Camellia Japonica Leaf Extract - Safety Assessment

Safety Assessment of
Camellia Sinensis-Derived Ingredients

as Used in Cosmetics
Status: Draft Final Report for Panel Review

Release Date: May 16, 2014
Panel Meeting Date: June 9-10, 2014
The 2014 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V.
Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A. Hill, 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 Lillian C. Becker, Scientific Analyst/Writer.
© Cosmetic Ingredient Review

1620 L Street, NW, Suite 1200  Washington, DC 20036-4702  ph 202.331.0651  fax 202.331.0088  cirinfo@cir-safety.org
i
Commitment & Credibility since 1976
MEMORANDOM
To: CIR Expert Panel and Liaisons
From: Lillian C. Becker, M.S.

Scientific Analyst and Writer
Date: May 16, 2014
Subject: Camellia sinensis – Derived Ingredients As Used In Cosmetics
This is the Draft Final Report of Camellia sinensis-derived ingredients. In March 2014, the Panel concluded that
camellia sinensis leaf extract is safe up to 0.86% in leave-on products and up to 1% in rinse-off products; and
that camellia sinensis catechins is safe as used. There is not enough data to come to a conclusion of safety for
the ingredients that are not derived from the leaves and stems. To make a determination of safety for these
ingredients, the Panel indicated that the following data are needed:
• method of manufacture
• characterization of these ingredients
• human sensitization data, in particular for camellia sinensis leaf powder at 50%
• concentration of use in cosmetics
The CIR Science Support Committee has submitted comments, included with this packet, in which they suggest
that portions of the conclusion be reconsidered:
• Catechins should not be safe as used if there are no uses reported. There is also concern about the
positive guinea pig sensitization studies.
• The leaf extract only has data for “black tea” and not for other possible forms for which this ingredient
may be used.
• The conclusion for the leaf extract could be extended to the other leaf-derived ingredients.
No new data were submitted to address the identified needs. Information from two repeated dose inhalation
papers have been added to this safety assessment.
There has been no confirmation that camellia sinensis leaf water is used only as a fragrance. Therefore, the
ingredient remains in this report.
The National Toxicology Program has issued a report on green tea extract for public comment but is not
available for attribution. The abstract of this report, included in this package, contains robust summaries of the
studies performed. The Panel should review the summaries and decide if any of this information is important
enough to this safety assessment to wait for the data or if it would change the conclusions set by the Panel in
March. If so, then the Panel may elect to table this report until this data is available to site. If the information
does not significantly add to this report, the Panel may advance the progress of the safety assessment. The
entire 230 page report is available at:
http://ntp.niehs.nih.gov/ntp/about_ntp/trpanel/2014/may/draft_tr585_508.pdf#search=Camellia%20sinensis
__________________________________________________________________________________________
1620 L Street, NW Suite 1200, Washington, DC 20036
(Main) 202-331-0651 (Fax) 202-331-0088
(Email) cirinfo@cir-safety.org (Website) www.cir-safety.org
The Panel is to review the presented data and review the Abstract, Discussion, and Conclusion to ensure that
they reflect the Panel’s thinking. If the Panel is satisfied, and the report is not tabled for the NTP data, then the
Panel is to issue a Final Report.
__________________________________________________________________________________________
1620 L Street, NW Suite 1200, Washington, DC 20036
(Main) 202-331-0651 (Fax) 202-331-0088
(Email) cirinfo@cir-safety.org (Website) www.cir-safety.org
History
August, 2013 – SLR posted for comment.
December, 2013 – An insufficient data announcement was issued. The data needs were:
• Method of manufacture, including removal of impurities and constituents of concern (such as

linalool)
• Composition data for camellia sinensis root extract, seedcoat powder, flower extract, and
flower/leaf/stem juice
• Concentration of use data for camellia sinensis root extract, seedcoat powder, flower extract,
flower/leaf/stem juice, and the catechins
• Human repeated insult patch test (HRIPT) on camellia sinensis leaf (100%), camellia sinensis
stem/leaf extract (3%), and camellia sinensis catechins (at use concentrations)
• Confirmation that camellia sinensis leaf water is only used as a fragrance ingredient
• Information on the difference between leaf oil and leaf essential oil
Camellia sinensis seed oil was removed from the report because it was included in the oils report.
March, 2014 - Panel examined the draft report with the additional data and updated concentration of use
information. A Tentative Report was issued with a mixed conclusion. The Panel concluded that
camellia sinensis leaf extract is safe up to 0.86% in leave-on products and up to 1% in rinse-off
products. Camellia sinensis catechins is safe as used. There is not enough data to come to a
conclusion of safety for the ingredients that are not derived from the leaves and stems. To make
a determination of safety of these ingredients, the Panel needs data on:
The Panel also requests confirmation that camellia sinensis leaf water is used only as a
fragrance.
No new data have been submitted to meet these data needs.
June, 2014 – The Panel is to issue a Final Report.

Camellia Sinensis-Derived Ingredients Data Profile for December, 2013. Writer - Lillian Becker
Repeated dose
ADME Acute toxicity Irritation Sensitization
toxicity
Penetration
Dermal
Log K ow
Use
Oral
Dermal
Inhale
Oral
Dermal
Ocular
Animal
Dermal Irr.
Human
Dermal Irr
Animal
Sensitization
Human
Sensitization
toxicity
Repro/Devel
Genotoxicity
Carcinogenicity
Phototoxicity
Inhale
Irritation
Camellia Sinensis X X X X X X X
Leaf Extract
Camellia Sinensis X X X X X X X X X X
Catechins
Camellia Sinensis
Flower Extract
Camellia Sinensis
Flower/Leaf/Ste
m Juice
Camellia Sinensis X
Leaf
Camellia Sinensis X
Leaf Oil
Camellia Sinensis X
Leaf Powder
Camellia Sinensis X X X
Leaf Water
Camellia Sinensis
Root Extract
Camellia Sinensis
Seedcoat Powder
Camellia Sinensis
Seed Extract
Camellia Sinensis
Seed Oil
REMOVED
Camellia Sinensis
Seed Powder
Hydrolyzed
Camellia Sinensis
Leaf
Hydrolyzed
Camellia Sinensis
Seed Extract
Camellia sinensis-Derived Ingredients
Search Strategy
SciFinder – “camellia sinensis dermal” culled for toxicity and relevant terms. 17 results
Internet Search – “Camellia sinensis”. Tea Association information; Committee on Diet, Nutrition, and
Cancer; European Medicines Agency; FDA Drug application and GRAS submission; and IARC.
SciFinder – “camellia sinensis” and “UV”. 19 hits ordered

And “inhalation”. Papers on using C. sinensis to treat pulmonary MRSA.
Transcripts – Camellia sinensis-Derived Ingredients
Dr. Marks’ Team
DR. MARKS: So, next, we're to camellia, which is -- we saw the draft tentative report and
issued an insufficient data announcement at the December 2013 meeting, and there were a number of
data needs -- method of manufacture, composition, concentration of use, HRIPT, differences between the
leaf oil and essential oil. So, let's -- Tom and Rons, what's you feeling about these tea products? Should
we go down each one of those needs as were bolded by Lillian? And, is Lillian here? Oh, yes. Good.
Thank you.
So, method of manufacture, including removal of impurities and constituents of concern,
such as linolol. (inaudible). There was some concern about whether the cosmetic is the same as the
food.
DR. SLAGA: I thought we said it was last time.
DR. MARKS: Lillian, we didn't receive anything on that, did we?
MS. BECKER: We didn't by the time of this report. I'm trying to remember what came in
Wave 2.
DR. HILL: It was Wave 2 and Wave 3. There is material --
MS. BECKER: Mm-hmm. Yes.
DR. MARKS: So, Ron, Ron, and Tom. I can't remember whether this was a concern by
the Belsito team or by us.
DR. SLAGA: Well, to me, I think some of the needs last time were based on that this was
the first time and therefore we'll see if we can get it, and I think there's enough information in Wave 1 and
2 and in the document that it's safe.
DR. MARKS: You're good.
DR. HILL: If you remember how this came, this actually was mixed with the other tea
plant, wasn't it? Ginseng?
MS. BECKER: No.
DR. HILL: This wasn't the one that was split out from -- okay.
MS. BECKER: No. It wasn't with Ginseng now.
DR. HILL: Not Ginseng. Weren't there two types of tea and lumped into one report and
then we -- okay. I got this crossed in my mind.
MS. GILL: Yes.
DR. HILL: Okay.
DR. MARKS: Composition. So, I don't get the sense that there's a concern at this point
with the method of manufacture. Let's go to composition data for the root extract, seedcoat powder,
flower extract, flower/leaf/stem juice.
DR. SHANK: We have in Table 5 the phenols in green and black tea, but what is meant
by black tea? Is that leaf, leaf extract, water extract, flower, root? It doesn't say.
MS. BECKER: We don't know, just that it's black tea. The black, green oolong tea all
has to do with when the leaf was picked and how it was processed, and it's from the same plant, and then
what extract it is we don't know.
DR. SHANK: Okay. Well, I had only a data need, HRIPT on the leaf powder at 50
percent, and I don't know what to do with leaf water. Is that a fragrance or not? Those are the two I had.
DR. BERGFELD: I had a question on the leaf powder at 50 percent. Do you think it's
used at a low enough concentration, not to be a worry? The leaf powder at 50 percent. Is it used in a low
enough concentration not to be a worry?
MR. ANSELL: Our notes suggest that the 50 percent leaf powder as mentioned is as
sold as a professional product, but it's actually applied in diluted form before use.
DR. MARKS: Yes, I had the same need as Ron Shank. I wanted an HRIPT for the leaf
powder at 50 percent, since that's what we're told is the use concentration.
MS. BECKER: Well, though --
DR. MARKS: Even though you say it may get diluted, we don't know what it's diluted
down to. Is that correct, Lillian? Fifty percent under the use?
DR. BERGFELD: It says face and neck products, not spray, up to 50 percent. Most of
it's under.0-something.
DR. MARKS: Yes, but, obviously we have to pay attention to the --
DR. BERGFELD: Yes, either that or restrict it.
DR. MARKS: So, I had that -- let me see -- concentrate -- limit -- I had limits stem/leaf
extract to 0.86 percent, again, based on the sensitization data. But, then, we come with the -- if, from the
memo, you sent -- Lillian, I think that's Wave 3.
MS. GILL: Wave 2.
DR. MARKS: IFRA standard shows the tea left extract varies with category from 0.1 to
2.5 percent, and if IFRA's ruling on it that the tea left abstract is a fragrance, then should we even be
reviewing it? That's from this memo dated March 14, 2014. So, it would make it a little simpler, because
they really vary. Category 1 is .01 as I mentioned, and then if you look at Category 10 they divide their
restrictions based on these 11 categories. So, I would say that the tea leaf absolute or the synonym
extract, the leaf extract, should be eliminated from this report since it's covered by IFRA as a fragrance.
And, then, I don't know about the leaf water. Did we get any feedback on the leaf water? Is that a
fragrance?
MS. BECKER: We have not gotten anything that it's just used as a fragrance or used as
a fragrance in other uses. But, we are scheduled to get their full report by end of March. So, if we find
that it is used solely as a fragrance, to get the report. If we find out it is used as a fragrance, we will take
it out.
DR. MARKS: And, what would you suggest to do with the tea leaf extract? Should we
take that out, too, Lillian?
MS. BECKER: If it's used for other things besides a fragrance, we might want to keep it
in, because it would be different concentrations. So, I'm checking the table real quick to see what else it's
used for.
DR. MARKS: Okay. So, team, how do you want to deal with the -- if we limit -- if we say
keep the leaf extract in? In Lillian's memo, it talks about HRIPTs. They were clean up to 0.86 percent, but
then when we look at the IFRA recommendations, they make limits depending on what region of the body
you're going to apply it. Category 1 is lip product. Going from there to Category 11 is in candies. That's
not an issue for us, but 10 is hard-surface cleaners. That isn't an issue, but 8, 9 is rinse-off hair
conditioners.
MS. BECKER: Mm-hmm. Yes. And, Dr. Marks, the leaf extract has the most number of
potential uses or functions in cosmetics. It has a large list.
DR. MARKS: Yes.
MR. ANSELL: I think the IFRA limits are informative, but they'd be difficult to adopt
wholesale, because they're exposure-based and not all the exposure categories are relevant. I'm not
actually aware of whether the material is a dual-use product or not. I think we can find that out. But, until
we conclude that it has no cosmetic applications, I would recommend that we keep the leaf extract
present and, if necessary, with the limitation relative to the demonstrated HRIPTs.
DR. MARKS: Which is the 0.86.
MR. ANSELL: Yes.
DR. MARKS: It's safe.
MR. ANSELL: Because, from my notes, the 2.5 would be the 2.5 percent and the IFRA
would be for like household cleaning products, and it would be hard to --
DR. MARKS: Right.
MR. ANSELL: -- adopt that. But, we do have data on the 0.86. We do have a number of
ingredients which are dual use, both fragrance and cosmetic, and it's important I think to be informed by
the IFRA assessments but not necessarily have to adopt them as such.
DR. MARKS: It actually -- Jay, the way you're looking at it, I think it's quite correct. The
only one where there's a concentration that they approve higher than that in a personal care product
would be a rinse-off. So, the .86 should be fine.
MS. BECKER: The list of functions are on PDF page 36.
DR. MARKS: So, let's summarize where we are at this point.
DR. HILL: I have one more question before you do that.
DR. MARKS: Sure.
DR. HILL: (Coughs) Excuse me. We don't have any use concentrations for camellia
sinensis leaf.
DR. SHANK: It's no longer used, right?
DR. HILL: The leaf is no longer -- it says 38 leave-on applications. Am I missing
something?
DR. SHANK: Was it in Wave 2?
DR. HILL: No.
DR. SHANK: Someplace we have that.
DR. HILL: But, the leaf itself is no longer used?
DR. SHANK: Based on teabags placed on the eyelids of (inaudible) --
MS. BECKER: Yes. And, the teabags -- they said that's no longer on the market, and it's
now used.
DR. HILL: Was that the only leave-on? That says different leave-on uses. Is that the
only one?
MS. BECKER: That was the one that was the high percentage at --
DR. HILL: Well, we didn't have any used concentrations on the other 37 uses? That's
what I'm driving at.
MS. BECKER: All right. Okay.
DR. BERGFELD: Are you all comfortable with the seed and the --
MS. BECKER: Okay.
DR. BERGFELD: -- seedcoat powder, and the root, and the oil? I mean, there are lots of
different parts of the plant that's being used there's no data on.
MS. BECKER: Okay. And, just to quickly answer Dr. Hill's question, the leaf. You're
asking about the leaf, right?
DR. HILL: Leaf.
MS. BECKER: It's used up to 0.05, and it's diluted for bath in those uses.
DR. HILL: That wouldn't be leave-on, and it lists leave-on uses.
MS. BECKER: Right. And, we have no report from the Council of concentrations of use
for those uses.
DR. HILL: Yes. So, if we're approving the safety with no idea of the concentration, that
seems like a bad plan. And, I'm particularly interested, I guess, because there is no repeated dose
toxicity of any kind on any of these, and, I guess, thinking as well as tea, but that comes back to the
question that Dr. Bergfeld just asked. We don't grind up the seeds when we make tea. I don't think we
use the root, in the U.S. at least for foodstuff.
MS. BECKER: However, we do have concentration of use for the seed extract.
DR. HILL: Yes. And, you're saying that to point out that they're all really low? Is that --
MS. BECKER: Just to fill in the information of the question.
DR. HILL: Okay. So, they are all really low? I'm looking for the table again.
MS. BECKER: The table's on page 39 of the PDF.
DR. HILL: I'm almost there.
MS. BECKER: And, yes, the highest concentration is 0.1 percent.
DR. HILL: Okay.
DR. MARKS: Okay. So, let me see if I have the Panel's -- have captured where the
Panel is at this point. So, I would move that we have a tentative report, issue a tentative report tomorrow,
with these ingredients safe. The exception that we would limit the stem leaf extract, or stem leaf -- yes,
extract, to 0.86 percent. We have an insufficient of the leaf powder at 50 percent. We need an HRIPT.
And, the leaf water may be a fragrance and deleted, based on what we find out from RIFM. And, all the
other ingredients then would be safe, as I said. Does that sound -- Ron, Ron, and Tom, does that --
DR. SHANK: Sounds good. Well, there are no uses for root.
DR. MARKS: Yes, but, we --
DR. SHANK: It's not in Table, whatever it is, 7?
DR. BERGFELD: No. No root and no oil and no seed.
DR. MARKS: But, in the past, when we had ingredients or no uses we will still would say
(inaudible).
DR. BERGFELD: But, rice was the key for us in the past. Every part of that rice kernel
was different. So, how can you just say that the seed is okay? You haven't got anything on it --
DR. SHANK: Right.
DR. BERGFELD: -- or the root. You're dealing mainly with the leaf. So, wouldn't you
say they were insufficient for those?
DR. SHANK: I would. Yes.
DR. BERGFELD: You said it in your initial tentative report that you needed
concentrations of use of the root and the seed power and the flower. I forgot the flower. And, you get
those.
DR. SLAGA: No, we didn't get any of them.
DR. BERGFELD: But, you don't have any chemistry on them either.
MR. ANSELL: We do have chemistry.
DR. BERGFELD: You have chemistry, I believe.
MR. ANSELL: Yeah, I'm trying to find the constituents of concern by plant part.
DR. HILL: I'm on 37. I think PDF, 38, isn't it? Maybe not.
MR. ANSELL: No, I think it's earlier than that. It's --
DR. BERGFELD: Twenty-three.
DR. SHANK: Twenty-three. Yeah. Thank you.
DR. BERGFELD: PDF page 23.
MR. ANSELL: Materials of concern in the leaf plant shoot predominant in the seeds,
seed coatings.
DR. HILL: On my PDF 23 -- oh, no. Okay. That's 24.
DR. MARKS: So, let's go back to Lillian's memo and trying to arrive at a conclusion here.
Are we going to go back to -- are we going to put insufficient for the root extract, the seedcoat powder, the
flower extract? So, now we're down to we limit the stem/leaf extract to 0.86 percent insufficient for the
leaf powder. We need an HRIPT. The leaf water may be a fragrance. What do we do with the rest of
those? We aren't going to rule that they're safe.
DR. SHANK: When you say rest of those, what is --
DR. MARKS: Like the root extract, the seedcoat powder, the flower extract.
DR. SHANK: Insufficient.
DR. MARKS: Insufficient.
DR. HILL: I had flagged, too. It's just taken me a while to read back through -- I left my
notes in disarray, but a lot of the -- what we're relying on there is the fact that these are being consumed
heavily as foodstuff, but those aren't. So, we're lacking data that we can rest on a little bit. I think it is
insufficient.
DR. MARKS: And, we want the concentration of use. Is that it? So, there are one, two,
three, four, five ingredients mentioned there. Does that cover the rest? Are there a couple of ingredients
which we didn't mention?
DR. HILL: What did we say about the flower extract?
DR. MARKS: That's insufficient.
DR. HILL: Okay. So, I got a total of six. Flower extract, flower/leaf stem juice, root,
seedcoat powder, seed extract, seed powder.
MS. BECKER: And, how about the hydrolyzed seed extract?
DR. HILL: Mmm. Yes. I would think that one would be in there, too.
DR. MARKS: So, I'm on page 5 in the PDF with the table with all the ingredients. Is
there anything on there that -- let's see, other than seed/leaf extract? Let me see. So, we're limiting the
concentration on the leaf extract. And, where is the seed extract? Down here. And, then, everything
else is essentially --
DR. HILL: Insufficient.
DR. MARKS: -- insufficient. Is that right? The leaf powder we want at 50 percent, and
everything else we want use concentration. Is that correct?
DR. HILL: I think so.
DR. MARKS: Do we have the (inaudible)?
DR. BERGFELD: Do you feel that you have the constituents though? Do you feel you
have constituents in those? Because, you might want to ask for that. You have a summary statement. Is
that the whole plant that they gave you that? On page 5 -- no, it was on another page -- 25.
DR. MARKS: So, do I have it summarized pretty well? We have leaf extract and seed
extract. We set a limit, and then all the rest is insufficient. Either the powder or an HRIPT at 50 percent,
and the rest for use.
MS. BECKER: Say that again, please. Leaf extract and --
DR. MARKS: So, limit stem and leaf extract to 0.8 percent. We have that information
and that the HRIPT was good for that. Insufficient for the leaf powder -- 50 percent. We need an HRIPT.
The leaf water may be a fragrance. That may be deleted, so that's also -- and then insufficient
concentration of use -- concentration of use for the other ingredients.
MS. BECKER: Do you want further characterization of those ingredients, and do you
want any testing, like an HRIPT, if there's a use concentration?
DR. MARKS: Right. I think it depends on what we get. We'll get as much as we can.
DR. HILL: What about the leaf oil?
DR. MARKS: That was deleted, wasn't it or not?
DR. HILL: Leaf oil? I don't think so.
DR. MARKS: Let me see. Which one --
MS. BECKER: Seed oil was deleted.
DR. MARKS: Okay. Does that sound reasonable, Tom, Rons? Tomorrow I'll present a
tentative move that a tentative report be issued limiting the stem/leaf extract to 0.8 percent, insufficient for
the leaf powder, and all the other ingredients. The leaf powder, we need an HRIPT. The other
ingredients, we need the concentration of use, and then, depending on what we get from that, we may
need some more, but, whatever you can find (inaudible). Does that sound reasonable?
DR. SHANK: Uh-huh.
DR. MARKS: Okay. Any other comments? Just diminished my thirst for tea. (Laughter)
Okay. I have a feeling we're going to come up with safe one way or another, but --
DR. SHANK: Eventually.
DR. MARKS: Yeah, eventually. It's going to be painful getting there. Okay.
Dr. Belsito’s Team
DR. BELSITO: …Okay. So, we are moving on to camellia sinensis- derived ingredients.
In the interest of time, we are just going to keep going, and I'll take a bio break, and if anyone needs to
duck out, because otherwise I think we will be here until tomorrow morning possibly.
SPEAKER: We have four more.
DR. BELSITO: Yes, we have four more, but that doesn't mean anything. It only mean
that there may be alcohol left at the bar for us this time. Okay. Camellia sinensis.
DR. LINTNER: I'll be here tomorrow.
DR. BELSITO: Thank you, Dr. Lintner, very much.
DR. LINTNER: Thank you very much. See you tomorrow.
DR. BELSITO: Yeah. Okay.
(Recess)
DR. BELSITO: At the December meeting we evaluated ingredients and found that leaf
extract is save as used, catechins are safe at 0.1 (inaudible) used in cosmetics. And the -- and
insufficient data announcement was issued for the other ingredients. Is that correct?
SPEAKER: Mm-hmm.
DR. BELSITO: Additional data requested included method of manufacture, the
composition data for the root extracts, (inaudible) cauliflower or extract flower -- stem leaf through
concentration of leaves for all ingredients. HRIPT and leaf at a 100 percent stem leaf extract at 3
percent, and catechins at use confirmation, and clarification that tea leaf water is used only as a
fragrance.
We've got some new data, and I don't know what's happening but have to wring this,
suddenly like PDR is not opening -- PDF rather. Some new data is added to report, information that the
leaf is no longer in teabags for the eyes at 97 percent, so that request for 100 percent goes away.
We have HRIPT on the leaf extract at 0.86 percent new use data indicated that the leaf is
used at a maximum of 0.5 in a bubble bath, and 50 percent on the face and neck product. And no
additional data were received on method of manufacture composition, concentration of use, difference
between oil and essential oil, or leaf water only as a fragrance, but we did get data from -- where
from -- this is the one where we got the data on --
DR. SNYDER: QRA, yeah.
DR. BELSITO: -- QRA on leaf water.
MS. EISENMANN: It's on -- it's tea leaf absolute.
DR. BELSITO: Tea leaf absolute.
MS. EISENMANN: So it's (inaudible) --
DR. BELSITO: Yeah, it's here someplace, and I'd better get it someplace.
SPEAKER: Oh, it's down here. Yeah, here it is.
DR. BELSITO: Tea leaf absolute. But its synonym is camellia sinensis leaf extract, if you
read under the synonyms. So, I'm assuming the leaf extract is used as a fragrance, and that's what
they're talking about.
MS. EISENMANN: This one. This leaf -- the leaf extract with alcohol, yes.
DR. BELSITO: No. But here it says synonyms, camellia sinensis leaf extract, it doesn't
say leaf extract to alcohol.
MS. EISENMANN: Other than the name is -- I'm saying because it's tea leaf absolute, I
presume that's how they name --
DR. BRESLAWEC: Don't they use -- I saw naming principles that there's an ISO
Standard for botanical names, and that may -- I think that's what they are using, so it probably has some
kind of other meaning, and I don't know what it is.
MS. EISENMANN: Oh. So it was one of the things that there's -- as an absolute ethanol
extract of tea leaves, tea leaves absolute.
DR. BELSITO: Hmm?
DR. LIEBLER: Where are we?
DR. BELSITO: On camellia sinensis-derived ingredients.
DR. LIEBLER: Yeah. But is there a document paper referring to it, and way to --
SPEAKER: No.
DR. BELSITO: No. It's wave --
SPEAKER: Three documents.
DR. BELSITO: Wave 3 document from (inaudible)
SPEAKER: I see. We are sorry. Okay.
DR. LIEBLER: So the question is, what do they mean by tea leaf absolute, it has heavily
(inaudible) ingredients.
DR. BELSITO: Yes.
DR. LIEBLER: Okay. (Inaudible)
DR. BELSITO: Well, the synonym is tea leaf extract, so I'm assuming that what people
call the absolute is also tea leaf extract and the extract is the fragrance. And if in the cosmetic dictionary,
is there any other listed use of leaf extract other than as a fragrance?
MS. EISENMANN: Yes.
MS. BECKER: Yes. It's the one that has the most other uses.
DR. BELSITO: So then we need to review it?
MS. BECKER: Yes.
DR. LIEBLER: All the skin conditioning is in here.
MS. EISENMANN: Miscellaneous?
DR. LIEBLER: Or the miscellaneous.
MS. EISENMANN: Miscellaneous, the difference --
MS. BECKER: Leaf extracts and antifungal agent, and antimicrobial agent,
and --astringent. White stabilizer, oral care agent it has --
DR. LIEBLER: Or covered.
MS. EISENMANN: It's a natural ingredient.
DR. LIEBLER: We are so covered.
MS. BECKER: Plus skin-conditioning agent is used.
MS. EISENMANN: No. The oil -- the leaf oil is defined -- in the dictionary, it's in the
chemical class, essential oils and water. So it's safe to assume that the leaf oil is the essential oil.
SPEAKER: Okay.
MS. EISENMANN: Okay?
DR. BELSITO: But absolute doesn't mean essential oil?
MS. EISENMANN: Correct. I'm just saying had that question -- it did respond because
we felt the dictionary answered that question.
DR. BELSITO: Oh, Christ. Of all the times for my PDF to act up. Okay. I can't search
my comments, but I can at least open the document, so I'll scroll down. I'll open it up to other people. So,
basically, I'm thinking, and this is only from memory, because I'm scrolling down, and not seeing any
comments at this point, that we really didn't get a lot of new information other than, there wasn't a 97
percent, and we got and HRIPT on leaf extract at 0.86 percent.
But the leaf is used to the maximum of 0.5 but up -- in a bubble bath, but up to 50 percent
in the face product, and we have this QRA on the leaf extract that tells us the different concentrations of
use that would be safe for different consumer products for the leaf extract, and so --
MS. BECKER: Also and we told you that a summary of RB teas, from several different
kinds of teas.
DR. BELSITO: Right. Yeah. I've got my comments on Wave 2, and they say Wave
2 -- those comments weren't necessarily on Wave 2. I can't open this document, so help me out folks.
Talk about it yourselves.
DR. LIEBLER: I'm not sure how much of our (inaudible) data were satisfied by the Wave
2.
DR. BELSITO: So, we are basically that the -- found that the leaf extract is safe as used,
and the catechins are safe at 0.1 percent, and all of the other ingredients are insufficient. Is that correct?
DR. LIEBLER: Right.
DR. BELSITO: Okay. Yeah. I've just scrolled to my first comment, which is on the
conclusion. Okay. Same conclusion as before -- Oh, same conclusion as before, or the is the blurb that
we got about the seed, the general composition of the seed, was that sufficient to allow or to pass the
seed extracted, 0.1 percent, but we had no concentrations for the powder?
So we've got a little blurb about the concentration of the seed in this document, and I
guess I'll have to continue to scroll down. I don't know why it won't open my comment section. It just
circles around when I try to get it to open my comments.
(RECESS)
DR. LIEBLER: But for all these ingredients where we have no concentration -- or
frequency of use or concentration data, do we still keep them? Or are we going to go insufficient for all of
them?
MS. BECKER: In general, we tend to keep them.
DR. BELSITO: You know, I mean, we just go insufficient so -- but I guess the only
question is before we just set 0.2 percent and the -- or leaf extract safe as used, and catechins safe at 0.1
percent is used in cosmetics. And again, I'm just going to have to scroll down. I tried doing it and it's still
not bringing up my comments for reasons that I don't know. I just raised the issue in a general
conclusion. There must be a blurb we got about some components of the flower that -- technology is
wonderful when it works. Yeah?
MS. BECKER: Nothing in Wave 2 or 3.
DR. BELSITO: Yeah but -- or seeds rather, not flowers. So on page 23, PDF 23, it says,
"Constituents reported to be predominantly in C. sinensis seeds, include caffeine, glucothia, saponins,
stearic acid, theospomine and theobromine. Constituents reported to be in C. sinensis seed coat include
caffeine and theobromine. Is that enough for us to rule on the seed and seed coat, or do we need more
specific constituent information?
DR. LIEBLER: That's not enough.
DR. BELSITO: Okay. I'm just saying we did get some.
DR. SNYDER: Others, in particular -- just to know that a little -- some of the others were
in other components, right.
DR. LIEBLER: Right.
DR. BELSITO: Okay. Fine. So then, it doesn't change our conclusion, so we don't have
the data. So then we just have the same conclusion as before, that the leaf extract is safe as used. The
catechins are safe up to 0.1 percent as used in cosmetics, and the others are insufficient for all the
reasons that we asked for before.
DR. SNYDER: The catechins are based on a negative. Tested 0.1 percent. We don't
have concentration.
DR. BELSITO: Right. We don't have -- which is why we said that.
DR. SNYDER: Okay.
DR. BELSITO: Okay. Anything else with these Camellia sinensis-derived ingredients?
Okay. Seeing no comments, and moving on along, and let's hope that the thought with my search was
only with camellia, and then not that tea brought me down.
DAY TWO
DR. MARKS: Tea. So a draft tentative report on these tea-derived ingredients was
issued in December of last year. An insufficient data announcement. There are a number of needs and
our team felt that we could move forward with a tentative report that limits the leaf extract to 0.86 percent.
Insufficient for the leaf powder at 50 percent. We need an HRIPT to support the safety of that ingredient.
The leaf water may be a fragrance, and that may be deleted. We still don't know the answer to that yet.
And then insufficient for concentration of use and composition of the other 11 ingredients -- the roots,
seed, flower, stem, catechin. So we're still a lot of needs. A lot of insufficients. The only one we felt we
could move forward safe was limiting the leaf extract.
I'm sure you have --
DR. BELSITO: No, I mean, we just felt -- I mean, we learned that the tea bags at 100
percent weren't used, so we thought that moved it down to the safe as used, the catechins at 0.1 percent,
and all of the other data needs that we had asked for before still exist.
Did I hear you say method of manufacturer and composition data?
DR. MARKS: Yes.
DR. BELSITO: Okay. You know, excuse me, so you wanted to limit the leaf --
DR. MARKS: To 0.86. 0.86 percent. We've got -- that was really the data we received
that showed that the leaf of the HRIPT --
DR. BELSITO: The leaf extract or the leaf?
DR. MARKS: Leaf extract.
DR. BERGFELD: Leaf stem extract.
DR. MARKS: That's actually in Lillian's memo right after the needs. It's in that second
paragraph, HRIPTs, cosmetic products containing leaf extract at 0.86 percent. When you look at the
studies, it's nonsensitizing.
MS. BECKER: The studies are on page 32, PDF 32.
DR. MARKS: So I think on the other things, the modifications you made are fine.
DR. BELSITO: Well, we do have a QRA from RIFM on the leaf extract.
DR. MARKS: Yes. We discussed that, and having all the categories, we decided the
ones where there were high concentration, the categories wouldn't be used as a cosmetic product. So
that's how we came back to the concentration we had had before with that HRIPT of 0.86 percent.
DR. BELSITO: And what is the use concentration on this?
Find table.
UNIDENTIFIED SPEAKER: Three percent.
DR. BELSITO: Three percent?
MS. BECKER: The table is on page 39 of the PDF.
DR. MARKS: I have up to 2 percent is what I see. That's why I think we need to
put -- we don't have data --
DR. BELSITO: Up to 2 percent on leave-ons. So are you going to limit it in rinse-offs to
0.86, as well?
DR. MARKS: No, I don't think we have to.
DR. BELSITO: So then your limit is restricted to leave-ons?
DR. MARKS: Yes.
DR. HILL: The use there right now says 1 percent, so 0.86 percent for leave-on, 1
percent for rinse-off doesn't seem at all unreasonable with the data we have; right? I think. One percent
on rinse-off is what state-of-the-art is according to our report.
DR. BELSITO: Right. Yeah.
DR. HILL: But 2 percent for leave-on is what we're questioning, isn't it?
DR. BELSITO: Yeah, but you said you were going to restrict it to 0.86, which would be --
DR. HILL: But not for rinse-off. Not for rinse- off.
DR. BELSITO: Not for rinse-off. So that's what I wanted to clarify there.
DR. MARKS: Thank you, Don.
DR. BELSITO: For some reason I didn't have any problems with it. So they did a dermal
non-human with 100 percent of the leaf extract was dermally applied to New Zealand rabbits. Note, that
was irritation. Dermal human.
So it's all over the board. Yeah, so the HRIPT, yeah, I see what you're referring to.
So I'm fine with that, you know, if you want 0.86.
DR. BERGFELD: It's going to go out for comment.
DR. BELSITO: Yeah. And you could probably stretch it to one, but if you want to be
compulsive and go by the number they used and stay with 0.86 percent.
Okay. So your motion was the leaf extract safe up to 0.86 percent and leave-on safe as
used in rinse-offs. The catechins safe at 0.1 percent. The other constituents, insufficient for all of the
data that we had requested before.
I'll second that if my teammates are okay with it.
DR. BERGFELD: Everyone shaking their heads are agreeable to that?
UNIDENTIFIED SPEAKER: Yes.
DR. BERGFELD: All right. Any other comments? Seeing none, I'll call the question. All
those in favor? Excuse me. Unanimous.
(Motion passed)
Safety Assessment of
as Used in Cosmetics
Status: Draft Final Report for Panel Review

Release Date: May 16, 2014
Panel Meeting Date: June 9-10, 2014
The 2014 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V.
Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A. Hill, 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 Lillian C. Becker, Scientific Analyst/Writer.
© Cosmetic Ingredient Review

1620 L Street, NW, Suite 1200  Washington, DC 20036-4702  ph 202.331.0651  fax 202.331.0088  cirinfo@cir-safety.org
i
ABSTRACT
Cosmetic ingredients derived from Camellia sinensis (tea) plant parts function as antioxidants, and skin-conditioning agents –
humectant and miscellaneous. The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed relevant animal and
human data related to these ingredients. The use of the leaf ingredients in beverages result in larger oral exposures than those
from cosmetic uses. Therefore, oral toxicity potential was not the focus of this safety assessment. Because formulations may
contain more than one botanical ingredient, caution was urged to avoid reaching levels of toxicity for constituents. Industry
should use good manufacturing practices to limit impurities. The Panel concluded that camellia sinensis leaf extract is safe
up to 0.86% in leave-on products and up to 1% in rinse-off products. Camellia sinensis catechins is safe as used. The
available data are insufficient to determine that the remaining non-leaf/stem-derived ingredients are safe under the intended
conditions of use in cosmetics.
INTRODUCTION
This is a safety assessment of cosmetic ingredients derived from Camellia sinensis (tea) plant parts. The functions
of these ingredients include: antifungal agent; antimicrobial agent; antioxidant; cosmetic astringent; fragrance ingredient;
light stabilizer; oral care agent; skin protectant; skin-conditioning agent – emollient; skin-conditioning agent – humectant;
and skin-conditioning agent – miscellaneous (Table 1).1 The 14 ingredients in this report are:
• camellia sinensis leaf extract • camellia sinensis leaf water

• camellia sinensis catechins • camellia sinensis root extract
• camellia sinensis flower extract • camellia sinensis seedcoat powder
• camellia sinensis flower/leaf/stem juice • camellia sinensis seed extract
• camellia sinensis leaf • camellia sinensis seed powder
• camellia sinensis leaf oil • hydrolyzed camellia sinensis leaf
• camellia sinensis leaf powder • hydrolyzed camellia sinensis seed extract
It is not known if camellia sinensis leaf water is solely used as a fragrance ingredient. If the fragrance-only function is
confirmed, it will be removed from this report. The safety of fragrance ingredients is reviewed by the Research Institute for
Fragrance Materials (RIFM).
Camellia sinensis seed oil was included in a 2011 CIR safety assessment of plant based oils with the conclusion that
it was safe in the present practices of use and concentration.2
The C. sinensis-derived ingredients in this safety assessment are from edible plant sources. Exposures to the leaf-
derived ingredients in beverages results in much larger systemic oral exposures than would result from cosmetic uses.
Therefore, the oral toxicity potential of the leaf-derived cosmetic ingredients will not be addressed in this report. While data
on the potential for reproductive toxicity, genotoxicity, and carcinogenicity are presented, the primary focus of this report is
on the potential for irritation and sensitization.
CHEMISTRY
Definition and Description
The definitions and functions of Camellia sinensis-derived ingredients are provided in Table 1.
CAMELLIA SINENSIS
There are four varieties of the C. sinensis plant: sinensis, assamica, pubilimba, and dehungensis. The first two are
most commonly used to prepare tea for human consumption. The type of tea (i.e., white, green, oolong, black) depends on
time of year harvested, age of leaves when harvested, location/soil/climate, and processing after harvest. The processing of
tea for a beverage is referred to as fermentation, because it was originally believed that the leaves were fermented, but the
process actually involves an enzymatic oxidation.3,4 It is not known which of these teas or which specific processes are used
to produce cosmetic ingredients.
The C. sinensis is native to East, South and Southeast Asia.4-6 However, it is also cultivated in other tropical and
subtropical regions. The leaves of this evergreen shrub can be lanceolate to obovate, up to 30 cm long (usually 4 - 15 cm)
and 2 - 5 cm broad, pubescent, sometimes becoming glabrous, serrate, acute, or acuminate. The plant has a strong taproot.
The 3 – 5 cm, yellow/white flowers are globular and have a delicate fragrance.
These plants are not the source of, nor are they related to, tea tree oil, which is derived from Malaleuca alternifolia.
CONSTITUENTS
The constituent groups of fresh green leaf C. sinensis are provided in Table 2. The constituent group having the
highest concentrations is the flavanols (25.0% dry weight), which is followed by proteins (15.0%) and polysaccharides
(13.0%).4
Other constituent groups found in C. sinensis plant parts include:
2
Amino acids – The most abundant amino acid is one not typically found in proteins, theanine (5-N-
ethylglutamine).4,7
Carotenoids – These are present in low levels in the leaves. They include neoxanthin, violaxanthin, lutein,
chlorophylls a and b, and β-carotene.4,8,9 Seventy-nine pigments, 41 chlorophylls and 38 other carotenoids have been
detected.10
Enzymes – Fresh C. sinensis leaves contain high levels of the enzyme polyphenol oxidase.
Methylxanthines - Theobromine can range from 0.16% - 0.2% of a dry-weight leaf.4,11,12 Dried leaves contain not
less than 2% caffeine (dried weight). Increased use of nitrogen fertilizer can increase caffeine content by up to 40%.
Theophylline is present at < 0.04% dry leaf weight.
Flavonoids – These include flavonols, flavanols, and glycosides. Flavanols include catechins, which are present in
small amounts, and may occur as flavonols and glycosides.4,13,14 Flavonols reported to be in leaf extract are kaempferol,
quercetin, and myricetin.4,15
Catechins - These polyphenolic molecules are a subgroup belonging to the flavanol family.4,16-18 They typically
make up 20% - 30% of the weight of tea leaves. Catechins are especially concentrated in the leaves of green tea wherein they
account for 30% - 40% of the dry weight of the leaves. The most abundant type of catechin in green tea is epigallocatechin
gallate (EGCG; 12%). The other catechins are catechin (C), epicatechin (EC), gallocatechin (GC), epigallocatechin (EGC),
catechin gallate (CG), gallocatechin gallate (GCG), and epicatechin gallate (ECG; Figure 1).
Minerals elements - Potassium is the most abundant mineral element, present at 40% of the total mineral element
content of dry matter of fresh leaves. The leaves are rich in fluoride and they also accumulate aluminum and manganese.4,19,20
Other elements present in mineral form include calcium, magnesium, sodium, phosphorus, and sulfur. Minor elements
include boron, barium, chromium, copper, iron, molybdenum, nickel, rubidium, strontium, and zinc.19 Trace elements include
silver, arsenic, beryllium, bismuth, cadmium, cerium, cobalt, cesium, mercury, indium, lithium, lead, rare earth elements,
antimony, selenium, tin, tellurium, thallium, uranium, vanadium, ytterbium, and zirconium.
Volatiles – There are a large number of volatile constituents in fresh leaves. Trans-2-hexenal and cis-3-hexenol are
present in the greatest amounts.4,14,21,22
Climatic conditions during cultivation may affect the content of theanine, standard α-amino acids (i.e., isoleucine,
leucine, valine, alanine, threonine, and glutamine), quinic acid, EC, EGC, EGCG and caffeine levels in C. sinensis leaf
extract (as green tea).23,24 Soil conditions and cultivation methods may markedly affect mineral levels.19
Constituents reported to be predominately in C. sinensis seeds include caffeine, glucothea saponin, stearic acid,
theasponin, and theobromine.25
CONSTITUENTS OF CONCERN
Linalool and several compounds containing linalool (i.e., R-linalool, linalool-oxide-(cis-furanoid), linalool-oxide-
(cis-pyranoid), linalool-oxide-(trans-pyranoid), linalool-β-D-glucopyranoside, and linalool-oxides) have been reported in the
leaves (6 -1984 ppm), leaf essential oil (31800 – 198 400 ppm), and shoot (600 – 10300 ppm) of C. sinensis (Table 3).25
Quercetin and several compounds containing quercetin (i.e., quercetin-glucosides) have been reported in the leaf
(760 - 10000 ppm), plant, and shoot of C. sinensis (Table 3).
Constituents reported to be predominately in C. sinensis seeds include caffeine, glucothea saponin, stearic acid,
theasponin, and theobromine.25
Constituents reported to be in C. sinensis seed coat include caffeine and theobromine.25
SAMPLE ANALYSIS
Constituents in medical grade C. sinensis extract include methylxanthines, flavanols (10% - 25%), flavonols,
flavones, phenolic acids, amino acids (including theanine, 3%), terpene saponins, polysaccharides, proanthocyanidins,
vitamins, and minerals (Table 4).16,26-30
Analyses of three lots of C. sinensis catechins (each prepared as a food additive) indicated 28% - 90% total catechin
monomers and 37% - 100% polyphenols.31
CHARACTERIZATION
As herbal supplements, extracts are characterized by the drug/extract ratio (DER), which is the ratio of the quantity
of herbal substance used in the manufacture of an herbal preparation (given as a range) to the quantity of the herbal
preparation obtained in the finished product.32 The specifications for C. sinensis folium as an herbal supplement in the
European Union (EU) for the dry extract, purified (DER 45-56:1, extraction solvent: water) corresponds to 55% - 72% (-)-
epigallocatechin-3-O-gallate.26,32 The decaffeinated dry extract (DER 6:1 to 10:1, solvents such as alcohol, methanol,
acetone, or water or mixtures of these solvents) contains not less than 60% of polyphenols, calculated as (-)-epigallocatechin-
3-O-gallate, not less than 40% of (-)-epigallocatechin-3-O-gallate, and not more than 0.1% of caffeine, calculated on the
anhydrous basis.
3
OH OH
HO O HO O
OH OH
OH OH
OH OH
Catechin Epicatechin
OH OH
OH OH
HO O HO O
OH OH
OH OH
OH OH
Gallocatechin Epigallocatechin
OH OH
HO O HO O
OH OH
O O
OH OH OH OH
O O
OH OH
OH OH
OH OH
Catechin gallate
Epicatechin gallate
OH OH
HO O HO O
OH OH
O O
OH OH OH OH
O O
OH OH
OH OH
Gallocatechin gallate
Epigallocatechin gallate
Figure 1. Catechins from Camellia sinensis
Physical and Chemical Properties

C. sinensis catechins have an astringent taste and are soluble in water.4,16
Three lots of oolong tea with C. sinensis catechins were stable for 18 months in unopened packaging at -20°C.31
Total catechin monomers were decreased from 100% to 97% and 98% after 6 months of storage at 25°C in polyethylene
terephthalate (PET) bottles and steel cans, respectively. At 37° for 2 months, catechin content was decreased to 96% in both
types of containers.
A sunscreen with C. sinensis (2%, 3%, 4%, or 5%) in the form of green tea extract was stable for up to 6 months.33
4
Method of Manufacture
No information on the method of manufacture for C. sinensis-derived cosmetic ingredients was discovered or
submitted. The methods below are general to the processing of C. sinensis for food or food ingredients and it is unknown if
they apply to cosmetic ingredients. The makeup of the C. sinensis extract will differ with the manufacturing process.
C. sinensis leaf in the form of green tea consists of whole or cut young, unfermented, rapidly heat-dried leaves.17,26
The fresh leaves are processed by a method designed to prevent the enzymatic oxidation of catechins. The enzymes are
inactivated by heat (pan-fried or steamed).
There are different harvesting and manufacturing processes for white, green, black and oolong teas for
drinking.17,19,26,34 White tea is made from very young leaves and leaf buds. Green tea is made from new, fully-formed leaves.
These two types of tea are minimally processed, steamed, and dried. Black tea and oolong tea are made from older, fully-
formed leaves. Oolong tea is withered, and rolled during “fermentation”, then fired and dried. Black tea is withered,
crushed, and rolled during “fermentation” then fired and dried. Phenolics content typically differs substantially between
green and black teas (Table 5).
Catechins are isolated through an initial hot water extraction with ethyl acetate, and then separation by
chromatography, followed by spray-drying.35 The spray-dried catechins may be recrystallized. Two other processes for the
extraction of catechins from C. sinensis leaves are conducted with or without enzymatic treatment with tannase. The initial
extract is further extracted with water and ethanol, and then filtered through multiple media. The product of the process
without tannase is sterilized above 100°C., whereas the product obtained with the tannase treatment is sterilized below
100°C.
The presence of minerals and elements in an extract depends on the extent of entrapment in the organic matrix, the
degree of solubility/choice of solvent, the duration of extraction, temperature, pH, and agitation.19 Most elements, especially
the metals, are complexed with the flavonols, catechols, tannins, and polyphenols.
The most widely used method for preparing Essential Oils from plants is associated with steam distillation.1 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 ingredients from the plant that are water
soluble. The water insoluble fraction from steam distilled plant materials is identified as "oil" in the International
Nomenclature of Cosmetic Ingredients (INCI) name. The water soluble fraction from the steam distilled plant material is
identified as "water" in the INCI name.
Impurities
No published data on impurities of these cosmetic ingredients were discovered and no unpublished data were
submitted. The information below applies to impurities found in C. sinensis as a food or as food ingredients.
In analyses of twelve C. sinensis catechins lots extracted as food ingredients, arsenic (< 0.2 ppm), cadmium (< 0.1
ppm), lead (, 0.4 ppm), and tin (not more than 150 ppm) were below levels of detection.31 Three lots of C. sinensis catechins
were analyzed for other components: caffeine (≤7%), organic acids (≤10%), protein and amino acids (≤10%), saccharide
(≤12%), fiber (≤1%), fat (≤1%), and ash (≤5%). No microbial contamination was detected.
Ten commercial C. sinensis teas for drinking were analyzed for metals.36 The ranges for metal content were: zinc
1.05 – 3.21 mg/kg; iron, 5.47 - 8.41 mg/kg; manganese, 1.27 – 2.73 mg/kg; copper, 0.01 – 0.93 mg/kg; nickel, 0.01 – 0.64
mg/kg; lead, 0.26 – 1.25 mg/kg; and cadmium, 0.01 – 0.05 mg/kg. The authors asserted that differences in content of the
samples were attributable to differences in geographic region of cultivation.
Aflatoxigenic molds and aflatoxins have been reported to be present on C. sinensis teas for drinking.37 In a
sampling of 27 commercial black teas (7 branded, 20 nonbranded), aflatoxigenic molds were detected in one branded and 6
unbranded (25.9%) tea samples. Only one of the samples (nonbranded) had detectable aflatoxins (19.2 µg/kg). In black teas
that had been spiked with aflatoxins, most of the aflatoxins residue was still present in the leaves after boiling in water, but
only 30.6% was present in the final beverage.
It was reported that levels of 712 – 1530, 166 – 280, 1.7 – 7.5, and 1.51 – 2.63 µg/g of aluminum, iron, chromium,
and lead, respectively, were found in commercial tea samples (n = 2) using electrothermal atomic absorption spectrometry
(ETAAS) and inductively coupled plasma atomic emission spectrometry (ICP-AES; Table 6).38 For two types of green tea,
the ranges were 605 – 620, 1486 – 1550, 4.5 – 4.7, and 2.20-2.34 µg/g, respectively. For infusions of these teas, the levels
for aluminum, iron, copper, and zinc were 149 – 367, 7.6 – 11.0, 0.7 – 3.2, and 36 - 50 µg/g, respectively. For green tea
infusions, these values were 124-127, 22 – 23, 0.2 – 0.5, and 31-32 µg/g, respectively.
USE
Cosmetic
Data on ingredient usage are provided to the Food and Drug Administration (FDA) Voluntary Cosmetic Registration
Program (VCRP; Table 7).39 A survey was conducted by the Personal Care Products Council (Council) of the maximum use
concentrations for these ingredients.40,41
Data were available from both the VCRP and the Council for the following ingredients:
• Camellia sinensis leaf extract was reported to be used in 1083 leave-on, 747 rinse-off, and 35 bath cosmetic
5
products.39 There are reported uses in every exposure type (Table 7). Usage of cosmetic ingredients called
“green tea” and “green tea extract” were also reported in the VCRP. Since these are technical names for
camellia sinensis leaf extract, the VCRP numbers for these three listings were combined. Camellia sinensis
leaf extract was reported to be use up to 2% in leave-on products (the highest concentrations in body and
hand products) and up to 1% in rinse-off products (the highest concentration in bath soaps and
detergents).40 It is also reported to be used in products diluted in the bath at up to 0.1% (the highest
concentration in bubble baths).
• Camellia sinensis leaf was reported to be used in 38 leave-on, 15 rinse-off, and 1 bath product.39 Camellia
sinensis leaf was reported to be used up to 0.05% in bubble baths.40 A previously reported product of tea
bags for the eyes at 97% is no longer sold.40,42
• Camellia sinensis leaf powder was reported to be used in 11 leave-on, 10 rinse-off products, and 1 bath
product.39 Camellia sinensis leaf powder was reported to be used up to 7% in leave-on and up to 0.01% in
rinse-off products (highest concentration in bath soaps and detergents).40 It is also used in a professional
face and neck product that is diluted before use at 50%.
• Camellia sinensis leaf water was reported to be used in 26 leave-on and 10 rinse-off products.43 Camellia
sinensis leaf water was reported to be used up to 30% in mascara.40
Data were available only on the frequency of use (VCRP) for the following ingredient; no concentration of use data
were reported by industry:
• Camellia sinensis leaf oil was reported to be used in 24 leave-on products and 9 rinse-off products.39
Data were available only on concentration of use for the following ingredient; uses were not reported in the VCRP:
• Camellia sinensis seed extract was reported to be used in leave-on products up to 0.1% (highest
concentration in moisturizing creams and lotions) and in rinse-off products up to 0.0013% (highest
concentration in bath soaps and detergents).40
There were no frequency of use or concentration of use data reported for:

• Camellia sinensis catechins
• Camellia sinensis flower extract
• Camellia sinensis flower/leaf/stem juice
• Camellia sinensis root extract
• Camellia sinensis seedcoat powder
• Camellia sinensis seed powder
• Hydrolyzed camellia sinensis leaf
• Hydrolyzed camellia sinensis seed extract
Non-Cosmetic
Tea, under the previous name Thea sinensis, is generally regarded as safe (GRAS) by the FDA. (21 CFR 582.20)
In Europe, C. sinensis preparations are used to treat asthenia and as an adjuvant treatment in weight loss/control.26
Preparations are also used in cutaneous treatment of external genital and perianal warts (condylomata acuminata) in immune-
compromised patients.26,44
In the United States, green tea products are used as dietary supplements, primarily for purported weight loss and
antioxidant properties.17,18,45-54 Other health benefits attributed to green tea include prevention and/or control of
atherosclerosis, hypertension, coronary heart disease, diabetes, metabolic syndrome, obesity, and cancer as well as
antibacterial, antiviral, antifungal, and neuroprotective effects.
Annual tea consumption varies from country to country, ranging from negligible to approximately 3 kg per person.55
Worldwide average consumption is approximately 0.5 kg per person.
In 2012, over 79 billion servings of tea were consumed in the United States (over 3.60 billion gallons).56 Of this,
Americans consumed approximately 84% black tea, 15% green tea, and the rest oolong and white tea.
TOXICOKINETICS
Absorption, Distribution, Metabolism, and Excretion
Dermal/Percutaneous
CAMELLIA SINENSIS CATECHINS
When camellia sinensis leaf extract (0.32, 0.68, 1.03, 1.35 mg/cm2 in methanol; as green tea) was applied to full
thickness pig ear skin using a Franz cell, there was a dose-dependent penetration of the catechins EGCG, EGC, and EC.57
Saturated solutions of camellia sinensis were formulated using water, polyethylene glycol 400, citrate/phosphate buffer (pH
5.5), and a 50:50 mixture of polyethylene glycol 400 and the buffer. The solutions were applied to drug-in-adhesive
6
transdermal patches under occlusion in methanol and applied to the pig skin. The receptor cell was sampled periodically for
48 h.
Penetration by the catechins was fastest in the buffer solution and slowest in polyethylene glycol 400 solution. In
the buffer solution, EGCG permeated the skin at 1.37 ± 0.40 and 1.88 ± 0.45 μg/cm2 at 24 and 48 h, EGC permeated at 0.189
± 4.10 x 10-2 and 0.342 ± 7.48 x 10-2 μg/cm2, EC permeated at 32.4 ± 11.3 and 71.2 ± 35.2 μg/cm2, respectively. In the mixed
solution, EGCG permeated the skin at 1.27 ± 0.38 and 1.62 ± 0.18 μg/cm2 at 24 and 48 h, EGC permeated at 0.128 ± 1.71 x
10-3 and 0.392 ± 0.004 μg/cm2, EC permeated at 22.2 ± 17.3 and 40.2 ± 43.8 μg/cm2, respectively. In polyethylene glycol
400solution, EGCG permeated the skin at 1.37 ± 0.40 and 1.88 ± 0.45 μg/cm2 at 24 and 48 h, EGC permeated at 0.189 ± 4.10
x 10-2 and 0.342 ± 7.48 x 10-2 μg/cm2, EC permeated at 32.4 ± 11.3 and 71.2 ± 35.2 μg/cm2, respectively. In water, EGCG
permeated the skin at 0.27 ± 0.15 and 0.66 ± 0.30 μg/cm2 at 24 and 48 h, EGC permeated at 0.06 ± 0.02 and 0.10 ± 0.03
μg/cm2, EC permeated at 1.32 ± 0.22 and 2.34 ± 0.34 μg/cm2, respectively.
Caffeine in the buffer solution permeated at 0.32 ± 0.05 and 0.49 ± 0.01 μg/cm2 at 24 and 48 h; 173 ± 24.6 and 368
± 52.9 μg/cm2 in the mixed solution; 46.8 ± 3.43 and 88.9 ± 0.08 μg/cm2 in the PEG-400 solution; and 28.4 ± 2.46 and 50.2 ±
1.54 μg/cm2 in water, respectively.57
When EGCG was dermally applied in a transdermal gel (50 mg/kg; 28.6 μg/cm2) to female SKH-1 mice (n = 4, 5, or
6), EGCG was detected in the skin, plasma, liver, small intestines, and colon for at least 24 h.58 The test material was
administered once. Over the next 24 h, blood was collected under anesthesia and dorsal skin was removed, fractioned into
epidermis and dermis, and analyzed. Liver, small intestine, and colon tissues were removed and analyzed.
In the total plasma, the C max was 44.5 ± 8.4 ng/mL, the t 1/2 was 94.4 ± 13.2 h, and the AUC 0→24 was 881.5 ± 123.4
ng/mL/h. The C max for the epidermis and dermis were 1365.7 ± 613.8 ng/mL and 411.2 ± 21.5 ng/mL, respectively; the
AUC 0→24 was 5978.3 ± 2779.9 and 1729.5 ± 259.4 ng/g/h, respectively. The t 1/2 was 9.3 ± 4.3 and 10.9 ± 1.6 h, respectively.
The C max of EGCG in the liver was 164.8 ± 83.0 ng/g with a t 1/2 of 74.6 ± 20.1 h and an AUC 0→24 2494.8 ± 673.6
ng/g/h. The C max in the small intestine was 203.1 ± 64.0 ng/g with a t 1/2 of 26.8 ± 5.6 h and an AUC 0→24 2802.8 ± 588.5
ng/g/h. The C max in the colon was 77.0 ± 22.4 ng/g with a t 1/2 of 21.3 ± 3.2 h and an AUC 0→24 715.0 ± 107.3 ng/g h. The
C max , t 1/2 , AUC 0→24 for EGCG in the urine were 177 ng/mL, 3427.9 ng/mL h, and 70.0 h, respectively.58
Antimicrobial Activity
CAMELLIA SINENSIS LEAF EXTRACT
The decaffeinated methanolic extract of the leaves of C. sinensis exhibited in-vitro antimicrobial properties against
111 bacteria comprising 2 genera of Gram-positive and 7 genera of Gram-negative bacteria.59 The extract was active in the
range of 10 - 50 μg/ml. A few strains were sensitive at lower concentrations (5 μg/ml). In decreasing order of sensitivity, the
bacterial groups were: Staphylococcus aureus, Vibrio cholerae, Escherichia coli, Shigella spp., Salmonella spp., Bacillus
spp., Klebsiella spp. and Pseudomonas aeruginosa.
When the above extract (30, 60 μg/mouse) was intraperitoneally administered to a Swiss strain of white mice (n =
20; control = 60), the mice were protected from a challenge of a medium lethal dose injection of S. typhimurium.59 In the
control group (no C. sinensis), 48 mice died. In the low-dose group, 4 mice died and no mice died in the high-dose group.
Dermal Effects
There was decreased healing time and no adverse effects in burned rabbits (n = 5) administered an aqueous camellia
sinensis leaf extract (100%; 0.05 mL) compared to controls.60 The rabbits were burned with a heated glass rod applied to
shaved skin, then the extract, antibiotic, or nothing was administered. The rabbits were observed for 5 weeks. The size of
the wounds decreased faster with the extract and the antibiotic compared to controls. Closure time for the treatment groups
was 8 – 10 days for antibiotics and 7 – 9 days for the extract. At five weeks, the wounds were almost healed in the treated
groups (0.25 ± 0.02 cm2) while the average size of the wound in the control group was 0.92 ± 0.15 cm2. Hair growth also
began sooner in both of the treated groups. Microscopic examination showed skin with a more normal appearance in the
camellia sinensis leaf extract group compared to the antibiotic and controls groups.
Anti-Inflammatory Effects
CAMELLIA SINENSIS EXTRACT
When saponins (0, 50, 100, 200 mg/kg) extracted from C. sinensis leaf were orally administered to rats prior to a
subcutaneous injection of carrageenan (1%; 0.5 mL) in a rat hind-paw edema assay, edema in response to carrageenan was
mitigated in a dose-dependent manner.61
Cytotoxicity and Cellular Effects

CAMELLIA SINENSIS EXTRACT
Camellia sinensis extract (10, 50, 100 μg/mL) was not cytotoxic to rat pheochromocytoma (PC12) cells when
exposed in vitro for 24 h.34 However, at higher concentrations (250, 500, 100 μg/mL), the extract was cytotoxic with < 40%
viability at the two highest concentrations. When the cells were incubated with the extract and hydrogen peroxide (250 μM),
7
hydrogen peroxide poisoning was mitigated by the extract at 5, 100, and 250 μM.
Camellia sinensis water extract (as Korean green tea) had a 50% inhibitory dose (ID 50 ) of 2.05% (0.28 mg/mL dry
matter) in the inhibition of protein synthesis in Sprague-Dawley rat hepatic cells.62 The 25% effective dose (ED 25 ) for lactate
dehydrogenase (LDH) release was 1.84% (0.25 mg/mL). Camellia sinensis extract (in the form of black tea) had an ID 50 of
2.50% (0.46 mg/mL) for protein synthesis and an ED 25 for LDH release of 5.11% (0.94 mg/mL).

In a 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl-tetrazolium bromide (MTT) test (n = 6), camellia sinensis leaf extract
(0, 0.00013%, 0.0006%, 0.0032%, 0.016%, 0.08%, 0.4%, 2%, and 10%) was cytotoxic at 2% and 10% to human
keratinocytes.63 Morphological modifications of the cells were observed at 0.4%. The test substance was a cold extract of
green tea using water/propylene glycol (10% dry plant material) prepared in the same manner as that used to prepare tea for
drinking.
When human keratinocytes were incubated in camellia sinensis leaf extract (0.05% and 0.1%) there was a 43%
protection against oxidation when the cells were exposed to UV radiation (312 nm; 160 mJ/cm2; time not provided).63
EGCG induced apoptosis at 400 and 800 μM in neonatal human dermal fibroblasts.64 At 200 μM EGCG, a decrease
in the proportion of cells in the S and G 2 /M phases of the cell cycle and an increase in the proportion of cells in the G 0 /G 1
phase was observed. Regulation of the expression of pNF-KB was concentration dependent but EGCG did not affect NF-KB
expression. cDNA microarray analysis revealed that EGCG (200 μM) down-regulated cell cycle-related genes. A/B cyclins
and cyclin-dependent kinase 1 was reversibly effected by EGCG (200 μM).
TOXICOLOGICAL STUDIES
The C. sinensis-derived ingredients in this safety assessment are from consumable sources and exposure to these
ingredients in beverages would result in much greater oral doses than those from oral exposures from the use of cosmetic
products. Consequently, their oral toxicity potential is not addressed in this report. Though data are presented on the
potential for reproductive toxicity, genotoxicity, and carcinogenicity, the focus in this report is primarily on the potential for
irritation and sensitization.
Acute Toxicity
Oral – Non-Human
When camellia sinensis leaf extract (2 g/kg; 1.94 mL/kg) was orally administered to Sprague-Dawley (SPF) rats (n =
5/sex), it was concluded that the minimum lethal dose is > 2 g/kg.65 The test substance was administered after 16 h on a
hydric diet. After administration, the rats were observed for 6 h for clinical signs and then followed for 14 days. There were
no effects on weight gains and there were no mortalities. Necropsy was unremarkable. The test substance was a cold extract
of green tea using water/propylene glycol (10% dry plant material) and prepared in the same manner as that used to prepare
tea for drinking.
The above experiment was repeated with an extract of black tea (2 g) provided to the laboratory as a brown powder
with the same conclusion.66 Decreased motility and ptosis of the eyelids was observed in all rats 1 h after administration.
Necropsies were unremarkable.
The oral LD 50 of a Chinese tea extract (0.85% solids) was >2000 mg/kg for mice.67
The oral LD 50 of a green tea extract (1.6% solids) was >2000 mL/kg for rats.67
The oral LD 50 of a oolong tea extract (1.0% solids) was >2000 mg/kg for mice.67
Dermal – Non-Human
The dermal LD 50 of EGCG (2000 mg/kg extract; 1860 mg EGCG/kg; 4 mL/kg) was > 1860 mg/kg for
HanBrl:WIST (SPF) rats (n = 5/sex).35 The acute dermal toxicity test was conducted in accordance with the Organization for
Economic Co-operation and Development (OECD) guideline number 402 under semi occlusion. The day before the study,
the backs of the rats were clipped with an electric clipper exposing approximately 10% of the total body surface. The
dressing covering the test site was removed at 24 h and flushed with lukewarm tap water and dried. The rats were observed
twice daily for 15 days. Macroscopic examination of all animals was performed at day 15.
There were no signs of systemic toxicity in any of the rats. A slight to moderate erythema was observed in all
treated rats after removal of the dressing, which persisted for up to 5 days. Body weights were within standard range for this
strain and age of rat. No abnormal macroscopic findings were observed at necropsy.35
8
Repeated Dose Toxicity
Inhalation - Human
There were no adverse effects, such as respiratory tract obstruction, allergic bronchial spasm, or skin eruption,
including laboratory changes observed when subjects suffering from cerebrovascular diseases (n = 36) inhaled catechins (3.7
mg/mL in saline; 2 mL; 43% of catechins composed of EGCG) or the vehicle (n = 33) three times/day for 7 days.68 The test
substance was delivered by a handheld nebulizer. The sputum of the subjects all tested positive for methicillin-resistant
Staphylococcus aureus (MRSA). Total catechin content was 73.0% (31% (-)-EGCG, 21% (-)-EGC, 8.6% (-)-EC, 8.6% (-)-
ECG, 2.9% (-)-GCG, and 0.8% (-)-CG.
No adverse effects were observed when tea catechins extract (10 or 20 mg/mL in saline; 2 mL; ≥ 30% tea
polyphenol and ≥10% EGCG; assumed to be C. sinensis) were inhaled using a nebulizer by subjects (n = 26) being treated
for MRSA three times per day for 79 days.69
No adverse effects were observed when tea catechins extract (10 or 20 mg/mL in saline; 2 mL; ≥ 38% tea
polyphenol and ≥14% EGCG; assumed to be C. sinensis) were inhaled using a nebulizer by subjects (n = 26) being treated
for MRSA three times per day for 79 days.70
REPRODUCTIVE AND DEVELOPMENTAL TOXICITY

There were no adverse effects when pregnant Wistar rats (n = 6) were orally administered camellia sinensis extract
(0, 84, 167, 501, and 1336 mg/mL/d; in the form of black tea).71 The caffeine content was 4.14% (865 mg for the highest
dose). The test material was administered either on gestation days 1 – 7, 8 – 14, or 15 – 21. Internal examinations of the
dams were conducted by laparoscopy under anesthesia on gestation day10 (early dose groups) or 15 (mid dose groups). Pups
were examined daily until the appearance of hair and the opening of the eyelids. The test doses were calculated to be
equivalent to 1.5, 3, 9, and 24 cups of tea. There were no mortalities. There were no differences in number of pregnancies,
number of uterine implants, number of viable implants, implantation index, pre-implantation loss, post-implantation loss,
gestation index, number of pups born, litter index, live birth index, and viability index compared to controls. There were no
differences in length of the implants/fetus, gestation duration, cranial length, cranial diameter, and tail length of pups. There
were no differences in time taken to open eyes, eruption of incisors and appearance of fur. There were no gross
morphological birth abnormalities observed.

Unpublished studies were submitted to the FDA for the approval of a topical ointment as a drug that contains up to
15% camellia sinensis catechins to treat warts.72 These studies are summarized in Table 8. In oral studies, there were
increased resorptions at 1000 mg/kg/d in rats. In subcutaneous studies, the test substance was not well tolerated;
subcutaneous lesions with necrosis developed. There were spontaneous abortions, increased resorptions, and increased fetal
malformations at doses as low as 12 mg/kg/d. Intravaginal administrations up to 0.15 ml/d yielded fewer adverse effects.
When camellia sinensis catechins (1400, 4200, 14000 ppm in feed; EGCG 90%, ECG ≤3.01%, GCG ≤0.12%, other
catechins ≤0.54%) were administered to pregnant Wistar (SPF) rats (n = 25) on gestation days 6 - 20, there were no adverse
effects observed.73 All rats survived treatment and there were no clinical signs. There was a transient reduction in feed
consumption in the high-dose group and an increase in water consumption in the mid- and high-dose groups. There were no
treatment-related macroscopic findings in the dams. There was no effect to embryo/fetal survival, fetal weights, or sex ratios.
In a two generation study of camellia sinensis catechins (1200, 3600, 12000 ppm in feed) using Sprague-Dawley rats
(n = 30/sex), there were no adverse effects in either generation. The rats were treated for 10 weeks and then paired for
mating. The diet continued through gestation until after weaning. The dams were killed and necropsied after weaning. The
pups were culled to 25/sex and the above treatment repeated with mating taking place after 8 weeks.
The offspring of the high-dose group had decreased growth rates, and there was an increase in pup loss. A growth
effect among pups was also observed at 3600 ppm, but only in the second generation. Both sexes of the F 1 generation in the
high-dose group showed decreased absolute kidney and liver weights. The F 1 males had decreased spleen and prostate
weights, but the females’ spleens were normal. Histological examination revealed no abnormalities. The lowest dose was
considered the overall NOAEL. The authors derived a NOAEL of 200 mg/kg body weight per day EGCG preparation.
Because dams consumed twice the amount of feed during the crucial lactation period, during which effects occurred, twice
the lowest dose (i.e., 2 x 100 mg/kg/d) was estimated to be the NOAEL.73
GENOTOXICITY
Catechins were not genotoxic in multiple in vitro and in vivo assays including Ames tests (up to 5000 µg/plate),
mouse micronucleus assays (up to 2000 mg/kg), and micronucleus assays. A polyphenol mixture was lethal at 2000 mg/kg/d
to mice. Mixed results were reported in a mouse lymphoma assay at concentrations > 100 µg/mL (Table 9).67,72,74-76
9
CARCINOGENICITY
In 1997, the International Agency of Research in Cancer (IARC) listed green tea in group 3, meaning that it is not
classifiable according to its carcinogenicity to humans.55
Camellia sinensis extract (125, 250, 500 mg/kg/d; as green tea; 85% - 95% catechins w/w, 55% EGCG) did not
increase the incidence of neoplastic or non-neoplastic lesions in the organs and tissues of p53 transgenic heterozygous mice
(n = 25).72 The mice were treated by gavage daily for 26 weeks. p-Cresidine and water served as controls.
Anti-Carcinogenicty
The catechins in C. sinensis, especially EGCG, have been shown to have preventive and treatment effects in cancer
cell lines related to cancers of the prostate, lung, skin, pancreas, breast, and ovaries.18
In a population-based case-control study of residents of southern Arizona (n = 404, males = 238, females = 166;
mean age 66.6 ± 10), subjects who consumed black tea within the last year had fewer instances of squamous cell carcinoma
(SCC) of the skin (odds ratio 0.60) than controls, residents of Tucson, (n = 391, males = 226, females = 165; average age
66.2 ± 11.1 y).77 Arizona was chosen because it has one of the highest risks of skin SCC worldwide. Variables were
controlled for tanning ability, antioxidant intake, education, gender, smoking, and average sun exposure.
When female SKH-l mice (n = 28, 29) were orally administered C. sinensis as lyophilized green tea (0.3%, 0.9%; 3,
9 mg of tea solids/mL) in place of drinking water and exposed to UVB (30 mJ/cm2) twice per week for 35 weeks, there was a
decrease in the number of tumors per mouse by 35% and 94%, respectively, compared to controls exposed to UVB without
C. sinensis treatment.78 The tumor volume per mouse was decreased by 49% and 97%, respectively. The composition of the
green tea polyphenol fraction was: (-)-epigallocatechin gallate (49.5%), (-)-epigallocatechin (11.5%), (-)-epicatechin gallate
(11.4%), caffeine (7.6%), (-)-epicatechin (6.1%), (+)-catechin (0.5%), and gallic acid (0.4%).
When female SKH-1 mice (n = 29) were orally administered C. sinensis (as green tea for their drinking water; 1.25
g steeped in100 mL hot water; ~4 mg tea solids/mL) UVB-induced complete carcinogenesis was inhibited. This was not the
case with decaffeinated green tea. The C. sinensis extract was administered for 2 weeks before and concurrently with twice
per week treatment with enhanced UVB (280-320 nm; 75% - 80% total energy; 30 mJ/cm2 for 25 – 30 s) exposure. There
were increases in apoptosis in the epidermis observed, but no effect in non-UVB treated normal epidermis. The authors
concluded that administration of green tea and caffeine may inhibit UVB-induced carcinogenesis, at least in part, by
enhancing UVB-induced apoptosis.
Oral administration of C. sinensis (1.25% as green or black tea leaf extract; 1.25 g of tea leaf steeped in100 mL
water; 4.0 or 4.4 mg tea solids/ml) as the drinking water to the UVB-treated mice decreased the number of tumors per mouse
by 51% and 41%, respectively. Tumor volume/mouse was decreased by 79% and 70%, respectively. The mice were treated
with gradually increasing doses of the test substances for 2 weeks before the start of the twice/week treatment with UVB for
40 weeks. The mice were killed 4 weeks after the end of the UVB administration. Decaffeinated green or black C. sinensis
leaf extracts (1.25%) containing 3.6 or 3.9 mg of tea solids/mL, respectively, were less effective than regular green or black
tea extracts, and decaffeinated black tea was less effective than decaffeinated green tea at inhibiting the formation of skin
tumors. Adding 0.36 mg of caffeine/mL to the decaffeinated extracts either fully or partially restored the inhibitory effects on
UVB-induced tumorigenesis.78
IRRITATION AND SENSITIZATION

Irritation
When camellia sinensis leaf extract (100%; 0.5 mL) was dermally administered to the clipped skin of albino New
Zealand rabbits (n = 3), there were no signs of irritation.79 The test substance was a cold extract of green tea using
water/propylene glycol (10% dry plant material) and prepared in the same manner as that used to prepare tea for drinking. It
was provided to the laboratory as a brown liquid. The test substance was applied to a 2.5-cm2 gauze pad, which was then
kept in contact with the skin for 24 h using hypoallergenic adhesive tape. The test site was examined within 1 h of removal
and at 24 and 72 h after removal.
The above experiment was repeated as stated with an extract of black tea (0.5 g), provided to the laboratory as a
brown powder, with a conclusion that the test substance was a slight irritant.80 A slight to definite erythema was observed on
all treated rabbits. Cutaneous dryness and a slight decrease in skin suppleness were observed. The test sites were observed
at 1, 25, and 72 h after removing the pad.
Chinese tea extract (10%, 100%; 0.85% solids) was negative for dermal irritation in rabbits.67 No further details
were provided.
Green tea extract (100%; 1.6% solids) was negative for dermal irritation in rabbits.67 No further details were
provided.
Oolong tea extract (10%, 100%; 1.0% solids) was negative for dermal irritation in rabbits.67 No further details were
provided.
10
There were no signs of irritation when EGCG (0.47 g in 3 ml distilled water) was administered to the clipped flanks
of male New Zealand White rabbits (n = 3) for 4 h under semi-occluded patch.35 The tests were conducted according to the
EC Commission Directive 92/69/EEC, B.4, ‘‘Acute Toxicity—Skin Irritation’’ and OECD guideline number 404 (1992).
The dorsal fur of three male rabbits was removed with electric clippers 24 h before the administration of the test material.
Each rabbit was treated with 0.5 g of EGCG preparation (93.4% EGCG) dissolved in 0.3 ml distilled water and applied to the
skin of one flank using a semi-occlusive patch. After removing the patch, the skin was cleaned with water. Skin reactions
and irritation effects were assessed at approximately 1, 24, 48 and 72 h after patch removal. Adjacent areas of untreated skin
from each animal served as controls. There were no signs of toxicity observed.
In a preliminary study for a guinea pig maximization test, an intradermal injection of 0.09% EGCG was found to be
the greatest tolerable dose.35 A grade 3 erythema was produced, but not necrosis. At 48 h of dermal exposure, there was no
reaction in the preliminary test at concentrations up to 50%.
Dermal – Human
When C. sinensis preparations (DER ranging from 1/1000 - ≥1/10; 0.1% - >10%) were used in dermal applications
of ointments(compositions not provided) to treat genital warts, the following were among the adverse effects: erythema,
pruritus, irritation/burning, pain, ulcer, edema, induration, and vesicles.26 A full list of reported effects is provided in Table
10.
A black tea extract (100%; 1.0% solids) was negative in a patch test (n = 100). No further details were provided.67

In a trial of an ointment containing camellia sinensis catechins (10% and 15%) for the treatment of anogenital warts,
there was no irritation or other adverse effects, reported.81 The ointment was administered three times per day for up to 16
weeks. No adverse effects were reported during treatment, or during the 12-week follow-up, and the ointment was reported
to be well tolerated.
CAMELLIA SINENSIS LEAF WATER

In a patch test (n = 10) of a mascara containing camellia sinensis leaf water (30%), there were no signs of irritation
at 30 min, and 24 and 48 h after the removing the patch.82 The test substance was administered to the inner side of the upper
arm for 24 h.
Mucosal – Non-Human
Intravaginal administration of an ointment containing camellia sinensis catechins (15%) to pregnant SD rats (n = 25)
from gestation day 6 to the end of lactation caused ulceration and erosion of the vaginal mucosa with inflammation for the
duration of treatment.72 The control group (no catechins) did not exhibit damage to the vaginal mucosa. The effects resolved
when treatment stopped.
Ocular
Camellia sinensis leaf extract (100%; 0.1 mL) administered to the lower conjuctival sac of the right eye of albino
New Zealand rabbits (n = 3) was a slight ocular irritant.83 There was slight irritation of the conjuctiva at 1 h; there were no
iris lesions. Two rabbits had a very slight superficial epithelial attack of the cornea. All signs of irritation were resolved
within 24 h. The test substance was a cold extract of green tea using water/propylene glycol (10% dry plant material) and
prepared in the same manner as that used to prepare tea for drinking. It was provided to the laboratory as a brown liquid.
The eyes were examined 1 h after instillation and 1, 2, and 3 days later.
The above experiment was repeated with an extract of black tea (0.1 g), provided to the laboratory as a brown
powder, with the same conclusion.84 There was a slight irritation of the conjuctiva observed at 1h; there were no lesions of
the iris. All rabbits had a slight epithelial attack of the cornea. All signs of irritation were resolved within 48 h.
Green tea extract100% 1.6% solids) was not irritating to the eyes of rabbits. No further information was provided.

The administration of EGCG preparation (0.093 g EGCG; 0.1 g total) into the eye of a single female New Zealand
White rabbit resulted in moderate to severe irritation including reddened conjunctivae and sclera, discharge and chemosis.35
A slight to moderate corneal opacity affecting the whole area of the cornea was observed up to 72 h after administration of
the test material. No damage to the iris, and no corrosion or staining of the eye by EGCG was observed throughout this
study. The test was done in compliance with OECD guideline number 405. Both eyes of the rabbits were examined at the
beginning of the study. The lids were briefly held together after administration; the eyes were not rinsed. The animal was
11
observed for ocular irritancy for 17 days. Because EGCG was suspected to be an ocular irritant, a single animal was treated
first and observed to recovery. Based on the results from this preliminary study, no additional rabbits were tested.
Sensitization
Oolong tea extract (; 1.0% solids) was not sensitizing to guinea pigs (n not provided).67 First induction was at 50%;
second induction was at 25%. Challenge was at 5% and 10%. No further details were provided.
International Fragrance Association (IFRA) reported that in a local lymph node assay (LLNA) reported an EC 3 of >
1250 µg/cm2 for camellia sinensis leaf extract (as tea leaf absolute).85 Irritation was observed at higher concentrations (not
provided) so the actual EC 3 could not be calculated.

In a sensitization assay using female GOHI (SPF) guinea pigs (n = 6), camellia sinensis catechins (5%, 10%, 30% in
ethanol; 100 µL/8 cm2; 4%, 8%, 24% EGCG) was sensitizing at challenge (1%, 3%, 5%, and 10%) as well as at a second
challenge (0.1%, 0.5%, 1%, 3%, 5% and 10%) two weeks later.35 The skin sensitization assay was performed using a
procedure adopted from OECD guideline number 406 (OECD, 1992b). During the induction phase of the assay, an EGCG
preparation (80% EGCG) was applied to the shaved right flanks of the guinea pigs 5 days/week for 4 weeks. Control animals
were treated with ethanol. Treatment sites were left open between applications. During induction, new treatment sites were
chosen whenever the irritation became considerable. Immediately following the induction period, the guinea pigs were
challenged with EGCG (25 µL/2 cm2 on the left flank). During the induction period the guinea pigs were observed for signs
of erythema and edema on each test site. Challenge reactions were assessed at 24 and 48 h after application.
Irritation responses increased throughout the induction period starting with the fifth application; the 30% group had
the greatest frequency of reactions. Erythema became evident in the 10% and 5% groups after the 13th and 16th
administrations, respectively. In the 10% group, a slight erythema was observed in 2/6 guinea pigs after the 13th application,
with all guinea pigs showing similar signs by the 16th application. For the 5% group, erythema was observed only for 3 days
in 1/6 guinea pigs. Both EGCG preparations elicited positive effects in the test groups during the challenges.
Control animals showed no response after the first challenge; one or two of the six control guinea pigs had slight or
well defined erythema after the second challenge with 0.8% or higher EGCG. Although there was a positive dose–response
effect for the challenge, it did not clearly correlate to the induction doses. There were a greater number of reactions in the 5%
induction group (6 at 24h, 5 at 48 h) than in the 30% induction group (2 at 24 h, 1 at 48 h). No mortalities or symptoms of
systemic toxicity were observed in any of the guinea pigs, and body weights of the test animals were in the same range as
those of the controls during the study period.35
In a maximization test using female Himalayan strain albino guinea pigs (n = 10; control n = 5), camellia sinensis
catechins (0.1% in distilled water; 0.1 ml; 90% EGCG) was a sensitizer.35 All guinea pigs had grade 3 or 4 erythema
following challenge by dermal administration of the test material (50%; 0.15 mL). Grade 1 erythema was observed following
the first test challenge in 3/10 in the test group and 0/5 in the control group. In a second challenge 1 week later, 9/10 in the
test group showed stronger (grade 2) erythema. No mortalities or signs of systemic toxicity were observed in any of the
guinea pigs and body weights of the test group were in the same range as those of the controls during the study period.
Dermal – Human
A facial line filler treatment product containing camellia sinensis leaf extract (0.86%; 150 µL; black tea) was not
irritating or sensitizing in an HRIPT (n = 101).86,87 The test substance was administered nine times on a 2 x 2 cm absorbent
pad under occlusion. No reactions were observed in any of the 106 to complete the induction phase. No reactions were
observed in any of the 101 to complete the challenge phase.
An eye cream containing camellia sinensis leaf extract (0.86%; black tea) was not irritating or sensitizing in an
HRIPT (n = 638). The test substance was administered under occlusion.87,88
A black tea extract (100%; 1.0% solids) was negative in a HRIPT (n = 100). No further details were provided.67
Camellia sinensis leaf extract (as tea leaf absolute) was reported to have a no observed effect level (NOEL) of 480
µg/cm2.85
CAMELLIA SINENSIS LEAF WATER

In an HRIPT (n = 110) of a mascara containing camellia sinensis leaf water (30%), there were no signs of irritation
or sensitization.89
Phototoxicity
There were no signs of erythema on treated sites on the forearms of subjects (n = 6) treated with camellia sinensis
12
leaf extracts (10%; in the form of green or black tea) then exposed to UVA, B, and C.90 Freeze-dried green and black tea
extracts were used to make gels with 1% carbomer solution and sodium hydroxide. These were administered to a 4 cm2 area.
The controls were an untreated area and an area treated with just the gel. The arms were then exposed to UVA/UVB/UVC
(UVA 4550 µW/cm2; UVB = 2800 µW/cm2; UVC = 500 µW/cm2) for 2.5 min. Erythema was observed in the control and
carbomer treated sites but not the treatment sites.
Photo Effects
A sunscreen containing various concentrations of camellia sinensis leaf extract (0, 2%, 3%, 4%, 5%; in the form of
green tea) protected against photoaging and photoimmunology-related biological measurements in female human subjects (n
= 20); especially at 3%.33 The melanoma index decreased in a dose-dependent manner until 4%; effectiveness decreased at
4% and 5%. The same pattern was observed for the thickness of the stratum cornium and total epidermis measurements.
Cytokeratins CK5/6, CK16 were overexpressed on the site irradiated with or without the base cream; the decreased effect
followed the same pattern as the other markers. Matrix metalloproteinases MMP-2 and MMP-9 were slightly to moderately
expressed on unirradiated skin. Expression of MMP-2 and MMP-9 was decreased on the 2%, 3%, and 4% sites.
The sunscreen was applied 30 min before each irradiation (290–400nm) at 1.5 x each individual’s minimal
erythemal dose (MED) and 6, 24, and 48 h after the last irradiation. The subjects’ backs were irradiated on four consecutive
days (duration of treatment was not provided). The MED of the subjects ranged from 25 to 40 mJ/cm2, with an average of
32.46mJ/cm2. Punch biopsies were obtained from all the seven sites 72 h after the last UVR exposure and analyzed.
Standardized photographs were taken with a digital camera before each procedure and at the follow-up examinations.33

Topical treatment with green tea polyphenols (3 mg/2.5 cm2 in acetone) on human skin decreased the UVB
induction of cyclobutane pyrimidine dimer formation and erythema in a dose-dependent manner.91 The polyphenols
consisted of EC at 6%, EGC at 5%, EGCG at 65%, and ECG at 24%. Green tea polyphenols were administered to the
buttocks of Caucasian subjects (n = 6) 20 min before the skin was exposed to 0.5%, 1.0%, 2.0%, or 4.0% of the previously
established minimal erythema dose. The test sites were examined and skin punch biopsies taken 24 h after UVB treatment.
Cyclobutane pyrimidine dimers and erythema were decreased in the treated sites exposed to 1.0%, 2.0, and 4.0% of a
minimal erythema dose of UVB in a dose-dependent manner.
Metalloproteinase activity in cultured fibroblasts and keratinocytes decreased when incubated in EGCG (0.01, 0.1
μM in propylene glycol:ethanol 3:7) for 24 h before exposure to UVA radiation.92 This indicated possible protection of the
cells by EGCG from oxidative stress from UVA exposure. An artificial skin was prepared using human keratinocytes and
dermal fibroblasts on a lattice of bovine type I collagen. The skin was incubated in EGCG for 24 h and washed. The skin
was exposed to UVA (340 – 400 nm; 20 J/cm2; duration not provided) 6 h later. Supernatant was collected 24 h after
irradiation and analyzed.
The dermal administration of either EGCG (1 mg/cm2 in a hydrophilic ointment ; >98% pure) or green tea catechins
(0.2% in a hydrophilic ointment ; > 86% catechins) to female SKH-1 hairless mice (n = not provided) prevented single and
multiple UV (180 mJ/cm2) exposure-induced depletion of catalase activity and prevented the depletion of antioxidant
enzymes (e.g., glutathione peroxidase, catalase, and glutathione).93 Treatment also inhibited UVB-induced oxidative stress
when measured in terms of lipid peroxidation and protein oxidation. The test substances were administered to the backs of
the mice either once or daily for 10 consecutive days prior to UVB (290 – 320 nm) and UVA exposure. The mice were killed
24 h after the last UV exposure and the skin was biopsied. The green tea catechins were composed of: EC, 10.4%; EGC,
8.3%; EGCG, 55.8%; GCG, 4.4%; and ECG, 6.9%.
Female SKH-1 hairless mice were administered green tea catechins (0.2% in drinking water) for 10 days before and
during UV exposure as described above. Treatment with green tea catechins prevented single or multiple UVB irradiation-
induced depletion of antioxidant enzymes, oxidative stress, and phosphorylation of proteins. However, the photoprotective
efficacy was less than that of topical treatments of EGCG and green tea catechins. The authors stated that this may be due to
less bioavailability in skin target cells.93
Green tea catechins at 70 and 140 mg/L were reported to protect human retinal pigment epithelial (RPE) cells, in
vitro, from the cytotoxic effects of UVB radiation.94 The protective effect observed at these concentrations was suggested to
be the result of the attenuation of the UVB-induced suppression of survivin gene expression and resultant suppression of
mitochondrion-mediated apoptosis. However, 700 and 1400 mg/L appeared to have a toxic rather than protective effect on
the UVB-irradiated cells. RPE cells were treated with green tea catechins for 2 h before or after exposure to UVB (100
µw/cm2) for 2 h. Viability of UVB-irradiated RPE cells decreased by 49.2% compared with unirradiated controls. The
protective effects of catechin pretreatment were more effective than post-treatment. Viability of RPE cells was assessed by
3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Survivin gene expression was examined by
real-time PCR analysis. Ultrastructure of RPE cells was examined by transmission electron microscopy. The composition of
the catechins was: GC, 44.38; EGC, 85.47; C 14.09; EGCG, 344.73; GCG, 42.49; ECG 103.37; CG 8.80 mg/g.
13
CLINICAL USE
Case Studies
A 51-year-old man was diagnosed with hypersensitivity pneumonitis (HP) after undergoing catechin inhalation
therapy for 1 month.95 The diagnosis was based on the clinical course, bronchoscopy, and a challenge test. The subject was
being treated for tuberculosis and had been administered the catechin inhalation therapy when MRSA was observed in his
sputum. He was administered catechin-rich green tea extract solution (2 mL) dissolved in distilled water (50 mg/ml) once or
twice daily using a handheld nebulizer. There were no initial symptoms, but the subject later noticed that he coughed
frequently during and after inhalation of the extract.
OTHER ASSESSMENTS
An IFRA standard for tea leaf absolute (aka camellia sinensis leaf extract; CAS no. 84650-60-2) had the following
restrictions for use: lip products, 0.01%; deodorants/antiperspirants, 0.02%; hydroalcoholics for shaved skin, 0.07%;
hydroalcoholics for unshaved skin, 0.2%; hand cream, 0.1%; mouthwash, 0.3%; intimate wipes, 0.04%; hair styling aids,
0.5%; and rinse-off hair conditioners, 2.4%.85 Based on animal data, green tea absolute was determined to be a moderate
sensitizer. These limits were derived from the application of the exposure-based quantitative risk assessment approach for
fragrance ingredients; a dose of 480 J.µg/cm2 was the weight of evidence (WoE) no expected sensitization level (NESIL)
used to develop the IFRA standard based on a QRA for sensitization.
In a safety assessment of C. sinensis as green tea used in dietary supplement products, the U.S. Pharmacopeia
Dietary Supplement Information Expert Committee concluded that when supplements containing concentrated green tea
extracts are used and formulated appropriately, there are no significant safety issues with the caveat that a caution statement
be included in the labeling section.96 The caution statement warns of the potential of liver damage when concentrated green
tea supplements are consumed on an empty stomach. This does not apply to C. sinensis as a beverage.
There are several reviews regarding the protective effects of green tea extracts and its catechins, especially EGCG,
against chemical carcinogens.47,97-100
According to Yang et al.98, there are more than 133 studies published from 1991 to 2008 on the effectiveness of C.
sinensis on cancers (Table 11). Inhibitory effects of tea and/or tea constituents on lung, oral, stomach, intestine, dermal,
prostrate, breast, liver, bladder, pancreas, and thyroid cancers were found.
SUMMARY
This is a safety assessment of Camellia sinensis (tea)-derived cosmetic ingredients. These ingredients function
mostly as antioxidants and skin-conditioning agents – miscellaneous. Because tea leaves are ingested in food and drink, this
safety assessment does not address systemic toxicity but is primarily focused on the potential for irritation and sensitization.
The constituents of C. sinensis include amino acids, carotenoids, catechins, enzymes, flavonoids (including
flavanols and flavonols), and glycosides. The concentrations of these constituents in plant parts is influenced by growing
conditions, geographical location, soil conditions, and processing.
Camellia sinensis leaf extract was reported to be used in 1083 leave-on, 747 rinse-off, and 35 bath cosmetic
products; it was used up to 3% in leave-on products, 1% in rinse-off products, and up to 0.1% in bath products. Camellia
sinensis leaf was reported to be used in 38 leave-on, 15 rinse-off, and 1 bath product; it was used up 0.05% in bubble baths.
Camellia sinensis leaf powder was reported to be used in 11 leave-on and 10 rinse-off products; it was used up to 7% in
leave-on products, up to 50% in a professional product that is diluted before use, and up to 0.01% in rinse-off products.
Camellia sinensis leaf water was reported to be used in 26 leave-on and 10 rinse-off products; it was used up to 30% in
mascara. Camellia sinensis leaf oil was reported to be used in 24 leave-on products and 9 rinse-off products. Camellia
sinensis seed extract was reported to be used in leave-on products up to 0.1% and in rinse-off products up to 0.0013%. There
are no reported uses or concentrations of use for the rest of the ingredients.
The FDA considers C. sinensis to be GRAS for use as a food additive.
Catechins from camellia sinensis leaf extract penetrated pig ear skin as did caffeine. EGCG penetrated mouse skin.
Camellia sinensis leaf extract exhibited antimicrobial properties towards multiple bacterial species and wound-
healing properties.
Camellia sinensis extract was not cytotoxic to rat pheochromocytoma cells up to 100 μg/mL but induced apoptosis
to neonatal human dermal fibroblasts at 400 and 800 μmol/L.
The oral LD 50 for rats was > 2 g/kg for camellia sinensis leaf extract as both green and black tea. The dermal LD 50
of EGCG was > 1860 mg/kg for rats. There was slight to moderate erythema observed.
There were no adverse effects when up to 20 mg/mL tea catechins (assumed to be C. sinensis) were inhaled for up to
79 days by human subjects.
Reproduction and developmental studies of an ointment that contained up to 15% camellia sinensis catechins were
conducted using rats. In oral studies, there were increased resorptions at 1000 mg/k/d in rats. In subcutaneous studies, the
test substance was not well tolerated; subcutaneous lesions with necrosis developed. There were spontaneous abortions,
increased resorptions, and increased fetal malformation as low as 12 mg/kg/d. Intravaginal administration up to 0.15 mL/d
had fewer adverse effects.
14
Camellia sinensis extract had no adverse effects when orally administered to pregnant rats up to 1336 mg/mL/d in
drinking water. In a two-generation study, camellia sinensis catechins up to 12000 ppm in feed caused no clinical signs and
no effects to embryo/fetal survival, fetal weights, or sex ratios. The offspring of the high-dose group had decreased growth
rates, and there was an increase in pup loss. While there were some decreased organ weights, histological examination
revealed no abnormalities. The NOAEL was 200 mg/kg/d EGCG.
Catechins were not mutagenic in multiple in vitro and in vivo assays including Ames test (up to 5000 µg/plate),
mouse micronucleus assays (up to 2000 mg/kg), and micronucleus assays. A polyphenol mixture was lethal at 2000 mg/kg/d
to mice. Mixed results were reported in a mouse lymphoma assay at concentrations > 100 µg/mL.
Camellia sinensis extract at 500 mg/kg/d was not carcinogenic to p53 mice after 26 weeks.
Camellia sinensis leaf extracts, that contained 10% dry green or black tea, were not dermally irritating to rabbits.
Camellia sinensis leaf extract at 100% caused no adverse effect to the skin of burned rabbits. Camellia sinensis catechins
were not irritating to rabbits with intact skin at 0.47 g.
There were no adverse effects in a human patch test of mascara containing camellia sinensis leaf water at 30%.
There were no adverse effects in a trial of an ointment containing camellia sinensis catechins at 10% and 15%.
C. sinensis preparations with > 10% plant material caused erythema, pruritus, irritation/burning, pain, ulcer, edema,
induration, and vesicles in human dermal tests.
The intravaginal administration of an ointment containing camellia sinensis catechins at 15% caused ulceration and
erosion of the vaginal mucosa with inflammation for four weeks in rats.
Camellia sinensis leaf extracts from green or black tea were slight ocular irritants. The administration of a
preparation containing 0.093% EGCG into the eye of a single rabbit resulted in moderate to severe irritation including
reddened conjunctivae and sclera, discharge and chemosis.
Camellia sinensis catechins were sensitizing to guinea pigs at 5%. In another guinea pig test, camellia sinensis
catechins was a sensitizer at 0.1%.
Camellia sinensis leaf extract was not irritating or sensitizing in two HIRPTs conducted on two cosmetic products
that contain this ingredient at 0.86%. A black tea extract was negative in a HRIPT at 100% (1% solids). In an HRIPT of a
mascara product containing camellia sinensis leaf water at 30%, there were no signs of irritation or sensitization
There was no sign of erythema at treatment sites on the forearms of subjects treated with 10% camellia sinensis leaf
extract in the form of green or black tea then exposed to UVA and B. Topical treatment with green tea polyphenols at 3
mg/2.5 cm2 to human skin decreased the UVB induction of cyclobutane pyrimidine dimer formation and erythema in a dose-
dependent manner. Metalloproteinase activity in cultured fibroblasts and keratinocytes decreased when incubated in EGCG
at 0.01 and 0.1 μM for 24 h before exposure to UVA radiation. Multiple in vitro and in vivo studies demonstrated UV-
protective effects of camellia sinensis catechins.
DISCUSSION
Tea, under the previous name Thea sinensis, is a GRAS substance for food. The C. sinensis-derived leaf ingredients
in this safety assessment are consumed in beverages and exposure to these ingredients in beverages would result in much
greater oral doses than exposures from use of cosmetic products. Consequently, their oral toxicity potential is not addressed
in this report. Though data are presented on the potential for reproductive toxicity, genotoxicity, and carcinogenicity, the
focus of the Panel was primarily on the potential for irritation and sensitization for the leaf-derived ingredients.
Linalool and several compounds containing linalool have been reported in the leaves ranging from 6 to 1984 ppm
and in the leaf essential oil ranging from 31800 to 198 400 ppm in C. sinensis plants. Linalool is a dermal sensitizer that has
been found to be used safely up to 4.3%. However, it should also be noted that oxidation products of linalool are thought to
be the source of sensitization, rather than linalool itself.
Also, quercetin and several compounds containing quercetin have been reported in the leaf, plant, and shoot
ranging from 760 to 10000 ppm. A positive genotoxic effect in an Ames assay has been reported and genotoxicity in in vitro
tests and in some in vivo studies of i.p. exposures, but results were consistently nongenotoxic in oral exposure studies using
mice and rats.
The Panel has noted that linalool and quercetin are found in C. sinensis leaves and essential oil and acknowledges
that, depending on growing conditions and methods of manufacture, these constituents may or may not be found in the
cosmetic ingredients. The Panel further noted that the use of other botanical ingredients that may contain linalool and
quercetin in combination with C. sinensis-derived ingredients in a single formulation, or in formulations that are used at the
same time or in close time proximity, could result in exposures that exceed levels of toxicological concern. Thus, cosmetic
products containing one or more botanical ingredient(s) should be formulated to ensure concentrations of linalool and does
not exceed the limit set by the Panel, and that total exposures to such constituents remain below the levels of toxicological
concern, whether these products typically are used simultaneously or sequentially.
The Panel recognized that every leaf extract would likely be somewhat different and that the characterization of the
composition of the plant-derived ingredients addressed in this safety assessment is broad. Nonetheless, the available
composition data represent what would be found commonly in ingredients prepared in the manner described. The Panel
assumes that the manufacturing process is the same for oral consumption and cosmetics. The conclusion regarding safety,
15
therefore, is valid only for ingredients prepared in a manner that produces a chemical profile similar to that described in this
report. Extracts not prepared in a manner that produces similar chemical profiles, could be considered safe only if they have
similar safety test profiles.
The Panel expressed concern about pesticide residues and heavy metals that may be present in botanical ingredients.
Aflatoxins have been detected in dried C. sinensis leaves for drinking. The Panel believes that aflatoxins will not be
present at levels of toxicological concern in C. sinensis-derived ingredients. The Panel recognizes the United States
Department of Agriculture (USDA) designation of ≤ 15 ppb as corresponding to “negative” aflatoxin content. They stressed
that the cosmetics industry should continue to use current good manufacturing practices (cGMPs) to limit impurities.
There were several studies showing photoprotective, not phototoxic effects. Therefore, the Panel is not concerned
that phototoxicity is a problem.
There is not enough data to come to a conclusion of safety for the ingredients that are not derived from the leaves
and stems. To make a determination of safety of these ingredients, the Panel needs data on:
• confirmation that camellia sinensis leaf water is used only as a fragrance
Should this data be provided, the Panel would reopen this safety assessment.
CONCLUSION
The CIR Expert Panel concluded that camellia sinensis leaf extract is safe in cosmetics up to 0.86% in leave-on products and
up to 1% in rinse-off products. Camellia sinensis catechins is safe as used. The Panel also concluded that the available data
or information are insufficient to make a determination that camellia sinensis flower extract, camellia sinensis
flower/leaf/stem juice, camellia sinensis leaf, camellia sinensis leaf oil, camellia sinensis leaf powder, camellia sinensis leaf
water, camellia sinensis root extract, camellia sinensis seedcoat powder, camellia sinensis seed extract, camellia sinensis seed
powder, hydrolyzed camellia sinensis leaf, and hydrolyzed camellia sinensis seed extract are safe under the intended
conditions of use in cosmetics.
16
TABLES
Table 1. Definitions and functions of Camellia s.-derived ingredients in this report.1

Ingredient CAS No. Definition Function
Camellia Sinensis Leaf Extract The extract of the leaves of Camellia sinensis. Antifungal agent; antimicrobial agent;
84650-60-2 antioxidant; cosmetic astringent; fragrance
ingredient; light stabilizer; oral care agent; skin
protectant; skin-conditioning agent – emollient;
skin-conditioning agent – humectant; skin-
conditioning agent - miscellaneous
Camellia Sinensis Catechins A mixture of catechins obtained from the leaves Antioxidants
of Camellia sinensis.
Camellia Sinensis Flower Extract The extract of the flowers of Camellia sinensis. Skin-conditioning agents – miscellaneous
Camellia Sinensis Flower/Leaf/Stem Juice The juice expressed from the flowers, leaves and Antioxidant
1196791-49-7 stems of Camellia sinensis.
Camellia Sinensis Leaf The leaf of Camellia sinensis. Skin-conditioning agent – miscellaneous
Camellia Sinensis Leaf Oil The oil derived from the leaves of Camellia Antioxidant; skin-conditioning agent -
68916-73-4 sinensis. This is an essential oil. miscellaneous
Camellia Sinensis Leaf Powder A powder derived from the dried, ground leaves Exfoliant
of Camellia sinensis.
Camellia Sinensis Leaf Water An aqueous solution of the steam distillate Fragrance ingredient
obtained from the leaves of Camellia sinensis.
Camellia Sinensis Root Extract The extract of the roots of Camellia sinensis. Skin-conditioning agent – miscellaneous
Camellia Sinensis Seedcoat Powder The powder obtained from the dried, ground Skin conditioning agent – miscellaneous
seedcoats of Camellia sinensis.
Camellia Sinensis Seed Extract The extract of the seeds of Camellia sinensis. Skin-conditioning agent – humectant
Camellia Sinensis Seed Powder The powder obtained from the dried, ground Antioxidant; skin-conditioning agent –
seeds of Camellia sinensis. miscellaneous
Hydrolyzed Camellia Sinensis Leaf The hydrolysate of Camellia Sinensis Leaf (q.v.) Skin-conditioning agent – humectant
derived by acid, enzyme or other method of
hydrolysis.
Hydrolyzed Camellia Sinensis Seed Extract The hydrolysate of Camellia Sinensis Seed Antioxidant; skin protectant; skin-conditioning
Extract derived by acid, enzyme or other method agent - miscellaneous
of hydrolysis.
Table 2. Constituent groups of fresh green C. sinensis leaf.4

Constituent % of dry weight
Flavonols 25.0
Flavonols and flavonol glycosides 3.0
Polyphenolic acids and depsides 5.0
Other polyphenols 3.0
Caffeine 3.0
Theobromine 0.2
Amino acids 4.0
Organic acids 0.5
Monosaccharides 4.0
Polysaccharides 13.0
Cellulose 7.0
Protein 15.0
Lignin 6.0
Lipids 3.0
Chlorophyll and other pigments 0.5
Ash 5.0
Volatiles 0.1
17
Table 3. Constituents of concern in C. sinensis.
Constituent Effects Reference
101
Linalool Dermal sensitizer. Used safely at up to 4.3% (20% in a consumer fragrance).
102
Quercetin Positive genotoxic effect in an Ames assay
103
Consistently genotoxic in in vitro tests and in some in vivo studies of i.p.
exposures, but was consistently nongenotoxic in oral exposure studies using
mice and rats.
Table 4. Constituent groups in medical grade Camellia sinensis leaf extract.16,26-30

Constituent group Constituent Concentration (%)
Methylxanthines Caffeine 2.5-4.2
Theophylline 0.02-0.04
Theobromine 0.15-0.2
Flavanols (flavan-3-ols) 10-25
Monomers (catechins)
(-)-epicatechin (EC)
(-)-epicatechin-3-O-gallate (ECG)
(-)-epigallocatechin (EGC)
(-)-epigallocatechin-3-O-gallate (EGCG)
Dimers (theaflavins)
Theaflavin
Theaflavin 3-gallate
Theaflavin 3-O-gallate
Theaflavin3,3-O-digallate
Flavonols
Quercetin (and its glycosides)
Kaempferol (and its glycosides)
Myricetin (and its glycosides)
Flavones
Apigenin
Luteolin
Phenolic acids
Chlorogenic acid
Gallic acid
Theogallin
Amino acids Theanine (5-N-ethyl glutamine) 3
18 other amino acids
Therpene saponins (theafolia saponins) Aglycones
Barringtogenol C
R1-barringenol
And others
Polysaccharides 13
Proanthocyanidins (tannins)
Vitamins
Ascorbic acid
α-Tocopherol
Other compounds
Fluoride
Chlorophyll
Organic acids
Constituent group Constituent Concentration (ppm)
Elements
Copper 270
Iron 13040
Nickel 1340
Sodium 1.800
Potassium 262
Magnesium 30,800
Calcium 13,750
Zinc 630.0
Chromium 10.0
18
Table 5. Phenolic composition of green and black tea from young
leaves and leaf buds.53
Constituent Green tea (%w/w) Black tea (%w/w)
Catechins 30-42 3-10
Flavonols 5-10 6-8
Other flavonoids 2-4 -
Theagallin 2-3 -
Gallic acid 0.5 -
Quinic acid 2.0 -
Theanine 4-6 -
Methylxanthines 7-9 8-11
Theaflavins - 3-6
Thearubigins - 12-18
Table 6. Trace elements in commercial teas and their infusions.38

Na K Rb Ca Mg Al Fe Mn Cu Zn Cr
Tea (µg/g) (mg/g) (µg/g) (mg/g) (mg/g) (µg/g) (µg/g) (µg/g) (µg/g) (µg/g) (µg/g) Pb (µg/g)
Dried tea leaves
Unbranded 75±5 17±1.6 50±2.3 4.50±0.21 6.23±0.31 757±28 211±20 420±37 32.3±2.1 87±6 5.8±0.4 1.51±0.14
1
Unbranded 84±4 14.5±0.7 41.5±1.8 4.42±0.23 2.34±0.15 712±36 185±15 372±29 21.4±1.7 93±8 3.6±0.1 1.82±0.16
2
Unbranded 65±5 11.3±0.4 43±1.7 6.24±0.35 3.52±0.20 925±44 187±21 738±53 40.3±3.4 97±7 7.5±0.3 2.00±0.13
3
Red Label 81±6 16.2±0.8 46.7±2.4 5.31±0.38 2.81±0.08 1530±67 280±24 864±47 33.6±2.8 96±10 3.5±0.1 1.58±0.17
Tata Gold 48±4 17.0±1.5 42.8±1.9 2.44±0.08 3.95±0.32 891±51 190±13 1130±96 21.9±2.3 111±8 5.7±0.3 2.63±0.14
Society 39±2 17.4±1.4 43.4±2.1 6.25±0.47 5.76±0.30 713±41 166±9 258±18 29.5±0.8 85±6 1.7±0.1 166±0.20
Tetley 18±0.8 10.2±0.4 17.2±0.7 3.87±0.28 1.97±0.10 605±29 1550±74 1120±65 8.2±0.2 80±7 4.5±0.2 2.20±0.19
Green 1
Tetley 21±1 11.3±0.5 19.3±0.8 3.20±0.31 2.31±0.09 620±38 1486±82 1030±82 7.3±0.3 78±5 4.7±0.2 2.34±0.23
Green 2
Aqueous infusion (percentage of total leached into the infusion)
Unbranded 68 (90) 11.6 37 (74) 0.20 (5) 1.31 (21) 196 (26) 8.5 (4.3) 168 (40) 0.7 (2.2) 36 - -
1 (68) (42)
Unbranded 90 10.1 30 (75) 0.18 (4) 0.56 (24) 149 (21) 9.6 (5.2) 122 (33) 1.0 (5) 40 - -
2 (107) (70) (43)
Unbranded 51 (73) 7.6 (67) 32 (74) 0.37 (6) 1.09 (31) 278 (30) 7.6 (4.1) 273 (37) 3.2 (8) 43 - -
3 (44)
Red Label 78 (96) 11.3 33 (71) 0.27 (5) 0.76 (27) 367 (24) 11.0 259 (30) 2.3 (7) 40 - -
(70) (4.7) (42)
Tata Gold 41 (85) 12.4 32 (75) 0.17 (7) 1.03 (26) 196 (22) 9.3 (4.9) 452 (41) 1.8 (8) 30 - -
(73) (45)
Society 42 12.0 30 (70) 0.31 (5) 1.44 (25) 192 (27) 7.6 (4.6) 80 (31) 1.2 (4) 38 - -
(108) (69) (45)
Tetley 14 (77) 6.6 (65) 4.1 (23) 0.12 (3) 0.57 (29) 127 (21) 22 (1.4) 380 (34) 0.2 (3) 32 - -
Green 1 (41)
Tetley 19 (95) 7.5 (66) 4.8 (25) 0.10 (3) 0.72 (31) 124 (20) 23 (1.5 ) 360 (35) 0.5 (7) 31 - -
Green 2 (40)
19
Table 7. Frequency of use according to duration and exposure of C. sinensis-derived ingredients.39-42
Maximum Maximum Maximum Maximum
Concentration Concentration Concentration Concentration
Use type Uses (%) Uses (%) Uses (%) Uses (%)
Camellia sinensis leaf Camellia sinensis leaf
extract1 Camellia sinensis leaf Camellia sinensis leaf oil powder
Total/range 1865 0.00002-3 54 0.05 33 NR 22 0.005-50
Duration of use
Leave-on 1083 0.00002-2 38 NR 24 NR 11 0.005-7
Rinse-off 747 0.00002-1 15 NR 9 NR 10 0.01
Diluted for (bath)
35 0.0001-0.1 1 0.05 NR NR 1 50
use
Exposure type
Eye area 131 0.00002-0.87 6 NRg NR NR 1 0.3
Incidental a
36 0.001-0.14 NR NR 5 NR NR NR
ingestion
0.0005b,c;
Incidental
676d 0.0001- 31d NR NR NR 8d 0.005-50h
Inhalation-sprays
0.0055d
Incidental 0.0003-
590d NR NR 1d NR 6d 0.005-50b
inhalation-powders 0.0037d;
Dermal contact 1484 0.00002-3 51 0.05 20 NR 22 0.005-50
Deodorant 0.0055b, e;
13d NR NR NR NR NR NR
(underarm) 0.0055-0.023f
0.000055-
Hair-noncoloring 279 3 NR 8 NR NR NR
0.0063
Hair-coloring 60 0.003-0.006 NR NR NR NR NR NR
Nail 1 0.00002-0.53 NR NR NR NR NR NR
Mucous
369 0.0001-1 1 0.05 10 NR 9 0.01
Membrane
Baby 12 NR NR NR 1 NR NR NR
Camellia sinensis leaf Camellia sinensis seed

water extract
Total/range 36 30 NR 0.001-0.1
Duration of use
Leave-on 26 30 NR 0.001-0.1
Rinse-off 10 NR NR 0.001-0.0013
Diluted for (bath)
NR NR NR NR
use
Exposure type
Eye area 4 30 NR NR
Incidental
NR NR NR NR
ingestion
Incidental
21d NR NRd 0.1d
Inhalation-sprays
Incidental
20 NR NR NR
inhalation-powders
Dermal contact 36 NR NR 0.001-0.1
Deodorant
NR NR NR NR
(underarm)
Hair-noncoloring NR NR NR NR
Hair-coloring NR NR NR NR
Nail NR NR NR NR
Mucous
NR NR NR 0.0013
Membrane
Baby NR NR NR NR
1
“Green tea” and “green tea extract” are not INCI names of cosmetic ingredients but were listed in the VCRP. Since these are technical
names for camellia sinensis leaf extract, these total were combined with this ingredient.
NR = Not Reported; Totals = Rinse-off + Leave-on Product Uses.
Note: Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure type uses may not equal the
sum total uses.
a
Ingestible oral hygiene product – 0.14%
b
Aerosol product(s)
c
Pump hair spray – 0.0005%
d
May or may not be an aerosol product(s) or powders that could be inhaled
e
Deodorant pump spray – 0.0055%
f
Not aerosol product(s)
g
Tea bags for the eyes (97%) is no longer sold
h
50% in a professional product that is diluted with water for use
20
Table 8. Reproductive and developmental studies submitted to the FDA for the approval of an ointment containing 15%
polyphenols.72
Species (n); administration Results
Oral
Pregnant rats (6-7); 0, 125, 250, 500, 750, 1000 Complete resorptions in 2/6 dams in the highest dose group. No other treatment related effects.
mg/kg ointment in water (assume by gavage) on
gestation days 6-15
Sprague-Dawley rats (27); 0, 250, 500, 1000 Body weight gains were decreased in all treatment groups compared to controls (14%, 7%, 10%,
mg/kg ointment on gestations days 6-18 by respectively). No effects on fertility, embryo/fetal development.
gavage
Rabbits (not provided); 0, 62.5, 125, 250, 500, No treatment related effects observed.
1000 mg/kg ointment on gestations days 6-18 by
gavage
White rabbits (not provided); 0, 100, 300, 1000 Mortality due to gavage trauma. Body weight gains were decreased in the low- and high-treatment
mg/kg ointment on gestations days 6-18 by groups (-31%, +10%, 84%, respectively). Feed consumption was decreased in the high-dose group.
gavage No effects on fertility, embryo/fetal development.
Subcutaneous
Rabbits (6); 0, 37.5, 150 mg/kg/d on gestation High-dose group- irritation with severe subcutaneous lesions/necrosis at injection sites. Treatment was
days 6-19 discontinued after 6 days. One rabbit aborted. There was body weight loss, decreased feed
consumption, and embryonic resorptions. Two fetuses from separate litters had umbilical hernia (one
with hyperflexed limb), one fetus had a short tail.
Low-dose group-Local irritation, decreased body weight gain. Increased early and late resorptions,
Decreased corpora lutea, implants, litter size. No effect to fetal weights.
Rabbits (at least 6); 0,4, 12, 36 mg/kg/d on High-dose group-severe local irritation at injection sites, decreased weight gain and feed consumption,
gestation days 6-19 decreased fetal weight. Abortions on gestation day 26. Decreased fetal weights. There were 3
malformed fetuses from 2 litters. Number of corpora lutea, pre-implantation loss, number of
implantations, and sex ratios were similar to controls.
Mid-dose group- one abortion on last day of gestation. 6 fetuses (from 5 litters) were malformed. One
aborted fetus had a domed head. Number of corpora lutea, pre-implantation loss, number of
implantations, and sex ratios were similar to controls.
Low-dose group- Seven fetuses (from 4 litters) were malformed.
Control group had 3 malformed fetuses from 2 litters.
Blood tests show no accumulation of EGCG in the plasma during treatment.
Intravaginal
Sprague-Dawley rats (25); 0.15 ml administered 4 No adverse effect on reproductive ability or embryo/fetal development. There were no mortalities.
days before mating through gestation day 17 There were no differences in feed consumption.
Rats (25); 0.05, 0.10, 0.15 mL/d administered 4 rats in the high-dose group and 3 in the mid-dose groups died possibly due to parturition
gestation day 6 - weaning complications. Dam in high-dose group killed after both pups died. There were no clinical signs
observed.
High-dose group-Increased stillborn pups (23 from 6 dams). There was decreased litter size and live
birth index.
There were no other treatment-related effects on pre- and –postnatal development.
Controls-5 stillborn pups from 3 dams
Rats (25); 0, 0.05. 0.10, 0.15 mL/rat/d F 0 - High-dose group-4 dams killed due to possible parturition complications. 20 dams delivered
administered gestation day 6 – weaning. F1 successfully with 23 stillborn pups from 2 litters.
generation were paired (25) and were mated Mid-dose group-3 dams killed due to possible parturition complications. 22 dams delivered
untreated successfully with 9 stillborn pups from 7 litters
Low-dose group-22 dams delivered successfully
Controls-5 stillborn pups from 3 litters.
F 1 – No mortalities. One male in the mid-dose group was missing the tip of his tail and one female had
dental abnormalities. No clinical signs, body weight gains, pinna unfolding, incisor eruption, eye
opening, surface righting, gripping pupillary and auditory reflex, age of vaginal opening, and balano-
preputial separation were normal. Water maze field tests were normal. All mating and fertility
parameters were normal.
21
Table 9. Genotoxicity studies of C. sinensis extracts and constituents.
Assay Ingredient/constituent (concentration) Results Reference
In vitro
74
Ames test (S. typhimurium strains Polyphenol mixture containing 51.4% EGCG Not mutagenic with or without metabolic
TA98, TA100, TA1535, TA1537 and 4 other catechins (0-5000 μg/plate in activation. Not cytotoxic.
and E. coli WP2uvrA); sterile water); Metabolic activation at 4% and
10%
76
Ames test (S. typhimurium strains Camellia sinensis flower extract (0.008, 0.04, Not mutagenic with or without metabolic
TA97, TA98, TA100, TA102) 0.1, 1.0, 5.0 mg/plate; water extract) with and activation.
without metabolic activation
75
Ames test (S. typhimurium strains EGCG (88.1%-95% pure) (50-5000µg/plate) Not mutagenic with or without metabolic
TA97, TA98, TA100, TA102, with and without metabolic activation activation.
TA1535)
67
Ames test (S. typhimurium strains Chinese tea extract (0.85% solids) Negative
TA98, TA100, TA1535, TA1537 (5000µg/plate)
and E. coli WP2uvrA)
67
Ames test (S. typhimurium strains Oolong tea extract (1.0% solids) Negative
TA98, TA100, TA1535, TA1537 (5000µg/plate)
and E. coli WP2uvrA)
74
Mouse lymphoma assay Polyphenol mixture containing 51.4% EGCG Not mutagenic with or without metabolic
and 4 other catechins (0-625 μg/mL in sterile activation. Cytotoxic at ≥375 μg/mL.
water)
Mouse lymphoma assay Polyphenol mixture containing 51.4% EGCG Mutagenic at ≥164 μg/mL without metabolic 74
and 4 other catechins (0-500 μg/mL without; activation; mutagenic at ≥375 μg/mL with
0-625 with metabolic activation in sterile metabolic activation. Cytotoxic at ≥500 μg/mL.
water)
75
Mouse lymphoma assay EGCG (77% pure) with and without Not mutagenic without metabolic activation up to
metabolic activation 100 µg/mL; mutagenic ≥ 125 µg/mL with
metabolic activation
72
Mouse lymphoma assay Polyphenol mixture (0, 87, 155, 276, 492, Not mutagenic with or without metabolic
878, 1568, 2800, 5000 µg/mL) with and activation.
without metabolic activation
In vivo
74
Mouse micronucleus assay (n = Polyphenol mixture containing 51.4% EGCG Not mutagenic
5/sex) and 4 other catechins (0-1500 mg/kg) by
gavage
75
Mouse micronucleus assay (n = EGCG (91.9% pure) (500, 1000, 2000 Not mutagenic
5/sex) mg/kg) by gavage
74
Big blue mutation assay Swiss- Polyphenol mixture containing 51.4% EGCG No increase in cII mutant frequencies in the
Webster mice (n = 7/sex) and 4 other catechins (0, 500, 1000, 2000 livers, lungs, and spleen tissues at 500 and 2000
mg/kg/d for 28 d) by gavage. Necropsied 28 mg/kg.
days after final dose. Tissues analyzed for Mice died during treatment in the 2000 mg/kg
mutations. group and were not analyzed.
75
Micronucleus assay diet study using EGCG (80% pure) (4200, 8400, 12600 ppm in No increase in frequency of micronucleated
CD-1 mice (6/sex) feed) polychromatic erythrocytes
75
Micronucleus assay intravenous EGCG (92.6% pure) (15, 25, 50 mg/kg/d No increase in frequency of micronucleate
study using Wistar rats (5/sex) intravenously for 2 days polychromatic erythrocytes
72
Micronucleus assay intraperitoneal Polyphenol mixture (0, 8500 mg/kg). Bone No increase in frequency of micronucleate
study using Sprague-Dawley rats marrow sampled 24 and 48 h after treatment polychromatic erythrocytes
(7/sex)
22
Table 10. Dermal reactions to C. sinensis leaf (aqueous extract or dried leaves) application in ointments for dermal treatment
of genital and perianal warts.26
DER Very common Common Uncommon
≥ 1/10 Local reactions at the application site
including erythema, pruritus,
irritation/burning, pain, ulcer, edema,
induration and vesicles
≥1/100 – 1/10 Local reactions at the application site
including exfoliation, discharge, bleeding
and swelling
≥1/1,000 - ≤100 Local reactions at the application site
including discoloration, discomfort,
dryness, erosion, fissure, hyperesthesia,
anesthesia, scar, nodule, dermatitis,
hypersensitivity, local necrosis, papules,
and eczema
≥1/1,000 - ≤100 Application site infection, application site
pustules, herpes simplex, infection,
pyoderma, staphylococcal infection,
urethritis, vaginal candidiasis,
vulvovaginitis and vulvitis
DER = drug/extract ratio
Table 11. The number of published studies discovered in a PubMed search (1965-
2008) for the carcinogenicity inhibitory effect of green tea extracts and its catechins
in animal models.98
Inhibitory effect
Organ/tissue (xenograft studies) No inhibitory effect
Lung 20 (1) 2
Oral cavity 6 0
Esophagus 4 0
Stomach 9 0
Small intestine 8 1
Colon 11 (3) 6
Skin 27 (1) 0
Prostate 4 (5) 0
Breast 10 (8) 0
Liver 7 1
Bladder 3 (1) 0
Pancreas 2 (2) 0
Thyroid 1 0
23
REFERENCES
1. Nikitakis, J and Breslawec HP. International Cosmetic Ingredient Dictionary and Handbook. 15 ed. Washington, DC: Personal Care Products
Council, 2014.
2. Burnett C, Fiume M, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks Jr JG, Shank RC, Slaga TJ, Snyder PW, and Andersen
FA. Plant-derived fatty acid oils as used in cosmetics. Washington, DC, Cosmetic Ingredient Review. 2011. pp. 1-100.
3. Aso D. On the role of xoidase in the preparation of commercial tea. In: Bulletin of the College of Agriculture, Tokyo Imperial Univeristy. Vol.
IV, 1900-1902. 1901:255-259.
4. Balentine DA, Harbowy ME, and Graham HN. Tea: The plant and its manufacture; chemistry and consumption of the beverage. Spiller GA.In:
Caffeine. Boca Raton: CRC Press; 1998:
5. Flora of China: Camellia sinensis (linnaeus) Kuntze. http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200014043. Science Press &
Missouri Botanical Garden: Beijing and St. Louis. 1987.
6. Center for New Crops & Plants Products. Camellia sinensis (L.)
Kuntze. http://www.hort.purdue.edu/newcrop/duke_energy/camellia_sinensis.html#Description. 1996.
7. Sabato J. On a new amide - theanine. Journal of the Agricultural Chemical Society of Japan. 1950;23:262.
8. Taylor S, Baker D, Owuor P, Orchard J, Othieno C, and Gay C. A model for predicting black tea quality from the cartenoid and chlorophyll
composition of fresh green tea leaf. Journal of the Science of Food and Agriculture. 1992;58:185-191.
9. Venkatakrshna S, Premachandra BR, and Cama HR. Distribution of carotenoid pigments in tea leaves. Tea Q. 1977;47:28.
10. Suzuki Y and Shioi Y. Identification of chlorophylls and carotenoids in major teas by high-performance liquid chromatography with photodiode
array detection. Journal of Agricultural and Food Chemistry. 2003;51:(18):5307-5314.
11. Hicks M, Hsieh Y-, and Bell L. Tea preparation and its influence on methylzanthine concentration. Food Research International. 1996;29:325-
330.
12. Jalal MAF and Collin HA. Estimation of caffeine, theophylline and theobromine in plant material. New Phytologist. 1976;76:(2):277-281.
13. Takino Y. Reddish orange pigments of black tea structure and oxidative formation from catechins. JARQ. 1978;12:(2):94-98.
14. Wickremashinghe RI. Tea. Chickester CD, Mrak EM, and Stewart GF.In: Advances in Food Reasearch. New York: Academic Press; 1978:22
15. Berkowitz JE, Coggon P, and Sanderson GW. Formation of epitheaflavic acid and its transformation to thearubigins during tea fermentation.
Phytochemistry. 1971;10:2271-2278.
16. Balentine D, Wiseman S, and Bouwens L. The chemistry of tea flavonoids. Critical Reviews in Food Science and Nutrition. 1997;37:(8):693-704.
17. Kapetanovic IM, Crowell JA, Krishnaraj R, Zakharov A, Lindeblad M, and Lyubimov A. Exposure and toxicity of green tea pholyphenols in
fasted and non-fasted dogs. Toxicology. 2009;260:(1-3):28-36.
18. Shankar S, Ganapathy S, and Srivastava RK. Green tea polyphenols: Biology and therapeutic implications in cancer. Frontiers in Bioscience.
2007;12:(Sep 1):4881-4899.
19. Szymczycha-Madeja A, Welna M, and Pohl P. Elemental analysis of teas and their infusions by sectrometric methods. Trends in Analytical
Chemistry. 2012;35:(May):165-181.
20. Eden T. Tea. 3 ed. London: Longman, 1976.
21. Hatanaka A and Kajiwara T. Occurrence of trans-3-hexenal in Thea sinensis leaves. Z Naturforschung. 1981;36:755.
22. Yaminishi T. Tea, coffee, cocoa and other beverages. Teranishi R, Flath RA, and Sugisawa H.In: Flavor Research: Recent Advances. New York:
Dekker; 1981:231
23. Sekiya J, Kajiwara T, and Hatanaka A. Seasonal changes in activites of enzymes responsible for the formation of C 6 -aldehydes and C 6 alcohols in
tea leaves, and the effects of environmental temperatures on the enzyme activities. Plant & Cell Physiology. 1984;25:(2):269-280.
24. Lee JE, Lee BJ, Chung JO, Hwang JA, Lee SJ, Lee CH, and Hong YS. Geographical and climatic dependencies of green tea (Camelia sinensis)
metabolites: A h NMR-based matabolonics study. Journal of Agricultural and Food Chemistry. 2010. 58:(19): pp.10582-10589.
25. Duke JA. Dr. Duke's Phytochemical and Ethnobotanical Databases. Chemicals in Rosmarinus officinalis L. (Lamiaceae) --
rosemary. http://www.ars-grin.gov/duke/. 1998. Date Accessed 2-19-2013.
24
26. European Medicines Agency (EMEA). Assessment report on Camellia sinensis (L.) Kuntze, non fermentatum folium. Canary Warf, London,
United Kingdom, European Medicines Agency. 2013. Report No. EMA/HMPC/283629/2012 . pp. 1-39.
27. Ferrara L, Montesano D, and Senatore A. The distribution of minerals and flavonoids in the tea plant (Camellia sinensis). Il Farmaco.
2001;56:397-401.
28. Gruenwald J, Brendler T, and Jaenike C. PDR for Herbal Medicines. 2th edition. Montvale, NJ:Medical Economics Company, Inc.; 2004.
29. Peterson J, Dwyer J, Bhagwat S, Haytowitz D, Holden J, Eldridge AL, Beecher G, and Aladesanmi J. Major flavonoids in dry tea. Journal of
Food Composition and Analysis. 2005;18:487-501.
30. Sharma VK, Bhattacharya A, Kumar A, and Sharma HK. Health benefits of tea consumption. Tropical Journal of Pahrmaceutical Research.
2013;6:(3):785-792.
31. Kao Corporation. Clarification for GRN 000259 (Catechins from Green Tea Extract). U.S.FDA website. 2008. pp.1-269. Correspondence with
the FDA for the application of GRAS status. http://www.accessdata.fda.gov/scripts/fcn/gras_notices/grn000259-2.pdf
32. European Medicines Agency (EMEA). Guideline on quality of herbal medicine products/traditional herbal medicinal products. Canary Wharf,
London, UK, European Medicines Agency.
2006. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003370.pdf. Report No.
CPMP/QWP/2819/00 Rev 1; EMEA/CVMP/814/00 Rev 1. pp. 1-11.
33. Li Y-H, Wu Y, Wei H-C, Xu Y-Y, Jia L-L, Chen J, Yang X-S, Dong G-H, Gao X-H, and Chen H-D. Protective effects of green tea extracts on
photoaging and photommunosuppression. Skin Research and Technology. 2009;15:(3):338-345.
34. López V and Calvo MI. White tea (Camellia sinensis Kuntze) exerts neuroprotection against hydrogen peroxide-induced toxicity in PC12 cells.
Plant Foods for Human Nutrition. 2011;66:22-26.
35. Isbrucker, R. A., Edwards, J. A., Wolz, E., Davidovich, A., and Bausch, J. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2:
dermal, acute and short-term toxicity studies. Food and chemical toxicology : an international journal published for the British
Industrial Biological Research Association. 2006;44:(5):636-650.
36. Ahmad S, Khader JA, Gilani SS, Khan S, Noor S, Ullah R, Hussain I, Kanwal F, Ullah H, and Shah Z. Determination of mineral and toxic heavy
elements in different brands of black tea of Pakistan. African Journal of Pharmacy and Pharmacology. 2012;6:(15):1194-1196.
37. Viswanath P, Nanjegowda DK, Govindegowda H, Dattatreya AM, and Siddappa V. Aflatoxin determination in black tea (Camellia sinensis) -
status and development of a protocol. Journal of Food Safety. 2011;32:(1):13-21.
38. Dash K, Manjusha R'Thangavel S, and Arunachalam J. UV Photolysis-assisted digestion of tea (Camellia sinensis) and Tulsi (Ocimum sanctum)
and their infusions: Comparison of available trace elements. Atomic Spectroscopy. 2008;29:(2):56-62.
39. Food and Drug Administration (FDA). Frequency of use of cosmetic ingredients. FDA Database. 2014. Washington, DC: FDA.
40. Personal Care Products Council. 1-16-2014. Updated Concentration of Use by FDA Product Category: Camellia sinensis-Derived Ingredients.
Unpublished data submitted by Personal Care Products Council. 1 pages.
41. Personal Care Products Council. 12-31-2014. Updated Concentration of Use by FDA Product Category for Camellia Sinensis- Derived
Ingredients. Unpublished data submitted by Personal Care Products Council.
42. Personal Care Products Council. 6-6-2013. Concentration of Use by FDA Product Category: Camellia sinensis-Derived Ingredients. Unpublished
data submitted by Personal Care Products Council. 5 pages.
43. Food and Drug Administration (FDA). Frequency of use of cosmetic ingredients. FDA Database. Washington, DC: FDA.
44. Food and Drug Administration (FDA). Veregen Ointment. Department of Health & Human Services.
2007. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021902s000TOC.cfmDate Accessed 8-8-2013
45. Cabrera C, Artacho R, and Gimenez R. Beneficial effects of green tea - a review. Journal of the American College of Nutrition. 2006;25:(2):79-
99.
46. Cheng TO. All teas are not created equal: The Chinese gren tea and cardiovasclar health. International Journal of Cardiology. 2006;108:(3):301-
308.
47. Cooper R, Morre DJ, and Morre DM. Medicinal benefits of green tea: Part I. Review of noncancer health benefits. Journal of Alternative
Complementary Medicine. 2005;11:(3):521-528.
48. Cooper R, Morre DJ, and Morre DM. Medicinal benefits of green tea: Part II. Review of anticancer properties. Journal of Alternative
Complementary Medicine. 2013;11:(4):639-652.
25
49. Friedman M. Overview of antibacterial, antitoxin, antiviral, and antifungal activites of tea flavonoids and teas. Molecular Nutrition & Food
Research. 2007;51:(1):116-134.
50. Fujiki H. Green tea: Health benefits as cancer preventive for humans. Chemical Record. 2005;5:(3):119-132.
51. Khan N and Mukhtar H. Tea polyphenols for health promotion. Life Sciences. 2007;81:(7):519-533.
52. Pham-Huy L, He H, and Pham-Huy C. Green tea and health: an overview. Journal of Food Agriculture and Environment. 2008;6:(1):6-13.
53. Shukla Y. Tea and cancer cemoprevention: A comprehensive review. Asian Pacific Journal of Cancer Prevention. 2007;8:(2):155-166.
54. Zaveri NT. Green tea and its polyphenolic catechins: Medicinal uses in cancer and noncancer applications. Life Sciences. 2006;78:(18):73-80.
55. International Agency for Reseach on Cancer (IARC). Coffee, tea, mate, methylxanthines and methylglyoxal: Summary of data reported and
evaluation. Volume 51. World Health Organization. 1997. http://monographs.iarc.fr/ENG/Monographs/vol51/volume51.pdf. pp. 1-23.
56. The Tea Association of the USA, Inc, Tea Council of the USA, Inc., and Specialty Tea Institute. Tea fact sheet -
2013. http://www.teausa.com/14655/tea-fact-sheet. New York, NY. 2013. Date Accessed 10-23-2013.
57. Batchelder RJ, Calder RJ, Thomas CP, and Heard CM. In vitro transdermal delivery of the major catechins and caffeine from extract of Camellia
sinensis. International Journal of Pharmaceutics. 2004;28:45-51.
58. Lambert JD, Kim DH, Zheng R, and Yang CS. Transdermal delivery of (-)-epigallocatechin-3-gallate, a green tea polyphenol, in mice. Journal of
Pharmacy and Pharmacology. 2006;58:599-604.
59. Bandyopadhyay D, Chatterjee TK, Dasgupta A, Lourduraja J, and Dastidar S. In vitro and in vivo antimicrobial action of tea: The commonest
beverage of Asia. Biological & Pharmaceutical Bulletin. 2005;28:(11):2125-2127.
60. Obaid AY, Abu-Zinadah OA, and Hussein HK. The beneficial effects of green tea extract and its main derivatives in repairing skin burns of
rabbit. International Journal of Biological Chemistry. 2011;5:(2):103-115.
61. Sagesaka, YM, Uemura T, Suzuki Y, Sugiura T, Yoshida M, Yamaguchi K, and Kyuki K. Antimicrobial and anti-inflammatory actions of tea-
leaf saponin. Yakugaku Zassi. 1996;116:(3):238-243.
62. Phillips BJ. Development of cell culture techniques for assessment of the toxicity of plant products. Toxicology in Vitro. 1996;10:(1):69-76.
63. Laboratoire Dermascan. 1999. Evaluation of the scavenging effect of a product (Herbasol extrait the vert (Camellia Sinensis Leaf Extract- green
tea extract) by quantifying the H 2 0 2 production induced by UV rays on keratinocytes in culture. Report No. 99225. Unpublished data
submitted by Personal Care Products Council.
64. Han D-W, Lee MH, Kim HH, Hyon S-H, and Park J-C. Epigallocatechin-3-gallate regulates cell growth, cell cycle and phosphorylated nuclear
factor-kB in human dermal fibroblasts. Acta Pharmacologica Sinica. 2011;32:637-646.
65. Biogir SA. 1991. Assessment of acute oral toxicity in rat Herbasol extrait the vert hydrosoluble (Camellia Sinensis Leaf Extract- green tea
extract). Report: TAO 91-1939. Unpublished data submitted by Personal Care Products Council.
66. Biogir SA. 1991. Assessment of acute oral toxicity in rat Black tea Extract (Camellia Sinensis Leaf Extract - Black tea extract). Report: TAO 91-
1940. Unpublished data submitted by Personal Care Products Council.
67. Anonymous. 2014. Summary safety information on various Camellia Sinensis Leaf Extracts. Unpublished data submitted by Personal Care
Products Council. 1 pages.
68. Yamada H, Tateish M, Harada K, Ohashi T, Shimizu T, Atsumi T, Komagata Y, Iijima H, Komiyama K, Watanabe H, Hara Y, and Ohashi K. A
randomized clinical study of tea catechin inhalation effects on methicillin-resistant Staphylococcus aureus in disabled elderly patients.
Journal of American Medical Directors Association. 2006;7:(February):79-83.
69. Hirano, S, Muto, R, Ikeda, T, and Watanabe, M. Effect of catechin inhalation therapy on control of MRSA. Nippon Byoin Yakuzaishikai Zasshi.
2002;38:(4):441-443.
70. Yamada H, Muto, R, Kanazawa, M, Yamashiro, E, and Ikeda, T. Effect of catechin inhalation therapy on control of MRSA. 2. Nippon Byoin
Yakuzaishikai Zasshi. 2003;39:(1):45-48.
71. Ratnosooriya WD and Fernando TSP. Effects of Sri Lankan black tea (Camellia sinensis L.) on pregnancy of rats. Basic and Clinical
Pharmacology & Toxicology. 2009;105:361-365.
26
72. Center for Drug Evaluation and Research. Application number: 21-902: Pharmacology Review (PolyPhenon® E Ointment, 15%). U.S. Food and
Drug Administration. 2006. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021902s000_pharmr.pdf. Report No. 21-902.
pp. 1-52.
73. Isbrucker, R. A., Edwards, J. A., Wolz, E., Davidovich, A., and Bausch, J. Safety studies on epigallocatehin gallate (EGCG) preparations. Part 3.
Teratogencity and reproductive toxicity studies in rats. Food and chemical toxicology : an international journal published for the
British Industrial Biological Research Association. 2006;44:(5):651-661.
74. Chang PY, Mirsalis J, Riccio ES, Bakke JP, Lee PS, Shimon J, Phillips S, Fairchild D, Hara Y, and Crowell JA. Genotoxicity and toxicity of he
potential cancer-preventive agent Polyhenon E. Environmental and Molecular Mutagenesis. 2003;41:43-54.
75. Isbrucker, R. A., Bausch, J., Edwards, J. A., and Wolz, E. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 1: genotoxicity.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.
2006;44:(5):626-635.
76. Li B, Jin Y, Xu Y, Wu Y, Xu J, and Tu Y. Safety evaluation of tea (Camellia sinensis (L.) O. Kuntze) flower extract: Assessment of
mutagenicity, and acute and subchronic toxicity in rats. Journal of Ethanopharmacology. 2011;133:(2):583-590.
77. Hakim IA and Harris RB. Joint effects of citrus peel use and black tea intake on the risk of squamous cell carcinoma of the skin. BMC
Dermatology. 2001;1:(1):3-11.
78. Huang M-T, Xie J-G, Wang ZY, Ho C-T, Lou Y-R, Wang C-X, Hard GC, and Conney AH. Effects of tea, decaffeinated tea, and caffeine on
UVB light-induced complete carcinogenesis in SKH-1 mice: Demonstration of caffeine as a biologically important constituent of tea.
Cancer Research. 1997;57:(July 1):2623-2629.
79. Biogir SA. 1991. Assessment of cutaneous tolerance in rabbit: Index of primary cutaneous irritation Herbasol Extrait The Vert Hydrosoluble
(Camellia Sinensis Leaf Extract- green tea extract). Report: IC 91.1939. Unpublished data submitted by Personal Care Products
Council.
80. Biogir SA. 1991. Assessment of cutaneous tolerance in rabbit: Index of primary cutaneous irritation Black tea Extract (Camellia Sinensis Leaf
Extract- Black tea extract). Report: IC 91.1940. Unpublished data submitted by Personal Care Products Council.
81. Tatti S, Swinehart JM, Thielert C, Tawfik H, Mescheder A, and Beutner KR. Sinecatechins, a defined green tea extract, in the treatment of
external anogenital warts: a randomixed controlled trial. Obstetrics and Gynecology. 2008;111:(6):1-9.
82. Anonymous. 2011. Mascara (contains 30% Camellia Sinensis Leaf Water) patch test results. Unpublished data submitted by Personal Care
Products Council.
83. Biogir SA. 1991. Assessment of ocular tolerance in rabbit: Index of ocular irritation Herbasol extrait the vert hydrosoluble (Camellia Sinensis
Leaf Extract- green tea extract). Report: IO 91.1939. Unpublished data submitted by Personal Care Products Council.
84. Biogir SA. 1991. Assessment of ocular tolerance in rabbit: Index of ocular irritation Black tea Extract (Camellia Sinensis Leaf Extract- black tea
extract). Report: 10 91.1940. Unpublished data submitted by Personal Care Products Council.
85. International Fragrance Association (IFRA). 2009. IFRA Standard on Tea Leaf Absolute. 3 pages.
86. Product Investigations Inc. 2006. Determination of the irritating and sensitizing propensities of a facial product (containing 0.86% Camellia
Sinensis Leaf Extract) on Human Skin. Unpublished data submitted by Personal Care Products Council.
87. Personal Care Products Council. 4-24-2014. Comments on the Tentative Report: Safety Assessment of Camellia sinensis Derived Ingredients as
Used in Cosmetics. Unpublished data submitted by Personal Care Products Council. 3 pages.
88. Clinical Research Laboratories Inc. 2012. Repeated insult patch test of an eye cream containing 0.86% Camellia Sinensis Leaf Extract.
Unpublished data submitted by Personal Care Products Council.
89. Consumer Product Testing Co. 2011. Repeated insult patch test of a mascara containing 30% Camellia Sinensis Leaf Water. Experiment
Reference Number: C11-2402.03. Unpublished data submitted by Personal Care Products Council.
90. Türkoðlu M, Uðurlu T, Gedik G, Yilmaz AM, and Yalçin S. In vivo evaluation of back and green tea dermal products against UV radiation. Drug
Discoveries & Therapeutics. 2010;4:(5):362-367.
91. Katiyar SK, Perez A, and Mukhtar H. Green tea polyphenol treatment to human skin prevents formation of ultraviolte light B-induced pyrimidine
dimers in DNA. Clinical Cancer Research. 2000;6:3864-3869.
92. Lee JH, Chung JH, and Cho KH. The effects of epigallocatechin-3-gallate on extracellular matrix metabolism. Journal of Dermatological
Science. 2005;40:195-204.
27
93. Vayalil PK, Elmets CA, and Katiyar SK. Treatment of green tea polyphenols in hydorphilic cream prevents UVB-induced oxidation of lipids and
proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin. Carcinogenesis.
2003;24:(5):927-936.
94. Xu J-Y, Wu L-Y, Zheng Z-Q, Lu J-L, Wu M-Y, and Liang Y-R. Green tea polyphenols attenuating ultraviolet B-induced damage to human
retinal pigment epithelial cells in vitro. Investigative Ophthalmology & Visual Science. 2010;51:(12):6665-6670.
95. Otera H, Tada K, Sakurai T, Hashimoto K, and Ikeda A. Hypersensitivity pneumonitis associated with inhalation of cataechin-rich extracts.
Respiration. 2011;82:(388):392.
96. Sarma DN, Barrett ML, Chavez ML, Gardiner P, Ko R, Mahady GB, Marles RJ, Pellicore LS, Giancaspro GI, and Dog TL. Safety of green tea
extracts; A systematic reveiw by the US Pharmacopeia. Drug Safety. 2008;31:(6):469-484.
97. Crespy V and Williamson G. A reviw of the health effects of green tea catechins in in vivo animal models. Journal of Nutrition. 2004;134:(12
Suppl):3431S-3440S.
98. Yang CS, Welna M, Lu G, and Picinich SC. Cancer prevention by tea: animal studies, molecular mechinisms and human relevance. Nature.
2009;9:(June):429-439.
99. Yang CS, Maliakal P, and Meng X. Inhibition of carcinogenesis by tea. Annual Reveiw of Phamrmacology and Toxicology. 2002;42:25-54.
100. Ju J, Lu G, Lambert JD, and Yang CS. Inhibition of carcinogenesis by tea constituents. Seminars in Cancer Biology. 2007;17:395-402.
101. Bickers D, Calow P, Greim H, Hanifin JM, Rogers AE, Saurat JH, Sipes IG Smith RL, and Tagami H. A toxicologic and dermatologic
assessment of linalool and realated esters when used as fragrance ingredients. Food and Chemical Toxicology. 2003;41:(7):919-942.
102. Poginsky B, Westendorf N, Prosenc N, Kuppe M, and Marquardt H. St. John's wort (Hypericum perforatum L.). Genotoxicity induced by
quercetin content. Deutsche Apotheker Zeitung. 1988;128:13464-13466.
103. Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, and Lines TC. A critical review of the data related to the safety of
quercetin and lack of evidene of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food and Chemical Toxicology.
2007;45:(11):2179-2205.
28
NTP TECHNICAL REPORT
ON THE
TOXICOLOGY STUDIES OF GREEN TEA EXTRACT

IN F344/NTac RATS AND B6C3F1/N MICE
AND TOXICOLOGY AND CARCINOGENESIS STUDIES
OF GREEN TEA EXTRACT
IN WISTAR HAN[Crl:WI(Han)] RATS
AND B6C3F1/N MICE
(GAVAGE STUDIES)
Scheduled Peer Review Date: May 22, 2014
NOTICE
This DRAFT Technical Report is distributed solely for the purpose of predissemination peer review under the applicable information
quality guidelines. It has not been formally disseminated by the NTP. It does not represent and should not be construed to represent
NTP determination or policy.
NTP TR 585
NIH Publication No. 14-5927
National Toxicology Program
National Institutes of Health

Public Health Service
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
5
ABSTRACT
GREEN TEA EXTRACT
CAS No. None Available
Synonyms: Green tea catechin polyphenols; green tea; green tea polyphenols
Botanical name: Camellia sinensis
Dried concentrated extracts from green tea containing high amounts of catechins are a popular source for
nutraceutical and medicinal uses. Green tea extracts are commonly consumed as weight loss supplements and are
popular ingredients in sunblocks, cream rinses, and other cosmetics. Numerous studies in both experimental
animals and clinical settings have studied the possible anticancer, anti-inflammatory, antimicrobial, and cardio- and
neuroprotective properties of green tea extract. The active ingredient of green tea extract, epigallocatechin gallate
(EGCG), was originally nominated by the National Cancer Institute for toxicity and carcinogenicity studies because
it is the most abundant catechin in green tea extract, it is being investigated as a potential chemotherapeutic agent,
and there was a lack of adequate information with regard to its toxicity. However, the NTP selected green tea
extract [containing EGCG (48.4% by weight) and other green tea catechins] for study because there is more human
exposure to green tea extract and to products containing a concentrated mixture of various green tea catechins. The
NTP analyzed four lots of green tea extract and selected a source based on quantities of EGCG, consistency with
Peer Review Draft NOT FOR ATTRIBUTION

6 Green Tea Extract, NTP TR 585
other products on the market, and availability in bulk quantity. Oral gavage was chosen as the route of
administration because it was considered most relevant to human exposure. Male and female F344/NTac rats and
B6C3F1/N mice were administered green tea extract in water by gavage for 3 months and male and female Wistar
Han [Crl:WI(Han)] rats (referred to as Wistar Han rats) and B6C3F1/N mice were administered green tea extract in
water by gavage for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia
coli, and mouse peripheral blood erythrocytes.
3-MONTH STUDY IN F344/NTAC RATS
Groups of 10 male and 10 female core study rats were administered 0, 62.5, 125, 250, 500, or 1,000 mg green tea
extract/kg body weight in deionized water by gavage, 5 days per week for 14 weeks. Groups of 10 male and
10 female clinical pathology study rats were administered the same doses for 23 days. One 125 mg/kg female died
during week 7. Mean body weights of males and females administered 250 mg/kg or greater were significantly less
than those of the vehicle controls.
The cauda epididymis, epididymis, and testes weights of 1,000 mg/kg males were significantly less than those of the
vehicle controls. Females administered 1,000 mg/kg had longer estrous cycles and spent significantly more time in
extended diestrus than did the vehicle controls. These data indicate that green tea extract exhibits the potential to be
a reproductive toxicant in male and female F344/NTac rats.
Several nonneoplastic liver lesions were observed in three of ten 1,000 mg/kg females. Lesions included hepatocyte
necrosis, bile duct hyperplasia, oval cell hyperplasia, and mitosis. There were significant increases in the incidences
of several nonneoplastic lesions in the nose of 1,000 mg/kg males and females including inflammation (females);
hyperplasia in the Bowman’s gland of the olfactory epithelium; nerve atrophy; and atrophy, metaplasia, and
pigmentation in the olfactory epithelium; the increased incidences of inflammation (females), nerve atrophy, and
olfactory epithelium metaplasia and pigmentation (males) were also significant in the 500 mg/kg groups. The
incidences of histiocyte cellular infiltration in the mesenteric lymph node in 125 mg/kg or greater males were
significantly increased compared to that in the vehicle control group.
NOT FOR ATTRIBUTION Peer Review Draft

Green Tea Extract, NTP TR 585 7
3-MONTH STUDY IN MICE
Groups of 10 male and 10 female mice were administered 0, 62.5, 125, 250, 500, or 1,000 mg green tea
extract/kg body weight in deionized water by gavage, 5 days per week for 14 weeks. Six males and four females
administered 1,000 mg/kg died before the end of the study; early deaths were due to liver necrosis. Mean body
weights of males administered 250 mg/kg or greater and females administered 125 mg/kg or greater were
significantly less than those of the vehicle controls. Clinical findings included lethargy, abnormal breathing, and
ataxia in females that died early.
A significantly decreased spermatid per testis count was observed in 500 mg/kg males. Females administered
500 mg/kg spent significantly more time in extended diestrus than did the vehicle controls. These data indicate that
green tea extract exhibits the potential to be a reproductive toxicant in male and female mice.
In the liver, the incidences of glycogen depletion were significantly increased in 250 and 500 mg/kg males and 500
and 1,000 mg/kg females. In addition, the incidences of centrilobular necrosis were significantly increased in
1,000 mg/kg males and females, and the incidence of karyomegaly was significantly increased in 1,000 mg/kg
females. The incidences of nerve atrophy, olfactory epithelium atrophy, and olfactory epithelium metaplasia of the
nose were significantly increased in males administered 250 mg/kg or greater and in 500 and 1,000 mg/kg females;
the incidence of olfactory epithelium necrosis was significantly increased in 1,000 mg/kg females. The incidences
of lymphoid atrophy in the spleen were significantly increased in 500 and 1,000 mg/kg females. The incidences of
atrophy of the mandibular lymph node and thymus were significantly increased in 1,000 mg/kg males and females.
2-YEAR STUDY IN WISTAR HAN RATS
Groups of 60 male and 60 female rats were administered 0 or 1,000 mg green tea extract/kg body weight and groups
of 50 male and 50 female rats were administered 100 or 300 mg/kg in deionized water by gavage, 5 days per week
for up to 105 weeks. Ten male and 10 female rats randomly selected from the vehicle control and 1,000 mg/kg
groups were evaluated at 3 months; no significant increases in mortality or nonneoplastic lesion incidences were
observed at 3 months. In the 2-year study, there were significant decreases in survival in 1,000 mg/kg males and

females compared to the vehicle control groups. Mean body weights of 300 and 1,000 mg/kg males were at least
10% less than those of the vehicle control groups after weeks 41 and 9 of the study, respectively; mean body weights
of dosed groups of female rats were at least 10% less after weeks 65 (100 mg/kg), 61 (300 mg/kg), and 57
(1,000 mg/kg).
No increases in the incidences of neoplasms in male or female rats were attributed to the administration of green tea
extract.
At 2 years, the incidences of hepatic necrosis were significantly increased in 1,000 mg/kg males and females, and
the incidence of oval cell hyperplasia was significantly increased in 1,000 mg/kg females.
In the glandular stomach of 1,000 mg/kg males and 300 and 1,000 mg/kg females at 2 years, the incidences of
mucosa necrosis were significantly greater than the vehicle control incidences. At 2 years, the incidences of mucosa
necrosis in all segments of the small intestine were significantly increased in 1,000 mg/kg males and females.
In the nose at 3 months, the incidences of nerve and olfactory epithelium atrophy in 1,000 mg/kg males and the
incidence of pigmentation in the olfactory epithelium of 1,000 mg/kg females were significantly increased. At
2 years, the incidences of numerous nonneoplastic lesions of the nose were generally significantly increased in all
dosed groups of males and females. These lesions included mineralization and pigmentation of the lamina propria;
suppurative inflammation of the nasopharyngeal duct; nerve atrophy; atrophy, respiratory metaplasia, and
pigmentation of the olfactory epithelium; respiratory epithelium atrophy; and deformity and hyperostosis of the
turbinate. The incidences of suppurative inflammation were significantly increased in 1,000 mg/kg males and in
300 and 1,000 mg/kg females, and the incidences of basal cell hyperplasia of the olfactory epithelium were
significantly increased in males and females administered 300 or 1,000 mg/kg. Incidences of additional
nonneoplastic nasal lesions were significantly increased in one or more dosed groups of males and/or females.
The incidences of suppurative inflammation in the lung and inflammation of the heart (epicardium) were
significantly increased in 1,000 mg/kg males and females at 2 years.

The incidences of bone marrow hyperplasia in all dosed groups of females were significantly greater than the
vehicle control incidence.
In the spleen of 1,000 mg/kg males and all dosed groups of females, the incidences of lymphoid depletion were
significantly increased.
2-YEAR STUDY IN MICE
Groups of 50 male and 50 female mice were administered 0, 30, 100, or 300 mg green tea extract/kg body weight in
deionized water by gavage, 5 days per week for 105 weeks. Survival of dosed groups was similar to that of the
vehicle control groups. Mean body weights of 100 and 300 mg/kg males were at least 10% less than those of the
vehicle control group after weeks 89 and 65, respectively, and mean body weights of 100 and 300 mg/kg females
were at least 10% less after weeks 25 and 17, respectively.
One squamous cell papilloma and one squamous cell carcinoma of the tongue were noted in 300 mg/kg females.
The incidences of hematopoietic cell proliferation and inflammation in the liver were significantly increased in
300 mg/kg males.
The incidences of numerous nonneoplastic lesions of the nose were generally significantly increased in all dosed
groups. These lesions included foreign body, suppurative inflammation, nerve atrophy, atrophy and respiratory
metaplasia of the olfactory epithelium, and squamous metaplasia and necrosis of the respiratory epithelium. The
incidences of hyperostosis, olfactory epithelium fibrosis, septum perforation, and turbinate atrophy were
significantly increased in 100 and 300 mg/kg males and females, and the incidences of respiratory epithelium
hyperplasia were significantly increased in 100 and 300 mg/kg females. The incidence of nasopharyngeal duct
degeneration was significantly increased in 300 mg/kg males.

The incidences of lymphoid hyperplasia and plasma cell infiltration of the mandibular lymph node were
significantly increased in 100 and 300 mg/kg males and females.
The incidences of bone marrow hyperplasia were significantly increased in all dosed groups except 30 mg/kg
females.
GENETIC TOXICOLOGY
Green tea extract was mutagenic in S. typhimurium strains TA98 and TA100 in the presence of induced rat liver S9;
no mutagenicity was observed in these strains without S9 or in the E. coli strain WP2 uvrA/pKM101, with or
without S9. In vivo, no increases in the frequencies of micronucleated erythrocytes were seen in peripheral blood of
male or female B6C3F1/N mice in the 3-month study.
CONCLUSIONS
Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity* of green tea
extract in male or female Wistar Han rats administered 100, 300, or 1,000 mg/kg. There was no evidence of
carcinogenic activity of green tea extract in male B6C3F1/N mice administered 30, 100, or 300 mg/kg. There was
equivocal evidence of carcinogenic activity of green tea extract in female B6C3F1/N mice based on occurrences of
squamous cell neoplasms of the tongue.
Administration of green tea extract resulted in increased incidences of nonneoplastic lesions of the liver, glandular
stomach, small intestine (duodenum, ileum, and jejunum), nose, lung, heart, and spleen in male and female rats;
bone marrow of female rats; the nose, mandibular lymph node, and bone marrow of male and female mice; and the
liver of male mice.
* Explanation of Levels of Evidence of Carcinogenic Activity is on page 13.

Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of Green Tea Extract
Male Female Male Female

Wistar Han Rats Wistar Han Rats B6C3F1/N Mice B6C3F1/N Mice
Doses in water by gavage 0, 100, 300, or 1,000 mg/kg 0, 100, 300, or 1,000 mg/kg 0, 30, 100, or 300 mg/kg 0, 30, 100, or 300 mg/kg
Body weights 300 and 1,000 mg/kg 100, 300, and 1,000 mg/kg 100 and 300 mg/kg 100 and 300 mg/kg groups
group at least 10% less groups at least 10% less groups at least 10% less at least 10% less than
than vehicle control group than vehicle control group than vehicle control vehicle control group after
after weeks 41 and 9, after week 65, 61, and 57, group after weeks 89 and weeks 25 and 17,
respectively respectively 65, respectively respectively
Survival rates 35/50, 37/50, 43/50, 24/50 26/50, 28/50, 23/50, 4/50 33/50, 36/50, 33/50, 37/50 34/50, 33/50, 44/50, 39/50
Nonneoplastic effects Liver: necrosis (1/50, Liver: necrosis (3/50, 2/48, Liver: hematopoietic Nose: foreign body (4/48,
2/50, 2/50, 13/50) 5/49, 24/46); cell proliferation (2/50, 8/48, 13/50, 17/50);
Stomach, glandular: oval cell hyperplasia (1/50, 2/50, 6/50, 10/50); hyperostosis (0/48, 0/48,
mucosa necrosis (0/49, 2/48, 3/49, 16/46) inflammation (4/50, 21/50, 48/50); suppurative
3/50, 3/50, 21/50) Stomach, glandular: 1/50, 5/50, 12/50) inflammation (4/48, 24/48,
Small intestine, mucosa necrosis (0/50, Nose: foreign body 44/50, 47/50); nerve,
duodenum: mucosa, 1/49, 7/49, 20/44) (1/50, 10/49, 16/50, atrophy (0/48, 13/48,
necrosis (0/50, 1/47, 1/49, Small intestine, duodenum: 25/50); hyperostosis 47/50, 48/50); olfactory
10/48) mucosa, necrosis (0/47, (0/50, 0/49, 28/50, epithelium atrophy (0/48,
Small intestine, ileum: 0/48, 1/48, 5/39) 46/50); suppurative 18/48, 26/50, 17/50);
mucosa necrosis (0/50, Small intestine, ileum: inflammation (14/50, olfactory epithelium,
1/48, 2/49, 6/45) mucosa necrosis (0/45, 40/49, 49/50, 48/50); fibrosis (0/48, 1/48, 39/50,
Small intestine, jejunum: 0/46, 0/47, 5/36) nasopharyngeal duct, 43/50); olfactory
mucosa necrosis (0/49, Small intestine, jejunum: degeneration (0/50, 0/49, epithelium, metaplasia,
0/47, 2/48, 9/46) mucosa necrosis (0/45, 4/50, 9/50); nerve, respiratory (2/48, 36/48,
Small intestine, 0/43, 1/45, 6/40) atrophy (0/50, 26/49, 49/50, 48/50); respiratory
(duodenum, ileum, Small intestine, (duodenum, 49/50, 50/50); olfactory epithelium, hyperplasia
jejunum): ileum, jejunum): epithelium, atrophy (1/48, 1/48, 22/50, 15/50);
Necrosis (0/49, 2/46, 4/48, Necrosis (0/44, 1/42, 2/44, (4/50, 24/49, 28/50, respiratory epithelium,
14/45) 10/33) 3/50); olfactory metaplasia, squamous
Nose: suppurative Nose: foreign body (3/49, epithelium, fibrosis (0/48, 8/48, 42/50, 42/50);
inflammation (11/50, 2/49, 4/50, 8/49); (0/50, 4/49, 37/50, respiratory epithelium,
12/50, 20/50, 42/50); suppurative inflammation 43/50); olfactory necrosis (0/48, 4/48,
lamina propria, (5/49, 3/49, 17/50, 35/49); epithelium, metaplasia, 28/50, 32/50); septum,
mineralization (0/50, epithelium, nasopharyngeal respiratory (11/50, perforation (0/48, 0/48,
33/50, 34/50, 44/50); duct, necrosis (0/49, 1/49, 45/49, 49/50, 49/50); 38/50, 42/50); turbinate,
lamina propria, 2/50, 7/49); epithelium, respiratory epithelium, atrophy (0/48, 0/48, 40/50,
pigmentation (0/50, 4/50, nasopharyngeal duct, metaplasia, squamous 48/50)
11/50, 25/50); regeneration (0/49, 0/49, (0/50, 14/49, 39/50, Mandibular lymph node:
nasopharyngeal duct, 0/50, 8/49); lamina propria, 46/50); respiratory lymphoid hyperplasia
suppurative inflammation mineralization (3/49, 23/49, epithelium, necrosis (0/50, 1/48, 8/49, 12/48);
(0/50, 6/50, 8/50, 20/50); 30/50, 22/49); lamina (0/50, 7/49, 16/50, plasma cell infiltration
nerve, atrophy (0/50, propria, pigmentation (1/49, 27/50); septum, (0/50, 0/48, 31/49, 18/48)
33/50, 44/50, 44/50); 0/49, 6/50, 14/49); perforation (1/50, 0/49, Bone marrow: hyperplasia
olfactory epithelium, nasopharyngeal duct, 26/50, 37/50); turbínate, (6/50, 11/50, 41/50, 34/50)
atrophy (1/50, 38/50, suppurative inflammation atrophy (0/50, 0/49,
41/50, 41/50); olfactory (0/49, 2/49, 5/50, 15/49); 41/50, 50/50)
epithelium, hyperplasia, nerve, atrophy (0/49, 38/49, Mandibular lymph node:
basal cell (0/50, 1/50, 9/50, 41/50, 38/49); olfactory lymphoid hyperplasia
28/50); olfactory epithelium, atrophy (2/49, (0/50, 1/50, 31/50,
epithelium, metaplasia, 35/49, 42/50, 34/49); 37/50); plasma cell
respiratory (4/50, 40/50, olfactory epithelium, infiltration (1/50, 1/50,
43/50, 47/50); olfactory hyperplasia, basal cell 24/50, 41/50)
epithelium, necrosis (1/50, (0/49, 0/49, 8/50, 20/49); Bone marrow:
3/50, 0/50, 12/50); olfactory epithelium, hyperplasia (5/50, 42/50,
olfactory epithelium, metaplasia, respiratory 38/50, 46/50)
pigmentation (6/50, 18/50, (1/49, 42/49, 43/50, 36/49);
12/50, 21/50); respiratory olfactory epithelium,
epithelium, atrophy (0/50, necrosis (0/49, 3/49, 1/50,
2/50, 5/50, 6/50) 18/49)

Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of Green Tea Extract
Male Female Male Female

Wistar Han Rats Wistar Han Rats B6C3F1/N Mice B6C3F1/N Mice
Nonneoplastic effects Nose (continued): Nose (continued):

(continued) respiratory epithelium, olfactory epithelium,
metaplasia, squamous pigmentation (0/49,
(0/50, 1/50, 3/50, 7/50); 11/49, 7/50, 5/49);
turbinate, deformity respiratory epithelium,
(0/50, 16/50, 22/50, atrophy (0/49, 8/49, 9/50,
35/50); turbinate, 3/49); respiratory
hyperostosis (0/50, 18/50, epithelium, necrosis
27/50, 40/50) (0/49, 1/49, 2/50, 17/49);
Lung: suppurative respiratory epithelium,
inflammation (0/50, 1/50, pigmentation (0/49, 1/49,
3/50, 10/50) 5/50, 5/49); turbinate,
Heart (epicardium): deformity (0/49, 6/49,
inflammation (0/50, 0/50, 20/50, 15/49); turbinate,
1/50, 5/50) hyperostosis (0/49, 18/49,
Spleen: lymphoid 32/50, 36/49)
depletion (1/50, 2/50, Lung: suppurative
1/50, 13/50) inflammation (1/50, 3/49,
2/50, 9/48)
Heart (epicardium):
inflammation (0/50, 2/48,
2/50, 4/48)
Bone marrow:
hyperplasia (6/50, 14/50,
16/50, 13/50)
Spleen: lymphoid
depletion (0/50, 7/49,
5/48, 17/43)
Neoplastic effects None None None None
Equivocal findings None None None Tongue: squamous cell

papilloma or squamous
cell carcinoma, (0/50,
0/50, 0/50, 2/50)
Level of evidence of No evidence No evidence No evidence Equivocal evidence

carcinogenic activity
Genetic toxicology
Bacterial gene mutations: Positive in S. typhimurium strains TA98 and TA100 with S9, negative in TA98 and
TA100 without S9, and negative in E. coli with or without S9
Micronucleated erythrocytes
Mouse peripheral blood in vivo: Negative

Personal Core Products Council
Committed to Safety,
Quality & Innovation
Memorandum
TO: Lillian Gill, D.P.A.

Director - COSMETIC INGREDIENT REVIEW (CIR)
CIR Expert Panel Members
Liaison Members of the CIR Expert Panel
FROM: CIR Science and Support Committee ofthe Personal Care Products Council
DATE: April30, 2014
SUBJECT: Comments Concerning the Conclusion of the Tentative Report: Safety Assessment of
Camellia sinensis-Derived Ingredients as Used in Cosmetics
The CIR Science and Support Committee (CIR SSC) ofthe Personal Care Products Council
appreciates the opportunity to comment on the Tentative Report: Safety Assessment of Camellia
sinensis-Derived Ingredients as Used in Cosmetics.
We are especially concerned about the "safe as used" conclusion for Camellia Sinensis Catechins. This
conclusion is difficult to justify when there are no reported uses or concentrations of use for this
ingredient presented in the report. Camellia Sinensis Catechins should be included with the
ingredients with insufficient data conclusions.
The guinea pig sensitization studies summarized in the CIR report suggest that catechins may be
sensitizing. Perhaps, the CIR Expert Panel should include catechins among the constituents of
concern for these ingredients. Currently, the subsection Constituents of Concern is not clear as to
which compounds are of concern to the CIR Expert Panel, compared to other compounds, such as
caffeine and stearic acid, that may also be present.
The CIR Expert Panel should also consider revising the conclusion for the leaf extract. As the
composition of Camellia Sinensis LeafExtract can be variable depending on how the leaves are treated
before extraction, e.g., green, black, oolong, as well as the extraction solvent and extraction conditions,
relying on two HRIPTs of products containing 0.86% of a black tea extract to set a concentration limit
for all tea leaf extracts does not seem appropriate. The Discussion of the report should be expanded to
note the RIFM review of tea leaf absolute that uses a dose of 480 !lg/cm2 as the weight of evidence
(WoE) No Expected Sensitization Induction Level (NESIL) for calculating the IFRA standards, as well
the negative animal and human studies on various other Camellia Sinensis Leaf Extracts summarized
in the CIR report. Based on the information in the report, safe when formulated to be non-sensitizing
would be a more appropriate conclusion for Camellia Sinensis Leaf Extract. When the
I
1620 L Street, N.W., Suite 1200 Washington, D.C. 200361202.331.1770 I 202.331.1969 (fax} I www.personalcarecouncil.org
"non-sensitizing" limitation is used in a conclusion for plant-derived ingredients, the Discussion of the
CIR report should clearly state the constituents of the plants that are known sensitizers.
The composition of Camellia sinensis leaves is well-described in the CIR report and other ingredients
derived from the leaves, e.g., Camellia Sinensis Leaf, Camellia Sinensis Leaf Oil, Camellia Sinensis
Leaf Powder and Camellia Sinensis Leaf Water, are expected to contain similar constituents as the leaf
extracts. Therefore, the CIR Expert Panel should consider extending a conclusion of "safe when
formulated to be non-sensitizing" to other leaf-derived ingredients. The conclusion for ingredients
derived from other plant parts should remain as insufficient data.
2
Personal Care Products Council
Committed to Safety,
Quality & Innovation
Memorandum
TO: Lillian Gill, D.P.A.

Director - COSMETIC INGREDIENT REVIEW (CIR)
FROM: Halyna Breslawec, Ph.D.

Industry Liaison to the CIR Expert Panel
DATE: April24, 2014
SUBJECT: Comments on the Tentative Report: Safety Assessment of Camellia sinensis-

Derived Ingredients as Used in Cosmetics
The company that provided the studies containing 0.86% Camellia Sinensis Leaf Extract has
indicated that it is an extract of black tea.
Key Issue
The Carcinogenicity section should at least mention that NTP has completed a 2 year oral study
on green tea extract (peer review is scheduled for May 22, 2014).
Additional Comments
p.2 - The Introduction should note that Camellia Sinensis Seed Oil is not included in this report.
p.3 - What are the constituents of concern in Camellia sinensis-derived ingredients? The current
section titled Constituents of Concern mentions theanine, standard a-amino acids,
caffeine and stearic acid. Are these substances all constituents of concern? The
following sentence is presented in the Constituents section and the section on
Constituents of Concern. It is not necessary to have it twice on the same page.
"Constituents reported predominantly in C. sinensis seeds include caffeine, glucothea
saponin, stearic acid, theasponin, and theobromine."
p.5 -As Camellia Sinensis Seed Oil is no longer in the report, the information on the
manufacture of triglyceride oils in the Method of Manufacture section (last 5 paragraphs)
should be deleted. Information from the Dictionary concerning the manufacture of
essential oils and waters should be added to this section.
p.6- The product containing 50% Camellia Sinensis Leaf Powder should be called a professional
face and neck product that is diluted with water before use, rather than a "leave-on"
product.
p.7- Polyethylene glycol400 (average MW 400) is PEG-8 or PEG 400. It should not be called
PEG-400 (average number of moles of ethylene oxide 400).
I
1620 L Street, N.W., Suite 1200 Washington, D.C. 20036 , 202.331.1770 I 202.331.1969 (fax) I www.personalcarecouncil.org
p.8- As saponins are not the same as catechins, the study on saponins extracted from C. sinensis
leaf should not be presented under the heading Camellia Sinensis Catechins.
p.8 - The study on Korean green tea (reference 64) should be presented under the subheading
Camellia Sinensis Leaf Extract.
p.9- The In Vitro subheading under Genotoxicity should be deleted as there are also in vivo
studies (micronucleus) studies summarized in this section.
p.9 - What concentration of catechins "have been shown to have preventive and treatment effects
in cancer cell lines related to cancers of the prostate, lung, skin, pancreas, breast, and
ovaries"?
p.12 -Rather than saying that the oolong tea extract was not irritating in the guinea pig study, it
should state that it was not sensitizing in the guinea pig study.
p.l2 - In the description of the IFRA standard, it should also state that based on animal data, it
was concluded that tea leaf absolute was a moderate sensitizer.
p.13 - The CIR report should also state that the 480 J.Lg/cm2 dose was the weight of evidence
(WoE) NESIL used to develop the IFRA standard based on a QRA for sensitization.
p.14 - The discussion of the IFRA standard should state that the endpoint on which it is based is
sensitization.
p.14- In the last paragraph ofthe "Other Reviews" section, it is not clear what is meant by "this
topic".
p.l4-15 - In the Summary, please note the FDA product categories associated with the reported
use concentrations.
p.14- As the product is diluted before use, it is not appropriate to state "it was used up to 50%".
p.15- In what species was the inhalation study oftea catechins conducted?
p.15 - The Summary should also mention the negative HRIPT of a black tea extract (1% solids)
that was completed in 100 subjects.
p.15-16 - The following sentence is misleading: "Linalool is a dermal sensitizer that has been
found to be safe up to 4.3%." The RIFM review actually concluded that at use
concentrations (maximum 4.3% (20% in a consumer fragrance)) linalool presented no
significant risk of sensitization. The 4.3% concentration was a use level, not a limit
based on sensitization. It should also be noted that oxidation products of linalool are
thought to be sensitizers, rather than linalool itself.
p.18, Table 3 - If it not explained elsewhere, the basis for the RIFM limit on linalool should be
explained in this table. It was not based on sensitization. It was based on the reported
highest use levels which were considered safe.
p.20, Table 3 (should be Table 7)- Camellia Sinensis Leaf Extract: The low concentration for
eye area products should be 0.00002% not 0.0002%.
In the most recent concentration of use information, there is no spray product containing
3% Camellia Sinensis Leaf Extract.
In the Council survey results, the products containing 0.00008% Camellia Sinensis Leaf
Extract and 50% Camellia Sinensis Leaf Powder are marked as not spray; therefore, these
Page 2 of 3
products should not be presented in the incidental inhalation spray row with a footnote
Not aerosol product(s).
Exposure from aerosol compared to pump sprays are different. Therefore, the pump
spray hair spray containing 0.0005% Camellia Sinensis Leaf Extract should not have a
footnote indicating that it is an aerosol product.
p.21, Table 8- Please add "rats" after "Sprague-Dawley" (second row under oral).
p.27, Reference 87- Although the Council may have brought the IFRA standard to the attention
of CIR, the standard is publically available on IFRA's website
http://www.ifraorg.org/en-us/standards#.U07XtUlOX5o. Therefore, it should be cited
to IFRA's website. It is not correct to state: "Unpublished data submitted by the Personal
Care Products Council.
p.28, Reference 97 - Please correct: "Drub Safety"
Page 3 of 3

Camellia Japonica Leaf Extract - Safety Assessment

Uploaded by

Copyright:

Available Formats

Camellia Japonica Leaf Extract - Safety Assessment

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Camellia Japonica Leaf Extract - Safety Assessment

Uploaded by

Copyright:

Available Formats

Safety Assessment of

Camellia Sinensis-Derived Ingredients

Status: Draft Final Report for Panel Review

© Cosmetic Ingredient Review

To: CIR Expert Panel and Liaisons

From: Lillian C. Becker, M.S.

Date: May 16, 2014

Subject: Camellia sinensis – Derived Ingredients As Used In Cosmetics

August, 2013 – SLR posted for comment.

• Method of manufacture, including removal of impurities and constituents of concern (such as

No new data have been submitted to meet these data needs.

June, 2014 – The Panel is to issue a Final Report.

SciFinder – “camellia sinensis” and “UV”. 19 hits ordered

Dr. Marks’ Team

Status: Draft Final Report for Panel Review

© Cosmetic Ingredient Review

• camellia sinensis leaf extract • camellia sinensis leaf water

Figure 1. Catechins from Camellia sinensis

Physical and Chemical Properties

There were no frequency of use or concentration of use data reported for:

Cytotoxicity and Cellular Effects

CAMELLIA SINENSIS LEAF EXTRACT

REPRODUCTIVE AND DEVELOPMENTAL TOXICITY

CAMELLIA SINENSIS CATECHINS

IRRITATION AND SENSITIZATION

CAMELLIA SINENSIS CATECHINS

CAMELLIA SINENSIS LEAF WATER

CAMELLIA SINENSIS CATECHINS

CAMELLIA SINENSIS CATECHINS

CAMELLIA SINENSIS LEAF WATER

CAMELLIA SINENSIS CATECHINS

Table 1. Definitions and functions of Camellia s.-derived ingredients in this report.1

Table 2. Constituent groups of fresh green C. sinensis leaf.4

Table 4. Constituent groups in medical grade Camellia sinensis leaf extract.16,26-30

Table 6. Trace elements in commercial teas and their infusions.38

Camellia sinensis leaf Camellia sinensis seed

20. Eden T. Tea. 3 ed. London: Longman, 1976.

TOXICOLOGY STUDIES OF GREEN TEA EXTRACT

Scheduled Peer Review Date: May 22, 2014

NIH Publication No. 14-5927

National Toxicology Program

National Institutes of Health

GREEN TEA EXTRACT

CAS No. None Available

Peer Review Draft NOT FOR ATTRIBUTION

coli, and mouse peripheral blood erythrocytes.

3-MONTH STUDY IN F344/NTAC RATS

than those of the vehicle controls.

a reproductive toxicant in male and female F344/NTac rats.

significantly increased compared to that in the vehicle control group.

NOT FOR ATTRIBUTION Peer Review Draft

3-MONTH STUDY IN MICE

ataxia in females that died early.

2-YEAR STUDY IN WISTAR HAN RATS

Peer Review Draft NOT FOR ATTRIBUTION

significantly increased in 1,000 mg/kg males and females at 2 years.

NOT FOR ATTRIBUTION Peer Review Draft

vehicle control incidence.

2-YEAR STUDY IN MICE