1. Novel databases for exposure to cosmetics and personal care products Damien Comiskey, Mathematical Models and Statistics Creme Global 13 th October 2014 Expert Models for Decision Makers TM G L O B A L

2. Aggregate Exposure Modelling

9. Daily Aggregate Exposure

10. Population Exposure Modelling

11. Databases Required  Frequency of use  Amount per use  Concentration of fragrance  Surface areas  Body weights  Retention  Penetration

12. Frequency of Use

13. Survey Demographics Age groupsEUUS MaleFemaleMaleFemale 18-24149025574121228 25-34298030786031954 35-49423047638382200 50-64321029667481541 65+560375289424 Total124701373928907347

14. Online Consumption Diaries

15. Personal Care Products Mass Market Prestige Other Body Lotion Deodorant/Anti-Perspirant Spray Deodorant/Anti-Perspirant NonSpray Body Spray Deodorant Toothpaste Mouthwash Oral Care Lipstick Liquid/Makeup Foundation Hair Styling Products (excl. Spray) Cosmetic Styling Eau de Toilette Eau de Parfum After Shave / Cologne (Splash-on) Hydroalcholics Showergel / Body Wash Shampoo Rinse-off Conditioner Shower Products Face Moisturizer Hand Cream Moisturizers

16. Application Sites Moisturizers Face+Eyes+Lips Mouth Chest Stomach Intimate Parts Neck Arms+Wrists Underarms Hands+Palms Legs Feet Scalp Back Bottom

17. Bodyweight and Height US  2007-2008 NHANES survey Bodyweight and height data for 8,861 US subjects EU  NHANES data scaled based on EU country average weights and heights

18. Surface Area Calculations Dubois Formula

19. Surface Area Calculations Body PartSurface Area Scalp1/2 Head Neck1/10 Trunk Chest1/4 Trunk Stomach1/5 Trunk Back3/10 Trunk ArmsArms – (1/4 Hands) Wrists1/4 Hands Palms1/2 Hands Intimate parts1/100 Total Body Body PartSurface AreaReference Face1/2 Head – 28.8cm 2 Api et al. (2008); 28.8 cm 2 refers to combined surface areas of eyes and lips Eyes24cm 2 Bremme et al. (2003) Lips4.8cm 2 Ferrario et al. (2000) Mouth212cm 2 Collins and Dawes, (1987), Ferrario et al. (2000) Behind ears36cm 2 Estimated based on expert judgement Underarms200cm 2 Bremme et al. (2003) Relative Absolute

20. Amount used

21. Fragrances and Mixtures

22. Concentration in Product = Level 1 x Level 2

23. Retention Product Dermal Retention Factor (%) Ingestion Factor (%) Body lotion (mass, prestige, or other)100- Deodorant spray23.5- Deodorant roll-on100- Body spray100- Toothpaste105* Mouthwash110* Lipstick100- Liquid makeup foundation100- Hair styling10- Eau de toilette100- Eau de parfum100- Aftershave100- Shower gel1- Shampoo1- Rinse-off conditioner1- Face moisturiser100- Hand cream100-

24. Aggregate Exposure Modelling

26. Combining Databases  Pick a subject in the diary

27. Combining Databases  Pick a subject in the diary  Find their age, gender and country

28. Combining Databases  Pick a subject in the diary  Find their age, gender and country  Select their height and weight –calculate their body surface areas

29. Combining Databases  Pick a subject in the diary  Find their age, gender and country  Select their height and weight –calculate their body surface areas  Determine which products they use in a day and how often

30. Combining Databases  Pick a subject in the diary  Find their age, gender and country  Select their height and weight –calculate their body surface areas  Determine which products they use in a day and how often  For each product randomly select: –Amount based on demographic –Fragrance concentration

31. Calculating Exposure  Calculate their daily aggregate exposure  Repeat for all subjects in survey

32. Lower-end consumer Higher-end consumer

33. Lower-end consumer Higher-end consumer Maximum Consumer Exposure

34. Lower-end consumer Higher-end consumer 95 th Percentile Consumer Exposure

35. Lower-end consumer Higher-end consumer Median Consumer Exposure

36. Lower-end consumer Higher-end consumer Average Consumer Exposure

37. Analysing the Databases  Product Use, Co-Use and Non-use statistics –per subject –Per occasion  Frequency of use

38. Per subject Product Combination% of Subjects DeoRollOn, Toothpaste, Shampoo6.19% DeoRollOn, Toothpaste, Shampoo, Showergel2.53% DeoRollOn, Toothpaste, AfterShave, Shampoo2.31% DeoRollOn, Toothpaste1.53% Toothpaste, Shampoo1.24% DeoSpray, Toothpaste, Shampoo1.21% DeoRollOn, Toothpaste, Mouthwash, Shampoo1.18%

39. Per occasion Product Combination% of Occasions Toothpaste25.60% Toothpaste, Mouthwash4.38% DeoRollOn, Toothpaste3.99% DeoRollOn3.75% Shampoo2.84% Showergel2.28% Toothpaste, FaceMoisturizer2.01% DeoRollOn, Toothpaste, Shampoo1.96%

40. Body Lotion Mass vs. Prestige (EU+US) Consumer TypeTotal Population Gender: Male Only Gender: Female Only Age: 18-34 Only Age: 35-49 Only Age: 50+ Only Non-Consumers 80.91%92.26%70.08%81.96%81.02%79.93% Consumers: Mass Only 10.87%5.19%16.28%10.00%10.63%11.79% Consumers: Prestige Only 2.99%0.47%5.40%2.94%3.12%2.93% Consumers: Mass and Prestige 0.67%0.03%1.28%0.71%0.89%0.44% Consumers: Other 4.57%2.05%6.96%4.39%4.34%4.91%

41. Co-use statistics on Per Subject basis, for Deodorants, and for the Total Population Product Combination% of Subjects% (Cumulative) DeoRollOn59.39% DeoSpray17.21%76.60% (no product)10.04%86.65% DeoRollOn, BodySpray5.55%92.19% DeoSpray, BodySpray4.25%96.44% DeoSpray, DeoRollOn2.07%98.50% BodySpray1.05%99.55% DeoSpray, DeoRollOn, BodySpray0.45%100.00%

42. Frequency of Use Interestingly, the usage frequency of Face Moisturizer is very similar to that of Mouthwash. Again, distinct modes are seen at ~1, ~7 and ~14 uses per week.

43. Frequency of Use In the 18-34 Age Group (below), the mean usage frequency for males is 4.53 times per week, and for females it is 3.85 times per week.

44. Thank you Damien Comiskey, CEO 13 th October 2014 Expert Models for Decision Makers TM G L O B A L

45. Thank you Damien Comiskey, CEO 13 th October 2014 Expert Models for Decision Makers TM G L O B A L

46. Product category Co-use Product Combination % of Subjects Deodorant, Oral Care, Shower Products 19.22% Deodorant, Oral Care, Hydro-alcoholics, Shower Products 11.78% Deodorant, Oral Care, Cosmetic Styling, Hydro-alcoholics, Shower Products, Moisturizers 8.07% Deodorant, Oral Care, Cosmetic Styling, Shower Products 6.77% Deodorant, Oral Care, Cosmetic Styling, Hydro-alcoholics, Shower Products 5.36% Deodorant, Oral Care, Cosmetic Styling, Shower Products, Moisturizers 4.20%

47. Product Category Product Combination % of Subjects Body lotion (no product) 81% Body lotion (mass) 11% Body lotion (other) 5% Body lotion (prestige) 3% Body lotion (mass), body lotion (prestige) 1% Deodorant Deodorant roll-on 59% Deodorant spray 17% (no product) 10% Deodorant roll-on, body spray 6% Deodorant spray, body spray 4% Deodorant spray, deodorant roll-on 2% Body spray 1% Deodorant spray, deodorant roll-on, body spray <1% Oral care Toothpaste 66% Toothpaste, mouthwash 27% (no product) 5% Mouthwash 2%

68. Benzaldehyde Cinnamaldehyde Limonene

76. Revolution in Safety Assessment Big DATA Statistical Analyses Intuitive Software Cloud Computing Aggregate Exposure Expert Models

78. New Assessment Benzaldehyde

79. New Assessment Benzaldehyde

80. New Assessment Benzaldehyde

81. New Assessment Benzaldehyde

82. New Assessment Benzaldehyde

83. New Assessment Benzaldehyde

84. New Assessment Benzaldehyde

85. New Assessment Benzaldehyde

86. Example - Vanillin Vanillin – Approximate relative contribution to P95 aggregate exposure

87. Example - PEA

88. PEA – Approximate relative contribution to P95 aggregate exposure

89. Inhalation Exposure – Limonene

90. Ingestion Exposure - Limonene

91. Dermal Exposure per Surface Area (BarSoap) - Limonene

92. Total Exposure (per unit BW) - Limonene

94. Revolution in Safety Assessment Big DATA Expert Models Statistical Analyses Intuitive Software Cloud Computing Aggregate Exposure

95. Revolution in Safety Assessment Big DATA Expert Models Statistical Analyses Intuitive Software Cloud Computing Aggregate Exposure

96. Thank you Damien Comiskey, Project Manager, Modelling and Statistics 13 th October 2014 Expert Models for Decision Makers TM G L O B A L

97. Thank you Cronan McNamara, CEO 20 th November 2013 Expert Models for Decision Makers TM G L O B A L

98. Thank you Cronan McNamara, CEO 20 th November 2013 Expert Models for Decision Makers TM G L O B A L

99. Creme RIFM Model Options RIFM Members Only

100. RIFM Model - Options

101. Level 0 User – Read Only

102. Level 1 User – Summary Statistics Graphs

104. Level 2 User – Create Tables

111. Level 3 User – Upload Large Data Tables; Advanced Features

118. Pricing Structure – Per Annum

119. Thank you Cronan McNamara, CEO 20 th November 2013 Expert Models for Decision Makers TM G L O B A L

120. Thank you Cronan McNamara, CEO 20 th November 2013 Expert Models for Decision Makers TM G L O B A L

121. Thank you Cronan McNamara, CEO 20 th November 2013 Expert Models for Decision Makers TM G L O B A L

122. EU amounts data Hall et al. (2007)  496 subjects: EU, M/F, aged 17-74  Empirical data: each subject’s average amount per use  Body Lotion  Deodorant Spray & Roll-on  Toothpaste  Lipstick  Shampoo  Face moisturizer

123. EU amounts data Hall et al. (2011)  501 subjects: EU, M/F, aged 17-74  Empirical data: each subject’s average amount per use Mouthwash  Liquid makeup foundation  Hair styling  Shower gel  Hand cream

124. US amounts data Loretz et al. (2005)  Summary statistics and distribution fit: average amount per use 360 subjects: US, F, aged 19-65