Perfumes _fragrances_ and colophony by liwenting

VIEWS: 18 PAGES: 76

									                                                               2003-01-29 CEN/BT/WG 132 N       29 Annex 4d - Perfumes and colophony 1 (76)



                                     Perfumes (fragrances) and colophony
Project group                        PG4 – Perfumes and Colophony

Participants and project leader      Ann-Therese Karlberg (project leader), Richard Brown, Stephen Carter, Alain Chaintreau, Roland
                                     Efraimson, An Goossens, Elisabet Jansson, Jean-Pierre Lepoittevin, Carola Lidén, Marie Norell, Suresh
                                     Rastogi, Maria Sköld and Louisane Vervaet

allergen                                                                                                                           page
Amyl cinnamal                                                                                                                      2
Amylcinnamyl alcohol                                                                                                               5
Benzyl alcohol                                                                                                                     8
Benzyl salicylate                                                                                                                  11
Cinnamyl alcohol                                                                                                                   13
Cinnamal                                                                                                                           16
Citral                                                                                                                             19
Coumarine                                                                                                                          22
Eugenol                                                                                                                            25
Geraniol                                                                                                                           28
Hydroxycitronellal                                                                                                                 31
Hydroxymethyl-pentylcyclo-hexenecarboxaldehyde (Lyral)                                                                             34
Isoeugenol                                                                                                                         37
Anisyl alcohol                                                                                                                     40
Benzyl benzoate                                                                                                                    43
Benzyl cinnamate                                                                                                                   46
Citronellol                                                                                                                        49
Farnesol                                                                                                                           52
Hexyl cinnamaldehyde                                                                                                               55
2-(4-tert-Butylbenzyl)propionaldehyde (Lilial)                                                                                     58
d-Limonene                                                                                                                         61
Linalool                                                                                                                           64
Methyl heptine carbonate                                                                                                           67
3-Methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one                                                                       70
colophony                                                                                                                          73
                                                        2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 2 (76)


1. Allergen                      Amyl cinnamal

                                              CHO




Synonyms, CAS, INCI              2-benzylideneheptanal, α-amyl cinnamic aldehyde. Cas. No. 122-40-7.
Type of material or product      Fragrance
Type of exposure/exposed         General exposure mainly from cosmetics, hygiene and household products; occupational exposure from
groups                           fragrance materials used to mask malodours in products such as cutting fluids or to give a certain smell to a
                                 product. Exposed groups: general population (1, 2)
Prevalence of allergy and        Amyl cinnamal is a well-known allergen as part of the diagnostic test, the fragrance mix. It accounts for
disease (describe type 1 allergy 2-3% of the reactions to the fragrance mix and has been identified as a cause of allergic reactions in
and type 4 allergy respectively, persons with eczema from cosmetic hygiene and household products (1, 2).
when relevant)
Type of allergy symptoms         Dermatitis
Other significant health effects Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                    Classification of priority or   Comment
                                 need
Potential for prevention of      1. high
sensitisation/elicitation by     2. possible
limitation                       3. low
Potential for development of     1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard     2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                 3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                 4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                 5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                 of MS using several ions. In case of interfering substances, since the
                                                                 fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                 should be selected after looking at the full mass spectra of the target
                                                                 substance and the interfering substances. Depending upon the concentration
                                                                 of target substances and interfering substances a perfume/product perfume
                                                        2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 3 (76)


                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                     2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 4 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                          2003-01-29 CEN/BT/WG 132 N               29 Annex 4d - Perfumes and colophony 5 (76)


1. Allergen                        Amylcinnamyl alcohol

                                                CH2 OH




Synonyms, CAS, INCI                2-Pentyl-3-phenylprop-2-en-1-ol, α-amyl cinnamic alcohol, Cas. No. 101-85-9.
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Five single cases reported of contact allergy to amyl cinnamyl alcohol and allergic reactions by patch
disease (describe type 1 allergy   testing were found in 7/179-2/20 (4-10%) of patients with contact eczema from cosmetics.
and type 4 allergy respectively,
when relevant)                     Amyl cinnamyl alcohol probably cross reacts with amyl cinnamal
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                                   has to be analysed at several dilutions. If technically possible, the method will
                                                        2003-01-29 CEN/BT/WG 132 N             29 Annex 4d - Perfumes and colophony 6 (76)


                                                               be validated for the limit of detection as required by the EU Directive(s).

                                                               The methods for sample preparation for various cosmetics and household
                                                               products should be developed when the method for the perfumes and similar
                                                               products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                     We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                   chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficienty covered by
                                      others

3. Summary - background          Reference (name, number)      Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG         Protection demanded for non-
EU/national/other                                              adults (<18 y in Sweden) in
Existing/planned                                               working life (All fragrance
                                                               chemicals but benzyl alcohol
                                                               are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey       GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                 identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-          fragrance chemicals at the
                                 Journal 127 2001:12:29-33     same time
                                 (4)

References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
                                                     2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 7 (76)


2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                          2003-01-29 CEN/BT/WG 132 N               29 Annex 4d - Perfumes and colophony 8 (76)


1. Allergen                        Benzyl alcohol

                                           CH2 OH




Synonyms, CAS, INCI                Benzyl alcohol (INCI). Cas. No. 100-51-6.
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Benzyl alcohol is found in several studies as a cause of allergic reactions in 1.2-15% (2-4 cases in each
disease (describe type 1 allergy   study) of patients with eczema from cosmetic products.
and type 4 allergy respectively,
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                                   has to be analysed at several dilutions. If technically possible, the method will
                                                        2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 9 (76)


                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number) Brief description              Comment
Regulation/limitation/standard   SANCO, SCCNFP/0017/98
EU/national/other                final, 18th December 1999
Existing/planned                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)
                                 Cosmetic Directive 76/768 Allows the use of benzyl
                                 EC Annex VI               alcohol < or =1% as a
                                                           preservative
                                 Cosmetic Directive 76/768 Allows the use of benzyl
                                 EC Annex III              alcohol as solvent for
                                                           perfumes and similar products
                                                           – no limits

Analytical methods               Cosmet Lex, Vol 2,             Method for analysis of benzyl
CEN/ISO/national standards       European Commission, p         alcohol in cosmetic products
Other methods                    141-145
                                 Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
                                 no.8-2002 (3)                  identification of the 24         validated method will be developed.
                                 Ellendt et al. SÖFW-Jour-      fragrance chemicals at the
                                 nal 127 2001:12:29-33 (4)      same time
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 10 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 11 (76)


1. Allergen                        Benzyl salicylate

                                     OH O

                                             O



Synonyms, CAS, INCI                Benzyl salicylate (INCI), Benzyl-o-hydroxybenzoate. Cas. No. 118-58-1
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Benzyl salicylate is a cause of allergic reactions in 0.2-10% of patients with eczema from cosmetic
disease (describe type 1 allergy   products and in one study accounted for 75% of reactions to commercial perfumes.
and type 4 allergy respectively,
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 12 (76)


                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                         2003-01-29 CEN/BT/WG 132 N               29 Annex 4d - Perfumes and colophony 13 (76)


1. Allergen                        Cinnamyl alcohol

                                                CH2 OH




Synonyms, CAS, INCI                Cinnamyl alcohol [INCI], Cinnamic alcohol. Cas. No. 104-54-1
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Cinnamyl alcohol is a well-known allergen as part of the diagnostic test, the fragrance mix. It accounts for
disease (describe type 1 allergy   5-14% of the reactions to the fragrance mix. In addition, it has been shown to be a cause of allergic
and type 4 allergy respectively,   reactions by patch test in 1.7%-75% of patients with eczema from cosmetic products.
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                                   has to be analysed at several dilutions. If technically possible, the method will
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 14 (76)


                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)
                                 IFRA limit: 0.8% in the
                                 final product

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 15 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N               29 Annex 4d - Perfumes and colophony 16 (76)


1. Allergen                        Cinnamal

                                                CHO




Synonyms, CAS, INCI                Cinnamal [INCI], Cinnamaldehyde, 3-phenyl-2-propenal, Cinnamic aldehyde. Cas. No. 104-55-2
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Cinnamal is a well-proven allergen as part of the diagnostic test, the fragrance mix. It accounts for 5-36%
disease (describe type 1 allergy   of the reactions to the fragrance mix. It gives reactions in 2-3% of consecutively patch tested patients, most
and type 4 allergy respectively,   of which are of relevance. In addition, it has been shown to be a cause of allergic reactions by patch test in
when relevant)                     1-30% of patients with eczema from cosmetic products in several studies.
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                                   has to be analysed at several dilutions. If technically possible, the method will
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 17 (76)


                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)
                                 IFRA requires “quenching
                                 agents”
Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 18 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 19 (76)


1. Allergen                        Citral


                                            CHO

                                                            CHO




Synonyms, CAS, INCI                3,7-dimethyl-2,6-octadien-1-al, mix of cis and trans isomers. Cas. No. 5392-40-5
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Citral is a cause of allergic reactions in about 1% of consecutively patch-tested patients. It was the most
disease (describe type 1 allergy   frequent cause of reactions to a new diagnostic test for fragrance contact allergy and proved to cause
and type 4 allergy respectively,   contact allergic reactions in 2.6% of patients with eczema from cosmetic products.
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 20 (76)


                                                                substance and the interfering substances. Depending upon the concentration
                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 EU Directive 67/548/EEC,       Citral is classified as a
                                 Annex I (Dangerous             sensitizer by skin contact
                                 substances in chemical         (R43)
                                 products)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)
                                 IFRA requires “quenching
                                 agents”
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 21 (76)



Analytical methods             Rastogi SC. DEPA Survey      GC-MS methods for              Main methods available from which the
CEN/ISO/national standards     no.8-2002 (3)                identification of the 24       validated method will be developed.
Other methods                  Ellendt et al. SÖFW-         fragrance chemicals at the
                               Journal 127 2001:12:29-33    same time
                               (4)

References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 22 (76)


1. Allergen                        Coumarine



                                           O    O

Synonyms, CAS, INCI                Coumarine (INCI), 1-benzopyran-2-one, cis-o-coumarinic acid lactone. Occurs naturally in tonka beans
                                   and other plants. Cas. No. 91-64-5
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Coumarine is a cause of allergic reactions in about 0.4-0.8% of consecutively patch tested patients. 1/3 of
disease (describe type 1 allergy   these cases is not detected by the fragrance mix. Coumarin has caused contact allergic reactions in 0.8-10%
and type 4 allergy respectively,   of patients with eczema from cosmetic products.
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 23 (76)


                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 24 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 25 (76)


1. Allergen                        Eugenol

                                     OH
                                           OCH3




Synonyms, CAS, INCI                Eugenol (INCI). Cas. No. 97-53-0
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Eugenol is a well-known contact allergen. Many investigations have been performed. It is the cause of
disease (describe type 1 allergy   sensitization in 1.2% of consecutive eczema patients and accounts for 4-16% of reactions to the fragrance
and type 4 allergy respectively,   mix. Eugenol has caused contact allergic reactions in 0.7-20% of patients with eczema from cosmetic
when relevant)                     products.
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 26 (76)


                                                                substance and the interfering substances. Depending upon the concentration
                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 27 (76)



References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 28 (76)


1. Allergen                        Geraniol


                                           CH2 OH




Synonyms, CAS, INCI                Geraniol (INCI). Cas. No. 106-24-1
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Geraniol is a well-known contact allergen as an ingredient in the diagnostic test, the fragrance mix. It is a
disease (describe type 1 allergy   cause of sensitization in 0.4% of consecutive eczema patients and accounts for 3-7% of reactions to the
and type 4 allergy respectively,   fragrance mix.
when relevant)                     Geraniol has caused contact allergic reactions in 1.2-30% of patients with eczema from cosmetic products.
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 29 (76)


                                                                substance and the interfering substances. Depending upon the concentration
                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 30 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 31 (76)


1. Allergen                        Hydroxycitronellal


                                           CHO


                                        OH



Synonyms, CAS, INCI                7-Hydroxycitronellal, Laurine. Cas. No. 107-75-5
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Hydroxycitronellal is a well-known contact allergen as ingredient in the diagnostic test, the fragrance mix.
disease (describe type 1 allergy   It is a cause of sensitization in 0.75% of consecutive eczema patients and accounts for 6-16% of reactions
and type 4 allergy respectively,   to the fragrance mix. Hydroxycitronellal has caused contact allergic reactions in 10-45% of patients with
when relevant)                     eczema from cosmetic products.
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 32 (76)


                                                                substance and the interfering substances. Depending upon the concentration
                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)
                                 IFRA limit: 1.0% in the
                                 final product
Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 33 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N               29 Annex 4d - Perfumes and colophony 34 (76)


1. Allergen                        Hydroxymethyl-pentylcyclo-hexenecarboxaldehyde, (Lyral)

                                                           CHO
                                   HO                              HO
                                                                                           CHO

Synonyms, CAS, INCI                4-(4-Hydroxy-4-methylpentyl)cyclohex-3-ene-carbaldehyde, Lyral. Cas. No. 31906-04-4
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Lyral was a cause of allergic reactions in about 2.8% of consecutively patch-tested patients. 2/3 of the
disease (describe type 1 allergy   cases were relevant. In addition, three relevant cases of contact allergy to lyral from cosmetic products are
and type 4 allergy respectively,   established.
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                                   has to be analysed at several dilutions. If technically possible, the method will
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 35 (76)


                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)

References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 36 (76)


2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 37 (76)


1. Allergen                        Isoeugenol.

                                                         OH
                                     OH
                                                               OCH3
                                           OCH3




Synonyms, CAS, INCI                Cas. No. 97-54-1
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Isoeugenol is a well-known contact allergen as ingredient in the diagnostic test, the fragrance mix. It is a
disease (describe type 1 allergy   cause of sensitization in 1.9% of consecutive eczema patients and accounts for 6-22% of reactions to the
and type 4 allergy respectively,   fragrance mix. Isoeugenol has caused contact allergic reactions in 2-25% of patients with eczema from
when relevant)                     cosmetic products.
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 38 (76)


                                                                should be selected after looking at the full mass spectra of the target
                                                                substance and the interfering substances. Depending upon the concentration
                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)
                                 IFRA limit: 0.02% in the
                                 final product
Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-Jour-      fragrance chemicals at the
                                 nal 127 2001:12:29-33 (4)      same time
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 39 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 40 (76)


1. Allergen                        Anisyl alcohol, 4-methoxybenzyl alcohol

                                   CH3O

                                                  CH2 OH

Synonyms, CAS, INCI                Cas. No. 105-13-5
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Two studies reported with contact allergy to anisyl alcohol among patients with cosmetic eczema. 3 and 4
disease (describe type 1 allergy   cases were documented (1.6-20%).
and type 4 allergy respectively,
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 41 (76)


                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 42 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 43 (76)


1. Allergen                        Benzyl benzoate

                                           O

                                               O



Synonyms, CAS, INCI                Benzyl benzoate (INCI), Cas. No. 120-51-4
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Benzyl benzoate is positive in several studies, but only a single case is reported in each experiment for
disease (describe type 1 allergy   patients sensitive to Peru balsam.
and type 4 allergy respectively,
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 44 (76)


                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 45 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 46 (76)


1. Allergen                        Benzyl cinnamate

                                                O

                                                    O



Synonyms, CAS, INCI                Benzyl cinnamate (INCI), Benzyl 3-phenyl-2-propenoate, Cinnamein, Cas. No. 103-41-3
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Benzyl cinnamate is positive in one study of patients with contact allergy to cosmetic products and in a
disease (describe type 1 allergy   high proportion of patients with contact allergy to Peru balsam.
and type 4 allergy respectively,
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 47 (76)


                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 48 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 49 (76)


1. Allergen                        Citronellol


                                        CH2 OH




Synonyms, CAS, INCI                Citronellol (INCI), 3,7-Dimethyl-6-octenol, Cas. No. 106-22-9
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          One case of contact allergy to citronellol of uncertain relevance found by testing consecutive patients.
disease (describe type 1 allergy   Two studies of eczema patients with cosmetic eczema show more than one case each of patch test reactions
and type 4 allergy respectively,   to citronellol.
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 50 (76)


                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 51 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 52 (76)


1. Allergen                        Farnesol




                                           CH2 OH


Synonyms, CAS, INCI                Farnesol (INCI), 3,7,11-trimethyldodeca-2,6,10-trienol, Cas. No. 4602-84-0. 4 possible isomers
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          One study of eczema patients with cosmetic eczema shows two cases of contact allergy to farnesol.
disease (describe type 1 allergy   Additional cases in Peru balsam positive patients are found.
and type 4 allergy respectively,
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 53 (76)


                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 54 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N               29 Annex 4d - Perfumes and colophony 55 (76)


1. Allergen                        Hexyl cinnamaldehyde

                                                CHO




Synonyms, CAS, INCI                α-Hexyl cinnamaldehyde, Cas. No. 101-86-0.
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          One case of contact allergy to hexyl cinnamic aldehyde in each of two studies and 7 cases in one study,
disease (describe type 1 allergy   were found among patients with eczema from cosmetic products.
and type 4 allergy respectively,
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                                   has to be analysed at several dilutions. If technically possible, the method will
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 56 (76)


                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others



3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 57 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 58 (76)


1. Allergen                        2-(4-tert-Butylbenzyl)propionaldehyde (lilial)

                                                      CHO




Synonyms, CAS, INCI                2-(4-tert-butylbenzyl)propionaldehyde, 4-(1,1-dimethyl-ethyl)-a-methylbenzenepropanal;p-tert-butyl-a-
                                   methylhydrocinnamaldehyde, lilial, lilestral, Cas. No. 80-54-6
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Two cases of contact allergy to lilial were found in a study of 176 eczema patients with cosmetic eczema
disease (describe type 1 allergy   and one case with contact allergy to lilial from a deodorant. More cases found, but these may have been
and type 4 allergy respectively,   falsely positive.
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 59 (76)


                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).
                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 60 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 61 (76)


1. Allergen                        d-Limonene




Synonyms, CAS, INCI                R-Limonene, (R)-p-Mentha-1,8-diene. Cas. No. 5989-27-5
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Oxidation products of limonene are strong allergens. The frequency of contact allergy to oxidized limonene
disease (describe type 1 allergy   is about 2% in consecutive eczema patients. Contact allergy upon occupational exposure has been reported
and type 4 allergy respectively,   in several cases. However, the majority (33/63) of patients allergic to oxidized limonene reacted to
when relevant)                     fragrances or markers of fragrance allergy.
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                       2003-01-29 CEN/BT/WG 132 N               29 Annex 4d - Perfumes and colophony 62 (76)


                                                                substance and the interfering substances. Depending upon the concentration
                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 EU Directive 67/548/EEC,       d-Limonene is classified as a    d-Limonene forms allergenic compounds
                                 Annex I (Dangerous             sensitizer by skin contact (R    when exposed to air.
                                 substances in chemical         43)
                                 products)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)
                                 IFRA requires less than 20
                                 mmol of peroxide per liter
Analytical methods               Rastogi SC. DEPA Survey GC-MS methods for                       Main methods available from which the
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 63 (76)


CEN/ISO/national standards     no.8-2002 (3)             identification of the 24          validated method will be developed.
Other methods                  Ellendt et al. SÖFW-      fragrance chemicals at the
                               Journal 127 2001:12:29-33 same time
                               (4)

References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 64 (76)


1. Allergen                        Linalool

                                        OH




Synonyms, CAS, INCI                Linalool (INCI), Cas. No. 78-70-6
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          One case of contact allergy to linalool in one study and 3 cases in another study, were found among
disease (describe type 1 allergy   patients with eczema from cosmetic products. Linalool itself is not an allergen, but oxidized linalool
and type 4 allergy respectively,   contains allergens. The purity of the linalool used in reported patch test studies is not mentioned or
when relevant)                     discussed and the results are therefore not informative.
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 65 (76)


                                                                substance and the interfering substances. Depending upon the concentration
                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 66 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N               29 Annex 4d - Perfumes and colophony 67 (76)


1. Allergen                        Methyl heptine carbonate

                                                       O

                                                       O CH3

Synonyms, CAS, INCI                Methyl oct-2-ynoate, Cas. No. 111-12-6.
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Single cases were reported. It is a strong sensitizer according to IFRA.
disease (describe type 1 allergy
and type 4 allergy respectively,
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                                   of target substances and interfering substances a perfume/product perfume
                                                                   has to be analysed at several dilutions. If technically possible, the method will
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 68 (76)


                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/EG          Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)

References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 69 (76)


2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                         2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 70 (76)


1. Allergen                        3-Methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one


                                                   O



Synonyms, CAS, INCI                γ-isomethylionone, Cas. No. 127-51-5.
                                   The names and the CAS number do not fit together. Some mistake in the SCCNFP report
Type of material or product        Fragrance
Type of exposure/exposed           General population
groups
Prevalence of allergy and          Two cases of contact allergy to γ-methylionone in one study and one case in each of two studies, were
disease (describe type 1 allergy   found among patients with eczema from cosmetic products.
and type 4 allergy respectively,
when relevant)
Type of allergy symptoms           Dermatitis
Other significant health effects   Besides irritancy to the respiratory tract no other significant health effects to the best of our knowledge.

2. Evaluation                      Classification of priority or   Comment
                                   need
Potential for prevention of        1. high
sensitisation/elicitation by       2. possible
limitation                         3. low
Potential for development of       1. Almost ready                 A validated method using GC-MS with all analytical parameters clearly
clinically relevant standard       2. Testing                      defined i.e. column, elution conditions, MS, etc for simultaneous
                                   3. Development                  quantification of the 24 fragrance chemicals in fragrance concentrates
                                   4. Research                     (mixtures of fragrance chemicals used as raw material) is possible to develop.
                                   5. Not realistic                The quantification will be performed in SIM (Selective Ion Monitoring) mode
                                                                   of MS using several ions. In case of interfering substances, since the
                                                                   fragrance mixtures are very complex, the quantification ion for a fragrance
                                                                   should be selected after looking at the full mass spectra of the target
                                                                   substance and the interfering substances. Depending upon the concentration
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 71 (76)


                                                                of target substances and interfering substances a perfume/product perfume
                                                                has to be analysed at several dilutions. If technically possible, the method will
                                                                be validated for the limit of detection as required by the EU Directive(s).

                                                                The methods for sample preparation for various cosmetics and household
                                                                products should be developed when the method for the perfumes and similar
                                                                products has been validated. A period of 3-5 years is necessary for this work.
Priority for development of      1.   high                      We suggest one method for simultaneous quantification of all 24 fragrance
standard                         2.   medium                    chemicals listed by SCCNFP (1).
                                 3.   low
                                 4.   sufficiently covered by
                                      others


3. Summary - background          Reference (name, number)       Brief description                Comment
Regulation/limitation/standard   EU Directive 94/93/            Protection demanded for non-
EU/national/other                                               adults (<18 y in Sweden) in
Existing/planned                                                working life (All fragrance
                                                                chemicals but benzyl alcohol
                                                                are included)
                                 SANCO, SCCNFP/0017/98
                                 final, 18th December 1999
                                 (1)
                                 EU Commission, DG,
                                 SANCO, SCCNFP/588/02
                                 final, 4th June 2002 (2)

Analytical methods               Rastogi SC. DEPA Survey        GC-MS methods for                Main methods available from which the
CEN/ISO/national standards       no.8-2002 (3)                  identification of the 24         validated method will be developed.
Other methods                    Ellendt et al. SÖFW-           fragrance chemicals at the
                                 Journal 127 2001:12:29-33      same time
                                 (4)
                                                    2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 72 (76)


References
1.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Fragrance Allergy in Consumers. A review of the problem.
Brussels, EU Commission, DG, SANCO, SCCNFP/0017/98 final, 18th December 1999
2.EU Scientific Committee on Cosmetic and Non-Food Products intended for consumers. Position statement concerning fragrance chemicals in
detergents and other household products. Brussels, EU Commission, DG, SANCO, SCCNFP/588/02 final, 4th June 2002
3.Rastogi SC. Survey of chemical compounds in consumer products. Contents of selected fragrance materials in cleaning products and other consumer
products. Danish Environmental Protection Agency, Copenhagen, Denmark. DEPA Survey no. 8, 2002
4.Ellendt K, Hempel G, Köbler H. Analysis of sensitizing fragrances by gas chromatography – mass spectrometry. SÖFW-Journal 127 2001:12:29-33
                                                       2003-01-29 CEN/BT/WG 132 N               29 Annex 4d - Perfumes and colophony 73 (76)


1. Allergen                      Colophony
Synonyms, CAS, INCI              Colophonium (INCI), rosin, gum rosin, tall oil rosin, wood rosin
Type of material or product      Natural material that can be used modified or unmodfied using different chemicals. See below.
Type of exposure/exposed         Normal population and occupational exposure.
groups                           Areas of use: Unmodified colophony: soldering fluxes, paper, depilatory waxes, cosmetics, dancers’ and
                                 string players rosin, wood and gum from pine trees. Modified colophony (modification types):
                                 Esterfication with polyalcohols: adhesieve tackifiers, printing inks, bubble gum; Diels-Alder addition of
                                 maleic acid, maleic anhydride or fumaric acid: paper size, printing inks, shoe glues; Hydrogenation:
                                 printing inks, soldering fluxes, emulsifiers in the production of synthetic rubber, adhesive tackifiers;
                                 Polymerization/dimerization: adhesives, printing inks varnishes; disproportionation/dehydrogenation:
                                 polymerization emulsifiers in the production of synthetic rubber, paper size, adhesive tackifiers, printing
                                 inks, insulating material in electronics industry; formaldehyde modification: paper size, printing inks; salt
                                 formation: soap, detergents, paper size, drier formulations, printing inks.
                                 Note! In principal all modified colophony products contain components from unmodified colophony, since
                                 modifications are performed just until the desired technical quality is obtained. The residue of unmodified
                                 colophony is often not declared. Also after two modifications oxidation products of unmodified
                                 components i.e. abietic acid, can be present in amounts high enough to cause dermatitis in allergic
                                 individuals.
Prevalence of allergy and        Colophony is one of the most common causes of contact allergy in dermatitis patients (3.4% of consecutive
disease (describe type 1 allergy patients reacted at patch testing1) and in the general population (0.7%2). Numerous case reports of contact
and type 4 allergy respectively, dermatitis from both occupational as well as non-occupational exposure to colophony can be found in the
when relevant)                   literature. Colophony also causes occupational asthma due to exposure to colophony-based solder flux
                                 fumes3.
Type of allergy symptoms         Dermatitis; the immunologic status of asthma caused by exposure to solder flux fumes is not yet settled
Other significant health effects Asthma due to colophony-based solder flux fumes3

2. Evaluation                    Classification of priority or   Comment
                                 need
Potential for prevention of      1. high                         A common cause of allergic contact dermatitis and of occupational asthma.
sensitisation/elicitation by     2. possible                     See above.
limitation                       3. low
Potential for development of     1. Almost ready                 Methodologies exist for the evaluation of the resin acids in the solder flux
                                                       2003-01-29 CEN/BT/WG 132 N              29 Annex 4d - Perfumes and colophony 74 (76)


clinically relevant standard     2.   Testing                   fume based on GC technique (See below). However, the active/allergenic
                                 3.   Development               ingredients are not identified and the “total resin acids” is taken to be a
                                 4.   Research                  surrogate. Instead, we recommend development and verification of an HPLC
                                 5.   Not realistic             method to detect selected representative oxidation products that are the main
                                                                allergens in unmodified colophony.
                                                                In principle a method for resin acids and oxidation products can be used to
                                                                determine any unmodified material in modified materials and different
                                                                products but research is needed to be able to find methods to handle various
                                                                matrixes before the HPLC analysis.
Priority for development of      1.   high                      Colophony is present in a large number of products under various names and
standard                         2.   medium                    is difficult to detect without analysis.
                                 3.   low
                                 4.   sufficiently covered by
                                      others

3. Summary - background          Reference (name, number)       Brief description               Comment
Regulation/limitation/standard   Classified with R43 as a       Products containing >1%         Very difficult to define 1% of colophony
EU/national/other                skin sensitizer within EU.     colophony should be labelled    since it has a complex composition and not
Existing/planned                                                with warning “Can cause skin    all components are allergenic. Research has
                                                                sensitization”                  shown that oxidation products of the major
                                                                                                resin acid, abietic acid, cause sensistization4-7

                                 The UK (HSE, EH40) has a       The UK limit is 0.05 mg/m3      Evidence is present in Criteria Document EH
                                 “maximum exposure limit”       TWA and 0.15mg/m3 STEL          65/31 from January 1997. (for solder flux
                                 (MEL) i.e. a requirement to    as a MEL. (for solder flux      fume)
                                 reduce exposure to as low      fume)
                                 as is reasonably practicable
                                 (for solder flux fume)

Analytical methods               GC analysis of fatty and                                       None of the methods detect the true allergens
CEN/ISO/national standards       resin acid mixtures8.                                          in colophony i.e. the oxidation products of
Other methods                                                                                   the abietan type resin acids, mainly abietic
                                 MDHS 839                       HSE Methods for                 acid.
                                                      2003-01-29 CEN/BT/WG 132 N             29 Annex 4d - Perfumes and colophony 75 (76)


                                                               Determination of hazardous       The abietic acid hydroperoxide which is
                                                               Substances: Resin acids in       described as the major allergen10 will be
                                                               rosin (colophony) solder flux    decomposed due to heating when using the
                                                               fume                             GC method.
                                 ISO 9454-1 Soft soldering Flux classification on the basis     Requires major revision
                                 fluxes. Classification and    of 16 crude tests specified in
                                 requirements. Part 1:         ISO 9455-1 to –16, including
                                 Classification, labelling and an “acid value” with no
                                 packaging                     specified range corresponding
                                                               to a solder containing resin
                                                               acids

                                  HPLC method for                                               The HPLC method is not developed for
                                 detection of abietic and                                       detection of abietic and dehydroabietic acid
                                 dehydro-abietic acid in                                        but could be further developed to detect also
                                 products11                                                     the hydroperoxide and one secondary
                                                                                                oxidation product such as 7-
                                                                                                oxodehydroabietic acid.

References

1. Schnuch A, Geier J, Uter W et al. National rates and regional differences in sensitization to allergens of the standard series. Population-adjusted
   frequencies of sensitization (PAFS) in 40,000 patients from a multicenter study (IVDK). Contact Dermatitis 1997:37:200-209.
2. Nielsen NH, Menné T. Allergic contact sensitization in an unselected Danish population. The Glostrup Allergy Study, Denmark. Acta Derm
   Venereol (Stockh) 1992:72:456-460.
3. HSE Asthmagen? Critical assessments of the evidence for agents implocated in occupational asthma. HSE Books (2001).
4. Karlberg A-T. Contact allergy to colophony. Chemical identification of allergens, sensitization experiments and clinical experiences. Acta Derm
   Venereol (Stockh) 1988:Suppl.139, 1-43.
5. Hausen BM, Kreruger A, Mohnert J et al. Contact allergy due to colophony (III). Sensitizing potency of resin acids and some related
     products. Contact Dermatitis 1989:20:41-50.
6.   Hausen BM, Börries M, Budianto E, Krohn K. Contact allergy due to colophony (IX). Sensitization studies with further products isolated after
     oxidative degradation of resin acids and colophony. Contact Dermatitis 1993:29:234-240.
7.   Karlberg A-T, Gäfvert E. Isolated colophony allergens as screening substances for contact allergy. Contact Dermatitis 1996:35:201-207.
                                                   2003-01-29 CEN/BT/WG 132 N           29 Annex 4d - Perfumes and colophony 76 (76)


8.  Holmbom B. Improved GC analysis of fatty and resin acid mixtures with special reference to tall oil. J Am Oil Chem Soc 1977:54:289-293.
9.  HSE Methods for the determination of hazardous substances: Resin acids in rosin (colophony) solder flux fume. In HSE Books ISBN 0-7176-
    1363-1 (1997).
10. Karlberg A-T, Bohlinder K, Boman A, Hacksell U, Hermanson J, Jacobsson S, Nilsson JLG. Identification of 15-hydroperoxyabietic acid as a
    contact allergen in Portuguese colophony. J Pharm Pharmacol 1988:40:42-47.
11. Ehrin E, Karlberg A-T. Detection of rosin (colophony) components in technical products using an HPLC technique. Contact Dermatitis
    1990:23:359-366.

								
To top