Document 7640J0egkdGY145R67kxJ70R

Safety Assessment of Polysilsesquioxanes as Used in Cosmetics Status: Release Date: Panel Meeting Date: Draft Final Report for Panel Review November 10, 2017 December 4-5, 2017 The 2017 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Executive Director is Bart Heldreth, Ph.D. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 0 Washington, DC 20036-4702 0 ph (&,cir-safetv.org 0 fax To: From: Date: Subject: Cosmetic Ingredient Review MEMORANDUM CIR Expert Panel and Liaisons Commitment & Credibility since 1976 Lillian C. Becker, M.S. Scientific Analyst and Writer November 10, 2017 Polysilsesquioxanes as used in cosmetics Attached is the draft final report of 18 polysilsesquioxanes as used in cosmetics. [PLYSIL122017Rep]. The ingredients in this group comprise the polymeric ingredients resulting from the hydrolysis and condensation of alkylalkoxysilanes. In June 2017, a tentative report was issued with the conclusion of safe as used. Since then, more data were submitted by the Council. These data, plus the data submitted in Wave 3, are marked in the report with vertical lines in the margins. The newly submitted acute oral data fill an additional data point. The dermal irritation and genotoxicity data adds additional ingredients to already addressed data points. In general, the oral LD5os were > 5000 mg/kg, the ingredients were non-irritating to rabbits at 100%, and were not genotoxic. Polymethylsilsesquioxane - HRIPT (22%; Wave 3 from June) [PLYSIL122017Data_1] Methoxy PEG-10 Polysilsesquioxane -- Physical and chemical properties, acute oral toxicity in rats, dermal irritation in rabbits, and bacterial reverse mutation assay; Trimethylpentyl Polysilsesquioxane - bacterial reverse mutation assay [PLYSIL 122017Data_2] Trimethylpentyl Polysilsesquioxane (two forms of this ingredient) - Physical and chemical properties, acute oral toxicity in rats, dermal irritation in rabbits [PLYSIL 122017Data_3] Isobutyl/Methoxy PEG-10 Polysilsesquioxane - Physical and chemical properties, acute oral toxicity in rats, dermal irritation in rabbits [PLYSIL122017Data_4] 1620 L Street, NW Suite 1200, Washington, DC 20036 (Main) (Fax) (Email) @cir-safety.org (Website) www.cir-safety.org  Methacryloyloxypropyl Polysilsesquioxane - Physical and chemical properties, acute oral toxicity in rats, dermal irritation in rabbits, and two bacterial reverse mutation assays [PLYSIL122017Data_5] Isobutyl Polysilsesquioxane - Physical and chemical properties, acute oral toxicity in rats, dermal irritation in rabbits [PLYSIL122017Data_6] Also, concentration of use data for the remaining ingredients were submitted. There were no reported concentrations of use for Trimethylpentyl Polysilsesquioxane, Isobutyl/Methoxy PEG-10 Polysilsesquioxane, and Methoxy PEG-10 Polysilsesquioxane. [PLYSIL 122017Data_7] Council comments have been addressed. [PLYSIL122017PCPC 1, 2] In response to discussion on the monomers of these ingredients, a summary of the key European Chemicals Agency (ECHA) data on trimethoxysilane (a monomer of polysilsesquioxanes) is included in this memo (Table 1). Does the Panel want to include this data in the report? If the new data warrant a change to the Conclusion of this report, the Panel should provide the rationale to be included in the Discussion. If the data do not warrant a change to the Conclusion, the Panel should review the Abstract, Conclusion, and Discussion ensuring that each captures the Panel's thinking. 1620 L Street, NW Suite 1200, Washington, DC 20036 (Main) (Fax) (Email) @cir-safety.org (Website) www.cir-safety.org Table 1. Summaries of toxicity studies of trimethoxysilane from the ECHA database.' Assay Animal (n) Concentration Results Acute Dermal Toxicity (OECD GL 402) -- Under occlusion (time not specified). Rabbits observed for 14 days. Acute Dermal Toxicity -- 24 h under occlusion Acute Dermal Toxicity -- 24 h under occlusion. Rabbits observed for 14 days. Acute Oral Toxicity -- Oral gavage. Observed for 14 days. Acute Inhalation Toxicity -- whole body for 4h Subchronic Inhalation Toxicity; 90Day Study -- OECD GL 413 (whole body 6 h/day, 5 day/week followed by 4 week recovery Rabbit (4 or 5/sex) Female Rabbit (4) Male New Zealand White Rabbit (4) Rat (5/sex, with the exception of 2 males in the 8.0 mL/kg group) SpragueDawley rat (5/sex) SpragueDawley rat (10 with an additional 5 rats/sex in the control and high dose groups) 4.0, 8.0, and 16.0 mL/kg 4.0 and 12.0 mL/kg 5.0 or 10.0 mL/kg Males: 1.0, 2.0, 4.0, and 8.0 ml/kg; females: 1.0, 1.41, 2.0, and 4.0 ml/kg 19, 39, 71, and 166 ppm 0.02, 0.1, and 0.5 ppm The LD50 = 7.46 mL/kg in males and 6.73 mL/kg in female rabbis. Local cutaneous effects included erythema, edema, necrosis, ecchymosis, fissuring (one rabbit), ulceration, desquamation, scabs and alopecia. Sluggishness, salivation, prostration, emaciation, and a clear or red discharge around the nose were among the clinical findings. Gross pathological findings included bright or dark red lungs, tan to red raised nodules or foci on the lungs, lungs of one with necrotic areas, tan livers, liquid-filled hemorrhaged intestines, white or black foci on stomach or intestines, cream colored foci on intestines, one with mottled and dark red kidneys and one with tan raised mass on kidney. Histopathology of lungs with tan nodules showed abscesses, congestion, hemorrhages, edema, alveolar histiocytosis, mononuclear cells and black deposits. Histopathology of the kidney with raised mass showed effect due to infection. Microscopic examination did not reveal any significant lesions. One rabbit died after 4.0 mL/kg and all of the animals died after receiving 12.0 mL/kg. The LD50 was not determined. After both doses rabbits appeared sluggish. After 12.0 mL/kg, rabbits were also found to be prostrate, one animal had a protruding red eye, and one animal had foam on the perinasal area at death. In rabbits that died gross pathology revealed dark red lungs, and trace amounts of blood in the urine. All of the rabbits died within 4 days of exposure to 10.0 mL/kg, and 1 rabbit in the 5.0 mL/kg group died on day 3. Gross findings at necropsy included congested lungs, mottled livers, and bright mottled kidneys with prominent surface markings. Marked erythema of the skin was also observed. There was no effect on body weight gain in the 5.0 mL/kg group. The LD50 was calculated to be 6.3 ml/kg. The LD50 was 2.46 and 1.56 mL/kg for males and females, respectively. Signs of toxicity included sluggishness, lacrimation, unsteady gait, distended abdomen, head and body twitches (2 rats), piloerection, prostration, moribund appearance (1 rat), red crust around nose and eyes, diarrhea (2 rats), unkempt appearance and emaciation. Most deaths occurred between 1 and 4 days after application. At necropsy, the rats that died had gas-filled stomachs and intestines, red and/or thick stomachs, a hard white material in the stomach, red intestines and red liquid-filled abdominal cavities. In survivors, the only macroscopic finding was mottled and tan to dark red appearance of several kidneys. There was no effect on body weights. There were deaths at all concentrations, except 19 ppm groups. Deaths occurred primarily on post-exposure days 6 to 13. Males in the 166 ppm group had blepharospasm, abdominal breathing, decreased motor activity, ataxia, slow surface-righting reflex on the day of exposure. Females in the 166 ppm group had blepharospasm, periocular wetness, decreased breathing and motor activity. Males of the 71 ppm group had blepharospasm, abdominal breathing, decreased motor activity, ataxia, a slow surface righting reflex on the day of exposure, and unkempt fur. In females, periocular wetness, abdominal breathing and decreased motor activity were observed during exposure and unkempt fur and decreased motor activity on post-exposure days 10 -14. Similar clinical signs were also observed in the 39 ppm group. Losses in body weight were observed during both post-exposure weeks. There were no abnormal findings in the gross necropsy examination. The LC50 was 60 (45 to 80) ppm; there was no significant difference in LC50 values between male and female rats. There were no exposure-related effects upon clinical signs, body weight and body weight gains, feed and water consumption, ophthalmic evaluations, hematology, clinical chemistry, serum protein fractions, urine chemistry, urinalysis, absolute and relative organ and tissue weights, or gross and microscopic evaluations of organs and tissues. The NOAEL was determined to be at least 0.51 ppm under the conditions of this study. 1620 L Street, NW Suite 1200, Washington, DC 20036 (Main) (Fax) (Email) @cir-safety.org (Website) www.cir-safety.org Table 1. Summaries of toxicity studies of trimethoxysilane from the ECHA database.' Assay Animal (n) Concentration Results Bacterial Reverse Mutation Assay Micronucleus Assay by noseonly inhalation for 4 h then 30h rest period. Acute Dermal Irritation/ Corrosion -- 4 h under occlusion the observed for 14 days. Guinea pig maximization assay (OECD GL 406) Acute Eye Irritation/ Corrosion -- Instilled one eye and observed for 7 days. S. typhimurium (TA98, TA100, TA1535, TA1537); E. coli (WP2 and WP2 uvrA) Female SpragueDawley rat (5) Rabbit (6) Guinea pig (10) Rabbit (6) 100, 333, 1000, 3333, and 5000 ug/plate in DMSO with and without metabolic activation 100 ppm 100%; 0.5 mL 1st application: Induction 5% trimethoxysilane in cottonseed oil, 5% Trimethoxysilane in a 1:1 mixture of Freund's Complete Adjuvant: cottonseed oil and FCA (0.1 mL) intracutaneously. 2nd application: Induction 25 % occlusive epicutaneous. 3rd application: Challenge 2.5 % open epicutaneous. 0.1 mL Not mutagenic Under test conditions, trimethoxysilane did not induce chromosome breakage or act as a spindle poison in the rodent micronucleus assay even when animals were exposed to lethal concentrations. Moderate to severe erythema, severe edema and necrosis was observed on 6 of 6 rabbits. Ecchymosis was present on 3 rabbits. The dose site of 1 rabbit could not be scored until 2 days because the gauze patch (used in dose application) had completely adhered to the skin. Four rabbits exhibited fissuring within 3 days. Erythema was no longer present on any of rabbit at 7 days and edema was no longer observed after 14 days. However, desquamation, ulceration, scabs and alopecia developed on all rabbits within 7 to 14 days. Thus, severe irritation was present through 14 days. Trimethoxysilane was corrosive to the skin of rabbits after a four hour exposure. There were no sensitization reactions in the test group following challenge, and the Sensitization Incidence Index was calculated to be 0%. Based on these results, the test material, Trimethoxysilane, was found to be nonsensitizing in albino guinea pigs under the conditions of this study. The test material vehicle, cottonseed oil, was also nonsensitizing under the conditions of this study. Minor corneal opacity in 3 rabbits. Iritis and moderate to severe conjunctival irritation (including necrosis in five) were observed in all six animals. All rabbits had a purulent ocular discharge. Except for alopecia in the periocular area of each dosed eye and a substantial discharge in one eye, all eyes appeared to be essentially healed by seven days. Alopecia was still evident in each rabbit on day 14 but no other effects were observed. It was concluded that trimethoxysilane was moderately irritating to the eyes of rabbits. REFERENCES 1. European Chemicals Agency (ECHA). Trimethoxysilane. European Chemicals Agency. 4-202017. http://echa.europa.eu/reqistration-dossierNreqistered-dossier/16258Date Accessed 10-16-2017 1620 L Street, NW Suite 1200, Washington, DC 20036 (Main) (Fax) (Email) @cir-safety.org (Website) www.cir-safety.org SAFETY ASSESSMENT FLOW CHART INGREDIENT/FAMILY ____Polysilsesquioxanes ______________ ____________________ MEETING _____Dec 2017_____________________________________________________________ Public Comment CIR Priority List INGREDIENT Expert Panel PRIORITY LIST Report Status 60 day public comment period SLR April 13, 2017 Draft Report Table IDA Notice Draft TR Table 60 day Public comment period Tentative Report June 22, 2017 Draft FR Table PUBLISH Final Report DRAFT REPORT June 2017 Table IDA TR IDA DRAFT TENTATIVE REPORT Table Issue TR DRAFT FINAL REPORT Dec 2017 Table Different Conclusion Issue FR Distributed for comment only -- do not cite or quote History - Polysilsesquioxanes 2016 - Added to the Priority List. April, 2017 - An SLR was posted with the following data request: All toxicological data that pertains to these ingredients, especially from dermal exposure. Chemical and physical properties data are also desirable. The data requested include, but are not limited to: Chemical and physical properties, including mean molecular weight and molecular weight distribution Method of manufacture Impurity data, including residual monomer content Dermal penetration Chronic dermal toxicity Inhalation toxicity Carcinogenicity Dermal irritation and sensitization June, 2017 - Panel issued a tentative report with the conclusion of safe as used. The Panel received much data in Wave 2 and Wave 3. The Panel was satisfied that these ingredients were large and would not penetrate the skin and that monomer impurities would be below levels of detection. December, 2017 - More data were submitted for this report on different ingredients. Distributed for comment only -- do not cite or quote Polymethylsilsesquioxanes Data Profile for December, 2017. Writer - Lill Becker Acute Repeated ADME toxicity dose toxicity Irritation Sensitization Phototoxicity Carcinogenicity Genotoxicity Repro/Devel In Vitro Human Animal Dermal In Vitro Dermal Human Dermal Animal Ocular In Vitro Ocular Animal Inhale Dermal Oral Inhale Dermal Oral Use Log Kow Dermal Penetration Polymethylsilsesquioxane Acryloyloxypropyl Polysilsesquioxane C26-28 Alkyldimethylsilyl Polypropylsilsesquioxane C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane Dimethicone/Silsesquioxane Copolymer Dimethiconol/ Caprylylsilsesquioxane/Silicate Crosspolymer Ethyl Polysilsesquioxane Hydrogen Dimethicone/Octyl Silsesquioxane Copolymer Isobutyl Polysilsesquioxane Methacryloyloxypropyl Polysilsesquioxane Polycaprylylsilsesquioxane Polydimethylsiloxy PEG/ PPG24/19 Butyl Ether Silsesquioxane Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane Polymethylsilsesquioxane/ Trimethylsiloxysilicate Polypropylsilsesquioxane Trimethylpentyl Polysilsesquioxane Isobutyl/Methoxy PEG-10 Polysilsesquioxane Methoxy PEG-10 Polysilsesquioxane X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X Distributed for comment only -- do not cite or quote Search Strategy - Polysilsesquioxanes Ingredient Polymethylsilsesquioxane Acryloyloxypropyl Polysilsesquioxane C26-28 Alkyldimethylsilyl Polypropylsilsesquioxane C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane Dimethicone/Silsesquioxane Copolymer Dimethiconol/ Caprylylsilsesquioxane/ Silicate Crosspolymer Ethyl Polysilsesquioxane Hydrogen Dimethicone/ Octyl Silsesquioxane Copolymer Isobutyl/Methoxy PEG-10 Polysilsesquioxane Isobutyl Polysilsesquioxane Methoxy PEG-10 Polysilsesquioxane Methylacryloxypropyl Polysilsesquioxane Polycaprylylsilsesquioxane Polydimethylsiloxy PEG/PPG-24/19 Butyl Ether Silsesquioxane Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane Polymethylsilsesquioxane/ Trimethylsiloxysilicate Polypropylsilsesquioxane Trimethylpentyl Polysilsesquioxane CAS # 68554-70-1 1204591-17-2 None None 68440-84-6 1802406-18-3 None None None 221326-46-1 1838163-04-4 160185-24-0 1385031-14-0 68554-65-4 none 1402155-47-8 36088-62-7 190732-67-3 444619-08-3 InfoBase N N N Y N N N N N N N N N N N N N N SciFinder 1/0 16/0 0 0 0 0 72/0 0 0 213/0 0 1/0 1/0 0 0 0 26/0 20/0 50/0 PubMed N N N N N N N N N N N N N N N N N N TOXNET N N N N N N N N N N N N N N N N N N FDA N N N N N N N N N N N N N N N N N N EU ECHA IUCLID SIDS N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N HPVIS N N N N N N NICNAS N N N Y N N NTIS 3/0 N N N 2/0 N N N 36/0 N N N N N N N N N N N N N N N N N N 2/0 N N N N N N N N 2/0 N N N NTP N N N N N N N N N N N N N N N N N N WHO FAO N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N FEMA N N N N N N N N N N N N N N N N N N Web Y N N Y N N N N N N N N N N N N N Y Distributed for comment only -- do not cite or quote Search Strategy Substance Identifiers (INCI names and CAS Nos.) Distributed for comment only -- do not cite or quote TRANSCRIPTS - POLYSILSESQUIOXANES June, 2017 Dr. Marks' Team DR. MARKS: ...Okay. Next ingredient -- gosh, this is a mouthful. I wonder why it was named that way. This -- the polysils, I'll ask Ron or Tom to pronounce it or since Lillian, you wrote the memo -- DR. SLAGA: Polysils sounds good. MS. BECKER: Polysilsesquioxanes. DR. MARKS: Yes. Polysilsesquioxanes. Okay. I'm going to call it polysils. There's a draft report from Lillian, so this is the first time we've seen these ingredients. And, of course, the first question is always, do we like these 18 ingredients? Do they all fit together? And then the second, of course, is whether we need -- and we did get a waive 2 on this -- these ingredients. So, first, Tom, Ron and Ron, do you like the ingredients? Is there anything that stands out that shouldn't be among these 18? DR. SLAGA: That's a question for the chemist. DR. HILL: I thought it was -- given the complexities associated with this, I thought the set of ingredients was fine. DR. MARKS: Okay. Great. Next, of course, is what needs do we have? Comments? It's interesting under method of manufacturer, the actual method was not found, but then in waive 2 there was a method of manufacture for one ingredient. So is method of manufacture okay or do we need a more elucidation than we had in -- I can't imagine we would go out the actual method of manufacturer -- that was on page 10; did you guys pick that up? DR. SHANK: Yeah. DR. MARKS: I can't imagine we want to go in a final documentary -- I mean, we've -- where is it? Actual methods of manufacture of these ingredients were not found. That will be changed, because we found method of manufacture -DR. SLAGA: In waive 2. DR. HILL: Let me remind myself -DR. MARKS: -- in waive 2 the dyemethaconesilsbioxin [Dimethicone/Silsesquioxane?]? Is that how you say that? DR. SLAGA: Yes. DR. MARKS: Yeah. Okay. There was some method of manufacture in waive 2, is that enough to go for the entire group? DR. HILL: There's practically nothing there. It says metheltrimathoxyciline [methyltrimethoxysilane] is hydrolyzed at specified temperate and duration followed by condensation. And in this particular case, that's actually fairly clear, but there's some others that there's a lot more than goes on. In reality it's not the method of manufacture that at least I'm interested in, it's what impurities might be there. So, for example, when you have the ones that are asterified [esterfied?] with crolian Acrylic Acid, what's left in there. So we don't have, I think, on any of these we don't have any information about low molecular weight fractions or low molecular weight fractions, some combination of both. And, I mean, we've got language we used in a couple reports to sort of escape that trap, but getting zero information whatsoever in some of these is bothersome, not all of them, some of them. MS. BECKER: There's also some method of manufacture in waive 2 for polysilsesquioxanes. DR. HILL: That's the one I'm looking at. MS. BECKER: Right. DR. HILL: That's the one I just read about. MS. BECKER: And then there's some in the dyemethol [Dimethicone?], the one above it. DR. HILL: The -- which one? MS. BECKER: Dyemetholconesilsesquioxanes [Dimethicone/Silsesquioxane] materials. DR. MARKS: Yeah, that's the one I was reading. MS. BECKER: Right. So we have a little on two. DR. HILL: Yeah, but what it says is the starting materials have done methelconesilsesquioxane copolymer are preliminarized [polymerized?] following the removal of excess dyemethycone [dimethicone]. Each batch is tested for quality and microbial contamination. That's what we've got. MS. BECKER: Right. That's what they gave us. Distributed for comment only -- do not cite or quote DR. MARKS: So is that enough to put in insufficient data? Ron Shank, would you want more data on method of manufacturing? DR. EISENMANN: Well, if you want more data and impurities -DR. HILL: That's what I'm looking at. DR. EISENMANN: -- then that's when you need to be specific and say impurities, because the method of manufacture is hard to get -- they don't want to give any details. DR. HILL: Yeah. And impurities at a level provides the same sort of information in terms of what they're using to put things together with and that's the problem here, which I keep poking at. So I have written here is, we do not know what these prospective molymers [polymers?] might be and we have not sensitization. So wouldn't expect high molecular weight things to sensitize. DR. EISENMANN: I think we do have some sensitization data on the polysilsesquioxanes. DR. HILL: Yes. That's probably the least concerning of any of them. DR. EISENMANN: The difficulty with this report is there's 11 ingredients that have no uses. Eleven of the 18 ingredients have no uses, so it's going to be difficult -- other than the few that uses, it's going to be difficult to get anybody to provide any -DR. HILL: I continue to argue that that's the perfect time to do a split conclusion. We feel like we're covered here, we're not covered there. DR. EISENMANN: Right. DR. MARKS: On page 10 it has impurities constituents and it says the polymetholsils [Polymethylsilsesquioxane] is 100 percent pure and then it tox about these couple others; is that going to be adequate? It says that -- and then they mention a report, there's no detectable residual silene monitors. Is that going to be adequate or do you want more -- again, do you want more impurities constituents? Because if we do then we -- you know, again, it's an insufficient data. I actually -- we flipped over to the irritation sensitization, I thought it was okay when I looked at it, but I'll take another look in a minute. To me, let's -DR. SLAGA: Yeah, well I thought there was sufficient irritation sensitization and -If you looked at all the related compounds that we reviewed, those were all safe. So I had no concern, in the past we didn't anyway. DR. SHANK: Can you read across all of these for sensitization? DR. MARKS: Yeah, I think we always have difficulty with that, yeah. DR. SHANK: It says here, the chemical physical properties vary a lot, this is a challenge. DR. MARKS: Yeah, I was reassured because one of them -- the accrual had 100 percent and HRIPT was okay and the polypropalsil [Polymethylsilsesquioxane] was 50 percent, so high concentrations, but no irritation sensitization. I mean read across is also and always hazardous in this case, but I felt with such high concentrations with these two. And they're the ones -- particularly the polymethol [Polymethylsilsesquioxane] has 397 uses, so that's -- that was the one which overwhelming had the most uses. The others had uses in the teens or none. As you've said Carol, lots of them are none. DR. SHANK: And these are not likely to penetrate the skin? DR. MARKS: I think so, yeah. Particularly if there's not much in the way of residual or molecular weight compounds or monitors. DR. HILL: Again, that's information we lack for quite a few of these. Because looking at this one, it's isobutolpolysilsesquioxane [Isobutyl Polysilsesquioxane], we don't guarantee you that that's put together from somewhere in the production process, perhaps, early isobutoltriclorosilene and probably by way of isobutoltrimathoxysilene based on what they're saying is production process is. Were there residual low molecular weight things, there is the possibility of sensitization. So I always think, you look at the sensitization -- if you have sensitization studies, you look at the one -- the monomers that would be covered by those things that were tested and there you have some assurance. And then we could bring in past studies of anything similar and make sure we're capturing that in the read across correctly and figure out what's, in fact, covered. DR. MARKS: And the other thing we fall back on as I've said before, there notation for -DR. HILL: And how many of those were not in use? DR. MARKS: Well, and the ones that are they're low concentration. And some of these are used -- whatever our concentration use table -- I actually have that -MS. BECKER: 18 in the PDF. Polysilsesquioxane is used up to 55.2 percent. DR. SHANK: Right. And then the other in the polypropal [Polypropylsilsesquioxane] was at 2.4 percent and then after that the accrual is at 5 percent and the others are out. Distributed for comment only -- do not cite or quote DR. MARKS: I didn't think we had reassurance that that 55 percent was not a concern since it was tested neat and it didn't cause sensitization. DR. HILL: That is the one where I would think based on its structure would be the least likely to cause any concerns. So it always bothered me when here we've got this big group and we have good test data for the ones least likely to cause any concern, least likely structurally to sensitize and then we're going to try to read across for the whole group where we have other places where we can see where the residual is and there we could have a problem and we've not got any data. Of course, the ones that are not in use, as far as I'm concerned if there are any of those where that's applicable and sufficient. DR. MARKS: Actually when I looked there wasn't anything that jumped out to me that was a sensitizer in these. DR. HILL: It wouldn't be ingredients. It would be residual or low molecular weight fraction, as usual. DR. MARKS: So let's get back, we haven't in my mind concluded whether or not the method of manufacture/impurities is adequate for this. Do we want to have an insufficient data notice and get more? We aren't going to use actually not found, because that's not the case anymore, we do have two ingredients where we have some suggestion of how it's manufactured. MS. BECKER: Right. Do we want more or better or -DR. MARKS: Yes, exactly, that's where I'm at. Ron Hill, we've talked about it but we haven't come to a conclusion and I think, Ron Shank, if I heard you correctly, I leave this to the chemist. DR. HILL: What I think what I would like to see is a list -- a selective list, these particular ones for these particular potential concerns. I did not write that list up, but I could supply that by morning. DR. MARKS: So with that in mind if you want to see more you would do an insufficient data announcement? DR. HILL: Yeah, I think that's it. They didn't have any other needs other than either monomers or impurities. DR. MARKS: Ron Shank. DR. SHANK: Well, you can always use the escape clause and formulate maybe non-sensitizing. DR. HILL: Then no, because then people who -- I mean, these ones that clearly don't have a risk, then they're stuck doing tests that they shouldn't have to do. DR. MARKS: Well, we don't have a lot of data on any of the others. I mean -DR. HILL: No. DR. MARKS: -- we don't have it on anything. (Participants speaking over each other) DR. MARKS: But otherwise we're relying on -DR. SLAGA: Related compounds. DR. MARKS: Yeah. DR. HILL: Sensitization is the only big concern I have unless, hypothetically, something to do with dermal cancer issues. DR. MARKS: Tom doesn't have a problem with that. DR. SLAGA: I don't. DR. HILL: And, again, it would have to be a low molecular weight, some low molecular weight monomer that was residual. DR. SLAGA: Yeah, it would be the large -DR. HILL: No. So if -DR. SLAGA: -- impurities -- if you're giving it the large molecule complex with a relatively low amount, impurities is much lower than that then the odds that you're going to get -DR. SHANK: Some are used at 50 percent or so. DR. MARKS: Yeah, 55, that's the polymethol. But that was also -DR. SHANK: We have tested -DR. MARKS: That was the one that said there was no monomers in it -- in the final product. It's hard to believe, but that's what it says, right? MS. BECKER: That's what it said. DR. HILL: Well, again, when you say no, that's impossible, that's physically impossible. DR. MARKS: No, I hear you, that's why I said it's impossible to -- (Participants speaking over each other) DR. MARKS: We'll be seconding -- or I'll be seconding a motion for our team. I -DR. SHANK: We could see what they say. DR. MARKS: Well no, we need know our -- exactly. My feeling is that we be safe and in the discussion can address the monomers and low molecular weight concern that there are significant residual that could cause any toxic effects. I like that better than no sensitization. Ron, I think you're -- I'm disappointed Distributed for comment only -- do not cite or quote Ron, you're suggesting that a lot today. You're usually a purist. DR. SHANK: Well, later in the day that might come out. MR. STEINBERG: The one that we have the data on, the manufacturing and the largest volume is water insoluble, so in the production you can steam strip it and get the monomers out, which is what I think they're doing. DR. HILL: Well, I always -- since you're sitting there, I posed a hypothetical and I have yet to see any research come from the industry side that making something this cage like, there's always a possibility you're entrapping something. I'm not worried about that releasing in some cream that's being smeared on the skin, but what about something being hit with a hot hair dryer? MR. STEINBERG: I think the use was in eye area, wasn't -DR. HILL: You're right. MR. STEINBERG: -- that the one that was used in eye area? DR. HILL: So, yeah. Something -- as long we -MR. STEINBERG: I think it was an eye gel. DR. HILL: -- as long we know it's not being used on hair under a hot hair dryer then that becomes not a concern as well. MR. STEINBERG: That's something we can find out, yeah. DR. HILL: You're right. I mean, stripping out low molecular weight things we're in this particular case making sure that if we have to try chlorcyline, that it's hydrolyzed. They don't last very long if they see water down the street somewhere. Similarly with end capping agents and there are end capping agents being used here, because you can see that clearly in terms of the final structure. And you know they've done end capping with something like trymetholcyline -- trymetholchlorocyline or something like that, you can see those. DR. MARKS: So I think we have a choice, insufficient data announcement concerning monomers and low molecular weight compounds residual in these ingredients or we move with a tented [tentative] report and a safe conclusion and address that in the discussion. Which would you prefer, team? DR. HILL: And let me just -- I'll just say and then they can tell me what -- it may be selective for one or two or three ingredients where -- that feel there's an information gap, that's number one. And number two, we had a paper come out, one of the IJA papers, probably two and a half years ago now-ish, I don't have the particular one in my head where I thought the discussion handled all of this very, very nicely. I think Allen worked on it and the final form of the discussion was very robust. DR. SLAGA: I think we can it from the discussion. DR. HILL: So it may be the case and I need to look a little more carefully at specifics -DR. MARKS: Okay. Ron Shank? DR. SHANK: Yeah, I'll see what the conversation is tomorrow. I'm not easy with the read across at all. MS. BECKER: Dr. Hill, it would be one of those reports in Table 2. DR. HILL: Table 2, let me get there. It probably is, but I'm not certain. I thought it was one that had a chrolio in it, so it probably is. Table 2. DR. SLAGA: Page 17. DR. HILL: I had the report open and I somehow managed to shut it. Page 17 is Table 2. DR. MARKS: I'll probably mention that tomorrow. We'll see what -- the Belsito Team, how they handle it. Obviously, if they would prefer an insufficient data announcement we may end up that way. I think at least for our team at this point we'll go forward with a tentative safe report with a safe conclusion and then handle the issues particularly with monomer and low molecular weight residuals in the discussion. Okay. Any other comments about -DR. SHANK: I would like to forward that Table 2 now that we're on it. Is it possible to have the structures for these compounds to help people like me read across? MS. BECKER: They should especially if they're supplied by the dictionary. At least some -- there should be some structures in there. DR. EISENMANN: -- frequently do not provide structures. MS. BECKER: We can use the monomer -DR. SHANK: The names, of course, help but the variation in chemical structure is huge in this stuff and it does not give me comfort with how these help for read across I'm not sure. MS. FIUME: So you're asking for the structures to be added to the table? DR. SHANK: If they're available to Table 2. Cosmetic ingredients have already been reviewed. Okay. So -- and they've been found safe. Now if these apply to the current ingredients then that's very helpful, but I don't Distributed for comment only -- do not cite or quote know if it -MS. BECKER: Is that something you wanted to add to the report or something you just want to look at? DR. SHANK: I would add it to the report. MS. BECKER: So you want another column or section on each of these? Like what we normally have in figure 1 with the basic -DR. SHANK: Yes. Bart should be able to help with how to squeeze the structures into Table 2. MS. BECKER: Yes. He'll be delighted. DR. SHANK: With my blessing. There will be no easy way to do that. DR. HILL: I don't know if it's one of those reports, there's a pretty good chance that it is and I'll try to answer that question again later. DR. SLAGA: If you squeeze it too much you won't be able to see anything. MS. FIUME: We'll make sure that they're visible. We will do our best. DR. SLAGA: Thank you. DR. HILL: I actually read that discussion when I read it in the hard copy that was mailed to me of the IJT and so it's bound to be on -- well, I don't know that I have the final version on here, I probably don't, in fact. MS. BECKER: Well, you can get it from the website. DR. HILL: Yes. Yes. I'll figure it out. DR. MARKS: Okay. So tomorrow I may be seconding a report with a safe conclusion and in the discussion deal with the monomers, low molecular weight residual -- and adding structures into Table 2. Okay. Any other comments about the polysils? If not -- okay, let's move along to the next ingredient. Dr. Belsito's Team DR. BELSITO: ...Okay. Anything more? Polysilsesuioxanes. I guess, we got a whole bunch of wave 3 data, right? MS. BECKER: Yes, we did. DR. BELSITO: Okay. So I guess the major issue always is, is that -- and this happens all the time -- is we get all of this information only from one supplier, so this all from a supplier. Active Concepts, so it's presumably their material. And since these are not unique chemicals, it always raises that concern for me. In the end, we have no data on dermal penetration for any of these. We have one Ames, but no mammalian and no carcinogenicity for any of them. We have an Ames for polymethalsesquioxane, and we have no reproductive toxicity, so we don't have dermal penetration, and we don't have those toxicity end points. We do have manufacturing. I think we have enough data for irritation and sensitization. DPRA is negative. The keratin (inaudible) is negative. And then we have a 50 percent HRIPT in wave 2. So my concerns were lack of dermal absorption and the lack of repro and tinotox [genotox?] data. And I'll pass it on to you guys. DR. LIEBLER: So these are very large molecules. And none of the ingredients in this report are likely to have any absorption. These are big polymer molecules. Having said that, I do -- I struggled a little bit with just trying to determine which of these went together. They had to give similar uses, but which of these in this report actually go together. My suggestion -- I considered the suggestion at the end of the report in a counsel [Counsel] letter that two of the ingredients were chemically dissimilar from the others, and these were the polydimethyl (inaudible) PPG-24/19 butyl ether silsesquioxane, and the polydimethylsiloxi (phonetic 3:52:01 PPG-13 butyl ether scilsesquioxane [Polydimethylsiloxy PEG/PPG-24/19 Butyl Ether Silsesquioxane and Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane]. Those two I suggested we could leave from the report. DR. BELSITO: So the ones that are more linear -DR. LIEBLER: Correct. DR. BELSITO: --and not quite as caged -DR. LIEBLER: Yes. DR. BELSITO: -- for lack of a better word. DR. LIEBLER: The others either had the polyalkyscilsesquioxane structures. Let me say that again. Polyalkylsilsesquioxane structure, so that can include polymethyl like the first one in the left-hand column of the ingredient list. It can include the ethylpoly. I also included in these the copolymers and the cross polymers, so I felt that they could all go together. And that left these other two that I just mentioned which were also pointed out by the letter from the guy at the Distributed for comment only -- do not cite or quote end of the report. And so I thought that all of these could go together. All of these are going to be very large molecules. They're going to have no significant dermal penetration. I also was not worried about genotox. We did have one AMES from I believe was the polymethyl which is the most widely used, the most ever used. I think that's reasonably representative of this class because of the lack of absorption with these things. I think that, you know, the systemic toxicity, genotox, and carcinogenicity really aren't going to be issues, and the issues would be irritation and sensitization. Io if you are good with where we are on those, then I -- it's basically said safe as used and drop those two compounds. DR. BELSITO: I'm okay. I mean, I guess the only thing for spin is if you look on page 10 of the PDF under "Physical and Chemical Properties," it says that, "Another supplier reported particle size range is 15 to 30 microns with less than 10 percent at less than two to six microns." And then another supplier of the polymethylsesquioxane is a powder with a particle size of five microns. So that -- I mean, just what we're being told, I mean, gives me pause for respiration, and then are they such large molecules, because they are used in (inaudible) products. DR. LIEBLER: Yeah. So they could be large molecules and still make -DR. BELSITO: No, I understand. DR. LIEBLER: Yeah. DR. BELSITO: But then are we not concerned because if they're inhaled could they be -- enter the body system as - - even though they're large molecules? We're now not dealing with the stratem corneum barrier. DR. LIEBLER: Right. I guess if they're large molecules and they get, and they were respirable particles, they would be taken off by microphages, and then -DR. SNYDER: We've kept (inaudible) boilerplate (inaudible). I don't that's any different than before. DR. BELSITO: Well, we've had discussions too about the size of deodorant sprays, and whether they are, in fact, the size that we assume. Right? And one of the future things we're going to do is invite experts in the field to address those. MS. FIUME: (Indiscernible 3:57:00.) DR. BELSITO: Yeah. But I mean, I don't think that we've completely -- I mean, I just -- again, I'm just raising these issues that, you know, we have no genotox. We have no reproductive, and we're being told that one supplier says that the particle size could be in the respiratory range, and I am not a pulmonologist, so, yeah, I mean, would they all be taken up by microphages and cleared that way? Could they get into the blood stream? I mean, I don't -- I don't know any of those issues. I'm just pointing it out. DR. ANSELL: Yeah, this is the first review, so, you know, I think all these issues are addressable, but, you know, at least in terms of particle size, the toxicology of inhaled particles of insoluble particles is pretty much all the same. It's not driven by chemistry, per se, but rather by being insoluble. But more importantly, when we talk about the exposure, that's what we're really interested in, which is not simply driven by particle size. It's driven by particle size, concentration, duration, and in those cases we continue to believe that the exposure is very, very low because even if they were all respirable, you know, the amount in the breathing zone of a particle is measured in minutes, and the concentration is measured in typically micrograms per kilogram, so, you know, we do have this on the agenda, but I think we need to focus not exclusively on particle size, but refocus our energies on exposure. DR. BOYER: Also, another consideration is that the particle size of the ingredient itself might differ substantially from the particle sizes that are released from scrape -- from a formulation that's released to the air from spry [spray]. And so it's an important distinction. It can be an important distinction. DR. LIEBLER: So these are actually -- they have an interesting -- they have an interesting property. So they've got this because of the way silicon oxygen can bond to, you know, four different ligands, you can have different places to hang these hydrocarbons on. So you've got these little caged structures with these hydrocarbons chains dangling on them, so they're actually pretty hydrophobic. That gives them the ability to act as film formers. I mean, that gives them their physical chemical property which makes them of value in a cosmetic product as a film former. These things are basically -- film formers are insoluble compounds, and so that's consistent with these -- the ability to, you know, have any kind of biological effects usually depends on -- either on solubility of the molecule to some extent, the ability to break down non-enzymatically to release things, but the ability to bind something like metals. We think of that in pollutant particles. They're basically delivery vehicles for metals that produce many of the -- that drive many of the toxic responses. And here we've got data, or at least a statement of impurities saying that, you know, a long string of metals tested not present. Distributed for comment only -- do not cite or quote So these are things that mitigated my concern about these as having potentially any biological effects. Hadn't thought really, you know, until this discussion just now about respiration of these particles. We might need to deal with that in the discussion, you know, unless we decided we want some data. But, you know, these molecules being large molecules, and insoluble molecules, and relatively clean with respect to heavy metals, it kind of removed most of the things that I would be concerned about, which is classic chemicals. DR. BELSITO: And the last question that I had going through this, Dan, again for you is polymethylsilsesquioxane is the lead chemical for all of these. Essentially, we have no structure for it. Does that bother you? DR. LIEBLER: Well, that would be -- that would be the -- you could take the example structure, and then add the methyl alkoxy substituent and come up with that. Right? MS. BECKER: As far as I know, yes. DR. BELSITO: Ivan, you following that? DR. BOYER: Yes. DR. BELSITO: Made no sense to me. DR. LIEBLER: So the X's -- so on Figure 1 -DR. BELSITO: Figure 1. What page of the PDF is this? MS. BECKER: Nine. DR. LIEBLER: I'm sorry. Figure 1 is PDF page 9. DR. BELSITO: Okay. DR. ANSELL: Thirty-six. DR. BELSITO: Yeah. DR. LIEBLER: Yeah. Or in the table, what, page 36. DR. ANSELL: Yeah, page 36. DR. LIEBLER: Let's get out the 36. DR. BELSITO: Well, that has no figure. DR. ANSELL: Yes. DR. BELSITO: That's what I'm saying. DR. LIEBLER: Oh. DR. BELSITO: We don't have a figure for the lead molecule. DR. ANSELL: It's in -- we provide it in our comments. If it's the last set starting the letter -- starting on Page 34, which includes the structure on page 36. DR. LIEBLER: So what you could do, on page 9, PDF 9, where you have Figure 1, and you've got this little cage structure, you have room to put another cage structure next to it. So you could have representative core structure of a closed framework case. And then next to it, you could have example, or the polymethylsilsesquoxane structure, and it's a portion of that structure. So you can put those side-by-side. Then you have a structure of the lead compound, or at least a substructure of the lead compound. DR. BELSITO: Good. DR. KLAASSEN: On PDF page 14, I think that's the most beautiful molecule I've ever seen. (Laughter). Isn't that nice? Gotta put that on my bedroom wall. DR. LIEBLER: Looks like soft shell crab, and they're in season, yes. DR. BECKER: I thought it looked like a creepy eye myself, but that's okay. DR. KLAASSEN: Beauty is in the eye of the beholder. DR. LIEBLER: Anyway, but that's an example of one of the structures. DR. BELSITO: Okay. So we're okay with that. So then what are we saying, safe as used? DR. LIEBLER: Yes. DR. BELSITO: Comments on that? Linda, Jay, anyone? DR. LIEBLER: And deleting two molecules. DR. BELSITO: Deleting two molecules, right. So the molecules we're deleting are the linear ones. DR. LIEBLER: So it's the third and fourth entries on the right-hand column on PDF page 9. DR. BELSITO: So the third -DR. LIEBLER: And fourth. DR. BELSITO: On the right? DR. LIEBLER: On the right-hand, yeah. DR. BELSITO: So polydimethysesqui PPG and polydimethylsesqui PPG? DR. LIEBLER: Right. And I'd like -- I'd really like to hear Ron, both Rons' opinion about that, about deleting Distributed for comment only -- do not cite or quote these, and the suitability of retaining these, because these aren't all just a simple series of compounds where you're just changing out of fatty acids, something like that. You've got a general chemical similarity, and these two seem to be the least similar, but they probably have some more properties, although I think these two aren't used. So anyway, I'd like to -- I'm potentially open to being -- to further discussion on the point of inclusion and exclusion for some of these in (inaudible) DR. BELSITO: Okay. DR. LIEBLER: So hear what they say. DR. BELSITO: Anything else? DR. BERGFELD: So your discussion is going to include what? DR. BELSITO: Not much other than the large molecules, and not likely to be absorbed so we're not concerned about the lack of carcinogenicity and reproductive toxicity. MS. FIUME: Okay. And the inhalation -DR. BELSITO: Inhalation, obviously. MS. FIUME: -- discussion as well? DR. BELSITO: Yeah. MS. FIUME: Is the rationale to include a discussion as to how the information reads across to the group that could be used as well? DR. BELSITO: Well, that would be Dan. I mean, I can't go with what you said about that the read-across document is we need to start to justifying the read-across. DR. LIEBLER: Right. So specifically here, Monique [Monice], could you restate? MS. FIUME: Just are there any statements -- I know that you described how they all fit together, but I believe there's information mostly on one ingredient in the report, so is there any specific language that could be used to identify how that applies to the rest of the ingredients? DR. LIEBLER: So we have information about the chemistry and chemical properties of all the ingredients. And they are -- they are analogous chemical properties which is consistent with their common uses, and we have data on one of these ingredients, and given the restrictions of the chemistry imposes the data, you know, the lack of absorption, high molecular weight, et cetera, the data for this allows reasonable inference about the behavior of the other ingredients. DR. BERGFELD: You are using the word, "inference," instead of read-across? DR. LIEBLER: Yeah, I mean, I -DR. BERGFELD: I mean, there is a difference as to (inaudible). DR. LIEBLER: Inference and read-across? DR. BERGFELD: Uh-huh. DR. LIEBLER: Oh, dear, I missed that. DR. ANSELL: Carol will give you a lesson tomorrow on it where the inference goes out -- one goes in, and one goes out. DR. LIEBLER: Sounds like this could be a faculty meeting. Any subject (inaudible). DR. BELSITO: Using the word, "inference" is more of an impression of expert judgment as opposed to read-across where you have some -DR. BERGFELD: Quantitative. DR. BELSITO: -- data giving you a reason why you can use these. DR. LIEBLER: Okay. So now I understand what you're saying. So I think read-across as practiced in 2017 still is mostly inference expert judgment. And we are developing tools to allow us to make quantitative comparisons (inaudible), and some day those will be a reasonable substitute for expert testimony, but we still look at the results of all those, and we either say, yes, we buy it, or, no, we don't. DR. BERGFELD: So is it inference or read-across for this document? DR. LIEBLER: Whatever makes you happy. DR. BERGFELD: I just -- I think we have a new definition, we have to use it. DR. LIEBLER: I mean, you could call it read-across, and I'm fine with what I just said, and substitute read-across instead of the word, "inference." DR. BERGFELD: Okay. Anymore comments? If not, monoalkylglycol diakyl acid esters. My goodness. Lillian, you're up again. And you have parabens too? MS. BECKER: Yes, I do. Distributed for comment only -- do not cite or quote Day Two DR. BERGFELD: Moving on to the next ingredient, Dr. Belsito? DR. BELSITO: Polysilsesquioxanes. DR. BERGFELD: Thank you. DR. BELSITO: So this is the first time that we're looking at the report of 18 polysilicon ingredients. The SLR was just released in April of 2017. We got data primarily on polymethyl and silsesquioxane. Limited data on another ingredient. We got a lot of data in wave two, all from one specific manufacturer, Active Concepts, and we looked at that data as well. And based -DR. MARKS: The drum roll. DR. BELSITO: What? DR. MARKS: The drum roll. DR. BELSITO: Yeah. And based upon all of that we felt that it was safe as used. In the discussion, we should point out that these are large molecules, so we were not concerned about the relative lack of carcinogenicity and reproductive toxicity. And since they are used in aerosolized products, that the respiratory boilerplate would need to be enacted in the discussion as well. DR. MARKS: Second, safe in a tentative report. DR. SHANK: All of these? DR. BELSITO: Yes. We're deleting two, okay, molecules because they're not caged structures. Thank you, Paul, for reminding me. It's a problem when you're trying to scan through your notes. And those two are the right-hand column of the list on page -- PDF page -DR. LIEBLER: PDF 9. DR. BELSITO: -- nine. They would be polydimethylsiloxy PEG/PPG-24/19 butyl ether silsesquioxane and polydimethylsiloxy PG 13 butyl ether Silsesquioxane [Polydimethylsiloxy PEG/PPG-24/19 Butyl Ether Silsesquioxane and Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane]. And I'll let Don comment why we should delete those. DR. LIEBLER: Well, this was called -- my attention was called to this by the memo from the council [Council] at the very end of our document. I considered this -- I actually struggled a little bit with the structures in trying to, you know, come up with a rhyme or reason for what should be grouped together in the report. These have a common theme that don't play the same tune necessarily. So, but these two appear to be structurally distinct and different enough that I thought that they could be deleted from the report. DR. BERGFELD: Ron Hill? DR. LIEBLER: And I was looking forward to hearing what Ron thought, Dan. DR. HILL: So I don't necessarily concur with that. But what I will say is this -- I went back carefully, which I did not really do thoroughly in preparation for yesterday's meeting in that context because I wanted to get other people's take. There are, if I counted correctly, last night and early this morning, 20 unique monomers that are used in the production of these. We -- I agree, possible exception of those that are open chain, which if we had some information about the local molecular weight fraction that exists would be of value because otherwise, dermal penetrability, even mucosal penetrability I would expect to be nonexistent with these. But I don't have information from this report about the potential for persistent trimethoxysilane, and there are a mess of trimethoxysilanes to exist in the finished product in a way that could then react with tissue, amino acids. So if it can react with water or other silanol groups, it could also react with the hydroxyl group of the serine or a threonine or a tyrosine and generate a hapton. Well and good. If that happens, then somebody gets a rash and they realize they have to stop using that product. But are they there at a level that they could persist and react with DNA? And I don't have any information about that either. So when we have test data and we get sensitization results for the ones that we have test data that we get something about the monometers [monomers?] as a sentinel, then I feel a lot more comfortable, because if there's going to be reactivity, then that will show up in that form. If we do not have that data, for any given one of these where we have not covered the monomer and they're, again, all unique, and some of them, if they were just present on the skin, again, I don't know, if you have a trimethylsilane in any given one of these, and in a couple of cases there are chlorosilanes, and that's even more of an issue. I think those would immediately react with water and be deactivated. But the trimethoxy I'm not sure. So I think at least some chemistry about how long could one of these trimethoxys sit in water and be stable? Because if that's the case and we have a little molecular weight and it's dermally penetrable, then I need to have some assurance that the amounts there are very low. And while Distributed for comment only -- do not cite or quote I've got them looking for one of the reports, and I think I have it narrowed down to four where there was some very nice language written about -- we acknowledged that there could be monomers present and industry needs to take every step to minimize and consider these issues, it's a very good discussion for that report. Still not sure that we're 100 percent covered. And so I guess, you know, at this point, I'm likely to vote to abstain while we get some further information and then see where that leaves us. But I feel like we should cover all the monomers, and we certainly haven't done that in terms of the data we've got. DR. LIEBLER: So, Ron, let me just clarify one thing. Your points that you just made are really more about impurities. DR. HILL: They are totally about impurities. DR. LIEBLER: And so, yeah, I want to get back to the question of inclusion of all the ingredients or not. Do any of you guys, either of the Rons or any of the other members of the team have any further opinion on whether or not you feel that those two ingredients that we identified should be kept in the report or deleted from the report? Because I was inclined to accept the suggestion of the individual on behalf of the counsel who made a suggestion, but I thought that, you know, I could be convinced otherwise. But I wanted to know if anybody had a strong opinion about that issue. DR. HILL: I personally think they should be retained because even the ones that are cage-like, we have information to suggest that depending on the exact reaction conditions used to produce them, which would still fall under the same INCI name, you might have more or less open chain structures. And some lower molecular weights. So I think from the standpoint of do they belong in this group because of chemical similarity, I think they should stay. DR. MARKS: I'd just add that Bart, for your purposes, Ron Shank suggested that we have the structures in Table 2. It would be quite nice to have illustrations with the structures of those ingredients. DR. HELDRETH: We could certainly do that, and you'll find that many of those structures that we'll draw that related cosmetic ingredients in Table 2 will be more of a linear nature. DR. HILL: And the 11th and 12th ones are certainly erroneous as drawn because they've got a silicon atom with only two attachments. So, I mean, I flagged those. I just want to make sure if we put structures, that any available industry consultants be brought in to have a look at those if at all possible and see if the structures that land in the report are actually -- and we won't get that for all of them, but at least that they are faithful to what they should be if we're going to do that. DR. LIEBLER: Okay. So maybe I can make this suggestion then. It sounds like we might get a better representation of the structural features of these molecules in some redrawn figures in the table. And I would like to suggest that we keep everything in the report for the time-being. And if we, with a better representation of the structures, feel that we want to -- that something obviously doesn't belong, then we can come back next time and say that one goes. So, you know, I think we can let that go. Now, with respect to the issue of the residual monomers, you know, this is a common issue with polymer chemistry we've covered many times. And, you know, given the nature of the finished products and their uses, I expect that monomer concentrations would be very minimal. But I think that we've handled this in the discussion by simply advising industry to ensure that minimal quantities of residual monomers. The other thing is we do have good sensitization data. So I think my concern about this is a little bit less, and I probably will support these. DR. HILL: And I think part of it might be able to be answered by just going out to the chemistry literature and getting some information about the reactivity of trimethoxysilane -- alkylsilane, and getting that rolled into the chemistry section. It wouldn't -- a couple of seminal references. I mean, I certainly can do that on my own, but I believe that kind of information belongs in the report in the context of safety review. DR. BERGFELD: So Don, how would you like to proceed? DR. BELSITO: Well, I guess -DR. BERGFELD: We've had -DR. BELSITO: -- we started with safe as used and moving two ingredients. And then Dan said we don't need to remove the two. And then I'm hearing some hints that there are some data requested. It's insufficient. DR. BERGFELD: No, clarifications, I think. DR. BELSITO: I think -DR. MARKS: All clarification. DR. BELSITO: Yeah. Clarification discussion. DR. MARKS: Safe as used. DR. BELSITO: Second. Distributed for comment only -- do not cite or quote DR. MARKS: And formulated to be nonirritating. DR. SHANK: May I ask a question? DR. BERGFELD: Certainly. DR. SHANK: Are you saying these are all safe as used because they're so large they won't penetrate the skin? DR. BELSITO: That's what (inaudible) is telling me. DR. SHANK: You're not using read-cross? DR. BELSITO: There's really not -- we're using the read-across that we have for one molecule. DR. LIEBLER: Yes? DR. SHANK: And you're happy reading across from one molecule to cover all of these others? DR. LIEBLER: Yes. DR. SHANK: Why? Because you say they won't be penetrating the skin? DR. LIEBLER: right. DR. SHANK: Okay. So it's not really -- it's not really read-across. It's just -- none of these, the chemists are saying without data, will penetrate the skin. DR. LIEBLER: Yeah. I'm not saying without data, but it depends on what you're saying without -- yeah, these are all insoluble polymers. They share common structural features -DR. BELSITO: We don't need the irritation -DR. LIEBLER: -- the dominant effect of which is to produce no skin absorption. And so I think there is no real plausible, you know, given their use, there is no plausible argument to be made in my opinion that there is hazard to consider. You know, if we already have data for the leading ingredient and we have good data on that for sensitization, irritation a little bit, so I think we're okay. That was how I got to -DR. SHANK: Thank you. DR. HILL: Well, let me then follow up on that because I'm looking at page 10 of the report and the last line of this that's about description, definition of structure says polydimethylsiloxy PEG/PPG-24/19 butyl ether, silsesquioxane and polydimethylsiloxy PPG-13 butyl ethyl silsesquioxane are significantly more linear. Are those the ones you were proposing to remove, perhaps? And then it says consisting mostly of polyol chains with small amounts of silsesquioxane monomers. DR. MARKS: Yeah, I mean, probably tested at need. Nothing -DR. BELSITO: Just a correction. We don't need this irritating restriction in the conclusion. DR. MARKS: Thank you. DR. BERGFELD: Okay. DR. MARKS: I didn't have that in there. DR. BELSITO: Okay. DR. MARKS: I had notes of irritation sensitization was okay. DR. BELSITO: Right. DR. BERGFELD: So it appears that we're moving forward with an approval, safe, with clarification of the chemical structures? DR. BELSITO: Right. DR. BERGFELD: Is that what I see? DR. MARKS: Yeah. And I think the discussion that Ron Shank and Dan so clearly indicated why we can feel they're safe on the chemicals we do not have the data for. DR. BERGFELD: And you will talk about the monometers that Dr. Hill talked about? DR. MARKS: Correct. DR. BERGFELD: Thank you. Okay. All right. Any other discussion? Jay, anything? No. I call the question in. All those in favor of safe with the clarifications? Unanimous. (The motion passed unanimously.) Distributed for comment only -- do not cite or quote Safety Assessment of Polysilsesquioxanes as Used in Cosmetics Status: Release Date: Panel Meeting Date: Draft Final Report for Panel Review November 10, 2017 December 4-5, 2017 The 2017 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Executive Director is Bart Heldreth, Ph.D. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 0 Washington, DC 20036-4702 0 ph (&,cir-safety.org 0 fax Distributed for comment only -- do not cite or quote ABSTRACT The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 18 polysilsesquioxane ingredients as used in cosmetics. The majority of the ingredients named in this assessment have several functions, with most reported to function as film formers, opacifying agents, and nail conditioning agents. The Panel reviewed relevant data related to these ingredients. The CIR Expert Panel concluded that these polysilsesquioxanes are safe in cosmetics in the present practices of use and concentration described in this safety assessment. INTRODUCTION This is a safety assessment of 18 polysilsesquioxanes as used in cosmetics. The ingredients in this group comprise the polymers resulting from the hydrolysis and condensation of alkyltrialkoxysilanes or alkyltrichlorosilanes, and typically comprise three-dimensional frameworks. According to the web-based Cosmetic Ingredient Dictionary and Handbook (wINCI Dictionary), many of the ingredients named in this assessment have several functions, with most reported to function as film formers, opacifying agents, and/or nail conditioning agents (Table 1).1 Acryloyloxypropyl Polysilsesquioxane C26-28 Alkyldimethylsilyl Polypropylsilsesquioxane C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane Dimethicone/Silsesquioxane Copolymer Dimethiconol/Caprylylsilsesquioxane/Silicate Crosspolymer Ethyl Polysilsesquioxane Hydrogen Dimethicone/Octyl Silsesquioxane Copolymer Isobutyl/Methoxy PEG-10 Polysilsesquioxane Isobutyl Polysilsesquioxane Methacryloyloxypropyl Polysilsesquioxane Methoxy PEG-10 Polysilsesquioxane Polycaprylylsilsesquioxane Polymethylsilsesquioxane Polydimethylsiloxy PEG/ PPG-24/19 Butyl Ether Silsesquioxane Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane Polymethylsilsesquioxane/Trimethylsiloxysilicate Polypropylsilsesquioxane Trimethylpentyl Polysilsesquioxane There are several related polymer ingredients that have been reviewed by the CIR Panel; these ingredients are listed in Table 2. These previously reviewed polymers were all found to be safe as used.2-4 Some of the precursors and monomers were also reviewed by the Panel and are also listed in Table 2.3,5,6 CHEMISTRY Definition and Structure The ingredients in this group comprise polymers resulting from the hydrolysis and condensation of alkyltrialkoxysilanes or alkyltrichlorosilanes. These polysiloxanes typically comprise, at least in part, extended threedimensional networks. Under carefully controlled conditions, closed cage structures can be formed (Figure 1). More commonly, however, open chain polysilsesquioxanes composed of partial cages connected to other partial cages via siloxane bonds are formed (Figure 2). These open structures will also contain silanol (SiOH) groups. Figure 1. Example of a polysilsesquioxane "closed" framework or cage. "R" represents an alkylalkoxy substituent (or hydroxyl group) and "X" represents a continuation of the siloxy framework. Distributed for comment only -- do not cite or quote Figure 2. Example of a partial cage. "R" represents an alkylalkoxy substituent (or hydroxyl group) and "X" represents a continuation of the siloxy framework or a hydrogen atom. Many of the monomers used in the manufacture of these polymeric ingredients are multi-functional, which results in extensive branching, crosslinking, and cage-like structures in the final ingredient product. The degree of polymerization of these ingredients can be controlled to obtain a product having a desired functionality, such as an emulsifying agent. Accordingly, the molecular weights and molecular volumes of these ingredients can vary widely, unless otherwise noted in use specifications. These polymers, by virtue of their monomers, contain both hydrophilic and hydrophobic groups. The ratio of hydrophilic and hydrophobic groups of the components of each ingredient within a single ingredient name may vary. In the absence of explicit ingredient specifications, estimating some of the chemical and physical properties of these ingredients is challenging. Polydimethylsiloxy PEG/PPG-24/19 Butyl Ether Silsesquioxane and Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane are significantly more linear than the other ingredients in this group, comprising mostly polyol chains with small amounts of silsesquioxane monomers.7 However, these two ingredients are still likely to have significant molecular volumes, and share much in common, structurally, with previously reviewed ingredients listed in Table 2. Physical and Chemical Properties Physical and chemical properties are cited in Table 3. Dimethicone/Silsesquioxane Copolymer Dimethicone/Silsesquioxane Copolymer is characterized as having randomly distributed polydimethylsiloxane and Polymethylsilsesquioxane domains with interpenetrating, interlacing networks of differing chemistries.8,9 A photomicrograph shows a heterogeneous appearance. The average particle size is 7 m. Dimethicone/Silsesquioxane Copolymer is not soluble in organic solvents, and will not swell or introduce film-forming properties in the presence of organic solvents. Polymethylsilsesquioxane One supplier of Polymethylsilsesquioxane reported that it has a bulk density of 0.35 and is stable for 24 months when stored at < 60C.10 Another supplier reported that Polymethylsilsesquioxane is available as a powder of sphericalshaped particles, with particle sizes of 2 or 5 m.11 A third supplier reported the particle size range as 15 to 30 m (with 10% 2.6 m) and a bulk density of 500 kg/m3.12 A fourth supplier reports that Polymethylsilsesquioxane is a powder with a particle size of 5 m and virtually infinite molecular weight.13 A fifth supplier reported a particle size range of 1 to 10 m.14 C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane is stable for 24 months when stored 32C, according to one supplier.15 Method of Manufacture These types of polymers typically result from the hydrolysis and condensation of alkylalkoxysilanes. The definitions of several of the polysilsesquioxane polymers in this safety assessment give insight into possible methods of manufacture. For example, the definition for Dimethiconol/Caprylylsilsesquioxane/Silicate Crosspolymer states that this ingredient is a highly crosslinked silicone polymer that is made by the hydrolysis and condensation of tetraethyl orthosilicate (silicic acid tetra-ethyl ester) and triethoxycaprylylsilane with dimethiconol (Table 1).1 Distributed for comment only -- do not cite or quote Dimethicone/Silsesquioxane Copolymer The starting materials (not specified) of Dimethicone/Silsesquioxane Copolymer are polymerized followed by the removal of excess dimethicone. Each batch is tested for quality and microbial contamination.16 Polymethylsilsesquioxane For the manufacture of Polymethylsilsesquioxane, methyltrimethoxysilane is hydrolyzed at specified temperature and duration followed by condensation. Each batch is tested for quality and microbial contamination.17 Impurities/Constituents Dimethicone/Silsesquioxane Copolymer The residual monomer content of Dimethicone/Silsesquioxane Copolymer was reported to have a maximum concentration of 100 ppm.9 It was reported that heavy metals were present at < 20 ppm and arsenic at < 2 ppm. Microbial content was reported to be < 100 organisms/gram (opg). Polymethylsilsesquioxane Polymethylsilsesquioxane is reported to be 100% pure by a supplier.10 A supplier reported that analysis of three batches of Polymethylsilsesquioxane showed no Al, As, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sb, Sn, Sr, V, W, Zn, and Zr (< 2 ppm).12 The sum of the heavy metal content was < 20 ppm. There was a trace of toluene at < 0.1%. Another supplier reported that there are no detectible residual silane monomers in Polymethylsilsesquioxane.13 It was reported by another supplier that heavy metals were present at < 20 ppm, lead at < 20ppm, and arsenic at < 5 ppm.14 Microbial content was reported to be < 100 opg. Polymethylsilsesquioxane/Trimethylsiloxysilicate Polymethylsilsesquioxane/Trimethylsiloxysilicate is supplied at 50% in cyclopentasiloxane.18 It is reported to contain no residual monomers. USE Cosmetic The safety of the cosmetic ingredients included in this assessment is evaluated based on data received from the U.S. Food and Drug Administration (FDA) and the cosmetic industry on the expected use of these ingredients in cosmetics. Use frequencies of individual ingredients in cosmetics are collected from manufacturers and reported by cosmetic product category in FDA's Voluntary Cosmetic Registration Program (VCRP) database. Use concentration data are submitted by the cosmetic industry in response to surveys, conducted by the Personal Care Products Council (Council), of maximum reported use concentration by product category. According to VCRP survey data received in 2017, Polymethylsilsesquioxane was reported to be used in 397 formulations, i.e., 374 in leave-on formulations, 22 in rinse-off formulations, and 1 diluted for the bath (Table 4).19 All other in-use ingredients were reported to be used in 14 formulations or fewer. The results of the concentration of use survey conducted by the Council in 2016 indicate Polymethylsilsesquioxane has the highest reported maximum concentration of use; it is used at up to 55.2% (highest in the category of other eye preparations).20,21 The rest of the in-use ingredients are reported to be used at 4.9% (C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane in foundations) or less. In some cases, reports of uses were received in the VCRP, but concentration of use data were not provided. For example, Dimethicone/Silsesquioxane Copolymer was reported to be used in 7 cosmetic formulations, but no use concentration data were reported. In other cases, no uses were reported in the VCRP, but concentration of use data were received from the Council; Polydimethylsiloxy PEG/PPG-24/19 Butyl Ether Silsesquioxane had no reported uses in the VCRP, but a use concentration in the category of hair spray was provided in the Council survey. Therefore, it should be presumed there is at least one use in every category for which a concentration is reported. The ingredients not in use according to the VCRP and industry survey are listed in Table 5. Some of the polysilsesquioxanes are used in products that are used near the eye (e.g., Polymethylsilsesquioxane in the category of other eye makeup preparations at up to 55.2%), products that could possibly be ingested, or products that come in contact with mucus membranes (e.g., Polymethylsilsesquioxane in lipstick at up to 20.7%). Additionally, some of the polysilsesquioxanes are used in cosmetic sprays and could possibly be inhaled; for example, Polymethylsilsesquioxane was reported to be used at 52% in perfumes and Polydimethylsiloxy PEG/PPG-24/19 Butyl Ether Silsesquioxane is used up to 0.023% in aerosol hair sprays. In practice, 95% to 99% of the droplets/particles released from cosmetic sprays have aerodynamic equivalent diameters > 10 m, with propellant sprays yielding a greater fraction of droplets/particles < 10 m compared with pump sprays.22,23 Therefore, most droplets/particles incidentally inhaled from cosmetic sprays would be deposited in the nasopharyngeal and thoracic regions of the respiratory tract and would not be respirable (i.e., they would not enter the lungs) to any appreciable amount.24,25 There is some evidence indicating that deodorant spray products (e.g., Polymethylsilsesquioxane at up to 4%) can release substantially larger Distributed for comment only -- do not cite or quote fractions of particulates having aerodynamic equivalent diameters in the range considered to be respirable.24 However, the information is not sufficient to determine whether significantly greater lung exposures result from the use of deodorant sprays, compared to other cosmetic sprays. Polymethylsilsesquioxane was reported to be used in face powders at concentrations up to 49.8%. Conservative estimates of inhalation exposures to respirable particles during the use of loosepowder cosmetic products are 400- to 1000-fold less than protective regulatory and guidance limits for inert airborne respirable particles in the workplace.26-28 None of the polysilsesquioxanes named in the report are restricted from use in any way under the rules governing cosmetic products in the European Union.29 Non-Cosmetic Polymethylsilsesquioxane may be used as a surface lubricant or anti-blocking agent in films as basic components of single and repeated use food contact surfaces. [21CFR177.1520] TOXICOKINETIC STUDIES Dermal Penetration Data on dermal penetration of polysilsesquioxanes ingredients were not found in the published literature and no unpublished data were submitted. However, the cage-like structures of many of these ingredients encompass large molecular volumes, which likely decrease the potential for these ingredients to penetrate the skin significantly. Absorption, Distribution, Metabolism, and Excretion (ADME) Data on the ADME of polysilsesquioxane ingredients were not found in the published literature and no unpublished data were submitted. TOXICOLOGICAL STUDIES Acute Toxicity Studies Data on acute dermal or inhalation toxicity studies of polysilsesquioxane ingredients were not found in the published literature and no unpublished data were submitted. Oral Summaries of acute oral studies of polysilsesquioxanes are presented in Table 6. The reported LD50 for Isobutyl/Methoxy PEG-10 Polysilsesquioxane, Isobutyl Polysilsesquioxane, Methacryloyloxypropyl Polysilsesquioxane, Methoxy PEG-10 Polysilsesquioxane, and Trimethylpentyl Polysilsesquioxane was > 5000 mg/kg. 30-35 Short-Term Toxicity Studies Dermal A Polymethylsilsesquioxane emulsion (0 or 200 mg/kg/day; concentration of solids not specified; not known if it is a grade that is used in cosmetics) was dermally administered to rabbits (n=10) for 28 days.36 The rabbits were weighed prior to study initiation and on days 7, 14, 21, and 28. The rabbits were observed for mortality, behavioral changes, and adverse skin reactions throughout the study period and were killed on day 28 for gross necropsy and histopathological examination. The testes were weighed at necropsy and testes to body weight ratios were calculated. There were no statistically-significant treatment-related changes in mortality, body weight, behavior, or gross pathology. In addition, there were no changes in mean testes weight or testes to body weight ratio. No abnormal histopathological findings were reported. DEVELOPMENTAL AND REPRODUCTIVE TOXICITY (DART) STUDIES Data on the DART of polysilsesquioxane ingredients were not found in the published literature and no unpublished data were submitted. GENOTOXICITY STUDIES Genotoxicity studies of polysilsesquioxanes are presented in Table 7. Methacryloyloxypropyl Polysilsesquioxane, Methoxy PEG-10 Polymethylsilsesquioxane, Polymethylsilsesquioxane, and Trimethylpentyl Polymethylsilsesquioxane were not genotoxic in bacterial reverse mutation assays at up to 5000 g/plate. 13,37-39,39 CARCINOGENICITY STUDIES Data on the carcinogenicity of polysilsesquioxane ingredients were not found in the published literature and no unpublished data were submitted. Distributed for comment only -- do not cite or quote OTHER RELEVANT STUDIES Cytotoxicity An agar diffusion test was conducted on Polymethylsilsesquioxane (65% in water) to determine the biological activity of this ingredient on mammalian cell cultures following indirect contact with the test substance.13 The test was run on three plates with an exposure period of 24 h. There was no reactivity observed. This test suggests that this ingredient does not have a toxic diffusible (low molecular weight) fraction.40 DERMAL IRRITATION AND SENSITIZATION STUDIES Irritation In Vitro In an EpiDermTM assay, reconstructed human epidermis was exposed to Polymethylsilsesquioxane (neat, 25 mg) for 60 min. The negative control was sterile deionized water and the positive control was sodium dodecyl sulfate (5%). The test substance had similar results as the negative control and was predicted to be non-irritating.41 Animal Dermal irritations studies of polysilsesquioxanes using rabbits are summarized in Table 8. The Primary Irritation Index (PII) was 0.05 out of 8 for Isobutyl Polysilsesquioxane (100%) administered to the intact and abraded skin of New Zealand White rabbits.42 The PII was 0.55 for Methacryloyloxypropyl Polysilsesquioxane, 0.40 for Methoxy PEG-10 Polysilsesquioxane (100%), 0.30 for Trimethylpentyl Polysilsesquioxane (100%), and 0.78 for another form of Trimethylpentyl Polysilsesquioxane (100%).35,43,44 A Polymethylsilsesquioxane emulsion (200 mg/kg/day) dermally administered to rabbits for 28 days caused slight local erythema and dryness following 7 to 14 dermal applications.36 Isobutyl/Methoxy PEG-10 Polysilsesquioxane (100%) caused very slight to well defined, transient erythema after dosing, which resolved by day 7. 45 Sensitization In Vitro Polymethylsilsesquioxane In an in vitro dermal sensitization assay of Polymethylsilsesquioxane conducted in accordance with the Organisation for Economic Co-operation and Development Test Guideline (OECD TG) 442C (In Chemico Skin Sensitization, Direct Peptide Reactivity Assay [DPRA]), the incubation with the test substance for approximately 24 h resulted in a mean percent depletion of the peptides of 3.22%, which is within the range of non-sensitization prediction model. Therefore, Polymethylsilsesquioxane was predicted to be a non-sensitizer.46 In an in vitro dermal sensitization assay conducted in accordance with OECD TG 442D (in vitro Skin Sensitization, ARE-Nrf2 Luciferase Test Method), the IC50 (the concentration at which inhibition is 50%) for Polymethylsilsesquioxane was > 1000 M, there was no luciferase induction, and the Imax was 0.36.47 The criteria for a positive prediction include an IC50 greater than 70% the lowest luciferase induction concentration and an Imax greater than 1.5-fold (and statisticallysignificantly different from) the Imax of the negative control (solvent; 0.16). This ingredient was not predicted to be a skin sensitizer. Human Summaries of human repeated insult patch tests (HRIPT) of polysilsesquioxanes are presented in Table 9. In HRIPTs of makeup products that contain C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane (4.337%)48 or Polymethylsilsesquioxane (50% or 22.0%),49,50 there was no evidence of sensitization. Polymethylsilsesquioxane (100%)13 and Polymethylsilsesquioxane/Trimethylsiloxysilicate (50%)18 were not sensitizing in HRIPTs. Photosensitization/Phototoxicity A phototoxicity test was conducted on a foundation product containing Polymethylsilsesquioxane (5%) using subjects (n = 20) with Fitzpatrick skin types of I, II, or III.13 The test material (0.2 g) was applied to the inner surface of both arms of the subjects after tape stripping 3 times. The right arm was irradiated at a distance of 10 cm resulting in a UV-A light dosage of > 4.4 J/cm2 (spectrum range 320 to 400 nm with peak at 365 nm). After irradiation, the test site was covered with an occlusive patch containing an additional 0.2 g of the test material. The test sites were scored immediately after irradiation and at 24 and 48 h and 1 week after patch removal. There were no adverse effects or reactions of any kind observed. OCULAR IRRITATION STUDIES In Vitro In an EpiOcularTM assay, human-derived epidermal keratinocytes cultured to form cornea epithelium were exposed to Polymethylsilsesquioxane for 90 min. The negative control was sterile deionized water and the positive control was methyl acetate. The test substance had similar results as the negative control and was predicted to be non-irritating.41 Distributed for comment only -- do not cite or quote SUMMARY This is a safety assessment of 18 polysilsesquioxanes as used in cosmetics. The ingredients in this group comprise the polymers resulting from the hydrolysis and condensation of alkylalkoxysilanes. These siloxy polymers typically comprise three-dimensional frameworks. Many of the ingredients named in this assessment have several functions, with most reported to function as film formers and/or nail conditioning agents. Polymethylsilsesquioxane was reported to be used in 397 formulations (e.g., 374 in leave-on formulations, 22 in rinse-off formulations, and 1 diluted for the bath). All other in-use ingredients were reported to be used in 14 formulations or fewer. Polymethylsilsesquioxane has the highest reported maximum concentration of use; it is used at up to 55.2% in the category of other makeup preparations. The rest of the in-use ingredients are reported to be used at 4.9% (C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane in foundations) or less. The reported LD50 for Isobutyl/Methoxy PEG-10 Polysilsesquioxane, Isobutyl Polysilsesquioxane, Methacryloyloxypropyl Polysilsesquioxane, Methoxy PEG-10 Polysilsesquioxane, and Trimethylpentyl Polysilsesquioxane was > 5000 mg/kg. In a 28-day dermal toxicity study of a Polymethylsilsesquioxane emulsion at 200 mg/kg/day using rabbits, there were no remarkable toxicological findings. Slight local erythema and dryness were observed following 7 to 14 dermal applications. Methacryloyloxypropyl Polysilsesquioxane, Methoxy PEG-10 Polymethylsilsesquioxane, Polymethylsilsesquioxane, and Trimethylpentyl Polymethylsilsesquioxane were not genotoxic in bacterial reverse mutation assays at up to 5000 g/plate. There was no biological activity from Polymethylsilsesquioxane (65%) in an agar diffusion test. Polymethylsilsesquioxane (neat) was predicted to be a non-irritant in an EpiDermTM assay. Polysiloxanes were not dermally irritating to rabbits. The PII was 0.05 out of 8 for Isobutyl Polysilsesquioxane (100%) administered to the intact and abraded skin of New Zealand White rabbits. The PII was 0.55 for Methacryloyloxypropyl Polysilsesquioxane, 0.40 for Methoxy PEG-10 Polysilsesquioxane (100%), 0.30 for Trimethylpentyl Polysilsesquioxane (100%), and 0.78 for Trimethylpentyl Polysilsesquioxane (100%). Isobutyl/Methoxy PEG-10 Polysilsesquioxane (100%) caused very slight to well defined, transient erythema was observed after dosing, which resolved by day 7. Polymethylsilsesquioxane (neat) was predicted to be a non-sensitizer in two in vitro assays conducted in accordance with OECD TGs 442C and 442D. In HRIPTs of polysilsesquioxanes and products containing polysilsequioxanes, there were no signs of irritation or sensitization. In HRIPTs of makeup products that contain C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane (4.337%), Polymethylsilsesquioxane (50%), or Polymethylsilsesquioxane (22.0%), there was no evidence of sensitization. Polymethylsilsesquioxane (100%) and Polymethylsilsesquioxane/Trimethylsiloxysilicate (50%) were not sensitizing in HRIPTs. A product containing 5% Polymethylsilsesquioxane was not phototoxic. Polymethylsilsesquioxane (neat) was predicted to be a non-irritant in an EpiOcularTM assay. DISCUSSION The Panel examined the available data for these 18 polysilsesquioxane cosmetic ingredients, including physical and chemical properties, dermal and oral toxicity, genotoxicity, and dermal irritation and sensitization. The majority of these data were on a few ingredients (i.e., Polymethylsilsesquioxane and Dimethicone/Silsesquioxane Copolymer) with some data on a few of the other ingredients (i.e., C30-45 Alkyldimethyl-silyl Polypropylsilsesquioxane, Methacryloyloxypropyl Polysilsesquioxane, and Polymethylsilsesquioxane/Trimethylsiloxysilicate). The Panel noted a lack of systemic toxicity data (i.e., reproductive and developmental toxicity and carcinogenicity data), but agreed that these ingredients are large, insoluble molecules that share dominant features/structures, and are not expected to penetrate the skin. The Panel also agreed that the weight of the evidence alleviated concerns about the potential for local effects, such as dermal irritation and sensitization. The available data show that the concentrations of monomer impurities are low or below detection. The monomers of these ingredients are highly reactive in the context of the synthetic process and are unlikely to survive hydrolysis in biological systems. However, manufacturers should use current good manufacturing practices (cGMP) to ensure that monomers and source materials are limited. The Panel discussed the issue of incidental inhalation exposure from hair sprays and perfumes. There were no inhalation toxicity data available. However, the particle sizes of these ingredients were reported to range from 2 to 30 m. The Panel believes that the sizes of a substantial majority of the particles of these ingredients, as manufactured, are larger than the respirable range and/or aggregate and agglomerate to form much larger particles in formulation. These ingredients are reportedly used at concentrations up to 52% in cosmetic products that may be sprayed and up to 49.8% in loose powder products that may become airborne. The Panel noted that droplets/particles from cosmetic products would not be respirable to any appreciable amount. Furthermore, these ingredients are not likely to cause any direct toxic effects in the upper respiratory tract, based on the properties of the polysilsesquioxanes and on data that shows that these ingredients are not expected to be irritants. Coupled with the small actual exposure in the breathing zone and the concentrations at which the ingredients are used, the available information indicates that incidental inhalation would not be a significant route of exposure that might lead to local respiratory or systemic effects. Polysilsesquioxanes are large macromolecules and insoluble Distributed for comment only -- do not cite or quote in water, which supports the view that they are unlikely to be absorbed or cause local effects in the respiratory tract. A detailed discussion and summary of the Panel's approach to evaluating incidental inhalation exposures to ingredients in cosmetic products is available at http://www.cir-safety.org/cir-findings. CONCLUSION The CIR Expert Panel concluded that the following polysilsesquioxane ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment: Acryloyloxypropyl Polysilsesquioxane* C26-28 Alkyldimethylsilyl Polypropylsilsesquioxane* C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane Dimethicone/Silsesquioxane Copolymer Dimethiconol/Caprylylsilsesquioxane/Silicate Crosspolymer* Ethyl Polysilsesquioxane* Hydrogen Dimethicone/Octyl Silsesquioxane Copolymer Isobutyl/Methoxy PEG-10 Polysilsesquioxane* Isobutyl Polysilsesquioxane* Methacryloyloxypropyl Polysilsesquioxane* Methoxy PEG-10 Polysilsesquioxane* Polycaprylylsilsesquioxane Polymethylsilsesquioxane Polydimethylsiloxy PEG/ PPG-24/19 Butyl Ether Silsesquioxane Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane* Polymethylsilsesquioxane/Trimethylsiloxysilicate* Polypropylsilsesquioxane Trimethylpentyl Polysilsesquioxane* * Not reported to be in current use. Were ingredients in this group not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group. Distributed for comment only -- do not cite or quote TABLES Table 1. Definitions, Ingredient CAS No. Acryloyloxypropyl Polysilsesquioxane 1204591-17-2 idealized structures, and functions of the ingredients in this safety assessment.(1; CIR Staff) Definition & Monomer Structuresa Function(s) Acryloyloxypropyl Polysilsesquioxane is a resinous material composed of a mixture of three-dimensional siloxane polymers and oligomers with cage structures. For the oligomers, each silicon atom in the polysilsesquioxane is connected via oxygen atoms to three other silicon atoms and can be represented by the empirical formulation RSiO3/2 where R represents the acryloxypropyl group. For the larger polymeric polysilsesquioxanes, some of the silicon atoms [siloxy groups (SiO)] are not connected [through the oxygen atom] to other silicon atoms and instead [terminate as] have a silanol (SiOH) groups. [Silicon atoms that do not have silanol groups connect to other partial cage structures via siloxane linkages.] Acryloxypropyl Polysilsesquioxane is prepared by the hydrolysis and condensation of acryloyloxy propyltrimethoxysilane. Nail conditioning agent C26-28 Alkyldimethylsilyl Polypropylsilsesquioxane C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane "closed cage" "partial cage" [Polymethylsilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is methacryloxypropyl or OH, and X is a continuation of the polymer.] C26-28 Alkyldimethylsilyl Polypropylsilsesquioxane is the silicone compound that conforms generally to the formula: Film former; viscosity increasing agent - nonaqueous where n has a value between 25 and 27 [x and y are not defined]. C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane is the silicone compound that conforms generally to the formula: Film former Dimethicone/Silsesquioxane Copolymer 68440-84-6 Dimethiconol/ Caprylylsilsesquioxane/Silicate Crosspolymer 1802406-18-3 where n has a value between 29 and 44 [x and y are not defined]. Dimethicone/Silsesquioxane Copolymer is a siloxane polymer consisting of methyl trimethoxysilane and dimethylsiloxane. Dimethiconol/Caprylylsilsesquioxane/Silicate Crosspolymer is a highly crosslinked silicone polymer that is made by the hydrolysis and condensation of tetraethyl orthosilicate [(silicic acid (H4SiO4) tetra-ethyl ester)] and triethoxycaprylylsilane with dimethiconol. Film former; hair conditioning agent; hair fixative Opacifying agent Distributed for comment only -- do not cite or quote Table 1. Definitions, Ingredient CAS No. Ethyl Polysilsesquioxane idealized structures, and functions of the ingredients in this safety assessment.(1; CIR Staff) Definition & Monomer Structuresa Function(s) Ethyl Polysilsesquioxane is a resinous material composed of a mixture of threedimensional siloxane polymers and oligomers with cage structures. For the oligomers, each silicon atom in the polysilsesquioxane is connected via oxygen atoms to three other silicon atoms and can be represented by the empirical formulation RSiO3/2, where R represents the ethyl group. For the larger polymeric polysilsesquioxanes, some of the silicon atoms [siloxy groups (SiO)] are not connected [through the oxygen atom] to other silicon atoms and instead [terminate as] have a silanol (SiOH) group. [Silicon atoms that do not have silanol groups connect to other partial cage structures via siloxane linkages.] Ethyl Polysilsesquioxane is prepared by the hydrolysis and condensation of ethyl trimethoxysilane.* Nail conditioning agent Hydrogen Dimethicone/Octyl Silsesquioxane Copolymer "closed cage" "partial cage" [Polymethylsilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is ethyl, and X is a continuation of the polymer.] Hydrogen Dimethicone/Octyl Silsesquioxane Copolymer is the silicone polymer that conforms generally to the formula: Surface modifier Isobutyl Polysilsesquioxane 221326-46-1 Isobutyl Polysilsesquioxane is a resinous material composed of a mixture of three-dimensional siloxane polymers and oligomers with cage structures. For the oligomers, each silicon atom in the polysilsesquioxane is connected via oxygen atoms to three other silicon atoms and can be represented by the empirical formulation RSiO3/2 where R represents the isobutyl group. For the larger polymeric polysilsesquioxanes, some of the silicon atoms [siloxy groups (SiO)] are not connected [through the oxygen atom] to other silicon atoms and instead [terminate as] have a silanol (SiOH) groups. [Silicon atoms that do not have silanol groups connect to other partial cage structures via siloxane linkages.] Isobutyl Polysilsesquioxane is prepared by the hydrolysis and condensation of 2-methylpropyl trimethoxysilane.* Nail conditioning agent "closed cage" "partial cage" [Polymethylsilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is isobutyl or OH, and X is a continuation of the polymer.] Distributed for comment only -- do not cite or quote Table 1. Definitions, Ingredient CAS No. Methacryloyloxypropyl Polysilsesquioxane 160185-24-0 idealized structures, and functions of the ingredients in this safety assessment.(1; CIR Staff) Definition & Monomer Structuresa Function(s) Methacryloyloxypropyl Polysilsesquioxane is a resinous material composed of a mixture of three-dimensional siloxane polymers and oligomers with cage structures. For the oligomers, each silicon atom in the polysilsesquioxane is connected via oxygen atoms to three other silicon atoms and can be represented by the empirical formulation RSiO3/2 where R represents the methacryloxypropyl group. For the larger polymeric polysilsesquioxanes, some of the silicon atoms [siloxy groups (SiO)] are not connected [through the oxygen atom] to other silicon atoms and instead [terminate as] have a silanol (SiOH) groups. [Silicon atoms that do not have silanol groups connect to other partial cage structures via siloxane linkages.] Methacryloyloxypropyl Polysilsesquioxane is prepared by the hydrolysis and condensation of methacryloyl propyltrimethoxysilane.* Abrasive Polycaprylylsilsesquioxane 1385031-14-0 "closed cage" "partial cage" [Polymethylsilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is methacryloxypropyl or OH, and X is a continuation of the polymer.] Polycaprylylsilsesquioxane is a polymer formed by the hydrolysis and condensation of triethoxycaprylylsilane. Anticaking agent; binder; opacifying agent; surface modifier Polydimethylsiloxy PEG/ PPG-24/19 Butyl Ether Silsesquioxane 68554-65-4 "closed cage" "partial cage" [Polymethylsilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is caprylyl or OH, and X is a continuation of the polymer.] Polydimethylsiloxy PEG/PPG-24/19 Butyl Ether Silsesquioxane is the silicone polymer that conforms generally to the formula: Skin-conditioning agent - humectant; surfactant-cleansing agent; surfactant - dispersing agent; surfactant - emulsifying agent Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane is the silicone polymer that conforms generally to the formula: Hair conditioning agent; humectant; surfactant - cleansing agent; surfactant - dispersing agent; surfactant - emulsifying agent Distributed for comment only -- do not cite or quote Table 1. Definitions, idealized structures, and functions of the ingredients in this safety assessment.(1; CIR Staff) Ingredient CAS No. Definition & Monomer Structuresa Function(s) Polymethylsilsesquioxane 68554-70-1 Polymethylsilsesquioxane is a polymer formed by the hydrolysis and condensation of methyltrimethoxysilane. Opacifying agent Polymethylsilsesquioxane/ Trimethylsiloxysilicate 1402155-47-8 Polypropylsilsesquioxane 36088-62-7 "closed cage" "partial cage" [Polymethylsilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is methyl or OH, and X is a continuation of the polymer.] Polymethylsilsesquioxane/Trimethylsiloxysilicate is the product of the hydrolysis and subsequent condensation polymerization of trialkoxymethylsilane, alkylorthosilicate and trimethylchlorosilane. Polypropylsilsesquioxane is a polymer formed by the hydrolysis and condensation of propyltrichlorosilane. Film former Binder; film former "closed cage" "partial cage" Trimethylpentyl Polysilsesquioxane 190732-67-3 444619-08-3 [Polymethylsilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is propyl or OH, and X is a continuation of the polymer.] Trimethylpentyl Polysilsesquioxane is a resinous material composed of a mixture of three-dimensional siloxane polymers and oligomers with cage structures. For the oligomers, each silicon atom in the polysilsesquioxane is connected via oxygen atoms to three other silicon atoms and can be represented by the empirical formulation RSiO3/2 where R represents the trimethylpentyl group. For the larger polymeric polysilsesquioxanes, some of the silicon atoms [siloxy groups (SiO)] are not connected [through the oxygen atom] to other silicon atoms and instead [terminate as] have a silanol (SiOH) groups. [Silicon atoms that do not have silanol groups connect to other partial cage structures via siloxane linkages.] Trimethylpentyl Polysilsesquioxane is prepared by the hydrolysis and condensation of 2,4,4-trimethylpentyl trimethoxysilane.* Nail conditioning agent "closed cage" "partial cage" [Polymethylsilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is Trimethylpentyl or OH, and X is a continuation of the polymer.] Distributed for comment only -- do not cite or quote Table 1. Definitions, idealized structures, and functions of the ingredients in this safety assessment.(1; CIR Staff) Ingredient CAS No. Definition & Monomer Structuresa Function(s) Isobutyl/Methoxy PEG-10 Polysilsesquioxane Isobutyl/Methoxy PEG-10 Polysilsesquioxane is the Methoxy PEG-10 derivative of Isobutyl Polysilsesquioxane. [a copolymer of:] Viscosity decreasing agent Methoxy PEG-10 Polysilsesquioxane 1838163-04-4 "closed cage" "partial cage" [Isobutyl Polysilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is isobutyl, and X is a continuation of the polymer.] Methoxy PEG-10 Polysilsesquioxane is a resinous material composed of a mixture of three-dimensional siloxane polymers and oligomers with cage structures. For the oligomers, each silicon atom in the polysilsesquioxane is connected via oxygen atoms to three other silicon atoms and can be represented by the empirical formulation RSiO3/2 where R represents the methoxy PEG-10 propyl moiety. For the larger polymeric polysilsesquioxanes, some of the silicon atoms [siloxy groups (SiO)] are not connected [through the oxygen atom] to other silicon atoms and instead [terminate as] have a silanol (SiOH) groups. [Silicon atoms that do not have silanol groups connect to other partial cage structures via siloxane linkages.] Methoxy PEG-10 Polysilsesquioxane is prepared by the hydrolysis and condensation of methoxy PEG-10 propyltrimethoxysilane.* [a copolymer mixture of:] Skinconditioning agent - humectant; surfactant - cleansing agent; surfactant - solubilizing agent "closed cage" "partial cage" [Polysilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is methoxy PEG-10 propyl, methyl, or OH, and X is a continuation of the polymer.] a Some of the definitions and structures were edited by CIR staff for clarity. Words that are to be removed have a strike through and added language is in [brackets]. Table 2. Related cosmetic ingredients and precursors that have been reviewed by CIR. Ingredient Conclusiona and structures Reference Related Ingredients Dimethicone/Divinyldimethicone/ Safe in the practices of use and concentration 2 Silsesquioxane Crosspolymer as given in this safety assessment. [a crosspolymer mixture of:] "closed cage" "partial cage" [Polysilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is methyl, and X is a continuation of the polymer.] Distributed for comment only -- do not cite or quote Table 2. Related cosmetic ingredients and precursors that have been reviewed by CIR. Ingredient Conclusiona and structures Reference Dimethicone/ Safe in the practices of use and concentration 2 Bis-Vinyldimethicone/ Silsesquioxane Crosspolymer as given in this safety assessment. [a crosspolymer mixture of:] "closed cage" "partial cage" [Polysilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is methyl, and X is a continuation of the polymer.] Dimethiconol/Silsesquioxane Safe as cosmetic ingredients in the present 3 Copolymer practices of use and concentration described in this safety assessment. [a copolymer mixture of:] "closed cage" "partial cage" [Polysilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is methyl, and X is a continuation of the polymer.] Methoxy PEG-13 Ethyl Safe in cosmetics in the practices of use and 4 Polysilsesquioxane concentration of this safety assessment. [a copolymer mixture of:] "closed cage" "partial cage" [Ethyl Polysilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is ethyl, and X is a continuation of the polymer.] Vinyl Dimethicone/Methicone Safe in the practices of use and concentration 2 Silsesquioxane Crosspolymer as given in this safety assessment. "closed cage" "partial cage" [Polysilsesquioxane is a mixture of closed and partial caged structures, wherein "R" is methyl, and X is a continuation of the polymer.] Distributed for comment only -- do not cite or quote Table 2. Related cosmetic ingredients and precursors that have been reviewed by CIR. Ingredient Conclusiona and structures Reference Monomers/Precursors Dimethiconol Safe as cosmetic ingredients in the present 3 practices of use and concentration described in this safety assessment. Methoxy PEG-10 Triethoxycaprylylsilane Safe as used when formulated to be 6 nonirritating. Safe as cosmetic ingredients in the practices 5 of use and concentration described in this safety assessment. a Please see the original reports for details (http://www.cir-safety.org/ingredients). Table 3. Chemical and physical properties of polysilsesquioxanes. Property Value Reference C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane Physical Form Color Odor Specific Gravity Melting Point oC Solid, flakes 15 Wax 51 White to off-white 15,51 Characteristic 15 0.8 15 66 15 63-71 51 Dimethicone/Silsesquioxane Copolymer Physical Form Color Odor Powder 9 Off white 9 Characteristic 9 Other Solubility Organic solvents Not soluble 8 Isobutyl/Methoxy PEG-10 Polysilsesquoxane Physical Form Color Semi-solid 52 Clear, pale 52 yellow/orange Molecular Volume m3/kmol 1330.13 52 Melting Point oC 65 52 Water Solubility Insoluble 52 Other Solubility Ethanol (95%) Hexane (aliphatics) Mineral Oil Petrolatum Soluble 52 Soluble 52 Soluble 52 Dispersible 52 Isobutyl Polysilsesquioxane Physical Form Color Formula Weight g/mol Density Water Solubility Powder 53 White 53 873.60 53 1.13 53 Not Soluble 53 Other Solubility Ethanol (95%) Hexane (aliphatics) Mineral Oil Petrolatum Dispersible 53 Mostly Soluble 53 Soluble 53 Soluble 53 Distributed for comment only -- do not cite or quote Table 3. Chemical and physical properties of polysilsesquioxanes. Property Value Reference Methacryloyloxypropyl Polysilsesquioxane Physical Form Color Formula Weight Liquid Oil 54 Clear, colorless 54 1433.97 54 Density Viscosity kg/(s m) Water Solubility 1.20 1.8 54 Not soluble 54 Other Solubility Ethanol (95%) Soluble 54 Isopropyl Propanol (99%) Soluble 54 Hexanes (aliphatics) Unstable 54 Glycerin Soluble 54 Parafin Wax Stable 54 Methoxy PEG-10 Polysilsesquioxane Physical Form Color Formula Weight g/mol Density Water Solubility Liquid 55 Clear/colorless 55 4525.83 55 1.09 55 Soluble 55 Other Solubility Ethanol (95%) Soluble 55 Isopropyl Propanol (99%) Soluble 55 Hexanes (aliphatics) Not Soluble 55 Glycerin Soluble 55 Parafin Wax Stable 55 Polymethylsilsesquioxane Physical Form Color Odor Specific Gravity @ 25oC Water Solubility Solid; powder White Characteristic Odorless 1.3 1.32 Insoluble Trimethylpentyl Polysilsesquioxanea Physical Form Color Liquid Liquid Colorless to pale yellow Colorless to pale yellow Molecular Weight g/mol Formula Weight Density Viscosity kg/(s m) Water Solubility Other Solubility Ethanol (95%) Isopropyl Propanol (99%) Hexanes (aliphatics) Glycerin Parafin Wax 1322.46 1184.16 0.97 1.01 27.5 1.9 Not soluble Not soluble Soluble Soluble Soluble Not Soluble Soluble 10,11,14,56 10,11,14,56 56 14 56 10,11 56 57,58 59 57,58 59 58 57 57 59 57 59 57 59 57 57 57 57 57 Isopropyl Propanol (99%) Soluble 59 Hexanes (aliphatics) Soluble 59 Glycerin Soluble 59 Parafin Wax Soluble 59 a These are the chemical and physical properties of two different forms of Trimethylpentyl Polysilsesquioxane. Distributed for comment only -- do not cite or quote Table 4. Frequency of use according to duration and exposure of Maximum Maximum Concentration Concentration Use type Uses (%) Uses (%) Total/range Duration of usea Leave-on Rinse-off Diluted for (bath) use Exposure type Eye area Incidental ingestion Incidental Inhalation-sprays Incidental inhalation-powders Dermal contact Deodorant (underarm) Hair-noncoloring Hair-coloring Nail Mucous Membrane Baby C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane 12 0.2-4.9 12 0.2-4.9 NR NR NR NR 8 0.2-3.9 3 1 NR NR NR 4.6 9 0.2-4.9 NR NR NR NR NR NR NR NR 3 1 NR NR Dimethicone/ Silsesquioxane Copolymer 7 NR 7 NR NR NR NR NR 1 NR NR NR NR NR 1 NR 7 NR NR NR NR NR NR NR NR NR NR NR NR NR polysilsequioxanes.19-21 Maximum Concentration Uses (%) Hydrogen Dimethicone/Octyl Silsesquioxane Copolymer 3 NR 3 NR NR NR NR NR NR NR NR NR 3b NR NR NR 3 NR NR NR NR NR NR NR NR NR NR NR NR NR Maximum Concentration Uses (%) Polycaprylylsilsesquioxane 3 0.0025-0.005 3 0.0025-0.005 NR 0.0025 NR NR 3 0.005 NR NR NR NR NR NR NR NR NR NR NR 0.0025 NR NR NR NR NR NR NR NR Polydimethylsiloxy PEG/PPG-24/19 Butyl Polymethylsilsesquioxane Ether Silsesquioxane Polypropylsilsesquioxane Total/range 397 0.00001-55.2 NR 0.023 14 0.8-2.4 Duration of use Leave-on 374 0.00001-55.2 NR 0.023 14 0.8-2.4 Rinse-off 22 0.01-7.5 NR NR NR NR Dilutedufsoer (bath) 1 NR NR NR NR NR Exposure type Eye area 87 0.02-55.2 NR NR 8 2 Iinncgiedsetniotanl 17 0.03-20.7 NR NR 4 NR InhaIlnactiidoenn-staplrays 4;6650cb; 01..038-5-5.52b; NR 0.023 NR NR Incidental inhalation-powders 38; 65c 0.1-49.8; 0.01-28d NR NR NR NR Dermal contact 342 0.001-55.2 NR NR 9 0.8-2.4 (Duneodderoarramnt) NR 4e NR NR NR NR Hair-noncoloring 27 0.11-7 NR 0.023 NR NR Hair-coloring NR NR NR NR NR NR Nail NR 0.00001-0.77 NR NR NR NR MMemucboruans e 20 0.03-20.7 NR NR 4 NR Baby NR NR NR NR NR NR NR = Not Reported; Totals = Rinse-off + Leave-on + Diluted for Bath Product Uses. a Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure types may not equal the sum of total uses. b It is possible these products may be sprays, but it is not specified whether the reported uses are sprays. c Not specified whether a powder or a spray, so this information is captured for both categories of incidental inhalation. d It is possible these products may be powders, but it is not specified whether the reported uses are powders. e Spray products. Distributed for comment only -- do not cite or quote Table 5. Polysilsesquioxane ingredients that have no reported uses in the VCRP or the Council survey.19-21 Acryloyloxypropyl Polysilsesquioxane Dimethiconol/Caprylylsilsesquioxane/Silicate Crosspolymer Isobutyl/Methoxy PEG-10 Polysilsesquioxane Methacryloyloxypropyl Polysilsesquioxane Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane Trimethylpentyl Polysilsesquioxane C26-28 Alkyldimethylsilyl Polypropylsilsesquioxane Ethyl Polysilsesquioxane Isobutyl Polysilsesquioxane Methoxy PEG-10 Polysilsesquioxane Polymethylsilsesquioxane/Trimethylsiloxysilicate Table 6. Acute oral toxicity studies of polysilsesquioxanes in this safety assessment. Ingredient (concentration) Animal (n) Methods Results Isobutyl/Methoxy PEG-10 Polysilsesquioxane (5000 mg/kg) Isobutyl Polysilsesquioxane (5000 mg/kg) Methacryloyloxypropyl Polysilsesquioxane (5000 mg/kg) Methoxy PEG-10 Polysilsesquioxane (5000 mg/kg) Trimethylpentyl Polysilsesquioxane (5000 mg/kg) Trimethylpentyl Polysilsesquioxane (5000 mg/kg) Female Sprague Dawley albino rats (5) Female Wistar albino rats (10) Female Sprague Dawley albino rats (3) Female Sprague Dawley albino rats (3) Female Sprague Dawley albino rats (3) Female Sprague Dawley albino rats (3) Single oral dose after fasting. Rats observed first 30 min and 1, 3, 6, and 24 h after dosing; then daily for 14 days. Results were scored according to U.S. Environmental Protection Agency (EPA) established four Toxicity Categories for acute hazards of pesticide products [40 CFR 156.62] Single oral dose after fasting. Rats observed first 30 min and 1, 3, 6, and 24 h after dosing; then daily for 14 days Single oral dose after fasting. Rats observed first 30 min and 1, 3, 6, and 24 h after dosing; then daily for 14 days Single oral dose after fasting. Rats observed first 30 min and 1, 3, 6, and 24 h after dosing; then daily for 14 days Single oral dose after fasting. Rats observed first 30 min and 1, 3, 6, and 24 h after dosing; then daily for 14 days Single oral dose after fasting. Rats observed first 30 min and 1, 3, 6, and 24 h after dosing; then daily for 14 days Two rats died. Clinical signs included foaming of the mouth, red nasal discharge, dehydration, and slight depression. Two necropsies were unremarkable; masses were attached to the uterine horn in two necropsies (one rat died), blanching on the lungs, reddened small intestine and black spleen were observed in one rat (this rat died); and white matter in the thoracic cavity and portions of stomach appeared slightly reddened were observed in the fifth rat. LD50 = > 5000 mg/kg, Toxicity Category III (slightly toxic and slightly irritating) There were no mortalities. Clinical signs included: moist, matted hair, probable inner ear infection, diarrhea, dehydrated appearance, convulsions, muscle tremors, and rales. LD50 = > 5000 mg/kg, Toxicity Category III There were no mortalities. All rats gained weight. Necropsy was unremarkable. LD50 = > 500 mg/kg, Toxicity Category III There were no mortalities. All rats gained weight. Clinical signs: slight depression and muscle tremors. Necropsy was unremarkable. LD50 = > 5000 mg/kg, Toxicity Category III There were no mortalities. All rats gained weight. Necropsy was unremarkable. LD50 = > 5000 mg/kg, Toxicity Category III There were no mortalities. All rats gained weight. Necropsy was unremarkable. LD50 = > 5000 mg/kg, Toxicity Category III Reference 30 31 32 33 34 35 Distributed for comment only -- do not cite or quote Table 7. Genotoxicity studies of polysilsesquioxanes. Ingredient (concentration) Assay Methacryloyloxypropyl Polysilsesquioxane (50, 100, 500, 1000, and 5000 g/plate; in 2-propanol) Methacryloyloxypropyl Polysilsesquioxane (50, 100, 500, 1000, and 5000 g/plate; in 2-propanol) Methoxy PEG-10 Polymethylsilsesquioxane (5000 g/plate; in 2-propanol) Polymethylsilsesquioxane (50, 100, 500, 1000, and 5000 g/plate; in DMSO) Trimethylpentyl Polymethylsilsesquioxane (5000 g/plate; in 2-propanol) Bacterial reverse mutation assay using S. typhimurium (strains TA97a, TA98, TA100, TA102, and TA1535), with and without metabolic activation Bacterial reverse mutation assay using S. typhimurium (strains TA97a, TA98, TA100, TA102, and TA1535), with and without metabolic activation Bacterial reverse mutation assay using S. typhimurium (strains TA97a, TA98, TA100, TA102, and TA1535), with and without metabolic activation Bacterial reverse mutation assay using S. typhimurium (strains TA97a, TA98, TA100, TA102, and TA1535), with and without metabolic activation Bacterial reverse mutation assay using S. typhimurium (strains TA97a, TA98, TA100, TA102, and TA1535), with and without metabolic activation DMSO = dimethyl sulfoxide Results Not cytotoxic or genotoxic, with or without metabolic activation Not cytotoxic or genotoxic, with or without metabolic activation Not cytotoxic or genotoxic, with or without metabolic activation Not cytotoxic or genotoxic, with or without metabolic activation Not cytotoxic and there were no detectable genotoxic activity Reference 37 38 39 13 39 Table 8. Dermal irritation studies of polysilsesquioxanes using New Zealand White rabbits. Ingredient (concentration) n Procedure Results Isobutyl Polysilsesquioxane 6 Test substance was moistened with distilled PII was 0.05 out of 8. All 6 rabbits (100%; 0.5 g) water then applied to clipped intact and had a score of 0 for erythema on abraded skin of for 24 h under occlusion. After intact skin at 24 h 1 rabbit had a 24 h, test substance was washed from rabbit's score of 1 at 72 h. There was no skin with water and paper towels. Test sites edema observed. were observed at 24 and 72 h after application. Isobutyl/Methoxy PEG-10 3 OECD GL 404. Test substance was moistened Very slight to well defined, Polysilsesquioxane (100%; with distilled water then applied to clipped transient erythema was observed 0.5 g) intact skin for 4 h under occlusion. Test sites after dosing, which resolved by day were observed at removal through 14 days. 7. No corrosive effects were observed. Methacryloyloxypropyl 6 Applied to the intact and abraded skin of for 24 PII was 0.55 out of 8. All 6 rabbits Polysilsesquioxane h under occlusion. After 24 h, test substance had a score of 1 for erythema on was washed from rabbit's skin with water and intact skin at 24 h, which was paper towels. Test sites were observed at 24 resolved in all but 1 rabbit at 72 h. and 72 h after application. There was no edema observed. Methoxy PEG-10 6 Applied to the intact and abraded skin of for 24 PII was 0.40 out of 8. Five of 6 Polysilsesquioxane (100%; h under occlusion. After 24 h, test substance rabbits had a score of 1 for 0.5 mL) was washed from rabbit's skin with water and erythema on intact and abraded paper towels. Test sites were observed at 24 skin at 24 h. One rabbit had a score and 72 h after application. of 0. All erythema were resolved at 72 h and all rabbits had scores of 0. There was no edema observed. Polymethylsilsesquioxane (0 10 Dermally administered to rabbits for 28 daysa Only adverse effect reported was or 200 mg/kg/day; slight local erythema and dryness concentration of solids not following 7 to 14 dermal specified) applications of the emulsion. Trimethylpentyl 6 Applied to the intact and abraded skin of for 24 PII was 0.30 out of 8. Three of 6 Polysilsesquioxane (100%; 0.5 mL)b h under occlusion. After 24 h, test substance was washed from rabbit's skin with water and rabbits had a score of 1 for erythema on intact and abraded paper towels. Test sites were observed at 24 skin at 24 h, 1 rabbit had a score of and 72 h after application. 1 for erythema on abraded skin, and 2 scored 0. All erythema was resolved at 72 h and all rabbits had scores of 0. At 24 and 72 h, all scored 0 for edema. Reference 42 45 60 43 36 44 Distributed for comment only -- do not cite or quote Table 8. Dermal irritation studies of polysilsesquioxanes using New Zealand White rabbits. Ingredient (concentration) n Procedure Results Trimethylpentyl Polysilsesquioxane (100%; 0.5 mL)b 6 Applied to the intact and abraded skin of for 24 PII was 0.78 out of 8. Four of 6 h under occlusion. After 24 h, test substance rabbits had a score of 1 for was washed from rabbit's skin with water and erythema on intact and abraded paper towels. Test sites were observed at 24 skin at 24 h, 1 rabbit had a score of and 72 h after application. 1 for erythema on abraded skin, and 1 scored 2 on intact and 1 on abraded skin. All erythema was resolved at 72 h and all rabbits had scores of 0. At 24 and 72 h, all scored 0 for edema. PII = Primary Irritation Index a Breed/strain of rabbit not known. b Two different forms of Trimethylpentyl Polysilsesquioxane Reference 35 Table 9. HRIPT studies of polysilsesquioxanes. Ingredient (concentration) n Proceedure C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane (4.337%) Polymethylsilsesquioxane (100%; 0.2 g) Polymethylsilsesquioxane (50%) Polymethylsilsesquioxane (22.0%) Polymethylsilsesquioxane/ Trimethylsiloxysilicate (50% in cyclopentasiloxane) 218 A product (0.2 g; neat) that is used near the eyes, containing ingredient at 4.337%, was applied to the infrascapular area of the back or the upper arm under occlusion three times per week for 3 weeks. Patches were left in place for 24 h. Challenge application was made (neat) after a one-week rest period to nave sites. Test sites were examined before next application. 50 Induction applications were made three times per week for 3 weeks. After a rest period of 10 to 14 days, challenge patch, also containing 0.2 g Polymethyl-silsesquioxane, was administered. 100 A makeup product, containing the ingredient at 50%, was applied to upper backs under occlusion three times per week for 3 weeks. After at least a two-week rest, challenge application was made (neat) to a nave site on the back. Test sites were examined before next application. 108 A makeup product, containing the ingredient at 22.0%, was applied to backs under occlusion three times per week for 3 weeks. Patches remained in place for at least 24 h. After a 12 to 14-day rest, the challenge application was applied (neat) to a nave site on backs and to the upper arm. Test sites were examined before the next application during induction and at 24 and 72 h after the removal of the challenge patch. 50 Induction applications were made with test substance (0.2 g) three times per week for 3 weeks to infrascapular region of backs. Subjects removed occlusive hypoallergenic patches after 24 h. After a rest period of 10 to 14 days, the challenge patch, also containing 0.2 g test substance (50%) was administered. Results There were no adverse events reported at any time during the test. There was no evidence of sensitization during test period. It was concluded that that test substance was non-sensitizing. There were no adverse reactions of any type observed during the course of this study. There were no signs of erythema or other signs of irritation or sensitization at any time during test. It was concluded that test substance was non-sensitizing. There were two instances of barely perceptible erythema () after the removal of an induction patch; there were no other signs of erythema, or signs of irritation or sensitization, at any time during the test. It was concluded that the test substance was non-sensitizing. There were no adverse reactions of any type observed during course of this study, and test substance was considered a non-primary irritant and a non-primary sensitizer to the skin. Reference 48 13 49 50 18 Distributed for comment only -- do not cite or quote REFERENCES 1. Nikitakis, J and Lange B (eds). Web-Based Ingredient Dictionary (wINCI). http://webdictionary.personalcarecouncil.org/jsp/Home.jsp. Washington, DC. Last Updated 2017. 2. Becker, LC, Bergfeld, W, Belsito, D, Hill, R, Klaassen, C, Liebler, D, Marks Jr, J, Shank, R, Slaga, T, Snyder, P, and Andersen, F. Safety assessment of dimethicone crosspolymers as used in cosmetics. International Journal of Toxicology. 2014;33(Suppl. 2):65S-115S. 3. Bergfeld, WF, Belsito, DV, Klaassen, CD, Liebler, DC, Hill, RA, Marks Jr, JG, Shank, RC, Slaga, TJ, Snyder, PW, Andersen, FA, and Johnson Jr., W. Final report: Dimethiconol and its derivatives as used in cosmetics. Washington, DC, Cosmetic Ingredient Review. 2010. http://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/FR571.pdf. pp. 1-36. 4. Bergfeld, WF, Belsito, DV, Hill, RA, Klaassen, CD, Liebler, DC, Marks Jr, JG, Shank, RC, Slaga, TJ, Snyder, PW, Gill, LJ, and Becker, LC. Safety assessment of polyoxyalkylene siloxane copolymers, alkyl-polyoxyalkylene siloxane copolymers, and related ingredients as used in cosmetics. Washington, DC, Cosmetic Ingredient Review. 2014. http://online.personalcarecouncil.org/ctfastatic/online/lists/cir-pdfs/FR664.pdf. pp. 1-46. 5. Bergfeld, WF, Belsito, DV, Hill, RA, Klaassen, CD, Liebler, DC, Marks Jr, JG, Shank, RC, Slaga, TJ, Snyder, PW, Gill, LJ, and Becker, LC. Safety assessment of alkoxyl alkyl silanes as used in cosmetics. Washington, DC, Cosmetic Ingredient Review. 2016. http://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/FR716.pdf. pp. 1-16. 6. Fiume, MM, Heldreth, B, Bergfeld, W, Belsito, D, Hill, R, Klaassen, C, Liebler, D, Marks Jr, J, Shank, R, Slaga, T, Snyder, P, and Andersen, F. Safety assessment of alkyl PEG ethers as used in cosmetics. International Journal of Toxicology. 2012;31(Supp. 2):169S-244S. 7. Personal Care Products Council. 5-2-2017. Polymethylsilsesquioxane: Comments from Michael Starch, member of the INCI Committee. Unpublished data submitted by Personal Care Products Council. 8. Active Concepts. 2012. Technical data sheet: SilDerm EPSQ (Dimethicone/Silsesquioxane Copolymer). Unpublished data submitted by Personal Care Products Council. 9. Active Concepts. 2015. Product specification: SilDerm EPSQ (Dimethicone/Silsesquioxane Copolymer). Unpublished data submitted by Personal Care Products Council. 10. China Senior Supplier. Batai bt-9276 cosmetic grade; Guangzhou Batai Chemical Co., Ltd. http://www.chinaseniorsupplier.com/Environment/Daily_Chemical_Raw_Materials/60314891569/Cosmetic_grade_polymethylsilsesq uioxane.html. Last Updated 2017. Date Accessed 3-29-2017. 11. Shin-Etsu Chemical Co., Ltd. Silicone products for personal care (for North and South America) [pamphlet]. United States: Shin-Etsu Chemical Co., Ltd.; 2017. 12. Anonymous. 2017. Information concerning Polymethylsilsesquioxane. Unpublished data submitted by Personal Care Products Council. 13. Anonymous. 2017. Summary information Polymethylsilsesquioxane. Unpublished data submitted by Personal Care Products Council. 14. Active Concepts. 2014. Product specification SilDerm SQ (Polymethylsilsesquioxane). Unpublished data submitted by Personal Care Products Council. 15. Dow Corning Corporation. Product Information, Personal Care: Dow Corning SW-8005 C30 Resin Wax [pamphlet].Dow Corning Corporation; 2009. 16. Active Concepts. 2012. Manufacturing flow chart: SilDerm EPSQ (Dimethicone/Silsesquioxane Copolymer). Unpublished data submitted by Personal Care Products Council. 17. Active Concepts. 2012. Manufacturing flow chart: SilDerm SQ (Polymethylsilsesquioxane). Unpublished data submitted by Personal Care Products Council. 18. Anonymous. 2017. Summary information Polymethylsilsesquioxane/Trimethylsiloxysilicate. Unpublished data submitted by Personal Care Products Council. 19. Food and Drug Administration (FDA). Frequency of use of cosmetic ingredients; FDA Database. Washington, DC, FDA. 2017. 20. Personal Care Products Council. 7-6-2017. Concentration of Use by FDA Product Category: Trimethylpentyl Polysilsesquioxane, Isobutyl/Methoxy PEG-10 Polysilsesquioxane and Methoxy PEG-10 Polysilsesquioxane. Unpublished data submitted by Personal Care Products Council. 21. Personal Care Products Council. 10-31-2016. Concentration of Use by FDA Product Category: Polysilsesquioxanes. Unpublished data submitted by Personal Care Products Council. 22. Johnsen MA. The Influence of Particle Size. Spray Technology and Marketing. 2004;14(11):24-27. Distributed for comment only -- do not cite or quote 23. Rothe H. Special aspects of cosmetic spray safety evaluation. 2011. Unpublished information presented to the 26 September CIR Expert Panel. Washington D.C. 24. Bremmer HJ, Prud'homme de Lodder LCH, and van Engelen JGM. Cosmetics Fact Sheet: To assess the risks for the consumer; Updated version for ConsExpo 4. 2006. http://www.rivm.nl/bibliotheek/rapporten/320104001.pdf. Date Accessed 8-24-2011. Report No. RIVM 320104001/2006. pp. 1-77. 25. Rothe H, Fautz R, Gerber E, Neumann L, Rettinger K, Schuh W, and Gronewold C. Special aspects of cosmetic spray safety evaluations: Principles on inhalation risk assessment. Toxicol Lett. 8-28-2011;205(2):97-104. PM:21669261. 26. Aylott RI, Byrne GA, Middleton, J, and Roberts ME. Normal use levels of respirable cosmetic talc: preliminary study. Int J Cosmet Sci. 1979;1(3):177-186. PM:19467066. 27. Russell RS, Merz RD, Sherman WT, and Sivertson JN. The determination of respirable particles in talcum powder. Food Cosmet Toxicol. 1979;17(2):117-122. PM:478394. 28. CIR Science and Support Committee of the Personal Care Products Council (CIR SSC). 11-3-2015. Cosmetic Powder Exposure. Unpublished data submitted by the Personal Care Products Council. 29. European Commission. CosIng. http://ec.europa.eu/growth/tools-databases/cosing/. Last Updated 2017. 30. Consumer Product Testing Co. 2016. Acute oral toxicity in rats -limit test (lsobutyl/Methoxy PEG-10 Polysilsesquioxane). Unpublished data submitted by Personal Care Products Council. 31. Consumer Product Testing Co. 2014. Acute oral toxicity in rats (Isobutyl Polysilsesquioxane). Unpublished data submitted by Personal Care Products Council. 32. Consumer Product Testing Co. 2015. Acute oral toxicity in rats - limit test (Methacryloyloxypropyl Polysilsesquioxane ). Unpublished data submitted by Personal Care Products Council. 33. Consumer Product Testing Co. 2015. Acute oral toxicity in rats - limit test (Methoxy PEG-10 Polysilsesquioxane). Unpublished data submitted by Personal Care Products Council. 34. Consumer Product Testing Co. 2015. Acute oral toxicity in rats - limit test (Trimethylpentyl Polysilsesquioxane SO1455). Unpublished data submitted by Personal Care Products Council. 35. Consumer Product Testing Co. 2015. Acute oral toxicity in rats - limit test (Trimethylpentyl Polysilsesquioxane MS0805). Unpublished data submitted by Personal Care Products Council. 36. Dow Corning Corporation. Report to Dow Corning Corportation 28-day subacute RBA study on TX-125C, TA-125F and TX-125I with cover letter dated 042094 [Dow Corning Corporation; 28 day subacure RBA study on F 67085 A1482 20, X5 41042, LOT 103, AND XEF 11075, LOT 1; 10/14/66; EPA DOC. NO. 86940001091; FICHE NO. OTS0556545; Submitted by Industry, Modified] . 1994. https://yosemite.epa.gov/oppts/epatscat8.nsf/ReportSearchView/38287380FA5AA4A285256930004C2F47. 37. Consumer Product Testing Co. 2015. Bacterial reverse mutation assay (Methacryloyloxypropyl Polysilsesquioxane). Unpublished data submitted by Personal Care Products Council. 38. Consumer Product Testing Co. 2017. Bacterial reverse mutation assay (Methacryloyloxypropyl Polysilsesquioxane). Unpublished data submitted by Personal Care Products Council. 39. Consumer Product Testing Co. 2016. Bacterial reverse mutation assay (Methoxy PEG-10 Polysilsesquioxane and Trimethylpentyl Polysilsesquioxane [SO 1455]). Unpublished data submitted by Personal Care Products Council. 40. Personal Care Products Council. 6-7-2017. Draft Report: Safety Assessment of Polysilsesquioxanes as Used in Cosmetics. Unpublished data submitted by Personal Care Products Council. 41. Active Concepts. 2014. Dermal and ocular irritation tests: SilDerm SQ (Polymethylsilsesquioxane). Unpublished data submitted by Personal Care Products Council. 42. Consumer Product Testing Co. 2014. Primary dermal irritation in rabbits (Isobutyl Polysilsesquioxane). Unpublished data submitted by Personal Care Products Council. 43. Consumer Product Testing Co. 2014. Primary dermal irritation in rabbits (Methoxy PEG-10 Po1ysilsesquioxane ). Unpublished data submitted by Personal Care Products Council. 44. Consumer Product Testing Co. 2014. Primary dermal irritation in rabbits (Trimethylpentyl Polysilsesquioxane SO1455). Unpublished data submitted by Personal Care Products Council. 45. Consumer Product Testing Co. 2016. Acute dermal irritation/corrosion in rabbits (OECD) (lsobutyl/Methoxy PEG-10 Polysilsesquioxane). Unpublished data submitted by Personal Care Products Council. Distributed for comment only -- do not cite or quote 46. Active Concepts. 2016. In Chemico skin sensitization OECD TG 442C: SilDerm SQ (Polymethylsilsesquioxane). Unpublished data submitted by Personal Care Products Council. 47. Active Concepts. 2016. OECD TG 442C: In vitro skin sensitization: SilDerm SQ (Polymethylsilsesquioxane ). Unpublished data submitted by Personal Care Products Council. 48. TKL Research Inc. 2014. Repeated insult patch test of an eye area product containing 4.337% C30-45 Alkyldimethylsilyl Polypropylsilsequioxane. Unpublished data submitted by Personal Care Products Council. 49. EVIC Romania. 2013. Human repeated insult patch test with challenge of a face product containing 50% Polymethylsilsesquioxane. Unpublished data submitted by Personal Care Products Council. 50. Clinical Research Laboratories Inc. 2012. Executive summary of human repeat insult patch test of a skin care product containing 22% Polymethylsilsesquioxane. Unpublished data submitted by Personal Care Products Council. 51. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). Polymer of low concern public report: C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane. Sidney NSW, Australia, National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 2013. Date Accessed 3-28-2017. Report No. PLC/1097. pp. 1-5. 52. Hybrid Plastics Inc. 2017. Product information - PG 1192 (Isobutyl/Methoxy PEG-10 Po1ysilsesquioxane). Unpublished data submitted by Personal Care Products Council. 53. Hybrid Plastics Inc. 2017. Product information- MS0825 Octalsobutyl POSS (Isobutyl Polysilsesquioxane ). Unpublished data submitted by Personal Care Products Council. 54. Hybrid Plastics Inc. 2017. Product information- MA0735 Methacryl POSS (Methacryloyloxypropyl Polysilsesquioxane ). Unpublished data submitted by Personal Care Products Council. 55. Hybrid Plastics Inc. 2017. Product information - PG 1190 (Methoxy PEG-I 0 Polysilsesquioxane ). Unpublished data submitted by Personal Care Products Council. 56. Kobo Products, Inc. Diasphere KS-500. http://www.koboproductsinc.com/SDSs/Diasphere-KS-500-SDS.pdf. Last Updated 2014. 57. Hybrid Plastics Inc. 2017. Product information- SOI455 TriSilanollsooctyl POSS (Trimethylpentyl Polysilsesquioxane ). Unpublished data submitted by Personal Care Products Council. 58. Hybrid Plastics. Product Information - MS0805; Isooctyl POSS; INCI Name: Trimethylpentyl Polysilsesquioxane [pamphlet]. 2017. 59. Consumer Product Testing Co. 2017. Product information- MS0805 Isooctyl POSS (Trimethylpentyl Polysilsesquioxane ). Unpublished data submitted by Personal Care Products Council. 60. Consumer Product Testing Co. 2014. Primary dermal irritation in rabbits (Methacryloyloxypropyl Polysilsesquioxane ). Unpublished data submitted by Personal Care Products Council. Distributed for comment only -- do not cite or quote 2017 VCRP Data for Polysilsesquioxanes 02B - Bubble Baths 03B - Eyeliner 03C - Eye Shadow 03D - Eye Lotion 03F - Mascara 03G - Other Eye Makeup Preparations 04C - Powders (dusting and talcum, excluding aftershave talc) 04E - Other Fragrance Preparation 05A - Hair Conditioner 05B - Hair Spray (aerosol fixatives) 05F - Shampoos (non-coloring) 05G - Tonics, Dressings, and Other Hair Grooming Aids 05I - Other Hair Preparations 07A - Blushers (all types) 07B - Face Powders 07C - Foundations 07E - Lipstick 07F - Makeup Bases 07H - Makeup Fixatives 07I - Other Makeup Preparations 10A - Bath Soaps and Detergents 11G - Other Shaving Preparation Products 12C - Face and Neck (exc shave) 12D - Body and Hand (exc shave) 12F - Moisturizing 12G - Night 12I - Skin Fresheners 12J - Other Skin Care Preps 13A - Suntan Gels, Creams, and Liquids POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE POLYMETHYLSILSESQUIOXANE 1 13 31 12 11 20 2 3 4 1 15 6 1 16 36 54 17 9 1 11 2 1 59 6 42 10 1 11 1 397 03A - Eyebrow Pencil C30-45 ALKYLDIMETHYLSILYL 1 POLYPROPYLSILSESQUIOXANE 03B - Eyeliner C30-45 ALKYLDIMETHYLSILYL 3 POLYPROPYLSILSESQUIOXANE 03C - Eye Shadow C30-45 ALKYLDIMETHYLSILYL 1 POLYPROPYLSILSESQUIOXANE 03D - Eye Lotion C30-45 ALKYLDIMETHYLSILYL 1 POLYPROPYLSILSESQUIOXANE 03G - Other Eye Makeup C30-45 ALKYLDIMETHYLSILYL 2 Preparations POLYPROPYLSILSESQUIOXANE 07C - Foundations C30-45 ALKYLDIMETHYLSILYL 1 POLYPROPYLSILSESQUIOXANE 07E - Lipstick C30-45 ALKYLDIMETHYLSILYL 3 POLYPROPYLSILSESQUIOXANE 12 Distributed for comment only -- do not cite or quote 03G - Other Eye Makeup Preparations DIMETHICONE/SILSESQUIOXANE COPOLYMER 1 07B - Face Powders DIMETHICONE/SILSESQUIOXANE COPOLYMER 1 07C - Foundations DIMETHICONE/SILSESQUIOXANE COPOLYMER 4 07I - Other Makeup Preparations DIMETHICONE/SILSESQUIOXANE COPOLYMER 1 7 13A - Suntan Gels, Creams, and Liquids HYDROGEN DIMETHICONE/OCTYL 3 SILSESQUIOXANE COPOLYMER 03F - Mascara POLYCAPRYLYLSILSESQUIOXANE 3 03A - Eyebrow Pencil POLYPROPYLSILSESQUIOXANE 1 03B - Eyeliner POLYPROPYLSILSESQUIOXANE 2 03C - Eye Shadow POLYPROPYLSILSESQUIOXANE 2 03F - Mascara POLYPROPYLSILSESQUIOXANE 1 03G - Other Eye Makeup Preparations POLYPROPYLSILSESQUIOXANE 2 07C - Foundations POLYPROPYLSILSESQUIOXANE 1 07E - Lipstick POLYPROPYLSILSESQUIOXANE 4 07I - Other Makeup Preparations POLYPROPYLSILSESQUIOXANE 1 14 There were no reported uses in the VCRP for: Acryloyloxypropyl Polysilsesquioxane C26-28 Alkyldimethylsilyl Polypropylsilsesquioxane Dimethiconol/Caprylylsilsesquioxane/Silicate Crosspolymer Ethyl Polysilsesquioxane Isobutyl Polysilsesquioxane Methacryloyloxypropyl Polysilsesquioxane Polydimethylsiloxy PEG/ PPG-24/19 Butyl Ether Silsesquioxane Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane Polymethylsilsesquioxane/Trimethylsiloxysilicate Trimethylpentyl Polysilsesquioxane Isobutyl/Methoxy PEG-10 Polysilsesquioxane Methoxy PEG-10 Polysilsesquioxane Distributed for comment only -- do not cite or quote Personal Care Products Council Committed to Safety, Quality & Innovation Memorandum TO: COSMETIC INGREDIENT REVIEW (CIR) FROM: Beth A. Jonas, Ph.D. Industry Liaison to the CIR Expert Panel DATE: June 6, 2017 SUBJECT: Polymethylsilsesquioxane Clinical Research Laboratories, Inc. 2012. Executive summary of human repeat insult patch test of a skin care product containing 22% Polymethylsilsesquioxane. 1620 L Street, N.W., Suite 1200 I Washington, D.C. 20036 I 202.331.1770 I (fax) www.personalcarecouncil.org Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Personal CareeProducts Council Distributed for comment only -- do not cite or quote Committed to Safety, Quality & Innovation Memorandum TO: Bart Heldreth, Ph.D., Interim Director COSMETIC INGREDIENT REVIEW (CIR) FROM: Beth A. Jonas, Ph.D. Industry Liaison to the CIR Expert Panel DATE: July 20, 2017 SUBJECT: Methoxy PEG-10 Polysilsesquioxane and Trimethylpentyl Polysilsesquioxane (S01455) Hybrid Plastics, Inc. 2017. Product information - PG1190 (Methoxy PEG-10 Polysilsesquioxane). Consumer Product Testing Co. 2015. Acute oral toxicity in rats - limit test (Methoxy PEG-10 Polysilsesquioxane). Consumer Product Testing Co. 2014. Primary dermal irritation in rabbits (Methoxy PEG-10 Polysilsesquioxane). Consumer Product Testing Co. 2016. Bacterial reverse mutation assay (Methoxy PEG-10 Polysilsesquioxane and Trimethylpentyl Polysilsesquioxane [S01455]). 1620 L Street, N.W., Suite 1200 Washington, D.C. 20036 I 202.331.17701 (fax) I www.personalcarecounciLorg Distributed for comment only -- do not cite or quote uistriouteu 101 ournmeoL (July uu 1101 0110 01 ul-IULC 03 Consumer Product Testing Co. Ftil, 1975 FINAL REPORT CLIENT: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: Acute Oral Toxicity in Rats -- Limit Test TEST ARTICLE: POSS PG1I90; Lot 2015.038EP Mel-hz,ey PE (.3 O Pd 1st S 7`)CO)Cgile EXPERIMENT REFERENCE NUMBER: T15-1227-1 teven Nitka Vice President Laboratory Director This report is submitted for tlic exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name of these Laboratories nor any member of its staff, may be used in connection with the advertising or sale of any product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote 0 0 Consumer Product Testing Co. 1St. 11175 QUALITY ASSURANCE UNIT STATEMENT Study No.: T15-1227-1 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: Signature/Date c/a /6- 70 New Dutch Lane FairfieId, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote 4 rIra Consumer Product Testing Co. ktil 1075 Final Report Summary CLIENT: Hybrid Plastics, Inc. STUDY NO.: T15-1227-1 REFERENCE: Purchase Order No. 2015-050 TEST ARTICLE: POSS PG1190; Lot 2015.038EP TEST ARTICLE RECEIPT DATE: March 12, 2015 EXPERIMENTAL INTERVAL: April 7, 2015 to April 24, 2015 Method: Acute Oral Toxicity in Rats -- Limit Test Three (3) female, Sprague Dawley strain albino rats, 154 - 160 g, each received a single oral dose of the test article at a dose level of five (5) grams per kilogram body weight. Animals were observed for pharmacological activity and drug toxicity at least once during the first 30 minutes after dosing and then at 1, 3, 6 and 24 hours post-dosage, and daily thereafter for a total of 14 days. Interim body weights were recorded on day seven (7). All animals were subjected to gross necropsy, with all findings noted. The test article was used as received (Sp.g. = 1.08). Results: LD50 > 5 g/kg Dose Level (g/kg) #/Sex 5.00 3/F No. E.T.*/No. Dosed No. Dead/No. Dosed Mortality (%) 3/3 0/3 0 Conclusion: According to OPPTS 870.1100, and under the conditions of this test, this test article has an oral LD50 greater than 5 grams per kilogram bodyweight. All animals gained weight. Toxic signs exhibited included slight depression and muscle tremors. According to OPPTS 870.1000, and under the conditions of this test, this test article has an acute oral toxicity rating of Category IV (see page 6). *Exhibiting toxic signs. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote IJISUIUULUU !Ur 00011110111 (July uu 11010110 01 quote Consumer Product Testing Co. 11175 FINAL REPORT CLIENT: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: Primary Dermal Irritation in Rabbits TEST ARTICLE: EXPERIMENT REFERENCE NUM]3ER: PGI190 - PEG POSS Cage Mixture; Lot Number: Project 2014 172EP ,PEU- 7J.c,eczne T14-5007-8 teven Nitka Vice President Laboratory Director This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name of these Laboratories nor any member of its staff; may be used in connection with the advertising or sale of any product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote 43 Consumer Product Testing Co. F.S1. 11171 QUALITY ASSURANCE UNIT STATEMENT Study No.: T14-5007-8 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: Signature/Date 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Consumer Product Testing Co. Ftil. I li75 Final Report Summary CLIENT: Hybrid Plastics, Inc. STUDY NO.: T14-5007-8 REFERENCE: Purchase Order No. 2014 131 TEST ARTICLE: PG1190 - PEG PUSS Cage Mixture; Lot Number: Project 2014 172EP TEST ARTICLE RECEIPT DATE: October 21, 2014 EXPERIMENTAL INTERVAL: November 18, 2014 to November 21, 2014 Method: Primary Dermal Irritation in Rabbits Six (6) New Zealand White rabbits each received a single dermal application of onehalf of one (0.5) milliliter of the test article on each of two (2) test sites, one (1) abraded and one (1) non-abraded. The test sites were occluded for 24 hours and were observed individually for erythema, edema, and other effects 24 and 72 hours after application. Mean scores from the 24 and 72 hour readings were averaged to determine the primary irritation index. The test article was dosed as received. Results: Primary Irritation Index:* 0.40 Conclusion: According to Federal Hazardous Substances Act Regulations (16 CFR 1500.41), and under the conditions of this test, this test article is not a primary dermal irritant. *Refer to Table 2 for specific evaluation. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 - Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote 4070 Consumer roduct Testing Co. BACTERIAL REVERSE MUTATION ASSAY FINAL REPORT STUDY NUMBER: M16-I 865 SPONSOR: Hybrid PIastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, MS 39401 SPONSOR'S REPRESENTATIVE: Michael Carr TESTING FACILITY: Consumer Product Testing Company, Inc. 70 New Dutch Lane Fairfield NJ 07004 PH: Ext. 202 FX: Email: c tclabs.com STUDY DIRECTOR: D. Keith Goins, Ph.D. Director, Microbiology STUDY INITIATION DATE: May 6, 2016 STUDY COMPLETION DATE: May 20, 2016 REPORT PREPARED BY: D. Keith Goins, Ph.D. Director, Microbiology REPORT REVIEWED BY: Quality Assurance ff 420/2z Date (35 -00 -/ea Date This report is submitted for the exclusive use of the person, partnership, or corporation to whom it Is addressed, and neither the report nor the name of these Laboratories nor any member of its staff may be used in connection with the advertising or sale of any product or process without authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote UlbillUULUU IUI GUIIIIIICIIL (July uu nut. uue ut quuLe Personal Care Products Council Committed to Safety, Quality & Innovation Memorandum TO: Bart Heldreth, Ph.D., Interim Director COSMETIC INGREDIENT REVIEW (CIR) FROM: Beth A. Jonas, Ph.D. Industry Liaison to the CIR Expert Panel DATE: July 20, 2017 SUBJECT: Trimethylpentyl Polysilsesquioxane (see memo on Methoxy PEG-10 Polysilsesquioxane and Trimethylpentyl Polysilsesquioxane for an Ames assay on SO1455) Hybrid Plastics, Inc. 2017. Product information - SO1455 TriSilanollsooctyl POSS (Trimethylpentyl Polysilsesquioxane). Consumer Product Testing Co. 2015. Acute oral toxicity in rats - limit test (Trimethylpentyl Polysilsesquioxane SO1455). Consumer Product Testing Co. 2014. Primary dermal irritation in rabbits (Trimethylpentyl Polysilsesquioxane SO1455). Consumer Product Testing Co. 2017. Product information - MS0805 Isooctyl POSS (Trimethylpentyl Polysilsesquioxane). Consumer Product Testing Co. 2015. Acute oral toxicity in rats - limit test (TrimethylpentyI Polysilsesquioxane MS0805). Consumer Product Testing Co. 2014. Primary dermal irritation in rabbits (Trimethylpentyl Polysilsesquioxane MS0805). 1620 L Street, N.W., Suite 1200 Washington, D.C. 20036 1202.331.1770 (fax) www.personalcarecouncil.org LJISUIEJULeU or 001111110111 only uu nut O11C vi t. UVIC Product Information - SO1455 TriSilanollsooctyl POSS Mi r INCE NAME: Trimethylpentyl Polysilsesquioxane FEATURES Clear, colorless. Alcohol emulsification. Oil compatible. ti \ _0.O74r APPLICATIONS Lubrication and plasticization, carrier for ingredients in lotions gels, coatings. Non-migrating. TYPICAL PROPERTIES Appearance Clear, pale yellow viscous liquid Viscosity (@35%) 275 poise Density 0.97 glml Refractive Index 1.45 Formula Weight 1 184.16 Resin Solubility aliphatic and aromatic monomers, oligomers, PP, PE, PA cellulosics, silicones REGULATORY STATUS INCI, REACH pending, CAS 444619-08-3 Not a primary dermal irritant. HANDLING PRECAUTIONS Product safety information requiredfor safe use is not included in this document. Before handling, read product and material safety data sheets and container labelsfor safe use, physical health and hazard information. For material safety data information, contact Hybrid Plastics. *bnd BENEFITS Rheological diluent lubricious hydrophobe. Nonmigrating. Skin adhesion, hemostatic and antimicrobial and outstanding gloss enhancement. DESCRIPTION SO1455 is a hybrid molecule with an inorganic silsequioxane at the core and organic isooctyl groups attached at the corners of the cage and three active silanol functionalities. It has shown effectiveness toward skin adhesion. COMPATIBILITY Water Alcohols Ethanol (95%) Ethanol (70%) iPropanol (99%) iPropanol (70%) Solvents & Propellants Hexane (aliphatics) PMGEA Cosmetic Materials Beeswax Mineral Oil Petrolatum 1,2 Propylene diol Glycerin DC556 (PhSi(OSiMe3)3 Fluoralkyls Shea Butter Cocoa Butter Hydroxy Methylcellulose Lanolin Paraffin Wax Caprylyl Glycol (1,2 Octanediol) Cetearyl Alcohol (Cl 80H) Veggie Oil www.hyb Not Soluble Soluble Stable Soluble Stable Soluble Soluble Soluble Soluble Soluble Stable Not Soluble Soluble Not Soluble Soluble Soluble Not Soluble Soluble Soluble Soluble Soluble Soluble corn uistriouteu 101 ournmeoL (July uu 1101 0110 01 ul-IULC O..w.5 Consumer Product Testing Co. WE. I tri.1 FINAL REPORT CLIENT: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: TEST ARTICLE: Acute Oral Toxicity in Rats -- Limit Test 7:-. rite 14)4 e POSS SO1455 #2015 076 EP EXPERIMENT REFERENCE NUMBER: T15-2977-3 Steven Nitka Vice President Laboratory Director 1140/,(- This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name of these Laboratories nor any member of its stag may be used in connection with the advertising or sale of any product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 ' Fax Distributed for comment only -- do not cite or quote 0 0. Consumer Product Testing Co. QUALITY ASSURANCE UNIT STATEMENT Study No. T15-2917-3 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study, The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: Signature/Date W/O(/ 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical ChemMillology Distributed for comment only -- do not cite or quote 0 5 Consumer Product Testing Co. ; `.1 1073 Final Report Summary CLIENT: Hybrid Pjasties, Inc. STUDY NO.: T151977-3 REFERENCE: Purchase Order No. 2015-115 TEST ARTICLE; k)SS SO1455 #2015 076 EP TEST ARTICLE RECEIPT DATE: June 16, 2015 EXPERIMENTAL INTERVAL: July 7, 2015 to July 24, 2015 Method: Acute Oral Toxicity in Rats -- Limit Test Three (3) female, Sprague Dawley strain albino rats, 170 - 196 g, each received a single oral dose of the test article at a dose level of five (5) grams per kilogram body weight. Animals were observed for pharmacological activity and drug toxicity at least once during the first 30 minutes after dosing and then at 1, 3, 6 and 24 hours post-dosage, and daily thereafter for a total of 14 days. Interim body weights were recorded on day seven (7). All animals were subjected to gross necropsy, with all findings noted. The test article was used as received (Sp.g. = 0.97). Results: LD50 > 5 g/kg Dose Level (g/kg) #/Sex 5.00 3/F No. E.T.*/No. Dosed 0/3 No. Dead/No. Dosed Mortality (%) 0/3 0 Conclusion: According to OPPTS 870.1100, and under the conditions of this test, this test article has an oral LD50 greater than 5 grams per kilogram bodyweight. All animals gained weight. According to OPPTS 870.1000, and under the conditions of this test, this test article has an acute oral toxicity rating of Category IV (see page 6). *Exhibiting toxic signs. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemilst"liliology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote IJ I.LI ILJULGU IL, UlJI III I !GI IL WI HH y uu i rut WILD VI quote Consumer Ftill; it roduct Testing Co. FINAL REPORT CLIENT: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: TEST ARTICLE: EXPERIMENT REFERENCE NUMBER: Primary Dermal Irritation in Rabbits Trimefi-ly pc,-N4y1 Pc) lysi lsrsq,j, 0 ,,,,,,,_e SO1455 - TriSilanollsooctyl POSS; Lot Number: Project 2014 172EP T14-5007-10 1 z-(c-dezi teven Nitka Vice President Laboratory Director This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name of these Laboratories nor any member of its staff, may be used in connection with the advertising or sale of any product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote deff, Consumer Product Testing Co. 1'Ni: 11175 QUALITY ASSURANCE UNIT STATEMENT Study No.: T14-5007-10 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: Signature/Date 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote I 1. Consumer Product Testing Co. F.!, I Mi .; Final Report Summary CLIENT: Hybrid Plastics, Inc. STUDY NO.: T14-5007-10 REFERENCE: Purchase Order No. 2014 131 TEST ARTICLE: SO1455 - TriSilanollsooctyl POSS; Lot Number: Project 2014 172EP TEST ARTICLE RECEIPT DATE: October 21, 2014 EXPERIMENTAL INTERVAL: November 18, 2014 to November 21, 2014 Method: Primary Dermal Irritation in Rabbits Six (6) New Zealand White rabbits each received a single dermal application of onehalf of one (0.5) milliliter of the test article on each of two (2) test sites, one (1) abraded and one (1) non-abraded. The test sites were occluded for 24 hours and were observed individually for erythema, edema, and other effects 24 and 72 hours after application. Mean scores from the 24 and 72 hour readings were averaged to determine the primary irritation index. The test article was dosed as received. Results: Primary Irritation Index:* 0.30 Conclusion: According to Federal Hazardous Substances Act Regulations (16 CFR 1500.41), and under the conditions of this test, this test article is not a primary dermal irritant. *Refer to Table 2 for specific evaluation. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chenust.Rgiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote duct Information - MS0805 Isooctyl POSSE INCI NAME: Trimethylpentyl Polysilsesquioxane FEATURES Clear, colorless. Alcohol, silicone and oil compatible. Outstanding UVB sorption and color/effects dispersion. 3013- APPLICATIONS Color and effect dispersion, lubrication and plasticizer in lotions gels, coatings.Non-migrating. BENEFITS Rheological diluent and lubricious hydrophobe. Low migration and high skin adhesion. Outstanding gloss enhancement. TYPICAL PROPERTIES Appearance Colorless to pale-yellow liquid Viscosity (@2,5%) 19 poise Density 1.01 glmL Refractive Index 1.45 SUGGESTED FORMULATION MS0805 can be utilized with nearly all oils and waxes and will mix readily. It will serve to reduce viscosity and will enhance long wear. MS0805 also wets lake pigments and can be utilized to enhance their gloss and dispersion. It is suggested to add sufficient MS0805 to wet the pigment. It will then serve to keep the pigment dispersed and in high concentration in organic oils. MS0805 also greatly enhances gloss. In most cases, milling is not necessary. The use of MS0805 in combination with MQ resin eliminates the shrinkage (itchy, tight feel) on skin and enhances gloss while retaining transfer resistance. This achieves more comfort and gloss at the lipstick-air interface. The suggested formulation is 2.5 parts MQ 2.5 parts trimethicone and 0.5 parts MS0805. However, higher loadings of MS0805 further improve comfort and feel. DESCRIPTION MS0805 is a hybrid molecule with an inorganic silsequioxane at the core and organic isooctyl groups attached at the corners of the cage. COMPATIBILITY Water Alcohols Not Soluble Formula Weight Resin Solubility 1322.46 silicones and aliphatic resins iPro.anol 99% Solvents & Propellants Hexane ali.hatics Cosmetrc Materials Soluble Soluble REGULATORY STATUS INCI, TSCA, REACH pending, CAS 190732-67-3. Not a primary dermal irritant. HANDLING PRECAUTIONS Product safety information required for safe use is not included in this document. Before handling, read product and material safety data sheets and container labels for safe use, physical health and hazard information. For material safety data information, contact Hybrid. hybrid Beeswax Mineral Oil Petrolatum 1,2 Propylene diol Glycerin DC556 (PhSi(OSiMe3)3 Shea Butter Cocoa Butter Lanolin Paraffin Wax Caprylyl Glycol (I, 2 Octanediol) Cetearyl Alcohol (C I 13OH) Veggie Oil Soluble Soluble Soluble Stable Soluble Soluble Soluble Soluble Soluble Soluble Soluble Soluble Soluble www.hybridplastics.com 55 W.L. RUNNELS INDUSTRIAL DR., HATTIESBURG, MS 39401 P: FAX: uisiriouieu ICH uummem only uu IIOL ULU of LtUVle Consumer Product Testing Co. FINAL REPORT CLIENT: - Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: TEST ARTICLE: EXPERIMENT REFERENCE NUMBER: Acute Oral Toxicity in Rats -- Limit Test ri-e`iiree.111 Pd 115r I SeS go O,,e-ct o PUSS MS0805 #2015 076 EP T15-2977-2 Yi Steven Nitka Vice President Laboratory Director This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name of these Laboratories nor any member ofits staff, may be used in connection with the advertising or sale ofany product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote 4:2 Consumer Product Testing Co. I?tiI. IU77, QUALITY ASSURANCE UNIT STATEMENT Study No.: T15-2917-2 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: Signature/Date cqic. (15- 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote 4.20r Consumer Product Testing Co. 11175 Final Report Summary CLIENT: Hybrid Nesties, Inc. STUDY NO.: T15:977-2 REFERENCE: PurOase Order No. 2015-115 TEST ARTICLE: POSS MS0805 #2015 076 EP TEST ARTICLE RECEIPT DATE: June 16, 2015 EXPERIMENTAL INTERVAL: July 7, 2015 to July 24, 2015 Method: Acute Oral Toxicity in Rats -- Limit Test Three (3) female, Sprague Dawley strain albino rats, 172 - I84 g, each received a single oral dose of the test article at a dose level of five (5) grams per kilogram body weight. Animals were observed for pharmacological activity and drug toxicity at least once during the first 30 minutes after dosing and then at 1, 3, 6 and 24 hours post-dosage, and daily thereafter for a total of 14 days. Interim body weights were recorded on day seven (7). All animals were subjected to gross necropsy, with all findings noted. The test article was used as received (Sp.g. = 0.97). Results: LD50 > 5 g/kg Dose Level (g/kg) #/Sex 5.00 3/F No. E.T.*/No. Dosed No. Dead/No. Dosed Mortality (%) 0/3 0/3 0 Conclusion: According to OPPTS 870.1100, and under the conditions of this test, this test article has an oral LD50 greater than 5 grams per kilogram bodyweight. All animals gained weight. According to OPPTS 870.1000, and under the conditions of this test, this test article has an acute oral toxicity rating of Category IV (see page 6). *Exhibiting toxic signs. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 - Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote LJISLIRJULUU KM 001111110111 Ul Ily UU 1101 0110 Ul t4LIUL.0 Consumer Product Testing Co. FINAL REPORT CLIENT: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: TEST ARTICLE: EXPERIMENT REFERENCE NUMBER: Primary Dermal Irritation in Rabbits Pdits, ise5cio,o/Cciri. ( MS0805 - Isooctyl POSS Cage Mixture; Lot Number: Project 2014 172EP T14-5007-7 teven Nitka Vice President Laboratory Director This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name of these Laboratories nor any member of its staff, may be used in connection with the advertising or sale of any product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote 4077, Consumer Product Testing Co. rtil. 1975 QUALITY ASSURANCE UNIT STATEMENT Study No.: T14-5007-7 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: Signature/Date 10-/eV/ 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Consumer Product Testing Co. I.:tit: 1975 Final Report Summary CLIENT: Hybrid PIastics, Inc. STUDY NO.: T14-5007-7 REFERENCE: Purchase Order No. 2014 131 TEST ARTICLE: MS0805 - Isooctyl POSS Cage Mixture; Lot Number: Project 2014 172EP TEST ARTICLE RECEIPT DATE: October 21, 2014 EXPERIMENTAL INTERVAL: November 4, 2014 to November 7, 2014 Method: Primary Dermal Irritation in Rabbits Six (6) New Zealand White rabbits each received a single dermal application of onchalf of one (0.5) milliliter of the test article on each of two (2) test sites, one (1) abraded and one (1) non-abraded. The test sites were occluded for 24 hours and were observed individually for erythema, edema, and other effects 24 and 72 hours after application. Mean scores from the 24 and 72 hour readings were averaged to determine the primary irritation index. The test article was dosed as received. Results: Primary Irritation Index:* 0.78 Conclusion: According to Federal Hazardous Substances Act Regulations' 16 CFR 1500.41), and under the conditions of this test, this test article is not a primary dermal irritant. *Refer to Table 2 for specific evaluation. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote I Personal Care Products Council Committed to Safety, Quality & Innovation Memorandum TO: Bart Heldreth, Ph.D., Interim Director COSMETIC INGREDIENT REVIEW (CIR) FROM: Beth A. Jonas, Ph.D. Industry Liaison to the CIR Expert Panel DATE: July 20, 2017 SUBJECT: Isobutyl/Methoxy PEG-10 Polysilsesquioxane Hybrid Plastics, Inc. 2017. Product information - PG1192 (Isobutyl/Methoxy PEG-10 Polysilsesquioxane). Consumer Product Testing Co. 2016. Acute oral toxicity in rats - limit test (Isobutyl/Methoxy PEG-10 PolysiIsesquioxane). Consumer Product Testing Co. 2016. Acute dermal irritation/corrosion in rabbits (OECD) (Isobutyl/Methoxy PEG-10 PolysiIsesquioxane). 1620 L Street, N.W., Suite 1200 I Washington, D.C. 20036 202.331.1770 I (fax) I www.personalcarecouncil.org Distributed for comment only -- do not cite or quote Product Information - PG1192 MethoxyPEGIsobutyl-PASS INC1NAME: lsobutyl/Methoxy PEG-10 Polysilsesquioxane FEATURES Translucent moisturizing wax with hydrophobic and hydrophilic properties. 51, FEATURED IMAGE OF PG1192: BENEFITS Hydrating comfortable and non-greasy feel for long wear. Excellent compatibilizer of ingredients, dispersion and carrier for actives. Non-cytotoxic and non-irritating. UVB sorption. APPLICATIONS Hair and skin adhesion for lotions and gels. A substitute for petrolatum and related waxes. TYPICAL PROPERTIES Appearance Melting Point Clear, pale yellow/orange, semi-solid 65C Refractive Index 1.46 Molecular Weight 1330.13 Solubility resins and common diluents and carriers REGULATORY STATUS INCI, CAS pending. Not a primary dermal irritant. DESCRIPTION PG1192 is a hybrid molecule with an inorganic silsequioxane at the core and precisely configured PEG and isobutyl groups attached at the corners of the cage. PG1192 provides an alternate to petrolatum and related waxes. PG1192 has a smooth feel and provides comfort to skin. COMPATIBILITY Water Insoluble Ethanol (95%) Soluble Hexane (aliphatics) Soluble Cosmetic Materials Mineral Oil Soluble Petrolatum Dispersable HANDLING PRECAUTIONS Product safety information requiredfor safe use is DC 556 [PhSi(OSiMe3)3] Dispersable not included in this doctunent. Before handling, read product and material safety data sheets and container labels for safe use, physical health and Shea Butter Dispersable hazard information. For material safety data information, contact Hybrid Plastics. Lanolin Soluble bred 55 W.L. RUNNELS INDUSTRIAL DR., HATTIESBURG, MS 39401 www.hybridplastics.com uistriumeu for uummem only uu nur are ut quuLu AP Consumer Product Testing Co. Pit'. 1117.5 FINAL REPORT CLIENT: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: TEST ARTICLE: EXPERIMENT REFERENCE NUMBER: Acute Oral Toxicity in Rats -- Limit Test 7sinbAil /Met-410n/ iy si/3 s c,o c..))ecte PG1192 POSS; Lot Number: 2015 224 EP T16-0183-5 Steven Nitka Vice President Laboratory Director This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, end neither the report nor the name of these Laboratories nor any member ofits stag may be used in connection with the advertising or sale ofany product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote ; l Or Consumer 11175 roduct Testing Co. QUALITY ASSURANCE UNIT STATEMENT Study No.: T16-0183-5 The objective of the Quality Assurance Unit (QAU) is to monitor thd conduct and. reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: Signature/Date 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Consumer Product Testing C NSI. 1975 Final Report Summary CLIENT: Hybrid Plastics, Inc. STUDY NO.: T16-0183-5 REFERENCE: Purchase Order No. 2016-005 TEST ARTICLE: PG1192 POSS; Lot Number: 2015 224 EP TEST ARTICLE RECEIPT DATE: ,January 14, 2016 EXPERIMENTAL INTERVAL: February 16, 2016 to April 20, 2016* Method: Results: Acute Oral Toxicity in Rats -- Limit Test Five (5) female, Sprague Dawley strain albino rats, 182 - 244 g, each received a single oral dose of the test article at a dose level of five (5) grams per kilogram body weight. The animals were dosed sequentially (see Page 4). Animals were observed for pharmacological activity and drug toxicity at least once during the first 30 minutes after dosing and then at 1, 3, 6 and 24 hours post-dosage, and daily thereafter for a total of 14 days. Interim body weights were recorded on day seven (7). All animals were subjected to gross necropsy, with all findings noted. The test article was dosed as received (Sp.g. = 1.10). LD50 > 5 g/kg Dose Level (g/kg) #/Sex No. E.T.**/No. Dosed No. Dead/No. Dosed Mortality (%) 5.00 1/F 1/1 5.00 2/F 2/2 5.00 1/F 1/1 5.00 1/F 0/1 0/1 0 1/2 50 1/1 100 0/1 0 Conclusion: According to OPPTS 870.1100, and under the conditions of this test, this test article has an oral LD50 greater than 5 grams per kilogram bodyweight. The toxic signs observed included foaming of the mouth, red discharge at snout, dehydration, slight depression and death. According to OPPTS 870.1000, and under the conditions of this test, this test article has an acute oral toxicity rating of Category IV (see page 6). *One (1) animal was dosed on February 11, 2016. The dosage was possibly misdirected and the animal was replaced. **Exhibiting toxic signs. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 - Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Consumer Product Testing Co. ILST iii75 FINAL REPORT CLIENT: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: TEST ARTICLE: Acute Dermal Irritation/Corrosion in Rabbits (OECD) 25d 6J4i I /NI e 4-1-)vxy PL Ca --/o Po lysi-)5 es 7vi o,cc c PG1192 POSS; Lot Number: 2015 224 EP EXPERIMENT REFERENCE NUMBER: T16-0183-4 ,t, 4,2cht, Steven Nitka Laboratory Director Vice President This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name ofthese Laboratories nor any member of iLs staff; may be used in connection with the advertising or sale ofany product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote 0.43 Consumer Product Testing Co. u175 QUALITY ASSURANCE UNIT STATEMENT Study No.: T16-0183-4 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: Signature/Date Lda at C 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Faxi Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote AXO Consumer roduct Testing C HI75 Final Report Summary CLIENT: Hybrid Plastics, Inc. STUDY NO.: T16-0183-4 REFERENCE: Purchase Order Number 2016-005 TEST ARTICLE: PG1192 POSS; Lot Number: 2015 224 EP TEST ARTICLE RECEIPT DATE: January 14, 2016 EXPERIMENTAL INTERVAL: February 2, 2016 to February 17, 2016 Method: Acute Dermal Irritation/Corrosion in Rabbits (OECD) One (1) New Zealand White rabbit received three (3) dermal applications of the test article. Each application was one-half of one (0.5) gram of the test article to an intact test site. The first test site was semi-occluded for three (3) minutes. The second test site was semi-occluded for one (1) hour. The third test site was semioccluded for four (4) hours. The sites were observed individually for erythema, edema, and other effects after patch removal through 14 days if irritation persisted. Because corrosive effects were not observed with the initial animal, two (2) additional animals were dosed. Each site on these animals was semioccluded for four (4) hours. The test article was moistened with distilled water upon dosing. Observations: Very slight to well defined, transient erythema was observed after dosing. No corrosive effects were observed. Conclusion: According to 49 CFR 173.137, OECD 404 and UN/SCEGHS/25/1NF.19 and under the conditions of this test, this test article is not corrosive to rabbit skin. According to UN/SCEGHS/24/1NF'.3/Add.1 (2012), the test article elicited minimal irritation and it would be considered "not classified". 70 New Dutch Lane Fairfield, New Jersey 07004-2514 - Faxi Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote I Personal Care Products Council Committed to Safety, Quality & Innovation Memorandum TO: Bart Heldreth, Ph.D., Interim Director COSMETIC INGREDIENT REVIEW (CIR) FROM: Beth A. Jonas, PhD. Industry Liaison to the CIR Expert Panel DATE: July 20, 2017 SUBJECT: Methacryloyloxypropyl Polysilsesquioxane Hybrid PIastics, Inc. 2017. Product information - MA0735 Methacryl POSS (MethacryIoyloxypropyl Polysilsesquioxane). Consumer Product Testing Co. 20I5. Acute oral toxicity in rats - limit test (Methacryloyloxypropyl Polysilsesquioxane). Consumer Product Testing Co. 20I4. Primary dermal irritation in rabbits (Methacryloyloxypropyl Polysilsesquioxane). Consumer Product Testing Co. 2017. Bacterial reverse mutation assay (Methacryloyloxypropyl PoIysilsesquioxane). Consumer Product Testing Co. 20I5. Bacterial revers mutation assay (Methacryloyloxypropyl Polysilsesquioxane). 1620 L Street, N.W., Suite 1200 Washington, D.C. 20036 202.331.17701 (fax) www.personalcarecouncii.org Distributed for comment only -- do not cite or quote c2o Product Information - MA0735 Methacryl POSS INCI NAME: Methacryloyloxypropyl Polysilsesquioxane FEATURES Clear, colorless liquid oil. c'-,.si o ' o\ cii I -------fl....,/----ci o ,\.,...,,(0-......n7sL---of--r-.......----.0 o-- \____\0 BENEFITS Enhances adhesion and strengthens coatings and gels while providing gloss and transfer resistance. Compatibilizer, rheological diluent and carrier of active ingredients. APPLICATIONS Adhesives and coatings that benefit from reduced shrinkage, water fastness, increased durability and gloss enhancement. DESCRIPTION MA0735 is a hybrid molecule with an inorganic silsequioxane at the core and organic methacrylate groups attached at the corners of the cage. MA0735 can provide fast UV stability, enhanced mechanical properties, excellent moisture resistance, increased adhesion and gloss. TYPICAL PROPERTIES COMPATIBILITY Appearance Clear colorless liquid oil Water Alcohols Not Soluble Viscosity (@2.5%) IS Poise Ethanol (95%) Soluble Density 1.20 g/mL Ethanol (70%) iPropanol (99%) Unstable Soluble Refractive Index 1.46 iPropanol (70%) Solvents & Propellants Soluble Formula Weight 1433.97 Hexane (aliphatics) PMGEA Unstable Soluble Resin Solubility acrylic, epoxy, urethane, olefin Cosmetic Materials REGULATORY STATUS INCI, REACH pending, TSCA, CAS 160185-24-0. Not a primary dermal irritant. Beeswax Mineral Oil Petrolatum 1,2 Propylene diol Stable Soluble Stable Not Soluble HANDLING PRECAUTIONS Product safety information required for safe use is not included in this document. Before handling, read product and material safety data sheets and container labels for safe use, physical health and hazard information. For material safety data information, contact Hybrid. Glycerin DC556 (PhSi(OSiMe3)3 Fluoralkyls Shea Butter Cocoa Butter Hydroxy Methylcellulose Lanolin Soluble Soluble Not Soluble Stable Stable Not Soluble Soluble Paraffin Wax Stable Caprylyl Glycol (I, 2 Octanediol) Not Soluble Cetearyl Alcohol (CI8OH) Soluble litnd Veggie Oil Soluble www.hybridplastics.com 55 W.L. RUNNELS INDUSTRIAL DR., HATTIESBURG, MS 39401 P: FAX: utstriumeu 101 001111110/11 oiiiy uu ttuLufle ut quut. 4,2,r Consumer Product Testing Co. 1...51. I:171 FINA1, REPORT CLIENT: - Hybrid Plastics, Inc. 55 J.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: Acute Oral Toxicity in Rats -- Limit Test e441 q cf. yieti o<-slio cop yi Pe I ys, I sc-570,.0 A-4 vie TEST ARTICLE: POSS MA0735 #2015 076 EP EXPERIMENT REFERENCE NUMBER: T15-2977-1 teven Nitka Vice President Laboratory Director This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name ofthese Laboratories nor any member ofits staff; may be used in connection with the advertising or sale of any product or process without written authorization, 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote ..v Consumer Product Testing Co. 1-N S: ItI75 QUALITY ASSURANCE UNIT STATEMENT Study No.: T15-2977-1 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: cs, Signature/Date 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology LJIJUIUULCU IUI I.UIIIIIICI IL utily UU I IUL une UI yuuLe Consumer Product Testing Co. 1 175 Final Report Summary CLIENT: Hybrid Plastics, Inc. STUDY NO.: T154977-1 REFERENCE: Purchase Order No. 2015-115 TEST ARTICLE: POSS MA0735 42015 076 EP MEA'frl (1Cr yI O Ki pi or,11 TEST ARTICLE RECEIPT DATE: June 16, 2015 EXPERIMENTAL INTERVAL: July 7, 2015 to July 24, 2015 Pct I?, 5, I 5c) To, o)Ca n e Method: Acute Oral Toxicity in Rats -- Limit Test Three (3) female, Sprague Dawley strain albino rats, 164 - 182 g, each received a single oral dose of the test article at a dose level of five (5) grams per kilogram body weight. Animals were observed for pharmacological activity and drug toxicity at least once during the first 30 minutes after dosing and then at 1, 3, 6 and 24 hours post-dosage, and daily thereafter for a total of 14 days. Interim body weights were recorded on day seven (7). All animals were subjected to gross necropsy, with all findings noted. The test article was used as received (Sp.g. = 1.20). Results: LD50 > 5 g/kg Dose Level (g/kg) 4/Sex 5.00 3/F No. E.T.*/No. Dosed No. Dead/No. Dosed Mortality (%) 0/3 0/3 Conclusion: According to OPPTS 870.1100, and under the conditions of this test, this test article has an oral LD50 greater than 5 grams per kilogram bodyvveight. All animals gained weight. According to OPPTS 870.1000, and under the conditions of this test, this test article has an acute oral toxicity rating of Category W (see page 6). *Exhibiting toxic signs. 70 New Dutch Lane Fairfield, New Jersey 07004-25I4 Fax Clinical Toxicology . Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote L/IblI ILJULCU IV! LAJI I II ' ICI IL Only UV I Itil UILC VI t_ILIULC . TConsumer F.S1 1!175 roduct Testing Co. FINAL REPORT CLIENT: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: Primary Dermal Irritation in Rabbits TEST ARTICLE: EXPERIMENT REFERENCE NUMBER: MA0735 - Methacryl POSS Cage Mixture; Lot Number: Project 2014 172EP M e 1-hcl cey lot/ ogytf"-vey Pdly s, I Stf-- 7U,ccan TI4-5007-5 Steven Nitka Vice President Laboratory Director This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name ofthese Laboratories nor any member of its staff, may be used in connection with the advertising or sale of any product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote Consumer Product Testing Co. F:ail. Inv QUALITY ASSURANCE UNIT STATEMENT Study No.: T14-5007-5 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable Standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director. Quality Assurance: Signature/Date 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Micro Distributed for comment only -- do not cite or quote Consumer ESE 11171 roduct Testing Co. Final Report Summary CLIENT: Hybrid Plastics, Inc. STUDY NO.: T14-5007-5 REFERENCE: 'Purchase Order No. 2014 131 TEST ARTICLE: MA0735 - Methacryl POSS Cage Mixture; Lot Number: Project 2014 172EP TEST ARTICLE RECEIPT DATE: October 21, 2014 EXPERIMENTAL INTERVAL: November 4, 2014 to November 7, 2014 Method: Primary Dermal Irritation in Rabbits Six (6) New Zealand White rabbits each received a single dermal application of onehalf of one (0.5) milliliter of the test article on each of two (2) test sites, one (1) abraded and one (1) non-abraded. The test sites were occluded for 24 hours and were observed individually for erythema, edema, and other effects 24 and 72 hours after application. Mean scores from the 24 and 72 hour readings were averaged to determine the primary irritation index. The test article was dosed as received. Results: Primary Irritation Index:* 0.55 Conclusion: According to Federal Hazardous Substances Act Regulations (16 CFR 1500.41), and, under the conditions of this test, this test article is not a primary dermal irritant. *Refer to Table 2 for specific evaluation. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 - Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Consumer Product Testing C , ' IT BACTERIAL REVERSE MUTATION ASSAY FINAL REPORT REPORT NUMBER: M17-1334 SPONSOR: Hybrid Plastics, inc. 55 W.L. Runnels industrial Drive Hattiesburg, MS 39401 SPONSOR'S REPRESENTATIVE: Michael Carr TESTING FACILITY: Consumer Product Testing Company, inc. 70 New Dutch Lane Fairfield NJ 07004 PH: Ext. 202 FX: Email: @cptclabs.com STUDY DIRECTOR: D. Keith Goins, Ph.D. Director, Microbiology STUDY INITIATION: April 3, 2017 STUDY COMPLETION: April 25, 2017 APPROVED: D. Keith Goins, Ph.D. Study Director REVIEWED BY: da./O&A) A/Ialka, Quality Assurance 61/2 Sj-zo Date Date This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed and neither the report nor the name of these laboratories nor any member of its staff, may be used in connection with the advertising or sale of any product or process without authorization 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Consumer roduct Testing Co. BACTERIAL REVERSE MUTATION ASSAY FINAL REPORT STUDY NUMBER: M15-3346 SPONSOR: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, MS 39401 SPONSOR'S REPRESENTATIVE: Joseph Liclitenhan, Ph.D. TESTING FACILITY: Consumer Product Testing Company, Inc. 70 New Dutch Lane Fairfield NJ 0 00 PH: Ext. 202 FX: Email: c tclabs.com STUDY DIRECTOR; D. Keith Gains, Ph.D. Director, Microbiology STUDY INITIATION DATE: July 6, 2015 STUDY COMPLETION DATE: July 16, 2015 REPORT PREPARED BY: D. Keith Goias, Ph.D. Director, Microbiology REPORT REVIEWED BY: LIZ& Pa--6utitzo Quality Assurance 401 I Fs' Date 01- He --/ Date This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name of these Laboratories nor any member of its staff, may be used in connection with the advertising or sale of any product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 - Fax Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote vistriouteu for comment only -- uo Hot 0110 or quote Personal Care Products Council Committed to Safety, Quality & Innovation Memorandum TO: Bart Heldreth, Ph.D., interim Director COSMETIC INGREDIENT REVIEW (C1R) FROM: Beth A. Jonas, Ph.D. Industry Liaison to the CIR Expert Panel DATE: July 20, 2017 SUBJECT: Isobutyl Polysilsesquioxane Hybrid Plastics, Inc. 2017. Product information - MS0825 OctaIsobutyl POSS (Isobutyl Polysi lsesquioxane). Consumer Product Testing Co. 2004. Acute oral toxicity in rats (Isobutyl Polysilsesquioxane). Consumer Product Testing Co. 20I4. Primary dermal irritation in rabbits (Isobutyl Polysi lsesquioxane). 1620 L Street, N.W., Suite 1200 Washington, D.C. 20036 202.331.17701 (fax) www.personalcarecouncil.org Distributed for comment only -- do not cite or quote Product Information - MS0825 Odalsobutyl POSSE INCI NAME: Isobutyl Polysilsesquioxane FEATURES White solid, organic soluble similar to PTFE. Aliphatics soluble- M50825/E anolwG 00 17 , 1/ \sto 01.4 APPLICATIONS PTFE-like lubricious effect without use of fluorinated chemicals in lotions and gels. SUGGESTED FORMULATION Eutanor G is especially efficient at swelling and dispersing MS0825. It renders the skin hydrated and extra smooth. Applications for Eutanolt G and MS0825 include foundation and skin-topowder primer. The suggested procedure is to high sheer mix 60'i. MS0825 with 40'4 Eutanor C and use as a coat formulation. This formulation renders the skin hydrated and extra smooth and soft. POSP MS0825 provides UVB sorption. BENEFITS Provides silky, low COF feel and can be solubilized for optical clarity. Provides soft focus and oil control. TYPICAL PROPERTIES Appearance White powder Surface Free Energy 17.1 mj/m2 Density 1.13 gfmL ' Refractive Index 1.47 Formula Weight 873.60 DESCRIPTION MS0825 is a hybrid molecule with an inorganic silsequioxane at the core and organic isobutyl groups attached at the corners of the cage. MS0825 is a white, crystalline powder. It is soluble in many organic solvents and most thermoplastic resins. COMPATIBILITY Water Not Soluble Alcohols Ethanol (95%) Dispersable Ethanol (70%) Dispersable iPropanol (99%) Dispersable iPropanol (70%) Dispersable Solubility solvents, most thermoplastic resins REGULATORY STATUS INCI, TSCA, R22, REACH pending Not a primary dermal irritant Solvents & Propellants Hexane (aliphatics) Cosmetic Materials Mineral Oil Petrolatum Mostly Soluble Soluble Soluble HANDLING PRECAUTIONS Product safety information requiredfor safe use is DC556 (PhSi(OSiMe3)3 Shea Butter Soluble Stable not included in this document. Before handling, read product and material safety data sheets and container labelsfor safe use, physical health and hazard information. For material safety data information, contact Hybrid. Cocoa Butter Lanolin Paraffin Wax Cetearyl Alcohol (Cl 8OH) Stable Dispersable Stable Soluble hybrid Eutanole G Stable Suspension www.hybridplastics.com 55 W.L. RUNNELS INDUSTRIAL DR., HATTIESBURG, MS 39401 P: FAX: 60I-545-3101 UlbLIIUULUU IUI GUIIIIIICIIL only uu nui une ut quuLe Consumer Product Testing Co. l'AT, 197t' FINAL REPORT CLIENT: Hybrid Plastics, Inc. 18237 Mt. Baldy Circle Fountain Valley, California 92708 ATTENTION: Carl Hagstrom Chief Operating Officer GUIDELINE: Health Effects Test Guidelines -- OPPTS 870.1.100 TEST: TEST ARTICLE: EXPERIMENT REFERENCE NUMBER: Acute Oral Toxicity in Rats Octalsobutyl-FOSS (MS0825), Lot#0403 Palysi lses 70 ,0 K oo, e T04-0027 Scott Krupa Quality Assurance Su sor Steven Nitka Laboratory Director Vice President Page 1 of 13 This report Is submitted for the exclusive use of the person, partnership, or corporation to whom Z Is addressed, and neither the report nor the name of those Laboratories nor any member of its staff, may be used In connection with the advertising or sae of any product or process without written authorization, 70 New Dutch Lane Fairfield, New Jersey 07004-2514 {973) 808-7 Fax Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Consumer Product Testing Co. IS 1: 07r, QUALITY ASSURANCE UNIT STATEMENT Study No.: T04-0027 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of non clinical laboratories studies. These studies have been performed under Good Laboratory Practice regulations (40 CFR 160 and 40 CFR 792) and in accordance to standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study on the date(s) listed below. Studies are inspected at time intervals to assure the integrity of the study. The findings of these inspections have been reported to management and Study Director on the dates listed below. All materials and data pertinent to this study will be stored in the Archives Facility, at 70 New Dutch Lane, Fairfield, New Jersey, unless specified otherwise, in writing, by the sponsor. Dates of biophase: March 16, 2004, March 23, 2004, March 30, 2004, April 8, 2004 Dates of data inspection: April 26, 2004 Professional personnel involved: Steven Nitka, B.S. Lillian Vasquez, B.S. Melissa Pandorf, B.S. Scott Krupa V.P./Laboratory Director (Study Director) Laboratory Supervisor Technician Quality Assurance Supervisor The representative signature of the Quality Assurance Unit on the front page signifies that this study has been performed in accordance with standard operating procedures, study protocols, and the Good Laboratory Practice principles. Page 3 of 13 70 New Dutch Lane Fairfield, New Jersey 07004.2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Consumer Product Testing Co. EST. Final Report Summary CLIENT: Hybrid Plastics, Inc. STUDY NO.: T04-0027 REFERENCE: C. Hagstrom TEST ARTICLE: Octalsobutyl-POSS (MS0825), Lot#0403 TEST ARTICLE RECEIPT DATE: February 27, 2004 EXPERIMENTAL INTERVAL: (males) March 16, 2004 to March 30, 2004 (females) March 30, 2004 to April 13, 2004 Acute Oral Toxicity in Rats - Limit Test Method: Ten (5M:5F) albino rats, 212 - 240 g, each received a single oral dose of the test article at a dose level of five (5) grams per kilogram body weight. Animals were observed for pharmacological activity and drug toxicity I, 3, 6, and 24 hours after treatment, and daily thereafter for a total of I4 days. Interim body weights were recorded on day seven (7). All animals were subjected to gross necropsy, with all findings noted. The test article was used as a 12.5% suspension in corn oil. Results: LD50 > 5.0 g/kg Dose Level (g/kg) Sex 5.00 5M:5F No. E.T.*/No. Dosed No. Dead/No. Dosed (M:F) (M:F) 5/5:5/5 0/5:0/5 Mortality 0 Conclusion: According to the United States Environmental Protection Agency, Office of Prevention, Pesticides, and Toxic Substances Harmonized Test Guidelines (Series 870 Health Effects, Volume I of III, Guidelines OPPTS 870.1000 - OPPTS 870.4300, August 1998) and under the conditions of this test, this test article is an acute oral toxicity Category IV material. See Table I for details. *Exhibiting toxic signs. Toxic signs observed were mucoid diarrhea and moist, matted and unkempt hair. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote LJ1J1.1 11,JULCU IV! LAJI I II ' ICI IL Only UV I Itil UILC VI I~UVLC 43 Consumer Product Testing Co. 'S I. tctT5 FINAL REPORT CLIENT: Hybrid Plastics, Inc. 55 W.L. Runnels Industrial Drive Hattiesburg, Mississippi 39401 ATTENTION: Joseph Lichtenhan, Ph.D. TEST: Primary Dermal Irritation in Rabbits TEST ARTICLE: ~sabJ4y1 EXPERIMENT REFERENCE NUMBER: MS0825 - Octalsobutyl POSS; Lot Number: Project 2014 172EP Po lysi lse5 4.) o?cav e T14-5007-6 O.141(4 Steven Nitka Vice President Laboratory Director This report is submitted for the exclusive use of the person, partnership, or corporation to whom it is addressed, and neither the report nor the name of these Laboratories nor any member of its staff, may be used in connection with the advertising or sale of any product or process without written authorization. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Distributed for comment only -- do not cite or quote 'TA Consumer Product Testing Co. R.60: 1075 QUALITY ASSURANCE UNIT STATEMENT Study No.: T14-5007-6 The objective of the Quality Assurance Unit (QAU) is to monitor the conduct and reporting of nonclinical laboratory studies. This study has been performed in accordance with standard operating procedures and applicable standard protocols. The QAU maintains copies of study protocols and standard operating procedures and has inspected this study. The findings of this inspection may have been reported to management and the Study Director, Quality Assurance: a ct-c4 1 Signature/Date i4q cf 70 New Dutch Lane Fairfield, New Jersey 07004-25I4 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote :IA Consumer roduct Testing Co. Final Report Summary CLIENT: Hybrid PIastics, Inc. STUDY NO.: T14-5007-6 REFERENCE: Purchase Order No, 2014 131 TEST ARTICLE: MS0825 - Octalsobutyl POSS; Lot Number: Project 2014 172EP TEST ARTICLE RECEIPT DATE: October 21, 2014 EXPERIMENTAL INTERVAL: November 4, 2014 to November 7, 2014 Method: Primary Dermal Irritation in Rabbits Six (6) New Zealand White rabbits each received a single dermal application of onehalf of one (0.5) gram of the test article on each of two (2) test sites, one (1) abraded and one (1) non-abraded. The test sites were occluded for 24 hours and were observed individually for erythema, edema, and other effects 24 and 72 hours after application. Mean scores from the 24 and 72 hour readings were averaged to determine the primary irritation index. The test article was moistened with saline upon dosing. Results: Primary Irritation Index:* 0.05 Conclusion: According to Federal Hazardous Substances Act Regulations (16 CFR 1500.41), and under the conditions of this test, this test article is not a primary dermal irritant. *Refer to Table 2 for specific evaluation. 70 New Dutch Lane Fairfield, New Jersey 07004-2514 Fax Clinical Toxicology Analytical Chemistry Microbiology Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Memorandum TO: Bart Heldreth, Ph.D., Interim Director COSMETIC INGREDIENT REVIEW (CIR) FROM: Beth A. Jonas, Ph.D. Industry Liaison to the CIR Expert Panel DATE: July 6, 2017 SUBJECT: Concentration of Use by FDA Product Category: Trimethylpentyl Polysilsesquioxane, Isobutyl/Methoxy PEG-10 Polysilsesquioxane and Methoxy PEG-10 Polysilsesquioxane Trimethylpentyl Polysilsesquioxane, Isobutyl/Methoxy PEG-10 Polysilsesquioxane and Methoxy PEG-10 Polysilsesquioxane were included in the May 2017 concentration of use survey. No uses of these three ingredients were reported. Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote Distributed for comment only -- do not cite or quote I Personal Care Products Council Committed to Safety, Quality & Innovation Memorandum TO: Bart Heldreth, Ph.D., Interim Director COSMETIC INGREDIENT REVIEW (CIR) FROM: Beth A. Jonas, Ph.D. Industry Liaison to the CIR Expert Panel DATE: June 28, 2017 SUBJECT: Tentative Report: Safety Assessment of Polysilsesquioxanes as Used in Cosmetics Short-Term Toxicity Studies - Please correct "day 28 days" Dermal and Ocular Irritation - As the cell-culture systems are studied to determine if there is an effect from chemical exposure, it should state that the culture system was exposed to the ingredient (rather than e.g., "Polymethylsilisesquioxane was exposed to reconstructed human epidermis"). Ocular Irritation - Please correct "keratonocytes" Summary - Please correct "conducted and in accordance with..." Discussion - As the form of powder is not included in the concentration of use survey, please delete the word "loose". All that is known is that some products are powders. 1620 L Street, N.W., Suite 1200 Washngton, D.C. 20036 I 202.331.17701 (fax) www.personalcarecouncilorg