PRODUCT INFORMATION FILEbritishbeauty.london/pdf/nappy-balm-30ml-50ml-CU00068641-CU00009903.pdf · The calculation of Margin of Safety (MOS): NOAEL SED NOAEL data is derived from

functional ingredient solutions

Inovia International, a division of Stan Chem International Ltd. Manufacturing Site: Unit 11, Kings Cliffe Industrial Estate,

Wansford, Peterborough, Cambridgeshire, PE8 6PB. Tel: 01780 – 782 319 Fax: 01780 – 781 398

Email: [email protected]

PRODUCT INFORMATION FILE Prepared according to EC 1223/2009 Product Name: Tiddley Pom Organic Nappy Balm 30ml

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Product Code: CU00068641

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Product Name: Tiddley Pom Organic Nappy Balm 50ml Product Code: CU00009903 Responsible Person: Tiddley Pom Ltd, 15 Rose Hill, Dorking, Surrey, RH4 2ED, UK. 1 – Tiddley Pom Organic Baby Massage Experience (Product Code CU00068643) is a “gift set” containing the products below: Tiddley Pom Organic Nappy Balm 30ml (Product Code CU00068641) Tiddley Pom Organic Soothing Lotion 50ml (Product Code CU00037529) Tiddley Pom Organic Massage Oil 50ml (Product Code CU00037528) Tiddley Pom Organic Baby Wash 50ml (Product Code CU00037530)





CONTENTS

Volume 1 A statement confirming the name and place of manufacture A statement confirming compliance with good manufacturing practice (GMP) and referring to a description of the method of manufacturing A statement confirming that no animal testing is performed by the manufacturer, his agents or suppliers, relating to the safety of this product Composition of the Product Physical / Chemical Characteristics Raw Material Quality / Purity Stability Microbial Quality – Ingredients Microbial Quality – Finished Product Finished Product Safety Challenge Test Data Packaging Information Allergens Declaration IFRA Statement Wording or Artwork for the Pack Labelling Undesirable Effects and Serious Undesirable Effects Appendix 1 – GMP Certificate

Volume 2 Cosmetic Product Safety Assessment and Cosmetic Product Safety Report according to Regulation (EC) No. 1223/2009





VOLUME 1

Name and Place of Manufacture The products are manufactured at: Inovia International, Unit 11, King’s Cliffe Industrial Estate, Wansford, Peterborough, Cambridgeshire, PE8 6PB.

Good Manufacturing Practice Statement The management system of Inovia International has been assessed by SGS United Kingdom Ltd and certified as meeting the requirements of ISO 22716:2007, Cosmetics – Guidelines on Good Manufacturing Practices (GMP). A copy of the certificate can be seen in Appendix 1. It is confirmed that the products are manufactured to Cosmetic Good Manufacturing Practice (GMP). A description of the method of manufacturing is held on file at Inovia International.

Animal Non-testing Declaration It is confirmed that the products, and the individual ingredients in the products, have not been the subject of animal testing or retesting since 31 December 1990. It is also confirmed that no animal testing is carried out via third parties on behalf of the company.

Composition of the Product The detailed quantitative formulation (exact % of each ingredient) is held on file at Inovia International.

Physical/Chemical Characteristics The raw material specifications and the finished product specifications are held on file at Inovia International.





Raw Material Quality/Purity Raw Material Manufacturers’ material safety data sheets, specifications and certificates of analysis are held on file at Inovia International.

Stability The stability of the product is acceptable. Stability data is held on file at Inovia International.

Microbial Quality - Ingredients It is a requirement that all raw materials / ingredients meet a microbial quality of < 100 cfu/gram for infant products (from the SCCS Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation, 8th Revision, 2012). All the raw materials / ingredients comply with this requirement.

Microbial Quality – Finished Product It is a requirement that the finished product meets a microbial quality of < 100 cfu / gram for infant products and zero harmfuls (from the SCCS Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation, 8th Revision, 2012). The finished products comply with this requirement.

Finished Product Safety The microbial content (Total Viable Count) at time of manufacture must be within recognised limits: nmt 1000 cfu and zero harmfuls / gram (from the SCCS Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation, 8th Revision, 2012). The microbial content at time of manufacture complies with these recognised limits.

Challenge Test Data The product will pass a Microbial Challenge Test. As the formulation of the product is water-free, it is considered that it will not require a preservative and will not pose a microbiological hazard.

Packaging Information Packaging Information is held on file at Inovia International.





Allergens Declarations Allergens Declarations are held on file at Inovia International.

IFRA Statement IFRA Statements are held on file at Inovia International.

Wording or Artwork for the Pack Labelling The following pack labelling artworks are held on file at Inovia International. Artwork PDF file name “Box_Step 4__Organic Nappy Balm 50ml - CU00009903” Artwork PDF file name “Label_Step 4_Organic Nappy Balm_50ml - CU00009903” Artwork PDF file name “TP Gift Set - Tiddley Pom_4 Step Massage_Box_Base - CU00068643” Artwork PDF file name “TP Gift Set - Tiddley Pom_4 Step Massage_Box_Top - CU00068643” Artwork PDF file name “TP Gift Set Labels_Step 4_30ml - CU00068643”

Undesirable Effects and Serious Undesirable Effects Inovia International is not aware of any available data on undesirable effects and serious undesirable effects relating to the product, or other similar cosmetic products.

…………………………… Technical and Regulatory Department For Inovia International 17th March 2014





Appendix 1 – GMP Certificate





VOLUME 2

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The Elms · Oxford Rd · Chieveley · Newbury · RG20 8RT· United Kingdom

Telephone: +44 1635 248830 Fax: +44 1635 247206 Email: [email protected]

SAFETY ASSESSMENT/ CONSUMER PRODUCT SAFETY REPORT

Product Name: Tiddley Pom Organic Nappy Balm 30ml Ref: CU 00068641 Product Name: Tiddley Pom Organic Nappy Balm 50ml Ref: CU 00009903 our ref: K1292 PART A, SAFETY REPORT This Safety Report/Assessment is conducted to EC1223-2009. It takes account of the requirements of the EC 1223/2009 for a special assessment for baby products. The Assessment is conducted in accordance with the principles of Good Laboratory Practice referred to in Article 1 of Council Directive 2004/10/EC on the applications of the principles of good laboratory practice and the verification of their application for tests on chemical substances. This assessment takes account of:

a) the general toxicological profile of each ingredient used: b) the chemical structure of each ingredient: c) the level of exposure of each ingredient; d) the specific exposure characteristics of the areas on which the cosmetic

product will be applied; e) the specific exposure characteristics of the class of individuals for whom the

cosmetic product is intended. REVIEW OF INGREDIENTS All of the ingredients have a history of use in cosmetic and toiletry products. Ingredients that are:

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• Prohibited under EU Cosmetics Regulations • Restricted when used beyond the allowed authorised conditions • With toxicological data incompatible with the intended concentration and

use • Which have insufficient toxicological data nor safety in use experience • Which are not properly characterised with regard to purity and analytical

composition are excluded. ASSESSMENT Assessment is based on ingredient safety review and information on the final formulation, including the intended and reasonably foreseeable use, the physico-chemical and microbiological specifications of the raw materials and the finished product, stability and a history and record of any reported undesirable effects linked to the use of the product. DESCRIPTION OF THE PRODUCT This is a leave-on product for application to infant nappy areas as a skin protectant and soother and moisturiser. DESCRIPTION OF INTENDED AND REASONABLY FORESEEABLE USE The product may reasonably be typically used up to 1-4 times daily as required, QUALITITATIVE COMPOSITION OF THE PRODUCT A FULL QUANTITATIVE VERSION OF THIS ASSESSMENT IS HELD ON FILE BY THE ASSESSOR AND THE MANUFACTURER Ingredients are listed below. Detailed information on the safety and toxicology of ingredients is presented below. Detailed Quantitative formula is held on file.

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The above ingredients have been reviewed for potential to be skin irritants, sensitisers or photo-sensitisers. Where data is available for systemic and sub-chronic toxicity this has been taken into account. A review of the literature and of the structural chemistry has been made for each ingredient to estimate the likely potential for genotoxicity, reproductive effects and carcinogenicity. No animal testing has been conducted on this formulation. All safety data is taken from existing published sources. EXPOSURE TO THE PRODUCT/ EXPOSURE TO THE SUBSTANCES MARGINS OF SAFETY Based on the available toxicological literature or on “read-across” data Margins of Safety have been calculated for both topical and systemic effects. The procedure is as described in: THE SCCS NOTES OF GUIDANCE, FOR THE TESTING OF COSMETIC INGREDIENTS AND THEIR SAFETY EVALUATION, 8th REVISION, 2012. Dermal Absorption reported as a % of the substance applied: EXPOSURE TO THE SUBSTANCES For a typical infant a median bodyweight of 10 kg is selected. The calculation of the SED is as follows: SED = A (g/day) x 1000mg/g x C (%)/100 x DAp (%)/100 10 kg SED (mg/kg bw/day) = Systemic Exposure Dosage A (g/day) = Amount of the cosmetic product applied daily: see the daily exposure values for different cosmetic product types C (%) = the Concentration of the ingredient under study in the finished cosmetic product on the application site DAp (%) = Dermal Absorption expressed as a percentage of the test dose assumed to be applied in real life conditions 10 kg = Typical Infant body weight The calculation of Margin of Safety (MOS): NOAEL SED NOAEL data is derived from published literature where available. Estimated Daily Exposure Levels:

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Data for Estimated daily exposure levels is taken from the current Colipa data as presented in THE SCCS NOTES OF GUIDANCE, FOR THE TESTING OF COSMETIC INGREDIENTS AND THEIR SAFETY EVALUATION, 8th REVISION, 2012. Table 3: Estimated daily exposure levels for different cosmetic product types according to Colipa data [SCCNFP/0321/02; Hall et al. 2007, 2011]. Product type

Estimated daily amount applied

Relative amount applied (mg/kg bw/day

Retention factor 1

Calculated daily exposure (g/day)

Calculated relative daily exposure (mg/kg bw/day)

Nappy cream 1.5 g 150.0 1.0 1.5 150.0

1 The retention factor was introduced by the SCCNFP to take into account rinsing off and dilution of finished products by application on wet skin or hair (e.g. shower gels, shampoos, …) [SCCNFP/0321/00] It was concluded that all ingredients, when considered both individually and in combination have an adequate Margin of Safety, ie > 100. PHYSICAL/CHEMICAL CHARACTERISTICS The raw material Specifications and the Finished Product Specification are provided. It is considered that all Specifications meet good standards for safe use of this product. See Appendix RAW MATERIAL QUALITY/ PURITY All raw materials are from reputable sources of supply and are considered to meet current standards of purity and quality. The physical and chemical properties and microbiological of the raw materials have been reviewed. It is noted that all are to current standards and there are no banned or restricted materials present. The Molecular formulae for defined chemical substances are as recorded in the current Edition of ICID. Manufacturers Material data sheets/ Certificates are Appended The raw materials meet current good standards for quality and purity. Manufacturers Material data sheets/ Certificates are presented in Appendix. GOOD MANUFACTURING PRACTICE The product is to be manufactured to adequate standards of Good Manufacturing Practice and there are to be adequate controls in regards to Microbial quality

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STABILITY The product is deemed stable under normal and foreseeable conditions of use. Stability data is summarised in Appendix. MICROBIAL QUALITY

INGREDIENTS It is a requirement that all raw materials/ ingredients meet a microbial quality of < 100 cfu/ gram for Infant products FINSHED PRODUCT It is a requirement that the Finished Product meets a microbial quality of < 100 cfu/ gram for Infant products and zero harmfuls. CHALLENGE TEST DATA The product is water-free and no added preservatives are required. PACKAGING The packaging is described as: SAN Jar, SAN Lid and a PP Shrive. The packaging materials are to meet acceptable standard of purity. Consideration has been given to interaction between the product and the packaging. It is considered there is no adverse interaction between product and packaging as regards safety to the consumer. FINISHED PRODUCT SAFETY The above formulation is based on known ingredients with history of safe use in cosmetic products. The product is considered to be protected from microbial growth. It is noted that all ingredients are used within limits as specified in the cosmetics Directive. The microbial content (Total Viable Count) at time of manufacture must be within recognised limits (nmt 1000cfu and zero harmfuls /gm). This Safety Assessment has taken account of: 1. The Quantitative/Qualitative composition of the product, 2. The intended and reasonably foreseeable use of the product, 3. Margins of Safety for all ingredients considered both individually and in

combination. 4. A review of raw material specifications for purity. 5. Standards of good manufacturing practice 6. A consideration of potential interactions of substances in the formulation. 7. A consideration of the stability of the formulation

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INGREDIENT TOXICOLOGY PROFILE & SAFETY REVIEW

HELIANTHUS ANNUUS (SUNFLOWER) SEED OIL

CAS: 8001-21-6 EINECS: 232-273-9 Sunflower seed oil is a vegetable oil with a safety and toxicity profile similar to vegetable oil and as described below. The fatty acid profile includes linoleic acid (63%), oleic acid (23%) and palmitic acid (6%) as the major fatty acids. In common with other vegetable oils this is a blend of C16-C18 triglycerides. Limited formal safety data is available since this is a GRAS substance (Generally Regarded As Safe). A human repeat insult patch test on vegetable oil on 88 subjects gave no signs of irritation or sensitisation. The fatty acid profile of Sunflower oil is similar to that of Coconut oil and Palm oil, and the safety of these oils is relevant to Sunflower oil. Coconut oil is the subject of a CIR monograph (2010) and of a review in JACT (1986). It is reported non-irritant to skin and eyes in animals nor is it a sensitiser. There was no indication that products containing coconut oil were phototoxic nor were primary irritants. Palm oil is the subject of a CIR monograph (2010) also shows no adverse toxicity. The oral LD50 in rats is low at >5g/kg. Short term and sub-chronic feeding studies showed no evidence of toxicity. In summary this ingredient is considered to be safe as used in this formulation. A NOAEL of 2000 mg/kg is established. (3)

REFERENCES 1 Cosmetic Ingredient Review (2010) 2 JACT (1986) 5(3) 103-121 3.http://ec.europa.eu/enterprise/sectors/chemicals/files/reach/dhi_report_app2_081211_en.pdf

BUTYROSPERMUM PARKII (SHEA) BUTTER

CAS: 194043-92-0 EINECS: 270-311-6 Butyrospermum parkii, also termed Shea butter is the natural oil/fat extract of the Shea nut. This ingredient has a toxicity profile similar to that of other vegetable oils, with a low order of oral toxicity. The main constituents are palmitic acid (4%), stearic acid (43%), oleic acid(47%) and linoleic acid(6%). A dose of 2g/kg, orally was not toxic to rats.

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Dermal irritation to the rabbit skin after 4 hours was rated as “not irritant” with only a slight erythema noted. Application to the mucous membrane of the rabbit eye gave no irritant response except for a slight conjunctival reaction that disappeared within 24 hrs. In a Guinea pig study there was no evidence of sensitisation potential, nor in a Guinea pig test was there evidence of photo-toxicity. In an Ames type test for genotoxicity there was no evidence of mutagenicity to this ingredient. Based on the chemical structure it is considered unlikely that this ingredient will have carcinogenic or reproductive toxicity potential. Based on the data for the fatty acids, a NOEAL of 1000mg/kg/day is established (2). Based on the known dermal penetration of stearic and oleic acid (0.004% and 0.0093% respectively) a dermal penetration of 0.01% is established (3). In summary Butyrospermum parkii is considered safe as used in this formulation.

REFERENCES 1 Data on file Innovant Research. 2.http://ec.europa.eu/enterprise/sectors/chemicals/files/reach/dhi_report_app2_081211_en.pdf 3. Maibach HI , Boisits EK in the book Neonatal Skin Structure and Function, Marcel Dekker, NY, USA 1982

CERA ALBA

CAS: 8012-89-3 Cera alba (also termed beeswax) is the subject of a CIR monograph (2) and a review in JACT (1984). It was concluded by CIR that on the basis of toxicological tests conducted, beeswax is safe for cosmetic use. This is a food-use ingredient and based on the chemical similarity to synthetic waxes is estimated to have an oral LD 50 in rats of >5Gg/kg. Products containing beeswax have been tested and do not have sensitisation potential. It is concluded that as used in this formulation beeswax can be regarded as safe A NOAEL of 1000 mg/kg/day is established (4).

REFERENCES

1 Data on file Innovant Research 2 Cosmetic Ingredient Review (2010) 3 JACT 3(3) 1-41 (1984) 4 JECFA Evaluations, Beeswax, Summary of Evaluations Performed by the

Joint FAO/WHO Expert Committee on Food Additives

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LAVANDULA ANGUSTIFOLIA (LAVENDER) OIL

CAS: 8000-28-0 EINECS: 289-995-2

This essential oil has a history of safe usage in cosmetics and skin care. Lavender oil has a long history of safe use topically and has been used in medicine as a carminative. It also has a function as an insect repellent in several commercial products. There have been occasional reports of contact dermatitis due to sensitisation from essential oils. However this is in fact very rare and this oil can be considered safe in the current application. The components of lavender oil, including one of the major ingredients linalool, are approved for intake with an acceptable daily intake (ADI) of 500 microgram/day. A review of the published dermatological literature indicates a good level of tolerance to the skin. A NOAEL is not applicable as the material is used in accordance with IFRA Guidelines. Based on the above and a long history of safe use lavender oil is considered safe in the current application.

REFERENCES

1. Data on file Innovant Research Ltd.

TOCOPHEROL CAS: 59-02-9; 2074-53-5 (dl-alpha) Tocopherol is naturally occurring vitamin E and is a naturally occurring food ingredient. The oral LD 50 in the rat is low at >5g/kg. Skin irritation data for primary irritation in the rabbit is rated as “non-irritant” as also is rabbit eye irritation data. In a Guinea pig maximisation study for sensitisation, no sensitising potential was seen at a 20% dilution. Clinical published data has found tocopherol acetate to have a low-grade sensitisation potential in use, although this is probably concentration dependent and not likely to occur as used in this formulation. No photo allergy or photo toxicity data is available, although formulations containing this ingredient have been tested and shown not to have photo-reactive potential. In an Ames test for mutagenicity, tocopherol acetate was found not to be mutagenic. In a 4-week systemic toxicity study to both dogs and rats dosed orally at up to 20,000 ppm in the diet there were no adverse effects seen.

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Based on the need for tocopherol in the diet, this material is considered unlikely to be a carcinogen or a reproductive-toxin at typical in use levels. An upper limit (UL) as 300mg/day (ie 5 mg/kg). Based on a 100x safety factor this is derived from a NOAEL of 500 mg/kg) (4) In summary this ingredient may be regarded as safe in skin care products as currently used.

REFERENCES

1. CIR Compendium 2010. 2. IJT,21 (S3):51-116,2002 3. Data on file Innovant Research. 4. Opinion of the Scientific Committee on Food on the Tolerable Upper Intake

Level of Vitamin E (expressed on 4 April 2003) SCF/CS/NUT/UPPLEV/31 Final 23 April 2003

ANTHEMIS NOBILIS FLOWER OIL

CAS: 84649-86-5 / 8015-92-7 Chamomile has a traditional use in herbal medicine. The flowers have been known for their healing properties since earliest times (AD 50). The constituents have anti-inflammatory, healing, anti-bacterial and cleansing properties. The important actives are the azulenes of the essential oil, including chamazulene and spathulenol. Among the sesquiterpenes the bisaboloids are recognized as anti-inflammatories. There are also several flavone glycosides. In a review of the safety of Chamomile by BIBRA (1), Chamomile oils were considered as non-irritant to the skin of humans, mice or pigs, although moderate irritation occurred when they were applied to rabbit skin. Inhalation of chamomile dust apparently caused irritation of the respiratory tract and eyes in tea factory works. The acute oral and dermal toxicity of chamomile oils was low in rats and rabbits respectively. Repeated injections of chamomile oil caused liver enlargement in rats. In a study on bacteria exposed to Roman chamomile oil, there was no evidence of mutagenicity (in an Ames assay) or of DNA damage (1). Although there area few isolated reports of skin sensitization, the incidence is considered to be very low considering the widespread use of the extract over many years. A Danish study of 686 patients with skin allergies only a low incidence to chamomile was reported on patch testing; and the chamomile extract did not elicit a photo-toxic response on patch testing (2). Chamomile extracts are considered to be non-irritant and non-sensitising, and are safe as used in the current formulation. Based on the reported NOAEL for bisabolol, the main active, a NOAEL of 200mg/kg /day is established (3). Chamomile flower oil is considered safe as used in the current formulation.

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REFERENCES

1. Chamomile, BIBRA Working Group (1992), 7p 2. Paulsen E et al, Compositae dermatitis in a Danish Dermatology

Department in One Year. Contact Dermatitis, 29 (1), 1993, 6-10. 3. Andersen A, Final Report on the Safety Assessment of Bisabol, Int J Toxicol,

18 (3), 1999, 33-40

LINALOOL CAS: 78-70-6 EINECS: 201-134-4 Linalool is a component of several essential oils, with lavender oil containing approx 45% linalool. The IFRA Guidelines state that linalool should only be used when the level of peroxides is kept to the lowest practical level. The IFRA Guidelines note that pure linalool is not a sensitizer while hydroperoxides and other oxidation products have shown sensitizing properties. It is recommended by IFRA to add antioxidants at the time of production of the raw material. The addition of 0.1% BHT or alpha- tocopherol for example has shown great efficiency. The maximum peroxide level for products in use should be 20 mmol/l. Linalool is considered safe as used in the current formulation. REFERENCES: M.Skold, A.Borje, M.Matura and A.-T.Karlberg., 2002. Studies on the autoxidation and sensitizing capacity of the fragrance chemical linalool, identifying a linalool hyperperoxide. Contact Dermatitis, 46(5), 267-272. M.Skold, A.Borje, M.Matura and A.-T.Karlberg., 2002. Sensitization studies on the fragrance chemical linalool, with respect to auto-oxidation. Contact Dermatitis, 46 (Suppl. 4), 20.

LIMONENE CAS: 5989-27-5 EINECS: 227-813-5 Limonene is a major component of citrus extracts which are used as both foods and as flavours and in the fragrance industry. D-limonene is one of the most common terpenes in nature. It is a major constituent in several citrus oils (orange, lemon, mandarin, lime, and grapefruit). D-limonene is listed in the Code of Federal Regulations as generally recognized as safe (GRAS) for a flavoring agent and can be found in common food items such as fruit juices, soft drinks, baked goods, ice cream, and pudding. D-limonene is considered to

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have fairly low toxicity. It has been tested for carcinogenicity in mice and rats. Although initial results showed d-limonene increased the incidence of renal tubular tumors in male rats, female rats and mice in both genders showed no evidence of any tumor. Subsequent studies have determined how these tumors occur and established that d-limonene does not pose a mutagenic, carcinogenic, or nephrotoxic risk to humans. In humans, d-limonene has demonstrated low toxicity after single and repeated dosing for up to one year. Being a solvent of cholesterol, d-limonene has been used clinically to dissolve cholesterol-containing gallstones. Because of its gastric acid neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD). D-limonene has well-established chemopreventive activity against many types of cancer. Evidence from a phase I clinical trial demonstrated a partial response in a patient with breast cancer and stable disease for more than six months in three patients with colorectal cancer. It is a requirement that the grade of Limonene used meets Cosmetics Directive specification for minimal levels of peroxides. The use of limonene in the current product is considered safe. REFERENCE

1. Sun J, D-Limonene: safety and clinical applications. Altern Med Rev. 2007 Sep;12(3):259-64.

GERANIOL CAS: 106-24-1 EINECS: 203-377-1 RIFM Summaries: Sensitization Potency Estimation Based on Weight of Evidence LLNA weighted mean EC3 values (µg/cm2) 3525 Potency Classification Weak Human Data NOEL – HRIPT (induction) (µg/cm2) 11811 NOEL – MAX (induction) (µg/cm2) N/A LOEL1 (induction) (µg/cm2) N/A REXPAN Rationale / Conclusion: The RIFM Expert Panel reviewed the critical effect data for geraniol and, based on the weight of evidence, established the No Expected Sensitization Induction Level (NESIL) as 11800 µg/cm². They recommend the limits for the 11 different product categories, which are the acceptable use levels of geraniol in the various product categories. These were derived from the application of the exposure-based quantitative risk assessment approach for fragrance ingredients, which is detailed in the QRA Expert Group Technical Dossier of June 22, 2006. Geraniol is safe as used in the current application REFERENCES:

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Isola, D., Lalko, J., 2001a. Vehicle effects in the murine local lymph node assay (LLNA). American College of Toxicology Meeting, November 4-7. Washington DC. Isola, D., Lalko, J., 2001b. Vehicle effects in the murine local lymph node assay (LLNA). International Journal of Toxicology, 20(6), 401. Gerberick, GF. et. al. (2001) Contact allergenic potency: Correlation of human and local lymph node assay data. American Journal of Contact Dermatitis, 12(3), 156-161. QRA Expert Group (AM Api, DA Basketter, PA Cadby, M-F Cano, G Ellis, GF Gerberick, P Griem, PM McNamee, CA Ryan and R Safford), Dermal Sensitization Quantitative Risk Assessment (QRA) for Fragrance Ingredients, Technical Dossier, March 15, 2006, http://www.rifm.org/pub/publications.asp. RIFM (Research Institute for Fragrance Materials, Inc.), 2004a. Repeated Insult Patch Test on Geraniol. RIFM report number 46888, August 9a. (RIFM, Woodcliff Lake, NJ, USA). RIFM (Research Institute for Fragrance Materials, Inc.), 2004b. Local Lymph Node Assay on Geraniol. RIFM report number 43812, December 17. (RIFM, Woodcliff Lake, NJ, USA).

SPECIAL ASSESSMENT FOR INFANTS It is a requirement of the Regulation that there is a special Assessment for infant products. This is given below. In assessing the safety for infants and children consideration has been given to several factors including the potential for accidental oral ingestion and the potential for dermal irritation, sensitisation and penetration with possible systemic effects. Accidental Oral Ingestion The potential of accidental oral ingestion is related to the problem that infants and children are recognised to eat or drink cosmetic products. It is therefore important that product formulations have a very low potential for acute toxic effects especially in infants where the bodyweight is much less than an adult. Based on the known acute toxicity to rodents of the components of the formulation, it is estimated that the formulation will have an LD50 of >10gm/kg bodyweight. This would indicate a very low order of acute oral toxicity. An infant aged 1 year and typically of weight 10kg, would not be harmed by oral ingestion of 100 gm of baby nappy cream. The potential for systemic adverse effects has been considered. Ingredients that have the potential for intestinal absorption are readily metabolised and excreted and are not considered likely to have systemic toxic effects.

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Dermal Penetration and Systemic Effects Consideration has been given to the potential for dermal penetration of the ingredients of the formulation. It is recognised that infants are not the same as small adults in assessing the safety and toxicity potential of materials. In particular the infant has a much greater surface area/ bodyweight ratio than an adult, resulting in a greater potential for systemic toxicity. It is recognised that pre-term (premature) infants have the potential for greater dermal penetration of any cosmetic ingredient as a result of thinner and immature skin. In addition, although the skin permeability of full-term infants is essentially identical to that of adults, occlusion of the scrotum in males and of damaged skin in the diaper area, may have the potential to increase dermal absorption of certain cosmetic ingredients. It is considered that the ingredients are readily metabolised where there is dermal absorption and are not likely to have adverse systemic toxicity. Local Dermal Effects, Irritation and Sensitisation Potential This assessment includes a review of the likely irritancy and sensitisation potential of each of the ingredients of the formulation. It is considered that there is an extremely low potential for dermal irritancy or allergenicity. It can therefore be concluded that the formulation is safe for the intended use and that there is no significant risk of irritancy or allergy.

PART A SAFETY SUMMARY In reviewing the safety and toxicity profile of the ingredients used and their history of safe use, it is concluded that there are no likely safety hazards from normal use of this product and when used as directed or from foreseeable conditions of misuse. The product is considered safe for sale in EU Countries. Dated: March 13th 2014.

Dr. JOHN HOPKINS BSc. PhD. MSB. C Biol. Safety Assessor

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PART B SAFETY ASSESSMENT SUMMARY According to EC1223-2009. SUMMARY Reasoning: This Assessment has considered the safety and toxicological profile of all raw materials and any trace components present. Consideration has been given to parameters of weight of evidence (particularly for long established materials) and also published toxicity data for NOAEL’s allowing calculations of Margins of Safety, based on established use of the product. Margins of Safety have been calculated to confirm safety from a systemic aspect. Assessment for local effects, including skin and eye irritation, dermal sensitization and photoallergenicity was evaluated based on established safe use for dermal safety, derived from manufacturers data, and data published by CIR and also in the public domain. Assessment for systemic effects including target organ toxicity, effects on maternal and reproductive toxicity and a review of genotoxic and carcinogenic safety was evaluated based on established safe use and from manufacturers data, and data published by CIR and also in the public domain. Established use and consumer exposure is derived from data produced by SCCS in Notes of Guidance. The above formulation is based on known ingredients with history of safe use in cosmetic products. The Assessment has considered the safety of the individual ingredients both separately and in combination to produce the final formulation. A review of the data relating to raw material purity indicates that all materials and packaging have a satisfactory physical and chemical profile. There are no unacceptable levels of prohibited substances or impurities. The product is deemed to have adequate stability. The product is considered to be adequately preserved. The finished product specification is considered to meet current standards for Microbial quality. This Safety Assessment has taken account of:

1. The Quantitative/Qualitative composition of the product, 2. The intended and reasonably foreseeable use of the product, 3. Margins of Safety for all ingredients considered both individually and in combination. 4. Standards of good manufacturing practice 5. A consideration of potential interactions of substances in the formulation.

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6. A consideration of the stability of the formulation.

Conclusion In reviewing the safety and toxicity profile of the ingredients and their history of safe use, raw material standards and labelling, it is concluded that there are no likely safety hazards from normal use of this product and when used as directed or from foreseeable conditions of misuse. The product is considered safe for sale in EU Countries. Dated: March 13th 2014.

Dr. JOHN HOPKINS BSc. PhD. MSB. C Biol. Safety Assessor

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The Elms ! Oxford Rd ! Chieveley ! Newbury ! RG20 8RT! United Kingdom

Telephone: +44 1635 248830 Fax: +44 1635 247206 Email: [email protected]

JOHN HOPKINS

CURRICULUM VITAE

Academic Qualifications. BSc (Honours) Biochemistry/Chemistry. University of St Andrews, UK. PhD Pharmacology/Toxicology. University of Dundee, UK. Membership of Societies Member of Institute of Biology. MSB. C Biol. Membership number 004007934 A Founder member of British Toxicology Society 1979. Member Company of CTPA Qualifications as a professional Toxicologist in respect of Directive 93/35/EEC Art 7a(1)(e) and Regulation EC 1223/2009 The Diploma C Biol. is within the meaning of Regulation 2 (1) of the European Communities (Recognition of Professional Qualifications) Regulations, 1991(b). The holder is recognised under European Community law to be a Safety Assessor for products under the Cosmetics Directive. Relevant Experience 2000- current, Director and Principal of Innovant Research Ltd, an independent Consultancy in Toxicology, Risk Assessment and Product Safety. Emphasis on the safety of chemicals, cosmetics and medical device products.

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1976-1999. Employed by Johnson and Johnson. Several positions from Toxicology head, Head of Medical Dept, and R&D Director in UK and Director in the USA. 1974-1976. Toxicologist for Smith Kline Beecham Pharmaceuticals, Responsible for antibiotic safety program. At Smith Kline Beecham Pharmaceuticals, developed methods for rapid evaluation of potential renal damage due to cephalosporin and penicillin antibiotics. Also developed methods to assess safety of anti-depressant medicines. At Johnson & Johnson, was responsible for safety of both medical devices and skin and hair care products in the European business. Developed methods for cell culture evaluation of shampoo and detergent products as an alternative to the rabbit eye test. Also cell culture methods for safety evaluation of implantable medical devices. Also developed methods for human dermal evaluation of skin-care products to assess for potential irritation and sensitisation. Developed methods for safety evaluation of bone repair plates, carbon fibre and polyester ligament repair systems, prior to human clinical studies. In positions of Research Director in Johnson & Johnson, was responsible for new product development for both adult and infant care areas of business. PUBLICATIONS Hopkins J and Tudhope GR. Glutathione peroxidase in Human Red Cells in Health and Disease. British J. Haematol. 25:563 (1973). Hopkins J and Tudhope GR. Red Cell Glutathione in Anaemia. Scottish Medical Journal 18:177 (1973) Hopkins J and Tudhope GR. Glutathione Peroxidase deficiency with increased susceptibility to erythrocyte Heinz Body formation. Clin Sci. & Mol.Med.47: 643 (1974) Tudhope GR and Hopkins J. Plasma tocopherol levels and the susceptibility of Erythrocytes to Heinz Body formation. Clin.Sci.& Mol.Med. 46: 635 (1974) Tudhope GR and Hopkins J. Lipid Peroxidation in Erythrocytes. Acta Haematologica 51: 29 (1974) Hopkins J and Tudhope GR. The effects of Drugs on erythrocytes in vitro. Brit. J. Clin. Pharmac. 1:191 (1974) Hopkins J. Baby Powder- exploring the Myths and Realities. Brit.J. Midwifery 9 (9) 545-547 (2001).

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Hopkins J. The safe and effective use of baby powder. RCM Midwives Journal 4 (9) 285-286 (2001). Bertin C, Zunino H, Pittet J-C, Beau P, Pineau P, Massonneau M, Robert C, Hopkins J. A double-blind evaluation of the activity of an anti-cellulite product containing retinol, caffeine and ruscogene by a combination of several non-invasive methods. J.Cosmet. Sci 52, 199-210 (2001). Hopkins J., Baby Powder – Dusting off the Myths. Chemist & Druggist, 15th Dec 2001. pp 32-33 (2001) Hopkins J. The Safe use of Fragrance in Cosmetics. Chemist & Druggist, 3rd August.2002, p 30 (2002). Hopkins J. Essentials of newborn skin care. Brit. J. Midwifery 12 (5) 314-317. (2004). PUBLISHED PROCEEDINGS Meeting of the Scottish Society for Experimental Medicine. Reported as Hopkins J and Tudhope GR. Erythrocyte Glutathione Peroxidase in patients with anaemia. Scot. Med. J. 17:376 (1972). Meeting of the Scottish Society for Experimental Medicine. Reported as Hopkins J and Tudhope GR. Vitamin E and the Red Blood Cell. Scot.Med.J.18: 216 (1973) PATENTS Application filed 1998: Composition for the Treatment of Prickly Heat Rash in Infants. Application filed 1999: Composition for the treatment of seborrheic dermatitis and dandruff in infants and children. Application filed 1999: Composition for a body wash with skin moisturising benefits. POSTERS /ORAL PRESENTATIONS Johnson and Johnson Skin Care Symposium, Hamburg, Germany. 1992. Role of D- Panthenol and Phytantriol when combined to increase the strength of human hair (poster). Hopkins 1992. Johnson & Johnson Skin Care Symposium, New Brunswick, USA. Role of Zinc oxide in the treatment of Nappy rash, studies in a rat model and human infant evaluation (poster). Hopkins J. 1994.

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European Soc. Dermatology. June 1999, London. Efficacy of the association of retinol and lactose and hydroxy acid on the signs of skin ageing. Clinical study with comparison to placebo (poster). Bertin C, Hopkins J. 21st Congress of International Federation of the Societies of Cosmetic Chemists, Berlin 2000. An original in-vivo method using uv spectroscopy to evaluate the performance of a new broadband uv filter (poster) Issachar N, Bruere V, Cambon M, Castelli D, Robert C, Hopkins J. 2000. Congress of the Polish Neonatal Society, Mikolajaki, Poland, 2001. Infant Skin and its special caring needs (lecture). Hopkins J. 2001. COMMITTEE MEMBERSHIPS AND TEACHING A Member of several Trade Association technical committees including CTPA (UK Trade Association) and Colipa (European Trade Association). Member of Colipa Committee, Brussels to present support to European Commission SCCNFP for use of salicylic acid at higher-than-preservative amounts in skin and hair care products (2001-2002). Member of Colipa Committee to present data to EU Scientific Steering Committee (SSC) for approval of azoles in non-drug applications in skin and hair care (2003). Member of Colipa Zinc Oxide task force to present safety data and support to European Commission SCCNFP for continued use of zinc oxide in skin care products (1999-2004). Member of Colipa Cosmetovigilance Task Force, Brussels 2005-06. Member of UK CTPA Scientific Advisory Committee (1999-current). Member of UK CTPA Toxicology Advisory Panel (2000- current) Member of COLIPA Committee, Brussels, representing CTPA (2010 – 2012) to draft Colipa Guidelines for format of Safety Assessment/Safety Report under new legislation Regulation EC 1223/2009 coming into effect June 2013. Lecturer at University of Surrey MSc Course in AppliedToxicology 2012.

Dated: February 20th 2013.

Documents

PRODUCT INFORMATION FILEbritishbeauty.london/pdf/nappy-balm-30ml-50ml-CU00068641-CU00009903.pdf · The calculation of Margin of Safety (MOS): NOAEL SED NOAEL data is derived from