A toxicologic and dermatologic assessment of salicylates when used as fragrance ingredients

Belsito, D.; Bickers, David R.; Bruze, M.; Calow, Peter; Greim, Helmut; Hanifin, Jon M.; Rogers, Adrianne E.; Saurat, J.‐H.; Sipes, I. G.; Tagami, Hachiro

doi:10.1016/j.fct.2007.09.066

Cited by 63 publications

(18 citation statements)

References 92 publications

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“…Of the four DPRA + h‐CLAT LLNA false negatives, two fall into the weak sensitizer range (EC3 > 10%) and two into the moderate range (1% < EC3 < 10%). One of the LLNA moderates (benzyl salicylate) is only a weak human sensitizer (Belsito et al, ). Thus, none of the DPRA + h‐CLAT LLNA false negatives are strong sensitizers.…”

Section: Discussionmentioning

confidence: 99%

Non‐animal assessment of skin sensitization hazard: Is an integrated testing strategy needed, and if so what should be integrated?

Roberts

Patlewicz

2017

J of Applied Toxicology

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There is an expectation that to meet regulatory requirements, and avoid or minimize animal testing, integrated approaches to testing and assessment will be needed that rely on assays representing key events (KEs) in the skin sensitization adverse outcome pathway. Three non-animal assays have been formally validated and regulatory adopted: the direct peptide reactivity assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (h-CLAT). There have been many efforts to develop integrated approaches to testing and assessment with the "two out of three" approach attracting much attention. Here a set of 271 chemicals with mouse, human and non-animal sensitization test data was evaluated to compare the predictive performances of the three individual non-animal assays, their binary combinations and the "two out of three" approach in predicting skin sensitization potential. The most predictive approach was to use both the DPRA and h-CLAT as follows: (1) perform DPRA -if positive, classify as sensitizing, and (2) if negative, perform h-CLAT -a positive outcome denotes a sensitizer, a negative, a non-sensitizer. With this approach, 85% (local lymph node assay) and 93% (human) of non-sensitizer predictions were correct, whereas the "two out of three" approach had 69% (local lymph node assay) and 79% (human) of non-sensitizer predictions correct. The findings are consistent with the argument, supported by published quantitative mechanistic models that only the first KE needs to be modeled. All three assays model this KE to an extent. The value of using more than one assay depends on how the different assays compensate for each other's technical limitations.

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Section: Discussionmentioning

confidence: 99%

Non‐animal assessment of skin sensitization hazard: Is an integrated testing strategy needed, and if so what should be integrated?

Roberts

Patlewicz

2017

J of Applied Toxicology

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“…In a review of the toxicological data of seventeen salicylate esters, including benzylsalicylate, the authors reported that in vitro mutagenicity studies (bacterial tests) gave negative results (Belsito et al, 2007). Methylsalicylate was the only compound for which a complete toxicological package was available; the lowest NOAEL (50 mg/kg body weight/day) was identified from subchronic and chronic oral toxicity data in both rats and dogs.…”

Section: Benzylsalicylate and Isoamylsalicylatementioning

confidence: 99%

Scientific Opinion on safety and efficacy of CRINA® Poultry Plus (preparation of benzoic acid and essential oil compounds) as feed additive for chickens for fattening

2012

EFS2

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CRINA® Poultry Plus (CPP) is a feed additive consisting on seven active substances: benzoic acid (83 %), thymol (1.9 %), eugenol (1 %), benzylsalicylate (0.3 %), piperine (0.1 %), isoamylsalicylate (0.1 %) and trans‐anethole (0.1 %). It is intended to be used as a zootechnical additive in complete feed for chickens for fattening (300–450 mg CPP/kg feed) to favourably affect their performance. Given the inconsistency of the data and the suggestion of adverse effects, albeit not dose‐related, the FEEDAP Panel is unable to conclude on the safety of the additive at the dose range proposed. None of the components of CPP are genotoxic and in vitro assays made with the additive gave no indication of a genotoxic potential. No metabolism/residue data are available for eugenol and piperine in chickens for fattening. Consequently, the FEEDAP Panel cannot draw any final conclusion on the safety for the consumer of CPP used as feed additive in chickens for fattening. CPP should be considered as irritant for the skin and eyes, as well as skin sensitiser; no adverse effects upon inhalation are to be expected. In the absence of data on the environmental fate of piperine, isoamylsalicylate and benzylsalicylate, or the additive itself, the safety for the environment cannot be assessed. A significant effect relative to performance was shown in only one of the eight studies taken for the demonstration of efficacy. There is insufficient evidence that CPP at the recommended dose can improve the zootechnical performance of chickens. The sensory properties of the meat from chickens fed CPP are not affected.

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“…This reaction has been used to fabricate photocrosslinked polymer materials [9][10][11][12][13][14] and photocrosslinked hydrogels [15][16][17], as well as materials for photoinduced alignment of liquid crystals [18][19][20][21][22]. Since cinnamoyl groups have proved to be low toxic [23,24], it is expected to apply the cinnamoyl-modified polymers to safety cell-contacting materials. Some research groups have studied the antioxidant activity of cinnamoyl derivatives [25,26].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Photocrosslinkable Copolymers of Cinnamoyl Group-modified Methacrylate and 2-Hydroxyethyl Methacrylate, and Fibroblast Cell Growth on Their Thin Films

Yano

Iwase

Shibata

et al. 2020

J. Photopol. Sci. Technol.

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Cinnamoyl-modified methacrylate, 2-cinnamoyloxyethyl methacrylate (CEMA), was synthesized from 2-hydroxyethyl methacrylate (HEMA) and cinnamoyl chloride. Copolymers with various cinnamoyl contents were synthesized by random copolymerization of HEMA and CEMA at different feed ratios. Thus three copolymers with different CEMA contents were synthesized, and the monomer composition ([HEMA]:[CEMA]) in the copolymers ranged from 75:25 to 0:100. The coating films of copolymers on glass plates were prepared by the dip-coating method. Photo-induced dimerization of the cinnamoyl groups in the copolymers was confirmed by the ultraviolet-visible (UV-Vis) spectral changes. The cell proliferation on the photocrosslinked copolymers was tested using 3T3 Swiss albino mouse embryo fibroblasts. The results of the cell proliferation assay revealed that the photocrosslinked copolymers carrying more cinnamoyl groups promoted the cell proliferation compared with the photocrosslinked copolymers carrying less cinnamoyl groups. According to the results in the present study and our previous studies on cinnamoyl-modified trehalose and cinnamoyl-modified hydroxypropyl cellulose, it is presumable that the photodimerized cinnamoyl groups existing on the surface of materials at high density have some preferable effect on promoting fibroblast cell adhesion.

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A toxicologic and dermatologic assessment of salicylates when used as fragrance ingredients

Cited by 63 publications

References 92 publications

Non‐animal assessment of skin sensitization hazard: Is an integrated testing strategy needed, and if so what should be integrated?

Non‐animal assessment of skin sensitization hazard: Is an integrated testing strategy needed, and if so what should be integrated?

Scientific Opinion on safety and efficacy of CRINA® Poultry Plus (preparation of benzoic acid and essential oil compounds) as feed additive for chickens for fattening

Synthesis of Photocrosslinkable Copolymers of Cinnamoyl Group-modified Methacrylate and 2-Hydroxyethyl Methacrylate, and Fibroblast Cell Growth on Their Thin Films

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