04N-0050
RPT 1
Volume 3-8

Volume 3

Cover Page

Safety and Effectiveness Information for Piroctone Olamine

List of References

Volume 4

Safety References

Report on a single-dose oral toxicity study of H 72 6146 A in female SPF Wistar rats

Report on a single-dose oral toxicity study of H 72 6146 A in male and female Beagle dogs

Octopirox testing of acute dermal toxicity in male and female Wistar rats

Octopirox test for primary dermal irritation in the rabbit

Primary Skin Irritation of a preparation of 0.5 % Octopirox, 12.5 % Steinapol SBFA 30 (40 %), 0.11 % citric acid and 86.89 % water (pH 7.0) in rabbits (patch test)

Primary Skin Irritation of a preparation of 1 % Octopirox, 0.33 % citric acid, 75, 0 % PEG 400 and 23.67 % water (pH 7.0) in rabbits (patch test)

Skin tolerance of a preparation of 1.0 % Octopirox (Op. E. 001), 0.3 % citric acid and 98.7 % 1, 2-propylene glycol (pH 7.0) in rabbits

Primary Skin Irritation of a preparation of 0.5 % Octopirox, 12.5 % Steinapol SBFA 30 (40 %), 0.11 % citric acid and 86.89 % water (pH 7.0) in New Zealand rabbits (patch test)

Primary Skin Irritation of a preparation of 1 % Octopirox, 0.33 % citric acid, 75 % PEG 400 and 23.67 % water (pH 7.0) in New Zealand rabbits (patch test)

Skin tolerance of a preparation of 1 % Octopirox (Op. E 001), 0.3 % citric acid and 98.7 % 1,2-propylene glycol (pH 7) in New Zealand rabbits

Mucosal tolerance to Ma Ref 0370 in the rabbit

Mucosal tolerance to Ma Ref 03701 in the rabbit

Mucosal tolerance to Ma Ref 0380 in the rabbit

Mucosal tolerance to Ma Ref 03801 in the rabbit

Mucosal tolerance to Shampoo Hs Ref 03790 in the rabbit

Mucosal tolerance to Shampoo Hs Ref 037901 in the rabbit

Mucosal tolerance to a preparation of 0.2 % (w/w) Octopirox and 50 % (w/w) Isopropanol in water (pH 7.0)
in the rabbit

Mucosal tolerance to 50 % (w/w) isopropanol in aqueous solution in the rabbit

Study of Sensitizing Properties of Octopirox in Guinea Pigs

Maximization Test of Piroctone Olamine in the Guinea Pig

Report on the testing of the dandruff active substance ASM-D (H 72 61 46 A) for sensitizing properties in humans

Photocontact Allergy Test of Piroctone Olamine in the Guinea Pig

Phototoxicity study of Octopirox

Report on oral range-finding study (30 days) of Octopirox in SPF Wistar rats, part 2, part 3

Report on a repeated-dose (30 days) oral toxicity study of Octopirox in beagle dogs

Five Weeks Subacute Subcutaneous Toxicity of Piroctone Olamine in Rats

Volume 5

References

Subacute (30 times) dermal toxicity study of Octopirox as hair lotion and shampoo in rabbits, part 2

Report on a repeated-dose (90 days) oral toxicity study of Octopirox in rats, part 2, part 3, part 4, part 5

Report on a repeated-dose (90 days) oral toxicity study of Octopirox in beagle dogs

6 months chronic percutaneous toxicity of piroctone olamine in rats

One-year chronic percutaneous toxicity of piroctone olamine in rats

Volume 6

References

Test for mutagenicity in bacteria strains in the absence and presence of a liver preparation

Mutagenicity test of Piroctone Olamine

Study of the mutagenic potential of the compound Octopirox Charge W 020 in strains of Salmcnella typhimurium (Ames Test)

Study of the mutagenic potential of the compound Octopirox OP. A 038 in strains of Salmonella typhimurium (Ames Test)

Report on an oral mutagenicity study (micronucleus test) with octopirox in mice

Micronucleus Test of Piroctone Olamine in Mice

Mutagenicity evaluation of PKOD-A038 in the Chinese hamster bone marrow cytogenetic assay

Lack of in Viva Binding to DNA of Piroctone-olamine

An oral embryotoxicity study of octopirox in rabbits

Teratological Study of Piroctone Olamine in Rats - Subcutaneous Administra:ion during Organogenesis -
(Experimental period: March - April, 1981)

Teratological Study of Piroctone Olamine (PO) in Rats - Subcutaneous Administration at Different Times during Organogenesis

Subcutaneous administration of piroctone olamine to rats from preconceptional period through early stage of gestation

Effects of piroctone olamine subcutaneously given during the last third of gestation and the period of lactation in the rats

Pharmacokinetic studies of Octopirox-14C after dermal, oral and intravenous administration to rats

Kinetics of Octopirox after oral administration to dogs and rats

Percutaneous absorption of Octopirox

Report on general pharmacology of Octopirox

The effect of Piroctone Olamine on reproduction of male and female rats; Allgood, G.S. et al., Fundamental and Applied Toxicology 16, 3 l-40, 1991.

The effects of dietary iron supplementation on the toxicity of Piroctone Olamine in the growing rat; Nolen, G.A. et al., Drug and Chemical Toxicology 12: 111-121, 1989

Percutaneous Absorption of Octopirox; Black, J.G. and Kamat, V.B., Fd Chem. Toxic. 26: 53-58, 1988

Patch test for investigating the skin-irritant effect of cosmetic products in humans; Tronnier, H., Institute for experimental dermatology, June 17, 1991

Patch test for investigating the skin-irritant effect of cosmetic products in humans; Trormier, H., Institute for experimental dermatology, June 17, 1991

OECD Acute Inhalation Toxicity Evaluation of Octopirox; Study No. 191-1456, International Research and Development Corporation, 2 1.2.1990

Volume 7

References

The aetiology of dandruff and the mode of action of the therapeutic agents. S. Shuster, British Journal of Dermatology 111 (1984) 235-242

Fast, noninvasive method for molecular detection and differentiation of Malassezia yeast species on human skin and application of the method to danduff microbiology. C. M. Gemmer, Y. M. DeAngelis, B. Theelen, T. Boekhout, T. L. Dawson, Journal of Clinical Microbiology, 40 (2002) 3350-3357

Brochure Olctopirox, Hoechst AG, 1991

Brochure Antidandruff Active Ingredient Octopirox, Clariant GmbH, 2003

Specification Piroctone Olamine, Hoechst AG, 1983

Specification Octopirox (Piroctone Olamine) Clariant GmbH, 2001

Report Hoechst AG, H 726146A, January 5, 1977

Report Hoechst AG, H 726146A, October 26, 1981

Testing of Octopirox against Pityrosorum Ovale (orbiculare) in vitro/Dr. Hanel, Hoechst AG, 1990

Report on tests for the determination of the substantivity of Octopirox on the scalp, Dr. Futterer, Hoechst AG, December 20, 1976

Stability test of Octopirox (piroctone olamine) substance for 3 years at room temperature, Dr. Futterer, Hoechst AG, June 30, 1981

Stability test of Octopirox shampoo (0,5 % w/w) for 3 years at room temperature, Dr. Futterer, Hoechst AG, September 25, 1981

In vitro susceptibility of Malassezia furfur. A. Schmidt, B. Ruhl-Horster, Arzneim.- Forsch./Drug Res;. 46 (1996) 442-444

Radiometrische Untersuchungen zur Substantivitat des Antischuppenwirkstoffs Piroctone Olamine an Humanhaar. K. Lotsch, J. Herok, 11th International ISFCC Congress, Cosmetics: Reserach and
Technology, Venezia-Lido, September 23-26, 1980

Comparaison de la thermostabilite d’antipelliculaires naturels et de synthese (climbazole et piroctone olamine). C. Coiffard, L. Coiffard, Y. de Roeck-Holtzhauer, Ann. Pharm. Fr. 57 (1999) 392-396

Photodegredation of piroctone olamine in aqueous diluted solutions - Effect of the presence of anionic surfactants, M. T. Le, L. J. M. Coiffard, F. Peigne, Y. de Roeck-Holtzhauer, S.T.P. Pharma Sciences 6 (1996) 455-458

HPLC determination of Ciclopirox, Octopirox and Pyrithiones in Pharmaceuticals and Antidandruff Preparations. L. Gagliardi, G. Multari, G. Cavazzutti, D. De Orsi, D. Tonelli, J.
Liq. Chrom & REI. Technol. 21 (1998) 2365-2373

Simultaneous determination of four anti-dandruff agents including octopirox in shampoo products by reversed-phase liquid chromatography. L. Chao, International Journal of Cosmetics Science, 23 (2001) 183-188

Spectrophotometric determination of Octopirox in cosmetic compositions (e.g. Shampoo), Clariant GmbH, May 2000

Determination of Octopirox in Shampoos by HPLC, Clariant GmbH, March 2, 2001

Dr. Futterer, Antidandruff activity of Octopirox, Hoechst AG, April 18, 1978

Piroctone Olamine shampoo vs. an inactive shampoo anti-dandruff activity using the half-head technique/Life Science Research, April 24, 1980. Continued

Piroctone Olamine shampoo vs. a competitor’s shampoo, anti-dandruff activity using the half-head-technique. Life Science Research, 1981

Piroctone Olamine shampoo vs. 1 % DTPD/MgSO4 Shampoo, comparative trial of antidandruff efficacy using the half-head technique/Life Science Research Ltd, June 27, 1984

Volume 8

References

Shampoo HAG 099A Hair Tonics HAG 099B, HAG 099C and HAG 099D. Comparative Trial of antidandruff efficacy using the whole-head technique. Life Science Research, December 19, 1986

Bericht tiber die vergleichende Prufung von Octopyrox und Climbazol auf Antischuppen-Wirkung, Cosmital SA, Marly 13.12.1994

Efficacy report: A double-blind placebo-controlled four-way parallel group trial to evaluate the efficacy of Octopirox 0.75 % compared to Zinc Pyrithione 1 % and Climbazole 0.75 % in the treatment of seborrhoeic dandruff on the scalp, Hoechst AG and Parexel GmbH, January 8, 1997. Continued

Clinical Study to evaluate the anti-dandruff efficacy of Shampoos, proDerm Instutute, study 99. 110-11, February 4, 2000

A practice-oriented test method of active ingredients to control dandruff, G. Dietrich, V. Biillert, Medical Cosmetology 10 (1980) 34-45

Evaluation of the efficacy of antidandruff agents, E. Futterer, J. Soc. Cosmet. Chem. 32 (1981) 327-338

Clinical Evaluation of Hair Shampoo and Hair rinse containing piroctone olamine parts I, II and III, Y. Watanabe, M. Yokoyama, K. Yamada, M. Arima, T. Hori, M. Sadai, J. Japanese Cosmet. Science Soc. 6 (1982) 79-99

Investigations into the efficacy of soluble anti-dandruff agents, Dr. E. Futterer, Medical Cosmetology, 15 (1985) 421-435

Antidandruff Hair Tonic containing piroctone olamine, Dr. Eberhard Futterer, Cosmetics & Toiletries 103 (1988), 47-49

The role of the resident microflora in the pathogenesis of dandruff, D. Saint Leger, A.M. Kligman, T. J. Stoudemayer, J. Soc. Cosmet. Chem 40 (1989) 109-117

Comparative anti-dandruff efficacy between a tar and a non-tar shampoo, C. Pierard- Franchimont, G. E. Pierard, V. Vroome, G. C. Lin, Dermatology 200 (2000), 181-184

Synergistic behaviour between AHA and BHA’s esters with MEA-Piroctone Olamine for antidandruff shampoo formulation, F. Montesion, C. Genova, G. Calloni, The world directory for the cosmetic industry 2000, pp. 54-56

The antidandruff efficacy of a shampoo containing piroctone olamine and salicylic acid in comparison to that of a zinc pyrithione shampoo, M. Loden, C. Wessman, International Journal of Cosmetic Science, 22 (2000) 285-289

Head & Shoulders - New Improved Head & Shoulders, Product Brochure, Procter & Gamble 2000

Nudging hair shedding by antidandruff shampoos. A comparison of 1 % ketoconazole, 1 % piroctone olamine and 1 % zinc pyrithione formulations, C. Pierard-Franchimont, V. Goffin, F. Henry, I. Uhoda, C. Braham, G. E. Pierard, International Journal of Cosmetic Science 24 (2002), 249-256

Efficacy and skin tolerability of saliker in the treatment of dandruff, S. Humke, M.-A. Budde, T. Ruzicka, A. Richard, A. Rougier, J. Krutrnanrr, Eur. J. Dermatology, 12 (2002) LII-LIII

Effect of residence time on the efficacy of antidandruff shampoos, C. Pierard-Franchimont, E. Uhoda, G. Loussouam, D. Saint-Leger, G. E. Pierard, International Journal of Cosmetic Science, 25 (2003) 267-271

Intemet page www.wella.de, June 2003

Sperimentazione di nuovi farmaci: Attivita antipitiriasica di una linea di prodott contenente piroctone olamina (Trials on new drugs, Antipyriasis activity of a product line containing piroctone olamine), P. Bartalini, R. Bilenchi, F. Dina, Giomale Italiano di Dermatologia e Venereologia, 122 (1987) 11-19

Certificate of Analysis H 72 6146 A, Hoechst AG, February 18, 1974

Certificate of Analysis H 72 6146 A, Hoechst AG, September 10, 1975

Certificate of Analysis Octopirox (H 72 6146 A), Hoechst AG, January 16, 1976

Product documentation Octopirox, 1976