The IFRA Compliance 1. General description of the IFRA Standards Q. What is an “IFRA Standard”? Q. What does IFRA compliance mean in practice? Q. What is the IFRA policy in terms of unavoidable traces of prohibited materials? Q. How many Standards have been implemented by IFRA until now? Q. How many fragrance ingredients does it make? Q. Why are some ingredients banned whilst others are restricted ? Q. Does the timeline provided in the IFRA Standard relate to the compliance of the finished product with the latest IFRA Amendment?
2. The IFRA Standards Development Process Q. How do you create the IFRA Standards? Q. Does the absence of an IFRA Standard mean that the fragrance ingredient is 100% safe?
3. The QRA methodology Q. What is the QRA methodology? Q. How do QRA Standards work? Q. What is the difference between an IFRA category and an IFRA class?
4. The IFRA Compliance and the IFRA Certificate
Q. A natural extract is covered by an IFRA Standard. Does a fragrance formula additionally also have to comply with the IFRA Standards for each of the constituents in that oil ? Q. What is the IFRA Certificate and who makes this document? Q. If a fragrance becomes used in an application different from that for which an original IFRA Certificate has been made, can the client still use the same IFRA certificate?
More things to know about the Standards IFRA UK Ivy Cottage Cosgrove MK19 7JJ
1. General description of the IFRA Standards Q. What is an “IFRA Standard”? IFRA Standards are part of the IFRA Code of Practice and are the outcome of the industry’s self regulated risk management system related to the use of fragrance ingredients. This self-‐regulating system is based on risk assessments carried out by an independent academic Expert Panel. This Expert Panel is made up of renowned independent experts from fields such as dermatology, toxicology, pathology and environmental sciences. Their role is to evaluate the data on a fragrance ingredient to ensure the current accepted use level is still valid, in turn this assures the safe use by consumers. In cases where the safety assessment does not support the current use, the Expert Panel instructs IFRA to issue a Standard. There are three types of IFRA Standards: -‐ Standards of restriction; limiting the use of fragrance ingredients to a certain level -‐ Standards of prohibition; banning the use of the material as a fragrance ingredient -‐ Standards of specification; establishing purity criteria that the material must meet to enable use as a fragrance ingredient. The IFRA Standards of restriction could be based on each of the following specific toxicological endpoints which consequently is reflected in , specific risk management measures: -‐ Protection against induction of skin sensitization (a term related to skin allergies) via the QRA methodology (see section 3). -‐ Protection against systemic toxicity (a term related to the toxicity of a substance when entering the body). -‐ Protection against photo toxicity (a term linked to chemically induced skin effects requiring light that does not involve the immune system). All members of IFRA are required, as a condition of membership, to observe the IFRA Code of Practice and, consequently, to comply with the IFRA Standards. When a new IFRA Standard is published, a transition period is granted to ensure its proper implementation by the industry: this transition period is usually 2 months for new submissions and 14 months for existing fragrance compounds. IFRA Standards are published on a 2-‐yearly basis, unless there is an urgent need for action at which point the industry will publish a new standard immediately. Q. What does IFRA compliance mean in practice? In practice, to 'comply' with the IFRA Standards means that a fragrance formula does not contain prohibited fragrance ingredients nor does it contain restricted fragrance ingredients beyond their safe use level. Furthermore, the fragrance compound resulting will be accompanied by an IFRA certificate giving the safe use level in each product category.
Q. What is the IFRA policy in terms of unavoidable traces of prohibited materials? Unavoidable traces of prohibited substances might be acceptable provided that these traces are safe based on individual safety considerations and intended uses determined by member companies within any applicable regulatory requirements. If a company does not have the internal resources necessary to assess acceptable trace levels, IFRA recommends that this evaluation is outsourced to a consultant who specializes in safety assessment of finished fragranced products. Please, consult the respective IFRA Standards to know more about specific trace levels enforced by IFRA. Q. How many Standards have been implemented by IFRA until now? At the time of the 47th Amendment (published on June 10th, 2013), 196 IFRA Standards are implemented (respectively 99 Standards of restriction, 80 Standards of prohibition and 17 Standards of specification). These IFRA Standards are publicly available and can be consulted on the IFRA website. The IFRA Standards can also be consulted offline by downloading the overview of all IFRA Standards (Excel spreadsheet) and the IFRA Standards Booklet (pdf). Q. How many fragrance ingredients are covered by IFRA Standards ? This is not an easy question and the actual number of fragrance ingredients covered by an IFRA Standard is difficult to estimate. Hundreds of fragrance ingredients are in the scope of the IFRA Risk Management system. There are basically three reasons for this • Some IFRA Standards cover more than one fragrance ingredient. Indeed, a given IFRA Standard might restrict, prohibit or set specifications for a full group of substances linked by chemical similarities. Additionally, and by default, all stereoisomers enter in the scope of a given Standard: -‐ Chemical groups (e.g. 2,4-‐Dienals): some Standards cover groups of chemical substances belonging to the same structural family although the molecular weights and other properties of these substances can vary. -‐ Structural isomers (e.g. o,m,p-‐tolualdehydes): some Standards cover several substances that only differ by the position of their chemical functions. -‐ Stereoisomers (cis/trans isomers, enantiomers, diastereoisomers): some Standards cover all isomers of a given substance as the safety assessment of fragrance ingredients is usually conducted on mixtures of isomers. Therefore, unless something else is specified, all isomers are implicitly covered by its IFRA Standard. • Most Natural Complex Substance's (also called NCS or natural extracts ) contain at least one substance covered by an IFRA Standard; through the nature and the concentration of their constituents, the use of a Natural Complex Substance might be restricted as well although there is not an IFRA Standard for each NCS that contains a restricted substance. A list of the main NCS's and their constituents covered by an IFRA Standard as reported in Annex I of the IFRA Standards.
A few fragrance ingredients, called Schiff bases, are synthesized by combining an aldehyde and an amine. These fragrance ingredients are relatively fragile and usually disassociate in the finished product and return in part to the starting materials. For this reason, an IFRA Standard covering an aldehyde will also cover all the Schiff bases made with this aldehyde. For more information about Schiff bases, please, consult Annex II of the IFRA Standards.
Q. Why are some ingredients banned whilst others are restricted ? IFRA represents the fragrance industry and is well aware of the difficulties that the implementation of IFRA Standards causes to the perfumers and their companies. However, IFRA represents a responsible industry for which consumer safety is the first priority. The fragrance industry takes its regulation seriously and is committed to undertaking its responsibilities thoroughly. All of its ingredients are rigorously assessed for toxicity and IFRA works closely with regulators and stakeholders to issue and update comprehensive safety standards. Because of their toxicological profile some materials need to be covered by an IFRA Standard. Amongst them, some fragrance ingredients can be safely used under a given concentration in the finished product and an IFRA Standard of restriction is established to control the consumer exposure. For others, the establishment of a safe use level is impossible because of their strong toxicity. In this case, an IFRA Standard of prohibition is necessary. Q. Does the timeline provided in IFRA Standards relate to the compliance of the finished product with the latest IFRA Amendment? No – the timelines in the Standards relate to the compliance (supply) of fragrance compounds only, not to the finished product in the marketplace. This is explicitly mentioned on each Standard. 2. The IFRA Standards Development Process Q. How do you create the IFRA Standards? The fragrance industry spends approximately $8 million (annually) in joint research on the safety of fragrances, and much more at the individual company level. IFRA provides information on the exposure situation such as: usage concentration, variety of use, volume of use chemical composition as well as the olfactory profile and olfactory potential (importance) of a fragrance ingredient to the Research Institute for Fragrance Materials (RIFM), the scientific arm of IFRA. RIFM then prepares comprehensive dossiers on the materials including all available safety data and, if necessary, initiates and organizes any missing safety studies on the fragrance ingredient. The Standards are established according to the following process (see Annex I):
1. IFRA provides information on the exposure situation (usage concentration, variety of use, volume of use), chemical composition as well as the olfactory profile and olfactory potential (importance) of a fragrance ingredient to RIFM; 2. RIFM prepares a comprehensive dossier on the material including all available safety data and, if necessary, initiates and organizes any missing safety studies on the fragrance ingredient; 3. The RIFM Panel of independent experts, evaluates the data to see if it supports the current use level to make sure that there is no risk to the consumer. If the safety assessment does not support the current use, the Panel instructs IFRA to issue a Standard1; 4. IFRA prepares a Standard in accordance with the Panel's instructions and conclusions; 5. The draft Standard is consulted with the IFRA membership and stakeholders for a period of about a month, to ensure that IFRA/RIFM are aware of all data on the material and to provide holders of additional data that might alter the outcome of the Panel's risk assessment with the opportunity to share those with IFRA/RIFM; 6. If no additional information is received via the Consultation phase, the final Standard is published in a notification procedure as part of an “Amendment to the IFRA Code of Practice”. Q. Does the absence of an IFRA Standard means that the fragrance ingredient is 100% safe? The current set of IFRA Standards is a list of ingredients that have undergone the IFRA Standards Development Process and were found to be needing risk management measures This means that those fragrance ingredients that cause or are supposed to cause, adverse effects to the human health are part of this list. This includes all high volume fragrance ingredients and those with “structural alerts” on particular toxicological endpoints. Practically speaking, all fragrance ingredients have not been fully examined by RIFM yet. The most important fragrance ingredients, sold in big quantities or presenting obvious safety issues have already been evaluated but more time is needed to complete the safety assessment of the other materials. In this regard, RIFM launched an ambitious program intended to assess the safety of all remaining ingredients, listed on the IFRA Transparency list, in the next five years. In the interim, The IFRA Code of Practice prescribes that the absence of an IFRA Standard could mean that the material is safe for use under any condition or it has not been assessed yet. For this reason, and in addition to the compliance with the IFRA Standards, a responsible company should ensure that the fragrance ingredients not covered by an IFRA Standard can reasonably be used in the fragrance formula based on all available data at hand. On this last point, the company having the appropriate staff will make its own safety assessment using reputed toxicological database (e.g. RIFM database). The company which does not have sufficient resources to complete this exercise is advised to outsource it to a competent consultant.
3. The QRA methodology Q. What is the QRA methodology? The Dermal Sensitization QRA (Quantitative Risk Assessment) is used to evaluate the risk of skin sensitization resulting from the exposure to allergens via consumer products. This methodology was adapted to fragrance allergens and its main features are published in the peer-‐reviewed journal 'Regulatory Toxicology and Pharmacology'. This article can be downloaded from the RIFM website. All IFRA Standards of restriction intended to protect consumers against the risk of skin sensitization are based on this methodology. The QRA intends to prevent individuals from getting sensitized to fragrance allergens by deriving maximum use levels for 11 consumer product categories. Allergic Contact Dermatitis (ACD) is a skin disease involving the immune system. This is a two step process: 1) an induction phase, which primes and sensitizes the immune system for an allergic response, and 2) an elicitation phase, in which the actual allergic response is triggered. Elicitation occurs after subsequent exposures to the skin sensitizer having gone through the induction phase. It is now generally accepted in the scientific community that both the sensitization and the elicitation phases are triggered by a threshold mechanism. Preventing induction automatically prevents the issue of sensitization and elicitation. For this reason, safe use levels preventing induction are established for each allergen via an appropriate risk assessment methodology. The QRA methodology is based on many parameters but, before all, on the skin sensitizing potency. The potency determination is the usual result of the hazard assessment of a substance. Skin sensitizing potency can range from very weak to extreme but the majority of fragrance allergens are weak sensitizers. All available scientific studies on the skin sensitizing potency are combined using the Weight of Evidence (WoE) approach to give a quantitative value: the NESIL or “No Expected Sensitization Induction Level”. The NESIL is translated in terms of real risk for the consumer by taking several factors into account. Together, these factors make the Sensitization Assessment Factor (SAF). In the current QRA methodology these factors are: • The inter-‐individual susceptibility; some people are more sensitive than others to skin sensitizers which can be due to genetic predisposition, age or skin condition. • The matrix effect; some products are more aggressive than others (e.g. acid/alkaline products,
presence of certain solvents, additional irritants, etc). • The use pattern; the area where the skin sensitizer is applied and the amounts of product used
have an importance in the sensitization process (e.g. a deodorant applied to an occlusive and sensitive area is more problematic than a shampoo).
The QRA methodology combines the NESIL and the SAF to define a maximum use level for each fragrance allergen and product type in order to avoid induction. This maximum use level has to be compared with the real exposure to this allergen on the marketplace and risk management measures, in the form of an IFRA Standard, will be proposed where the exposure observed on the marketplace goes beyond the maximum determined use level. Q. How do QRA Standards work? Eleven values are reported in every QRA Standard – one per IFRA category. A product type can be linked to an IFRA category by consulting the IFRA-‐RIFM QRA Informational Booklet. This information is reported in all details between pages 13 and 21 but a few examples of product types for each IFRA category can be found in the table below. For more information on the QRA methodology, please, consult the booklet between pages 32 and 36 (frequently asked questions).
These QRA values are the maximum use levels that should be present in the finished consumer product. Important: this limit applies to the finished consumer product. Two strategies are possible in this case: -‐ You ask your client (the finished product manufacturer) how much of your fragrance he plans to add to his finished product. -‐ You provide your client with the maximum concentration of fragrance that he can add to his formula. This maximum concentration is determined by the most restricted ingredient of your composition. For instance, an eau-‐de-‐toilette for man is IFRA category 3. The table provided below is an excerpt of the IFRA Standard set for alpha-‐Amyl cinnamic aldehyde. This means that alpha-‐Amyl cinnamic aldehyde is limited at 3.6% in the finished eau-‐de-‐toilette. If your client told you that the finished eau-‐de-‐toilette will contain 10% of fragrance, this means that your fragrance compound should not contain more than 36% of alpha-‐Amyl cinnamic aldehyde.
Q. What is the difference between an IFRA category and an IFRA class? An IFRA category only relates to sensitization QRA Standards, it is a way to classify consumer products by foreseeable exposure and by specificity (a cream being, for instance, a chemical environment completely different from an hydroalcoholic lotion). IFRA classes are a subdivision of IFRA categories that take other types of Standards into account (i.e. systemic toxicity and phototoxicity.). You will find the IFRA classes in the IFRA-‐RIFM QRA Informational Booklet between pages 25 and 30. 4. The IFRA Compliance and the IFRA Certificate Q. A natural extract is covered by an IFRA Standard. Does a fragrance formula additionally also have to comply with the IFRA Standards for each of the constituents in that oil ? Yes, compliance of a fragrance compound includes both the IFRA Standard covering this natural extract (e.g. Ylang ylang essential oil) but also the IFRA Standards of all of its components (e.g. Benzyl alcohol, Benzyl benzoate, Benzyl salicylate, Eugenol, Farnesol, Geraniol, iso-‐Eugenol). Q. What is the IFRA Certificate and who makes this document? The IFRA Certificate is a document established by the fragrance compound manufacturer for its customer. It means that, using this certificate, a fragrance supplier assures to his customer that they work according to the good manufacture practices described in the IFRA Code of Practice. This certificate can be completed with in-‐house expertise at the fragrance manufacturer or by appropriately educated external resources. Q. If a fragrance becomes used in an application different from that for which an original IFRA Certificate has been made, can the client still use the same IFRA certificate? No, the IFRA certificate is IFRA class-‐specific. The IFRA compliance has to be recalculated and the IFRA certificate redistributed if the class changes.
5. More things to know about the Standards Almost all IFRA Standards are based on the same principle and their implementation is relatively straightforward. However, some IFRA Standards are tricky or present exceptions. Special attention should be paid to the following materials: -‐ Methyl eugenol: the maximum use level for non-‐skin contact products applies to the concentration in the fragrance compound (and not in the finished product). -‐ Acceptable trace levels of toluene and benzene also pertain to their levels in fragrance compounds. -‐ Methyl heptine carbonate and Methyl octine carbonate are linked: they have different maximum use levels but the co-‐use of these two fragrance ingredients should not go beyond 100 % of what is allowed. Example: an eau-‐de-‐toilette for woman (IFRA category 4), containing 0.005 % of Methyl heptine carbonate (maximum use level = 0.01 %) and 0.0015 % of Methyl octine carbonate (maximum use level = 0.002 %). Both ingredients are used below their individual maximum use levels but the formula is not IFRA compliant because 0.005 / 0.01 + 0.0015 / 0.002 = 50 % + 75 % = 125 % beyond the limit of 100 %. -‐ Rose ketones are linked: the same principle applies to rose ketones but all rose ketones are grouped under the same IFRA Standard and are limited at the same maximum use levels. Nevertheless, the co-‐use of several rose ketones should not go beyond 100 % of what is allowed. -‐ Phototoxic substances: as of today, 12 materials are restricted due to their phototoxic properties (5-‐Acetyl-‐1,1,2,3,3,6-‐hexamethyl indan (AHMI), Angelica root oil, Bergamot oil expressed, Bitter orange peel oil expressed, Cumin oil, Grapefruit oil expressed, Lemon oil cold pressed, Lime oil expressed, Methyl N-‐methylanthranilate, Methyl β-‐naphthyl ketone, Rue oil, Tagetes oil and absolute). These 12 materials are linked by the same principle: the co-‐use of phototoxic materials should not go beyond 100 % of what is permitted. Furthermore, the citrus oils (Angelica root oil, Bergamot oil expressed, Bitter orange oil expressed, Cumin oil, Grapefruit oil expressed, Lemon oil cold pressed, Lime oil expressed, Rue oil) are linked by the IFRA Standard on “Citrus oils and other furocoumarins-‐containing essential oils (Bergapten)”.
In case you determined the exact content of bergapten in the natural oils containing them, you can simply apply this Standard restricting the trace level of furocoumarins at 15ppm in the finished product. If you did not, you have to apply the individual IFRA Standards developed for the furocoumarins-‐containing essential oils.