Safety Assessment of Citrus Plant- and Seed-Derived Ingredients as Used in Cosmetics
Status: Draft Revised Final Report for Panel Review Release Date: November 11, 2016 Panel Meeting Date: December 5-6, 2016
The 2016 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D., Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Christina Burnett, Senior Scientific Analyst/Writer.
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Memorandum
To: CIR Expert Panel Members and Liaisons From: Christina L. Burnett, Senior Scientific Writer/Analyst Date: November 11, 2016 Subject: Draft Revised Final Safety Assessment on Citrus Plant- and Seed-Derived Ingredients
Enclosed is the Draft Revised Final Report of the Safety Assessment of Citrus Plant- and Seed-Derived Ingredients as Used in Cosmetics. (It is identified as cplant122016rep in the pdf document).
At the September meeting, the Panel issued a revised tentative report with the conclusion that the following 13 ingredients are safe as used in the present practices of use and concentration when formulated to be non-irritating and non-sensitizing.
Citrus Aurantium Amara (Bitter Orange) Citrus Grandis Peel/Seed Extract Leaf/Twig Extract Citrus Grandis (Grapefruit) Seed Extract Citrus Aurantium Amara (Bitter Orange) Citrus Junos Seed Extract Leaf/Twig Oil Citrus Junos Seed Oil Citrus Aurantium Dulcis (Orange) Seed Extract Citrus Paradisi (Grapefruit) Seed Extract Citrus Australasica Seed Oil Citrus Sunki Seed Extract Citrus Depressa Seed Oil Citrus Sunki Seed Oil Citrus Glauca Seed Oil
The Panel concluded that the data on the remaining 19 ingredients are insufficient to determine safety. The data needed to evaluate the safety of these 19 ingredients are:
• Method of manufacturing • Chemical composition and impurities • Irritation and sensitization data • If the composition data for these Citrus plant- and seed-derived ingredients are substantially different from that of the Citrus peel-, flower-, and leaf-derived ingredients, then systemic toxicity studies such as a 28-day dermal toxicity, reproductive and developmental toxicity, and genotoxicity studies are needed, as well as UV absorption spectra
Since September, CIR staff received updated concentration of use data. The updates on the concentration of use had no great impact on the Use Table (Table 7 in the report). Staff also received a letter from Dr. Lena Struwe, which describes the pericarp of a fruit according to current biology academia. While the letter clarifies what the term “pericarp” technically means in relation to Citrus, it is unclear if this is what the supplier(s) meant/means by the term when the 2 pericarp ingredients were reviewed during the INC submission for inclusion in the International Cosmetic Ingredient Dictionary and Handbook. Comments provided by Council on the previous draft final and revised tentative reports have been considered. The comments and data are included in this report package (cplant122016pcpc1 and cplant122016pcpc2 and cplant 122016data1 to cplant122016data3, respectively).
The Panel should carefully review the abstract, discussion, and conclusion of this report and issue a Final Safety Assessment. Distributed for Comment Only -- Do Not Cite or Quote SAFETY ASSESSMENT FLOW CHART
INGREDIENT/FAMILY ____Citrus Whole Plant & Seed-Derived Ingredients______
MEETING ______Dec 2016______
Public Comment CIR Expert Panel Report Status
Priority List INGREDIENT At the Mar 2014 meeting, the PRIORITY LIST Panel reviewed a report on 198 citrus-derived ingredients, and split the report into sub-groups. SLR This is the citrus whole plant and Dec 2013 seed-derived subgroup.
DRAFT REPORT Draft Report Dec 2015
60 day public comment period
Table
Table IDA TR
IDA Notice IDA Dec 18, 2015
DRAFT TENTATIVE REPORT Draft TR June 2016
Table
Table
Tentative Report Issue TR June 16, 2016 Oct 7, 2016
DRAFT FINAL REPORT Draft FR Sept 2016
60 day Public comment period Dec 2016
Table
Table Different Conclusion
PUBLISH Final Report Issue FR
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Citrus Plant- and Seed-Derived Ingredients History
December 2013 – Scientific Literature Review announced.
March 2014 - The Panel tabled further discussion of 198 citrus-derived ingredients to allow CIR staff to reorganize the report and to obtain clarification from RIFM on the functions of some of the ingredients. These ingredients were presented in a single safety assessment report addressing ingredients from all of the citrus plant species currently reported to be used in cosmetics in the International Cosmetic Ingredient Dictionary and Handbook. The Panel felt revising this report into smaller subgroups would be a manageable and meaningful alternative approach to assessing the safety of these ingredients. Based on the Panel’s recommendation of grouping the ingredients by plant parts according to greatest number of uses, the first assessment reviewed by the Panel was citrus-derived peel oils, followed by citrus fruit-derived ingredients.
September 2015 – The Panel reviewed the report strategy for the remaining citrus ingredients. The Panel agreed that the remaining ingredients could be divided into 3 reports: citrus flower- and leaf-derived ingredients, citrus peel-derived ingredients, and citrus plant- and seed-derived ingredients. These reports can be reviewed concurrently.
December 2015 - The Panel requested additional data to support the safety of the 33 Citrus plant- and seed-derived ingredients. The additional data needed are:
• Method of manufacturing • Chemical composition and impurities • Irritation and sensitization, especially human repeated insult patch tests (HRIPT) on citrus aurantium amara (bitter orange) leaf/twig oil and citrus grandis (grapefruit) seed extract at maximum use concentrations or greater • If the composition for these Citrus plant- and seed-derived ingredients are significantly different from that of the Citrus peel-, flower-, and leaf-derived ingredients, then data on systemic endpoints such as a 28-day dermal toxicity, reproductive and developmental toxicity, and genotoxicity, as well as UV absorption spectra are needed
June 2016 - The Panel issued a tentative report with the conclusion that the available data are insufficient to make a determination that the 32 Citrus plant- and seed-derived ingredients included in this report are safe under the intended conditions of use in cosmetic formulations. The data requested by the Panel included: • Method of manufacturing for all these ingredients, except the seed extracts • Chemical composition and impurities for all these ingredients, except the seed oils and seed extracts • Irritation and sensitization, especially human repeated insult patch tests (HRIPT) on Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil and Citrus Grandis (Grapefruit) Seed Extract at maximum use concentrations or greater. • If the composition for these Citrus plant- and seed-derived ingredients are significantly different from that of the Citrus peel-, flower-, and leaf-derived Distributed for Comment Only -- Do Not Cite or Quote
ingredients, then data on systemic endpoints such as a 28-day dermal toxicity, reproductive and developmental toxicity, and genotoxicity, as well as UV absorption spectra are needed.
The Panel removed Citrus Tangerina (Tangerine) Extract from this report because it was identical to another ingredient in the Citrus fruit-derived ingredient report, bringing the total number of ingredients in this report to 32.
September 2016 - The Panel issued a revised tentative report with the conclusion that the following 13 ingredients are safe as used in the present practices of use and concentration when formulated to be non-irritating and non-sensitizing.
Citrus Aurantium Amara (Bitter Orange) Citrus Glauca Seed Oil Leaf/Twig Extract Citrus Grandis Peel/Seed Extract Citrus Aurantium Amara (Bitter Orange) Citrus Grandis (Grapefruit) Seed Extract Leaf/Twig Oil Citrus Junos Seed Extract Citrus Aurantium Dulcis (Orange) Seed Citrus Junos Seed Oil Extract Citrus Paradisi (Grapefruit) Seed Extract Citrus Australasica Seed Oil Citrus Sunki Seed Extract Citrus Depressa Seed Oil Citrus Sunki Seed Oil
The Panel concluded that the data on 19 ingredients listed below are insufficient to determine safety.
Citrus Aurantifolia (Lime) Oil Citrus Limon (Lemon) Citrus Aurantium (Bitter Orange) Oil Flower/Leaf/Stem Extract Citrus Aurantium Dulcis (Orange) Citrus Limon (Lemon) Flower/Leaf/Stem Powder Flower/Leaf/Stem Oil Citrus Aurantium Dulcis (Orange) Oil Citrus Limon (Lemon) Leaf/Peel/Stem Citrus Aurantium Sinensis Powder Oil Citrus Grandis (Grapefruit) Citrus Nobilis (Mandarin Orange) Citrus Grandis (Grapefruit) Extract Citrus Nobilis (Mandarin Orange) Oil Citrus Iyo Oil Citrus Nobilis (Mandarin Orange) Water Citrus Jabara Pericarp Extract Citrus Reticulata (Tangerine) Extract Citrus Junos Extract Citrus Unshiu Extract Citrus Unshiu Pericarp Extract
The data needed to evaluate the safety of these 19 ingredients are: • Method of manufacturing • Chemical composition and impurities • Irritation and sensitization data • If the composition data for these Citrus plant- and seed-derived ingredients are substantially different from that of the Citrus peel-, flower-, and leaf-derived ingredients, then systemic toxicity studies such as a 28-day dermal toxicity, reproductive and developmental toxicity, and genotoxicity studies are needed, as well as UV absorption spectra. Distributed for Comment Only -- Do Not Cite or Quote
Citrus Plant- and Seed-Derived Ingredients Data Profile – December 2016 – Writer, Christina Burnett
/Impurities
Use - Nonhuman Clinical In Physical/Chemical Physical/Chemical Properties Method of Manufacturing Composition Acute Toxicity Carcinogenicity Irritation/Sensitization - Irritation/Sensitization - Ocular/Mucosal Phototoxicity Case Studies
Citrus Aurantifolia (Lime) Oil X Citrus Aurantium Amara (Bitter Orange) X X X X X X X Leaf/Twig Oil Citrus Aurantium Dulcis (Orange) Oil X Citrus Aurantium Dulcis (Orange) Seed Extract X Citrus Aurantium Sinensis Powder X Citrus Australasica Seed Oil X X Citrus Glauca Seed Oil X X Citrus Grandis (Grapefruit) Extract X Citrus Grandis (Grapefruit) Seed Extract X X Citrus Junos Extract X Citrus Junos Seed Extract X X X Citrus Junos Seed Oil X Citrus Limon (Lemon) Flower/Leaf/Stem X Extract Citrus Nobilis (Mandarin Orange) X Citrus Nobilis (Mandarin Orange) Oil X Citrus Paradisi (Grapefruit) Seed Extract X X X Citrus Reticulata (Tangerine) Extract X Citrus Tangerine (Tangerine) Extract X
Citrus Aurantium (Bitter Orange) Oil (not INCI X ingredient) Citrus sinensis leaves and branches X Citrus sinensis seed flour X NO USES OR DATA WERE AVAILABLE FOR THE REMAINING CITRUS INGREDIENTS LISTED IN TABLE 1.
“X” indicates that data were available in the category for that ingredient.
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Search Strategy for Citrus Plant- and Seed-Derived Ingredients
• August 2014 – miscellaneous searches for additional data on constituents • Scifinder – February 26, 2013 o Search for INCI citrus ingredients w/ CAS No. – 99 hits, 10 ordered • PubMed – March 5,2013 o Search for “citrus cosmetics” – 65 hits, 1 ordered o Search for “citrus sensitization” – 36 hits, 8 ordered o Search for “citrus dermal” – 12 hits, 0 ordered o Search for “citrus phototoxicity” – 24 hits, 10 ordered • SciFinder – Aug 19 2013 o toxicity of citrus ingredients – 11 hits; 1 ordered o carcinogenicity of citrus – 466 hits; 8 ordered • SciFinder – Aug 20, 2013 o Phototoxicity of citrus – 47 hits; 21 ordered o Dermal effects of citrus – 51 hits; 1 new ref found o Dermal absorption of citrus – 1 hit; not useful o Constituents of citrus – 116 hits; o Citrus – Belsito, Marks, Bergfeld, Api, RIFM– 2 found Ordered a few others; printed some directly
Updated searches in November, 2013 – ordered an additional 4 references Updated searches July 2015 with the term “citrus” – 1 new relevant reference found. Updated searches October 2015 with the term “citrus AND toxicity” or “citrus AND irritation”– 0 new relevant references found. Updated searches February –May 2016 with the term “citrus seed composition” (29 hits) and “citrus plant composition” (555 hits) and “citrus branch composition” (5 hits) and “citrus stem composition” (7 hits) – 4 relevant references found. Updated search August 1, 2016. Updated searches October 24, 2016.
Online Info • FDA o GRAS definitions • Dr. Duke’s Phytochemical and Ethnobotanical Databases o Due to volume of data, limited search to Citrus limon (Lemon), Citrus aurantifolia (Lime), Citrus paradisi (Grapefruit), Citrus sinensis (Sweet Orange), and Citrus aurantium (Bitter Orange) • National Toxicology Program (NTP) o Bitter Orange Extract (mixture) • SCCS/SCCP o Opinion on fragrance allergens in cosmetic products o Opinion on Furocoumarins in cosmetic products • Sigma Aldrich o Citrus aurantiifolia (lime) o Citrus aurantium (bitter orange) o Citrus paradisi (grapefruit) o Citrus reticulata (tangerine) • IFRA o 7-methoxycoumarin o Standard for citrus oils and other furocoumarins containing essential oils.
• General Google Search on food use/GRAS status (updated JULY/AUGUST 2016)
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Citrus Plant- and Seed-Derived Ingredients September 26-27, 2016
Dr. Marks’ Team DR. MARKS: Okay. So next we have the citrus plant and seed. So presumably, tomorrow I'll be seconding a final report with a conclusion that safe when non-irritating or sensitized for bitter orange leaf and twig oil and insufficient conclusion for the rest. At the June meeting we, we sent out a conclusion with insufficient and there 32 citrus plant and seed derived ingredients, method of manufacture, chemical composition, grapefruit-, et cetera down here, that's all listed by Christina. Staff received unpublished data just on grapefruit, no other data was received. So why did I feel now that we could do bitter orange, leaf and twig oil as safe and insufficient for the rest.
DR. SHANK: We got new information.
DR. MARKS: Yeah.
MS. BURNETT: Well, that data was already in the fruit report and, not the fruit, the flower and leaf and it was moved over to this report because we determined that it belonged in this report and not the flower and leaf report. So the data already existed, it's just fills in data gaps in this report.
DR. MARKS: Got it.
DR. EISENMANN: And that material is GRAS.
DR. MARKS: Great.
DR. EISENMANN: And we do have composition on a couple of the oils that are very similar to the seed oils you've previously reviewed. The concentration of use of grapefruit seed oil which was already found safe was 20 percent in the seed oil report and the maximum concentration of use for the citrus junos seed oil is.1 percent. And the compositions are very similar.
DR. SLAGA: So, safe formulated to be non-irritating and non-sensitizing.
DR. MARKS: For all of them.
DR. EISENMANN: I would want to--
DR. SLAGA: The composition serves very similar. That was a question we had.
DR. MARKS: Actually, it's interesting because I had I wanted to see sensitization on the grapefruit seed extract, which is used at.15 percent. But you're right, we have eight percent sensitivity data for the leaf twig oil, which was fine. The composition is similar, then that shouldn't be an issue. And then bitter orange, I had, oh, bitter orange and also use concentration. So safe for all. We had a long list under the needs. We feel comfortable now? Ron Shank?
DR. SHANK: I, I'm happy with that, safe for all.
DR. BERGFELD: You're going to have to expand your discussion there.
DR. MARKS: Mm-hmm.
DR. SHANK: Well, we got a lot in, new data.
DR. BERGFELD: To include all of this.
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DR. MARKS: Ron Hill, what -- you were kind of -- I'm not sure whether you were in agreement with that final read. And then, Carol, remind me, do any of these have 5-MOP in them that we need to put that? Because I know one of the citrus groups, there was no 5-MOP in it, so we didn't feel we needed to include that in the conclusion.
MS. BURNETT: That was the flower and leaf.
DR. MARKS: Yeah. Do the plant and seed, do they have 5-MOP in it?
DR. EISENMANN: Well, since I questioned whether the plant exists, I don't know.
DR. HILL: Yeah.
DR. SLAGA: What do you question?
DR. EISENMANN: That's, whether or not these plants, I mean they are defined as whole plant extracts. But I don't think they're whole plant extracts because I just don't quite imagine somebody taking a citrus tree, or even flowering citrus, you know. They would call it something different I think. And I don't think they're -- I don't know if you can find that material in (inaudible). I suspect they're like the lime is (inaudible) peel. It's not a whole plant.
DR. MARKS: So it would be safer to put the 5-MOP this is going out again.
DR. EISENMANN: I know. I'll let you decide what you want to do.
DR. SLAGA: It's definitely in the peel, but I don't see any indication it's (inaudible). So I don't think that's- -
DR. MARKS: So, you wouldn't put it in, Tom? Okay.
MS. BURNETT: Well, I will point out there are two ingredients on the list that say peel. The citrus granus peel / seed extract and the citrus limon lemon leaf peel stem oil.
DR. MARKS: Okay. It goes back in. Okay, so obviously, this is going to go back out since we're changing the conclusion. So we'll see if our team seconds a final report tomorrow with safe for all these ingredients at present use and concentration when formulated to be not irritating and not sensitizing and have the 15 part per million limit per 5- MOP. Does that sound good, Tom, Ron, Ron?
DR. SHANK: Yes.
DR. HILL: I can live with that.
DR. MARKS: Okay. Any other comments?
DR. BERGFELD: Did you want to add in current practice concentrations?
DR. MARKS: It will be just the, as Ron said earlier.
DR. SLAGA: Good.
DR. MARKS: Present usage and concentrations when formulated to be not irritating or sensitizing. Okay. And then the five, and then the limit. Getting closer, Christina. So this will go back out again.
MS. BURNETT: Yes.
DR. MARKS: But hopefully it will be less of a discussion the next time, but we'll see. Okay. Distributed for Comment Only -- Do Not Cite or Quote
Dr. Belsito’s Team DR. BELSITO: So plant and seed-derived ingredients. At the last meeting we again said this group was insufficient to determine safety. We wanted manufacturing for all the ingredients except the seed extracts; chemical composition and impurities data for all the ingredients except the seed oils and seed extracts; irritation and sensitization, especially HRIPT, on bitter orange leaf twig oil and grapefruit seed extract at maximum concentration of use; composition data on the plant and seed-derived ingredients and if they're significantly different from the peel/flower/leaf-derived ingredients, then a 28-day dermal, repro, genotox, UV absorption. We wanted the whole nine yards on those. Again we got some information here. Let me go back to this one.
DR. SNYDER: We got some composition data. We got additional GRAS data, and then we got a conclusive patch test study in humans on.15 percent grapefruit seed extract.
DR. BELSITO: So we got GRAS -- the orange leaf twig oil is GRAS -- but we have no composition. I don't know if that bothers anyone. We have a seed extract patch, but we don't have a twig oil patch.
DR. SNYDER: That patch test was only 12 people.
DR. BELSITO: Yeah, but again I think we have a sense of what's in there.
DR. LIEBLER: I think we were really okay for the seed stuff with method of manufacture, impurities, and composition. What we were really lacking was for the plant stuff, and we're still in the same place there.
DR. BELSITO: Yeah, I said are we okay with seed oils and leaf twig oil since they're GRAS? Other insufficient for prior listed reasons.
DR. SNYDER: Pending -- yeah, I think -- and then what about the GRAS? Was that on the petitgrain --
MS. BURNETT: Yeah, that's on the bitter orange leaf twig oil.
DR. SNYDER: So is that relevant? How closely is it?
MS. BURNETT: So it's the same thing. I think in the fragrance industry that's what -- they need it.
DR. BELSITO: I'm sorry, Paul. I missed your question.
DR. SNYDER: Well, I noticed when I was reading the additional data we received that the GRAS data was on this petitgrain bigarade oil.
DR. BELSITO: Right, and if you read in the report that's apparently the same thing as the leaf twig oil.
MS. BURNETT: The bitter orange seed oil.
DR. BELSITO: So it's referred to as the non-INCI name.
DR. SNYDER: Okay.
MS. BURNETT: And that data was originally in the other report, but once we figured out what it was, we added it to this one.
DR. SNYDER: So we really ended up -- the composition data we see accommodate the composition to see if it's significantly different between the plant and seed? Is that one of the issues that we had?
DR. BELSITO: Did we get composition for -- we got composition for not plant, did we? I didn't think we did.
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MS. BURNETT: We didn't. We just had the leaf twig oil for the bitter orange leaf twig oil and then we have some for the seeds and that's it.
DR. BELSITO: Yeah. We don't have the plant, which is why I think we could go with the oil and the leaf twig oil as being safe and then everything else still insufficient based upon our prior --
MS. BURNETT: Just that one species and leaf twig, the bitter orange?
DR. BELSITO: If I wanted to be totally OCD about it, I would go just with that species, but I think what we've been seeing is that there are minor variations between the species, but not major variations. That's my own thought.
MS. BURNETT: I guess there is only one link.
DR. LIEBLER: So if we were going to use that to rescue the others for which we have no data, we would have to make the argument that the other citrus plant-derived ingredients, whether they be fruit peel, leaves --
DR. BELSITO: No. We're not doing all of them. We're trying to do leaf -- same parts of the different --
DR. LIEBLER: I know, but I think -- are you not referring to the idea that we have tended to see that these species in the various parts of the plant tend to have the same chemical constituents?
DR. BELSITO: Yes.
DR. LIEBLER: And we've learned that not just from the plant and seed, but also from the leaf and flowers and fruit and peels and so on. I think in a way it has sort of a commonsense appeal, but on the other hand we're really lacking data on what these are.
DR. SNYDER: So what do we have in regards to composition data that we think is sufficient, for which components?
DR. BELSITO: When you go to the tables, there's a whole bunch. I think the first Tables 3 through whatever. So we have the species names; that's Table 3. And then Table 4 is -- well that's just the SCCS allergens. So Table 5 is citrus seed oils --
DR. SNYDER: Just the fatty acid profile.
DR. BELSITO: And we have the fatty acid profile, which is pretty much what you're going to see in a seed oil, right, and we have it for five of them. And then Table 6 we have key constituents of the bitter orange leaf twig oil.
DR. LIEBLER: So that's about the only thing that we have for leaf twig whole plant ingredients is that table. And if we want to say we feel that the Panel's experience looking across a wide variety of citrus ingredients, it is a broad similarity in composition; and therefore with this one bitter orange leaf twig oil in hand --
DR. BELSITO: We have data for fatty acid composition and for the seed oils.
DR. LIEBLER: Right. Again it's seed stuff.
DR. BELSITO: We're at Table 5 and Table 7. And are they different -- australasica, glauca, juno? So we have essentially eight different seed oil compositions that don't, I mean --
DR. LIEBLER: So the fatty acids are sort of biologically/biochemically constrained to just be -- here's the list of chain lengths and some double bonds and that's it, and we're not really concerned about those. What Distributed for Comment Only -- Do Not Cite or Quote
we potentially might be concerned about is the wild card citrus-derived ingredient that has a lot of some other terpene or some other organic that's of potential concern.
DR. BELSITO: I guess. I understand where you're coming from, but then on the other hand we've already gone safe with several of these citrus ingredients without having the composition of every single one.
DR. LIEBLER: Right, I agree. That was the second part of what I was going to say. I think what we would need to do is craft some discussion language to help us bring that in by saying we have one, which is I think the Table 6. That's the closest thing we have to data on the kinds of ingredients or the kinds of chemical constituents we'd be most likely to be concerned about. They're there not surprisingly. They vary somewhat not surprisingly. And this has been our experience across the entire family of ingredients in other reports as well. And, therefore, we're prepared to argue that when formulated to be nonsensitizing and nonirritating, these will be safe as used.
DR. BELSITO: Right, but we're talking now simply about the seed oils and leaf twig oils.
DR. LIEBLER: Correct.
DR. BELSITO: All the others remain insufficient.
DR. LIEBLER: Yes.
DR. BELSITO: But haven't we drafted some language like that that said that we didn't have chemical composition for all of these, but we're assuming they're similar? Haven't we done that for some of the other botanicals in the discussion? I mean we say we assume if it's not reported to be used, it will be used in a similar fashion, similar concentration. We have that language. We haven't crafted language for the botanicals?
MS. BURNETT: Where we assume they're similar?
DR. SNYDER: Yeah, I think that the latter thing that you say, but not the former. I don't think we've done the first thing you said.
DR. BELSITO: So how have we dealt with the fact that we've lacked the constituents of many of the botanicals that we've signed off on based upon our assumption that they would be similar compositions?
DR. SNYDER: I think it's when we took the individual components to see which ones were derived from different ones. And if we had to piecemeal it together, I think that's what we've done.
MS. BURNETT: I think in this case citrus is different from the other botanicals because we looked at one species; whereas we're looking at several species that are the same. So I'm not sure that would work. We haven't done that before because we haven't had --
DR. SNYDER: We said we wanted a 28 day dermal and if it was absorbed, we want a reproductive developmental genotox to give the absorption unless they showed us that the composition was not significantly different, but we haven't reached that first hurdle. We don't know that it's not significantly different other than for the twig oil and the seed oil, right?
DR. BELSITO: Well, we have only one twig oil. We have eight seed oils. But I guess the question is what is - - I hear Dan's point. I mean we don't know. I guess my question is what are we afraid of, and Dan is saying well we don't what we're afraid of because we don't have the data. I don't have an answer to that. I think from a skin standpoint what I'm seeing, plus the boilerplate that should be not a dermal sensitizer/irritant, I'm fine.
DR. ANSELL: Isn't that what we'd be afraid of, that there could be a sensitizer buried in there unless you take care of it in your boilerplate? Distributed for Comment Only -- Do Not Cite or Quote
DR. BELSITO: No because the other team is asking for dermal absorption genotox, repro tox, and all of these other endpoints.
DR. SNYDER: Very different endpoints versus the skin stuff.
DR. BELSITO: I mean it's like you would think that this is DNCB.
DR. SNYDER: Well, I think it's okay, but I think we have to then be ready to formulate some language of why we don't need that, why we don't think it's necessary. But I think that's where it becomes problematic because Dan says we don't have the data.
DR. BELSITO: Right.
DR. SNYDER: And another point I had is I thought we took tangerine out of here.
MS. BURNETT: We took the one tangerine, tangerine extract.
DR. SNYDER: It's still in there, third from the bottom on the right.
DR. BELSITO: Where?
DR. SNYDER: Underneath the ingredients.
DR. LIEBLER: In the conclusion.
DR. SNYDER: Introduction and the conclusion, citrus reticulata tangerine extract.
MS. BURNETT: I'll check that. It might be a different one, but I'll check to make sure. I thought I removed it. It was only one ingredient because it was the same as another ingredient in a different report we had to do.
DR. LIEBLER: So then we're okay with all the seed stuff?
DR. BELSITO: Seed oil.
DR. LIEBLER: Seed oil and seed extract, right?
DR. BELSITO: I didn't think we were okay with the seed extract.
MS. BURNETT: You have composition data on the juno seed extract and the paradisi grapefruit seed extract.
DR. LIEBLER: So our requirements -- I'm looking at PDF page 30, which is right above the conclusion. It's at the end of the discussion, a listing of things that we were insufficient for. It says "Method of manufacture for all these ingredients except the seed extracts, chemical composition and impurities for all ingredients except the seed oils and seed extracts." So it seems to me that the seed oils and the extracts are okay, at least for those. And then irritation/sensitization on the bitter leaf or twig oil and grapefruit seed extract at maximum use concentration. And we have irritation data on the grapefruit seed extract, but not sensitization.
DR. BELSITO: We have seed extract patch tests. We have a patch test, but we don't have sensitization.
DR. SNYDER: And only on 12 people at.15 percent, so that's not much.
DR. LIEBLER: So that was --
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DR. BELSITO: But it's at the concentration of use, or it's above the concentration of use. I'll have to check that. What is the use concentration for the --
DR. SNYDER: Grapefruit seed extract.
MS. BURNETT: .15 percent. It's right at it.
DR. BELSITO: It's at the same, and the patch test was done at.15.
DR. SNYDER: Why do we have Table 4 in there?
MS. BURNETT: I can delete it.
DR. SNYDER: It doesn't have any purpose to me because it doesn't give us composition of the ingredients or anything related to them.
DR. BELSITO: This is Table 4, so in the EU they came up with 26 fragrance ingredients that they thought were significant sensitizers and they need to be on product labels in the EU. So these are those fragrances, and I think it's just probably a way for the writers to alert us to chemicals that we might look at --
DR. SNYDER: Of concern.
DR. BELSITO: -- and we would be concerned as a sensitizer that could be stacked with other botanicals.
DR. SNYDER: But we don't know the level of any of these.
DR. BELSITO: We don't know.
DR. SNYDER: So to me it doesn't really add anything.
DR. BELSITO: Except that if we want to point out in the discussion in chemicals of concern. When we're using a boilerplate for sensitization we can say by the way, these contain coumarin, farnesol, et cetera.
DR. SNYDER: Well, I think in this case it actually lends itself to going against what we're going to conclude because we don't have the data. Yet we're saying these are potential allergens, but we don't know what their composition is or whether they're even present or not. So to me I was like -- I expected to see this as --
DR. ANSELL: Present or not.
DR. LIEBLER: Rather than have this table in here, which I agree could be misleading to the reader --
DR. BELSITO: Well, we do because on the leaf twig oil again these are all fragrance ingredients. So you're seeing minimal acetate. You're seeing linalool. And those are some of the ingredients that need to be labeled.
DR. ANSELL: Why these 12 as opposed to the whole 26?
DR. BELSITO: I don't know.
DR. SNYDER: I thought they were going to be in there and they were at low levels or something.
MS. BURNETT: I don't know if I crosschecked it somewhere. This was part of the bigger thing, so it might be just a carryover from the original main report and I just haven't deleted it. I might have class-referenced it. I saw some of the repeats that were pertinent and just left those in and deleted the other ingredients. Distributed for Comment Only -- Do Not Cite or Quote
DR. LIEBLER: I would propose that this be deleted from the report and a reference substituted that refers to the list. This gives the reader the impression that this is a list of things in these ingredients and many of these may indeed be present in these ingredients, but in many cases we don't have the data and it's not specified which ingredient has which of these compounds. And, furthermore, it's only a sublist of the list, of the SCCS list. So I would suggest we have a reference to the SCCS list instead and then delete this table.
MS. BURNETT: I know I have something referenced.
DR. SNYDER: And then we could go to the point that Don made that the Panel assumes that the formulators will be aware of the 26 identified ingredients that are commonly present blah, blah, blah, and to not --
DR. ANSELL: It's really not an allergens list per se. It's a right-to-know list that fragrances by regulation are disclosed under the word "fragrance." But the SCCS felt there were certain ingredients that deserved to be pulled out of that exemption and put on the label. So it's hard to see why that and not also reference the ACDS list frankly.
DR. SNYDER: For me I read it and I couldn't find any context for the table.
DR. LIEBLER: You're not disagreeing with taking this table out of the report?
DR. ANSELL: Just the opposite. I'm wondering once we take it out, why would we --
DR. LIEBLER: What to refer to, if you're going to refer to anything.
DR. ANSELL: Yeah.
MS. BURNETT: So just delete it completely?
DR. LIEBLER: Where do you refer to it in the text?
DR. GILL: It's on page 27 of the PDF.
MS. BURNETT: I'm just saying go to Table 4 to see these constituents that are established contact allergens. Like I said, I think it's a carryover from one of the other reports because I saw that these ingredients here and I just deleted the ones that --
DR. SNYDER: Well, I guess the first question is, are we concerned about those being constituents of those ingredients? That's the first level. And if so, then how are we going to address it because we don't have data to have knowledge of what the levels are that are in there.
DR. ANSELL: Since it's a sensitizer, doesn't the "formulated to be nonsensitizing" capture everything under that umbrella phrase?
DR. SNYDER: I think we're using it a bit too --
DR. LIEBLER: I don't remember seeing this table in every report on ingredients that may contain these compounds. I know that we don't do that, so this is sort of -- somehow appeared as Christina said after so many iterations of this ingredient family. This is just unnecessary.
MS. BURNETT: I'm going to check to see if we previously did or not. It's also in the peels report and probably most likely in the leaf.
DR. LIEBLER: I think we need to add a trigger warning that --
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DR. SNYDER: Yep, it's in there as Table 4.
DR. LIEBLER: You're going to see a table that may make you upset.
DR. ANSELL: That is uninterpretable in terms of - -
DR. SNYDER: It only took me three times to recognize it. I didn't recognize it on the first two. So I think it has to come out of all three.
DR. LIEBLER: But that's really a side issue. What we're really dealing with is what more do we need? So it sounds like we're okay with the seeds, and we've got the --
DR. BELSITO: Yeah, I mean I'm okay with the seed oil seed extracts assuming you're okay with that patch test. It's just a patch test for the seed extracts.
DR. LIEBLER: If you're fine with it, then I'm fine.
DR. BELSITO: Because we say "not to be sensitizing or irritating." And then I'm okay with the leaf twig oil, if you're okay reading across to all the other leaf twig oils. If you're not, then there's only one leaf twig oil that is okay that we have composition for and that's the citrus.
MS. BURNETT: That might technically be the only leaf twig oil because the other ones have stem/leaf/flower or something.
DR. BELSITO: Okay, let's take a look. Also I don't see citrus tangerine. It looks like it has been removed. I don't see it in the list.
MS. BURNETT: It might be just in the introduction.
DR. BELSITO: Oh, citrus reticulata, but that wasn't the one we removed, or it wasn't the reason we removed it.
MS. BURNETT: I'll go back and look.
DR. BELSITO: Citrus tangerina was the one we removed.
MS. BURNETT: Yeah, I think that tangerina tangerine, it's the same as the -- I think that was the problem.
DR. BELSITO: Here, let me go back and look at that.
MS. BURNETT: We found that the tangerina extract was actually a fruit ingredient.
DR. BELSITO: "Panel removed citrus tangerina tangerine extract from this report because it was identical to another ingredient in the citrus fruit-derived ingredient report.
DR. SNYDER: So it is tangerine extract here.
DR. BELSITO: No. It's citrus tangerina tangerine extract and this is citrus reticulata.
DR. SNYDER: Ahh, okay.
MS. BURNETT: But based on the definitions, the tangerina tangerine extract was a fruit. And based on the definition of the reticulata, tangerina is the whole plant. So that one remains.
DR. SNYDER: All right, okay, sorry.
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DR. LIEBLER: So we have bitter orange leaf twig extract and the question is can we use that information to make the argument we're fine with the leaf twig oil -- or actually we have the leaf twig oil. We can make that argument. Certainly we're okay with the leaf twig extract, but then are we okay with the lemon flower/leaf/stem extract?
DR. BELSITO: No. We don't have any data on the flowers, so we're saying that we're insufficient for --
DR. LIEBLER: Lemon leaf/peel/stem. I mean how far -- the question I'm trying to get at is how far would we try and extend this line of reasoning?
DR. BELSITO: Okay. So all of the oils that aren't seed oils we're saying are still insufficient. So as we go down the list, we have -- look to the conclusion for the list. So the lime oil, the bitter orange oil. The bitter orange would be insufficient. The leaf twig extract I don't know what that is of. If we're saying we can generalize, we'd say that's sufficient. If we feel we can't, then that would be insufficient. The orange is insufficient. The flower/leaf/stem powder is insufficient. Next, the orange oil is insufficient. The orange seed extract is sufficient. The powder I'm assuming is insufficient. The seed oil, the next three seed oils, are sufficient. Grapefruit, grapefruit extract are insufficient. The peel seed extract I would presume is insufficient, although we've approved the peel so I don't know why we wouldn't approve the peel seed extract if we're approving seed extracts. So I would say that's probably sufficient. Grapefruit seed extract is sufficient. The iyo oil insufficient. Sphaerocarpa insufficient. Extract insufficient. Juno seed extract, juno seed oil fine. Lemon flower/leaf/stem, no. Flower/leaf/stem oil, no. Flower or leaf/peel/stem oil, no. Mandarin orange, no. Mandarin orange oil, no. Mandarin orange water, no. Grapefruit seed extract, yes. Sunki seed extract, yes. Sunki seed oil, yes. Tangerine extract, no. Unshiu extract and the sphaerocarpa extract, no. So basically anything that is seed, seed oil, or leaf twig, but not flower, is okay. So there's only -- I'm just looking now. So we've got leaf twig and bitter orange. So I'm assuming this leaf twig extract that occurs under bitter orange is the bitter orange leaf twig extract and it's just not further defined? Or was this supposed to say citrus aurantium --
MS. BURNETT: I'm sorry, where --
DR. BELSITO: I'm on the conclusion.
DR. SNYDER: Fifth one down.
DR. BELSITO: So if you look at the list of ingredients where it says -- so you're doing citrus aurantium bitter orange, bitter orange oil, bitter orange, and then the next one underneath that, the fourth one down, says leaf twig extract.
MS. BURNETT: It's all one thing that carried over.
DR. BELSITO: Ah, I see. So the only leaf twig extract that we have is the bitter orange and we have the data for that.
MS. BURNETT: For the oil.
DR. LIEBLER: That was the leaf twig oil. So the question is, do we group the leaf twig extract with the leaf twig oil? I'm okay with that.
DR. BELSITO: Okay.
DR. LIEBLER: And then the rest of the list of sufficient/insufficient, I agree with what you read through essentially a minute ago.
DR. BELSITO: I'm just highlighting the ones that we think are sufficient and then I'll read them off and going down the list you can tell me if I've got them right. So you have 12, Christina, that you say we have sufficient. So I have four, five, eight, nine. I have 12 also. So I have bitter orange leaf twig extract, bitter Distributed for Comment Only -- Do Not Cite or Quote
orange leaf twig oil, orange seed extract, australasica seed oil, depressa seed oil, glauca seed oil, the juno seed oil, the grapefruit seed extract, the sunki seed extract, and the sunki seed oil as sufficient. And all the others remain insufficient for the data we had previously asked for.
DR. LIEBLER: Just so I can highlight these fast enough, can you just read one more time?
DR. BELSITO: So the insufficient or sufficient?
DR. LIEBLER: Sufficient.
DR. BELSITO: Sufficient, so going down the list under the conclusion: The bitter orange leaf twig extract, sufficient. The bitter orange leaf twig oil, sufficient. The orange seed extract, which is now a few more down, sufficient. Australasica seed oil, sufficient. Depressa seed oil, sufficient. Glauca seed oil, sufficient. Going over to the second column, fifth one down, juno seed oil, sufficient. Going further down in that column, grapefruit seed extract. And then the two below that, sunki seed extract and sunki seed oil, sufficient.
MS. BURNETT: And what about the citrus grandis peel seed extract? Did you not want that one done?
DR. BELSITO: Oh, I missed that one. So then there are 13. Where are we?
DR. SNYDER: Bottom left.
DR. BELSITO: Oh, yeah, so then there are 13.
DR. ANSELL: And then the juno seed extract, citrus juno seed extract, the fourth one down in the right column.
DR. BELSITO: Oh, yeah, 14. Thank you.
DR. SNYDER: You should have 12 that aren't.
MS. BURNETT: Still 12.
DR. BELSITO: 12 sufficient?
MS. BURNETT: Yeah.
DR. BELSITO: Yeah. I guess I double counted because of the double line.
DR. SNYDER: There's 20 that are insufficient.
DR. LIEBLER: So citrus grandis peel seed extract, bottom left, second to the bottom left, is okay?
DR. BELSITO: Citrus grandis peel seed extract? No.
MS. BURNETT: Yes.
DR. BELSITO: Oh, it is.
DR. LIEBLER: Because peel we already have.
DR. BELSITO: So we have 13 now, right.
MS. BURNETT: No, we're still 12 I think.
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DR. ANSELL: Citrus grandis peel seed extract.
MS. BURNETT: I have 12.
DR. BELSITO: I have 13. So let's count them again.
MS. BURNETT: I missed the grapefruit seed extract.
DR. BELSITO: So insufficient, just to make sure I haven't failed to highlight something: Insufficient will be the lime oil, bitter orange oil, citrus aurantium dulcis orange flower/leaf/stem powder, orange oil, the sinensis powder, grapefruit, grapefruit extract, iyo oil, sphaerocarpa extract, juno extract, lemon flower/leaf/stem extract, lemon flower/leaf/stem oil, lemon leaf/peel/stem oil. So we need to think about that. Okay, so we don't have any stem data. The mandarin orange, mandarin orange oil, mandarin orange water, tangerine extract, unshiu extract, and sphaerocarpa extract are all insufficient.
DR. SNYDER: So they're insufficient for composition. If the composition is significantly different, then we want to go with the same language, right?
DR. BELSITO: Right.
DR. SNYDER: Not changing any of the language of the data needs.
DR. BELSITO: Nope. Any other points with this -- Curt, Paul, Dan -- going through this?
DR. LIEBLER: No, I'm fine. Nothing else.
DR. SNYDER: Removing Table 4 from all three of these, right?
MS. BURNETT: Uh-hum.
DR. BELSITO: Then have we decided how we're going to reference these, or we're not even going to mention the fragrances that Europe allows?
DR. KLAASSEN: Don't even mention it.
DR. BELSITO: It's up to all of us to pick out key ingredients of concern in our areas of expertise to put in the discussion so I don't have a problem with removing it. But that will go across all botanicals because we've included this type of table with all botanicals I'm assuming, correct?
MS. BURNETT: I'm not sure. This is the only one I've had so far.
DR. SNYDER: I don't recall seeing it. I recall seeing that we had data, composition data, and talked about the percentage, but I don't recall seeing a table like that.
MS. BURNETT: It might just be in mine. We've been looking at citrus forever, so it could just seem like it's a lot of botanicals and it's just mine. Sorry.
DR. SNYDER: No, no. It's all right.
DR. BELSITO: As I was reading depressa and glauca, I was thinking I'm getting depressed and getting glaucoma from reading these reports. Anything else on these citrus ones?
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Full Panel Meeting DR. BERGFELD: Moving on to the third ingredient then on the Citrus plant and seed. Dr. Belsito?
DR. BELSITO: Yes. At the June meeting, we came to the conclusion that the available data at that time were insufficient to determine the safety of the 32 Citrus plant- and seed-derived ingredients. We requested method of manufacturing information for all of the ingredients except the seed extracts; chemical composition and impurities data for all of these ingredients except the seed oils and seed extracts; irritation and sensitization data, particularly in HIRPT, on bitter orange leaf/twig oil and Citrus grandis seed extract at maximum use concentrations; composition data for the Citrus plant- and seed-derived ingredients. And if they are significantly different from those of the peel, flower, and leaf, the data on systemic endpoints such as a 28-day dermal tox, repro and development tox, and genotox, as well as UV absorption would be needed.
We did get some irritation data that was added to the report. We got information about the GRAS status of bitter orange leaf/twig oil and the IFRA standards on the hydroperoxides of linalool and limonene were added. There were some technical comments from the council that were also added.
And when we looked at this report, okay, we felt that -- no, I don't have my conclusion here. Dan, help me out. It was the seed extracts and the seed oils were safe as used and the other remained insufficient for all the previously --
DR. LIEBLER: Right. If it will help, I could read the list. We went through it a couple times on our team.
SPEAKER: Highlighted.
DR. LIEBLER: The ones that were --
DR. BELSITO: Ah, yes, that's what I did. I just highlighted it.
DR. LIEBLER: Yes, the ones that were considered sufficient by the Belsito team were: Citrus Aurantium Amara, bitter orange leaf/twig extract; Citrus Aurantium Amara, bitter orange leaf/twig oil; Citrus Aurantium Dulcis orange seed extract; Citrus Australasica seed oil; Citrus Depressa seed oil; Citrus Glauca seed oil; Citrus Grandis peel/seed extract; Citrus Grandis grapefruit seed extract; Citrus Junos seed extract; Citrus Junos seed oil; Citrus Paradisi grapefruit seed extract; Citrus sunki seed oil.
DR. BELSITO: Correct. And all the others were insufficient for the reasons that we had previously asked. So essentially, it was the leaf/twig extract, the seed oils, and the seed extracts.
DR. MARKS: Our team actually felt that we could issue a draft final report that all were safe. What were the needs? What were the insufficient needs for --
DR. LIEBLER: Method of manufacture, impurities, composition -- method of manufacture, composition, and impurities primarily.
DR. MARKS: Team, any comments? I think, again, to be on the safe side, we certainly can second that motion.
DR. BELSITO: I mean, Dan felt very strongly that we just really had no information on that.
DR. MARKS: Yes. No, that's fine. As I said, we can second it.
DR. LIEBLER: This is just a chronic problem trying to interpret between the whole plant or when you have data on leaf/twig, but not stem, you know. I mean, at what point does it become something that you cannot justify? So we ended up coming down basically saying if we don't have a reasonable inference to be made across these ingredients, then we can't support them.
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DR. BERGFELD: Ron Shank, did you have a comment?
DR. SHANK: No, nothing here.
DR. BERGFELD: Ron Hill, nothing to add? Tom, nothing?
DR. SLAGA: I agree.
DR. BERGFELD: So there's a second to the motion. Any other discussion? Oh, yes?
DR. BELSITO: Yes. So we wanted to remove Table 4 from this document and similar tables like Table 4 from other botanical reports where they're essentially listing the 26 fragrance ingredients that Europe requires to be labeled. We really don't see the need for including that table. I think that was the really only major thing that we had determined on this.
DR. BERGFELD: Anything else? Seeing no other comments, then call for the question. All those in favor of safe on part of this and insufficient for the other parts? Thank you. Unanimous. So it's a mixed report -- or conclusion.
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Safety Assessment of Citrus Plant- and Seed-Derived Ingredients as Used in Cosmetics
Status: Draft Revised Final Report for Panel Review Release Date: November 11, 2016 Panel Meeting Date: December 5-6, 2016
The 2016 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D., Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Christina Burnett, Senior Scientific Analyst/Writer.
Cosmetic Ingredient Review 1620 L Street NW, Suite 1200 ♢ Washington, DC 20036-4702 ♢ ph 202.331.0651 ♢ fax 202.331.0088 ♢ [email protected] Distributed for Comment Only -- Do Not Cite or Quote
ABSTRACT The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 32 Citrus plant- and seed- derived ingredients, which are most frequently reported to function in cosmetics as fragrances and/or skin conditioning agents. Because final product formulations may contain multiple botanicals, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. Industry should use good manufacturing practices to limit impurities that could be present in botanical ingredients. The Panel reviewed the available data presented and concluded that 13 of these ingredients are safe in the present practices of use and concentration when formulated to be non-irritating and non-sensitizing. The data for the remaining 19 ingredients are insufficient to determine safety.
INTRODUCTION This report assesses the safety of the 32 Citrus plant- and seed-derived ingredients listed below, which are reported in the International Cosmetic Ingredient Dictionary and Handbook (Dictionary) to mainly function as skin conditioning agents-miscellaneous in cosmetic products (Table 1).1 Citrus Aurantium (Bitter Orange) Oil is not currently listed in the Dictionary, but has been included in this report because of its high reported number of uses in the Food and Drug Administration (FDA) Voluntary Cosmetic Registration Program (VCRP) database and presumed similarities to the other ingredients in this report. Two ingredients (Citrus Sunki Seed Extract and Citrus Sunki Seed Oil) are reported to function as skin bleaching agents; use as a skin bleaching agent is classified as a drug use and, as such, does not fall under the purview of CIR.
Citrus Aurantifolia (Lime) Oil Citrus Iyo Oil Citrus Aurantium (Bitter Orange) Oil Citrus Jabara Pericarp Extract Citrus Aurantium Amara (Bitter Orange) Citrus Junos Extract Leaf/Twig Extract Citrus Junos Seed Extract Citrus Aurantium Amara (Bitter Orange) Citrus Junos Seed Oil Leaf/Twig Oil Citrus Limon (Lemon) Flower/Leaf/Stem Extract Citrus Aurantium Dulcis (Orange) Citrus Limon (Lemon) Flower/Leaf/Stem Oil Flower/Leaf/Stem Powder Citrus Limon (Lemon) Leaf/Peel/Stem Oil Citrus Aurantium Dulcis (Orange) Oil Citrus Nobilis (Mandarin Orange) Citrus Aurantium Dulcis (Orange) Seed Extract Citrus Nobilis (Mandarin Orange) Oil Citrus Aurantium Sinensis Powder Citrus Nobilis (Mandarin Orange) Water Citrus Australasica Seed Oil Citrus Paradisi (Grapefruit) Seed Extract Citrus Depressa Seed Oil Citrus Sunki Seed Extract Citrus Glauca Seed Oil Citrus Sunki Seed Oil Citrus Grandis (Grapefruit) Citrus Reticulata (Tangerine) Extract Citrus Grandis (Grapefruit) Extract Citrus Unshiu Extract Citrus Grandis Peel/Seed Extract Citrus Unshiu Pericarp Extract Citrus Grandis (Grapefruit) Seed Extract
The Panel previously reviewed the safety of Citrus-derived peel oils, Citrus peel-derived ingredients, and Citrus fruit-derived ingredients in separate assessments and concluded that 14 Citrus-derived peel oil, 47 Citrus peel-derived ingredients, and 80 Citrus fruit-derived ingredients are safe for use in both rinse-off and leave-on cosmetic products when formulated to be non-sensitizing and non-irritating, provided that leave-on products do not contain more than 0.0015% (15 ppm) 5-methoxypsoralen (5-MOP).2-4 The Panel has also reviewed the safety of Citrus Aurantifolia (Lime) Seed Oil, Citrus Aurantifolia (Lime) Seed Oil Unsaponifiables, Citrus Aurantium Dulcis (Orange) Seed Oil, Citrus Aurantium Dulcis (Orange) Seed Oil Unsaponifiables, Citrus Grandis (Grapefruit) Seed Oil, Citrus Grandis (Grapefruit) Seed Oil Unsaponifiables, Citrus Limon (Lemon) Seed Oil, and Citrus Paradisi (Grapefruit) Seed Oil, and concluded that these ingredients are safe in the present practices of use and concentration as described in the safety assessment of plant-derived fatty acid oils.5 Citrus flower- and leaf-derived ingredients are being reviewed in a separate report.6 To avoid redundancy of effort, CIR generally excludes from review ingredients that are known to function exclusively as fragrance ingredients when the ingredient has been or will be evaluated by the Research Institute for Fragrance Materials (RIFM). According to the Dictionary, three of the Citrus plant- and seed-derived ingredients in this report are reported to function exclusively as fragrance ingredients (see Table 2).1 However, personal communications with RIFM in March 2015 revealed that these ingredients have neither been assessed for safety by the RIFM Expert Panel, nor are these ingredients on RIFM’s prioritized agenda to be reviewed in the foreseeable future. Thus CIR is reviewing the safety of these ingredients as part of this current assessment.
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Botanical ingredients are composed of numerous constituents, some of which have the potential to cause toxic effects. For example, bergapten (aka 5-methoxysporalen or 5-MOP) is a naturally-occurring phototoxic furanocoumarin (psoralen) found in some Citrus ingredients. In this assessment, CIR is reviewing the potential toxicity of each Citrus plant- or seed-derived ingredient as a whole, complex substance. Except for specific constituents of concern that the Panel has identified, CIR is not reviewing the potential toxicity of the individual constituents of the Citrus plants and seeds from which the ingredients in this report are derived. Note: In many of the published studies included in this assessment, the information provided is not sufficient to determine how well the substance being tested represents the cosmetic ingredient. In this safety assessment, if a substance tested in a study is not clearly a cosmetic ingredient, because of lack of information on the genus and species from which the substance was derived and/or the method of extraction used, the test substance will be referred to by a common name (e.g. lemon extract). If the substance is clearly a cosmetic ingredient, the International Nomenclature of Cosmetic Ingredients (INCI) name will be used (e.g. “Citrus Limon (Lemon) Extract”). Additionally, some inconsistencies were noted in both taxonomic and INCI naming conventions. For example, this report includes the sweet orange ingredient described as Citrus Aurantium Dulcis (Orange) in the Dictionary.1 In contrast, most of the published literature and the FDA VCRP refer to this ingredient as Citrus Sinensis (Sweet Orange). Another example of a naming inconsistency is Citrus Grandis (Grapefruit); Citrus grandis is generally considered a name for a pomelo, which may also be referred to as Citrus maxima. Citrus paradisi appears to be the more widely accepted nomenclature for grapefruit. Finally, Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil is also known as petitgrain bigarade oil. The INCI Committee of the Personal Care Products Council (Council) is working to correct some of these inconsistencies. The genus and species names associated with the ingredient names designated by the INCI Committee are listed in Table 3.7
CHEMISTRY Definition and General Characterization The definitions and functions of the Citrus plant- and seed-derived ingredients included in this report are provided in Table 1. The definition indicates what part(s) of the plant from which an ingredient is obtained. In some cases, the definition provides insight on the method(s) of manufacture. Essential oils are the hydrophobic, liquid, volatile aromatic compounds in the insoluble condensate fraction, and typically are small molecules, but their chemical structures can vary widely. Fixed oils, on the other hand, are hydrophobic, nonvolatile, fatty compounds from plants (including Citrus seeds), animals or algae. These are primarily composed of glycerides and, to some extent, free fatty acids. Constituents of these Citrus-derived ingredients may include both oil types. The volatile nature of essential oils makes them more likely to be useful as fragrances, but use as fragrances is not their only reported function. According to the Dictionary, essential oils and waters are prepared from leaves, stems, flowers, bark, roots, or other parts of a plant or the whole plant.1 Essential oils are prepared by a number of processes including, but not limited to, steam or dry distillation, flash pasteurization and mechanical processes such as cold-pressing; however, the most widely used method for preparing essential oils from plants is steam distillation. The condensate from steam distillation produces two distinct fractions that contain the volatile ingredients from the plant. The water insoluble fraction contains the "oil." The water soluble fraction contains constituents of the plant that are dissolved in water. The name assigned to the water insoluble fraction from steam distilled plant materials includes the term "oil" in the INCI name. The water soluble fraction from the steam distilled plant material includes the term "water" in the INCI name.
Physical and Chemical Properties Citrus Australasica Seed Oil Citrus Australasica Seed Oil is reported to be a straw/yellow colored liquid with a refractive index of 1.476 (specification range 1.450-1.490 at 20º C) and a specific gravity of 0.917 (specification range 0.900-0.940 at 20º C).8 Citrus Glauca Seed Oil According to a supplier, Citrus Glauca Seed Oil is a light brown to dark brown liquid.9 At 20º C, the refractive index is 1.472 (specification range 1.450-1.490) and the specific gravity is 0.921 (specification range 0.900-0.940). Distributed for Comment Only -- Do Not Cite or Quote
Method of Manufacturing Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil According to the Food Chemicals Codex, “petitgrain oil, Paraguay type” is a volatile oil obtained by steam distillation from the leaves and small twigs of the bitter orange tree, Citrus aurantium L. subspecies amara.10 Citrus Junos Seed Extract A supplier has reported that Citrus Junos Seed Extract is produced by extracting dried seeds with 90% ethanolic solution, which is then filtered.11 The material then undergoes sedimentation, filtration, and adjustment before packaging. Citrus Paradisi (Grapefruit) Seed Extract A supplier reported that Citrus Paradisi (Grapefruit) Seed Extract is manufactured by first grinding grapefruit seeds and then extracting in a mix of water and glycerin.12 The mixture is then clarified and decontaminated by heat.
Constituents/Composition The Citrus ingredients are complex botanicals composed of numerous constituents. Table 4 lists the fatty acid profiles for Citrus seed-derived oils that were previously reviewed in the safety assessment of plant-derived fatty acid oils.5 The major fatty acid components in Citrus seed-derived oils are palmitic acid, oleic acid, and linoleic acids. The International Fragrance Association (IFRA) has issued standards for limonene and linalool in natural products, stating that these constituents “should only be used when the level of peroxides is kept to the lowest practical level, for instance by adding antioxidants at the time of production.”13,14
Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil According to the Food Chemicals Codex, “petitgrain oil, Paraguay type” contains not less than 45.0% and not more than 60% esters calculated as linalyl acetate.10 A fragrance raw materials monograph lists the components of petitgrain bigarade oil as α-pinene, β-pinene, sabinene, myrcene, limonene, cis-β-ocimene, trans-β-ocimene, linalool, linalyl acetate, terpineol-4, β-caryophyllene, α-terpineol, neryl acetate, geranyl acetate, nerol, geraniol, and nerolidol.15 A breakdown of the key constituents of Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil is detailed in Table 5. Citrus Australasica Seed Oil and Citrus Glauca Seed Oil The fatty acid profiles for Citrus Australasica Seed Oil and Citrus Glauca Seed Oil are listed in Table 6. Citrus Junos Seed Extract A supplier reports that Citrus Junos Seed Extract is composed of saponin and sugar.11 The concentrations of heavy metal impurities are not more than 20 ppm and the concentration of arsenic is not more than 2 ppm. The fatty acid profile for Citrus junos Sieb. ex Tanaka is also listed in Table 6. Citrus Paradisi (Grapefruit) Seed Extract A supplier reported that a trade name material contains 67.0% to 73.0% glycerin, 26.0% to 32.8% water, and 0.2% to 1.0% Citrus Paradisi (Grapefruit) Seed Extract.12 Citrus Sinensis In gas chromatography and gas chromatography-mass spectroscopy analysis of the essential oils from the leaves and green branches of Egyptian navel orange trees (Citrus sinensis (L.) Osbeck var. Malesy), 33 and 24 compounds were identified for the leaves and branches, respectively.16 These compounds made up 96.0% and 97.9%, respectively, of the total detected constituents. The major constituents were sabinene (36.5% leaves, 33.0% branches), terpinen-4-ol (8.2% leaves, 6.2% branches), δ-3-carene (7.0% leaves, 9.4% branches), limonene (6.8% leaves, 18.7% branches), trans-ocimene (6.7% leaves, 6.1% branches), and β-myrcene (4.5% leaves, 9.4% branches). The composition of samples of dehulled sweet orange (Citrus sinensis) seed flour (dry weight) was reported to be 54.2% fat, 28.5% carbohydrate, 5.5% crude fiber, 3.1% crude protein, and 2.5% ash.17 Mineral analysis showed high levels of calcium and potassium.
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USE Cosmetic The safety of the cosmetic ingredients included in this assessment is evaluated based on data received from the FDA and the cosmetics industry on the expected use of these ingredients in cosmetics. Use frequencies of individual ingredients in cosmetics are collected from manufacturers and reported by cosmetic product category in FDA’s VCRP database. Use concentration data are submitted by Industry in response to surveys, conducted by the Council, of maximum reported use concentrations by product category. According to 2016 VCRP data, Citrus Aurantium (Bitter Orange) Oil has the most reported uses of the cosmetic ingredients in this report, with a total of 295; more than half are in leave-on skin care preparations (Table 7).18 This ingredient is not currently in the Dictionary, but has been included in this report because of the number of uses and presumed similarities to the other ingredients in this report. The ingredients with the next highest frequency of use are Citrus Aurantifolia (Lime) Oil (169 total uses) and Citrus Grandis (Grapefruit) Seed Extract (144 total uses); a majority of the uses for these ingredients are in leave-on skin care preparations. The results of the concentration of use survey indicate Citrus Aurantium Dulcis (Orange) Oil has the highest reported maximum concentration of use; it is used at up to 1% in a body and hand formulation.19 Citrus Aurantifolia (Lime) Oil had the second highest reported maximum concentration of use; it is used at up to 0.36% in a lipstick. In some cases, reports of uses were received from the VCRP, but no concentration of use data were provided. For example, Citrus Limon (Lemon) Flower/Leaf/Stem Extract is reported to be used in 8 formulations, but no use concentration data were available. In other cases, no uses were reported to the VCRP, but a maximum use concentration was provided in the industry survey. For example, Citrus Junos Seed Oil was not reported in the VCRP database, but the industry survey indicated that it is used in face and neck and body and hand formulations at up to 0.1%. It is presumed that Citrus Junos Seed Oil is used in at least one cosmetic formulation. Table 8 lists all Citrus plant- and seed-derived ingredients not currently in use based on the VCRP data or the results of the Council concentration of use survey. Some of these ingredients may be used in products that can come into contact with the eye or mucous membranes. For example, Citrus Aurantifolia (Lime) Oil is used in a lipstick at up to 0.36%. Additionally, some of these ingredients were reported to be used in hair sprays, fragrance preparations, face powder and body powders, spray deodorants, and spray skin care preparations and could possibly be inhaled. For example, Citrus Aurantifolia (Lime) Oil was reported to be used in body and hand sprays at a maximum concentration of 0.12% and Citrus Junos Seed Oil was reported to be used in face powders at up to 0.1%. In practice, 95% to 99% of the droplets/particles released from cosmetic sprays have aerodynamic equivalent diameters >10 µm, with propellant sprays yielding a greater fraction of droplets/particles below 10 µm compared with pump sprays.20-23 Therefore, most droplets/particles incidentally inhaled from cosmetic sprays would be deposited in the nasopharyngeal and bronchial regions and would not be respirable (i.e., they would not enter the lungs) to any appreciable amount.21,22 There is some evidence indicating that deodorant spray products can release substantially larger fractions of particulates having aerodynamic equivalent diameters in the range considered to be respirable.22 However, the information is not sufficient to determine whether significantly greater lung exposures result from the use of deodorant sprays, compared to other cosmetic sprays. Conservative estimates of inhalation exposures to respirable particles during the use of loose powder cosmetic products are 400-fold to 1000-fold less than protective regulatory and guidance limits for inert airborne respirable particles in the workplace.24-26 The Citrus ingredients described in this safety assessment are not restricted from use in any way under the rules governing cosmetic products in the European Union (EU). However, furocoumarins are prohibited from use in cosmetics, except for normal content in natural essences and in sun protection and bronzing products where the content shall be below 1 mg/kg.27
Non-Cosmetic Petitgrain bigarade oil (Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil) is generally recognized as safe (GRAS) for intended use in foods for human consumption (21CFR182.20) and in animal drugs, feeds, and related products (21CFR582.20).
TOXICOKINETICS No relevant published toxicokinetics studies on Citrus plant- and seed-derived ingredients were identified in a literature search for these ingredients, and no unpublished data were submitted; toxicokinetics data are not expected to be found because botanical ingredients are mixtures of hundreds of constituents. Distributed for Comment Only -- Do Not Cite or Quote
TOXICOLOGICAL STUDIES Acute Toxicity Dermal – Animal Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil The dermal LD50 of Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil (described as petitgrain bigarade oil) was reported to be greater than 2 g/kg in rabbits; however, only 2 rabbits were used in the study.15 An occlusive patch of undiluted test material was applied for 24 h.
Repeated Dose Toxicity No relevant published repeated dose toxicity studies on Citrus plant- and seed-derived ingredients were identified in a literature search for these ingredients, and no unpublished data were submitted.
REPRODUCTIVE AND DEVELOPMENTAL TOXICITY No relevant published reproductive and developmental studies on Citrus plant- and seed-derived ingredients were identified in a literature search for these ingredients, and no unpublished data were submitted.
GENOTOXICITY No relevant published genotoxicity studies on Citrus plant- and seed-derived ingredients were identified in a literature search for these ingredients, and no unpublished data were submitted.
CARCINOGENICITY No relevant published carcinogenicity studies on Citrus plant- and seed-derived ingredients were identified in a literature search for these ingredients, and no unpublished data were submitted.
IRRITATION AND SENSITIZATION Dermal Irritation Dermal irritation studies are summarized in Table 9.15,28,29 In rabbit studies, slight erythema was observed after exposure to 2g/kg Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil (described as petitgrain bigarade oil). In human subjects, no irritation was observed after topical exposure to petitgrain bigarade oil (up to 8% in petrolatum) or Citrus Grandis (Grapefruit) Seed Extract (0.15% in formulation).
Dermal Sensitization Dermal sensitization studies are presented in Table 10.15,30 Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil (described as petitgrain bigarade oil) at up to 8% in petrolatum was not sensitizing in humans.
Photosensitization Photosensitization studies are presented in Table 11.31 Undiluted Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil (described as petitgrain bigarade oil) was not photosensitizing in tests with hairless mice or miniature swine.
CLINICAL STUDIES No relevant published clinical studies on Citrus plant- and seed-derived ingredients were identified in a literature search for these ingredients, and no unpublished data were submitted.
SUMMARY The 32 Citrus plant- and seed-derived ingredients described in this report function primarily as skin conditioning agents-miscellaneous. Botanical ingredients are composed of hundreds of constituents, some of which Distributed for Comment Only -- Do Not Cite or Quote
have the potential to cause toxic effects; for example, bergapten (aka 5-methoxypsoralen or 5-MOP) is a naturally- occurring, phototoxic furanocoumarin (psoralen) in Citrus. Presently, CIR reviewed the information available on the potential toxicity of each Citrus plant- and seed-derived ingredient as a whole, complex substance; CIR does not review the potential toxicity information on the individual constituents of which the Citrus plant- and seed-derived ingredients are comprised. Citrus seed oils are fixed oils that are composed primarily of glycerides, and to some extent, free fatty acids while the other Citrus oils in this safety assessment are essential oils that primarily contain volatile compounds. No composition information was found for ingredients defined as being derived from the whole plant. Citrus Aurantium (Bitter Orange) Oil has the most reported uses of the ingredients in this report in cosmetic products, with a total of 295; more than half of the uses are in leave-on skin care preparations. This ingredient is not currently in the Dictionary but has been included in this report because of its high reported number of uses and presumed similarities to the other ingredients in this report. The ingredients with the next highest frequency of use are Citrus Aurantifolia (Lime) Oil (169 total uses) and Citrus Grandis (Grapefruit) Seed Extract (144 total uses); a majority of the uses for these ingredients are in leave-on skin care preparations. The results of the concentration of use survey indicate Citrus Aurantium Dulcis (Orange) Oil has the highest reported maximum concentration of use; it is used at up to 1% in a body and hand formulation. Citrus Aurantifolia (Lime) Oil had the second highest reported maximum concentration of use; it is used at up to 0.36% in a lipstick. The Citrus ingredients described in this safety assessment are not restricted from use in any way under the rules governing cosmetic products in the European Union (EU); however, furocoumarins are prohibited from use in cosmetics except for normal content in natural essences and in sun protection and bronzing products where the content shall be < 1 mg/kg. Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil is considered GRAS in foods for human consumption and in animal drugs, feed, and related products. The dermal LD50 of Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil (described as petitgrain bigarade oil) was reported as greater than 2 g/kg in rabbits. In rabbit dermal irritation studies, slight erythema was observed after exposure to unreported concentrations of Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil (described as petitgrain bigarade oil). In human subjects, no irritation was observed after topical exposure to petitgrain bigarade oil (up to 8%). Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil (described as petitgrain bigarade oil) at up to 8% was not sensitizing in humans and undiluted petitgrain bigarade oil was not photosensitizing in tests with hairless mice or miniature swine. No relevant published studies on the toxicokinetics, repeated dose toxicity, reproductive and development toxicity, carcinogenicity, genotoxicity, or clinical assessments of Citrus plant- and seed-derived ingredients were discovered and no unpublished data were submitted to address these topics.
DISCUSSION During its review of Citrus plant- and seed-derived ingredients, the Panel noted that, because botanical ingredients are complex mixtures, there is concern that multiple botanical ingredients may each contribute to the final concentration of a single constituent. Therefore, when formulating products, manufacturers should avoid reaching levels in final formulation of botanical constituents that may cause sensitization or other adverse effects. Specific examples of constituents that could induce adverse effects include the hydroperoxides of limonene and linalool. The issue of incidental inhalation exposure from hair sprays, fragrance preparations, face powder and body powders, spray deodorants, and spray skin care preparations was discussed by the Panel. There were no inhalation toxicity data available. The Panel noted that droplets/particles from cosmetic products would not be respirable to any appreciable amount. The potential for inhalation toxicity is not limited to respirable droplets/particles deposited in the lungs. In principle, inhaled droplets/particles deposited in the nasopharyngeal and thoracic regions of the respiratory tract may cause toxic effects depending on their chemical and other properties. However, coupled with the small actual exposure in the breathing zone and the concentrations at which the ingredients are used, the available information indicates that incidental inhalation would not be a significant route of exposure that might lead to local respiratory or systemic effects. A detailed discussion and summary of the Panel’s approach to evaluating incidental inhalation exposures to ingredients in cosmetic products is available at http://www.cir-safety.org/cir- findings. Distributed for Comment Only -- Do Not Cite or Quote
The Panel also expressed concern about pesticide residues, heavy metals, and other plant species that may be present in botanical ingredients. They stressed that the cosmetics industry should continue to use current good manufacturing practices (cGMPs) to limit impurities. The Panel determined that the composition data on the Citrus seed-derived ingredients found in this report were sufficient and no individual component of the seeds yielded any toxicological concern. The Panel also considered the composition, GRAS status, and safety test data on Citrus Aurantium Amara (Bitter Orange) Twig/Leaf Oil to be sufficient to support the safety of the use of this ingredient and the extract in cosmetics. However, the Panel concluded that the data are insufficient to make a conclusion on the safety of 19 Citrus plant- derived ingredients found in this safety assessment. The data that are needed to properly evaluate the safety of these ingredients are: • Method of manufacturing • Chemical composition and impurities • Irritation and sensitization data • If the composition data for these Citrus plant-derived ingredients are substantially different from that of the Citrus peel-, flower-, leaf- and seed-derived ingredients, then studies of systemic endpoints such as a 28- day dermal toxicity, reproductive and developmental toxicity, and genotoxicity are needed, as well as UV absorption spectra.
CONCLUSION The CIR Expert Panel concluded that the following 13 ingredients are safe in the present practices of use and concentration when formulated to be non-irritating and non-sensitizing.
Citrus Aurantium Amara (Bitter Orange) Citrus Glauca Seed Oil* Leaf/Twig Extract* Citrus Grandis Peel/Seed Extract* Citrus Aurantium Amara (Bitter Orange) Citrus Grandis (Grapefruit) Seed Extract Leaf/Twig Oil Citrus Junos Seed Extract Citrus Aurantium Dulcis (Orange) Seed Citrus Junos Seed Oil Extract Citrus Paradisi (Grapefruit) Seed Extract Citrus Australasica Seed Oil* Citrus Sunki Seed Extract* Citrus Depressa Seed Oil* Citrus Sunki Seed Oil*
The Panel concluded the data on the remaining 19 ingredients listed below are insufficient to determine safety.
Citrus Aurantifolia (Lime) Oil Citrus Limon (Lemon) Flower/Leaf/Stem Citrus Aurantium (Bitter Orange) Oil Extract Citrus Aurantium Dulcis (Orange) Citrus Limon (Lemon) Flower/Leaf/Stem Flower/Leaf/Stem Powder* Oil* Citrus Aurantium Dulcis (Orange) Oil Citrus Limon (Lemon) Leaf/Peel/Stem Oil* Citrus Aurantium Sinensis Powder Citrus Nobilis (Mandarin Orange) Citrus Grandis (Grapefruit)* Citrus Nobilis (Mandarin Orange) Oil Citrus Grandis (Grapefruit) Extract Citrus Nobilis (Mandarin Orange) Water* Citrus Iyo Oil* Citrus Reticulata (Tangerine) Extract Citrus Jabara Pericarp Extract* Citrus Unshiu Extract* Citrus Junos Extract Citrus Unshiu Pericarp Extract*
*Not reported to be in current use. Were ingredients in this group not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group.
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TABLES
Table 1. Definitions and functions of Citrus plant- and seed-derived ingredients.1 Ingredient Definition* Function Citrus Aurantifolia (Lime) Oil Citrus Aurantifolia (Lime) Oil is the volatile oil obtained from the Fragrance Ingredients; Skin- CAS No. 8008-26-2 whole plant, Citrus aurantifolia. Conditioning Agents - Miscellaneous Citrus Aurantium (Bitter Orange) Oil Not in Dictionary. Not in Dictionary. Citrus Aurantium Amara (Bitter Orange) Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Extract is the Skin-Conditioning Agents - Leaf/Twig Extract extract of the leaves and twigs of Citrus aurantium amara. Miscellaneous CAS No. 72968-50-4; 8016-38-4 Citrus Aurantium Amara (Bitter Orange) Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil is the Flavoring Agents; Fragrance Leaf/Twig Oil volatile oil obtained from the leaves and twigs of Citrus aurantium Ingredients amara. Citrus Aurantium Dulcis (Orange) Citrus Aurantium Dulcis (Orange) Flower/Leaf/Stem Powder is the Exfoliants Flower/Leaf/Stem Powder powder obtained from the dried, ground flowers, leaves and stems of Citrus aurantium dulcis. Citrus Aurantium Dulcis (Orange) Oil Citrus Aurantium Dulcis (Orange) Oil is the volatile oil obtained Fragrance Ingredients from the whole plant, Citrus aurantium dulcis. Citrus Aurantium Dulcis (Orange) Seed Citrus Aurantium Dulcis (Orange) Seed Extract is the extract of the Skin-Conditioning Agents - Extract seeds of Citrus aurantium dulcis. Miscellaneous Citrus Aurantium Sinensis Powder Citrus Aurantium Sinensis Powder is the powder obtained the dried Exfoliants ground plant, Citrus aurantium sinensis. Citrus Australasica Seed Oil Citrus Australasica Seed Oil is the fixed oil expressed from the Antioxidants; Hair Conditioning CAS No. 1174331-57-7 (generic) seeds of Citrus australasica. Agents; Humectants; Skin- Conditioning Agents - Miscellaneous Citrus Depressa Seed Oil Citrus Depressa Seed Oil is the oil expressed from the seeds Skin-Conditioning Agents - of Citrus depressa. Emollient Citrus Glauca Seed Oil Citrus Glauca Seed Oil is the oil expressed from the seeds of Citrus Antioxidants; Humectants; Skin glauca. Protectants; Skin-Conditioning Agents - Emollient; Skin- Conditioning Agents - Humectant Citrus Grandis (Grapefruit) Citrus Grandis (Grapefruit) is a plant material derived from the Not reported whole plant, Citrus grandis. Citrus Grandis (Grapefruit) Extract Citrus Grandis (Grapefruit) Extract is the extract of the whole plant, Skin-Conditioning Agents - Citrus grandis. Miscellaneous Citrus Grandis Peel/Seed Extract Citrus Grandis Peel/Seed Extract is the extract of the peel and seeds Antifungal Agents; Antimicrobial of Citrus grandis. Agents; Preservatives Citrus Grandis (Grapefruit) Seed Extract Citrus Grandis (Grapefruit) Seed Extract is the extract of the seeds Preservatives; Skin-Conditioning of Citrus grandis. Agents - Miscellaneous Citrus Iyo Oil Citrus Iyo Oil is the oil expressed from the whole plant, Citrus iyo. Skin-Conditioning Agents - Emollient Citrus Jabara Pericarp Extract Citrus Jabara Pericarp Extract is the extract of the pericarp of Citrus Humectants; Skin-Conditioning jabara. Agents - Miscellaneous Citrus Junos Extract Citrus Junos Extract is the extract of the whole plant, Citrus junos. Antioxidants Citrus Junos Seed Extract Citrus Junos Seed Extract is the extract of the seeds of Citrus junos. Antioxidants Citrus Junos Seed Oil Citrus Junos Seed Oil is the oil expressed from the seeds of Citrus Skin-Conditioning Agents - junos. Emollient Citrus Limon (Lemon) Flower/Leaf/Stem Citrus Limon (Lemon) Flower/Leaf/Stem Extract is the extract of Fragrance Ingredients; Skin- Extract the flowers, leaves and stems of Citrus limon. Conditioning Agents - CAS No. 84929-31-7; 85085-28-5 Miscellaneous Citrus Limon (Lemon) Flower/Leaf/Stem Citrus Limon (Lemon) Flower/Leaf/Stem Oil is the volatile oil Fragrance Ingredients Oil obtained from the flowers, leaves and stems of Citrus limon. CAS No. 84929-31-7; 85085-28-5 Citrus Limon (Lemon) Leaf/Peel/Stem Oil Citrus Limon (Lemon) Leaf/Peel/Stem Oil is the volatile oil Skin-Conditioning Agents - CAS No. 84929-31-7; 85085-28-5 obtained from the leaves, peels, and stems of Citrus limon. Miscellaneous
Citrus Nobilis (Mandarin Orange) Citrus Nobilis (Mandarin Orange) is a plant material derived from Not reported the whole plant, Citrus nobilis. Citrus Nobilis (Mandarin Orange) Oil Citrus Nobilis (Mandarin Orange) Oil is the volatile oil obtained Fragrance Ingredients from the whole plant, Citrus nobilis. Citrus Nobilis (Mandarin Orange) Water Citrus Nobilis (Mandarin Orange) Water is an aqueous solution of Skin-Conditioning Agents - the steam distillate obtained from Citrus nobilis. Miscellaneous Citrus Paradisi (Grapefruit) Seed Extract Citrus Paradisi (Grapefruit) Seed Extract is the extract of the seeds Skin-Conditioning Agents - CAS No. 90045-43-5 (generic) of Citrus paradisi. Miscellaneous
Citrus Reticulata (Tangerine) Extract Citrus Reticulata (Tangerine) Extract is the extract of the whole Skin-Conditioning Agents - plant, Citrus reticulata. Miscellaneous Citrus Sunki Seed Extract Citrus Sunki Seed Extract is the extract of the seeds of Citrus Antioxidants; Skin Bleaching sunki. Agents; Skin-Conditioning Agents - Miscellaneous Citrus Sunki Seed Oil Citrus Sunki Seed Oil is the oil expressed from the seeds of Citrus Antioxidants; Skin Bleaching sunki. Agents; Skin-Conditioning Agents - Miscellaneous Distributed for Comment Only -- Do Not Cite or Quote
Table 1. Definitions and functions of Citrus plant- and seed-derived ingredients.1 Ingredient Definition* Function Citrus Unshiu Extract Citrus Unshiu Extract is the extract of the whole plant, Citrus Skin-Conditioning Agents - CAS No. 98106-71-9 unshiu. Miscellaneous Citrus Unshiu Pericarp Extract Citrus Unshiu Pericarp Extract is the extract of the pericarp of Skin-Conditioning Agents - Citrus unshiu. Miscellaneous *Accepted or alternate scientific names for these Citrus ingredients are found in Table 3.
Table 2. Citrus plant- and seed-derived ingredients that potentially function solely as fragrance ingredients.
Citrus Aurantium Dulcis (Orange) Oil Citrus Limon (Lemon) Flower/Leaf/Stem Oil Citrus Nobilis (Mandarin Orange) Oil
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. Table 3.Review of Citrus species names7 Species Name Used in INCI Names (common name) Accepted Species Name Citrus aurantifolia (lime) Citrus x aurantifolia Citrus aurantium amara (bitter orange) Citrus x aurantium Citrus aurantium bergamia (bergamot) Citrus x limon Citrus aurantium dulcis (orange) ALSO Citrus sinensis (orange) Citrus x aurantium Citrus clementina (clementine) Citrus x aurantium Citrus depressa Citrus reticulata Citrus glauca Citrus glauca Citrus grandis (grapefruit or pomelo) Citrus maxima or Citrus x aurantium Citrus hassaku Citrus medica x Citrus x aurantium Citrus iyo Citrus x aurantium Citrus jabara Not known Citrus japonica (kumquat) Citrus japonica Citrus junos Citrus x junos Citrus limon (lemon) Citrus x limon Citrus madurensis Citrus x microcarpa Citrus medica vulgaris Citrus reticulata Citrus natsudaidai Citrus x aurantium Citrus nobilis (mandarin orange) Citrus reticulata Citrus paradisi (grapefruit) Citrus x aurantium Citrus reticulata (tangerine) Citrus reticulata Citrus shunkokan Cultivated hybrid Citrus sinensis (orange) ALSO Citrus aurantium dulcis (orange) Citrus x aurantium Citrus sphaerocarpa Cultivated hybrid Citrus sudachi Citrus reticulata Citrus tachibana Not listed Citrus tamurana Cultivated hybrid Citrus tangelo (tangelo) Citrus x aurantium Citrus tangerine (tangerine) Citrus reticulata Citrus tankan Citrus reticulata Citrus unshiu Citrus reticulata
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Table 4. Total fatty acid composition of Citrus seed oils, as previously reported (%).5 Citrus Citrus Aurantium Citrus Grandis Citrus Limon Aurantifolia Dulcis (Orange) (Grapefruit) (Lemon) Seed Citrus Paradisi
Fatty Acids (Lime) Seed Oil Seed Oil Seed Oil Oil (Seed) Oil Lauric (C12) NR NR 1.5 NR 2.95 Myristic (C14) 1 NR 1 NR 1.01 Palmitic (C16) 20-30 14-22 18-30 18.8 36.25 Heptadecanoic (C17:0) NR NR NR 0.08 NR Stearic (C18) 3-8 2-6 2-8 3.5 5.95 Oleic (C18:1) 20-38 26-35 20-38 30.1 18.34 Linoleic (C18:2) 30-45 35-45 30-48 33.4 29.26 Linolenic (C18:3) 5-15 2-6 2-6 13.5 3.58 Arachidic (C20) 2 0.5 NR 0.3 0.38 Eicosenoic (C20:1) NR NR NR 0.03 0.84 Behenic (C22) NR NR NR 0.08 NR Lignoceric (C24) NR NR NR 0.2 NR C23:0 = <0.01; Others NR NR NR C26:0 = 0.01 C12:1=1.44 NR = Not Reported
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Table 5. Key constituents (%) of Citrus Aurantium Amara (Bitter Orange) Leaf /Twig Oil*32 Bigarade Paraguayan Type Type linalyl acetate 51.0-71.0 47.4-58.0 linalool 12.3-24.2 20.8-25.2 (+)-limonene 0.4-8.0 0.3-1.1 α-terpineol 2.1-5.2 4.4-6.8 geranyl acetate 1.9-3.4 2.9-4.5 β -pinene 0.3-2.7 0.3-1.2 neryl acetate 0-2.6 2.1-3.0 geraniol 1.4-2.3 2.1-3.0 (E)-β-ocimene 0.2-2.2 0-2.0 β-myrcene 0-2.0 0-2.0 nerol 0.4-1.1 NR NR = Not reported *Composition reported down to the level of 1%, or lower for known toxic constituents.
Table 6. Fatty acid profiles (area %) by gas chromatography.8,9,33 Fatty acid Citrus Australasica Seed Oil Citrus Glauca Seed Oil Citrus junos Sieb. ex Takana seed oil* undecanoic acid NR NR 3.27 myristic acid 0.07 NR NR palmitic acid 10.50 8.07 19.16 palmitoleic acid 0.24 0.17 0.62 margaric acid 0.08 0.05 NR heptadecanconic acid 0.07 NR NR stearic acid 3.36 2.52 3.76 elaidic acid 0.11 NR NR oleic acid 36.55 47.39 32.01 cis-vaccenic acid 1.67 2.00 NR linolelaidic acid 0.05 NR NR linoleic acid 41.01 36.28 33.99 α-linolenic acid 4.70 1.28 2.05 arachadic acid 0.40 0.31 0.26 11-eicosenoic acid 0.28 0.42 NR behenic acid 0.42 0.61 NR lignoceric acid 0.15 0.32 NR unknown NR NR 4.48 *Reported as acid methyl esters.
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Table 7. Frequency and concentration of use according to duration and type of exposure for Citrus plant- and seed-derived ingredients.18,19 # of Uses Max Conc of Use (%) # of Uses Max Conc of Use (%) # of Uses Max Conc of Use (%) # of Uses Max Conc of Use (%) Citrus Aurantium Amara (Bitter Citrus Aurantifolia (Lime) Oil Citrus Aurantium (Bitter Orange) Oile Citrus Aurantium Dulcis (Orange) Oilf Orange) Leaf/Twig Oild Totals† 169 0.00000051-0.36 43 0.0000000026-0.0032 295 NR 4 0.0000032-1 Duration of Use Leave-On 90 0.00049-0.36 25 0.00000014-0.0032 178 NR 3 0.000094-1 Rinse Off 69 0.00015-0.17 14 0.00000015-0.000013 96 NR NR 0.000026-0.81 Diluted for (Bath) Use 10 0.00000051 4 0.0000000026 21 NR 1 0.0000032-0.94 Exposure Type Eye Area NR NR NR NR NR NR NR 0.00078-0.034 Incidental Ingestion NR 0.0015-0.36 NR NR 2 NR NR 0.034-0.95 0.00000014- 0.00049-0.12; 0.0015- 0.0022-0.12; 0.0053- Incidental Inhalation-Spray 9; 34a; 29b 11a; 11b 0.00000043; 31; 37a; 49b NR 1; 2a 0.1a; 0.00067b 0.26a; 0.000094b 0.0000025a 0.022; 0.0075- 0.0012-0.0014; 0.18-1c; Incidental Inhalation-Powder 1c; 29b 11b 0.000011c 1; 3c; 49b NR NR 0.023c;0.00067 0.000094b Dermal Contact 147 0.00000051-0.17 40 0.0000000026-0.0032 250 NR 3 0.0000032-1 Deodorant (underarm) NR NR NR NR NR NR NR 0.039a; 0.038-0.06g 0.00000014- Hair - Non-Coloring 22 0.00049-0.02 3 32 NR 1 0.0022-0.81 0.0000025 Hair-Coloring NR 0.00015 NR NR 11 NR NR 0.000026-0.042 Nail NR NR NR NR NR NR NR NR 0.0000000026- Mucous Membrane 35 0.00000051-0.36 11 53 NR 1 0.0000032-0.95 0.000013 Baby Products 3 NR NR NR 9 NR NR NR
Citrus Aurantium Dulcis (Orange) Seed Citrus Grandis (Grapefruit) Citrus Aurantium Sinensis Powderi Citrus Grandis (Grapefruit) Extract Extracth Seed Extract Totals† 2 NR 1 NR NR 0.0017-0.0059 144 0.0004-0.15 Duration of Use Leave-On 2 NR 1 NR NR 0.0017-0.003 85 0.076-0.15 Rinse Off NR NR NR NR NR 0.0022-0.0059 51 0.0004-0.12 Diluted for (Bath) Use NR NR NR NR NR NR 8 NR Exposure Type Eye Area NR NR NR NR NR NR 5 NR Incidental Ingestion NR NR NR NR NR NR 12 0.076 Incidental Inhalation-Spray 2b NR 1b NR NR 0.0017-0.003 2; 28a; 17b NR Incidental Inhalation-Powder 2b NR 1b NR NR NR 17b; 2c 0.1c Dermal Contact 2 NR 1 NR NR 0.0022-0.0059 106 0.02-0.15 Deodorant (underarm) NR NR NR NR NR 0.0024g 14a NR Hair - Non-Coloring NR NR NR NR NR 0.0017-0.005 23 0.0004 Hair-Coloring NR NR NR NR NR NR NR NR Nail NR NR NR NR NR NR NR NR Mucous Membrane NR NR NR NR NR 0.0022-0.0059 26 0.076 Baby Products NR NR NR NR NR NR 7 NR
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Table 7. Frequency and concentration of use according to duration and type of exposure for Citrus plant- and seed-derived ingredients.18,19 # of Uses Max Conc of Use (%) # of Uses Max Conc of Use (%) # of Uses Max Conc of Use (%) # of Uses Max Conc of Use (%) Citrus Limon (Lemon) Flower/Leaf/Stem Citrus Junos Extract Citrus Junos Seed Extractj Citrus Junos Seed Oil Extract Totals† NR 0.0001 7 0.001-0.0045 NR 0.001-0.1 8 NR Duration of Use Leave-On NR NR 7 0.001-0.0045 NR 0.01-0.1 8 NR Rinse Off NR 0.0001 NR 0.001 NR 0.001 NR NR Diluted for (Bath) Use NR NR NR 0.001 NR NR NR NR Exposure Type Eye Area NR NR 1 0.001 NR NR NR NR Incidental Ingestion NR NR NR NR NR NR NR NR Incidental Inhalation-Spray NR NR 4a; 2b NR NR NR 6a; 1b NR Incidental Inhalation-Powder NR NR 2b 0.0045c NR 0.1; 0.1c 1b NR Dermal Contact NR NR 7 0.001-0.0045 NR 0.001-0.1 8 NR Deodorant (underarm) NR NR NR NR NR NR NR NR Hair - Non-Coloring NR NR NR NR NR 0.01 NR NR Hair-Coloring NR 0.0001 NR NR NR NR NR NR Nail NR NR NR NR NR NR NR NR Mucous Membrane NR NR NR 0.001 NR NR NR NR Baby Products NR NR NR NR NR NR NR NR
Citrus Nobilis (Mandarin Orange) Citrus Nobilis (Mandarin Orange) Citrus Paradisi (Grapefruit) Seed Extract Citrus Reticulata (Tangerine) Extract Oil Totals† NR 0.0005 36 0.0009-0.035 52 NR NR 0.0001-0.0051 Duration of Use Leave-On NR NR 28 NR 39 NR NR 0.0002-0.0051 Rinse Off NR NR 4 0.0009-0.035 13 NR NR 0.0001-0.005 Diluted for (Bath) Use NR NR 4 NR NR NR NR NR Exposure Type Eye Area NR NR NR NR NR NR NR NR Incidental Ingestion NR NR 1 0.035 1 NR NR NR Incidental Inhalation-Spray NR NR 8; 2a; 4b NR 16a; 17b NR NR 0.0051a Incidental Inhalation-Powder NR NR 4b; 1c NR 17b; 1c NR NR 0.0002c Dermal Contact NR 0.0005 35 0.0009-0.0017 50 NR NR 0.0002 Deodorant (underarm) NR NR NR NR NR NR NR NR Hair - Non-Coloring NR 0.0005 NR NR 1 NR NR 0.0001-0.0051 Hair-Coloring NR NR NR NR NR NR NR NR Nail NR NR NR NR NR NR NR NR Mucous Membrane NR 0.0005 7 0.0009-0.035 8 NR NR NR Baby Products NR NR 2 NR 2 NR NR NR NR = Not reported. † Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure types may not equal the sum of total uses. a. It is possible these products may be sprays, but it is not specified whether the reported uses are sprays. b. Not specified whether a powder or a spray, so this information is captured for both categories of incidental inhalation. c. It is possible these products may be powders, but it is not specified whether the reported uses are powders. d Listed as Citrus Aurantium (Bitter Orange) Leaf/Twig Oil in the VCRP database. e Only listed in the VCRP database, not in the INCI dictionary. Included because of assumed similarity. f Listed as Citrus Sinensis (Sweet Orange) Plant Oil in the VCRP database. gNot a spray deodorant. h Listed as Citrus Sinensis (Sweet Orange) Seed Extract in the VCRP database. i Listed as Citrus Sinensis (Orange) Powder in the VCRP database. j Listed as Citrus Junos (Xiang Cheng) Seed Extract in the VCRP database. Distributed for Comment Only -- Do Not Cite or Quote
Table 8. Ingredients that are not reported to be in use
Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Extract Citrus Aurantium Dulcis (Orange) Flower/Leaf/Stem Powder Citrus Australasica Seed Oil Citrus Depressa Seed Oil Citrus Glauca Seed Oil Citrus Grandis (Grapefruit) Citrus Grandis Peel/Seed Extract Citrus Iyo Oil Citrus Jabara Pericarp Extract Citrus Limon (Lemon) Flower/Leaf/Stem Oil Citrus Limon (Lemon) Leaf/Peel/Stem Oil Citrus Nobilis (Mandarin Orange) Water Citrus Sunki Seed Extract Citrus Sunki Seed Oil Citrus Unshiu Extract Citrus Unshiu Pericarp Extract
Distributed for Comment Only -- Do Not Cite or Quote
Table 9. Dermal irritation studies for Citrus plant- and seed-derived ingredients. Test Article Concentration/Dose Test Population Procedure Results Reference ANIMAL Citrus Aurantium Amara (Bitter Orange) 2g/kg; undiluted 2 rabbits 24-h occlusive, single dose study slight erythema 15 Leaf/Twig Oil (described as “petitgrain bigarade oil”) HUMAN Citrus Aurantium Amara (Bitter Orange) 0.1%, 2% or 5%; 48 subjects at 0.1%, 30 24-72 h occlusive patch tests no irritation 28 Leaf/Twig Oil (described as “petitgrain multiple vehicles subjects at 2%, and 30 bigarade oil”) subjects at 5% Citrus Aurantium Amara (Bitter Orange) 8% in petrolatum 25 subjects 48 h occlusive patch applied to the no irritation 15 Leaf/Twig Oil (described as “petitgrain forearm or back bigarade oil”) Citrus Grandis (Grapefruit) Seed Extract 0.15% in a foot gel 12 subjects with normal, 48 h occlusive patch (Finn chambers) no irritation (mean irritation index = 29 lesion-free skin on external arm, single application of 0.13) 0.02 ml
Table 10. Sensitization studies for Citrus plant- and seed-derived ingredients. Test Article Concentration/Dose Test Population Procedure Results Reference HUMAN Citrus Aurantium Amara (Bitter Orange) 2% in paraffin 200 patients with sensitization patch study, details not 3 positive reactions, details not 30 Leaf/Twig Oil (described as “petitgrain dermatitis tested with 35 provided provided bigarade oil”) essential oils plus an additional 50 patients with balsam sensitivity Citrus Aurantium Amara (Bitter Orange) 8% in petrolatum 25 subjects maximization study, details not not sensitizing 15 Leaf/Twig Oil (described as “petitgrain provided bigarade oil”)
Table 11. Photosensitization studies. Test Article Concentration/Dose Test Population Procedure Results Reference NON-HUMAN Citrus Aurantium Amara (Bitter Orange) undiluted hairless mice (#/group not test material was applied, and the test sites not photosensitizing 31 Leaf/Twig Oil (described as “petitgrain stated) were irradiated with UVA irradiation by bigarade oil”) blacklight or xenon lamp Citrus Aurantium Amara (Bitter Orange) undiluted miniature swine (#/group test material was applied, and the test sites not photosensitizing 31 Leaf/Twig Oil (described as “petitgrain not stated) were irradiated with UVA irradiation by bigarade oil”) blacklight or xenon lamp
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REFERENCES
1. Nikitakis J and Lange B. International Cosmetic Ingredient Dictionary and Handbook. 16 ed. Washington, DC: Personal Care Products Council, 2016.
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5. Burnett CL, Fiume MM, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. Final Report on Plant-Derived Fatty Acid Oils as Used in Cosmetics. Cosmetic Ingredient Review. 2011.
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7. Personal Care Products Council. 6-5-2015. Review of Citrus Genus Species Names.
8. Native Extracts. 2015. Certificate of analysis NSO Finger Lime Seed Oil Organic (Citrus Australasica Seed Oil).
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11. Anonymous. 2016. Summary information: Junos Seed Extract.
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14. International Fragrance Association. IFRA Standards for Linalool. http://www.ifraorg.org/en-us/standards- library#.V6JPMDsrK70. Last Updated 2016. Date Accessed 8-5-2016.
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16. Eldahshan OA and Halim AF. Comparison of the composition and antimicrobial activities of the essential oils of green branches and leaves of Egyptian navel orange (Citrus sinensis (L.) Osbeck var. Malesy). Chem Biodivers. 2016;
17. Akpata MI and Akubor PI. Chemical composition and selected functional properties of sweet orange (Citrus sinensis) seed flour. Plant Foods Hum Nutr. 1999;54(4):353-362.
18. Food and Drug Administration (FDA). Frequency of use of cosmetic ingredients. FDA Database. 2016. Washington, DC: FDA.
19. Personal Care Products Council. 2-11-2016. Concentration of Use by FDA Product Category: Citrus Seed- and Plant- Derived Ingredients.
Distributed for Comment Only -- Do Not Cite or Quote
20. Rothe H, Fautz R, Gerber E, Neumann L, Rettinger K, Schuh W, and Gronewold C. Special aspects of cosmetic spray safety evaluations: Principles on inhalation risk assessment. Toxicol Lett. 2011;205(2):97-104.
21. Rothe H. Special Aspects of Cosmetic Spray Evalulation. 9-26-2011.
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29. Anonymous. 2016. Study of acute skin compatibility of a test item (foot gel containing 0.15% Citrus Grandis (Grapefruit) Seed Extract): 48-hours occlusive patch-test.
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32. Tisserand R and Young R. Essential Oil Safety. 2nd ed. Churchill Livingston Elsevier, 2014.
33. Kim TW, Kim KK, Kang YH, Kim DJ, and Choe M. Fatty acid analysis and regulatory effects of citron (Citrus junos Sieb. ex Tanaka) seed oil on nitric oxide production, lipid acculation, and leptin secretion. J Nutr Health. 2014;47(4):221-228. http://synapse.koreamed.org/DOIx.php?id=10.4163/jnh.2014.47.4.221.
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2016 FDA VCRP RAW DATA – Citrus Plant and Seed 01A - Baby Shampoos CITRUS AURANTIFOLIA (LIME) OIL 1 01B - Baby Lotions, Oils, CITRUS AURANTIFOLIA (LIME) OIL 1 Powders, and Creams 01C - Other Baby Products CITRUS AURANTIFOLIA (LIME) OIL 1 02A - Bath Oils, Tablets, and CITRUS AURANTIFOLIA (LIME) OIL 6 Salts 02B - Bubble Baths CITRUS AURANTIFOLIA (LIME) OIL 4 04B - Perfumes CITRUS AURANTIFOLIA (LIME) OIL 1 04E - Other Fragrance CITRUS AURANTIFOLIA (LIME) OIL 8 Preparation 05A - Hair Conditioner CITRUS AURANTIFOLIA (LIME) OIL 9 05F - Shampoos (non-coloring) CITRUS AURANTIFOLIA (LIME) OIL 6 05G - Tonics, Dressings, and CITRUS AURANTIFOLIA (LIME) OIL 5 Other Hair Grooming Aids 05I - Other Hair Preparations CITRUS AURANTIFOLIA (LIME) OIL 1 07F - Makeup Bases CITRUS AURANTIFOLIA (LIME) OIL 1 07I - Other Makeup CITRUS AURANTIFOLIA (LIME) OIL 3 Preparations 10A - Bath Soaps and CITRUS AURANTIFOLIA (LIME) OIL 17 Detergents 10E - Other Personal CITRUS AURANTIFOLIA (LIME) OIL 8 Cleanliness Products 11B - Beard Softeners CITRUS AURANTIFOLIA (LIME) OIL 6 11D - Preshave Lotions (all CITRUS AURANTIFOLIA (LIME) OIL 1 types) 11E - Shaving Cream CITRUS AURANTIFOLIA (LIME) OIL 5 11F - Shaving Soap CITRUS AURANTIFOLIA (LIME) OIL 1 11G - Other Shaving CITRUS AURANTIFOLIA (LIME) OIL 2 Preparation Products 12A - Cleansing CITRUS AURANTIFOLIA (LIME) OIL 18 12C - Face and Neck (exc CITRUS AURANTIFOLIA (LIME) OIL 17 shave) 12D - Body and Hand (exc CITRUS AURANTIFOLIA (LIME) OIL 12 shave) 12F - Moisturizing CITRUS AURANTIFOLIA (LIME) OIL 21 12G - Night CITRUS AURANTIFOLIA (LIME) OIL 1 12H - Paste Masks (mud packs) CITRUS AURANTIFOLIA (LIME) OIL 1 12I - Skin Fresheners CITRUS AURANTIFOLIA (LIME) OIL 6 12J - Other Skin Care Preps CITRUS AURANTIFOLIA (LIME) OIL 5 13A - Suntan Gels, Creams, and CITRUS AURANTIFOLIA (LIME) OIL 1 Liquids
02A - Bath Oils, Tablets, and CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 3 Salts 02B - Bubble Baths CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 1 05A - Hair Conditioner CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 2 05F - Shampoos (non-coloring) CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 1 Distributed for Comment Only -- Do Not Cite or Quote
10A - Bath Soaps and CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 5 Detergents 10E - Other Personal CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 2 Cleanliness Products 12A - Cleansing CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 4 12C - Face and Neck (exc CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 6 shave) 12D - Body and Hand (exc CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 5 shave) 12F - Moisturizing CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 7 12G - Night CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 4 12J - Other Skin Care Preps CITRUS AURANTIUM (BITTER ORANGE) LEAF/TWIG OIL 3
01A - Baby Shampoos CITRUS AURANTIUM (BITTER ORANGE) OIL 1 01B - Baby Lotions, Oils, CITRUS AURANTIUM (BITTER ORANGE) OIL 3 Powders, and Creams 01C - Other Baby Products CITRUS AURANTIUM (BITTER ORANGE) OIL 5 02A - Bath Oils, Tablets, and CITRUS AURANTIUM (BITTER ORANGE) OIL 16 Salts 02B - Bubble Baths CITRUS AURANTIUM (BITTER ORANGE) OIL 3 02C - Bath Capsules CITRUS AURANTIUM (BITTER ORANGE) OIL 1 02D - Other Bath Preparations CITRUS AURANTIUM (BITTER ORANGE) OIL 1 04A - Cologne and Toilet CITRUS AURANTIUM (BITTER ORANGE) OIL 1 waters 04B - Perfumes CITRUS AURANTIUM (BITTER ORANGE) OIL 14 04E - Other Fragrance CITRUS AURANTIUM (BITTER ORANGE) OIL 15 Preparation 05A - Hair Conditioner CITRUS AURANTIUM (BITTER ORANGE) OIL 10 05B - Hair Spray (aerosol CITRUS AURANTIUM (BITTER ORANGE) OIL 1 fixatives) 05C - Hair Straighteners CITRUS AURANTIUM (BITTER ORANGE) OIL 1 05E - Rinses (non-coloring) CITRUS AURANTIUM (BITTER ORANGE) OIL 1 05F - Shampoos (non-coloring) CITRUS AURANTIUM (BITTER ORANGE) OIL 13 05G - Tonics, Dressings, and CITRUS AURANTIUM (BITTER ORANGE) OIL 4 Other Hair Grooming Aids 05I - Other Hair Preparations CITRUS AURANTIUM (BITTER ORANGE) OIL 2 06A - Hair Dyes and Colors (all CITRUS AURANTIUM (BITTER ORANGE) OIL 4 types requiring caution statements and patch tests) 06D - Hair Shampoos (coloring) CITRUS AURANTIUM (BITTER ORANGE) OIL 7 07E - Lipstick CITRUS AURANTIUM (BITTER ORANGE) OIL 1 07F - Makeup Bases CITRUS AURANTIUM (BITTER ORANGE) OIL 1 07G - Rouges CITRUS AURANTIUM (BITTER ORANGE) OIL 1 07I - Other Makeup CITRUS AURANTIUM (BITTER ORANGE) OIL 3 Preparations 09C - Other Oral Hygiene CITRUS AURANTIUM (BITTER ORANGE) OIL 1 Products 10A - Bath Soaps and CITRUS AURANTIUM (BITTER ORANGE) OIL 20 Distributed for Comment Only -- Do Not Cite or Quote
Detergents 10E - Other Personal CITRUS AURANTIUM (BITTER ORANGE) OIL 10 Cleanliness Products 11E - Shaving Cream CITRUS AURANTIUM (BITTER ORANGE) OIL 2 12A - Cleansing CITRUS AURANTIUM (BITTER ORANGE) OIL 23 12C - Face and Neck (exc CITRUS AURANTIUM (BITTER ORANGE) OIL 14 shave) 12D - Body and Hand (exc CITRUS AURANTIUM (BITTER ORANGE) OIL 35 shave) 12F - Moisturizing CITRUS AURANTIUM (BITTER ORANGE) OIL 24 12G - Night CITRUS AURANTIUM (BITTER ORANGE) OIL 2 12H - Paste Masks (mud packs) CITRUS AURANTIUM (BITTER ORANGE) OIL 4 12I - Skin Fresheners CITRUS AURANTIUM (BITTER ORANGE) OIL 6 12J - Other Skin Care Preps CITRUS AURANTIUM (BITTER ORANGE) OIL 44 13B - Indoor Tanning CITRUS AURANTIUM (BITTER ORANGE) OIL 1 Preparations
01B - Baby Lotions, Oils, CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 2 Powders, and Creams 01C - Other Baby Products CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 5 02A - Bath Oils, Tablets, and CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 5 Salts 02B - Bubble Baths CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 3 03D - Eye Lotion CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 2 03F - Mascara CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 3 04E - Other Fragrance CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 1 Preparation 05A - Hair Conditioner CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 8 05B - Hair Spray (aerosol CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 1 fixatives) 05E - Rinses (non-coloring) CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 1 05F - Shampoos (non-coloring) CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 9 05G - Tonics, Dressings, and CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 4 Other Hair Grooming Aids 07C - Foundations CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 10 07F - Makeup Bases CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 1 09A - Dentifrices CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 9 09B - Mouthwashes and Breath CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 2 Fresheners 09C - Other Oral Hygiene CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 1 Products 10A - Bath Soaps and CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 6 Detergents 10B - Deodorants (underarm) CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 14 12A - Cleansing CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 13 12C - Face and Neck (exc CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 6 shave) 12D - Body and Hand (exc CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 11 Distributed for Comment Only -- Do Not Cite or Quote
shave) 12F - Moisturizing CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 10 12H - Paste Masks (mud packs) CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 2 12I - Skin Fresheners CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 12 12J - Other Skin Care Preps CITRUS GRANDIS (GRAPEFRUIT) SEED EXTRACT 3
03G - Other Eye Makeup CITRUS JUNOS (XIANG CHENG) SEED EXTRACT 1 Preparations 12C - Face and Neck (exc CITRUS JUNOS (XIANG CHENG) SEED EXTRACT 1 shave) 12D - Body and Hand (exc CITRUS JUNOS (XIANG CHENG) SEED EXTRACT 1 shave) 12F - Moisturizing CITRUS JUNOS (XIANG CHENG) SEED EXTRACT 4
12C - Face and Neck (exc CITRUS LIMON (LEMON) FLOWER/LEAF/STEM EXTRACT 1 shave) 12F - Moisturizing CITRUS LIMON (LEMON) FLOWER/LEAF/STEM EXTRACT 6 12J - Other Skin Care Preps CITRUS LIMON (LEMON) FLOWER/LEAF/STEM EXTRACT 1
01B - Baby Lotions, Oils, CITRUS NOBILIS (MANDARIN ORANGE) OIL 1 Powders, and Creams 01C - Other Baby Products CITRUS NOBILIS (MANDARIN ORANGE) OIL 1 02A - Bath Oils, Tablets, and CITRUS NOBILIS (MANDARIN ORANGE) OIL 4 Salts 04B - Perfumes CITRUS NOBILIS (MANDARIN ORANGE) OIL 4 04E - Other Fragrance CITRUS NOBILIS (MANDARIN ORANGE) OIL 4 Preparation 07I - Other Makeup CITRUS NOBILIS (MANDARIN ORANGE) OIL 1 Preparations 09A - Dentifrices CITRUS NOBILIS (MANDARIN ORANGE) OIL 1 10A - Bath Soaps and CITRUS NOBILIS (MANDARIN ORANGE) OIL 2 Detergents 12A - Cleansing CITRUS NOBILIS (MANDARIN ORANGE) OIL 1 12D - Body and Hand (exc CITRUS NOBILIS (MANDARIN ORANGE) OIL 4 shave) 12F - Moisturizing CITRUS NOBILIS (MANDARIN ORANGE) OIL 2 12J - Other Skin Care Preps CITRUS NOBILIS (MANDARIN ORANGE) OIL 11
01B - Baby Lotions, Oils, CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 1 Powders, and Creams 01C - Other Baby Products CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 1 05A - Hair Conditioner CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 1 07I - Other Makeup CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 1 Preparations 09A - Dentifrices CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 1 10A - Bath Soaps and CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 7 Detergents 11B - Beard Softeners CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 1 Distributed for Comment Only -- Do Not Cite or Quote
12A - Cleansing CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 4 12C - Face and Neck (exc CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 4 shave) 12D - Body and Hand (exc CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 13 shave) 12F - Moisturizing CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 14 12G - Night CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 1 12J - Other Skin Care Preps CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 2 13A - Suntan Gels, Creams, and CITRUS PARADISI (GRAPEFRUIT) SEED EXTRACT 1 Liquids
02A - Bath Oils, Tablets, and CITRUS SINENSIS (SWEET ORANGE) PLANT OIL 1 Salts 04B - Perfumes CITRUS SINENSIS (SWEET ORANGE) PLANT OIL 1 05G - Tonics, Dressings, and CITRUS SINENSIS (SWEET ORANGE) PLANT OIL 1 Other Hair Grooming Aids 12I - Skin Fresheners CITRUS SINENSIS (SWEET ORANGE) PLANT OIL 1
12C - Face and Neck (exc CITRUS SINENSIS (SWEET ORANGE) POWDER 1 shave)
12D - Body and Hand (exc CITRUS SINENSIS (SWEET ORANGE) SEED EXTRACT 2 shave)
04E - Other Fragrance CITRUS TANGERINA (TANGERINE) EXTRACT 1 Preparation 05A - Hair Conditioner CITRUS TANGERINA (TANGERINE) EXTRACT 4 05F - Shampoos (non-coloring) CITRUS TANGERINA (TANGERINE) EXTRACT 6 05G - Tonics, Dressings, and CITRUS TANGERINA (TANGERINE) EXTRACT 1 Other Hair Grooming Aids 10A - Bath Soaps and CITRUS TANGERINA (TANGERINE) EXTRACT 2 Detergents 12C - Face and Neck (exc CITRUS TANGERINA (TANGERINE) EXTRACT 1 shave) 12D - Body and Hand (exc CITRUS TANGERINA (TANGERINE) EXTRACT 1 shave) 12J - Other Skin Care Preps CITRUS TANGERINA (TANGERINE) EXTRACT 1
Distributed for Comment Only -- Do Not Cite or Quote
Memorandum
TO: Lillian Gill, D.P.A. Director - COSMETIC INGREDIENT REVIEW (CIR)
FROM: Beth A. Jonas, Ph.D. Industry Liaison to the CIR Expert Panel
DATE: September 27, 2016
SUBJECT: Updated Concentration of Use by FDA Product Category: Citrus seed and plant ingredients Distributed for Comment Only -- Do Not Cite or Quote
Concentration of Use by FDA Product Category – Citrus Seed-and Plant Derived Ingredients*
Citrus Aurantium Dulcis (Orange) Seed Extract Citrus Aurantium Dulcis (Orange) Citrus Australasica Seed Oil Flower/Leaf/Stem Powder Citrus Depressa Seed Oil Citrus Aurantium Dulcis (Orange) Oil Citrus Glauca Seed Oil Citrus Aurantium Sinensis Powder Citrus Grandis (Grapefruit) Seed Extract Citrus Grandis (Grapefruit) Extract Citrus Jabara Pericarp Extract Citrus Grandis (Grapefruit) Citrus Junos Seed Extract Citrus Grandis Peel/Seed Extract Citrus Junos Seed Oil Citrus Iyo Oil Citrus Paradisi (Grapefruit) Seed Extract Citrus Junos Extract Citrus Sunki Seed Extract Citrus Limon (Lemon) Flower/Leaf/Stem Extract Citrus Sunki Seed Oil Citrus Limon (Lemon) Flower/Leaf/Stem Oil Citrus Unshiu Pericarp Extract Citrus Limon (Lemon) Leaf/Peel/Stem Oil Citrus Aurantifolia (Lime) Oil Citrus Nobilis (Mandarin Orange) Oil Citrus Aurantium Amara (Bitter Orange) Citrus Nobilis (Mandarin Orange) Water Leaf/Twig Extract Citrus Nobilis (Mandarin Orange) Citrus Aurantium Amara (Bitter Orange) Citrus Reticulata (Tangerine) Extract Leaf/Twig Oil Citrus Tangerina (Tangerine) Extract** Citrus Aurantium (Bitter Orange) Oil Citrus Unshiu Extract Ingredient Product Category Maximum Concentration of Use Citrus Grandis (Grapefruit) Seed Extract Hair conditioners 0.0004% Citrus Grandis (Grapefruit) Seed Extract Lipstick 0.076% Citrus Grandis (Grapefruit) Seed Extract Skin cleansing (cold creams, cleansing 0.02% lotions, liquids and pads) Citrus Grandis (Grapefruit) Seed Extract Face and neck products Not spray 0.1% Citrus Grandis (Grapefruit) Seed Extract Night products Not spray 0.15% Citrus Grandis (Grapefruit) Seed Extract Paste masks and mud packs 0.1-0.12% Citrus Junos Seed Extract Bath oils, tablets and salts 0.001% Citrus Junos Seed Extract Eye lotions 0.001% Citrus Junos Seed Extract Foundations 0.001% Citrus Junos Seed Extract Skin cleansing (cold creams, cleansing 0.001% lotions, liquids and pads) Citrus Junos Seed Extract Face and neck products Not spray 0.0045% Citrus Junos Seed Extract Moisturizing products Not spray 0.001% Citrus Junos Seed Oil Tonics, dressings and other hair grooming aids Not spray 0.01% Citrus Junos Seed Oil Face powders 0.1%
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Citrus Junos Seed Oil Skin cleansing (cold creams, cleansing 0.001% lotions, liquids and pads) Citrus Junos Seed Oil Face and neck products Not spray 0.1% Citrus Junos Seed Oil Body and hand products Not spray 0.1% Citrus Aurantifolia (Lime) Oil Bath oils, tablets and salts 0.00000051% Citrus Aurantifolia (Lime) Oil Powders (dusting and talcum) 0.022% Citrus Aurantifolia (Lime) Oil Hair conditioners 0.00057% Citrus Aurantifolia (Lime) Oil Hair sprays Pump spray 0.00049% Citrus Aurantifolia (Lime) Oil Shampoos (noncoloring) 0.00057-0.02% Citrus Aurantifolia (Lime) Oil Tonics, dressings and other hair 0.02% grooming aids Not spray 0.0027% Citrus Aurantifolia (Lime) Oil Hair dyes and colors 0.00015% Citrus Aurantifolia (Lime) Oil Blushers 0.01% Citrus Aurantifolia (Lime) Oil Lipstick 0.36% Citrus Aurantifolia (Lime) Oil Mouth washes and breath fresheners 0.0015% Citrus Aurantifolia (Lime) Oil Bath soaps and detergents 0.0014-0.17% Citrus Aurantifolia (Lime) Oil Skin cleansing (cold creams, cleansing 0.083% lotions, liquids and pads) Citrus Aurantifolia (Lime) Oil Face and neck products Not spray 0.019% Citrus Aurantifolia (Lime) Oil Body and hand products Not spray 0.0075-0.023% Spray 0.0075-0.12% Citrus Aurantifolia (Lime) Oil Foot powders and sprays 0.00067% Citrus Aurantifolia (Lime) Oil Skin fresheners 0.1%
Citrus Aurantium Amara (Bitter Orange) Bath oils, tablets and salts 0.0000000026% Leaf/Twig Oil Citrus Aurantium Amara (Bitter Orange) Hair conditioners 0.00000015% Leaf/Twig Oil Citrus Aurantium Amara (Bitter Orange) Hair sprays Leaf/Twig Oil Aerosol 0.00000014% Pump spray 0.00000043% Citrus Aurantium Amara (Bitter Orange) Shampoos (noncoloring) 0.00000084% Leaf/Twig Oil Citrus Aurantium Amara (Bitter Orange) Tonics, dressings and other hair 0.0000025% Leaf/Twig Oil grooming aids Citrus Aurantium Amara (Bitter Orange) Bath soaps and detergents 0.000013% Leaf/Twig Oil Citrus Aurantium Amara (Bitter Orange) Body and hand products Leaf/Twig Oil Not spray 0.000011% Citrus Aurantium Amara (Bitter Orange) Face and neck products Leaf/Twig Oil Not spray or powder 0.0032%
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Citrus Aurantium Amara (Bitter Orange) Other skin care preparations 0.0032% Leaf/Twig Oil Citrus Aurantium Dulcis (Orange) Oil Bath oils, tablets and salts 0.0000032-0.94% Citrus Aurantium Dulcis (Orange) Oil Eye shadows 0.004% Citrus Aurantium Dulcis (Orange) Oil Eye lotions 0.034% Citrus Aurantium Dulcis (Orange) Oil Eye makeup removers 0.00078% Citrus Aurantium Dulcis (Orange) Oil Perfumes 0.0034% Citrus Aurantium Dulcis (Orange) Oil Powders (dusting and talcum) 0.0012% Citrus Aurantium Dulcis (Orange) Oil Hair conditioners 0.016-0.13% Citrus Aurantium Dulcis (Orange) Oil Hair sprays Aerosol 0.063% Pump spray 0.0022% Citrus Aurantium Dulcis (Orange) Oil Rinses (noncoloring) 0.034% Citrus Aurantium Dulcis (Orange) Oil Shampoos (noncoloring) 0.0025-0.81% Citrus Aurantium Dulcis (Orange) Oil Tonics, dressings and other hair 0.0053-0.26% grooming aids Not spray 0.0053% Citrus Aurantium Dulcis (Orange) Oil Hair dyes and colors 0.000026% Citrus Aurantium Dulcis (Orange) Oil Other hair coloring preparations 0.042% Citrus Aurantium Dulcis (Orange) Oil Face powders 0.0014% Citrus Aurantium Dulcis (Orange) Oil Foundations 0.014-0.02% Citrus Aurantium Dulcis (Orange) Oil Lipstick 0.034-0.95% Citrus Aurantium Dulcis (Orange) Oil Makeup bases 0.05% Citrus Aurantium Dulcis (Orange) Oil Other makeup preparations 0.024% Citrus Aurantium Dulcis (Orange) Oil Dentifrices 0.06% Citrus Aurantium Dulcis (Orange) Oil Bath soaps and detergents 0.022-0.12% Citrus Aurantium Dulcis (Orange) Oil Deodorants Not spray 0.038-0.06% Aerosol 0.039% Citrus Aurantium Dulcis (Orange) Oil Shaving cream 0.0015-0.03% Citrus Aurantium Dulcis (Orange) Oil Skin cleansing (cold creams, cleansing 0.05-0.2% lotions, liquids and pads) Citrus Aurantium Dulcis (Orange) Oil Face and neck products Not spray 0.18% Spray 0.011% Citrus Aurantium Dulcis (Orange) Oil Body and hand products Not spray 0.2-1% Spray 0.12% Citrus Aurantium Dulcis (Orange) Oil Foot products 0.000094% Citrus Aurantium Dulcis (Orange) Oil Moisturizing products Not spray 0.05% Citrus Aurantium Dulcis (Orange) Oil Night products Not spray 0.05% Citrus Aurantium Dulcis (Orange) Oil Paste masks and mud packs 0.1% Citrus Aurantium Dulcis (Orange) Oil Suntan products Not spray 0.02%
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Distributed for Comment Only -- Do Not Cite or Quote
Citrus Grandis (Grapefruit) Extract Hair conditioners 0.005% Citrus Grandis (Grapefruit) Extract Hair sprays Pump spray 0.0017% Citrus Grandis (Grapefruit) Extract Shampoos (noncoloring) 0.003% Citrus Grandis (Grapefruit) Extract Tonics, dressings and other hair grooming aids Aerosol 0.003% Citrus Grandis (Grapefruit) Extract Bath soaps and detergents 0.0022-0.0059% Citrus Grandis (Grapefruit) Extract Deodorant Not spray 0.0024% Citrus Junos Extract Shampoos (noncoloring) 0.0001% Citrus Nobilis (Mandarin Orange) Oil Dentifrices 0.035% Citrus Nobilis (Mandarin Orange) Oil Bath soaps and detergents 0.0009-0.0017% Citrus Nobilis (Mandarin Orange) Shampoos (noncoloring) 0.0005% Citrus Nobilis (Mandarin Orange) Bath soaps and detergents 0.0005% Citrus Reticulata (Tangerine) Extract Permanent waves 0.00013% Citrus Reticulata (Tangerine) Extract Shampoos (noncoloring) 0.005% Citrus Reticulata (Tangerine) Extract Tonics, dressings and other hair 0.0051% grooming aids Citrus Reticulata (Tangerine) Extract Face and neck products Not spray 0.00016% Citrus Reticulata (Tangerine) Extract Moisturizing products Not spray 0.00016% Citrus Reticulata (Tangerine) Extract Night products Not spray 0.00016% Citrus Tangerina (Tangerine) Extract Other bath preparations 0.0005% Citrus Tangerina (Tangerine) Extract Colognes and toilet waters 0.0005% Citrus Tangerina (Tangerine) Extract Hair conditioners 0.00035% Citrus Tangerina (Tangerine) Extract Shampoos (noncoloring) 0.00001-0.00035% Citrus Tangerina (Tangerine) Extract Tonics, dressings and other hair 0.00001% grooming aids Not spray 0.0000025% Citrus Tangerina (Tangerine) Extract Bath soaps and detergents 0.0001% Citrus Tangerina (Tangerine) Extract Skin cleansing (cold creams, cleansing 0.00025% lotions, liquids and pads) Citrus Tangerina (Tangerine) Extract Face and neck products Not spray 0.0001-0.0045% Citrus Tangerina (Tangerine) Extract Body and hand products Not spray 0.0005% *Ingredients included in the title of the table but not found in the table were included in the concentration of use survey, but no uses were reported. **The Dictionary defined Citrus Tangerina (Tangerine) Extract as “ the extract of the tangerine, Citrus tangerina”, rather than as an extract of the whole plant. Information collected 2015-2016 Table prepared February 10, 2016
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Updated September 27, 2016: Citrus Aurantifolia (Lime) Oil: skin cleansing, deleted low concentration 0.0035%; Citrus Aurnatium Dulcis (Orange) Oil: Blushers deleted, face products low concentration 0.14% deleted
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