Inc.), 1980d. Primary skin irritation study of methyl jasmonate in rabbits. RIFM report number 38754, March 28. RIFM, Woodcliff Lake, NJ, USA. RIFM (Research Institute for Fragrance Materials, Inc.), 1980e. Primary eye irritation study of methyl jasmonate in rabbits. RIFM report number 38755, April 1. RIFM, Woodcliff Lake, NJ, USA. RIFM (Research Institute for Fragrance Materials, Inc.), 1980f. Delayed contact hypersensitivity of 2-oxabicyclo[2.2.2]octane, 1,5-dimethyl-3-(2-propen-1-yl (allyl cyclo octyl ether) in a guinea pig sensitization (Buehler and Griffith). RIFM report number 47726, February 11. RIFM, Woodcliff Lake, NJ, USA.