exposure data: rifm's human health safety assessment
TRANSCRIPT
Exposure Data: RIFM’s Human Health Safety Assessment
Anne Marie Api, PhD Vice President, Human Health Sciences
RIFM Exposure Webinar May 8, 2013
General Safety Assessment Principles Hazard identification
Inherent ability of a material to cause an adverse effect Dose-response assessment
Addresses derivation of a NOEL Establishes relationship between level of exposure and
probability that an adverse event will occur Exposure assessment
Uses habits and practices data and established human parameters data
Risk Characterization Placement of identified hazard in context of human
experience
2
Safety Assessment using Margin Of Exposure (MOE )
MOE compares the magnitude of NOAEL (No Observed Adverse Effect Level) with that of Human Exposure
MOE needs to be compared with product of Uncertainty Factors (UF)
3
If MOE ≤ UFs Risk If MOE > UFs No Risk
Systemic Exposure to Fragrance Materials
Current Method*: Cumulative dermal exposure from 10 cosmetic products
Modify the current method to include Oral exposure (toothpaste/mouthwash) Inhalation from air care products Indirect oral and inhalation exposure (e.g. oral
exposure from dishwashing products; inhalation exposure from cleaners)
Household and functional care product types Aggregate exposure
*Cadby et al., 2002. Reg. Tox. & Pharm., 36, 246-252.
*Ford et al., 2000. Reg. Tox. & Pharm., 31, 166-181.
5
RIFM Aggregate Exposure Model To develop a standard approach that can be used
widely for industry where total systemic exposure includes: Estimate for entire population (preferably World Wide
but initially for Europe and North America) From all exposure pathways – dermal, oral and
inhalation From all key products in which fragrance ingredients
are used The data will also be made available in a software
model which can be used to perform assessments in the future
6
RIFM Aggregate Exposure Model – Products Included
Phase I Body Lotion (prestige vs.
mass market) Deodorant/antiperspirants Face cream/Moisturizers Shampoo/Conditioners Hair Styling Products
(excluding hair spray) Hand Cream Hydroalcoholics Lipstick Liquid/Makeup Foundation Mouthwash Shower Gel Toothpaste
Phase II Bar Soap Liquid Hand Soap Body Spray Inhalation
Air Fresheners Candles Hair Spray, Perfume,
Deodorant Spray Combined Food &
Cosmetics exposure
7
These products cover the major exposure contribution to fragrance ingredients
RIFM Aggregate Exposure Model
The RIFM Creme model includes detailed usage data for over 36,000 consumers representing the European and US populations. This robust population sample allows us to generate accurate and realistic exposure results.
8
RIFM Requests for Concentration Data RIFM will be requesting concentration data for
most of the fragrance materials in use today and will use the concentration data to calculate the total systemic exposure needed for a safety assessment.
The concentration data will remain confidential. RIFM’s first request issued on May 2.
Concentration Survey 001 is RIFM’s first request for data on 60 fragrance ingredients.
Each organization has a separate upload site. Please complete and return this survey by May
31, 2013.
9
RIFM Requests for Concentration Data Anticipated that each month there will be
another request for data; this may be scaled up such in a more expedited
manner. The data will be entered into the model and
sources of the data will not be made available.
10
RIFM Concentration Survey 001
11
RIFM Concentration Survey 001 Request for Concentration Data on 60 Fragrance Ingredients
RIFM is evolving its safety evaluation process to more rapidly incorporate advances in in vitro and in silico methodologies. The focus of the evaluation is now on the individual fragrance material. This will allow RIFM to take of advantage of advances in the science of safety evaluations, as well as meet the increasingly stringent requirements from regulatory bodies and the increased expectations of fragrance users. Exposure data are essential for the completion of a safety assessment for all human health endpoints. RIFM, with member company representatives and Creme Global (a well-established partner to Industry in modeling exposure for cosmetics and foods, and their methodology is used and accepted by regulators), developed a probabilistic aggregate exposure model to calculate total systemic exposure, with distributions used to model various parameters. The new model will enable the measurement of real life consumer exposure to a fragrance material. RIFM will be requesting concentration data for most of the fragrance materials in use today and will use the concentration data to calculate the total systemic exposure needed for a safety assessment. The concentration data will remain confidential. This Concentration Survey is RIFM’s first request for data on 60 fragrance ingredients. The link below will provide information on registration for transferring survey data and on completing the survey:
https://cremeglobal.com/rifmfiletransfer/register.php Once registration is complete, Creme Global will provide login details and the responder will be able to download the Excel spreadsheet and upload responses for each fragrance ingredient. Each organization has a separate upload site. Please complete and return this survey by May 31, 2013. A RIFM Webinar will be held on Wednesday May 8, 2013 to explain in detail how this survey should be completed. More information on the Webinar is available in the Member area of the RIFM website at www.rifm.org. RIFM will issue a new survey each month. The concentration data will be entered into the model but the sources of the data will not be made available. The information must be provided from fragrance compounders (companies that blend fragrance ingredients) for marketed fragrance mixtures only. Please do not enter exposures that are not currently in use. RIFM will follow due diligence to obtain exposure information. Materials for which usage concentration data are not provided will be eliminated from the RIFM evaluation process. At that time, RIFM will inform IFRA that due to lack of data a safety evaluation cannot be completed. The material will then be reviewed by IFRA for possible risk management actions which may include removal from the IFRA Transparency List and/or a ban due to insufficient data. For more information, please contact Dr. Anne Marie Api, [email protected].
Research Institute for Fragrance Materials, Inc. 50 Tice Boulevard • Woodcliff Lake, NJ 07677
Phone: 201.689.8089 • Fax: 201.689.8090 www.rifm.org [email protected]
RIFM Concentration Survey 001 Request for Concentration Data on 60 Fragrance Ingredients
12
CAS Number EINECS Principal Name Synonyms 1 100-52-7 202-860-4 Benzaldehyde Artificial almond oil; Benzene carboxaldehyde;
Benzenecarbonal; Benzenecarboxaldehyde; Benzenemethylal; Benzoic aldehyde; Bitter almond oil, synthetic; Phenylformaldehyde; Phenylmethanol aldehyde
2 101-86-0 202-983-3 alpha-Hexylcinnamaldehyde 2-Benzylideneoctanal; alpha-n-Hexyl-beta-phenylacrolein; alpha-n-Hexylcinnamic aldehyde; H.C.A.; Hexyl cinnamal; Hexyl cinnamic aldehyde; Hexyl cinnamyl; Jasmonal H.; Octanal, 2-(phenylmethylene)-
3 104-20-1 203-184-2 4-(p-Methoxyphenyl)-2-butanone 2-Butanone, 4-(4-methoxyphenyl)-; 4-(4-Methoxyphenyl)butan-2-one; 4-(p-Methoxyphenyl)butan-2-one; Anisylacetone; Methyl oxanone; p-Methoxybenzylacetone; Raspberry ketone methyl ether
4 104-54-1 203-212-3 Cinnamyl alcohol 2-Propen-1-ol, 3-phenyl-; 3-Phenyl-2-propen-1-ol; 3-Phenylallyl alcohol; 3-Phenylprop-2-en-1-ol; Cinnamic alcohol; Styrone; Styryl alcohol; Styryl carbinol; Zimtalcohol
5 104-55-2 203-213-9 Cinnamaldehyde 2-Propenal, 3-phenyl-; 3-Phenyl-2-propen-1-al; 3-Phenyl-2-propenal; 3-Phenylacrylaldehyde; 3-Phenylpropenal; Cinnamal; Cinnamic aldehyde; Phenylacrolein
6 115-95-7 204-116-4 Linalyl acetate 1,5-Dimethyl-1-vinylhex-4-en-1-yl acetate; 1,6-Octadien-3-ol, 3,7-dimethyl-, acetate; 3,7-Dimethyl-1,6-octadien-3-ol acetate; 3,7-Dimethyl-1,6-octadien-3-yl acetate; Bergamol; Linalool acetate
7 117-98-6 204-225-7 Vetiveryl acetate 2-Isopropylidene-4,8-dimethyl-1,2,3,3a,4,5,6,8a-octahydroazulen-6-yl acetate; 6-Azulenol, 1,2,3,3a,4,5,6,8a-octahydro-4,8-dimethyl-2-(1-methylethylidene)-, acetate; 6-Azulenol, 1,2,3,3a,4,5,6,8a-octahydro-4,8-dimethyl-2-(methylethylidene)-, acetate; Vetiver acetate; Vetivert Acetate; Vetivert acetate (Haiti); Vetyvenyl acetate
8 118-58-1 204-262-9 Benzyl salicylate 2-Hydroxybenzoic acid, benzyl ester; Benzoic acid, 2-hydroxy-, phenylmethyl ester; Benzyl 2-hydroxybenzoate; Benzyl o-hydroxybenzoate; Phenylmethyl 2-hydroxybenzoate; Salicylic acid, benzyl ester
9 119-61-9 204-337-6 Benzophenone alpha-Oxodiphenylmethane; alpha-Oxoditane; Benzene, benzoyl-; Benzophenon krist; Benzoylbenzene; Diphenyl ketone; Diphenylmethanone; Methanone, diphenyl-; Phenyl ketone
10 121-32-4 204-464-7 Ethyl vanillin 3-Ethoxy-4-hydroxybenzaldehyde; 3-Ethoxyprotocatechualdehyde; Benzaldehyde, 3-ethoxy-4-hydroxy-; Bourbonal; Ethyl protal; Ethylprotocatechualdehyde-3-ethyl ether
RIFM Requests for Concentration Data
The information must be provided from fragrance compounders (companies that blend fragrance ingredients) for marketed fragrance mixtures only.
Please do not enter exposures that are not currently in use Data Needed from Fragrance Compounders
Report data on materials used as such only. RIFM will follow due diligence in order to
obtain exposure information.
13
RIFM Requests for Concentration Data
Materials for which exposure is not provided will be eliminated from the RIFM evaluation process
At that time, RIFM will inform IFRA that due to lack of data a safety evaluation cannot be completed. The material will then be reviewed by IFRA for possible risk management actions which may include removal from the IFRA Transparency List and/or a ban due to insufficient data.
14
Examples
How do I enter data? Need to register for transferring survey data
and on completing the survey:
https://cremeglobal.com/rifmfiletransfer/register.php
15
Fragrance Ingredient A
Extract & gather data for Fragrance Ingredient
2 year sold formulae? All data points Clean-up data Remove chemical sales, bases etc. (Need final
concentration in marketed formulae) Translate internal classifications to RIFM
product types Fill-in template
16
?
Fragrance Ingredient A Formula Name Application Sector % Conc.
Formula 1 Air Freshener - Electrical Home Care 0.5333 Formula 2 Skin Care/Face Body Care 0.05 Formula 3 Body Deo Cream/Stick/Solid Body Care 0.125 Formula 4 Perfume/Edp/Edt/Col (FW) Fine Fragrance 0.0014 Formula 5 AntiP/Deo (FW) Fine Fragrance 0.0003 Formula 6 Soap Bar Body Care 0.0487 Formula 7 Skin Care/Face Body Care 0.1 Formula 8 All Purpose Cleaner Home Care 0.0645 Ingredient Chemicals Chemicals 100 Formula 10 Perfume/Edp/Edt/Col (FW) Fine Fragrance 0.017 Formula 11 Shampoo Body Care 0.0006 Formula 12 Hand Liquid Soap Body Care 0.0031 Formula 13 Laundry Rinse/Condit. Home Care 0.0667 Formula 14 Shower Product (BC) Body Care 0.0045 Formula 15 Skin Care/Hand & Body Body Care 0.0005 Formula 16 AntiP/Deo (FW) Fine Fragrance 0.0012 Formula 17 Soap (FM) Fine Fragrance 0.0029 Formula 18 Hair Rinse/Conditioner Body Care 0.0008 Formula 19 Body Deo Spray/Aer./Pump Body Care 0.001 Formula 20 Liquid Detergent Home Care 6.6667 Formula 21 Men Deocol/Splash (BC) Body Care 0.0758 Base Body AntiP Spray/Aer./Pump Body Care 71.4286 Formula 23 All Purpose Cleaner Home Care 0.4 Formula 25 Shower Product (BC) Body Care 0.0032
Fragrance Ingredient B
18
Formula Name Application Sector % Conc. Formula 1, 2, 3, 4, 5 Air Freshener - Electrical Home Care 0.5333Formula 5, 16 AntiP/Deo (FW) Fine Fragrance 0.0003 - .0012Formula 3, 19 Body Deo Cream/Stick/Solid Body Care 0.001- 0.125Formula 18 Hair Rinse/Conditioner Body Care 0.0008Formula 12 Hand Liquid Soap Body Care 0.0031Formula 13 Laundry Rinse/Condit. Home Care 0.0667Formula 21 Men Deocol/Splash (BC) Body Care 0.0758Formula 4, 10 Perfume/Edp/Edt/Col (FW) Fine Fragrance 0.0014-0.0017Formula 11 Shampoo Body Care 0.0006Formula 14, 25 Shower Product (BC) Body Care 0.0032-0.0045Formula 15 Skin Care/Face Body Care 0.0005-0.01Formula 2,7 Skin Care/Face Body Care 0.01-0.1Formula 17, 6 Soap (FM) Fine Fragrance 0.0029-0.0487
Fragrance Ingredient C
19
Formula Name Application Sector Min % Conc Max %
Conc Typical % Conc
Formula 1, 2, 3, 4, 5 Air Freshener - Electrical Home Care 0.01 0.0533 0.03
Formula 5, 16 AntiP/Deo (FW) Fine Fragrance 0.0003 0.0012 0.0005
Formula 3, 19 Body Deo Cream/Stick/Solid Body Care 0.001 0.00125 0.0011
Formula 18-20 Hair Rinse/Conditioner Body Care 0.0008 0.001 0.0005
Formula 12-13 Hand Liquid Soap Body Care 0.0031 0.0667 0.005
Formula 21-30 Men Deocol/Splash (BC) Body Care 0.0758 0.1 0.08
Formula 35-30 Perfume/Edp/Edt/Col (FW) Fine Fragrance 0.0014 0.0017 0.0015
Formula 11 Shampoo Body Care 0.0006 0.001 0.007
Formula 14, 25 Shower Product (BC) Body Care 0.0032 0.0045 0.004
Formula 2,7,15 Skin Care/Face Body Care 0.0005 0.01 0.0008
Formula 17, 6 Soap (FM) Fine Fragrance 0.0029 0.0487 0.003
Cronan McNamara, CEO
E.J. Daly, CTO 15th May 2013
RIFM Webinar – Data Collection Expert Models for Decision Makers TM
G L O B A L
Creme Global - Overview
RIFM – Creme Global – Partnership: Project Commenced in 2010 – 3 Work Packages over Two Phases
RIFM Creme Model – Aggregate Exposure Assessment – Fragrances and Flavorings – Dermal, Inhalation, Oral and Ingestion
Creme Global - Services
High Performance Cloud Software
Technical Services & Projects
Data Validation &
Curation
Calculating Exposure
Exposure per unit body weight (mg/kg/day) = 𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹 × 𝐴𝐴𝐴𝐹𝐹𝐴 × 𝐶𝐴𝐹𝐹𝐹𝐹𝐴𝐹𝐶𝐴𝐶𝐴𝐹 × 𝑅𝐹𝐹𝐴𝐹𝐹𝐴𝐶𝐴𝐹 × 𝑃𝐹𝐹𝐹𝐴𝐹𝐶𝐴𝐶𝐴𝐹
𝐵𝐴𝐵𝐹 𝑊𝐹𝐶𝑊𝑊𝐴
Dermal Exposure (mg/cm2/day) =
𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹 × 𝐴𝐴𝐴𝐹𝐹𝐴 × 𝐶𝐴𝐹𝐹𝐹𝐹𝐴𝐹𝐶𝐴𝐶𝐴𝐹 × 𝑅𝐹𝐹𝐴𝐹𝐹𝐴𝐶𝐴𝐹𝑆𝐹𝐹𝑆𝐶𝐹𝐹 𝐴𝐹𝐹𝐶
Calculation repeated for: Each subject Each product Each body part
Exposure Algorithm
1. Choose fragrance of interest
3. Find all usage events in the diary involving those products
4. Determine the exposure to the fragrance at each usage event
5. Determine the aggregate exposure to the fragrance for each subject
2. Find all products that contains that fragrance
6. Collate exposures for each subject to give the distribution of exposure in the population
MORE INFORMATION
20 Api PCPC SRTC June 2011
Research Institute for Fragrance Materials, Inc.Tel.: +1-201-689-8089
[email protected]@rifm.org
https://cremeglobal.com/rifmfiletransfer/register.php
http://www.cremeglobal.com/products/cremerifm/Data%20Collection/