IFRA-RIFM QRA Information Booklet V7.1 (July 9, 2015)

IFRA RIFM QRA Information Booklet Version 7.
1
Revised July 9, 2015
The purpose of this booklet is to provide basic guidance to fragrance suppliers and users on the
implementation of the Quantitative Risk Assessment (QRA) approach for fragrance ingredients.
The Information Booklet was first issued on May 12, 2006 to provide assistance in implementing
the 40th Amendment to the IFRA Code of Practice.
This booklet is a dynamic document that will change and require periodic updating to reflect the
most up-to-date Amendments to the IFRA Code of Practice. As such, it will be important to check
the issue date (located at the bottom of each page) of this booklet. The current version of the
booklet is the seventh update (Version 7.1, July 9, 2015) and can be found on both the IFRA and
RIFM websites (http://rifm.org/publications-sort-title.php and http://www.ifraorg.org/enus/standards).
This Booklet (Version 7.1, July 9, 2015) includes important updated information on:
what is part of the 48th Amendment (Spring 2015) in terms of number of fragrance
ingredients affected and the implementation time
definition of the IFRA product categories
guidance on preparing IFRA Certificates
defining the scope of use for the QRA for fragrance ingredients
refining the definition of products used on the axillae (Category 2)
categorization of product types not previously included:
o Fragranced Face Masks (not intended to be used as medical device)
o Gloves/socks
o Nose Pore Strips
o Solid perfumes
re-categorization for:
o Waxes for mechanical hair removal
IFRA RIFM QRA Information Booklet V7.1
Last updated: July 9, 2015
QRA INFORMATIONAL BOOKLET VERSION 7.1

QUANTITATIVE RISK ASSESSMENT (QRA) for FRAGRANCE INGREDIENTS
Although some substances in common use today may have the potential to cause dermal
sensitization, they can still be formulated into consumer products at safe levels. This is the case
for fragrance ingredients. Based on the chemical, cellular and molecular understanding of dermal
sensitization, it is possible to conduct an exposure-based Quantitative Risk Assessment (QRA)
to determine safe use levels of fragrance ingredients in a variety of consumer product types.
Significant developments have been incorporated in the way dermal sensitization risk
assessments are conducted for fragrance ingredients. This methodology is a major improvement
over former risk assessment practices because it specifically addresses the elements of
exposure-based risk assessment that are unique to the induction of dermal sensitization, while
being consistent with the principles of general toxicology risk assessment. As such, it is a clear
improvement over the risk management strategies formerly used by IFRA under which each
specific fragrance ingredient identified as an allergen was limited to the same concentration
across all skin contact product types (Api et al., 2008, Dermal sensitization Quantitative Risk
Assessment (QRA) for fragrance ingredients. Regulatory Toxicology and Pharmacology, Volume
52, pages 3-23, 2008). [Note: The original technical dossier authored by the QRA Expert Group*,
Dermal Sensitization Quantitative Risk Assessment (QRA) for Fragrance Ingredients, Technical
Dossier, March 15, 2006, Revised June 22, 2006, is also still available on the IFRA and RIFM
websites (http://rifm.org/publications-sort-title.php and http://www.ifraorg.org/en-us/guidelines/).
In a brief overview, key steps of the QRA process are the determination of benchmarks for the
induction potential (No Expected Sensitization Induction Level or NESIL); application of
sensitization assessment factors (SAF) and calculation of consumer exposure (CEL) through
product use. Using these parameters, an acceptable exposure level (AEL) can be calculated and
compared with the consumer exposure level (CEL). The ratio of the AEL to CEL must be favorable
to support the safe use of the skin sensitizer. This ratio must be calculated for the skin sensitizer
in each product type. For more details, see Api et al., 2008 as referenced above and also the
QRA Expert Group*, Dermal Sensitization Quantitative Risk Assessment (QRA) for Fragrance
Ingredients, Technical Dossier, March 15, 2006, Revised June 22, 2006,
(http://rifm.org/publications-sort-title.php and http://www.ifraorg.org/en-us/guidelines/).
Based on RIFMs Expert Panel recommendation, RIFM and IFRA formally adopted
beginning with the 40th Amendment to the IFRA Code of Practice in May 2006 the QRA
approach, refined for fragrance ingredients identified as dermal sensitizers, as the core
strategy for primary prevention of dermal sensitization to these materials in consumer
products. This methodology is now being used to determine global fragrance industry
product management practices (IFRA Standards) for potentially sensitizing fragrance
ingredients on an ongoing basis.
Given the impact of this major change, it is important that global fragrance suppliers and users
are fully informed about the changes, the implementation of this new approach and how this will
impact them. It mainly affects them in terms of the identification of acceptable levels of fragrance
ingredients in different product types and how this will be managed on a practical basis through
grouping of certain product types into product categories with specific limitations.

48th Amendment to the IFRA Code of Practice (Spring 2015)
In the 48th Amendment to the IFRA Code of Practice (June 2015) the QRA approach is used to
set 3 new IFRA Standards. These new IFRA Standards restrict fragrance ingredients that can
also be present in other sources (e.g. essential oils). As such, Annex 1 to the IFRA Code of
Practice, which provides guidance on the presence of IFRA restricted materials in other sources,
has been updated accordingly.
The timing for implementation of these Standards in an existing fragrance mixture (i.e., fragrance
compound or fragrance oil) will follow the regular timing for Amendments. Note: the timing refers
to the mixture of fragrance ingredients, the so-called fragrance compound (fragrance oil), and
NOT to the finished consumer product.
47th Amendment to the IFRA Code of Practice (Spring 2013)

set 6 new IFRA Standards and four revised Standards. These new IFRA Standards restrict
fragrance ingredients that can also be present in other sources (e.g. essential oils). As such,
Annex 1 to the IFRA Code of Practice, which provides guidance on the presence of IFRA
restricted materials in other sources, has been updated accordingly.
It is important to note that with the 47th Amendment to the IFRA Code of Practice, all existing IFRA
Standards based on dermal sensitization were revised according to the QRA approach.
46th Amendment to the IFRA Code of Practice (June 2011)

set 6 new IFRA Standards. These new IFRA Standards restrict fragrance ingredients that are not
present in other sources (e.g. essential oils). As such, Annex 1 to the IFRA Code of Practice,
which provides guidance on the presence of IFRA restricted materials in other sources, will remain
unchanged.
compound or fragrance oil) will follow the regular timing for Amendments. Note: the timing refers
to the mixture of fragrance ingredients, the so-called fragrance compound (fragrance oil), and
NOT to the finished consumer product.
45th Amendment to the IFRA Code of Practice (June 2010)

review and re-define existing Standards set on the basis of dermal sensitization, for which
additional data are now available (1 Standard). In addition 3 new IFRA Standards are introduced.
These new IFRA Standards restrict fragrance ingredients that are not present in other sources
(e.g. essential oils). As such, Annex 1 to the IFRA Code of Practice, which provides guidance on
the presence of IFRA restricted materials in other sources, will remain unchanged.
compound or fragrance oil) will not be extended as was done for the 40th, 42nd, 43rd and 44th
Amendment, and follow the regular timing for Amendments. Note: the timing refers to the mixture
of fragrance ingredients, the so-called fragrance compound (fragrance oil), and NOT to the
finished consumer product.
44th Amendment to the IFRA Code of Practice (July 2009)

In the 44th Amendment to the IFRA Code of Practice (July 2009), the QRA approach was used to
review and re-define existing Standards set on the basis of dermal sensitization, for which
additional data were available (1 Standard). In addition 11 new IFRA Standards were introduced.
Some of these new IFRA Standards restrict fragrance ingredients that are present in other

sources (e.g. essential oils). As such, some essential oils were impacted and Annex 1 to the IFRA
Code of Practice, which provides guidance on the presence of IFRA restricted materials in other
sources, will be modified accordingly.
compound or fragrance oil) was again extended to 25 months due to the extensive number of
Standards that were revised. Note: the timing refers to the mixture of fragrance ingredients, the
so-called fragrance compound (fragrance oil), and NOT to the finished consumer product.
43rd Amendment to the IFRA Code of Practice (July 2008)

In the 43rd Amendment to the IFRA Code of Practice (Spring 2008), the QRA approach was used
to review and re-define existing Standards set on the basis of dermal sensitization, for which
additional data were available (10 Standards). In addition 8 new IFRA Standards were introduced.
Some of these new IFRA Standards restrict fragrance ingredients that are present in other
sources (e.g. essential oils). As such, some essential oils were impacted and Annex 1 to the IFRA
Code of Practice, which provides guidance on the presence of IFRA restricted materials in other
sources, was modified accordingly.
The timing for implementation of this Amendment in an existing fragrance mixture (i.e., fragrance
42nd Amendment to the IFRA Code of Practice (Spring 2007)

In the 42nd Amendment to the IFRA Code of Practice (Spring 2007), the QRA approach was used
to review and re-define all existing Standards set on the basis of dermal sensitization, for which
adequate data exist (14 Standards, covering 25 materials which includes isomers of the 14). In
addition 14 new IFRA Standards covering 26 materials (including isomers of the 14) are
introduced. Some of these new IFRA Standards restrict fragrance ingredients that are present in
other sources (e.g. essential oils). As such, some essential oils were impacted and Annex 1 to
the IFRA Code of Practice, which provides guidance on the presence of IFRA restricted materials
in other sources, was modified accordingly.
The timing for implementation of this Amendment in an existing fragrance mixture (i.e., fragrance
40th Amendment to the IFRA Code of Practice (May 2006).

The QRA methodology can be used both to set IFRA Standards for fragrance ingredients
identified as dermal sensitizers where none previously existed as well as for review of current
IFRA Standards. The use of QRA to set IFRA Standards began with the 40th Amendment to the
IFRA Code of Practice (May 2006). There were major implications that included time for industry
to become familiar with the changes and to update company computer systems. This all had to
occur while maintaining the old system for existing IFRA Standards. Given this complexity, a
staggered approach was chosen in which four materials were selected (citral, farnesol,
phenylacetaldehyde and tea leaf absolute) for setting new IFRA Standards and the fragrance
industry supplier compliance time was extended (13 months after the date of the letter of
notification for new creations; 25 months after the date of the letter of notification for existing
fragrance compounds). This timing refers to the mixture of fragrance ingredients, the so-called
fragrance compound (fragrance mixture or fragrance oil), not the finished consumer product.

Compliance Timelines for the 48th Amendment
The compliance timelines for the Standards based on the quantitative risk assessment for dermal
sensitization that will be introduced in the 48th Amendment is detailed in the Notification Letter.
They follow the revised implementation timeline that was detailed in IFRA Information Letter 870
(Revised implementation timeline for Amendments to the IFRA Code of Practice), which was
issued on May 21, 2010. In brief, the compliance timeline is as follows:
Date for Standards for new creations:
Date for Standards for existing creations:
2 months after the date of the Notification Letter

14 months after the date of the Notification Letter
New creations are defined as any fragrance compound (or fragrance oil) for which the brief has
been issued after the publication date of the Amendment. This does not include fragrance
compounds that were already in development or in the hands of either fragrance supplier or
consumer product manufacturer, before the date of the Amendment (the latter are referred to as
pipeline fragrances and are treated like 'existing creations').
Existing creations are those fragrance compounds (or fragrance oils) that have already been
placed on the market in a consumer product or are already in the development pipeline.
Definition of IFRA Categories

While the old approach of two product categories (skin contact and non-skin contact products), is
no longer considered sufficient for application to the new QRA approach, it is also not desirable
or practical to set IFRA Standards based on dermal sensitization for every individual product type.
A realistic application of the recommended QRA approach for fragrance ingredients is to use
multiple product categories for the implementation of IFRA Standards. This is achieved by
grouping consumer product types according to key parameters identified within the QRA
approach. These parameters are Sensitization Assessment Factors (SAFs) and consumer
product exposure, which when combined, lead to similar acceptable use levels of a fragrance
ingredient. Using these parameters, Table 2 outlines 11 different IFRA categories for dermal
sensitization, which have been specified by the QRA Expert Group* and explained by Api and
Vey, 2008 on Implementation of the dermal sensitization Quantitative Risk Assessment (QRA)
for fragrance ingredients in Regulatory Toxicology and Pharmacology, Volume 52, pages 53-61.
Table 3 outlines the different IFRA categories by product type. For many categories it may appear
that there is a wide diversity of product types. However, this is because the categories are based
on scientific rationale (SAF and consumer product exposure), and not on the functional similarity
of each product type.
Guidance for completion of IFRA Certificates

With the introduction of the first QRA Standards as part of the 40th Amendment to the IFRA Code
of Practice, the preparation of the certificates to declare compliance with the IFRA Code of
Practice and Standards that are part of this Code gained some additional complexity. Table 4
gives information to provide guidance intended to help you find your way through combining
information about different types of Standards (QRA, systemic toxicity etc.) in one certificate. Of
great importance is the introduction of classes for reporting IFRA compliance and how they are
set up. This table was established with the intention of covering the majority of possible cases of
combinations but might not be absolutely comprehensive. This table will be updated with any
additions or revisions, and will be included in this booklet.
Important information relevant to the product types included in each Category

There are several key considerations regarding the product types and categories that must be
noted:
The QRA addresses the protection of human health and is specifically aimed at ideally
eliminating the acquisition of dermal sensitization to fragrance ingredients under their
conditions of use. The fragrance industry QRA approach defined for dermal sensitization
should not be applied to other toxicological effects or usage patterns as it is specific for dermal
sensitization.
The products described are all retail consumer products. As such QRA for fragrance
ingredients is applied to consumer use of these products only. End uses that are not listed in
this booklet have not been reviewed by RIFM in the risk assessment process and therefore
not included in the IFRA risk management.
The QRA methodology as it exists today does not cover occupational use of consumer
products, mainly due to missing exposure data to build into the risk assessment.
Fragrance compounds in medical devices, OTC drugs and topical drugs are not covered by
the current QRA methodology. This is mainly due to the potential or intended application on
compromised or diseased skin and a different risk benefit consideration than for typical
consumer products is needed. In addition, these product types are under the scope of specific
regulations with defined safety assessment requirements.
Product types are placed into IFRA product categories on the basis of grouping consumer
product types according to key parameters identified within the QRA approach. These
parameters are Sensitization Assessment Factors (SAFs) and consumer product exposure,
which when combined, lead to similar acceptable use levels of a fragrance ingredient. It is
not possible to list every conceivable type of product in this document. Several product types
have been placed in specific IFRA categories even in the absence of exposure data by taking
into account how the product is used, what it contains and the extent of likely skin exposure.
However, should consumer product exposure data become available; these product types
may be re-categorized. Also, if additional relevant exposure data become available on any
product type, this may also result in re-categorization of the product type.
It should be noted that the acceptable exposure levels will be expressed as accurate to two
decimal places unless the NESIL is low enough that the acceptable exposure level needs to
be expressed to three decimal places. The NESIL is expressed in two significant figures.
For example, if the NESIL is set at two significant digits (e.g. 3500 based on a calculated
value of 3564), then the acceptable exposure levels will be limited to two decimal places (e.g.
for category 1 the result would be 0.10%, in category 2 the result would be 0.13%, in category
4 the result would be 1.60%). If the NESIL is 64 then category 1 would be 0.002%, but
category 4 would be 0.41%.
In cases, where a product is not currently categorized and/or there are newly available data
on consumer product exposure or surface area, then it is incumbent on the fragrance supplier
to submit these data with undue delay. Data should be sent to either Dr. Matthias Vey, IFRA
Scientific Director ([email protected]) or Dr. Anne Marie Api, Vice President Human Health
Sciences ([email protected]). RIFM and IFRA have developed a form to providing all the
necessary information. The form can be found at IFRA Information Letter 796 and also on
the
RIFM
and
IFRA
websites
(http://rifm.org/publications-sort-title.php
and
http://www.ifraorg.org/en-us/guidelines/). When the provided information is sufficiently
robust, modification of this information booklet will be done and the IFRA membership and
stakeholders would be adequately informed about the change(s).
Aerosols:
o Pressurized aerosols: When calculating fragrance ingredient concentration in
pressurized aerosols, to determine compliance with an IFRA Standard (determining
the concentration reaching the skin), the limit is the one in the finished product.
o Aerosol skin contact: Skin contact from aerosol products (e.g. aerosol air freshener)
as defined in Category 9 relates to those aerosol products that are not intended for
skin contact, but their use may result in skin contact. This excludes
deodorant/antiperspirants, hair styling aids and sprays, which are part of other
categories.
After Sun Creams and Self-tanning Products: After sun and sunless tanning products are
not addressed separately, but are included in the appropriate major product types (e.g. facial
cream, body cream) in line with other sun care products. Products used on mildly sunburned
skin are also expected to fit into the appropriate major product categories without amendment
to their QRA which is already sufficiently conservative. Use of products for severely
sunburned skin could constitute a different exposure scenario, but since this borders on
needing professional medical advice for treatment, this is considered to be outside the scope
of this QRA activity.
Sunscreens: Products that contain sunscreen or sun-block are not listed separately but are
included in the appropriate major product type (e.g. lip creams containing sunscreen are
included in the lip products category).
Animal sprays: Animal sprays (or pet sprays), are categorized in IFRA QRA Category 11
(non-skin, incidental skin contact). For this specific type of product (where there is no direct
application to humans) it is not necessary to differentiate between aerosol and pump
applications.
Childrens toys: IFRA prohibits the use of fragrance materials and mixtures in toys or other
childrens products where there is the likelihood of mouth contact. Following the criteria
established by the toy industry, these include: 1) toys for children less than 3 years of age;
2) any toy designed and intended to go into the mouth; and/or 3) those toys for which mouth
contact is reasonably foreseeable. This product type has been placed in Category 1 based
on the absence of exposure data. Should exposure data become available, these product
types may be re-categorized. Regarding IFRAs policy on toys please refer to the Annex 8 of
the IFRA Code of Practice Introduction to the IFRA Standards.
Concentrated aerosol air fresheners: These air fresheners are differentiated from other
aerosol air fresheners in the following two characteristics:
o These air fresheners are part of a device that either delivers the fragrance
automatically or the device has an activation mechanism that is not located near
where the aerosol is discharged, so there is essentially no dermal exposurefrom
activation and at best incidental through exposure. Such concentrated aerosol air
fresheners deliver a metered spray (typically 0.05 - 0.5 ml/spray) and are placed in
Category 11.
o Other aerosol air fresheners deliver a continuous spray at 1-1.5 ml/second spray for
as long as the consumer pushes the activation button, which is typically 2 to 10
seconds for a total volume of 2 - 15 ml/spray. Those products are placed in Category
9C, as they are typically manually activated by a push button near the spray, which
can result in some dermal exposure.
Dental Products
o Toothpaste and Mouthwash Products: With the implementation of the QRA
approach, the IFRA Standards will include oral care products. Mouthwash and
toothpastes are the principal oral care products currently identified in IFRA Category
6. Exposure limits for these products are established to reduce the risk of peri-oral
dermal sensitization and as such, are not related to considerations of safe levels for
ingestion.
See the section labeled Oral intake of products for specifics related to the flavor
material status needed for fragrances used in oral care products.
o
Denture adhesives and tooth whiteners: These are regulated globally as medical
devices. Since medical device regulations include separate safety assessment
guidelines, these product types are not included in the IFRA categorization based on
the QRA approach.
Diapers, feminine hygiene pads, liners and tampons: As with all other product types,
levels of fragrance ingredients in diapers and feminine hygiene products are being based on
the final product. For clarification, the final products here are the diaper, feminine hygiene
pad or liner or tampon. It is recognized that products such as these involve special
considerations because the fragrance mixture or compound is included in the final product
based on weight rather than percent concentration. A re-categorization of these product types
may be necessary as additional understanding of these special considerations as they relate
to the expression of IFRA Standards is further developed.
Hydroalcoholics for shaved skin: Men's aftershaves, colognes and toilet waters are all
likely to be applied to recently shaved skin and hence all of these types of products fall under
IFRA QRA category 3.
Maximum Pragmatic Level: Practical considerations require setting a default maximum

level of the fragrance ingredients identified as dermal sensitizers for some product types.
This pragmatic level is defined as that not exceeding the usual concentration of the fragrance
compound in the finished product. In Table 1 these levels are indicated in the column
identified as Maximum Pragmatic Level. If the Acceptable Exposure Level (AEL) derived
from the QRA for a fragrance ingredient in a specific product type is less than the
concentration identified as the Maximum Pragmatic Level, the AEL will take precedence
and be applied. IFRA and RIFM will determine whether the AEL or the Maximum Pragmatic
Level should be applied. The appropriate value will be given in the IFRA Standard.
The pragmatic level used is NOT meant to be a maximum use level for fragrance oils (or
fragrance mixtures or fragrance compounds) in consumer products. It is used to set limits for
individual fragrance ingredients (not fragrance oils or fragrance mixtures or fragrance
compounds) when the QRA AEL gives an unusual and unrealistic maximum use level for a
fragrance ingredient.
Non-skin contact or incidental skin contact products: Most of the non-skin contact or
incidental skin contact products (as defined in the Code of Practice) are included in Category
11. Due to the expected negligible skin exposure from such products the risk of induction of
dermal sensitization through the normal formulation and use of such products is considered
to be negligible. As such, the concentration of fragrance ingredient is not restricted in the
finished product.
Oral intake of products: All oral care products that carry a fragrance, like any other
fragranced product, must follow the IFRA Standards and general guidelines as contained in
the IFRA Code of Practice. IFRA Standards for oral care products, when based on the QRA,
only address the issue of the endpoint of dermal sensitization.
Besides oral care products, there are certain other products containing fragrance materials
that are not intended for ingestion but have the possibility of ingestion of minute amounts of
the fragrance like lip products of all types (solid and liquid lipsticks, balms, etc.), or toys.
Due to the possibility of ingestion of small amounts of fragrance ingredients from the use of
the aforementioned allowable product categories (such as oral care, lip products and certain
toys), materials present in the fragrance compound must not only comply with IFRA
Standards but must also have an approved flavor materials status as defined by the IOFI
Code of Practice. Such materials are those that meet one or more of the following
requirements:
o
Accepted by the authoritative body the Joint FAO/WHO Expert Committee on Food
Additives (JECFA) as acceptable flavoring materials that pose no safety concerns at
current levels of intake;
Have been evaluated and found, using the same or similar methodology as used by
JECFA, to present no safety concern under conditions of intended use by
authoritative bodies such as the European Food Safety Authority (EFSA) or the
Japanese Food safety Authority (FSC);
Deemed to be Generally Recognized As Safe (GRAS) or approved food additives by

the US Food and Drug Administration (FDA) including GRAS determinations
published by the independent Expert Panel of the Flavor and Extract Manufacturers
Association of the United States (FEMA);
Are compliant with appropriate national/regional regulation covering the use of

flavorings for local use and respective product uses as outlined above.

Materials without an approved flavor status according to the criteria above are not permitted
in products where incidental oral ingestion may occur.
Novel delivery systems: Novel delivery systems (e.g. encapsulated fragrances) vary
considerably in their delivery and therefore are not generally categorized.
Scent pads and foil packs: Scent pads and foil packs are two types of fragrance sampling
technology that contain the hydroalcoholic product for unshaved skin on a pad or in a foil
pack. As such these product types are categorized in IFRA QRA Category 4.
Scent Strips: The concentration of the fragrance compound or fragrance oil that is used for
IFRA compliance review of a fragrance to be used in a scent strip product (a sampling
technology that potentially gets rubbed on the skin) should be the same concentration that is
used for the related fragrance oil (or fragrance mixture or compound) in the consumer product
for which the scent strip is meant to be a sampled. For example, if the consumer product is
a hydroalcoholic product for unshaved skin containing 15% fragrance compound or fragrance
oil, then the concentration of the fragrance compound or fragrance oil to be used in the scent
strip should be 15% for review in IFRA QRA Category 4.
Tissues: Tissues or facial tissues are soft (dry) tissues (IFRA QRA Category 9) that are
usually contained in boxes. Wipes or refreshing tissues (IFRA QRA Category 5) are moist
towels and are usually contained in (re)sealable plastic packages.
Wheat bags: Heating pads of various shapes or size filled with grain to be applied on different
areas of the body and presented as providing soothing effect by applying it either warm or
cold.
Table 1 provides the SAF and product type consumer exposure levels that drive the IFRA QRA
category. These data are used with the NESIL to calculate the acceptable exposure levels to
individual fragrance ingredients. Table 2 gives the 11 IFRA QRA categories for dermal
sensitization based on the QRA approach. It also gives detailed comments for specific product
types. Table 3 is an alphabetical list of product types and their corresponding IFRA QRA Category.
*QRA Expert Group Membership
Anne Marie Api (RIFM)
David A. Basketter (SEAC, Unilever)*
Peter A. Cadby (Firmenich)
Marie-France Cano (LVMH)*
Graham Ellis (Givaudan)
G. Frank Gerberick (Procter & Gamble)

Peter Griem (Symrise)
Pauline M. McNamee (Procter & Gamble)
Cindy A. Ryan (Procter & Gamble)
Robert Safford (SEAC, Unilever)*
*No longer with company
Api et al., 2008, Dermal sensitization Quantitative Risk Assessment (QRA) for fragrance
ingredients. Regulatory Toxicology and Pharmacology, Volume 52, pages 3-23.
10

Table 1: SAF and Product Type Consumer Exposure Levels that Drive the IFRA QRA Category.
IFRA QRA
Category
SAF
Category 1
300
Category
Consumer
Exposure1
mg/cm2/day
11.7
Category 2
300
9.1
Category 3
300
Category 4
Product Type That Drives

the Category Consumer
Exposure Level
Maximum Pragmatic Level
Lip Products
Not Necessary
Acceptable Exposure Level derived from QRA
Deodorants/Antiperspirants
Not Necessary
2.2
Hydroalcoholics for Shaved

Skin
Not Necessary
100
2.2
Hydroalcoholics for
Unshaved Skin
Not Necessary
Category 5
100
4.2
Hand Cream
Not Necessary
Category 6
100
1.4
Mouthwash
Not Necessary
Category 7
300
4.4
Intimate Wipes
Not Necessary
Category 8
100
1.0
Hair Styling Aids
2%
The maximum concentration will not exceed 2%
and may be lower if determined by the QRA.
Rinse-off Hair Conditioners
5%
The maximum concentration will not exceed 5%
Hard Surface Cleaners
2.5%
The maximum concentration will not exceed 2.5%
Candles
Due to the expected negligible skin exposure from

such products the risk of induction of dermal
sensitization through the normal formulation and
use of such products is considered to be negligible.
As such, the concentration of fragrance ingredient
is not restricted in the finished product.
Category 9
Category 10
Category 11
100
100
10
0.2
0.1
0.00033
The Category Consumer Exposure Level (mg/cm 2/day) is driven by the product type in that category with the combined highest
consumer exposure level and highest Sensitization Assessment Factor (SAF). In order to identify the product type consumer exposure
that drives the category consumer exposure please refer to the Api and Vey 2008, Regulatory Toxicology and Pharmacology, Volume
52, pages 53-61, Table 2.
11

Table 2: IFRA Categories For Dermal Sensitization, QRA Approach, Arranged By Category.
Product Type
Category 1
Not Necessary
Acceptable Exposure Level
derived from QRA
Comments
Products that contain sunscreen or sun-block are not listed separately and are
included in the major product type (e.g. lip creams containing sunscreen are
Lip Products of all types (solid and liquid lipsticks, balms,
clear etc.)
Due to the possibility of ingestion of small amounts of fragrance ingredients,

materials present in the fragrance compound for use in this category must be
approved for use in food, meaning that all ingredients should be listed as having
"no safety concern", for example by the Joint FAO/WHO Expert Committee on
Food Additives (JECFA) and/or as Generally Recognized As Safe (GRAS) in
accordance with the US Federal Food, Drug and Cosmetic Act
IFRA prohibits the use of fragrance materials and mixtures in toys or other childrens
products where there is the likelihood of mouth contact. Following the criteria
established by the toy industry, these include: 1) toys for children less than 3 years
of age; 2) any toy designed and intended to go into the mouth; and/or 3) those toys
for which mouth contact is reasonably foreseeable.
This product type has been placed in Category 1 based on the absence of exposure
data. Should exposure data become available, these product types may be recategorized.
Childrens Toys
Due to the possibility of ingestion of small amounts of fragrance ingredients from the
use of the aforementioned allowable product categories (such as oral care, lip
products or certain types of toys), materials present in the fragrance compound must
not only comply with IFRA Standards but must also have an approved flavour
materials status as defined by the IOFI Code of Practice.
Category 2
Not Necessary
derived from QRA
Deodorant and Antiperspirant Products of all types including

any product with intended or reasonably foreseeable use on
the axillae or labelled as such (spray, stick, roll-on, underarm, deo-cologne and body spray, etc.)
Nose Pore Strips
These product types have been placed in Category 2 based on the absence of
exposure data and on assumptions which include the occluded use on skin. Should
exposure data become available, this product type may be re-categorized.
Fragranced Bracelets
12
Product Type
Category 3
Not Necessary
derived from QRA
Comments
Hydroalcoholic Products applied to recently shaved skin

(includes After Shave)
Eye Products of all types
(eye shadow, mascara, eyeliner, eye make-up, eye masks,
eye pillows, etc.) including eye care
Mens Facial Creams, Balms
Tampons
Baby Creams, Lotions, Oils
exposure data, with the assumption that this product is similar to a baby
cream/lotion/oil. Should exposure data become available, this product type may be
re-categorized.
Body Paint for Children
13
Product Type
Category 4
Not Necessary
derived from QRA
Comments
Hydroalcoholic Products applied to unshaved skin (includes

aqueous based, alcoholic based and hydroalcoholic) like
Cologne, Eau de Cologne, Eau de Parfum or Parfum
Body sprays (including Body Mist) with no intended or
reasonably foreseeable use on the axillae
Hair Styling Aids, Hair Sprays of all types (pumps, aerosol
sprays, etc.)
Products that contain sunscreen or sun-block are not listed separately and are
included in the major product type (e.g. lip creams containing sunscreen are
Body Creams, Oils, Lotions, Solid Perfumes, Fragrancing

Creams of all types (except baby creams and lotions)
Ingredients of Perfume Kits
Fragrance Compounds for Cosmetic Kits
Scent Pads, Foil Packs
exposure data, but it is recognized that these products have similarities to
hydroalcoholic products applied to unshaved skin. Should exposure data become
available, these product types may be re-categorized.
This product type has been placed in Category 4 based on the absence of
exposure data, but it is recognized that this product is similar to body creams,
lotions. Should exposure data become available, this product type may be recategorized.
exposure data, but it is recognized that this product is similar to hair styling aids
and hair sprays. Should exposure data become available, this product type may be
re-categorized.
exposure data, with the assumption that this product is similar to body creams.
Should exposure data become available, this product type may be re-categorized.
Scent Strips for Hydroalcoholic Products
Foot Care Products
Hair Deodorant
Body Paint (except those for children)
14
Product Type
Category 5
Not Necessary
derived from QRA
Comments
Womens Facial Creams/Facial Make-up

Hand Cream
Facial Masks
Baby Powder and Talc
Fragrance ingredients in hair permanent and other hair chemical treatments have
been placed in Category 5. There are no exposure data on these product types. It
is recognized that these product types involve repeated low frequency exposure.
In order to define a per diem exposure, a conservative surrogate product has been
chosen, which is leave-on conditioners. Should exposure data become available,
these product types may be re-categorized.
exposure data, but it is recognized that these products are generic to males and
females and have similarities with the product types in this category. Should
exposure data become available, these product types may be re-categorized.
exposure data, but it is recognized that this product is similar to hand creams.
exposure data, with the assumption that this product is similar to hair treatments.
Hair Permanent and other hair chemical treatments (e.g.

relaxers) but not hair dyes
Wipes or Refreshing Tissues for Face, Neck, Hands, Body
Hand Sanitizers
Dry Shampoo or Waterless Shampoo
15
Product Type
Category 6
Not Necessary
derived from QRA
Comments
Toothpaste and Mouthwash Products: With the implementation of the QRA

approach, the IFRA Standards will include oral care products. Mouthwash and
toothpastes are the principal oral care products currently identified in IFRA
Category 6. Exposure limits for these products are established to reduce the risk of
peri-oral skin sensitization and as such, are not related to considerations of safe
levels for ingestion.
Mouthwash, including Breath Sprays
Due to the possibility of ingestion of small amounts of fragrance ingredients from

the use of the aforementioned allowable product categories (such as oral care, lip
products), materials present in the fragrance compound must not only comply with
IFRA Standards but must also have an approved flavor materials status. As defined
by the IOFI Code of Practice, such materials are those that meet one or more of the
following requirements:
Toothpaste
Existing IFRA Standards will not be applied to these oral care product types in
IFRA Category 6. As the QRA approach for fragrance ingredient dermal
sensitizers is implemented, then maximum use levels of these ingredients in
toothpaste and mouthwash products will be introduced through definition of new or
revised IFRA Standards.
Category 7
Not Necessary
derived from QRA
Intimate Wipes
Baby Wipes
Insect Repellent (intended to be applied to the skin)
16
Product Type
Category 8
2%
Comments
Make-up Removers of all types (not including face cleansers)

Hair Styling Aids Non-Spray of all types (mousse, gels, leavein conditioners, etc.)
Nail Care
Powders and talcs, all types (except baby powders and talcs)
The maximum concentration

will not exceed 2% and may be
lower if determined by the
QRA.
Hair Dyes
17
exposure data, but it is recognized that the exposure would be similar to body
creams, lotions. Although the exposure is expected to be similar to body creams,
lotions, the overall SAF for powders and talcs is, however, lower and so these
products are placed into a different category compared to body creams, lotions.
Should exposure data become available, these product types may be recategorized.
Fragrance ingredients in hair dyes have been placed in Category 8. In the SCCP
Notes of Guidance, 2003, the daily exposure to hair dyes was not calculated due to
the low frequency of exposure. Since there are no daily exposure data to hair dyes
and exposure in this QRA for fragrance ingredient approach is expressed as per
diem, a similar product type is identified as a surrogate to define per diem exposure.
The product type chosen as this surrogate is leave-on conditioners. However, it is
recognized that this is a very simplistic and very conservative approach since the
actual exposure to hair dyes is not per diem, but a repeated low frequency exposure.
Product Type
Category 9
5%
Comments
Bar Soap (Toilet Soap)

Bath Gels, Foams, Mousses, Salts, Oils and Other Products
added to bathwater
Body Washes of all types (including baby washes) and
Shower Gels of all types
Conditioner (Rinse-Off)
All Depilatories (including waxes for mechanical hair removal)
Face Cleansers of all types (washes, gels, scrubs, etc.)
Facial Tissues
Feminine Hygiene Pads
Feminine Hygiene Liners
Fragranced Face Masks (not intended to be used as medical
device)
Liquid Soap
Napkins
Paper Towels
Shampoos of all types (including baby shampoos)
Shaving Creams of all types (stick, gels, foams, etc.)

will not exceed 5% and may be
lower if determined by the
QRA.
Toilet Paper
Wheat Bags
Other Aerosols (including air freshener sprays and air

freshener pump sprays, but not including
deodorant/antiperspirants, hair styling aids sprays)
18
Product Type
Category 10
Handwash Laundry Detergents of all types including
concentrates
Fabric Softeners of all types including fabric softener sheets
Household Cleaning Products, other types (fabric cleaners,
soft surface cleaners, carpet cleaners, etc.)
Machine Wash Laundry Detergents (liquids, powders, tablets,
etc.) including laundry bleaches and concentrates
Hand Dishwashing Detergent including concentrates
Hard Surface Cleaners of all types (bathroom and kitchen
cleansers, furniture polish, etc.)
Diapers
2.5%
Shampoos for pets

will not exceed 2.5% and may
be lower if determined by the
QRA.
Dry Cleaning Kits
Toilet Seat Wipes
Scented gloves, socks, tights with moisturizers
19
Comments
It was assumed that the exposure to humans from shampoos for pets could be
expected to be similar to hand dishwashing liquids.
exposure data, but it is recognized that this product is similar to fabric softener
sheets. Should exposure data become available, this product type may be recategorized.
exposure data, but it is recognized that this product is similar to hard surface
cleaner. Should exposure data become available, this product type may be recategorized.
exposure data, but it is recognized that this product is similar to diapers. Should
exposure data become available, this product type may be re-categorized.
Product Type
Category 11
All non-skin contact or incidental skin contact. Including:
Air Fresheners and Fragrancing of all types (concentrated
aerosol with metered doses (range 0.05-0.5mL/spray), plugins, solid substrate, membrane delivery, electrical, pot pourri,
powders, fragrancing sachets, incense, liquid refills, air
freshening crystals)
Air Delivery Systems
Animal Sprays (all types)
Candles
Cat litter
Cell phone cases
Deodorizers/Maskers not intended for skin contact (e.g. fabric
drying machine deodorizers, carpet powders)
Floor wax
Fragranced lamp ring
Fuels
Insecticides (e.g. mosquito coil, paper, electrical, for clothing)
excluding aerosols
Joss Sticks or Incense Sticks
Machine Dishwash Detergent and Deodorizers
Machine-only Laundry Detergent (e.g. liquitabs)
Odored Distilled Water (that can be added to steam irons)
Paints
Plastic articles (excluding toys)
Reed diffusers
Scratch and Sniff (sampling technology)
Scent delivery system using a dry air technology
Scent pack
Shoe Polishes
Toilet Blocks
Treatment products for textiles (e.g. starch sprays, fabric
treated with fragrances after wash, deodorizers for textiles or
fabrics)
Due to the expected negligible

skin exposure from such
products the risk of induction of
dermal sensitization through
the normal formulation and use
of such products is considered
to be negligible. As such, the
concentration of fragrance
ingredient is not restricted in
the finished product.
20
Comments

Table 3: IFRA Categories For Dermal Sensitization, QRA Approach, Arranged By Product Type.
Product Type
IFRA QRA
Category
Other Aerosols (including air freshener sprays and air freshener pump sprays, but not including
deodorant/antiperspirants, hair styling aids sprays)
Category 9
Air delivery systems
Category 11
Air Fresheners and Fragrancing of all types (concentrated aerosol with metered doses (range 0.05-0.5mL/spray),
plug-ins, solid substrate, membrane delivery, electrical, pot pourri, powders, fragrancing sachets, incense, liquid
refills, air freshening crystals)
Animal Sprays (all types)
Category 11
Category 11
Baby Lotion, Cream and Oil
Category 3
Category 5
Baby Wipes
Category 7
Category 9
Bath Gels, Foams, Mousses, Salts, Oils and other products added to bathwater
Body Creams, Oils, Lotions, Fragrancing Creams of all types (except baby creams and lotions)
Category 9
Category 4
Category 4
Category 3
Body sprays (including Body Mist) with no intended or reasonably foreseeable use on the axillae
Category 4
Body Washes of all types (including baby washes) and Shower Gels of all types
Category 9
Candles
Category 11
Cat litter
Category 11
Cell phone cases
Category 11
Category 9
Cosmetic Kits - Fragrance Compounds

Deodorant and Antiperspirant Products of all types including any product with intended or reasonably foreseeable
use on the axillae or labelled as such (spray, stick, roll-on, under-arm, deo-cologne and body spray, etc.)
Category 4
Deodorizers/Maskers not intended for skin contact (e.g. fabric drying machine deodorizers, carpet powders)
Category 11
Category 2
All Depilatories (including waxes for mechanical hair removal))
Category 9
Diapers
Category 10
Dry Cleaning Kits
Category 10
Dry Shampoo (or Waterless Shampoo)

Eye Products of all types
(eye shadow, mascara, eyeliner, eye make-up, eye masks, eye pillows, etc.) including eye care
Category 5
Category 10
Category 9
Facial Masks
Category 5
Feminine Hygiene Liners
Category 9
Category 3
Feminine Hygiene Pads
Category 9
Floor wax
Category 11
Foot Care Products
Category 4
Fuels
Category 11
Facial Tissue
Category 9
Fragranced Bracelet
Category 2
Fragranced Lamp Ring
Category 11
Fragranced Face Masks (not intended to be used as medical device)
Category 9
Hair Deodorant
Category 4
Hair Dyes
Category 8
Hair Permanent and other hair chemical treatments (e.g. relaxers) but not hair dyes
Category 5
21
Product Type
IFRA QRA
Category
Hair Styling Aids Non-Spray of all types (mousse, gels, leave-in conditioners, etc.)
Category 8
Hair Styling Aids, Hair Sprays of all types (pumps, aerosol sprays, etc.)
Category 4
Hand Cream
Category 5
Category 10
Hand Sanitizer
Category 5
Handwash Laundry Detergents of all types including concentrates
Category 10
Hard Surface Cleaners of all types (bathroom and kitchen cleansers, furniture polish, etc.)
Category 10
Household Cleaning Products, other types (fabric cleaners, soft surface cleaners, carpet cleaners, etc.)
Category 10
Hydroalcoholic Products applied to recently shaved skin (includes After Shave)

Hydroalcoholic Products applied to unshaved skin (includes aqueous based, alcoholic based and hydroalcoholic)
like Cologne, Eau de Cologne, Eau de Parfum or Parfum
Category 3
Insecticides (e.g. mosquito coil, paper, electrical, for clothing) excluding aerosols
Category 11
Category 4
Category 7
Intimate Wipes
Category 7
Category 11
Lip Products of all types (solid and liquid lipsticks, balms, clear or colored, etc.)
Category 1
Liquid Soap
Category 9
Category 11
Machine-only Laundry Detergent (e.g. liquitabs)
Category 11
Machine Wash Laundry Detergents (liquids, powders, tablets, etc.) including laundry bleaches and concentrates
Category 10
Category 8
Mens Facial Creams, Balms
Category 3
Category 6
Nail Care
Category 8
Napkins
Category 9
Nose Pore Strips
Category 2
Category 11
Paints
Category 11
Paper Towels
Category 9
Perfume Kit Fragrance Ingredients
Category 4
Category 8
Category 11
Reed Diffusers
Category 11
Scent delivery system using a dry air technology
Category 11
Scent pack
Category 11
Scent Pad and Foil Pack
Category 4
Scent Strips for Hydroalcoholic Products
Category 4
Shampoos for pets
Category 10
Category 11
Scented Gloves
Category 10
Scented Socks
Category 10
Category 9
Category 9
Shoe Polishes
Category 11
Solid Perfume
Category 4
Tampons
Category 3
22
Product Type
IFRA QRA
Category
Tights with moisturizers
Category 10
Toilet Blocks
Category 11
Toilet Paper
Category 9
Toilet Seat Wipes
Category 10
Toothpaste
Category 6
Toys
Treatment products for textiles (e.g. starch sprays, fabric treated with fragrances after wash, deodorizers for
textiles or fabrics)
Wheat bags
Category 1
Category 11
Category 5
Category 5
23
Category 9

Table 4: Guidance for preparing IFRA Certificates.
Category for
systemic toxicity
Max use level

for
Methyl
eugenol
Max use level

for
Estragole
Phototox
Food
use
approval
Class for
IFRA
Certificate
Lip Products of all types (solid and liquid lipsticks, balms, clear or
colored, etc.)
leave-on
4 ppm
0.01%
Applicable
YES
Class 1
Childrens Toys
leave-on
4 ppm
0.01%
Applicable
YES
Class 1
Deodorant and Antiperspirant Products of all types including any

product with intended or reasonably foreseeable use on the
axillae or labelled as such (spray, stick, roll-on, under-arm, deocologne and body spray, etc.)
leave-on
4 ppm
0.01%
Applicable
Class 2
Nose pore strips
leave-on
4 ppm
0.01%
Applicable
Class 2
Fragranced Bracelets
leave-on
4 ppm
0.01%
Applicable
Class 2
EDT
80 ppm
0.2%
Applicable
Class 3.A
Fine Fragrance
200 ppm
0.2%
Applicable
Class 3.B
Eye Products of all types (eye shadow, mascara, eyeliner, eye

make-up, etc.) including eye care
leave-on
4 ppm
0.01%
Applicable
Class 3.C
Mens Facial Creams and Balms
leave-on
4 ppm
0.01%
Class 3.C
Tampons
leave-on
4 ppm
0.01%
Baby Creams, Lotions, Oils
leave-on
4 ppm
0.01%
Applicable
Not
applicable
Applicable
leave-on
4 ppm
0.01%
Applicable
Class 3.C
Product Type (QRA)

Category 1
Category 2
Category 3
Hydroalcoholic Products applied to recently shaved skin (includes
After Shave)
24
Class 3.D
Class 3.C
Product Type (QRA)
Category for
systemic toxicity
Max use level

for
Methyl
eugenol
Max use level

for
Estragole
Phototox
EDT
80 ppm
0.2%
Applicable
Class 4.A
fine fragrance
200 ppm
0.2%
Applicable
Class 4.B
leave-on
4 ppm
0.01%
Applicable
Class 4.C
leave-on
4 ppm
0.01%
Applicable
Class 4.C
fragrancing cream
40 ppm
0.01%
Applicable
Class 4.D
Leave-on
4ppm
0.01
Applicable
Class 4.C
fragrancing cream
40 ppm
0.01%
Applicable
Class 4.D.
EDT
80 ppm
0.20%
Applicable
Class 4.A
Food
use
approval
Class for
IFRA
Certificate
Category 4
Hydroalcoholic Products applied to unshaved skin (includes
aqueous based, alcoholic based and hydroalcoholic) like Cologne,
eau de cologne, Eau de Parfum or Parfum
Hair Styling Aids Sprays of all types (pumps, aerosol sprays, etc.)
Body Creams, Oils, Lotions of all types (except baby creams,
lotions and oils)
Fragrancing Cream
Body sprays (including Body Mist) with no intended or reasonably
foreseeable use on the axillae
Solid perfumes
Ingredients of Perfume Kits
Fragrance Compounds for Cosmetic Kits
leave-on
4 ppm
0.01%
Applicable
Class 4.C
Scent Pads, Foil packs
EDT
80 ppm
0.2%
Applicable
Class 4.A
Scent Strips for hydroalcoholic products
EDT
80 ppm
0.2%
Applicable
Class 4.A
Foot Care Products
leave-on
4 ppm
0.01%
Applicable
Class 4.C
Hair deodorant
leave-on
4 ppm
0.01%
Applicable
Class 4.C
leave-on
4 ppm
0.01%
Applicable
Class 4.C
leave-on
4 ppm
0.01%
Applicable
Class 5
Hand Cream
leave-on
4 ppm
0.01%
Apliccable
Class 5
Hand sanitizers
leave-on
4 ppm
0.01%
Applicable
Class 5
Facial Masks
leave-on
4 ppm
0.01%
Applicable
Class 5*
leave-on
4 ppm
0.01%
Applicable
Class 5
Hair Permanent and other hair chemical treatments (e.g. relaxers)

but not hair dyes
leave-on
4 ppm
0.01%
Applicable
Class 5
leave-on
4 ppm
0.01%
Applicable
Class 5
Dry Shampoo or Waterless Shampoo
leave-on
4 ppm
0.01%
Applicable
Class 5
rinse-off
10 ppm
0.01%
Toothpaste
rinse-off
10 ppm
0.01%
Category 5
Category 6
25
Not
applicable
Not
applicable
YES
Class 6
YES
Class 6

Category for
systemic toxicity
Max use level

for
Methyl
eugenol
Max use level

for
Estragole
Intimate Wipes
leave-on
4 ppm
0.01%
Baby Wipes
leave-on
4 ppm
0.01%
leave-on
4 ppm
0.01%
Not
applicable
Not
applicable
Applicable
leave-on
4 ppm
0.01%
Applicable
Class 8.A
Hair Styling Aids Non-Spray of all types (mousse, gels, leave-in

conditioners, etc.)
leave-on
4 ppm
0.01%
Applicable
Class 8.A
Nail Care
leave-on
4 ppm
0.01%
Applicable
Class 8.A
leave-on
4 ppm
0.01%
Class 8.A
Hair Dyes
rinse-off
10 ppm
0.01%
Applicable
Not
applicable
Product Type (QRA)
Phototox
Food
use
approval
Class for
IFRA
Certificate
Category 7
Class 7.A
Class 7.A
Class 7.B
Category 8
26
Class 8.B

Category for
systemic toxicity
Max use level

for
Methyl
eugenol
Max use level

for
Estragole
rinse-off
10 ppm
0.01%
Liquid Soap
rinse-off
10 ppm
0.01%
rinse-off
10 ppm
0.01%
rinse-off
10 ppm
0.01%
rinse-off
10 ppm
0.01%
All Depilatories (including waxes for mechanical hair removal)
rinse-off
10 ppm
0.01%
Body Washes of all types (including baby washes) and Shower

Gels of all types
rinse-off
10 ppm
0.01%
Product Type (QRA)
Phototox
Food
use
approval
Class for
IFRA
Certificate
Category 9

Feminine hygiene pads, liners
Bath Gels, Foams, Mousses, Salts, Oils and Other Products
added to bathwater
Facial tissues
Fragranced Face Masks (not intended to be used as medical
device)
Napkins
Paper towels
Toilet paper
Wheat bags
Other Aerosols (including air freshener sprays and air freshener
pump sprays, but not including deodorants/antiperspirants, hair
styling aids sprays)
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Class 9.A
Class 9.A
Class 9.A
Class 9.A
Class 9.A
Class 9.A
Class 9.A
rinse-off
10 ppm
0.01%
non-skin, incidental
skin contact
100 ppm
0.2%
rinse-off
10 ppm
0.01%
Not
applicable
Class 9.A
100 ppm
0.2%
Applicable
Class 9.C
100 ppm
0.2%
Applicable
Class 9.C
100 ppm
0.2%
Applicable
Class 9.C
100 ppm
0.2%
Applicable
Class 9.C
100 ppm
0.2%
Not
applicable
Class 9.B
100 ppm
0.2%
Not
applicable
Class 9.B
100 ppm
0.2%
Applicable
Class 9.C
skin contact
skin contact
skin contact
skin contact
skin contact
skin contact
skin contact
27
Class 9.A
Class 9.B
Product Type (QRA)
Category for
systemic toxicity
Max use level

for
Methyl
eugenol
Max use level

for
Estragole
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
4 ppm
0.01%
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
4 ppm
0.01%
Phototox
Food
use
approval
Class for
IFRA
Certificate
Category 10
Household Cleaning Products, Other Types (fabric cleaners, soft

surface cleaners, carpet cleaners, etc.)
skin contact
skin contact
skin contact
Machine Wash Laundry Detergents (liquids, powders, tablets,

etc.) including laundry bleach and concentrates
skin contact
Handwash Laundry Detergents of all types including concentrates


Hard Surface Cleaners of all types (bathroom and kitchen
cleansers, furniture polish, etc.)
Diapers
Shampoos for pets
Dry cleaning kits
Scented gloves, socks, tights with moisturizers
Toilet seat wipes
skin contact
skin contact
other leave-on
skin contact
skin contact
skin contact
other leave-on
28
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Not
applicable
Class 10.A
Class 10.A
Class 10.A
Class 10.A
Class 10.A
Class 10.A
Class 10.B
Class 10.A
Class 10.A
Class 10.A
Class 10.B

Category for
systemic toxicity
Max use level

for
Methyl
eugenol
Max use level

for
Estragole
Phototox
All non-skin contact or incidental skin contact including:
skin contact
100 ppm
0.2%
not
applicable
Class 11
Candles
skin contact
100 ppm
0.2%
not
applicable
Class 11
skin contact
100 ppm
0.2%
not
applicable
Class 11
Air Delivery Systems
skin contact
100 ppm
0.2%
not
applicable
Class 11
Cell phone cases
skin contact
100 ppm
0.2%
Not
applicable
Class 11
Pot pourri, powders, fragrancing sachets, liquid refills for air

fresheners (non-cartridge systems), Reed diffusers
skin contact
100 ppm
0.2%
not
applicable
Class 11
Liquid refills for air fresheners (cartridge systems)
skin contact
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
skin contact
100 ppm
0.2%
not
applicable
Class 11
skin contact
100 ppm
0.2%
not
applicable
Class 11
Air freshening crystals
skin contact
100 ppm
0.2%
not
applicable
Class 11
Toilet Blocks
skin contact
100 ppm
0.2%
not
applicable
Class 11
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
Product Type (QRA)
Food
use
approval
Class for
IFRA
Certificate
Category 11
Air Fresheners and Fragrancing of all types (concentrated aerosol

with metered doses (range 0.05-0.5mL/spray), plug-ins, solid
substrate, membrane delivery, electrical)
Shoe Polishes
Deodorizers/Maskers not intended for skin contact (e.g. fabric
drying machine deodorizers, carpet powders)
Insecticides (mosquito coil, paper, electrical, for clothing etc.)
excluding aerosols
Scent delivery system using a dry air technology that releases a
fragrance without sprays, aerosols or heated oils (technology of
nebulization)
skin contact
skin contact
not
applicable
not
applicable
not
applicable
Class 11
Class 11
Machine-only Laundry Detergent (e.g. liquitabs)**
skin contact
skin contact
skin contact
skin contact
100 ppm
0.2%
not
applicable
Class 11
Fuels
skin contact
100 ppm
0.2%
not
applicable
Class 11

29
not
applicable
not
applicable
not
applicable
Class 11
Class 11
Class 11
Class 11
Product Type (QRA)
Category for
systemic toxicity
Max use level

for
Methyl
eugenol
Max use level

for
Estragole
Phototox
Fragranced lamp ring
skin contact
100 ppm
0.2%
not
applicable
Scent pack
skin contact
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%
100 ppm
0.2%

Paints
skin contact
skin contact
Treatment products for textiles (e.g. starch sprays, fabric treated

with fragrances after wash, deodorizers for textiles or fabrics)
skin contact
skin contact
skin contact
Floor wax
skin contact
100 ppm
0.2%
skin contact
100 ppm
0.2%
Cat litter
Animal sprays (all types)
not
applicable
not
applicable
not
applicable
not
applicable
not
applicable
not
applicable
not
applicable
not
applicable
Food
use
approval
Class for
IFRA
Certificate
Class 11
Class 11
Class 11
Class 11
Class 11
Class 11
Class 11
Class 11
Class 11
Comments
* Class 5, Facial masks: There are several types of masks: peel off (similar to rinse-off, rinse-off and leave-on (you only remove the excess with a facial tissue). To ease the split the
most restrictive, i.e. leave-on is applied for all.
** Liquitabs corresponds to a dose of liquids wrapped in a film: no contact with hands is expected under normal conditions of use
The table was prepared with the intention to cover the vast majority of the products; however it may not cover some specific applications. In this case other classes may be
attributed based on a specific risk assessment.
30

Example: Citral
Citral has been chosen as an example to demonstrate the practical application of the principles
of QRA. This material is one of the four fragrance ingredients that were part of the 40th
Amendment to the IFRA Code of Practice for which Standards have been set based on the QRA
approach. The dermal sensitization data on citral include the availability of robust animal
sensitization data, confirmatory human sensitization data as well as diagnostic patch test studies.
Table 5 shows the practical application of the dermal sensitization QRA approach for fragrance
ingredients, in the 11 IFRA QRA categories. It lists the acceptable levels for citral in each IFRA
QRA category.
Following Table 5 some frequently asked questions (FAQ) about the implementation and
designation of IFRA categories are given.
Table 5: Acceptable Levels Of Citral In Each Of The 11 IFRA Categories Based On QRA.
IFRA
Category
SAF
Category 1
300
Category
Consumer
Exposure1
mg/cm2/day
11.7
Category 2
300
9.1
Category 3
300
2.2
Category 4
100
2.2
Category 5
100
4.2
Category 6
100
1.4
Category 7
300
4.4
Category 8
Category 9
100
100
1.0
0.2
Category 10
100
0.1
IFRA Standard Limit

for Citral2

Not Necessary
Not Necessary
Not Necessary
Not Necessary
Not Necessary
Not Necessary
Not Necessary
Not Applicable3
5%
The maximum concentration will not exceed 5% and may be
lower if determined by the QRA.
2.5%
The maximum concentration will not exceed 2.5% and may be
lower if determined by the QRA.
0.04%
0.05%
0.20%
0.60%
0.30%
1.0%
0.10%
1.40%
Maximum Pragmatic
Level Used
Maximum Pragmatic
Level Used
Category 11
10
0.00033
Due to the expected negligible skin exposure from such

products the risk of induction of dermal sensitization through
the normal formulation and use of such products is considered
to be negligible. As such, the concentration of fragrance
ingredient is not restricted in the finished product.
NA
1
The Category Consumer Exposure Level (mg/cm 2/day) is driven by the product type in that category with the combined highest consumer
exposure level and highest Sensitization Assessment Factor (SAF). In order to identify the product type consumer exposure that drives the
category consumer exposure please refer to Api and Vey 2008, Regulatory Toxicology and Pharmacology, Volume 52, pages 53-61, Table
2.
2
Note: It is important to note that although the WoE NESIL (Weight of Evidence No Expected Sensitization Induction Level) is not included
in the table above it is essential to the determination of the IFRA Standard since the Acceptable Exposure Level (AEL) is derived from the
WoE NESIL divided by the Sensitization Assessment Factor (SAF) and multiplied by the consumer exposure level. The WoE NESIL for citral
is 1400 g/cm2.
3
The maximum pragmatic level of 2% was not invoked for Category 8 because the acceptable exposure level derived from the QRA is less
than 2% (the maximum pragmatic level).
This Table is a reprint from Api and Vey 2008, Regulatory Toxicology and Pharmacology, Volume 52, pages 53-61, Table 6.
31

Frequently Asked Questions (FAQs)
How does IFRA/RIFM calculate the AEL that defines a product category?
The table listed below demonstrates how all the data are used to determine acceptable level of
use for citral in IFRA QRA Category 4. It also demonstrates how important consumer exposure
levels are to a risk assessment. The exposures and SAFs listed in Table 2 provide the information
that is used to calculate the Acceptable Exposure Level (in the Citral column) for each product
category. For a detailed description of exposure levels and SAFs for each product type, please
refer to Api et al., 2008, Dermal sensitization Quantitative Risk Assessment (QRA) for fragrance
ingredients. Regulatory Toxicology and Pharmacology,Volume 52, pages 3-23, 2008.
Citral
WoE NESIL (from Table 2)
SAF (from Technical Dossier)
AEL
Category 4 Consumer Exposure
Level (CEL)
AEL/CEL
Concentration of citral
in the product based on
AEL CEL
Risk Assessment
Calculation of Acceptable Level for IFRA Category 4

1400 ug/cm2
100 (10 X 3 X 3)
14.0 ug/cm2
2.2 mg/cm2/day1
AEL/CEL
(14.0 ug/cm2 X 0.001 mg/g) 2.2 mg/cm2/day
= 0.0064
0.64%
Acceptable if citral level is less than 0.64%
WoE NESIL = Weight of Evidence No Expected Sensitization Induction Level

Sensitization Assessment Factor
AEL = Acceptable Exposure Level
CEL = Consumer Exposure Level
32

What product types are used to derive the different IFRA categories?
The Table below from Api and Vey, 2008, Implementation of the dermal sensitization Quantitative
Risk Assessment (QRA), for fragrance ingredients, Regulatory Toxicology and Pharmacology,
Volume 52, pages 53-61, 2008. outlines 11 different IFRA categories for dermal sensitization. For
many categories it may appear that there is a wide diversity of product types. However, this is
because the categories are based on scientific rationale (SAF and consumer product exposure),
and not on the functional similarity of each product type.
IFRA
Category
Category
Consumer
Exposure
mg/cm2/day
SAF
Product Type Designating

IFRA Category
Category 1
300
11.7
Lipstick
AEL derived from QRA
Category 2
300
9.1
Solid Antiperspirant
Category 3
300
2.2
Aftershave
Category 4
100
2.2
Hydroalcoholic for
unshaved skin
Category 5
100
4.2
Hand Cream
Category 6
100
1.4
Toothpaste
Category 7
300
4.4
Intimate Wipes
Category 8
100
1.0
Hair Styling Aids
Category 9
100
0.2
Conditioners, Rinse-Off
Category 10
100
0.1
Hard Surface Cleaners
Category 11
10
0.00033
Candles
2% The maximum concentration will not

exceed 2% and may be lower if determined
by the QRA
5% The maximum concentration will not
exceed 5% and may be lower if determined
by the QRA
2.5% The maximum concentration will not
exceed 2.5% and may be lower if
determined by the QRA
These products result in negligible skin contact.
The approach for a pragmatic
concentration of fragrance ingredient in this
category is explained in the notes
section and below in the Frequently Asked
Questions section
Why do some product categories have a Maximum Pragmatic Level?

For some IFRA QRA Categories, the calculated acceptable concentrations of fragrance
ingredients in the final product may be unrealistically high because the calculated consumer
exposure levels for certain product types are very low. Practical reasons dictate setting a default
maximum level of the fragrance ingredients identified as dermal sensitizers for these product
types. This pragmatic level is defined as that not exceeding the concentration of the fragrance
compound that has been stipulated in the fragrance brief for the finished product. In Tables 1
and 2 these levels are indicated in the column identified as Maximum Pragmatic Level. If the
AEL derived from the QRA for a fragrance ingredient in a specific product type is less than the
33

concentration identified as the Maximum Pragmatic Level, the AEL must take precedence and
be applied.
Why should levels of citral be limited?

The patch test database survey from the Contact Allergy Unit, University Hospital Leuven,
Belgium indicates, at least for toilet water/perfume products that a limit for citral should be
established. A total of 3323 subjects were investigated by the Contact Allergy Unit. 9.1% of these
patients were found to have a positive patch test reaction to the fragrance-mix; 6.7% to balsam
of Peru; 4.8 % to colophony. Some of these patients showed positive reactions to multiple
fragrance ingredients. Of the patients who reacted positively to the fragrance mix, 133 exhibited
positive patch tests to their own cosmetic products. Of these 133 patients, 66 involved fragrancerelated contact-allergic reactions and 6 reacted to citral in hydroalcoholic products.
IFRA reported in 2001 that the average maximum concentration of citral in hydroalcoholic
products was 1.76% or 37.4 g/cm2 /day. Figure 1 shows how the average maximum
concentration reported in 2001 is unacceptable (i.e. the Acceptable Exposure Level or AEL is less
than the customer exposure level or CEL). The figure also demonstrates how the current IFRA
limit for this product type (Category 4, hydroalcoholic product for unshaved skin) is acceptable
(i.e. the AEL is greater than the CEL).
0.6%
13 g/cm2 1.7%
CEL 37 g/cm2
CEL
14 g/cm2
AEL
Legend:
WoE NESIL =
Weight of
Evidence No
Expected
Sensitization
Induction Level
1400 g/cm2
WoE NESIL
SAF =
Sensitization
Assessment
Factor
0.01
0. 1
1.0
AEL =
Acceptable
Exposure Level
= WoE
NESIL/SAF
SAF = 100
AEL/CEL
Unacceptable
AEL/CEL
Acceptable
10
100
Citral Level - log g/cm2
1000
10,000
CEL =
Consumer
Exposure Level
Figure 1: Illustration of AEL/CEL ratio for the current average maximum dermal use level for citral
(1.7%; IFRA, 2001) in a hydroalcoholic product for unshaved skin.
34

Are any other oral care products included?
No. Other oral care products (tooth whiteners and denture adhesives) were considered, but were
specifically excluded from the QRA approach. This is because these products are regulated
globally as medical devices and regulations covering such products include specific safety
assessment guidelines.
For perspective, mouthwash and toothpastes are the principal oral care products currently
identified in IFRA Category 6. Exposure limits for these products are established to reduce the
risk of peri-oral dermal sensitization and as such, are not related to considerations of safe levels
for ingestion.
Do I have to calculate the NESIL and AELs?

No. NESILs and AELs will be determined by RIFM and approved by the RIFM Expert Panel
(REXPAN) and will be the basis for the QRA derived IFRA Standards.
What happens if I have a product that is not in a category?

In cases, where a product is not currently categorized and/or there are newly available data on
consumer product exposure or surface area, then it is incumbent on the fragrance supplier to
submit these data with undue delay. Data should be sent to either Dr. Matthias Vey, IFRA
Scientific Director ([email protected]), the IFRA Secretariat ([email protected]) or Dr. Anne
Marie Api, Vice President Human Health Sciences ([email protected]). RIFM and IFRA have
developed a form to providing all the necessary information. The form can be found at IFRA
Information Letter 796 and also on the RIFM and IFRA websites (http://rifm.org/publications-sorttitle.php or http://www.ifraorg.org/en-us/guidelines/). Supposed the provided information is
sufficiently robust, this would lead to a modification of this information booklet and the IFRA
membership and stakeholders would be adequately informed about the change(s).
Why was the QRA developed? What was wrong with the old method?
The QRA approach was defined to address limitations in the historical methodology that related
to the more qualitative nature of the dermal sensitization risk assessments and the definition of
only two product categories (skin contact and non-skin contact). This new methodology is a major
improvement over former risk assessment practices because it is quantitative in nature and
specifically addresses the elements of exposure-based risk assessment that are unique to the
induction of dermal sensitization, while being consistent with the principles of general toxicology
risk assessment. Since exposure is a key element of category determination, this enables
maintenance of relevant exposure and therefore safety, while providing greater flexibility to the
perfumer because the limit is no longer the same across all skin contact applications. This means
that compared to what has been used in the past, in some product applications, a higher fragrance
ingredient concentration will be possible, while in others, a lower level may be specified, .
Why is capping implemented on some Standards?

In some cases, due to the more exact science of the QRA approach, and especially because it is
an exposure based risk assessment and specific to various product applications, the QRA
methodology would suggest that a higher use level could be established for certain materials
which have an existing IFRA Standard. This is particularly true for rinse-off product types. This
would result in raising the maximum use level of materials known to have some capacity for
inducing contact allergy for a number of specific product applications.
Raising the limit for fragrance ingredients on the basis of the QRA methodology is not expected
to result in new inductions. However, increased exposure due to elevated use levels presents the
theoretical possibility that certain pre-sensitized individuals might experience an allergic contact
35

dermatitis where previously they had not. Should this occur, it would be impossible for the
dermatologists to distinguish whether such an effect is the result of elicitation of an existing allergy
or the result of a new induction. The scientific tools are not available today to allow for this
distinction to be made.
Therefore, for materials that already have an IFRA Standard, IFRA and its members have
decided, as a precautionary measure to cap at the level of the previous IFRA Standard on a
temporary basis until the end of a 5 year monitoring phase. At the end of those 5 years, the
position will be re-evaluated. This excludes category 11 (non-skin contact products) as well as
oral care products, which had no IFRA restriction before the introduction of the QRA. Therefore,
for oral care products the limits as determined by the QRA will remain in place even if they are
higher than the limits in the original Standards.
The QRA methodology is being used prospectively (creation of new Standards for formerly nonrestricted materials) as well as retrospectively (creation of revised Standards for materials that
already had a restriction based on sensitization). Its prospective use will continue to result in the
establishment of IFRA Standards where none currently exist. Based on our discussions with key
dermatologists, this community supports this prospective use of the QRA methodology. For all
prospective uses (new IFRA Standards), restrictions will be established by the QRA methodology
(for example, Citral, where the QRA Standard was introduced with the 40th Amendment in 2006).
There will be no changes to the acceptable exposure levels established by the QRA methodology
for all prospective uses of the QRA method.
Where can I get help in understanding the QRA approach and making the
appropriate procedural changes?
This booklet is the first interface for global fragrance suppliers and users. For more in-depth
understanding of the QRA approach it is important to read Api et al., 2008, Dermal sensitization
Quantitative Risk Assessment (QRA) for fragrance ingredients. Regulatory Toxicology and
Pharmacology, Volume 52, pages 3-23, 2008. The original technical dossier authored by the QRA
Expert Group*, Dermal Sensitization Quantitative Risk Assessment (QRA) for Fragrance
Ingredients, Technical Dossier, March 15, 2006, Revised June 22, 2006, is also still available on
the
IFRA
and
RIFM
websites
(http://rifm.org/publications-sort-title.php
and
http://www.ifraorg.org/en-us/guidelines/).
Will the NESILS and AELs ever change requiring reformulation as a result of a
revised QRA?
While highly improbable it is not impossible that a fragrance ingredient NESIL once defined would
be changed. However, the additional data would need to provide significant additional perspective
for such a change to be necessary. It is more likely that the AEL could change on the basis of
additional relevant exposure data becoming available. Such changes would be incorporated into
future IFRA Amendments and updated versions of this information booklet.
36
Glossary
AEL Acceptable Exposure Level
CEL Consumer Exposure Level
FAQ Frequently Asked Question
IOFI - International Organization of Flavor Industries
SAF Sensitization Assessment Factor
NESIL No Expected Sensitization Induction Level
NOEL No Observed Effect Level
QRA Quantitative Risk Assessment
REXPAN RIFM Expert Panel
WoE Weight of Evidence
37

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IFRA RIFM QRA Information Booklet V7.1

Last updated: July 9, 2015

QRA INFORMATIONAL BOOKLET VERSION 7.1

IFRA RIFM QRA Information Booklet V7.1

Last updated: July 9, 2015

QRA INFORMATIONAL BOOKLET VERSION 7.1

47th Amendment to the IFRA Code of Practice (Spring 2013)

46th Amendment to the IFRA Code of Practice (June 2011)

45th Amendment to the IFRA Code of Practice (June 2010)

44th Amendment to the IFRA Code of Practice (July 2009)

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QRA INFORMATIONAL BOOKLET VERSION 7.1

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42nd Amendment to the IFRA Code of Practice (Spring 2007)

40th Amendment to the IFRA Code of Practice (May 2006).

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QRA INFORMATIONAL BOOKLET VERSION 7.1

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Definition of IFRA Categories

Guidance for completion of IFRA Certificates

Important information relevant to the product types included in each Category

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Deemed to be Generally Recognized As Safe (GRAS) or approved food additives by

Are compliant with appropriate national/regional regulation covering the use of

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*No longer with company

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Product Type That Drives

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Hydroalcoholics for Shaved

Rinse-off Hair Conditioners

Hard Surface Cleaners

Due to the expected negligible skin exposure from

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