The purpose of the Creme RIFM model is to provide an aggregate systemic and dermal exposure assessment for fragrance compounds.

1. Aggregate Exposure Assessment for
the Safety Evaluation of Fragrance
Materials
Cian O’ Mahony, Chief Science Officer

2. Aggregate Exposure for Fragrances

3. Aggregate Exposure

4. Data Sources
Creme RIFM

5. Aggregate Exposure Modelling
𝐴𝑔𝑔 𝐸𝑥𝑝 =
𝐹𝑟𝑒𝑞𝑢𝑒𝑛𝑐𝑦 × 𝐴𝑚𝑜𝑢𝑛𝑡 × 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝐴𝑟𝑒𝑎

6. Aggregate Exposure Modelling
𝐴𝑔𝑔 𝐸𝑥𝑝 =
𝐹𝑟𝑒𝑞𝑢𝑒𝑛𝑐𝑦 × 𝐴𝑚𝑜𝑢𝑛𝑡 × 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝐴𝑟𝑒𝑎

7. Aggregate Exposure Modelling
𝐴𝑔𝑔 𝐸𝑥𝑝 =
𝐹𝑟𝑒𝑞𝑢𝑒𝑛𝑐𝑦 × 𝐴𝑚𝑜𝑢𝑛𝑡 × 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝐴𝑟𝑒𝑎

8. Aggregate Exposure Modelling
𝐴𝑔𝑔 𝐸𝑥𝑝 =
𝐹𝑟𝑒𝑞𝑢𝑒𝑛𝑐𝑦 × 𝐴𝑚𝑜𝑢𝑛𝑡 × 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝐴𝑟𝑒𝑎

9. Aggregate Exposure Modelling
𝐴𝑔𝑔 𝐸𝑥𝑝 =
𝐹𝑟𝑒𝑞𝑢𝑒𝑛𝑐𝑦 × 𝐴𝑚𝑜𝑢𝑛𝑡 × 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝐴𝑟𝑒𝑎

10. Aggregate Exposure Modelling
𝐴𝑔𝑔 𝐸𝑥𝑝 =
𝐹𝑟𝑒𝑞𝑢𝑒𝑛𝑐𝑦 × 𝐴𝑚𝑜𝑢𝑛𝑡 × 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝐴𝑟𝑒𝑎

11. Aggregate Exposure Modelling
𝐴𝑔𝑔 𝐸𝑥𝑝 =
𝐹𝑟𝑒𝑞𝑢𝑒𝑛𝑐𝑦 × 𝐴𝑚𝑜𝑢𝑛𝑡 × 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 × 𝑃𝑒𝑛𝑒𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝐵𝑜𝑑𝑦 𝑊𝑒𝑖𝑔ℎ𝑡

12. Daily Aggregate Exposure

13. Population Exposure Modelling

14. Frequency of Use

15. Survey Demographics
Age groups EU US
Male Female Male Female
18-24 1490 2557 412 1228
25-34 2980 3078 603 1954
35-49 4230 4763 838 2200
50-64 3210 2966 748 1541
65+ 560 375 289 424
Total 12470 13739 2890 7347

16. Online Consumption Diaries

17. •Mass Market
•Prestige
•Other
Body Lotion
•Deodorant/Anti-Perspirant Spray
•Deodorant/Anti-Perspirant NonSpray
•Body Spray
Deodorant
•Toothpaste
•MouthwashOral Care
•Lipstick
•Liquid/Makeup Foundation
•Hair Styling Products
•Hairspray
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 CreamMoisturizers
•Liquid hand soap
•Bar SoapSoaps

18. Application Sites

19. 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
Bodyweight and Height

20. Surface Area Calculations
𝑆𝐴 = 𝑎 × 𝑊 𝑏
× 𝐻 𝑐
Dubois Formula
→ head, trunk, arms, hands,
legs and feet

21. Surface Area Calculations
Body Part Surface Area
Scalp 1/2 Head
Neck 1/10 Trunk
Chest 1/4 Trunk
Stomach 1/5 Trunk
Back 3/10 Trunk
Arms Arms – (1/4 Hands)
Wrists 1/4 Hands
Palms 1/2 Hands
Intimate parts 1/100 Total Body
Body Part Surface Area Reference
Face 1/2 Head – 28.8cm2 Api et al. (2008); 28.8 cm2 refers to combined surface areas of eyes and lips
Eyes 24cm2 Bremme et al. (2003)
Lips 4.8cm2 Ferrario et al. (2000)
Mouth 212cm2 Collins and Dawes, (1987), Ferrario et al. (2000)
Behind ears 36cm2 Estimated based on expert judgement
Underarms 200cm2 Bremme et al. (2003)
Relative
Absolute

22. • Europe → COLIPA (Hall et al., 2007; 2011)
• USA → CTFA (Loretz et al., 2005; 2006; 2008)
• Hydro alcoholics → Tozer et al. (2004)
Amount Used

23. Retention
Product Dermal Retention Factor (%)
Body lotion (mass, prestige, or other) 100
Deodorant spray 23.5
Deodorant roll-on 100
Body spray 100
Toothpaste 10
Mouthwash 1
Lipstick 100
Liquid makeup foundation 100
Hair styling 10
Eau de toilette 100
Eau de parfum 100
Aftershave 100
Shower gel 1
Shampoo 1
Rinse-off conditioner 1
Face moisturiser 100
Hand cream 100

24. Aggregate Exposure Modelling
𝐴𝑔𝑔 𝐸𝑥𝑝 =
𝐹𝑟𝑒𝑞𝑢𝑒𝑛𝑐𝑦 × 𝐴𝑚𝑜𝑢𝑛𝑡 × 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 × 𝑃𝑒𝑛𝑒𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝐵𝑜𝑑𝑦 𝑊𝑒𝑖𝑔ℎ𝑡

25. Concentrations in Products
Fragrances

26. Fragrance Concentration

27. Fragrance Concentration
Fragrance
Manufacturers

28. Fragrance Concentration
Consumer Product
Companies

29. Fragrance Concentration

30. SUBSTANCE
CONCENTRATIONS

32. Exposure =
𝐴𝑚𝑜𝑢𝑛𝑡 ×𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 ×𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛×𝑃𝑒𝑛𝑒𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝐵𝑜𝑑𝑦 𝑊𝑒𝑖𝑔ℎ𝑡
Aggregate Exposure Modelling

33. The Model
Creme RIFM

45. Daily
Average

46. Acute

48. Mean

51. Routes of Exposure
Inhalation Ingestion Dermal

52. Fragrance
Cramer Class
Reference
Dose
Concentration
Data
Aggregate
Exposure
Linking with TTC

53. Software

58. New Assessment
Benzaldehyde

59. New Assessment
Benzaldehyde

60. • Risk Assessment
– Determine high-risk products or application sites
– Assess safety of contaminants or by-products
• Assigning safe concentrations
• Product Development
– Bringing new fragrances/substances/products to market
– Integrate with existing market data
Predictive Uses

61. Optimisation Model
Max Allowed Exposure

62. Max Allowed Exposure
Optimisation Model

63. • Updated survey data: 2013 – 2014
• New countries: Italy and Poland
• New product categories:
– Eye cream
– Facial washes/cleansers/toners
– Makeup remover
– Shaving preps
• New age groups: 10 – 17 year olds
• Household cleaning products
• Browser-based version
Future Directions and Expansions

64. • Regulatory Toxicology and Pharmacology:
– Novel database for exposure to fragrance ingredients in cosmetics and
personal care products
• Comiskey et al 2015
– Use of an aggregate exposure model to estimate consumer exposure to
fragrance ingredients in personal care and cosmetic products
• Safford et al 2015
– Application of the expanded Creme RIFM consumer exposure model to
fragrance ingredients in cosmetic, personal care and air care products
• Safford et al 2017
References

65. Expert Models for Decision Makers
Thank You
Cian O’ Mahony, Chief Science Officer
cian.omahony@cremeglobal.com
@CianOnData

66. Expert Models for Decision Makers
Thank You
Cian O’ Mahony, Chief Science Officer
cian.omahony@cremeglobal.com
@CianOnData

67. Expert Models for Decision Makers
Thank You
Cian O’ Mahony, Chief Science Officer
cian.omahony@cremeglobal.com
@CianOnData