Announcement. March 25, Cosmetic Ingredient Review Expert Panel 126 th Meeting (March 18-19, 2013) - Findings

Transcription

1 March 25, 2013 Csmetic Ingredient Review Expert Panel 126 th Meeting (March 18-19, 2013) - Findings Final Safety Assessments Alkyl esters 237 ingredients Alkyl ethylhexanates 16 ingredients 6-Hydrxyindle 1 ingredient Mdified terephthalate plymers 6 ingredients Nyln plymers - 8 ingredients Talc 1 ingredient Tentative Safety Assessments Animal- and plant-derived amin acids 21 ingredients Brn nitride 1 ingredient Methyl glucse plyethers & esters 25 ingredients Nitrcellulse 2 ingredients Re-review and New Data HC range n. 1 nt repened HC yellw n. 4 nt repened Hydrquinne and p-hydrxyanisle - repened Methylisthiazlinne - repened 126 th Meeting Ntes Directr s reprt Reprts tabled Animal- and plant-derived hydrlyzed prteins Hypericum perfratum-derived ingredients Palmityl ligpeptides Trmethamine Draft 2014 ingredient review pririties cmments sught Scientific literature reviews psted n the CIR website Re-reviews fr the next Panel meeting Scientific Literature Reviews under develpment Next CIR Expert Panel Meeting Mnday and Tuesday, June 10-11, 2013 Annuncement Csmetic Ingredient Review th Street, NW, Suite 412, Washingtn, DC ph fax cirinf@cir-safety.rg

2 Final Safety Assessments Any interested persn wh believes that a final safety assessment r final amended safety assessment is incrrect may petitin the CIR Expert Panel t amend the safety assessment. Unpublished data cited as references in CIR safety assessments are psted n the CIR website and available fr review at the CIR ffice. Final safety assessments and final amended safety assessments will be psted n the CIR website at Alkyl Esters The 237 alkyl esters listed belw are safe as csmetic ingredients in the present practices f use and cncentratin described in the safety assessment when frmulated t be nn-irritating. arachidyl behenate arachidyl erucate* arachidyl prpinate batyl isstearate* batyl stearate* behenyl beeswax behenyl behenate behenyl erucate behenyl isstearate* behenyl livate behenyl/isstearyl beeswax* butyl avcadate butyl babassuate* butyl isstearate* butyl myristate butyl leate* butyl stearate butylctyl beeswax* butylctyl behenate* butylctyl candelillate* butylctyl cetearate* butylctyl leate* butylctyl palmitate* C10-40 isalkyl acid ctylddecanl esters* C14-30 alkyl beeswax* C16-36 alkyl stearate* C18-38 alkyl beeswax* C18-38 alkyl c24-54 acid ester* C20-40 alkyl behenate* C20-40 alkyl stearate C30-50 alkyl beeswax* C30-50 alkyl stearate* c32-36 isalkyl stearate* C40-60 alkyl stearate* C4-5 isalkyl ccate* caprylyl butyrate* caprylyl caprylate caprylyl eicsenate cetearyl behenate cetearyl candelillate cetearyl isnnanate cetearyl nnanate* cetearyl livate cetearyl palmate* cetearyl palmitate* cetearyl rice branate* cetearyl stearate cetyl babassuate cetyl behenate* cetyl caprate cetyl caprylate cetyl dimethylctanate* cetyl esters cetyl isnnanate* cetyl laurate cetyl myristate cetyl myristleate* cetyl leate* cetyl palmitate cetyl ricinleate cetyl stearate cetyl tallwate chimyl isstearate* chimyl stearate* cc-caprylate cc-caprylate/caprate cc-rapeseedate* decyl castrate* decyl ccate decyl isstearate* decyl jjbate* decyl laurate* decyl myristate* decyl leate decyl livate decyl palmitate* decyltetradecyl cetearate* erucyl arachidate* erucyl erucate* erucyl leate* ethylhexyl adipate/palmitate/stearate* ethylhexyl C10-40 isalkyl acidate* ethylhexyl ccate ethylhexyl hydrxystearate ethylhexyl isnnanate ethylhexyl ispalmitate ethylhexyl isstearate ethylhexyl laurate ethylhexyl myristate ethylhexyl nepentanate* ethylhexyl leate* ethylhexyl livate ethylhexyl palmitate ethylhexyl pelargnate ethylhexyl stearate heptyl undecylenate heptylundecyl hydrxystearate hexyl isstearate hexyl laurate hexyldecyl hexyldecanate* hexyldecyl isstearate hexyldecyl laurate hexyldecyl leate* hexyldecyl palmitate* hexyldecyl stearate hexylddecyl/ctyldecyl hydrxystearate* hydrgenated castr il behenyl esters* hydrgenated castr il cetyl esters * hydrgenated castr il stearyl esters* hydrgenated ethylhexyl livate hydrgenated ethylhexyl sesamate* hydrgenated iscetyl livate* hydrgenated isprpyl jjbate* hydrxycetyl isstearate* hydrxyctacsanyl hydrxystearate isamyl laurate isbutyl myristate* isbutyl palmitate* isbutyl perlargnate* isbutyl stearate* isbutyl tallwate* iscetyl behenate* iscetyl isdecanate* iscetyl isstearate* iscetyl laurate* iscetyl myristate iscetyl palmitate iscetyl stearate isdecyl ccate isdecyl hydrxystearate* isdecyl isnnanate isdecyl laurate isdecyl myristate isdecyl nepentanate isdecyl leate isdecyl palmitate* isdecyl stearate* ishexyl caprate ishexyl laurate* ishexyl nepentanate* ishexyl palmitate* islauryl behenate* isnnyl isnnanate isctyl caprylate/caprate* isctyl tallate* isprpyl isstearate isprpyl arachidate* isprpyl avcadate* isprpyl babassuate* isprpyl behenate* isprpyl hydrxystearate isprpyl isstearate isprpyl jjbate isprpyl laurate* isprpyl linleate isprpyl myristate isprpyl leate* isprpyl palmitate isprpyl ricinleate isprpyl stearate isprpyl tallwate* isstearyl avcadate isstearyl behenate isstearyl erucate* isstearyl hydrxystearate isstearyl isnnanate isstearyl isstearate isstearyl laurate isstearyl linleate isstearyl myristate isstearyl nepentanate isstearyl palmitate istridecyl isnnanate istridecyl laurate* istridecyl myristate* istridecyl stearate lauryl behenate* lauryl ccate* lauryl isstearate* lauryl laurate lauryl myristate* lauryl leate/ lauryl palmitate lauryl stearate/ lignceryl erucate* myristyl isstearate* myristyl laurate

3 myristyl myristate myristyl nepentanate myristyl stearate ctyldecyl leate* ctylddecyl avcadate* ctylddecyl beeswax* ctylddecyl behenate* ctylddecyl ccate* ctylddecyl erucate ctylddecyl hydrxystearate* ctylddecyl isstearate ctylddecyl meadwfamate* ctylddecyl myristate ctylddecyl nedecanate* ctylddecyl nepentanate ctylddecyl ctylddecanate ctylddecyl leate* ctylddecyl livate ctylddecyl ricinleate ctylddecyl safflwerate* ctylddecyl stearate leyl arachidate* leyl erucate leyl linleate leyl myristate* leyl leate leyl stearate* prpylheptyl caprylate stearyl beeswax stearyl behenate* stearyl caprylate stearyl erucate* stearyl heptanate stearyl linleate* stearyl livate stearyl palmitate stearyl stearate tetradecyleicsyl stearate* tetradecylctadecyl behenate* tetradecylctadecyl hexyldecanate* tetradecylctadecyl myristate* tetradecylctadecyl stearate tetradecylprpinates* tridecyl behenate* tridecyl ccate* tridecyl erucate* tridecyl isnnanate tridecyl laurate* tridecyl myristate* tridecyl nepentanate tridecyl stearate *Nt reprted t be in current use. Were ingredients in this grup nt in current use t be used in the future, the expectatin is that they wuld be used in prduct categries and at cncentratins cmparable t thers in this grup. Alkyl esters is the name that CIR devised t describe this large grup f csmetic ingredients, which are reactin prducts f fatty acids and alchls. Althugh there are data gaps in this reprt, the relatedness f mlecular structures, physicchemical prperties, and functins and cncentratins in csmetics allw gruping these ingredients tgether and extraplating the txiclgical data t supprt the safety f the entire grup. The data n many f the ingredients, especially the previusly reviewed ingredients and n sme f the cnstituent alchls and acids, are sufficient, and similar structure-prperty relatinships, bilgic characteristics, and csmetic prduct usage suggest that the data may be extraplated t supprt the safety f the entire grup. One ingredient riginally included in this safety assessment, isprpyl srbate, was remved because it differs in functin and chemical structure frm the ther ingredients in this grup. The Panel recgnized that sme f these ingredients can enhance the penetratin f ther ingredients thrugh the skin and cautined that care shuld be taken in frmulating csmetic prducts that cntain these ingredients in cmbinatin with any ingredients the safety f which was based n their lack f dermal absrptin, r when dermal absrptin was a cncern. The Panel als recgnized that the ptential exists fr dermal irritatin with the use f prducts frmulated with sme f the alkyl esters. Therefre, the Panel specified that prducts using these ingredients must be frmulated t be nn-irritating. Alkyl Ethylhexanates The 16 alkyl ethylhexanates listed belw are safe as csmetic ingredients in the present practices f use and cncentratin described in this safety assessment when frmulated t be nn-irritating. C12-13 alkyl ethylhexanate C12-15 alkyl ethylhexanate C14-18 alkyl ethylhexanate* cetearyl ethylhexanate cetyl ethylhexanate decyltetradecyl ethylhexanate* ethylhexyl ethylhexanate hexyldecyl ethylhexanate* iscetyl ethylhexanate isdecyl ethylhexanate* isstearyl ethylhexanate* lauryl ethylhexanate* myristyl ethylhexanate* ctylddecyl ethylhexanate* stearyl ethylhexanate tridecyl ethylhexanate *Nt reprted t be in current use. Were ingredients in this grup nt in current use t be used in the future, the expectatin is that they wuld be used in prduct categries and at cncentratins cmparable t thers in this grup. A cmmn cncern addressed in the review f the safety f alkyl ethylhexanates was that 2-ethylhexanic acid, a pssible metablite, is a liver and develpmental txicant in animal studies at high dses. The mechanism is attributed t a cascade f effects that includes metallthinein (MT) inductin fllwed by zinc accumulatin in the liver due t MT binding, and a cnsequent zinc deficiency in the develping embry. The Panel determined that results f testing with di-2-ethylhexyl terephthalate (a 2- ethylhexanic acid precursr used as a mdel fr ethylhexanic acid expsures that d nt induce MT in the liver) suggested that the lw rate f metablic cnversin f di- 2-ethylhexyl terephthalate fllws a time curse that allws clearance f the 2-ethylhexanic acid metablite befre sufficient levels can arise t prduce zinc deficiency. The Panel cncluded that the lw rate f metablism f alkyl ethylhexanate cmpunds that culd be absrbed thrugh the skin wuld nt generate 2-ethylhexanic acid at levels sufficient t trigger the MT-inductin-dependent effects bserved in animal studies. The Panel cnsidered that the ratinale described abve applied t the entire grup f alkyl ethylhexanates. Additinally, the similar chemical structures, physicchemical prperties, functins, and cncentratins in csmetics allw interplatin f the available txiclgical data t supprt the safety f the entire grup. 6-Hydrxyindle 6-Hydrxyindle is safe as a hair dye ingredient in the present practices f use and cncentratin. The Panel expressed cncern that 6-hydrxyindle appears t be a phtsensitizer at a cncentratin f 5%. Data, hwever, did nt indicate phtsensitizatin at 2%. The Panel nted that this ingredient has 104 uses in hair dye prducts at cncentratins up t 0.5%. The Panel recgnized that 6-hydrxyindle is cnsidered a cal tar hair dye. Accrdingly, prducts cntaining this ingredient are exempt frm certain adulteratin and clr additive prvisins f the Federal Fd, Drug, and Csmetic Act, when the prduct label bears a cautin statement and patch test instructins fr determining whether the prduct causes skin irritatin. The Panel cnsidered cncerns abut such selftesting, but agreed that fllwing this prcedure enables cnsumers t determine, prspectively, whether they will have an irritatin/sensitizatin reactin, and allw them t avid subsequent significant expsures. In the future, the Panel will cnsider the results f nging studies by the industry t evaluate the risks and benefits f cnsumer self-testing.

4 Mdified terephthalate plymers The 6 mdified terephthalate plymers listed belw are safe fr use in csmetics in the present practices f use and cncentratin. adipic acid/1,4 butanedil/terephthalate cplymer* plybutylene terephthalate plyethylene isterephthalate plyethylene terephthalate plypentaerythrityl terephthalate* plyprpylene terephthalate *Nt reprted t be in current use. Were ingredients in this grup nt in current use t be used in the future, the expectatin is that they wuld be used in prduct categries and at cncentratins cmparable t thers in this grup. These ingredients mstly functin as exfliants, bulking agents, hair fixatives, and viscsity increasing agents-nnaqueus. Plyethylene terephthalate (PET) is used in leave-n prducts up t 100%. The Panel cnsidered the presence f a phthalate miety in these ingredients. Terephthalates incrprate a para-phthalate ismer. This is different frm the rth-phthalate esters (cmmn plasticizers such as di(2-ethylhexyl)phthalate (DEHP)) that have been cnsidered as ptential endcrine disruptrs. Given the nature f the terephthalates used in csmetics, there wuld nt be any significant rth-phthalate impurities in these terephthalate plastics, and n reasn that rth-phthalate esters wuld be added t them as sfteners during manufacturing. The data indicate the absence f endcrine disruptin assciated with mdified terephthalate plymers as used in csmetics. The lack f case reprts, alng with several use tests f eye prducts cntaining mdified terephthalate plymers up t 46%, led the Panel t cnclude that cular injury frm these prducts is unlikely. Nyln Plymers The 8 nyln plymers listed belw are safe in the present practices f use and cncentratin in csmetics. nyln-6 nyln-11 nyln-10/10* nyln-12 nyln 6/12 nyln-66 nyln-611* nyln-12/6/66* *Nt reprted t be in current use. Were ingredients in this grup nt reprted t be in current use t be used in the future, the expectatin is that they wuld be used in prduct categries and at cncentratins cmparable t thers in this grup. The Panel cnsidered that unpublished data submitted by the Cuncil supprted the cnclusin that nyln ingredients in csmetics wuld nt cause irritatin r sensitizatin. The Panel reviewed human repeat insult patch test data n nyln-12 at its maximum use cncentratin f 35%. N sensitizatin r irritatin was bserved in this study. Likewise, in vitr studies f nyln, as used in csmetics, fund n evidence f gentxicity. Frm these data, the Panel determined that residual mnmers in nyln-12 were nt present, r nt released, at cncentratins sufficient t cause dermal reactins in subjects tested at the maximum use cncentratin. Talc Talc is safe in the present practices f use and cncentratin in csmetics. The Panel warned that talc shuld nt t be used n skin where the epidermal barrier is remved r n skin that has greater than 1st degree burns, because case reprts indicate that granulmas frmed when talc was applied t skin where the epidermal barrier was nt intact. The Panel received dcumentatin frm industry f the analytical methds used t cnfirm the purity f talc, particularly the absence f asbests, quartz and ther inrganic substances. The Panel als reviewed representative certificates f analysis f talc frm tw suppliers. Taken tgether, the infrmatin prvided sufficient evidence f cmpliance with the 1976 csmetics industry specificatin that talc used in csmetic prducts is free f asbestifrm fibers. Tentative Safety Assessments These tentative safety assessments will be psted n the CIR website at n r befre March 29, Interested persns are given 60 days t cmment, prvide infrmatin and/r request an ral hearing befre the CIR Expert Panel. Infrmatin may be submitted withut identifying the surce r the trade name f the csmetic prduct cntaining the ingredient. All unpublished data submitted t CIR will be discussed in pen meetings, psted n the CIR website, and are available at the CIR ffice fr review by any interested party. Please submit data and/r cmments t CIR by May 10, 2013, r sner if pssible. These reprts may be scheduled fr review by the CIR Expert Panel at its June 10-11, 2013 meeting. Animal- and plant-derived amin acids The Panel issued a tentative safety assessment fr public cmment fr the 21 animal- and plant-derived amin acids ingredients listed belw with the cnclusin that they are safe in the present practices f use and cncentratin as described in the safety assessment. aprict kernel amin acids* cllagen amin acids crn gluten amin acids* elastin amin acids* garcinia mangstana amin acids* hair keratin amin acids jjba amin acids* keratin amin acids lupine amin acids lycium barbarum amin acids* milk amin acids at amin acids rice amin acids sesame amin acids* silk amin acids sy amin acids spirulina amin acids* sweet almnd amin acids* vegetable amin acids wheat amin acids yeast amin acids* *Nt reprted t be in current use. Were ingredients in this grup nt reprted t be in current use t be used in the future, the expectatin is that they wuld be used in prduct categries and at cncentratins cmparable t thers in this grup.

5 The abve ingredients had been included in a safety assessment that als included plant- and animal-derived hydrlyzed prteins, but the Panel segregated the amin-acid grup and tabled the hydrlyzed-prtein grup (see 126 th meeting ntes). The Panel expressed cncern abut the lack f infrmatin regarding methd f manufacturing and impurities that may be present in these amin acids derived frm plant and animal surces. The Panel cnsidered that vigrus acid hydrlysis wuld yield amin acids with little r n residual peptides, because such acid hydrlysis attacks all f the peptide bnds in a prtein in a nn-preferential manner. The Panel was cncerned that enzymatic hydrlysis f prteins can disrupt the peptide bnds in a prtein in a site-specific manner, and may prduce di-, tri- r ther peptides, as well as amin acids. Such residual impurities may have the ptential t cause allergic reactins in sensitive individuals. Input was sught n the usual methds used t prduce amin acids frm animal and plant prteins. If the methdlgy invlves rigrus acid hydrlysis, there is less cncern that residual small peptides will be present. In any case, the Panel wuld emphasize that industry shuld manufacture plant- and animalderived amin acids in a way that ensures that residual peptides culd nt cause allergic reactins in sensitive individuals. Brn Nitride The Panel issued a tentative safety assessment fr public cmment with the cnclusin that brn nitride is safe in the present practices f use and cncentratin. The Panel remarked, hwever, that irritatin and sensitizatin data were nt prvided frm tests f the maximum reprted use cncentratin (25%) in eye frmulatins. Because human repeat insult patch test (HRIPT) data were available fr 18.7% in frmulatin, the Panel determined that the data culd be cnsidered adequate, althugh HRIPT data frm tests using up t the 25% maximum wuld be preferable. Further, the available HRIPT study tested nly 55 subjects. Thus, additinal HRIPT data wuld greatly imprve the basis fr the Panel s cnclusin. The Panel als nted that, althugh there are data gaps, this ingredient is an insluble plymer that is nt expected t penetrate the skin and, even if it did, it wuld nt be expected t cause adverse effects. Althugh nanparticles f brn nitride are nt reprted t be used in csmetic frmulatins, the lack f txicity bserved in a single-dse intravenus study f brn nitride nantubes supprts the safety f the ther frms f brn nitride that are used in csmetics. The discussin f the physical/chemical frm(s) f brn nitride that are used in csmetics indicated that further chemical characterizatin data culd clarify their chemical structures and strengthen the safety assessment. Methyl Glucse Plyethers and Esters The Panel issued a revised tentative safety assessment fr public cmment with a cnclusin that the 25 methyl glucse plyethers and esters listed belw are safe as used in csmetics in the present practices f use and cncentratin, except that the available data are insufficient fr evaluating the safety f methyl glucse sesquistearate and PEG- 20 methyl glucse sesquistearate in lipsticks. Ethers: Plyethers Esters and plyethers: methyl glucse caprylate/caprate* PPG-10 methyl glucse ether PEG-120 methyl glucse dileate methyl glucse dileate PPG-20 methyl glucse ether PEG-20 methyl glucse distearate methyl glucse isstearate* PPG-25 methyl glucse ether* PEG-80 methyl glucse laurate* methyl glucse laurate* PPG-20 methyl glucse ether acetate* PEG-20 methyl glucse sesquicaprylate/ sesquicaprate* methyl glucse sesquicaprylate/ sesquicaprate* PPG-20 methyl glucse ether distearate PEG-20 methyl glucse sesquilaurate* methyl glucse sesquiccate* methyl gluceth-10 PEG-20 methyl glucse sesquistearate methyl glucse sesquiisstearate methyl gluceth-20 PEG-120 methyl glucse triisstearate* methyl glucse sesquilaurate* PEG-120 methyl glucse trileate methyl glucse sesquileate methyl glucse sesquistearate *Nt reprted t be in current use. Were ingredients in this grup nt reprted t be in current use t be used in the future, the expectatin is that they wuld be used in prduct categries and at cncentratins cmparable t thers in this grup. As previusly issued, the tentative reprt n these ingredients indicated that the plyether frm f these methyl glucse ingredients reprtedly functin as skin and hair cnditining agents, whereas the methyl glucse esters and the ester/plyether frms functin nly as skin cnditining agents in csmetic prducts. Uses f three ingredients in lipsticks raised the cncern abut repeated ingestin as a rute f expsure that Panel had nt previusly cnsidered. There was, hwever, sme cnfusin regarding use f these ingredients in lipsticks. Infrmatin frm FDA s 2013 VCRP database indicated uses f methyl glucse sesquistearate and PEG-20 methyl glucse sesquistearate in lipsticks. Use cncentratin data were supplied by the Persnal Care Prducts Cuncil fr methyl glucse sesquistearate and PEG-20 methyl glucse distearate (nt reprted in the VCRP) in lipsticks, but n use cncentratin data were available fr PEG-20 methyl glucse sesquistearate. The absence f use cncentratin data fr PEG-20 methyl glucse sesquistearate in lipsticks was particularly cncerning because n systemic txicity data sufficient t supprt the safety f uses in lipsticks were available. Until such infrmatin is available, the Panel determined that the data are insufficient fr evaluating the safety f these methyl glucse plyethers and esters in lipsticks. Use cncentratin data are needed fr PEG-20 methyl glucse sesquistearate in lipsticks (r a determinatin that this ingredient is nt actually used in lipsticks). Regardless, tw ingredients clearly are used in lipsticks and, s that the Panel can assess the risks f ingestin, adequate repeated-dse ral txicity data r ther apprpriate systemic txicity data are needed. Nitrcellulse The CIR Expert Panel issued a tentative safety assessment fr public cmment with the cnclusin that nitrcellulse and clldin are safe in the present practices f use and cncentratin. The Panel debated the need t include clldin in this reprt. While nitrcellulse is widely used in nail plish and nail enamel, basecat, and undercat frmulatins, n uses f clldin appeared in the VCRP data. It is presumed, hwever, that there is at least ne use f clldin, because a maximum cncentratin f use in a nail prduct was reprted in respnse t a survey cnducted by the Persnal Care Prducts Cuncil. The Panel cnsidered, therefre, that the tentative reprt can address clldin as well as nitrcellulse.

6 Clldin is listed in the Internatinal Csmetic Ingredient Dictinary and Handbk as a csmetic ingredient. Based n its definitin, hwever, it appeared t the Panel that clldin is a slutin f nitrcellulse, ethanl, and ether, which culd be termed a trade name mixture rather than a distinct ingredient. Accrdingly, the Panel remved the wrd clldin frm the reprt title. If the Panel is crrect that clldin is simply nitrcellulse in a vlatile vehicle, then data supprting the stability f nitrcellulse in that matrix wuld be useful. If clldin is the de nv prduct f a manufacturing prcess, rather than the prduct f simply disslving nitrcellulse in ethanl and ether, then data n that methd f manufacture wuld be essential; Otherwise, clldin culd be mitted frm the cnclusin, r require an insufficient data annuncement. The Expert Panel did nte that sensitizatin testing was cnducted using a cncentratin that was less than the maximum reprted use cncentratin. Because mst use is in nail care prducts, significant expsure t the skin wuld be minimized, s that these data likely are adequate. Als, the high mlecular weight and chemical prperties preclude significant absrptin f this nail frmulatin ingredient. Re-review and New Data HC range n. 1 nt repened The Panel reaffirmed the riginal cnclusin that HC range n. 1 is safe as a hair dye ingredient at cncentratins 3%. The Panel reviewed the evaluatin f this hair clr ingredient in Eurpe and nted n new safety issues. The cncentratin f use fr this hair dye has increased frm 0.15% t 0.55%, but the use cncentratin is still well belw the maximum cncentratin f 3% supprted by the available data. The Panel recgnized that HC range n.1 can be cnsidered a cal tar hair dye. Accrdingly, prducts cntaining this ingredient are exempt frm certain adulteratin and clr additive prvisins f the Federal Fd, Drug, and Csmetic Act, when the prduct label bears a cautin statement and patch test instructins fr determining whether the prduct causes skin irritatin. The Panel has cnsidered cncerns abut such self-testing, but agreed that fllwing this prcedure enables cnsumers t determine, prspectively, whether they will have an irritatin/sensitizatin reactin, and allw them t avid subsequent significant expsures. In the future, the Panel will cnsider the results f nging studies by the industry t evaluate the risks and benefits f cnsumer self-testing HC yellw n. 4 nt repened The Panel reaffirmed the riginal cnclusin that HC yellw n.4 is safe fr use in hair dyes in the present practices f use and cncentratin. The Panel reviewed the evaluatin f this hair clr ingredient in Eurpe and nted that this clr culd be subject t n-nitrsatin t frm ptentially carcingenic reactin prducts. Accrdingly, the Panel cautined frmulatrs that HC yellw n. 4 shuld nt be used in frmulatins where N-nitrs cmpunds may be frmed. The Panel als cnsidered new studies examining reprductive utcmes in rats dsed with HC yellw n.4. While there was sme evidence f reprductive txicity in these studies using rats, all were ral txicity studies using high cncentratins, and the findings are nt relevant t csmetics uses. HC yellw n.4 is nt expected t penetrate the skin in hair clring usage, s n systemic expsure wuld ccur, and reprted use cncentratin fr csmetics are nly 0.75%. These new reprductive txicity data, therefre, d nt suggest a cncern fr use f HC yellw n.4 in hair clring. New data shwing an absence f sensitizatin ptential at cncentratins up t 10% added supprt that the riginal safety cnclusin was crrect. The Panel recgnized that HC yellw n. 4 can be cnsidered a cal tar hair dye. Accrdingly, prducts cntaining this ingredient are exempt frm certain adulteratin and clr additive prvisins f the Federal Fd, Drug, and Csmetic Act, when the prduct label bears a cautin statement and patch test instructins fr determining whether the prduct causes skin irritatin. The Panel has cnsidered cncerns abut such self-testing, but agreed that fllwing this prcedure enables cnsumers t determine, prspectively, whether they will have an irritatin/sensitizatin reactin, and allw them t avid subsequent significant expsures. In the future, the Panel will cnsider the results f nging studies by the industry t evaluate the risks and benefits f cnsumer self-testing Hydrquinne and p-hydrxyanisle - repened These ingredients were previusly reviewed by the Panel in separate reprts. A new use f these ingredients, alne r in cmbinatin, has been reprted in UV-cured nail plish gels, and this use is nt addressed in either f the previus safety assessments. The Panel agreed t repen these safety assessments t address the new usage. Interested parties are encuraged t prvide all available data relevant t this new use. Methylisthiazlinne - repened The Panel reviewed newly prvided clinical data indicating a higher than expected frequency f individuals wh have allergic reactins t the preservative methylisthiazlinne. In sme cases, cmparative data are available indicating a higher frequency f psitive reactins than currently seen with the cmbinatin preservative, methylisthiazlinne/methychlristhiazlinne. The Panel repened this safety assessment t gather and evaluate further clinical data. Interested parties are encuraged t prvide all available data relevant t this cncern abut allergic reactins. 126 th Meeting Ntes Directr s Reprt Dr. Andersen cngratulated the Panel n their handling f the review material presented t them slely as PDF and Micrsft Wrd files. While the mve t ging paperless has been discussed ver the past year, he explained that the equipment needed t prduce the paper cpies was n lnger ging t be available, and the cst f printing the bks using an utside vendr was prhibitive. S, CIR just did it. In additin t making safety assessment decisins, this meeting was a learning experience n the new paperless apprach. Prjecting the reprts n a screen turned ut t be unnecessary, because everyne fcused n using their laptps instead! Feedback frm the audience and the Panel members still will be needed, s that we may imprve hw we d this in the future.

7 Dr. Andersen als fficially annunced that he will retire frm CIR effective at the end f June, Dr. Gill will take ver the prgram and wrk t develp a plan t address CIR s nging staffing needs. Dr. Andersen indicated that he will cntinue t be available n a cnsultant basis after he retires. Reprts Tabled Animal- and plant-derived hydrlyzed prteins - The Panel tabled further discussin n animal- and plant-derived hydrlyzed prteins t allw CIR staff t rerganize the reprt and t analyze further data frm Japan regarding Type I allergic reactins t hydrlyzed wheat prtein in a sap prduct. These ingredients had been presented in a single reprt package with animal- and plant-derived amin acids, but the Panel split the amin acid ingredients int their wn reprt (see Tentative Reprts). Amng the appraches that have been prpsed as alternatives t gruping all hydrlyzed prteins tgether is t rganize the ingredients by plant/animal surce. In that scheme, prteins derived frm wheat, fr example, wuld be the fcus f a grup that culd include hydrlyzed wheat prteins and hydrlyzed wheat prtein derivatives. Ideally, such an apprach wuld facilitate cnsideratin f the cncern abut hydrlyzed wheat prtein in Japan and nt dilute the evaluatin with ther unrelated ingredients. The ther perspective is that, while the parent prteins are frm different animal and plant surces, the prtein hydrlysates are unlikely t represent nvel prtein sequences with unique txicities. In this view, hydrlyzed wheat prtein and the Type I allergic reactins reprted in Japan are unique t hydrlyzed wheat prtein, and are nt assciated with expsures t hydrlyzed prteins frm ther surces. At the time the reprt was tabled, the 54 ingredients included in this safety assessment were: ammnium hydrlyzed cllagen* calcium hydrlyzed cllagen* hydrlyzed actin hydrlyzed albumen hydrlyzed amaranth prtein hydrlyzed avcad prtein* hydrlyzed barley prtein hydrlyzed brazil nut prtein hydrlyzed casein hydrlyzed cnalbumin* hydrlyzed cnchilin prtein hydrlyzed cttnseed prtein hydrlyzed egg prtein* hydrlyzed elastin hydrlyzed extensin hydrlyzed fibrin hydrlyzed fibrnectin hydrlyzed gadidae prtein hydrlyzed gelatin* *Nt reprted t be in current use. hydrlyzed hair keratin hydrlyzed hazelnut prtein hydrlyzed hemglbin* hydrlyzed hemp seed prtein* hydrlyzed hney prtein hydrlyzed jjba prtein hydrlyzed keratin hydrlyzed lactalbumin* hydrlyzed lupine prtein hydrlyzed maple sycamre prtein* hydrlyzed milk prtein hydrlyzed at prtein hydrlyzed pea prtein hydrlyzed ptat prtein hydrlyzed reticulin* hydrlyzed ryal jelly prtein* hydrlyzed sericin hydrlyzed serum prtein* hydrlyzed sesame prtein* hydrlyzed silk hydrlyzed sy prtein hydrlyzed symilk prtein hydrlyzed spngin* hydrlyzed sweet almnd prtein hydrlyzed vegetable prtein hydrlyzed wheat gluten hydrlyzed wheat prtein hydrlyzed whey prtein hydrlyzed yeast prtein hydrlyzed ygurt prtein hydrlyzed zein* MEA hydrlyzed cllagen MEA hydrlyzed silk* sdium hydrlyzed casein* zinc hydrlyzed cllagen* Hypericum perfratum- derived ingredients - The Panel tabled further discussin f hypericum perfratum-derived ingredients t develp language fr the discussin t reflect a grwing cncern abut cnstituents that may be present in multiple btanical ingredients in csmetic frmulatins, resulting in greater than expected expsures t said cnstituents. Fr these ingredients, hypericin, a knwn phtsensitizer, might be a gd example f such cnstituents f cncern. The seven ingredients in this amended safety assessment are: hypericum perfratum extract, hypericum perfratum flwer extract, hypericum perfratum flwer/leaf extract, hypericum perfratum flwer/leaf/stem extract, hypericum perfratum flwer/twig extract, hypericum perfratum leaf extract, and hypericum perfratum il. Palmityl ligpeptides - The reprt was tabled pending rerganizatin f this dcument. These ingredients were preliminarily gruped tgether, as they are related structurally by an identical fatty, hydrphbic tail cnnected t a variable sequence f peptides. The Panel nted, hwever, that the terminlgy used fr these ingredients des nt enable adequate evaluatin. Further infrmatin is sught t better understand the extent and manner in which slid-phase peptide synthesis is used t create the peptide prtin f such fatty acid peptide ingredients. If additinal infrmatin enables a better understanding f the amin acid sequences f the peptides f these ingredients than affrded by their definitins in the dictinary, then gruping them tgether in sme fashin may be reasnable. If there is a substantial degree f randmness assciated with the peptides f these ingredients, then it wuld be imprtant fr the Panel t cnsider hw that might influence the safety evaluatin. Fr example, sme small peptides are ptent stimulatrs f angigenesis. The ptential fr such an activity t prmte tumr grwth and metastasis in peple with undiagnsed skin cancer might then be an issue. Given the present uncertainties, gruping a large number f these ingredients tgether might be inapprpriate. At the time the reprt was tabled, the fllwing ingredients were included: palmityl ligpeptide palmityl dipeptide-7

8 palmityl dipeptide-10 palmityl dipeptide-13 palmityl dipeptide-17 palmityl dipeptide-18 palmityl tripeptide-1 palmityl tripeptide-4 palmityl tripeptide-5 palmityl tripeptide-8 palmityl tripeptide-28 palmityl tripeptide-29 palmityl tripeptide-31 palmityl tripeptide-36 palmityl tripeptide-37 palmityl tripeptide-38 palmityl tripeptide-40 palmityl tripeptide-42 palmityl tetrapeptide-7 palmityl tetrapeptide-10 palmityl tetrapeptide-20 palmityl pentapeptide-4 palmityl pentapeptide-5 palmityl hexapeptide-12 palmityl hexapeptide-14 palmityl hexapeptide-15 palmityl hexapeptide-19 palmityl hexapeptide-26 palmityl hexapeptide-32 palmityl hexapeptide-36 palmityl hexapeptide-27 acetate palmityl heptapeptide-5 palmityl nnapeptide-6 palmityl decapeptide-21 palmityl ligpeptide-70 palmityl hydrlyzed cllagen palmityl hydrlyzed milk prtein palmityl hydrlyzed wheat prtein ptassium palmityl hydrlyzed crn prtein ptassium palmityl hydrlyzed at prtein ptassium palmityl hydrlyzed rice prtein ptassium palmityl hydrlyzed sweet almnd prtein ptassium palmityl hydrlyzed wheat prtein sdium palmityl hydrlyzed cllagen sdium palmityl hydrlyzed wheat prtein Trmethamine - The Panel tabled the safety assessment f trmethamine s that aminmethyl prpanedil (AMPD) and aminethyl prpandil (AEPD) may be incrprated int the reprt. The Panel nted that there were n sensitizatin data fr trmethamine and that it is used up t 4% in bth leave-n and rinse-ff prducts. The nly available sensitizatin data is fr AEPD up t 0.5%. It was als nted that impurity data were lacking. The Panel invites additinal sensitizatin data at the maximum use cncentratin and data n impurities. If such data are nt submitted, the CIR Expert Panel may issue an insufficient data annuncement r a maximum cncentratin f use may be specified in the cnclusin f a tentative reprt psted fr public cmment in the future. Draft 2014 Ingredient Review Pririties Interested parties are invited t cmment n the inclusin f the ingredients listed belw as 2014 CIR pririties based n thse unreviewed ingredients with the largest number f 2013 VCRP uses. Cmment als is sught n the additinal ingredients that might be included in each ingredient family. Nte that the first three are gruped tgether in anticipatin that they wuld be evaluated as a grup. It is likely that nt all f thse listed will be chsen fr wrk in Ingredient Number f frmulatins cntaining ingredient sdium hydrxide 3961 ptassium hydrxide 1032 ammnium hydrxide 946 algae extract 805 ginkg bilba leaf extract 530 phsphlipids 527 sdium benztriazlyl butylphenl sulfnate 473 sdium methylparaben 466 ethylene/prpylene/styrene cplymer 449 avena sativa (at) kernel extract 444 plysilicne butylene/ethylene/styrene cplymer 435 centella asiatica extract 420 buteth PEG-150 pentaerythrityl tetrastearate 408 cetyl PEG/PPG-10/1 dimethicne 387 malus dmestica (apple) fruit extract 382 ptassium cetyl phsphate 377

9 butyrspermum parkii (shea) butter extract 363 hydrflurcarbn 152a 360 triethxycaprylylsilane 354 tridecyl trimellitate 353 panthenyl ethyl ether 351 t be determined hair dye na 2014 Re-reviews While there is n requirement fr CIR t publish an annual list f scheduled re-reviews, belw is the list f the ptential re-reviews fr This list is based n thse safety assessments cmpleted in 1999 r earlier, and nt yet re-reviewed. The need fr re-review f ne r mre f these ingredients may already have been addressed, met by ther effrts already underway (e.g. PEG-5 ccamine), r planned fr Ingredient glyceryl stearate plysrbate 20 ascrbyl palmitate plysrbate 60 sdium PCA glyceryl stearate se bisabll srbitan stearate plysrbate 80 erythrbic acid PEG-7 glyceryl ccate PEG-150 distearate prpylene glycl dicaprylate/dicaprate sdium lactate azulene hydrxystearic acid isstearamidprpyl mrphline lactate nnxynl-4 PEG-5 ccamine PEG-20 hydrgenated lanlin PPG-9 diethylmnium chlride Scientific Literature Reviews These literature reviews are currently psted n the CIR website at amin acid alkyl amides alumina hydrxyprpyl bis(n-hydrxyethyl-p-phenylenediamine) HCl alkyl PEG-PPG ethers Chammilla recutita-derived ingredients Draft reprts fr these ingredients, alng with any unpublished data submitted by interested parties may be presented t the Panel at its meeting n June 10-11, In additin, re-reviews f the safety assessment listed belw may be cnsidered at the June 2013 meeting: dictyl sdium sulfsuccinate plyvinylpyrrlidne These literature reviews are currently in preparatin betaine camellia sinensis leaf citrus limn (lemn) fruit hydrgenated plydecene magnesium sulfate pentaerythrityl tetra-di-t-butyl hydrxyhydrcinnamate phytsterls plant plysaccharide gums (maltdextrin, etc.) rsemarinus fficinalis (rsemary) leaf trehalse & glucse Next CIR Expert Panel Meeting - Mnday and Tuesday, June 10-11, 2013 at the Madisn Htel, 1177 Fifteenth Street, NW, Washingtn, DC Please cntact Carla Jacksn (jacksnc@cir-safety.rg) at CIR befre the meeting if yu plan t attend. IMPORTANT CHANGE CIR n lnger includes an rder frm listing CIR safety assessments available fr sale. Because all CIR dcuments frm this meeting will be psted n the web site, they will be freely available.