G POLYPLANT HAIR GNBN Version: 21-08/05/2012

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1 1. PRODUCT IDENTIFICATION Trade Name: POLYPLANT HAIR GNBN Manufacturer: PROVITAL,S.A. Responsible for the Safety Assessment: Lourdes Mayordomo Tf./Fax: / Kind of Raw Material: Active Ingredient Function of the Ingredient (CTFA Handbook): Antimicrobial Agents; Antioxidants; Cosmetic Astringents; Fragrance Ingredients; Oral Care Agents; Skin Protectants; Skin-Conditioning Agents - Emollient; Skin-Conditioning Agents - Humectant; Skin-Conditioning Agents - Miscellaneous; Skin- Conditioning Agents - Occlusive Function of the Ingredient (UE Inventory): Anticaking, Antimicrobial, Antidandruff, Astringent, Cleansing, Emollient, Masking, Oral care, Perfuming, Skin conditioning, Skin protecting, Soothing, Tonic Maximum Suggested Concentration: 100 % INCI approved in: Registered in EU, USA, Japan Japanese Name: JCLS: Matricaria Extract, Arnica Extract, Rosemary Extract, Sage Extract, ---, Watercress Extract, Burdock Root Extract, ---, Ivy Extract, Calendula Extract, ---, White Nettle Extract. Japanese translation from PCPC:,,, ,,,,,,, 2. PRODUCT COMPOSITION Components Breakdown (INCI). Including actives, solvents, s, preservatives, antioxidants and other additive dditives: [EU] CAS EINECS Aqua % Glycerin % Rosmarinus Officinalis Leaf Extract 0,1-0,3 % Chamomilla Recutita Flower Extract 0,1-0,3 % Arnica Montana Flower Extract 0,1-0,3 % Lamium Album Extract 0,1-0,3 % Salvia Officinalis Leaf Extract 0,1-0,3 % Pinus Sylvestris Bud Extract 0,1-0,3 % Nasturtium Officinale Extract 0,1-0,3 % Arctium Majus Root Extract 0,1-0,3 %

2 Citrus Limon Peel Extract 0,1-0,3 % Hedera Helix Leaf Extract 0,1-0,3 % Calendula Officinalis Flower Extract 0,1-0,3 % Tropaeolum Majus Flower Extract 0,1-0,3 % Preservatives Sodium Benzoate 0,2-0,3 % Potassium Sorbate 0,2-0,3 % PCPC [CTFA] CAS EINECS Water % Glycerin % Rosmarinus Officinalis (Rosemary) Leaf Extract 0,1-0,3 % Chamomilla Recutita (Matricaria) Flower Extract 0,1-0,3 % Arnica Montana Flower Extract 0,1-0,3 % Lamium Album Extract 0,1-0,3 % Salvia Officinalis (Sage) Leaf Extract 0,1-0,3 % Pinus Sylvestris Bud Extract 0,1-0,3 % Nasturtium Officinale Extract 0,1-0,3 % Arctium Majus Root Extract 0,1-0,3 % Citrus Limon (Lemon) Peel Extract 0,1-0,3 % Hedera Helix (Ivy) Leaf Extract 0,1-0,3 % Calendula Officinalis Flower Extract 0,1-0,3 % Tropaeolum Majus Flower Extract 0,1-0,3 % Preservatives Sodium Benzoate 0,2-0,3 % Potassium Sorbate 0,2-0,3 % Impurities: Heavy Metals (as Pb) Pesticides Less than 20 ppm. No data available. Not expected to be found. 3. TOXICOLOGICAL INFORMATION Data obtained in our own toxicological tests and/or bibliographical research Animal testing: This product has not been the subject of animal testing or retesting for cosmetic purposes by or on behalf of this company. General information: The following substances are used as Food Additives permitted for human consume by FDA: Arnica montana (21CFR ); Salvia officinalis (21CFR ); Pinus sylvestris (21CFR ) The following substances have the GRAS status ('Generally Recognized As Safe'): Rosmarinus officinalis (21CFR182.20); Chamomilla recutita (21CFR182.20); Salvia officinalis(21cfr182.20); Lemon Peel (21CFR182.20).; Glycerin (21CFR ) The following herbs have been approved by the German Commission E Monographs: Rosemary Leaf (published November 30, 1985; revised November 28, 1986, and March 13, 1990).; Matricariae flos (Published Dic.1984; Revised March 1990); Arnica flower (Published December 5,1984); Salvia leaf ( 2

3 Published May 15, 1985; Revised March 13, 1990 ); Burdock root (published February 1, 1990).; Hedera helix (Published July 6, 1988).; Calendula Flower (Published March 13, 1986) American Herbal Products Association: Matricaria recutita flower- Herbs that can be safely consumed when used appropriately (Class 1) American Herbal Products Association classifies Arnica montana (whole plant, flower and rhizome) as herb that can be used with following restriction: External use- Do not use on open wounds or broken skin (Class 2d). American Herbal Products Association: Arctium majus root - Herb that can be safely consumed when used appropriately (Class 1). American Herbal Products Association: Lemon peel is classified as herb that can be safely consumed when used appropriately (Class 1). The CIR Expert Panel concluded that Calendula Officinalis Extract, Calendula Officinalis Flower, Calendula Officinalis Flower Extract, Calendula Officinalis Flower Oil, and Calendula Officinalis Seed Oil are safe for use in cosmetics.(final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) American Herbal Products Association: Calendula officinalis flower - Herbs that can be safely consumed when used appropriately (Class 1) The CIR Final Report on Safety Assessment of Sodium Benzoate exists, including all the toxicological data: IJT, 20(S3):23-50, 2001, reopened 06/10. The CIR Final Report on Safety Assessment of Potassium Sorbate exists, including all the toxicological data: JACT 7(6): , 1988, confirmed 04/06. Classification according to Council of Europe (*): Rosmarinus: 3; Chamomilla: 3; Arnica: 3; Lamium: 3; Salvia: 3; Pinus: 3; Nasturtium: 3; Arctium: 3; Citrus: 3; Hedera: 3; Calendula: 3; Tropaeolum: 3. *(1)- Non-recommended ingredients (2)-Ingredients which could not be assessed (3) Recommended ingredients Cytotoxicity: Chamomilla matricaria: Ethanolic and water extract showed no cytotoxic effects. (Tratado de Fito. y Nutra.; Dr. J. Alonso pag. 723) Methanol and ethyl acetate extracts of Lamium album were incubated during 24h at a density of 1x10(5) HSFcells/mL and no cytotoxicity was observed. Low density cell incubation (2x10(4)) during 24-72h cytotoxicity was observed at concentrations greater than 125 microg/ml. At concentration of 25 microg/ml cells remained intact: J Ethnopharmacol. 2007, Mar 1; 110(1): In a study of cytotoxicity using 5 extract of C. officinalis on mouse Ehrlich ascites carcinoma, the results reported that one extract had no effect on tumour growth, three extracts were minimally effective in limiting tumour growth and the 5th extract was effective in curtailing tumour growth. (Final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) Glycolic extract of Tropaeolum majus flowers. Cytotoxicity study in CHO K-1 cells, counting live cells with Tripan blue. Product tested at 1/10, 1/100 and 1/100 dilutions was considered innocuous. (BIOFARBO, Vol. VI, December 1998, pp37-40) Skin Irritation: Test done with other Provital products: (Cod.4230) Patch Test (30 h), IP = 0% Patch Test (48 h), IP = 0%; SKINTEX (UMA) : 2.14 Mild / Moderate Arnica's flowers extract (ESCOP 2 º ed. 2003): not irritant in skin of mouse and not irritant in guinea pig's skin. No adverse effects were noted from topical application of an arnica gel twice daily for 2 weeks by 19 patients. (British Herbal Compendium, volume 2, pp 31, 2006) Citric acid (RTECS no. GE ): Draize test skin: rabbit 500 mg/24h = mild; rabbit 0.5 ml = moderate. Several calendula preparations in patch tests assays in volunteers showed unimportant effects of dermic irritation. (The essential guide to herbal safety, Elsevier, First edition, 2005, pp 310) 3

4 Different skin test in animals whit extracts of Calendula officinalis classified the different extracts as non-irritant. (Final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) Glycolic extract of Tropaeolum majus flowers. Skin irritation test in hamsters. Product was applied at 6% in an emulsion form. After 15 days of application, no irritation effects were detected. (BIOFARBO, Vol. VI, December 1998, pp37-40) Glycolic extract of Tropaeolum majus flowers. Skin irritation test in 8 volunteers (Patch Test). Product was applied at 6% in an emulsion form. Any subject showed irritation effects in area of treatment. (BIOFARBO, Vol. VI, December 1998, pp37-40) Glycerin (RTECS no. MA ): Draize Test in the skin of rabbit, 500 mg, 24h, mild. Skin Sensitization: ESCOP (2ªed. 2003): Allergic reactions due to Matricaria flower can be considered to be extremely rare. Extract of Arnica's flower (ESCOP 2 º ed. 2003): not sensitizing in skin of mouse and not sensitizing in guinea pig. After topical application of an arnica gel twice daily for 6 weeks, minor skin reactions were reported by 6 out of 79 patients (7.6%), including one allergic reaction which persisted beyond the end of the treatment. (British Herbal Compendium, volume 2, pp 31, 2006) Topical administration of an aqueous extract of Arctium majus (5 mg/animal) on the ear of mice, 4 hours before challenge with whey in the ear, inhibited acute ear swelling by 50% in an vivo cow's milk allergic model. Arctium majus has an important potential of use in anti-allergic treatments (Exp Biol Med 2008 Nov; 233(11): ). Calendula officinalis showed no sensitization effects in animal tests ( Int. J. Toxicol. 2001;20 Suppl 2:13-20) Different studies of Dermal sensitization in volunteers using Calendula officinalis concluding that C. officinalis was not considered a sensitizer. (Final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) Eye Irritation: Test done with other Provital products: Rosemary Extract H.G. (Cod. 4430): In-vitro Irritation Index (HET-CAM, 5% solution) = 7.3 +/- 0.8.; Chamomile Extract HG (4370): In-vitro Irritation Index (HET- CAM, 5% solution) = 2.2 +/- 1.6.; Arnica Extract H.G. (4480):In-vitro Irritation Index: HET-CAM (con.25%) :3.3; Sage Extract HG (4440): In-vitro Irritation Index (HET-CAM, 5% solution) = 2.2 +/- 1.6.; Lemon Peel Extract HG (Cod. 4340): In-vitro Irritation Index: HET-CAM (con. 100%): 3.90.; Ivy Extract HG (4310): In-vitro Irritation Index (HET-CAM, 5% solution) = 7.3 +/- 0.8.; Calendula-Extract H.G. (4230): In-vitro Irritation Index (HET-CAM) = 2.2 (sol. 2%), 4.62 (sol. 100%) Extract of Arnica's flower (ESCOP 2 º ed. 2003): not produced ocular significant irritation in mouse or guinea pig. Minimal irritant activity was observed when the 50% extract was instilled in the eyes of rabbits (The essential guide to herbal safety, Elsevier, First edition, 2005, pp 247). Citric Acid (RTECS no. GE ): Standard Draize test, rabbit eye = 750 µg/24h, severe irritation. Hedera saponin : irritant in rabbit eye at a concentration of 1:10000 (ARZNAD 12,815,62) Draize test whit different extracts of Calendula officinalis were not irritating to rabbit eyes. (Final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) An oily extract of Calendula is tolerable to mucosa in the Draize primary mucosa irritation test using the rabbit eye (ESCOP,1,1996) Glycerin (RTECS no. MA ): Draize Test eye rabbit = 500 mg/24h, mild. Mutagenicity: A rosemary extract with high amount of antioxidants, as well as isolated carnosic acid, showed antimutagenic effects on S. typhimurium TA102 (ESCOP 2nd Ed., 2003, p. 433). Matricaria chamomilla Linn.flower extract (RTECS no. OQ ): Specific locus test in Drosophila melanogaster mul = 32.4 gm/l/48h. 4

5 ESCOP (2ªed. 2003): Ames test: apigenin and an aqueous matricaria flower extract showed no mutagenic or toxic activity. Hydroethanolic extract of Arnica's flower (ESCOP 2 ª ed. 2003): in Ames Test showed weakly mutagenic potential, possibly for the present flavonoids in the extract. Sage leaf tincture (ESCOP, 2ªEd. 2003):No mutagenic activity in Ames Test at 200 ul/plate using strains TA98 and TA100, with and without metabolic activation Sage Extract: DNA Inhibition (human lymphocytes) : 2500 ppm (CNREA8 39, 4802, 79) Salvia officinalis, in the form of tea infusion, showed antimutagenic potential in the somatic mutation and recombination test (SMART) on Drosophila melanogaster.(food Chem Toxicol (1):180-3) Salvia officinalis administered to mice at 25 microl/kg caused no increment in the frequency of chromosome aberrations respect to the control. (Acta Vet Hung 2004;52(4):439-43) Ascorbic acid (RTECS nº CI ): Mutation in microorganism : Salmonella typhimurium 500 ug/plate, Neurospora crassa = 2 mmol/l; DNA repair: Saccharomyces cerevisiae = 100 mg/l; Gene conversion and mitotic recombination: Saccharomyces cerevisiae = 300 mg/l; DNA damage: Human fibroblast = 200 umol/l, mammal lymphocyte = 500 umol/l, oral mouse = 1 mg/kg; DNA inhibition: human HeLa cell = 2500 umol/l; cytogenetic analysis: i.p. mouse = 1600 mg/kg; Sister chromatid exchange: i.p. mouse = 1600 mg/kg; Micronucleous test: oral mouse = 30 mg/kg. Arctium majus root: Presents antimutagenic activity (ADEFHEDRU, 2, 144, 93). Calendula officinalis extract (RTECSnºEW ): Genetic conversion and mitotic recombination in Aspergillus nidulans, 0.1g/L/72h Fluid extract of Calendula: negative in Ames Test at ug/plate (+/- S9) and negative in micronucleous test in mouse at 1g/kg p.o. (JEtn (1):49-55) Isorhamnetin: (RTECS no.lk ): mutation in Salmonella typhimurium: 1mg/plate An Ames test of 6 saponins isolated from the dried flowers of Calendula officinalis using Salmonella typhimurium TA98 did not show increase in mutation frequency. (Final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) Somatic an recombination assays using Drosophila melanogaster exposed to C. officinalis herbal tea extract did not show increase in mutation frequency.(final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) Glycerin: DNA inhibition in human lymphocyte, 200 mmol/l (PNASA, 6, 79, 1171, 1982); Cytogenic Analysis rat p.o., 1 g/kg (TGANAK 19, 436, 1985). a-hederin: not mutagenic in the AmesTest (TA98, +/- S9) (MUTA 5,327,90) Glycerin: DNA inhibition in human lymphocyte, 200 mmol/l (PNASA, 6, 79, 1171, 1982); Cytogenic Analysis rat p.o., 1 g/kg (TGANAK 19, 436, 1985). Acute toxicity: Rosmarinus Officinalis (Rosemary) oil (RTECS no. VL ): LD50 p.o rat = 5 g/kg; LD50 rabbit skin > 10 g/kg. Alcoholic Extract of Rosemary: Rat and mouse i.p. LD50 >2 g/kg (PlMEPHT, 25, 6-11, 91). In a study with supercritical fluid extracts of rosemary on rats (p.o.), the LD50 >2000 mg/kg was established (J Food Prot. 2009, Apr; 71(4):790-5). Rosmarinus officinalis, leaf, ethanol extract (RTECS no. VL ): TDLo p.o. rabbit = 200 mg/kg. Rosmarinus officinalis, extract (RTECS no. VL ): TDLo p.o. in rat = 100 mg/kg; TDLo p.o. in mouse = 30 mg/kg. Heteropolysaccharides from Matricaria chamomilla (RTECS nº MK ): TDLo p.o. mouse 10 mg/kg Methanolic extract of Chamomilla: LD50 i.p. rat >4g/Kg; LD50 skin rabbit >5g/Kg (Tratado de Fito. y Nutra.; Dr. J. Alonso pag. 723) Matricaria chamomilla, raw, flower extract: LD50 p.o. mouse 670 mg/kg (Tratado de Fito. y Nutra.; Dr. J. Alonso pag. 723) Matricaria chamomilla, flower extract:(rtecs no.oq ) LD50 i.p. rat >4gm/kg 5

6 Arnica flower's extract (ESCOP 2 º ed. 2003): LD50 p.o. in rate :> 5 g/kg; LD50 p.o. in mouse: 123 mg/kg; LD50 i.p. in mouse: 31 mg/kg. Arnica montana extract: LD50 p.o. rat > 5 g/kg; Sesquiterpene lactone enriched extract of Arnica montana: LD50 i.p. mice = 280 mg/kg (The essential guide to herbal safety, Elsevier, First edition, 2005, pp 247). White Nettle Extract: LD50 i.p. mouse = 750 mg/kg (IJEBA 6, 18, 594, 80) Salvia extract (RTECS nº: VP ): LD50 i.p. in mouse: >1 g/kg. Rosmarinic Acid (RTECS no. GD ): LD50 i.v. mouse = 561mg/kg; TDLo i.p. mouse = 2mg/kg and 0.5 mg/kg; TDLo p.o. rat = 100 mg/kg. Ascorbic acid (RTECS nº CI ): LDLo i.v. Human = 900 mg/kg; TDLo i.v. Human = 2300 mg/kg/2d; TDLo skin mouse = 50 mg/kg; TDLo i.v. mammal =500 mg/kg; TDLo oral mouse = 100 mg/kg; LD50 oral rat = mg/kg; LD50 i.v. rat > 4 g/kg; LD50 oral mouse = 3367 mg/kg; LD50 i.v. mouse = 518 mg/kg. Watercress Extract : LD50 i.p. rat = 1 g/kg (IJEBA 6 16, 228, 78) Arctium Lappa Linn., root extract (RTECS no. CE ): LD50 i.p. in rat = 700 mg/kg. Arctium Lappa Linn. extract (RTECS no. CE ): LD50 i.p. in mouse = 681 mg/kg. Citric acid (RTECS no. GE ): LD50 p.o. rat = 3 g/kg; LD50 i.p. rat = 290 mg/kg; LD50 s.c. rat = 5500 mg/kg; LD50 p.o. mouse = 5040 mg/kg; LD50 i.p. mouse = 903 mg/kg; LD50 s.c. mouse = 2700 mg/kg; LD50 i.v. mouse = 42 mg/kg; LD50 i.v. rabbit = 330 mg/kg; LD16 i.p. rat = 197 mg/kg; LD16 p.o. rat = 5 g/kg; LD16 p.o. mouse = 5440 mg/kg; LD i.p. rat = 382 mg/kg; LD p.o rat = 83 g/kg; LD p.o mouse = 9080 mg/kg; LDLo p.o. rabbit =7 g/kg; TDLo intratraqueal guinea pig = 118 g/kg; TDLo i.v. dog = 64 mg/kg/30m; TDLo i.v. dog = 256 mg/kg/1h; TCLo inhalation guinea pig = 20 pph/10m; TCLo inhalation monkey = 2.5 pph/5m; TCLo inhalation guinea pig = g/m3/3m; TCLo inhalation rat = 180 mg/m3; TCLo inhalation guinea pig = g/m3/10m; TCLo inhalation human = g/m3/0.0083m. Citrus limon (L.) Burm.f. extract: Acute toxicity study on mouse, intraperitoneal, LD50 > 250 mg/kg (RTECS - Registry of Toxic Effects of Chemical Substances, number: GE , last update: ). Ivy Leaf Extract: LD50 p.o. mice > 3 g/kg, LD 50 p.o. rat > 4.1 g/kg. Ivy Saponine mixture:ld50 p.o. mice > 4 g/kg, LD50 i.p. mice 2.3 g/kg (ESCOP 2ªEd. 2003) Hedera helix saponin:: (RTECSno.MH ): LD50 p.o. rat> 100 mg/kg LD50 i.v. rat = 13 mg/kg Hederagenin:(RTECS no.rk ): LD50 i.p. mouse=600mg/kg Hederagenin: LD 50 i.p. mouse > 2 g/kg (YAHOA3,39,137,95) a-hederin: LD50 p.o. mouse > 4g/Kg, LD50 i.p. mouse 1.8 mg/kg (ANPHAFR,38,545,80) Aqueous extract from Calendula flower (ESCOP,2nd ed. 2003): LD100 i.p. in mouse: 580 mg/kg; LD50 i.v. mouse 375 mg/kg Hydro-alcoholic extracts from Calendula flower showed a LD50 of 45mg/mouse(s.c.) and a LD50 of 526 mg/100g in rat (i.v.)(escop,1,1996) An ethylene glycol extract of Calendula is non-toxic in albino mice after subcutaneous administration of 10ml/kg (ESCOP,1,1996) Calendula extract: LD50 p.o., rat > 4.6 g/kg (The essential guide to herbal safety, Elsevier, First edition, 2005, pp 310). Hydroalcohol extract of calendula: LD50 > 5g/kg p.o. in rat and mouse. (Phytother Res. 2007, Apr; 21(4):332-6.] Isorhamnetin. (RTECS no.lk ): LD50 i.v. rat = 11.1g/Kg Calendula officinalis flower extract: i.p. LD50 in mice = 300mg/kg. (Final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) A study in which groups of mice were given a mixture of Calendula officinalis flower extract, butylene glycol, and water daily for 14 days at 5-20ml/kg. No animals died and the LD50 was >20ml/kg.(Final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) Glycerin (RTECS no. MA ): TDLo oral in human = 1428 mg/kg. 6

7 Glycerin (RTECS no. MA ): LD50 in rat: p.o. = mg/kg, i.p. = 4420 mg/kg, s.c. = 100 mg/kg, i.v. = 5566 mg/kg. LDLo in rat i.m. = 10 mg/kg, TDLo in rat i.m. = 5 g/kg. Glycerin (RTECS no. MA ): LD50 oral mouse = 4090 mg/kg, LD50 i.p. mouse = 8700 mg/kg, LD50 s.c. mouse = 91 mg/kg, LD50 i.v. mouse = 4250 mg/kg, LD50 oral rabbit = 27 g/kg, LD50 i.v. rabbit = 53 g/kg, TDLo i.m. rat = 4 ml/kg, TDLo i.m. rat = 4000 mg/kg. Subchronic and chronic toxicity: Rosmarinus Officinalis, leaves (RTECS: VL ): TDLo p.o. rat = 9.52 g/kg/2 weeks. Heteropolysacharides from Matricaria chamomilla (RTECS no. MK ): TDLo p.o. rat 50 mg/kg/5 D-I Salvia officinalis, extract (RTECS nº: VP ):TDLo mouse = 9800 mg/kg/14d-c A water infusion of Salvia officinalis administered to mice and rats for 14 days in the diet did not affect the body weight and food consumption and did not induce liver toxicity.(j Ethnopharmacol 2005; 97(2):383-9) Rosmarinic Acid (RTECS no. GD ): TDLo p.o. rat = 41.4 g/kg/2w. Ascorbic acid (RTECS nº CI ): TDLo oral human = 72,96 g/kg/313w; TDLo oral human = 600 mg/kg/14d-i; TDLo oral monkey = 6000 mg/kg/30d; TDLo oral mouse = 3000 mg/kg/30d-i; TDLo oral mouse = 546 g/kg/13w-i; TDLo oral mouse = 210 mg/kg/2w; TDLo piel mouse = 120 g/kg/30d-i; TDLo i.p. mouse = 750 mg/kg/3d-i; TDLo oral rat = 1200 mg/kg/30d-i; TDLo oral rat = mg/kg/28d; TDLo oral rat = 2100 mg/kg/12w-i; TDLo parenteral rat = 28 mg/kg/7d; TDLo oral rabbit = 1680 mg/kg/12w-i. Nasturtium officinale, 70% ethanol extract (RTECS nº QN ): TDLo p.o. rat = 5000 mg/kg/10d-i; TDLo p.o. rat = mg/kg/30d-i. Citric Acid (RTECS no. GE ): TDLo p.o. rat = 9.3 g/kg/15d-i; TDLo p.o. rat = 18.6 g/kg/30d-i; TDLo p.o. rat = 12.6 g/kg/21d-i. Ivy leaf extract: rat p.o. 1.5 g/kg/day for 100 days caused no toxic effects (ESCOP 2ª Ed. 2003) Saponina Hedera Helix: (RTECSnºMH ): TDLo p.o. rat = 200 mg/kg/4d-i. The aqueous extract of Calendula is not toxic in chronic administration to mice (ESCOP,1,1996) No symptoms of toxicity have been found after administration of a Calendula flower extract at 0.15 g/kg to hamsters over 18 months and to rats over 21 months (ESCOP,1,1996) Calendula extracts tested for acute and chronic toxicity studies in animals at doses higher than 50mg/kg showed no histophatological changes or toxicity symptoms. (Tratado de Fitofármacos y Nutracéuticos; Dr. Jorge Alonso, pag 254) Hydroalcoholic extract of calendula tested in subacute studies in rat and mouse at doses up to 1g/kg was non-toxic, although theres was evidence of renal and liver effects. (Phytother Res. 2007, Apr; 21(4):332-6.] Glycerin (RTECS no. MA ): TDLo oral rat = 96 g/kg/30d-i, TDLo oral mouse = 560 g/kg/8w-c, TDLo oral mouse = 2800 mg/kg/25w-c. Reproductive effects: Rosemary aqueous extract 30%: No teratogenic effects on rats at 26 mg/day, p.o. (Braz J Med Biol Res 1996 Feb; 29(2): 223-7). ESCOP (2nd ed 2003): alfa-bisabolol p.o. rats and rabbits: 1 ml/kg, produce no discernible effects Arnica montana: For topical use only in pregnancy. Risk of damage to the foetus when taken internally. (The essential guide to herbal safety, Elsevier, First edition, 2005, pp 245). Extract Lamium (IJEBA6 18,594,80):Post-implantation mortality and abortion: rat p.o TDL0=150 mg/kg, days pregnant; Pre-implantation mortality: hamster p.o TDLo=500mg/kg, days 1-5 pregnant. Ascorbic acid (RTECS nº CI ): TDLo oral rat female 1-22 days after conception = 2500 mg/kg; TDLo i.v. mouse female 8 days after conception = 800 mg/kg; TDLo oral guinea pig female 1-58 ddays after conception = 5800 mg/kg. Arctium majus extract: Does not affect fertility of female mice when injected subcutaneously twice a day for five days (ADEFHEDRU, 2, 144, 93). 7

8 Calendula: Pregnancy category B2: no increase in frequency of malformation or other harmful effects on the foetus from limited use in women. Animal studies are lacking (The Essential Guide to Herbal Safety, Simon Mills and Kerry Bone, Elsevier, First edition 2005, pp ). Glycerin (RTECS no. MA ): rat, i.t. TDL0 = 280 mg/kg, 2 days, male; rat oral TDL0 = 100 mg/kg, 1 day, male; rat, i.t., TDL0 = 862 mg/kg, 1 day, male. Other data: Rosemary Leaf Extract in acetone (ESCOP, 2ª Ed., 2003): No tumours in 19 weeks study on mouse skin at 3.6 mg. Calendula flower extract: Not carcinogenic in rat ( p.o., 0.15 g/kg, 22 months) and hamster (p.o., 0.15 g/kg, 18 months) (MEBIIN4,28-32,88) Rosemary Extract and its active components, carnosol or carnosic acid, showed anticarcinogenic effects on in vitro human liver and bronchial cells (Cancer Lett 1997, 114 (1-2):275-81). Extract of Arnica's flower (ESCOP 2 º ed. 2003): not phototoxic in skin of mouse and guinea pig. Arnica montana: For topical use only in breastfeeding. Internal use is contraindicated. (The essential guide to herbal safety, Elsevier, First edition, 2005, pp 245). Absolute of Arnica montana at 75% was not phototoxic to the skin of mice (The essential guide to herbal safety, Elsevier, First edition, 2005, pp 247). A clinic study was realized in 286 patients with acute viral pharyngitis. Patients were treated for 3 days with a spray containing 140 microl Salvia officinalis extract per dose; the product showed very good tolerability and was considered safe.(eur J Med Res 2006;11(1):20-6) Ascorbic acid (RTECS nº CI ): Tumorigenic data, TDLo oral rat = mg/kg/103w. Hepatoprotective effect of Great Burdock: Study in rats - Great Burdock at dose of 300 mg/kg shows a protective effect on the hepatotoxicity induced by ethanol and CCI4 (J Biomed Sci 2002; 9(5): 401-9). Study in mice - Great Burdock shows a protective effect on CCI4 and acetaminophen-induced liver damage ( Am J Chin Med 2000; 28(2):163-73). Arctium majus rhizomes: Carcinogenicity test, rats treated with a diet containing 33% of rhizomes for 120 days, without detecting tumours in any animal (ADEFHEDRU, 2, 144, 93). A clinical prospective assay with patients with bronchitis concluded that the safety of the therapy with ivy leaf extract was very good with an overall incidence of adverse events of 2.1% (mainly gastrointestinal disorders with 1.5%). (Phytomedicine; 2006 Jul 20). The use of Calendula officinalis L. is compatible with breastfeeding (The Essential Guide to Herbal Safety, Simon Mills and Kerry Bone, Elsevier, First edition 2005, pp ). A study of phototoxicity with a mixture of Calendula officinalis flower extract, Butylene glycol, and water using guinea pigs showered that Calendula Officinalis flower extract mixture did not produced phototoxicity (Final Report. Amended Safety Assessment of Calendula Officinalis, March 23,2009) Glycolic extract of Tropaeolum majus flowers. Skin photodermatosis test in hamsters. Product was applied at 6% in an emulsion form. After 10 days of application with sun exposure, no cutaneous effects were detected. (BIOFARBO, Vol. VI, December 1998, pp37-40) Glycolic extract of Tropaeolum majus flowers. Photodermatosis test in volunteers. Product was applied at 6% in an emulsion form. Any subject showed cutaneous effects. (BIOFARBO, Vol. VI, December 1998, pp37-40) 8

9 4. ECOLOGICAL DATA Biodegradability: Glycerin (HSDB no. 492, revision: ): Activated sludge test: 220 mg/l resulted in a COD of 97%; Test in a 5 days: BOD = 82%. Glycerin is considered an easily degradable substance. Aquatic Toxicity: Glycerin: Multiplication inhibition test in algae (Microcystis aeruginosa) and protozoa (Entosiphon sulcatum): Toxicity threshold = 2900 mg/l and 3200 mg/l (HSDB no. 492, revision: ). Glycerin (HSDB no. 492, revision: ): LC50 goldfish > 5000 mg/l/24h. Other data: No data available. 5. CONCLUSION The components of this product have registered adverse effects neither in its traditional uses nor in the historical marketing of this company. These data and the available toxicological information lead to the conclusion that the use of this product, under the normal conditions of cosmetic use and at the maximum recommended concentration, involves no risk for consumers. 9